MUC1* antibodies
The present describes monoclonal antibody to MUC1*.
1. A method of inhibiting cell proliferation, comprising contacting cells expressing MUC1* with an isolated monoclonal antibody to MUC1*, which is monovalent for MUC1*, wherein the monoclonal antibody specifically binds to the amino acid sequence of SEQ ID NO:1 and has
an amino acid sequence in the heavy chain variable region in CDR1 region comprising SEQ ID NO:331, in CDR2 region comprising SEQ ID NO:334, and in CDR3 region comprising SEQ ID NO:374,
and an amino acid sequence in the light chain variable region in CDR1 region comprising SEQ ID NO:340, in CDR2 region comprising SEQ ID NO:342, and in CDR3 region comprising SEQ ID NO:344;
wherein the monoclonal antibody comprises:
in its heavy chain, a FWR1 sequence that is at least 90% identical to SEQ ID NO:362, a FWR2 sequence that is at least 90% identical to SEQ ID NO:363, or a FWR3 sequence that is at least 90% identical to SEQ ID NO:364, and
in its light chain, a FWR1 sequence that is at least 90% identical to SEQ ID NO:365, a FWR2 sequence that is at least 90% identical to SEQ ID NO:366, or a FWR3 sequence that is at least 90% identical to SEQ ID NO:367.
2. The method according to claim 1 , wherein the cells are cancer cells.
3. The method of claim 1 , wherein the monoclonal antibody comprises:
a variable heavy chain region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 11, and
a variable light chain region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 13.
4. The method of claim 1 , wherein the monoclonal antibody is monovalent, an Fab, or a single chain variable fragment antibody (scFv).
5. The method of claim 4 , wherein the Fab comprises a heavy chain region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 47 and/or a kappa chain region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 48.
6. The method of claim 1 , wherein the monoclonal antibody is bi-valent, bi-specific, or tri-specific.
7. The method of claim 6 , wherein a portion of the monoclonal antibody binds to MUC1* and another portion binds to a tumor-specific antigen on a cell surface.
8. The method of claim 1 , wherein the monoclonal antibody is fused to a label, a tag, a toxin, a radioactive substance, a targeting motif a leader sequence peptide, a toxic material, a protein, or a peptide.
9. The method of claim 8 , wherein the protein is a toxin, or a cytokine.
10. The method of claim 3 , wherein the monoclonal antibody is monovalent, an Fab, or a single chain variable fragment antibody (scFv).
11. The method of claim 10 , wherein the Fab comprises a heavy chain region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 47 and/or a kappa chain region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 48.
12. The method of claim 3 , wherein the monoclonal antibody is bi-valent, bi-specific, or tri-specific.
13. The method of claim 12 , wherein a portion of the monoclonal antibody binds to MUC1* and another portion binds to a tumor-specific antigen on a cell surface.
14. The method of claim 3 , wherein the monoclonal antibody is fused to a label, a tag, a toxin, a radioactive substance, a targeting motif, a leader sequence peptide, a toxic material, a protein, or a peptide.
15. The method of claim 14 , wherein the protein is a toxin, or a cytokine.
16. The method of claim 1 , wherein
the amino acid sequence in the heavy chain variable region in CDR1 region consists of SEQ ID NO:331, in CDR2 region consists of SEQ ID NO:334, and in CDR3 region consists of SEQ ID NO:374, and
the amino acid sequence in the light chain variable region in CDR1 region consists of SEQ ID NO:340, in CDR2 region consists of SEQ ID NO:342, and in CDR3 region consists of SEQ ID NO:344.
17. The method of claim 3 , wherein
the amino acid sequence in the heavy chain variable region in CDR1 region consists of SEQ ID NO:331, in CDR2 region consists of SEQ ID NO:334, and in CDR3 region consists of SEQ ID NO:374, and
the amino acid sequence in the light chain variable region in CDR1 region consists of SEQ ID NO:340, in CDR2 region consists of SEQ ID NO:342, and in CDR3 region consists of SEQ ID NO:344.