Humanized anti-beta7 antagonists and uses therefor

Abstract

The invention provides therapeutic anti-beta7 antibodies, compositions comprising, and methods of using these antibodies.

1 - 64 . (canceled) 
     
     
         65 . An isolated nucleic acid encoding a humanized anti-beta7 antibody comprising: a variable region heavy chain framework sequence comprising the amino acid sequences set forth as SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 45, and SEQ ID NO: 41, and a variable region light chain framework sequence comprising amino acid residues 1-23, 24-37, 38-69 and 70 to last residue of the amino acid sequence set forth as SEQ ID NO: 15, and an HVR-L1, HVR-L2, HVR-L3, HVR-HI, HVR-H2 and HVR-H3, wherein each, in order, comprises RASESVDDLLH (SEQ ID NO:9), KYASQSIS (SEQ ID NO:2), QQGNSLPNT (SEQ ID NO:3), GFFITNNYWG (SEQ ID NO:4), GYISYSGSTSYNPSLKS (SEQ ID NO:5), and MTGSSGYFDF (SEQ ID NO:6). 
     
     
         66 . An isolated nucleic acid encoding a humanized anti-beta7 antibody comprising: a variable region heavy chain framework sequence comprising the amino acid sequences set forth as SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 45, and SEQ ID NO: 41, and a variable region light chain framework sequence comprising amino acid residues 1-23, 24-37, 38-69 and 70 to last residue of the amino acid sequence set forth as SEQ ID NO: 15, and an HVR-L1, HVR-L2, HVR-L3, HVR-HI, HVR-H2 and HVR-H3, wherein each, in order, comprises RASESVDDLLH (SEQ ID NO:9), KYASQSIS (SEQ ID NO:2), QQGNSLPNT (SEQ ID NO:3), GFFITNNYWG (SEQ ID NO:4), GYISYSGSTSYNPSLKS (SEQ ID NO:5), and RTGSSGYFDF (SEQ ID NO:66). 
     
     
         67 . An isolated nucleic acid encoding a humanized anti-beta7 antibody comprising: a variable region heavy chain framework sequence comprising the amino acid sequences set forth as SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 45, and SEQ ID NO: 41, and a variable region light chain framework sequence comprising amino acid residues 1-23, 24-37, 38-69 and 70 to last residue of the amino acid sequence set forth as SEQ ID NO: 15, and an HVR-L1, HVR-L2, HVR-L3, HVR-HI, HVR-H2 and HVR-H3, wherein each, in order, comprises RASESVDSLLH (SEQ ID NO:7), KYASQSIS (SEQ ID NO:2), QQGNSLPNT (SEQ ID NO:3), GFFITNNYWG (SEQ ID NO:4), GYISYSGSTSYNPSLKS (SEQ ID NO:5), and MTGSSGYFDF (SEQ ID NO:6). 
     
     
         68 . A vector comprising the nucleic acid of any one of  claims 65  to  67 . 
     
     
         69 . A host cell comprising the vector of  claim 68 . 
     
     
         70 . The host cell of  claim 69 , wherein the host cell is a prokaryotic cell. 
     
     
         71 . The host cell of  claim 70 , wherein the host cell is  E. coli.    
     
     
         72 . The host cell of  claim 69 , wherein the host cell is a eukaryotic cell. 
     
     
         73 . The host cell of  claim 72 , wherein the host cell is a mammalian cell. 
     
     
         74 . The host cell of  claim 73 , wherein the host cell is a Chinese hamster ovary cell. 
     
     
         75 . A method of producing a humanized anti-beta7 antibody comprising culturing the host cell of  claim 69 . 
     
     
         76 . The method of  claim 75 , further comprising purifying the antibody expressed by the host cell.