Regeneron Pharmaceuticals, Inc.

Medarex Inc.

University of Massachusetts

E. R. Squibb Sons, Inc.

Duke University

Inovio Pharmaceuticals, Inc.

Israel Lowy

Gavin Thurston

Gregory Babcock

Robert F Graziano

William D Thomas, Jr

Teresa J Broering

Robert Barry Mandell

Donna Ambrosino

Hector Javier Hernandez

Geoffrey M Nichol

Deborah Molrine

Hui-Fen Zhang

Carrie Brownstein

Andrew J Murphy

George D Yancopoulos

Lynn Macdonald

Cagan Gurer

Mohan Srinivasan

John R McWhirter

Tibor P Keler

Aris I Baras

Karolina Meagher

Christopher Daly

Elena Burova

Ella Ioffe

Laura A Vitale

Bindu Varghese

Garnett Kelsoe

Eric L Smith

Jian Yan

Samuel H Davis

Jessica Kirshner

Eric B Smith

Matthew P Morrow

Dimitris Skokos

Barton F Haynes

Diann Blanset

Petra Rietschel

Lieve Lucille Adriaens

Tasha Nicholle Sims

Bo Gao

Matthew G Fury

Steven Alan Fischkoff

Jewell Walters

Bernadette Ferraro

Anne Gurnett-Bander

Carlos Arrecubieta

Michael Yellin

James Chung-Yin Yang

Kimberly A Kraynyak

Albert J Sylvester

Jeffrey Skolnik

Amy-Lee Bredlau

Elisabeth Gillespie

David Sternberg

Manish Sharma

Robert Mandell

William Thomas

Theresa Broering

William D Thomas

Eric Smith

Gregory J Babcock

Jessica R Kirshner

Samuel Davis

Provided herein are methods of treating brain cancer in a subject, comprising evaluating one or more biological samples from a subject who has brain cancer for the presence of a miRNAs and administering interleukin-12 (IL-12); an immunogenic composition of human telomerase reverse transcriptase (hTERT), Wilms Tumor-1 (WT-1), and prostate specific membrane antigen (PSMA); and an anti-programmed cell death receptor 1 (PD-1) antibody to said subject if the subject has an increased expression level of the mIR-331-3p miRNA or isomiRs thereof and the miR-1537-3p miRNA or isomiRs thereof relative to a control population of subjects. Also provided herein are methods of treating brain cancer in a subject, comprising measuring an expression level of at least one mRNA biomarker selected from SYNGR3, OTX1, GABBR2, LHX1, CADM3, MLLT11, MNX1, GRB14, SLC34A2, PHYHIP, WNT10B, SLC17A6, CRLF1, HOXD13, TGFβR3, UBA7, SFRP4, or any combination thereof, in a tumor sample from a subject and administering IL-12; an immunogenic composition hTERT, WT-1, and PSMA; and an anti-PD-1 antibody to said subject if the expression level of SYNGR3, OTX1, GABBR2, LHX1, CADM3, MLLT11, MNX1, GRB14, SLC34A2, PHYHIP, WNT10B, SLC17A6, CRLF1 and HOXD13 is decreased or if the expression level of TGFβR3, UBA7, SFRP4 is increased.

Combination therapy to treat brain cancer

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

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., lung cancer). The methods of the present invention comprise administering a therapeutically effective amount of a programmed death 1 (PD-1) antagonist (e.g., an anti-PD-1 antibody), to a subject with lung cancer wherein the cancer tissue expresses PD-L1.

Anti-PD-1 antibodies for treatment of lung cancer

B-cell maturation antigen (BCMA) is expressed on malignant plasma cells. The present invention provides methods for treating multiple myeloma using bispecific antibodies (bsAbs) that bind to both BCMA and CD3 and activate T cells via the CD3 complex in the presence of BCMA-expressing tumor cells. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing BCMA.

Methods of treating multiple myeloma with bispecific anti-BCMA x anti-CD3 antibodies

Administration regimens for therapeutic proteins (e.g., T cell-activating bispecific antibodies) that mitigate cytokine release syndrome and infusion-related reaction are disclosed. The methods employ initial fractional dosing with optional administration of additional agents such as steroids or cytokine antagonists that are discontinued with maximal weekly dosing over the course of the dosing regimen.

Dosing strategy that mitigates cytokine release syndrome for therapeutic antibodies

The present invention provides methods for treating, reducing the severity, or inhibiting the growth of cancer (e.g., skin cancer). The methods of the present invention comprise administering to a subject in need thereof a therapeutically effective amount of a programmed death 1 (PD-1) antagonist (e.g., an anti-PD-1 antibody). In certain embodiments, the skin cancer is cutaneous squamous cell carcinoma or basal cell carcinoma.

Methods of treating skin cancer by administering a PD-1 inhibitor

The present invention provides methods for treating metastatic cancer comprising identifying subjects who will respond favorably to anti-VEGF therapy. According to certain aspects of the invention, subjects are identified based on their expression level of one or more predictive biomarkers. Favorable response to anti-VEGF therapy is indicated by high expression levels of certain biomarkers or by low expression levels of certain biomarkers. An exemplary predictive biomarker is VEGF-A. Also disclosed herein are prognostic biomarkers useful for identifying cancer-bearing subjects who are expected to have better relative survival outcomes.

Anti-angiogenic therapy of metastatic colorectal cancer

The present invention relates to a method (dosage regimen) for administering a CD3&#xd7;CD20 bispecific antibody to a human patient, comprising (a) administering a first dose of said antibody in a specific dosage; and consecutively (b) administering a second dose of said antibody after a period of time, wherein said second dose exceeds said first dose. The methods of the invention (and likewise the dosage regimen of the invention) are also suitable for treating B cell (CD20-positive) cancer in a human patient, or for ameliorating and/or preventing a medical condition mediated by the periodic or continued administration of a CD3&#xd7;CD20 bispecific antibody to a human patient. The present invention also relates to the use of a CD3&#xd7;CD20 bispecific antibody for the preparation of a pharmaceutical composition to be used in a method or treatment regime as defined in any one of the preceding claims. A pharmaceutical package or kit comprising the first dose, the second dose, and any subsequent doses are also part of the present invention.

Methods for tumor treatment using CD3XCD20 bispecific antibody

Non-human animals with humanized immunoglobulin loci and methods of using them in vaccine design are described, as well as methods for making broadly neutralizing antibodies against infectious agents and pathogens are provided. Non-human animals with humanized immunoglobulin loci used in B-cell-lineage immunogen design in vaccine development are provided, as are methods of carrying out such design.

B cell lineage based immunogen design with humanized animals

The present invention provides pharmaceutical compositions comprising a VEGF antagonist and an anti-CTLA-4 antibody, and methods of use thereof. The compositions and methods of the present invention are useful for the treatment of cancers and other diseases and disorders in which anti-angiogenic therapies and/or targeted immune responses may be beneficial.

Methods and compositions comprising a combination of a VEGF antagonist and an anti-CTLA-4 antibody

Predictive and prognostic biomarkers related to anti-angiogenic therapy of metastatic colorectal cancer

Methods and compositions comprising a combination of a VEGF Trap and an anti-CTLA-4 antibody

Growing community of inventors

Dobbs Ferry, NY, United States of America

Israel Lowy