Merus N.v.

Crucell Holland B.v.

Ono Pharmaceutical Co., Ltd.

Janssen Vaccines & Prevention B.v.

Johns Hopkins University

Institucio Catalana De Recerca I Estudis Avancats

Merus Biopharmaceuticals B.v.

Fundacio Institut De Recerca Biomedica

Koninklijke Nederlandse Akademie Van Wetenschappen

Fundacio Institut De Recerca Biomedica (Irb Barcelona)

Merus B.v.

Ocello B.v.

Mark Throsby

Cornelis Adriaan De Kruif

Ton Logtenberg

Robert Arjen Kramer

Cecilia Anna Wilhelmina Geuijen

Erwin Houtzager

Rui Daniel Pinto

Rinse Klooster

Edward Norbert Van Den Brink

Robertus Cornelis Roovers

Paulus Johannes Tacken

Shiro Shibayama

Tim Beaumont

Pieter Fokko Van Loo

John De Kruif

Tomoya Tezuka

Alexander Berthold Hendrik Bakker

David Andre Baptiste Maussang-Detaille

Cecilia A W Geuijen

Takuya Shimbo

Johannes Carolus Clevers

Adrianus Quirinus Bakker

Theodorus H J Kwaks

Theodorus Hendrikus Jacobus Kwaks

Robert Heinz Edward Friesen

Robert H E Friesen

Marja Van Meijer

Mandy Antonia Catharina Jongeneelen

Eduard Batlle

Robert Gerhardus Jacob Vries

Bram Herpers

Ada M Kruisbeek

Robert J Arceci

Wilfred T V Germeraad

Theodorus Hendrikus Kwaks

Mandy A C Jongeneelen

Cornelis A Dekruif

Ada Maria Kruisbeek

Wilfred Thomas Vincent Germeraad

Robert John Arceci

Cecilia AW Geuijen

Hergen Spits

Mark Kwakkenbos

Robert Heinz Friesen

Mandy Antonia Jongeneelen

Cecilia Anna Geuijen

An agent for preventing, suppressing the progression of symptoms of, suppressing the recurrence of or treating autoimmune diseases, comprising a bispecific antibody or an antibody fragment thereof, having a first arm specifically binding to PD-1 and a second arm specifically binding to CD19, as described herein.

Bispecific antibody

Provided are methods for efficiently and comprehensively screening antibody repertoires from B cells to obtain and produce molecules with binding characteristics and functional activities for use in human therapy.

Generation of binding molecules

The invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells. More in particular it relates to treating of cells comprising an NRG1 fusion gene comprising at least a portion of the NRG1-gene fused to a sequence from a different chromosomal location.

ERBB-2 and ERBB-3 binding bispecific antibodies for use in the treatment of cells that have an NRG1 fusion gene

The invention relates among others to antibodies comprising a first antigen-binding site that binds Erb B-2 and a second antigen-binding site that binds Erb B-3. The antibodies can typically reduce a ligand-induced receptor function of Erb B-3 on a Erb B-2 and Erb B-3 positive cell. Also described are method for the treatment and use of the antibodies in imaging and in the treatment of subjects having an Erb B-2, Erb B-3 or Erb B-2/3 positive tumor.

Antibody that binds ErbB-2 and ErbB-3

A bispecific antibody which is capable of specifically binding to PD-1 and CD3 is disclosed. The bispecific antibody is suitable for preventing, suppressing symptom progression or recurrence of, and/or treating autoimmune diseases. Also disclosed is a formulation which can reduce occurrence of adverse infusion reactions or adverse reaction called cytokine release syndrome. The bispecific antibody has the feature to allow interaction between PD-1 and PD-L1 as its ligand, contributes enhancement or duration of its effects.

The invention provides means and methods for inhibiting growth of a cancer. The means in some embodiments comprise proteins and antibodies that binds an extracellular part of a membrane associated member of the epidermal growth factor (EGF) receptor family and an extracellular part of a membrane associated member of a WNT signaling pathway. Further provided are various cells and assays that are helpful in the production of the proteins, antibodies and cells.

Binding molecules that inhibit cancer growth

The invention relates in one aspect to bispecific antibodies comprising a first antigen-binding site that binds EGFR and a second antigen-binding site that binds Erb B-3, wherein the antibody has a half maximal growth inhibitory concentration (IC50) of less than 200 pM for inhibiting EGFR and/or Erb B-3 ligand induced growth of Bx PC3 cells or Bx PC3-luc2 cells. Further described are method for producing the bispecific antibodies and means and methods for the treatment of subjects with the antibodies.

Methods of treating a subject having an EGFR-positive and/or ErbB-3-positive tumor

Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is human, human-like, or humanized. The nucleic acid is provided with a means that renders it resistant to DNA rearrangements and/or somatic hypermutations. In one embodiment, the nucleic acid comprises an expression cassette for the expression of a desired molecule in cells during a certain stage of development in cells developing into mature B cells. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.

Antibody producing non-human animals

ErbB-2 and ErbB3 binding bispecific antibodies for use in the treatment of cells that have an NRG1 fusion gene

The invention as disclosed herein relates to bispecific antibodies that comprises a first variable domain that can bind an extracellular part of epidermal growth factor receptor (EGFR) and a second variable domain that can bind an extracellular part of MET Proto-Oncogene, Receptor Tyrosine Kinase (cMET). The antibody may comprise a common light chain. It may be a human antibody. The antibody may be a full length antibody. In some embodiments the bispecific antibody is an IgG1 format antibody having an anti-EGFR, anti-cMET stoichiometry of 1:1. In some embodiment the antibody has one variable domain that can bind EGFR and one variable domain that can bind cMET.

Antibodies that bind EGFR and cMET

The disclosure provides means and methods for interfering with Programmed Cell Death 1 protein (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) mediated inhibition in a PD-1 and/or TIM-3 positive cell. A method may comprise contacting said cell with an antibody or a functional part, derivative and/or analogue thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3, thereby inhibiting PD-1 and/or TIM-3 mediated activity in said cell. The invention also provides antibodies or variants thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of TIM-3.

Bispecific anti PD1-anti TIM3 antibodies

The invention provides means and methods for interfering with Programmed Cell Death 1 protein (PD-1) and Lymphocyte activation 3 (LAG 3) mediated inhibition in a PD-1 and/or LAG3 positive cell. A method may comprise contacting said cell with an antibody or a functional part, derivative and/or analogue thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of LAG3, thereby inhibiting PD-1 and/or LAG3 mediated activity in said cell. The invention also provides antibodies or variants thereof that comprises a variable domain that can bind to an extracellular part of PD-1 and a variable domain that can bind to an extracellular part of LAG3.

Antibodies that modulate a biological activity expressed by a cell

The invention provides means and methods of stimulating activity of a member of the TNF receptor superfamily on a cell. The invention also provides binding molecules such as antibodies that comprises at least two antigen binding sites, wherein a first antigen binding site can bind an extracellular part of CD137 and a second antigen binding site can bind an extracellular part of PD-L1.

Binding molecules that bind CD137 and PD-L1

The invention provides means and methods for inhibiting a biological activity of cells. In one embodiment the invention is concerned with a method of inhibiting a biological activity in a first or second cell mediated by the binding of two membrane proteins that are binding partners for each other. The mentioned biological activity is inhibited by providing the cells with an antibody or antibody like molecule that can bind to each of the mentioned binding partners and the binding blocks the binding of the two binding partners thereby inhibiting the mentioned biological activity.

Binding molecules that modulate a biological activity expressed by a cell

Growing community of inventors

Utrecht, Netherlands

Mark Throsby