Antibodies that specifically bind to the EphA2 receptor

1. A conjugate of an antibody or an epitope-binding fragment thereof, wherein said conjugate specifically binds to an EphA2 receptor, said conjugate comprising at least one heavy chain and at least one light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 12 and the light chain comprises the amino acid sequence of SEQ ID NO: 14, wherein said conjugate further comprises a cytotoxic agent.

2. The conjugate of claim 1 , wherein the cytotoxic agent is a maytansinoid.

3. The conjugate of claim 2 , wherein the cytotoxic agent and the antibody or epitope-binding fragment thereof are covalently bound to each other.

4. The conjugate of claim 1 , wherein the cytotoxic agent is of formula (XIII):

5. The conjugate of claim 1 , wherein the cytotoxic agent is of formula (XIV):

6. The conjugate of claim 1 , wherein the cytotoxic agent is of formula (XXIV):

7. The conjugate of claim 1 , wherein the cytotoxic agent is of formula (XXV):

8. The conjugate of claim 1 , wherein the cytotoxic agent is of formula (XXVI):

9. The conjugate of claim 1 , wherein the cytotoxic agent is of formula (XXVII):

10. The conjugate of claim 1 having an average DAR above 4, the DAR being measured with a UV spectrophotometer and determined by the following equation

DAR= C D /C A

with:

C D =[(ε A280 ×A 252 )−(ε A252 ×A 280 )]/[(ε D252 ×ε A280 )−(ε A252 ×ε D280 )]

C A =[ A 280 −(C D ×ε D280 )]/ε A280

ε D252 =26,159 M −1 cm −1

ε D280 =5,180 M −1 cm −1

ε A280 =224,000 M −1 cm −1

ε A252 =82,880 M −1 cm −1

A 252 and A 280 being the absorbances of the conjugate measured on the UV spectrophotometer at 252 and 280 nm, respectively.

11. The conjugate of claim 10 having an average DAR between 4 and 10, or 5 and 8.

12. The conjugate of claim 11 having an average DAR between 5.9 and 7.5.

13. A pharmaceutical composition comprising the conjugate of claim 1 , and a pharmaceutically acceptable carrier or excipient.

14. An article of manufacture comprising:

a) a packaging material;

b) the conjugate of claim 1 ; and

c) a label or package insert contained within the packaging material indicating that the antibody or epitope-binding fragment thereof is effective for treating cancer.

15. A method for treating cancer comprising administering to a subject in need thereof the conjugate of claim 1 .

16. The method of claim 15 , wherein the cancer is selected from the group consisting of: carcinoma, bladder carcinoma, breast carcinoma, colon carcinoma, kidney carcinoma, liver carcinoma, lung carcinoma, ovary carcinoma, pancreas carcinoma, stomach carcinoma, cervix carcinoma, thyroid carcinoma, skin carcinoma, squamous cell carcinoma, hematopoietic tumors of lymphoid lineage, leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Burkitt's lymphoma, hematopoietic tumors of myeloid lineage, acute and chronic myelogenous leukemias, promyelocytic leukemia, tumors of mesenchymal origin, fibrosarcoma, rhabdomyosarcoma, melanoma, seminoma, teratocarcinoma, neuroblastoma, glioma, tumors of the central and peripheral nervous system, astrocytoma, schwannomas, osteosarcoma, xeroderma pigmentosum, keratoacanthoma, and thyroid follicular cancer.

17. A method for inhibiting the growth of an EphA2 receptor-expressing cancer cell comprising administering to the cell the conjugate of claim 1 .

18. A method for inhibiting the migration of a metastatic cancer cell expressing the EphA2 receptor comprising administering to the cell the conjugate of claim 1 .

19. A method for inhibiting EphA2 autophosphorylation activity in an EphA2 receptor-expressing cancer cell comprising administering to the cell the conjugate of claim 1 .