Patent ID: 7951918

Claim:
A stabilized scFv molecule which comprises a V H domain and a V L domain derived from the V H domain and the V L domain of SEQ ID NO: 4; wherein said scFv V H domain comprises the three complementarity determining regions (CDRs) of the V H domain of SEQ ID NO: 4 and said scFv V L domain comprises the three CDRs of the V L domain of SEQ ID NO: 4 except for at least one stabilizing mutation selected from the group consisting of: a) substitution at Kabat position 13 of VH to Glutamic acid (E); b) substitution at Kabat position 16 of VH to Glutamic acid (E) or Glutamine (Q); c) substitution at Kabat position 20 of VH to Isoleucine (I); d) substitution at Kabat position 46 of VL to Leucine (L); e) substitution at Kabat position 49 of VL to Tyrosine (Y) or Serine (S); f) substitutions at Kabat position 49 of VL to Tyrosine (Y) or Serine (S) and at Kabat position 50 of VL to Alanine (A); g) substitution at Kabat position 101 of VH to Aspartic acid (D); h) substitution at Kabat position 48 of VH to Isoleucine (I) or Glycine (G); i) substitution at Kabat position 3 of VL to Alanine (A), Serine (S), Valine (V), Aspartic acid (D), or Glycine (G); j) substitution at Kabat position 55 of VH to Glycine (G); k) substitution at Kabat position 67 of VH to Isoleucine (I) or Leucine (L); l) substitutions at Kabat position 16 of VH to Glutamic acid (E) or Glutamine (Q) and at Kabat position 46 of VL to Leucine (L); m) substitutions at Kabat position 16 of VH to Glutamic acid (E) or Glutamine (Q), at Kabat position 55 of VH to Glycine (G), and at Kabat position 46 of VL to Leucine (L); n) substitutions at Kabat position 16 of VH to Glutamic acid (E) or Glutamine (Q), at Kabat position 55 of VH to Glycine (G), at Kabat position 101 of VH to Aspartic acid (D), and at Kabat position 46 of VL to Leucine (L); o) substitutions at Kabat position 44 of VH to Cysteine (C) and at Kabat position 100 of VL to Cysteine (C); and p) a combination of two or more of said substitution, wherein said scFv molecule specifically binds to Lymphotoxin-β Receptor (LTβR) and the thermal stability of said stabilized scFv molecule is higher than that of a corresponding conventional scFv molecule without said stabilizing mutation.