Variants of humanized anti carcinoma monoclonal antibody cc49
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsSyed V. S. Kashmiri, Eduardo A. Padlan, Jeffrey Schlom
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Abstract
The invention is directed towards mouse-human chimeric variants of CC49 monoclonal antibodies with minimal murine content. A first aspect of the invention provides CDR variants of humanized monoclonal antibody (HuCC49) in which less than all six (three heavy chain and three light chain) Complementarity Determining Regions (CDRs) of CC49 are present. A second aspect of the invention provides SDR variants of humanized monoclonal antibody (HuCC49) in which only Specificity Determining Regions (SDRs) of at least one CDR from CC49 are present. The invention is also directed towards biotechnological methods of making the variants and therapeutic methods of using the variants.
Claims47
A humanized anti-TAG-72 CC49 antibody comprising:
- a light chain Complementarity Determining Region (L-CDR)1, a L-CDR2, and a L-CDR3;
- and a heavy chain Complementarity Determining Region (H- CDR) I, a H-CDR2, and a H-CDR3,
- wherein L-CDR3, H-CDR1, H-CDR2 and H-CDR3 comprise murine monoclonal CC49 antibody Complementarity Determining Regions (CDRs) and at least one of L-CDR1 and L-CDR2 are a human monoclonal LEN antibody L-CDR1 and L-CDR2,
- wherein the humanized CC49 antibody retains binding affinity for TAG-72 and has reduced immunogenicity, as compared to a parental humanized CC49 antibody.
A humanized anti-TAG-72 CC49 antibody comprising:
- a light chain Complementarity Determining Region (L-CDR) 1, a L- CDR2, and a L-CDR3;
- and a heavy chain Complementarity Determining Region (H- CDR)1, a H-CDR2, and a H-CDR3,
- wherein L-CDR3, H-CDR1, H-CDR2 and H-CDR3 are of a murine CC49 monoclonal antibody, and L-CDR1 and L-CDR are of a human monoclonal LEN antibody L-CDR1 and L-CDR2 respectively, and wherein at least one amino acid at position 60, 61, 62, or 64 in the murine CC49H-CDR2 is replaced with an amino acid at a corresponding position in the human monoclonal 21/28′CL antibody,
- wherein the humanized CC49 antibody retains binding affinity for TAG-72 and has reduced immunogenicity, when compared to a parental humanized CC49 antibody.
A humanized anti-TAG-72 CC49 antibody comprising:
- a light chain Complementarity Determining Region (L-CDR)1, a L- CDR2, and a L-CDR3;
- and a heavy chain Complementarity Determining Region (H- CDR)1, a H-CDR2, and a H-CDR3,
- wherein L-CDR3, H-CDR1, H-CDR2 and H-CDR3 are of a murine CC49 monoclonal antibody, and L-CDR1 and L-CDR2 are of a human monoclonal LEN antibody L-CDR1 and L-CDR respectively, and wherein a threonine at position 97 in the murine CC49 L-CDR3 is replaced with a serine,
- wherein the humanized CC49 antibody retains binding affinity for TAG-72 and has reduced immuunogenicity, when compared to a parental humanized CC49 antibody.
The humanized antibody of claim wherein both L-CDR1 and L-CDR2 are human monoclonal LEN antibody L-CDR1 and L- CDR2, respectively.
A humanized anti-TAG-72 CC49 antibody comprising:
- a light chain Complementarity Determining Region (L-CDR)1, a L- CDR2, and a L-CDR3;
- and a heavy chain Complementarity Determining (H-CDR)1, a H-CDR2, and a H-CDR3,
- wherein L-CDR3, H-CDR1, H-CDR2 and H-CDR3 are of a murine CC49 antibody and L-CDR1 and L-CDR2 are of a human monoclonal LEN antibody L-CDR1 and L-CDR2 respectively, and
- wherein (1) a threonine is at position 94 in the L-CDR3, or (2) a serine is at position 97 in the L-CDR3, or (3) a threonine is at position 94 and a serine is at position 97 in the L-CDR3,
- wherein the humanized CC49 antibody retains binding affinity for TAG-72 and has reduced immunogenicity, when compared to a parental humanized CC49 antibody.
A humanized anti-TAG-72 CC49 antibody comprising:
- a light chain Complementarity Determining Region (L-CDR1), a L- CDR2, and a L-CDR3;
- and a heavy chain Complementarity Determining (H-CDR)1, a H-CDR2, and a H-CDR3.
- wherein L-CDR3. H-CDR1. H-CDR2 and H-CDR3 are of a murine CC49 antibody and L-CDR1 and L-CDR2 are of a human monoclonal LEN antibody L-CDR1 and L-CDR2 respectively, and
- wherein a threonine is at position 94 in the L-CDR3,
- wherein the humanized CC49 antibody retains binding affinity for TAG-72 and has reduced immunogenicity, when compared to a parental humanized CC49 antibody.
The humanized antibody of claim, wherein the human L-CDR2 comprises an amino acid sequence as set forth in SEQ ID NO:
- 8.
Dependencies are inferred from the claim text.