Utrecht, Netherlands
Utrecht, Netherlands

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Patent
Merus N.V. | Date: 2015-02-27

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.


Patent
Merus N.V. | Date: 2017-01-11

The present disclosure relates to human CD3 binding antibodies comprising a heavy chain and light chain wherein said heavy chain comprises a variable region that comprises the amino acid sequence: QVQLV QSGGG VVQPG RSLRL SCVAS GFTFS SYGMH WVRQA PGKGL EWVAA IWYX _(1) X _(2) RKQDY ADSVK GRFTI SRDNS KNTLY LQMNS LRAED TAVYY CTRGT GYNWF DPWGQ GTLVT VSS with 0-5 amino acid insertions, deletions, substitutions, additions or a combination thereof , The disclosure also relates to bispecific antibodies that have a heavy chain as defined herein above. Methods of production of the antibody, cells producing the antibody and with (medical) uses of the antibody are provided.


Colorectal cancer (CRC) was diagnosed in 1.23 million people worldwide (EU 333,000) in 2008 and 608,000 (EU 148,000) died of the disease. While some new treatments have been advanced in CRC many have failed clinical testing; metastatic CRC is still largely incurable. In CRC, Cancer Stem Cells (CSC) are responsible for tumour progression and resistant to standard chemotherapies. The Wnt signal transduction cascade controls normal colon physiology but also CSC maintenance. Deregulation of Wnt and other mitogenic pathways results in formation of aggressive tumours with metastatic potential. Novel combinatorial drugs targeting CSCs are required to address signalling redundancy and subvert resistance and escape mechanisms. However to test them effectively better drug screening tools must be developed. The high failure rate in cancer drug research has been linked to the poor predictive capacity of drug screening models for cancer and the inability to select the right patients for treatment. In SUPPRESSTEM, novel antibody-based therapeutics will be designed to modulate the Wnt pathway externally in combination with mitogenic receptors resulting in specific inhibition of CSCs with minimal toxicity on healthy tissue. The likelihood of clinically translating these goals will be enhanced because testing will be performed on relevant human patient material (both tumour and normal) using organoid technology and novel imaging readouts. In depth analysis of the phenotype of responsive organoids (patient material) will be used to identify a lead product. Successful execution of SUPPRESSTEM will provide an innovative drug product and drug screening tool ready for clinical validation that ultimately will increase the life expectancy and quality of cancer patients. Funding of SUPPRESSTEM will enable three research-focused SMEs to establish an innovative drug discovery paradigm with broad application in the cancer drug development.


Patent
Merus B.V. | Date: 2015-09-16

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.


Patent
Merus N.V. | Date: 2016-07-08

The invention is among others concerned with human CD3 binding antibodies comprising a heavy chain and light chain wherein said heavy chain comprises a variable region that comprises the amino acid sequence: QVQLV QSGGG VVQPG RSLRL SCVAS GFTFS SYGMH WVRQA PGKGL EWVAA IWYX_(1)X_(2)RKQDY ADSVK GRFTI SRDNS KNTLY LQMNS LRAED TAVYY CTRGT GYNWF DPWGQ GTLVT VSS with 0-5 amino acid insertions, deletions, substitutions, additions or a combination thereof at one or more positions other than the position indicated by X_(1)X_(2); wherein X_(1)=N and X_(2)=A; X_(1)=N and X_(2)=T; X_(1)=S and X_(2)=G; X_(1)=H and X_(2)=G; X_(1)=D and X_(2)=G; or X_(1)=H and X_(2)=A. The invention is also concerned with bispecific antibodies that have a heavy chain as defined herein above. The invention is also concerned with methods of production of the antibody, cells producing the antibody and with (medical) uses of the antibody.


Patent
Merus B.V. | Date: 2014-04-30

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.


Patent
Merus B.V. | Date: 2014-04-29

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.


Patent
Merus N.V. | Date: 2016-04-04

Provided is methods for producing mixtures of antibodies from a single host cell clone, wherein, a nucleic acid sequence encoding a light chain and nucleic acid sequences encoding different heavy chains are expressed in a recombinant host cell. The recombinantly produced antibodies in the mixtures according to the invention suitably comprise identical light chains paired to different heavy chains capable of pairing to the light chain, thereby forming functional antigen-binding domains. Mixtures of the recombinantly produced antibodies are also provided by the invention. Such mixtures can be used in a variety of fields.


Patent
Merus B.V. | Date: 2015-12-18

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.


Described are combinations of specific binding proteins, such as immunoglobulins, that are designed to be true combinations, essentially all components of the combination being functional and compatible with each other. Further provided are methods for producing a composition comprising at least two different proteinaceous molecules comprising paired variable regions, the at least two proteinaceous molecules having different binding specificities, comprising paired variable regions, at least two proteinaceous molecules having different binding specificities, comprising contacting at least three different variable regions under conditions allowing for pairing of variable regions and harvesting essentially all proteinaceous molecules having binding specificities resulting from the pairing.

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