Humanized antibodies

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 finding an ICAM-1 epitope are also provided. Methods of inhibiting pathogen infection (e.g., HRV) of a cell employing humanized antibodies capable of finding an ICAM-1 epitope are further provided.

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 t 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.