	US 11,718,678 B2
	Method for altering plasma retention and immunogenicity of antigen-binding molecule
Tomoyuki Igawa, Shizuoka (JP); Atsuhiko Maeda, Shizuoka (JP); Kenta Haraya, Shizuoka (JP); Yuki Iwayanagi, Shizuoka (JP); Tatsuhiko Tachibana, Shizuoka (JP); Futa Mimoto, Shizuoka (JP); Taichi Kuramochi, Shizuoka (JP); Hitoshi Katada, 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 Mar. 2, 2020, as Appl. No. 16/806,027.
Application 16/806,027 is a division of application No. 14/007,947, granted, now 10,618,965, previously published as PCT/JP2012/058603, filed on Mar. 30, 2012.
Claims priority of application No. PCT/JP2011/001888 (WO), filed on Mar. 30, 2011; application No. PCT/JP2011/072550 (WO), filed on Sep. 30, 2011; and application No. PCT/JP2012/054624 (WO), filed on Feb. 24, 2012.
Prior Publication US 2020/0199241 A1, Jun. 25, 2020
Int. Cl. C07K 16/28 (2006.01); C07K 16/30 (2006.01); C07K 16/08 (2006.01); C07K 16/18 (2006.01)

CPC C07K 16/2866 (2013.01) [C07K 16/08 (2013.01); C07K 16/18 (2013.01); C07K 16/303 (2013.01); C07K 2317/524 (2013.01); C07K 2317/72 (2013.01)]

16 Claims

1. A method for improving pharmacokinetics of an antigen-binding molecule, the method comprising:

identifying a first antigen-binding molecule comprising (a) an antigen-binding domain whose antigen-binding activity varies depending on pH or on calcium ion concentration, and (b) an Fc region that has FcRn-binding activity at pH 7.0;

producing a second antigen-binding molecule that is identical to the first antigen-binding molecule except for at least one amino acid mutation in the Fc region, wherein the ability of the second antigen-binding molecule to form a heterocomplex with two molecules of FcRn and one molecule of an activating Fcγ receptor at pH 7.4 is reduced compared to the ability of the first antigen-binding molecule to form such a heterocomplex at pH 7.4; and

conducting one or more assays to confirm that the second antigen-binding molecule has one or both of the following properties:

(1) increased plasma retention compared to the first antigen-binding molecule,

(2) decreased plasma clearance compared to the first antigen-binding molecule;

wherein the second antigen-binding molecule's ability to bind to the activating Fcγ receptor is decreased compared to the ability of an Fc region of a native human IgG to bind to the activating Fcγ receptor, and wherein the at least one amino acid mutation in the Fc region of the second antigen-binding molecule comprises substitution at one or more of the following EU numbering positions with an amino acid indicated below for each position:

Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Lys, Met, Phe, Pro, Ser, Thr, or Trp at position 234;

Ala, Asn, Asp, Gln, Glu, Gly, His, Ile, Lys, Met, Pro, Ser, Thr, Val, or Arg at position 235;

Arg, Asn, Gln, His, Leu, Lys, Met, Phe, Pro, or Tyr at position 236;

Ala, Asn, Asp, Gln, Glu, His, Ile, Leu, Lys, Met, Pro, Ser, Thr, Val, Tyr, or Arg at position 237;

Ala, Asn, Gln, Glu, Gly, His, Ile, Lys, Thr, Trp, or Arg at position 238;

Gln, His, Lys, Phe, Pro, Trp, Tyr, or Arg at position 239;

Ala, Arg, Asn, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr, or Val at position 265;

Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Lys, Phe, Pro, Ser, Thr, Trp, or Tyr at position 266;

Arg, His, Lys, Phe, Pro, Trp, or Tyr at position 267;

Ala, Arg, Asn, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val at position 269;

Ala, Arg, Asn, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val at position 270;

Arg, His, Phe, Ser, Thr, Trp, or Tyr at position 271;

Arg, Asn, Asp, Gly, His, Phe, Ser, Trp, or Tyr at position 295;

Arg, Gly, Lys, or Pro at position 296;

Ala at position 297;

Arg, Gly, Lys, Pro, Trp, or Tyr at position 298;

Arg, Lys, or Pro at position 300;

Lys or Pro at position 324;

Ala, Arg, Gly, His, Ile, Lys, Phe, Pro, Thr, Trp, Tyr, or Val at position 325;

Arg, Gln, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val at position 327;

Arg, Asn, Gly, His, Lys, or Pro at position 328;

Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Ser, Thr, Trp, Tyr, Val, or Arg at position 329;

Pro or Ser at position 330;

Arg, Gly, or Lys at position 331;

Arg, Lys, or Pro at position 332.