Heterodimerized polypeptide

  • US 9,890,218 B2
  • Filed: 06/29/2012
  • Issued: 02/13/2018
  • Est. Priority Date: 06/30/2011
  • Status: Active Grant
First Claim
Patent Images

1. A molecule comprising a heterodimeric Fc region that is a heterodimer of a first polypeptide comprising a first CH2 domain and a second polypeptide comprising a second CH2 domain that differs in amino acid sequence from the first CH2 domain,wherein the first CH2 domain is an IgG1 CH2 domain comprising a set of amino acid mutations selected from sets (i)-(vi) (all positions by EU numbering):

  • (i) substitution of L at position 234 with Y,substitution of L at position 235 with Y,substitution of G at position 236 with W,substitution of H at position 268 with D, andsubstitution of S at position 298 with A;

    (ii) substitution of L at position 234 with Y,substitution of L at position 235 with Y,substitution of G at position 236 with W,substitution of H at position 268 with D,substitution of D at position 270 with E, andsubstitution of S at position 298 with A;

    (iii) substitution of L at position 234 with Y,substitution of L at position 235 with Q,substitution of G at position 236 with W,substitution of S at position 239 with M,substitution of H at position 268 with D,substitution of D at position 270 with E, andsubstitution of S at position 298 with A;

    (iv) substitution of L at position 234 with Y,substitution of L at position 235 with Y,substitution of G at position 236 with W,substitution of H at position 268 with D,substitution of S at position 298 with A, andsubstitution of A at position 327 with D;

    (v) substitution of L at position 234 with Y,substitution of L at position 235 with Y,substitution of G at position 236 with W,substitution of S at position 239 with M,substitution of H at position 268 with D,substitution of S at position 298 with A, andsubstitution of A at position 327 with D;

    (vi) substitution of L at position 234 with Y,substitution of L at position 235 with Y,substitution of G at position 236 with W,substitution of S at position 239 with M,substitution of H at position 268 with D,substitution of S at position 298 with A,substitution of A at position 327 with D,substitution of L at position 328 with W, andsubstitution of K at position 334 with L;

    and the second CH2 domain is an IgG1 CH2 domain comprising a set of amino acid mutations selected from sets (vii)-(ix) (all positions by EU numbering);

    (vii) substitution of K at position 326 with D,substitution of A at position 330 with M, andsubstitution of K at position 334 with E;

    (viii) substitution of D at position 270 with E,substitution of K at position 326 with D,substitution of A at position 330 with M, andsubstitution of K at position 334 with E;

    (ix) substitution of D at position 270 with E,substitution of K at position 326 with D,substitution of A at position 330 with K, andsubstitution of K at position 334 with E.

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