MONOCLONAL ANTIBODIES FOR TREATMENT OF CANCER

• US 20110223182A1
• Filed: 09/16/2009
• Published: 09/15/2011
• Est. Priority Date: 09/16/2008
• Status: Active Grant

• Current Assignee: Astellas Pharma Incorporated, TRANSLATIONALE ONKOLOGIE AN DER UNIVERSITATSMEDIZIN DER JOHANNES GUTENBERG-UNIVERSITAT MAINZ GEMEINNUTZIGE GMBH
• Original Assignee: Ganymed Pharmaceuticals AG (Astellas Pharma Incorporated), Johannes Gutenberg-Universitã¤T Mainz
• Inventors: Mitnacht-Kraus, Rita, Sahin, Ugur, Koslowski, Michael, Tureci, Ozlem
• Granted Patent: US 8,946,388 B2
• Time in Patent Office: Days
• US Class Current: 424/174.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing GT468, including tumor-related diseases such as breast Cancer, lung Cancer, gastric Cancer, ovarian Cancer, hepatocellular Cancer, colon Cancer, pancreatic Cancer, esophageal Cancer, head & neck Cancer, kidney Cancer, in particular renal cell Carcinoma, prostate Cancer, liver cancer, melanoma, sarcoma, myeloma, neuroblastoma, placental choriocarcinoma, cervical cancer, and thyroid Cancer, and the metastatic forms thereof. In one embodiment, the rumor disease is metastatic cancer in the lung.

Claims

1. An antibody which has the ability of binding to GT468 and has one or more of the following activities:

(i) killing of tumor cells expressing GT468,

(ii) inhibition of proliferation of tumor cells expressing GT468,

(iii) inhibition of colony formation of tumor cells expressing GT468, and

(iv) inhibition of metastasis of tumor cells expressing GT468.

2. The antibody of claim 1 wherein said one or more activities are induced by binding of said antibody to the extracellular domain of GT468 expressed by said cells.

3. The antibody of claim 1 wherein said tumor cells expressing GT468 are cancer cells.

4. The antibody of claim 3 wherein the cancer cells are from a cancer selected from the group consisting of breast cancer, lung cancer, gastric cancer, ovarian cancer, hepatocellular cancer, colon cancer, pancreatic cancer, esophageal cancer, head &

neck cancer, kidney cancer, in particular renal cell carcinoma, prostate cancer, liver cancer, melanoma, sarcoma, myeloma, neuroblastoma, placental choriocarcinoma, cervical cancer, and thyroid cancer, and the metastatic forms thereof, and metastatic cancer in the lung.

5. The antibody of claim 1 which is a monoclonal, chimeric, human or humanized antibody, or a fragment of an antibody.

6. The antibody of claim 1 wherein GT468 has the amino acid sequence according to SEQ ID NO:

2.

7. The antibody of claim 1 wherein the antibody binds specifically to GT468.

8. The antibody of claim 1 which binds to native epitopes of GT468.

9. The antibody of claim 1 which is obtainable by a method comprising the step of immunizing an animal with a protein or peptide having an amino acid sequence selected from the group consisting of SEQ ID NO:

2-10 and 35-82, or an immunogenic fragment or derivative thereof, or a nucleic acid or host cell expressing said protein or peptide, or immunogenic fragment or derivative thereof.

12. A hybridoma capable of producing the antibody of claim 1.

14. A conjugate comprising an antibody of claim 1 coupled to a therapeutic agent.

15. The conjugate of claim 14 wherein the therapeutic agent is a toxin, a radioisotope, a drug or a cytotoxic agent.

16. A pharmaceutical composition comprising an antibody of claim 1 and a pharmaceutically acceptable carrier.

17. A method of inhibiting growth, killing, and/or inhibiting metastatic spread of a cell expressing GT468 and/or being characterized by association of GT468 with its cell surface, comprising contacting the cell with an antibody of claim 1.

20. A method of treating or preventing a disease or disorder involving cells expressing GT468 and/or being characterized by association of GT468 with their cell surface in a subject, comprising administering to said subject an antibody of claim 1.

21. The method of claim 20 wherein the disease or disorder is a tumor-related disease.

22. The method of claim 21 wherein the tumor-related disease is cancer.

23. The method of claim 22 wherein the cancer is selected from the group consisting of breast cancer, lung cancer, gastric cancer, ovarian cancer, hepatocellular cancer, colon cancer, pancreatic cancer, esophageal cancer, head &

neck cancer, kidney cancer, in particular renal cell carcinoma, prostate cancer, liver cancer, melanoma, sarcoma, myeloma, neuroblastoma, placental choriocarcinoma, cervical cancer, and thyroid cancer, and the metastatic forms thereof, and metastatic cancer in the lung.

24. A pharmaceutical composition comprising a conjugate of claim 14 and a pharmaceutically acceptable carrier.

25. A method of inhibiting growth, killing, and/or inhibiting metastatic spread of a cell expressing GT468 and/or being characterized by association of GT468 with its cell surface, comprising contacting the cell with a conjugate of claim 14.

26. A method of treating or preventing a disease or disorder involving cells expressing GT468 and/or being characterized by association of GT468 with their cell surface in a subject, comprising administering to said subject a conjugate of claim 14.

27. A method of treating or preventing a disease or disorder involving cells expressing GT468 and/or being characterized by association of GT468 with their cell surface in a subject, comprising administering to said subject a pharmaceutical composition of claim 16.

10. An antibody selected from the group consisting of:

(i) an antibody produced by or obtainable from a clone deposited under the accession no. DSM ACC2822 (4E9-1H9), DSM ACC2826 (9B6-2A9), DSM ACC2824 (59D6-2F2), DSM ACC2825 (61C11-2B5), DSM ACC2823 (78H11-1H6), DSM ACC2895 (22-1A-1), DSM ACC2893 (22-2A-1), DSM ACC2896 (22-9B-1), DSM ACC2897 (23-33A-1), DSM ACC2891 (23-19A-1), DSM ACC2894 (F11#33F7D12), DSM ACC2892 (4A12 2D4 1A10), DSM ACC2898 (4E9 1D12 2D4), DSM ACC2961 (42H11 ICM 2B2), DSM ACC2962 (51G6 2H3 2B4), DSM ACC2943 (16-5B-1), DSM ACC2956 (20-11A-1), DSM ACC2947 (29-1A-2), DSM ACC2964 (29-8B-1), DSM ACC2959 (35-48B-1), DSM ACC2963 (35-50A-2a), DSM ACC2957 (38-10B-1), DSM ACC2958 (38-1A-1), DSM ACC2948 (44-3A-2), DSM ACC2949 (45-2A-1), DSM ACC2950 (45-8A-2), DSM ACC2951 (48-3B-1), DSM ACC2952 (48-4A-1), DSM ACC2946 (49-3A-1), DSM ACC2945 (49-8A-1), DSM ACC2944 (51-1A-1), DSM ACC2953 (53-13A-2), DSM ACC2955 (53-29A-1), DSM ACC2960 (54-4B-2), DSM ACC2954 (56-4A-2), or DSM ACC3001 (62-9B-1),

(ii) an antibody which is a chimerized or humanized form of the antibody under (i),

(iii) an antibody which has the specificity of the antibody under (i), and

(iv) an antibody comprising the antigen binding portion or antigen binding site of the antibody under (i).

11. The antibody of claim 10, wherein the antigen binding portion or antigen binding site of the antibody under (i) comprises the variable region of the antibody under (i).

13. A hybridoma deposited under the accession no. DSM ACC2822 (4E9-1H9), DSM ACC2826 (9B6-2A9), DSM ACC2824 (59D6-2F2), DSM ACC2825 (61C11-2B5), DSM ACC2823 (78H11-1H6), DSM ACC2895 (22-1A-1), DSM ACC2893 (22-2A-1), DSM ACC2896 (22-9B-1), DSM ACC2897 (23-33A-1), DSM ACC2891 (23-19A-1), DSM ACC2894 (F11#33F7D12), DSM ACC2892 (4A12 2D4 1A10), DSM ACC2898 (4E9 1D12 2D4), DSM ACC2961 (42H11 1C11 2B2), DSM ACC2962 (51G6 2H3 2B4), DSM ACC2943 (16-5B-1), DSM ACC2956 (20-11A-1), DSM ACC2947 (29-1A-2), DSM ACC2964 (29-8B-1), DSM ACC2959 (35-48B-1), DSM ACC2963 (35-50A-2a), DSM ACC2957 (38-10B-1), DSM ACC2958 (38-1A-1), DSM ACC2948 (44-3A-2), DSM ACC2949 (45-2A-1), DSM ACC2950 (45-8A-2), DSM ACC2951 (48-3B-1), DSM ACC2952 (48-4A-1), DSM ACC2946 (49-3A-1), DSM ACC2945 (49-8A-1), DSM ACC2944 (51-1A-1), DSM ACC2953 (53-13A-2), DSM ACC2955 (53-29A-1), DSM ACC2960 (54-4B-2), DSM ACC2954 (56-4A-2), or DSM ACC3001 (62-9B-1).

18-19. -19. (canceled)