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Machine Learning of Doppler Echocardiographic Coronary Blood Flow
TS-001178 — Currently there are few existing methods on coronary flow pattern automation. The DECFA platform fulfills this unmet need by predicting diseased coronary blood flow by integrating previously unutilized data features from (sonographic) Doppler echocardiography measurements, cardiac functional and other physiological data (e.g. heart rate, body weight, etc) using machine learning. The DECFA program is superior to manual intervention as it provides more efficient analysis, more accurately, and can accept raw video files of PW Doppler and Color Doppler B-mode files, applicable on mouse models, potentially applicable to humans. DECFA can analyze raw PW Doppler AND Color Doppler B-Mode AVI video files to calculate overall coronary blood flow and coronary flow reserve, and the separation of each coronary flow pattern into 4 distinct phases representative of the stages in a cardiac cycle. Benefits: More efficient analysis over manual intervention, less error than manual intervention, capable of accepting raw video files of PW Doppler and Color Doppler B-mode files, applicable on mouse models, potentially applicable to humans (not yet validated). New features include the analysis of raw PW Doppler AND Color Doppler B-Mode AVI video files to calculate overall coronary blood flow and coronary flow reserve, and the separation of each coronary flow pattern into distinct phases representative of the stages in a cardiac cycle. The machine learning aspect brings state-of-the-art technology to determine whether it may be useful in directly predicting/diagnosing coronary microvascular disease. Stage of Development: We are currently in the final stages of completing the data analysis for all of the in vivo coronary and cardiac physiological parameters that will be used to perform the final runs through the machine learning process. We did perform an “interim” analysis using about half of the data, the results of which were promising (inconclusive at this point, but they put the predictive value of coronary flow patterns above 90% for identifying diseased coronary blood flow). This process also uses the whole envelope instead of discrete points of the coronary flow pattern, in addition to the texture-analysis extension. After this process is complete in mice, we plan to obtain human coronary blood flow patterns to determine whether this could be clinically useful beyond research applications. Potential Applications/Markets: Our program could be utilized in a research setting for robust, comprehensive, and more efficient analysis of coronary flow patterns in mice measured through Doppler Echocardiography (It solves the problem of large inter/intra observer error and time required for manual analysis). The program could also be used clinically for use in the medical field for the same analysis if adjusted for human use. It could also be used as an add on feature to the VisualSonics Vevo 2100 software for added capabilities in analyzing PW Doppler coronary flow patterns and Color Doppler B-mode files. The parameters that we identify in our program could be potentially useful in clinical diagnostics/machine learning/prediction modeling for better identifying and predicting disease. Furthermore, we envision that this could be tested and applied to clinical coronary Doppler echocardiograms, with the readout being predictability of coronary microvascular disease based on the machine learning algorithm of coronary flow patterns. Opportunity/Seeking: Development Partner Commercial Partner Licensing IP Status: Know-how based Copyright
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  • Inventors: Trask, Aaron; Bartlett, Christopher; Bossenbroek, Jamie; McCallinhart, Patricia; McDermott, Michael; Ray, Will; Sunyecz, Ian; Ueyama, Yukie
  • Licensing Officer: Corris, Andrew

Overcoming Immune Checkpoint Inhibition with VISTA Deficient NK Cells – ViDe* NK Cells
TS-000972 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. When an NK cell is deficient or dysfunctional, the efficiency of the NK cells is severely limited. VISTA is a protein sequence that activates T cells and acts as a moderator for the immune system. It has low-to-moderate expression but has been the target of study by a team of researchers at Nationwide Children’s Hospital led by Dr. Dean Lee. By removing VISTA in expanded NK cells, the inhibitory signal will be eliminated and thus resulting in an enhanced ability of NK cells to target cancers and overcome the immune-suppressive signals for improved cancer immunotherapy.
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  • Inventors: Lee, Dean; Pereira, Marcelo
  • Licensing Officer: Corris, Andrew

Generation of Antigen-Specific Chimeric Antigen Receptor T cells Using Cas9/RNP and AAV
TS-000969 — Gene therapy experts at Nationwide Children’s Hospital have made significant advancements in designing optimal viral vectors for producing Good Manufacturing Practice (GMP)-grade viral vector products. Adeno-associated virus (AAV) serotypes such as AAV1, 2, 2.5, 3, 5, 6, 8, 9 and rh74 have properties optimized by these researchers. Chimeric Antigen Receptor T cells (CAR T) are comprised of an extracellular antigen recognition domain, intracellular T cell activation and co-stimulatory domains. These cells allow for potent and specific targeting of cancer cells, bypassing the need for antigen presentation and T cell receptor recognition. Generating CAR T cells using the process of lentiviral transduction has limitations stemming from the random integration of transgenesis, where oncogene activation, gene silencing, or negative effects on the CAR T antitumor efficacy are possible.
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  • Inventors: Lee, Dean; Naeimi Kararoudi, Meisam
  • Licensing Officer: Corris, Andrew

Priming Peptide Pools for Isolation of SARS-CoV-2-Specific T Cells
TS-000913 — Peptides can be used to stimulate antigen-specific T cells, allowing activated T cells to be isolated from immune individuals to be used in vaccination or treatment in others. The novel disease Coronavirus, also denoted as 2019-nCoV, was recognized by the World Health Organization as an unknown etiology in December of 2019. Severe Acute Respiratory Syndrome (SARS) is a disease that presents flu-like symptoms that is caused by coronavirus (SARS-CoV). A current process widely applicable to many pathogens uses the Miltenyi Prodigy device. In a study led by Dr. Dean Lee, his team found that this process can be adapted to SARS-CoV-2 using a specialty mix of peptides to isolate T cell immunity.
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  • Inventors: Lee, Dean
  • Licensing Officer: Corris, Andrew

A Novel Compound, GQ-16 Protects Against Kidney Disease with Additional Insulin Sensitizing Benefits and Reduced Side Effects
TS-000912 — There are a few prominent diseases that affect the kidney, such as nephrotic syndrome and diabetic nephropathy. To treat Type II diabetes, there is a readily available pharmaceutical known as pioglitazone that is often used in conjuncture with other compounds to reduce proteinuria in patients with kidney diseases. A team of researchers at Nationwide Children’s Hospital have developed a novel compound to act as a treatment agent in cases of kidney disease. The new design has similar insulin sensitizing effects as pioglitazone as well as its ability to reduce proteinuria. This compound, titled GQ-16, has similar efficacy as traditional Type II diabetes drugs and acts as a new indication for nephrotic syndrome or kidney diseases, with a significant reduction in side effects such as weight gain or adipogenesis.
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  • Inventors: Agrawal, Shipra
  • Licensing Officer: Corris, Andrew

Dual Targeting CD38KO and CARKI NK Cell Immunotherapy
TS-000906 — Natural Killer (NK) cells express a range of receptors to activate or inhibit certain cellular behavior to kill cancer cells. Additionally, CD38 presenting cells have been used as a marker for cancer stem cells, specifically those that often avoid recognition when common surface antigen processes are used. CARK1 is a phosphorylate that impacts cell growth and development. A team led by Dr. Dean Lee has developed CD38k0 NK cells that they combine with CARK1 to create a series of monoclonal antibodies that targets cancer cells. Along with better cell targeting, this combination improves the efficacy of treatment in comparison to the CAR, NK, or CD38 antibodies as independent components.
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  • Inventors: Lee, Dean; Naeimi Kararoudi, Meisam
  • Licensing Officer: Corris, Andrew

Oncolytic Activity Using Existing OV Stocks
TS-000873 — The current timeframe required for current Good Manufacturing Product (cGMP) validation and approval is significant. The delay between development and approval is time intensive and the advancements that can improve treatment can be outdated by the time they reach the market. Genetic modifications would lead to restarting the production and approval process and delaying the introduction of the entry into human trials. Dr. Kevin Cassady and his team found that combinations of oncolytic viruses (OV) can be combined using current, approved cGMP stocks can be employed effectively and subsequently saving time that would have been spent on re-engineering, production, and validation, as well as the expense associated. The clinical outcome would be improved as this new process allows for a more rapid and cost-effective approach to clinical translation using existing stock of virus.
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  • Inventors: Cassady, Kevin
  • Licensing Officer: Corris, Andrew

Glomerular Transcriptomic Analysis of Glucocorticoid- and Pioglitazone-Treated Nephrotic Syndrome
TS-000859 — Nephrotic syndrome (NS) is a common kidney disease found in children that creates an overabundance of protein in the urine, comparable to proteinuria in adults. As of now, there are no approved safe and effective treatment for NS, especially for those whose NS is steroid or multi-drug resistant. A team of researchers have identified a series of new molecular targets for future drug development. Using glomerular transcriptomes and informatic analysis, clinicians will be able to identify immunosuppressive approaches that are distinct from the current procedures.
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  • Inventors: Smoyer, William; Agrawal, Shipra; Bhayana, Sagar
  • Licensing Officer: Corris, Andrew

CD33-CAR NK Cells
TS-000857 — CD33 is a receptor that spans multiple membranes and is expressed on myeloid lineage cells and sometimes lymphoid cells. A team of researchers led by Dr. Dean Lee have found a new way to modify existing CD33 processes to provide Natural Killer (NK) cells the additional ability to recognize cell targets expressing CD33. Acute Myeloid Leukemia (AML) expresses multiple antigens, where CD33 is the most common. This new process, labeled as CD33-CAR, shows a significant advantage in targeting AML that presents with CD33, especially in cases that resist unmodified NK cells.
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  • Inventors: Lee, Dean; Naeimi Kararoudi, Meisam
  • Licensing Officer: Corris, Andrew

Biomarkers for Urinary Tract Infections
TS-000855 — To diagnose urinary tract infections (UTI), the current strategies use leukocyte esterase, a urine test to look for white blood cells and other signs of infection. which have limited accuracy. These inaccuracies put patients at risk for unneeded antibiotics or delayed treatments, that can allow for UTI progression. Studies have found that the protein levels in urine could differentiate positive and negative results of UTIs. This new testing strategy can improve diagnostics and subsequent patient care.
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  • Inventors: Watson, Joshua; Schwaderer, Andrew
  • Licensing Officer: Corris, Andrew

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