Patent ID: 11952422
Assignee: CHUGAI SEIYAKU KABUSHIKI KAISHA
Field: Biotechnology (Chemistry)
Classification: CPC C | IPC C

Claim 12:
13. A tri-specific IgG antibody comprising:
a dual-binding Fab comprising a first variable region that binds to human CD3 epsilon and human CD137, but does not bind to human CD3 epsilon and human CD137 at the same time;
a second Fab comprising a second variable region that binds to a third antigen different from human CD3 epsilon and human CD137, wherein the third antigen is a cancer antigen; and
an Fc region,, wherein the first variable region comprises:
(1) a VL having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 51, 52, 53, 54, 55, 56, or 57, and
(2) a VH that comprises an amino acid sequence comprising SEQ ID NO: 135 with a substitution at 2 to 10 positions, and wherein the VH comprises, at one or more positions selected from the following Kabat numbering positions, one of the amino acids indicated for that position:
Ile, Asn, or Ser at position 31;
Arg or Lys at position 52b;
Ala, Gly, Leu, Gln, Val, or Ser at position 52c;
Gln, Ser, or Asn at position 53;
Ala, Gly, Leu, Gln, Ser, or Asn at position 54;
Leu, Asn, or Ala at position 56;
Ala, Asn, or Thr at position 57;
Pro or Glu at position 61;
Ala, Gly, Pro, Ser, Thr, Gln, or His at position 98;
Ala, Leu, Ser, Gln, or Thr at position 99;
Ala, Val, Gly, Ser, Thr, Tyr, or Phe at position 100;
Ala, Val, Gly, Ser, Thr, Tyr, Phe, or Asp at position 100a;
Gly, Ser, Thr, Tyr, Phe, or Asp at position 100b;
Ala, Val, Leu, Gly, Ser, Tyr, or Phe at position 100c;
Leu, Gly, Ser, Tyr, or Phe at position 100d;
Pro, Gly, Ser, Tyr, or Phe at position 100e;
Ala, Ser, Gln, Lys, Tyr, or Gly at position 100f;
Tyr, Phe, or Gly at position 100g.