Humanized immunoglubulin reactive with alph4beta7 integrin

Abstract

The present invention relates to isolated nucleic acids encoding humanized immunoglobulins having binding specificity for α4β7 integrin, isolated nucleic acids encoding a humanized immunoglobulin heavy chain and isolated nucleic acids encoding a humanized light chain having binding specificity for α4β7 integrin. The invention also relates to expression vectors and host cells comprising a nucleotide sequence which encodes a humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for α4β7. The invention further relates to methods of preparing a humanized immunoglobulin, humanized immunoglobulin heavy chain and humanized immunoglobulin light chain that has binding specificity for α4β7 integrin.

1 . An isolated nucleic acid molecule encoding a humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for α4β7 integrin, wherein said humanized immunoglobulin or antigen-binding fragment thereof comprises a heavy chain and a light chain, said heavy chain comprising the variable region of SEQ ID NO:19, and said light chain comprising the variable region of SEQ ID NO:21. 
     
     
         2 . The isolated nucleic acid molecule of  claim 1 , wherein said isolated nucleic acid molecule comprises a first nucleotide sequence encoding the variable region of SEQ ID NO:19, and a second nucleotide sequence encoding the variable region of SEQ ID NO:21. 
     
     
         3 . The isolated nucleic acid molecule of  claim 2 , wherein said first nucleotide sequence further encodes an IgG constant region or a modified IgG constant region with reduced Fc receptor binding activity, reduced complement fixing activity, or reduced Fc receptor binding activity and reduced complement fixing activity. 
     
     
         4 . An expression vector comprising a nucleotide sequence which encodes a humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for α4β7 integrin, wherein said humanized immunoglobulin or antigen-binding fragment thereof comprises a heavy chain and a light chain, said heavy chain comprising the variable region of SEQ ID NO:19, and said light chain comprising the variable region of SEQ ID NO:21. 
     
     
         5 . The expression vector of  claim 4 , wherein said expression vector comprises a first nucleotide sequence that encodes the variable region of SEQ ID NO:19, and a second nucleotide sequence that encodes the variable region of SEQ ID NO:21. 
     
     
         6 . The expression vector of  claim 5 , wherein said first nucleotide sequence further encodes an IgG constant region or a modified IgG constant region with reduced Fc receptor binding activity, reduced complement fixing activity, or reduced Fc receptor binding activity and reduced complement fixing activity. 
     
     
         7 . A host cell comprising the expression vector of  claim 4 . 
     
     
         8 . A method of preparing a humanized immunoglobulin or antigen-binding fragment thereof, comprising maintaining a host cell of  claim 7  under conditions suitable for expression of a humanized immunoglobulin or antigen-binding fragment thereof, whereby a humanized immunoglobulin or antigen-binding fragment thereof is produced. 
     
     
         9 . The method of  claim 8 , further comprising isolating the humanized immunoglobulin or antigen-binding fragment. 
     
     
         10 . An isolated nucleic acid molecule encoding a humanized immunoglobulin heavy chain or antigen-binding portion thereof, wherein said heavy chain or antigen-binding portion thereof comprises the variable region of SEQ ID NO:19. 
     
     
         11 . The isolated nucleic acid molecule of  claim 10 , wherein said heavy chain comprises an IgG constant region or a modified IgG constant region with reduced Fc receptor binding activity, reduced complement fixing activity, or reduced Fc receptor binding activity and reduced complement fixing activity. 
     
     
         12 . An expression vector comprising a nucleotide sequence that encodes a humanized immunoglobulin heavy chain or antigen-binding portion thereof, wherein said heavy chain or antigen-binding portion thereof comprises the variable region of SEQ ID NO:19. 
     
     
         13 . The expression vector of  claim 12 , wherein said heavy chain comprises an IgG constant region or a modified IgG constant region with reduced Fc receptor binding activity, reduced complement fixing activity, or reduced Fc receptor binding activity and reduced complement fixing activity. 
     
     
         14 . A host cell comprising the expression vector of  claim 12 . 
     
     
         15 . A method of preparing a humanized immunoglobulin heavy chain or antigen-binding portion thereof, comprising maintaining a host cell of  claim 14  under conditions suitable for expression of a humanized immunoglobulin heavy chain or antigen-binding portion thereof, whereby a humanized immunoglobulin heavy chain or antigen-binding portion thereof is produced. 
     
     
         16 . The method of  claim 15 , further comprising isolating the humanized immunoglobulin heavy chain or antigen-binding portion thereof. 
     
     
         17 . An isolated nucleic acid molecule encoding a humanized immunoglobulin light chain or antigen-binding portion thereof, wherein said light chain or antigen-binding portion thereof comprises the variable region of SEQ ID NO:21. 
     
     
         18 . The isolated nucleic acid molecule of  claim 17 , wherein said humanized immunoglobulin light chain further comprises a constant region. 
     
     
         19 . An expression vector encoding a humanized immunoglobulin light chain or antigen-binding portion thereof, wherein said light chain or antigen-binding portion thereof comprises the variable region of SEQ ID NO:21. 
     
     
         20 . The expression vector of  claim 19 , wherein said humanized immunoglobulin light chain further comprises a constant region. 
     
     
         21 . A host cell comprising the expression vector of  claim 19 . 
     
     
         22 . A method of preparing a humanized immunoglobulin light chain or antigen-binding portion thereof, comprising maintaining a host cell of  claim 21  under conditions suitable for expression of a humanized immunoglobulin light chain or antigen-binding portion thereof, whereby a humanized immunoglobulin light chain or antigen-binding portion thereof is produced. 
     
     
         23 . The method of  claim 22 , further comprising isolating the humanized immunoglobulin light chain or antigen-binding portion thereof.