Antibodies for treatment of cancer expressing claudin 6
The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLDN6, including tumor-related diseases such as ovarian cancer, lung cancer, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, malignant melanoma, head and neck cancer, sarcoma bile duct cancer, cancer of the urinary bladder, kidney cancer, colon cancer, placental choriocarcinoma, cervical cancer, testicular cancer, and uterine cancer.
1. A method of producing an antibody, or an antigen binding fragment thereof, that binds to CLDN6, the method comprising the steps of:
(a) culturing a human host cell transformed with one or more expression vectors under conditions in which the host cell expresses the antibody or antigen binding fragment thereof; and
(b) harvesting a preparation of the antibody or antigen binding fragment thereof expressed by the human host cell;
wherein the one or more expression vectors comprise:
(i) a nucleic acid sequence encoding a polypeptide comprising the antibody heavy chain CDR1, CDR2, and CDR3 regions having the amino acid sequences of positions 26-33, positions 51-58, and positions 97-106 of SEQ ID NO: 36, respectively; and a nucleic acid sequence encoding a polypeptide comprising the antibody light chain CDR1, CDR2, and CDR3 regions having the amino acid sequences of positions 27-31, positions 49-51, and positions 88-97 of SEQ ID NO: 35, respectively.
2. The method of claim 1 , wherein the antigen binding fragment is a Fab, F(ab′) 2 , Fv, or single chain Fv.
3. The method of claim 1 , wherein the human host cell is a lymphocytic cell.
4. A recombinant nucleic acid comprising:
a first nucleic acid sequence encoding a first polypeptide comprising heavy chain CDR1, CDR2, and CDR3 regions having the amino acid sequences of positions 26-33, positions 51-58, and positions 97-106 of SEQ ID NO: 36, respectively; and a second nucleic acid sequence encoding a second polypeptide comprising light chain CDR1, CDR2, and CDR3 regions have the amino acid sequences of positions 27-31, positions 49-51, and positions 88-97 of SEQ ID NO: 35, respectively.
5. A human cell expressing the first and second polypeptides encoded by the recombinant nucleic acid of claim 4 .
6. The recombinant nucleic acid of claim 4 , further comprising a third nucleic acid sequence encoding a linker for joining the first polypeptide and the second polypeptide.
7. The recombinant nucleic acid of claim 4 , wherein the first polypeptide comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 36 and the second polypeptide comprises a light chain variable region having the amino acid sequence of SEQ ID NO: 35.
8. A transformed host cell comprising one or more expression vectors, the one or more expression vectors comprising:
a first nucleic acid sequence encoding a first polypeptide comprising heavy chain CDR1, CDR2, and CDR3 regions having the amino acid sequences of positions 26-33, positions 51-58, and positions 97-106 of SEQ ID NO: 36, respectively; and a second nucleic acid sequence encoding a second polypeptide comprising light chain CDR1, CDR2, and CDR3 regions have the amino acid sequences of positions 27-31, positions 49-51, and positions 88-97 of SEQ ID NO: 35, respectively.
9. The transformed host cell of claim 8 , wherein the first polypeptide comprises a heavy chain variable region having the amino acid sequence of SEQ ID NO: 36 and the second polypeptide comprises a light chain variable region having the amino acid sequence of SEQ ID NO: 35.
10. The transformed host cell of claim 8 , wherein the host cell is a human cell.
11. The transformed host cell of claim 8 , wherein the host cell is a lymphocytic cell.
12. The transformed host cell of claim 8 , wherein the one or more expression vectors further comprise a third nucleic acid sequence encoding a linker for joining the first polypeptide and the second polypeptide.