Polypeptides with altered binding to neonatal Fc receptor (FcRn) and methods of use
AssigneeInvetx, Inc.
InventorsWilliam Brondyk, Brett Chevalier, Juergen Horn, Madhusudan Natarajan
Life of this patent
Estimating the term…
Abstract
Provided are compositions for increasing the half-life of a polypeptide or polypeptides in a canine and methods of their use. The compositions involve variant canine IgG Fc regions.
Claims13
A polypeptide comprising a canine IgG Fc region variant, or a canine FcRn-binding region thereof, wherein the canine IgG Fc region variant, or the canine FcRn-binding region thereof, comprises amino acid substitutions at positions selected from the group consisting of:
- (i) positions that correspond to amino acid positions 426 and 286 of a wild type canine IgG;
- (ii) positions that correspond to amino acid position 426 and 312 of a wild type canine IgG;
- (iii) positions that correspond to amino acid position 426 and 434 of a wild type canine IgG;
- (iv) positions that correspond to amino acid position 426 and 436 of a wild type canine IgG;
- and
- (v) positions that correspond to amino acid position 286, 426 and 436 of a wild type canine IgG
- wherein the amino acid positions are based on EU numbering, wherein the polypeptide has increased binding affinity to canine FcRn when compared to an Fc domain of the wild type canine IgG, and wherein the wild type canine IgG is a canine IgG.B comprising an Fc domain having the amino acid sequence of SEQ ID NO:
- 10.
A polypeptide comprising a canine IgG Fc region variant, or a canine FcRn-binding region thereof, wherein the canine IgG Fc region variant, or the canine FcRn-binding region thereof, comprises amino acid substitutions at positions selected from the group consisting of:
- (i) A426Y in combination with one or more of T286L, D312P, N434R and Y436H;
- (ii) A426H in combination with one or more of T286L, T286Y, D312P, N434R and Y436H;
- and
- (iii) N434R in combination with one or more of T286L, T286Y, D312P and Y436H;
- wherein the amino acid positions are based on EU numbering, wherein the polypeptide has increased binding affinity to canine FcRn when compared to an Fc domain of a wild type canine IgG, and wherein the wild type canine IgG is a canine IgG.B comprising an Fc domain having the amino acid sequence of SEQ ID NO:
- 10.
A polypeptide comprising a canine IgG Fc region variant, or a canine FcRn-binding region thereof, wherein the canine IgG Fc region variant, or the canine FcRn-binding region thereof, comprises amino acid substitutions A426Y and T286L;
- wherein the amino acid positions are based on EU numbering, wherein the polypeptide has increased binding affinity to canine FcRn when compared to an Fc domain of a wild type canine IgG, and wherein the wild type canine IgG is a canine IgG.B comprising an Fc domain having the amino acid sequence of SEQ ID NO:
- 10.
Dependencies are inferred from the claim text.