Vaccinia virus H3L and B5R specific monoclonal antibodies and methods of making and using same

• US 8,623,370 B2
• Filed: 10/06/2008
• Issued: 01/07/2014
• Est. Priority Date: 10/10/2007
• Status: Active Grant

• Current Assignee: Kyowa Kirin Co., Ltd. (Kirin Holdings Company Limited), La Jolla Institute For Allergy And Immunology
• Original Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited), La Jolla Institute For Allergy And Immunology
• Inventors: Kato, Shinichiro, Crotty, Shane, Tahara, Tomoyuki, Granger, Steve, Rickert, Sandra, Koriazova, Lilia
• Primary Examiner(s): Stucker, Jeffery
• Assistant Examiner(s): SNYDER, STUART
• Application Number:
  US12/682,539
• Publication Number:
  US 20100215658A1
• Time in Patent Office: 1,919 Days
• Field of Search: None
• US Class Current: 424/159.1
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: C07K 16/081 from DNA viruses
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]

Abstract

The invention relates to antibodies and subsequences thereof that specifically bind to poxvirus B5R envelope protein, antibodies and subsequences thereof that specifically bind to pox virus H3L envelope protein, and combinations thereof.

Claims

1. An isolated or purified antibody or subsequence thereof that specifically binds to poxvirus B5R envelope protein, wherein said antibody or subsequence comprises a heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as SSAMS, VISISGGSTYYADSVKG, and ETRYYYSYGMDV (SEQ ID NOs:

17-19), respectively, and a light chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as RASQRIGFALA, DASSLET, and QQFNTYPFT, (SEQ ID NOs;

29-31) respectively.

5. The antibody of claim 1, 3 or 4, wherein the antibody inhibits at least 50% of the binding of the antibody or subsequence thereof of claim 1 or 3 or 4 to variola poxvirus B5R envelope protein or to poxvirus B6 envelope protein, or to the monkeypox B5 homolog, as determined in an ELISA assay.

7. The antibody subsequence of any of claims 1 to 4, wherein the antibody subsequence is selected from Fab, Fab′

, F(ab′

)2, Fd, single-chain Fvs (scFv), disulfide-linked Fvs (sdFv) and VL and VH domain fragments.

8. The antibody or the subsequence thereof of any of claims 1 to 4, wherein the antibody is produced by a hybridoma deposited as PTA-8654;

PTA-8562;

PTA-8653;

or PTA-8564 (ATCC 110801 University Blvd., Manassas, Va. 20110-2209).

9. A nucleic acid that encodes the antibody or the subsequence of any of claims 1 to 4.

10. A vector comprising a nucleic acid that encodes the antibody or the subsequence of any of claims 1 to 4.

11. A host cell that expresses the antibody or the subsequence of any of claims 1 to 4.

12. A pharmaceutical composition, comprising the antibody of any of claims 1 to 4, and a pharmaceutically acceptable excipient or carrier.

13. A method for providing a subject with protection against poxvirus infection or pathogenesis, comprising administering an amount of the antibody or subsequence thereof of any of claims 1 to 4 sufficient to provide the subject with protection against poxvirus infection or pathogenesis.

14. A method for protecting or decreasing susceptibility of a subject to a poxvirus infection or pathogenesis, comprising administering an amount of the antibody or subsequence thereof of any of claims 1 to 4 sufficient to protect or decrease susceptibility of the subject to poxvirus infection or pathogenesis.

15. A method for decreasing or preventing an adverse side effect or complication associated with or caused by vaccination with a Vaccinia virus, comprising administering an amount of the antibody or subsequence thereof of any of claims 1 to 4 to a subject sufficient to decrease or prevent an adverse side effect or complication associated with or caused by vaccination with a Vaccinia virus.

16. The method of claim 13, further comprising administering an additional antibody or subsequence thereof that binds to a poxvirus protein.

17. The method of claim 16, wherein the additional antibody comprises VIG.

18. The isolated or purified antibody or subsequence thereof of claim 1, wherein said antibody or subsequence comprises a heavy chain variable region sequence set forth as SEQ ID NO:

2 or a light chain variable region sequence set forth as SEQ ID NO;

4.

22. The method of claim 14, further comprising administering an additional antibody or subsequence thereof that binds to a poxvirus protein.

23. The method of claim 22, wherein the additional antibody comprises VIG.

24. The method of claim 15, further comprising administering an additional antibody or subsequence thereof that binds to a poxvirus protein.

25. The method of claim 24, wherein the additional antibody comprises VIG.

2. An isolated or purified antibody or subsequence thereof that specifically binds to poxvirus H3L envelope protein, wherein said antibody or subsequence comprises a heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as DYAIH, GISWNGRSIGYADSVKG, and DIGFYGSGSLDY (SEQ ID NOs:

26-28), respectively and a light chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as RASQSVSSYLA, DASNRAT and QQRSNWPALT (SEQ ID NOs;

38-40), respectively.

6. The antibody of claim 2, wherein the antibody inhibits at least 50% of the binding of the antibody or subsequence thereof of claim 2 to poxvirus H3L envelope protein, as determined in an ELISA assay.

19. The isolated or purified antibody or subsequence thereof of claim 2, wherein said antibody or subsequence comprises a heavy chain variable region sequence set forth as SEQ ID NO:

14 or a light chain variable region sequence set forth as SEQ ID NO;

16.

3. An isolated or purified antibody or subsequence thereof that specifically binds to poxvirus B5R envelope protein, wherein said antibody or subsequence comprises a heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as SYSMN, SISSSRSFIYYADSVKG and ERRYYYSYGLDV (SEQ ID NOs:

20-22), respectively, and a light chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as RASQGISSALA, DASSLES and QQFNSYPYT (SEQ ID NOs;

32-34) respectively.

20. The isolated or purified antibody or subsequence thereof of claim 3, wherein said antibody or subsequence comprises a heavy chain variable region sequence set forth as SEQ ID NO:

6 or a light chain variable region sequence set forth as SEQ ID NO;

8.

4. An isolated or purified antibody or subsequence thereof that specifically binds to poxvirus B5R envelope protein, wherein said antibody or subsequence comprises a heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as SYSMN, SISSSSSYIYYADSVKG and ERRYYYSYGMDV (SEQ ID NOs:

23-25), respectively, and a light chain variable region sequence comprising CDR1, CDR2 and CDR3 sequences set forth as RASQRIGFALA, DASSLET and QQFNTYPFT (SEQ ID NOs;

29-31), respectively.

21. The isolated or purified antibody or subsequence thereof of claim 4, wherein said antibody or subsequence comprises a heavy chain variable region sequence set forth as SEQ ID NO:

12 or a light chain variable region sequence set forth as SEQ ID NO;

10.