Recombinant monoclonal antibodies and corresponding antigens for colon and pancreatic cancers
Inventors
Bristol, J. Andrew • Kantor, Judith A.
Assignees
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Publication Number
US-11952429-B2
Publication Date
2024-04-09
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 document discloses recombinant monoclonal antibody 16C3 that binds CPAA (colorectal and pancreatic carcinoma-associated antigen) for colon and pancreatic cancer. It defines antibody variable region light-chain and heavy-chain complementarity determining regions (CDR1, CDR2, and CDR3) using specific amino-acid residue sequences and corresponding SEQ ID options. The antibody variable regions are provided as nucleic acids encoding the defined light and heavy chain regions, including associated complementary sequences.
The disclosure further provides antibody variants described as humanized antibody variants, including ven16C3, cdr16C3, abb16C3, sdr16C3, fra16C3, and H16C3-Abb*. It also describes nucleic acid molecules and antibody variable region constructs that correspond to these CDR-defined regions, including designs that preserve the specified CDR residue sets. Related embodiments include isolated nucleic acid molecules selected from defined SEQ ID NOs and their complementary sequences.
The document additionally provides expression-linked embodiments for the nucleic acids encoding the CPAA-binding antibody variable regions, including the use of vectors and host cells for expression of the encoded antibody components. Specific host-cell containment is described, including CHO cells. The disclosure is supported by binding and specificity assessments and includes mention of antibody-dependent cellular cytotoxicity (ADCC) activity, together with described diagnostic and therapeutic use cases for CPAA.
Claims Coverage
The provided independent claims focus on three core inventive subject matters: (i) isolated nucleic acid molecules defined by selection from particular SEQ ID NOs and their complementary sequences, (ii) isolated nucleic acid molecules encoding an antibody variable region light chain with defined CDR1/CDR2/CDR3 amino-acid residue options, and (iii) isolated nucleic acid molecules encoding an antibody variable region heavy chain with defined CDR1/CDR2/CDR3 amino-acid residue options. A further dependent coverage specifies expression contexts (genetic regions directing expression), vector containment, and particular host-cell containment such as CHO cells.
Selected isolated nucleic acid sequence set
An isolated nucleic acid molecule selected from the group consisting of a nucleic acid molecule with the nucleic acids of SEQ ID NO:12, a nucleic acid molecule with the complementary sequence of SEQ ID NO:12, a nucleic acid molecule with the sequence of SEQ ID NO:13, and the complementary sequence of SEQ ID NO:13.
CDR-defined antibody variable region light chain encoding
An isolated nucleic acid molecule that encodes an antibody variable region light chain comprising a complementarity determining region (CDR) 1 comprising the amino acid residues GASENIYGALN (SEQ ID NO:1) or QASENIYGALN (SEQ ID NO:4); a CDR2 comprising the amino acid residues GASNLAD (SEQ ID NO:2) or GASNLAT (SEQ ID NO:5); and a CDR3 comprising the amino acid residues QNVLSSPYT (SEQ ID NO:3) or QQVLSSPYT (SEQ ID NO:6).
CDR-defined antibody variable region heavy chain encoding
An isolated nucleic acid molecule that encodes an antibody variable region heavy chain comprising a CDR1 comprising the amino acid residues GYTFTDYAMH (SEQ ID NO:7); a CDR2 comprising the amino acid residues LISTYSGDTKYNQNFKG (SEQ ID NO:8) or LISTYSGDTKYNQKFQG (SEQ ID NO:10) or LISTYSGDTKYSQKFQG (SEQ ID NO:30); and a CDR3 comprising the amino acid residues GDYSGSRYWFAY (SEQ ID NO:9) or GDYSGSRYWFAY (SEQ ID NO:11).
Across the independent claims, the nucleic acid scope is anchored by selection from specific SEQ ID-defined sequences or by nucleic acids encoding antibody variable region light-chain or heavy-chain CDRs defined by particular amino-acid residue options. Dependent claims further add genetic regions configured to direct expression and specify vector and host-cell containment, including CHO cells.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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