Tnf-alpha binding proteins

Abstract

Isolated binding proteins, e.g., antibodies or antigen binding portions thereof, which bind to tumor necrosis factor-alpha (TNF-α), e.g., human TNF-α, and related antibody-based compositions and molecules are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, as well as therapeutic and diagnostic methods for using the antibodies.

1 - 48 . (canceled) 
     
     
         49 . An isolated nucleic acid encoding a humanized binding protein comprising an antigen binding domain capable of binding human tumor necrosis factor-alpha (TNF-α), the antigen binding domain comprising at least one CDR comprising an amino acid sequence of residues 31-35 of SEQ ID NO:22; residues 50-65 of SEQ ID NO:22; residues 98-106 of SEQ ID NO:22; residues 24-34 of SEQ ID NO:23; residues 50-56 of SEQ ID NO:23; or residues 89-97 of SEQ ID NO:23, wherein the binding protein comprises a human acceptor framework and/or an immunoglobulin constant domain. 
     
     
         50 . The isolated nucleic acid of  claim 49 , further comprising an immunoglobulin constant domain. 
     
     
         51 . A vector comprising the isolated nucleic acid of  claim 49  or  50 . 
     
     
         52 . The vector of  claim 51 , wherein the vector is selected from the group consisting of pcDNA, pTT, pTT3, pEFBOS, pBV, pJV, and pBJ. 
     
     
         53 . A host cell comprising a vector of  claim 51 . 
     
     
         54 . The host cell of  claim 53 , wherein the host cell is a prokaryotic cell. 
     
     
         55 . The host cell of  claim 53 , wherein the host cell is a eukaryotic cell. 
     
     
         56 . The host cell of  claim 55 , wherein the eukaryotic cell is a protist cell, an animal cell, a plant cell, a fungal cell, a yeast cell, a mammalian cell, an avian cell, or an insect cell. 
     
     
         57 . The host cell of  claim 55 , wherein the eukaryotic cell is a CHO cell, a COS cell, or  Saccharomyces cerevisiae.    
     
     
         58 . A method of producing a protein that binds TNF-α, the method comprising the steps of culturing a host cell of  claim 53  in culture medium under conditions sufficient to produce a binding protein that binds TNF-α. 
     
     
         59 - 76 . (canceled) 
     
     
         77 . The nucleic acid of  claim 49 , wherein the antigen binding domain comprises a VH region. 
     
     
         78 . The nucleic acid of  claim 77 , wherein the VH region comprises an amino acid sequence of SEQ ID NOs: 24, 25, 28, 29, 30, 31, 32, or 33. 
     
     
         79 . The nucleic acid of  claim 49 , wherein the antigen binding domain comprises a VL region. 
     
     
         80 . The nucleic acid of  claim 79 , wherein the VL region amino acid sequence is SEQ ID NOs: 26, 27, 34, 35, or 36. 
     
     
         81 . The nucleic acid of  claim 49 , wherein the antigen binding domain comprises a VH region and a VL region. 
     
     
         82 . The nucleic acid of  claim 81 , wherein the VH region comprises an amino acid sequence of SEQ ID NO: 24, 25, 28, 29, 30, 31, 32, or 33 and the VL region comprises an amino acid sequence of SEQ ID NO: 26, 27, 34, 35, or 36.