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AssigneeCancer Research Institute of Contra Costa
InventorsFernando J. R. do Couto, Roberto L. Ceriani, Jerry A. Peterson
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The present invention provides recombinant peptides that specifically and selectively bind to the human milk fat globule (HMFG) antigen, BA46. In particular, the present invention provides recombinant variants of the Mc3 antibody, including humanized versions of Mc3. The variant Mc3 peptides are particularly useful for diagnostic, prognostic, and therapeutic applications in the field of breast cancer. The present invention also provides methods for the humanization of antibodies such as murine monoclonal antibodies. The novel humanization methods are applied to the production of humanized Mc3 antibodies and it is shown that these humanized antibodies retain the ability to engage in high affinity binding to their cognate antigen. Such humanization enables the use of these antibodies for immunodiagnostic and immunotherapeutic applications in humans.
A modified Mc3 antibody that binds to BA46 antigen of human milk fat globule (HMFG) wherein the sequence of the parent Mc3 heavy chain variable region is SEQ ID NO. 76 and the sequence of the parent Mc3 light chain variable region is SEQ ID NO. 79, said antibody comprising both a light chain variable region and a heavy chain variable region, wherein at least one variable region is selected from the group consisting of a humanized Mc3 heavy chain variable region and a humanized Mc3 light chain variable region, wherein said at least one variable region is humanized in a region that is neither contained in a CDR, nor in contact with a CDR, nor in contact with an opposing variable region of Mc3 antibody, and wherein said antibody when introduced into an individual with cells expressing BA46, targets the BA46-expressing cells.
A modified Mc3 antibody that binds to BA46 antigen of human milk fat globule (IIMFG) wherein the sequence of the parent Mc3 heavy chain variable region is SEQ ID NO. 76 and the sequence of the parent Mc3 light chain variable region is SEQ ID NO. 79, said antibody comprsing both a light chain variable region and a heavy chain variable region, wherein at least one variable region is selected from the group consisting of a humanized Mc3 heavy chain variable region and a humanized Mc3 light chain variable region, wherein said humanized Mc3 heavy chain variable region is an Mc3 heavy chain variable region comprising at least one amino acid that has been substituted with a different amino acid in the corresponding position from a human heavy chain variable region consensus sequence, and said humanized Mc3 light chain variable region is an Mc3 light chain variable region comprising at least one amino acid that has been substituted with a different amino acid in the corresponding position from a human light chain variable region consensus sequence, wherein the sequence of the human heavy chain variable region consensus sequence is the sequence in SEQ ID NO. 77, and the scquence of the human light chain variable region consensus sequence is the sequence in SEQ ID NO. 80, and wherein said at least one amino acid that has been substituted is neither contained in a CDR, nor in contact with a CDR, nor in contact with an opposing variable region of Mc3 antibody.
Dependencies are inferred from the claim text.