HUMANIZED ANTIBODIES

• US 20110044976A1
• Filed: 03/26/2010
• Published: 02/24/2011
• Est. Priority Date: 11/30/1998
• Status: Active Grant

• Current Assignee: Perlan Therapeutics, Inc.
• Original Assignee: Perlan Therapeutics, Inc.
• Inventors: FANG, FANG, KOHLSTAEDT, LORI, RENO, JOHN
• Granted Patent: US 8,586,712 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 33/00 Antiparasitic agents
• CPC Class Codes: A61P 33/06 Antimalarials
• CPC Class Codes: C07K 16/2821 against ICAM molecules, e.g. CD50, CD54, CD102
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Humanized antibodies that bind ICAM-1 are provided. Antibodies include those selected from: SEQ ID NO:1 and 3 (HumA); SEQ ID NO:5 and 7 (HumB); SEQ ID NO:9 and 11 (HumC); SEQ ID NO:13 and 15 (HumD); SEQ ID NO:17 and 19 (HumE); SEQ ID NO:21 and 23 (HumF); SEQ ID NO:25 and 27 (HumG); SEQ ID NO:29 and 31 (HumH); and SEQ ID NO:33 and 35 (HumI). Subsequences of the humanized antibodies capable of binding an ICAM-1 epitope are also provided. Methods of inhibiting pathogen infection (e.g., HRV) of a cell employing humanized antibodies capable of binding an ICAM-1 epitope are further provided.

Claims

1. An antibody that binds ICAM-1 comprising:

i) a V_H region having at least 60% sequence homology to SEQ ID NO;

9, or

ii) a V_L region having at least 60% sequence homology to SEQ ID NO;

11.

2. The antibody or antibody subsequence of claim 1 having a protective efficacy against pathogen infection greater than an antibody having mouse monoclonal antibody 1A6 variable domains.

3. The antibody of claim 1 having a binding affinity for ICAM-1 greater than an antibody having mouse monoclonal antibody 1A6 variable domains.

4. The antibody of claim 2, wherein said pathogen is human rhinovirus (HRV), coxackie A virus, respiratory syncytial virus (RSV) or malaria.

5. The antibody of claim 1, wherein said antibody or antibody subsequence is linked to one or more identical or different antibodies to form a multimeric antibody complex.

6. The antibody of claim 5, wherein said multimeric complex is formed via a multimerization domain.

7. The antibody of claim 6, further comprising a linker between said multimerization domain and said antibody.

8. The antibody of claim 5, wherein said multimeric complex is a homo- or hetero-dimer, trimer, tetramer or pentamer.

9. The antibody of claim 1, wherein said antibody or antibody subsequence has 1-10 amino acid substitutions.

10. The antibody of claim 9, wherein said substitutions are conservative substitutions.

11. The antibody of claim 2, wherein said mouse monoclonal antibody 1A6 variable domains comprise a heavy and light chains of SEQ ID NOs:

77 and 79, respectively.

12. The antibody of claim 3, wherein said mouse monoclonal antibody 1A6 variable domains comprise a heavy and light chains of SEQ ID NOs:

77 and 79, respectively.

13. The antibody or antibody subsequence of claim 1, said antibody having a protective efficacy at least 2 times greater than mouse monoclonal antibody 1A6.

14. The antibody of claim 1, wherein said antibody is an intact immunoglobulin molecule comprising 2 full-length heavy chains and 2 full-length light chains.

15. The antibody of claim 1, wherein an acceptor variable framework region of said V_H or V_L region has at least one non-human donor amino acid.

16. A nucleic acid sequence encoding the antibody or antibody subsequence of claim 1.

17. A vector comprising the nucleic acid sequence of claim 16.

18. A pharmaceutical composition comprising the antibody or antibody subsequence of claim 1 and a pharmaceutically acceptable carrier.

19. A method for inhibiting pathogen infection of a cell, said method comprising contacting a pathogen or cell susceptible to the pathogen infection with an amount of antibody or antibody subsequence of claim 1 in an amount sufficient to inhibit pathogen infection of the cell.

20. The method of claim 19, wherein said cell is an epithelial cell.