Syntonix Pharmaceuticals, Inc.

Bioverativ Therapeutics Inc.

Eli Lilly and Company

Biogen Ma Inc.

Biogen Idec Hemophilia Inc.

The Brigham and Women's Hospital, Inc.

Other

Bioverative Therapeutics Inc.

Adam Robert Mezo

Robert T Peters

Susan C Low

Daniel S Rivera

Alan J Bitonti

Kevin McDonnell

Richard S Blumberg

Zachary R Taylor

Joe Salas

Vu Phong Hong

Timo Rath

Kristi Baker

Rosa Maria Silva Garcia Grenha

Francisco Alcides Valenzuela

Alfredo C Castro

Wen K Liu

Cristina A Tan Hehir

Hongchang Qu

James Stattel

Garabet G Toby

Alan J Bitoni

Elena Kistanova

James McGivney

Yanyun Chen

Karina Thorn

Wen Liu

James M Stattel

The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

Immunoglobulin chimeric monomer-dimer hybrids

The present disclosure provides protease-activatable procoagulant compounds comprising a procoagulant polypeptide, e.g., a procoagulant peptide and/or clotting factor, and a linker comprising a protease-cleavable substrate (e.g., a synthetic thrombin substrate) and a self-immolative spacer (e.g., p-amino benzyl carbamate). Upon cleavage of the protease-cleavable substrate by a protease (e.g., thrombin), the self-immolative spacer cleaves itself from the procoagulant polypeptide such that the polypeptide is in an underivatized and active form. Also provided are pharmaceutical compositions, methods for treating bleeding disorders using the disclosed compounds, methods of enhancing in vivo efficacy of procoagulant polypeptides, methods of increasing the efficacy of proteolytic cleavage of compounds comprising procoagulant polypeptides, methods of activating procoagulant polypeptides, and methods of releasing a procoagulant polypeptide from a heterologous moiety such as PEG.

Procoagulant compounds

The invention provides chimeric clotting factors comprising an activatable clotting factor and an enhancer moiety. The activatable clotting factor allows the chimeric clotting factor to be activated at the site of coagulation. The enhancer moiety can additionally improve procoagulation activities of the chimeric clotting factors. The chimeric clotting factors can further be improved by fusion to a half-life extender, which improves a pharmacokinetics property of the chimeric clotting factor. The invention also includes methods of making and methods of using these chimeric clotting factors.

Chimeric clotting factors

The presently described compounds relate to the treatment of diabetes and/or hyperglycemia. More particularly, the described compounds relate to acylated insulin compounds that lower blood glucose, pharmaceutical compositions containing such compounds, therapeutic uses of such compounds, and an intermediate compound used to make the acylated insulin compounds.

Acylated insulin compound

The invention provided herein includes isolated polypeptides that specifically block the interaction between neonatal Fc receptor (FcRn) and albumin. Blocking the interaction treats diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties wherein it is deemed desirable to decrease albumin levels. Accordingly, also provided are methods of using these isolated polypeptides to treat various diseases and conditions caused by increased amounts of albumin or modified albumin that possesses pathogenic properties. The invention provided herein also includes isolated polypeptides capable of binding to a non-IgG and non-albumin competitive site on an FcRn alpha 3 domain. These can be useful for tracking FcRn without inhibiting IgG or albumin binding or function. Accordingly, the invention also includes methods and systems to track FcRn without inhibiting IgG or albumin binding or function.

FC receptor (FcRn) binding peptides and uses thereof

The present invention provides glucagon and GLP-1 co-agonist compounds that are useful in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH).

Glucagon and GLP-1 co-agonist compounds

The present invention provides pro-coagulant compounds (e.g., pro-coagulant peptides or peptide derivatives) and methods of using and making those compounds. The present disclosure further provides conjugates between a pro-coagulant compound of the present disclosure (e.g., pro-coagulant peptide or peptide derivative) and a polypeptide selected from FIX, FVIIa, FVIII, and platelet targeting moieties (e.g., PDG-13), wherein the compound is linked to the polypeptide optionally via a linker. The compounds and conjugates of the present disclosure are useful for the treatment of coagulation disorders, such as hemophilia A and hemophilia B. The present disclosure further provides methods of using and making the conjugates.

Pro-coagulant compounds and methods of use thereof

The invention relates to peptides which bind to human FcRn and inhibit binding of the Fc portion of an IgG to an FcRn, thereby modulating serum IgG levels. The disclosed compositions and methods may be used for example, in treating autoimmune diseases and inflammatory disorders. The invention also relates to methods of using and methods of making the peptides of the invention.

Peptides that block the binding of IgG to FcRn

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Waltham, MA, United States of America

Adam Robert Mezo