Rinat Neuroscience Corporation

Pfizer Corporation

Alx Oncology Inc.

Labrys Biologics, Inc.

Teva Pharmaceuticals International Gmbh

Tallac Therapeutics, Inc.

Apg Therapeutics, Inc.

Jaume Pons

Arnon Rosenthal

Yasmina Noubia Abdiche

Kristian Todd Poulsen

Joerg Zeller

Sierra Jones Collier

Tracy Chia-Chien Kuo

Bang Janet Sim

Hong Wan

Wei-Hsien Ho

Arvind Rajpal

Pavel Strop

Steven Elliot Kauder

Javier Fernando Chaparro Riggers

Hong Liang

Bruce Charles Gomes

David L Shelton

Julie Jia Li Hawkins

Yuli Wang

Jan Markus Grimm

Mei Li

William Don Harriman

Russell Dushin

Shu-Hui Liu

Donna Marie Stone

Weihsien Ho

Sukumar Sakamuri

Magdalena Grazyna Dorywalska

Son Lam

Vishwas Madhav Paralkar

Shelley Izquierdo

Curt W Bradshaw

Sophia Randolph

Corey Goodman

Laura Deming

Hong I Wan

Edward HyungSuk Ha

David Shelton

Jeffrey Raymond Chabot

Xiayang Qiu

Marija Vrljic

Joaquim Trias

Sierra Lee Jones Collier

Sierra Leigh Jones Collier

Jerome Thomas Mettetal, Ii

Kapil Mayawala

Antoni Planas

Julie Jia Hawkins

Provided are methods of treating cancer that comprise administering a polypeptide (e.g. a fusion polypeptide) that comprises a SIRPα D1 domain variant and an Fc domain variant in combination with at least one chemotherapy agent and/or at least one therapeutic antibody. Also provided are related kits.

Combination therapies for treating cancer

The present application provides activatable antibodies comprising an antibody comprising an antigen-binding domain (ABD), wherein the ABD comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the N-terminus of the VH is fused to a first polypeptide shield moiety (S1), and the N-terminus of the VL is fused to a second polypeptide shield moiety (S2), wherein S1 comprises a first disease-sensing releasable moiety (DS1) and/or S2 comprises a second disease-sensing releasable moiety (DS2), wherein association of S1 with S2 blocks binding of the ABD to its target, and wherein the ABD does not specifically bind to S1, S2, or association thereof. Composition, methods of treatment using the activatable antibodies, and methods of preparation thereof are further provided.

Activatable antibodies and methods of use thereof

Provided herein, inter alia, are isolated, humanized antibodies that bind an extracellular domain of a human SIRP-α polypeptide. Also provided are polynucleotides, vectors, host cells, and methods of production and use related thereto.

Antibodies against signal-regulatory protein alpha and methods of use

The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Transglutaminase-mediated conjugation

The present disclosure features signal-regulatory protein &#x3b1; (SIRP-&#x3b1;) polypeptides and constructs that are useful, e.g., to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T-cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof. The SIRP-&#x3b1; constructs include a high affinity SIRP-&#x3b1; D1 domain or variant thereof that binds CD47 with higher affinity than a wild-type SIRP-&#x3b1;. The SIRP-&#x3b1; polypeptides or constructs include a SIRP-&#x3b1; D1 variant fused to an Fc domain monomer, a human serum albumin (HSA), an albumin-binding peptide, or a polyethylene glycol (PEG) polymer. Compositions provided herein include (i) a polypeptide including a signal-regulatory protein &#x3b1; (SIRP-&#x3b1;) D1 variant and (ii) an antibody.

Constructs having a SIRP-&#x3b1; domain or variant thereof

Provided are methods of treating cancer (e.g., non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), HER2-positive gastric/gastroesophageal junction (GEJ) cancer, de novo or transformed diffuse large B cell lymphoma (DLBCL), or indolent lymphoma) in an individual that comprise administering to the individual (a) a polypeptide comprising a SIRP&#x3b1; D1 domain variant and an Fc domain variant, and (b) an anti-cancer antibody (e.g., an anti-PD1 antibody, anti-HER2 antibody, or an anti-CD20 antibody). Also provided are related kits pharmaceutical compositions.

Methods of treating cancer

Provided herein, inter alia, are isolated antibodies that bind an extracellular domain of a human SIRP-&#x3b1; v1 polypeptide (e.g., the D1 domain), an extracellular domain of a human SIRP-&#x3b1; v2 polypeptide, or both. In some embodiments, the antibodies also bind an extracellular domain of a monkey SIRP-&#x3b1; polypeptide, an extracellular domain of a mouse SIRP-&#x3b1; polypeptide, an extracellular domain of a human SIRP-&#x3b2; polypeptide, and/or an extracellular domain of a human SIRP-&#x3b3; polypeptide. In some embodiments, the antibodies block or do not binding between an extracellular domain of a human SIRP-&#x3b1; polypeptide and an IgSF domain of a human CD47 polypeptide, while in some embodiments, the antibodies reduce the affinity of a human SIRP-&#x3b1; polypeptide for binding an IgSF domain of a human CD47 polypeptide. Further provided herein are methods, polynucleotides, vectors, and host cells related thereto.

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.

Heterodimeric proteins and methods for producing and purifying them

Provided herein, inter alia, are isolated, humanized antibodies that bind an extracellular domain of a human SIRP-&#x3b1; polypeptide. Also provided are polynucleotides, vectors, host cells, and methods of production and use related thereto.

Antibodies against signal-regulatory protein &#x3b1; and methods of use

Constructs having a SIRP-alpha domain or variant thereof

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 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.

Anti-NGF antibodies and methods using same

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

Growing community of inventors

San Bruno, CA, United States of America

Jaume Pons