Crucell Holland B.v.

Merus N.v.

Merus B.v.

Janssen Vaccines & Prevention B.v.

Cornelis Adriaan De Kruif

Mark Throsby

Ton Logtenberg

Robert Arjen Kramer

Linda Johanna Aleida Hendriks

Erwin Houtzager

Cecilia Anna Wilhelmina Geuijen

Edward Norbert Van Den Brink

Rui Daniel Pinto

Alexander Berthold Hendrik Bakker

Rinse Klooster

Paulus Johannes Tacken

Willem Egbert Marissen

Jaap Goudsmit

Cecilia A W Geuijen

Adrianus Quirinus Bakker

Robertus Cornelis Roovers

Jan Henrik Ter Meulen

Jan H Ter Meulen

Alexander Berthold Bakker

Cecilia Anna Geuijen

Cecilia AW Geuijen

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

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

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 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

Described are transgenic, non-human animals comprising a nucleic acid encoding an immunoglobulin light chain, whereby the immunoglobulin light chain is a common human, human-like, or humanized light chain. Further provided is methods for producing an immunoglobulin from the transgenic, non-human animal.

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De Bilt, Netherlands

Cornelis Adriaan De Kruif