Regeneron Pharmaceuticals, Inc.

Gensun Biopharma Inc.

Xilio Development, Inc.

Amgen Inc.

City of Hope

Margaret Karow

Sean Stevens

Andrew J Murphy

Lynn Macdonald

George D Yancopoulos

David M Valenzuela

Aris N Economides

Jeanette L Fairhurst

Joel H Martin

Kevin J Pobursky

Nicholas J Papadopoulos

Eric L Smith

Gang Chen

James P Fandl

Tammy T Huang

Ashique Rafique

Jackie Zeqi Sheng

Huawei Qiu

Allen Radin

Dheeraj Singh Tomar

Parker Johnson

Raphael Rozenfeld

Deborah Moore Lai

Ronan O'Hagan

Wei Zhang

John R McWhirter

Li Erran Li

Gunasekaran Kannan

Marc A Gavin

Joshua T Pearson

Bo Liu

Scott Mellis

Joan A Windsor

Joanne Papadopoulos

Tammy H Huang

Prerna Sharma

Neil E Stahl

Warren R Mikulka

Richard Yau

Naxin Tu

Thomas Daly

John C Williams

Steven P Weinstein

Khue Truong

Warren R Mikluka

Denise Calaprice

The invention provides anti-CTLA4 binding proteins (e.g., antibodies, bispecific antibodies, and chimeric receptors) and their use in treating and preventing cancer, as well as compositions and kits comprising the anti-CTLA4 binding proteins.

Anti-CTLA4 antibodies and methods of use thereof

Antitumor antagonists that bind specifically to immune checkpoint regulator are disclosed. Also disclosed is a method of treating proliferative disorders with the anti-tumor antagonists.

Bispecific antagonist comprising a LAG-3 binding domain

The invention provides activatable masked anti-CTLA4 binding proteins (e.g., antibodies, bispecific antibodies, and chimeric receptors) and their use in treating and preventing cancer, as well as compositions and kits comprising the activatable masked anti-CTLA4 binding proteins.

Activatable masked anti-CTLA4 binding proteins

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

ADAM6 mice

Provided are trispecific T Cell Engagers or TSMAb's, antibodies that can simultaneously engage three different types of epitopes on the same target or on different targets. More specifically, the invention is directed to trispecific molecules that bind to DLL3, MUC17 or CLDN18.2 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and/or CD137.

Trispecific T cell engagers

Antitumor antagonists that bind specifically to immune checkpoint regulators, angiogenesis pathway regulators and/or TGF pathway regulators are disclosed. Also disclosed are methods for treating proliferative disorders, infections, and immunological disorders with the antitumor antagonists described herein.

Antagonists targeting the TGF-β pathway

Provided are bispecific T Cell Engagers. More specifically, the invention is directed to bispecific molecules that bind to DLL3, MUC17 or CLD18 and activate CD (cluster of differentiation) molecules (e.g. CD3, CD28 and CD137). Also provided are methods of treating an ailment such as cancer using an antibody (or fragment) against DLL3, MUC17 or CLD18 paired with an antibody (or fragment) of an agonist antibody that activates CD3, CD28 and/or CD137.

Bispecific T cell engagers

Provided herein are IL-2 muteins and IL-2 mutein Fc-fusion molecules that preferentially expand and activate T regulatory cells and are amenable to large scale production. Also provided herein are variant human IgG1 Fc molecules lacking or with highly reduced effector function and high stability despite lacking glycosylation at N297. Also, provided herein are linker peptides that are glycosylated when expressed in mammalian cells.

Interleukin-2 muteins for the expansion of T-regulatory cells

Antitumor antagonists

Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

Masked IL-2-Fc fusion polypeptides

Masked cytokine polypeptides

Masked interleukin-12 polypeptides

Antitumor antagonists that bind specifically to immune checkpoint regulator are disclosed. Also disclosed is a method of treating proliferative disorders with the antitumor antagonists.

Growing community of inventors

Santa Rosa, CA, United States of America

Margaret Karow