ANTI-TSG101 ANTIBODIES AND THEIR USES FOR TREATMENT OF VIRAL INFECTIONS

• US 20080187528A1
• Filed: 11/15/2007
• Published: 08/07/2008
• Est. Priority Date: 11/15/2006
• Status: Active Grant

• Current Assignee: Eli Lilly and Company
• Original Assignee: Functional Genetics Incorporated
• Inventors: Goldblatt, Michael, Kinch, Michael, Li, Limin
• Granted Patent: US 7,964,708 B2
• Time in Patent Office: Days
• US Class Current: 424/131.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• 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 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present invention provides antibodies that bind to the C-terminal region of TSG101. The invention also provides methods of using the TSG101 antibodies for the treatment of viral infections, including HIV and Ebola virus infection.

Claims

1. A method for inhibiting virus infection in a mammalian subject, comprising providing to said subject an effective amount of an anti-TSG101 antibody, wherein said antibody binds TSG101 present on cells of said subject which may become infected with said virus.

2. The method of claim 1, wherein the anti-TSG111 antibody is a monoclonal antibody.

3. The method of claim 2, wherein the monoclonal antibody is selected from the group consisting of antibodies C, D1, E, SG1 and CB8.

4. The method of claim 2, wherein the monoclonal antibody binds to an epitope in the C-terminal region of TSG101.

5. The method of claim 1, wherein the anti-TSG101 antibody is a humanized antibody.

6. The method of claim 5, wherein the humanized antibody comprises at least one amino acid sequence selected from the group consisting of SEQ ID NOS:

30-41.

7. The method of claim 6, wherein the humanized antibody comprises amino acid sequences recited in SEQ ID NOS:

30-35.

8. The method of claim 6, wherein the humanized antibody comprises amino acid sequences recited in SEQ ID NOS:

36-41.

9. The method of claim 1, wherein said virus is a human immunodeficiency virus, marburg virus, ebola virus, influenza virus, respiratory syncytial virus, encephalitis virus, rous sarcoma virus, lassa fever virus, hepatitis virus, Epstein-barr virus, vaccine virus, herpes virus or junin virus.

10. The method of claim 1, wherein said mammal is a non-human and said virus is pseudorabies virus, pseudorabies virus II, swine rotavirus, swine parvovirus, bovine viral diarrhea virus, Newcastle disease virus h, swine flu virus, swine flu virus, foot and mouth disease virus, hog colera virus, swine influenza virus, African swine fever virus, infectious bovine rhinotracheitis virus, infectious laryngotracheitis virus, La Crosse virus, neonatal calf diarrhea virus, Venezuelan equine encephalomyelitis virus, punta toro virus, murine leukemia virus, mouse mammary tumor virus, equine influenza virus or equine herpesvirus, bovine respiratory syncytial virus, bovine parainfluenza virus, PRRS virus, porcine or bovine circoviruses, porcine or bovine coronaviruses, porcine or bovine RSV, porcine, bovine or avian influenza, EIAV, or bluetongue.

11. The method of claim 1, wherein said anti-TSG101 antibody is provided to said mammal by administering said antibody to dais mammal.

12. The method of claim 1, where said anti-TSG101 antibody is provided to said mammal by inoculating said mammal with a TSG101 immunogen that induces an immune response in said human including the preparation of antibodies which bind to an epitope of TSG101.

13. An anti-TSG101 monoclonal antibody, said antibody binds to a TSG101 C-terminal region consisting of an amino acid sequence recited in SEQ ID NO:

3.

14. The anti-TSG101 monoclonal antibody of claim 13, wherein in said monoclonal antibody comprises a polypeptide comprising an amino acid sequence recited in SEQ ID NO:

19, 22, 25 or 28.

16. The monoclonal antibody of claim 14, wherein said antibody is a humanized antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:

30-41.

15. A monoclonal antibody that binds to TSG101 selected from the group consisting of antibodies C, D1, E, 3G1 and CB8.

17. A pharmaceutical composition for inhibiting viral infection in a mammal, comprising:

1) an effective amount of an anti-TSG101 antibody; and

2) a pharmaceutically acceptable carrier,

wherein said anti-TSG101 antibody binds to an epitope within the TSG101 C-terminal region consisting of the amino acid sequence recited in SEQ ID NO;

3.

18. A pharmaceutical composition for inhibiting viral infection in a mammal, comprising:

1) an effective amount of an anti-TSG101 antibody; and

2) a pharmaceutically acceptable carrier,

wherein said anti-TSG101 antibody is selected from the group consisting of antibodies C, D1, E, 3G1 and CB8.