Patent ID: 7365167

Claim:
An antibody, or antigen-binding fragment thereof, which is a variant of monoclonal antibody HUIV26 having one or more complementarity determining regions (CDRs) having an amino acid sequence differing from the corresponding CDRs of monoclonal antibody HUIV26, and which has higher binding affinity for denatured collagen type IV over native collagen type IV comprising a heavy chain variable region and a light chain variable region, wherein said heavy chain variable region comprises: (i) a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 26 or the amino acid sequence of SEQ ID NO: 26 but for one or more substitutions selected from the group consisting of: (a) substitution of arginine at position 6 therein by histidine; (b) substitution of methionine at position 9 therein by isoleucine; and (c) substitution of serine at position 10 therein by threonine, alanine or glycine; (ii) a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 28 or the amino acid sequence of SEQ ID NO: 28 but for one or more substitutions selected from the group consisting of: (a) substitution of isoleucine at position 9 therein by alanine, serine or valine; (b) substitution of serine at position 14 therein by tyro sine, alanine, histidine or glycine; (c) substitution of lysine at position 16 therein by aspartic acid or glutamine; and (d) substitution of aspartic acid at position 17 therein by lysine or serine; and (iii) a more heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 30 or the amino acid sequence of SEQ ID NO: 30 but for one or substitutions selected from the group consisting of: (a) substitution of aspartic acid at position 3 therein by proline, glycine, threonine or alanine; (b) substitution of glycine at position 4 therein by proline, alanine or histidine; and (c) substitution of tyrosine at position 11 therein by proline or asparagine; and wherein said light chain variable region comprises: (iv) a light chain CDR1 having the amino acid sequence of SEQ ID NO: 20 or the amino acid sequence of SEQ ID NO: 20 but for one or more substitutions selected from the group consisting of: (a) substitution of glutamine at position 4 therein by arginine or serine; (b) substitution of asparagine at position 8 therein by serine; (c) substitution of serine at position 9 therein by tyrosine, tryptophan, histidine or arginine; (d) substitution of glycine at position 10 therein by tyrosine, arginine, histidine or isoleucine; and (e) substitution of glutamine at position 12 therein by lysine; (v) a light chain CDR 2 having the amino acid sequence of SEQ ID NO: 22; and (vi) a light chain CDR3 having the amino acid sequence of SEQ ID NO: 24 or the amino acid sequence of SEQ ID NO: 24 but for one or more substitutions selected from the group consisting of: (a) substitution of serine at position 5 therein by glutamine, glycine, leucine, alanine, threonine or valine; and (b) substitution of tyrosine at position 6 therein by asparagine, serine, proline or methionine.