HUMANIZED ANTI-LT-beta-R ANTIBODIES

Abstract

Humanized antibodies to LT-β-R and methods of use thereof are provided.

1 . A humanized anti-lymphotoxin-beta receptor (LT-β-R) antibody whose light chain complementary determining regions are defined by amino acid residues 24 to 34, 50 to 56 and 89 to 97 of SEQ ID NO:1, and whose heavy chain complementary determining regions are defined by amino acid residues 31 to 35, 50 to 66 and 99 to 109 of SEQ ID NO: 2 and wherein the antibody comprises at least one of the following residues in its light chain: K3, W41, I46, Q69 and Y71; or at least one of the following residues in its heavy chain: F37, T40, A49, M89 and V93 (Kabat numbering convention). 
   
   
       2 . A humanized anti-lymphotoxin-beta receptor (LT-β-R) antibody whose light chain complementary determining regions are defined by amino acid residues 24 to 34, 50 to 56 and 89 to 97 of SEQ ID NO:1, and whose heavy chain complementary determining regions are defined by amino acid residues 31 to 35, 50 to 66 and 99 to 109 of SEQ ID NO:2 and wherein the antibody comprises residue Y71 in its light chain (Kabat numbering convention). 
   
   
       3 . A humanized anti-lymphotoxin-beta receptor (LT-β-R) antibody whose light chain complementary determining regions are defined by amino acid residues 24 to 34, 50 to 56 and 89 to 97 of SEQ ID NO:1, and whose heavy chain complementary determining regions are defined by amino acid residues 31 to 35, 50 to 66 and 99 to 109 of SEQ ID NO:2 and wherein the antibody comprises residues F37 and A49 in its heavy chain (Kabat numbering convention). 
   
   
       4 . The antibody of  claim 1 , wherein the antibody comprises a light chain variable domain sequence defined by amino acid residues 1 to 107 of SEQ ID NO:8. 
   
   
       5 . The antibody of  claim 1 , wherein the antibody comprises a heavy chain variable domain sequence defined by amino acid residues 1 to 120 of SEQ ID NO:16. 
   
   
       6 . The antibody of  claim 4 , wherein the antibody further comprises a heavy chain variable domain sequence defined by amino acid residues 1 to 120 of SEQ ID NO:16 
   
   
       7 . An antibody comprising the same heavy and light chain polypeptide sequences as an antibody produced by cell line E46.4 (ATCC patent deposit designation PTA-3357) or cell line E77.4 (ATCC patent deposit designation 3765). 
   
   
       8 . The antibody according to anyone of  claims 1 - 7  wherein the antibody substantially retains the binding properties of the parent antibody. 
   
   
       9 . The antibody according to anyone of  claims 1 - 7  wherein the antibody is further linked to an immunotoxin. 
   
   
       10 . The antibody according to anyone of  claims 1 - 7  wherein the antibody is further linked to a chemotherapeutic drug. 
   
   
       11 . A composition comprising an antibody of any one of  claims 1 - 7  and a pharmaceutically acceptable carrier. 
   
   
       12 . A method of treating or reducing the advancement, severity or effects of neoplasia in a human comprising administering the composition of  claim 11 . 
   
   
       13 . An isolated nucleic acid comprising a coding sequence for the light chain of an antibody produced by cell line E46.4 (ATCC patent deposit designation PTA-3357) or cell line E77.4 (ATCC patent deposit designation 3765). 
   
   
       14 . An isolated nucleic acid comprising a coding sequence for the heavy chain of an antibody produced by cell line E46.4 (ATCC patent deposit designation PTA-3357) or cell line E77.4 (ATCC patent deposit designation 3765). 
   
   
       15 . An isolated nucleic acid comprising a coding sequence for residues 1 to 107 of SEQ ID NO:8. 
   
   
       16 . An isolated nucleic acid comprising a coding sequence for residues 1 to 120 of SEQ ID NO:16. 
   
   
       17 . A cell of cell line E46.4 (ATCC patent deposit designation PTA-3357) or cell line E77.4 (ATCC patent deposit designation 3765).