Antibodies that bind cell-associated CA 125/O772P
The present invention provides antibodies, and antigen-binding fragments of antibodies, fusion polypeptides and analogs that preferentially bind cell-associated CA 125/O772P polypeptides relative to shed CA 125/O772P polypeptides. The present invention further provides methods of preventing, managing, treating or ameliorating one or more symptoms associated with a CA 125/O772P-related disorder. In particular, the present invention provides methods of preventing, managing, treating, or ameliorating one or more symptoms associated with a cell proliferative disorder, such as cancer, e.g., ovarian cancer. The present invention still further provides methods for diagnosing a CA 125/O772P-related disorder or predisposition to developing such a disorder, as well as methods for identifying antibodies, and antigen-binding fragments of antibodies, that preferentially bind cell-associated CA 125/O772P polypeptides relative to shed CA 125/O772P polypeptides.
1. An isolated monoclonal antibody, or an antigen-binding antibody fragment, that binds cell-associated CA 125/O772P polypeptide and comprises (a) a VH CDR1 sequence of SEQ ID NO:21, (b) a VH CDR2 sequence of SEQ ID NO:22, (c) a VH CDR3 sequence of SEQ ID NO:23, (d) a VL CDR1 sequence of SEQ ID NO:24, (e) a VL CDR2 sequence of SEQ ID NO:25, and (f) a VL CDR3 sequence of SEQ ID NO:26, wherein the sequence of (a)-(e) and (f) has less than 4 conservative substitutions.
2. The antibody or antigen-binding antibody fragment of claim 1 , wherein the sequence of (a)-(e) and (f) has less than 3 conservative substitutions.
3. The antibody or antigen-binding antibody fragment of claim 1 , which comprises (a) a VH CDR1 sequence of SEQ ID NO:21, (b) a VH CDR2 sequence of SEQ ID NO:22, (c) a VH CDR3 sequence of SEQ ID NO:23, (d) a VL CDR1 sequence of SEQ ID NO:24, (e) a VL CDR2 sequence of SEQ ID NO:25, and (f) a VL CDR3 sequence of SEQ ID NO:26.
4. The antibody or antigen-binding antibody fragment of claim 1 , which is humanized.
5. The antibody or antigen-binding antibody fragment of claim 3 , which humanized.
6. The antibody of claim 1 , wherein the antibody is an IgG class antibody.
7. The antibody of claim 6 , wherein the antibody is an IgG 1 isotype.
8. The antibody of claim 1 , wherein the antibody is a chimeric monoclonal antibody.
9. The antibody of claim 1 , wherein the antibody comprises a Cγ1 constant region.
10. The antibody of claim 1 , wherein the antibody comprises a Cγ4 constant region.
11. The antibody or antigen-binding antibody fragment of claim 1 , which is conjugated to a cytotoxic agent.
12. The antibody or antigen-binding antibody fragment of claim 11 , wherein the cytotoxic agent is a radioisotope.
13. The antibody or antigen-binding antibody fragment of claim 12 , wherein the radioisotope is selected from the group consisting of 125 I, 131 I, 111 In, 99m Tc, and 90 Y.
14. A pharmaceutical composition comprising the antibody or an antigen-binding antibody fragment of claim 1 and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising the antibody or an antigen-binding antibody fragment of claim 11 and a pharmaceutically acceptable carrier.