About
Intravenous (IV) catheters and needles are used for numerous procedures, yet the insertion of the catheters and needles can be difficult, painful, and anxiety provoking to both the healthcare provider and the patient. Methods that can improve the insertion of peripheral IV catheters would decrease the need for multiple sticks, less wasted IV catheters, and less wasted time by the clinician. Failure of the IV insertion with the first attempt may require several attempts before being successful. Worse yet, the healthcare provider may not even be able to successfully insert the IV catheter, requiring more invasive procedures to obtain the necessary IV catheter or needle access. In addition, safety is always a concern when using sharp medical instruments. When attempting to insert an IV catheter or needle, the healthcare provider often needs to stabilize the vein with their non-dominant hand, close to the insertion site. This increases the risk of an accidental needle stick into the hand. We have developed a device to solve this problem

A device that improves the insertion of the IV catheter into the vein would significantly improve the success rate and ease of insertion of the IV. This would minimize the anxiety of the patient and healthcare provider, and decrease the pain and potential complications of unguided IV needle insertions. By using the guide, the healthcare provider also minimizes the possibility of an accidental injury to themselves, thus making the IV catheter or needle insertion safer. The current device accomplishes each of these needs with a simple design that stabilizes the vein and guides the needle into the vein. Trials with IV nurses using a prototype device have been universally beneficial to the nurses such that they desired to have them available. As noted, the device is a simple, yet elegant functional design that is inexpensive to manufacture. Estimated production cost is approximately $0.20 per unit, which would allow for packaging with most IV infusion and access kits, along with any needles used for blood draws.

Proposed Use
Guiding IV needles and catheters

Creator(s)
Eric Gokcen

Patent
Provisional patent filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Other (Medical Devices); Clinical Applications; Life Sciences

About
The present invention provides novel methods and systems to detect mechanical damages in energy storage systems, particularly lithium-ion batteries. These novel methods enable the safety evaluation of Li-ion batteries. The methods are based on applying inputs in the form of voltage or current to Li ion batteries and measuring current or voltage as the output. The inputs can be in sinusoidal form. The measurements will be used to detect damaged batteries from intact ones. The tests are nondestructive, and the batteries can be returned to service if they pass the evaluation.

The first method proposed in this invention is to perform impedance spectra measurements on batteries after cooling/warming them to specific set temperatures to determine their safety status. The second method includes performing impedance spectra measurement on the batteries in situ, without any need for an environmental chamber. In this method, after recording the spectra, an advanced analysis is applied to the result to extract the time constants of the system, the time constants then will be used to make predictions about the safety of the battery. The benefit of using this system includes: • Non-invasive and non-destructive, so that the cells and modules can be returned to service if they pass the test. • Fast and efficient, as there is no need to take CT-scan or other expensive and slow methods to detect the damage. • The testing and analysis can be done while the system is in operational mode with no required downtime. • Portable: the system requires small equipment and can be moved easily. • Increase the safety of energy systems and the useful life of their energy storage devices as they can stay in service without fear of fire and other hazards due to undetected mechanical damages.

Proposed Use
Portable, reliable, and safe battery safety testing system

Creator(s)
Mohsen Derakhshan, Elham Sahraei, Damoon Soudbakhsh

Patent
Provisional Application Filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Electronics & Circuits; Energy Storage; Energy

About
A machine learning approach was used to analyze previously published periodontitis/health microbiome data sets (449 samples in total) to develop an intuitive, clinically relevant subgingival microbiome dysbiosis index as a summary statistic of microbiome sequencing data. The index can have important applications including identification of patients/sites at risk of periodontitis as well as active sites, assessment of microbial response to treatment, and, importantly, as a quantitative tool in microbiome modulation studies.

We performed machine learning analysis of published periodontitis/health 16S microbiome data. The raw sequencing data, split into training and test sets, were quality filtered, taxonomically assigned to the species level, and centered log-ratio transformed. The training data set was subject to random forest analysis to identify discriminating species (DS) between periodontitis and health. DS lists, compiled by various “Gini” importance score cutoffs, were used to compute the SMDI for samples in the training and test data sets as the mean centered log-ratio abundance of periodontitis-associated species subtracted by that of health-associated ones. Diagnostic accuracy was assessed with receiver operating characteristic analysis. An SMDI based on 49 DS provided the highest accuracy with areas under the curve of 0.96 and 0.92 in the training and test data sets, respectively, and ranged from −6 (most normobiotic) to 5 (most dysbiotic) with a value around zero discriminating most of the periodontitis and healthy samples. The index was highly reproducible by hypervariable region. Applying the index to additional test data sets in which nitrate had been used to modulate the microbiome demonstrated that nitrate has dysbiosis-lowering properties in vitro and in vivo. Finally, 3 genera were identified that could be used for calculation of a simplified SMDI with comparable accuracy. This simplified index can be used as a basis for a point-of-care diagnostic kit.

Proposed Use
1- Diagnosis of chronic periodontitis. 2- Identify patients with high susceptibility to periodontitis, e.g. patients with severe disease despite low dysbiosis. 3- Identify people at risk of developing periodontitis, e.g. patients with clinically healthy periodontium but high dysbiosis. 4- Assess response to periodontal treatment; identify sites/patients at risk of relapse. 5- Assess response to oral microbiome modulation therapies/interventions

Creator(s)
Nezar Al-Hebshi

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Artificial Intelligence; Diagnostics; Clinical Applications; Bioinformatics

About
This invention focuses on novel biomarkers for prenatal diagnosis of neural tube defects (NTDs) based on differences in the abundance and composition of central nervous system (CNS)-specific proteoglycans in amniotic fluid. NTDs occur very early in gestation (first trimester) and increase in severity during fetal development. Accurate, reliable, early diagnosis is therefore vital. Currently, NTD prenatal screening and diagnosis is based on a combination of serum alfa fetoprotein (AFP) levels and fetal ultrasound imaging. However, these methods present several disadvantages that can lead to unreliable diagnoses. More accurate and objective biomarkers for early detection of NTDs would provide not only a more reliable diagnosis, but one that would support more informed patient management decisions at much earlier timepoints.

We have developed an ELISA-based diagnostic test for 2 CNS Chondroitin Sulfate Proteoglycans, that have been confirmed in a rat model. When fully developed, the test would: 1. Be more specific and accurate than the current standard for diagnosis via serum AFP plus ultrasound. 2. Be usable earlier in pregnancy than current methods. AFP is widely used but has a time window for accurate correlation with NTD and thus may not be accurate outside the time window. 3. Be less reliant on expensive imaging studies such as ultrasound that require interpretation of results by qualified technicians. Our method will be much less expensive, and performed very early in pregnancy and will benefit patients in countries with limited access to advanced prenatal care and imaging facilities.

Proposed Use
Early detection of neuraltube birth defects

Creator(s)
Barbara Krynska, Oleg Gordiienko, Karolina Janik, George Smith

Patent
Provisional PCT filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Biotechnology; Diagnostics

About
Spatially Resolved Diffuse Reflectance (SRDR) is a technique for performing the TransCutaneous (TC) estimation of tissue chromophores with reduced influence from confounding parameters associated with tissue layers adjacent to the layer where the chromophores of interest reside. In contrast with prior point-of-care devices, SRDR images diffuse reflectance point-spread functions with a 2D camera module instead of the reflectance at a finite set of positions using single-point detectors. In our preliminary studies, we have performed computer simulations of the technique for estimation of both oxygenation saturation levels and bilirubin levels, indicating reduced pigmentation-dependent measurement bias and error across both scenarios when regression models are created using multiple regions of interest digitially defined across the 2D sensor field of view. In addition, we have completed human-subjects pilot studies which using this approach using a mobile-phone camera platform to quantify bilirubin in neonates. The results indicate indicate a good ability to predict bilirubin.

The invention consists of an optical detection system in which a 2D sensor (camera) images the diffuse reflectance spatial decay function generated from a light source/multiple light sources incident on the surface of the tissue at certain distance offset from the camera's field of view. We have developed a multi-variate regression model constructed against the gold standard clinical measurement (i.e. Serum Bilirubin in bilirubinometry or Arterial Blood Gas Oxygenation Saturation in oximetry) using multiple spatial regions of interest in the camera field of view. In a color camera, there are 3 different (red/green/blue) detector color channels from which to extract unique regions of interest, as is the case in bilirubinometry. In the case of oximetry, these wavelength dependent channels can be the result of different light sources. An optimization algorithm is used to identify the coordinates and sizes for regions of interest which minimize model error. This device can consist of a snap on adapter to any consumer camera or mobile phone camera, or alternatively be a custom built device centered around a consumer 2D imaging module.

Proposed Use
-point of care bilirubinometer for screening newborns for neonatal jaundice, either as a smart phone case style adaptor/mobile phone app pair for at-home use by nurse midwives or parents, or a specific use handheld measurement device for use in low-resource settings gobally. -clinical oximeter for use in patient care , surgical, pre/post-operative settings, as well as in respiratory therapy etc. -standalone wearable consumer device measuring physiological parameters such as oximetry -electronic sensor modules which can be integrated into existing multifunction wearable technologies.

Creator(s)
Chetan Patil, Mohammed Shahriar Arefin, Alexander P. Dumont, Brandon Keith Harrison

Patent
Provisional Application filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Medical Devices; Clinical Applications; Instrumentation; Imaging; Diagnostics

About
Arthroscopy is a routine surgical procedure used to assess joint health. With advancements in technology and improvements to traditional devices, the arthroscopic procedure volume is expected to substantially rise. We aim to develop a novel way to provide real time analysis of joint tissues by a near infrared (NIR) fiber optic probe that allows for the objective evaluation of compositional properties during routine knee arthroscopy. Our non-destructive NIR probe represents a fundamentally new and powerful approach for evaluating and guiding cartilage therapeutics.

Our new NIR arthroscopic probe is designed to be externally similar to a traditional arthroscopic hook probe, but with the internal structure of a NIR fiber optic probe with fibers that span the visible and NIR spectral regions. Our innovation is a novel tool for collecting visible (Vis) and NIR spectral data that reflects composition during arthroscopic procedures. This type of device is currently not commercially available and can be competitively inserted in both the arthroscopy device market and medical fiber optics market. Our innovation is advantageous in comparison to the current joint assessment procedure of subjective palpation and interpretation using the traditional arthroscopic hook probe by providing objective quantitative information. Our design is an improved technological advance that can be easily advertised and absorbed into the surgical marketplace. Our NIR arthroscopic probe was designed with clinicians in mind to guide management of joint diseases. As noted externally, it will be similar to conventional arthroscopic hook probes in design, but with the capability of obtaining compositional information from tissues. This design criteria will facilitate its market placement and integration into routine surgical practice. NIR is a well-established and non-harmful light technology that is currently used in several FDA-approved medical devices.

Proposed Use
• A tool used by surgeons during routine arthroscopy to monitor (i) joint lesions (ii) joint lesions post-surgery (iii) implant integration with surrounding tissue (iv) optimal donor tissue site • Identification of optimal sites for autologous chondrocyte implantation • Objective and quantitative device for orthopedic surgeons • Real-time monitoring of biochemical composition of joint and/or implant and surrounding tissue • Real-time monitoring of degeneration and healing of joint and/or implants

Creator(s)
Nancy Pleshko, Jessica M Falcon, Shital Kandel, Jack Oswald, William Querido Maciel

Patent
Provisional Application

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Diagnostics; Instrumentation; Imaging

About
The main embodiment of this medication delivery system invention is the endotracheal tube (ETT). The ETT is used to intubate the respiratory channel (i.e., the trachea) of a patient to deliver air, oxygen, and/or anesthetic gases during procedures under general anesthesia (use # 1) and for mechanical ventilation of critically ill patients in the intensive care unit (use # 2). Finally, the endotracheal tube has the added benefit of preventing gastric contents from entering the airway which can lead to aspiration pneumonia and lung damage (use # 3). The ETT is a fundamental and essential component of modern medicine with more than 313 million procedures performed annually in addition to the ETT used for mechanically ventilated patients. While ETT has multiple uses, it’s application is inherently associated with multiple adverse consequences primarily resulting from the increased circumferential pressure exerted by the inflation ETT on the tracheal mucosa enclosed within the rigid tracheal rings. The adverse consequences of the ETT include: (1) bronchospasm: constriction of the airways; (2) emergence reactions: violent and combative emergence, coughing, retching; (3) application of higher doses of anesthetic beyond the need of the procedure to counteract the stimulating effect of the ETT leading to hemodynamic instability and complications; (4) Tracheal stenosis around the inflated cuff due to prolonged endotracheal intubation in critically ill patients in intensive care unit. The aforementioned 4 adverse consequences are experienced by every medical center worldwide performing procedures and/or managing critically ill patient in the intensive care unit.

The invention provides a medication delivery device configured to allow precise and controlled circumferential (or sectional) medication delivery to the interface between the endoluminal device cuff and the compressed surrounding tissue lining the lumen. The invention allows for precise, timely and accurate delivery of medication only to the surrounding compressed mucosa abutting the endoluminal tube cuff. This precise and time-controlled administration of the medication allows for using the smallest doses possible of the medication minimizing the likelihood of complication while achieving maximum clinical benefit. Injected medications include local anesthetics (solves problem 1-3), and steroids (solves problem 4). The invention is expected to minimize complication rate associated with ETT, improve clinical outcomes, and reduce healthcare cost. The invention has been experimentally verified in vitro using a calibrated setup simulating intraoperative clinical conditions encountered in everyday practice as described in peer-reviewed literature. Compared to existing and suggested solutions to the problem, the invention was proven to unequivocally solve the problem. Based on in vitro experiments and existing body of literature detailing current clinical practices, the invention is far superior to existing prior art and clinical practices. The invention can be added to all existing endoluminal devices including ETT (main embodiment)

Proposed Use
1- Endotracheal tubes used during general anesthesia (main embodiment) 2- Endotracheal tubes used in the intensive care unit (main embodiment) 3- Laryngeal mask airway used during anesthesia 4- Endoluminal catheters and devices used for urological, gastroenterological, and vascular procedures.

Creator(s)
Ihab Kamel

Patent
Provisional Patent Application filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Medical Device; Therapeutic delivery; Clinical Applications

About
The Novartis iron chelator Deferasirox was used to test its antimicrobial activity against oral bacteria in an in vitro biofilm. Deferasirox was able to selectively reduce the population of periodontal disease causing bacteria.

This is a novel application of an existing drug belonging top the class if iron chelators. The drug was able to reduce the numbers of oral bacteria that cause periodontal disease, in vitro. Bacteria were enumerated in the in vitro biofilm after day 3 and day 7 of drug application. And the dug was tested at two different concentrations. Dose-dependent antimicrobial effect was observed. The drug was selective in the eradication of mostly periodontal bacteria; and most importantly, majority of the healrthy oral bacteria were not affected.

Proposed Use
The drug can be incorporated into oral mouthwashes and gels for easy application through oral rinses.

Creator(s)
Sumant Puri, Nezar Al-Hebshi

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Clinical Applications

About
A system or method for a combination of MAP antibody tests for detection of MAP infection and the diagnosis of disease for patients with Crohn's disease, autoimmune diseases and in asymptomatic individuals, is provided.

MAP is the cause of Crohn's disease (CD) first described in 1895, a zoonotic infection that affects cattle, goats, sheep and most species of wildlife throughout the world. The human population is widely exposed to the organism in the food chain since it is found in asymptomatic beef cattle and in the milk of dairy cows. Multiple international studies have shown that a proportion of MAP organisms survive the current conditions of HTST pasteurization. Two meta-analyses have concluded that the MAP organism is present in a majority of patients with CD as compared to a control population. Since the MAP theory of causation of CD gained interest following the growth of MAP from the intestinal tissues of CD patients by Rod Chiodini in 1984, multiple clinical trials of antibiotics have failed to cure CD and gastroenterologists have dismissed the MAP theory. However, this theory remains plausible and valid. What is needed is a system and/or method that satisfies one or more of these needs or provides other advantageous features. Other features and advantages will be made apparent from the present specification. The teachings disclosed extend to those embodiments that fall within the scope of the claims, regardless of whether they accomplish one or more of the aforementioned needs. The inventors have found a inventor modified modified veterinary ELISA assay detects the greatest number of subjects with MAP antibodies (70% of CD patients and 63% of non-CD controls) followed by the Bach anti Cl1 antibody (42% of CD patients and 53% of non-CD controls). These two antibodies could be used either singly or in the form of a sum of a positive result in either or both tests to screen for the presence of MAP antibodies. This part of the combination of antibodies would be useful for identifying the presence of the organism in the host, i.e., infection, rather than identifying the presence of disease. In the current MAP/CD study, the two antibodies which are best at discriminating the presence of disease include the Zhang Hsp65 antibody and the Bach pKnG antibody. Amongst the several serology tests, the highest correlation to the presence of CD 5 occurred with the Zhang Hsp antibody. At a cutoff value > 0.74, this method had the best ability to discriminate between CD patients and non-CD controls (OR (95% CI) of having CD comparing Zhang Hsp > 0.74 vs. Zhang Hsp ≤ 0.74: 2.40 (1.25, 4.61)) with p-value 0.009 and fisher exact p value 0.020. The Bach pknG anitbody also had a significant correlation to the CD/UC patients as compared to the non-CD/UC controls.These antibodies could be used individually to identify those patients with CD or Sjogren’s Syndrome (SJS). In as yet unpublished work, the Zhang Hsp65 antibody is positive in similar proportions among patients with CD (67.9% or 74 of 109 patients) and SJS (85.7% or 24 of 28 patients). In a population of 288 healthy blood donors, only 8 donors or 2.8% had Hsp65 IgG antibodies. Based on previously published MAP prevalence studies in multiple sclerosis (MS) and type I diabetes mellitus (T1DM), there is a high probability that patients with these diseases also have a high rate of Hsp65 IgG. The discriminatory ability of these antibodies to identify the presence of a MAP caused disease would be increased when both antibodies are positive. In other words, any subject with positive results in both the Hsp65 and the Bach pKnG has a very high probability of suffering from a MAP caused illness.

Proposed Use
The final product includes a panel of serologic antibody tests for the detection of infection by Mycobacterium avium ssp. paratuberculosis (MAP) organisms. The kit will include all of the items required for the detection of MAP infection in a routine hospital microbiology laboratory. Adoption of these antibody methods will lead to widespread testing for this bacterium in the general population. Most diseases considered of unknown or “autoimmune” etiology including Crohn’s disease (CD), complex regional pain syndrome (CRPS) and Alzheimer’s disease (AD) will be investigated for a MAP causation and MAP will be implicated in some of these diseases. Published studies from Europe indicate an increased prevalence of MAP infection in patients with type I diabetes mellitus (T1DM) and multiple sclerosis (MS) thus raising the possibility of an etiologic role of MAP in these conditions. This phenomenon will lead to widespread testing of the human population and to improved public health measures that limit the introduction of MAP to the food supply.

Creator(s)
John Todd Kuenstner, Raghava Potula

Patent
62/942,480; PCT/US20/62642

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

About
The US Preventive Services Task Force and the National Academy of Medicine (formerly the Institute of Medicine) have called for improved circulating biomarkers of vitamin D status to be used in screening healthy adults for low vitamin D status. In light of this recognized need, we propose the calcitriol-24,25-dihydroxyvitamin D3-calcifediol proportion ratio (C24CPR). Higher C24CPR values theoretically describe a greater production of 1,25(OH)2D3 relative to 24,25(OH)2D3, adjusted for the upstream reserve of 25(OH)D3. Adjustment using genetic ancestry informative markers (AIMs) will further improve the use of C24CPR in precision medicine settings.

CYP24A1 is the major vitamin D catabolic enzyme for which at least three major metabolites compete. These include 25(OH)D3, 24,25(OH)2D3, and the active form of vitamin D (1,25(OH)2D3). The C24CPR biomarker is developed under the concept of CYP24A1 enzyme metabolite competition. All three metabolites which make up the balance of C24CPR compete for catabolism by this mitochondrial enzyme. The "active" form of vitamin D, known as calcitriol (aka 1,25(OH)2D3) is the only vitamin D metabolite known to influence downstream gene function via the vitamin D receptor (VDR) at picomolar concentrations. Higher C24CPR values theoretically describe a greater production of 1,25(OH)2D3 relative to 24,25(OH)2D3, adjusted for the upstream reserve of 25(OH)D3. C24CPR calculation requires plasma measurement of all three metabolites using high performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Details regarding the assay and development of ancestry informative markers are provided in Wilson (2018) and Wilson (2011); details regarding the calculation are provided in Wilson (2020); and molecular rationale for differential CYP24A1 expression according to genetic ancestry (Wilson, 2008). Ancestry-adjustment of C24CPR requires genotyping for Ancestry Informative Markers (AIMs) (Wilson, 2018; Wilson, 2020). Globally, genetic variability (i.e., frequency of novel single nucleotide polymorphic variants) among African populations is greatest and consistent with the “out of Africa” hypothesis (McEvoy, 2011). This is a major reason why we have developed a West African genetic-ancestry-adjusted measure of C24CPR. We propose that our novel model will permit a more accurate analysis and management of vitamin D and its metabolites in an individual.

Proposed Use
Potential uses of C24CPR: 1) The system can be used for screening for CYP24A1 Inhibitor Therapy. 2) Monitoring for Risk of Bone Depletion in Glucocorticoid Treatment. 3) Screening for Idiopathic Infantile Hypercalcemia (IIH) and Reduced Function CYP24A1 Mutations. 4) Screening Among Healthy Individuals. Calcitriol (1,25(OH)2D3) and 25(OH)2D3 alone has been associated with a healthy lifestyle (Kohler, 2017). a. We have shown that, compared with a crude ratio, improved distributional characteristics of C24CPR using our method. b. Our model assess C24CPR in healthy individuals to identify decrements in renal function which may be a consequence of cumulative environmental insults through heavy metals and persistent per- and poly-fluorinated compounds (PFAS) in ambient air and drinking water. c. C24CPR appears to be a distinct marker of vitamin D status in healthy young adults that is capturing something distinct from the “active form” of vitamin D, calcitriol (1,25(OH)2D3). i. Our model accounts for the observed gene variants associated with the C24CPR biomarker that are not the same as the pattern of gene variants associated with calcitriol (1,25(OH)2D3). ii. Sunlight and tanning bed induced a significant dose-response decrease in C24CPR. This unexpected result may have important health consequences. iii. Oral contraceptive use is well-known to increase plasma/serum calcitriol (1,25(OH)2D3) and 25(OH)D concentrations. We observed a significant decrease in C24CPR with among oral contraceptive users that appeared to be dose-dependent. iv. Compared with calcitriol (1,25 (OH)2D3), a greater proportion of the C24CPR biomarker can be explained by known genetic and environmental factors (49.5 versus 37.4 percent, respectively). d. Factors associated with higher bone mineral density (i.e., male sex, higher BMI, and African American ancestry) are associated with higher C24CPR values in young healthy adults (ages 18-35). These associations are distinct from those with calcitriol.

Creator(s)
Robin T Wilson

Patent
Provisional Patent Application has been filed.

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Diagnostics; Therapeutics; Research Tools

About
STAT2 is a transcription factor and key signaling molecule in the transcriptional response to type I and type III interferon (IFN). IFNs belong to a family of cytokines that play an important role in activating a protective response against pathogenic infections and cancer. New evidence, however, is emerging depicting STAT2 as damaging in human autoimmune diseases, in certain bacterial infections and super-infections as well as in certain types of cancer as a tumor promoter. With the development of a traditional STAT2 knockout mouse, this model proved to be instrumental in addressing important questions regarding STAT2 function in host defense as a downstream activator of the IFN signaling pathway. Nonetheless, the utility of this model has been limited because it does not permit the study of STAT2 function in the context of specific tissues and cell types that pertain to a given disease. To overcome this barrier, my lab generated a conditional Stat2 knockout mouse to enable specific and efficient deletion of STAT2 in cell types and tissues of interest. This new mouse is a powerful model system to study the contribution of STAT2 in multiple diseases.

We generated Stat2 floxed mice to enable excision of STAT2 in a tissue specific manner. These mice were developed by first designing a targeting vector that flanked exons 5-8 of Stat2 with loxP sites. The distal loxP site was introduced with a flip recombinase target (FRT) flanked neomycin resistant cassette. The Stat2 targeting vector was then electroporated in embryonic stem cells (ES) of C57Bl/6 (B6) genetic background. Integration of the targeting construct was confirmed by Southern blotting and ES cells were used for implantation. The neomycin resistance cassette was later removed with deleter-mice carrying Flp recombinase (Jax labs). F1 offspring heterozygote for Stat2 floxed allele were interbred to generate homozygous Stat2 floxed mice. Successful tissue specific deletion of STAT2 in conventional CD11c+ dendritic cells, colonic epithelial cells and complete STAT2 deletion has been achieved with the use of tissue specific and global Cre-recombinase mice.

Proposed Use
Targeted deletion of Stat2 in cells/tissues of interest opens the unprecedented opportunity to define STAT2 function in multiple diseases by identifying novel and unique targets appropriate for specific diseases. Additionally, these mice could be used to develop better models of human disease. This critical information would provide the platform for developing therapeutics that target STAT2 signaling to treat diseases. Presently, there are no pharmacological inhibitors to STAT2. These mice could be used as a pre-clinical model to test the specificity of drugs that target STAT2 signaling.

Creator(s)
Ana M. Gamero

Patent
Proprietary Mouse Line available for licensure

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Diagnostics; Biotechnology; Research Tools

About
Dry eye disease is a very common problem, especially with face mask wear during the COVID-19 pandemic. A subset of patients have dry eye disease from lagophthalmos, or incomplete closure of the eyelids. This subset of patients includes those with facial paralysis (including Bell’s palsy); nocturnal lagophthalmos, a naturally-occurring incomplete closure of the eyelids while sleeping; or those in the hospital on ventilators. For many of these patients, simply lubricating the eye with ointment is insufficient, and the standard therapy of patching the eye can be irritating to the skin or uncomfortable. In these patients, a moisture chamber to enclose the peri-ocular area can provide substantial benefit. Moisture chambers such as polyethylene covers (plastic wrap), goggles, and Tegaderm have been described in the medical literature. However, these can be messy, ineffective, or inconvenient to use.

We propose a modification of existing technologies to create a moisture chamber that does not stick to the eyelid, while providing superior moisture retention. We have been using our prototype in the clinical setting and believe this could be an important new product in the field of dry eye treatments. We are seeking a partnership to further develop our approach.

Proposed Use
Moisture chamber for the eye.

Creator(s)
Mark Krakauer

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Polymers (Materials); Clinical Applications; Therapeutic (Medical Devices)

About
The Research Perfusion Rig is an apparatus to proficiently and consistently remove fixed tissue via tool dissection of a specimen by permitting simultaneous fixation and perfusion of an research subject. The Rig also results in facilitating fluid collection for analysis processing and/or biohazard elimination.

The Research Perfusion Rig is an apparatus that consists of a perforated platform which sits slightly above a collection basin that is sufficiently angled for proficient disposal or analysis of fluids via a drain, at the bottom of which has a tube connected that goes down to a fluid collection container. Moreover, the Rig enables immobilization of a research subject within a superstructure that has hooks to attach one or more tools to consistently immobilize the subject in place prior to the fixation and perfusion process to commence. More specifically, the Rig is an apparatus that allows for easy and clean perfusion of a rodent model (although it can be easily adapted to be used with larger model species). Our design allows for the rodent to be held in place with hooks, that are part of the device, using tools that are not part of the device that are attached from the subject to the hooks. As the subject is perfused, its body fluids go out of the body cavity, into the basin of the device, down the drain of the device, and into the biohazard container (not part of the device). We have designed a perforated platform (i.e. metal grate) for the rodent to lie on so that it is elevated above the basin where its fluids are being collected. The Rig is small enough to fit inside a fume hood and light enough to be carried with ease. The basin can be removed from the frame for easy sanitizing.

Proposed Use
The end product is to provide research and commercial laboratories with an apparatus that holds research subjects for whole-body immobilization, fixation and perfusion, dissection, and analysis and/or biohazard collection of the specimen.

Creator(s)
Jaclyn Taylor Eisdorfer, George Smith, Andrew Spence

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

About
Poly-phenylene terephthalamide (PPTA) material has been widely used in body armor applications. Our previous work demonstrated that the mechanical properties of PPTA fibers in the transverse direction could be improved by coating the fibers with ultrahigh molecular weight polyethylene (UHMWPE). This work aims to evaluate the effect of UHMWPE coating on the anti-ballistic behavior of PPTA fabrics through fabrication and testing of UHMWPE-PPTA composite panels.

Three types of samples were fabricated: 1) Kevlar® fabrics, 2) Kevlar® fabrics reinforced with UHMWPE, and 3) Kevlar® fabrics reinforced with plasma-treated UHMWPE. For the Kevlar® fabric sample, 6” x 6” squares were cut from a roll of Kevlar® 29 and stitched together. For the composite panels, 6”x6” Kevlar® fabrics and a selected number of UHMWPE thin films were layered and hot pressed. Plasma treatment was also performed on some UHMWPE thin films prior to the hot pressing process to promote binding between the Kevlar® and the UHMWPE layers. Bullet testing was conducted according to the NIJ Standard 0101.06. Our preliminary results on the protection against .22LR ammunition indicate the composite panel consisting of Kevlar® fabrics and plasma-treated UHMWPE had a better performance than the Kevlar® sample.

Proposed Use
• Body armor and personal protection • Lightweight hard armor • Sport protective wear

Creator(s)
Jacob Daniel Celli, Fei Ren, Simona Percec

Patent
Provisional Patent Filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Polymers (Materials); Chemicals; Materials

About
Rabbit Crowd Library was built as a companion tool to the MonQle. The Rabbit Crowd Library has five distinct features: 1) a 50-state legislative law scraper that can scrape all of the law that is codified each night across all 50 states, compare the law to existing law in the law library, identify what is similar to laws being tracked, identify what has changed, and create a diff file for the human content expert to review; 2) a scraper for municipal law; 3) NLP/AI algorithms to enable machine-assisted coding of law using training data housed in the MonQcle; 4) A front-end user-interface that allows access to structured city council data and the bills proposed and passed; and 5) a public engagement and discussion platform via like/dislike/comment responses for proposed or codified law. Rabbit Crowd library is part of the foundation for integration of machine assisted research and coding in the MonQcle legal research architecture

The Rabbit Crowd Library utilized the Natural Language Processing (NLP) based machine learning algorithm developed via a NSF funded project. The algorithm trains a machine learning model using training data (legal datasets that are labeled and stored in MonQcle). These datasets are created in MonQcle by legal experts, and generate semantic corpuses and keywords for each provision in the law. Then the algorithms create a classifier that can classify the existing laws in Rabbit Crowd Library and tag them with the topic tag. This classifier is executed using training data in a the MonQcle graph database. MonQcle users are able to search and import laws with the topic they specify or be notified when there’s a change of law related to the dataset they have been working on. This technology also enables users to automatically locate the legal text that provides the most relevant answer to their legal question. Moreover, Rabbit Crowd Library has keyword search functionality for laws using Elasticsearch Technology; a production level legal text scraping pipeline is also supporting Rabbit Crowd Library that can fetch and clean the legal text from the states and cities, and monitor the change; the site is also optimized with Search Engine Optimization (SEO) so the whole contents and features is visible worldwide.

Proposed Use
The original purpose for the technology was to create the 50-state and municipal law scraper and integrated NLP-based, machine assisted legal coding for MonQcle. Actualizing this integration will increase lawyer/policy analyst productivity, reduce errors, and reduce the time to production for updated legal information products. In addition, the Rabbit Crowd Library was to move into bill tracking, a crowded but lucrative and complementary space to tracking codified laws. The tool can be used by lobbyists, lawyers, policy makers and the public.

Creator(s)
Ning Gong, Heidi Grunwald, Elizabeth Platt, Scott Burris

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

About
The Health Outcome Policy Evaluation (HOPE) laboratory is a platform designed to enable better science faster through a cloud-based, collaborative research space. Researchers can upload and share data, analytic code, codebooks, study protocols, and publications. The platform directly addresses the need for tools that increase scientific efficiency (by reducing redundancy in data preparation), increases transparency (by making analytic code available along with summary methods information), and advances an open-source data culture. The HOPE contains an integrated computational space where researchers using R, Python can conduct analyses inside the platform, validate others’ analyses, or build upon their work. It can be offered as a general repository for researchers, or can be packaged for semi-private use by academic centers, professional organizations, research networks and affinity groups. It is intended to create transparency, validity and accountability for research data, analyses, and publications.

The software architecture for HOPE was designed by Legal Science and is now owned by Temple University. It is deployed through Amazon Web Services. It was designed to be a cloud-based Software as a Service (SaaS) platform. As is shown in Figure 1, the software architecture consists of two parts: NodeJS server on AWS EC2 instance and JupyterHub server on AWS EMR Clusters. The NodeJS server is derived from MonQcle integrated Content Management System (CMS) templates. It was designed to provide all basic interfaces between users and data. It takes the Health Outcome data and Policy Surveillance data as input and offers features such as dataset management, review/rating, uploading/downloading and analysis management. All datasets created by the users are saved in a Versioning Enabled Amazon S3 container, which is object-based storage technology to store and host data. The other part of the software architecture is the AWS EMR Cluster that runs the Jupyterhub server. The EMR cluster is load balanced cluster that deployed Jupyterhub servers in a distributed way. Load Balancing technology allows HOPE efficiently distributes incoming network traffic across a group of backend servers. The Jupyterhub platform is utilized to host Jupyter Notebook services for users to write their analysis using the datasets saved on S3. Jupyter Notebook is an interactive coding software that provides code editing and running functions. The supported programming languages for HOPE Jupyter Notebook are Python, R and Spark. The Jupyterhub service is deployed using Docker Container, which provides a standard software environment to increase portability. In between these two core parts, AWS Coginto Federation is utilized to manage the user authorizations. Overall, the NodeJS server provides basic functionalities for HOPE while the EMR clusters offers reliable software environments to run an analysis. All the technology utilized in this design, i.e. Load Balancing, Docker, Jupyterhub and S3, significantly increased the scalability, efficiency and reliability of HOPE platform.

Proposed Use
Universities, researchers, research groups, laboratories, policy affinity groups, academics, NIH, other places where the advancement of science relies on access to data, methods, analytics, and publications can use HOPE to promote open, transparent and efficient science.

Creator(s)
Ning Gong, Heidi Grunwald, Elizabeth Platt, Scott Burris

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

About
MonQcle is a Software-as-a-Service platform designed specifically to track law, policy, regulations over time and across multiple jurisdictions (e.g. state, counties, countries). The platform provides tools to create legal data (conversion of text to numbers) in a question and answer format that makes getting access to the answer to a question about the law faster than with traditional legal information products. The data (legal text, questions, answers, pin-citations) reside in a backend database that connects the exact place in the text of the law to the answer using hyperlinked pin-citations. The platform also provides a front-end user-interface for lawyers, policymakers, researchers and the public to access the Q&A format, maps, tables, pdfs, and the data and codebooks. All of the software runs in industry standard hosting services provided by large cloud service providers such as Amazon Web Services and mLab.

Below is a brief description of our software environment, tools and technical infrastructure: Infrastructure & Frameworks Cloud Hosting Amazon Web Services ● All MonQcle services are hosted on AWS using EC2 instances fronted by Amazon provided Load Balancers with Auto-scaling groups. All instances and tools are managed by Legal Science. Operating Systems ● Ubuntu 16.04 LTS Server Daemons ● NGINX ○ All MonQcle services are run behind NGINX, employing SSL Frameworks Symfony2 ● PHP Framework derived from Ruby-on-rails, very mature and well supported Nodejs ● Using Node v.6.* and NPM package manager. ● Modules ○ Express - web framework ○ PM2 - to daemonize and cluster ○ Mongoose - Mongodb library ○ Dust - templating ○ Uglify, Less, Lodash, D3 Software & Libraries Languages: PHP ● Deployed for the Syfmony2 MVC Framework Python ● Deployed for custom daemons, web-scrapers and system code JavaScript ● Employed within Nodejs and client-side for all services Datastores: MongoDB ● The main database for all MonQcle assets, an open-source cross-platform document- oriented database program. Neo4j ● A native graph database where we transform data and do analysis Elasticsearch ● Store many of the artefacts within ES for easy application of NLP search techniques. Software Development Ops/Management Tools Github ● Storing and collaborating on code, we use an organization JIRA ● Project management and issue tracking built on JIRA Jenkins ● Continuous Delivery & Integration, all MonQcle assets are built, tested and deployed using CI Elastic Stack ● Elasticsearch ● Kibana ● Filebeat Monit ● Monitoring software with the ability to manage running processes RabbitMQ • Messaging queue services for data collection Gensim • Natural language processing library for supervised learning Docker • Deployment management framework

Proposed Use
The technology is used by researchers, lawyers and policy analysts to more efficiently track laws and features of the law over time and across jurisdictions. The technology is also used by policymakers, advocates, newsmedia and the public to access answers to questions about the law. The back-end technology enables content experts (humans) to create the datasets in a machine-assisted environment. The front-end technology enables legal information providers (Wolters Kluwer, for example) to offer clients more efficient and graphical ways of accessing legal information; advocates to show policy progress, and researchers and evaluators access to data for evaluation purposes. Once the text has been converted to data via a Q&A format, the data can be accessed via an API for use in compliance engines or white-labelled websites.

Creator(s)
Scott Burris, Ning Gong, Heidi Grunwald, Elizabeth Platt

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Other (Software); Software (Copyright)

About
Bacterial pneumonia remains a leading cause of morbidity and mortality worldwide. A defining feature of pneumonia is lung injury, leading to protracted suffering and vulnerability long after bacterial clearance. Little is known about which cells are damaged during bacterial pneumonia and if the regenerative process can be harnessed to promote tissue repair and host recovery.

We have now shown that infection of mice with Streptococcus pneumoniae (Sp) caused substantial damage to alveolar epithelial cells (AEC), followed by a slow process of regeneration. Concurrent with AEC regeneration, the expression of miRNA-302 is elevated in AEC. Treatment of Sp-infected mice with miRNA-302 mimics improved lung functions, host recovery and survival. miRNA-302 mediated its therapeutic effects, not by inhibiting apoptosis and preventing damage, but by promoting proliferation of local epithelial progenitor cells to regenerate AEC. These results demonstrate the ability of miRNA-based therapy to promote AEC regeneration and enhance host recovery from bacterial pneumonia.

Proposed Use
To enable alveolar epithelial calls regeneration and enhance host recovery from bacterial pneumonia

Creator(s)
Ying Tian

Patent
62/823,400; PCT/US2020/024206

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Diagnostics; Clinical Applications; Biotechnology; Therapeutics

About
Bioorthogonal reactions have greatly facilitated protein labeling in complex biological systems. Current chemical reporters are bulky in length and size, thereby impeding their general applications. Even alkyne or azide- based minimalist reporters for copper-catalyzed azide-alkyne cycloaddition (CuAAC) are still larger than the inherent carbon-hydrogen bond. This intrinsic steric hindrance has largely limited the application of chemical reporters to metabolic incorporation by enzymes possessing spacious active site pockets. For example, alkyne/azide-labelled PTM precursors or cofactors for acetylation and methylation were too bulky to be incorporated by many cognate transferases. While “bump-hole” protein engineering strategy could work for a given enzyme, careful balances between mutations, structure folding, and function (potency, selectivity, etc) are required, which undermines this approach’s broad applications. Elucidating the molecular targets of these PTM transferases has been thereby compromised, despite being a key step towards the systematic dissection of PTMs and their roles in biological and pathology-related cellular signaling regulation. We have created a kit using steric-free Bioorthogonal reactions to solve this problem.

Bioorthogonal reactions facilitate protein labeling in complex biological systems and led to widespread applications including imaging, enrichment, and identification. The fluorine labels can be further converted to biotin or fluorophore tags using FTDR, enabling the general detection and imaging of acetyl substrates. This strategy should lead to a steric-free labeling platform for substrate proteins, expanding our chemical toolbox for functional annotation of post-translational modifications (PTMs) in a systematical manner. Along with the benzenethiol derived functional tags, the FTDR-based imaging and detection of substrates demonstrated great potential for globally profiling Lysine acetyltransferases substrates, which are of vital significance for understanding the roles of acetylation in physiology and disease. This tool kit, together with additional applications to quantitative proteomics studies, will offer versatile probes for identifying targets of acetylation, and many other post translational modifications that are mediated by transferases with restricted active sites. In addition, this powerful FTDR reaction can be applied to peptide macrocyclization and stapling as well, resulting in a class of peptide therapeutics with enhanced cell penetration.

Proposed Use
Protein target profiling; Peptide stapling; Site-specific antibody drug conjugates

Creator(s)
Rongsheng Wang, Zakey Yusuf Buuh, Zhigang Lyu, Yue Zhao

Patent
Patent application filed February 2020

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Chemicals; Research Tools; Protein chemistry; Biologic function analysis

About
Standard fluorescence and super-resolution microscopy are widely-used techniques for visualizing cellular structures in fixed and live samples. To obtain the best optical resolution, collection of the maximum number of photons from each fluorophore is essential and achieved mainly by engineering higher numerical aperture objectives, designing higher quantum yield and photostable fluorophores, or increasing the excitation laser or lamp power. While great advancement has been made on objectives and fluorophores, progress cannot proceed linearly and simply increasing the laser power photobleaches fluorophores more quickly, causes more out of focus fluorescence, and is more phototoxic in live cell imaging. Here, we demonstrate that a 4f system and mirror can reflect and focus photons emitted away from the objective back toward the exact location of the fluorophore at the focal plane in both standard epifluorescence and confocal microscopy for immobile and mobile fluorescent beads as well as cell samples. In this way, we can double the number of photons from a variety of samples which are collected by the objective and reach the camera. We have developed a device to improve photon enhancement microscopy that can be broadly implemented in principle on any modern fluorescence microscopy method to increase photon collection efficiency and optical resolution.

Fluorescence microscopy and 4Pi microscopy are the two current states of the technology. Fluorescence microscopy, in general, places an objective on one side of the emitter and, thus, collects photons from only one side of the fluorophore. It is only able to collect about 30 percent of the total amount of emitted photons. 4Pi microscopy places two objectives on opposing sides of the fluorophore but also essentially implements two entire microscopy setups (two objectives, 2 filter sets, 2 tube lenses, and 2 cameras). In this way, axial optical resolution is improved through interference but the photons from either side of the fluorophore never reconverge at a common detector (camera) and, thus, photon collection efficiency is never improved. Our invention reconverges the photons emitted from both sides of the fluorophore. The main limitation is that some microscopes have the space to implement our invention while others do not have the space. However, all future microscope designs would likely incorporate our invention. The device is designed to improve photon collection efficiency and optical resolution on all fluorescence microscopes. The device is inexpensive, particularly when compared to the cost of a microscope, at about $1,000 assuming parts are purchased individually. The device allows for a lower power illumination source which reduces photobleaching, out-of-focus fluorescence, and phototoxicity in cells.

Proposed Use
The main end product would be incorporation of this photon enhancement setup into the design of future fluorescence microscopes and current fluorescence microscopes which have the space requirements in order to increase the photon collection efficiency and optical resolution.

Creator(s)
Weidong Yang

Patent
62/941,118

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Research Tools; Imaging; Instrumentation

About
The present invention is in the field of pharmacology. Specifically, the present invention relates to pyrazolylbenzene-1,3-diols as cannabidiol derivatives, its use for the manufacture of a medicament, the use of this medicament for the treatment and/or prevention of the many disorders associated with the GPR18 and/or TRPV1 receptors and the use of these compounds for pharmacological assays related to GPR18 and/or TRPV1.

The invention relates to compounds that are preferential ligands of GPR18 or have dual activity on GPR18 and TPRV1. G Protein-coupled receptor 18 (GPR18) is related to the endocannabinoid system due to its interactions with cannabinoids such as cannabidiol, abnormal cannabidiol and ∆9-tetrahydrocannabinol. GPR18 is expressed within the central nervous system including in the striatum, cerebral cortex, hippocampus and cerebellum. GPR18 is also highly expressed in lymphoid tissues such as the spleen and thymus, as well as bone marrow, peripheral immune cells, peripheral organs (testes, lung, kidneys, skin) and the retina. The distribution pattern suggests a potential role of GPR18 in immune system activity. GPR18 contributes to directed microglial migration, which is involved in the defense of the central nervous system in several neurodegenerative diseases including multiple sclerosis and Alzheimer's disease. The GPR18 ligand NAGly has neuroprotective properties in a hippocampal slice model of excitotoxicity. these effects were abolished by a GPR18 antagonist. Another potential therapeutic application is endometriosis, since there is evidence that endo- and phyto -cannabinoids regulate human endometrial cell migration through a GPR18 signaling mechanism. Further, in a mouse peritonitis model, NAGly showed anti-inflammatory activity. There is evidence that acute inflammation triggered by infectious agents also involve GPR18. The endogenous lipid mediator RvD2 stimulates human and mouse phagocyte clearance of microbes through GPR18 to protect the host during infections. Thus, GPR18 may be a therapeutic target to control bacterial infections and promote organ protection. GPR18 may play a potential role for endocannabinoid signaling in metabolic dysfunction; GPR18 expressed in hypothalamic proopiomelanocortin and neuropeptide-Y neurons may be involved in diet-induced hypothalamic inflammation and dietary fats. An increase of RvD2 results in reduced adiposity, improved glucose tolerance and increased hypothalamic expression of anti-inflammatory cytokines implicating GPR18 as a novel therapeutic target for metabolic disorders such as obesity and diabetes. O-1918, an antagonist for GPR55 and biased agonist for GPR18, may be a beneficial compound in the treatment of obesity-related kidney disease. Activation of GPR18 lowers intraocular pressure, thus, GPR18 ligands could have therapeutic applications in glaucoma. Studies in human spermatozoa suggest a potential role of GPR18 in sperm physiology, particularly immediately prior to fertilization. GPR18 may be involved in cancer. For instance, GPR18 is a potential novel anticancer target in metastatic melanoma. GPR18 may be molecular target for developing new antihypertensive drugs that improve cardiac function, since Abn-CBD acting on GPR18 causes reduction in rostral ventrolateral medulla oxidative stress and blood pressure. More recently, GPR18 has been suggested as an alternative biological target for pain relief. For instance, nerve injury enhances expression of GPR18 mRNA in spinal cord and/or the dorsal root ganglia of rats, suggesting a potential role of GPR18 in the modulation of neuropathic pain. The transient receptor potential vanilloid 1(TRPV1) is a cation channel with high permeability for calcium. TRPV1 is activated by a large variety of physical and chemical stimuli such as heat, capsaicin, and resiniferatoxin. It is critically involved in sensory and pain perception. Thus, several clinical trials have been conducted with TRPV1 antagonists for acute migraine pain (clinicaltrial.gov number NCT002269022), tooth extraction pain (clinicaltrial.gov number NCT00281684), and for retrosternal pain in children (clinicaltrial.gov number NCT00677378), among others type of pain. Targeting TRPV1 in diabetes type-2 results in improving insulin secretion, minimizing insulin resistance, and slowing disease progression in animal models. The translation to humans is currently ongoing with a clinical trial (clinicaltrial.gov number NCT03278158) using a TRPV1 antagonist in patients with diabetes mellitus type-2 disorders. TRPV1 also plays an important role in neurological and psychiatric disorders such as epilepsy, anxiety, depression, and drug-addiction disorders.

Proposed Use
Immune regulation, Neuroprotection and treatment of neurodegenerative diseases, Metabolic dysfunction, cardiovascular disease, pain relief, glaucoma, diabetes.

Creator(s)
Pingwei Zhao, Mary E Abood, Eugen Brailoiu, Luciana M Leo

Patent
Provisional Patent Application Filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

About
We have prepared a series of luminescent organometallic complexes, which emit visible light in the presence of ultraviolet light. Based on this behavior, we hypothesize the materials may be useful as organic light emitting diodes (OLEDS).

The materials are homogeneous gold(I) and copper(I) complexes of an N-heterocycle carbene featuring a weakly coordinating anionic substituent. The compounds phosphoresce under UV light. At this stage we do not have enough information to demonstrate the critical properties needed for use as OLEDs. OLEDs remain an area of active research. Blue-emitting OLEDs remain less stable than red or green emitting-compounds. Rational design principles for tuning OLED emission, lifetimes and electrochromic response are a continuing challenge in the area.

Proposed Use
Recent work has shown other similar compounds demonstrate useful decay properties. We have not yet performed the needed experiments to ascertain if our work provides any advantage over existing materials. Moreover, others in the area have already filed patents and our compounds likely fall under their existing disclosures. Eliminating nonradiative decay in Cu(I) emitters: >99% quantum efficiency and microsecond lifetime. Science, 2019, 363, 601-606. DOI:10.1126/science.aav2865 Materials for organic light-emitting diodes (OLEDS).

Creator(s)
Graham Dobereiner, William A Sabbers

Patent
PCT filed

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Imaging; Energy; Photonics; Displays

About
Aphasia is an acquired impairment of language abilities resulting from damage to the left hemisphere from stroke, head trauma or other neurological conditions. It can affect any aspect of spoken and/or written language processing and can range from mild to severe. As language provides us with a unique form of communication, aphasia can have profound adverse effects on one's quality of life. Aphasia is common in older populations but can occur at any age. Many people with aphasia want to return to their premorbid lifestyles, including active careers, to the extent that this is possible, but communication abilities are a huge barrier to successful return to work.. This possibility is more likely than once thought. More than 30 years of rehabilitation research provides strong evidence that even in chronic stages of aphasia, behavioral interventions lead to improved language function and changes in neural activity of cortical areas known to support language. Thus, there is a need and market for effective clinical tools to diagnose and treat aphasia. The Temple Assessment of Language and Short-term memory in Aphasia (TALSA) is a theory-driven and empirically supported diagnostic battery for aphasia that probes the language impairment more deeply than standard screening tests for aphasia. Unique to the TALSA is the incorporation of memory load into the language tests and inclusion of verbal span measures. These features have two important benefits: (1) They provide a window into the potential for functional communication in which language is often produced under high memory load conditions (e.g., give and take in conversation) and (2) They enable detection of specific language impairment in cases of mild aphasia. The original, laboratory-developed version of the TALSA is comprehensive with over 20 subtests, and although it is administered on a computer it is lengthy and not practical to use in a clinical setting. This new clinical version is streamlined and implemented on a website, but like the original version, it allows clinicians to sample subtests that yield a screening overview of a person's abilities or explore specific modalities and linguistic elements to inform treatment approach that will inform treatment direction.

The product we are submitting to the Tech Transfer office is the second version of the TALSA ("Clinical TALSA"). It includes 18 subtests that assess language processing with and without manipulations to increase short-term memory (STM) and working memory (WM) load. There are tasks that assess input and output processing of single words and sentences as well as verbal span tasks. This streamlined clinical version is implemented on a website. As in the original version, the Clinical TALSA allows clinicians to sample subtests that yield a screening overview of a person's abilities or explore specific modalities and linguistic elements to inform treatment approach that will inform treatment direction. Characteristics of the word and sentence level stimuli are varied to be sensitive to phonological, lexical and semantic levels of processing. When appropriate, stimuli in a task are controlled or systematically varied for frequency, imageability and syllable length. This information is provided on scoresheets in and in the Clinical TALSA manual along with rationales for varying or controlling specific factors. The subtests of the Clinical TALSA can be grouped in to three areas: (1) Tests with added processing time. These subtests assess input and output language processing abilities with and without a 5-second (sec) response delay or 5-sec interval between two stimuli that are compared in some way (e.g., phoneme discrimination). These tests add processing time to the language task. We have observed three diagnostically relevant effects on accuracy when this delay is incorporated into the word processing tasks: (1) improved performance, indicating that more time to process a word is beneficial, (2) worse performance, indicating that activation of word representations cannot be maintained for 5 seconds, and (3) no change in performance, indicating that activation of word representations can be sustained for at least 5 seconds. (2) Tasks that increase working memory load. The tasks in this group are designed to test language processing under high and low memory conditions. They involve making judgments about semantic or phonological similarity, but vary the number of items that need to be considered in making such judgments (more items to consider = higher memory load. (3) Verbal span tasks. This section of the TALSA includes standard digit and word span tasks, but also includes a series of span tasks that vary the content of the words to be recalled. The words are varied for characteristics that are sensitive to semantic (e.g., imageability) and phonological aspects of words (e.g., word vs. nonword). These tests are especially sensitive to language impairment in individuals with very mild aphasia.

Proposed Use
1. Currently used with adults who have been diagnosed with aphasia. 2. We are currently investigating its use with individuals who are high risk for Mild Cognitive Impairment, Alzheimer''''s Disease and Dementia. 3. In theory, the assessments in this test battery would be appropriate to evaluate language and cognitive skills in people with traumatic brain injury.

Creator(s)
Nadine Martin, Wendy Greenspan, Kevin Mccaffery, Carole A. Tucker

Patent
Copyrighted code

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Clinical Applications; Health IT; Mobile Applications; Computer Aided Design & Learning

About
Epiprinter™ technology will enable the sensitive and accurate detection of RNA of clinical, agricultural and environmental interest, in diverse point-of-need settings, and with minimal requirement for equipment or highly trained personnel. RNA is a key diagnostic biomarker for many diseases, especially those caused by RNA viruses. For example, the COVID-19 infection, caused by the SARS-CoV-2 RNA virus, emerged in late 2019 and quickly spread to become a pandemic. The ongoing challenges in establishing extensive diagnostic screening has underscored the limited capability for diagnosing SARS-CoV-2 infection outside of clinical settings. Current diagnostic tests for SARS-CoV-2 (e.g., the Cepheid GeneXpertSystem) involve the enzymatic amplification (RT-PCR) of RNA, and must be performed in a CLIA-approved laboratory or select patient care setting. Epiprinting is designed to be a portable technology, involving the novel entity, epiprinter™, which is used in conjunction with a custom DNA nanostructure (epitape™) to provide a permanent recording of the occurrence of specific RNA sequences in diverse samples, without the need for enzymatic amplification. Readout of the recording event is provided by portable, solid-state nanopore technology (USB memory stick size). Epiprinting RNA detection technology is envisioned not only to be deployable in resource-limited, point-of-need settings for disease surveillance, but also as a standard item in diagnostic laboratories. With modification, epiprinting technology can be used to detect DNA, protein, or other biomolecules of interest.

The epiprinter™ is a synthetic molecular entity that recognizes and binds RNA-DNA hybrids with high affinity and selectivity. The epiprinter™ works in conjunction with an epitape™- a custom-designed, self-assembled DNA nanostructure that contains a probe site with a sequence complementary to the RNA target. Addition of the epitape to the RNA sample allows formation of a hybrid at the epitape™ probe site, which then is recognized and bound by the added epiprinter™. The epiprinting reaction then occurs, where the epitape™ is modified to provide a permanent recording of the RNA binding event. The modified epitape™ is subjected to solid-state nanopore-based analysis that provides a recordable readout in the form of a characteristic current change that occurs during epitape™ translocation across the nanopore. The epiprinter™ thus acts as a “bead” that binds a “wire” (epitape™), with nanopore analysis registering the presence of the bead on the wire. Computer software, available on a laptop or cloud, analyzes the recorded signal data to provide the assay results. The solid-state nanopore detection device is anticipated to be similar in size to the Oxford Nanopore Technologies Minion unit (the size of a USB drive) and can be powered and controlled by a USB-linked laptop computer. The epiprinting technology will allow analysis of RNA isolated from serum, saliva, or other sources, as isolated using commercially available RNA purification kits. The RNA target is selectively recognized in the first step, which relies on the high specificity of hybrid formation involving complementary RNA and DNA sequences. Epiprinter™ then binds the hybrid structure on the epitape™ with a high (sub-nanomolar) affinity, that equals, if not surpasses, that of other molecular entities that recognize hybrids, such as monoclonal antibodies and synthetic small molecule constructs. The high affinity is essential for sensitive RNA detection, as required in the laboratory, clinic, or field that routinely analyze samples of limited size and low RNA amounts. Epiprinting also can enable multiplexed RNA detection. Here, epitapes can be designed for each RNA target, with each epitape™ carrying a unique structural identifier (“barcode”) that is decoded during the nanopore analysis. Multiple epitapes are combined in the analysis of RNA samples, and Nanopore devices can provide high throughput capacity by integrating multiple nanopores in a single device (e.g. PromethION, Oxford Nanopore Technologies). The portability of the technology (as a kit), with no requirement for enzyme, will add to the cost-effectiveness of the technology and minimize the need for highly trained operators. Modifications to the epitape™ can allow detection of DNA or protein biomarkers of interest, thus broadening the capacity of this technology.

Proposed Use
• Detection of RNA in clinical and patient samples (blood, saliva); monitoring of viral load (e.g. HIV) during antiviral therapy. • Surveillance of disease vectors such as mosquitoes and ticks. • Clean room monitoring of pathogens • Detection of DNA (using riboepitapes) • Detection of protein (using epiprinter™ in conjunction with antibody-DNA conjugates) • Detection of RNA-DNA hybrids in cells, tissues, and other biological and clinical samples.

Creator(s)
Allen Nicholson, Alex Stopar

Patent
US provisional patent application was filed on April 30, 2020.

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Diagnostics; Clinical Applications; Biotechnology

About
The BAG family, including BAG3, through its role in regulating protein quality control, including autophagy and mitophagy, plays a critical role in the regulation of Tau protein, which accumulates in neurological disorders, including neurodegenerative diseases and HIV infection of the brain. Rebalancing of protein quality control through targeting the BAG3 pathway may lead to an improvement in the clearance of toxic proteins and restoration of normal cellular protein quality control mechanisms and improvement of mitochondrial function in the brain.

Targeting the BAG family for the treatment of neurodegenerative disease. Accumulation and aggregation of toxic proteins in response to environmental stressors including infection are a critical feature of several neurodegenerative diseases. The heat shock pathway is the first line of defense and is designed for the surveillance of proteins post-translationally after cellular insults or stress. Aberrant proteins that cannot be repaired may be targeted to the ubiquitin-proteasome system for degradation. Upon significant accumulation of toxic proteins, the cell undergoes more drastic measures including induction of apoptotic or autophagic processes leading to cell death. Under stress conditions, the inability of the cell to clear abnormal or misfolded proteins resulting in the accumulation of aberrant proteins, such as hyperphosphorylated tau, may lead to disease. The heat shock response works with the ubiquitin-proteasome system for the recognition and clearance of aberrant proteins through the binding of a series of chaperone proteins including the heat shock protein 70 (HSP70) for attachment of ubiquitin molecules. Recent studies also confirm important roles for Hsp70 in controlling abnormal tau accumulation by altering function and accumulation of specific tau isoforms. In addition to impacting microtubule formation, dysfunction of the mitochondrial is an important mechanism contributing to neuronal loss in AD. Alterations in mitochondria, with an increase in fission and a decrease infusion, have been reported in neurons of AD brains along with a drop in GTPase activity. Further, the interaction between Drp1 and hyperphosphorylated tau has also recently been shown in Alzheimer's Disease brains demonstrating that tau can directly impact mitochondrial function and bioenergetics. Viral infections, such as HIV, can be a significant source of cell stress on neuronal cells. A large number of HIV- 1 positive individual exhibit progressive neurological disorders even under conditions when the virus is well controlled with antiretroviral therapy (ARTI. Results from several laboratories established the ability of the HIV regulatory protein, Tat, to trigger pathways that lead to neuronal dysfunction and injury including energy metabolism. Tat possesses neurotoxic activity, one mechanism by which may be inflicting stress and increasing the levels of cytosolic and/or mitochondrial reactive oxygen species (ROS) leading to cellular and mitochondrial damage, transcriptional and post-transcriptional dysregulation including premature degradation and misfolding of proteins, cytoplasmic and nuclear autophagy, as well as mitochondrial dysfunction and decreases in oxidative phosphorylation (OxPhos) efficiency. We demonstrate that In the presence of Tat, several factors associated with pro-survival and pro-apoptosis are affected. Among them, BAG3 protein which is a co-chaperone/partner of HSP70 and is involved in the removal of dysfunctional and obsolete organelles including mitochondria through a process called mitophagy and participates in autophagy and clearance of damaged and misfolded proteins by the protein quality control (PQC) pathway. Thus, Tat may inflict damage to proteins and organelles by inducing ROS production, which prevents the repair and/or removal of inefficient and toxic proteins from the cell environment by interfering with BAG3 function, all of which results in neuronal cell injury and damage. Taken together, the HIV Tat protein and BAG-3 can be linked to the accumulation of hyperphosphorylated tau and, ultimately, synergistic effects in their impact on neuronal bioenergetics and survival. For example, the HIV protein Tat has been shown to induce hp-tau in human primary neurons in vitro and in the brains of Tat transgenic mice in vivo. In addition, studies show that in the frontal cortex of HIVE patients, hyperphosphorylated tau levels are also increased. The strong association between Tat, BAG3, and HSP70, as well as between HSP70 and tau, suggests a molecular cross-talk between these two pathways which ultimately controls tau accumulation and clearance, as well as mitochondrial bioenergetic function in neurons. Targeting BAG3 will lead to new therapeutic strategies for the treatment and prevention of dementia in aging HIV+ individuals.

Proposed Use
Delivery of supplemental BAG domain or BAG3 to the brain through gene therapy, increasing transcription, translation; or protein half-life of existing BAG family members including BAG3; delivery of small molecules to promote BAG and BAG3 expression and/or stability; repair of BAG family and BAG3 mutations with reduced function to treat neurodegenerative diseases

Creator(s)
Kamel Khalili, T. Dianne Langford, Jennifer Gordon

Patent
PCT/US20/13724

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics

About
Two of the biggest challenges of implanted biomaterials and medical devices are infections and loosening. Colonies of bacteria/fungi form biofilms that adhere to the surfaces of the implanted biomaterial causing infections, failure, and death of the patients in the worst case. Implant-associated infections result in more than 110,000 deaths each year in the United States of America alone. Strategies developed in preventing implant-associated infections include inhibiting the adhesion of bacteria onto the implant surface, preventing the formation of biofilm, and directly killing the bacterial/fungal cells. Traditional anti-infective agents include silver, quaternary ammonium, copper, zinc oxide among others. Two major limitations of these agents include their characteristic “burst effect” (short-term therapy < 1 year) and their inability to repair gaps and promote tissue growth at the interface. Furthermore, implants or medical devices fixed to bone or body tissues must remain firmly attached to guarantee proper functionally (e.g. hip implants). Over time, however, an implant may loosen from the underlying bone/tissue due to infection, wear, stress shielding, and unwanted cellular response. This complication produces pain and instability. As a result, implant is replaced on a second complicated procedure. Strategies developed to improve biomaterial-tissue integration by regenerating tissue at the interface include coating the implant surfaces with bioactive compounds such as calcium phosphates, bioactive glasses, and growth factors. A major limitation of these approaches includes the limited ingrowth of tissue, lack of mechanical strength, and lack to prevent inflammation/infection. Due to increasing life expectancy, implants are required to remain in the body much longer than before (>25 years). There is an unmet need for implantable biomaterials that offer both long-term anti-infection and tissue regeneration therapies. Such technology will increase the longevity of implanted biomaterials by preventing infection while simultaneously repairing/promoting the growth of tissue at the bonded interface. As a result, an increase in the effectiveness of the medical procedure is expected to reflect on fewer complications and follow-up treatments and a reduction of the associated cost burden on the health system.

We are developing a novel smart biocomposite initially to be used for dental applications (e.g. sealers) with both antimicrobial and remineralizing effects in a single filler. The therapeutic agent is implanted with piezoelectric nanoparticles. Mastication forces excite the piezoelectric filler generating electrical charges at the material surfaces. Electrostatic forces will simultaneously repel biofilms and precipitate new minerals from saturated Calcium solutions from dentinal fluid or blood. Our unique approach uses one agent to obtain both antimicrobial and self-remineralizing effects, overcoming limitations of current fillers including leaching, alteration of polymerization and use of multiple agents for similar bioactive uses Thus, the expected outcome of this research is to elucidate the role of electrical charges on self-mineralization and biofilm modulation advancing the field of infection-free implantable biomaterials. In the future, our invention will be applied to any implanted site, such as a hip or knee, to reduce infection and improve healing.

Proposed Use
Our technology could be applied to any implanted biomaterial: from titanium implants as surface coatings, to resin composites as nano-filler, but will initially be applied for dental purposes. Our formulation is simple, inexperience, prevents bacterial and fungal infections. Our technology could be used in many biomedical fields including dental, orthopedic, medical devices. For example, hip or dental implants incorporated treated with piezoelectric coatings, that help prevent infections. This will prevent complications post-surgery and extend the clinical service of implants.

Creator(s)
Maobin Yang, Cemil Yesilsoy, Santiago Orrego

Patent
62/823,833

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Implantable/prosthetic; Biomaterials

About
The invention is a rapid detection method for viable Mycobacterium avium paratuberculosis (MAP) in human blood. This organism has been found in higher prevalence in Crohn’s disease (CD) patients than in healthy subjects. The test uses a bacteriophage, D29, which attacks the viable MAP cells which are released from human white blood cells (WBCs). The MAP organisms released from the patient’s lysed WBCs are inoculated onto a medium containing Mycobacterium smegmatis organisms that support D29 growth. The infected M. smegmatis cells burst and the phages infect surrounding M. smegmatis cells leaving a zone of clearing called a plaque. The DNA from the center of the plaque contains the DNA from the MAP cell that infected the patient. This DNA is harvested and then tested against a Taqman qPCR probe for IS900 which is specific for MAP. The number of plaques in the phage culture correlates to the number of viable MAP cells in the host and is a semiquantitative measure of the burden of infection. When this test becomes widely available, physicians will test various therapies which attempt to eradicate MAP and cure the associated CD. There are some (but not many) patients who have been reported in the medical literature that have experienced profound remission/cure for many years.

One of the greatest obstacles to understanding that infection by Mycobacterium avium paratuberculosis (MAP) causes Crohn’s disease (CD) and other “autoimmune” diseases has been the difficulty in consistently and rapidly detecting and/or culturing the organism from human samples. Until recently, the gold standard of detection/culture of human samples for MAP is the method of Dr. Saleh Naser which was published in the Lancet in 2004 (Naser SA, Ghobrial G, Romero C and Valentine JF. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. Lancet 2004; 364: 1039-1044). This method requires up to six months of incubation and thus has never been adopted by clinical laboratories. Recently, more rapid methods of detection and or culture of the organism in human samples have been developed but not yet reported in the medical literature. Samples from 201 human subjects have been collected for the large study which is funded by the Human Paratuberculosis Foundation entitled, “A comparison of laboratory culture methods and antibody assays to assess the prevalence of infection by Mycobacterium avium subsp. paratuberculosis in the blood of patients with Crohn’s disease and control subjects“. The study is blinded and compares the detection and/or culture recovery rates using 8 testing methods in 6 laboratories to examine differences between the CD subjects and the non-CD controls. An examination of the data without knowledge of the disease status of the subjects has revealed some interesting findings that will have application to the use of this rapid assay in the human population. Application of the MAP phage detection method to the human population has shown that only 44% of the study population is without evidence of MAP infection. Overall, 56% of the study population is positive for MAP, which was identified by an IS900 Taqman probe-based qPCR, which is specific for MAP. The proportion of CD patients with positive MAP phage tests is 46%. Dr.Tim Bull from one of the participating laboratories in the study is growing MAP colonies on solid media with a new rapid culture method and this material will be used for confirmation of organism identity by whole genome sequencing. This work will be completed as soon as his laboratory can access the WGS technology at St. George’s University Hospital in London which is currently exclusively used for COVID-19 testing., An article summarizing the results of the study has been submitted to a a respected, open access, peer reviewed journal for publication. The WGS portion of the study will be submitted as an addendum when this portion of the study is completed. The MAP phage assay is a semi-quantitative method and the plaque count correlates to the number of viable MAP organisms in the subject sample. In the overall study, the plaque count ranged from none to as many as 700 plaques in some of the subjects. In a related mycobacterial infection, leprosy, the bacterial burden correlates with the severity of the disease. For example, in the lepromatous form of the disease, there are innumerable organisms in the lesions and the disease is severe. It is highly probable that the subject with the plaque count of 700 is a CD patient and that this subject has a high Crohn’s disease activity index (CDAI). The plaque count may be used in conjunction with the CDAI or may be incorporated into a modified form of the CDAI for an assessment of disease severity. Another use of the plaque count will be to assess whether elimination of the viable MAP organism detected by the plaque assay and using an undetectable plaque count as the target will lead to elimination of the underlying CD. This goal may be difficult or impossible to achieve using already available antibiotics. When latent tuberculosis infection is identified, subjects are treated to eradicate the latent tuberculosis infection. Similarly, the MAP phage assay will probably be used to identify latent paratuberculosis infection and subjects who are asymptomatic but infected by MAP will be treated for this infection. Ultimately, public health measures that reduce the burden of MAP in the environment will lead to lower rates of infection and vaccines will be developed to prevent human infection from occurring in the first place. Veterinarians from around the world have already banded together in the past year to improve Johne’s disease (JD) control. We are confident that once all the data are fully analyzed our new assay will be useful for therapeutic decision-making.

Proposed Use
1. This test will be used for the detection of viable MAP organisms in human blood using a mycobacterial phage assay, thereby being used to diagnose MAP infection. 2. This test will also be used to diagnose infection by other mycobacteria, e.g., MTB and MAH (but not limited to these organisms). 3. The semiquantitative MAP phage assay will be used to discriminate between diseased and asymptomatic human hosts who are infected by MAP. 4. The semiquantitative MAP phage assay will be used as an additional measure to assess CD severity. 5. The semiquantitative MAP phage assay will be used to identify latent paratuberculosis in humans. 6. The semiquantitative MAP phage assay will be used as a guide to therapy in humans and correlating treatment outcomes with the MAP phage plaque count. 7. The mycobacterial phage assay will be used to identify other mycobacterial human infections and guide public health measures.

Creator(s)
John Todd Kuenstner

Patent
PCT filed September, 2019

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Clinical Applications; Diagnostics

About
Assembly to reduce dark noise of silicon photomultipliers (SiPM) by cooling them with several stages of thermoelectric coolers (TEC), in a controlled atmosphere enclosure with a transparent window for coupling to scintillation crystal or another weak light source. Results reduce background and improve sensitivity, particularly in low light applications.

We have constructed a prototype that uses two stages of commercial TEC to cool commercial SiPM array to -20 C. Prototype exhibits dark noise reduced by more than 100x compared to room temperature operation. Cooling requires an evacuated or controlled atmosphere enclosure to avoid condensation. Performance of cooled array (energy resolution) exceeds that of a conventional photomultiplier tube (PMT) for nuclear spectroscopy with NaI, particularly for low energy gamma rays.

Proposed Use
Replace PMT in nuclear spectroscopy products such as NaI detectors. Provide detection with spatial resolution and high quantum efficiency for other large-area, weak light sources in scientific applications.

Creator(s)
Donald Charles Jones, Charles Jeffrey Martoff

Patent
PCT/US20/53338

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Research Tools

About
Pain is one of the most significant healthcare problems faced today. It impacts hundreds of millions of people across the world, profoundly affecting their quality of life and costing society countless billions of dollars in treatment along with lost productivity. Escalation in use of pharmaceutical opioids and opioid-related harms such as overdose and addiction in North America, Europe, and Australia is well-documented. The data for the United States show 18,000 deaths in 2012 vs 33,000 deaths in 2015 (Center for Disease Control: 2016; 'Vol.' 65, pp 1445–1452). Modified release tamper-resistant (MRTR) opioid formulations, intended to prevent dosage form manipulation by making them harder to “crush, chew, inhale, insufflate, snort or inject,” have been promoted as one strategy to prevent opioid misuse. This approach has made it more difficult to misuse MRTR formulations, leading to a declining trend tread in the use of MRTR opioids (Lancet, 2018, Vol. 5, pp 155-166). Nonetheless, the strategy does not address all the issues related to detrimental effects of opioids including overuse and overprescribing at the population level. There remains a need in the art for novel tamper-resistant drug dosage forms. We have created a tamper resistant form by developing a matrix polymer, a scaffold polymer, and a therapeutic agent, and the porosity of the drug dosage form is less than 10%. We provide methods for making and using the tamper resistant drug dosage form within the patent application.

A drug dosage form comprising:a matrix polymer; a scaffold polymer; and a therapeutic agent; excipients; resulting in a product with the porosity of the drug dosage form is less than about 10%. We combine a variety of materials in a scaffold polymer that may include polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, polyethylene oxide, polymeric cellulose, and mixtures, co-polymers, and block co-polymers, carnauba wax, and fatty acids and then place them under pressure to create an uncrushable tablet that is truly tamper proof. By utilizing our novel approach to tablet manufacture, the step of tablet sintering can be avoided altogether. The novel tablets include a pore forming polymer with an insoluble but soft backbone incorporated in the PEO matrix. Both polymers have the ability to consolidate to near zero porosity due their physical nature, extensive viscoelasticity, low glass transition temperature (Tg, -70°C), and low melting point (60-70°C). These characteristics are able to reach their full utility as far as ADF properties are concerned. In effect, an insoluble but porous scaffold is created within a gelling, plastically deforming, and mechanically bonding larger matrix of PEO. We believe that this invention represent a major improvement in fight against opioid addiction.

Proposed Use
Prevent opioid abuse Permit better pain management

Creator(s)
A.reza Fassihi

Patent
PCT/US19/056652; WO 2020/081762 A1

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Biotechnology; Therapeutics

About
The invention relates to the treatment of depressive disorders and mania. The invention is based on the discovery of compounds that are selective for kappa opioid receptors. The modulation of activity at kappa opioid receptors can be useful for the treatment of mood disorders. For example, the compounds exhibiting antagonist activity, biased agonist, or inverse agonist activity at kappa receptors are useful for the treatment of depressive disorders, among other conditions. The compounds exhibiting partial agonist or biased agonist activity at kappa receptors are useful for the treatment of bipolar disorder, e.g., as mood stabilizers, among other conditions. The compounds exhibiting full agonist or biased agonist activity at kappa receptors are useful for the treatment of the manic phase of bipolar disorder, among other conditions.

Stressors that cause symptoms of depression increase the activation of cAMP response element-binding protein (CREB) in the nucleus accumbens. CREB activation results in the activation of the prodynorphin gene, which encodes the opioid peptide dynorphin. Dynorphin is an agonist of the kappa opioid receptors in the brain, and enhances symptoms of depression. It has been shown that kappa receptor antagonists can act as antidepressants by mediating a disinhibition of dopamine release in the nucleus accumbens. It has been shown that antimanic/antipsychotic drugs increase the activity of dynorphinergic neurons, which have their effects through kappa receptors. The diterpene salvinorin A, derived from Salvia divinorum, has recently been shown to be a high affinity and selective kappa opioid receptor agonist. New compounds which are highly selective for kappa opioid receptors over mu and delta opioid receptors and which have kappa inverse agonist, kappa biased agonist, kappa antagonist, kappa partial agonist, or kappa agonist activity are needed to provide improved methods for the treatment of affective disorders and other conditions for which kappa opioid receptor signaling plays a role in the pathogenesis of disease. We have developed such compounds.

Proposed Use
Selective treatment of mood disorders

Creator(s)
Lee-Yuan Liu-Chen

Patent
62/885,495; 62/716,539

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Research Tools; Clinical Applications; Biotechnology; Therapeutics

About
There is currently no cure or viable option for the treatment of neuronopathic conditions associated with lysosomal dysfunction or storage. Enzyme replacement therapy is not an option because the enzyme cannot cross the blood-brain barrier. Small molecules can be optimized to penetrate the CNS and developed as therapeutics to treat these disorders. Gaucher Type 1 patients have residual symptoms which are not addressed by enzyme replacement treatment (ERT) and a small molecule therapeutic may prove to be beneficial as an add-on therapy in this patient population. We describe novel functionalized N,N-dialkylamino phenyl ethers as well as compositions and their methods of use to prevent and/or treat lysosomal storage disorders and diseases associated with lysosomal dysfunction including Parkinson’s disease and Lewy Body Dementia (LBD). Our molecules are non-polar small molecules that will penetrate into the CNS and thus provide a viable treatment option for neuronopathic diseases. The end result of our work would be the creation of a small molecule drug that would be used to treat these poorly managed diseases.

Lysosomal storage disorders (LSDs) are inheritable metabolic diseases with deficiencies in enzymes that function within the glycosphingolipid biosynthetic and metabolic pathway. As a consequence, non-degraded substrates accumulate and normal lysosomal function is compromised, resulting in impaired autophagy, disruption of cell signaling and eventually cell death. Two thirds of LSDs have central nervous system (CNS) involvement resulting in a progressive neurodegeneration and the leading cause of patient death. A group of more than 50 diseases have been classified as LSDs, including Gaucher, Tay-Sachs, Sandhoff and Fabry disease, Niemann-Pick type C and GM1 gangliosidosis. The most common LSD is Gaucher disease, with a prevalence of 1 in 57,000 births. Gaucher disease (GD) is an autosomal recessive disorder resulting from mutations in the gene GBA1, encoding the lysosomal enzyme β-glucocerebrosidase (GCase). Reduced or loss of GCase activity leads to accumulation of glucosylceramide and glucosylsphingosine. GD is clinically defined into three types based on the age of disease onset and clinical manifestations of organ involvement. Type 1 GD is non-neuronopathic while types 2 and 3 GD have CNS involvement. Neuronopathic GD is a devastating early onset neurodegenerative LSD. As a result of the GCase deficiency, glucosylceramide accumulates, disrupts normal cell function, leading to neurodegeneration in neuronal cell types. While Gaucher Type 1, a peripheral disease, is treated with enzyme replacement therapy or by small molecule substrate reduction therapy (miglustat, (Zaveska®) eliglustat, (Cerdelga®)) to reduce abnormal glucosylceramide accumulation. Because of their poor CNS penetration, neither drug can be used to treat neuronopathic Gaucher disease. There is currently no cure or viable option for the treatment of neuronopathic conditions. With the goal to discover small molecule therapeutics for neuronopathic GD, we developed a phenotypic screening approach utilizing patient-derived cells to identify small molecules with activity to reverse the diseased lysosomal phenotype as an alternative to target-based screening strategies. Disruption of calcium homeostasis and impaired lysosomal function are measurable, phenotypic characteristics of LSD patient-derived cells, including GD. Neuronopathic diseases including Parkinson’s disease and LBD have also been shown to exhibit impaired lysosomal function. Therefore, novel compounds which improve lysosomal function have therapeutic potential in treating these diseases. Screening of a small molecule collection in a patient-derived phenotypic assay lead to the identification of hits. Medicinal chemistry around one of these led to the discovery of novel agents that restore a normal phenotype to diseased patient cells with improved potency and drug-like properties. Since these novel compounds are able to penetrate the CNS they may be useful for treating neuronopathic Gaucher disease and other disorders associated with lysosomal dysfunction.

Proposed Use
Treatment of lysosomal storage diseases including neuronopathic Gaucher, Tay-Sachs, Niemann-Pick Type C diseases, Parkinson’s disease and Lewy Body Dementia (LBD).

Creator(s)
Magid Abou-Gharbia, Marlene A. Jacobson, Wayne E Childers

Patent
PCT/US18/61911

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Biotechnology; Chemicals; Therapeutics

About
We have developed a methodology to control the micro-structural and mechanical properties of poly(phenylene terephthalamide) (PPTA) fibers and fabrics, through modifications of their surface by sulfuric acid treatment. This treatment enhanced the adhesion and permitted the deposition of ultra-thin inorganic coatings. This hybrid material approach integrating ultra-thin ceramic coatings onto the PPTA fibers and fabrics led to an enhancement of their compressive mechanical properties and energy absorption, as well as their thermal conductivity and chemical stability. In addition to a low processing cost, by applying few nanometer-thick coatings on single fibers, the light weight and flexibility of pristine PPTA fibers are maintained. This provides a new route for obtaining high performance PPTA fibers with a compressive Young’s modulus which is about 2.5 times higher than that of the untreated fibers and fabrics.

A novel surface treatment of PPTA fibers and fabrics with sulfuric acid, which fuses together the fibrils generating a fully consolidated and self-reinforced structure. In a second step, a scalable technique was designed for coating the surface-modified PPTA fibers and fabrics with ultra-thin ceramic shells of alumina and silica materials. This methodology allowed the production of lightweight and strong fibers and fabrics by hybridizing mechanically robust ceramics with polymeric fibers. Uniform alumina shells were coated through atomic layer deposition method while the silica shells were produced through solution-based sol-gel technique. The shell thickness of ceramic materials was controlled by the precursor concentration and the processing time. The crystallinity and structural properties of uniform ceramic shell coating are being investigated by using X-ray diffraction and scanning electron microscopy techniques. The untreated Kevlar® 29 fibers show the compressive (transverse) Young’s modulus of 4.38 GPa while the alumina and silica coated Kevlar® 29 fibers exhibit compressive (transverse) Young’s modulus of 13.35 GPa and 13.65 GPa, respectively.

Proposed Use
This new route that can be applied to improve the mechanical and thermal properties of high performance polymer engineering fibers and fabrics with potential applications in: • Advanced fabrics, coatings and fillers • Advanced composites in the aerospace industry • Nano-composites • Bullet-proof helmets and body armor • Protective and sport materials

Creator(s)
Simona Percec, Zhuolei Zhang, Shenqiang Ren

Patent
16/767,496; PCT/US18/62934; 62/591,788

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Polymers (Materials); Chemicals; Materials

About
A High Aspect Ratio Vessel (HARV) is a type of rotatory bioreactor which, by maintaining an optimized suspension culture can expose cells or organoids to simulated microgravity conditions. One major limitation of conventional microgravity bioreactor technology, is the tendency to generate air bubbles, which induce turbulence and disrupt microgravity fluid dynamics. This invention overcomes this limitation by actively removing gas bubbles from the system before they are able to affect bioreactor performance. This invention improves current HARV technology by facilitating continual gas / air bubble removal using a novel, partially segregated, uni-directional channel.

A HARV is a type of rotatory bioreactor that exposes cells, cell aggregates, or organoids to optimal nutrient circulation under simulated microgravity conditions. One major limitation of microgravity bioreactor technology is the tendency to generate air bubbles, which introduce damaging turbulence and disrupt its unique microgravity fluid dynamics. Our invention overcomes this limitation by actively and continually removing gas bubbles from the system before they affect bioreactor performance. The device contains a central cylindrical volume that is standard among all HARV designs. The novel aspect of this device is the thin semi-circular channel that runs around the majority of the perimeter of the main volume. A flat silicone gasket in the shape of the interior channel walls prevents the flow of fluid between the cylinder and the channel. As the HARV rotates (counter-clockwise in this design), any bubbles rise to the top due to buoyancy. When the entrance to the channel is at the top of the system, all bubbles automatically enter the channel as they are displaced by media that was added to the channel before the experiment began. As the device rotates, the bubbles stay on the top moving further and further away from the entrance to the chamber. When they encounter the back wall of the channel, they are pulled around the circumference of the circle until they reach the rear of the channel , where they are held near the back for all subsequent rotations.* This process can repeat itself many times, theoretically limited only when there is insufficient media in the channel. A port at the back of the channel enables for the periodic addition of media and / or removal of bubbles, as necessary, enabling the device to be maintained indefinitely with only minor upkeep and operator intervention. Current prototypes, constructed out of acrylic plates sealed with a gas-permeable membrane and a silicone gasket ring, are held together with bolts and nuts. Future generations of commercializable bioreactors will be manufactured from autoclavable plastics, such as polycarbonate. Quantitative experiments are ongoing, but qualitative experiments show that the segregated bubbles do not disrupt the bulk flow and solids in suspension in the bulk flow will not end up in the channel, provided the rotatory speed of the system is sufficient to simulate microgravity. This bubble catching technology is currently being leveraged in an advanced low-volume, perfusing bioreactor which will enable reliable and user-friendly organoid culture for extended timepoints (longer than 30 days). *A video demonstrating this process may be obtained upon request. Please email tug80380@temple.edu with the subject line "Bubble Catch HARV Video Request".

Proposed Use
Short-term, this product will be desirable to tissue engineering laboratories in academia as well as in industry that work on microgravity bioreactors or developmental biology, organoid models for diseases, and drug delivery. Long-term, we are adapting this technology for the rapidly expanding personalized cancer therapy industry. Current patient-derived xenograft (PDX) technology (expanding patient tumors in mice for later testing) offers promising therapeutics identification for cancer patients. However, this is limited by the high cost of animal care, inaccuracies associated with non-human animal models, and obvious ethical limitations. We anticipate that under the right culture conditions, our bioreactor technology could replace animal testing, improving accuracy at a fraction of the cost of currently used for PDX technology.

Creator(s)
Peter I. Lelkes, Michael Alexander Phelan

Patent
PCT/US18/54937; 62/570,177

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Research Tools; Therapeutics; Clinical Applications; Biotechnology; Synthetic Biology

About
In the context of a hydrogen economy, research across the globe has been interested in developing earth abundant catalysts for hydrogen evolution from the electrolysis of water (i.e., water splitting). The present invention is a novel multi-metal phosphide electrodeposited catalyst made of cobalt, molybdenum, iron, and phosphorous, that exhibits exceptional catalytic properties for the hydrogen evolution reaction (HER). This catalyst, which is composed of earth abundant elements, shows remarkable catalytic properties, equal to the precious metal and costly platinum catalyst (the best known HER catalyst). Furthermore, the electrodeposited catalyst is synthesized by a very simple and cost-effective electrochemical deposition method. The invention has a potential broad and transformative impact as a commercial earth abundant catalyst for hydrogen generation and sustainable energy.

The present invention relates to the development of a multi-metal electrocatalyst in the field of water electrolysis. More specifically, the present invention relates to an energy-efficient electrocatalyst which can be utilized in the electrolysis of water to produce hydrogen gas. Research across the globe has keyed in on making an electrocatalyst to generate hydrogen during the electrolysis of water that could compete with the efficiency of the precious metal platinum. (While platinum is an excellent catalyst it is very expensive making its use in commercial processes an unattractive option.) The invention described here is an electrocatalyst as active as platinum, but made out of earth-abundant materials using a straightforward and rapid electrochemical synthesis method making it a cost-effective solution. We feel the development and implementation of the novel catalyst developed at Temple University will have a positive and broad impact on the field of sustainable energy on a global scale.

Proposed Use
Can be used as a cost-effective catalyst for hydrogen generation in commercial alkaline water electrolysis.

Creator(s)
Akila Chathurang Thenuwara, Daniel Strongin

Patent
PCT/US2018/042988

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Hydrocarbons; Energy Efficiency; Energy Harvesting; Chemicals; Energy Storage; Materials; Fuel Cells

About
Soft robotics has received increasing research interest due to their compliance and safe interaction with the environment. So far, most designed locomotive soft robots can only perform on horizontal and lightly-tilted surfaces, while it remains a great challenge to design climbing soft robots on vertical surfaces, which could largely expand their horizons in potential applications of intelligent surveillance, inspection, and detection. Here, we propose a new pneumatic-actuated bioinspired soft adhesion actuator, which exhibits rapid switchable adhesion/deadhesion on target surfaces upon pressurizing/depressurizing the embedded spiral pneumatic channels. Based on the switchable adhesion actuator, we design and fabricate a novel load-carrying climbing soft robot (CSR), which can operate on a wide range of foreign horizontal and vertical surfaces including dry, wet, slippery, smooth and semi-smooth ones. We expect that CSR can realize an effective locomotion and exhibits a good load-carrying capability on vertical surfaces.

We designed a bioinspired simple, novel proof-of-concept soft robot that can walk horizontally and climb vertically on different types of smooth and semi-smooth substrate with a certain load-carrying capability. The targeted surfaces can be dry, semi-smooth, wet, slippery, and even under water. The success lies in our new design of soft adhesion actuators with embedded spiral pneumatic channels for switchable, strong, and mechanically robust adhesion on different types of surfaces upon pressurization. The soft adhesion actuator provides a new platform for designing soft robots that can operate on vertical surfaces and work under water, which could find potential applications in design of switchable adhesion materials, object transportation, wall-cleaning, camouflage machine, and underwater soft machines etc. Additionally, climbing soft robotics is much lighter than its counterpart made of rigid components. Compared to the complicated structures and controlling system of a rigid climbing robot, our climbing soft robot exhibits easiness in fabrication and controlling. The low-cost of climbing soft robot is also advantageous over its rigid counterparts.

Proposed Use
Rigid climbing robots can only perform on flat and smooth surfaces (like glass surface or polished metallic surfaces). In the contrary, due to the good conformability of soft materials, our climbing soft robot has potential to work on curved and rougher surfaces. In the manuscript, we successfully demonstrate the climbing of CSR on semi-rough surface, which is difficult for rigid robot to perform on.

Creator(s)
Yichao Tang, Jie Yin

Patent
16/623,393; 62/520,686; 62/661,771; PCT/US18/38027

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Robotics

About
There are very few if any therapeutics available for treating radiation induced vascular injury resulting from exposure during radiotherapy or accidents. While the use of Neupogen and Neulasta to treat hematopoietic acute radiation syndrome (H-ARS) is approved by the FDA, therapeutic approaches to the treatment of radiation-induced vascular/ endothelial injury are largely supportive and there are no specific pharmacologic therapies available that protect from radiation-mediated tissue damage. Potential therapeutic target sites include local control of the vascular endothelial response to systemic inflammation as well as direct modulation of leukocyte migration. We identified Protein Kinase C-delta (PKCδ) as a critical regulator of the inflammatory response post-irradiation.

In the event of radiation therapy for treatment of cancer or a nuclear or radiological catastrophe, affected individuals will be exposed to a wide range of radiation doses with the extent of injury depending on the duration of exposure and the inherent sensitivity/resistance of the patient to ionizing radiation. While the use of Neupogen and Neulasta to treat hematopoietic acute radiation syndrome (H-ARS) was recently approved by the FDA, therapeutic approaches to the treatment of radiation-induced vascular/endothelial injury are largely supportive and there are no specific pharmacologic therapies available that protect from leukocyte-mediated tissue damage. We have identified Delta-Protein Kinase C (PKCδ) as a critical regulator of the inflammatory response controlling recruitment and activation of inflammatory cells and have shown that that inhibiting PKCδ protects critical organs in inflammatory diseases such as sepsis. Our data indicate that PKCδ inhibition dramatically attenuates radiation-induced leukocyte adhesion and migration as well as vascular endothelial permeability even when administered 24hrs post radiation exposure. Our data indicates that PKCδ has a critical role in mediating leukocyte activation and migration after radiation injury and that inhibition of PKCδ post- ionizing radiation (IR) will significantly attenuate radiation-mediated vascular injury.

Proposed Use
Treatment to reduce radiation-induced vascular/endothelial damage.

Creator(s)
Laurie Kilpatrick, Fariborz Soroush, Yuan Tang, Mohammad F Kiani

Patent
16/621,720; 62/518,058; PCT/US18/36987

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Therapeutics; Environment

About
We have created a series of apparatuses that significantly improves the efficiency of burning a gas fuel involving the use of a magnetic field.

According to one aspect of the invention, apparatus for efficiently burning hydrocarbons includes a housing having a first opening for receiving a fuel, a second opening for expelling the fuel, and a tubular passageway extending between the first opening and the second opening. The tubular passageway includes a central region and an outer region surrounding the central region. The apparatus also includes a plurality of magnets disposed within the passageway. Each of the magnets has a spherical or an ovoid shape. The plurality of magnets define void spaces for passing the fuel such that a central flow rate of the fuel in the central region of the passageway is equivalent to the an outer flow rate of the fuel in an outer region of the passageway. Results have demonstrated a significant increase in efficiently burning fuels.

Proposed Use
Can be used in kitchens, including restaurants and home settings Outdoor camping setting to reduce heating time Units have been designed to increase efficiency of heating buildings

Creator(s)
Oleksandr Diloyan

Patent
PCT/US2018/039287; 62/524,797

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Energy; Environment; Hydrocarbons; Energy Efficiency

About
The preparation of chemical agents to counter the spread of human pathogens has been a challenge long before the term medicinal chemistry was coined. From the fermentation of beverages to the preparation of bleach, the facile production of compounds to minimize the pathogenic effects of microbes has been a key concern. Development of bacterial resistance to even the most potent antibiotics, and more recent devastating viral outbreaks, have ensured that continued research into antimicrobial compounds will remain crucial. We have developed a suite of antimicrobial compositions comprising polycationic amphiphiles including biscationic, triscationic and tetracationic amphiphiles of varying architectures, along with the method of making such antimicrobial compositions, and how to use these compounds for antimicrobial use. The compound or the composition provided has an ability to kill or inhibit the growth of microorganisms, including but not limited to bacteria, viruses, yeast, fungi, and protozoa, or to inhibit formation of a biofilm or eradicate pre-established biofilms. Three patents have been issued and one more is pending for this body of work, on top of two-dozen academic publications by the inventors.

We have developed a wide range of novel and potent antimicrobial compounds, particularly well suited to destroy biofilms. Over 600 compositions have been constructed in the labs of the inventors for antimicrobial testing. Despite numerous reports of the antimicrobial activity of monocationic amphiphiles, there are no investigations to the inventors' knowledge correlating antimicrobial activity to amphiphiles with three or four quaternary ammonium groups, and significantly fewer investigations of biscationic amphiphiles. This stands in stark contrast to the wide variety of bioactive natural products (and derivatives thereof) incorporating multiple primary, secondary, and tertiary amines; common examples include spermine, spermidine, squalamine, and others. While these are generally drawn as neutral compounds, they will have multiple cations at physiological pH; related compounds have been investigated as possible biofilm disruptors. The inventors have demonstrated for the first time that Quaternary Amine Compounds (QAC)x, are potent eradicators of pre-established bacterial biofilms. The compounds are synthesized in one or two steps from commercially available material, making them attractive alternatives to existing methods for a eradication of a variety of pathogens, even those entrenched in biofilms. With the ready availability of compounds with two, three, or four tertiary amines at modest commercial cost, the inventors continued correlating bioactivity to amphiphilic structure, specifically the number of cations present, as well as the number and lengths of non-polar side chains. The target set of compounds varies in each of the three issued patents and one patent application. The inventors aimed to develop unified synthetic methods for the amphiphiles presented.

Proposed Use
The antimicrobial composition is used to kill or inhibit growth of at least one group of microorganisms selected from the group consisting of bacteria, viruses, yeast, fungi, and protozoa, or to inhibit formation of a biofilm or eradicate a pre-established biofilm.

Creator(s)
Megan Jennings, William Wuest

Patent
US10398142B2; US10301254B2; US10136639B2

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Agriculture; Clinical Applications; Biotechnology; Chemicals

About
We identified IFN-gamma and CRISPR/Cas mediated editing strategies as a possible therapeutic compound for the treatment of Zika virus infection. Our observations are mostly from in vitro cell culture model system where we have Zika virus infection and observed anti-Zika virus activity. This invention suggests that combination of CRISPR/Cas9 approach with IFN-gamma therapy can be a novel approach to inhibit Zika virus. There is no available therapy for the diseases associated with Zika virus infection.

Zika virus is an emerging virus with important public health consequences. Zika virus disease is caused by the Zika virus, which is spread to people primarily through the bite of an infected mosquito (Aedes aegypti and Aedes albopictus). Many people infected with Zika will have no symptoms or mild symptoms that last several days to a week. However, Zika infection during pregnancy can cause a serious birth defect called microcephaly and other severe fetal brain defects. Guillain-Barre syndrome (GBS), an uncommon sickness of the nervous system, is also very likely triggered by Zika in a small number of cases. Zika virus is an arbovirus (arthropod-borne virus) and a member of the family Flaviviridae, genus Flavivirus. Zika virions are enveloped and icosahedral, and contain a nonsegmented, single-stranded, positive-sense RNA genome, which encodes 3 structural and 7 nonstructural proteins that are expressed as a single polyprotein that undergoes cleavage. Zika genomic RNA replicates in the cytoplasm of infected host cells. Zika virus was first detected in 1947 in the blood of a febrile monkey in Uganda's Zika Forest and in crushed suspensions of the Aedes mosquito, which is one of the vectors for Zika virus. The virus remained obscure, with a few human cases confined to Africa and Asia. There are two lineages of the Zika virus, African and Asian, with the Asian strain causing outbreaks in Micronesia in 2007 and French Polynesia in 2013-2014. From here, the virus spread to Brazil with the first report of autochthonous Zika transmission in the Americas in March 2015. The rapid advance of the virus in the Americas and its likely association with microcephaly and Guillain-Barré syndrome make Zika an urgent public health concern. Currently, there is no targeted therapy for people infected with Zika virus. In order to gain insight into the possible infection of human primary glial cells, we have infected human astrocytes and microglial cells with Zika virus. Our results suggest that Zika virus can actively replicate and cause lytic infection in both astrocyte and microglia cells. Interestingly, astrocytes are more susceptible to Zika virus replication than microglial cells. Since IFN-gamma is known for its anti-viral activities and our previous experience on its suppressive effects on human polyomaviruses, we sought to investigate possible anti-viral activity of IFN-gamma for Zika virus infection. Our data have revealed that IFN-gamma can suppress the replication of Zika virus in both primary astrocytes and microglial cells. IFN-gamma was able to reduce the rate of viral propagation in both cell types up to 16 fold and maintained their viability through the infection. These observations demonstrate, for the first time, a novel role of IFN-γ in suppression of Zika virus replication and may provide a novel approach to treat the diseases associated with Zika virus infection, in particular when combined with CRISPR/Cas targeting the virus.

Proposed Use
This invention suggests that combination of CRISPR/Cas approach with IFN-gamma therapy can be a novel approach to inhibit Zika virus. There is no available therapy for the diseases associated with Zika virus infection.

Creator(s)
Kamel Khalili, Hassen Wollebo, Iiker Sariyer

Patent
16/341,481; 62/406,976

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Clinical Applications; Biotechnology

About
The present invention relates in part to short-wave IR (SWIR) materials comprising generic mixed salts of empirical formula AaBbMcXd that are composition-dependent, broadband, and tunable. These materials have unique light absorbance wavelengths from 0.4 to 2.6 μm, including both the visible and SWIR. The preparation procedure for the SWIR materials is simple, including the use of widely available, cheap, and non-toxic precursors, unlike existing state of the art alloy SWIR materials. These novel materials have broad applications in security, surveillance, military, machine vision, photovoltaic solar cells, medical treatments, spectroscopy detector, and thermography. The present invention also relates to methods of fabricating a film comprising the composition of the invention and to photovoltaic stacks comprising the composition of the invention.

The short-wave infrared (SWIR) materials are an important focus of defense, security, and scientific research and development. The demand for the short-wave IR materials has increased for scientific, defense applications, and sustainable energy sources. For security and defense applications, short-wave infrared (SWIR) detectors find a number of advantages compared to visible when used in a variety of applications including electronic board inspection, produce inspection, identifying and sorting, surveillance, anti-counterfeiting, process quality control, and much more. However, traditional inorganic short-wave IR materials are expensive, environmentally toxic with small-area and under highly-demanding detection conditions. In the photovoltaic applications, existing materials suffer from a narrow UV-visible absorption of solar radiation and leave near-IR to short-wave IR unexploited. Therefore, there is a need in the art for novel short-wave IR materials with improved optoelectronic and photovoltaic properties. Other applications and related industries, such as security, surveillance, military, machine vision, medical devices and treatments, spectroscopy detectors, and thermography, can likewise benefit from the development of novel short-wave IR materials. The present invention addresses these continuing needs in the art.

Proposed Use
Electronic board inspection, produce inspection, identifying and sorting, surveillance, anti-counterfeiting, process quality control, such as security, surveillance, military, machine vision, medical devices and treatments, spectroscopy detectors, and thermography.

Creator(s)
Xia Li, Yi Rao, Bradford Wayland, Hai-Lung Dai

Patent
16/345,829; 62/417,024; PCT/US17/59151

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Thin Films; Telecommunications; Electronic Components; Chemicals; Materials; Sensors (Photonics); Medical Devices; Health IT

About
This invention discloses two designs for eliminating the scalability barriers of multiprocessor/multicore computer applications in deliverable performance and reliability. The first is the use of proven statistic multiplexing principle for an intelligent network-scale transient memory. The reliable transient network memory architecture works in tandem with a statistic multiplex runtime kernel for real time automatic SIMD, MIMD and pipelined processor scheduling and synchronous data replication and resynchronization. These designs enable automated parallel processing by multiplexing any number of computing, networking and storage devices concurrently. The performance and reliability benefits enable extreme application security measures without performance penalties. Application of this invention requires wrapping legacy programs to become stateless multiprocessor/multicore programs. The stateless programs can be deployed on any minimally connected computing and storage devices. The procedures of stateless programming wrappers are also disclosed. Stateless applications are mission critical applications that can scale indefinitely with deterministic performance gains and are resilient to partial processor, network and storage failures.

Traditional distributed and parallel computer applications are composed of multiple stateful communicating programs. The scalability of these applications are inherently challenged since expanding the processing infrastructure can only enhance performance at the expense of diminishing application's reliability. Application's reliability measures, such as program checkpoint/recovery and data backup/restore, incur inevitable performance penalties. This invention was first inspired by the hidden insight of the Amdahl's Law that has governed the parallel computing architecture designs for the past half century. Amdahl's hidden insight revealed the unlimited application scalability as long as the application's size is unconstrained. The disclosed network-scale transient memory and statistic multiplexing runtime kernel fulfill this need by allowing stateless applications of unconstrained sizes to scale in performance and reliability at the same time indefinitely as the number of compute, network and storage components grows. The network-scale transient memory employs the Tuple Space abstraction. A stateless application comprises of any number of stateless master and workers. A stateless master is any legacy stateful controlling program wrapped by a blockchain-like protocol without the cost-prohibitive consensus algorithm. A stateless worker is a wrapped legacy message-passing, remote procedure or method without direct program-program communications. Since the stateless programs can be deployed on any number of processors and networks, the application can scale indefinitely in performance and reliability. The peak deliverable application performance is only subject to the economic law of diminishing returns. A similar architecture is for data intensive applications, such as database and permanent object stores where synchronous data replication is carried out automatically. Given sufficient network and storage resources, this invention enables synchronous data replication without performance penalties. Since synchronous data replication and automatic data resynchronization ensures data consistency and reliability, growing the number of parallel data partitions to be greater than the number of replicas ensures deterministic performance gains without application reliability degradation. Increasing the number of data replicas enhances application reliability exponentially. These performance and reliability benefits enable extreme data and application security measures without negative performance impacts. Due to the extreme stability of the stateless applications, formal application safety validation and verification become practical.

Proposed Use
Mission critical compute intensive applications Mission critical data intensive applications Mission critical transactional systems Mission critical storage systems.

Creator(s)
Yuan Shi

Patent
16/348,899; 17869136.6; 62/421,642; PCT/US17/61492

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Data Communications; Artificial Intelligence; Computer Science & Information Technology; Communication & Networking

About
The bitter taste of many oral medications complicates the administration of drugs to children and elderly individuals. A related concern is that children or elderly individuals may have trouble consuming drugs in capsule or tablet form. Also, individuals with xerostomia (dry mouth syndrome) may have problems consuming caplets, capsules, and tablets. In particular, the development of new delivery methods for dispensing bitter tasting medications to children and the elderly is an unmet need. One approach to alleviate these problems is to minimize the bitter taste of a drug, and secondly to develop a delivery method that does not use capsules or tablets. One promising mechanism to overcome these two problems is the incorporation of bitter tasting drugs within stearic acid microspheres, and then incorporating these microspheres into rapidly dissolving edible strips that contain sweet taste stimuli and peppermint oil that minimize bitter taste. Alternatively, stearic acid microspheres may be incorporated into chocolate or gelatin-based candies (i.e., gummy bears) for minimizing bitter taste. Stearic acid is an excellent molecule for encapsulating molecules because this saturated lipid has no taste. This novel approach of encapsulating a molecule in microspheres and then masking the bitter taste of the encapsulated molecule is a promising method for delivering bitter tasting drugs to young children, adults, and elderly individuals. In this approach, bitter taste is minimized or completely eliminated. As opposed to tablets, small microspheres are not broken up by chewing, but readily release their contents in the oral cavity. Finally, different vehicles (films, candy, gummy bears, etc.) can be tailored to deliver encapsulated drugs to specific human populations.

This invention has three major components. The first component is the development of stearic acid microspheres that encapsulate drugs and taste stimuli. Stearic acid was used because this saturated fat has essentially no taste, is safe, and is a solid at room temperature. The encapsulation of molecules by microspheres delays their release in the oral cavity. At the present time, both bitter and sweet taste stimuli have been incorporated into microspheres. The incorporation of the non-caloric sweetener sucralose is noteworthy because this compound is difficult to incorporate into microspheres (see: Stabilized sucralose complex, US 4971797 A). We are the first to incorporate this non-caloric acid sweetener into stearic acid microspheres. The second component of this disclosure is the development of edible taste strips that contain SOA micro-spheres. SOA-containing microspheres is used as a model compound for bitter taste. Encapsulated SOA is then incorporated into edible taste films that contain the sweet taste stimuli sucralose, glycerol, and mannitol along with peppermint oil in order to block and mask the (delayed) bitter taste of SOA from microspheres. The three sweet taste stimuli described above are released from strips when the strips initially dissolve in the oral cavity (i.e., as soon as the strips come in contact with saliva). We have also incorporated sucralose-containing microspheres into edible taste films that are described above. These edible taste strips contain the polymers pullulan and hydroxypropyl methylcellulose along with xanthan gum [thickener] as the base. Thirdly, both sweetened and unsweetened candy has been used as a means to deliver loaded microspheres to the oral cavity. As with edible films, microsphere-containing candies can be prepared in a variety of shapes and sizes. Visual inspection has indicated that microspheres are uniformly distributed in chocolate candies.

Proposed Use
Bitter taste in the oral cavity is initially blocked by encapsulating a bitter tasting molecule in stearic acid, and by the incorporation of sweet taste and trigeminal stimuli to edible taste strips; Delayed release of sucralose-containing microspheres in the oral cavity for use in chewing gum, drug release, etc.; Delayed release of drugs in the oral cavity from edible taste strips or chocolate candies; Development of sucralose containing microspheres for delaying the release of sucralose to match the delayed release of bitter tasting drugs from microspheres so that bitter taste is further minimized; Elimination of tablets or capsules for drug delivery to pediatric populations or elderly individuals; Development of a new drug delivery system for young children and elderly individuals; A new research tool to examine interactions between bitter and sweet taste stimuli in the oral cavity.

Creator(s)
Gregory S. Smutzer

Patent
PCT/US17/45244; 62/370,427

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Micro & Nanotech; Therapeutics

About
Dual Leucine-zipper Kinase is an ‘executioner’ enzyme that controls degeneration of death of several types of neurons. DLK critically requires modification with the lipid palmitate, a process called palmitoylation, to perform this role. We have already demonstrated neuroprotective effects of a chemical inhibitor of DLK palmitoylation and propose to use a novel screening method to identify additional compounds of this type.

The signaling enzyme Dual Leucine-zipper Kinase (DLK) plays key roles in several forms of neurodegeneration. There is therefore great interest in identifying inhibitors of DLK as potential neuroprotectants. However, current strategies all seek to inhibit DLK’s kinase activity, an approach prone to undesired ‘off-target’ effects due to the large number of similar kinases. We recently found that DLK, but not homologous kinases, is covalently modified with the lipid palmitate. This process, palmitoylation, dramatically affects DLK localization in cells and is also essential for DLK’s pro-degenerative role. We plan to exploit the palmitoylation-dependence in three distinct ways to identify novel neuroprotective compounds: i) we have found that a broad spectrum inhibitor of cellular palmitoylation can protect neurons from degeneration, likely by targeting DLK. We propose that this compound, 2-Bromopalmitate, could serve as a novel neuroprotectant. ii) we have established a novel cell-based assay of DLK palmitoylation, which we propose to use in a High-Content Imaging screen to identify novel small molecules that prevent this modification. This work will be a collaboration between the Thomas laboratory and Dr Marlene Jacobson at Temple University’s Moulder Center for Drug Discovery. After confirming the validity of initial ‘hits’ we will then perform a follow-up assay to determine whether such compounds can protect primary neurons from degeneration. iii) Small molecules identified in the screen will be classified and likely functional groups identified. These compounds may represent a novel class of neuroprotectants.

Proposed Use
Prevention of neurodegeneration following acute injury (stroke, traumatic brain injury, peripheral nerve injury) Prevention of neurodegeneration in chronic conditions (Alzheimer's Disease, Amyotrophic Lateral Sclerosis) Amelioration of symptoms for those suffering from chemotherapy-induced peripheral neuropathy (CIPN), diabetic neuropathy, HIV-associated neuropathies Potential treatments for conditions in which aberrant palmitoylation likely contributes to disease progression e.g. certain cancers Basic research into neurodegeneration mechanisms Basic research into roles of palmitoylation in other tissues and cells

Creator(s)
Wayne E Childers, Sabrina M Holland, Marlene A. Jacobson, Dale Martin, Jingwen Niu, Gareth Thomas

Patent
16/631,969; 62/534,347; PCT/US18/42620

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Therapeutics; Research Tools

About
Signaling via G protein-coupled receptors (GPCRs) is critical for normal heart function, and during disease GPCRs are uncoupled from their downstream effectors and receptor number is reduced. Signaling through these receptors is tightly controlled by GPCR kinases (GRKs) and one in particular, GRK2 (originally known as βARK1), has been shown to be intimately involved in heart failure (HF) progression. GRK2 up-regulation in failing hearts represents one of the first molecular changes that occur after cardiac injury, and lowering GRK2 restores GPCR levels and preserves cardiac function. However, ongoing research has demonstrated great diversity in the functional roles of GRK2, including phosphorylation of non-GPCR substrates and numerous phosphorylation-independent regulatory binding partners. Many binding sites within GRK2 have been identified for such protein-protein interactions, and several are important for adaptive and maladaptive myocyte growth. Therefore, we began investigating whether domain-specific interactions with signaling and regulatory molecules could lead to novel targets for HF therapy. For instance, GRK2 contains a putative amino-terminal Regulator of G protein Signaling (RGS) domain (βARKrgs) that directly interacts with Gq and appears to inhibit signaling without altering Gq enzymatic activity. Our lab has now demonstrated that cardiac-specific transgenic (Tg) expression of both the RGS domain of GRK2 and a shorter N-terminal peptide (βARKnt) can alter cardiac physiology when expressed in myocytes. Of note, they both halt HF progression in mice after pressure overload but have differential effects on the initial hypertrophic response. We have developed peptide therapeutics for heart failure that can be delivered via a viral vector to treat this important unmet medical need.

The invention is an adeno-associated viral vector of serotypes 6 and 9 expressed under an alpha cardiac actin enhancer and EF1alpha promoter containing mir122 inserts that reduce liver retention. This construct allows the virus to be injected systemically. This system allows delivery of the virus at any time point prior to or after disease development to investigate the disease states that are positively affected by βARKnt expression. Further, this method of delivery facilitates a detailed determination of the doseresponse relationship to determine the optimal dose range for patient therapy. This is particularly important given the vast array of cardiovascular disease etiologies and contributing factors including lifestyle and medical history, wherein intravenous viral delivery could be titrated up to each patients individual effective dose.

Proposed Use
A method for treating or preventing heart failure, the method comprising administering an effective amount of a composition comprising a nucleic acid encoding a beta-adrenergic receptor kinase N-terminal (βARKnt) peptide, wherein the βARKnt peptide and the nucleic acid encoding a βARKnt peptide, a variant thereof or a fragment thereof is contained within a vector.

Creator(s)
Sarah Bass, Walter J Koch

Patent
16/306,718; 62/345,273; PCT/US17/35897

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Clinical Applications; Therapeutics; Life Sciences; Cell and Gene Therapy

About
In recent years, with the development of expensive therapeutics, biomarkers, and tracers for inhaled delivery to the lung, there is a need for optimizing deposition of these media in the lung while, while minimizing loss of these media during administration with the supplemental flow. Despite the advent of patient or ventilator triggered devices for output only during the inspiratory cycle, there remains the loss of these media both during inspiration and expiration due to flow through the media reservoir and adjustments to the supplemental flow associated pressure and/or volume-controlled respiratory assist devices (i.e., ventilators, CPAP, etc). The design of our respiratory adaptor for optimizing the deposition of inhaled media (see schematic in Fig 1) allows a single device to interface with standard respiratory fittings to functionally direct flow through a bridge and a series of one-ways in order to present media loss during both inspiration and expiration. This has the effect to more efficiently deliver media to the lung supporting improved therapeutic/diagnostics outcomes while reducing the economic cost of the wasted media in the flow path.

Benchtop studies were performed using the bread-board arrangement of the Respiratory Adaptor with a pneumotachometer at various locations to demonstrate sparing of flow: media contact which effectively reduces the loss of media during both inspiratory and expiratory flow cycles. A pneumotachometer was placed in line with the inspiratory arm, distal to the media generator and bypass flow bridge. This configuration supports flow only in the inspiratory phase (downward of second tracing on screen). In addition to this configuration, we positioned the pneumotachometer in two additional locations: the bridge and in the expiratory limb just distal to the artificial lung. When combined in these configurations, the flow tracings demonstrated media sparing at the appropriate phases of respiration. For example, when positioned in the expiratory limb, no flow was observed during inspiration as all flow was directed either into the artificial lung or across the bridge. When placed in the bridge, no flow was observed during expiration, demonstrating sparing of flow recycling through the bridge onward through the media driver. Based on these experiments, we envision a Respiratory Adaptor design in which the prototype could be produced by a 3D printer as a single device with channels and one-valves, with universal sized respiratory tubing/fittings such that it could be easily connected between the patient and the inspiratory/expiratory lines of the respiratory assist device (ie ventilator). In addition, our adaptor will have an opening for standard-sized (ie Aeroneb Nebulizer) for in-line delivery within the inspiratory channel of the respiratory adapter.

Proposed Use
For inhaled drug delivery in Intensive Care; Emergency Department; Urgent Care; Radiology; even Home or Outpatient Clinics

Creator(s)
Thomas Shaffer, Marla R. Wolfson

Patent
PCT/US17/28038

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Synthetic Biology; Medical Devices; Therapeutic (Medical Devices)

About
We have developed a method of treating or preventing heart failure using a tyrosine receptor kinase B (TrkB) agonist, a polypeptide that mimics the effects of the endogenously produced neurotrophic factor - brain-derived neurotrophic factor (BDNF) – whose systemic and local content is likely reduced in subjects suffering from heart failure. We envision the use of these selective TrkB agonists alone or in combination with a β-adrenergic receptor (βAR) antagonist (βARblocker). And/Or using gene therapy with a vector encoding TrkB, and a vector encoding an antisense nucleic acid molecule targeting GRK2.

Our new approach should be effective in treating a broad array of heart failure including those with impaired left ventricular ejection fraction (“systolic” heart failure), preserved ejection fraction (HFpEF or “diastolic” heart failure), heart failure associated with low BDNF level, heart failure associated with high cardiac fibrosis level, heart failure associated with ventricular remodeling following a cardiac event, heart failure associated with non-ischemic cardiomyopathy, heart failure associated with mitral valve regurgitation, heart failure associated with ischemic cardiomyopathy, and heart failure associated with aortic regurgitation. We provide a method of treating or preventing heart failure using a tyrosine receptor kinase B (TrkB) agonist, a mimetic of the endogenously-produced brain-derived neurotrophic factor (BDNF) polypeptide, and a β-adrenergic receptor (βAR) antagonist (βARblocker). The therapeutic approach includes using βAR-blockers including Bisoprolol, Carvedilol, Carvedilol phosphate, Metoprolol, Succinate, and Nebivolol. While the TrkB agonist include N,N′,N′′-tris(2-hydroxyethyl)-1,3,5 benzenetricarboxamide (LM22A-4), LM22A-4, 7,8-dihydroxyflavone, 7,8-dihydroxyflavone, and/or a vector encoding TrkB, and a vector encoding an antisense nucleic acid molecule targeting GRK2.

Proposed Use
Treatment of Heart failure

Creator(s)
Walter J Koch, Alessandro Cannavo

Patent
15/916,494; 62/469,287

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics

About
Currently, methods used for immunotherapy typically incorporate ex vivo stimulated dendritic cells (DCs), which are cultured after collection from the patient, loaded with tumor-reactive antigen, and then infused into the patient. DCs are required for not only initiating primary T cell immune responses but also augmenting effector T cell function. They process and present Ag peptides, activate naive T cells in lymphoid organs, and promote activated T cell expansion and survival in peripheral non-lymphoid tissues. DCs also are crucial in directing the generation of effector T cells that specifically kill the target, such as virus infected cells and cancerous cells. Notch signaling is critical for adaptive T cell immune responses. Notch ligands expressed on the surface of DCs have broad roles in promoting the generation of effector T cells. Notch ligands (DLL1, DLL 3, DLL4, Jagged1 and Jagged2) interact with Notch receptors (Notch 1, 2, 3, and 4), triggering the release of intracellular Notch and the subsequent transcription of Notch target genes. Inhibiting pan-Notch signaling in donor T cells reduced their production of IFN-γ and IL-17 (Zhang et al., Blood, 2011, 117:299-308). The Notch ligand DLL4 mediates a dominant role for activating Notch signaling in alloreactive T cells (Tran et al., J Clin Invest, 2013, 123:1590-604). A specific type of DCs that express high levels of DLL4 and these so called DLL4+ DCs have greater ability than DLL4-negative conventional DCs to induce IFN--producing CD4+ effector cells and CD8+ cytotoxic T lymphocyte (CTLs). However, existing methods that produce human DCs from monocytes do not naturally induce their expression of DLL4. Thus, there is a need in the art for efficient and directed means of obtaining a high density population of DLL4-expressing DCs. The present invention satisfies this need.

The present invention is based on the unexpected results that DLL4+ DC-induced T cells provide a superior immunotherapeutic composition as they have a reduced risk of associated graft versus host disease toxicity. The invention provides compositions and methods of producing a population of immune cells useful in generating an immune response, and methods of use of the compositions of the invention as a vaccine in the treatment of cancer. The present invention relates to methods and use of DLL4-expressing immune cells (DLL4-IC) to induce clinically effective immune responses. In one embodiment, the DLL4-IC of the invention is a BM derived DC matured in a manner to activate DLL4 expression. In one embodiment, the DLL4-IC of the invention is a DC genetically engineered to express DLL4. In another embodiment, a DLL4-expressing DC (DLL4-DC) of the invention is a DLL4-expressing antigen presenting cell (DLL4-APC). However, the invention is not limited to antigen presenting cells (APCs), rather it includes any immune cell cultured or genetically modified to express DLL4. For example, the DLL4-IC could be a T-cell genetically engineered to express DLL4 and/or a T-cell genetically engineered to express DLL4 further comprises a chimeric antigen receptor (CAR). We envision that our approach will permit greater effectiveness with an augmented anti-tumor immunity (in the context of T cell immunotherapy), as well as a reduced risk for graft-versusphost disease (in the setting of allogeneic hematopoietic stem cell transplantation). We have conceived of a large variety of combinations of modified signaling molecule expression and cytokine that have the capacity to condition toward strong TH17 cellular responses to produce desirable levels of cytokines and chemokines, and have the capacity to induce apoptosis of tumor cells and induction of NK cell responses against tumors. We believe that our approach could be applicable to virtually all CAR therapies and an attractive technology for many emerging cell and gene cancer therapeutics.

Proposed Use
A novel approach to enhance CAR T therapies. This technology could be applied to improve responses to tumor vaccines We envision an extensive use in treatments where enhanced immune responses are desired.

Creator(s)
Yi Zhang

Patent
PCT/US17/29601

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Biotechnology; Therapeutics

About
Exosomes are tiny vesicles produced by most cell types that carry signals representative of the parent cell. Recent studies indicate that cell-based therapies enhance cardiac structure and function by releasing reparative factors derived from transplanted cells in the heart. Additionally, the administration of exosomes by themselves carries similar reparative responses as the stem cells without adverse consequences associated with cell transplantation circumventing the need to have stem cells processed. We have developed a novel protocol for the development of CPC exosomes enriched with Lin28, a developmental protein that regulates several tissue regenerative processes. CPC exosomes will be next tested for in vivo repair efficacy and their ability to enhance cardiac structure and function after myocardial repair.

Cellular replacement in the heart under pathologic stress is limited, meriting the need for the development of alternate strategies. Cardiac progenitor cells (CPC) have been proposed as a viable therapy for enhancement of cardiac function but are affected by patient age and disease progression limiting their performance. In contrast, CPCs from the fetal and neonatal stages exhibit higher growth properties and reparative potential. Nevertheless, CPCs in the adult and disease heart loses the ability to repair the heart and whether CPCs can be reversed back into a higher reparative stage remains unknown. We have identified a novel embryonic signaling pathway based on miR-294 and its target Lin28a that may have implications for cardiac repair. Lin28a has been implicated in reprogramming tissue repair and regeneration (ref) together with enhancing expression of mRNA targets for proliferation, survival and metabolism. Nevertheless, there are no reports showing the role of the miR-294-Lin28a axis in the context of the heart. Our findings show that miR-294 and Lin28a mRNA expression coincides during embryonic heart development and declines rapidly after birth with complete abrogation in the 3-week old adult heart. Next, we determined whether miR-294 drives Lin28a expression. Increased Lin28a expression was observed in CPCs, neonatal rat cardiomyocytes (NRCMs) and adult cardiomyocytes both at the protein and mRNA level after treatment with miR-294 compared to control-treated cells. Alternatively, CPCs lentivirally engineered to express miR-294 were treated with antagomiR for miR-294 to determine its consequences on Lin28a expression. Indeed, CPCemiR had decreased protein levels of Lin28a compared to control-treated cells. Moreover, miR-294 administered hearts showed increased Lin28a mRNA expression confirming correlation with miR-294 and Lin28a. CPCs were lentivirally engineered to express Lin28a to determine its effect on CPC function. Increased mRNA expression of glycolytic and fatty acid oxidation enzymes was observed in the cells together with increased ATP content and maximal respiration in CPCs overexpressing Lin28a compared to control indicating higher metabolic rates. Lin28a CPC demonstrated increased proliferation as measured by CyQuant assay and increased survival in response to H2O2 stress compared to controls. To test whether the therapeutic efficacy of Lin28a, human CPCs were engineered to express Lin28a and exosome from Lin28a human CPCs were isolated. Analysis of Lin28a human CPC exosomes showed increased mRNA expression of Lin28a along with the upregulation of survival genes compared to control exosomes. Thus, we have now developed 2 possible therapies, CPC exosomes containing Lin28a, and CPCs overpressing Lin28a as a cell-based treatment for heart disease.

Proposed Use
CPCs and their exosomes enhanced with Lin28 will be used for delivery into patients with cardiac disorders. The aim would be to enhance cardiac repair processes in the heart via delivery of reparative factors by direct CPC injection or transfer for CPC exosomes both modified with Lin28.

Creator(s)
Raj Kishore, Mohsin Khan

Patent
PCT/US17/27876

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Clinical Applications; Therapeutics

About
Acetaminophen is a popular and widely used drug for pain relief. Although its mode of action is still unknown, recent studies have shown that acetaminophen indirectly activates cannabinoid CB1 receptors. As recent studies have shown that topical cannabinoid agonists are effective for itch relief, the efficacy of topical acetaminophen was tested for histaminergic and non-histaminergic itch relief.

The topical acetaminophen cream significantly reduced itch over the vehicle cream (p=0.05) in healthy subjects. Peak itch relief was seen after 30 minutes of the topical application. During this time, the duration of itch was significantly reduced by 2 minutes and the intensity of the itch was reduced by half (p=0.03). Furthermore, redness was also reduced.

Proposed Use
The topical acetaminophen will be available without prescription and will be able to reduce both histaminergic and non-histaminergic itch. Furthermore, this topical cream will be safe to use in children, pregnant women, and women who are breastfeeding.

Creator(s)
David Lebo, Leigh Ann Nattkemper, Gil Yosipovitch

Patent
PCT/US2018/041555; 62/511,221; 18832675.5; 62/531,221

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Life Sciences

About
NAD+ is an important metabolite in virtually every biological process. Here we postulate that immune suppression, in HIV infection is driven by the turnover of NAD+. We postulate that NAD+ turnover is driven by two things, the hydrolysis of NAD+ by the ectoenzyme CD38, as well as the increased production of via the catabolism of tryptophan as well as salvage pathways involving niacin and nicotinamide riboside. The demand and degradation of tryptophan results in immune suppression, immune-suppressive metabolites derived from the kynurenine pathway. Immunosuppression and CNS disease arise form these processes. The catabolism of tryptophan reduces the amount of tryptophan shunted to the production of serotonin and melatonin. Hence, this process promotes sleep disorders and depression. Since NAD+ is required for the action of the sirtuin deacetylases, NAD+ catabolism results in reduced SIRT activity. SIRT-1 controls inflammation and controls the effects of aging through NAD+ which is limiting. Reduced SIRT-1 activity also promotes latency by stalling HIV-I protein within the HIV-1 promoter in association with cyclinT/CDK9. As deacetylation is required to recycle new rounds of Tat-mediated transcription, the reduction ofNAD induces a latent state in otherwise active chromatin.

The combined use of nicotinamide riboside as an AD+ precursor is provided in combination with a CD38 antagonist, which represent the major source of NAD degradation. CD38 expression remains elevated in the context of antiretroviral treatment and expression on CD8-A T cells appears to be a biomarker for continued virus replication. CD38+ CD4+ Th cells which harbor virus are also cleared more slowly than CD38- T cells. As our model predicts the importance of SIRT-, we postulate that Nicotinamide Riboside would be more effective than nicotinamide, as an NAD+ precursor. This treatment could also benefit from SIRT-1 agonists such as resveratrol or SRT-210.

Proposed Use
This invention details an approach to prevent tryptophan catabolism, increase SIRT-1 activity, reduce inflammation increase immunity, reverse V latency, and effectively treat accelerated aging in HIV infection. The strategy described could also be used to treat diseases of aging and inflammation in persons not infected with HIV.

Creator(s)
Jay Rappaport

Patent
15/780,664; 62/262,739; PCT/US16/64748

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Research Tools; Therapeutics; Clinical Applications; Biotechnology; Chemicals

About
The invention provides an econazole nitrate and thiourea medical patch for the treatment of nail and skin onychomycosis, achieving improved drug penetration, and thus allowing more drug to penetrate into the nail bed and reach the minimum inhibitory concentration.

Our invention relates to the unexpected discovery that the antifungal drug econazole nitrate can successfully penetrate the human skin and nail from a formulation when accompanied by the appropriately selected penetration enhancer. To treat fungal infection of the nail, and potentially the skin around and under the nail, penetration of the therapeutic(s) is key to successful treatment. Thus, the invention relates to a pharmaceutical composition comprising an imidazole class drug, such as econazole nitrate alone or in combination with therapeutics, and a permeability enhancer, such as thiourea. Our invention also includes the use of a medical patch comprising a backing membrane and a pharmaceutical composition of the invention. The invention achieves improved drug nail penetration, and allows more drug to penetrate into the nail bed and reach the minimum inhibitory concentration in order to treat the nail fungus disease onychomycosis.

Proposed Use
We have developed a method for treating a fungal infection, in the nail or nail associated skin comprising administering a pharmaceutically effective amount of the composition comprising an imidazole class drug and a permeability enhancer including but not limited to econazole nitrate when applied with a permeability enhancer such as thiourea or delivered via patch membrane.

Creator(s)
Cong Li, David Lebo

Patent
16/488,250; 62/301,001; PCT/US18/20080; 62/464,483

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Clinical Applications; Therapeutic (Medical Devices)

About
Diagnosis of abnormal fetal or neonatal brain injury can be challenging: in utero or neonatal brain biopsy is impossible and brain imaging is imperfect. Early and accurate diagnosis is critical to optimize clinical outcomes. Multiple biomarkers have been tested, however none have translated into a clinically used test to guide therapy or to predict prognosis. In part this is because markers may be blocked by the blood brain barrier, degraded peripherally, or non-specific to the central nervous system (CNS). CNS derived exosomes are nanovesicles that package and protect proteins and freely cross the blood brain barrier bearing surface markers from their cell of origin (neurons). Purification of CNS derived neural exosomes (CNSEs) from blood using these markers allows evaluation of CNS responses without significant contamination from non-CNS sources. CNSE turnover in peripheral blood is rapid, permitting tracking of acute brain injury in real time from microscale blood volumes (50µL). During pregnancy, exosomes from the fetal CNS cross the placenta and can be purified from maternal blood using the same technique. Potential biomarkers inside these exosomes can be used to detect a wide array of pertubations including: cell injury, oxidative stress and inflammation. Finally, CNS exosomes have been used to measure the effects of both therapeutic agents and xenobiotics in the fetal and neonatal brain. Therefore CNSEs may be a power adjunct to pharmacologic studies - providing a real time measure of therapeutic drug effect at the target to predict individual response to treatment.

Novel technique for isolating neurally derived exosomes from developing neurons using a specific cell surface marker. Potential applications include: 1. Neonatal hypoxic ischemic encephalopathy - assess degree of injury for prognosis, identify neonates who are not responding to primary therapy, identify pathologic processes such as inflammation and oxidative stress. 2. Neonatal pharmacology studies - assess effects of medication on fetal brain targets in real time - examples a. Anesthetics b. Neuroprotectants c. Narctoics d. Anti-seizure medications. Data may be combined with pK data to assess both optimal dosing and, for non-neurolgic drugs - off-target effects. 3. Neonatal viral disease - follow neurologic injury in infants with viral disease such as congential CMV to predict developmental delay and/or deafness. 4. Fetal hypoxia - follow high risk pregnancies complicated by conditions such as growth restriction. CNSE biomarkers may be able to identify early signs of oxidative stress prior to irreversible hypoxic injury, identifying ideal time for delivery. 5. Fetal viral illness - identify pregnancies that may benefit from anti-viral therapy (eg. CMV, Zika) 6. Fetal drug effects - identify fetal side effects of common maternal medications such as narcotics, antidepressants, etc. 7. Drug Discovery - monitor or exclude adverse fetal effects from maternal medications 8. Fetal response to maternal disease or exertion - measure fetal tolerance to maternal illness (eg Covid pneumonia) to identify ideal point for delivery, or measure response to transient stressors such as maternal exercise to determine safe levels of exertion.

Proposed Use
A new technique isolates neural exosomes as biomarkers for brain injury in the perinatal setting (fetus or neonate) for use in clinical practice or research (clinical or pharmacologic).

Creator(s)
Laura Goetzl

Patent
62/340,779; PCT/US17/12478; 16/068,738

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Research Tools; Diagnostics

About
Methods and compositions for preparing a single or multiple layered biodegradable scaffold with biomimetic microstructures for regenerative dentistry. Each layer of the scaffold contains graded tunable channels that provide spatial control for cells penetration. Potential applications in regenerative dentistry include the regeneration of a missing interface tissue between two adjacent tissues, or regeneration and integration of two adjacent tissues directly, such as, but not limited to the periodontium, including alveolar bone, periodontal ligament and cementum.

The invention is a single layered or multilayered degradable scaffold that can be used to guide the regeneration of dental tissues such as the periodontal ligament, pulp-dentine complex and alveolar bone. -The single layer scaffold has two distinct surfaces: a 'permissive' and a 'non-permissive' / 'limited permissive side'. -The multilayer scaffold consists of two (hereafter referred to as a "bilayer") or more fused sheets. The multiple layers can be fused back-to-back or end-to-end. -Scaffold can support cell proliferation both on its surfaces. -Scaffold contains graded penetrating channels that transition into open pores on the flat surface of the scaffold. -The channel diameter are reduced in tapered way throughout the thickness of the scaffold and allows to control cell penetration. For example, when inserted scaffold between two tissues with different cell sources, the 'permissive' side enables rapid cell penetration and facilitates integration, while the 'non-permissive' or 'limited permissive' side delays cell penetration without affecting cell proliferation. -The tampered channels are oriented perpendicular to the surface of scaffold, which can create a passageway for nutrient or paracrine transport, or for guiding cell penetration and growth towards the adjacent layer. -Scaffold composition, degradation rates (in the case of degradable materials) and channel diameters can be tuned for different purpose of tissue regeneration. -Scaffolds can guide osteogenic differentiation in the absence of exogenous osteogenic inducers. -Scaffolds can be made of or augmented with various synthetic or natural biomaterials. -Scaffolds can be made into different shapes to fit different requirements for dental tissue regeneration. For example, bilayered membranes can be rolled into tubes, and allow the regeneration of different tissues inside and outside the lumen. -Scaffolds may be used in conjunction with conductive/inductive materials (e.g., calcium phosphates, apatite, chitosan, other bone graft materials, or extracellular matrix proteins such as silks, collagen gel, gelatin or other proteins such as enamel matrix derived proteins). -The surface of the scaffolds may be modified in order to allowing additional control of physical dynamics or cellular activities. For example, bioactive molecules may be bioprinted on the scaffold in either an even or graded fashion, allowing specific spatial control for cell activity. -Layers combined into bilayered asymmetric polymeric scaffolds provide a spatial control for cells by allowing differential cell penetration into different layers. -The degradation rate of each layer of the multilayered scaffold can be tuned to match different tissue regeneration or integration of different tissues. In one case this enables one type of tissue regeneration and integration with native tissue on a rapidly degrading layer, prior to integration with second type of tissue, which is regenerated on the secondary, slowly degrading layer.

Proposed Use
Regenerative Periodontal therapy: A novel bilayered scaffold for biomimetic regeneration of the periodontal ligament (PDL). Regenerative endodontics: A novel bilayered scaffold to biomimetic regeneration of the pulp dentine complex. Guided tissue regeneration (GTR) and guided bone regeneration (GBR) membrane: A novel resorbable polymeric barrier membrane with dual channel structure to facilitate bone regeneration and prevent epithelial migration..

Creator(s)
Sean Michael Devlin, Riddhi A Gangolli, Jonathan Arye Gerstenhaber, Peter I. Lelkes, Maobin Yang

Patent
62/024,180; US2015/40391; 15/326,189

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Therapeutics; Polymers (Materials); Clinical Applications; Micro & Nanotech; Materials; Biomaterials

About
This invention uses nanoparticle supported lipid bilayers (NP-SLBs) to remediate the removal of organic toxins from contaminated water and soil. Predominantly hydrophobic organic toxins such as polychlorinated biphenyls (PCBs) or polyaromatic hydrocarbons (PACs) have limited or no solubility in aqueous media, making them unavailable for bioremediation by micro-organisms. While lipids/fatty acid can incorporate these contaminants, they are themselves biodegradable, and so may be degraded before solubilizing the organic contaminants. Lipids on nanoparticles have greater stability compared with free lipids or lipid vesicles. If sufficient lipid is adsorbed to the NPs, they can be made colloidally stable. This makes them suitable as carriers to contaminated sites, where they can absorb hydrophobic organic toxins bound to natural organic matter (NOM)/humic substances. Once solubilized by the lipids on the NP-SLBs, the contaminants are more readily available for bioremediation by micro-organisms. If the NPs are composed of SiO2, the latter serves as an inexpensive carrier. If the NPs are composed of iron or manganese oxides, the NPs may serve to also oxidize the toxins. In this case, the lipids serve as carriers to contaminated sites, and once degraded, the NPs can oxidize polar molar organic species. Fatty acids are an inexpensive and sustainable means to solubilize organic material, and thus as a method of bioremediation.

Currently used NPs and methods for their suspension for environmental remediation have the following concerns. First, these NPs are highly unstable under ambient conditions so that their reactivity to organic toxins is dramatically decreased by aging or oxidation. Second, there may be unfavorable ecological effects of zero-valent iron, such as toxicity to freshwater and marine organisms and potential neurotoxicity. Third, the use of water-soluble polymers that are not readily biodegradable or recyclable is not a sustainable way to resolve complicated environmental problems. Last, they are at an economic disadvantage for application to large contaminated areas, for example current costs can be between $50/kg and $110/kg for nano-iron. The removal of PAHs is complicated by their low water solubility and strong adsorption onto environmental surfaces, particularly when there is little organic carbon present, and then accumulate in soils and sediments PAHs preferentially bind to NOM, which in turn can also interact with naturally occurring inorganic NPs. Components of NOM include humin and humic acid, and lipids and their degradation products (e.g., fatty acids). Thus, there is a continuing need in the art for methods of environmental remediation that use environmentally friendly compositions to absorb, degrade, and/or remove contaminants from the environment. The present invention addresses this continuing need in the art.

Proposed Use
Remediation of contaminated soil of compounds that are water insoluble such as PCBs. Specifically: A method of in situ environmental remediation comprising: contacting contaminated soil or water with a remediation composition, said remediation composition comprising a silica nanoparticle supported phospholipid bilayer (NP-SLB) composition, wherein the NP-SLB composition is a silica nanoparticle having a single phospholipid bilayer attached thereto; wherein the NP-SLB composition absorbs one or more hydrophobic organic contaminants from said contaminated soil or water; and degrading or decomposing the one or more hydrophobic contaminants adsorbed to the NP-SLB composition with a microorganism while maintaining the NP-SLB composition in contact with the soil or water.

Creator(s)
Bojeong Kim, Stephanie Wunder

Patent
PCT/US15/19223; 61/949,645; 15/123,711 Issued patent number: US 10,843,243 B2 Nov 2020

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Hydrocarbons; Chemicals; Polymers (Materials); Environment

About
There is a need in the art for a method capable of identifying a curable subset of AML that cannot otherwise be identified with cytogenetics and genetics alone. The present invention addresses this unmet need. We discovered that the DNA methylation status of specific regions in the promoters of SP140, MCCC1 and MTSS1 genes can individually and collectively predict survival after standard chemotherapy in acute myelogenous leukemia. DNA methylation of these marker genes can significantly discriminate the patients with good or poor survival, independently of any known classification systems currently in use such as clinical characteristics, cytogenetics or mutations in known predictive genes in AML. Patients with high DNA methylation levels of each gene have such poor outcome after standard of care that alternate therapies (including stem cell transplantation) should be sought for them.

Experimental data: We measured DNA methylation of several genes in AML by bisulfite-pyrosequencing, which is one of the most reliable ways to analyze DNA methylation for individual genes. We studied over 300 patients with AML; we divided them into groups according to their DNA methylation level in each gene. We compared the groups for treatment outcome and survival after chemotherapy. We compared the methylation-based classifiers to known prognostic factors in AML such as age and type of cytogenetics. Results: We found three genes that strongly predicted survival in AML: SP140: Component of the nuclear body, assumed to have function in the pathogenesis of acute promyelocytic leukemia and viral infection. MCCC1: This gene encodes the large subunit of 3-methylcrotonyl-CoA carboxylase. This enzyme functions as a heterodimer and catalyzes the carboxylation of 3-methylcrotonyl-CoA to form 3-methylglutaconyl-CoA. MTSS1: Assumed to be related to cancer progression or tumor metastasis in a variety of organ sites through an interaction with the actin cytoskeleton. None of these genes were previously reported as prognostic markers in cancer or leukemias (including AML). For each gene, patients with low DNA methylation levels (equivalent to normal blood) showed significant longer survival compared to patients with high DNA methylation (Median survival; 12~15months vs. 20~37 months in the high and low group, respectively, p=0.003~0.009 for each gene) (Figure 1). A classifier that averaged DNA methylation level of these three genes had even greater significance than single gene measurements (Median survival; 13 months vs. 31 months in high and low methylation groups, respectively, p=0.0008) (Figure 2). Furthermore, in multivariate analysis with other covariates including known AML prognostic factors such as age, cytogenetics and common AML mutations (FLT3, DNMT3a, IDH1, IDH2, RAS, NPM1), we found that the DNA methylation status of these genes is an independent prognostic factor for survival in AML. Discussion: These novel biomarkers of outcome in AML may be useful to stratify patients at diagnosis and identify those patients which such poor outcomes that alternate therapies should be sought early on (such as stem cell transplantation). These biomarkers also identify patients with greater benefit from established therapies and thus could be useful adjuncts in precision medicine (personalized therapy). The technology tested (bisulfite-pyrosequencing) is simple and applicable to CLIA approved labs/commercial labs, but similar results would be obtained by other technologies used to measure these particular regions of the genome (for example but not limited to: MSP, qMSP, bis.sequencing, RRBS, methyl-seq etc.)

Proposed Use
These markers, are an important improvement in evaluating prognosis of an individual with AML.

Creator(s)
Jumpei Yamazaki, Jean-Pierre Issa

Patent
62/065,073; 61/891,754; PCT/US16/57670; 15/769,157; 62/243,231

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Clinical Applications; Diagnostics

About
Infections by Enterococcal bacterial species, including Enterococcus faecalis, have emerged as a significant health problem, including infections of the urinary tract, the abdomen, the biliary tract, intravascular catheters and burn wounds, and they are the third leading cause of infectious endocarditis, being responsible for approximately 20% of all cases. They are a major cause of nosocomial infections. Dentally, E. faecalis is the most commonly isolated species from the root canals of teeth that fail to heal following endodontic treatment. Many E. faecalis strains have developed antibiotic resistance including reports of resistance among E. faecalis strains to some of the most recently developed antibiotics, such as linezolid and daptomycin. To respond to this important un-met medical need, Temple University has developed a potent new treatment for disease causing E. faecalis.

Our approach has been to modify viruses that infect bacteria, known as bacteriophage. This approach is based upon the fact that the final step of a virulent bacteriophage infection results in the lysis of the infected bacteria. The key to our successful implementation of this strategy was to develop a virulent bacteriophage that has a broad host range of susceptible strains within the targeted pathogenic bacterial species. The bacteriophage has been genetically modified, rendering it more virulent than wild-type bacteriophage as well as to increase the range of sensitive E. faecalis strains, including antibiotic resistant strains: Of a panel of 67 E. faecalis strains tested, the wild type bacteriophage produced a lytic infection in 4 (6%), whereas our modified virulent virus produced lytic infections in 33 (49%). To further develop our novel therapeutic additional genetic modifications are required to complete the engineering of a bacteriophage that would be clinically useful. First we need to remove the current nisin-inducible promoter system that controls the lytic infection functions of the virus for our laboratory experiments because the inducing agent, nisin, is a toxic protein. Several options are presently being evaluated. Similarly, we need to remove the antibiotic (erythromycin) resistance used in our clonal selection process. Finally, while the virulent mutant bacteriophage that we have constructed possesses an eminently greater host range than the wild type virus, there are still E. faecalis strains that do not appear to be sensitive to this virus. Additional strategies are being explored to further expand the host range and we have several options to accomplish this goal. Incorporation of these additional genetic modifications will complete the development of a powerful new, clinically useful therapeutic agent. Furthermore, this approach is a platform technology that can be applied to treat other intractable bacterial species.

Proposed Use
Treatment of antibiotic-resistant Enterococcus faecalis infections

Creator(s)
Hongming Zhang, Roy H Stevens

Patent
2978841; 9,795,642

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Life Sciences; Clinical Applications; Biotechnology; Diagnostic

About
Neuro-AIDS encompass wide range of neurological abnormalities including asymptomatic neurocognitive impairment (ANI), mild neuro-cognitive disturbance (MNCD) and HIV associated dementia (HAD). Currently there are no early biomarkers or therapy for neuroAIDS. We have used biogenic amine targeted metabolomics studies and have identified acetylspermidine and acetylspermine as biomarkers of the disease. These acetylated polyamines were found to be statistically elevated both MNCD and HAD as compared to normal cognitive function controls. In addtion SSAT activity was elevated in neuroAIDS. Collectively, these findings offer a potential biomarker and treatment of disease.

Polyamines are essential small molecules present in all organisms. Their concentration is highly regulated by a strict control of their synthesis and catabolism and also by cellular import and export. Spermine/Spermidine Acetyl transferase (SSAT) is the enzyme that inactivates the polyamines, once inactivated they are exported and excreted. The mRNA of this gene is present in every cell but normally is not translated. Small increments in the polyamines stimulate the translation of the protein, which them control the amount of active polyamines. We have determined that individuals with mild neurocognitive disturbance (MNCD) or HIV associated dementia (HAD) were elevated when compared to those of control sample or to a control value for individuals that lack of neurocognitive impairment, MNCD or HAD. We also describe a method for evaluating the progression of an HIV-1-associated neurocognitive disorder, as well as methods for staging this disorder.

Proposed Use
Biomarker for HIV associated dementia; Biomarker for mild neuro-cognitive disturbance; indicates a therapeutic approach

Creator(s)
Carlos Barrero, Kamel Khalili, Salim Merali

Patent
61/789,866; 61/969,620; PCT/US15/22201; 10,161,925

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Diagnostics; Biotechnology; Therapeutics

About
Breast cancer is the most common cancer and second leading cause of cancer death in American women. We seek to explore the feasibility of a novel combination therapy with targeted delivery of three therapeutic agents to two targeted sites by a two-component drug delivery system that can overcome all barriers as discussed above. An extracellular agent (Bevacizumab) will be selectively delivered to the interstitial space of the breast cancer tissue by long circulating liposomes. A combination of a high dose intracellular therapeutic drug (Doxorubicin) and its chemo-sensitizing agent (Verapamil) will be selectively delivered into breast tumor cells by immunoliposomes to overcome the chemoresistance. The Her-2/neu antibody will be used as a targeting ligand in the immunoliposomes to facilitate the internalization of the immunoliposomes by the ligand-receptor interaction with the Her-2/neu receptor overexpressed on the surface of the breast cancer. This combination therapy will maintain efficacious systemic drug levels with a better sustained release profile and without added toxicity. The innovation in this approach lies in the design of a combination of two delivery systems to deliver three different classes of therapeutic drugs to breast cancer. We propose that combining both carrier designs to deliver three therapeutic drugs would provide a significantly more efficacious platform for breast cancer treatment.

The primary treatments for breast cancer, such as hormonal therapy and chemotherapy, often result in high toxicity, non-specific side effects and /or chemoresistance. Therefore, targeted delivery of therapeutic drugs to the disease site has gained much attention recently. With the ability to modify the biodistribution of therapeutic agents, liposome has been studied intensively as a drug delivery carrier in past several decades. Both long circulation non-targeted liposomes and targeted immunoliposomes accumulate in the tumor tissue by the enhanced permeability and retention effect. Thereafter, non-targeted liposomes remain in the interstitial space, and eventually release the encapsulated drug there by decomposition, or degradation. Targeted immunoliposomes, on the other hand, bind to and internalize into the tumor cell via ligand-receptor interaction, and release the encapsulated drug in the tumor cell. The treatment efficacy of a targeted immunoliposome drug delivery system relies on the choice of the targeting moiety. Thus far antibody-based targeting schemes for targeted drug delivery to tumors have had limited success in part due to targeted molecule expression differential between normal and tumor tissues is often not high, leading to poor treatment efficacy. Another major factor that decreases treatment efficacy is acquired drug resistance. For these reasons, combination therapy with targeted delivery of multiple agents from different classes to multiple targets in the tumor may overcome drug resistance, improve therapeutic efficacy, and reduce side effects. We propose a novel combination therapy with targeted delivery of three therapeutic agents to two targeted sites. A combination of an intracellular therapeutic drug and its sensitizer will be selectively delivered into tumor cells by targeted immunoliposomes. An extracellular agent will be selectively delivered to the interstitial space by long circulation non-targeted liposomes. Our rationale is that successful preclinical proof of concept of this novel combination therapy would lead to immediate phase I and II human trials in this disease with the potential for better efficacy and lower toxicity than standard therapies.

Proposed Use
This targeted drug delivery system can be used to treat cancer, especially chemoresistant breast cancer. Furthermore, this system can be adapted to treat other diseases such as cardiovascular diseases and diabetes.

Creator(s)
Mohammad F Kiani, Bin Wang

Patent
PCT US2013/065164; Issued patent number 2013360302; 2,894,846; Divisional Issued Patent 10,188,728; 2013360302; 10-2015-7018521

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Clinical Applications; Biotechnology

About
Bacterial infections are among the most common causes of medical complications and illness in developed countries. That said, many bacterial infections develop resistance to conventional antibiotics. There is a need to develop new antibacterial compound to address the problem of drug- resistant strains of bacteria. Thus, identifying new effective drugs for bacterial infections is a continuing focus of medical research. The molecule plays an important role in chemical signaling and is involved in numerous enzymatic processes. Our group has developed chemical analogues which will act as structural mimics of pGpG and inhibit these processes.

pGpG is a secondary messenger molecule which is vital for many pathogenic bacteria. pGpG plays an important role in chemical signaling and is vital in numerous enzymatic processes. To date, little is known about the specific targets that recognize pGpG and the method by which pGpG signaling occurs. Accordingly, the development of a chemical probe which can be used to identify pGpG-binding domains would be a significant advance. Key structural changes introduced in our analogs are: (1) the substitution of the phosphate linkage with a more chemically robust squaric diamide, (2) replacement of the primary and secondary alcohols in guanine with amines, and (3) masking the primary phosphate as an uncharged derivative. These changes will all impact the compounds efficacy in vivo. We believe that our compounds represent an important new approach to treating antibiotic resistant infections

Creator(s)
William Wuest

Patent
US patent 9,688,715; issued on Jun 27, 2017

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Clinical Applications; Chemicals

About
To date, lithium ion batteries offer the highest amount of power and the longest length of charge retention of any battery type on the market. Lithium ion batteries can be composed of multiple types of chemical combinations inclusive of lithium. Some forms have proven to be less stable and more susceptible to charging issues than others. Lithium battery chemistry research at Temple University has led to the development of novel battery compositions that should be stable, retain a larger power reserve for a greater length of time than presently available batteries.

The lithium ion battery technology developed at Temple University involves a lithium ion battery that is capable of delivering a significantly greater charge level while maintaining this greater charge level for a significantly longer period of time. The novel battery technology utilizes a unique polyoctahedral silsesquioxane formulation that is laboratory tested and shown to surpass pre-existing lithium ion battery formulations. Further, because this is a solid polymer technology, there is no free liquid to leak, corrode other parts that it may come into contact with, or ignite fires due to leakage. With low reactivity towards electrodes, a thin-flexible shape, high ionic conductivity over a broad ranges (-70C to 150C), high resiliency and durability during rapid and intense charge periods, and minimal to no internal pressure, this novel lithium ion battery technology should prove to be a safe and viable alternative to current lithium ion battery technology used in airplanes, automobiles, laptop computers, and any other environment where human safety and minimal risk of injury or damage is a high priority. Also, given the novel battery’s ability to hold larger amplitudes during a greater range of time, this lithium ion battery should surpass the service life of many current lithium ion batteries in use today.

Proposed Use
Automobiles, labtop computers, airplanes and in any other environment where human safety and minimal risk of injury or damage is a high priority

Creator(s)
Stephanie Wunder

Patent
9,680,182

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Energy Efficiency; Biofuels Electric Vehicles; Energy; Materials; Chemicals; Energy Storage

About
We have invented a new dosage form for delivery of a therapeutic agents comprising a polymer matrix comprising arabinogalactan and a therapeutic agent uniformly dispersed within the polymer matrix. We envision several forms of this mixture one where the dosage form is selected from the group consisting of a microsphere, a nanosphere, a powder, a tablet, a film or a pellet enclosed in a capsule. We have developed complete methods for preparing these dosage forms as demonstrated by the preparation of larch arabinogalactan microsphere solid dispersions that enhanced the dissolution of the poorly water soluble model drug Ibuprofen.

In recent years, many natural polymers have been used as drug carriers for preparation of solid dispersion of poorly water soluble drugs. The basic reasons for selection of these polymers are their biodegradability; biocompatibility; low toxicity and well tolerability. Although the drug solubilization effect of many of these polymers was profound, their low aqueous solubility and high viscosity associated with gel forming properties have limited their application as a dissolution enhancer. Because of their low aqueous solubility and high viscosity, the drug diffusion through the resulting gel to the dissolution media is slow. In addition, the high viscosity of the carriers results in processing and handling difficulties. This leads to the exploration of novel low viscosity natural polymers with high aqueous solubility, as a carrier for the dissolution enhancement of poorly water soluble drugs. To demonstrate our our new method, we developed microsphere solid dispersion using the highly water soluble, low viscosity polysaccharide larch arabinogalactan and demonstrated the dissolution enhancement of the poorly water soluble model drug ibuprofen. The ibuprofen arabinogalactan microsphere solid dispersions with 80% encapsulation efficiency have significantly enhanced the ibuprofen dissolution compared to the neat ibuprofen and ibuprofen arabinogalactan physical mixtures. The order of dissolution rate enhancement for the microsphere solid dispersions is 10% drug load>20% drug load> 30% drug load. The increase in the rate of dissolution for ibuprofen is higher from ibuprofen-arabinogalactan physical mixture than ibuprofen-hydroxypropylmethyl cellulose (HPMCK3) physical mixture at the same drug load. The results of the physical characterization of microsphere solid dispersions show reduced or no detectable ibuprofen crystallinity in the microsphere solid dispersions. This correlates to the dissolution enhancement observations. The dramatic solubilizing effect of larch arbainogalactan is contributed to the ibuprofen dissolution enhancement. The ibuprofen recrystallization inhibition effect of larch arabinogalacatan is moderate and comparable to hydroxypropylmethyl cellulose (HPMCK3) which is the contributing factor for the dissolution enhancement as well. Thus the results of the in vitro dissolution study, equilibrium solubility study, drug recrystallization inhibition study together with physico-chemical characterization lead to the conclusion that larch arabinogalactan can be considered as a novel carrier for solid dispersion preparations for the dissolution enhancement of poorly water soluble drugs.

Proposed Use
Larch arabinogalactan is a novel carrier for solid dispersion preparations for the dissolution enhancement of poorly water soluble drugs.

Creator(s)
Kalpana Thakare, David Lebo

Patent
PCT/US2014/035225; 61/815,333; 61/815.333; 14/784,079

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Life Sciences; Clinical Applications; Therapeutics

About
The present invention includes methods and compositions for treating a transplant recipient by administration of a CB2 receptor agonist either alone or in combination with one or more active pharmaceutical ingredients to block the rejec­tion of foreign tissue and prolong grafted organs, tissues and cells. In some embodiments, the methods include methods of reducing the likelihood of graft rejection in a patient in need thereof comprising the administration of a therapeuti­cally effective amount of either a selective CB2 receptor agonist or CB/CB2 receptor agonist. The methods can further include administration of a therapeutically effective amount of a CBI receptor antagonist, and in some embodi­ments, administration of a therapeutically effective amount of an immunosuppressive agent.

The present invention features methods of reducing the likelihood of graft rejection in a patient. The invention are directed to meth­ods and compositions used for blocking or preventing rejection of foreign tissue in a transplant recipient that is respon­sive to CB2 receptor activation. The types of foreign tissue targeted include organ and skin transplants as well as the transplant of foreign cells such as bone marrow cells, stem cells or other purified cell populations. The method includes, for example, administering a therapeutically effective amount of: 1) a selective CB2 receptor agonist administered either alone, or in combination with an immunosuppressive agent, 2) a selective CB2 receptor agonist administered in combination with an immunosuppressive agent, and a CBI receptor antagonist, 3) a selective CB2 receptor agonist administered in combination with a CB I receptor antagonist, 4) a CB/CB2 receptor agonist administered either alone, or in combination with an immunosuppressive agent, 5) a CB/CB2 receptor agonist administered with a CBI receptor antagonist and an immunosuppressive agent, and 6) a CB/ CB2 receptor agonist administered with a CBI receptor antagonist. The graft can be an allograft or xenograft and can be of an organ, such as a heart, kidney, liver or a lobe thereof, lung or a lobe thereof, pancreas or a portion thereof, bone marrow, cartilage, skin, a cornea, neuronal tissue, or muscle. The graft can also include a population of cells that do not define an intact organ. Transplanted cells can also include stem cells ( e.g., mesenchymal stem cells, adult stem cells, or fetal stem cells).

Proposed Use
1. A method of reducing the likelihood of graft rejection in a patient in need thereof comprising the administration of a therapeutically effective amount of a selective CB2 recep­tor agonist. 2. The method of claim 1, further comprising administra­tion of a therapeutically effective amount of an immuno­suppressive agent, a CB1 receptor antagonist or a combina­tion thereof. 3. The method of claim 1, wherein the graft is an allograft or a xenograft. 4. The method of claim 1, wherein the graft is an organ graft. 5. The method of claim 4, wherein the organ is or comprises a heart, kidney, liver or a lobe thereof, lung or a lobe thereof, pancreas or a portion thereof, bone marrow. 6. The method of claim 3, wherein the graft comprises a population of cells that do not define an intact organ.

Creator(s)
Toby Eisenstein, Martin W Adler, Rebecca R Hartzell, Joseph Meissler

Patent
9,855,225; PCT/US2012/51330; PCT/US2012/044681; 61/524,883

Contact
J. Todd Abrams, PhD
Senior Director, New Ventures and Business Development
Office of the Vice President for Research
Technology Commercialization and Business Development
techtran@temple.edu
http://www.temple.edu/research

Keywords
Therapeutics; Clinical Applications; Biotechnology