Recombinant monoclonal antibodies and corresponding antigens for colon and pancreatic cancers

Inventors

Bristol, J. Andrew • Kantor, Judith A.

Assignees

Precision Biologics Inc

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Publication Number

US-11401341-B2

Patent

Publication Date

2022-08-02

Expiration Date


Abstract

The present invention provides for recombinant monoclonal antibodies that bind to human colorectal and pancreatic carcinoma-associated antigens, along with nucleic acid sequences encoding the antibody chains, and the amino acid sequences corresponding to the nucleic acids, and uses for these antibodies, nucleic acids and amino acids.

Core Innovation

The invention relates to recombinant monoclonal antibodies that bind 16C3 CPAA, including antibody and antigen-binding fragment formats. The disclosed antibody binding specificity is based on defined CDR amino acid sequences for the light chain and heavy chain, and also includes antibodies defined by complete variable region amino acid sequences.

Nucleic acids encoding the corresponding light and heavy chain CDRs or variable region sequences are expressed in a cell to produce an antibody or an antigen-binding fragment that binds the 16C3 CPAA. The disclosed formats include recombinant antibody embodiments such as chimeric and humanized variants, and constant-region configurations including IgG1 and specific constant regions such as gamma-1 and kappa-1.

The invention further characterizes and supports CPAA antigen binding using epitope behavior and tissue binding specificity, including immunohistochemistry specificity in tumor versus normal tissues. In addition, functional activity is supported by ADCC cytotoxicity described for both murine and humanized formats, and the document describes mapping of epitopes or peptide concepts associated with CPAA, including a cancer vaccine concept based on epitope/peptide mapping.

Claims Coverage

The provided material includes two independent claims, each directed to a method of producing an antibody or antigen-binding fragment that binds the 16C3 CPAA. Across these claims, the core inventive features are centered on the use of defined nucleic-acid-encoded light-chain and heavy-chain sequence regions, including CDR-specific sequences and variable-region sequences.

Cdr-defined light and heavy chain encoding for 16C3 CPAA binding

A method of producing an antibody or an antigen-binding fragment thereof that binds the 16C3 CPAA by expressing in a cell nucleic acid(s) that encode a light chain comprising specified CDR1, CDR2, and CDR3 amino acid sequences and a heavy chain comprising specified CDR1, CDR2, and CDR3 amino acid sequences.

Variable-region sequence encoding for 16C3 CPAA binding

A method of producing an antibody or an antigen-binding fragment thereof that binds the 16C3 CPAA by expressing in a cell nucleic acid(s) that encode the antibody variable region light chain region amino acid sequence contained in SEQ ID NO: 28 and the antibody variable region heavy chain region amino acid sequence contained in SEQ ID NO: 29.

Claim coverage is focused on producing CPAA-binding antibodies through specified sequence definitions encoded in nucleic acids. One independent claim defines binding through explicit CDR amino acid sequences for both light and heavy chains, while the other independent claim defines binding through specified variable region light and heavy sequences. Dependent claims further constrain antibody forms and constant-region compositions within these sequence-defined production methods.

Stated Advantages

Not explicitly described in patent.

Documented Applications

Diagnostic use is described, including immunoassays, immunohistochemistry, and immunometric/sandwich assays using the CPAA-binding antibodies.

Therapeutic use is described, including tumor regression or cell death and ADCC-associated cytotoxicity with murine and humanized formats.

A cancer vaccine concept is described based on epitope/peptide mapping of CPAA.

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