T-Cell Immunotherapy that Targets Aggressive Epithelial Tumors

Metastatic cancers cause up to 90% of cancer deaths, yet few treatment options exist for patients with metastatic disease. Adoptive transfer of T cells that express tumor-reactive T-cell receptors (TCRs) has been shown to mediate regression of metastatic cancers in some patients. Unfortunately, identification of antigens expressed solely by cancer cells and not normal tissues has been a major challenge for the development of T-cell based immunotherapies. Thus, it is essential to find novel target antigens differentially expressed in cancer versus normal tissues.

CNS Therapeutics That Target Neuronal Ceroid-Lipofuscinoses and Thioesterase Deficiency Disorders

Clinically known as Neuronal Ceroid-Lipofuscinoses (NCL), Batten disease, is a rare neuron killing disease and one of the lysosomal storage disorders (LSDs).  It is associated with a mutation or lack of palmitoyl-protein thioesterase-1 (PPT1) gene. It manifests very early in a child's life causing absence of brain activity as early as 4 years of age.

Compositions and Methods for Reducing Serum Triglycerides

This technology includes a vaccine for lowering plasma triglycerides by inducing the formation of autoantibodies against either ANGPTL3 or ANGPTL4, which are inhibitors of Lipoprotein Lipase. This was done by conjugating synthetic peptides based on ANGPTL3 or ANGPTL4 to virus- like particles (VLPS). Injection of the vaccine in animal models was shown to induce the autoantibody against the target and to lower plasma triglycerides.

A New Molecular Scaffold for Targeting hRpn13 as a Treatment for Cancer

This technology includes a new chemical scaffold (with lead compound XL5) against hRpn13 that induces apoptosis, which may have clinical efficacy against cancer. The structure of XL5-conjugated hRpn13 guided the design of XL5-PROTAC degrader compounds that exhibit greater efficacy than previous hRpn13-targeting compounds, as evaluated by selectivity for hRpn13, induction of apoptosis, and loss of cell viability. In cells, XL5-PROTACs revealed the presence of a truncated hRpn13 product that binds to proteasomes and is selectively degraded by XL5-PROTACs.

Isotopes of Alpha Ketoglutarate and Related Compounds for Hyperpolarized MRI Imaging

This technology includes 1-13C-ketoglutarate which can be used for imaging the conversion to hydroxyglutarate (HG) or Gln in cancer cells with an IDH1 mutations by hyperpolarized MRI. The ability to detect the status of IDH1 mutations is clinically prognostic for multiple cancers. These exciting observations are limited by two factors, the major one being that the natural abundance of 13C at position C5 overlaps with 1-13C-2-hydroxyglutarate peak, which limits the sensitivity of analysis and prevents simultaneous observations of HG and Gln formation.

Systems and Methods for Applying Pressure to the Heart for the Treatment of Tricuspid Valve Regurgitation

This technology includes structures and methods for cinching a band around the heart for treating conditions including tricuspid valve regurgitation (TR). When positioned appropriately along the atrioventricular groove, the band is tightened around the heart which narrows the tricuspid annulus and relieves TR.

Helical Guidewires and Related Systems for Transcatheter Heart Valve Procedures

This technology includes a guidewire purpose-built for delivery of bulky transcatheter heart valves (THV). Conventional THV guidewires are rigid and have a distal tip shaped like a pigtail to prevent apical ventricular perforation. This invention is a 3-dimensional helical or antihelical curve that can protect against apical perforation, possibly better, and that allows subtle 3-mensional deflection to aid the operator in achieving coaxiality or overcoming delivery obstacles such as calcific spicules.

Device for Closure of Transvascular or Transcameral Access Ports

This technology includes a novel method to access the arterial circulation to allow introduction of large devices, such as transcatheter aortic valve replacement, percutaneous left ventricular assist devices, and thoracic aortic endografts. It also can be used in most labeled and off-label applications of Amplatzer nitinol occluder devices to occlude intracardiac holes and to allow non-surgical direct access to the heart. This new disclosure adds additional design features that have been tested in vivo.

Methods to Produce Very Long Chain Fatty Acids (VLCFA) for Use as Nutritional Formulas and as Therapeutics for Disease

This technology includes a new method to prepare very long chain fatty acids (VLCFA), which does not use the previously reported toxic mercury amalgam, for use as nutritional supplements, and as therapeutics for various diseases. The key coupling step involves an organocopper mediated coupling of the Grignard regent derived from the bromo alkyl tetraene with a bromoalkyl containing a protected alcohol. After the coupling the alcohol Is deprotected and oxidized to prepare the very long fatty acid. The synthetic approach is flexible and can be used to prepare the other VLCFA compounds.

High Relaxivity Mulitivalent Gadolinium on a Peptide Scaffold for Targeted MRI Applications in Disease Diagnosis

This technology includes a peptide containing alternating Alanine and Lys(DOTA-Gd) residues can be used to increase the MRI relaxivity of a peptide. The low molecular weight construct can be appended to proteins, antibodies and peptides to increase MRI signals. This approach offers advantages over previous dendrimeric constructs.