Rinat Neuroscience Corporation

Genentech, Inc.

Pfizer Corporation

University of Minnesota

Teva Pharmaceuticals International Gmbh

Labrys Biologics, Inc.

Apg Therapeutics, Inc.

David L Shelton

Leonard G Presta

Arvind Rajpal

Pavel Strop

Magdalena Grazyna Dorywalska

Arnon Rosenthal

Kristian Todd Poulsen

Joerg Zeller

Shu-Hui Liu

Roman Urfer

Patricia Ann Walicke

Paul J Godowski

Jaume Pons

Wei-Hsien Ho

Patrick William Mantyh

Thomas-Toan Tran

Ian Machin

Laura Corradini

German J Vergara

Russell Dushin

Austin L Gurney

William I Wood

Audrey Goddard

J Christopher Grimaldi

Luc Roland Desnoyers

Napoleone Ferrara

Kevin P Baker

Ellen Filvaroff

Avi J Ashkenazi

Dan L Eaton

Daniel Tumas

Sherman Fong

Kenneth J Hillan

Timothy Andrew Stewart

David Botstein

Margaret Ann Roy

James Pan

Mary E Gerritsen

Wei-Qiang Gao

Nicholas F Paoni

P Mickey Williams

Brigitte Devaux

Jo-Anne Hongo

Melanie Rose Mark

Mary A Napier

Javier Fernando Chaparro Riggers

Hanspeter Gerber

Ivar J Kljavin

Sophia S Kuo

Wai Lee Wong

Michael D Sadick

Davide Foletti

Ariel Ates Pios

Carole M Loo

Wenwu Zhai

Jeffrey Raymond Chabot

Hong Liang

Bruce Charles Gomes

Stephen Charles Phillips

Leonard Presta

Joaquim Trias

Jerome Thomas Mettetal, Ii

Roman Ufer

Jacob Eli Gunn Glanville

Lee Mary Beth Shaughnessy

Ian William Mills

David Peter Scholfield

Antoni Planas

Katherine Anne Delaria

Kapil Mayawala

Jo-Anne S Hongo

The present invention provides transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates.

Antibody-drug conjugates with high drug loading

The present application provides PEI compounds comprising a linker, PEI-polypeptide conjugates (e.g., PEI-antibody conjugates), and complexes thereof comprising a biologically active molecule. Methods of preparing and using the compounds, conjugates and complexes are further provided. The PEI-polypeptide conjugates and complexes are useful for delivering biologically active molecules to the cytoplasm of cells and promoting release of the biologically active molecules from the endo-lysosomal pathway.

Polyethylenimine (PEI)-polypeptide conjugates and methods of use thereof

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Antibodies specific for Trop-2 and their uses

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

Engineered polypeptide conjugates and methods for making thereof using transglutaminase

The invention features methods for preventing or treating visceral pain, including pain associated with functional bowel disorder, inflammatory bowel disease and interstitial cystitis, by administering an anti-CGRP antagonist antibody.

Methods for treating visceral pain associated with interstitial cystitis by administering antagonist antibodies directed against calcitonin gene-related peptide

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same

The invention relates to an anti-CGRP antibody for use in the prevention and/or treatment of chronic pain and/or symptoms of chronic pain, and to a method of treating and/or preventing chronic pain and/or symptoms of chronic pain using an anti-CGRP antibody.

Methods of treating fibromyalgia

Antibodies specific for TROP-2 and their uses

Antibodies specific for trop-2 and their uses

Methods of treating chronic pain

The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the Kor kratio at pH 5.5/pH 7.4 or at pH 6.0/pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent Ks at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present at high levels (e.g., IgE, DKK1, C5 and SOST). In addition, such antibodies can increase antigen half life when the antigen is a receptor and the receptor has increased clearance when bound to antibody (e.g., GMCSF receptor).

Anti-PCSK9 antibodies with pH dependent antigen binding

Growing community of inventors

Pacifica, CA, United States of America

David L Shelton