Regeneron Pharmaceuticals, Inc.

Yale University

Institute for Research in Biomedicine (irb)

Regeneran Pharmaceuticals, Inc.

Cadus Technologies, Inc.

Cadus Pharmaceutical Corp.

Other

Duke University

Institute for Research in Biomedicine

Andrew J Murphy

Lynn Macdonald

Sean Stevens

Cagan Gurer

George D Yancopoulos

John R McWhirter

Naxin Tu

Karolina Meagher

Vera Voronina

David M Valenzuela

Margaret Karow

Jamie M Orengo

Aris N Economides

Richard A Flavell

Markus G Manz

Jesper Gromada

Ka-Man Venus Lai

Nicholas J Papadopoulos

Li-Hsien Wang

William C Olson

Elena Burova

Eric L Smith

Neil E Stahl

Panayiotis Stevis

Elizabeth Eynon

Till Strowig

Anthony Rongvaux

Yingzi Xue

David Frendewey

Alexander O Mujica

Viktoria Gusarova

Jose F Rojas

Samuel H Davis

Christos Kyratsous

Anthony T Dore, Jr

Tim Willinger

Faith Harris

Karolina A Hosiawa

Jee Hwan Kim

Chia-Yang Lin

O Gavin Thurston

Jeremy I Paul

Christine A Klein

Bindu Varghese

Gavin Thurston

Joshua Trueheart

Dana M Fowlkes

Robert Babb

John P Manfredi

Susan D Croll

Tammy T Huang

Erica Pyles

Tong Zhang

Amy Han

Brian Zambrowicz

Dimitris Skokos

Ivan Borisovich Lobov

Jorge E Galan

Supriya Patel

Michael Rosconi

Nina Liu

Gang Chen

Neil John Graham

Lauric Haber

Michael L LaCroix-Fralish

Namita A Gandhi

Alina Baum

Ying Hu

Stanley J Wiegand

Ella Ioffe

Kara Olson

Jingtai Cao

Aynur Hermann

Joel H Martin

Haruka Okamoto

Marc R Morra

Yajun Tang

Gustavo Droguett

Mark Sleeman

Noah Palm

Nicole M Alessandri-Haber

Marcel De Zoete

Aris I Baras

Wojtek Auerbach

Israel Lowy

Eric B Smith

Lori C Morton

Esther Latres

Katherine Cygnar

Judith Altarejos

Robert B Evans

Peter W Mason

Thomas Nittoli

Allen Radin

Ashique Rafique

Guochun Gong

Lisa A Purcell

Alison Crawford

Sarah Jane Hatsell

Cheng Wang

Methods for modifying a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising conditional by inversion elements. Methods are provided which afford the ability in a single targeting step to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a conditional by inversion element. Introduced alleles comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a conditional by inversion element, wherein upon action of a recombinase a conditional allele with a conditional by inversion element is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a conditional by inversion element in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation.

Methods for modifying a genome

According to certain embodiments, the present disclosure provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds a target antigen and a second antigen binding domain that binds a complement component. In certain embodiments, the bispecific antigen-binding molecules of the present disclosure are capable of binding to the target antigen with an ECof about 10 nM or less, and/or are capable of promoting complement deposition on the target antigen with an ECof about 10 nM. In certain embodiments, the bispecific antigen-binding molecules of the disclosure are useful for treating diseases in which inhibition or reduction of the growth of an infectious agent or cancer cell is desired and/or therapeutically beneficial.

Compositions and methods for using bispecific antibodies to bind complement and a target antigen

Provided herein are monoclonal antibodies that bind to the transmembrane serine protease 6 (TMPRSS6) protein, and methods of use thereof. In various embodiments of the disclosure, the antibodies are fully human antibodies that bind to TMPRSS6. In some embodiments, the antibodies disclosed herein are useful in a method for treating or preventing a disease, disorder or condition associated with TMPRSS6 in humans.

Anti-TMPRSS6 antibodies and uses thereof

The present invention provides novel full-length human antibodies that bind to human Fc epsilon-R1 alpha (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both Fc epsilon-R1 alpha and CD3 and activate T cells via the CD3 complex in the presence of Fc epsilon-R1 alpha-expressing cells. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced Fc epsilon-R1 alpha-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of allergies, including anaphylaxis.

Anti-FC ϵ-R1 α (FCϵR1α) antibodies, bispecific antigen-binding molecules that bind FCϵR1α and CD3, and uses thereof

The present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD28, and a second antigen-binding molecule that specifically binds human PSMA. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing PSMA, such as prostate tumors. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an up-regulated or induced targeted immune response is desired and/or therapeutically beneficial.

Bispecific anti-PSMA x anti-CD28 antibodies and uses thereof

The present disclosure provides antibodies and antigen-binding fragments thereof that bind to human artemin. Methods for using anti-artemin antibodies and antigen-binding fragments are also provided.

Human antibodies to artemin and methods of use thereof

Non-human animals, tissues, cells, and genetic material are provided that comprise a modification of an endogenous non-human heavy chain immunoglobulin sequence and that comprise an ADAM6 activity functional in a mouse, wherein the non-human animals express a human immunoglobulin heavy chain variable domain and a cognate human immunoglobulin λ light chain variable domain.

Humanized light chain mice

Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized a proliferation-inducing ligand gene. Non-human animals and cells that express a human or humanized a proliferation-inducing ligand protein from an endogenous a proliferation-inducing ligand locus are described.

Non-human animals having a humanized a proliferation-inducing ligand gene

Non-human animals (and/or non-human cells) and methods of using and making the same are provided, which non-human animals (and/or non-human cells) have a genome comprising human antibody-encoding sequences (i.e., immunoglobulin genes). Non-human animals described herein express antibodies that contain human Igλ light chains, in whole or in part. In particular, non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Igλ light chains, in whole or in part, that are encoded by human Igλ light chain-encoding sequences inserted into an endogenous Igλ light chain locus of said non-human animals. Methods for producing antibodies from non-human animals are also provided.

Non-human animals having an engineered immunoglobulin lambda light chain locus

Non-human animals, expressing humanized CD3 proteins are provided. Non-human animals, e.g., rodents, genetically modified to comprise in their genome humanized CD3 proteins are also provided. Additionally, provided are methods and compositions of making such non-human animals, as well as methods of using said non-human animals.

Non-human animals expressing humanized CD3 complex

The present invention provides multispecific antibodies that bind to EGFR and CD28 (EGFR×CD28) as well as anti-EGFR antibodies. Such antibodies may be combined with a further therapeutic agent such as an anti-PD1 antibody. Methods for treating cancers (e.g., EGFR-expressing cancer) by administering the antibodies (e.g., and combinations thereof with anti-PD1) are also provided. The EGFR×CD28 antibodies of the present invention embody a tumor-targeted immunotherapeutic modality combined with PD-1 inhibition. These bispecific antibodies bind a tumor-specific antigen (TSA) (EGFR) with one arm and the co-stimulatory receptor, CD28, on T-cells with the other arm. Combination therapy with PD-1 inhibitors specifically potentiated intra-tumoral T cell activation, promoting an effector memory-like T cell phenotype without systemic cytokine secretion in a variety of syngeneic and human tumor xenograft models. Combining this class of CD28-co-stimulatory bispecific antibodies with the clinically validated anti-PD-1 treatment provides a well-tolerated antibody therapy with markedly enhanced anti-tumor efficacy.

EGFR x CD28 multispecific antibodies

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I and MHC II polypeptides and/or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Genetically modified major histocompatibility complex mice

The invention provides a recombinant RNA molecule comprising (i) a sequence of a gene-editing molecule mRNA, or a sequence of a functional fragment or derivative thereof, and (ii) at least one sequence of a coding or non-coding enrichment RNA, or a sequence of a functional fragment or derivative thereof, wherein the enrichment RNA, or functional fragment or derivative thereof, is capable of enhancing inclusion of the gene-editing molecule mRNA, or functional fragment or derivative thereof, into a retroviral particle. The invention provides a method of producing the retroviral particles of the invention, the method comprising culturing a packaging cell in conditions sufficient for the production of a plurality of retroviral particles.

Delivery of a gene-editing system with a single retroviral particle and methods of generation and use

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g.,oris described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

Genetically modified mice and engraftment

Antigen binding molecules (ABMs) comprising Fab domains in non-native configurations, ABM conjugates comprising the ABMs and cytotoxic or cytostatic agents, pharmaceutical compositions containing the ABMs and ABM conjugates, methods of using the ABMs, ABM conjugates and pharmaceutical compositions for treating cancer, nucleic acids encoding the ABMs, cells engineered to express the ABMs, and methods of producing ABMs.

Antigen binding molecule formats

Growing community of inventors

Croton-on-Hudson, NY, United States of America

Andrew J Murphy