Monoclonal antibodies against HER2 epitope and methods of use thereof
Inventors
Bodyak, Natalya D. • DeVit, Michael J. • Krauland, Eric M. • Lowinger, Timothy B. • Park, Peter U. • Prinz, Bianka • Yurkovetskiy, Aleksandr V.
Assignees
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Publication Number
US-11518812-B2
Publication Date
2022-12-06
Expiration Date
Abstract
This invention provides fully human monoclonal antibodies that recognize HER2. The invention further provides methods of using such monoclonal antibodies in a variety of therapeutic, diagnostic, and prophylactic indications.
Core Innovation
The invention relates to a method of identifying an antibody or antigen binding fragment thereof that binds a human HER2 receptor at a defined epitope. The method uses a first antibody or antigen binding fragment comprising specified variable heavy chain and variable light chain CDR sequences, immobilized on a solid substrate, and an immobilized HER2 receptor polypeptide. A second antibody or antigen binding fragment is contacted with the immobilized HER2 receptor polypeptide, and competitive binding with the first antibody is used as the indicator of epitope binding.
When the second antibody competes for binding to the HER2 receptor with the first antibody, it indicates that the second antibody binds the human HER2 receptor at the defined epitope. The first antibody comprises variable heavy chain CDR1, CDR2, and CDR3 sequences FTFSSYSMN, YISSSSSTIYYADSVKG, and GGHGYFDL, and variable light chain CDR1, CDR2, and CDR3 sequences RASQSVSSSYLA, GASSRAT, and QQYHHSPLT. Competition-based determination is presented as the defining criterion linking the second antibody’s behavior to epitope binding.
Claims Coverage
The independent claim is directed to an identification method in which competition between a second antibody and a first HER2-binding antibody indicates whether the second antibody binds a human HER2 receptor at a defined epitope. The inventive features center on an immobilized HER2 receptor polypeptide, a first antibody with specified CDR sequences on a solid substrate, and determining competition to infer defined epitope binding by the second antibody.
Competitive epitope identification by antibody binding competition
A method comprising contacting an immobilized HER2 receptor polypeptide with a first antibody or antigen binding fragment having specified CDR sequences, and a second antibody or antigen binding fragment, and determining whether the second antibody competes for binding to HER2 receptor with the first antibody, wherein competition indicates that the second antibody binds the human HER2 receptor at a defined epitope.
Defined first antibody CDR sequences
The first antibody or antigen binding fragment comprises variable heavy chain CDR1, CDR2, and CDR3 amino acid sequences FTFSSYSMN, YISSSSSTIYYADSVKG, and GGHGYFDL, and variable light chain CDR1, CDR2, and CDR3 amino acid sequences RASQSVSSSYLA, GASSRAT, and QQYHHSPLT.
Coverage centers on a competition-based method that uses a first antibody with specified CDR sequences to identify a second antibody that binds the human HER2 receptor at a defined epitope through competitive binding behavior.
Stated Advantages
Enables identification of a second antibody or antigen binding fragment that binds a human HER2 receptor at a defined epitope based on competition with a first HER2-binding antibody.
Documented Applications
Identifying a second antibody or antigen binding fragment that binds a human HER2 receptor at a defined epitope through competition with a first HER2-binding antibody.
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