Compositions for increasing half-life of a therapeutic agent in livestock animals and methods of use

A polypeptide comprising an IgG Fc region variant of a livestock animal, or an FcRn-binding region thereof, wherein the polypeptide comprises an amino acid substitution at at least one position selected from the group consisting of:

• (i) a position that corresponds to amino acid position 250 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of S250Q, S250E, T250Q, T250E, I250Q, I250E, A250Q, A250E, V250Q and V250E;
• (ii) a position that corresponds to amino acid position 252 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of M252Y, M252W, M252F, T252Y, T252W, T252F, K252Y, K252W and K252F;
• (iii) a position that corresponds to amino acid position 254 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of S254T, S254R, S254K, S254H, T254R, T254K and T254H;
• (iv) a position that corresponds to amino acid position 256 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of T256A, T256D, T256E, M256A, M256D, M256E, K256A, K256D and K256E;
• (v) a position that corresponds to amino acid position 286 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of S286Y, S286F, S286W, S286L, S286D, S286E, T286Y, T286F, T286W, T286L, T286D and T286E;
• (vi) a position that corresponds to amino acid position 309 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of Q309V, Q309D and Q309E;
• (vii) a position that corresponds to amino acid position 311 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of Q311V, Q311K, Q311R, Q311L, Q311H, E311V, E311K, E311R, E311L, E311H, K311V, K311R, K311L, K311H, D311V, D311K, D311R, D311L and D311H;
• (viii) a position that corresponds to amino acid position 426 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of A426Y, A426F, A426H, V426Y, V426F, V426H, G426Y, G426F and G426H;
• (ix) a position that corresponds to amino acid position 428 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of M428L, M428Y, M428F, H428L, H428Y and H428F;
• (x) a position that corresponds to amino acid position 434 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of N434A, N434H, N434F, N434S, N434W, N434Y, H434A, H434F, H434S, H434W and H434Y;
• and
• (xi) a position that corresponds to amino acid position 436 of a wild type IgG of the livestock animal, wherein the amino acid substitution is selected from the group consisting of Y436H, T436H, F436H and V436H;
• wherein the amino acid positions are based on EU numbering, and wherein the polypeptide has increased binding affinity to an FcRn of the livestock animal when compared to an Fc domain of the wild type IgG.