Bristol-myers Squibb Compnay

Genpharm International, Inc.

Medarex Inc.

E. R. Squibb Sons, Inc.

Kyowa Hakko Kirin Co., Limited

Other

University of Cincinnati

Five Prime Therapeutics, Inc.

Biosite Incorporated

Biograph 55, Inc.

Kirin Brewery Company, Limited

Nils Lonberg

Alan J Korman

Robert M Kay

Mohan Srinivasan

Guodong Chen

Richard Y Huang

Mark J Selby

Karla Ann Henning

Haichun Huang

Michelle Minhua Han

Edward L Halk

Changyu Wang

Indrani Chakraborty

Huiming Li

Aaron Paul Yamniuk

Isao Ishida

Kazuma Tomizuka

Bryan C Barnhart

Ming Lei

Susan Wong

Tibor P Keler

Yashwant M Deo

Jeff Gray

Gunars E Valkirs

Maria N Jure-Kunkel

Joe Buechler

Martin J Corbett

John S Sack

Leonard G Presta

Arvind Rajpal

Xi-Tao Wang

Katherine E Lewis

John P Cogswell

Christine Bee

Andrew Rankin

Sanjeev Gangwar

Qian Zhang

Kent B Thudium

Han Chang

Vincent Guerlavais

Mark F Maurer

Linda Liang

Denise Leah Williams

Brenda L Stevens

Xiao Min Schebye

Amelia Nancy Black

Jochem Gokemeijer

Alexander T Kozhich

Raphael Clynes

Ekaterina G Deyanova

Thomas D Kempe

Michael Quigley

Sandra V Hatcher

Xiang Shao

Liang Schweizer

Joseph E Myers, Jr

Pingping Zhang

Emanuela Sega

Angela Goodenough

Susan Chien-Szu Wong

Dianne M Fishwild

Hong-An Truong

Xiaodi Deng

Robin Edwards

Joseph Toth

David J Fontana

Andrew B Norman

Diana Yuhui Chen

Anne C Lewin

Darren Locke

Liang Chen

Omar Duramad

Hadia Lemar

Jeffrey Jackson

William Ying

Zhehong Cai

Marie-Michelle Navarro Garcia

Christina Maria Milburn

Patrick Guirnalda

William J Ball, Jr

Olufemi A Adelakun

Joseph E Myers

Paul Tumeh

James Novotny, Jr

Andres A Gutierrez

Cyrus Hedvat

Christopher Harbison

Daniel K Rohrer

Lori S Burton

Nancy Amelia Black

Praveen Aanur

Zheng Yang

Sudhir Chakravarthi

Pedro Smith

Christine Huang

Yan Feng

Ed Halk

Maria Rodriguez

Kazuma c/o Discovery Research Laboratories Kirin Pharma Kabushiki Kaisha Tomizuka

The present application relates to antibodies specifically binding to immunoglobulin-like transcript 4 (ILT4), which is also known as LILRB2, LIR2, MIR10, and CD85d, and corresponding nucleic acids, host cells, compositions, and uses. In some embodiments, the antibodies bind specifically to human ILT4, but do not significantly bind to ILT2, ILT3, or ILT5, or to other members of the LILRA or LILRB families.

Antibodies binding to ILT4

Provided herein are common light chain bispecific antibodies that bind CD38 and CD19. The common light chain bispecific antibodies comprise an anti-CD38 heavy chain variable region and anti CD19 heavy chain variable region that each have a negatively-charged amino acid at a terminal heavy chain variable region position. The common light chain bispecific antibodies comprise further comprise an anti-CD38 heavy chain constant region and anti-CD19 heavy chain constant region that each lack a C-terminal lysine residue. Further provided are nucleic acids encoding such common light chain bispecific antibodies and host cells comprising the nucleic acids. Also provided are methods of making such common light chain bispecific antibodies.

CD19/CD38 multispecific antibodies

The invention provides a method of treating a tumor in a human patient comprising (i) identifying a patient as having a LAG-3 positive tumor and (ii) administering to the patient a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor, or an anti-CTLA4 antibody. In some embodiments, the method further comprises identifying the patient as having a LAG-3 positive PD-L1 positive tumor. In some embodiments, the LAG-3 inhibitor is an anti-LAG-3 antibody and the PD-1 pathway inhibitor is an anti-PD-1 antibody. The methods of the invention can improve response rates to treatment with a PD-1 pathway inhibitor, a combination of a PD1 pathway inhibitor and an immune checkpoint inhibitor, or a combination of a LAG-3 inhibitor and a PD-1 pathway inhibitor.

Treatment of LAG-3 positive tumors

Provided herein are antibodies, or antigen binding portions thereof, that bind to glucocorticoid-inducible TNF receptor (GITR). Also provided are uses of these proteins in therapeutic applications, such as in the treatment of cancer. Further provided are cells that produce the antibodies, polynucleotides encoding the heavy and/or light chain variable region of the antibodies, and vectors comprising the polynucleotides encoding the heavy and/or light chain variable region of the antibodies.

Antibodies against glucocorticoid-induced tumor necrosis factor receptor (GITR) and uses thereof

This provides pharmaceutical compositions that comprise (i) an anti-LAG-3 antibody or antigen binding fragment thereof or (ii) an anti-LAG-3 antibody or antigen binding fragment thereof and an anti-PD-1 antibody, anti-PD-L1 antibody, or antigen binding fragment thereof. Also provided are pharmaceutical compositions that comprise a buffering agent, stabilizing or bulking agent, and a surfactant. The disclosure also provides a vial, syringe, intravenous bag, or kit that comprises the compositions, and methods for using the compositions.

Compositions comprising an anti-LAG-3 antibody or an anti-LAG-3 antibody and an anti-PD-1 or anti-PD-L1 antibody

Provided herein are diagnostic antibodies that bind to glucocorticoid-induced tumor necrosis factor receptor (GITR). Such antibodies are useful for methods of detecting the expression of GITR in biological samples, for example, tumor tissue, and identifying a cancer patient likely to respond to anti-GITR immunotherapy or predicting whether a cancer patient will respond to anti-GITR immunotherapy.

Anti-GITR antibodies for cancer diagnostics

The instant invention relates to transgenic non-human animals capable of producing heterologous antibodies, transgenes used to produce such transgenic animals, transgenes capable of functionally rearranging a heterologous D gene in V-D-J recombination, immortalized B-cells capable of producing heterologous antibodies, methods and transgenes for producing heterologous antibodies of multiple isotypes, methods and transgenes for producing heterologous antibodies wherein a variable region sequence comprises somatic mutation as compared to germline rearranged variable region sequences, transgenic nonhuman animals which produce antibodies having a human primary sequence and which bind to human antigens, hybridomas made from B cells of such transgenic animals, and monoclonal antibodies expressed by such hybridomas.

HCO32 and HCO27 and related examples

The present invention provides isolated monoclonal antibodies, particularly human antibodies, that bind to human Cluster of Differentiation 73 (CD73) with high affinity, and inhibit the activity of CD73, and optionally mediate antibody dependent CD73 internalization. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the growth of a tumor cell expressing CD73 using the antibodies of the invention, including methods for treating various cancers.

Antibodies against CD73 and uses thereof

The present invention provides isolated monoclonal antibodies that specifically bind LAG-3, and have optimized functional properties compared to previously described anti-LAG-3 antibodies, such as antibody 25F7 (US 2011/0150892 A1). These properties include reduced deamidation sites, while still retaining high affinity binding to human LAG-3, and physical (i.e., thermal and chemical) stability. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided, as well as immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies. The present invention also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which the antibodies are co-administered with at least one additional immunostimulatory antibody, is also provided.

Optimization of antibodies that bind lymphocyte activation gene-3 (LAG-3), and uses thereof

Provided are anti-CD19 and anti-CD38 common light chain bispecific antibodies. The anti-CD19 and anti-CD38 bispecific antibodies described herein are useful in methods for treating a cancer or a tumor.

Composite binding molecules targeting immunosuppressive B cells

Provided are methods for clinical treatment of tumors (e.g., advanced solid tumors) using an anti-LAG-3 antibody in combination with an anti-PD-1 antibody.

Combination of anti-LAG-3 antibodies and anti-PD-1 antibodies to treat tumors

Antibodies against glucocorticoid-induced tumor necrosis factor receptor (GITR)

Growing community of inventors

Woodside, CA, United States of America

Nils Lonberg