Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Robert Babb

Gang Chen

James P Fandl

Andrew J Murphy

William C Olson

Tammy T Huang

Wen-Yi Lee

George D Yancopoulos

Christos Kyratsous

Lynn Macdonald

Sean Stevens

Neil E Stahl

Alina Baum

Cindy Gerson

Marine Malbec

Darya Burakov

Dimitris Skokos

Cagan Gurer

Samuel H Davis

Johanna Hansen

Ergang Shi

Drew Dudgeon

Yu Huang

Bei Wang

Matthew Sleeman

Rosalynn Molden

Thomas Nittoli

Douglas MacDonald

Ashique Rafique

Christopher Daly

Lauric Haber

David R Buckler

John Mcwhirter

John DaSilva

Yu Zhao

David Suh

Glen Farr

Douglas Macdonald

Eric Smith

Karolina A Meagher

Wen-yi Lee

The present disclosure relates to a method for identifying cells that express antigen-specific antibodies with a high binding affinity for a monomeric antigen. Using fluorescence activated cell sorting, cells expressing high affinity antigen-specific antibodies are selected from a population of immune cells isolated from a mammal that has been immunized with or otherwise exposed to the antigen. Nucleic acids encoding the high affinity antibodies can then be cloned into other lymphoid and non-lymphoid cells where the antibody can be expressed and from which the antibodies can be secreted.

Method for generating high affinity antibodies

Disclosed are methods for obtaining cells that express antibodies that bind transmembrane proteins, methods for generating antibodies from such cells, antibodies to transmembrane proteins and fragments thereof, and nucleic acids encoding the antibodies. More particularly, the disclosure relates to methods for obtaining antibody-producing cells that express an antibody that binds to a transmembrane protein based on the use of lipid bilayer-membrane scaffold protein complexes to present transmembrane protein antigens to cells.

Methods for obtaining antibodies that bind transmembrane proteins and cells that produce the same

Provided herein are antibodies, and antigen-binding fragments thereof that specifically bind glucocorticoid-induced tumor necrosis factor receptor (GITR), compositions comprising the antibodies or antigen-binding fragments thereof, and methods of using the same, including, e.g., methods of treatment using the same.

Therapeutic uses of anti-GITR antibodies

The present disclosure provides antibodies and antigen-binding fragments thereof that bind specifically to a coronavirus spike protein and methods of using such antibodies and fragments for treating or preventing viral infections (e.g., coronavirus infections).

Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments

Anti-GITR antibodies and uses thereof

This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antibodies including bispecifc antibodies in eukaryotic cells, particularly Chinese hamster () cell lines, by employing an expression-enhancing locus.

Compositions and methods for making antibodies based on use of an expression-enhancing locus

This invention relates to site-specific integration and expression of recombinant proteins in eukaryotic cells. In particular, the invention includes compositions and methods for improved expression of antigen-binding proteins including monospecific and bispecifc antibodies in eukaryotic cells, particularly Chinese hamster () cell lines, by employing multiple expression-enhancing locus.

Compositions and methods for making antibodies based on use of an expression-enhancing loci

Provided herein are antibodies and bispecific antigen-binding molecules that bind MET and methods of use thereof. The bispecific antigen-binding molecules comprise a first and a second antigen-binding domain, wherein the first and second antigen-binding domains bind to two different (preferably non-overlapping) epitopes of the extracellular domain of human MET. The bispecific antigen-binding molecules are capable of blocking the interaction between human MET and its ligand HGF. The bispecific antigen-binding molecules can exhibit minimal or no MET agonist activity, e.g., as compared to monovalent antigen-binding molecules that comprise only one of the antigen-binding domains of the bispecific molecule, which tend to exert unwanted MET agonist activity. Also included are antibody-drug conjugates (ADCs) comprising the antibodies or bispecific antigen-binding molecules provided herein linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treating cancer in a subject by administering to the subject a bispecific antigen-binding molecule or an ADC thereof.

Anti-MET antibodies, bispecific antigen binding molecules that bind MET, and methods of use thereof

Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise an immunoglobulin heavy chain locus that includes unrearranged human immunoglobulin light chain gene segments and an immunoglobulin light chain locus that includes a single rearranged human light chain variable region nucleotide sequence. The unrearranged human light chain gene segments may be operably linked to a heavy chain constant region nucleotide sequence and the rearranged human immunoglobulin light chain variable region nucleotide sequence may be operably linked to a light chain constant region nucleotide sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a cognate variable domain, and expressing such nucleic acid sequences in a host cell, e.g., to generate a multispecific antigen-binding protein.

Non-human animals that select for light chain variable regions that bind antigen

Anti-SARS-CoV-2-Spike glycoprotein antibodies and antigen-binding fragments

Methods for making, identifying, isolating and/or making binding proteins that contain an immunoglobulin light chain variable domain, including a somatically hypermutated light chain variable domain, fused with a heavy chain constant region, are provided. Exemplary binding proteins specific to small molecules are also provided.

Vantigen binding proteins exhibiting distinct binding characteristics

Growing community of inventors

River Edge, NJ, United States of America

Robert Babb