Regeneron Pharmaceuticals, Inc.

Regeneran Pharmaceuticals, Inc.

Other

Gavin Thurston

Jessica Kirshner

Nicholas J Papadopoulos

Frank Delfino

William C Olson

Marcus Kelly

Ella Ioffe

Eric L Smith

Joel H Martin

Christopher Daly

Thomas Nittoli

Elena Burova

Andrew J Murphy

Douglas MacDonald

Dangshe Ma

Irene Noguera-Troise

Israel Lowy

Richard Tavare

Cagan Gurer

Ka-Man Venus Lai

Alexander O Mujica

Bindu Varghese

Aynur Hermann

Julian Andreev

Samuel H Davis

Ashique Rafique

Lauric Haber

Kara Olson

Alison Crawford

Katherine Cygnar

Matthew Franklin

Elena Garnova

Drew Dudgeon

Dayong Guo

Kevin A Bray

Jason T Giurleo

Nithya Thambi

Jessica R Kirshner

George D Yancopoulos

Erica Ullman

Carrie Brownstein

Alain Thibault

Eric Smith

David Frendewey

Aris I Baras

Eric B Smith

Amy Han

Gustavo Droguett

Goncalo Abecasis

Chia-Jen Siao

Matthew Koss

Nicholas W Gale

Yashu Liu

Douglas Macdonald

Julie Horowitz

Eric Jorgenson

Tara Young

Hoi-Ching Lee

Zhe Li

Lisa Purcell Ngambo

Donald Mc Donald

Chitra Suri

Xinyuan Zhang

Stefan Semrau

Andres Perez Bay

Alexander Mujica

Samuel Davis

William Olson

Cagen Gurer

Kara L Olson

Irene Noguera

METHODS AND COMPOSITIONS FOR SENSITIZATION OF TUMOR CELLS TO IMMUNE THERAPY

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

Non-human animals, and methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of an endogenous cluster of differentiation (CD) gene, in particular a humanization of a CD47 gene. Said non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous CD47 gene so that said non-human animals express a CD47 polypeptide that includes a human portion and a non-human portion (e.g., a murine portion).

Mouse having a humanized cluster of differentiation 47 gene

The present invention provides antibodies that bind to prostate-specific membrane antigen (PSMA), bispecific antibodies that bind to PSMA and CD3, and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PSMA with high affinity and bind CD3 to induce human T cell proliferation. The invention includes antibodies that bind PSMA and CD3 and induce T cell-mediated killing of PSMA-expressing tumor cells. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3, 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 prostate tumors expressing PSMA. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and/or therapeutically beneficial. For example, the antibodies of the invention are useful for the treatment of various cancers.

Anti-PSMA antibodies, bispecific antigen-binding molecules that bind PSMA and CD3, and uses thereof

The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the invention, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention causes or facilitates the targeted killing of tumor cells.

Multispecific antigen-binding molecules and uses thereof

The present invention provides antigen-binding proteins that specifically bind to an HLA-displayed human papillomavirus (HPV) peptide, and therapeutic and diagnostic methods of using those binding proteins.

Anti-human papillomavirus (HPV) antigen-binding proteins and methods of use thereof

Anti-CD8 antibodies, radiolabeled anti-CD8 antibodies, fluorescently labeled anti-CD8 antibodies and their use in imaging are provided herein. Included are methods of detecting the presence of CD8 proteins in a subject or sample.

Anti-CD8 antibodies and uses thereof

The present disclosure provides methods of treating a subject having skin cancer or preventing a subject from developing skin cancer, and methods of identifying subjects having an increased risk of developing skin cancer.

Methods of treating skin cancer with Carboxypeptidase Vitellogenic Like (CPVL) inhibitors

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., a B-cell cancer such as Hodgkin's lymphoma or acute lymphoblastic leukemia). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to programmed death 1 (PD-1) receptor in combination with a therapeutically effective amount of a bispecific antibody that specifically binds to CD20 and CD3.

Combination of anti-PD-1 antibodies and bispecific anti-CD20/anti-CD3 antibodies to treat cancer

Radiolabeled anti-PD-L1 antibodies and their use in immuno-PET imaging are provided herein. Included are methods of detecting the presence of PD-L1 proteins in a patient or sample.

Radiolabeled anti-PD-L1 antibodies for immuno-PET imaging

The present invention provides antibodies that bind to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and methods of use. In various embodiments of the invention, the antibodies are fully human antibodies that specifically bind to CTLA-4. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing CTLA-4 activity, thus providing a means of activating T-cells and/or for treating a disease or disorder such as cancer or viral infection.

Anti-CTLA-4 antibodies and uses thereof

Provided herein are methods and compositions related to the treatment or prevention of cancer (e.g., by targeting a tumor in a subject with cancer) by administering to a subject an agent that inhibits autophagy. In certain aspects, provided herein are methods of compositions related to methods of sensitizing cancer cells to tumor necrosis factor-alpha (TNF-α) mediated killing by contacting the cells or administering the agent that inhibits autophagy.

Methods and compositions for sensitization of tumor cells to immune therapy

Provided herein are bispecific antigen-binding molecules that bind HER2 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 HER2. The bispecific antigen-binding molecules cluster on the surface of HER2 IHC2+ and IHC3+ cells, and are internalized into the cellular lysosomes. 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.

Bispecific antigen binding molecules that bind HER2, and methods of use thereof

Growing community of inventors

Briarcliff Manor, NY, United States of America

Gavin Thurston