Humanised anti kallikrein-2 antibody
The present invention provides antibody polypeptides with binding specificity for human kallikrein-2 (hK2), wherein the antibody polypeptide comprises (a) a heavy chain variable region comprising the amino acid sequences of SEQ ID NO: 1 and SEQ ID NO: 2 and SEQ ID NO: 3 and/or (b) a light chain variable region comprising the amino acid sequences of SEQ ID NO: 4 and SEQ ID NO: 5 and SEQ ID NO: 6, and wherein the heavy chain variable region and light chain variable region comprise framework amino acid sequences from one or more human antibodies. The invention further provides use of said antibody polypeptides in the diagnosis and treatment of prostate cancer.
1. An antibody polypeptide with binding specificity for human kallikrein-2 (hK2), wherein the antibody polypeptide comprises
(a) a heavy chain variable region comprising the amino acid sequences of SEQ ID NO:1 and SEQ ID NO:2 and SEQ ID NO:3; and
(b) a light chain variable region comprising the amino acid sequences of SEQ ID NO:4 and SEQ ID NO:5 and SEQ ID NO:6,
wherein the heavy chain variable region and light chain variable region comprise framework amino acid sequences from one or more human antibodies, and
wherein the antibody polypeptide is an intact IgG antibody.
2. An antibody polypeptide according to claim 1 wherein the antibody polypeptide exhibits an enhanced therapeutic ratio compared to the murine 11B6 antibody.
3. An antibody polypeptide according to claim 1 comprising a heavy chain variable region which comprises the amino acid sequence of SEQ ID NO: 8 and a light chain variable region which comprises the amino acid sequence of SEQ ID NO: 9.
4. An antibody polypeptide according to claim 1 comprising a heavy chain constant region which comprises the amino acid sequence of SEQ ID NO: 10 and a light chain constant region which comprises the amino acid sequence of SEQ ID NO: 11.
5. An antibody polypeptide according to claim 1 comprising a heavy chain which consists of the amino acid sequence of SEQ ID NO: 12 and a light chain which consists of the amino acid sequence of SEQ ID NO: 13.
6. An antibody polypeptide according to claim 1 wherein the antibody polypeptide is linked, directly or indirectly, to a therapeutic moiety.
7. An antibody polypeptide according to claim 6 wherein the therapeutic moiety is a cytotoxic moiety that comprises one or more radioisotopes.
8. An antibody polypeptide according to claim 6 wherein the therapeutic moiety is a cytotoxic moiety that comprises one or more cytotoxic drugs.
9. An antibody polypeptide according to claim 1 wherein the antibody polypeptide further comprises a detectable moiety.
10. An antibody polypeptide according to claim 9 wherein the detectable moiety comprises a radioisotope.
11. An antibody polypeptide according to claim 10 wherein the radioisotope is capable of simultaneously acting in a multi-modal manner as a detectable moiety and also as a cytotoxic moiety.
12. A pharmaceutical composition comprising an antibody polypeptide according to claim 1 and a pharmaceutically acceptable excipient, diluent or carrier.
13. A method for the treatment or diagnosis of prostate cancer in a patient, the method comprising the step of administering an effective amount of an antibody polypeptide according to claim 1 .
14. A method according to claim 13 wherein the prostate cancer to be treated is non-localised prostate cancer.
15. A method according to claim 13 wherein the prostate cancer to be treated is metastatic prostate cancer.
16. A method according to claim 15 wherein the metastatic prostate cancer to be treated is metastases of the lymph system; metastases of the bone; or metastasis within the pelvis, rectum, bladder or urethra.
17. A method according to claim 13 wherein the prostate cancer to be treated is castration-resistant prostate cancer (CRPC).
18. A method according to claim 13 wherein radioguided surgery is performed on the patient following administration of the antibody polypeptide in order to remove prostate cancer cells.