Eli Lilly and Company

The UAB Research Foundation (The University of Alabama at Birmingham)

Nab Research Foundation

Robert John Konrad

Robert William Siegel

Jonathan Wesley Day

Qing Chai

Oliver Schroeder

Yuewei Qian

Richard Earl Higgs, Jr

Brian Jeffrey Nickoloff

Jeffrey Kudlow

The present invention provides compounds and methods targeting human interleukin-19, including therapeutic antibodies, pharmaceutical compositions and diagnostic applications useful in the field of immune-mediated diseases including psoriasis, atopic dermatitis, psoriatic arthritis, bronchial asthma and diabetic nephropathy.

Compounds and methods targeting interleukin-19

Angiopoietin-like protein (ANGPTL)3/8 complexes and antibodies are disclosed, where the antibodies bind to and thereby neutralize ANGPTL3/8 complexes. Pharmaceutical compositions also are disclosed that include one or more anti-ANGPTL3/8 complex antibodies herein in a pharmaceutically acceptable carrier. Methods of making and using the same also are disclosed, especially for increase lipoprotein lipase activity and lowering triglycerides. In this manner, the compounds and compositions may be used in treating lipid metabolism-related and glucose metabolism-related diseases and disorders.

Anti-ANGPTL 3/8 complex antibodies and methods of using the same

Angiopoietin-like protein (ANGPTL)3/8 fusion proteins are disclosed. Nucleic acid constructs encoding ANGPTL3/8 fusion proteins also are disclosed. Methods of making and using the same also are disclosed, especially for generating antibodies against ANGPTL3 and/or ANGPTL8.

Polynucleotides for preparing ANGPTL 3/8 complexes

Anti-ANGPTL &#x215c; complex antibodies and methods of using the same

Angiopoietin-like protein (ANGPTL)3/8 complexes and antibodies are disclosed, where the antibodes bind to and thereby neutralize ANGPTL3/8 complexes. Pharmaceutical compositions also are disclosed that include one or more anti-ANGPTL3/8 complex antibodies herein in a pharmaceutically acceptable carrier. Methods of making and using the same also are disclosed, especially for increase lipoprotein lipase activity and lowering triglycerides. In this manner, the compounds and compositions may be used in treating lipid metabolism-related and glucose metabolism-related diseases and disorders.

ANGPTL3/8 complexes and methods of using the same

The present invention demonstrates a method for inhibiting O-linked protein glycosylation in a tissue or cell, comprising the step of contacting said tissue or cell with (Z)-1-&lsqb;N-(3-Ammoniopropyl)-N-(n-propyl)amino&rsqb; diazen-ium-1,2-diolate or a derivative thereof. The present invention is also directed to a method of treating or inhibiting the onset of diabetes mellitis in an individual in need of such treatment, comprising the step of admininstering to said individual a pharmacological dose of a compound which inhibiting O-linked protein glycosylation in a tissue or cell of said individual. Further, the present invention provides a pharmaceutical composition, comprising (Z)-1-&lsqb;N-(3-Ammoniopropyl)-N-(n-propyl)amino&rsqb; diazen-ium-1,2-diolate and a pharmaceutically acceptable carrier or a derivative thereof.

Method of inhibiting pancreatic &bgr;-cell p135 O-glycosylation

Standard pancreatic islet isolation results in &bgr;-cell toxicity due to nitric oxide and/or streptozotocin-like molecules that are generated during the isolation process. This toxicity can be limited by the addition of compounds that work through the glucosamine pathway in islets and/or by the addition of nitric oxide inhibitors. Unless prevented, this toxicity results in &bgr;-cells being unable to properly respond to high glucose, glucosamine, N-acetylglucosamine, or streptozotocin by increasing their relative amount of O-glycosylated protein. Likewise, in order to assess islet viability or the effect of diabetes drugs on &bgr;-cell function, islets that have been adequately protected during their isolation can be stimulated with low glucose, high glucose, glucosamine, N-acetylglucosamine, or streptozotocin with or without the drug(s) of interest present. By analyzing the pattern of islet protein O-glycosylation that occurs, one can determine whether the islets are viable and whether or not the candidate drug(s) might be useful in the treatment of diabetes.

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Carmel, IN, United States of America

Robert John Konrad