US 12,371,511 B2
Heterodimerized polypeptide
Futa Mimoto, Shizuoka (JP); Taichi Kuramochi, Shizuoka (JP); Tomoyuki Igawa, Shizuoka (JP); Meiri Kawazoe, Shizuoka (JP); Hitoshi Katada, Shizuoka (JP); Hirotake Shiraiwa, Shizuoka (JP); and Shojiro Kadono, Kanagawa (JP)
Assigned to Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed by Chugai Seiyaku Kabushiki Kaisha, Tokyo (JP)
Filed on Jan. 2, 2018, as Appl. No. 15/860,163.
Application 15/860,163 is a continuation of application No. 14/127,576, granted, now 9,890,218, previously published as PCT/JP2012/066665, filed on Jun. 29, 2012.
Claims priority of application No. 2011-146778 (JP), filed on Jun. 30, 2011; and application No. 2011-288240 (JP), filed on Dec. 28, 2011.
Prior Publication US 2018/0155451 A1, Jun. 7, 2018
This patent is subject to a terminal disclaimer.
Int. Cl. C07K 16/00 (2006.01); C07K 1/107 (2006.01); C07K 16/18 (2006.01); C07K 16/22 (2006.01); C07K 16/28 (2006.01); C07K 16/30 (2006.01); C07K 16/36 (2006.01); C07K 16/46 (2006.01); G01N 33/566 (2006.01)
CPC C07K 16/46 (2013.01) [C07K 1/1075 (2013.01); C07K 16/00 (2013.01); C07K 16/18 (2013.01); C07K 16/22 (2013.01); C07K 16/2866 (2013.01); C07K 16/30 (2013.01); C07K 16/303 (2013.01); C07K 16/36 (2013.01); G01N 33/566 (2013.01); C07K 2317/52 (2013.01); C07K 2317/524 (2013.01); C07K 2317/71 (2013.01); C07K 2317/72 (2013.01); C07K 2317/732 (2013.01); C07K 2317/92 (2013.01); C07K 2317/94 (2013.01)] 29 Claims
 
1. A molecule comprising a heterodimeric Fc region that is a heterodimer of a first Fc polypeptide and a second Fc polypeptide that differs in amino acid sequence from the first Fc polypeptide,
wherein the first Fc polypeptide comprises a hinge region or a part thereof, a first human IgG1 CH2 domain and a CH3 domain, wherein the first human IgG1 CH2 domain comprises a set of substitutions selected from sets (i) to (vi), and wherein all positions are by EU numbering:
(i) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser,
substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp,
substitution of Gly at position 236 with Trp or Tyr,
substitution of His at position 268 with Asp, Glu, or Ala, and
substitution of Ser at position 298 with Ala;
(ii) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser,
substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp,
substitution of Gly at position 236 with Trp or Tyr,
substitution of His at position 268 with Asp, Glu, or Ala,
substitution of Asp at position 270 with Glu, and
substitution of Ser at position 298 with Ala;
(iii) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser,
substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp,
substitution of Gly at position 236 with Trp or Tyr,
substitution of Ser at position 239 with Met,
substitution of His at position 268 with Asp, Glu, or Ala,
substitution of Asp at position 270 with Glu, and
substitution of Ser at position 298 with Ala;
(iv) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser,
substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp,
substitution of Gly at position 236 with Trp or Tyr,
substitution of His at position 268 with Asp, Glu, or Ala,
substitution of Ser at position 298 with Ala, and
substitution of Ala at position 327 with Asp;
(v) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser,
substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp,
substitution of Gly at position 236 with Trp or Tyr,
substitution of Ser at position 239 with Met,
substitution of His at position 268 with Asp, Glu, or Ala,
substitution of Ser at position 298 with Ala, and
substitution of Ala at position 327 with Asp;
(vi) substitution of Leu at position 234 with Tyr, Ala, Glu, Gly, His, or Ser,
substitution of Leu at position 235 with Tyr, Ala, Glu, Phe, Ile, Leu, Met, Asn, Pro, Gln, Thr, Val, or Trp,
substitution of Gly at position 236 with Trp or Tyr,
substitution of Ser at position 239 with Met,
substitution of His at position 268 with Asp, Glu, or Ala,
substitution of Ser at position 298 with Ala,
substitution of Ala at position 327 with Asp,
substitution of Leu at position 328 with Trp, and
substitution of Lys at position 334 with Ile, Glu, or Asp;
and wherein the second Fc polypeptide comprises a hinge region or a part thereof, a second human IgG1 CH2 domain and a CH3 domain, wherein the second human IgG1 CH2 domain comprises a set of substitutions selected from sets (vii) and (viii), and wherein all positions are by EU numbering:
(vii) substitution of Lys at position 326 with Thr, Asp, or Ile,
substitution of Ala at position 330 with Lys, Pro, Met, or Phe, and
substitution of Lys at position 334 with Ile, Glu, or Asp;
(viii) substitution of Asp at position 270 with Glu,
substitution of Lys at position 326 with Thr, Asp, or Ile,
substitution of Ala at position 330 with Lys, Pro, Met, or Phe, and
substitution of Lys at position 334 with Ile, Glu, or Asp.