Merus N.v.

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Crucell Holland B.v.

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Institucio Catalana De Recerca I Estudis Avancats

Merus Biopharmaceuticals B.v.

Merus Biopharmaceuticals, B.v.i.o.

Fundacio Institut De Recerca Biomedica

Koninklijke Nederlandse Akademie Van Wetenschappen

Fundacio Institut De Recerca Biomedica (irb Barcelona)

Ocello B.v.

Ton Logtenberg

Cornelis Adriaan De Kruif

Mark Throsby

Erwin Houtzager

Linda Johanna Aleida Hendriks

Cecilia Anna Wilhelmina Geuijen

Rui Daniel Pinto

Abraham Bout

Robert Arjen Kramer

Hendricus Renerus Jacobus Mattheus Hoogenboom

Alexander Berthold Hendrik Bakker

Rinse Klooster

Paulus Johannes Tacken

Robertus Cornelis Roovers

John De Kruif

Patrick H C Van Berkel

Ronald Hendrik Brus

Pieter Fokko Van Loo

Ronald Hendrik Peter Brus

David Andre Baptiste Maussang-Detaille

Patricius H C Van Berkel

Leon W M M Terstappen

Leon W Terstappen

Johannes Carolus Clevers

Ronald H P Brus

Eduard Batlle

Bram Herpers

Robert Gerhardus Jacob Vries

Patricius Hendrikus Van Berkel

Cornelis A Dekruif

Hendricus Renerus Hoogenboom

Ronald Hendrik Pieter Brus

Patrick Hendrikus Cornelis Van Berkel

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

The invention provides means and methods for producing one or more Ig-like molecules in a single host cell. Novel CH3 mutations enabling the production of monospecific and/or bispecific Ig-like molecules of interest are also provided.

Methods and means for the production of Ig-like molecules

Bispecific IgG antibodies which bind to CLEC12A and an antigen on an immune effector cell are provided.

Bispecific IgG antibodies as T cell engagers

The invention relates to a multivalent antibody which comprises: a base antibody portion which comprises two binding domains; and at least one additional binding domain, wherein the base antibody portion is connected by a linker to the at least one additional binding domain, wherein each binding domain of the base antibody portion and each of the at least one additional binding domains all have a common variable region, and wherein the linker comprises a hinge sequence or a sequence derived from a hinge sequence. The invention also relates to a multivalent antibody which comprises: a base antibody portion which comprises two binding domains; and at least one additional binding domain, wherein at least one additional binding domain comprises a CH1 region and is connected to the base antibody portion by said linker, linking a variable region of the base antibody portion and the CH1 region, and wherein the multivalent antibody binds to at least three different epitopes.

Multivalent antibody

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

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

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

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

Growing community of inventors

Utrecht, Netherlands

Ton Logtenberg