Antibodies that bind to the C35 polypeptide

• US 7,750,125 B2
• Filed: 08/17/2007
• Issued: 07/06/2010
• Est. Priority Date: 06/10/2002
• Status: Expired due to Fees

• Current Assignee: University of Rochester
• Original Assignee: University of Rochester
• Inventors: Zauderer, Maurice, Evans, Elizabeth E.
• Primary Examiner(s): Helms; Larry R.
• Assistant Examiner(s): GUSSOW, ANNE
• Application Number:
  US11/892,017
• Publication Number:
  US 20080089886A1
• Time in Patent Office: 1,054 Days
• Field of Search: None
• US Class Current: 530/388.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The present invention relates to a novel human gene that is differentially expressed in human carcinoma. More specifically, the present invention relates to a polynucleotide encoding a novel human polypeptide named C35 that is overexpressed in human breast and bladder carcinoma. This invention also relates to C35 polypeptide, in particular C35 peptide epitopes and C35 peptide epitope analogs, as well as vectors, host cells, antibodies directed to C35 polypeptides, and the recombinant methods for producing the same. The present invention further relates to diagnostic methods for detecting carcinomas, including human breast carcinomas. The present invention further relates to the formulation and use of the C35 gene and polypeptides, in particular C35 peptide epitopes and C35 peptide epitope analogs, in immunogenic compositions or vaccines, to induce antibody or cell-mediated immunity against target cells, such as tumor cells, that express the C35 gene. The invention further relates to screening methods for identifying agonists and antagonists of C35 activity.

Claims

1. An antibody or antigen binding fragment thereof comprising a heavy chain variable domain and a light chain variable domain, wherein said heavy chain variable domain comprises the same three CDRs encoded by a polynucleotide having the sequence of SEQ ID NO:

151; and

wherein said light chain variable domain comprises the same three CDRs encoded by a polynucleotide having the sequence of SEQ ID NO;

150, and wherein said antibody or antigen binding fragment thereof specifically binds C35.

2. A composition comprising the antibody or antigen binding fragment thereof according to claim 1.

3. The composition according to claim 2, wherein said composition further comprises a therapeutic agent.

4. The composition according to claim 3, wherein said therapeutic agent is selected from the group consisting of:

an anti-tumor drug, a cytotoxin, and a radioactive agent.

5. The composition according to claim 4, wherein said therapeutic agent is a cytotoxin.

6. The composition according to claim 5, wherein said cytotoxin is selected from the group consisting of:

taxol, ricin, doxorubicin, cytochalasin B, gramicidin D, ethidium bromide, etoposide, tenoposide, colchicin, dihydroxy anthracin dione, 1-dehydrotestosterone, and glucocorticoid.

7. The composition according to claim 6, wherein said cytotoxin is taxol.

8. The composition according to claim 3, wherein said therapeutic agent is conjugated to or complexed with said antibody or antigen binding fragment.

9. The composition according to claim 2, wherein said composition further comprises a pharmaceutically acceptable carrier.

15. The antibody or antigen binding fragment thereof according to claim 1, wherein polynucleotides encoding the heavy chain variable domain CDRs in SEQ ID NO:

151 comprise;

(a) nucleotides 145 to 159 of SEQ ID NO;

151;

(b) nucleotides 202 to 249 of SEQ ID NO;

151; and

(c) nucleotides 346 to 387 of SEQ ID NO;

151.

16. The antibody or antigen binding fragment thereof according to claim 1, wherein said heavy chain variable domain is encoded by SEQ ID NO:

151.

17. The antibody or antigen binding fragment thereof according to claim 1, further comprising a human immunoglobulin heavy chain constant region or fragment thereof.

18. The antibody or antigen binding fragment thereof according to claim 17, wherein said heavy chain constant region is human IgG.

19. The antibody or antigen binding fragment thereof according to claim 1, wherein polynucleotides encoding the light chain variable domain CDRs in SEQ ID NO:

150 comprise;

(a) nucleotides 130 to 162 of SEQ ID NO;

150;

(b) nucleotides 208 to 228 of SEQ ID NO;

150; and

(c) nucleotides 325 to 351 of SEQ ID NO;

150.

20. The antibody or antigen binding fragment thereof according to claim 15, wherein polynucleotides encoding the light chain variable domain CDRs in SEQ ID NO:

150 comprise;

(a) nucleotides 130 to 162 of SEQ ID NO;

150;

(b) nucleotides 208 to 228 of SEQ ID NO;

150; and

(c) nucleotides 325 to 351 of SEQ ID NO;

150.

21. The antibody or antigen binding fragment thereof according to claim 1, wherein said light chain variable domain is encoded by SEQ ID NO:

150.

22. The antibody or antigen binding fragment thereof according to claim 1, further comprising a human immunoglobulin light chain constant region or fragment thereof.

23. The antibody or antigen binding fragment thereof according to claim 22, wherein said light chain constant region is human kappa.

24. The antibody or antigen binding fragment thereof according to claim 1, wherein said antigen binding fragment is selected from the group consisting of:

a Fab fragment, a F(ab′

)2 fragment, a scFv fragment, and a dAb fragment.

25. The antibody or antigen binding fragment thereof according to claim 1, wherein said antibody is monoclonal.

26. The antibody or antigen binding fragment thereof according to claim 1, wherein said antibody is humanized.

27. The antibody or antigen binding fragment thereof according to claim 1, wherein said antibody or antigen binding fragment is chimeric.

28. The antibody or antigen binding fragment thereof according to claim 16, wherein said light chain variable domain is encoded by SEQ ID NO:

150.

29. The antibody or antigen binding fragment thereof according to claim 16, wherein said polynucleotide encoding the light chain variable domain has the sequence of SEQ ID No. 150.

10. A method of producing an antibody or antigen binding fragment thereof that specifically binds C35 comprising:

(a) culturing a host cell, wherein said host cell comprises an expression vector, wherein said expression vector comprises a polynucleotide encoding an antibody or antigen binding fragment thereof comprising a heavy chain variable domain and a light chain variable domain, wherein said heavy chain variable domain comprises the same three CDRs encoded by SEQ ID NO;

151, wherein said light chain variable domain comprises the same three CDRs encoded by SEQ ID NO;

150, and wherein said antibody or antigen binding fragment thereof specifically binds C35; and

(b) recovering said antibody or antigen binding fragment thereof from said host cell.

11. The method according to claim 10, wherein said antigen binding fragment is selected from the group consisting of:

a Fab fragment, a F(ab′

)2 fragment, a scFv fragment, and a dAb fragment.

12. The method according to claim 10, wherein said antibody is monoclonal.

13. The method according to claim 10, wherein said antibody is humanized.

14. The method according to claim 10, wherein said antibody or antigen binding fragment is chimeric.