Medical Diagnostic Laboratories, LLC

Other

Rutgers, the State University of New Jersey

Venenum Biodesign, LLC

Grant E Gallagher

Raymond Yu

Joyce Eskdale

Jonathan Brazaitis

Rachael Siegel

Nicholas Megjugorac

Brian F McGuinness

David J Diller

Axel Metzger

Gary L Schieven

Sergei V Kotenko

Michael S McQueney

Rachel Siegel

David E Kaelin

Rukiye Nazan Eraslan

Jason Trama

Jihong Dai

Venugopalareddy Bommireddy Venkata

Shih-hsin Kan

Giacomo Mancini

Shekar Srinivas

Adam Swider

Joyce Gallagher

Sshekar Srinivas

Methods for treating bladder cancer and solid tumors are disclosed. The methods include administering to a patient a compound of formula 1 Pharmaceutical compositions of compound 1 are also disclosed.

Sting agonists for treating bladder cancer and solid tumors

The present invention relates to novel linear and cyclic polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WXXXW, where W is tryptophan, and X, Xand Xare amino acids, with the proviso that when one of X, Xor Xis W, the remaining two of X, Xor Xcannot be W. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides (linear or cyclic), and use of same in inhibiting cell functions including production of IL-22 and IL-17F from immune cells as well as in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease, ulcerative colitis and multiple sclerosis.

Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof

A novel IFN-&#x3b1;/&#x3b2; independent ligand receptor system which upon engagement leads, among other things, to the establishment of an anti-viral state is disclosed. Further disclosed are three closely positioned genes on human chromosome 19 that encode distinct but highly homologous proteins, designated IFN-&#x3bb;1, IFN-&#x3bb;2, IFN-&#x3bb;3, based inter alia, in their ability to induce antiviral protection. Expression of these proteins is induced upon viral infection. A receptor complex utilized by all three IFN-&#x3bb; proteins for signaling is also disclosed. The receptor complex is generally composed of two subunits, a novel receptor designated IFN-&#x3bb;R1 or CRF2-12, and a second subunit, IL-10R2 or CRF2-4, which is also a shared receptor component for the IL-10 and IL-22 receptor complexes. The gene encoding IFN-&#x3bb;R1 is generally widely expressed, including many different cell types and tissues. Expression of these proteins is induced by immune events, including, for example, upon viral infection. Apoptotosis may also be induced under effective conditions.

Methods for increasing levels of interferon activity with an interferon lambda 3 polypeptide

The present invention relates to an isolated naturally-occurring soluble truncated IL-23R&#x3b1; protein, which is a translated protein resulting from a mRNA splice variant of IL-23R&#x3b1;. The soluble IL-23R&#x3b1; proteins (e.g., &#x394;9 and &#x394;8,9) represents a novel soluble IL-23R&#x3b1; protein, which is lacking a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end (due to frame-shift). ELISA reveals that &#x394;9 is present in blood and can serve as a diagnostic tool for auto-immune diseases including Crohn's disease. There is also provided a method of recombinant production for this soluble truncated form of IL-23R&#x3b1; protein. More importantly, the present invention provides an utility application of the &#x394;9 and &#x394;8,9 protein in inhibit IL-23R-mediated cell signaling. More particularly, &#x394;9 and &#x394;8,9 blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of &#x394;9 and &#x394;8,9 in treating a human patient inflicted with Crohn's disease.

Recombinant soluble truncated IL-23 receptor (IL-23R) capable of inhibiting IL-23R-mediated cell signaling

The present invention provides a method of specifically detecting IFN-&#x3bb;2 mRNA or IFN-&#x3bb;3 mRNA. There is provided a qRT-PCR method specifically detecting, discriminating and quantifying IFN-&#x3bb;2 and IFN-&#x3bb;3 mRNA in a biological sample obtained from a human. There is provided qRT-PCR methods and primers and probes that specifically detect IFN-&#x3bb;2 mRNA but not IFN-&#x3bb;3 mRNA and vice versa in humans in order to detect, quantify and discriminate IFN-&#x3bb;2 mRNA and IFN-&#x3bb;3 mRNA.

Methods and reagents that specifically detect, distinguish and quantify IFN-LAMBDA2 mRNA from IFN-LAMBDA3 mRNA in humans

A novel IFN-&#x3b1;/&#x3b2; independent ligand receptor system which upon engagement leads, among other things, to the establishment of an anti-viral state is disclosed. Further disclosed are three closely positioned genes on human chromosome 19 that encode distinct but highly homologous proteins, designated INF-&#x3bb;1, IFN-&#x3bb;2, IFN-&#x3bb;3, based inter alia, in their ability to induce antiviral protection. Expression of these proteins is induced upon viral infection. A receptor complex utilized by all three IFN-&#x3bb; proteins for signaling is also disclosed. The receptor complex is generally composed of two subunits, a novel receptor designated IFN-&#x3bb;R1 or CRF2-12, and a second subunit, IL-10R2 or CRF2-4, which is also a shared receptor component for the IL-10 and IL-22 receptor complexes. The gene encoding IFN-&#x3bb;R1 is generally widely expressed, including many different cell types and tissues. Expression of these proteins is induced by immune events, including, for example, upon viral infection. Apoptotosis may also be induced under effective conditions.

Method for increasing interferon activity in an individual

The present invention relates to anti-sense oligonucleotides (AONs) used to induce exon 9 skipping in IL-23R&#x3b1; gene. Exon 9 skipping of the IL23R&#x3b1; gene ultimately causes specific induction of a novel soluble truncated IL-23R&#x3b1; (&#x394;9) protein, characterized by a lack in a transmembrane domain and has a unique eight (8) amino acids (GLKEGSYC) at its C-terminus end as a result of frame-shift. The present invention provides a utility application of the use of AONs to induce production of a &#x394;9 protein which inhibits IL-23R-mediated cell signaling. More particularly, &#x394;9 protein blocks STAT3 formation as well as Th17 maturation. There is provided a therapeutic application of AONs in treating a mammal such as a human patient inflicted with Crohn's disease.

Anti-sense oligonucleotides targeted against exon 9 of IL-23R-alpha gene and method of using same to induce exon skipping and to treat inflammatory bowel diseases

The present invention is directed to the identification of a novel repressor located between &#x2dc;1.2 kb to &#x2dc;1.6 kb from the translation start site of the IFN-&#x3bb;1 promoter. The present invention provides a method of using siRNAs against ZEB1 (binds to the repressor region) and BLIMP-1 (binds outside the repressor region) and increases the promoter activity of IFN-&#x3bb;1 (i.e., increases the production of IFN-&#x3bb;1 protein). siRNAs against ZEB1 mRNA or BLIMP-1 mRNA increase IFN-&#x3bb;1 gene activity. There is provided a therapeutic application of siRNAs against ZEB1 and BLIMP-1 mRNAs in treating a mammal (including a human) by increasing the production of IFN-&#x3bb;1 protein that promotes an anti-viral response as well as treats asthma diseases and colon diseases.

Repressor on IFN-&#x3bb; promoter and siRNA against GATA1, EVI1, and CRX to alter IFN-&#x3bb; gene activity

A naturally-occurring soluble truncated IL-23R&#x3b1; protein (i.e., &#x394;9 IL-23R&#x3b1;) is shown to be present in a biological sample and can serve as a diagnostic tool for autoimmune diseases. There is provided an enzyme-linked immunosorbent assay (ELISA) and test kit for the serological detection of the soluble truncated form of IL-23R&#x3b1; protein. More particularly, antibody-sandwich ELISA method and kits for &#x394;9 IL-23R&#x3b1; as an antigen were developed to detect &#x394;9 IL-23R&#x3b1; levels in biological samples from a mammal and a human patient and are used as a diagnostic index. The present disclosed ELISA has utility as a diagnostic tool to detect Crohn's disease in patients using EDTA-plasma.

Elisa for a naturally-occurring soluble truncated form of IL-23 receptor

Methods and reagents that specifically detect, distinguish and quantify IFN-&#x3bb;2 mRNA from IFN-&#x3bb;3 mRNA in humans

Anti-sense oligonucleotides targeted against exon 9 of IL-23R&#x3b1; gene and method of using same to induce exon skipping and to treat inflammatory bowel diseases

The present invention relates to novel polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WXXXW, where W is tryptophan, and X, Xand Xare amino acids, with the proviso that when one of X, Xor Xis W, the remaining two of X, Xor Xcannot be W. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides, and use of same in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease.

Growing community of inventors

Hamilton, NJ, United States of America

Grant E Gallagher