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

Sean Stevens

Cagan Gurer

Lynn Macdonald

Lynn MacDonald

George D Yancopoulos

John R McWhirter

Karolina Meagher

Naxin Tu

David M Valenzuela

Margaret Karow

Vera Voronina

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

Tim Willinger

Anthony T Dore, Jr

Christos Kyratsous

O Gavin Thurston

Jeremy I Paul

Christine A Klein

Bindu Varghese

Faith Harris

Karolina A Hosiawa

Joshua Trueheart

Dana M Fowlkes

Robert Babb

Jee Hwan Kim

John P Manfredi

Chia-Yang Lin

Gavin Thurston

Tammy T Huang

Erica Pyles

Tong Zhang

Amy Han

Brian Zambrowicz

Ivan Borisovich Lobov

Jorge E Galan

Susan D Croll

Supriya Patel

Gang Chen

Neil John Graham

Dimitris Skokos

Michael L LaCroix-Fralish

Namita A Gandhi

Alina Baum

Ying Hu

Stanley J Wiegand

Ella Ioffe

Lauric Haber

Jingtai Cao

Madhav Dhodapkar

Adrianna Latuszek

Joel H Martin

Haruka Okamoto

Marc R Morra

Kara Olson

Yajun Tang

Gustavo Droguett

Mark Sleeman

Noah Palm

Marcel De Zoete

Nicole M Alessandri-Haber

Aynur Hermann

Yashu Liu

Aris I Baras

Wojtek Auerbach

Israel Lowy

Lori C Morton

Esther Latres

Katherine Cygnar

Judith Altarejos

Ana Kostic

Robert B Evans

Peter W Mason

Thomas Nittoli

Allen Radin

Ashique Rafique

Guochun Gong

Lisa A Purcell

Alison Crawford

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

A genetically modified mouse is provided, wherein the mouse expresses an immunoglobulin light chain repertoire characterized by a limited number of light chain variable domains. Mice are provided that present a choice of two human light chain variable gene segments such that the immunoglobulin light chains expresses by the mouse comprise one of the two human light chain variable gene segments. Methods for making bispecific antibodies having universal light chains using mice as described herein, including human light chain variable regions, are provided. Methods for making human variable regions suitable for use in multispecific binding proteins, e.g., bispecific antibodies, and host cells are provided.

Mice expressing a limited immunoglobulin light chain repertoire

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a human or humanized T cell receptor (TCR) from a human or humanized TCR locus comprising a non-human TCR non-coding sequence, and optionally a humanized T cell co-receptor (e.g., humanized CD4 and/or CD8 (e.g., CD8α and/or CD8β)), and/or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II α and/or MHC II β chains) and/or MHC I (e.g., MHC Iα) respectively, and optionally human or humanized β2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making the genetically engineered animals are also provided. Methods for using the genetically engineered animals for developing human therapeutics are also provided.

Genetically modified mice comprising humanized cellular immune system components with improved diversity of TCRB repertoire

Described herein are protein steroid conjugates that are useful, for example, for the target-specific delivery of glucocorticoids (GCs) to cells.

Steroids and protein-conjugates thereof

Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.

Humanized IL-15 animals

Provided herein are therapeutic methods of treatment using agonist leptin receptor (LEPR) antibodies, antigen-binding fragments thereof, or compositions comprising the LEPR antibodies or antigen-binding fragments thereof. Such therapeutic methods include treatment for conditions related to metabolic dysfunction, including for example, lipodystrophy, adiposity or obesity, reducing body weight, non-alcoholic fatty liver disease, hyperphagia, hyperglycemia, insulin resistance, dyslipidemia, hepatic steatosis, and infertility.

Methods of treatment using a leptin receptor agonist antibody

Described herein are anchor-modified immunoglobulin polypeptides, wherein the anchor moors the immunoglobulin polypeptide to a receptor of interest. The anchor-modified immunoglobulin polypeptides are generally characterized at the N-terminus with an anchor, e.g., the receptor binding portion of a ligand that binds a receptor. Non-human animals genetically modified with recombinant immunoglobulin segments that encode the anchor-modified immunoglobulin polypeptides are capable of making the anchor-modified immunoglobulin polypeptides. Such non-human animals also provided, along with methods and compositions for making and using the non-human animals. Methods for producing anchor-modified immunoglobulins from non-human animals are also provided, as well as anchor-modified immunoglobulins generated therefrom.

Nucleic acids encoding anchor modified antibodies and uses thereof

Non-human animals (and/or non-human cells) and methods of using 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 immunoglobulin (Ig) light chains characterized by the presence of human Vλ domains. Non-human animals provided herein are, in some embodiments, characterized by expression of antibodies that contain human Vλ light chains that are encoded by human Igλ light chain-encoding sequences inserted into an endogenous Igκ light chain locus of said non-human animals. Methods for producing antibodies from non-human animals are also provided, which antibodies contain human variable regions and mouse constant regions.

Immunoglobulin lambda light chain and uses thereof

Methods and compositions are provided for generating antigen-binding proteins against a foreign antigen of interest.

Methods for producing antigen-binding proteins against foreign antigens

Provided herein are compounds, compositions and methods for the treatment of diseases and disorders associated with the liver X receptor, including bis-octahydrophenanthrene carboxamides and protein (e.g., antibody) drug conjugates thereof.

Bis-octahydrophenanthrene carboxamides and protein conjugates thereof

Growing community of inventors

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

Andrew J Murphy