FC variants with altered binding to neonatal FC receptor (FCRN) for veterinary use

Abstract

To provide variant IgG Fc polypeptides with altered binding to neonatal FC receptor.SOLUTION: Provided is a polypeptide comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide from a companion animal species, the variant Fc polypeptide being capable of binding to a neonatal Fc receptor with an increased affinity relative to the wild-type Fc polypeptide, and in one embodiment, binding to FcRn with an affinity greater than the wild-type IgG Fc polypeptide at a pH ranging from about 5.0 to about 6.5, as measured by biolayer interferometry, surface plasmon resonance, or any protein-protein interaction tool.SELECTED DRAWING: Figure 15

Description

Technical Field

[0001]

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 62 / 747,613, filed Oct. 18, 2018, and U.S. Provisional Patent Application No. 62 / 809,715, filed Feb. 24, 2019, the entire contents of each of which are incorporated herein by reference for all purposes.

[0002]

[0002] The present disclosure relates to variant IgG Fc polypeptides of companion animals in which the binding affinity for FcRn is altered, such as an improvement in the binding affinity for FcRn at acidic pH (e.g., a pH in the range of about 5.0 to about 6.5). The variant IgG Fc polypeptides of the present disclosure can extend the half-life or improve the pharmacokinetics of an antibody or IgG Fc fusion protein in vivo. In addition, the variant IgG Fc polypeptides can be used in the design and manufacture of antibodies or fusion proteins for treating various disorders in companion animals.

Background Art

[0003]

[0003] The neonatal Fc receptor (FcRn) is an Fc receptor that is structurally similar to MHC class I molecules. Similar to MHC class I molecules, FcRn also binds to beta-2-microglobulin (B2M). FcRn is understood to facilitate the transcytosis and recycling of IgG in vivo, and thus increase the in vivo half-life of IgG compared to the half-lives of other antibody isotypes.

[0004]

[0004] To improve the binding affinity of IgG for FcRn at acidic pH (e.g., a pH in the range of about 5.0 to about 6.5), the Fc region of IgG involved in binding to FcRn can be modified by mutagenesis.

[0005] Companion animals such as cats, dogs, and horses have species-specific IgG Fc sequences. Furthermore, there are multiple IgG subclasses, each with a different Fc sequence. For example, dogs have IgG-A, IgG-B, IgG-C, and IgG-D.

SUMMARY OF THE INVENTION

[0006] Embodiment 1. A polypeptide comprising a mutant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide derived from a companion animal species, wherein the mutant Fc polypeptide is capable of binding to the neonatal Fc receptor (FcRn) with increased affinity relative to the wild-type Fc polypeptide.

[0007] Embodiment 2. The polypeptide of Embodiment 1, wherein the mutant Fc polypeptide binds to FcRn with higher affinity than the wild-type IgG Fc polypeptide as measured by biolayer interferometry, surface plasmon resonance, or any protein-protein interaction tool at a pH in the range of about 5.0 to about 6.5, such as pH about 5.0, pH about 5.2, pH about 5.5, pH about 6.0, pH about 6.2, or pH about 6.5.

[0008] Embodiment 3. The mutant IgG Fc polypeptide binds to FcRn with higher affinity than the wild-type IgG Fc polypeptide as measured by biolayer interferometry, surface plasmon resonance, or any protein-protein interaction tool at a pH in the range of about 5.0 to about 6.5, such as pH about 5.0, pH about 5.5, pH about 6.0, or pH about 6.5, and is less than 5x10 -6 M, less than 1x10 -6 M, less than 5x10 -7 M, less than 1x10 -7 M, less than 5x10 -8 M, less than 1x10 -8 M, less than 5x10 -9 M, less than 1x10 -9 M, less than 5x10 -10 M, less than 1x10 -10 M, less than 5x10 -11 M, less than 1x10 -11 M, less than 5x10 -12less than M or 1x10 -12 The polypeptide of embodiment 1 or embodiment 2 that binds to FcRn with a dissociation constant (Kd) of less than M.

[0009] Embodiment 4. The polypeptide of any one of embodiments 1 to 3, having an increased serum half-life as compared to a polypeptide containing wild-type Fc.

[0010] Embodiment 5. The polypeptide of any one of embodiments 1 to 4, wherein the companion animal species is a dog, a cat or a horse.

[0011] Embodiment 6. The wild-type IgG Fc polypeptide is a) canine IgG-A Fc, IgG-B Fc, IgG-C Fc or IgG-D Fc; b) equine IgG1 Fc, IgG2 Fc, IgG3 Fc, IgG4 Fc, IgG5 Fc, IgG6 Fc or IgG7 Fc; or c) feline IgG1 Fc or IgG2 Fc The polypeptide of any one of embodiments 1 to 5.

[0012] Embodiment 7. A polypeptide according to any one of Embodiments 1 to 6, wherein the variant IgG Fc polypeptide is at least 90% identical, at least 95% identical, at least 97% identical, or at least 99% identical to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89 or SEQ ID NO: 91.

[0013] Embodiment 8. The variant IgG Fc polypeptide is a) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 83, 132, 149, 162, 183, 203, 205 and / or 209 of SEQ ID NO: 1; b) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 2; c) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204 and / or 208 of SEQ ID NO: 3; d) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 60, 79, 80, 83, 132, 149, 163, 183, 203, 205 and / or 209 of SEQ ID NO: 4; e) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 5; f) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 6; g) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 7; h) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 8; i) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 9; j) At least one amino acid substitution at at least one position corresponding to positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 10; k) At least one amino acid substitution at at least one position corresponding to positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 11; l) At least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 12; m) At least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 13; or n) At least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 54 A polypeptide according to any one of embodiments 1 to 7, comprising:

[0014] Embodiment 9. The variant IgG Fc polypeptide is a) At least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 83, 132, 149, 162, 183, 203, 205 and / or 209 of SEQ ID NO: 1; b) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 2; c) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204 and / or 208 of SEQ ID NO: 3; d) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 60, 79, 80, 83, 132, 149, 163, 183, 203, 205 and / or 209 of SEQ ID NO: 4; e) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 5; f) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 6; g) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 7; h) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 8; i) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 9; j) at least one amino acid substitution at at least one position selected from positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 10; k) at least one amino acid substitution at at least one position selected from positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 11; l) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 12; m) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 13; or n) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 54 A polypeptide according to any one of embodiments 1 to 8, comprising the above.

[0015] Embodiment 10. The variant IgG Fc polypeptide is a) Tyrosine at the position corresponding to position 9 of SEQ ID NO: 1; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 149; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 183; leucine or tryptophan at the position corresponding to position 203; proline at the position corresponding to position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 209; b) Tyrosine at the position corresponding to the 9th position of SEQ ID NO: 2; Proline at the position corresponding to the 18th position; Histidine, Isoleucine or Proline at the position corresponding to the 22nd position; Valine, Arginine or Lysine at the position corresponding to the 23rd position; Phenylalanine, Tyrosine, Methionine, Arginine or Valine at the position corresponding to the 24th position; Threonine at the position corresponding to the 25th position; Tryptophan, Tyrosine, Histidine, Leucine, Phenylalanine, Valine, Methionine, Threonine or Serine at the position corresponding to the 26th position; Leucine, Methionine, Proline, Isoleucine, Asparagine or Tryptophan at the position corresponding to the 27th position; Methionine, Glutamic acid, Asparagine, Histidine, Isoleucine or Valine at the position corresponding to the 28th position; Methionine or Valine at the position corresponding to the 30th position; Isoleucine at the position corresponding to the 31st position; Alanine at the position corresponding to the 60th position; Glutamine, Arginine, Alanine, Glutamic acid or Methionine at the position corresponding to the 79th position; Histidine or Phenylalanine at the position corresponding to the 80th position; Glutamic acid at the position corresponding to the 81st position; Alanine, Tyrosine or Phenylalanine at the position corresponding to the 83rd position; Isoleucine at the position corresponding to the 132nd position; Valine at the position corresponding to the 148th position; Leucine, Phenylalanine or Tyrosine at the position corresponding to the 162nd position; Isoleucine at the position corresponding to the 182nd position; Leucine or Tryptophan at the position corresponding to the 202nd position; Proline at the position corresponding to the 204th position; Serine, Alanine, Arginine, Phenylalanine, Tyrosine, Histidine or Tryptophan at the position corresponding to the 208th position; and / or Isoleucine or Valine at the position corresponding to the 213th position; c) Tyrosine at the position corresponding to position 9 of SEQ ID NO: 3; proline at the position corresponding to position 18; histidine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or arginine at the position corresponding to position 24; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; d) Tyrosine at the position corresponding to the 9th position of SEQ ID NO: 4; proline at the position corresponding to the 18th position; histidine or proline at the position corresponding to the 22nd position; valine, arginine or lysine at the position corresponding to the 23rd position; phenylalanine, tyrosine, methionine or valine at the position corresponding to the 24th position; threonine at the position corresponding to the 25th position; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to the 26th position; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to the 27th position; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to the 28th position; methionine or valine at the position corresponding to the 30th position; alanine at the position corresponding to the 60th position; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to the 79th position; histidine or phenylalanine at the position corresponding to the 80th position; alanine, tyrosine or phenylalanine at the position corresponding to the 83rd position; isoleucine at the position corresponding to the 132nd position; valine at the position corresponding to the 149th position; leucine, phenylalanine or tyrosine at the position corresponding to the 163rd position; isoleucine at the position corresponding to the 183rd position; leucine or tryptophan at the position corresponding to the 203rd position; proline at the position corresponding to the 205th position; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to the 209th position; e) Tyrosine at the position corresponding to position 9 of SEQ ID NO: 5; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; f) Tyrosine at the position corresponding to the 9th position of SEQ ID NO: 6; proline at the position corresponding to the 18th position; histidine, isoleucine or proline at the position corresponding to the 22nd position; valine, arginine or lysine at the position corresponding to the 23rd position; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to the 24th position; threonine at the position corresponding to the 25th position; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine or threonine at the position corresponding to the 26th position; leucine, methionine, proline, isoleucine, asparagine or valine at the position corresponding to the 27th position; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to the 28th position; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to the 79th position; histidine or phenylalanine at the position corresponding to the 80th position; glutamic acid at the position corresponding to the 81st position; alanine, tyrosine or phenylalanine at the position corresponding to the 83rd position; isoleucine at the position corresponding to the 132nd position; valine at the position corresponding to the 148th position; leucine, phenylalanine or tyrosine at the position corresponding to the 162nd position; isoleucine at the position corresponding to the 182nd position; leucine or tryptophan at the position corresponding to the 202nd position; proline at the position corresponding to the 204th position; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to the 208th position; and / or isoleucine or valine at the position corresponding to the 213th position; g) Tyrosine at the position corresponding to the 9th position of SEQ ID NO: 7; proline at the position corresponding to the 18th position; histidine, isoleucine, and / or proline at the position corresponding to the 22nd position; valine, arginine or lysine at the position corresponding to the 23rd position; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to the 24th position; threonine at the position corresponding to the 25th position; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to the 27th position; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to the 28th position; methionine or valine at the position corresponding to the 30th position; isoleucine at the position corresponding to the 31st position; alanine at the position corresponding to the 60th position; glutamine, glutamic acid or methionine at the position corresponding to the 79th position; histidine or phenylalanine at the position corresponding to the 80th position; glutamic acid at the position corresponding to the 81st position; alanine, tyrosine or phenylalanine at the position corresponding to the 83rd position; isoleucine at the position corresponding to the 132nd position; valine at the position corresponding to the 148th position; leucine, phenylalanine or tyrosine at the position corresponding to the 162nd position; isoleucine at the position corresponding to the 182nd position; leucine or tryptophan at the position corresponding to the 202nd position; proline at the position corresponding to the 204th position; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to the 208th position; and / or isoleucine or valine at the position corresponding to the 213th position; h) Tyrosine at the position corresponding to the 9th position of SEQ ID NO: 8; proline at the position corresponding to the 18th position; histidine, isoleucine or proline at the position corresponding to the 22nd position; valine, arginine or lysine at the position corresponding to the 23rd position; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to the 24th position; threonine at the position corresponding to the 25th position; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to the 27th position; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to the 28th position; methionine or valine at the position corresponding to the 30th position; isoleucine at the position corresponding to the 31st position; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to the 79th position; histidine or phenylalanine at the position corresponding to the 80th position; alanine, tyrosine or phenylalanine at the position corresponding to the 83rd position; isoleucine at the position corresponding to the 132nd position; valine at the position corresponding to the 148th position; leucine, phenylalanine or tyrosine at the position corresponding to the 162nd position; isoleucine at the position corresponding to the 182nd position; leucine or tryptophan at the position corresponding to the 202nd position; proline at the position corresponding to the 204th position; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to the 208th position; and / or isoleucine or valine at the position corresponding to the 213th position; i) Tyrosine at the position corresponding to position 9 of SEQ ID NO: 9; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine, phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; j) proline at the position corresponding to the 18th position of SEQ ID NO: 10; histidine, isoleucine or proline at the position corresponding to the 22nd position; valine, arginine or lysine at the position corresponding to the 23rd position; phenylalanine, tyrosine, arginine or valine at the position corresponding to the 24th position; threonine at the position corresponding to the 25th position; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to the 27th position; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to the 28th position; methionine or valine at the position corresponding to the 30th position; isoleucine at the position corresponding to the 31st position; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to the 79th position; histidine or phenylalanine at the position corresponding to the 80th position; glutamic acid at the position corresponding to the 81st position; alanine, tyrosine or phenylalanine at the position corresponding to the 83rd position; isoleucine at the position corresponding to the 132nd position; valine at the position corresponding to the 148th position; leucine, phenylalanine or tyrosine at the position corresponding to the 162nd position; isoleucine at the position corresponding to the 182nd position; leucine or tryptophan at the position corresponding to the 202nd position; proline at the position corresponding to the 204th position; serine, alanine, arginine, phenylalanine, tyrosine or tryptophan at the position corresponding to the 208th position; and / or isoleucine or valine at the position corresponding to the 213th position; k) Proline at the position corresponding to position 18 of SEQ ID NO: 11; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamate, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine, glutamate or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamate at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; l) Tyrosine at the position corresponding to the 9th position of SEQ ID NO: 12; proline at the position corresponding to the 18th position; histidine, isoleucine or proline at the position corresponding to the 22nd position; valine, arginine or lysine at the position corresponding to the 23rd position; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to the 24th position; threonine at the position corresponding to the 25th position; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to the 26th position; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to the 27th position; methionine, glutamate, asparagine, histidine, isoleucine or valine at the position corresponding to the 28th position; methionine or valine at the position corresponding to the 30th position; isoleucine at the position corresponding to the 31st position; alanine at the position corresponding to the 60th position; glutamine, arginine, alanine, glutamate or methionine at the position corresponding to the 79th position; histidine or phenylalanine at the position corresponding to the 80th position; glutamate at the position corresponding to the 81st position; alanine, tyrosine or phenylalanine at the position corresponding to the 83rd position; valine at the position corresponding to the 148th position; leucine, phenylalanine or tyrosine at the position corresponding to the 162nd position; isoleucine at the position corresponding to the 182nd position; leucine or tryptophan at the position corresponding to the 202nd position; proline at the position corresponding to the 204th position; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to the 208th position; and / or isoleucine or valine at the position corresponding to the 213th position; m) Tyrosine at the position corresponding to position 9 of SEQ ID NO: 13; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; or n) Tyrosine at the position corresponding to position 9 of SEQ ID NO: 54; Proline at the position corresponding to position 18; Histidine, Isoleucine or Proline at the position corresponding to position 22; Valine, Arginine or Lysine at the position corresponding to position 23; Phenylalanine, Tyrosine, Methionine, Arginine or Valine at the position corresponding to position 24; Threonine at the position corresponding to position 25; Tryptophan, Tyrosine, Histidine, Leucine, Phenylalanine, Valine or Methionine at the position corresponding to position 26; Leucine, Methionine, Proline, Isoleucine, Asparagine or Tryptophan at the position corresponding to position 27; Methionine, Glutamic acid, Asparagine, Histidine, Isoleucine or Valine at the position corresponding to position 28; Methionine or Valine at the position corresponding to position 30; Isoleucine at the position corresponding to position 31; Alanine at the position corresponding to position 60; Glutamine, Arginine, Alanine, Glutamic acid or Methionine at the position corresponding to position 79; Histidine or Phenylalanine at the position corresponding to position 80; Glutamic acid at the position corresponding to position 81; Alanine, Tyrosine or Phenylalanine at the position corresponding to position 83; Isoleucine at the position corresponding to position 132; Valine at the position corresponding to position 148; Leucine, Phenylalanine or Tyrosine at the position corresponding to position 162; Isoleucine at the position corresponding to position 182; Leucine or Tryptophan at the position corresponding to position 202; Proline at the position corresponding to position 204; Alanine, Arginine, Phenylalanine, Tyrosine, Histidine or Tryptophan at the position corresponding to position 208; and / or Isoleucine or Valine at the position corresponding to position 213 A polypeptide according to any one of embodiments 1 to 9, comprising

[0016] Embodiment 11. The mutant IgG Fc polypeptide is a) At position 9, tyrosine; at position 18, proline; at position 22, histidine, isoleucine or proline; at position 23, valine, arginine or lysine; at position 24, phenylalanine, tyrosine, methionine or valine; at position 25, threonine; at position 26, tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine; at position 27, leucine, methionine, proline, isoleucine, asparagine or tryptophan; at position 28, methionine, glutamic acid, asparagine, histidine, isoleucine or valine; at position 30, methionine or valine; at position 31, isoleucine; at position 60, alanine; at position 79, glutamine, arginine, alanine, glutamic acid or methionine; at position 80, histidine or phenylalanine; at position 83, alanine, tyrosine or phenylalanine; at position 132, isoleucine; at position 149, valine; at position 162, leucine, phenylalanine or tyrosine; at position 183, isoleucine; at position 203, leucine or tryptophan; at position 205, proline; and / or at position 209, serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan; b) For SEQ ID NO:2, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; c) For SEQ ID NO:3, tyrosine at position 9; proline at position 18; histidine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or arginine at position 24; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; d) For SEQ ID NO:4, tyrosine at position 9; proline at position 18; histidine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 149; leucine, phenylalanine or tyrosine at position 163; isoleucine at position 183; leucine or tryptophan at position 203; proline at position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 209; e) For SEQ ID NO: 5, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; glutamine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; f) For SEQ ID NO:6, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine or threonine at position 26; leucine, methionine, proline, isoleucine, asparagine or valine at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at the position corresponding to position 213; g) For SEQ ID NO: 7, tyrosine at position 9; proline at position 18; histidine, isoleucine and / or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamate, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, glutamate or methionine at position 79; histidine or phenylalanine at position 80; glutamate at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; h) For SEQ ID NO: 8, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine, lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamate, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; glutamine, arginine, alanine, glutamate or methionine at position 79; histidine or phenylalanine at position 80; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; i) For SEQ ID NO: 9, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; j) At position 18 of SEQ ID NO: 10, proline; at position 22, histidine, isoleucine or proline; at position 23, valine, arginine or lysine; at position 24, phenylalanine, tyrosine, arginine or valine; at position 25, threonine; at position 27, leucine, methionine, proline, isoleucine, asparagine or tryptophan; at position 28, methionine, glutamic acid, asparagine, histidine, isoleucine or valine; at position 30, methionine or valine; at position 31, isoleucine; at position 79, glutamine, arginine, alanine, glutamic acid or methionine; at position 80, histidine or phenylalanine; at position 81, glutamic acid; at position 83, alanine, tyrosine or phenylalanine; at position 132, isoleucine; at position 148, valine; at position 162, leucine, phenylalanine or tyrosine; at position 182, isoleucine; at position 202, leucine or tryptophan; at position 204, proline; at position 208, serine, alanine, arginine, phenylalanine, tyrosine or tryptophan; and / or at position 213, isoleucine or valine; k) At position 18 of SEQ ID NO: 11, proline; at position 22, histidine, isoleucine or proline; at position 23, valine, arginine or lysine; at position 24, phenylalanine, tyrosine, arginine or valine; at position 25, threonine; at position 27, leucine, methionine, proline, isoleucine, asparagine or tryptophan; at position 28, methionine, glutamic acid, asparagine, histidine, isoleucine or valine; at position 30, methionine or valine; at position 31, isoleucine; at position 79, glutamine, arginine, glutamic acid or methionine; at position 80, histidine or phenylalanine; at position 81, glutamic acid; at position 83, alanine, tyrosine or phenylalanine; at position 132, isoleucine; at position 148, valine; at position 162, leucine, phenylalanine or tyrosine; at position 182, isoleucine; at position 202, leucine or tryptophan; at position 204, proline; at position 208, serine, alanine, phenylalanine, tyrosine, histidine or tryptophan; and / or at position 213, isoleucine or valine; l) Tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; m) For SEQ ID NO: 13, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; or n) A polypeptide of any one of Embodiments 1 to 10, having tyrosine at position 9, proline at position 18, histidine, isoleucine or proline at position 22, valine, arginine or lysine at position 23, phenylalanine, tyrosine, methionine, arginine or valine at position 24, threonine at position 25, tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26, leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27, methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28, methionine or valine at position 30, isoleucine at position 31, alanine at position 60, glutamine, arginine, alanine, glutamic acid or methionine at position 79, histidine or phenylalanine at position 80, glutamic acid at position 81, alanine, tyrosine or phenylalanine at position 83, isoleucine at position 132, valine at position 148, leucine, phenylalanine or tyrosine at position 162, isoleucine at position 182, leucine or tryptophan at position 202, proline at position 204, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 A polypeptide of any one of Embodiments 1 to 10, comprising .

[0017] Embodiment 12. The mutant IgG Fc polypeptide has a) phenylalanine or tyrosine at the position corresponding to position 24 of SEQ ID NO: 1, threonine at the position corresponding to position 26, and / or glutamic acid at the position corresponding to position 28; b) phenylalanine at the position corresponding to position 24 of SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4, threonine at the position corresponding to position 26, and / or glutamic acid at the position corresponding to position 28; or c) phenylalanine or tyrosine at the position corresponding to the 24th position, threonine at the position corresponding to the 26th position, and / or glutamic acid at the position corresponding to the 28th position of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 A polypeptide according to any one of embodiments 1 to 11, comprising

[0018] Embodiment 13. The variant IgG Fc polypeptide is a) phenylalanine or tyrosine at the 24th position, threonine at the 26th position, and / or glutamic acid at the 28th position of SEQ ID NO: 1; b) phenylalanine at the 24th position, threonine at the 26th position, and / or glutamic acid at the 28th position of SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4; or c) phenylalanine or tyrosine at the 24th position, threonine at the 26th position, and / or glutamic acid at the 28th position of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 A polypeptide according to any one of embodiments 1 to 12, comprising

[0019] Embodiment 14. The variant IgG Fc polypeptide is a polypeptide according to any one of embodiments 1 to 13, comprising phenylalanine at the position corresponding to the 24th position of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0020] Embodiment 15. The variant IgG Fc polypeptide is a polypeptide according to any one of embodiments 1 to 14, comprising phenylalanine at the 24th position of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0021] Embodiment 16. The variant IgG Fc polypeptide has a) tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; b) tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208 of SEQ ID NO: 2 or SEQ ID NO: 3; or c) tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 and is a polypeptide according to any one of Embodiments 1 to 15.

[0022] Embodiment 17. The variant IgG Fc polypeptide has a) tyrosine at position 24, tyrosine at position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; b) tyrosine at position 24, tyrosine at position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208 of SEQ ID NO: 2 or SEQ ID NO: 3; or c) tyrosine at position 24, tyrosine at position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 and is a polypeptide according to any one of Embodiments 1 to 16.

[0023] Embodiment 18. The variant IgG Fc polypeptide has a) tyrosine at the position corresponding to position 24 and arginine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; b) tyrosine at the position corresponding to position 24 and arginine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; c) tyrosine at the position corresponding to position 24 and phenylalanine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; d) tyrosine at the position corresponding to position 24 and phenylalanine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; e) tyrosine at the position corresponding to position 24 and tyrosine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; f) tyrosine at the position corresponding to position 24 and tyrosine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; g) tyrosine at the position corresponding to position 24 and histidine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; h) tyrosine at the position corresponding to position 24 and histidine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; i) tyrosine at the position corresponding to position 24 and tryptophan at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; j) Tyrosine at the position corresponding to the 24th position and tryptophan at the position corresponding to the 208th position of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; k) Tyrosine at the position corresponding to the 83rd position and arginine at the position corresponding to the 209th position of SEQ ID NO: 1 or SEQ ID NO: 4; l) Tyrosine at the position corresponding to the 83rd position and arginine at the position corresponding to the 208th position of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; m) Tyrosine at the position corresponding to the 83rd position and phenylalanine at the position corresponding to the 209th position of SEQ ID NO: 1 or SEQ ID NO: 4; n) Tyrosine at the position corresponding to the 83rd position and phenylalanine at the position corresponding to the 208th position of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; o) Tyrosine at the position corresponding to the 83rd position and tyrosine at the position corresponding to the 209th position of SEQ ID NO: 1 or SEQ ID NO: 4; p) Tyrosine at the position corresponding to the 83rd position and tyrosine at the position corresponding to the 208th position of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; q) Tyrosine at the position corresponding to the 83rd position and histidine at the position corresponding to the 209th position of SEQ ID NO: 1 or SEQ ID NO: 4; r) Tyrosine at the position corresponding to the 83rd position and histidine at the position corresponding to the 208th position of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; s) Tyrosine at the position corresponding to the 83rd position and tryptophan at the position corresponding to the 209th position of SEQ ID NO: 1 or SEQ ID NO: 4; t) Tyrosine at the position corresponding to position 83 and tryptophan at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; u) Tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and arginine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; v) Tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and arginine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; w) Tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and phenylalanine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; x) Tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and phenylalanine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; y) Tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and tyrosine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; z) Tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and tyrosine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; aa) Tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and histidine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; bb) tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and histidine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; cc) tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and tryptophan at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; or dd) tyrosine at the position corresponding to position 24; tyrosine at the position corresponding to position 83, and tryptophan at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 A polypeptide according to any one of embodiments 1 to 17, comprising

[0024] Embodiment 19. The variant IgG Fc polypeptide is a) tyrosine at position 24 and arginine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; b) tyrosine at position 24 and arginine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; c) tyrosine at position 24 and phenylalanine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; d) tyrosine at position 24 and phenylalanine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; e) tyrosine at position 24 and tyrosine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; f) tyrosine at position 24 and tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; g) Tyrosine at position 24 and histidine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; h) Tyrosine at position 24 and histidine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; i) Tyrosine at position 24 and tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; j) Tyrosine at position 24 and tryptophan at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; k) Tyrosine at position 83 and arginine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; l) Tyrosine at position 83 and arginine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; m) Tyrosine at position 83 and phenylalanine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; n) Tyrosine at position 83 and phenylalanine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; o) Tyrosine at position 83 and tyrosine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; p) Tyrosine at position 83 and tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; q) Tyrosine at position 83 and histidine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; r) Tyrosine at position 83 and histidine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; s) Tyrosine at position 83 and tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; t) Tyrosine at position 83 and tryptophan at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; u) Tyrosine at position 24, tyrosine at position 83, and arginine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; v) Tyrosine at position 24, tyrosine at position 83, and arginine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; w) Tyrosine at position 24, tyrosine at position 83, and phenylalanine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; x) Tyrosine at position 24, tyrosine at position 83, and phenylalanine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; y) Tyrosine at position 24, tyrosine at position 83, and tyrosine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; z) Tyrosine at position 24, tyrosine at position 83, and tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; aa) Tyrosine at position 24, tyrosine at position 83 and histidine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; bb) tyrosine at position 24, tyrosine at position 83, and histidine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54; cc) tyrosine at position 24, tyrosine at position 83, and tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; or dd) tyrosine at position 24, tyrosine at position 83, and tryptophan at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 A polypeptide according to any one of embodiments 1 to 18, comprising:

[0025] Embodiment 20. A variant IgG Fc polypeptide, which is a polypeptide according to any one of embodiments 1 to 19, comprising the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89 or SEQ ID NO: 91.

[0026] Embodiment 21. A polypeptide according to any one of Embodiments 1 to 20, comprising the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89, SEQ ID NO: 91, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128 or SEQ ID NO: 129.

[0027] Embodiment 22. A polypeptide according to any one of Embodiments 1 to 21, wherein at least one amino acid substitution comprises an amino acid substitution with an amino acid derivative.

[0028] Embodiment 23. The polypeptide of Embodiment 22, wherein the amino acid derivative is a histidine derivative, a tryptophan derivative, a tyrosine derivative, a leucine derivative, a phenylalanine derivative, a valine derivative, a methionine derivative, an isoleucine derivative, an arginine derivative, a glutamic acid derivative, a proline derivative, a lysine derivative, a threonine derivative, an asparagine derivative, a glutamine derivative, a serine derivative, an alanine derivative or a glutamic acid derivative.

[0029] Embodiment 24. A polypeptide according to any one of Embodiments 1 to 23, which is an antibody, antibody fragment or fusion polypeptide.

[0030] Embodiment 25. Late embryogenesis abundant (LEA) protein polypeptide (e.g., LEA-3 polypeptide), NGF polypeptide, receptor for NGF polypeptide (e.g., ECD of receptor for NGF polypeptide), TrkA polypeptide (e.g., ECD of TrkA polypeptide), LNGFR polypeptide (e.g., ECD of LNGFR polypeptide), TNFα polypeptide, receptor for TNFα polypeptide, TNFR polypeptide (e.g., ECD of TNFR polypeptide), TNFR1 polypeptide (e.g., ECD of TNFR1 polypeptide), TNFR2 polypeptide (e.g., ECD of TNFR2 polypeptide), IL5 polypeptide, receptor for IL5 polypeptide, IL5R polypeptide (e.g., ECD of IL5R polypeptide), IL5Rα polypeptide (e.g., ECD of IL5Rα polypeptide), IL6 polypeptide, receptor for IL6 polypeptide, IL6R polypeptide (e.g., ECD of IL6R polypeptide), IL17 polypeptide, receptor for IL17 polypeptide, IL17R polypeptide (e.g., ECD of IL17R polypeptide), IL17RA polypeptide (e.g., ECD of IL17RA polypeptide), IL17RB polypeptide (e.g., ECD of IL17RB polypeptide), IL17RC polypeptide (e.g., ECD of IL17RC polypeptide), IL23 polypeptide, receptor for IL23 polypeptide, IL23R polypeptide (e.g., ECD of IL23R polypeptide), IL12Rβ1 polypeptide (e.g., ECD of IL12Rβ1 polypeptide), PDL1 polypeptide, receptor for PDL1 polypeptide, PDL2 polypeptide, receptor for PDL2 polypeptide, PD1 polypeptide (e.g., ECD of PD1 polypeptide), integrin polypeptide (e.g., ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7 or ITGB8 polypeptide), receptor for integrin polypeptide, fibronectin polypeptide (e.g., ECD of fibronectin polypeptide),Vitronectin polypeptide (e.g., ECD of vitronectin polypeptide), collagen polypeptide (e.g., ECD of collagen polypeptide), laminin polypeptide (e.g., ECD of laminin polypeptide), CD80 polypeptide, receptor of CD80 polypeptide, CD86 polypeptide, receptor of CD86 polypeptide, CTLA-4 polypeptide (e.g., ECD of CTLA-4 polypeptide), B7-H3 polypeptide, receptor of B7-H3 polypeptide (e.g., ECD of receptor of B7-H3 polypeptide), LAG-3 polypeptide (e.g., ECD of LAG-3 polypeptide), IL31 polypeptide, receptor of IL31 polypeptide, IL31RA polypeptide (e.g., ECD of IL31RA polypeptide), OSMR polypeptide (e.g., ECD of OSMR polypeptide), IL4 polypeptide, receptor of IL4R polypeptide, IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13 polypeptide, receptor of IL13 polypeptide, IL13RA1 polypeptide (e.g., ECD of IL13RA1 polypeptide), IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13Rα2 polypeptide (e.g., ECD of IL13Rα2 polypeptide), IL22 polypeptide, receptor of IL22 polypeptide (e.g., ECD of IL22 polypeptide), IL22Rα1 polypeptide (e.g., ECD of IL22Rα1 polypeptide), IL10Rβ2 polypeptide (e.g., ECD of IL10Rβ2 polypeptide), IL33 polypeptide, receptor of IL33 polypeptide, IL1RL1 polypeptide (e.g., ECD of IL1RL1 polypeptide), EGF polypeptide, receptor of EGF polypeptide, TGFα polypeptide, receptor of TGFα polypeptide, EGFR polypeptide (e.g., ECD of EGFR polypeptide), MMP9 polypeptide, FGF polypeptide (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22 or FGF23 polypeptide), receptor of FGF polypeptide, FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3,FGFR4 or FGFRL1 polypeptide), the ECD of an FGFR polypeptide (e.g., the ECD of an FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptide), an EGF polypeptide, the receptor of an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V or VI polypeptide), the receptor of a neuregulin polypeptide, a HER polypeptide (e.g., a HER1, HER2, HER3 or HER4 polypeptide), the ECD of a HER polypeptide (e.g., the ECD of a HER1, HER2, HER3 or HER4 polypeptide), an EpCAM polypeptide (e.g., the ECD of an EpCAM polypeptide), a CD20 polypeptide (e.g., the ECD of a CD20 polypeptide), the ligand of a CD20 polypeptide, a CD19 polypeptide (e.g., the ECD of a CD19 polypeptide), the ligand of a CD19 polypeptide, a CGRP polypeptide (e.g., an α-CGRP polypeptide or a β-CGRP polypeptide), the receptor of a CGRP polypeptide, the receptor of an α-CGRP polypeptide, the receptor of a β-CGRP polypeptide, a CALCRL polypeptide (e.g., the ECD of a CALCRL polypeptide), a RAMP polypeptide (e.g., a RAMP1, RAMP2 or RAMP3 polypeptide), the ECD of a RAMP polypeptide (e.g., the ECD of a RAMP1, RAMP2 or RAMP3 polypeptide), an IGF polypeptide (e.g., an IGF-1 or IGF-2 polypeptide), the receptor of an IGF polypeptide (e.g., the receptor of an IGF-1 or IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or IGFR2 polypeptide), the ECD of an IGFR polypeptide (e.g., the ECD of an IGFR1 or IGFR2 polypeptide), an IGFBP polypeptide (e.g., an IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5 or IGFBP6 polypeptide), a VEGF polypeptide (e.g., a VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptide), the receptor of a VEGF polypeptide (e.g., the receptor of a VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptide), a VEGFR polypeptide (e.g., a VEGFR1, VEGFR2 or VEGFR3 polypeptide),The ECD of VEGFR polypeptides (e.g., the ECD of VEGFR1, VEGFR2, or VEGFR3 polypeptides), FLT1 receptor polypeptides (e.g., the ECD of FLT1 receptor polypeptides), IL36 polypeptides (e.g., IL36A, IL36B, or IL36G polypeptides), receptors for IL36 polypeptides (e.g., receptors for IL36A, IL36B, or IL36G polypeptides), IL36R polypeptides (e.g., the ECD of IL36R polypeptides), IL1R1 polypeptides (e.g., the ECD of IL1R1 polypeptides), IL1R2 polypeptides (e.g., the ECD of IL1R2 polypeptides), IL1RL1 polypeptides (the ECD of IL1RL1 polypeptides), IL18R1 polypeptides (the ECD of IL18R1 polypeptides), bacterial toxin polypeptides, exotoxin polypeptides, endotoxin polypeptides, botulinum toxin polypeptides, tetanus toxin polypeptides, staphylococcal toxin polypeptides, CD52 polypeptides (e.g., the ECD of CD52 polypeptides), ligands for CD52 polypeptides, siglec-10 polypeptides, PCSK9 polypeptides, receptors for PCSK9 polypeptides, LDLR polypeptides (e.g., the ECD of LDLR polypeptides), CEA polypeptides (e.g., CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptides), the ECD of CEA polypeptides (e.g., the ECD of CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptides), BAFF polypeptides, receptors for BAFF polypeptides, TRAF polypeptides (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptides), receptors for TRAF polypeptides (e.g., receptors for TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 polypeptides), BCMA polypeptides, the ECD of BCMA polypeptides, SOST polypeptides, receptors for SOST polypeptides, LRP polypeptides (e.g., LRP5 or LRP6 polypeptides), the ECD of LRP polypeptides (e.g., the ECD of LRP5 or LRP6 polypeptides), DLL polypeptides (e.g., DLL4 polypeptides), receptors for DLL polypeptides, Jagged polypeptides (e.g., JAG1 or JAG polypeptides),Receptors for Jagged polypeptides (e.g., receptors for JAG1 or JAG polypeptides), NOTCH polypeptides (e.g., NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptides), ligands for NOTCH polypeptides (e.g., ligands for NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptides), VWF polypeptides, receptors for VWF polypeptides, Factor VIII polypeptides, receptors for Factor VIII polypeptides, platelet GP1b receptor polypeptides (e.g., ECD of platelet GP1b receptor polypeptides), integrin α, IIb β3 polypeptides (e.g., integrin α IIb ECD of β3 polypeptides), IL2 polypeptides, receptors for IL2 polypeptides, IL2R polypeptides (e.g., IL2Rα, IL2Rβ, or IL2Rγ polypeptides), ECD of IL2R polypeptides (e.g., ECD of IL2Rα, IL2Rβ, or IL2Rγ polypeptides), TGFβ polypeptides, receptors for TGFβ polypeptides, decorin polypeptides, EIF3I polypeptides, LTBP1 polypeptides, TGFβR1 polypeptides (e.g., ECD of TGFβR1 polypeptides), YWHAE polypeptides, IgE polypeptides, receptors for IgE polypeptides, Fc receptor polypeptides (e.g., FcεRI or FcεRII polypeptides), ECD of Fc receptor polypeptides (e.g., ECD of FcεRI or FcεRII polypeptides), KLK polypeptides (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14 or KLK15 polypeptide), Rankl polypeptide, receptor for Rankl polypeptide, RANK polypeptide (e.g., ECD of RANK polypeptide), TSLP polypeptide, receptor for TSLP polypeptide, CRLF2 polypeptide (e.g., ECD of CRLF2 polypeptide), IL7Rα polypeptide (e.g., ECD of IL7Rα polypeptide), S1P polypeptide, CD3 polypeptide (e.g., CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide), ECD of CD3 polypeptide (e.g., ECD of CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide), CD80 polypeptide, receptor for CD80 polypeptide, CD28 polypeptide (e.g., ECD of CD28 polypeptide), CTLA-4 polypeptide (e.g., ECD of CTLA-4 polypeptide), GnRH polypeptide, receptor for GNRH polypeptide, GnRHR polypeptide (e.g., ECD of GnRHR polypeptide), ICAM polypeptide (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), receptor for ICAM polypeptide (e.g., receptor for ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), JAM-A polypeptide, receptor for JAM-A polypeptide, LFA-1 polypeptide (e.g., ECD of LFA-1 polypeptide), Na v 1.7 polypeptide, C5 polypeptide (e.g., C5a or C5b polypeptide), receptor for C5 polypeptide (e.g., receptor for C5a or C5b polypeptide), C5aR polypeptide (e.g., ECD of C5aR polypeptide), C5L2 polypeptide (e.g., ECD of C5L2 polypeptide), IL17 polypeptide, receptor for IL17 polypeptide, IL17Ra polypeptide (e.g., ECD of IL17Ra polypeptide), IL17RC polypeptide (e.g., ECD of IL17RC polypeptide), EPO polypeptide, somatostatin polypeptide, GLP1 polypeptide, and glucagon polypeptide, a polypeptide of any one of Embodiments 1 to 24, comprising at least one therapeutic polypeptide selected from the group consisting of

[0031] The polypeptide according to embodiment 25, wherein the therapeutic polypeptide is a canine polypeptide, a feline polypeptide or a equine polypeptide.

[0032] Embodiment 27. Late embryogenesis abundant (LEA) protein polypeptide (e.g., LEA-3 polypeptide), NGF polypeptide, receptor for NGF polypeptide (e.g., ECD of receptor for NGF polypeptide), TrkA polypeptide (e.g., ECD of TrkA polypeptide), LNGFR polypeptide (e.g., ECD of LNGFR polypeptide), TNFα polypeptide, receptor for TNFα polypeptide, TNFR polypeptide (e.g., ECD of TNFR polypeptide), TNFR1 polypeptide (e.g., ECD of TNFR1 polypeptide), TNFR2 polypeptide (e.g., ECD of TNFR2 polypeptide), IL5 polypeptide, receptor for IL5 polypeptide, IL5R polypeptide (e.g., ECD of IL5R polypeptide), IL5Rα polypeptide (e.g., ECD of IL5Rα polypeptide), IL6 polypeptide, receptor for IL6 polypeptide, IL6R polypeptide (e.g., ECD of IL6R polypeptide), IL17 polypeptide, receptor for IL17 polypeptide, IL17R polypeptide (e.g., ECD of IL17R polypeptide), IL17RA polypeptide (e.g., ECD of IL17RA polypeptide), IL17RB polypeptide (e.g., ECD of IL17RB polypeptide), IL17RC polypeptide (e.g., ECD of IL17RC polypeptide), IL23 polypeptide, receptor for IL23 polypeptide, IL23R polypeptide (e.g., ECD of IL23R polypeptide), IL12Rβ1 polypeptide (e.g., ECD of IL12Rβ1 polypeptide), PDL1 polypeptide, receptor for PDL1 polypeptide, PDL2 polypeptide, receptor for PDL2 polypeptide, PD1 polypeptide (e.g., ECD of PD1 polypeptide), integrin polypeptide (e.g., ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7 or ITGB8 polypeptide), receptor for integrin polypeptide, fibronectin polypeptide (e.g., ECD of fibronectin polypeptide),Vitronectin polypeptide (e.g., ECD of vitronectin polypeptide), collagen polypeptide (e.g., ECD of collagen polypeptide), laminin polypeptide (e.g., ECD of laminin polypeptide), CD80 polypeptide, receptor of CD80 polypeptide, CD86 polypeptide, receptor of CD86 polypeptide, CTLA-4 polypeptide (e.g., ECD of CTLA-4 polypeptide), B7-H3 polypeptide, receptor of B7-H3 polypeptide (e.g., ECD of receptor of B7-H3 polypeptide), LAG-3 polypeptide (e.g., ECD of LAG-3 polypeptide), IL31 polypeptide, receptor of IL31 polypeptide, IL31RA polypeptide (e.g., ECD of IL31RA polypeptide), OSMR polypeptide (e.g., ECD of OSMR polypeptide), IL4 polypeptide, receptor of IL4R polypeptide, IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13 polypeptide, receptor of IL13 polypeptide, IL13RA1 polypeptide (e.g., ECD of IL13RA1 polypeptide), IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13Rα2 polypeptide (e.g., ECD of IL13Rα2 polypeptide), IL22 polypeptide, receptor of IL22 polypeptide (e.g., ECD of IL22 polypeptide), IL22Rα1 polypeptide (e.g., ECD of IL22Rα1 polypeptide), IL10Rβ2 polypeptide (e.g., ECD of IL10Rβ2 polypeptide), IL33 polypeptide, receptor of IL33 polypeptide, IL1RL1 polypeptide (e.g., ED of IL1RL1 polypeptide), EGF polypeptide, receptor of EGF polypeptide, TGFα polypeptide, receptor of TGFα polypeptide, EGFR polypeptide (e.g., ECD of EGFR polypeptide), MMP9 polypeptide, FGF polypeptide (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22 or FGF23 polypeptide), receptor of FGF polypeptide, FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3,FGFR4 or FGFRL1 polypeptide), ECD of FGFR polypeptide (e.g., ECD of FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptide), EGF polypeptide, receptor of EGF polypeptide, neuregulin polypeptide (e.g., neuregulin isoform I, II, III, IV, V or VI polypeptide), receptor of neuregulin polypeptide, HER polypeptide (e.g., HER1, HER2, HER3 or HER4 polypeptide), ECD of HER polypeptide (e.g., ECD of HER1, HER2, HER3 or HER4 polypeptide), EpCAM polypeptide (e.g., ECD of EpCAM polypeptide), CD20 polypeptide (e.g., ECD of CD20 polypeptide), ligand of CD20 polypeptide, CD19 polypeptide (e.g., ECD of CD19 polypeptide), ligand of CD19 polypeptide, CGRP polypeptide (e.g., α-CGRP polypeptide or β-CGRP polypeptide), receptor of CGRP polypeptide, receptor of α-CGRP polypeptide, receptor of β-CGRP polypeptide, CALCRL polypeptide (e.g., ECD of CALCRL polypeptide), RAMP polypeptide (e.g., RAMP1, RAMP2 or RAMP3 polypeptide), ECD of RAMP polypeptide (e.g., ECD of RAMP1, RAMP2 or RAMP3 polypeptide), IGF polypeptide (e.g., IGF-1 or IGF-2 polypeptide), receptor of IGF polypeptide (e.g., receptor of IGF-1 or IGF-2 polypeptide), IGFR polypeptide (e.g., IGFR1 or IGFR2 polypeptide), ECD of IGFR polypeptide (e.g., ECD of IGFR1 or IGFR2 polypeptide), IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5 or IGFBP6 polypeptide), VEGF polypeptide (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptide), receptor of VEGF polypeptide (e.g., receptor of VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptide), VEGFR polypeptide (e.g., VEGFR1, VEGFR2 or VEGFR3 polypeptide),The ECD of VEGFR polypeptides (e.g., the ECD of VEGFR1, VEGFR2, or VEGFR3 polypeptides), FLT1 receptor polypeptides (e.g., the ECD of FLT1 receptor polypeptides), IL36 polypeptides (e.g., IL36A, IL36B, or IL36G polypeptides), the receptors of IL36 polypeptides (e.g., the receptors of IL36A, IL36B, or IL36G polypeptides), IL36R polypeptides (e.g., the ECD of IL36R polypeptides), IL1R1 polypeptides (e.g., the ECD of IL1R1 polypeptides), IL1R2 polypeptides (e.g., the ECD of IL1R2 polypeptides), IL1RL1 polypeptides (the ECD of IL1RL1 polypeptides), IL18R1 polypeptides (the ECD of IL18R1 polypeptides), bacterial toxin polypeptides, exotoxin polypeptides, endotoxin polypeptides, botulinum toxin polypeptides, tetanus toxin polypeptides, staphylococcal toxin polypeptides, CD52 polypeptides (e.g., the ECD of CD52 polypeptides), the ligands of CD52 polypeptides, Siglec-10 polypeptides, PCSK9 polypeptides, the receptors of PCSK9 polypeptides, LDLR polypeptides (e.g., the ECD of LDLR polypeptides), CEA polypeptides (e.g., CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptides), the ECD of CEA polypeptides (e.g., the ECD of CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptides), BAFF polypeptides, the receptors of BAFF polypeptides, TRAF polypeptides (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptides), the receptors of TRAF polypeptides (e.g., the receptors of TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 polypeptides), BCMA polypeptides, the ECD of BCMA polypeptides, SOST polypeptides, the receptors of SOST polypeptides, LRP polypeptides (e.g., LRP5 or LRP6 polypeptides), the ECD of LRP polypeptides (e.g., the ECD of LRP5 or LRP6 polypeptides), DLL polypeptides (e.g., DLL4 polypeptides), the receptors of DLL polypeptides, Jagged polypeptides (e.g., JAG1 or JAG polypeptides),Receptors for Jagged polypeptides (e.g., receptors for JAG1 or JAG polypeptides), NOTCH polypeptides (e.g., NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptides), ligands for NOTCH polypeptides (e.g., ligands for NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptides), VWF polypeptides, receptors for VWF polypeptides, Factor VIII polypeptides, receptors for Factor VIII polypeptides, platelet GP1b receptor polypeptides (e.g., ECD of platelet GP1b receptor polypeptides), integrin α, IIb β3 polypeptides (e.g., integrin α IIb ECD of β3 polypeptides), IL2 polypeptides, receptors for IL2 polypeptides, IL2R polypeptides (e.g., IL2Rα, IL2Rβ, or IL2Rγ polypeptides), ECD of IL2R polypeptides (e.g., ECD of IL2Rα, IL2Rβ, or IL2Rγ polypeptides), TGFβ polypeptides, receptors for TGFβ polypeptides, decorin polypeptides, EIF3I polypeptides, LTBP1 polypeptides, TGFβR1 polypeptides (e.g., ECD of TGFβR1 polypeptides), YWHAE polypeptides, IgE polypeptides, receptors for IgE polypeptides, Fc receptor polypeptides (e.g., FcεRI or FcεRII polypeptides), ECD of Fc receptor polypeptides (e.g., ECD of FcεRI or FcεRII polypeptides), KLK polypeptides (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, or KLK15 polypeptides), Rankl polypeptide, receptor for Rankl polypeptide, RANK polypeptide (e.g., ECD of RANK polypeptide), TSLP polypeptide, receptor for TSLP polypeptide, CRLF2 polypeptide (e.g., ECD of CRLF2 polypeptide), IL7Rα polypeptide (e.g., ECD of IL7Rα polypeptide), S1P polypeptide, CD3 polypeptide (e.g., CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide), ECD of CD3 polypeptide (e.g., ECD of CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide), CD80 polypeptide, receptor for CD80 polypeptide, CD28 polypeptide (e.g., ECD of CD28 polypeptide), CTLA-4 polypeptide (e.g., ECD of CTLA-4 polypeptide), GnRH polypeptide, receptor for GNRH polypeptide, GnRHR polypeptide (e.g., ECD of GnRHR polypeptide), ICAM polypeptide (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), receptor for ICAM polypeptide (e.g., receptor for ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), JAM-A polypeptide, receptor for JAM-A polypeptide, LFA-1 polypeptide (e.g., ECD of LFA-1 polypeptide), Na v 1.7 polypeptide, C5 polypeptide (e.g., C5a or C5b polypeptide), receptor for C5 polypeptide (e.g., receptor for C5a or C5b polypeptide), C5aR polypeptide (e.g., ECD of C5aR polypeptide), C5L2 polypeptide (e.g., ECD of C5L2 polypeptide), IL17 polypeptide, receptor for IL17 polypeptide, IL17Ra polypeptide (e.g., ECD of IL17Ra polypeptide), IL17RC polypeptide (e.g., ECD of IL17RC polypeptide), EPO polypeptide, somatostatin polypeptide, GLP1 polypeptide, and an antibody or antibody fragment that binds to at least one target polypeptide selected from glucagon polypeptide, the polypeptide of any one of Embodiments 1 to 26.

[0033] Embodiment 28. The polypeptide according to Embodiment 27, wherein the target polypeptide is a canine polypeptide, a feline polypeptide or a equine polypeptide.

[0034] Embodiment 29. The polypeptide according to any one of Embodiments 1 to 24, comprising an antibody or antibody fragment that binds to canine or feline IL31.

[0035] Embodiment 30. The polypeptide according to any one of Embodiments 1 to 29, wherein the variant IgG Fc polypeptide has an altered binding affinity to Protein A, C1q, CD16, CD32 or CD64 as compared to the wild-type IgG Fc polypeptide.

[0036] Embodiment 31. A polypeptide comprising the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89, SEQ ID NO: 91, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128 or SEQ ID NO: 129.

[0037] Embodiment 32. An isolated nucleic acid encoding any one of the polypeptides of Embodiments 1 to 31.

[0038] Embodiment 33. A host cell containing the nucleic acid of Embodiment 32.

[0039] Embodiment 34. A host cell expressing any one of the polypeptides of Embodiments 1 to 31.

[0040] Embodiment 35. A method for producing a polypeptide, comprising culturing the host cell of Embodiment 33 or Embodiment 34 and isolating the polypeptide.

[0041] Embodiment 36. A pharmaceutical composition comprising any one of the polypeptides of Embodiments 1 to 31 and a pharmaceutically acceptable carrier.

[0042] Embodiment 37. A method for delivering a polypeptide to a companion animal species, comprising parenterally administering any one of the polypeptides of Embodiments 1 to 31 or the pharmaceutical composition of Embodiment 36.

[0043] Embodiment 38. A method for delivering a polypeptide to a companion animal species, comprising administering any one of the polypeptides of Embodiments 1 to 31 or the pharmaceutical composition of Embodiment 36 by intramuscular route, intraperitoneal route, intrathecal route, subcutaneous route, intraarterial route, intrasynovial route, intrathecal route or inhalation route.

[0044] Embodiment 39. The method of Embodiment 37 or Embodiment 38, wherein the companion animal species is a dog, a horse or a cat. Brief Description of the Drawings

[0045]

Fig. 1A - B

[0006] Subsequence of a mutant canine IgG Fc polypeptide having a single mutation screened from a 12-site single site NNK mutation library for enhancing binding to canine FcRn is shown.

Fig. 2A - F

[0007] Graphs of binding assays of wild type (Figure 2A), and mutant canine IgG-B Fc polypeptides having single mutations of L(24)Y (Figure 2B); L(24)F (Figures 2C and 2D); L(24)M (Figure 2E); and L(24)S (Figure 2F). These polypeptides showed off-rates (koff) of 1.22x10-1 (wild type); 1.38x10-2 (L(24)Y); 6.31x10-2 and 8.47x10-2 (L(24)F); 1.26x10-1 (L(24)M); and 2.41x10-1 (L(24)S) at pH 6.0.

Fig. 3

[0008] Biacore sensorgrams of various concentrations of canine FcRn (12.5, 25, 50, 100 and 200 nM) binding to wild type canine IgG-B Fc polypeptide are shown.

Fig. 4

[0009] Biacore sensorgrams of various concentrations of canine FcRn (12.5, 25, 50, 100 and 200 nM) binding to mutant canine IgG-B Fc polypeptide L(24)Y are shown.

Fig. 5

[0010] Biacore sensorgrams of various concentrations of canine FcRn (12.5, 25, 50, 100 and 200 nM) binding to mutant canine IgG-B Fc polypeptide L(24)F are shown.

Fig. 6

[0011] Biacore sensorgrams of various concentrations of canine FcRn (12.5, 25, 50, 100 and 200 nM) binding to mutant canine IgG-B Fc polypeptide L(24)M are shown.

Fig. 7

[0012] Biacore sensorgrams of various concentrations of canine FcRn (12.5, 25, 50, 100 and 200 nM) binding to mutant canine IgG-B Fc polypeptide YTE are shown.

Fig. 8

[0013] Disclosed is a partial sequence of a mutant canine IgG Fc polypeptide having two or more amino acid substitutions for enhancing binding to canine FcRn.

Fig. 9

[0014] It is a plot of a steady-state binding analysis between an antibody having a wild-type canine IgG-B Fc polypeptide and an FcRn / B2M complex.

Fig. 10

[0015] It is a plot of a steady-state binding analysis between an antibody having a YTE mutant canine IgG-B Fc polypeptide and an FcRn / B2M complex.

Fig. 11

[0016] It is a sensorgram of a kinetic binding analysis between an antibody having a Y0Y mutant canine IgG-B Fc polypeptide and an FcRn / B2M complex.

Fig. 12

[0017] It is a sensorgram of a kinetic binding analysis between an antibody having a YYY mutant canine IgG-B Fc polypeptide and an FcRn / B2M complex.

Fig. 13

[0018] It is an OctetRed sensorgram of the binding between feline FcRn and wild-type feline IgG1b (designated as B) and YTE mutant feline IgG1b (designated as A) at a low pH (pH 6.0) for association and a neutral pH (pH 7.2) for dissociation.

Fig. 14

[0019] It is an OctetRed sensorgram of chimeric mutant canine IgG-A Fc F00 antibody (A) and IgG-D Fc F00 antibody (B) that bind to canine FcRn, compared with those of chimeric mutant canine IgG-A Fc (C) without Phe mutation and IgG-D Fc (D) without Phe mutation.

Fig. 15

[0020] Shown is the serum pharmacokinetic profile after subcutaneous administration of chimeric mutant canine IgG-A F00 antibody ("IgG-A F00"; n = 2) and chimeric mutant canine IgG-A without Phe mutation ("IgG-A"; n = 2) to rats at 2 mg / kg.

Fig. 16

[0046] Description of specific sequences

[0022] Table 1 provides a list of specific sequences referred to herein. TIFF2025093964000002.tif227170TIFF2025093964000003.tif232170TIFF2025093964000004.tif235170TIFF2025093964000005.tif234170TIFF2025093964000006.tif232170TIFF2025093964000007.tif234170TIFF2025093964000008.tif234170TIFF2025093964000009.tif236170TIFF2025093964000010.tif236170TIFF2025093964000011.tif234170TIFF2025093964000012.tif232170TIFF2025093964000013.tif234170TIFF2025093964000014.tif232170TIFF2025093964000015.tif234170TIFF2025093964000016.tif234170TIFF2025093964000017.tif236170TIFF2025093964000018.tif228170TIFF2025093964000019.tif236170TIFF2025093964000020.tif234170TIFF2025093964000021.tif234170TIFF2025093964000022.tif234170TIFF2025093964000023.tif234170TIFF2025093964000024.tif234170TIFF2025093964000025.tif234170TIFF2025093964000026.tif234170TIFF2025093964000027.tif236170TIFF2025093964000028.tif234170TIFF2025093964000029.tif237170TIFF2025093964000030.tif234170TIFF2025093964000031.tif69170

[0047] Description of a Specific Embodiment Mutant IgG Fc polypeptides are described that are derived from companion animals such as dogs, horses, and cats and have an altered binding to FcRn. In some embodiments, an antibody, antibody fragment, or fusion protein comprises a mutant IgG Fc polypeptide. Also provided are methods of making or purifying a mutant IgG Fc polypeptide and methods of administering a mutant IgG Fc polypeptide to a companion animal.

[0048]

[0024] For the convenience of the reader, definitions of terms used herein are provided below.

[0049]

[0025] As used herein, numerical terms such as D K are calculated based on scientific measurements and are thus subject to the effects of appropriate measurement error. In some cases, numerical terms may include values rounded to the nearest significant digit.

[0050]

[0026] As used herein, "a" or "an" means "at least one" or "one or more / one or plural)" unless otherwise specified. As used herein, the term "or" means "and / or" unless otherwise specified. In the context of multiple dependent claims, "or" is used when referring back to other claims and the claims are cited only in the alternative form.

[0051] Exemplary mutant IgG Fc polypeptides

[0027] Novel mutant IgG Fc polypeptides are provided that have an altered binding affinity to FcRn, such as an improved binding affinity to FcRn at acidic pH (e.g., a pH in the range of about 5.0 to about 6.5).

[0052] As used herein, the term "amino acid sequence" means the sequence of amino acid residues of a peptide or protein. The terms "polypeptide" and "protein" are used interchangeably to refer to polymers of amino acid residues and are not limited to any minimum length. Such polymers of amino acid residues can include natural or unnatural amino acid residues and include, but are not limited to, peptides, oligopeptides, dimers, trimers, and multimers of amino acid residues. Both full-length proteins and fragments thereof are included in this definition. In addition, these terms also include post-expression modifications of polypeptides, such as glycosylation, sialylation, acetylation, phosphorylation, and the like. Further, in the context of the present disclosure, "polypeptide" refers to a protein that includes modifications such as deletions, additions, and substitutions (generally conservative in nature) to the native sequence, as long as the protein maintains the desired activity. These modifications can be intentional, such as by site-directed mutagenesis, or can be accidental, such as due to mutations in the host producing the protein or errors resulting from PCR amplification.

[0053] As used herein, "IgX Fc" or "IgX Fc polypeptide" refers to an Fc polypeptide derived from a specific antibody isotype (e.g., IgG, IgA, IgD, IgE, IgM, etc.), where "X" indicates the antibody isotype. Thus, "IgG Fc" indicates that the Fc polypeptide is derived from the γ chain, "IgA Fc" indicates that the Fc polypeptide is derived from the α chain, "IgD Fc" indicates that the Fc polypeptide is derived from the δ chain, "IgE Fc" indicates that the Fc polypeptide is derived from the ε chain, and "IgM Fc" indicates that the Fc polypeptide is derived from the μ chain. In some embodiments, the IgG Fc polypeptide comprises the hinge, CH2, and CH3, but does not include CH1 or CL. In some embodiments, the IgG Fc polypeptide comprises CH2 and CH3, but does not include CH1, the hinge, or CL. In some embodiments, the IgG Fc polypeptide comprises CH1, the hinge, CH2, and CH3, with or without CL1. In some embodiments, an Fc polypeptide such as an IgG Fc polypeptide lacks one or more C-terminal amino acids such as from 1 to 20, from 1 to 15, from 1 to 10, from 1 to 5, or from 1 to 2 amino acids while retaining biological activity. In some embodiments, the biological activity is the ability to bind to FcRn. The "effector function" of an Fc polypeptide is an action or activity that is carried out in whole or in part by any antibody in response to stimulation and may include complement binding and / or induction of ADCC (antibody-dependent cell cytotoxicity). "IgX-N Fc" indicates that the Fc polypeptide is derived from a specific subclass of an antibody isotype (e.g., canine IgG subclasses IgG-A, IgG-B, IgG-C or IgG-D; feline IgG subclasses IgG-1a, IgG-1b or IgG-2; or equine IgG subclasses IgG-1, IgG-2, IgG-3, IgG-4, IgG-5, IgG-6 or IgG-7, etc.), where "N" means subclass.

[0054]

[0030] In some embodiments, the companion animal species is a dog, a cat or a horse. In some embodiments, the companion animal species is a small mammal such as a dog, a cat, a rabbit, a ferret, a guinea pig, a rodent, etc. In some embodiments, the companion animal species is a domestic animal such as a horse, a cow, a pig, etc.

[0055]

[0031] In some embodiments, the IgX Fc polypeptide or the IgX-N Fc polypeptide is derived from a companion animal such as a dog, a cat or a horse. In some embodiments, the IgG Fc polypeptide is isolated from a canine γ heavy chain such as IgG-A, IgG-B, IgG-C or IgG-D. In some cases, the IgG Fc polypeptide is isolated from a feline γ heavy chain such as IgG1 (e.g., IgG1a or IgG1b) or IgG2. In other examples, the IgG Fc polypeptide is isolated from a equine γ heavy chain such as IgG-1, IgG-2, IgG-3, IgG-4, IgG-5, IgG-6 or IgG-7.

[0056]

[0032] The terms "IgX Fc" and "IgX Fc polypeptide" include wild-type IgX Fc polypeptides and variant IgX Fc polypeptides, unless otherwise specified.

[0057]

[0033] "Wild-type" refers to the non-mutated version of a polypeptide that exists in nature or a fragment thereof. A wild-type polypeptide can be produced recombinantly.

[0058] In some embodiments, the wild-type IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0059]

[0035] A "variant" is a polypeptide that is different from a reference polypeptide by the substitution, deletion, and / or addition of one or more non-natural amino acids. In some embodiments, the variant retains at least one biological activity of the reference polypeptide. In some embodiments, the variant has a biological activity that the reference polypeptide substantially lacks.

[0060]

[0036] As used herein, "variant IgG Fc" is an IgG Fc polypeptide that is different from a reference IgG Fc polypeptide by the substitution, deletion, and / or addition of one or more amino acids and that substantially retains at least one biological activity of the reference IgG Fc polypeptide.

[0061]

[0037] In some embodiments, the variant IgG Fc polypeptide includes a variant IgG Fc polypeptide of a companion animal species. In some embodiments, the variant IgG Fc polypeptide includes a variant canine IgG Fc polypeptide, a variant equine IgG Fc polypeptide, or a feline IgG Fc polypeptide. In some embodiments, the variant IgG Fc polypeptide is a variant canine IgG-A Fc polypeptide, a variant canine IgG-B Fc polypeptide, a variant canine IgG-C Fc polypeptide, or a variant canine IgG-D Fc polypeptide. In some embodiments, the variant IgG Fc polypeptide is a variant equine IgG1 Fc polypeptide, a variant equine IgG2 Fc polypeptide, a variant equine IgG3 Fc polypeptide, a variant equine IgG4 Fc polypeptide, a variant equine IgG5 Fc polypeptide, a variant equine IgG6 Fc polypeptide, or a variant equine IgG7 Fc polypeptide. In some embodiments, the variant IgG Fc polypeptide is a variant feline IgG1 Fc polypeptide or a variant feline IgG2 Fc polypeptide.

[0062] As used herein, "percent amino acid sequence identity (%)" and "homology" with respect to a nucleic acid molecule or polypeptide sequence refers to the percentage of nucleotide or amino acid residues in a reference sequence that are identical to the nucleotide or amino acid residues in the sequence after aligning the particular nucleic acid molecule or polypeptide sequence, introducing gaps as necessary to obtain the maximum percent sequence identity, and excluding any conservative substitutions as part of the sequence identity. Alignments for determining percent sequence identity can be obtained using a variety of methods within the skill in the art, such as BLAST, BLAST-2, CLUSTAL OMEGA, ALIGN or MEGALIGN TM (DNASTAR) software or other generally available computer software. One of ordinary skill in the art can determine appropriate parameters for measuring the alignment, including any parameters necessary to obtain the maximum alignment over the entire length of the sequences being compared.

[0063]

[0039] In some embodiments, the variant has at least about 50% sequence identity with the reference nucleic acid molecule or polypeptide after aligning the sequences, introducing gaps as necessary to obtain the maximum percent sequence identity, and excluding any conservative substitutions as part of the sequence identity. Such variants include, for example, polypeptides having one or more amino acid residues added or deleted at the N or C terminus of the polypeptide. In some embodiments, the variant has at least about 50% sequence identity, at least about 60% sequence identity, at least about 65% sequence identity, at least about 70% sequence identity, at least about 75% sequence identity, at least about 80% sequence identity, at least about 85% sequence identity, at least about 90% sequence identity, at least about 95% sequence identity, at least about 97% sequence identity, at least about 98% sequence identity, or at least about 99% sequence identity with the sequence of the reference nucleic acid or polypeptide.

[0064] As used herein, the "position corresponding to position n" (where n is any number) refers to the amino acid position of the target polypeptide that coincides with position n of the reference polypeptide after aligning the amino acid sequences of the target polypeptide and the reference polypeptide and introducing gaps. Alignment as to whether the position of the target polypeptide corresponds to position n of the reference polypeptide can be performed by various methods within the scope of the art, such as BLAST, BLAST-2, CLUSTAL OMEGA, ALIGN, or MEGALIGN TM (DNASTAR), and those skilled in the art can determine appropriate parameters for alignment, including any parameters necessary to obtain the maximum alignment over the full length of the two sequences being compared, using publicly available computer software such as software. In some embodiments, the target polypeptide and the reference polypeptide are of different lengths.

[0065]

[0041] "Point mutation" refers to a mutation involving one amino acid residue. This mutation can be a deletion of an amino acid, a substitution of one amino acid residue with another amino acid residue, or an insertion of an additional amino acid residue.

[0066]

[0042] "Amino acid substitution" refers to substituting one amino acid in a polypeptide with another amino acid. In some embodiments, the amino acid substitution is a conservative substitution. Non-limiting and exemplary conservative amino acid substitutions are shown in Table 2. Amino acid substitutions can be introduced into the molecule of interest and the product screened for the desired activity, such as retained / improved antigen binding, reduced immunogenicity, or improved ADCC or CDC, or improved pharmacokinetics.

[0067]

[0043] Table 2. TIFF2025093964000032.tif227170

[0068]

[0044] Amino acids can be grouped according to common side-chain characteristics. (1) Hydrophobic: Norleucine, Met, Ala, Val, Leu, Ile; (2) Neutral hydrophilic: Cys, Ser, Thr, Asn, Gln; (3) Acidic: Asp, Glu; (4) Basic: His, Lys, Arg; (5) Residues affecting chain orientation: Gly, Pro; (6) Aromatic: Trp, Tyr, Phe

[0069]

[0045] Non-conservative substitutions necessarily involve the exchange of an element of one of these classes for an element of another class.

[0070]

[0046] As used herein, "amino acid derivative" refers to any amino acid, modified amino acid and / or amino acid analog that is not one of the 20 common natural amino acids found in humans. Exemplary amino acid derivatives include natural amino acids not found in humans (e.g., selenocysteine and pyrrolysine, which may be found in some microorganisms) and non-natural amino acids. Exemplary amino acid derivatives include, but are not limited to, amino acid derivatives commercially available through chemical manufacturers (e.g., sigmaaldrich.com / chemistry / chemistry-products.html?TablePage=16274965, accessed on May 6, 2017 and incorporated herein by reference). One or more amino acid derivatives can be incorporated into a polypeptide at specific positions using a translation system that utilizes a host cell, an orthogonal aminoacyl-tRNA synthetase derived from an eubacterial synthetase, an orthogonal tRNA, and an amino acid derivative. For details, see, for example, U.S. Patent No. 9,624,485.

[0071]

[0047] In some embodiments, the variant IgG Fc polypeptide comprises an amino acid substitution with an amino acid derivative. In some embodiments, the amino acid derivative is an alanine derivative, a cysteine derivative, an aspartic acid derivative, a glutamic acid derivative, a phenylalanine derivative, a glycine derivative, a histidine derivative, an isoleucine derivative, a lysine derivative, a leucine derivative, a methionine derivative, an asparagine derivative, a proline derivative, a glutamine derivative, an arginine derivative, a serine derivative, a threonine derivative, a valine derivative, a tryptophan derivative, or a tyrosine derivative.

[0072] Exemplary variant IgG Fc polypeptides having modified FcRn binding

[0048] In some embodiments, the variant IgG Fc polypeptide (e.g., variant canine IgG Fc polypeptide, variant equine IgG Fc polypeptide, or variant feline IgG Fc polypeptide) has a modified FcRn binding affinity as compared to a reference polypeptide. In some embodiments, the variant IgG Fc polypeptide has an increased FcRn binding affinity as compared to the reference polypeptide at acidic pH (e.g., at a pH in the range of about 5.0 to about 6.5, such as at pH about 5.0, pH about 5.5, pH about 6.0, or pH about 6.5).

[0073]

[0049] In some embodiments, the variant IgG Fc polypeptide is at least 85% identical, at least 90% identical, at least 95% identical, at least 97% identical, at least 98% identical, or at least 99% identical to the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89 or SEQ ID NO: 91.

[0074] In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 83, 132, 149, 162, 183, 203, 205 and / or 209 of SEQ ID NO: 1. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 2. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204 and / or 208 of SEQ ID NO: 3. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 60, 79, 80, 83, 132, 149, 163, 183, 203, 205 and / or 209 of SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 5. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 6.In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 7. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 8. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 9. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 10. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 11. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 12.In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 13. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 54.

[0075]

[0051] In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 83, 132, 149, 162, 183, 203, 205, and / or 209 of SEQ ID NO: 1. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 2. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, and / or 208 of SEQ ID NO: 3. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 60, 79, 80, 83, 132, 149, 163, 183, 203, 205, and / or 209 of SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 5. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 6.In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 60, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 7. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 8. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 9. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 10. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 11. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 12.In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 13. In some embodiments, the variant IgG Fc polypeptide comprises at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 54.

[0076]

[0052] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 1; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 149; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 183; leucine or tryptophan at the position corresponding to position 203; proline at the position corresponding to position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 209.

[0077]

[0053] In some embodiments, the variant IgG Fc polypeptide has tyrosine at the position corresponding to position 9 of SEQ ID NO: 2; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0078]

[0054] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 3; proline at the position corresponding to position 18; histidine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or arginine at the position corresponding to position 24; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208.

[0079]

[0055] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 4; proline at the position corresponding to position 18; histidine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 149; leucine, phenylalanine or tyrosine at the position corresponding to position 163; isoleucine at the position corresponding to position 183; leucine or tryptophan at the position corresponding to position 203; proline at the position corresponding to position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 209.

[0080]

[0056] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 5; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0081]

[0057] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 6; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine or threonine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or valine at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0082]

[0058] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 7; proline at the position corresponding to position 18; histidine, isoleucine, and / or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0083]

[0059] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 8; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0084]

[0060] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 9; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0085]

[0061] In some embodiments, the variant IgG Fc polypeptide comprises proline at the position corresponding to position 18 of SEQ ID NO: 10; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0086]

[0062] In some embodiments, the variant IgG Fc polypeptide comprises proline at the position corresponding to position 18 of SEQ ID NO: 11; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0087]

[0063] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 9 of SEQ ID NO: 12; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0088]

[0064] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 9 of SEQ ID NO: 13; proline at a position corresponding to position 18; histidine, isoleucine or proline at a position corresponding to position 22; valine, arginine or lysine at a position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at a position corresponding to position 24; threonine at a position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at a position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at a position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at a position corresponding to position 28; methionine or valine at a position corresponding to position 30; isoleucine at a position corresponding to position 31; alanine at a position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at a position corresponding to position 79; histidine or phenylalanine at a position corresponding to position 80; glutamic acid at a position corresponding to position 81; alanine, tyrosine or phenylalanine at a position corresponding to position 83; isoleucine at a position corresponding to position 132; valine at a position corresponding to position 148; leucine, phenylalanine or tyrosine at a position corresponding to position 162; isoleucine at a position corresponding to position 182; leucine or tryptophan at a position corresponding to position 202; proline at a position corresponding to position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at a position corresponding to position 208; and / or isoleucine or valine at a position corresponding to position 213.

[0089]

[0065] In some embodiments, the variant IgG Fc polypeptide has tyrosine at the position corresponding to position 9 of SEQ ID NO: 54; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at the position corresponding to position 79; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213.

[0090]

[0066] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glycine, arginine or alanine at position 79; histidine or phenylalanine at position 80; alanine or tyrosine at position 83; isoleucine at position 132; valine at position 149; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 183; leucine or tryptophan at position 203; proline at position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 209 of SEQ ID NO: 1.

[0091]

[0067] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 2.

[0092]

[0068] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or arginine at position 24; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208 of SEQ ID NO: 3.

[0093]

[0069] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 9; proline at position 18; histidine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 149; leucine, phenylalanine or tyrosine at position 163; isoleucine at position 183; leucine or tryptophan at position 203; proline at position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 209 of SEQ ID NO: 4.

[0094]

[0070] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; glutamine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 5.

[0095]

[0071] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine or threonine at position 26; leucine, methionine, proline, isoleucine, asparagine or valine at position 27; methionine, glutamate, asparagine, histidine, isoleucine or valine at position 28; glutamine, arginine, alanine, glutamate or methionine at position 79; histidine or phenylalanine at position 80; glutamate at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 6.

[0096]

[0072] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine, isoleucine and / or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 7.

[0097]

[0073] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 8.

[0098]

[0074] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 9.

[0099]

[0075] In some embodiments, the variant IgG Fc polypeptide has proline at position 18, histidine, isoleucine or proline at position 22, valine, arginine or lysine at position 23, phenylalanine, tyrosine, arginine or valine at position 24, threonine at position 25, leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27, methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28, methionine or valine at position 30, isoleucine at position 31, glutamine, arginine, alanine, glutamic acid or methionine at position 79, histidine or phenylalanine at position 80, glutamic acid at position 81, alanine, tyrosine or phenylalanine at position 83, isoleucine at position 132, valine at position 148, leucine, phenylalanine or tyrosine at position 162, isoleucine at position 182, leucine or tryptophan at position 202, proline at position 204, serine, alanine, arginine, phenylalanine, tyrosine or tryptophan at position 208, and / or isoleucine or valine at position 213 of SEQ ID NO: 10.

[0100]

[0076] In some embodiments, the variant IgG Fc polypeptide has proline at position 18, histidine, isoleucine or proline at position 22, valine, arginine or lysine at position 23, phenylalanine, tyrosine, arginine or valine at position 24, threonine at position 25, leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27, methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28, methionine or valine at position 30, isoleucine at position 31, glutamine, arginine, glutamic acid or methionine at position 79, histidine or phenylalanine at position 80, glutamic acid at position 81, alanine, tyrosine or phenylalanine at position 83, isoleucine at position 132, valine at position 148, leucine, phenylalanine or tyrosine at position 162, isoleucine at position 182, leucine or tryptophan at position 202, proline at position 204, serine, alanine, phenylalanine, tyrosine, histidine or tryptophan at position 208, and / or isoleucine or valine at position 213 of SEQ ID NO: 11.

[0101]

[0077] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, serine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 12.

[0102]

[0078] In some embodiments, the variant IgG Fc polypeptide has tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 13.

[0103]

[0079] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213 of SEQ ID NO: 54.

[0104]

[0080] In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine or tyrosine at a position corresponding to position 24 of SEQ ID NO: 1, threonine at a position corresponding to position 26, and / or glutamate at a position corresponding to position 28. In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine at a position corresponding to position 24 of SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4, threonine at a position corresponding to position 26, and / or glutamate at a position corresponding to position 28. In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine or tyrosine at a position corresponding to position 24 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54, threonine at a position corresponding to position 26, and / or glutamate at a position corresponding to position 28.

[0105]

[0081] In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine or tyrosine at position 24, threonine at position 26, and / or glutamate at position 28 of SEQ ID NO: 1. In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine at position 24, threonine at position 26, and / or glutamate at position 28 of SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine or tyrosine at position 24, threonine at position 26, and / or glutamate at position 28 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0106]

[0082] In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine at a position corresponding to position 24 of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0107]

[0083] In some embodiments, the variant IgG Fc polypeptide comprises phenylalanine at position 24 of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0108]

[0084] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24, tyrosine at a position corresponding to position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at a position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24, tyrosine at a position corresponding to position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at a position corresponding to position 208 of SEQ ID NO: 2 or SEQ ID NO: 3. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24, tyrosine at a position corresponding to position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at a position corresponding to position 208 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0109]

[0085] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and / or arginine, phenylalanine, tyrosine, histidine, or tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and / or arginine, phenylalanine, tyrosine, histidine, or tryptophan at position 208 of SEQ ID NO: 2 or SEQ ID NO: 3. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and / or arginine, phenylalanine, tyrosine, histidine, or tryptophan at position 208 of SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 54.

[0110]

[0086] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 and arginine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 and arginine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 54.

[0111]

[0087] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 and phenylalanine at the position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 and phenylalanine at the position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 54.

[0112]

[0088] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24 of SEQ ID NO: 1 or SEQ ID NO: 4 and tyrosine at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24 and tyrosine at a position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0113]

[0089] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24 of SEQ ID NO: 1 or SEQ ID NO: 4 and histidine at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24 and histidine at a position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0114]

[0090] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24 of SEQ ID NO: 1 or SEQ ID NO: 4 and tryptophan at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24 and tryptophan at a position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0115]

[0091] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 1 or SEQ ID NO: 4 and arginine at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 and arginine at a position corresponding to position 208.

[0116]

[0092] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 1 or SEQ ID NO: 4 and phenylalanine at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 and phenylalanine at a position corresponding to position 208.

[0117]

[0093] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 1 or SEQ ID NO: 4 and tyrosine at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 and tyrosine at a position corresponding to position 208.

[0118]

[0094] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 1 or SEQ ID NO: 4 and histidine at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 and histidine at a position corresponding to position 208.

[0119]

[0095] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 1 or SEQ ID NO: 4 and tryptophan at a position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 83 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54 and tryptophan at a position corresponding to position 208.

[0120]

[0096] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24, tyrosine at a position corresponding to position 83, and arginine at a position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at a position corresponding to position 24, tyrosine at a position corresponding to position 83, and arginine at a position corresponding to position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0121]

[0097] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 1 or SEQ ID NO: 4, tyrosine at the position corresponding to position 83, and phenylalanine at the position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54, tyrosine at the position corresponding to position 83, and phenylalanine at the position corresponding to position 208.

[0122]

[0098] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 1 or SEQ ID NO: 4, tyrosine at the position corresponding to position 83, and tyrosine at the position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54, tyrosine at the position corresponding to position 83, and tyrosine at the position corresponding to position 208.

[0123]

[0099] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 1 or SEQ ID NO: 4, tyrosine at the position corresponding to position 83, and histidine at the position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54, tyrosine at the position corresponding to position 83, and histidine at the position corresponding to position 208.

[0124]

[0100] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 1 or SEQ ID NO: 4, tyrosine at the position corresponding to position 83, and tryptophan at the position corresponding to position 209. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at the position corresponding to position 24 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54, tyrosine at the position corresponding to position 83, and tryptophan at the position corresponding to position 208.

[0125]

[0101] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and arginine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and arginine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0126]

[0102] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and phenylalanine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and phenylalanine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0127]

[0103] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and tyrosine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0128]

[0104] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and histidine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and histidine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0129]

[0105] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24 and tryptophan tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0130]

[0106] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and arginine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and arginine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0131]

[0107] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and phenylalanine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and phenylalanine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0132]

[0108] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and tyrosine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0133]

[0109] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and histidine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and histidine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0134]

[0110] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 83 and tryptophan tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0135]

[0111] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and arginine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and arginine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0136]

[0112] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and phenylalanine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and phenylalanine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0137]

[0113] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and tyrosine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and tyrosine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0138] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and histidine at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and histidine at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0139]

[0115] In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4. In some embodiments, the variant IgG Fc polypeptide comprises tyrosine at position 24, tyrosine at position 83, and tryptophan at position 208 of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 54.

[0140]

[0116] In some embodiments, the variant IgG Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89 or SEQ ID NO: 91.

[0141]

[0117] In some embodiments, the polypeptide comprises the amino acid sequence of SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 58, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 61, SEQ ID NO: 62, SEQ ID NO: 63, SEQ ID NO: 64, SEQ ID NO: 65, SEQ ID NO: 66, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 77, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 85, SEQ ID NO: 87, SEQ ID NO: 89, SEQ ID NO: 91, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128 or SEQ ID NO: 129.

[0142]

[0118] In some embodiments, the variant IgG Fc polypeptide has an altered protein A binding affinity. In some embodiments, the variant IgG Fc polypeptide has an increased binding affinity for protein A. In some embodiments, the variant IgG Fc polypeptide can be purified using protein A column chromatography. In some embodiments, the variant IgG Fc polypeptide has an altered CD16, CD32, and / or CD64 binding affinity. In some embodiments, the variant IgG Fc polypeptide has a decreased binding affinity for CD16, CD32, and / or CD64. In some embodiments, the variant IgG Fc can have a decreased ADCC immune response. In some embodiments, the variant IgG Fc polypeptide has an altered C1q binding affinity. In some embodiments, the variant IgG Fc polypeptide has a decreased binding affinity for C1q. In some embodiments, the variant IgG Fc polypeptide can have a decreased complement binding. In some embodiments, the variant IgG Fc can have a decreased complement-mediated immune response.

[0143] Exemplary fusion molecules

[0119] Polypeptides and other molecules can include a variant IgG Fc polypeptide. In some embodiments, the fusion molecule includes a variant IgG Fc polypeptide, such as the variant IgG Fc polypeptides described herein. In some embodiments, the antibody or antibody fragment includes a variant IgG Fc polypeptide, such as the variant IgG Fc polypeptides described herein.

[0144] As used herein, "fusion molecule" refers to a molecule that includes one or more "fusion partners". In some embodiments, the fusion partners are covalently bound (i.e., "fused"). When both of the two fusion partners are polypeptides, the fusion partner polypeptides can be part of a continuous amino acid sequence (i.e., a continuous polypeptide). The first fusion partner polypeptide may be bound to either the N-terminus or the C-terminus of the second fusion partner. In some embodiments, the fusion partners are translated as a single polypeptide from coding sequences encoding both fusion partners. The fusion partners may be covalently bound by other means, such as, for example, chemical bonds other than peptide bonds. Many known methods for covalently attaching a polypeptide to another molecule (e.g., a fusion partner) can be used. In other embodiments, the fusion partners are fused via a "linker" composed of at least one amino acid or chemical moiety. In some embodiments, the fusion partners are non-covalently bound. In some such embodiments, the fusion partners can be bound, for example, using a binding pair. Exemplary binding pairs include, but are not limited to, biotin and avidin or streptavidin, an antibody and its antigen, etc.

[0145]

[0121] In some embodiments, the fusion partner is a therapeutic polypeptide. Exemplary therapeutic polypeptides include, but are not limited to, late embryogenesis abundant (LEA) polypeptides (e.g., LEA-3 polypeptide), NGF (or nerve growth factor) polypeptides, receptors for NGF polypeptides (e.g., extracellular domain of the receptor for NGF polypeptide), TrkA polypeptides (e.g., extracellular domain of TrkA polypeptide), LNGFR polypeptides (e.g., extracellular domain of LNGFR polypeptide), TNFα (or tumor necrosis factor alpha) polypeptides, receptors for TNFα polypeptides, TNFR (or tumor necrosis factor receptor) polypeptides (e.g., extracellular domain of TNFR polypeptide), TNFR1 polypeptides (e.g., extracellular domain of TNFR1 polypeptide), TNFR2 polypeptides (e.g., extracellular domain of TNFR2 polypeptide), IL5 (or interleukin 5) polypeptides, receptors for IL5 polypeptides, IL5R (or interleukin 5 receptor) polypeptides (e.g., extracellular domain of IL5R polypeptide), IL5Rα polypeptides (e.g., extracellular domain of IL5Rα polypeptide), IL6 (or interleukin 6) polypeptides, receptors for IL6 polypeptides, IL6R (or interleukin 6 receptor) polypeptides (e.g., extracellular domain of IL6R polypeptide), IL17 (or interleukin 17) polypeptides, receptors for IL17 polypeptides, IL17R (or interleukin 17 receptor) polypeptides (e.g., extracellular domain of IL17R polypeptide), IL17RA polypeptides (e.g., extracellular domain of IL17RA polypeptide), IL17RB polypeptides (e.g., extracellular domain of IL17RB polypeptide), IL17RC polypeptides (e.g., extracellular domain of IL17RC polypeptide), IL23 (or interleukin 23) polypeptides, receptors for IL23 polypeptides, IL23R (or interleukin 23 receptor) polypeptides (e.g., extracellular domain of IL23R polypeptide), IL12Rβ1 polypeptides (e.g., extracellular domain of IL12Rβ1 polypeptide), PDL (or programmed cell death ligand) polypeptides, PDL1 polypeptides, receptors for PDL1 polypeptides, PDL2 polypeptides, receptors for PDL2 polypeptides, PD1 polypeptides (e.g., extracellular domain of PD1 polypeptide),Integrin polypeptides (e.g., ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7 or ITGB8 polypeptides), receptors for integrin polypeptides, fibronectin polypeptides (e.g., ECD of fibronectin polypeptides), vitronectin polypeptides (e.g., ECD of vitronectin polypeptides), collagen polypeptides (e.g., ECD of collagen polypeptides), laminin polypeptides (e.g., ECD of laminin polypeptides), CD80 polypeptides, receptors for CD80 polypeptides, CD86 polypeptides, receptors for CD86 polypeptides, CTLA-4 (or cytotoxic T lymphocyte-associated protein 4) polypeptides (e.g., ECD of CTLA-4 polypeptides), B7-H3 polypeptides, receptors for B7-H3 polypeptides (e.g., ECD of receptors for B7-H3 polypeptides), LAG-3 (or lymphocyte activation gene 3) polypeptides (e.g., ECD of LAG-3 polypeptides), IL31 (or interleukin 31) polypeptides, receptors for IL31 polypeptides, IL31RA (interleukin 31 receptor A) polypeptides (e.g., ECD of IL31RA polypeptides), OSMR (or oncostatin M receptor) polypeptides (e.g., ECD of OSMR polypeptides), IL4 (or interleukin 4) polypeptides, receptors for IL4R polypeptides, IL4R (or interleukin 4 receptor) polypeptides (e.g., ECD of IL4R polypeptides), IL13 (or interleukin 13 receptor) polypeptides, receptors for IL13 polypeptides, IL13RA1 (or interleukin 13 receptor A1) polypeptides (e.g., ECD of IL13RA1 polypeptides), IL4R (or interleukin 4 receptor) polypeptides (e.g., ECD of IL4R polypeptides), IL13Rα2 (or interleukin 13 receptor α2) polypeptides (e.g., ECD of IL13Rα2 polypeptides), IL22 (or interleukin 22) polypeptides,Receptors for IL22 polypeptides (e.g., ECD of IL22 polypeptides), IL22Rα1 (or interleukin 22 receptor α1) polypeptides (e.g., ECD of IL22Rα1 polypeptides), IL10Rβ2 (or interleukin 10 receptor β2) polypeptides (e.g., ECD of IL10Rβ2 polypeptides), IL33 (or interleukin 33) polypeptides, receptors for IL33 polypeptides, IL1RL1 polypeptides (e.g., ED of IL1RL1 polypeptides), EGF (or epidermal growth factor) polypeptides, receptors for EGF polypeptides, TGFα (or transforming growth factor α) polypeptides, receptors for TGFα polypeptides, EGFR (or epidermal growth factor receptor) polypeptides (e.g., ECD of EGFR polypeptides), MMP9 (or matrix metallopeptidase 9) polypeptides, FGF (or fibroblast growth factor) polypeptides (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22 or FGF23 polypeptides), receptors for FGF polypeptides, FGFR (or fibroblast growth factor receptor) polypeptides (e.g., FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptides), ECD of FGFR polypeptides (e.g., ECD of FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptides), EGF (or epidermal growth factor) polypeptides, receptors for EGF polypeptides, neuregulin polypeptides (e.g., neuregulin isoform I, II, III, IV, V or VI polypeptides), receptors for neuregulin polypeptides, HER (human epidermal growth factor receptor) polypeptides (e.g., HER1, HER2, HER3 or HER4 polypeptides), ECD of HER polypeptides (e.g., ECD of HER1, HER2, HER3 or HER4 polypeptides), EpCAM (or epithelial cell adhesion molecule) polypeptides (e.g., ECD of EpCAM polypeptides), CD20 polypeptides (e.g., ECD of CD20 polypeptides), ligands for CD20 polypeptides,CD19 polypeptides (e.g., the ECD of CD19 polypeptides), ligands of CD19 polypeptides, CGRP (or calcitonin gene-related peptide) polypeptides (e.g., α-CGRP polypeptide or β-CGRP polypeptide), receptors for CGRP polypeptides, receptors for α-CGRP polypeptides, receptors for β-CGRP polypeptides, CALCRL (or calcitonin receptor-like) polypeptides (e.g., the ECD of CALCRL polypeptides), RAMP (or receptor activity-modifying protein) polypeptides (e.g., RAMP1, RAMP2 or RAMP3 polypeptides), the ECD of RAMP polypeptides (e.g., the ECD of RAMP1, RAMP2 or RAMP3 polypeptides), IGF (or insulin-like growth factor) polypeptides (e.g., IGF-1 or IGF-2 polypeptides), receptors for IGF polypeptides (e.g., receptors for IGF-1 or IGF-2 polypeptides), IGFR (or insulin-like growth factor receptor) polypeptides (e.g., IGFR1 or IGFR2 polypeptides), the ECD of IGFR polypeptides (e.g., the ECD of IGFR1 or IGFR2 polypeptides), IGFBP (or insulin-like growth factor binding protein) polypeptides (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5 or IGFBP6 polypeptides), VEGF (or vascular endothelial growth factor) polypeptides (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptides), receptors for VEGF polypeptides (e.g., receptors for VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF (or placental growth factor) polypeptides), VEGFR (or vascular endothelial growth factor receptor) polypeptides (e.g., VEGFR1, VEGFR2 or VEGFR3 polypeptides), the ECD of VEGFR polypeptides (e.g., the ECD of VEGFR1, VEGFR2 or VEGFR3 polypeptides, FLT1 (or FMS-like tyrosine kinase 1) receptor polypeptides (e.g., the ECD of FLT1 receptor polypeptides), IL36 (or interleukin 36) polypeptides (e.g., IL36A, IL36B or IL36G polypeptides), receptors for IL36 polypeptides (e.g., receptors for IL36A, IL36B or IL36G polypeptides),IL36R (or interleukin 36 receptor) polypeptide (e.g., ECD of IL36R polypeptide), IL1R1 polypeptide (e.g., ECD of IL1R1 polypeptide), IL1R2 polypeptide (e.g., ECD of IL1R2 polypeptide), IL1RL1 polypeptide (ECD of IL1RL1 polypeptide), IL18R1 polypeptide (ECD of IL18R1 polypeptide), bacterial toxin polypeptide, exotoxin polypeptide, endotoxin polypeptide, botulinum toxin polypeptide, tetanus toxin polypeptide, staphylococcal toxin polypeptide, CD52 polypeptide (e.g., ECD of CD52 polypeptide), ligand of CD52 polypeptide, siglec 10 (or sialic acid-binding immunoglobulin-like lectin 10) polypeptide, PCSK9 (or proprotein convertase subtilisin / kexin type 9) polypeptide, receptor of PCSK9 polypeptide, LDLR (or low density lipoprotein receptor) polypeptide (e.g., ECD of LDLR polypeptide), CEA (or carcinoembryonic antigen) polypeptide (e.g., CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptide), ECD of CEA polypeptide (e.g., ECD of CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptide), BAFF (or B cell activating factor) polypeptide, receptor of BAFF polypeptide, TRAF (or TNF receptor-associated factor) polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptide), receptor of TRAF polypeptide (e.g., receptor of TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 polypeptide), Receptors for BCMA polypeptide, ECD of BCMA (or B cell maturation antigen) polypeptide, SOST polypeptide, SOST (or sclerostin) polypeptide, LRP (or low density lipoprotein receptor-related protein) polypeptide (e.g., LRP5 or LRP6 polypeptide), ECD of LRP polypeptide (e.g., ECD of LRP5 or LRP6 polypeptide), DLL (or delta-like) polypeptide (e.g., DLL4 polypeptide), receptor for DLL polypeptide, Jagged polypeptide (e.g., JAG1 or JAG polypeptide), receptor for Jagged polypeptide (e.g., receptor for JAG1 or JAG polypeptide), NOTCH polypeptide (e.g., NOTCH1, NOTCH2, NOTCH3 or NOTCH4 polypeptide), ligand for NOTCH polypeptide (e.g., ligand for NOTCH1, NOTCH2, NOTCH3 or NOTCH4 polypeptide), VWF (or von Willebrand factor) polypeptide, receptor for VWF polypeptide, factor VIII polypeptide, receptor for factor VIII polypeptide, platelet GP1b receptor polypeptide (e.g., ECD of platelet GP1b receptor polypeptide), integrin α IIb β3 polypeptide (e.g., integrin α IIbECD of β3 polypeptide), IL2 (or interleukin 2) polypeptide, receptor of IL2 polypeptide, IL2R (or interleukin 2 receptor) polypeptide (e.g., IL2Rα, IL2Rβ or IL2Rγ polypeptide), ECD of IL2R polypeptide (e.g., ECD of IL2Rα, IL2Rβ or IL2Rγ polypeptide), TGFβ (or transforming growth factor β) polypeptide, receptor of TGFβ polypeptide, decorin polypeptide, EIF3I (or eukaryotic translation initiation factor 3 subunit 1) polypeptide, LTBP1 (or Latent-transforming Growth Factor Beta-Binding Protein 1) polypeptide, TGFβR1 polypeptide (e.g., ECD of TGFβR1 polypeptide), YWHAE polypeptide, IgE polypeptide, receptor of IgE polypeptide, Fc receptor polypeptide (e.g., FcεRI or FcεRII polypeptide), ECD of Fc receptor polypeptide (e.g., ECD of FcεRI or FcεRII polypeptide), KLK (or kallikrein) polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14 or KLK15 polypeptide), Rankl (or receptor activator of nuclear factor kappa B ligand) polypeptide, receptor of Rankl polypeptide, RANK (or receptor activator of nuclear factor kappa B) polypeptide (e.g., ECD of RANK polypeptide), TSLP (or thymic stromal lymphopoietin) polypeptide, receptor of TSLP polypeptide, CRLF2 (or cytokine receptor-like factor 2) polypeptide (e.g., ECD of CRLF2 polypeptide), IL7Rα polypeptide (e.g., ECD of IL7Rα polypeptide), S1P (or specificity protein 1) polypeptide, CD3 polypeptide (e.g., CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide), ECD of CD3 polypeptide (e.g., ECD of CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide, CD80 polypeptide, CD80Polypeptides, receptors for CD28 polypeptides (e.g., the ECD of CD28 polypeptides), CTLA-4 (or cytotoxic T lymphocyte-associated protein 4) polypeptides (e.g., the ECD of CTLA-4 polypeptides), GnRH (or gonadotropin-releasing hormone) polypeptides, receptors for GnRH polypeptides, GnRHR (or gonadotropin-releasing hormone receptor) polypeptides (e.g., the ECD of GnRHR polypeptides), ICAM (or intercellular adhesion molecule) polypeptides (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptides), receptors for ICAM polypeptides (e.g., receptors for ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptides), JAM-A polypeptides, receptors for JAM-A polypeptides, LFA-1 polypeptides (e.g., the ECD of LFA-1 polypeptides), Na v 1.7 polypeptides, C5 (or complement component 5) polypeptides (e.g., C5a or C5b polypeptides), receptors for C5 polypeptides (e.g., receptors for C5a or C5b polypeptides), C5aR polypeptides (e.g., the ECD of C5aR polypeptides), C5L2 polypeptides (e.g., the ECD of C5L2 polypeptides), IL17 polypeptides, receptors for IL17 polypeptides, IL17Ra polypeptides (e.g., the ECD of IL17Ra polypeptides), IL17RC polypeptides (e.g., the ECD of IL17RC polypeptides), EPO polypeptides, somatostatin polypeptides, GLP1 polypeptides, glucagon polypeptides, etc. are included.

[0146]

[0122] In some embodiments, the therapeutic polypeptide is a canine polypeptide, a feline polypeptide or a equine polypeptide.

[0147] Exemplary antibodies or antibody fragments include, but are not limited to, those that recognize one or more of the following polypeptides: late embryogenesis abundant (LEA) polypeptides (e.g., LEA-3 polypeptide), NGF polypeptide, the receptor for the NGF polypeptide (e.g., the ECD of the receptor for the NGF polypeptide), TrkA polypeptide (e.g., the ECD of the TrkA polypeptide), LNGFR polypeptide (e.g., the ECD of the LNGFR polypeptide), TNFα polypeptide, the receptor for the TNFα polypeptide, TNFR polypeptide (e.g., the ECD of the TNFR polypeptide), TNFR1 polypeptide (e.g., the ECD of the TNFR1 polypeptide), TNFR2 polypeptide (e.g., the ECD of the TNFR2 polypeptide), IL5 polypeptide, the receptor for the IL5 polypeptide, IL5R polypeptide (e.g., the ECD of the IL5R polypeptide), IL5Rα polypeptide (e.g., the ECD of the IL5Rα polypeptide), IL6 polypeptide, the receptor for the IL6 polypeptide, IL6R polypeptide (e.g., the ECD of the IL6R polypeptide), IL17 polypeptide, the receptor for the IL17 polypeptide, IL17R polypeptide (e.g., the ECD of the IL17R polypeptide), IL17RA polypeptide (e.g., the ECD of the IL17RA polypeptide), IL17RB polypeptide (e.g., the ECD of the IL17RB polypeptide), IL17RC polypeptide (e.g., the ECD of the IL17RC polypeptide), IL23 polypeptide, the receptor for the IL23 polypeptide, IL23R polypeptide (e.g., the ECD of the IL23R polypeptide), IL12Rβ1 polypeptide (e.g., the ECD of the IL12Rβ1 polypeptide), PDL1 polypeptide, the receptor for the PDL1 polypeptide, PDL2 polypeptide, the receptor for the PDL2 polypeptide, PD1 polypeptide (e.g., the ECD of the PD1 polypeptide), integrin polypeptides (e.g., ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7 or ITGB8 polypeptide), the receptor for the integrin polypeptide,Fibronectin polypeptide (e.g., ECD of fibronectin polypeptide), vitronectin polypeptide (e.g., ECD of vitronectin polypeptide), collagen polypeptide (e.g., ECD of collagen polypeptide), laminin polypeptide (e.g., ECD of laminin polypeptide), CD80 polypeptide, receptor of CD80 polypeptide, CD86 polypeptide, receptor of CD86 polypeptide, CTLA-4 polypeptide (e.g., ECD of CTLA-4 polypeptide), B7-H3 polypeptide, receptor of B7-H3 polypeptide (e.g., ECD of receptor of B7-H3 polypeptide), LAG-3 polypeptide (e.g., ECD of LAG-3 polypeptide), IL31 polypeptide, receptor of IL31 polypeptide, IL31RA polypeptide (e.g., ECD of IL31RA polypeptide), OSMR polypeptide (e.g., ECD of OSMR polypeptide), IL4 polypeptide, receptor of IL4R polypeptide, IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13 polypeptide, receptor of IL13 polypeptide, IL13RA1 polypeptide (e.g., ECD of IL13RA1 polypeptide), IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13Rα2 polypeptide (e.g., ECD of IL13Rα2 polypeptide), IL22 polypeptide, receptor of IL22 polypeptide (e.g., ECD of IL22 polypeptide), IL22Rα1 polypeptide (e.g., ECD of IL22Rα1 polypeptide), IL10Rβ2 polypeptide (e.g., ECD of IL10Rβ2 polypeptide), IL33 polypeptide, receptor of IL33 polypeptide, IL1RL1 polypeptide (e.g., ED of IL1RL1 polypeptide), EGF polypeptide, receptor of EGF polypeptide, TGFα polypeptide, receptor of TGFα polypeptide, EGFR polypeptide (e.g., ECD of EGFR polypeptide), MMP9 polypeptide, FGF polypeptide (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22 or FGF23 polypeptide), receptor of FGF polypeptide,FGFR polypeptides (e.g., FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptides), ECDs of FGFR polypeptides (e.g., ECDs of FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptides), EGF polypeptides, receptors of EGF polypeptides, neuregulin polypeptides (e.g., neuregulin isoform I, II, III, IV, V or VI polypeptides), receptors of neuregulin polypeptides, HER polypeptides (e.g., HER1, HER2, HER3 or HER4 polypeptides), ECDs of HER polypeptides (e.g., ECDs of HER1, HER2, HER3 or HER4 polypeptides), EpCAM polypeptides (e.g., ECDs of EpCAM polypeptides), CD20 polypeptides (e.g., ECDs of CD20 polypeptides), ligands of CD20 polypeptides, CD19 polypeptides (e.g., ECDs of CD19 polypeptides), ligands of CD19 polypeptides, CGRP polypeptides (e.g., α-CGRP polypeptides or β-CGRP polypeptides), receptors of CGRP polypeptides, receptors of α-CGRP polypeptides, receptors of β-CGRP polypeptides, CALCRL polypeptides (e.g., ECDs of CALCRL polypeptides), RAMP polypeptides (e.g., RAMP1, RAMP2 or RAMP3 polypeptides), ECDs of RAMP polypeptides (e.g., ECDs of RAMP1, RAMP2 or RAMP3 polypeptides), IGF polypeptides (e.g., IGF-1 or IGF-2 polypeptides), receptors of IGF polypeptides (e.g., receptors of IGF-1 or IGF-2 polypeptides), IGFR polypeptides (e.g., IGFR1 or IGFR2 polypeptides), ECDs of IGFR polypeptides (e.g., ECDs of IGFR1 or IGFR2 polypeptides), IGFBP polypeptides (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, or IGFBP6 polypeptides), VEGF polypeptides (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptides), receptors of VEGF polypeptides (e.g., receptors of VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptides), VEGFR polypeptides (e.g., VEGFR1,VEGFR2 or VEGFR3 polypeptide), ECD of VEGFR polypeptide (e.g., ECD of VEGFR1, VEGFR2 or VEGFR3 polypeptide), FLT1 receptor polypeptide (e.g., ECD of FLT1 receptor polypeptide), IL36 polypeptide (e.g., IL36A, IL36B or IL36G polypeptide), receptor of IL36 polypeptide (e.g., receptor of IL36A, IL36B or IL36G polypeptide), IL36R polypeptide (e.g., ECD of IL36R polypeptide), IL1R1 polypeptide (e.g., ECD of IL1R1 polypeptide), IL1R2 polypeptide (e.g., ECD of IL1R2 polypeptide), IL1RL1 polypeptide (ECD of IL1RL1 polypeptide), IL18R1 polypeptide (ECD of IL18R1 polypeptide), bacterial toxin polypeptide, exotoxin polypeptide, endotoxin polypeptide, botulinum toxin polypeptide, tetanus toxin polypeptide, staphylococcal toxin polypeptide, CD52 polypeptide (e.g., ECD of CD52 polypeptide), ligand of CD52 polypeptide, siglec-10 polypeptide, PCSK9 polypeptide, receptor of PCSK9 polypeptide, LDLR polypeptide (e.g., ECD of LDLR polypeptide), CEA polypeptide (e.g., CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptide), ECD of CEA polypeptide (e.g., ECD of CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptide), BAFF polypeptide, receptor of BAFF polypeptide, TRAF polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptide), receptor of TRAF polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, Receptors for TRAF5 polypeptides), BCMA polypeptides, ECDs of BCMA polypeptides, SOST polypeptides, receptors for SOST polypeptides, LRP polypeptides (e.g., LRP5 or LRP6 polypeptides), ECDs of LRP polypeptides (e.g., ECDs of LRP5 or LRP6 polypeptides), DLL polypeptides (e.g., DLL4 polypeptides), receptors for DLL polypeptides, Jagged polypeptides (e.g., JAG1 or JAG polypeptides), receptors for Jagged polypeptides (e.g., receptors for JAG1 or JAG polypeptides), NOTCH polypeptides (e.g., NOTCH1, NOTCH2, NOTCH3 or NOTCH4 polypeptides), ligands for NOTCH polypeptides (e.g., ligands for NOTCH1, NOTCH2, NOTCH3 or NOTCH4 polypeptides), VWF polypeptides, receptors for VWF polypeptides, Factor VIII polypeptides, receptors for Factor VIII polypeptides, platelet GP1b receptor polypeptides (e.g., ECDs of platelet GP1b receptor polypeptides), integrin α IIb β3 polypeptides (e.g., integrin α IIbECD of β3 polypeptide), IL2 polypeptide, receptor of IL2 polypeptide, IL2R polypeptide (e.g., IL2Rα, IL2Rβ or IL2Rγ polypeptide), ECD of IL2R polypeptide (e.g., ECD of IL2Rα, IL2Rβ or IL2Rγ polypeptide), TGFβ polypeptide, receptor of TGFβ polypeptide, decorin polypeptide, EIF3I polypeptide, LTBP1 polypeptide, TGFβR1 polypeptide (e.g., ECD of TGFβR1 polypeptide), YWHAE polypeptide, IgE polypeptide, receptor of IgE polypeptide, Fc receptor polypeptide (e.g., FcεRI or FcεRII polypeptide), ECD of Fc receptor polypeptide (e.g., ECD of FcεRI or FcεRII polypeptide), KLK polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14 or KLK15 polypeptide), Rankl polypeptide, receptor of Rankl polypeptide, RANK polypeptide (e.g., ECD of RANK polypeptide), TSLP polypeptide, receptor of TSLP polypeptide, CRLF2 polypeptide (e.g., ECD of CRLF2 polypeptide), IL7Rα polypeptide (e.g., ECD of IL7Rα polypeptide), S1P polypeptide, CD3 polypeptide (e.g., CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide), ECD of CD3 polypeptide (e.g., ECD of CD3γ polypeptide, CD3δ polypeptide or CD3ε polypeptide), CD80 polypeptide, receptor of CD80 polypeptide, CD28 polypeptide (e.g., ECD of CD28 polypeptide), CTLA-4 polypeptide (e.g., ECD of CTLA-4 polypeptide), GnRH polypeptide, receptor of GNRH polypeptide, GnRHR polypeptide (e.g., ECD of GnRHR polypeptide), ICAM polypeptide (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), receptor of ICAM polypeptide (e.g., receptor of ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), JAM-A polypeptide, receptor of JAM-A polypeptide,LFA-1 polypeptide (e.g., ECD of LFA-1 polypeptide), Na, v 1.7 polypeptide, C5 polypeptide (e.g., C5a or C5b polypeptide), receptor for C5 polypeptide (e.g., receptor for C5a or C5b polypeptide), C5aR polypeptide (e.g., ECD of C5aR polypeptide), C5L2 polypeptide (e.g., ECD of C5L2 polypeptide), IL17 polypeptide, receptor for IL17 polypeptide, IL17Ra polypeptide (e.g., ECD of IL17Ra polypeptide), EPO polypeptide, somatostatin polypeptide, GLP1 polypeptide, glucagon polypeptide, etc.

[0148]

[0124] In some embodiments, the target polypeptide is a canine polypeptide, a feline polypeptide or a equine polypeptide.

[0149]

[0125] "Linker" refers to one or more amino acid residues that connect a first polypeptide to a second polypeptide.

[0150]

[0126] In some embodiments, the linker is a flexible unstructured linker. In some embodiments, the linker is a glycine-rich, serine-rich, or glycine- and serine-rich linker. In some embodiments, the linker comprises 100%, at least 95%, at least 90%, or at least 85% serine and / or glycine amino acid residues.

[0151] Exemplary expression and production of IgG Fc variants and fusion molecules

[0127] The nucleotide sequence encoding a polypeptide of interest such as the mutant IgG Fc polypeptide or other polypeptide described herein can be inserted into an expression vector suitable for expression in a selected host cell. The mutant IgG Fc polypeptide or mutant IgG Fc fusion protein can be expressed by culturing a host cell transfected with an expression vector containing the nucleotide sequence.

[0152]

[0128] A "vector" is a plasmid that can be used to transfer a DNA sequence from one organism to another or to express a gene of interest. A vector usually contains an origin of replication and regulatory sequences that regulate the expression of the gene of interest, and may or may not carry a selectable marker gene such as an antibiotic resistance gene. The vector is suitable for the host cell in which it is to be expressed. When the gene of interest is present in the vector, the vector may be referred to as a "recombinant vector".

[0153]

[0129] A "host cell" can be a recipient of a vector or an isolated polynucleotide, or refers to a cell that was a recipient. A host cell can be a prokaryotic cell or a eukaryotic cell. Exemplary eukaryotic cells include mammalian cells such as primate or non-primate animal cells; fungal cells such as yeast; plant cells; and insect cells. Non-limiting and exemplary mammalian cells include, but are not limited to, NS0 cells, PER.C6® cells (Crucell), 293 cells, and CHO cells, and derivatives thereof such as 293-6E, DG44, CHO-S and CHO-K cells. Host cells include the progeny of a single host cell, and the progeny are not necessarily identical (either morphologically or in genomic DNA complementarity) to the original parent cell due to natural variation, accidental variation or intentional variation. Host cells include cells that have been transfected in vivo with a polynucleotide(s) encoding the amino acid sequence(s) provided herein.

[0154]

[0130] The term "isolated" as used herein refers to a molecule that is separated from at least some of the components that are normally found or produced in its natural environment. For example, a polypeptide is said to be "isolated" if it is separated from at least some of the cellular components from which it was produced. If the polypeptide is secreted by a cell after expression, physically separating the supernatant containing the polypeptide from the cell that produced it is considered to "isolate" the polypeptide. Similarly, a polynucleotide is said to be "isolated" when it is not part of a larger polynucleotide that is normally found in nature (e.g., in the case of a DNA polynucleotide, genomic DNA or mitochondrial DNA, etc.) or, for example, in the case of an RNA polynucleotide, when it is separated from at least some of the components of the cell from which it was produced. Thus, a DNA polynucleotide contained in a vector in a host cell can be said to be "isolated".

[0155]

[0131] "Signal sequence" refers to a sequence of amino acid residues or a polynucleotide encoding same that promotes secretion of a polypeptide of interest and is typically cleaved once the polypeptide is transported across the outside of the cell surface membrane.

[0156]

[0132] In some embodiments, the mutant IgG Fc polypeptides or other polypeptides described herein are isolated using chromatography, such as size exclusion chromatography, ion exchange chromatography, Protein A column chromatography, hydrophobic interaction chromatography, and CHT chromatography.

[0157]

[0133] The label can be attached to a polypeptide comprising a mutant IgG Fc polypeptide or a mutant Fc polypeptide. A "label" means a moiety attached to a molecule to make the molecule detectable. In some embodiments, the mutant IgG Fc polypeptide is labeled with a detectable moiety including, but not limited to, radioisotopes, fluorescent labels, and various enzyme substrate labels known in the art. In some embodiments, the label is a detectable marker that can generate a signal detectable by visual or instrumental means, for example, incorporation of radio-labeled amino acids or attachment of a biotinyl moiety to a polypeptide that can be detected by labeled avidin (e.g., streptavidin containing a fluorescent marker or enzyme activity that can be detected by optical or colorimetric methods). Examples of polypeptide labeling include, but are not limited to: radioisotopes or radionuclides (e.g., 3 H, 14 C, 35 S, 90 Y, 99 Tc, 111 In, 125 I, 131 I, 177 Lu, 166 Ho or 153 Sm); chromogens, fluorescent labels (e.g., FITC, rhodamine, lanthanide phosphors), enzyme labels (e.g., p-galactosidase, horseradish peroxidase, luciferase, alkaline phosphatase); chemiluminescent markers; biotinyl groups; predetermined polypeptide epitopes recognized by secondary reporters (e.g., leucine zipper pair sequences, binding sites for secondary antibodies, metal binding domains, epitope tags); and magnetic agents such as gadolinium chelates. Representative examples of labels commonly used in immunoassays include moieties that emit light (e.g., acridinium compounds) and moieties that emit fluorescence (e.g., fluorescein). In this case, the site itself may not be detectably labeled, but may become detectable by reaction with another moiety. General techniques used in performing the various immunoassays described above are known to those skilled in the art.

[0158] Affinity of an Exemplary Variant IgG Fc Polypeptide for FcRn

[0134] The variant IgG Fc polypeptides described herein may have altered binding affinity for FcRn, such as improved binding affinity for FcRn at acidic pH (e.g., pH in the range of about 5.0 to about 6.5). The variant IgG Fc polypeptides described herein may extend the half-life of an antibody or variant IgG Fc fusion protein in vivo or improve pharmacokinetics.

[0159]

[0135] As used herein, "neonatal Fc receptor" or "FcRn" is a polypeptide that includes all or a portion of FcRn that can bind to wild-type IgG of the same species, excluding canine IgG-C. In some embodiments, FcRn is the FcRn extracellular domain (ECD). In some embodiments, FcRn includes the amino acid sequence of SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 24, or SEQ ID NO: 25. In some embodiments, FcRn is associated with B2M in a protein complex ("FcRn / B2M protein complex" or "FcRn / B2M complex").

[0160]

[0136] "Extracellular domain" ("ECD") is the portion of a polypeptide that extends into the extracellular space beyond the transmembrane domain. As used herein, the term "extracellular domain" may refer to a complete extracellular domain, a truncated extracellular domain lacking one or more amino acids, that still binds its ligand. The composition of the extracellular domain may depend on the algorithm used to determine which amino acids are present in the membrane. Various algorithms are capable of predicting the various extracellular domains of a given protein, and various systems are capable of expressing the various extracellular domains of a given protein.

[0161] As used herein, "beta-2 microglobulin" or "B2M" is a polypeptide comprising all or part of B2M capable of associating with FcRn. In some embodiments, B2M comprises the amino acid sequence of SEQ ID NO: 20, SEQ ID NO: 23, or SEQ ID NO: 26.

[0162] The term "binds to" a substance is a term well understood in the art, and methods for determining such binding are also well known in the art. A molecule reacts with, associates with, or has an affinity for a particular cell or substance, and that reaction, association, or affinity is detected by one or more protein interaction tools known in the art, such as immunoblotting, ELISA, KinEx A, biolayer interferometry (BLI), surface plasmon resonance (SPR) devices, etc., is said to "bind".

[0163]

[0139] The term "affinity" means the strength of the sum of non-covalent interactions between a single binding site of a molecule (e.g., a receptor) and its binding partner (e.g., a ligand). Usually, the affinity of molecule X for its partner Y can be represented by the dissociation constant (K D ). Affinity can be measured by common protein interaction tools known in the art, such as immunoblotting, ELISA, KinEx A, biolayer interferometry (BLI), or surface plasmon resonance (SPR) devices.

[0164]

[0140] "Surface plasmon resonance" refers to an optical phenomenon by which real-time biospecific interactions can be analyzed by detecting changes in protein concentration within a biosensor matrix, for example, using a BIAcore TM system (Biacore International AB, Uppsala, Sweden and Piscataway, NJ, USA, a subsidiary of GE Healthcare). For details, see Jonsson et al. (1993) Ann. Biol. Clin. 51:19-26.

[0165]

[0141] "Biolayer interferometry" refers to an optical analysis technique that analyzes the interference pattern of light reflected from a layer of protein immobilized on a biosensor chip and an internal reference layer. A change in the number of molecules bound to the biosensor chip causes a change in the interference pattern that can be measured in real time. A non-limiting and exemplary device for biolayer interferometry is the Octet® system (Pall ForteBio). See, for example, Abdiche et al., 2008, Anal. Biochem. 377:209-277.

[0166]

[0142] "K" D ", "K" d ", "Kd" or "Kd value" are used interchangeably to refer to the equilibrium dissociation constant of a receptor-ligand interaction or an antibody-antigen interaction.

[0167]

[0143] In some embodiments, the mutant IgG Fc polypeptide binds to FcRn with a dissociation constant (KD) of less than 5x10 -6 M, less than 1x10 -6 M, less than 5x10 -7 M, less than 1x10 -7 M, less than 5x10 -8 M, less than 1x10 -8 M, less than 5x10 -9 M, less than 1x10 -9 M, less than 5x10 -10 M, less than 1x10 -10 M, less than 5x10 -11 M, less than 1x10 -11 M, less than 5x10 -12 M or less than 1x10 -12 M as measured by biolayer interferometry.

[0168]

[0144] In some embodiments, the polypeptide comprises a mutant IgG Fc polypeptide having an increased serum half-life compared to a polypeptide comprising a wild-type Fc polypeptide.

[0169]

[0145] In some embodiments, the K of an Fc polypeptide, such as a mutant IgG Fc polypeptide, for FcRn or the FcRn / B2M protein complex D is measured by biolayer interferometry using a biosensor such as the Octet® system (Pall ForteBio, Fremont, CA) according to the manufacturer's instructions. Briefly, a biotinylated FcRn or FcRn / B2M protein complex is bound to the sensor chip, and the association of the Fc polypeptide is monitored until a predetermined time or steady state is reached. Dissociation can be monitored until a predetermined time or steady state is reached. To correct for drift, a buffer-only blank curve is subtracted. The data is fit to a 2:1 binding model using ForteBio data analysis software to determine the association rate constant (k on ), the dissociation rate constant (k off ), and K d . The equilibrium dissociation constant (K D ) is calculated as the k off / k on ratio. The term "k on " refers to the rate constant at which molecule X associates with its partner Y, and the term "k off " refers to the rate constant at which molecule X or partner Y dissociates from the molecule X / partner Y complex.

[0170]

[0146] In some embodiments, the association of an Fc polypeptide, such as a variant IgG Fc polypeptide, with an FcRn or FcRn / B2M protein complex can be tested at various concentrations, such as concentrations less than about 0.5 μg / mL, concentrations in the range of about 0.5 μg / mL to about 100 μg / mL, concentrations in the range of about 0.5 μg / mL to about 10 μg / mL, concentrations in the range of about 10 μg / mL to about 100 μg / mL, or concentrations in the range of about 5 μg / mL to about 50 μg / mL. In some embodiments, the concentration of the Fc polypeptide tested for association with an FcRn or FcRn / B2M protein complex is about 0.5 μg / mL, about 1 μg / mL, about 5 μg / mL, about 10 μg / mL, about 15 μg / mL, about 20 μg / mL, about 25 μg / mL, about 30 μg / mL, about 40 μg / mL, about 50 μg / mL, about 60 μg / mL, about 70 μg / mL, about 75 μg / mL, about 80 μg / mL, about 90 μg / mL or about 100 μg / mL.

[0171]

[0147] In some embodiments, the association or dissociation of an Fc polypeptide, such as a variant IgG Fc polypeptide, with an FcRn or FcRn / B2M protein complex can be tested at various pHs. In some embodiments, the association or dissociation of an Fc polypeptide with an FcRn or FcRn / B2M protein complex is tested at acidic pH. In some embodiments, the association or dissociation of an Fc polypeptide with an FcRn or FcRn / B2M protein complex is tested at neutral pH. In some embodiments, the association or dissociation of an Fc polypeptide with an FcRn or FcRn / B2M protein complex is tested at a pH in the range of about 5.0 to about 6.5. In some embodiments, the association or dissociation of an Fc polypeptide with an FcRn or FcRn / B2M protein complex is tested at a pH of about 5.0, about 6.0, about 6.5 or about 7.0. In some embodiments, the association or dissociation of an Fc polypeptide with an FcRn or FcRn / B2M protein complex is tested at a pH of 5.0, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7.0, 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9 or 8.0.

[0172]

[0148] Buffers for the dilution and binding steps can be adjusted to the various pHs described above and are known to those skilled in the art. For example, a buffer of 20 mM MES and 15 mM NaCl adjusted to a pH in the range of about 5.0 to about 6.5 can be used in the binding assay. As another example, phosphate buffered saline (pH 7.4) can be used in the binding assay. As a further example, a buffer of 20 mM phosphate, 150 mM NaCl (pH 7.2) can be used in the binding assay.

[0173]

[0149] In some embodiments, the association or dissociation of an Fc polypeptide, such as a variant IgG Fc polypeptide, with an FcRn or FcRn / B2M protein complex is monitored until a predetermined time or a steady state is reached. In some embodiments, the association or dissociation of the Fc polypeptide with the FcRn or FcRn / B2M protein complex is monitored between 30 seconds, 60 seconds, 90 seconds, 120 seconds, 150 seconds, 180 seconds, 210 seconds, 240 seconds, 270 seconds, 300 seconds, 330 seconds, 360 seconds, 390 seconds, 420 seconds, 450 seconds, 480 seconds, 510 seconds, 540 seconds, 570 seconds, 600 seconds, 630 seconds, 660 seconds, 690 seconds, 720 seconds, 750 seconds, 780 seconds, 810 seconds, 840 seconds, 870 seconds or 900 seconds.

[0174]

[0150] In some embodiments, pharmacokinetic analysis is performed to determine any number of pharmacokinetic parameters, including Tmax, Cmax, and area under the curve (AUC). For example, the polypeptides described herein may be administered to an animal and serum samples may be taken at different time intervals (e.g., pre-dose, and / or 0.5, 1, 6, 24, 48, 72, 168, 216 and / or 336 hours post-dose). The polypeptide concentration in the serum sample can be determined, for example, by ELISA. "Increased" or "greater" means an increase compared to a reference. In some embodiments, "increased" or "greater" means the ability to cause an overall increase of about 5% or more, about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, about 90% or more, about 100% or more, about 125% or more, about 150% or more, about 200% or more relative to a reference value. In some embodiments, "increased" or "greater" means the ability to cause an overall increase of about 5% to about 50%, about 10% to about 20%, about 50% to about 100%, about 25% to about 70% relative to a reference value.

[0175]

[0151] In some embodiments, an Fc polypeptide, such as a variant IgG Fc polypeptide, can bind to FcRn or FcRn / B2M with an affinity increased by about 5% or more, about 10% or more, about 20% or more, about 30% or more, about 40% or more, about 50% or more, about 60% or more, about 70% or more, about 80% or more, about 90% or more, about 100% or more, about 125% or more, about 150% or more, about 200% or more relative to a reference Fc polypeptide. In some embodiments, a variant IgG Fc polypeptide can bind to FcRn or FcRn / B2M with an affinity increased by about 5% to about 50%, about 10% to about 20%, about 50% to about 100%, about 25% to about 70% relative to a reference Fc polypeptide. In some embodiments, the reference Fc polypeptide is a wild-type Fc polypeptide. In some embodiments, the Fc polypeptide is a different variant Fc polypeptide. In some aspects, the affinity is measured by biolayer interferometry at a pH in the range of about 5.0 to about 6.5.

[0176] Exemplary pharmaceutical compositions

[0152] The terms “pharmaceutical formulation” and “pharmaceutical composition” refer to a preparation that is in a form that enables the biological activity of the active ingredient and that contains no additional ingredients that are toxic to the subject to which the formulation is administered.

[0177]

[0153] As used herein, "pharmaceutically acceptable carrier" refers to a non-toxic solid, semi-solid or liquid filler, diluent, encapsulating material, formulation aid, or carrier commonly used in the art for use with a therapeutic agent, which together constitute a "pharmaceutical composition" for administration to a subject. A pharmaceutically acceptable carrier is non-toxic to the recipient at the dosages and concentrations employed and is compatible with the other ingredients of the formulation. A pharmaceutically acceptable carrier is suitable for use in the formulation employed. Examples of pharmaceutically acceptable carriers include, but are not limited to, alumina; aluminum stearate; lecithin; serum proteins such as human serum albumin, canine or other animal albumin; buffers such as phosphates, citrates, tromethamine or HEPES buffer; glycine; sorbic acid; potassium sorbate; partial glyceride mixtures of saturated vegetable fatty acids; water; salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts, colloidal silica or magnesium trisilicate; polyvinylpyrrolidone; cellulose-based substances; polyethylene glycol; sucrose; mannitol; or amino acids such as arginine.

[0178]

[0154] Pharmaceutical compositions can be stored in lyophilized form. Thus, in some embodiments, the preparation method includes a lyophilization step. Thereafter, the lyophilized composition can typically be reconstituted as an aqueous composition suitable for parenteral administration prior to administration to a dog, cat or horse. In other embodiments, particularly when the variant IgG Fc polypeptides or other polypeptides described herein are highly stable to heat and oxidative denaturation, the pharmaceutical composition can be stored as a liquid, i.e., an aqueous composition, and administered to a dog, cat or horse either neat or appropriately diluted. The lyophilized composition can be reconstituted with sterile water for injection (WFI). A bacteriostatic reagent such as benzyl alcohol may be included. Thus, the present invention provides pharmaceutical compositions in solid or liquid form.

[0179]

[0155] The pH of the pharmaceutical composition can be in the range of about pH 5 to about pH 8 when administered. The compositions of the present invention are sterile when used for therapeutic purposes. The sterile state can be achieved by any of several means known in the art, including filtration through a sterile filtration membrane (e.g., a 0.2 micron membrane). The sterile state can be maintained with or without an antibacterial agent.

[0180] Exemplary uses of the Fc polypeptide and pharmaceutical composition

[0156] A polypeptide comprising a variant Fc polypeptide of the present invention, such as a variant IgG Fc polypeptide, or a pharmaceutical composition comprising a variant Fc polypeptide of the present invention can be useful for extending the half-life of the product in vivo in companion animals including, but not limited to, dogs, cats or horses.

[0181] As used herein, "treatment" is an approach for obtaining a beneficial or desired clinical outcome. "Treatment" as used herein encompasses any administration or application of a therapeutic agent for a disease in a mammal, including companion animals. In the context of the present disclosure, beneficial or desired clinical outcomes include, but are not limited to, any one or more of the following: alleviation of one or more symptoms, reduction in the degree of the disease, prevention or delay of disease spread, prevention or delay of disease recurrence, delay or deceleration of disease progression, amelioration of the medical condition, suppression of the disease or disease progression, suppression or deceleration of the disease or its progression, arrest of its progression, and remission (partial or complete). Also, "treatment" encompasses reduction of the pathological consequences of a proliferative disease. The methods provided herein contemplate any one or more of these aspects of treatment. In connection with the foregoing, the term treatment does not require complete elimination of all aspects of the disorder.

[0182]

[0158] The "therapeutically effective amount" of a substance / molecule, agonist or antagonist can vary depending on factors such as the type of disease being treated, the medical condition, the severity and course of the disease, the type of therapeutic objective, any previous treatment, the clinical history, the response to previous treatment, the discretion of the attending veterinarian, the age, sex and weight of the animal, and the ability of the substance / molecule, agonist or antagonist to induce the desired response in the animal. Also, the therapeutically effective amount is an amount in which the therapeutically beneficial effects exceed the toxic or harmful effects of the substance / molecule, agonist or antagonist. The therapeutically effective amount can be delivered in one or multiple administrations. The "therapeutically effective amount" refers to an effective amount at the dosage and for the period required to achieve the desired therapeutic or prophylactic result.

[0183]

[0159] In some embodiments, a variant Fc polypeptide (such as a variant IgG Fc polypeptide), a variant Fc fusion molecule (such as a variant IgG Fc fusion protein), or a pharmaceutical composition comprising a variant Fc polypeptide or a variant Fc fusion molecule is administered parenterally by subcutaneous administration, intravenous infusion or intramuscular injection. In some embodiments, a pharmaceutical composition comprising a variant Fc polypeptide fusion molecule or a variant Fc polypeptide fusion molecule is administered as a bolus injection or by continuous infusion over a period of time. In some embodiments, a pharmaceutical composition comprising a variant Fc polypeptide fusion molecule or a variant Fc polypeptide fusion molecule is administered intramuscularly, intraperitoneally, intrathecally, subcutaneously, intraarterially, intrasynovially, intramedullary or by the inhalation route.

[0184]

[0160] In some embodiments, the variant Fc polypeptide fusion molecules described herein are administered in an amount in the range of 0.0001 mg / kg body weight to 100 mg / kg body weight per dose. In some embodiments, the variant Fc polypeptide fusion molecules described herein are administered to a companion animal once or over a series of treatments.

[0185]

[0161] In some embodiments, the variant IgG Fc polypeptide or other polypeptide described herein, or a pharmaceutical composition comprising the same, is administered to a companion animal either once or over a series of treatments. In some embodiments, the dosage is administered once a week for at least two or three consecutive weeks, and in some embodiments, this treatment cycle is repeated two or more times, optionally with a treatment-free period of one week or more in between. In other embodiments, the therapeutically effective dosage is administered once a day for at least two to five consecutive days, and in some embodiments, this treatment cycle is repeated two or more times, optionally with a treatment-free period of one day or more or one week or more in between.

[0186]

[0162] “Combined” administration with one or more additional therapeutic agents includes concurrent (simultaneous) and sequential or successive administration in any order. The term “concurrently” as used herein refers to the administration of two or more therapeutic agents, where at least a portion of the administrations overlap in time or where the administration of one therapeutic agent occurs within a short time period compared to the administration of the other therapeutic agent. For example, two or more therapeutic agents are administered at time intervals of approximately less than a specified fraction. The term “sequentially” as used herein refers to the administration of two or more therapeutic agents, where the administration of one or more agents continues after the cessation of the administration of one or more other agents, or where the administration of one or more agents is initiated before the administration of one or more other agents. For example, the administration of two or more therapeutic agents is at time intervals of approximately greater than a specified fraction. As used herein, “in combination with” means administering one therapy in addition to another therapy. Thus, “in combination with” refers to administering one therapy to an animal before, during, or after the administration of another therapy.

[0187]

[0163] The following examples illustrate certain aspects of the present disclosure and are not intended to limit the present disclosure in any way.

Example

[0188] Example 1 Expression and Purification of Canine FcRn and Beta-2-M

[0164] A nucleotide sequence encoding a canine FcRn ECD protein having a polyHis tag (SEQ ID NO: 18) at the C-terminus was synthesized and cloned into a mammalian expression vector. A nucleotide sequence (SEQ ID NO: 20) encoding a canine beta2 microglobulin (B2M) protein was synthesized and cloned into a mammalian expression vector. Both vectors were co-transfected into 293 cells or CHO S. The supernatant containing the canine FcRn / B2M protein complex was collected and filtered. The canine FcRn / B2M protein complex was affinity purified using a Ni-NTA column (CaptivA® Protein A Affinity Resin, manufactured by Repligen). FcRn / B2M protein complexes of cat and horse can also be generated using a similar method.

[0189] Example 2 Mutant Canine IgG-A Fc Polypeptide

[0165] Mutants of the canine IgG-A Fc polypeptide (e.g., mutants of SEQ ID NO: 1) may be prepared that have one or more of the amino acid substitutions described in Table 3 at positions corresponding to the positions described in SEQ ID NO: 1.

[0190]

[0166] Table 3. TIFF2025093964000033.tif180170

[0191]

[0167] The binding of the mutant canine IgG-A Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type canine IgG-A Fc polypeptide, another wild-type or mutant canine IgG Fc polypeptide, or a wild-type or mutant IgG Fc polypeptide of another companion animal, etc.).

[0192]

[0168] Binding analysis can be carried out using the BioSensor Octet. Briefly, the FcRn / B2M complex (e.g., the FcRn / B2M protein complex generated by the method of Example 1) can be biotinylated, and free unreacted biotin can be removed (e.g., by dialysis). The biotinylated FcRn / B2M complex is captured on a streptavidin sensor chip. The association of the FcRn / B2M complex with mutant IgG Fc polypeptides at various concentrations (e.g., 10 μg / mL) is monitored for a predetermined time or until a steady state is reached. Dissociation is monitored for a predetermined time or until a steady state is reached. To correct for drift, a blank curve of buffer only is subtracted. The data is TM fit to a 1:1 binding model using ForteBio

[0193] Example 3 Mutant canine IgG-B Fc polypeptide

[0169] Mutants of the canine IgG-B Fc polypeptide (e.g., the mutant of SEQ ID NO: 2) may be made that have one or more of the amino acid substitutions set forth in Table 4 at positions corresponding to the positions set forth in SEQ ID NO: 2.

[0194]

[0170] Table 4. TIFF2025093964000034.tif187170

[0195]

[0171] The binding of the variant canine IgG-B Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type canine IgG-B Fc polypeptide, another wild-type or variant canine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0196] Example 4 Variant canine IgG-C Fc polypeptide

[0172] Variants of canine IgG-C Fc (e.g., variants of SEQ ID NO: 3) may be made that have one or more of the amino acid substitutions described in Table 5 at positions corresponding to the positions described for SEQ ID NO: 3.

[0197]

[0173] Table 5. TIFF2025093964000035.tif173170

[0198]

[0174] The binding of the variant canine IgG-C Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type canine IgG-C Fc polypeptide, another wild-type or variant canine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0199] Example 5 Variant canine IgG-D Fc polypeptide

[0175] Variants of canine IgG-D Fc (e.g., variants of SEQ ID NO: 4) may be made that have one or more of the amino acid substitutions described in Table 6 at positions corresponding to the positions described for SEQ ID NO: 4.

[0200]

[0176] Table 6. TIFF2025093964000036.tif173170

[0201]

[0177] The binding of the variant canine IgG-D Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type canine IgG-D Fc polypeptide, another wild-type or variant canine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0202] Example 6 Variant equine IgG-1 Fc polypeptide

[0178] Variants of equine IgG-1 Fc (e.g., the variant of SEQ ID NO: 5) may be prepared to have one or more of the amino acid substitutions described in Table 7 at positions corresponding to the positions described in SEQ ID NO: 5.

[0203]

[0179] Table 7. TIFF2025093964000037.tif206170

[0204]

[0180] The binding of the variant equine IgG-1 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type equine IgG-1 Fc polypeptide, another wild-type or variant equine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0205] Example 7 Variant equine IgG-2 Fc polypeptide

[0181] Variants of equine IgG-2 Fc (e.g., the variant of SEQ ID NO: 6) may be prepared to have one or more amino acid substitutions described in Table 8 at positions corresponding to the positions described in SEQ ID NO: 6.

[0206]

[0182] Table 8. TIFF2025093964000038.tif166170

[0207]

[0183] The binding of the variant equine IgG-2 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type equine IgG-2 Fc polypeptide, another wild-type or variant equine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0208] Example 8 Variant equine IgG-3 Fc polypeptide

[0184] Variants of equine IgG-3 Fc (e.g., the variant of SEQ ID NO: 7) may be prepared to have one or more amino acid substitutions described in Table 9 at positions corresponding to the positions described in SEQ ID NO: 7.

[0209]

[0185] Table 9. TIFF2025093964000039.tif181170

[0210]

[0186] The binding of the variant equine IgG-3 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type equine IgG-3 Fc polypeptide, another wild-type or variant equine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0211] Example 9 Mutant equine IgG-4 Fc polypeptide

[0187] Variants of equine IgG-4 Fc (e.g., the variant of SEQ ID NO: 8) may be prepared to have one or more amino acid substitutions described in Table 10 at positions corresponding to the positions described in SEQ ID NO: 8.

[0212]

[0188] Table 10. TIFF2025093964000040.tif166170

[0213]

[0189] The binding of the mutant equine IgG-4 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type equine IgG-4 Fc polypeptide, another wild-type or mutant equine IgG Fc polypeptide, or a wild-type or mutant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0214] Example 10 Mutant equine IgG-5 Fc polypeptide

[0190] Variants of equine IgG-5 Fc (e.g., the variant of SEQ ID NO: 9) may be prepared to have one or more amino acid substitutions described in Table 11 at positions corresponding to the positions described in SEQ ID NO: 9.

[0215]

[0191] Table 11. TIFF2025093964000041.tif173170

[0216]

[0192] The binding of the variant equine IgG-5 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type equine IgG-5 Fc polypeptide, another wild-type or variant equine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0217] Example 11 Variant equine IgG-6 Fc polypeptide

[0193] Variants of equine IgG-6 Fc (e.g., variants of SEQ ID NO: 10) may be made that have one or more of the amino acid substitutions described in Table 12 at positions corresponding to the positions described for SEQ ID NO: 10.

[0218]

[0194] Table 12. TIFF2025093964000042.tif159170

[0219]

[0195] The binding of the variant equine IgG-6 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type equine IgG-6 Fc polypeptide, another wild-type or variant equine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0220] Example 12 Variant equine IgG-7 Fc polypeptide

[0196] Variants of equine IgG-7 Fc (e.g., variants of SEQ ID NO: 11) may be made that have one or more of the amino acid substitutions described in Table 13 at positions corresponding to the positions described for SEQ ID NO: 11.

[0221]

[0197] Table 13. TIFF2025093964000043.tif166170

[0222]

[0198] The binding of the variant equine IgG-7 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type equine IgG-7 Fc polypeptide, another wild-type or variant equine IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0223] Example 13 Variant feline IgG1a Fc polypeptide

[0199] Variants of feline IgG1a Fc (e.g., variants of SEQ ID NO: 12) may be made that have one or more of the amino acid substitutions listed in Table 14 at positions corresponding to the positions described for SEQ ID NO: 12.

[0224]

[0200] Table 14. TIFF2025093964000044.tif180170

[0225]

[0201] The binding of the variant feline IgG1a Fc polypeptide to FcRn / B2M can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc to FcRn (e.g., the corresponding wild-type feline IgG1a Fc polypeptide, another wild-type or variant feline IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0226] Example 14 Variant feline IgG1b Fc polypeptide

[0202] Variants of feline IgG1b Fc (e.g., the variant of SEQ ID NO: 13) may be prepared to have one or more amino acid substitutions described in Table 15 at positions corresponding to the positions described in SEQ ID NO: 13.

[0227]

[0203] Table 15. TIFF2025093964000045.tif187170

[0228]

[0204] The binding of the variant feline IgG1b Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type feline IgG1b Fc polypeptide, another wild-type or variant feline IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0229] Example 15 Variant feline IgG2 Fc polypeptide

[0205] Variants of feline IgG2 Fc (e.g., the variant of SEQ ID NO: 54) may be prepared to have one or more amino acid substitutions described in Table 16 at positions corresponding to the positions described in SEQ ID NO: 54.

[0230]

[0206] Table 16. TIFF2025093964000046.tif187170

[0231]

[0207] The binding of the variant feline IgG2 Fc polypeptide to the FcRn / B2M complex can be measured (e.g., at a pH in the range of about 5.0 to about 6.5) and compared to the binding of another IgG Fc polypeptide to the FcRn / B2M complex (e.g., the corresponding wild-type feline IgG2 Fc polypeptide, another wild-type or variant feline IgG Fc polypeptide, or a wild-type or variant IgG Fc polypeptide of another companion animal, etc.). The binding assay described in Example 2 can be used.

[0232] Example 16 Screening of Mutant Canine IgG-B Polypeptides with Enhanced Canine FcRn / B2M Binding at Acidic pH

[0208] Canine FcRn having a polyHis tag (SEQ ID NO: 18) and a canine B2M (SEQ ID NO: 20) heterodimer complex was transiently expressed in HEK cells and purified using Ni-NTA chromatography.

[0233]

[0209] Fast Screening for Expression, Biophysical Properties and Affinity (FASEBA) of a canine IgG-B Fc phage library was performed. Briefly, the open reading frame of the canine IgG-B Fc polypeptide was subcloned into plasmid pFASEBA. Based on the three-dimensional protein modeling of the canine IgG-B / Canine FcRn / Canine B2M complex, 12 amino acid positions of canine IgG-B were identified as potentially involved in the binding between IgG-B and FcRn / B2M. The 12 identified positions of canine IgG-B were Thr(22), Leu(23), Leu(24), Ile(25), Ala(26), Thr(28), Gly(81), His(82), Gln(83), Leu(86), Met(202), and Asn(208) of SEQ ID NO: 2.

[0234]

[0210] A 12-site single-point NNK mutant library of canine IgG-B Fc was prepared such that each library contained mutant IgG-B Fc polypeptides having each of the 20 possible amino acids substituted at each of the 12 sites. Each phage library was panned against the canine FcRn / B2M complex at pH 6.0. After 3 rounds of panning, a total of 53 Fc phage clones were identified as potentially having enhanced FcRn / B2M binding, and the mutations were identified by sequencing (see Figure 1).

[0235]

[0211] A single E. coli colony expressing each of 53 mutant canine IgG-B Fc polypeptides with SASA tags was cultured and induced to express the Fc polypeptide. The cell culture fluid containing the mutant canine IgG-B Fc polypeptide was exposed to BSA immobilized on a plate or on a Biacore chip. The plate or chip to which the mutant canine IgG-B Fc polypeptide was bound was exposed to the soluble canine FcRn / B2M complex to screen for the off-rate (koff) at pH 6. Each mutant IgG-B Fc polypeptide showing a slow koff with the canine FcRn / B2M complex was identified compared to the wild-type IgG-B Fc polypeptide. Four lead mutant canine IgG-B polypeptides: L(24)Y (SEQ ID NO: 14); L(24)F (SEQ ID NO: 15); L(24)M (SEQ ID NO: 16); and L(24)S (SEQ ID NO: 17) were identified.

[0236]

[0212] Further, the koff of each mutant canine IgG-B polypeptide was examined. The biotinylated canine FcRn / B2M complex was immobilized on a Biacore chip, and each mutant canine IgG-B polypeptide was exposed as an analyte at pH 6.0 using a Biacore T200. The results are shown in Figure 2. The koff (1 / s) of the wild-type canine IgG-B Fc polypeptide was 1.22x10 -1 (Figure 2A); the koff (1 / s) of the mutant canine IgG-B Fc polypeptide L(24)Y was 1.38x10 -2 (Figure 2B); the koff (1 / s) of the mutant IgG-B Fc polypeptide L(24)F was 6.31x10 -2 (Figure 2C) and 8.47x10 -2 (Figure 2D); the koff (1 / s) of the mutant canine IgG-B polypeptide L(24)M was 1.26x10 -1 (Figure 2E); and the koff (1 / s) of the mutant canine IgG-B polypeptide L(24)S was 2.41x10 -1 (Figure 2F).

[0237]

[0213] Binding analysis was performed using a Biacore T200. Briefly, lead mutant canine IgG-B Fc polypeptides with SASA tags were immobilized on Series S sensor chip CM55, respectively. The association of each mutant IgG-B Fc polypeptide with various concentrations of canine FcRn / B2M complex (12.5, 25, 50, 100, and 200 nM) was monitored at 25 o °C until a steady state was reached. A running buffer of 10 mM HEPES, 500 mM NaCl, 3 mM EDTA, 0.005% Tween-20 (pH 6.0) was used. A blank curve of buffer only was used as a control. The results are shown in Figures 3 - 7. The steady state Kd of wild-type canine IgG-B Fc polypeptide was 1.25x10 -6 (Figure 3); the steady state Kd of mutant canine IgG-B Fc polypeptide L(24)Y was 1.13x10 -7 (Figure 4); the steady state Kd of mutant canine IgG-B Fc polypeptide L(24)F was 3.67x10 -7 (Figure 5); the steady state Kd of mutant canine IgG-B Fc polypeptide L(24)M was 4.06x10 -7 (Figure 6); and the steady state Kd of mutant canine IgG-B Fc polypeptide YTE was 8.62x10 -8 (Figure 7).

[0238] Example 17 Combinations of IgG Fc mutations for enhancing FcRn / B2M binding at acidic pH

[0214] ELISA screening was performed to further identify combinations of IgG mutations with enhanced binding to FcRn / B2M. Figure 8 and Table 17 (below) describe 15 different combinations of substitutions tested at amino acid positions corresponding to position Leu24 (e.g., Leu24Tyr), position Gln83 (e.g., Gln83Tyr), and / or position Asn208 (e.g., Asn208Arg, Asn208Phe, Asn208Tyr, Asn208His, and Asn208Trp) of wild-type canine IgG-B Fc (SEQ ID NO: 2). The affinity of the 15 mutant IgG Fc polypeptides for FcRn / B2M was increased compared to the affinity of either the wild-type canine IgG-B Fc polypeptide (SEQ ID NO: 2) or the YTE mutant canine IgG-B Fc polypeptide (Leu24Tyr, Ala26Thr, Thr28Glu; SEQ ID NO: 48) for FcRn / B2M.

[0239]

[0215] Briefly, each of the 15 mutant canine IgG-B Fc polypeptides, the wild-type canine IgG-B Fc polypeptide, and the YTE mutant canine IgG-B Fc polypeptide (each with an SASA tag) was subcloned into plasmid pFASEBA. A single E. coli colony expressing the recombinant plasmid was cultured and induced to express the Fc polypeptide.

[0240]

[0216] Canine FcRn with a polyHis tag (SEQ ID NO: 18) and a canine B2M (SEQ ID NO: 20) heterodimer complex was transiently expressed in HEK cells and purified using Ni-NTA chromatography.

[0241]

[0217] Binding analysis was performed using a Biacore 8K. A cell culture solution containing the Fc polypeptide was exposed to BSA immobilized on a Biacore chip. The chip to which the Fc polypeptide had bound was exposed to soluble canine FcRn / B2M complex (400 nM) at a flow rate of 30 μl / min to determine the affinity at pH 6. A running buffer of 10 mM HEPES, 500 mM NaCl, 3 mM EDTA, 0.005% Tween-20 (pH 6.0) was used. The association of each mutant IgG-B Fc polypeptide with the canine FcRn / B2M complex was monitored for 150 seconds at 25 o °C. Dissociation was monitored for 150 seconds using the running buffer. A blank curve of buffer only was used as a control. A 10 mM glycine-HCl buffer was used for 30 seconds at a flow rate of 30 μl / min to regenerate the surface of the chip between samples. The affinities are shown in Table 17 below.

[0242]

[0218] Table 17. TIFF2025093964000047.tif126170

[0243]

[0219] Each of the 15 mutant IgG-B Fc polypeptides (SEQ ID NOs: 33 - 47) had a slower k off with the canine FcRn / B2M complex compared to the wild-type IgG-B Fc polypeptide (SEQ ID NO: 2) and the YTE mutant canine IgG-B Fc polypeptide (SEQ ID NO: 48). The dissociation of the YYF (Leu24Tyr, Gln83Tyr, Asn208Phe; SEQ ID NO: 44) and YYY (Leu24Tyr, Gln83Tyr, Asn208Tyr; SEQ ID NO: 45) mutant IgG Fc polypeptides exceeded the detection limit of the Biacore instrument.

[0244]

[0220] To enhance the affinity for FcRn, the corresponding substitutions (e.g., Y0R, Y0F, Y0Y, Y0H, Y0W, 0YR, 0YF, 0YY, 0YH, 0YW, YYR, YYF, YYY, YYH, and YYW) can be made to feline, equine, and other canine IgG Fc polypeptides. For example, combinations of substitutions at amino acid positions 24 (e.g., substitution by Tyr), 83 (e.g., substitution by Tyr), and / or 208 (e.g., substitution by Arg, Phe, Tyr, His or Trp) of wild-type canine IgG-B Fc (SEQ ID NO: 2) may be made at the corresponding amino acid positions of feline IgG1 and / or IgG2 Fc polypeptides (e.g., SEQ ID NO: 12 and 13), equine IgG1, IgG2, IgG3, IgG4, IgG5, IgG6, and / or IgG7 Fc polypeptides (e.g., SEQ ID NO: 5, 6, 7, 8, 9, 10, and 11), and / or canine IgG-A, IgG-C, and / or IgG-D Fc polypeptides (e.g., SEQ ID NO: 1, 3, and 4).

[0245] Example 18 Recombinant caninized antibody having a mutant IgG Fc with improved affinity for FcRn

[0221] 1) A full-length antibody was prepared having the caninized variable heavy chain of murine anti-canine IL31 clone M14 and either the wild-type canine IgG-B Fc polypeptide (SEQ ID NO: 49), the YYY mutant canine IgG-B Fc polypeptide (SEQ ID NO: 50), the Y0Y mutant canine IgG-B Fc polypeptide (SEQ ID NO: 51), or the YTE mutant canine IgG-B Fc polypeptide (SEQ ID NO: 52), and 2) the caninized light chain of murine anti-canine IL31 clone M14 and a canine kappa light chain (SEQ ID NO: 53). The nucleotide sequences of the heavy and light chains were chemically synthesized and inserted into an expression vector suitable for transfection into mammalian host cells. After transfecting the cell and culture with the heavy and light chain vector pairs, the antibody was purified from the culture medium by single-step protein A column chromatography.

[0246]

[0222] The affinity of four antibodies against the canine FcRn / B2M complex was measured using a Biacore T200. Briefly, the biotinylated FcRn / B2M complex was captured on a streptavidin sensor chip. The association of the FcRn / B2M complex with each of the four antibodies at various concentrations was monitored for 120 seconds at a flow rate of 30 μl / min. For the antibody with the wild-type canine IgG-B Fc polypeptide (SEQ ID NO: 49), concentrations of 18.75, 37.5, 75, 150, 300, 600, and 1200 nM were tested; for the antibody with the YTE mutant canine IgG-B Fc polypeptide (SEQ ID NO: 52), concentrations of 12.5, 25, 50, 100, 200, 400, and 800 nM were tested; for the antibody with the Y0Y mutant canine IgG-B Fc polypeptide (SEQ ID NO: 51), concentrations of 2.5, 5, 10, 20, 40, 80, and 160 nM were tested; for the antibody with the YYY mutant canine IgG-B Fc polypeptide (SEQ ID NO: 50), concentrations of 1.5625, 3.125, 6.25, 12.5, 25, 50, and 100 nM were tested. Since these Fc polypeptides have a lower affinity for FcRn / B2M than the YYY and Y0Y Fc polypeptides (see Example 17), higher concentrations of the antibodies with the wild-type and YTE Fc polypeptides were required to detect a signal.

[0247]

[0223] Dissociation was monitored for 120 seconds for the antibodies with the wild-type, YTE mutant or Y0Y mutant canine IgG-B Fc polypeptide, or for 300 seconds for the antibody with the YYY mutant canine IgG-B Fc polypeptide. A running buffer of 10 mM HEPES, 500 mM NaCl, 3 mM EDTA, 0.005% Tween-20 (pH 6.0) was used. A blank curve of buffer only was used as a control. A 10 mM glycine-HCl buffer was used at a flow rate of 30 μl / min for 40 seconds to regenerate the surface of the chip between samples.

[0248] The results are shown in Table 18 (below). Since the affinities of wild-type canine IgG-B Fc and YTE mutant canine IgG-B Fc for FcRn / B2M were low, the rate constants of these antibodies were not sufficiently observed. Therefore, in order to obtain the binding affinity, a steady-state binding analysis was performed in the same manner as described above. The affinity plots of the antibodies having wild-type and YTE mutant canine IgG-B Fc polypeptides are shown in FIGS. 9 and 10, respectively. The sensorgrams of the antibodies having Y0Y and YYY mutant IgG-B Fc polypeptides are shown in FIGS. 11 and 12, respectively.

[0249]

[0225] Table 18. TIFF2025093964000048.tif41170

[0250] Example 19 The YTE mutation in feline IgG enhances the feline FcRn interaction

[0226] The affinity of the mutant feline Fc polypeptide for FcRn was evaluated in the context of the chimeric D2E7 anti-TNFα antibody. The anti-TNFα variable heavy (VH) and variable light (VL) chain sequences derived from D2E7 were fused to the feline constant sequences. Specifically, the D2E7 VL chain was fused to the feline kappa light chain to generate SEQ ID NO: 117. Further, the D2E7 VH chain was fused to the wild-type feline IgG1b Fc polypeptide (including SEQ ID NO: 13) or the YTE mutant feline IgG1b Fc polypeptide (including SEQ ID NO: 82) to generate SEQ ID NO: 119 and SEQ ID NO: 121, respectively.

[0251]

[0227] Binding analysis was performed using a Biacore OctetRed as follows. Briefly, biotinylated feline FcRn was captured on a streptavidin sensor chip. The association of the antibody at 30 μg / mL was measured at pH 6.0, and dissociation was performed at pH 7.2. The YTE mutation in feline IgG Fc (FIG. 13, A) enhanced the association with feline FcRN at low pH compared to wild-type feline IgG Fc (FIG. 13, B).

[0252] Example 20 The Phe mutation in feline IgG enhances feline FcRn interaction

[0228] The affinity of mutant canine Fc polypeptides for FcRn was evaluated in the context of the chimeric D2E7 anti-TNFα antibody. The anti-TNFα variable heavy (VH) and variable light (VL) chain sequences derived from D2E7 were fused to the canine constant sequences. Specifically, the D2E7 VL chain was fused to the canine kappa light chain to generate SEQ ID NO: 93. Further, the D2E7 VH chain was fused to mutant canine IgG-A Fc polypeptides containing SEQ ID NO: 85 (F00; Protein A+; C1q-; CD16-) or SEQ ID NO: 86 (Protein A+; C1q+; CD16+) and mutant canine IgG-D Fc polypeptides containing SEQ ID NO: 89 (F00; Protein A+; C1q-; CD16-) or SEQ ID NO: 90 (Protein A+; C1q+; Cd16+), generating SEQ ID NOs: 110, 107, 112, and 115, respectively.

[0253]

[0229] Binding analysis was performed using the Biacore OctetRed as follows. Briefly, biotinylated TNFα was captured on a streptavidin sensor chip. A 20 μg / mL association antibody was bound to TNFα. Subsequently, this complex was used to bind to canine FcRn (50 μg / mL) at pH 6.0. Dissociation was performed at pH 7.2.

[0254]

[0230] The Phe mutation enhanced the binding to canine FcRn at low pH (pH 6.0, 20 mM sodium citrate, 140 mM NaCl), as shown in the binding profiles of chimeric mutant canine IgG-A "F00" antibody (SEQ ID NO: 93 and SEQ ID NO: 110) (Figure 14, A) and IgG-D "F00" antibody (SEQ ID NO: 93 and SEQ ID NO: 115) (Figure 14, B), compared to chimeric mutant canine IgG-A without Phe mutation (SEQ ID NO: 93 and SEQ ID NO: 107) (Figure 14, C) and IgG-D without Phe mutation (SEQ ID NO: 93 and SEQ ID NO: 112) (Figure 14, D). Chimeric mutant canine IgG-A and IgG-D antibodies with the Phe mutation (Figure 14, A and B) showed enhanced association with canine FcRn at low pH (pH 6.0) and rapid dissociation at neutral pH (PBS pH 7.2). A similar improved binding profile was also observed for chimeric mutant canine IgG-B "F00" antibody (SEQ ID NO: 93 and SEQ ID NO: 105).

[0255] Example 21 Pharmacokinetics of the Phe Mutation in Canine IgG

[0231] Pharmacokinetic analysis was performed using Sprague-Dawley rats. These rats were subcutaneously administered with chimeric mutant canine IgG-A "F00" antibody (SEQ ID NO: 93 and SEQ ID NO: 110) and chimeric mutant canine IgG-A without Phe mutation (SEQ ID NO: 93 and SEQ ID NO: 107) at 2 mg / kg (2 rats per group). Serum samples were collected from the rats before injection and at 0.5, 1, 6, 24, 48, 72, 168, 216, and 336 hours after injection. The canine chimeric antibody concentration in the serum samples was determined by ELISA as follows.

[0256] PBS containing 1 μg / mL of anti - adalimumab antibody (Bio - Rad, catalog number HCA202) was coated at 100 μL per well of a 96 - well Maxisorp plate. The plate was incubated overnight at 4°C and washed 5 times with PBST (PBS containing 0.05% Tween - 20). Each well was blocked with 200 μL of a PBST solution of 5% BSA, and the plate was incubated at room temperature for 1 hour. The plate was washed 5 times with PBST. An anti - TNFα antibody with a concentration of 1,000 ng / mL was prepared in 5% BSA - PBST and serially diluted to 0.1 ng / mL. This anti - TNFα serially diluted solution (1,000 ng / mL to 0.1 ng / mL) was added to the plate in two portions and used together with blank wells without anti - TNFα to create a standard curve. Serum samples were prepared by diluting 10 - fold, 20 - fold, and 40 - fold in 5% BSA - PBST and added to the plate. After the plate was incubated at room temperature for 1 hour, it was washed 5 times with PBST. 100 μL of HRP - conjugated antibody (Bio - Rad, catalog number HCA204P) at 0.25 μg / mL in 5% BSA - PBST was added to each well. The plate was incubated at room temperature for 1 hour and washed 5 times with PBST. 100 μL of QuantaBlu (Thermo Scientific, catalog number 15169) was added to each well. After an incubation of 10 - 15 minutes, fluorescence was measured at 325 nm / 420 nm (emission / excitation). The titer of anti - TNFα in the serum samples was calculated against the standard curve.

[0257]

[0233] AUC of IgG - A 0-336h was 150970, and IgG - A “F00” was 848924 ng / mL*hr (Figure 15). The terminal - phase half - lives were estimated to be 33 hours and 152 hours, respectively. Thus, a single Phe mutation significantly improved the pharmacokinetic profile of the anti - TNFα antibody in rats.

[0258] Example 22 Phe mutations in canine, feline, and equine IgG Fc

[0234] The interaction between the Phe mutations in canine IgG-A, IgG-B, IgG-C, and IgG-D Fc and FcRn was modeled using three-dimensional protein structure analysis. The aromatic side chain of Phe appears to have a hydrophobic interaction with canine FcRn in the Pro hydrophobic ring (π-CH) of the "WPE" motif. Furthermore, the hydrophobic side chain of Phe may be in direct contact with the Glu side chain adjacent to Pro in the same "WPE" motif. When the Glu side chain is deprotonated and negatively charged, such as at neutral pH, this interaction may incur an energy penalty. Therefore, some degree of protonation of the Glu residue may be required to minimize the interaction between the aromatic compound and Glu-H. This may explain why the interaction between the mutant IgG with the Phe mutation and FcRn decreases at neutral pH. Based on protein structure analysis, the above interaction appears to be conserved among canine IgG-A, IgG-B, IgG-C, and IgG-D Fc.

[0259]

[0235] Furthermore, the interaction between the Phe mutations in feline IgG1a and IgG2 Fc was modeled when complexed with feline FcRn. The same interaction observed in canine IgG Fc appears to be conserved in feline IgG Fc.

[0260]

[0236] Also, the interaction between the Phe mutations in equine IgG1, IgG2, IgG3, IgG4, IgG5, IgG6, and IgG7 Fc when complexed with equine FcRn was modeled. The same interaction appears to be maintained in equine IgG Fc.

[0261] Example 23 Other exemplary mutant canine IgG Fc enhances the canine FcRn interaction

[0237] The affinity of additional mutant canine Fc polypeptides for FcRn was evaluated in the context of a chimeric D2E7 anti-TNFα antibody. The anti-TNFα variable heavy (VH) and variable light (VL) chain sequences from D2E7 were fused to canine constant sequences. Specifically, the D2E7 VL chain was fused to the canine kappa light chain to generate SEQ ID NO: 93. Further, the D2E7 VH chain was fused to the wild-type IgG-B Fc polypeptide (including SEQ ID NO: 2), mutant canine IgG-B Fc polypeptide 0Y0 (including SEQ ID NO: 27), mutant canine IgG-B Fc polypeptide 0YH (including SEQ ID NO: 41), mutant canine IgG-B Fc polypeptide 0YY (including SEQ ID NO: 40), and mutant canine IgG-B Fc polypeptide 00Y (including SEQ ID NO: 30) to generate SEQ ID NO: 95, 97, 99, 101, 103, respectively.

[0262]

[0238] Binding assays were performed using a Biacore OctetRed as follows. Briefly, biotinylated TNFα was captured on a streptavidin sensor chip. A 20 μg / mL association antibody was bound to TNFα. This complex was then used to bind to canine FcRn (50 μg / mL) at pH 6.0. Dissociation was performed at pH 7.2.

[0263]

[0239] Each of the chimeric mutant canine IgG-B antibodies showed enhanced binding to canine FcRn at pH 6.0 and a significant dissociation rate at neutral pH compared to the chimeric wild-type canine IgG-B antibody (Figure 16).

Claims

1. 1. A polypeptide comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide derived from a companion animal species, wherein said variant Fc polypeptide is capable of binding to a neonatal Fc receptor (FcRn) with increased affinity relative to the wild-type Fc polypeptide.

2. 2. The polypeptide of claim 1, wherein the variant Fc polypeptide binds to FcRn with a higher affinity than a wild-type IgG Fc polypeptide at a pH ranging from about 5.0 to about 6.5, e.g., at about pH 5.0, about pH 5.2, about pH 5.5, about pH 6.0, about pH 6.2 or about pH 6.5, as measured by biolayer interferometry, surface plasmon resonance or any protein-protein interaction tool.

3. The variant IgG Fc polypeptide has a pH of 5×10 or more at a pH in the range of about 5.0 to about 6.5, e.g., at about pH 5.0, about pH 5.5, about pH 6.0 or about pH 6.5, as measured by biolayer interferometry, surface plasmon resonance or any protein-protein interaction tool. －６ Less than M, 1x10 －６ Less than M, 5x10 －７ Less than M, 1x10 －７ Less than M, 5x10 －８ Less than M, 1x10 －８ Less than M, 5x10 －９ Less than M, 1x10 －９ Less than M, 5x10 －１０ Less than M, 1x10 －１０ Less than M, 5x10 －１１ Less than M, 1x10 －１１ Less than M, 5x10 －１２ Less than M or 1x10 －１２ 3. The polypeptide of claim 1 or 2, which binds to FcRn with a dissociation constant (Kd) of less than M.

4. 4. A polypeptide according to any one of claims 1 to 3, having an increased serum half-life compared to a polypeptide comprising a wild-type Fc polypeptide.

5. 5. The polypeptide of any one of claims 1 to 4, wherein the companion animal species is a dog, a cat or a horse.

6. A wild type IgG Fc polypeptide, a) canine IgG-A Fc, IgG-B Fc, IgG-C Fc, or IgG-D Fc; b) an equine IgG1 Fc, IgG2 Fc, IgG3 Fc, IgG4 Fc, IgG5 Fc, IgG6 Fc or IgG7 Fc; or c) feline IgG1 Fc or IgG2 Fc 6. The polypeptide according to any one of claims 1 to 5,

7. The variant IgG Fc polypeptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, 7. The polypeptide of claim 1, which is at least 90% identical, at least 95% identical, at least 97% identical, or at least 99% identical to the amino acid sequence of SEQ ID NO:47, SEQ ID NO:48 or SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89 or SEQ ID NO:

91.

8. the variant IgG Fc polypeptide comprising: a) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 83, 132, 149, 162, 183, 203, 205, and / or 209 of SEQ ID NO:1; b) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:2; c) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204 and / or 208 of SEQ ID NO:3; d) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 60, 79, 80, 83, 132, 149, 163, 183, 203, 205, and / or 209 of SEQ ID NO:4; e) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:5; f) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:6; g) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:7; h) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:8; i) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:9; j) at least one amino acid substitution at at least one position corresponding to positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 10; k) at least one amino acid substitution at at least one position corresponding to positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:11; l) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:12; m) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO: 13; or n) at least one amino acid substitution at at least one position corresponding to positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:

54. The polypeptide of any one of claims 1 to 7, comprising:

9. the variant IgG Fc polypeptide comprising: a) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 83, 132, 149, 162, 183, 203, 205 and / or 209 of SEQ ID NO:1; b) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:2; c) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204 and / or 208 of SEQ ID NO:3; d) at least one amino acid substitution at at least one position selected from positions 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 60, 79, 80, 83, 132, 149, 163, 183, 203, 205 and / or 209 of SEQ ID NO:4; e) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:5; f) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 26, 27, 28, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:6; g) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:7; h) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:8; i) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208, and / or 213 of SEQ ID NO:9; j) at least one amino acid substitution at at least one position selected from positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 10; k) at least one amino acid substitution at at least one position selected from positions 18, 22, 23, 24, 25, 27, 28, 30, 31, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:11; l) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 12; or m) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO: 13; or n) at least one amino acid substitution at at least one position selected from 9, 18, 22, 23, 24, 25, 26, 27, 28, 30, 31, 60, 79, 80, 81, 83, 132, 148, 162, 182, 202, 204, 208 and / or 213 of SEQ ID NO:

54. The polypeptide of any one of claims 1 to 8, comprising:

10. the variant IgG Fc polypeptide comprising: a) tyrosine at the position corresponding to position 9 of SEQ ID NO:1; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; and methionine or valine at the position corresponding to position 30 of SEQ ID NO:

1. at position corresponding to position 31; an alanine at position corresponding to position 60; a glutamine, arginine, alanine, glutamic acid or methionine at position corresponding to position 79; a histidine or phenylalanine at position corresponding to position 80; an alanine, tyrosine or phenylalanine at position corresponding to position 83; an isoleucine at position corresponding to position 132; a valine at position corresponding to position 149; a leucine, phenylalanine or tyrosine at position corresponding to position 162; an isoleucine at position corresponding to position 183; a leucine or tryptophan at position corresponding to position 203; a proline at position corresponding to position 205; and / or a serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 209; b) in SEQ ID NO: 2, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31 leucine; alanine at position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at position corresponding to position 79; histidine or phenylalanine at position corresponding to position 80; glutamic acid at position corresponding to position 81; alanine, tyrosine or phenylalanine at position corresponding to position 83; isoleucine at position corresponding to position 132; valine at position corresponding to position 148; leucine, phenylalanine or tyrosine at position corresponding to position 162; isoleucine at position corresponding to position 182; leucine or tryptophan at position corresponding to position 202; proline at position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 208; and / or isoleucine or valine at position corresponding to position 213; c) in SEQ ID NO: 3, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or arginine at the position corresponding to position 24; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; and isoleucine at the position corresponding to position 31. isine; alanine at position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at position corresponding to position 79; histidine or phenylalanine at position corresponding to position 80; glutamic acid at position corresponding to position 81; alanine, tyrosine or phenylalanine at position corresponding to position 83; isoleucine at position corresponding to position 132; valine at position corresponding to position 148; leucine, phenylalanine or tyrosine at position corresponding to position 162; isoleucine at position corresponding to position 182; leucine or tryptophan at position corresponding to position 202; proline at position corresponding to position 204; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 208; d) in SEQ ID NO: 4, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; or methionine or no methionine at the position corresponding to position 30. or valine; alanine at position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at position corresponding to position 79; histidine or phenylalanine at position corresponding to position 80; alanine, tyrosine or phenylalanine at position corresponding to position 83; isoleucine at position corresponding to position 132; valine at position corresponding to position 149; leucine, phenylalanine or tyrosine at position corresponding to position 163; isoleucine at position corresponding to position 183; leucine or tryptophan at position corresponding to position 203; proline at position corresponding to position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 209; e) in SEQ ID NO:5, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; at position corresponding to position 79; glutamine, glutamic acid or methionine at position corresponding to position 79; histidine or phenylalanine at position corresponding to position 80; glutamic acid at position corresponding to position 81; alanine, tyrosine or phenylalanine at position corresponding to position 83; isoleucine at position corresponding to position 132; valine at position corresponding to position 148; leucine, phenylalanine or tyrosine at position corresponding to position 162; isoleucine at position corresponding to position 182; leucine or tryptophan at position corresponding to position 202; proline at position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 208; and / or isoleucine or valine at position corresponding to position 213; f) in SEQ ID NO: 6, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine or threonine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or valine at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; and glutamic acid at the position corresponding to position 79. glutamine, arginine, alanine, glutamic acid or methionine; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; g) in SEQ ID NO: 7, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine, isoleucine, and / or proline at the position corresponding to position 22; valine, arginine, or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine, or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine, or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine, or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at the position corresponding to position 60; at position corresponding to position 162; isoleucine at position corresponding to position 182; leucine or tryptophan at position corresponding to position 202; proline at position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 208; and / or isoleucine or valine at position corresponding to position 213; h) in SEQ ID NO:8, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine, lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; and glutamic acid at the position corresponding to position 79. at position corresponding to position 162; isoleucine at position corresponding to position 182; leucine or tryptophan at position corresponding to position 202; proline at position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 208; and / or isoleucine or valine at position corresponding to position 213; i) in SEQ ID NO:9, tyrosine at the position corresponding to position 9; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine at the position corresponding to position 79 histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; j) in SEQ ID NO: 10, proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; glutamine, arginine, alanine at the position corresponding to position 79, glutamic acid or methionine; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; k) in SEQ ID NO: 11, proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; and glutamine, arginine, glutamine at the position corresponding to position 79. acid or methionine; histidine or phenylalanine at the position corresponding to position 80; glutamic acid at the position corresponding to position 81; alanine, tyrosine or phenylalanine at the position corresponding to position 83; isoleucine at the position corresponding to position 132; valine at the position corresponding to position 148; leucine, phenylalanine or tyrosine at the position corresponding to position 162; isoleucine at the position corresponding to position 182; leucine or tryptophan at the position corresponding to position 202; proline at the position corresponding to position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208; and / or isoleucine or valine at the position corresponding to position 213; l) tyrosine at the position corresponding to position 9 of SEQ ID NO: 12; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; at position corresponding to position 162; isoleucine at position corresponding to position 182; leucine or tryptophan at position corresponding to position 202; proline at position corresponding to position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 208; and / or isoleucine or valine at position corresponding to position 213; m) tyrosine at the position corresponding to position 9 of SEQ ID NO: 13; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31; alanine at position corresponding to position 60; glutamine, arginine, alanine, glutamic acid or methionine at position corresponding to position 79; histidine or phenylalanine at position corresponding to position 80; glutamic acid at position corresponding to position 81; alanine, tyrosine or phenylalanine at position corresponding to position 83; isoleucine at position corresponding to position 132; valine at position corresponding to position 148; leucine, phenylalanine or tyrosine at position corresponding to position 162; isoleucine at position corresponding to position 182; leucine or tryptophan at position corresponding to position 202; proline at position corresponding to position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position corresponding to position 208; and / or isoleucine or valine at position corresponding to position 213; or n) tyrosine at the position corresponding to position 9 of SEQ ID NO:54; proline at the position corresponding to position 18; histidine, isoleucine or proline at the position corresponding to position 22; valine, arginine or lysine at the position corresponding to position 23; phenylalanine, tyrosine, methionine, arginine or valine at the position corresponding to position 24; threonine at the position corresponding to position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at the position corresponding to position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at the position corresponding to position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at the position corresponding to position 28; methionine or valine at the position corresponding to position 30; isoleucine at the position corresponding to position 31 alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213.

10. The polypeptide of claim 1 , comprising:

11. the variant IgG Fc polypeptide comprising: a) in SEQ ID NO: 1, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; and methionine at position 30. or valine; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 149; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 183; leucine or tryptophan at position 203; proline at position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 209; b) in SEQ ID NO: 2, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; and methionine or valine at position 30. isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; c) of SEQ ID NO:3, tyrosine at position 9; proline at position 18; histidine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or arginine at position 24; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine, threonine or serine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; and methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; d) in SEQ ID NO: 4, tyrosine at position 9; proline at position 18; histidine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; and methionine at position 30. leucine or tryptophan at position 203; proline at position 205; and / or serine, alanine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 149; leucine, phenylalanine or tyrosine at position 163; isoleucine at position 183; leucine or tryptophan at position 203; proline at position 205; and / or serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 209; e) in SEQ ID NO:5, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; and methionine or or valine; isoleucine at position 31; glutamine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; f) in SEQ ID NO: 6, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine, methionine or threonine at position 26; leucine, methionine, proline, isoleucine, asparagine or valine at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; and glutamic acid at position 79. glutamine, arginine, alanine, glutamic acid or methionine; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at the position corresponding to position 213; g) in SEQ ID NO: 7, tyrosine at position 9; proline at position 18; histidine, isoleucine and / or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; alanine at position 60; glutamine, glutamic acid or methionine at position 80; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; h) in SEQ ID NO:8, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine, lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; glycine, arginine at position 79, glutamine, arginine, alanine, glutamic acid or methionine; histidine or phenylalanine at position 80; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; i) in SEQ ID NO: 9, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; and glutamine, arginine at position 79. histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; j) in SEQ ID NO: 10, proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; and glutamine, arginine, alanine at position 79. alanine, glutamic acid or methionine; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, arginine, phenylalanine, tyrosine or tryptophan at position 208; and / or isoleucine or valine at position 213; k) In SEQ ID NO: 11, proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, arginine or valine at position 24; threonine at position 25; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 31; and glutamine or arginine at position 79. , glutamic acid or methionine; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; serine, alanine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; l) In SEQ ID NO: 12, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; and methionine or valine; isoleucine at position 31; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; m) in SEQ ID NO: 13, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine; alanine at position 60; glutamine, arginine, alanine, glutamic acid or methionine at position 79; histidine or phenylalanine at position 80; glutamic acid at position 81; alanine, tyrosine or phenylalanine at position 83; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213; or n) of SEQ ID NO:54, tyrosine at position 9; proline at position 18; histidine, isoleucine or proline at position 22; valine, arginine or lysine at position 23; phenylalanine, tyrosine, methionine, arginine or valine at position 24; threonine at position 25; tryptophan, tyrosine, histidine, leucine, phenylalanine, valine or methionine at position 26; leucine, methionine, proline, isoleucine, asparagine or tryptophan at position 27; methionine, glutamic acid, asparagine, histidine, isoleucine or valine at position 28; methionine or valine at position 30; isoleucine at position 132; valine at position 148; leucine, phenylalanine or tyrosine at position 162; isoleucine at position 182; leucine or tryptophan at position 202; proline at position 204; alanine, arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208; and / or isoleucine or valine at position 213.

11. The polypeptide of claim 1 , comprising:

12. the variant IgG Fc polypeptide comprising: a) a phenylalanine or tyrosine at the position corresponding to position 24, a threonine at the position corresponding to position 26, and / or a glutamic acid at the position corresponding to position 28 of SEQ ID NO:1; b) a phenylalanine at the position corresponding to position 24, a threonine at the position corresponding to position 26, and / or a glutamic acid at the position corresponding to position 28 of SEQ ID NO:2, SEQ ID NO:3, or SEQ ID NO:4; or c) phenylalanine or tyrosine at the position corresponding to position 24, threonine at the position corresponding to position 26, and / or glutamic acid at the position corresponding to position 28 of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

54.

12. The polypeptide of claim 1 , comprising:

13. the variant IgG Fc polypeptide comprising: a) a phenylalanine or tyrosine at position 24, a threonine at position 26, and / or a glutamic acid at position 28 of SEQ ID NO:1; b) a phenylalanine at position 24, a threonine at position 26, and / or a glutamic acid at position 28 of SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:4; or c) phenylalanine or tyrosine at position 24, threonine at position 26, and / or glutamic acid at position 28 of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

54.

13. The polypeptide of claim 1 , comprising:

14. 14. The polypeptide of any one of claims 1 to 13, wherein the mutant IgG Fc polypeptide comprises a phenylalanine at a position corresponding to position 24 of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:

54.

15. 15. The polypeptide of any one of claims 1 to 14, wherein the mutant IgG Fc polypeptide comprises a phenylalanine at position 24 of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:

54.

16. the variant IgG Fc polypeptide comprising: a) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and / or an arginine, phenylalanine, tyrosine, histidine or tryptophan at a position corresponding to position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; b) a tyrosine at the position corresponding to position 24, a tyrosine at the position corresponding to position 83, and / or an arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208 of SEQ ID NO: 2 or SEQ ID NO: 3; or c) tyrosine at the position corresponding to position 24, tyrosine at the position corresponding to position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at the position corresponding to position 208 of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

54.

16. The polypeptide of any one of claims 1 to 15, comprising:

17. the variant IgG Fc polypeptide comprising: a) a tyrosine at position 24, a tyrosine at position 83, and / or an arginine, phenylalanine, tyrosine, histidine or tryptophan at position 209 of SEQ ID NO: 1 or SEQ ID NO: 4; b) a tyrosine at position 24, a tyrosine at position 83, and / or an arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208 of SEQ ID NO: 2 or SEQ ID NO: 3; or c) tyrosine at position 24, tyrosine at position 83, and / or arginine, phenylalanine, tyrosine, histidine or tryptophan at position 208 of SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:

54.

17. The polypeptide of claim 1 , comprising:

18. the variant IgG Fc polypeptide comprising: a) a tyrosine at a position corresponding to position 24 and an arginine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; b) a tyrosine at a position corresponding to position 24 and an arginine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; c) a tyrosine at a position corresponding to position 24 and a phenylalanine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; d) a tyrosine at a position corresponding to position 24 and a phenylalanine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; e) a tyrosine at a position corresponding to position 24 and a tyrosine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; f) a tyrosine at a position corresponding to position 24 and a tyrosine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; g) a tyrosine at a position corresponding to position 24 and a histidine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; h) a tyrosine at a position corresponding to position 24 and a histidine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; i) a tyrosine at a position corresponding to position 24 and a tryptophan at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; j) a tyrosine at a position corresponding to position 24 and a tryptophan at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; k) a tyrosine at a position corresponding to position 83 and an arginine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; l) a tyrosine at a position corresponding to position 83 and an arginine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; m) a tyrosine at a position corresponding to position 83 and a phenylalanine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; n) a tyrosine at a position corresponding to position 83 and a phenylalanine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; o) a tyrosine at a position corresponding to position 83 and a tyrosine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; p) a tyrosine at a position corresponding to position 83 and a tyrosine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; q) a tyrosine at a position corresponding to position 83 and a histidine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; r) a tyrosine at a position corresponding to position 83 and a histidine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; s) a tyrosine at a position corresponding to position 83 and a tryptophan at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; t) a tyrosine at a position corresponding to position 83 and a tryptophan at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; u) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and an arginine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; v) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and an arginine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; w) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and a phenylalanine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; x) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and a phenylalanine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; y) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and a tyrosine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; z) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and a tyrosine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; aa) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and a histidine at a position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; bb) a tyrosine at a position corresponding to position 24, a tyrosine at a position corresponding to position 83, and a histidine at a position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; cc) a tyrosine at the position corresponding to position 24, a tyrosine at the position corresponding to position 83, and a tryptophan at the position corresponding to position 209 of SEQ ID NO:1 or SEQ ID NO:4; or dd) a tyrosine at the position corresponding to position 24, a tyrosine at the position corresponding to position 83, and a tryptophan at the position corresponding to position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

54.

18. The polypeptide of any one of claims 1 to 17, comprising:

19. the variant IgG Fc polypeptide comprising: a) a tyrosine at position 24 and an arginine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; b) a tyrosine at position 24 and an arginine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; c) a tyrosine at position 24 and a phenylalanine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; d) a tyrosine at position 24 and a phenylalanine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; e) a tyrosine at position 24 and a tyrosine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; f) a tyrosine at position 24 and a tyrosine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; g) a tyrosine at position 24 and a histidine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; h) a tyrosine at position 24 and a histidine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; i) a tyrosine at position 24 and a tryptophan at position 209 of SEQ ID NO:1 or SEQ ID NO:4; j) a tyrosine at position 24 and a tryptophan at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; k) a tyrosine at position 83 and an arginine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; l) Tyrosine at position 83 and Arginine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; m) a tyrosine at position 83 and a phenylalanine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; n) a tyrosine at position 83 and a phenylalanine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; o) a tyrosine at position 83 and a tyrosine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; p) a tyrosine at position 83 and a tyrosine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; q) a tyrosine at position 83 and a histidine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; r) a tyrosine at position 83 and a histidine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; s) a tyrosine at position 83 and a tryptophan at position 209 of SEQ ID NO:1 or SEQ ID NO:4; t) a tyrosine at position 83 and a tryptophan at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13 or SEQ ID NO:54; u) a tyrosine at position 24, a tyrosine at position 83, and an arginine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; v) a tyrosine at position 24, a tyrosine at position 83, and an arginine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; w) a tyrosine at position 24, a tyrosine at position 83, and a phenylalanine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; x) a tyrosine at position 24, a tyrosine at position 83, and a phenylalanine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; y) a tyrosine at position 24, a tyrosine at position 83, and a tyrosine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; z) a tyrosine at position 24, a tyrosine at position 83, and a tyrosine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; aa) a tyrosine at position 24, a tyrosine at position 83 and a histidine at position 209 of SEQ ID NO:1 or SEQ ID NO:4; bb) a tyrosine at position 24, a tyrosine at position 83, and a histidine at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:54; cc) a tyrosine at position 24, a tyrosine at position 83, and a tryptophan at position 209 of SEQ ID NO:1 or SEQ ID NO:4; or dd) tyrosine at position 24, tyrosine at position 83, and tryptophan at position 208 of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, or SEQ ID NO:

54.

19. The polypeptide of any one of claims 1 to 18, comprising:

20. The variant IgG Fc polypeptide is selected from the group consisting of SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, 20. The polypeptide of any one of claims 1 to 19, comprising the amino acid sequence of SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89 or SEQ ID NO:

91.

21. SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, 21. A polypeptide according to claim 1 comprising the amino acid sequence of SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128 or SEQ ID NO:

129.

22. 22. The polypeptide of claim 1, wherein the at least one amino acid substitution comprises an amino acid substitution with an amino acid derivative.

23. The polypeptide of claim 22, wherein the amino acid derivative is a histidine derivative, a tryptophan derivative, a tyrosine derivative, a leucine derivative, a phenylalanine derivative, a valine derivative, a methionine derivative, an isoleucine derivative, an arginine derivative, a glutamic acid derivative, a proline derivative, a lysine derivative, a threonine derivative, an asparagine derivative, a glutamine derivative, a serine derivative, an alanine derivative or a glutamic acid derivative.

24. 24. A polypeptide according to any one of claims 1 to 23 which is an antibody, an antibody fragment or a fusion polypeptide.

25. Late Embryogenesis Abundant (LEA) protein polypeptides (e.g., LEA-3 polypeptides), NGF polypeptides, receptors for NGF polypeptides (e.g., ECDs of receptors for NGF polypeptides), TrkA polypeptides (e.g., ECDs of TrkA polypeptides), LNGFR polypeptides (e.g., ECDs of LNGFR polypeptides), TNFα polypeptides, receptors for TNFα polypeptides, TNFR polypeptides (e.g., ECDs of TNFR polypeptides), TNFR1 polypeptides (e.g., ECDs of TNFR1 polypeptides), TNFR2 polypeptides (e.g., TNFR IL2 polypeptide ECD), IL5 polypeptide, a receptor for an IL5 polypeptide, IL5R polypeptide (e.g., an ECD for an IL5R polypeptide), IL5Rα polypeptide (e.g., an ECD for an IL5Rα polypeptide), IL6 polypeptide, a receptor for an IL6 polypeptide, IL6R polypeptide (e.g., an ECD for an IL6R polypeptide), IL17 polypeptide, a receptor for an IL17 polypeptide, IL17R polypeptide (e.g., an ECD for an IL17R polypeptide), IL17RA polypeptide (e.g., an ECD for an IL17RA polypeptide), IL17RB polypeptide a polypeptide (e.g., an ECD of an IL17RB polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an IL23 polypeptide, a receptor for an IL23 polypeptide, an IL23R polypeptide (e.g., an ECD of an IL23R polypeptide), an IL12Rβ1 polypeptide (e.g., an ECD of an IL12Rβ1 polypeptide), a PDL1 polypeptide, a receptor for a PDL1 polypeptide, a PDL2 polypeptide, a receptor for a PDL2 polypeptide, a PD1 polypeptide (e.g., an ECD of a PD1 polypeptide), an integrin polypeptide (e.g., an ECD of an ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGA12, ITGA13, ITGA14, ITGA15, ITGA16, ITGA17, ITGA18, ITGA19, ITGA20, ITGA210, ITGA211, ITGA22, ITGA23, ITGA24, ITGA25, ITGA26, ITGA27, ITGA28, ITGA29, ITGA30, ITGA31, ITGA32, ITGA33, ITGA34, ITGA35, ITGA36, ITGA37, ITGA38, ITGA39, ITGA40, ITGA41, ITGA51, ITGA52, ITGA63, ITGA64, ITGA75, ITGA86, ITGA97, ITGA108, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7 or ITGB8 polypeptide), a receptor for an integrin polypeptide, a fibronectin polypeptide (e.g., an ECD of a fibronectin polypeptide), a vitronectin polypeptide (e.g., an ECD of a vitronectin polypeptide),collagen polypeptides (e.g., ECDs of collagen polypeptides), laminin polypeptides (e.g., ECDs of laminin polypeptides), CD80 polypeptides, receptors for CD80 polypeptides, CD86 polypeptides, receptors for CD86 polypeptides, CTLA-4 polypeptides (e.g., ECDs of CTLA-4 polypeptides), B7-H3 polypeptides, receptors for B7-H3 polypeptides (e.g., ECDs of receptors for B7-H3 polypeptides), LAG-3 polypeptides (e.g., ECDs of LAG-3 polypeptides), IL31 polypeptides, receptors for IL31 polypeptides receptor, IL31RA polypeptide (e.g., ECD of IL31RA polypeptide), OSMR polypeptide (e.g., ECD of OSMR polypeptide), IL4 polypeptide, receptor of IL4R polypeptide, IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13 polypeptide, receptor of IL13 polypeptide, IL13RA1 polypeptide (e.g., ECD of IL13RA1 polypeptide), IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13Rα2 polypeptide (e.g., CD of IL13Rα2 polypeptide), IL22 polypeptide polypeptide, a receptor for an IL22 polypeptide (e.g., an ECD for an IL22 polypeptide), an IL22Rα1 polypeptide (e.g., an ECD for an IL22Rα1 polypeptide), an L10Rβ2 polypeptide (e.g., an ECD for an IL10Rβ2 polypeptide), an IL33 polypeptide, a receptor for an IL33 polypeptide, an IL1RL1 polypeptide (e.g., an ECD for an IL1RL1 polypeptide), an EGF polypeptide, a receptor for an EGF polypeptide, a TGFα polypeptide, a receptor for a TGFα polypeptide, an EGFR polypeptide (e.g., an ECD for an EGFR polypeptide), an MMP9 polypeptide, Peptides, FGF polypeptides (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22 or FGF23 polypeptides), receptors for FGF polypeptides, FGFR polypeptides (e.g., FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptides), ECDs for FGFR polypeptides (e.g., FGFR1, FGFR2,an ECD of an FGFR3, FGFR4 or FGFRL1 polypeptide), an EGF polypeptide, a receptor for an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V or VI polypeptide), a receptor for a neuregulin polypeptide, a HER polypeptide (e.g., a HER1, HER2, HER3 or HER4 polypeptide), an ECD of a HER polypeptide (e.g., an ECD of a HER1, HER2, HER3 or HER4 polypeptide), an EpCAM polypeptide (e.g., an EpCAM polypeptide a CD20 polypeptide (e.g., an ECD of a CD20 polypeptide), a ligand of a CD20 polypeptide, a CD19 polypeptide (e.g., an ECD of a CD19 polypeptide), a ligand of a CD19 polypeptide, a CGRP polypeptide (e.g., an α-CGRP polypeptide or a β-CGRP polypeptide), a receptor for a CGRP polypeptide, a receptor for an α-CGRP polypeptide, a receptor for a β-CGRP polypeptide, a CALCRL polypeptide (e.g., an ECD of a CALCRL polypeptide), a RAMP polypeptide (e.g., RAMP1, RAMP2 or RAMP3 polypeptide), an ECD of a RAMP polypeptide (e.g., an ECD of a RAMP1, RAMP2 or RAMP3 polypeptide), an IGF polypeptide (e.g., an IGF-1 or IGF-2 polypeptide), a receptor of an IGF polypeptide (e.g., a receptor of an IGF-1 or IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or IGFR2 polypeptide), an ECD of an IGFR polypeptide (e.g., an ECD of an IGFR1 or IGFR2 polypeptide), an IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGF BP3, IGFBP4, IGFBP5 or IGFBP6 polypeptides), VEGF polypeptides (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptides), receptors of VEGF polypeptides (e.g., receptors of VEGF-A, VEGF-B, VEGF-C, VEGF-D or PGF polypeptides), VEGFR polypeptides (e.g., VEGFR1, VEGFR2 or VEGFR3 polypeptides), ECDs of VEGFR polypeptides (e.g., ECDs of VEGFR1, VEGFR2 or VEGFR3 polypeptides),FLT1 receptor polypeptide (e.g., an ECD of a FLT1 receptor polypeptide), IL36 polypeptide (e.g., an IL36A, IL36B, or IL36G polypeptide), a receptor for an IL36 polypeptide (e.g., a receptor for an IL36A, IL36B, or IL36G polypeptide), an IL36R polypeptide (e.g., an ECD of an IL36R polypeptide), an IL1R1 polypeptide (e.g., an ECD of an IL1R1 polypeptide), an IL1R2 polypeptide (e.g., an ECD of an IL1R2 polypeptide), an IL1RL1 polypeptide (e.g., an ECD of an IL1RL1 polypeptide), an IL1 IL18R1 polypeptides (ECD of IL18R1 polypeptides), bacterial toxin polypeptides, exotoxin polypeptides, endotoxin polypeptides, botulinum toxin polypeptides, tetanus toxin polypeptides, staphylococcal toxin polypeptides, CD52 polypeptides (e.g., ECD of CD52 polypeptides), ligands of CD52 polypeptides, Siglec-10 polypeptides, PCSK9 polypeptides, receptors of PCSK9 polypeptides, LDLR polypeptides (e.g., ECD of LDLR polypeptides), CEA polypeptides (e.g., CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptides), ECDs of CEA polypeptides (e.g., ECDs of CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptides), BAFF polypeptides, receptors of BAFF polypeptides, TRAF polypeptides (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptides), receptors of TRAF polypeptides (e.g., receptors of TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 polypeptides), BCMA polypeptides, an ECD of a CMA polypeptide, a SOST polypeptide, a receptor for a SOST polypeptide, an LRP polypeptide (e.g., an LRP5 or LRP6 polypeptide), an ECD of an LRP polypeptide (e.g., an ECD of an LRP5 or LRP6 polypeptide), a DLL polypeptide (e.g., a DLL4 polypeptide), a receptor for a DLL polypeptide, a Jagged polypeptide (e.g., a JAG1 or JAG polypeptide), a receptor for a Jagged polypeptide (e.g., a receptor for a JAG1 or JAG polypeptide), a NOTCH polypeptide (e.g., NOTCH1, NOTCH2,NOTCH3 or NOTCH4 polypeptide), a ligand for a NOTCH polypeptide (e.g., a ligand for a NOTCH1, NOTCH2, NOTCH3 or NOTCH4 polypeptide), a VWF polypeptide, a receptor for a VWF polypeptide, a factor VIII polypeptide, a receptor for a factor VIII polypeptide, a platelet GP1b receptor polypeptide (e.g., the ECD of a platelet GP1b receptor polypeptide), integrin alpha, ＩＩｂ β ３ Polypeptides (e.g., integrin α ＩＩｂ β ３ an ECD of a polypeptide), an IL2 polypeptide, a receptor for an IL2 polypeptide, an IL2R polypeptide (e.g., an IL2Rα, IL2Rβ, or IL2Rγ polypeptide), an ECD of an IL2R polypeptide (e.g., an ECD of an IL2Rα, IL2Rβ, or IL2Rγ polypeptide), a TGFβ polypeptide, a receptor for a TGFβ polypeptide, a decorin polypeptide, an EIF3I polypeptide, an LTBP1 polypeptide, a TGFβR1 polypeptide (e.g., an ECD of a TGFβR1 polypeptide), a YWHAE polypeptide, an IgE polypeptide, a receptor for an IgE polypeptide, an Fc receptor polypeptide (e.g., an FcεRI or FcεRII polypeptide), an ECD of an Fc receptor polypeptide (e.g., an ECD of an FcεRI or FcεRII polypeptide), a KLK polypeptide (e.g., a KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14 or KLK15 polypeptide), a Rankl polypeptide, a receptor for a Rankl polypeptide, a RANK polypeptide (e.g., an ECD of a RANK polypeptide), a TSLP polypeptide, a receptor for a TSLP polypeptide, a CRLF2 polypeptide (e.g., an ECD of a CRLF2 polypeptide), an IL7Rα polypeptide (e.g., an ECD of an IL7Rα polypeptide), an S1P polypeptide, a CD3 polypeptide (e.g., a CD3γ polypeptide, a CD3δ polypeptide or a CD3ε polypeptide), an ECD of a CD3 polypeptide (e.g., a CD3γ polypeptide, a CD3δ polypeptide or a CD3ε polypeptide), an ECD of a CD3 polypeptide (e.g., a CD3γ polypeptide, a CD3δ polypeptide or a CD3ε polypeptide), a CD3γ polypeptide, a CD3δ polypeptide or a CD3ε polypeptide ECD), a CD80 polypeptide, a receptor for a CD80 polypeptide, a CD28 polypeptide (e.g., an ECD of a CD28 polypeptide), a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a GnRH polypeptide, a receptor for a GNRH polypeptide, a GnRHR polypeptide (e.g., an ECD of a GnRHR polypeptide), an ICAM polypeptide (e.g., an ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), a receptor for an ICAM polypeptide (e.g., a receptor for an ICAM-1, ICAM-2, ICAM-3 and an ICAM-4 or ICAM-5 polypeptide), a JAM-A polypeptide, a receptor for a JAM-A polypeptide, a LFA-1 polypeptide (e.g., an ECD of an LFA-1 polypeptide), a Na ｖ 25. The polypeptide of any one of claims 1 to 24, comprising at least one therapeutic polypeptide selected from a 1.7 polypeptide, a C5 polypeptide (e.g., a C5a or C5b polypeptide), a receptor for a C5 polypeptide (e.g., a receptor for a C5a or C5b polypeptide), a C5aR polypeptide (e.g., an ECD of a C5aR polypeptide), a C5L2 polypeptide (e.g., an ECD of a C5L2 polypeptide), an IL17 polypeptide, a receptor for an IL17 polypeptide, an IL17Ra polypeptide (e.g., an ECD of an IL17Ra polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an EPO polypeptide, a somatostatin polypeptide, a GLP1 polypeptide, and a glucagon polypeptide.

26. 26. The polypeptide of claim 25, wherein the therapeutic polypeptide is a canine polypeptide, a feline polypeptide or an equine polypeptide.

27. Late embryogenesis abundant (LEA) protein polypeptides (e.g., LEA-3 polypeptides), NGF polypeptides, receptors for NGF polypeptides (e.g., ECDs for receptors for NGF polypeptides), TrkA polypeptides (e.g., ECDs for TrkA polypeptides), LNGFR polypeptides (e.g., ECDs for LNGFR polypeptides), TNFα polypeptides, receptors for TNFα polypeptides, TNFR polypeptides (e.g., ECDs for TNFR polypeptides), TNFR1 polypeptides (e.g., ECDs for TNFR1 polypeptides), TNFR2 polypeptides (e.g., TNFR2 an ECD of an IL5 polypeptide), an IL5 polypeptide, a receptor for an IL5 polypeptide, an IL5R polypeptide (e.g., an ECD of an IL5R polypeptide), an IL5Rα polypeptide (e.g., an ECD of an IL5Rα polypeptide), an IL6 polypeptide, a receptor for an IL6 polypeptide, an IL6R polypeptide (e.g., an ECD of an IL6R polypeptide), an IL17 polypeptide, a receptor for an IL17 polypeptide, an IL17R polypeptide (e.g., an ECD of an IL17R polypeptide), an IL17RA polypeptide (e.g., an ECD of an IL17RA polypeptide), an IL17RB polypeptide tide (e.g., an ECD of an IL17RB polypeptide), IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), IL23 polypeptide, a receptor for an IL23 polypeptide, IL23R polypeptide (e.g., an ECD of an IL23R polypeptide), IL12Rβ1 polypeptide (e.g., an ECD of an IL12Rβ1 polypeptide), PDL1 polypeptide, a receptor for a PDL1 polypeptide, PDL2 polypeptide, a receptor for a PDL2 polypeptide, PD1 polypeptide (e.g., an ECD of a PD1 polypeptide), integrin polypeptide (e.g., ITGA1, I TGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11, ITGAD, ITGAE, ITGAL, ITGAM, ITGAV, ITGA2B, ITGAX, ITGB1, ITGB2, ITGB3, ITGB4, ITGB5, ITGB6, ITGB7 or ITGB8 polypeptide), a receptor for an integrin polypeptide, a fibronectin polypeptide (e.g., an ECD of a fibronectin polypeptide), a vitronectin polypeptide (e.g., an ECD of a vitronectin polypeptide),collagen polypeptides (e.g., ECDs of collagen polypeptides), laminin polypeptides (e.g., ECDs of laminin polypeptides), CD80 polypeptides, receptors of CD80 polypeptides, CD86 polypeptides, receptors of CD86 polypeptides, CTLA-4 polypeptides (e.g., ECDs of CTLA-4 polypeptides), B7-H3 polypeptides, receptors of B7-H3 polypeptides (e.g., ECDs of receptors of B7-H3 polypeptides), LAG-3 polypeptides (e.g., ECDs of LAG-3 polypeptides), IL31 polypeptides, receptor, IL31RA polypeptide (e.g., ECD of IL31RA polypeptide), OSMR polypeptide (e.g., ECD of OSMR polypeptide), IL4 polypeptide, receptor of IL4R polypeptide, IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13 polypeptide, receptor of IL13 polypeptide, IL13RA1 polypeptide (e.g., ECD of IL13RA1 polypeptide), IL4R polypeptide (e.g., ECD of IL4R polypeptide), IL13Rα2 polypeptide (e.g., ECD of IL13Rα2 polypeptide), IL22 polypeptide, a receptor for an IL22 polypeptide (e.g., an ECD for an IL22 polypeptide), an IL22Rα1 polypeptide (e.g., an ECD for an IL22Rα1 polypeptide), an IL10Rβ2 polypeptide (e.g., an ECD for an IL10Rβ2 polypeptide), an IL33 polypeptide, a receptor for an IL33 polypeptide, an IL1RL1 polypeptide (e.g., an ED for an IL1RL1 polypeptide), an EGF polypeptide, a receptor for an EGF polypeptide, a TGFα polypeptide, a receptor for a TGFα polypeptide, an EGFR polypeptide (e.g., an ECD for an EGFR polypeptide), an MM P9 polypeptide, FGF polypeptide (e.g., FGF1, FGF2, FGF3, FGF4, FGF5, FGF6, FGF7, FGF8, FGF9, FGF10, FGF11, FGF12, FGF13, FGF14, FGF15, FGF16, FGF17, FGF18, FGF19, FGF20, FGF21, FGF22 or FGF23 polypeptide), a receptor for an FGF polypeptide, an FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptide), an ECD for an FGFR polypeptide (e.g., FGFR1,an ECD of an FGFR2, FGFR3, FGFR4 or FGFRL1 polypeptide), an EGF polypeptide, a receptor for an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V or VI polypeptide), a receptor for a neuregulin polypeptide, a HER polypeptide (e.g., a HER1, HER2, HER3 or HER4 polypeptide), an ECD of a HER polypeptide (e.g., an ECD of a HER1, HER2, HER3 or HER4 polypeptide), an EpCAM polypeptide (e.g., an EpCAM polypeptide a polypeptide ECD), a CD20 polypeptide (e.g., a CD20 polypeptide ECD), a ligand for a CD20 polypeptide, a CD19 polypeptide (e.g., a CD19 polypeptide ECD), a ligand for a CD19 polypeptide, a CGRP polypeptide (e.g., an α-CGRP polypeptide or a β-CGRP polypeptide), a receptor for a CGRP polypeptide, a receptor for an α-CGRP polypeptide, a receptor for a β-CGRP polypeptide, a CALCRL polypeptide (e.g., a CALCRL polypeptide ECD), a RAMP polypeptide (e.g., RAMP1, RAM P2 or RAMP3 polypeptide), an ECD of a RAMP polypeptide (e.g., an ECD of a RAMP1, RAMP2 or RAMP3 polypeptide), an IGF polypeptide (e.g., an IGF-1 or IGF-2 polypeptide), a receptor of an IGF polypeptide (e.g., a receptor of an IGF-1 or IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or IGFR2 polypeptide), an ECD of an IGFR polypeptide (e.g., an ECD of an IGFR1 or IGFR2 polypeptide), an IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGF BP3, IGFBP4, IGFBP5, or IGFBP6 polypeptides), VEGF polypeptides (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptides), receptors for VEGF polypeptides (e.g., receptors for VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptides), VEGFR polypeptides (e.g., VEGFR1, VEGFR2, or VEGFR3 polypeptides), ECDs for VEGFR polypeptides (e.g., ECDs for VEGFR1, VEGFR2, or VEGFR3 polypeptides),FLT1 receptor polypeptide (e.g., an ECD of a FLT1 receptor polypeptide), IL36 polypeptide (e.g., an IL36A, IL36B, or IL36G polypeptide), a receptor for an IL36 polypeptide (e.g., a receptor for an IL36A, IL36B, or IL36G polypeptide), an IL36R polypeptide (e.g., an ECD of an IL36R polypeptide), an IL1R1 polypeptide (e.g., an ECD of an IL1R1 polypeptide), an IL1R2 polypeptide (e.g., an ECD of an IL1R2 polypeptide), an IL1RL1 polypeptide (e.g., an ECD of an IL1RL1 polypeptide), an IL1 IL18R1 polypeptides (ECD of IL18R1 polypeptides), bacterial toxin polypeptides, exotoxin polypeptides, endotoxin polypeptides, botulinum toxin polypeptides, tetanus toxin polypeptides, staphylococcal toxin polypeptides, CD52 polypeptides (e.g., ECD of CD52 polypeptides), ligands of CD52 polypeptides, Siglec-10 polypeptides, PCSK9 polypeptides, receptors of PCSK9 polypeptides, LDLR polypeptides (e.g., ECD of LDLR polypeptides), CEA polypeptides (e.g., CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptides), ECDs of CEA polypeptides (e.g., ECDs of CD66a, CD66b, CD66c, CD66d, CD66e or CD66f polypeptides), BAFF polypeptides, receptors of BAFF polypeptides, TRAF polypeptides (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptides), receptors of TRAF polypeptides (e.g., receptors of TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 polypeptides), BCMA polypeptides, an ECD of a CMA polypeptide, a SOST polypeptide, a receptor for a SOST polypeptide, an LRP polypeptide (e.g., an LRP5 or LRP6 polypeptide), an ECD of an LRP polypeptide (e.g., an ECD of an LRP5 or LRP6 polypeptide), a DLL polypeptide (e.g., a DLL4 polypeptide), a receptor for a DLL polypeptide, a Jagged polypeptide (e.g., a JAG1 or JAG polypeptide), a receptor for a Jagged polypeptide (e.g., a receptor for a JAG1 or JAG polypeptide), a NOTCH polypeptide (e.g., NOTCH1, NOTCH2,NOTCH3 or NOTCH4 polypeptide), a ligand for a NOTCH polypeptide (e.g., a ligand for a NOTCH1, NOTCH2, NOTCH3 or NOTCH4 polypeptide), a VWF polypeptide, a receptor for a VWF polypeptide, a factor VIII polypeptide, a receptor for a factor VIII polypeptide, a platelet GP1b receptor polypeptide (e.g., the ECD of a platelet GP1b receptor polypeptide), integrin alpha, ＩＩｂ β ３ Polypeptides (e.g., integrin α ＩＩｂ β ３ polypeptide ECD), IL2 polypeptide, a receptor for an IL2 polypeptide, IL2R polypeptide (e.g., an IL2Rα, IL2Rβ, or IL2Rγ polypeptide), an ECD for an IL2R polypeptide (e.g., an ECD for an IL2Rα, IL2Rβ, or IL2Rγ polypeptide), a TGFβ polypeptide, a receptor for a TGFβ polypeptide, a decorin polypeptide, an EIF3I polypeptide, an LTBP1 polypeptide, a TGFβR1 polypeptide (e.g., an ECD for a TGFβR1 polypeptide), a YWHAE polypeptide, an IgE polypeptide, a receptor for an IgE polypeptide, an Fc receptor polypeptide (e.g., an FcεRI or FcεRII polypeptide), an Fc receptor polypeptide ECD (e.g., an FcεRI or FcεRII polypeptide), a KLK polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, KLK15, KLK16, KLK17, KLK18, KLK19, KLK20, KLK21, KLK22, KLK23, KLK24, KLK25, KLK26, KLK27, KLK28, KLK29, KLK30, KLK31, KLK32, KLK33, KLK34, KLK35, KLK36, KLK37, KLK38, KLK39, KLK40, KLK41, KLK42, KLK43, KLK44, KLK45, KLK46, KLK47, KLK48, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14 or KLK15 polypeptide), Rankl polypeptide, a receptor for a Rankl polypeptide, a RANK polypeptide (e.g., an ECD of a RANK polypeptide), a TSLP polypeptide, a receptor for a TSLP polypeptide, a CRLF2 polypeptide (e.g., an ECD of a CRLF2 polypeptide), an IL7Rα polypeptide (e.g., an ECD of an IL7Rα polypeptide), an S1P polypeptide, a CD3 polypeptide (e.g., a CD3γ polypeptide, a CD3δ polypeptide or a CD3ε polypeptide), an ECD of a CD3 polypeptide (e.g., an ECD of a CD3γ polypeptide, a CD3δ polypeptide or a CD3ε polypeptide), a CD80 polypeptide, a receptor for a CD80 polypeptide, a CD28 polypeptide (e.g., an ECD of a CD28 polypeptide), a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a GnRH polypeptide, a receptor for a GNRH polypeptide, a GnRHR polypeptide (e.g., an ECD of a GnRHR polypeptide), an ICAM polypeptide (e.g., an ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), a receptor for an ICAM polypeptide (e.g., a receptor for an ICAM-1, ICAM-2, ICAM-3, ICAM-4 or ICAM-5 polypeptide), a JAM-A polypeptide, a receptor for a JAM-A polypeptide, an LFA-1 polypeptide (e.g., an ECD of an LFA-1 polypeptide), a Na ｖ 27. The polypeptide of any one of claims 1 to 26, comprising an antibody or antibody fragment that binds to at least one target polypeptide selected from a 1.7 polypeptide, a C5 polypeptide (e.g., a C5a or C5b polypeptide), a receptor for a C5 polypeptide (e.g., a receptor for a C5a or C5b polypeptide), a C5aR polypeptide (e.g., an ECD of a C5aR polypeptide), a C5L2 polypeptide (e.g., an ECD of a C5L2 polypeptide), an IL17 polypeptide, a receptor for an IL17 polypeptide, an IL17Ra polypeptide (e.g., an ECD of an IL17Ra polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an EPO polypeptide, a somatostatin polypeptide, a GLP1 polypeptide, and a glucagon polypeptide.

28. 28. The polypeptide of claim 27, wherein the target polypeptide is a canine polypeptide, a feline polypeptide or an equine polypeptide.

29. 25. A polypeptide according to any one of claims 1 to 24, comprising an antibody or antibody fragment that binds to canine and / or feline IL31.

30. 30. The polypeptide of any one of claims 1 to 29, wherein the variant IgG Fc polypeptide has an altered binding affinity to Protein A, C1q, CD16, CD32 or CD64 compared to a wild-type IgG Fc polypeptide.

31. SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, A polypeptide comprising the amino acid sequence of sequence number 71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:89, SEQ ID NO:91, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:110, SEQ ID NO:113, SEQ ID NO:114, SEQ ID NO:115, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:126, SEQ ID NO:127, SEQ ID NO:128 or SEQ ID NO:

129.

32. 32. An isolated nucleic acid encoding a polypeptide according to any one of claims 1 to 31.

33. A host cell comprising the nucleic acid of claim 32.

34. 34. A host cell expressing a polypeptide according to any one of claims 1 to 33.

35. 35. A method for producing a polypeptide comprising culturing a host cell of claim 33 or 34 and isolating the polypeptide.

36. 32. A pharmaceutical composition comprising a polypeptide according to any one of claims 1 to 31 and a pharma- ceutically acceptable carrier.

37. 37. A method of delivering a polypeptide to a companion animal species comprising parenterally administering a polypeptide according to any one of claims 1 to 31 or a pharmaceutical composition according to claim 36.

38. A method for delivering a polypeptide to a companion animal species comprising administering a polypeptide described in any one of claims 1 to 31 or a pharmaceutical composition described in claim 36 via an intramuscular, intraperitoneal, intracerebrospinal, subcutaneous, intraarterial, intrasynovial, intrathecal or inhalation route.

39. 39. The method of claim 37 or 38, wherein the companion animal species is a dog, a horse or a cat.

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