Variant FC sequences with altered binding for veterinary use

Abstract

The present disclosure relates to substituted and variant IgG Fc polypeptides of companion animals with altered binding affinity to FcRn, such as enhanced binding affinity to FcRn at acidic pH. The substituted Fc may contain a lysine at position 439 of the EU numbering convention. The substituted and variant IgG Fc polypeptides of the present disclosure may extend the half-life or improve pharmacokinetics of an antibody or IgG Fc fusion protein in vivo. In addition, substituted and variant IgG Fc polypeptides may be used in the design and production of antibodies or fusion proteins for treating various disorders in companion animals, such as feline and canine companion animals. Methods of using substituted and variant IgG Fc polypeptides are further provided.

Description

Attorney Reference No. 2920951-551977VARIANT FC SEQUENCES WITH ALTERED BINDING FOR VETERINARY USE CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U. S. Provisional Application No. 63 / 739,367, filed December 27, 2024, the entire content of which is herein incorporated herein by reference in its entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] Pursuant to the EFS-Web legal framework and 37 CFR §§ 1.831-835 (see MPEP § 2413.03), a Sequence Listing in extensible Markup Language (XML) format (entitled “2920951-551977_Sequence_Listing_2_ST26.xml” created on December 26, 2025, and 415,615 bytes in size) is submitted concurrently with the instant application, and the entire contents of the Sequence Listing are incorporated herein by reference.FIELD

[0003] The present disclosure relates to substituted and variant IgG Fc polypeptides of animals, for example companion animals, with altered binding affinity to FcRn, such as enhanced binding affinity to FcRn at acidic pH. The substituted and variant IgG Fc polypeptides of the present disclosure may extend the half-life or improve pharmacokinetics of an antibody or IgG Fc fusion protein in vivo. In addition, substituted and variant IgG Fc polypeptides may be used in the design and production of antibodies or fusion proteins for treating various disorders in companion animals, such as feline and canine companion animals. Methods of using substituted and variant IgG Fc polypeptides are further provided.BACKGROUND

[0004] The neonatal Fc receptor (FcRn) is an Fc receptor that is similar in structure to the MHC class I molecules. Like MHC class I molecules, FcRn also associates with beta-2-microglobulin (B2M). FcRn is understood to facilitate transcytosis and recycling of IgG in vivo, and hence increase the in vivo half-life of IgG compared to that of other antibody isotypes.

[0005] To improve the binding affinity of IgG to FcRn at an acid pH (e.g., at a pH in the range of from about 5.0 to about 6.5), the Fc region of IgG responsible for binding to FcRn may be modified through mutagenesis.Attorney Reference No. 2920951-551977

[0006] Companion species animals, such as cats, dogs, and horses, have species specific IgG Fc sequences. Furthermore, there are multiple IgG subclasses, each having Fc sequence differences. For example, canine has IgG-A, IgG-B, IgG-C and IgG-D. There is a need to generate variant IgG Fc polypeptides that improve the serum persistence and half-life of polypeptides in vivo in companion animals to aid in long lasting medical treatments.SUMMARY

[0007] The disclosure provides for a polypeptide or polypeptides comprising a variant or substituted IgG Fc polypeptide comprising at least one amino acid substitution described herein relative to a wild-type IgG Fc polypeptide derived from a companion animal species, wherein the variant Fc polypeptide is capable of binding to neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type Fc polypeptide.

[0008] In aspects, the disclosure provides for variant IgG Fc polypeptides comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises one or more of the following:i. a tyrosine at position 237;ii. a proline at position 246;iii. a methionine, histidine, proline, or isoleucine at position 250;iv. a valine, arginine, or lysine at position 251;v. a histidine, phenylalanine, tyrosine, methionine, valine, glutamine, arginine, or asparagine at position 252;vi. a threonine at position 253;vii. a tryptophan, tyrosine, threonine, histidine, leucine, proline, valine, phenylalanine, or methionine at position 254;viii. a leucine, methionine, proline, isoleucine, aspartate, or tryptophan at position 255; ix. a methionine, glutamate, aspartate, histidine, isoleucine, alanine or valine at position 256;x. a methionine, phenylalanine, or valine at position 258;xi. an isoleucine at position 259;xii. an arginine at position 279;Attorney Reference No. 2920951-551977 xiii. a tryptophan, tyrosine, arginine or glutamine at position 287;xiv. an alanine at position 288;xv. a glutamine at position 305;xvi. a valine at position 306;xvii. a histidine, threonine, glutamine, arginine, alanine, aspartate, glutamate, or methionine at position 307;xviii. a histidine, phenylalanine, or proline at position 308;ixx. a glutamate or isoleucine at position 309;xx. a tyrosine, tryptophan, alanine, or phenylalanine at position 311;xxi. a phenylalanine at position 317;xxii. an arginine at position 338;xxiii. an isoleucine at position 360;xxiv. a threonine at position 370;xxv. a valine at position 376;xxvi. a serine or histidine at position 380;xxvii. a leucine, phenylalanine, or tyrosine at position 389;xxviii. an isoleucine or asparagine at position 408;xxix. a glutamine, arginine, or histidine at position 426;xxx. a histidine or tryptophan at position 428;xxxi. a phenylalanine at position 430;xxxii. a glycine at position 431;xxxiii. a histidine at position 434;xxxiv. a threonine at position 436;xxxv. an arginine at position 437;xxxvi. an arginine or leucine at position 438;xxxvii. a lysine at position 439;xxxviii. a glutamate at position 440;Attorney Reference No. 2920951-551977 xxxix. a threonine, histidine, phenylalanine, tyrosine, methionine, valine, glutamine, arginine, or asparagine at position 252;xl. an alanine or isoleucine at position 259;xli. a phenylalanine, tyrosine, alanine, serine, or histidine at position 434; and wherein the variant IgG Fc polypeptide is capable of binding to a neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type IgG Fc polypeptide.

[0009] In aspects, variant IgG Fc polypeptides described herein bind to FcRn with an affinity greater 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 from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.2, a pH of about 5.5, a pH of about 6.0, a pH of about 6.2, or a pH of about 6.5.

[0010] In other aspects, variant IgG Fc polypeptides described herein bind to FcRn with a dissociation constant (Kd) of less than 5 x 10'6M, less than 1 x 10'6M, less than 5 x 10'7M, less than 1 x 10'7M, less than 5 x 10'8M, less than 1 x 10'8M, less than 5 x 10'9M, less than 1 x 10'9M, less than 5 x 1010M, less than 1 x 1010M, less than 5 x 1011M, less than 1 x 1011M, less than 5 x 1012M, or less than 1 x 1012M, as measured by biolayer interferometry, surface plasmon resonance, or any protein-protein interaction tool at a pH in the range of from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.5, a pH of about 6.0, or a pH of about 6.5.

[0011] In further aspects, variant IgG Fc polypeptides described herein have increased serum half-life relative to a polypeptide comprising a wild-type IgG Fc polypeptide.

[0012] In additional aspects, the serum half-life of the IgG Fc polypeptide is from 1.5 to 5 times, 1.5 to 4 times, 1.5 -3 times, 2 - 5 times, 2 to 4 times, more than 1.5 times, more than 2 times, more than 2.5 times, or more than 3 times greater than the corresponding wild-type IgG Fc polypeptide or non-mutated IgG Fc polypeptide.

[0013] The disclosure further provides for IgG Fc polypeptides, for example substituted or variant IgG polypeptides, at least 90% identical, at least 95% identical, at least 97% identical, at least 95% identical, or at least 99% identical to an amino acid sequence of 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 IDAttorney Reference No. 2920951-551977 NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, 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:84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, 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: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO:300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, or SEQ ID NO: 317.

[0014] The disclosure further provides for IgG heavy chain polypeptides, for example substituted or variant IgG polypeptides, at least 90% identical, at least 95% identical, at least 97% identical, at least 98% identical, or at least 99% identical to an amino acid sequence of SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO:Attorney Reference No. 2920951-551977 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, SEQ ID NO: 246, SEQ ID NO: 247, SEQ ID NO: 248, SEQ ID NO: 249, SEQ ID NO: 250, SEQ ID NO: 251, SEQ ID NO: 252, SEQ ID NO: 253, SEQ ID NO: 254, SEQ ID NO: 255, SEQ ID NO: 256, SEQ ID NO: 257, SEQ ID NO: 258, SEQ ID NO: 259, SEQ ID NO: 260, SEQ ID NO: 261, SEQ ID NO: 262, SEQ ID NO: 263, SEQ ID NO: 264, SEQ ID NO: 265, SEQ ID NO: 266, SEQ ID NO: 267, SEQ ID NO: 268, SEQ ID NO: 269, SEQ ID NO: 270, SEQ ID NO: 271, SEQ ID NO: 272, SEQ ID NO: 273, SEQ ID NO: 274, SEQ ID NO: 275, SEQ ID NO: 276, SEQ ID NO: 277, SEQ ID NO: 278, SEQ ID NO: 279, SEQ ID NO: 280, SEQ ID NO: 281, SEQ ID NO: 282, SEQ ID NO: 283, SEQ ID NO: 284, SEQ ID NO: 285, SEQ ID NO: 286, SEQ ID NO: 287, SEQ ID NO: 288, SEQ ID NO: 289, SEQ ID NO: 290, SEQ ID NO: 291, SEQ ID NO: 292, SEQ ID NO: 293, SEQ ID NO: 294, SEQ ID NO: 295, SEQ ID NO: 296, SEQ ID NO: 297, SEQ ID NO: 298, SEQ ID NO: 299, SEQ ID NO: 318, SEQ ID NO: 320, SEQ ID NO: 321, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 329, SEQ ID NO: 331, SEQ ID NO: 333, SEQ ID NO: 335, SEQ ID NO: 337, SEQ ID NO: 340, or SEQ ID NO: 342.

[0015] The disclosure further provides for a light chain polypeptide at least 90% identical, at least 95% identical, at least 97% identical, at least 98% identical, or at least 99% identical to an amino acid sequence of SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 236, SEQ ID NO: 237, SEQ ID NO: 238, SEQ ID NO: 239, SEQ ID NO: 240, SEQ ID NO: 319, SEQ ID NO: 324, SEQ ID NO: 327, SEQ ID NO: 328, SEQ ID NO: 330, SEQ ID NO: 332, SEQ ID NO: 334, SEQ ID NO: 336, SEQ ID NO: 338, SEQ ID NO: 341, or SEQ ID NO: 343.

[0016] The disclosure further provides for polypeptides at least 90% identical, at least 95% identical, at least 97% identical, at least 98% identical or at least 99% identical to an amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5,Attorney Reference No. 2920951-551977 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, or SEQ ID NO: 339.

[0017] In aspects, the disclosure provides for IgG Fc polypeptides, for example substituted or variant IgG polypeptides, comprising:a) one or more of a 252Y and a 408N amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;b) one or more of a 252Y, 408N, and a 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;c) one or more of a 252Y, an 287Q, and an 408N amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;d) one or more of a 252Y, and a 256D amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;e) one or more of a 287W, an 380S, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;f) one or more of a 287W, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;g) one or more of a 252H, an 380S, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;h) one or more of a 309E, an 380S, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;i) one or more of a 279R, an 287W, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;j) one or more of a 287Q, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;k) one or more of a 380S, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;l) one or more of a 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;m) one or more of a 309E, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 n) one or more of a 252H, an 279R, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;o) one or more of a 252H, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;p) one or more of a 309E, and an 428H amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;q) one or more of a 380S, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;r) one or more of a 252H, an 380S, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;s) one or more of a 287W, an 408N, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;t) one or more of a 252H, an 408N, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;u) one or more of a 250M, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;v) one or more of a 308S and an 428H amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;w) one or more of a 380H, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;x) one or more of a 307H, an 309E, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;y) one or more of a 252H, an 380S, and an 431G amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;z) one or more of a 252H, an 306V, and an 307T amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aa) one or more of a 250H, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ab) one or more of a 307H and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 ac) one or more of a 380H and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ad) one or more of a 428H and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ae) one or more of a 287W, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;af) one or more of a 426Q and an 428H amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ag) one or more of a 252H, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ah) one or more of a 307T, an 309E, and an 338R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ai) one or more of a 311 Y, 408N, 426Q, and a 437R (YRQN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aj) one or more of a 311 Y, 426Q, and an 437R (YRQ) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ak) one or more of a 287W, 311 Y, 408N, and a 426Q (YWQN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;al) one or more of a 287W, 311Y, 408N, and an 437R (YWRN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;am) one or more of a 252Y, and an 256D amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;an) one or more of a 287W, 311 Y, and an 408N (YWN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ao) a 311Y amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ap) one or more of a 311 Y, 408N, and a 437R (YRN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aq) one or more of a 311Y, and an 408N (0Y0N) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 ar) one or more of a 252Y, an 254T, and an 256E amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;as) one or more of a 252H, an 311 Y, and an 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;at) one or more of a 252H, an 311 Y, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;au) one or more of a 252H and an 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;av) one or more of a 252H and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;aw) one or more of a 252H, an 428F, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ax) one or more of a 428F, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ay) one or more of a 305Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;az) one or more of a 434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ba) one or more of a 434M amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bb) one or more of a 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;be) one or more of a 426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bd) one or more of a 426H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;be) one or more of a 252Q and an 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bf) one or more of a 252Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;Attomey Reference No. 2920951-551977 bg) one or more of a 252H, an 311Y, and an 426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bh) one or more of a 252H and an 311 Y amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bi) a 252H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14; bj) one or more of a 311 Y and an 426H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bk) a 311Y amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14; bl) one or more of a 3091 amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bm) one or more of a 317F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bn) one or more of a 428W amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bo) one or more of a 311 W amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bp) one or more of a 428W, and an 434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bq) one or more of a 252Y and an 256D amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;br) one or more of a 252H, an 408N, and an 426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bs) one or more of a 252H and an 434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bt) one or more of a 252H, an 408N, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14bu) a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;bv) one or more of a 252Y, 408N, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 bw) one or more of a 252Y, 408N, 426Q, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;bx) one or more of a 252Y, an 287Q,an 408N, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;by) one or more of a 252Y, a 256D, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;bz) one or more of a 287W, an 380S, an 426Q a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;ca) one or more of a 287W, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cb) one or more of a 252H, an 380S, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cc) one or more of a 309E, an 380S, an 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cd) one or more of a 279R, an 287W, an 426Q, an 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;ce) one or more of a 287Q, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cf) one or more of a 380S, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;eg) one or more of a 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;ch) one or more of a 309E, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;ci) one or more of a 252H, an 279R, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cj) one or more of a 252H, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;ck) one or more of a 309E, a 428H, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 cl) one or more of a 380S, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cm) one or more of a 252H, an 380S, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cn) one or more of a 287W, an 408N, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;co) one or more of a 252H, an 408N, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cp) one or more of a 250M, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cq) one or more of a 308S a 428H, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cr) one or more of a 380H, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cs) one or more of a 307H, an 309E, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;ct) one or more of a 252H, an 380S, a 431G, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cw) one or more of a 252H, an 306V, a 307T, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;ex) one or more of a 250H, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cy) one or more of a 307H a 309E, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;cz) one or more of a 380H a 426Q, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;da) one or more of a 428H a 437R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;db) one or more of a 287W, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 de) one or more of a 426Q a 428H, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dd) one or more of a 252H, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;de) one or more of a 307T, an 309E, a 338R, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;df) one or more of a 311 Y, 408N, 426Q, a 437R (YRQN), and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dg) one or more of a 311 Y, 426Q, a 437R (YRQ), and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dh) one or more of a 287W, 311 Y, 408N, a 426Q (YWQN), and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;di) one or more of a 287W, 311 Y, 408N, a 437R (YWRN), and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dj) one or more of a 252Y, a 256D, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dk) one or more of a 287W, 311 Y, a 408N (YWN), and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dl) one or more of a 311 Y and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dm) one or more of a 311Y, 408N, a 437R (YRN), and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dn) one or more of a 311Y, a 408N (OYON), and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4do) one or more of a 252Y and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dp) one or more of a 434H and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4;dq) one or more of a 311 Y and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4; orAttorney Reference No. 2920951-551977 dr one or more of a 252Y, 254T, 256D, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3 or SEQ ID NO: 4.

[0018] In other aspects, the disclosure provides for IgG Fc polypeptides, for example substituted or variant IgG polypeptides, comprising:a) 252Y and 408N amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;b) 252Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;c) P307T, G309E, and K338R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;d) L252Y, S408N, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;e) L252Y and S408N amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;f) L252Y, A287Q, and S408N amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;g) L252Y and T256D amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;h) A287W, E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;i) A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;j) L252H, E380S, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;k) G309E, E380S, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;l) V279R, A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;m) A287Q, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 n) E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;o) A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;p) G309E, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;q) L252H, V279R, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;r) L252H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;s) G309E and M428H amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;t) E380S and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;u) L252H, E380S, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;v) A287W, S408N, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;w) L252H, S408N, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;x) T250M, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;y) E308S and M428H amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;z) E380H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aa) P307H, G309E, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ab) L252H, E380S, and A431G amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 ac) L252H, L306V, and P307T amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ad) T250H, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ae) P307H and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;af) E380H and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ag) M428H and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ah) A287W, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ai) A426Q and M428H amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aj) L252H, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ak) Q311Y, S408N, A426Q, and T437R (YRQN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, OR SEQ ID NO: 4;al) Q311Y, A426Q, and T437R (YRQ) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;am) A287W, Q311Y, S408N, and A426Q (YWQN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;an) S252H, S408N, and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14.ao) L252Y and T256D amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ap) A287W, Q311Y, S408N, and T437R (YWRN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aq) A287W, Q311Y, and S408N (YWN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 ar) Q311Y, S408N, and T437R (YRN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;as) Q311Y and S408N (0Y0N) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;at) L252Y, A254T, and T256E amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;au) S252H, Q311Y, and S428F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;av) S252H, Q311Y, and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;aw) S252H and S428F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ax) S252H and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ay) S252H, S428F, and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bz) S428F and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ba) a V305Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bb) a S434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;be) a S434M amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bd) a S428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;be) a S426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bf) a S426H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;Attorney Reference No. 2920951-551977 bg) S252Q and S428F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bh) a S252Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, OR SEQ ID NO: 14;bi) S252H, Q311Y, and S426Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bj) S252H and Q311Y amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bk) a S252H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bl) Q311Y and S426H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bm) a Q311Y amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bn) a L309I amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bo) a K317F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bp) a S408N amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bq) a S428W amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;br) a Q311W amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bs) S428W and S434Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bt) S252Y and T256D amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bu) S252H, S408N, and S426Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;Attorney Reference No. 2920951-551977 bv) S252H and S434Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bw) a S252Y amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bx) 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;by) 252Y, 408N, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;bz) 252Y, 408N, 426Q, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ca) P307T, G309E, K338R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cb) L252Y, S408N, A426Q, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cc) L252Y, S408N, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cd) L252Y, A287Q, S408N, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ce) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cf) A287W, E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;eg) A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ch) L252H, E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ci) G309E, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cj) V279R, A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 ck) A287Q, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cl) E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cm) A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cn) G309E, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;co) L252H, V279R, A426Q, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cp) L252H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cq) G309E, M428H, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cr) E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cs) L252H, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ct) A287W, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cq) L252H, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cr) T250M, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cs) E308S M428H, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ct) E380H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cu) P307H, G309E, A426Q, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 cv) L252H, E380S, A431G, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cw) L252H, L306V, P307T, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ex) T250H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cy) P307H, G309E, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;cz) E380H, A426Q, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;da) M428H, T437R, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;db) A287W, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;de) A426Q, M428H, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;dd) L252H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;de) Q311Y, S408N, A426Q, T437R (YRQN), and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;df) Q311Y, A426Q, T437R (YRQ), and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;dg) A287W, Q311Y, S408N, A426Q (YWQN), and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;dh) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;di) A287W, Q311Y, S408N, T437R (YWRN), and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;dj) A287W, Q311Y, S408N (YWN), and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 dk) Q311Y, S408N, T437R (YRN), and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;dl) Q311Y, S408N (OYON), and 439K amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;do) one or more of a L252Y and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;dp) one or more of a N434H and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;dq) one or more of a Q311Y and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4; ordr) one or more of a L252Y, A254T, T256D, and a 439K amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

[0019] In aspects, IgG polypeptides, for example substituted or variant IgG polypeptides with the mutation combinations described herein, are at least 90% identical, at least 95% identical, at least 97% identical, at least 98% identical, or at least 99% identical to an 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: 14.

[0020] In additional aspects, the disclosure provides for IgG Fc polypeptides, for example substituted or variant IgG polypeptides, comprising:a) 252 Y and 408N amino acid substitutions in SEQ ID NO: 2;b) 252Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2;c) P307T, G309E, and K338R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;d) L252Y, S408N, and A426Q amino acid substitutions in SEQ ID NO: 2;e) L252Y and S408N amino acid substitutions in SEQ ID NO: 2;f) L252Y, A287Q, and S408N amino acid substitutions in SEQ ID NO: 2;g) L252Y and T256D amino acid substitutions in SEQ ID NO: 2;h) A287W, E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;i) A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 j) L252H, E380S, and A426Q amino acid substitutions in SEQ ID NO: 2;k) G309E, E380S, and T437R amino acid substitutions in SEQ ID NO: 2;l) V279R, A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2; m) A287Q, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;n) E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;o) A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;p) G309E, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;q) L252H, V279R, and A426Q amino acid substitutions in SEQ ID NO: 2;r) L252H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;s) G309E and M428H amino acid substitutions in SEQ ID NO: 2;t) E380S and A426Q amino acid substitutions in SEQ ID NO: 2;u) L252H, E380S, and T437R amino acid substitutions in SEQ ID NO: 2;v) A287W, S408N, and T437R amino acid substitutions in SEQ ID NO: 2;w) L252H, S408N, and T437R amino acid substitutions in SEQ ID NO: 2;x) T250M, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;y) E308S and M428H amino acid substitutions in SEQ ID NO: 2;z) E380H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;aa) P307H, G309E, and A426Q amino acid substitutions in SEQ ID NO: 2;ab) L252H, E380S, and A431G amino acid substitutions in SEQ ID NO: 2;ac) L252H, L306V, and P307T amino acid substitutions in SEQ ID NO: 2;ad) T250H, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;ae) P307H and G309E amino acid substitutions in SEQ ID NO: 2;af) E380H and A426Q amino acid substitutions in SEQ ID NO: 2;ag) M428H and T437R amino acid substitutions in SEQ ID NO: 2;ah) A287W, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;ai) A426Q and M428H amino acid substitutions in SEQ ID NO: 2;aj) L252H, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 ak) Q311Y, S408N, A426Q, and a T437R (YRQN) amino acid substitutions in SEQ ID NO: 2;al) Q311Y, A426Q, and T437R (YRQ) amino acid substitutions in SEQ ID NO: 2; am) A287W, Q311Y, S408N, and A426Q (YWQN) amino acid substitutions in SEQ ID NO: 2;an) S252H, S408N, and S434H amino acid substitutions in SEQ ID NO: 2;ao) L252Y and T256D amino acid substitutions in SEQ ID NO: 2;ap) A287W, Q311Y, S408N, and T437R (YWRN) amino acid substitutions in SEQ ID NO: 2;aq) A287W, Q311Y, and S408N (YWN) amino acid substitutions in SEQ ID NO: 2; ar) Q311Y, S408N, and T437R (YRN) amino acid substitutions in SEQ ID NO: 2;as) Q311Y and S408N (0Y0N) amino acid substitutions in SEQ ID NO: 2;at) L252Y, A254T, and T256E amino acid substitutions in SEQ ID NO: 12;au) S252H, Q311Y, and S428F amino acid substitutions in SEQ ID NO: 12;av) S252H, Q311Y, and S434H amino acid substitutions in SEQ ID NO: 12;aw) S252H and S428F amino acid substitutions in SEQ ID NO: 12;ax) S252H and S434H amino acid substitutions in SEQ ID NO: 12;ay) S252H, S428F, and S434H amino acid substitutions in SEQ ID NO: 12;bz) S428F andS434H amino acid substitutions in SEQ ID NO: 12;ba) a V305Q amino acid substitution in SEQ ID NO: 12;bb) a S434Q amino acid substitution in SEQ ID NO: 12;be) a S434M amino acid substitution in SEQ ID NO: 12;bd) a S428F amino acid substitution in SEQ ID NO: 12;be) a S426Q amino acid substitution in SEQ ID NO: 12;bf) a S426H amino acid substitution in SEQ ID NO: 12;bg) S252Q and S428F amino acid substitutions in SEQ ID NO: 12;bh) a S252Q amino acid substitution in SEQ ID NO: 12;Attorney Reference No. 2920951-551977 bi) S252H, Q311Y, and S426Q amino acid substitutions in SEQ ID NO: 12;bj) S252H and Q311Y amino acid substitutions in SEQ ID NO: 12;bk) a S252H amino acid substitution in SEQ ID NO: 12;bl) Q311Y and S426H amino acid substitutions in SEQ ID NO: 12;bm) a Q311Y amino acid substitutions in SEQ ID NO: 12;bn) a L309I amino acid substitutions in SEQ ID NO: 12;bo) a K317F amino acid substitutions in SEQ ID NO: 12;bp) a S408N amino acid substitutions in SEQ ID NO: 12;bq) a S428W amino acid substitutions in SEQ ID NO: 12;br) a Q311W amino acid substitutions in SEQ ID NO: 12;bs) S428W and S434Q amino acid substitutions in SEQ ID NO: 12;bt) S252Y and T256D amino acid substitutions in SEQ ID NO: 12;bu) S252H, S408N, and S426Q amino acid substitutions in SEQ ID NO: 12;bv) S252H and S434Q amino acid substitutions in SEQ ID NO: 12; orbw) S252Y amino acid substitution in SEQ ID NO: 12;bx) 439K amino acid substitutions in SEQ ID NO: 2;by) 252Y, 408N, and 439K amino acid substitutions in SEQ ID NO: 2;bz) 252Y, 408N, 426Q, and 439K amino acid substitutions in SEQ ID NO: 2;ca) P307T, G309E, K338R, and 439K amino acid substitutions in SEQ ID NO: 2;cb) L252Y, S408N, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cc) L252Y, S408N, and 439K amino acid substitutions in SEQ ID NO: 2;cd) L252Y, A287Q, S408N, and 439K amino acid substitutions in SEQ ID NO: 2; ce) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 2;cf) A287W, E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; eg) A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; ch) L252H, E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;ci) G309E, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 cj) V279R, A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; ck) A287Q, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cl) E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cm) A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cn) G309E, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;co) L252H, V279R, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2; cp) L252H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cq) G309E, M428H, and 439K amino acid substitutions in SEQ ID NO: 2;cr) E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cs) L252H, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;ct) A287W, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cq) L252H, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cr) T250M, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;cs) E308S M428H, and 439K amino acid substitutions in SEQ ID NO: 2;ct) E380H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cu) P307H, G309E, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cv) L252H, E380S, A431G, and 439K amino acid substitutions in SEQ ID NO: 2; cw) L252H, L306V, P307T, and 439K amino acid substitutions in SEQ ID NO: 2;ex) T250H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;cy) P307H, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;cz) E380H, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;da) M428H, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;db) A287W, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2; de) A426Q, M428H, and 439K amino acid substitutions in SEQ ID NO: 2;dd) L252H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;de) Q311Y, S408N, A426Q, T437R (YRQN), and 439K amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 df) Q311Y, A426Q, T437R (YRQ), and 439K amino acid substitutions in SEQ ID NO: 2; dg) A287W, Q311Y, S408N, A426Q (YWQN), and 439K amino acid substitutions in SEQ ID NO: 2;dh) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 2;di) A287W, Q311Y, S408N, T437R (YWRN), and 439K amino acid substitutions in SEQ ID NO: 2;dj) A287W, Q311Y, S408N (YWN), and 439K amino acid substitutions in SEQ ID NO: 2; dk) Q311Y, S408N, T437R (YRN), and 439K amino acid substitutions in SEQ ID NO: 2; or dl) Q311Y, S408N (OYON), and 439K amino acid substitutions in SEQ ID NO: 2.

[0021] In aspects, the disclosure provides for variant IgG Fc polypeptides comprising 287W, 311Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

[0022] In further aspects, the disclosure provides for variant IgG Fc polypeptides comprising 287W, 311Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2.

[0023] The disclosure further provides for variant IgG Fc polypeptides comprising 252Y, 408N, and 426Q amino acid substitutions in amino acid sequences at least about 90%, at least about 90%, at least about 95%, at least about 98%, or at least about 99% identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4..

[0024] In an aspect, the disclosure provides for variant IgG Fc polypeptides comprising 252Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2.

[0025] In additional aspects, the disclosure provides for variant IgG polypeptides comprising 287R, 311Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

[0026] In additional aspects, the disclosure provides for variant IgG polypeptides comprising 287R, 311Y, 408N, and 426Q amino acid substitutions in amino acid sequences at least about 90%, at least about 90%, at least about 95%, at least about 98%, or at least about 99% identical to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

[0027] The disclosure further provides for a variant IgG polypeptide comprising 287R, 311Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2.

[0028] In aspects, the disclosure provides for polypeptides comprising variant IgG Fc polypeptides comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:Attorney Reference No. 2920951-551977 (i) a 311Y amino substitution; and(ii) one or more amino acid substitutions selected from 252H, 287R, 287W, 408N, 426H, 426Q, 428F, 434H, and 437R.

[0029] In aspects, the disclosure provides for polypeptides comprising variant IgG Fc polypeptides comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 439K amino acid substitution; and(ii) one or more amino acid substitutions selected from 252H, 287R, 287W, 311Y, 408N, 426H, 426Q, 428F, 434H, and 437R.

[0030] In other aspects, the disclosure provides for polypeptides comprising the following amino acid substitutions in a sequence at least about 90% identical, at least about 95% identical, at least about 98% identical, at least about 99% identical, or 100% identical to SEQ ID NO: 2:(i) a 439K amino acid substitution; and(ii) one or more amino acid substitutions selected from 252H, 287R, 287W, 311Y, 408N, 426H, 426Q, 428F, 434H, and 437R.

[0031] The disclosure also provides for polypeptides comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 434H amino acid substitution; and(ii) one or more amino acid substitutions selected from 252H, 311Y, 408N and 428F.

[0032] The disclosure also provides for polypeptides comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 439K amino acid substitution; and(ii) one or more amino acid substitutions selected from 252H, 311Y, 408N, 434H, and 428F.

[0033] In other aspects, the disclosure provides for polypeptides comprising the following amino acid substitutions in a sequence at least about 90% identical, at least about 95% identical, at least about 98% identical, at least about 99% identical, or 100% identical to SEQ ID NO: 2:(i) a 439K amino acid substitution; and(ii) one or more amino acid substitutions selected from 252H, 311Y, 408N, 434H, and 428F.Attorney Reference No. 2920951-551977

[0034] In aspects, the disclosure provides for polypeptides comprising variant IgG Fc polypeptides comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 252H, 252Q, and / or 252Y amino acid substitutions; and(ii) one or more amino acid substitutions selected from a 287Q, 254T 256D, 256E, 279R, 306V, 307T, 309E, 311Y, 380S, 408N, 426Q, 428F, 431G, 434H, 434Q, and a 437R.

[0035] In aspects, the disclosure provides for polypeptides comprising variant IgG Fc polypeptides comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 439K amino acid substitution; and(ii) one or more amino acid substitutions selected from a 252H, 252Q, 252Y, 287Q, 254T, 256D, 256E, 279R, 306V, 307T, 309E, 311Y, 380S, 408N, 426Q, 428F, 431G, 434H, 434Q, and a 437R.

[0036] In other aspects, the disclosure provides for polypeptides comprising the following amino acid substitutions in a sequence at least about 90% identical, at least about 95% identical, at least about 98% identical, at least about 99% identical, or 100% identical to SEQ ID NO: 2:(i) a 439K amino acid substitution; and(ii) one or more amino acid substitutions selected from a 252H, 252Q, 252Y, 287Q, 254T 256D, 256E, 279R, 306V, 307T, 309E, 311Y, 380S, 408N, 426Q, 428F, 431G, 434H, 434Q, and a 437R.

[0037] In aspects, polypeptides, for example, variant IgG polypeptides, are incorporated or part of antibodies, antibody fragments, fusion polypeptides, bi-specific binders, bi-specific antibodies, or multi-specific antibodies. In further aspects, polypeptides, for example, variant IgG polypeptides described in Table 4, are incorporated or part of antibodies, antibody fragments, fusion polypeptides, bi-specific binders, bi-specific antibodies, or multi-specific antibodies. In aspects, antibodies, antibody fragments, fusion polypeptides, bi-specific binders, bi-specific antibodies, or multi-specific antibodies comprising variant IgG polypeptides described in Table 4 have improved or extended serum half-life relative to antibodies, antibody fragments, fusion polypeptides, bi-specific binders, bi-specific antibodies, or multi-specific antibodies comprising non-mutated or wild-type IgG polypeptides described in Table 4.

[0038] In other aspects, of antibodies, antibody fragments, fusion polypeptides, bi-specific binders, bi-specific antibodies, or multi-specific antibodies comprising variant IgGAttorney Reference No. 2920951-551977 polypeptides described in Table 4 are specific for binding to IL-31, NGF, IL-4, IL-13, IL-5, NGF, IL31RA, PD1, TGF 1, or parvovirus.

[0039] In other aspects, polypeptides described herein may include at least one therapeutic polypeptide selected from a late embryogenesis abundant (LEA) protein polypeptide (e.g., an LEA-3 polypeptide), an NGF polypeptide, a receptor of an NGF polypeptide (e.g., an ECD of a receptor of an NGF polypeptide), a TrkA polypeptide (e.g., an ECD of a TrkA polypeptide), an LNGFR polypeptide (e.g., an ECD of a LNGFR polypeptide), a TNFa polypeptide, a receptor of a TNFa polypeptide, a TNFR polypeptide (e.g., an ECD of a TNFR polypeptide), a TNFR1 polypeptide (e.g., an ECD of a TNFR1 polypeptide), a TNFR2 polypeptide (e.g., an ECD of a TNFR2 polypeptide), an IL5 polypeptide, a receptor of an IL5 polypeptide, an IL5R polypeptide (e.g., an ECD of an IL5R polypeptide), an IL5Ra polypeptide (e.g., an ECD of an IL5Ra polypeptide), an IL6 polypeptide, a receptor of an IL6 polypeptide, an IL6R polypeptide (e.g., an ECD of an IL6R polypeptide), an IL 17 polypeptide, a receptor of 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 (e.g., an ECD of an IL17RB polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an IL23 polypeptide, a receptor of an IL23 polypeptide, an IL23R polypeptide (e.g., an ECD of an IL23R polypeptide), an IL12Rpi polypeptide (e.g., an ECD of an IL12Rpi polypeptide), a PDL1 polypeptide, a receptor of a PDL1 polypeptide, a PDL2 polypeptide, a receptor of a PDL2 polypeptide, a PD1 polypeptide (e.g., an ECD of a PD1 polypeptide), an 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), a receptor of 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), a collagen polypeptide (e.g., an ECD of a collagen polypeptide), a laminin polypeptide (e.g., an ECD of a laminin polypeptide), a CD80 polypeptide, a receptor of a CD80 polypeptide, a CD86 polypeptide, a receptor of a CD86 polypeptide, a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a B7-H3 polypeptide, a receptor of a B7-H3 polypeptide (e.g., an ECD of receptor of a B7-H3 polypeptide), a LAG-3 polypeptide (e.g., an ECD of a LAG-3 polypeptide), an IL31 polypeptide, a receptor of an IL31 polypeptide, an IL31RA polypeptide (e.g., an ECD of an IL31RA polypeptide), an OSMR polypeptide (e.g., an ECD of an OSMR polypeptide), an IL4 polypeptide, a receptor of an IL4R polypeptide, an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL 13 polypeptide, a receptor of an IL 13 polypeptide, an IL13RA1 polypeptideAttorney Reference No. 2920951-551977 (e.g., an ECD of an IL13RA1 polypeptide), an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13Ra2 polypeptide (e.g., an ECD of an IL13Ra2 polypeptide), an IL22 polypeptide, a receptor of an IL22 polypeptide (e.g., an ECD of an IL22 polypeptide), an IL22Ral polypeptide (e.g., an ECD of an IL22Ral polypeptide), an IL10RP2 polypeptide (e.g., an ECD of an IL10Rβ2 polypeptide), an IL33 polypeptide, a receptor of an IL33 polypeptide, an IL1RL1 polypeptide (e.g., an ECD of an IL1RL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a TGFa polypeptide, a receptor of a TGFa polypeptide, an EGFR polypeptide (e.g., an ECD of an EGFR polypeptide), an MMP9 polypeptide, an 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 of an FGF polypeptide, an FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3, FGFR4, or FGFRL1 polypeptide), an ECD of an FGFR polypeptide (e.g., an ECD of an FGFR1, an FGFR2, an FGFR3, an FGFR4, or an FGFRL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V, or VI polypeptide), a receptor of a neuregulin polypeptide, a HER polypeptide (e.g., HER1, HER2, HER3, or HER4 polypeptide), an ECD of a HER polypeptide (e.g., an ECD of a HER1, a HER2, a HER3, or a HER4 polypeptide), an EpCAM polypeptide (e.g., an ECD of 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 CD 19 polypeptide, a CGRP polypeptide (e.g., an a-CGRP polypeptide or a P-CGRP polypeptide), a receptor of a CGRP polypeptide, a receptor of an a-CGRP polypeptide, a receptor of a P-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 an IGF-2 polypeptide), a receptor of an IGF polypeptide (e.g., a receptor of an IGF-1 or an IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or an IGFR2 polypeptide), an ECD of an IGFR polypeptide (e.g., an ECD of an IGFR1 or an IGFR2 polypeptide), an IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, or IGFBP6 polypeptide), a VEGF polypeptide (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptide), a receptor of a VEGF polypeptide (e.g., a receptor of a VEGF-A, a VEGF-B, a VEGF-C, a VEGF-D, or a PGF polypeptide), a VEGFR polypeptide (e.g., a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an ECD of a VEGFR polypeptide (e.g., an ECD of a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an FLT1 receptor polypeptide (e.g., an ECD of an FLT1 receptor polypeptide), an IL36 polypeptide (e.g., IL36A,Attorney Reference No. 2920951-551977 IL36B, or IL36G polypeptide), a receptor of an IL36 polypeptide (e.g., a receptor of an IL36A, an IL36B, or an 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 (an ECD of an IL1RL1 polypeptide), an IL18R1 polypeptide (an ECD of an IL18R1 polypeptide), a bacterial toxin polypeptide, an exotoxin polypeptide, an endotoxin polypeptide, a Botulinum neurotoxin polypeptide, a Tetanus toxin polypeptide, a Staphylococcal toxin polypeptide, a CD52 polypeptide (e.g., an ECD of a CD52 polypeptide), a ligand of a CD52 polypeptide, a SIGLEC10 polypeptide, a PCSK9 polypeptide, a receptor of a PCSK9 polypeptide, an LDLR polypeptide (e.g., an ECD of an LDLR polypeptide), a CEA polypeptide (e.g., CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptide), an ECD of a CEA polypeptide (e.g., an ECD of a CD66a, a CD66b, a CD66c, a CD66d, a CD66e, or a CD66f polypeptide), a BAFF polypeptide, a receptor of a BAFF polypeptide, a TRAF polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptide), a receptor of a TRAF polypeptide (e.g., a receptor of a TRAF1, a TRAF2, a TRAF3, a TRAF4, a TRAF5 polypeptide), a BCMA polypeptide, an ECD of a BCMA polypeptide, a SOST polypeptide, a receptor of a SOST polypeptide, an LRP polypeptide (e.g., an LRP5 or an LRP6 polypeptide), an ECD of an LRP polypeptide (e.g., an ECD of an LRP5 or an LRP6 polypeptide), a DLL polypeptide (e.g., a DLL4 polypeptide), a receptor of a DLL polypeptide, a Jagged polypeptide (e.g., JAG1 or JAG polypeptide), a receptor of a Jagged polypeptide (e.g., a receptor of a JAG1 or a JAG polypeptide), a NOTCH polypeptide (e.g., NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptide), a ligand of a NOTCH polypeptide (e.g., a ligand of a NOTCH1, a NOTCH2, a NOTCH3, or a NOTCH4 polypeptide), a VWF polypeptide, a receptor of a VWF polypeptide, a Factor VIII polypeptide, a receptor of a Factor VIII polypeptide, a platelet GPlb receptor polypeptide (e.g., an ECD of a platelet GPlb receptor polypeptide), an integrin anb03 polypeptide (e.g., an ECD of an integrin anb03 polypeptide), an IL2 polypeptide, a receptor of an IL2 polypeptide, an IL2R polypeptide (e.g., an IL2Ra, an IL2R0, or an IL2Ry polypeptide), an ECD of an IL2R polypeptide (e.g., an ECD of an IL2Ra, an IL2R0, or an IL2Ry polypeptide), a TGF0 polypeptide, a receptor of a TGF0 polypeptide, a Decorin polypeptide, an EIF3I polypeptide, a LTBP1 polypeptide, a TGF0R1 polypeptide (e.g., an ECD of a TGF0R1 polypeptide), a YWHAE polypeptide, an IgE polypeptide, a receptor or an IgE polypeptide, an Fc receptor polypeptide (e.g., an FCERI or an FCERII polypeptide), an ECD of an Fc receptor polypeptide (e.g., an ECD of an FCERI or an FCERII polypeptide), a KLK polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12,Attorney Reference No. 2920951-551977 KLK13, KLK14, or KLK15 polypeptide), a Rankl polypeptide, a receptor of a Rankl polypeptide, a RANK polypeptide (e.g., an ECD of a RANK polypeptide), a TSLP polypeptide, a receptor of a TSLP polypeptide, a CRLF2 polypeptide (e.g., an ECD of a CRLF2 polypeptide), an IL7Ra polypeptide (e.g., an ECD of an IL7Ra polypeptide), an SIP polypeptide, a CD3 polypeptide (e.g., a CD3y polypeptide, a CD38 polypeptide, or a CD3E polypeptide), an ECD of a CD3 polypeptide (e.g., an ECD of a CD3y polypeptide, a CD38 polypeptide, or a CD3E polypeptide), a CD80 polypeptide, a receptor of 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 of a GNRH polypeptide, a GnRHR polypeptide (e.g., an ECD of a GnRHR polypeptide), an ICAM polypeptide (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4, or ICAM-5 polypeptide), a receptor of an ICAM polypeptide (e.g., a receptor of an ICAM-1, an ICAM-2, an ICAM-3, an ICAM-4, or an ICAM-5 polypeptide), a JAM-A polypeptide, a receptor of a JAM-A polypeptide, an LFA-1 polypeptide (e.g., an ECD of an LFA-1 polypeptide), a Nav1.7 polypeptide, a C5 polypeptide (e.g., a C5a or a C5b polypeptide), a receptor of a C5 polypeptide (e.g., a receptor of a C5a or a 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 IL 17 polypeptide, a receptor of an IL 17 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.

[0040] In aspects, therapeutic polypeptides or target polypeptides described herein are canine polypeptides, feline polypeptides, or equine polypeptides.

[0041] In other aspects, polypeptides described herein comprise an antibody or antibody fragment that binds canine and / or feline neuron growth factor (NGF).

[0042] In yet other aspects, polypeptides described herein comprise an antibody or antibody fragment that binds canine and / or feline tumor necrosis factor alpha (TNFa).

[0043] In aspects, variant IgG Fc polypeptides described herein comprise altered binding affinity to Protein A, Clq, CD16, CD32, or CD64 relative to the wild-type IgG Fc polypeptide.

[0044] The disclosure provides for isolated nucleic acid encoding polypeptides described herein.

[0045] Host cells comprising nucleic acids described herein are further provided.

[0046] The disclosure further provides for methods of producing a polypeptide described herein comprising culturing the host cells and isolating the polypeptide.Attorney Reference No. 2920951-551977

[0047] The disclosure further provides for pharmaceutical compositions comprising polypeptides described herein and pharmaceutically acceptable carriers).

[0048] Methods of delivering polypeptides described herein to a companion animal species comprising administering a polypeptide described herein or pharmaceutical compositions described herein are further provided.

[0049] In aspects, companion animals are treated parenterally, by an intramuscular route, an intraperitoneal route, an intracerebrospinal route, a subcutaneous route, an intra-arterial route, an intrasynovial route, an intrathecal route, or an inhalation route. In aspects, companion animals described herein are canine, equine, or feline.

[0050] Uses of polypeptides described herein treat an animal, for example, a companion animal are further provided. Uses for extending the serum half-life of polypeptides in animals, for example, companion animals, is further provided.BRIEF DESCRIPTION OF THE DRAWINGS

[0051] FIG. 1A An alignment of canine Fc IgG-A (SEQ ID NO: 1), IgG-B (SEQ ID NO: 2), IgG-C (SEQ ID NO: 3), IgG-D (SEQ ID NO: 4), and human IgGl Fc sequences with EU IgG consensus numbering. Bracketed numbers are the number of residues since the first shown residue. EU consensus residue 439 is boxed.

[0052] FIG. IB An alignment of feline Fc IgGl A (SEQ ID NO: 12), IgGIB (SEQ ID NO: 13), IgG2 (SEQ ID NO: 14), an human IgGl Fc sequences with EU IgG consensus numbering. Bracketed numbers are the number of residues since the first shown residue.

[0053] FIG. 2A shows an alignment of canine IgG-B (AAL35301.1 ) EU positions 431 to 446 and immunoglobulin sequences from chimeric DNAs derived from Canis lupus familiaris.

[0054] FIG. 2B shows an alignment of canine IgG-B Fc region EU positions 431 to 446 and immunoglobulin sequences of giant panda - Ailuropoda malanoleuca, American mink -Neogale vison, ferret - Mustela putorius furo, cat - Felis catus, clouded leopard - Neofelis nebulosa, tiger - Panthera tigris, horse - Equus caballus, and human - Homo sapiens.

[0055] FIG.3A shows the crystal structure of the CH3 domain of human IgG wherein position 439 as lysine (K439) and E356 make a stable charge pair interaction as shown by the dashed line.

[0056] FIG.3B shows the crystal structure of the CH3 domain of canine IgG-B wherein position 439 as glutamate (IgG-B) is shown. A model of the K439 is shown overlain. In theAttorney Reference No. 2920951-551977 model the K439 and E356 make a stable charge pair interaction (dark ovals) whereas the E439 and E356 are show to be mutually repulsive (light ovals).

[0057] FIG. 3C shows a model of the IgG-B and K439 making a stable charge pair interaction as shown by the dashed line.

[0058] FIG. 4A shows plots of the raw data from differential scanning fluorimetry for AB233-IgG-B and AB233-K439. Below the plot is the observed values for the melting temperatures Tml, and Tm2.

[0059] FIG. 4B shows corrected plots from differential scanning fluorimetry for AB233-IgG-B and AB233-K439. The shaded area of the plot represents the stabilization of the CH3 domain in the IgG containing K439.

[0060] FIG. 5A shows corrected plots from differential scanning fluorimetry for AB 100-IgG-B and ABlOO-IgG-B K439 (top), plot of turbidity in relationship to temperature (middle), and calculated radius (bottom).

[0061] FIG. 5B shows corrected plots from differential scanning fluorimetry for KCBLIHl-IgG-B and KCBL1H1-K439 (top), plot of turbidity in relationship to temperature (middle), and calculated radius (bottom).

[0062] FIG. 6A shows surface plasmon resonance (SPR) traces for ABlOO-IgG-B, and AB100-K439 binding to IL- 10.

[0063] FIG. 6B shows SPR traces for AB171-IgG-B, and AB171-K439 binding to IL- 10.

[0064] FIG. 7 shows a solution neutralization assay of IL- 10 by antibodies AB 100 and AB 171. The readout is a normalized cell based response. The antibodies are either IgG-B or K439.

[0065] FIG. 8A shows SPR traces of ABlOO-IgG-B binding to FcRn.

[0066] FIG. 8B shows SPR traces of AB100-K439 binding to FcRn.

[0067] FIG. 9A: Shows the affinity measurement for the L4H1 WT antibody (heavy chain SEQ ID NO: 137; light chain SEQ ID NO: 103) for canine IL-13.

[0068] FIG. 9B: Shows the affinity measurement for the L4H1 antibody with heavy chain substitution L252Y (SEQ ID NO: 108; light chain SEQ ID NO: 103) for canine IL-13.

[0069] FIG. 9C: Shows the affinity measurement for the L4H1 antibody with heavy chain substitutions L252Y and S408N (SEQ ID NO: 107; light chain SEQ ID NO: 103) for canine IL-13.

[0070] FIG. 9D: Shows the affinity measurement for the L4H1 antibody with heavy chain substitutions L252Y, S408N, and A426Q (SEQ ID NO: 106; light chain SEQ ID NO: 103) for canine IL-13.Attorney Reference No. 2920951-551977

[0071] FIG. 9E: Shows the affinity measurement for the L4H1 antibody with heavy chain substitution Q311Y (SEQ ID NO: 112; light chain SEQ ID NO: 103) for canine IL-13.

[0072] FIG. 10A: Shows the affinity measurement for the S18-B antibody (heavy chain SEQ ID NO: 154; light chain SEQ ID NO: 104) for canine IL-31.

[0073] FIG. 10B: Shows the affinity measurement for the S18-B antibody with heavy chain substitution Q311Y, A426Q, and T437R (YRQ) (SEQ ID NO: 145; light chain SEQ ID NO: 104) for canine IL-31.

[0074] FIG. 11A: Shows the affinity measurement for the Frunevetmab antibody (heavy chain SEQ ID NO: 155; light chain SEQ ID NO: 105) for feline NGF.

[0075] FIG. 11B: Shows the affinity measurement for the Frunevetmab antibody with heavy chain substitution S252Y (YOO) (SEQ ID NO: 186; light chain SEQ ID NO: 105) for feline NGF.

[0076] FIG. 11C: Shows the affinity measurement for the Frunevetmab antibody with heavy chain substitution S252H (SEQ ID NO: 172; light chain SEQ ID NO: 105) for feline NGF.

[0077] FIG. 11D: Shows the affinity measurement for the Frunevetmab antibody with heavy chain substitution Q311Y (SEQ ID NO: 174; light chain SEQ ID NO: 105) for feline NGF.

[0078] FIG. HE: Shows the affinity measurement for the Frunevetmab antibody with heavy chain substitutions S252H, S408N, and S434H (SEQ ID NO: 187; light chain SEQ ID NO: 105) for feline NGF.

[0079] FIG. 11F: Shows the affinity measurement for the Frunevetmab antibody with heavy chain substitutions S252H, and S434Q (SEQ ID NO: 185; light chain SEQ ID NO: 105) for feline NGF.

[0080] FIG. 12: Shows a representative result of the mean serum concentration of NGF antibodies in treated cats. The representative result is the mean measurement of three cats for each antibody tested: NGF Ab (wild-type Fc); NGF Ab (S252Y Fc); NGF Ab I30K (S252Y Fc); NGF Ab (S252H, S436Q Fc).

[0081] FIG 13A: Shows a representative plot for serum concentration in each of three cats treated with NGF Ab (wild-type Fc).

[0082] FIG 13B: Shows a representative plot for serum concentration in each of three cats treated with NGF Ab (S252Y Fc).

[0083] FIG 13C: Shows a representative plot for serum concentration in each of three cats treated with NGF Ab I30K (S252Y Fc).Attorney Reference No. 2920951-551977

[0084] FIG 13D: Shows a representative plot for serum concentration in each of three cats treated with NGF Ab (S252H, S436Q Fc).

[0085] FIG. 14A: Shows a representative SPR binding result of a substituted a canine IgG-B anti IL-31 K439 binding to canine FcRn at pH 6.0. The anti IL-31 antibody is a substituted Lokivetmab.

[0086] FIG. 14B: Shows a representative SPR binding result of a canine IgG-B anti IL-31 K439 binding to canine FcRn at pH 6.0 to 7.4. The anti IL-31 antibody is a substituted Lokivetmab.

[0087] FIG. 14C: Shows a representative SPR binding result of a canine IgG-B anti IL-31 K439 binding to canine FcRn at pH 7.4. The anti IL-31 antibody is a substituted Lokivetmab.

[0088] FIG. 15A: Shows a representative SPR binding result of a canine IgG-B anti IL-31 A311Y, A426Q, T437R, E439 binding to canine FcRn at pH 6.0. The anti IL-31 antibody is a substituted Lokivetmab.

[0089] FIG. 15B: Shows a representative SPR binding result of a canine IgG-B anti IL-31 A311Y, A426Q, T437R, E439 binding to canine FcRn at pH 6.0 to 7.4. The anti IL-31 antibody is a substituted Lokivetmab.

[0090] FIG. 15C: Shows a representative SPR binding result of a canine IgG-B anti IL-31 A311Y, A426Q, T437R, E439 binding to canine FcRn at pH 7.4. The anti IL-31 antibody is a substituted Lokivetmab.

[0091] FIG. 16A: Shows a representative SPR binding result of a canine IgG-B anti IL-31 A311Y, A426Q, T437R, K439 binding to canine FcRn at pH 6.0. The anti IL-31 antibody is a substituted Lokivetmab.

[0092] FIG. 16B: Shows a representative SPR binding result of a canine IgG-B anti IL-31 A311Y, A426Q, T437R, K439 binding to canine FcRn at pH 6.0 to 7.4. The anti IL-31 antibody is a substituted Lokivetmab.

[0093] FIG. 16C: Shows a representative SPR binding result of a canine IgG-B anti IL-31 A311Y, A426Q, T437R, K439 binding to canine FcRn at pH 7.4. The anti IL-31 antibody is a substituted Lokivetmab.DESCRIPTION

[0094] Variant IgG Fc polypeptides derived from companion animals, such as canine, equine, and feline, having altered binding to FcRn are described. In some embodiments, antibodies, antibody fragments, or fusion proteins comprise a substituted or variant IgG Fc polypeptide. Methods of producing or purifying substituted or variant IgG Fc polypeptides andAttorney Reference No. 2920951-551977 methods of administering substituted or variant IgG Fc polypeptides to companion animals are also provided.Exemplary Variant IgG Fc Polypeptides

[0095] Substituted and variant IgG Fc polypeptides are provided, for example, substituted and variant IgG Fc polypeptides with altered binding affinity to FcRn, such as enhanced binding affinity to FcRn at an acidic pH (e.g., at a pH in the range of from about 5.0 to about 6.5).

[0096] “Amino acid sequence,” means a sequence of amino acids residues in a peptide or protein. The terms “polypeptide” and “protein” are used interchangeably to refer to a polymer of amino acid residues, and are not limited to a minimum length. Such polymers of amino acid residues may contain 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 encompassed by the definition. The terms also include post-expression modifications of the polypeptide, for example, glycosylation, sialylation, acetylation, phosphorylation, and the like. Furthermore, for purposes of the present disclosure, a “polypeptide” refers to a protein which 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 may be deliberate, as through site-directed mutagenesis, or may be accidental, such as through mutations of hosts which produce the proteins or errors due to PCR amplification.

[0097] “IgX Fc” or “IgX Fc polypeptide” refers to an Fc polypeptide derived from a particular antibody isotype (e.g., IgG, IgA, IgD, IgE, IgM, etc.), where “X” denotes the antibody isotype. Thus, “IgG Fc” denotes that the Fc polypeptide is derived from a y chain, “IgA Fc” denotes that the Fc polypeptide is derived from an a chain, “IgD Fc” denotes that the Fc polypeptide is derived from a 8 chain, “IgE Fc” denotes that the Fc polypeptide is derived from a E chain, “IgM Fc” denotes that the Fc polypeptide is derived from a p chain, etc. In some embodiments, the IgG Fc polypeptide comprises the hinge, CH2, and CH3, but does not comprise CHI or CL. In some embodiments, the IgG Fc polypeptide comprises CH2 and CH3, but does not comprise CHI, the hinge, or CL. In some embodiments, the IgG Fc polypeptide comprises CHI, 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 1 to 20, 1 to 15, 1 to 10, 1 to 5, or 1 to 2 amino acids, while retaining biological activity. In some embodiments, the biological activity of is the ability to bind FcRn. An “effector function” of theAttorney Reference No. 2920951-551977 Fc polypeptide is an action or activity performed in whole or in part by any antibody in response to a stimulus and may include complement fixation and / or ADCC (antibody-dependent cellular cytotoxicity) induction. “IgX-N Fc” denotes that the Fc polypeptide is derived from a particular subclass of antibody isotype (such as canine IgG subclass IgG-A, IgG-B, IgG-C, or IgG-D; feline IgG subclass IgG-la, IgG- lb, or IgG-2; or equine IgG subclass IgG-1, IgG-2, IgG-3, IgG-4, IgG-5, IgG-6, or IgG-7, etc.), where “N” denotes the subclass.

[0098] In some embodiments, a companion animal species is a canine (or dog), a feline (or cat), or an equine (or horse). In some embodiments, a companion animal species is a small mammal, such as a canine, feline, dog, cat, rabbit, ferret, guinea pig, rodent, etc. In some embodiments, a companion animal species is a farm animal, such as a horse, cow, pig, etc.

[0099] In some embodiments, an IgX Fc polypeptide or an IgX-N Fc polypeptide is derived from a companion animal, such as a dog, a cat, or a horse. In some embodiments, IgG Fc polypeptides are isolated from canine y heavy chains, such as IgG-A, IgG-B, IgG-C, or IgG-D. In some instances, IgG Fc polypeptides are isolated from feline y heavy chains, such as IgGl (e.g., IgGla or IgGlb) or IgG2. In other instances, IgG Fc polypeptides are isolated from equine y heavy chains, such as IgG-1, IgG-2, IgG-3, IgG-4, IgG-5, IgG-6, or IgG-7.

[0100] The terms “IgX Fc” and “IgX Fc polypeptide” include wild-type IgX Fc polypeptides and substituted IgX Fc polypeptides, unless indicated otherwise.

[0101] “Wild-type” refers to a non-mutated version of a polypeptide that occurs in nature, or a fragment thereof. A wild-type polypeptide may be produced recombinantly.

[0102] In some embodiments, a 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: 14. SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 4 correspond to various to canine wild-type IgG Fc polypeptides. SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 11 correspond to various to equine wild-type IgG Fc polypeptides. SEQ ID NO: 12, SEQ ID NO: 13, and SEQ ID NO: 14 correspond to various to feline wild-type IgG Fc polypeptides.

[0103] A “substituted polypeptide”, “variant polypeptide”, or “mutated polypeptide” is a polypeptide that differs from a reference polypeptide, for example a wild-type polypeptide, by single or multiple non-native amino acid substitutions, deletions, and / or additions. In some embodiments, a substituted, variant, or mutated polypeptide retains at least one biologicalAttorney Reference No. 2920951-551977 activity of the reference polypeptide. In some embodiments, a substituted, variant, or mutated polypeptide has a biological activity that the reference polypeptide substantially lacks.

[0104] A “substituted IgG Fc”, “variant IgG Fc”, or “mutated IgG Fc” as used herein is an IgG Fc polypeptide that differs from a reference IgG Fc polypeptide, for example a wild-type IgG polypeptide, by single or multiple amino acid substitutions, deletions, and / or additions.

[0105] In some embodiments, a substituted or variant IgG Fc polypeptide comprises a substituted or variant IgG Fc polypeptide of a companion animal species. In some embodiments, a substituted or variant IgG Fc polypeptide comprises a substituted or variant canine IgG Fc polypeptide, a substituted or variant equine IgG Fc polypeptide, or a feline IgG Fc polypeptide. In some embodiments, the substituted or variant IgG Fc polypeptide is a substituted or variant canine IgG-A Fc polypeptide, a substituted or variant canine IgG-B Fc polypeptide, a substituted or variant canine IgG-C Fc polypeptide, or a substituted or variant canine IgG-D Fc polypeptide. In some embodiments, the substituted or variant IgG Fc polypeptide is a substituted or variant equine IgGl Fc polypeptide, a substituted or variant equine IgG2 Fc polypeptide, a substituted or variant equine IgG3 Fc polypeptide, a substituted or variant equine IgG4 Fc polypeptide, a substituted or variant equine IgG5 Fc polypeptide, a substituted or variant equine IgG6 Fc polypeptide, or a substituted or variant equine IgG7 Fc polypeptide. In some embodiments, the substituted or variant IgG Fc polypeptide is a substituted or variant feline IgGla Fc polypeptide, a substituted or variant IgGlb polypeptide, or a substituted or variant feline IgG2 Fc polypeptide.

[0106] As used herein, “percent (%) amino acid sequence identity” and “homology” with respect to a peptide, polypeptide, or antibody sequence are defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific peptide or polypeptide sequence, after aligning the sequences and introducing gaps, if necessary to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or MEGALINE™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of sequences being compared.

[0107] In some embodiments, a substituted or variant sequence has at least about 50% sequence identity with the reference nucleic acid molecule or polypeptide after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequenceAttorney Reference No. 2920951-551977 identity, and not considering any conservative substitutions as part of the sequence identity. Such substituted or variant sequences include, for instance, polypeptides wherein one or more amino acid residues are added, deleted, at the N- or C-terminus of the polypeptide. In some embodiments, a substituted or variant sequence 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.

[0108] As used herein, “position corresponding to position n,” wherein n is any number, refers to an amino acid position of a subject polypeptide that aligns with position n of a reference polypeptide after aligning the amino acid sequences of the subject and reference polypeptides and introducing gaps. Alignment for purposes of whether a position of a subject polypeptide corresponds with position n of a reference polypeptide can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, CLUSTAL OMEGA, ALIGN, or MEGALIGN™ (DNASTAR) software. Those skilled in the art can determine appropriate parameters for alignment, including any parameters needed to achieve maximal alignment over the full length of two sequences being compared. In some embodiments, the subject polypeptide and the reference polypeptide are of different lengths.

[0109] An “point mutation” is a mutation that involves a single amino acid residue. The mutation may be the loss of an amino acid, substitution of one amino acid residue for another, or the insertion of an additional amino acid residue.

[0110] An “amino acid substitution” refers to the replacement of one amino acid in a polypeptide with another amino acid. In some embodiments, an amino acid substitution is a conservative substitution. Nonlimiting exemplary conservative amino acid substitutions are shown in Table 1. Amino acid substitutions may be introduced into an the polypeptide, protein, or antibody of interest and the products screened for a desired activity, for example, retained / improved antigen binding, decreased immunogenicity, or improved ADCC or CDC. In aspects, amino acid substitutions are introduced into polypeptides and IgG polypeptides and proteins described herein.Table 1Original Exemplary SubstitutionsResidueAla (A) Vai; Leu; lie_ Arg (R) Lys; Gin; AsnAttorney Reference No. 2920951-551977 Asn (N) Gin; His; Asp; Lys; ArgAsp (D) Glu; AsnCys (C) Ser; AlaGln (Q) Asn; GluGlu (E) Asp; GinGly (G) AlaHis (H) Asn; Gin; Lys; ArgHe (I) Leu; Vai; Met; Ala; Phe;NorleucineLeu (L) Norleucine; lie; Vai; Met;Ala; PheLys (K) Arg; Gin; AsnMet (M) Leu; Phe; HePhe (F) Trp; Leu; Vai; He; Ala; TyrPro (P) AlaSer (S) ThrThr (T) Vai; SerTrp (W) Tyr; PheTyr (Y) Trp; Phe; Thr; SerVal (V) lie; Leu; Met; Phe; Ala;Norleucine

[0111] Conservative substitutions may entail exchanging a member of one of these classes with a member of the same class. Non-conservative substitutions will entail exchanging a member of one of these classes with another class.

[0112] Conservative substitutions may be made in accordance with Table 2. Methods for predicting tolerance to protein modification may be found in, for example, Guo et al., Proc. Natl. Acad. Sci., USA, 101(25):9205-9210 (2004), the contents of which are incorporated by reference in their entireties.Table 2: Conservative Amino Acid substitutionAttorney Reference No. 2920951-551977Conservative Amino Acid SubstitutionszXmino Acid Substitutions (others are known in the ait)Ala Ser, Gly, CysArg Lys. Gin, HisAsn Gin, His, Ghi, AspAsp Glu, Asn, GinCys Ser, Met, ThrGin Asn, Lys, Glu, Asp, ArgGlu Asp, ASH, GtoGly Pro, Ala, SerHis Asn, Gin, Lyslie Leu, Vai, Met, AlaLeu He, Vai, Met AlaLys Atg, Gin, HisMet Leu, lie, Vai, Ala, PhePlie Met, Leu, Tyr, Tip, HisSer Thr, Cy s, AlaThr Ser, Vai, AlaTip Tyr, PheTyr Tip, Phe, HisVai He, Leu, Met, Ab, Thr

[0113] In another embodiment, conservative substitutions may be those shown in Table 2 under the heading of “conservative substitutions.” If such substitutions result in a change in biological activity, then more substantial changes, denominated “exemplary substitutions” in Table 3, may be introduced and the products screened if needed.Table 3: Amino Acid substitutionAttorney Reference No. 2920951-551977Amino A Sab Aitatieas.Original Residue{aAt liyoccurring am ino Conservativeacid) Substitutions Exemplary Substitutions Ah (A) Vai Vhl; Leu; HeArg (R) Lys Lys: Gia; AonAsn (N) Gin Gin; His; Asp, I.ys: ArgAsp (D) Glu Gia; AsnCys (Cj Ser Ser AlaGlu (Q) SH Asm GiaGlu (Es Asp Asp GiaGly (G) Ala AhHis (H) Arg Asn; Gia; lys; Arglie (I) Lett Lea; hl; Met; Ala: Phe;NorieadaeLea (L'j lie Norleucine; lie; Vai; Mel;Aha Phelys (KI) Arg Arg; Gin; AsaMet (M) Lea Leu; Phe; HePhe (F) Tyr Lea; Vsl; lie; Ala; TyrPre (P) Ala AlaSer (S) Thr ThrThr (T) Ser SerTip (W) Tyr Tvr; PheTyr i Y? Phe Tip; Phe; Thr; SerMil (V) Leu lie; Lea; Met; Phe; Ala;Norleucine

[0114] Amino acids may be grouped according to common side-chain properties:(1) hydrophobic: Norleucine, Met, Ala, Vai, Leu, He;(2) neutral hydrophilic: Cys, Ser, Thr, Asn, Gin;(3) acidic: Asp, Glu;(4) basic: His, Lys, Arg;(5) residues that influence chain orientation: Gly, Pro;(6) aromatic: Trp, Tyr, Phe.

[0115] Non-conservative substitutions will entail exchanging a member of one of these classes with another class.

[0116] An “amino acid derivative,” as used herein, refers to any amino acid, modified amino acid, and / or amino acid analogue, which 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., seleno cysteine and pyrrolysine, which may be found in some microorganisms)Attorney Reference No. 2920951-551977 and unnatural amino acids. Exemplary amino acid derivatives, include, but are not limited to, amino acid derivatives commercially available through chemical product manufacturers (e.g., sigmaaldrich.com / chemistry / chemistry-products.html? TablePage= 16274965, accessed on May 6, 2017, which is incorporated herein by reference). One or more amino acid derivatives may be incorporated into a polypeptide at a specific location using a translation system that utilizes host cells, orthogonal aminoacyl-tRNA synthetases derived from eubacterial synthetases, orthogonal tRNAs, and an amino acid derivative. For further descriptions, see, e.g., U. S. Patent No.9,624,485, the contents of which are incorporated by reference in their entities.

[0117] In some embodiments, a substituted or 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.Table 4: Representative SequencesSEQID SEQUENCE DESCRIPTION NO:1 CPVPEPLGGPSVLIFPPKPKDILRITRTPEVTCVVLD Exemplary wild-type LGREDPEVQISWFVDGKEVHTAKTQSREQQFNGT canine IgG- A Fc YRVVSVLPIEHQDWLTGKEFKCRVNHIDLPSPIERT EU Residues 228-447 ISKARGRAHKPSVYVLPPSPKELSSSDTVSITCLIKD FYPPDIDVEWQSNGQQEPERKHRMTPPQLDEDGS YFLYSKLSVDKSRWQQGDPFTCAVMHETLQNHYT DLSLSHSPGK2 CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary wild-type DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE EU Residues 228-447 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK3 CPGCGLLGGPSVFIFPPKPKDILVTARTPTVTCVW Exemplary wild-type DLDPENPEVQISWFVDSKQVQTANTQPREEQSNGT canine IgG-C Fc YRVVSVLPIGHQDWLSGKQFKCKVNNKALPSPIEE EU Residues 228-447 IISKTPGQAHQPNVYVLPPSRDEMSKNTVTLTCLV KDFFPPEIDVEWQSNGQQEPESKYRMTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQISLSHSPGKAttorney Reference No. 2920951-551977 CPVPESLGGPSVFIFPPKPKDILRITRTPEITCVVLDL Exemplary wild-type GREDPEVQISWFVDGKEVHTAKTQPREQQFNSTY canine IgG-D Fc RWSVLPIEHQDWLTGKEFKCRVNHIGLPSPIERTI EU Residues 228-447 SKARGQAHQPSVYVLPPSPKELSSSDTVTLTCLIKD FFPPEIDVEWQSNGQPEPESKYHTTAPQLDEDGSY FLYSKLSVDKSRWQQGDTFTCAVMHEALQNHYT DLSLSHSPGK CPAPELLGGPSVFIFPPNPKDTLMITRTPEVTCVW Exemplary wild-type DVSQENPDVKFNWYMDGVEVRTATTRPKEEQFNS equine IgGl Fc TYRWSVLRIQHQDWLSGKEFKCKVNNQALPQPIE EU Residues 228-447 RTITKTKGRSQEPQVYVLAPHPDELSKSKVSVTCL VKDFYPPEINIEWQSNGQPELETKYSTTQAQQDSD GSYFLYSKLSVDRNRWQQGTTFTCGVMHEALHN HYTQKNVSKNPGK YTHSKFLGGPSVFIFPPNPKDALMISRTPVVTCVW Exemplary wild-type NLSDQYPDVQFSWYVDNTEVHSAITKQREAQFNS equine IgG2 Fc TYRWSVLPIQHQDWLSGKEFKCSVTNVGVPQPIS EU Residues 228-447 RAISRGKGPSRVPQVYVLPPHPDELAKSKVSVTCL VKDFYPPDISVEWQSNRWPELEGKYSTTPAQLDG DGSYFLYSKLSLETSRWQQVESFTCAVMHEALHN HFTKTDISESLGK CPAPELLGGPSVFIFPPKPKDVLMITRTPEVTCLW Exemplary wild-type DVSHDSSDVLFTWYVDGTEVKTAKTMPNEEQNNS equine IgG3 Fc TYRWSVLRIQHQDWLNGKKFKCKVNNQALPAP EU Residues 228-447 VERTISKATGQTRVPQVYVLAPHPDELSKNKVSVT CLVKDFLPTDITVEWQSNEHPEPEGKYRTTEAQKD SDGSYFLYSKLTVETDRWQQGTTFTCWMHEALH NHVMQKNVSHSPGK CPAECLQVGPSVFIFPPKPKDVLMISRTPTVTCVW Exemplary wild-type DVGHDFPDVQFNWYVDGVETHTATTEPKQEQFNS equine IgG4 Fc TYRWSVLPIQHKDWLSGKEFKCKVNNKALPAPV EU Residues 228-447 ERTISKPTGQPREPQVYVLAPHRDELSKNKVSVTC LVKDFYPTDIDIEWKSNGQPEPETKYSTTPAQLDS DGSYFLYSKLTVETNRWQQGTTFTCAVMHEALHN HYTEKSVSKSPGK CPAPELPGGPSVFIFPPKPKDVLKISRKPEVTCVW Exemplary wild-type DLGHDDPDVQFTWFVDGVETHTATTEPKEEQFNS equine IgG5 Fc TYRWSVLPIQHQDWLSGKEFKCSVTNKALPAPVE EU Residues 228-447 RTTSKAKGQLRVPQVYVLAPHPDELAKNTVSVTC LVKDFYPPEIDVEWQSNEHPEPEGKYSTTPAQLNS DGSYFLYSKLSVETSRWKQGESFTCGVMHEAVEN HYTQKNVSHSPGK CCCPKCPGRPSVFIFPPNPKDTLMISRTPEVTCVW Exemplary wild-type DVSQENPDVKFNWYVDGVEAHTATTKAKEKQDN equine IgG6 Fc STYRWSVLPIQHQDWRRGKEFKCKVNNRALPAP EU Residues 228-447 VERTITKAKGELQDPKVYILAPHREEVTKNTVSVTCLVKDFYPPDINVEWQSNEEPEPEVKYSTTPAQLDAttorney Reference No. 2920951-551977 GDGSYFLYSKLTVETDRWEQGESFTCVVMHEAIR HTYRQKSITNFPGK TCPECLSVGPSVFIFPPKPKDVLMISRTPTVTCVW Exemplary wild-type DVGHDFPDVQFNWYVDGVETHTATTEPKQEQNN equine IgG7 Fc STYRWSILAIQHKDWLSGKEFKCKVNNQALPAPV EU Residues 228-447 QKTISKPTGQPREPQVYVLAPHRDELSKNKVSVTC LVKDFYPTDIDIEWKSNGQPEPETKYSTTPAQLDS DGSYFLYSKLTVETNRWQQGTTFTCAVMHEALHN HYTEKSVSKSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary wild-type LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI EU Residues 228-447 SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary wild-type LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGlb Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI EU Residues 228-447 SKDKGQPHEPQVYVLPPAQEELSRNKVSVTCLIEG FYPSDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF LYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPVPEIPGAPSVFIFPPKPKDTLSISRTPEVTCLWDL Exemplary wild-type GPDDSNVQITWFVDNTEMHTAKTRPREEQFNSTY feline IgG2 Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSAMER EU Residues 228-447 TISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLIK GFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDGT YFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHHT QKSLTQSPGK MGVPRPRSWGLGFLLFLLPTLRAADSHLSLLYHLT Exemplary canine FcRn AVSAPPPGTPAFWASGWLGPQQYLSYNNLRAQAE with poly-His PYGAWVWENQVSWYWEKETTDLRTKEGLFLEAL KALGDGGPYTLQGLLGCELGPDNTSVPVAKFALN GEDFMTFDPKLGTWNGDWPETETVSKRWMQQAG AVSKERTFLLYSCPQRLLGHLERGRGNLEWKEPPS MRLKARPGSPGFSVLTCSAFSFYPPELQLRFLRNGL AAGSGEGDFGPNGDGSFHAWSSLTVKSGDEHHYR CLVQHAGLPQPLTVELESPAKSSGSHHHHHH HLSLLYHLTAVSAPPPGTPAFWASGWLGPQQYLS Exemplary canine FcRn YNNLRAQAEPYGAWVWENQVSWYWEKETTDLR ECD TKEGLFLEALKALGDGGPYTLQGLLGCELGPDNTS VPVAKFALNGEDFMTFDPKLGTWNGDWPETETVS KRWMQQAGAVSKERTFLLYSCPQRLLGHLERGRG NLEWKEPPSMRLKARPGSPGFSVLTCSAFSFYPPEL QLRFLRNGLAAGSGEGDFGPNGDGSFHAWSSLTV KSGDEHHYRCLVQHAGLPQPLTVELESPAKAttorney Reference No. 2920951-551977 MAPRPALATAGFLALLLILLAACRLDAVQHPPKIQ Exemplary canine B2M VYSRHPAENGKPNFLNCYVSGFHPPEIEIDLLKNG KEMKAEQTDLSFSKDWTFYLLVHTEFTPNEQDEFS CRVKHVTLSEPQIVKWDRDN MGVPRPQPWGLGFLLFLLPTLRAAESHLSLLYHLT Exemplary feline FcRn AVSSPAPGTPAFWVSGWLGPQQYLSYNNMRAQA with poly-His EPCGAWVWENQVSWYWEKETTDLRNKQELFLEA LKVLGEGGPYTLQGLLGCELGPDNASVPVAKFAL NGEDFMDFDPKLGTWSGEWPETETISKRWMQEA GAVSKERTFLLNSCPQRLLGHLERGRGNLEWKEPP SMRLKARPGSPGFSVLTCSAFSFYPPELQLRFLRNG LAAGSGEGDFGPNGDGSFHAWSSLTVKSGDEHHY RCLVQHAGLPQPLTVELESPAKSSGSHHHHHH HLSLLYHLTAVSSPAPGTPAFWVSGWLGPQQYLS Exemplary feline FcRn YNNMRAQAEPCGAWVWENQVSWYWEKETTDLR ECD NKQELFLEALKVLGEGGPYTLQGLLGCELGPDNA SVPVAKFALNGEDFMDFDPKLGTWSGEWPETETIS KRWMQEAGAVSKERTFLLNSCPQRLLGHLERGRG NLEWKEPPSMRLKARPGSPGFSVLTCSAFSFYPPEL QLRFLRNGLAAGSGEGDFGPNGDGSFHAWSSLTV KSGDEHHYRCLVQHAGLPQPLTVELESPAK MARFWLVLLGLLYLSHLDAVQHSPKVQVYSRHP Exemplary feline B2M AENGKPNFLNCYVSGFHPPQIDITLMKNGKKMEA EQTDLSFNRDWTFYLLVHTEFTPTVEDEYSCQVNH TTLSEPKWKWDRDM CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, S408N, A426Q RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICQVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, S408N RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substitutedDLDPEDPEVQISWFVDGKQMQTQKTQPREEQFNG canine IgG-B FcAttorney Reference No. 2920951-551977 TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, A287Q, S408N RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE N434H RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHHHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARDPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, T256D RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287W, E380S, A426Q, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI T437R KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287W, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, E380S, A426Q RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQESLSHSPGKAttorney Reference No. 2920951-551977 CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIEHQDWLKGKQFTCKVNNKALPSPIE G309E, E380S, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFRDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE V279R, A287W, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI A426Q, T437R KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTQKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287Q, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380S, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIEHQDWLKGKQFTCKVNNKALPSPIE G309E, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFRDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, V279R, A426Q RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGAttorney Reference No. 2920951-551977 SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIEHQDWLKGKQFTCKVNNKALPSPIE G309E, M428H RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVHHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380S, A426Q RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, E380S, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287W, S408N, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, S408N, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDMLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE T250M, P307T, G309ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIAttorney Reference No. 2920951-551977 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380S, M428H RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVHHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380H, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVHWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLHIEHQDWLKGKQFTCKVNNKALPSPI P307H, G309E, A426Q ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICQVMHEALHNH YTQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, E380S, A431G RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEGLHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVVTIGHQDWLKGKQFTCKVNNKALPSPI L252H, L306V, P307T ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNH YTQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDHLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE T250H, P307T, G309E RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B FcTYRWSVLHIEHQDWLKGKQFTCKVNNKALPSPI P307H, G309EAttorney Reference No. 2920951-551977 ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNH YTQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380H, A426Q RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVHWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE M428H, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVHHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE A287W, P307T, G309E RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A426Q, M428H RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVHHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE L252H, P307T, G309E RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE P307T, G309E, K338R RTISRARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substitutedDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B FcAttorney Reference No. 2920951-551977 TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, S408N, A426Q, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI T437R (YRQN) KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI (YRQ) KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE A287W, Q311Y, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI S408N, A426Q KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG (YWQN) SYFLYNKLSVDKSRWQRGDTFICQVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARDPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, T256D (YD) RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE A287W, Q311Y, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI S408N, T437R (YWRN) KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE A287W, Q311Y, S408N RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI (YWN) KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y(0Y0) RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGKAttorney Reference No. 2920951-551977 CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, S408N, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI (YRN) KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY RQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRVVSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, S408N (0Y0N) RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYITREPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc (YTE) TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y A254T T256E RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQESLSHSPGK CPPPEMLGGPSIFIFPPKPKDTLYITREPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGlaFc (YTE) RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252Y, S254T, T256E SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLYITREPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGlb Fc (YTE) RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252Y, S254T, T256E SKDKGQPHEPQVYVLPPAQEELSRNKVSVTCLIEG FYPSDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF LYSRLSVDRSRWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPVPEIPGAPSVFIFPPKPKDTLYITREPEVTCLWD Exemplary substituted LGPDDSNVQITWFVDNTEMHTAKTRPREEQFNST feline IgG2 Fc (YTE) YRVVSVLPILHQDWLKGKEFKCKVNSKSLPSAME S252Y, S254T, T256E RTISKAKGQPHEPQVYVLPPTQEELSENKVSVTCLI KGFHPPDIAVEWEITGQPEPENNYQTTPPQLDSDG TYFLYSRLSVDRSHWQRGNTYTCSVSHEALHSHH TQKSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHYDWLKGKEFKCKVNSKSLPSPIERTI S252H, Q311Y, S428F SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYFAttorney Reference No. 2920951-551977 VYSKLSVDRSHWQRGNTYTCSVFHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHYDWLKGKEFKCKVNSKSLPSPIERTI S252H, Q311Y, S434H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHHHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252H, S428F SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVFHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252H, S434H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHHHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252H, S428F, S434H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVFHEALHHHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S428F S434H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVFHEALHHHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RVVSQLPILHQDWLKGKEFKCKVNSKSLPSPIERTI V305Q SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S434QSKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKSAttorney Reference No. 2920951-551977 FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHQHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S434M SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHMHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S428F SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVFHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S426Q SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCQVSHEALHSHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S426H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCHVSHEALHSHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLQISRTPEVTCLVVE) Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252Q, S428F SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVFHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLQISRTPEVTCLVVE) Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252Q SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla FcRWSVLPILHYDWLKGKEFKCKVNSKSLPSPIERTI S252H, Q311Y, S426QAttorney Reference No. 2920951-551977 SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCQVSHEALHSHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHYDWLKGKEFKCKVNSKSLPSPIERTI S252H, Q311Y SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGlaFc RWSVLPILHYDWLKGKEFKCKVNSKSLPSPIERTI Q311Y, S426H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCHVSHEALHSHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHYDWLKGKEFKCKVNSKSLPSPIERTI Q311Y SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPIIHQDWLKGKEFKCKVNSKSLPSPIERTI L309I SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGFEFKCKVNSKSLPSPIERTI K317F SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substitutedLGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla FcAttorney Reference No. 2920951-551977 RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S408N SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYNKLSVDRSHWQRGNTYTCSVSHEALHSHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S428W SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVWHEALHSHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHWDWLKGKEFKCKVNSKSLPSPIERTI Q311W SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S428W, S434Q SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVWHEALHQHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLYITREPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI (YTE) SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS S252Y, S254T, T256E FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLSISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S434H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHHHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLYISRDPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252Y, T256D (YD) SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQK SLTQSPGKAttorney Reference No. 2920951-551977 CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252H, S408N, S426Q SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYNKLSVDRSHWQRGNTYTCQVSHEALHSHHTQ KSLTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGla Fc RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S252H, S434Q SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYSKLSVDRSHWQRGNTYTCSVSHEALHQHHTQ KSLTQSPGK PPPEMLGGPSIFIFPPKPKDTLYISRTPEVTCLWDL Exemplary substituted GPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTYR feline IgGla Fc WSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTIS S252Y KAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKSF HPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYFV YSKLSVDRSHWQRGNTYTCSVSHEALHSHHTQKS LTQSPGK CPPPEMLGGPSIFIFPPKPKDTLHISRTPEVTCLVVD Exemplary substituted LGPDDSDVQITWFVDNTQVYTAKTSPREEQFNSTY feline IgGlb Fc S252H, RWSVLPILHQDWLKGKEFKCKVNSKSLPSPIERTI S408N, S434H SKAKGQPHEPQVYVLPPAQEELSRNKVSVTCLIKS FHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYF VYNKLSVDRSHWQRGNTYTCSVSHEALHHHHTQ KSLTQSPGK DIVMTQTPLSLSVSPGETASISCRASQDISNYLNWY L4H1 -Canine Antibody QQKPGQSPQLLIYYTSRVPSGVPDRFSGSGSGTDFT Light Chain LRISRVEAEDTGVYFCQQGNTVPLTFGAGTKVELK RNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYPK DINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSST LTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC DIVMTQTPLSLSVSPGETASISCSASSRVTYMHWY S18-B-Canine Antibody LQKPGQSPQLLIKDTYKQAIGVSKRFSGSGSGTDFT Light Chain LRISRVEADDTGIYYCQQYNTVPPTFGQGTKLEIKR NDAQPAVYLFQPSPDQLHTGSASWCLLNSFYPKD INVKWKVDGVIQDTGIQESVTEQDKDSTYSLSSTL TMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC DIEMTQSPLSLSVTPGESVSISCRASEDIYNALAWY Frunevetmab-feline LQKPGRSPRLLIYNTDTLHTGVPDRFSGSGSGTDFT Antibody Light Chain LKISRVQTEDVGVYFCQHYFHYPRTFGQGTKLELK RSDAQPSVFLFQPSLDELHTGSASIVCILNDFYPKE VNVKWKVDGWQNKGIQESTTEQNSKDSTYSLSS TLTMSSTEYQSHEKFSCEVTHKSLASTLVKSFNRSE CQREAttorney Reference No. 2920951-551977 EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, S408N, A426Q SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICQVMHEALHNHYTQESLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, S408N SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYTQESLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, A287Q, S408N SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQISWFVDGKQMQTQKTQPREEQFNGTYRWSVLPIGHAttorney Reference No. 2920951-551977 QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYTQESLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI N434H SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHHHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, T256D SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARDPEVTCVVVDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI Q311Y SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH YDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, E380S, A426Q, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF T437RFDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSVAttorney Reference No. 2920951-551977 LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, A426Q, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4H1- canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, E380S, A426Q SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI G309E, E380S, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4H1- canine IgG-B FcWVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTIAttorney Reference No. 2920951-551977 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF V279R, A287W, FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS A426Q, T437R TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFRDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287Q, A426Q, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTQKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380S, A426Q, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A426Q, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEAttorney Reference No. 2920951-551977 WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI G309E, A426Q, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, V279R, A426Q SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFRDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, A426Q, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI G309E, M428H SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQISAttorney Reference No. 2920951-551977 WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVHHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380S, A426Q SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, E380S, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, S408N, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYRQESLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, S408N, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDFFDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGSAttorney Reference No. 2920951-551977 TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYRQESLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI T250M, P307T, G309E SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDMLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380S, M428H SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVHHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380H, A426Q, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVH WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQESLSHSPGKAttorney Reference No. 2920951-551977 EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI P307H, G309E, A426Q SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLHIE HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, E380S, A431G SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEGLHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, L306V, P307T SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVVTIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI T250H, P307T, G309E SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDHLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEAttorney Reference No. 2920951-551977 WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI P307H, G309E SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLHIE HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4H1-canine IgG-B WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI heavy chain (no SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF substitutions) FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380H, A426Q SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVH WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI M428H, T437R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQISAttorney Reference No. 2920951-551977 WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVHHEALHNHYRQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, P307T, G309E SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTWKTQPREEQFNGTYRWSVLTIE HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A426Q, M428H SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVHHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, P307T, G309E SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI P307T, G309E, K338R SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSVAttorney Reference No. 2920951-551977 LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISRARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPGK EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y, S408N, A426Q, RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG T437R (YRQN) LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY NKLSVDKSRWQRGDTFICQVMHEALHNHYRQES LSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y, A426Q, T437R RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG (YRQ) LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICQVMHEALHNHYRQESL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG A287W, Q311Y, RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG S408N, A426Q LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS (YWQN) CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTWKTQPREEQFNGTYRV VSVLPIGHYDWLKGKQFTCKVNNKALPSPIERTIS KARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLAttorney Reference No. 2920951-551977 YNKLSVDKSRWQRGDTFICQVMHEALHNHYTQE SLSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG L252Y, T256D (YD) RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLYIARDPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQESL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG N434H RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHHHYTQESL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG A287W, Q311Y, RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG S408N, T437R (YWRN) LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTWKTQPREEQFNGTYRV VSVLPIGHYDWLKGKQFTCKVNNKALPSPIERTIS KARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFF PPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL YNKLSVDKSRWQRGDTFICAVMHEALHNHYRQE SLSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG A287W, Q311Y, S408N RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG (YWN)LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSGAttorney Reference No. 2920951-551977 VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTWKTQPREEQFNGTYRV VSVLPIGHYDWLKGKQFTCKVNNKALPSPIERTIS KARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFF PPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL YNKLSVDKSRWQRGDTFICAVMHEALHNHYTQES LSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y(0Y0) RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQESL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y, S408N, T437R RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG (YRN) LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY NKLSVDKSRWQRGDTFICAVMHEALHNHYRQESL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG 311Y, S408N (0Y0N) RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYAttorney Reference No. 2920951-551977 NKLSVDKSRWQRGDTFICAVMHEALHNHYTQESL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG heavy chain (no RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG substitutions) LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQESL SHSPG QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGla heavy chain WT TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS (no substitutions) SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGla Fc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, Q311Y, S428F SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHYDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVFHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGla Fc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, Q311Y, S434H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSCGTTSGATVALACLVLGYFPEPVTVSWNSGALTSGAttorney Reference No. 2920951-551977 VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHYDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHHHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, S428F SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVFHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, S434H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHHHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, S428F, S434H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKAttorney Reference No. 2920951-551977 LSVDRSHWQRGNTYTCSVFHEALHHHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S428F S434H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVFHEALHHHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS V305Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS QLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S434Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVSHEALHQHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S434MSSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSCGTTSGATVALACLVLGYFPEPVTVSWNSGALTSGAttorney Reference No. 2920951-551977 VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVSHEALHMHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S428F SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVFHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S426Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCQVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S426H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKLAttorney Reference No. 2920951-551977 SVDRSHWQRGNTYTCHVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252Q, S428F SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLQISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVFHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLQISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, Q311Y, S426Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHYDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCQVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, Q311Y SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSCGTTSGATVALACLVLGYFPEPVTVSWNSGALTSGAttorney Reference No. 2920951-551977 VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHYDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS Q311Y, S426H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHYDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCHVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS Q311Y SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHYDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKLAttorney Reference No. 2920951-551977 SVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS L309I SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPIIHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS K317F SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGFEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S408N SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYNKL SVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S428WSSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSCGTTSGATVALACLVLGYFPEPVTVSWNSGALTSGAttorney Reference No. 2920951-551977 VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVWHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS Q311W SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHWDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S428W, S434Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVWHEALHQHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS (YTE) SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC S252Y, S254T, T256E GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLYITREPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDIAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKAttorney Reference No. 2920951-551977 LSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S434H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLSISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVSHEALHHHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252Y, T256D (YD) SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLYISRDPEVTCLVVDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, S408N, S426Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYNK LSVDRSHWQRGNTYTCQVSHEALHSHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252H, S434Q SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSCGTTSGATVALACLVLGYFPEPVTVSWNSGALTSGAttorney Reference No. 2920951-551977 VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSK LSVDRSHWQRGNTYTCSVSHEALHQHHTQKSLTQ SPGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab-feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S252Y SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLYISRTPEVTCLWDLGPDD SDVQITWFVDNTQVYTAKTSPREEQFNSTYRWSV LPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAKG QPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPDI AVEWEITGQPEPENNYRTTPPQLDSDGTYFVYSKL SVDRSHWQRGNTYTCSVSHEALHSHHTQKSLTQS PGK QVQLVESGAELVQPGESLRLTCAASGFSLTNNNVN Frunevetmab- feline WVRQAPGKGLEWMGGVWAGGATDYNSALKSRL IgGlaFc S252H, TITRDTSKNTVFLQMHSLQSEDTATYYCARDGGYS S408N, S434H SSTLYAMDAWGQGTTVTVSAASTTAPSVFPLAPSC GTTSGATVALACLVLGYFPEPVTVSWNSGALTSG VHTFPAVLQASGLYSLSSMVTVPSSRWLSDTFTCN VAHPPSNTKVDKTVRKTDHPPGPKPCDCPKCPPPE MLGGPSIFIFPPKPKDTLHISRTPEVTCLWDLGPD DSDVQITWFVDNTQVYTAKTSPREEQFNSTYRWS VLPILHQDWLKGKEFKCKVNSKSLPSPIERTISKAK GQPHEPQVYVLPPAQEELSRNKVSVTCLIKSFHPPD IAVEWEITGQPEPENNYRTTPPQLDSDGTYFVYNK LSVDRSHWQRGNTYTCSVSHEALHHHHTQKSLTQ SPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, S408N, A426Q, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGAttorney Reference No. 2920951-551977 SYFLYNKLSVDKSRWQRGDTFICQVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, S408N, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTQKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, A287Q, S408N, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE N434H, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHHHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARDPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, T256D, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287W, E380S, A426Q,RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI T437R, K439Attorney Reference No. 2920951-551977 KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287W, A426Q, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI T437R, K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, E380S, A426Q, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIEHQDWLKGKQFTCKVNNKALPSPIE G309E, E380S, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFRDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE V279R, A287W, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI A426Q, T437R, K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTQKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287Q, A426Q, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380S, A426Q, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B FcTYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A426Q, T437R, K439Attorney Reference No. 2920951-551977 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIEHQDWLKGKQFTCKVNNKALPSPIE G309E, A426Q, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFRDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, V279R, A426Q, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, A426Q, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIEHQDWLKGKQFTCKVNNKALPSPIE G309E, M428H, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVHHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380S, A426Q, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, E380S, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substitutedDLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B FcAttorney Reference No. 2920951-551977 TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A287W, S408N, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, S408N, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDMLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE T250M, P307T, G309E, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380S, M428H, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVHHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380H, A426Q, T437R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVHWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLHIEHQDWLKGKQFTCKVNNKALPSPI P307H, G309E, A426Q, ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL K439 IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICQVMHEALHNH YTQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252H, E380S, A431G, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVSWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEGLHNHY TQKSLSHSPGKAttorney Reference No. 2920951-551977 CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVVTIGHQDWLKGKQFTCKVNNKALPSPI L252H, L306V, P307T, ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL K439 IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNH YTQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDHLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE T250H, P307T, G309E, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLHIEHQDWLKGKQFTCKVNNKALPSPI P307H, G309E, K439 ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNH YTQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE E380H, A426Q, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVHWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE M428H, T437R, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVHHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE A287W, P307T, G309E, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE A426Q, M428H, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGAttorney Reference No. 2920951-551977 SYFLYSKLSVDKSRWQRGDTFICQVHHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE L252H, P307T, G309E, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLTIEHQDWLKGKQFTCKVNNKALPSPIE P307T, G309E, K338R, RTISRARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, S408N, A426Q, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI T437R (YRQN), K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, A426Q, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI (YRQ), K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICQVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE A287W, Q311Y, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI S408N, A426Q KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG (YWQN), K439 SYFLYNKLSVDKSRWQRGDTFICQVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYIARDPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y, T256D (YD), RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIAttorney Reference No. 2920951-551977 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG A287W, Q311Y, SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY S408N, T437R RQKSLSHSPGK (YWRN), K439 CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTWKTQPREEQFNG canine IgG-B Fc TYRVVSVLPIGHYDWLKGKQFTCKVNNKALPSPIE A287W, Q311Y, S408N RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI (YWN), K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRVVSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y (0Y0), K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, S408N, T437R RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI (YRN), K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY RQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc TYRWSVLPIGHYDWLKGKQFTCKVNNKALPSPIE Q311Y, S408N (0Y0N), RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYNKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLYITREPEVTCVW Exemplary substituted DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG canine IgG-B Fc (YTE) TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252Y A254T T256E, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK EIVMTQSPASLSLSQEEKVTITCRASQDISNYLNWY KCB- LIHl-Canine QQKPGQAPKLLIYYTSRVPSGVPSRFSGSGSGTDFT Antibody Light Chain FTISSLEPEDVAVYYCQQGNTVPLTFGAGTKVELK RNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYPK DINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSST LTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC QAVLNQPASVSGALGQKVTISCSGSTNDIDIFGVS AB397-Canine WYQQLPGKAPKLLVDSDGDRPSGVPDRFSGSSSG Antibody Light Chain NSGTLTITGLQAEDEADYYCQSVDSTLGAYVFGSGTQLTVLGQPKASPSVTLFPPSSEELGANKATLVCLIAttorney Reference No. 2920951-551977 SDFYPSGVTVAWKADGSPVTQGVETTKPSKQSNN KYAASSYLSLTPDKWKSHSSFSCLVTHEGSTVEKK VAPAECS SSVLTQPPSVSVSLGQTVTISCSGESLSKYYAKWFQ ABIOO-Canine QKAGQAPVLVIYKDTERPSGIPDRFSGSSSGNTHTL Antibody Light Chain TISGARAEDEADYYCESTVTTDTGIVFGGGTHLTV LGQPKASPSVTLFPPSSEELGANKATLVCLISDFYP SGVTVAWKADGSPVTQGVETTKPSKQSNNKYAAS SYLSLTPDKWKSHSSFSCLVTHEGSTVEKKVAPAE CS QAVLTQPPSVSAALGQRVTISCTGSNTNIGNDYDV AB171-Canine HWYQQLPGKSPKTHYGDTYRPSGVPVRFSGSKSG Antibody Light Chain STATLTITGIQAEDEGDYYCQSHDDDLDGYVFGSG TQLTVLGQPKASPSVTLFPPSSEELGANKATLVCLI SDFYPSGVTVAWKADGSPVTQGVETTKPSKQSNN KYAASSYLSLTPDKWKSHSSFSCLVTHEGSTVEKK VAPAECS SYVLTQLPSVSVNLGKTASITCEGNNIGDKYVNWY AB233-Canine QQKPGQAPWIIYEDRRRPSGIPERFSGSNSGNTAT Antibody Light Chain LTISGAGAEDEAAYYCQLWDNSAKAAVFGGGTHL TVLGQPKASPSVTLFPPSSEELGANKATLVCLISDF YPSGVTVAWKADGSPVTQGVETTKPSKQSNNKYA ASSYLSLTPDKWKSHSSFSCLVTHEGSTVEKKVAP AECS EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS KCB- LIHl-Canine WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI Antibody IgG-B Heavy SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF Chain FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPG EIQLVESGGDLVKPAGSLRLSCVTSGFTFSSYGMS AB397-Canine WVRQAPGKGLQWVAGIDSGVNTGYADAVKGRFT Antibody IgG-B Heavy ISRDNAKNTVYLQMNSLRAEDTAVYYCAKDQWQ Chain LADFDYWGQGTLVTVSSASTTAPSVFPLAPSCGST SGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTF PSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHP ASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLG GPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPE VQISWFVDGKQMQTAKTQPREEQFNGTYRWSVL PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSKAttorney Reference No. 2920951-551977 LSVDKSRWQRGDTFICAVMHEALHNHYTQESLSH SPG EVQLVESGGDLAKPGGSLRLSCVASGLTFSSYSMI ABIOO-Canine WVRQAPGKGLQWVTTISYDGSTTYYTDAVKGRFT Antibody IgG-B Heavy ISRDNARNTVYLQMNSLRTEDTAVYYCRWPNW Chain GVEYWGQGTLVTVSSASTTAPSVFPLAPSCGSTSG STVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPS VLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPAS KTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPS VFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPG EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS AB171-Canine WVRQSPGKGLQWVADISSSGSTYYADAVKGRFTI Antibody IgG-B Heavy SRDNAKNTLYLQMNSLRAEDTAVYYCAKEGGSY Chain NYVEDWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPG EVELVESGGDLVKPGGSLRLSCVASGFTFSSYDMN AB233-Canine WVRQAPGKGLQWVAYISSVGSYTYYADGVKGRF Antibody IgG-B Heavy TISRDNAKNTLYLQMNSLRAEDTAMYYCAGGPDE Chain SNDNYLDAFGYWGQGTLVTVSSASTTAPSVFPLAP SCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTS GVHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCN VAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQESL SHSPG EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS KCB- LIHl-Canine WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI Antibody IgG-B Heavy SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF Chain, K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSVAttorney Reference No. 2920951-551977 FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPG EIQLVESGGDLVKPAGSLRLSCVTSGFTFSSYGMS AB397-Canine WVRQAPGKGLQWVAGIDSGVNTGYADAVKGRFT Antibody IgG-B Heavy ISRDNAKNTVYLQMNSLRAEDTAVYYCAKDQWQ Chain, K439 LADFDYWGQGTLVTVSSASTTAPSVFPLAPSCGST SGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTF PSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHP ASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLG GPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPE VQISWFVDGKQMQTAKTQPREEQFNGTYRWSVL PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPG EVQLVESGGDLAKPGGSLRLSCVASGLTFSSYSMI ABIOO-Canine WVRQAPGKGLQWVTTISYDGSTTYYTDAVKGRFT Antibody IgG-B Heavy ISRDNARNTVYLQMNSLRTEDTAVYYCRWPNW Chain, K439 GVEYWGQGTLVTVSSASTTAPSVFPLAPSCGSTSG STVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPS VLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPAS KTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPS VFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPG EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS AB171-Canine WVRQSPGKGLQWVADISSSGSTYYADAVKGRFTI Antibody IgG-B Heavy SRDNAKNTLYLQMNSLRAEDTAVYYCAKEGGSY Chain, K439 NYVEDWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPG EVELVESGGDLVKPGGSLRLSCVASGFTFSSYDMN AB233-Canine WVRQAPGKGLQWVAYISSVGSYTYYADGVKGRF Antibody IgG-B HeavyTISRDNAKNTLYLQMNSLRAEDTAMYYCAGGPDE Chain, K439Attorney Reference No. 2920951-551977 SNDNYLDAFGYWGQGTLVTVSSASTTAPSVFPLAP SCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTS GVHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCN VAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSL SHSPG EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, S408N, A426Q, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICQVMHEALHNHYTQKSLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, S408N, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYTQKSLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEAttorney Reference No. 2920951-551977 WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, A287Q, S408N, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTQKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYTQKSLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI N434H, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHHHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252Y, T256D, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLYIARDPEVTCVVVDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI Q311Y, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSVAttorney Reference No. 2920951-551977 FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH YDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, E380S, A426Q, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF T437R, K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, A426Q, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF T437R, K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4H1- canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, E380S, A426Q, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI G309E, E380S, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGSAttorney Reference No. 2920951-551977 TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4H1- canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI V279R, A287W, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF A426Q, T437R, K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFRDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287Q, A426Q, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTQKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380S, A426Q, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGKAttorney Reference No. 2920951-551977 EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A426Q, T437R, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI G309E, A426Q, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, V279R, A426Q, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFRDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, A426Q, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEAttorney Reference No. 2920951-551977 WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI G309E, M428H, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVHHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380S, A426Q, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, E380S, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, S408N, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQISAttorney Reference No. 2920951-551977 WFVDGKQMQTWKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYRQKSLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, S408N, T437R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYRQKSLSHSPG K EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI T250M, P307T, G309E, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDMLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380S, M428H, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVHHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380H, A426Q, T437R,SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439Attorney Reference No. 2920951-551977 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVH WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI P307H, G309E, A426Q, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLHIE HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, E380S, A431G, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVS WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEGLHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, L306V, P307T, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVVTIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGKAttorney Reference No. 2920951-551977 EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI T250H, P307T, G309E, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDHLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI P307H, G309E, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLHIE HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4H1-canine IgG-B WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI heavy chain, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI E380H, A426Q, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVHAttorney Reference No. 2920951-551977 WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI M428H, T437R, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVHHEALHNHYRQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A287W, P307T, G309E, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTWKTQPREEQFNGTYRWSVLTIE HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI A426Q, M428H, K439 SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICQVHHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI L252H, P307T, G309E, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSVFIFPPKPKDTLHIARTPEVTCVWDLDPEDPEVQISAttorney Reference No. 2920951-551977 WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISKARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVESGGNLVKPGGSLRLSCAASGFTFSDYYMS L4Hl-canine IgG-B Fc WVRQAPGKRLQWVATISDFGTYTFYPDSVKGRFTI P307T, G309E, K338R, SRDNAKNTLYLQMNSLRAEDSAVYYCARLTGTDF K439 FDWWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGS TVALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSV LQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASK TKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGPSV FIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQIS WFVDGKQMQTAKTQPREEQFNGTYRWSVLTIEH QDWLKGKQFTCKVNNKALPSPIERTISRARGQAH QPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPGK EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y, S408N, A426Q, RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG T437R (YRQN), K439 LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY NKLSVDKSRWQRGDTFICQVMHEALHNHYRQKS LSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y, A426Q, T437R RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG (YRQ), K439 LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICQVMHEALHNHYRQKS LSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKGRVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGGAttorney Reference No. 2920951-551977 LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS A287W, Q311Y, CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG S408N, A426Q VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV (YWQN), K439 AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTWKTQPREEQFNGTYRV VSVLPIGHYDWLKGKQFTCKVNNKALPSPIERTIS KARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFF PPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL YNKLSVDKSRWQRGDTFICQVMHEALHNHYTQK SLSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG L252Y, T256D (YD), RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG K439 LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLYIARDPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG N434H, K439 RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHHHYTQKSL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG A287W, Q311Y, RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG S408N, T437R LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS (YWRN), K439 CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTWKTQPREEQFNGTYRV VSVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFAttorney Reference No. 2920951-551977 PPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL YNKLSVDKSRWQRGDTFICAVMHEALHNHYRQK SLSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG A287W, Q311Y, S408N RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG (YWN), K439 LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPE DPEVQISWFVDGKQMQTWKTQPREEQFNGTYRV VSVLPIGHYDWLKGKQFTCKVNNKALPSPIERTIS KARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFF PPDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFL YNKLSVDKSRWQRGDTFICAVMHEALHNHYTQK SLSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y (0Y0), K439 RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSL SHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG Q311Y, S408N, T437R RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG (YRN), K439 LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY NKLSVDKSRWQRGDTFICAVMHEALHNHYRQKS LSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B Fc NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG 311Y, S408N (0Y0N), RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG K439LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPSAttorney Reference No. 2920951-551977 CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHYDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY NKLSVDKSRWQRGDTFICAVMHEALHNHYTQKS LSHSPG EVQLVQSGAEVKKPGASVKVSCKTSGYTFTNYGM S18-B-canine IgG-B NWVRQAPGAGLDWMGWIDTYTGEATYADNFKG heavy chain, K439 RVTLTADTSTSTAYMELSSLRAGDIAVYYCARSGG LIYRSYPMDYWGQGTSVTVSSASTTAPSVFPLAPS CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSL SHSPG CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE N434F, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHFHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE N434Y, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHYHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE N434A, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHYHY TQASLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE N434S, K439RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLIAttorney Reference No. 2920951-551977 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHSHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE Y436T, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHT TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE Q438R, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TRKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE K439, S440E RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKELSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE M428L, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVLHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPPGHQDWLKGKQFTCKVNNKALPSPI I308P, K439 ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNH YTQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPFGHQDWLKGKQFTCKVNNKALPSPI I308F, K439 ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHNH YTQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEATCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447,TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE V259A, K439Attorney Reference No. 2920951-551977 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLTIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252T, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE N434Y, Y436T, Q438R, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439, S440E KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHYHT TRKELSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE M428L, N434A, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI Q438R, K439, S440E KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVLHEALHAHY TRKELSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE M428L, N434S, K439 RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVLHEALHSHYT QKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEVTCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPPGHQDWLKGKQFTCKVNNKALPSPI I308P, N434Y, K439 ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVMHEALHYH YTQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLLIARTPEATCVW Canine IgG-B Fc EU DLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447, TYRWSVLPFGHQDWLKGKQFTCKVNNKALPSPI V259A, I308F, K439, ERTISKARGQAHQPSVYVLPPSREELSKNTVSLTCL M428L IKDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDED GSYFLYSKLSVDKSRWQRGDTFICAVLHEALHNH YTQKSLSHSPGK CPAPEMLGGPSVFIFPPKPKDTLTITREPEVTCVW Canine IgG-B Fc EUDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNG Residues 228-447,Attorney Reference No. 2920951-551977 TYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIE L252T, A254T, T256E, RTISKARGQAHQPSVYVLPPSREELSKNTVSLTCLI K439 KDFFPPDIDVEWQSNGQQEPESKYRTTPPQLDEDG SYFLYSKLSVDKSRWQRGDTFICAVMHEALHNHY TQKSLSHSPGK EVQLVESGGDLVKPGGSLRLSCVASGFTFSSHGMH Bedinvetmab heavy WVRQSPGKGLQWVAVINSGGSSTYYTDAVKGRFT chain Canine IgG-B ISRDNAKNTVYLQMNSLRAEDTAMYYCAKESVG K439 GWEQLVGPHFDYWGQGTLVIVSSASTTAPSVFPLA PSCGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTS GVHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCN VAHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE AAGAPSVFIFPPKPKDTLLIARTPEVTCVWDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSL SHSPGK QSVLTQPTSVSGSLGQRVTISCSGSTNNIGILGASW Bedinvetmab light chain YQLFPGKAPKLLVYGNGNRPSGVPDRFSGADSGD SVTLTITGLQAEDEADYYCQSFDTTLGAHVFGGGT HLTVLGQPKASPSVTLFPPSSEELGANKATLVCLIS DFYPSGVTVAWKADGSPVTQGVETTKPSKQSNNK YAASSYLSLTPDKWKSHSSFSCLVTHEGSTVEKKV APAECS GPGZXE5GPGLVOPSOTLSLTCTVSGFSLSSYHVH Chimeric variable heavy WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRLS chain of Parvovirus Mab ISRDTSKSQVFFKMSSLQTEDTATYYCARPELPGLT A and canine IgG-B; YGVWFPYWGQGTLVTVSSASTTAPSVFPLAPSCGS (Chimeric A HC IgG-B, TSGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHT K439) FPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHP ASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLG GPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPE VQISWFVDGKQMQTAKTQPREEQFNGTYRWSVL PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK GPGZXE5GPGLVAPSOTLSLTCTVSGFSLSSYHVH Chimeric variable heavy WVRQPPGKGLEWLGVMWNDGDTSYNLALNSRLS chain of Parvovirus Mab ISRDTSKSQVFFKMSSLQTEDTATYYCARPELPGLT A v2 and canine IgG-B YGVWFPYWGQGTLVTVSAASTTAPSVFPLAPSCG K439; HC-FR1 Q13A; STSGSTVALACLVSGYFPEPVTVSWNSGSLTSGVH HC-FR4 S11A; TFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAH (Chimeric A HC v2 PASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLG IgG-B, K439) GPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRWSVLAttorney Reference No. 2920951-551977 PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK QVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHVH Caninized variable WVRQPPGKGLEWVAVMWNDGDTSYNLAVKGRF heavy chain of TISRDNAKNTLYLQMNSLRAEDTAVYYCARPELP Parvovirus Mab A v3 GLTYGVWFPYWGQGTLVTVSSASTTAPSVFPLAPS and canine IgG-B K439 CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRW SVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISK ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSL SHSPGK EVQLVESGGDLVKPGGTLRLSCTVSGFSLSSYHVH Caninized variable WVRQPPGKGLEWLGVMWNDGDTSYNLAVKGRF heavy chain of TISRDNAKNTLYFQMNSLRAEDTATYYCARPELPG Parvovirus Mab A v4 LTYGVWFPYWGQGTLVTVSSASTTAPSVFPLAPSC and canine K439 IgG-B; GSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSGV (Caninized A HC v4 HTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVA IgG-B) HPASKTKVDKPVPKRENGRVPRPPDCPKCPAPEML GGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDP EVQISWFVDGKQMQTAKTQPREEQFNGTYRWSV LPIGHQDWLKGKQFTCKVNNKALPSPIERTISKAR GQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDroVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK EIVMTQSPASLSLSQEEKVTITCKASQNVDSNVDW Caninized variable light YQQKPGQAPKLLIYKASNRNTGVPSRFSGSGSGTD chain of Parvovirus Mab FSFTISSLEPEDVAVYYCMQSTSYPLTFGQGTKLEI A and canine K light KRNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYP constant region KDINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSS (Caninized A LC K) TLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC QRVD QVQLKESGPGLVQPSQTLSLTCTVSGFSLTSYGVS Chimeric variable heavy WVRQPPGKGLEWIGTMWNDGDTDYHSALRSRLSI chain of Parvovirus Mab SRDSSKSQVLLKMNSLQTEDTAMYFCARSQLPGY B and canine K439 IgG- NLRGWFVYWGQGTLVIVSASTTAPSVFPLAPSCGS B TSGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHT FPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHP ASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLG GPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQISWFVDGKQMQTAKTQPREEQFNGTYRWSVLAttorney Reference No. 2920951-551977 PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK QVQLKESGPGLVQPSETLSLTCTVSGFSLTSYGVS Chimeric variable heavy WVRQPPGKGLEWMGTMWNDGDTDYNSALRSKL chain of Mab B v2 and SISRDTSKSQVFLKMNSLQTEDTAIYYCARSQLPG canine IgG-B YNLRGWFVYWGQGTLVIVSAASTTAPSVFPLAPSC GSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSGV HC-FR1 Q16E HTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVA HC-FR2 IBM HPASKTKVDKPVPKRENGRVPRPPDCPKCPAPEML HC-FR3 H2N GGPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDP HC-FR3 R8K EVQISWFVDGKQMQTAKTQPREEQFNGTYRWSV HC-FR3 S15T LPIGHQDWLKGKQFTCKVNNKALPSPIERTISKAR HC-FR3 L21F GQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPD HC-FR3 M34I roVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK HC-FR3 F36Y LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK (Chimeric B HC v2 K439 IgG-B) DIVMTQTPSLLSASVGDRVTLNCKASHNINKNLEW Chimeric variable light YQQKLGEAPKLLIYYANNLQTGISSRFSGSGSGTD chain of Mab B and YTLTISSLQPEDVATYYCYQYNSGHTFGAGTKLEL canine K light constant KRNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYP region KDINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSS TLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC (Chimeric B LC K) QRVD DIQMTQSPPVLSASVGDRVTLSCKASHNINKNLEW Chimeric variable light YQQKLGEAPKLLIYYANNLQTGIPSRFSGSGSGTD chain of Mab B v2 and YTLTISSLQPEDVATYYCYQYNSGHTFGAGTKLEI canine K light constant KRNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYP region KDINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSS LC-FR1 V3Q TLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC LC-FR1 T7S QRVD LC-FR1 S9PLC-FR1 L10VLC-FR1 N22SLC-FR3 S3PLC-FR4 L8I (Chimeric B LC v2 K) EVQLVESGGDLVKPGGTLRLSCTVSGFSLTSYGVS Caninized variable WVRQSPGKGLEWIGTMWNDGDTDYHSAVKGQLS heavy chain of Mab B ISRDTSKSQVFLQMNSLRAEDTAMYYCARSQLPG v3 and canine K439 YNLRGWFVYWGQGTLVTVSSASTTAPSVFPLAPS IgG-B CGSTSGSTVALACLVSGYFPEPVTVSWNSGSLTSG (Caninized B HC v3 VHTFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNV IgG-B) AHPASKTKVDKPVPKRENGRVPRPPDCPKCPAPE MLGGPSVFIFPPKPKDTLLIARTPEVTCVVVDLDPE DPEVQISWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKAttorney Reference No. 2920951-551977 ARGQAHQPSVYVLPPSREELSKNTVSLTCLIKDFFP PDIDVEWQSNGQQEPESKYRTTPPQLDEDGSYFLY SKLSVDKSRWQRGDTFICAVMHEALHNHYTQKSL SHSPGK EIVLTQSPASLAVSLGQRATISCKASHNINKNLEWY Caninized variable light QQKPGQPPKLLIYYANNLQTGVPARFSGSGSGTDY chain of Mab B v3 and SLNIHPMEEDDTAMYYCYQYNSGHTFGGGTKLEI canine K light constant KRNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYP region KDINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSS TLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC (Caninized B LC v3 K) QRVD EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS Lokivetmab, Heavy WVRQAPGKGLQWVATISYGGSYTYYPDNIKGRFT Chain (K439) ISRDNAKNTLYLQMNSLRAEDTAMYYCVRGYGY DTMDYWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQKSLSHSPG EIVMTQSPASLSLSQEEKVTITCKASQSVSFAGTGL Lokivetmab, Light MHWYQQKPGQAPKLLIYRASNLEAGVPSRFSGSG Chain SGTDFSFTISSLEPEDVAVYYCQQSREYPWTFGQG TKLEIKRNDAQPAVYLFQPSPDQLHTGSASWCLL NSFYPKDINVKWKVDGVIQDTGIQESVTEQDKDST YSLSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSF QRSEC EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYWM Izenivetmab, Heavy HWVRQAPGKGLQWVARIDPYGGGTKHNEKFKRR Chain (K439) FTISRDNAKNTLYLQMNSLRAEDTAMYYCVRSGY DYYFDVWGQGTLVTVSSASTTAPSVFPLAPSCGST SGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTF PSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHP ASKTKVDKPVPKRENGRVPRPPDCPKCPAPEAAG APSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPE VQISWFVDGKQMQTAKTQPREEQFNGTYRWSVL PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK EIVMTQSPASLSLSQEEKVTITCRASENIYSFLAWY Izenivetmab, LightQQKPGQAPKLLIYNANTLAEGVPSRFSGSGSGTDF ChainAttorney Reference No. 2920951-551977 SFTISSLEPEDVAVYYCQHHFGTPFTFGQGTKLEIK RNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYPK DINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSST LTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC EVQLVQSGAEVKKPGASVKVSCKTSGYTFISSWM Cirevetmab, Heavy NWVRQAPGAGLDWMGQIYPGDGDTNYNGKFKG Chain (K439) RVTLTADTSTSTAYMELSSLRAGDIAVYYCARHY DGSTDYWGQGTLVTVSSASTTAPSVFPLAPSCGST SGSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTF PSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHP ASKTKVDKPVPKRENGRVPRPPDCPKCPAPEAAG APSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPE VQISWFVDGKQMQTAKTQPREEQFNGTYRWSVL PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK EIVMTQSPASLSLSQGEKVTITCRASENIYSNLAWY Cirevetmab, Light Chain QQRPGQAPKLLIYAATNLADGVPSRFSGSGSGTDF SLTISSLEPEDVAVYYCQHFWGTPYTFGQGTKLEI KRNDAQPAVYLFQPSPDQLHTGSASWCLLNSFYP KDINVKWKVDGVIQDTGIQESVTEQDKDSTYSLSS TLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC EVQLVQSGGDLVKPGGSVRLSCVASGFNIKNTYM Gilvetmab, Heavy Chain HWVRQAPGKGLQWIGRIAPANVDTKYAPKFQGK (K439) ATISADTAKNTAYMQLNSLRAEDTAVYYCVLIYY DYDGDIDVWGQGTLVTVSSASTTAPSVFPLAPSCG STSGSTVALACLVSGYFPEPVTVSWNSGSLTSGVH TFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAH PASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLG GPSVFIFPPKPKDTLLIARTPEVTCVWALDPEDPE VQISWFVDGKQMQTAKTQPREEQFAGTYRWSVL PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQKSLSH SPGK DIVMTQTPLSLSVSLGEPASISCHASQNINVWLSW Gilvetmab, Light Chain YRQKPGQIPQLLIYKASHLHTGVPDRFSGSGSGTDF TLRISRVEADDAGVYYCQQGQSWPLTFGQGTKVE IKRNDAQPAVYLFQPSPDQLHTGSASWCLLNSFY PKDINVKWKVDGVIQDTGIQESVTEQDSKDSTYSL SSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRS ECQRVD FVNQHLCGSHLVEALALVCGERGFHYGGGGGGSG Insulin, eflivet, Chain 1GGGGIVEQCCTSTCSLDQLENYCGGGGGQGGGGQ (K439)Attorney Reference No. 2920951-551977 GGGGQGGGGGDCPKCPAPEMLGGPSVFIFPPKPKD TLLIARTPEVTCVWDLDPEDPEVQISWFVDGKQM QTAKTQPREEQFSGTYRWSVLPIGHQDWLKGKQ FTCKVNNKALPSPIERTISKARGQAHQPSVYVLPPS REELSKNTVSLTCLIKDFFPPDIDVEWQSNGQQEPE SKYRTTPPQLDEDGSYFLYSKLSVDKSRWQRGDTF ICAVMHEALHNHYTQKSLSHSPG EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS Riltovetbart, Heavy WVRQAPGKGLQWVATISYGGSYTYYPDNIKGRFT Chain (K439) ISRDNAKNTLYLQMNSLRAEDTAMYYCVRGYGY DTMDYWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHHHYTQKSLSHSPGK EIVMTQSPASLSLSQEEKVTITCKASQSVSFAGTGL Riltovetbart, Light MHWYQQKPGQAPKLLIYRASNLEAGVPSRFSGSG Chain SGTDFSFTISSLEPEDVAVYYCQQSREYPWTFGQG TKLEIKRNDAQPAVYLFQPSPDQLHTGSASWCLL NSFYPKDINVKWKVDGVIQDTGIQESVTEQDKDST YSLSSTLTMSSTEYLSHELYSCEITHKSLPSTLIKSF QRSEC EVTLQESGPGLVKPSQTLSLTCVASGFSIKSSFIHW Nolavetbart, Heavy LRQRPGRGLEWIGRIDPAFGATEYNPAFQGRFSITA Chain (K439) DTAKNQASLQLSSMTTEDSAVYYCARYHYAASHF DAWGQGTLVTVSSASTTAPSVFPLAPSCGSTSGST VALACLVSGYFPEPVTVSWNSGSLTSGVHTFPSVL QSSGLYSLSSMVTVPSSRWPSETFTCNVAHPASKT KVDKPVPKRENGRVPRPPDCPKCPAPEAAGGPSVF IFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQISW FVDGKQMQTAKTQPREEQFNGTYRWSVLPIGHQ DWLKGKQFTCKVNNKALGSPIERTISKARGQAHQ PSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVEW QSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVDK SRWQRGDTFICAVMHEALHNHYTQKSLSHSPG RIVMTQSPGSLAGSVGESVSINCKSSQSVTNDLTW Nolavetbart, Light Chain YQQKPGEAPKVLITYASQRYTGVPARFSGSGYGTD FTLTINNLQAEDVGDYFCQQDYASPFTFGQGTKLE IKRNDAQPAVYLFQPSPDQLHTGSASWCLLNSFY PKDINVKWKVDGVIQDTGIQESVTEQDKDSTYSLS STLTMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSECAttorney Reference No. 2920951-551977 EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS Lokivetmab Heavy WVRQAPGKGLQWVATISYGGSYTYYPDNIKGRFT Chain ISRDNAKNTLYLQMNSLRAEDTAMYYCVRGYGY DTMDYWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIG HQDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHNHYTQESLSHSPG EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS Lokivetmab Heavy WVRQAPGKGLQWVATISYGGSYTYYPDNIKGRFT Chain Q311Y, A426Q, ISRDNAKNTLYLQMNSLRAEDTAMYYCVRGYGY T437D DTMDYWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIG HYDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYRQESLSHSPG EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS Lokivetmab Heavy WVRQAPGKGLQWVATISYGGSYTYYPDNIKGRFT Chain Q311Y, A426Q, ISRDNAKNTLYLQMNSLRAEDTAMYYCVRGYGY T437D, K439 DTMDYWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIG HYDWLKGKQFTCKVNNKALPSPIERTISKARGQA HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYNKLSV DKSRWQRGDTFICAVMHEALHNHYRQKSLSHSPG EVQLVESGGDLVKPGGSLRLSCVASGFTFSNYGMS Lokivetmab Heavy WVRQAPGKGLQWVATISYGGSYTYYPDNIKGRFT Chain N434H, K439 ISRDNAKNTLYLQMNSLRAEDTAMYYCVRGYGY DTMDYWGQGTLVTVSSASTTAPSVFPLAPSCGSTS GSTVALACLVSGYFPEPVTVSWNSGSLTSGVHTFP SVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAHPA SKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLGGP SVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPEVQI SWFVDGKQMQTAKTQPREEQFNGTYRWSVLPIGHQDWLKGKQFTCKVNNKALPSPIERTISKARGQAAttorney Reference No. 2920951-551977 HQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDIDVE WQSNGQQEPESKYRTTPPQLDEDGSYFLYSKLSVD KSRWQRGDTFICAVMHEALHHHYTQKSLSHSPG348 DIVMTQTPPSLSVSPGEPASISCRASQSISNNLNWY Caninized Tanezumab, QKPGQSPQLLIYYTSRFHSGVSDRFSGSGSGTDFTL light chain RISRVEADDTGIYYCQQEHTLPYTFGQGTKLEIKR NDAQPAVYLFQPSPDQLHTGSASWCLLNSFYPKD INVKWKVDGVIQDTGIQESVTEQDKDSTYSLSSTL TMSSTEYLSHELYSCEITHKSLPSTLIKSFQRSEC349 EVQLVESGGDLVKPGGTLRLSCVASGFSLIGYDLN Caninized Tanezumab, WVRQSPGKGLQWVAIIWGDGTTDYNSAVKSRFTI heavy chain SRDNAKNTLYLEMNSLRAEDTAVYYCATGGYWY ATSYYFDYWGQGTLVTVSSASTTAPSVFPLAPSCG STSGSTVALACLVSGYFPEPVTVSWNSGSLTSGVH TFPSVLQSSGLYSLSSMVTVPSSRWPSETFTCNVAH PASKTKVDKPVPKRENGRVPRPPDCPKCPAPEMLG GPSVFIFPPKPKDTLLIARTPEVTCVWDLDPEDPE VQISWFVDGKQMQTAKTQPREEQFNGTYRWSVL PIGHQDWLKGKQFTCKVNNKALPSPIERTISKARG QAHQPSVYVLPPSREELSKNTVSLTCLIKDFFPPDI DVEWQSNGQQEPESKYRTTPPQLDEDGSYFLYSK LSVDKSRWQRGDTFICAVMHEALHNHYTQESLSH SPGExemplary Substituted or Variant IgG Fc Polypeptides with Modified FcRn Binding

[0118] In some embodiments, a substituted or variant IgG Fc polypeptide is a companion animal IgG Fc. In some embodiments, a substituted or variant IgG Fc polypeptide is a substituted or variant canine IgG Fc polypeptide, a substituted or variant equine IgG Fc polypeptide, or a substituted or variant feline IgG Fc polypeptide. In some embodiments, a substituted or variant IgG Fc polypeptide has modified FcRn binding affinity compared to a reference polypeptide, such as a wild-type IgG Fc polypeptide. In some embodiments, a substituted or variant IgG Fc polypeptide has increased FcRn binding affinity at an acidic pH (e.g., at a pH in the range of from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.5, a pH of about 6.0, or a pH of about 6.5) compared to a reference polypeptide, such as a wild-type IgG Fc polypeptide. In aspects, substituted or variant IgG Fc polypeptides selected from Table 4, have increased FcRn binding affinity at an acidic pH (e.g., at a pH in the range of from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.5, a pH of about 6.0, or a pH of about 6.5) compared to a wild-type IgG Fc polypeptide selected from one of SEQ ID NO: 1 - 14.Attorney Reference No. 2920951-551977

[0119] In some embodiments, substituted or variant IgG Fc polypeptides described herein are at least 80% identical, 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: 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: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, 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:84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, 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: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 126, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO:Attorney Reference No. 2920951-551977 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, or SEQ ID NO: 317.

[0120] In other embodiments, substituted or variant IgG Fc polypeptides described herein include one, two, three, four, five, six, seven, eight, nine, ten, fifteen, at most one, at most two, at most three, at most four, at most five, at most six, at most seven, at most eight, at most nine, at most ten, or at most fifteen amino acid substitutions in the following amino acid sequences of 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: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, 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:84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, 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:Attorney Reference No. 2920951-551977 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 123, SEQ ID NO: 124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 126, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 150, SEQ ID NO: 151, SEQ ID NO: 152, SEQ ID NO: 153, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 156, SEQ ID NO: 157, SEQ ID NO: 158, SEQ ID NO: 159, SEQ ID NO: 160, SEQ ID NO: 161, SEQ ID NO: 162, SEQ ID NO: 163, SEQ ID NO: 164, SEQ ID NO: 165, SEQ ID NO: 166, SEQ ID NO: 167, SEQ ID NO: 168, SEQ ID NO: 169, SEQ ID NO: 170, SEQ ID NO: 171, SEQ ID NO: 172, SEQ ID NO: 173, SEQ ID NO: 174, SEQ ID NO: 175, SEQ ID NO: 176, SEQ ID NO: 177, SEQ ID NO: 178, SEQ ID NO: 179, SEQ ID NO: 180, SEQ ID NO: 181, SEQ ID NO: 182, SEQ ID NO: 183, SEQ ID NO: 184, SEQ ID NO: 185, SEQ ID NO: 186, SEQ ID NO: 187, SEQ ID NO: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, SEQ ID NO: 235, SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, or SEQ ID NO: 317.

[0121] In some embodiments, substituted or variant IgG Fc polypeptides described herein comprise at least one amino acid substitution at least in position 237, 246, 250, 251, 252, 253, 254, 255, 256, 258, 259, 279, 287, 288, 305, 306, 307, 308, 309, 311, 317, 338, 360, 370,Attorney Reference No. 2920951-551977 376, 380, 389A, 389B, 389C, 408, 426, 428, 431, 434, 436, 437, 438, 439, and / or 440 of a companion animal IgG Fc. In some embodiments, substituted or variant IgG Fc polypeptides described herein comprise at least one amino acid substitution at least in position 237, 246, 250, 251.252.253.254.255.256.258.259.279.287.288, 305, 306, 307, 308, 309, 311, 317, 338, 360, 370, 376, 380, 389 A, 389B, 389C, 408, 426, 428, 431, 434, 436, 437, 438, 439, and / or 440 of a canine IgG-A, canine IgG-B, canine IgG-C, canine IgG-D, equine IgGl, equine IgG2, equine IgG3, equine IgG4, equine IgG5, equine IgG6, equine IgG7, feline IgGla, feline IgGlb, or feline IgG2. In some embodiments, substituted or variant IgG Fc polypeptides comprises at least one amino acid substitution at least in position 237, 246, 250, 251, 252, 253, 254, 255, 256, 258.259.279.287.288, 305, 306, 307, 308, 309, 311, 317, 338, 360, 370, 376, 380, 389A, 389B, 389C, 408, 426, 428, 431, 434, 436, 437, 438, 439, and / or 440 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: 14.

[0122] In one aspect, substituted or variant IgG Fc polypeptides described herein comprise at least one of a tyrosine at position 237; a proline at position 246; a histidine, an isoleucine, a methionine, or a proline at position 250; a valine, an arginine, or a lysine at position 251; a phenylalanine, a tyrosine, a methionine, a histidine, an asparagine, a glutamine, an arginine, threonine, or a valine at position 252; a threonine at position 253; a tryptophan, a threonine, a tyrosine, a histidine, a leucine, a phenylalanine, a proline, a valine, or a methionine at position 254; a leucine, a methionine, a proline, an isoleucine, an aspartic acid, or a tryptophan at position 255; a methionine, a glutamic acid, an aspartic acid, a histidine, an isoleucine, an alanine, or a valine at position 256; a methionine or a valine at position 258; an isoleucine or alanine at position 259; an arginine at position 279; a tryptophan or a glutamine at position 287, an alanine at position 288; a glutamine at position 305; a valine at position 306; a glutamine, an arginine, an alanine, an aspartic acid, a glutamic acid, a histidine, a threonine, or a methionine at position 307; a histidine, a proline, or a phenylalanine at position 308; a glutamic acid or isoleucine at position 309; an alanine, a tryptophan, a tyrosine, or a phenylalanine at position 311; a phenylalanine at position 317; an arginine at position 338; an isoleucine at position 360; a threonine at position 370; a valine at position 376; a serine or a histidine at position 380; a leucine, a phenylalanine, or a tyrosine at position 389A; an isoleucine or an asparagine at position 408; a glutamine or a histidine at position 426; a leucine, a histidine, a tryptophan, or a phenylalanine at position 428; a glycine at position 431, a histidine, an alanine, an arginine, phenylalanine, a tyrosine; a tryptophan, a methionine, a serine, or a glutamine atAttorney Reference No. 2920951-551977 position 434; a threonine at position 436; an arginine at position 437; an arginine at position 438; a serine, an alanine, an arginine, a lysine, a phenylalanine, a tyrosine, a histidine, or a tryptophan at position 439; and / or a glutamate at position 439 of a companion animal Fc. In aspects, the above amino acid substitutions are present in a canine IgG-A, canine IgG-B, canine IgG-C, canine IgG-D, equine IgGl, equine IgG2, equine IgG3, equine IgG4, equine IgG5, equine IgG6, equine IgG7, feline IgGla, feline IgGlb, or feline IgG2. In aspects, the above amino acid substitutions are present in 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: 14.

[0123] In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, an 408N, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, and an 408N of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, an 287Q, and an 408N of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 434H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, and an 256D of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287 W, an 380S, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 380S, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 309E, an 380S, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In someAttorney Reference No. 2920951-551977 embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 279R, an 287W, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287Q, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 380S, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 309E, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 279R, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 309E, and an 428H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 380S, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 380S, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, an 408N, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 408N, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 250M, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 308S and an 428H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 380H, an 426Q, and anAttorney Reference No. 2920951-551977 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 307H, an 309E, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 380S, and an 431G of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 306V, and an 307T of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 250H, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 307H and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 380H and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 428H and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 426Q and an 428H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 307T, an 309E, and an 338R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y, 408N, 426Q and a 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4 (YRQN). In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311 Y, 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4 (YRQ). In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, 311Y, 408N, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4 (YWQN). In some embodiments, the substituted IgGAttorney Reference No. 2920951-551977 Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, 311Y, 408N, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4 (YWRN). In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, and an 256D of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, 311 Y, and an 408N of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4 (YWN). In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y, 408N and a 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4 (YRN). In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311 Y, and an 408N of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4 (0Y0N).

[0124] In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of a 252Y and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of a 434H and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of a 311 Y and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a 349K of SEQ ID NO: 2.1n some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, an 408N, a 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y,a 408N, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, and a 439K of SEQ ID NO: 2.. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, an 287Q, a 408N, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 434H, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, a 256D, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of anAttorney Reference No. 2920951-551977 287W, an 380S, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 380S, an 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 309E, an 380S, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 279R, an 287W, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287Q, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 380S, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 309E, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 279R, an 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 309E, an 428H, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 380S, an 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 380S, an 437R, and a 439K of SEQ ID NO: 2.. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, an 408N, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 408N, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 250M, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 308S an 428H, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of anAttorney Reference No. 2920951-551977 380H, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 307H, an 309E, an 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 380S, an 431G, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 306V, an 307T, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 250H, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 307H an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 380H an 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 428H an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 426Q an 428H, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 307T, an 309E, an 338R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y, 408N, 426Q a 437R (YRQN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y, 426Q, an 437R (YRQ), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, 311Y, 408N, an 426Q (YWQN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, 311 Y, 408N, an 437R (YWRN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, an 256D, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 287W, 311Y, an 408N (YWN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of anAttorney Reference No. 2920951-551977 311Y, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y, 408N and a 437R (YRN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y, an 408N (0Y0N), and a 439K of SEQ ID NO: 2.

[0125] In some embodiments, IgG Fc polypeptides described herein comprise a N434F substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a N434Y substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a N434A substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a N434S substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein.

[0126] In some embodiments, IgG Fc polypeptides described herein comprise a Y436T substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a S440E substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a M428L substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a I308P substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a I308F substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein. In some embodiments, IgG Fc polypeptides described herein comprise a V259A substitution together with a 439K in SEQ ID NO: 2 and optionally other substitutions described herein.

[0127] In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of a N434Y, a Y436T, a Q438R, a K439, and a S440E of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of a M428L, a N434A, a Q438R, a K439, and a S440E of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of a M428L, a N434S, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutionsAttorney Reference No. 2920951-551977 comprising any of a I308P, N434Y, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of aV259A, a I308F, a K439, and a M428L of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of a L252T, a A254T, a T256E, and a K439 of SEQ ID NO: 2.

[0128] In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y, an 254T, and an 256E of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 311 Y, and an 428F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 311Y, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H and an 428F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 428F, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 428F, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 305Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 434Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 434M of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 428F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 426Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 426H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Q and an 428F of SEQ ID NO: 12, SEQ ID NO: 13, orAttorney Reference No. 2920951-551977 SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 311Y, and an 426Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H and an 311Y of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y and an 426H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311Y of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 3091 of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 317F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 408N of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 428W of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 311W of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 428W, and an 434Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252Y and an 256D of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 408N, and an 426Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H and an 434Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutionsAttorney Reference No. 2920951-551977 comprising any of an 252Y of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising any of an 252H, an 408N, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14.

[0129] In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y, an 408N, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y, and an 408N of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y, an 287Q, and an 408N of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 434H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y, and an 256D of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, an 380S, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 380S, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 309E, an 380S, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 279R, an 287W, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287Q, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 380S, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising anAttorney Reference No. 2920951-551977 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 309E, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 279R, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 309E, and an 428H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 380S, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 380S, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, an 408N, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 408N, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 250M, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 308S and an 428H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 380H, an 426Q, and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 307H, an 309E, and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 380S, and an 431G of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 306V, and an 307T of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 250H, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 307H and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In someAttorney Reference No. 2920951-551977 embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 380H and an 426Q of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 428H and an 437R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 426Q and an 428H of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 307T, and an 309E of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 307T, an 309E, and an 338R of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y, 408N, 426Q, and a 437R (YRQN) of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311 Y, 426Q, and an 437R YRQ of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, 311Y, 408N, and an 426Q (YWQN) of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, 311Y, 408N, and an 437R (YWRN) of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y, and an 256D of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, 311 Y, and an 408N (YWN) of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y, 408N, and a 437R YRN of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y, and an 408N (0Y0N) of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

[0130] In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y, an 254T, and an 256E of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutionsAttorney Reference No. 2920951-551977 comprising an 252H, an 311Y, and an 428F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 311Y, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H and an 428F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 428F, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 428F, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 305Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 434Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 434M of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 428F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 426Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 426H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Q and an 428F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 311Y, and an 426Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H and an 311Y of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y and an 426H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In someAttorney Reference No. 2920951-551977 embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 3091 of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 317F of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 408N of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 428W of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311W of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 428W, and an 434Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y and an 256D of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 408N, and an 426Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H and an 434Q of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 408N, and an 434H of SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14.

[0131] In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 408N, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 250M, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 308S an 428H, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 380H, an 426Q, an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 307H, an 309E, an 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 380S, an 431G, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 306V, an 307T, and a 439K of SEQ ID NO: 2. In some embodiments, the substitutedAttorney Reference No. 2920951-551977 IgG Fc polypeptide comprises substitutions comprising an 250H, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 307H an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 380H an 426Q, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 428H an 437R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 426Q an 428H, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252H, an 307T, an 309E, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 307T, an 309E, an 338R, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y, 408N, 426Q, and a 437R (YRQN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311 Y, 426Q, 437R (YRQ), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, 311 Y, 408N, an 426Q (YWQN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, 311Y, 408N, an 437R (YWRN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 252Y, an 256D, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 287W, 311 Y, an 408N (YWN), and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311 Y, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311 Y, 408N, and a 437R YRN, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises substitutions comprising an 311Y, an 408N (0Y0N), and a 439K of SEQ ID NO: 2.

[0132] In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a N434F, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a N434Y, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a N434A, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutionsAttorney Reference No. 2920951-551977 comprising a N434S, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a Y436T, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a 439K, and a S440E of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a M428L, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising an I308P, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising an I308F, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a V259A, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a N434Y, a Y436T, a Q438R, a K439, and a S440E of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a M428L, a N434A, a Q438R, a K439, and a S440E of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a M428L, a N434S, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a I308P, N434Y, and a 439K of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising aV259A, a I308F, a K439, and a M428L of SEQ ID NO: 2. In some embodiments, the substituted IgG Fc polypeptide comprises a plurality of substitutions comprising a L252T, a A254T, a T256E, and a K439 of SEQ ID NO: 2.

[0133] In some embodiments, substituted or variant IgG Fc polypeptides described herein have modified or improved Protein A binding affinities. In some embodiments, substituted or variant IgG Fc polypeptides described herein have increased binding affinity to Protein A relative to a reference IgG Fc polypeptide, such as a non-mutated or wild-type IgG Fc polypeptide. In some embodiments, substituted or variant IgG Fc polypeptides described herein may be purified using Protein A column chromatography. In some embodiments, substituted or variant IgG Fc polypeptides described herein have modified CD 16, CD32, and / or CD64 binding affinity relative to a reference IgG Fc polypeptide, such as a non-mutated or wild-type IgG Fc polypeptide. In some embodiments, substituted or variant IgG Fc polypeptides described herein have decreased binding affinity to CD16, CD32, and / or CD64 relative to a reference IgG Fc polypeptide, such as a non-mutated or wild-type IgG Fc polypeptide.Attorney Reference No. 2920951-551977

[0134] In other embodiments, substituted or variant IgG Fc polypeptides described herein have a reduced ADCC immune response, relative to a reference IgG Fc polypeptide, such as a non-mutated or wild-type IgG Fc polypeptide. In some embodiments, substituted or variant IgG Fc polypeptides described herein have modified Clq binding affinity relative to a reference IgG Fc polypeptide, such as a non-mutated or wild-type IgG Fc polypeptide. In some embodiments, substituted or variant IgG Fc polypeptides have reduced binding affinity to Clq, relative to a reference IgG Fc polypeptide, such as a non-mutated or wild-type IgG Fc polypeptide. In some embodiments, substituted or variant IgG Fc polypeptides have a reduced complement fixation, relative to a reference IgG Fc polypeptide, such as a non-mutated or wildtype IgG Fc polypeptide. In some embodiments, substituted or variant IgG Fc polypeptides described herein may have a reduced complement-mediated immune response, relative to a reference IgG Fc polypeptide, such as a non-mutated or wild-type IgG Fc polypeptide.

[0135] In some embodiments, substituted or variant IgG Fc polypeptides described herein comprise at least one amino acid substitution comprises an amino acid substitution with an amino acid derivative. In some embodiments, 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.Exemplary Fusion Molecules

[0136] In some embodiments, the IgG Fc polypeptide is an antibody, an antibody fragment, or a fusion polypeptide. In other aspects, substituted or variant IgG Fc polypeptides described herein, for example, those in Table 4, mutated or substituted SEQ ID NOs: 1 - 14, or those polypeptides comprising SEQ ID NOs: 21 - 102, SEQ ID NOs: 188-235, or SEQ ID NOs: 300-317 are part of an antibody, an antibody fragment, or a fusion polypeptide.

[0137] In other embodiments, substituted or variant IgG Fc polypeptides described herein, for example, those in Table 4, mutated or substituted sequences with at least about 90% identity, at least about 95% identity, at least about 95% identity, or at least about 99% identity to SEQ ID NO: 1 - 14, or those polypeptides comprising at least about 90% identity, at least about 95% identity, at least about 95% identity, or at least about 99% identity to SEQ ID NO: 21 -102, SEQ ID NO: 188-235, or 300-317 are part of an antibody, an antibody fragment, or a fusion polypeptide.Attorney Reference No. 2920951-551977

[0138] In some embodiments, the IgG heavy chain polypeptide is an antibody, an antibody fragment, or a fusion polypeptide. In other aspects, substituted or variant IgG heavy chain polypeptides described herein, for example, those in Table 4, mutated or substituted SEQ ID NO: 137, SEQ ID NO: 154, SEQ ID NO: 155, SEQ ID NO: 241, SEQ ID NO: 242, SEQ ID NO: 243, SEQ ID NO: 244, SEQ ID NO: 245, or SEQ ID NO: 299 or those polypeptides comprising SEQ ID NO: 106-136, SEQ ID NO: 138-153, SEQ ID NO: 156- 187, SEQ ID NO: 246-281, SEQ ID NO: 283-298, SEQ ID NO: 318, SEQ ID NO: 320 SEQ ID NO: 321, SEQ ID NO: 322, SEQ ID NO: 323, SEQ ID NO: 325, SEQ ID NO: 326, SEQ ID NO: 329, SEQ ID NO: 331, SEQ ID NO: 333, SEQ ID NO: 335, SEQ ID NO: 337, SEQ ID NO: 340, or SEQ ID NO: 342 are part of an antibody, an antibody fragment, or a fusion polypeptide.

[0139] Polypeptides and other molecules may comprise substituted or variant IgG Fc polypeptides described herein. In some embodiments, a fusion molecule comprises substituted or variant IgG Fc polypeptides described herein. In some embodiments, an antibody or an antibody fragment comprises a substituted or variant IgG Fc polypeptides, such as the substituted or variant IgG Fc polypeptides described herein.

[0140] A “fusion molecule,” as used herein, refers to a molecule comprising one or more “fusion partners.” In some embodiments, the fusion partners are covalently linked (“fused”). If two fusion partners are both polypeptides, the fusion partner polypeptides may be part of a contiguous amino acid sequence (i.e., a contiguous polypeptide), linked by a crosslinking compound or linked by an amino acid side chain. A first fusion partner polypeptide may be linked to the N-terminus, the C-terminus or to an amino acid side chain of a second fusion partner. In some embodiments, the fusion partners are translated as a single polypeptide from a coding sequence that encodes both fusion partners. Fusion partners may be covalently linked through other means, such as, for example, a chemical linkage other than a peptide bond. Many known methods of covalently linking polypeptides to other molecules (for example, fusion partners) may be used. In other embodiments, the fusion partners are fused through a “linker,” which is comprised of at least one amino acid or chemical moiety. In some embodiments, fusion partners are noncovalently linked. In some such embodiments, they may be linked, for example, using binding pairs. Exemplary binding pairs include, but are not limited to, biotin and avidin or streptavidin, an antibody and its antigen, etc.

[0141] In ...

Claims

1. Attorney Reference No. 2920951-551977CLAIMS1. A polypeptide comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises one or more of the following:i. a tyrosine at position 237;ii. a proline at position 246;iii. a methionine, histidine, proline, or isoleucine at position 250;iv. a valine, arginine, or lysine at position 251;v. a histidine, phenylalanine, tyrosine, methionine, valine, glutamine, arginine, or asparagine at position 252;vi. a threonine at position 253;vii. a tryptophan, tyrosine, threonine, histidine, leucine, proline, valine, phenylalanine, or methionine at position 254;viii. a leucine, methionine, proline, isoleucine, aspartate, or tryptophan at position 255;ix. a methionine, glutamate, aspartate, histidine, isoleucine, alanine or valine at position 256;x. a methionine, phenylalanine, or valine at position 258;xi. an isoleucine at position 259;xii. an arginine at position 279;xiii. a tryptophan, tyrosine, arginine or glutamine at position 287;xiv. an alanine at position 288;xv. a glutamine at position 305;xvi. a valine at position 306;Attorney Reference No. 2920951-551977 xvii. a histidine, threonine, glutamine, arginine, alanine, aspartate, glutamate, or methionine at position 307;xviii. a histidine, phenylalanine, or proline at position 308;ixx. a glutamate or isoleucine at position 309;xx. a tyrosine, tryptophan, alanine, or phenylalanine at position 311;xxi. a phenylalanine at position 317;xxii. an arginine at position 338;xxiii. an isoleucine at position 360;xxiv. a threonine at position 370;xxv. a valine at position 376;xxvi. a serine or histidine at position 380;xxvii. a leucine, phenylalanine, or tyrosine at position 389;xxviii. an isoleucine or asparagine at position 408;xxix. a glutamine, arginine, or histidine at position 426;xxx. a histidine or tryptophan at position 428;xxxi. a phenylalanine at position 430;xxxii. a glycine at position 431;xxxiii. a histidine at position 434; andxxxiv. an arginine at position 437; andxxxv. a lysine at position 439; andwherein the variant IgG Fc polypeptide is capable of binding to a neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type IgG Fc polypeptide.

2. The polypeptide of claim 1, wherein the wild-type IgG Fc polypeptide comprisesAttorney Reference No. 2920951-551977 a), a canine IgG-A Fc comprising SEQ ID NO: 1, a canine IgG-B Fc comprising SEQ ID NO: 2, a canine IgG-C Fc comprising SEQ ID NO: 3, or a canine IgG-D Fc comprising SEQ ID NO: 4;b). a feline IgGla Fc comprising SEQ ID NO: 12, a feline IgGlb comprising SEQ ID NO: 13; or a feline IgG2 Fc comprising SEQ ID NO: 14.

3. The polypeptide of any one of claims 1 or 2, wherein the variant IgG Fc polypeptide binds to FcRn with an affinity greater 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 from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.2, a pH of about 5.5, a pH of about 6.0, a pH of about 6.2, or a pH of about 6.5.

4. The polypeptide of any one of claims 1 -3, wherein the variant IgG Fc polypeptide binds to FcRn with a dissociation constant (Kd) of less than 5 x 10'6M, less than 1 x 10'6M, less than 5 x 10'7M, less than 1 x 10'7M, less than 5 x 10'8M, less than 1 x 10'8M, less than 5 x 10'9M, less than 1 x 10'9M, less than 5 x IO10M, less than 1 x IO10M, less than 5 x 1011M, less than 1 x 1011M, less than 5 x 1012M, or less than 1 x 1012M, as measured by biolayer interferometry, surface plasmon resonance, or any protein-protein interaction tool at a pH in the range of from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.5, a pH of about 6.0, or a pH of about 6.5.

5. The polypeptide of any one of claims 1 -4, wherein the variant IgG Fc polypeptide has increased serum half-life relative to a polypeptide comprising a wild-type IgG Fc polypeptide and optionally wherein the serum half-life of the IgG Fc polypeptide is from 1.5 to 5 times, 1.5 to 4 times, 1.5 -3 times, 2 - 5 times, 2 to 4 times, more than 1.5 times, more than 2 times, more than 2.5 times, or more than 3 times greater than the corresponding wild-type IgG Fc polypeptide or non-mutated IgG Fc polypeptide.

6. The polypeptide of any one of claims 1 - 5, wherein the variant IgG Fc polypeptide is derived from canine, feline, or equine.

7. An IgG Fc polypeptide comprising at least 90% identity, at least 95% identity, at least 97% identity, at least 99% identity, or 100% identity to an amino acid sequence of 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, SEQAttorney Reference No. 2920951-551977 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: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, 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:84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, 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: 188, SEQ ID NO: 189, SEQ ID NO: 190, SEQ ID NO: 191, SEQ ID NO: 192, SEQ ID NO: 193, SEQ ID NO: 194, SEQ ID NO: 195, SEQ ID NO: 196, SEQ ID NO: 197, SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO: 200, SEQ ID NO: 201, SEQ ID NO: 202, SEQ ID NO: 203, SEQ ID NO: 204, SEQ ID NO: 205, SEQ ID NO: 206, SEQ ID NO: 207, SEQ ID NO: 208, SEQ ID NO: 209, SEQ ID NO: 210, SEQ ID NO: 211, SEQ ID NO: 212, SEQ ID NO: 213, SEQ ID NO: 214, SEQ ID NO: 215, SEQ ID NO: 216, SEQ ID NO: 217, SEQ ID NO: 218, SEQ ID NO: 219, SEQ ID NO: 220, SEQ ID NO: 221, SEQ ID NO: 222, SEQ ID NO: 223, SEQ ID NO: 224, SEQ ID NO: 225, SEQ ID NO: 226, SEQ ID NO: 227, SEQ ID NO: 228, SEQ ID NO: 229, SEQ ID NO: 230, SEQ ID NO: 231, SEQ ID NO: 232, SEQ ID NO: 233, SEQ ID NO: 234, or SEQ ID NO: 235.

8. A variant IgG Fc polypeptide comprising:a) one or more of a 252Y or 408N amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;b) one or more of a 252Y, 408N, or 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;c) one or more of a 252Y, an 287Q, and an 408N amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;d) one or more of a 252Y, and a 256D amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 e) one or more of a 287W, an 380S, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;f) one or more of a 287W, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;g) one or more of a 252H, an 380S, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;h) one or more of a 309E, an 380S, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;i) one or more of a 279R, an 287W, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;j) one or more of a 287Q, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;k) one or more of a 380S, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;l) one or more of a 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;m) one or more of a 309E, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;n) one or more of a 252H, an 279R, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;o) one or more of a 252H, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;p) one or more of a 309E, and an 428H amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;q) one or more of a 380S, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;r) one or more of a 252H, an 380S, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;s) one or more of a 287W, an 408N, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 t) one or more of a 252H, an 408N, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;u) one or more of a 250M, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;v) one or more of a 308S and an 428H amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;w) one or more of a 380H, an 426Q, and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;x) one or more of a 307H, an 309E, and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;y) one or more of a 252H, an 380S, and an 431G amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;z) one or more of a 252H, an 306V, and an 307T amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aa) one or more of a 250H, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ab) one or more of a 307H and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ac) one or more of a 380H and an 426Q amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ad) one or more of a 428H and an 437R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ae) one or more of a 287W, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;af) one or more of a 426Q and an 428H amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ag) one or more of a 252H, an 307T, and an 309E amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ah) one or more of a 307T, an 309E, and an 338R amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 ai) one or more of a 311 Y, 408N, 426Q, and a 437R (YRQN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aj) one or more of a 311 Y, 426Q, and an 437R (YRQ) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ak) one or more of a 287W, 311 Y, 408N, and an 426Q (YWQN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;al) one or more of a 287W, 311Y, 408N, and a 437R (YWRN) amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;am) one or more of a 252Y, and an 256D amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;an) one or more of a 287W, 311 Y, and an 408N YWN amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ao) a 311Y amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ap) one or more of a 311Y,4O8N and a 437R YRN amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aq) one or more of a 311Y, and an 408N OYON amino acid substitution in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ar) one or more of a 252Y, an 254T, and an 256E amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;as) one or more of a 252H, an 311 Y, and an 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;at) one or more of a 252H, an 311 Y, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;au) one or more of a 252H and an 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;av) one or more of a 252H and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;aw) one or more of a 252H, an 428F, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;Attorney Reference No. 2920951-551977 ax) one or more of a 428F, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ay) one or more of a 305Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;az) one or more of a 434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ba) one or more of a 434M amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bb) one or more of a 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;be) one or more of a 426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bd) one or more of a 426H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;be) one or more of a 252Q and an 428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bf) one or more of a 252Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bg) one or more of a 252H, an 311Y, and an 426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bh) one or more of a 252H and an 311 Y amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bi) a 252H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14; bj) one or more of a 311 Y and an 426H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bk) a 311Y amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14; bl) one or more of a 3091 amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bm) one or more of a 317F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;Attorney Reference No. 2920951-551977 bn) one or more of a 428W amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bo) one or more of a 311 W amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bp) one or more of a 428W, and an 434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bq) one or more of a 252Y and an 256D amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;br) one or more of a 252H, an 408N, and an 426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bs) one or more of a 252H and an 434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bt) one or more of a 252H, an 408N, and an 434H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14bu) a 439K amino acid substitution in SEQ ID NO: 2;bv) one or more of a 252Y, 408N, and a 439K amino acid substitution in SEQ ID NO: 2; bw) one or more of a 252Y, 408N, 426Q, and a 439K amino acid substitution in SEQ ID NO: 2;bx) one or more of a 252Y, an 287Q,an 408N, and a 439K amino acid substitution in SEQ ID NO: 2;by) one or more of a 252Y, a 256D, and a 439K amino acid substitution in SEQ ID NO: 2; bz) one or more of a 287W, an 380S, an 426Q a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;ca) one or more of a 287W, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;cb) one or more of a 252H, an 380S, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 2;cc) one or more of a 309E, an 380S, an 437R, and a 439K amino acid substitution in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 cd) one or more of a 279R, an 287W, an 426Q, an 437R, and a 439K amino acid substitution in SEQ ID NO: 2;ce) one or more of a 287Q, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;cf) one or more of a 380S, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;eg) one or more of a 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2; ch) one or more of a 309E, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;ci) one or more of a 252H, an 279R, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 2;cj) one or more of a 252H, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;ck) one or more of a 309E, a 428H, and a 439K amino acid substitution in SEQ ID NO: 2; cl) one or more of a 380S, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 2; cm) one or more of a 252H, an 380S, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;cn) one or more of a 287W, an 408N, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;co) one or more of a 252H, an 408N, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;cp) one or more of a 250M, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 2;cq) one or more of a 308S a 428H, and a 439K amino acid substitution in SEQ ID NO: 2; cr) one or more of a 380H, an 426Q, a 437R, and a 439K amino acid substitution in SEQ ID NO: 2;cs) one or more of a 307H, an 309E, a 426Q, and a 439K amino acid substitution in SEQ ID NO: 2;ct) one or more of a 252H, an 380S, a 431G, and a 439K amino acid substitution in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 cw) one or more of a 252H, an 306V, a 307T, and a 439K amino acid substitution in SEQ ID NO: 2;ex) one or more of a 250H, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 2;cy) one or more of a 307H a 309E, and a 439K amino acid substitution in SEQ ID NO: 2; cz) one or more of a 380H a 426Q, and a 439K amino acid substitution in SEQ ID NO: 2; da) one or more of a 428H a 437R, and a 439K amino acid substitution in SEQ ID NO: 2; db) one or more of a 287W, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 2;de) one or more of a 426Q a 428H, and a 439K amino acid substitution in SEQ ID NO: 2; dd) one or more of a 252H, an 307T, a 309E, and a 439K amino acid substitution in SEQ ID NO: 2;de) one or more of a 307T, an 309E, a 338R, and a 439K amino acid substitution in SEQ ID NO: 2;df) one or more of a 311 Y, 408N, 426Q, a 437R (YRQN), and a 439K amino acid substitution in SEQ ID NO: 2;dg) one or more of a 311 Y, 426Q, a 437R (YRQ), and a 439K amino acid substitution in SEQ ID NO: 2;dh) one or more of a 287W, 311 Y, 408N, a 426Q (YWQN), and a 439K amino acid substitution in SEQ ID NO: 2;di) one or more of a 287W, 311 Y, 408N, a 437R (YWRN), and a 439K amino acid substitution in SEQ ID NO: 2;dj) one or more of a 252Y, a 256D, and a 439K amino acid substitution in SEQ ID NO: 2; dk) one or more of a 287W, 311 Y, a 408N (YWN), and a 439K amino acid substitution in SEQ ID NO: 2;dl) a 311 Y, and a 439K amino acid substitution in SEQ ID NO: 2;dm) one or more of a 311Y, 408N, a 437R (YRN), and a 439K amino acid substitution in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 dn) one or more of a 311Y, a 408N (0Y0N), and a 439K amino acid substitution in SEQ ID NO: 2do) one or more of a 252Y and a 439K amino acid substitution in SEQ ID NO: 2;dp) one or more of a 434H and a 439K amino acid substitution in SEQ ID NO: 2;dq) one or more of a 311 Y and a 439K amino acid substitution in SEQ ID NO: 2; or dr) one or more of a 252Y, 254T, 256D, and a 439K amino acid substitution in SEQ ID NO: 2.

9. A variant IgG Fc polypeptide comprising:a) 252Y and 408N amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;b) 252Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;c) P307T, G309E, and K338R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;d) L252Y, S408N, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;e) L252Y and S408N amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;f) L252Y, A287Q, and S408N amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;g) L252Y and T256D amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;h) A287W, E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;i) A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;j) L252H, E380S, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;k) G309E, E380S, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 l) V279R, A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;m) A287Q, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;n) E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;o) A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;p) G309E, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;q) L252H, V279R, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;r) L252H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;s) G309E and M428H amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;t) E380S and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;u) L252H, E380S, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;v) A287W, S408N, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;w) L252H, S408N, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;x) T250M, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;y) E308S and M428H amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;z) E380H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 aa) P307H, G309E, and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ab) L252H, E380S, and A431G amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ac) L252H, L306V, and P307T amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ad) T250H, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ae) P307H and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;af) E380H and A426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ag) M428H and T437R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ah) A287W, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ai) A426Q and M428H amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aj) L252H, P307T, and G309E amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ak) P307T, G309E, and K338R amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;al) Q311Y, S408N, A426Q, and a T437R (YRQN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, OR SEQ ID NO: 4;am) Q311Y, A426Q, and T437R (YRQ) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;an) A287W, Q311Y, S408N, and A426Q (YWQN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ao) L252Y and T256D amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;Attorney Reference No. 2920951-551977 ap) A287W, Q311Y, S408N, and T437R (YWRN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;aq) A287W, Q311Y, and S408N (YWN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;ar) Q311Y, S408N, and T437R (YRN) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;as) Q311Y and S408N (0Y0N) amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;at) L252Y, A254T, and T256E amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;au) S252H, Q311Y, and S428F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;av) S252H, Q311Y, and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;aw) S252H and S428F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ax) S252H and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ay) S252H, S428F, and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bz) S428F and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;ba) a V305Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bb) a S434Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;be) a S434M amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bd) a S428F amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO:Attorney Reference No. 2920951-551977 be) a S426Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bf) a S426H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bg) S252Q and S428F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bh) a S252Q amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, OR SEQ ID NO: 14;bi) S252H, Q311Y, and S426Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bj) S252H and Q311Y amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bk) a S252H amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bl) Q311Y and S426H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bm) a Q311Y amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bn) a L309I amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bo) a K317F amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bp) a S408N amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bq) a S428W amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;br) a Q311W amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bs) S428W and S434Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;Attorney Reference No. 2920951-551977 bt) S252Y and T256D amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bu) S252H, S408N, and S426Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bv) S252H and S434Q amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14;bw) a S252Y amino acid substitution in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14; orbx) S252H, S408N, and S434H amino acid substitutions in SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14bx) 439K amino acid substitution in SEQ ID NO: 2;by) 252Y, 408N, and 439K amino acid substitutions in SEQ ID NO: 2;bz) 252Y, 408N, 426Q, and 439K amino acid substitutions in SEQ ID NO: 2;ca) P307T, G309E, K338R, and 439K amino acid substitutions in SEQ ID NO: 2;cb) L252Y, S408N, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cc) L252Y, S408N, and 439K amino acid substitutions in SEQ ID NO: 2;cd) L252Y, A287Q, S408N, and 439K amino acid substitutions in SEQ ID NO: 2; ce) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 2;cf) A287W, E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; eg) A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; ch) L252H, E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;ci) G309E, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cj) V279R, A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; ck) A287Q, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cl) E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cm) A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cn) G309E, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;co) L252H, V279R, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 cp) L252H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cq) G309E, M428H, and 439K amino acid substitutions in SEQ ID NO: 2;cr) E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cs) L252H, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;ct) A287W, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cq) L252H, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cr) T250M, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;cs) E308S M428H, and 439K amino acid substitutions in SEQ ID NO: 2;ct) E380H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cu) P307H, G309E, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cv) L252H, E380S, A431G, and 439K amino acid substitutions in SEQ ID NO: 2; cw) L252H, L306V, P307T, and 439K amino acid substitutions in SEQ ID NO: 2;ex) T250H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;cy) P307H, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;cz) E380H, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;da) M428H, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;db) A287W, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2; de) A426Q, M428H, and 439K amino acid substitutions in SEQ ID NO: 2;dd) L252H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;de) Q311Y, S408N, A426Q, T437R (YRQN), and 439K amino acid substitutions in SEQ ID NO: 2;df) Q311Y, A426Q, T437R (YRQ), and 439K amino acid substitutions in SEQ ID NO: 2; dg) A287W, Q311Y, S408N, A426Q (YWQN), and 439K amino acid substitutions in SEQ ID NO: 2;dh) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 2;di) A287W, Q311Y, S408N, T437R (YWRN), and 439K amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 dj) A287W, Q311Y, S408N (YWN), and 439K amino acid substitutions in SEQ ID NO: 2; dk) Q311Y, S408N, T437R (YRN), and 439K amino acid substitutions in SEQ ID NO: 2; dl) Q311Y, S408N (OYON), and 439K amino acid substitutions in SEQ ID NO: 2;do) one or more of a L252Y and a 439K amino acid substitution in SEQ ID NO: 2; dp) one or more of a N434H and a 439K amino acid substitution in SEQ ID NO: 2; dq) one or more of a Q311Y and a 439K amino acid substitution in SEQ ID NO: 2; or dr) one or more of a L252Y, A254T, T256D, and a 439K amino acid substitution in SEQ ID NO: 2.

10. A variant IgG Fc polypeptide comprising:a) 252 Y and 408N amino acid substitutions in SEQ ID NO: 2;b) 252Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2;c) P307T, G309E, and K338R amino acid substitutions in SEQ ID NO: 2;d) L252Y, S408N, and A426Q amino acid substitutions in SEQ ID NO: 2;e) L252Y and S408N amino acid substitutions in SEQ ID NO: 2;f) L252Y, A287Q, and S408N amino acid substitutions in SEQ ID NO: 2;g) L252Y and T256D amino acid substitutions in SEQ ID NO: 2;h) A287W, E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;i) A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;j) L252H, E380S, and A426Q amino acid substitutions in SEQ ID NO: 2;k) G309E, E380S, and T437R amino acid substitutions in SEQ ID NO: 2;l) V279R, A287W, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2; m) A287Q, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;n) E380S, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;o) A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;p) G309E, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;q) L252H, V279R, and A426Q amino acid substitutions in SEQ ID NO: 2;r) L252H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 s) G309E and M428H amino acid substitutions in SEQ ID NO: 2;t) E380S and A426Q amino acid substitutions in SEQ ID NO: 2;u) L252H, E380S, and T437R amino acid substitutions in SEQ ID NO: 2;v) A287W, S408N, and T437R amino acid substitutions in SEQ ID NO: 2;w) L252H, S408N, and T437R amino acid substitutions in SEQ ID NO: 2;x) T250M, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;y) E308S and M428H amino acid substitutions in SEQ ID NO: 2;z) E380H, A426Q, and T437R amino acid substitutions in SEQ ID NO: 2;aa) P307H, G309E, and A426Q amino acid substitutions in SEQ ID NO: 2;ab) L252H, E380S, and A431G amino acid substitutions in SEQ ID NO: 2;ac) L252H, L306V, and P307T amino acid substitutions in SEQ ID NO: 2;ad) T250H, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;ae) P307H and G309E amino acid substitutions in SEQ ID NO: 2;af) E380H and A426Q amino acid substitutions in SEQ ID NO: 2;ag) M428H and T437R amino acid substitutions in SEQ ID NO: 2;ah) A287W, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;ai) A426Q and M428H amino acid substitutions in SEQ ID NO: 2;aj) L252H, P307T, and G309E amino acid substitutions in SEQ ID NO: 2;ak) P307T, G309E, and K338R amino acid substitutions in SEQ ID NO: 2;al) Q311Y, S408N, A426Q, and T437R (YRQN) amino acid substitutions in SEQ ID NO: 2; am) Q311Y, A426Q, and T437R (YRQ) amino acid substitutions in SEQ ID NO: 2; an) A287W, Q311Y, S408N, and A426Q (YWQN) amino acid substitutions in SEQ ID NO: 2;ao) L252Y and T256D amino acid substitutions in SEQ ID NO: 2;ap) A287W, Q311Y, S408N, and T437R (YWRN) amino acid substitutions in SEQ ID NO: 2;aq) A287W, Q311Y, and S408N (YWN) amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 ar) Q311Y, S408N, and T437R (YRN) amino acid substitutions in SEQ ID NO: 2;as) Q311Y and S408N (OYON) amino acid substitutions in SEQ ID NO: 2;at) L252Y, A254T, and T256E amino acid substitutions in SEQ ID NO: 13;au) S252H, Q311Y, and S428F amino acid substitutions in SEQ ID NO: 13;av) S252H, Q311Y, and S434H amino acid substitutions in SEQ ID NO: 13;aw) S252H and S428F amino acid substitutions in SEQ ID NO: 13;ax) S252H and S434H amino acid substitutions in SEQ ID NO: 13;ay) S252H, S428F, and S434H amino acid substitutions in SEQ ID NO: 13;az) S428F and S434H amino acid substitutions in SEQ ID NO: 13;ba) a V305Q amino acid substitution in SEQ ID NO: 13;bb) a S434Q amino acid substitution in SEQ ID NO: 13;be) a S434M amino acid substitution in SEQ ID NO: 13;bd) a S428F amino acid substitution in SEQ ID NO: 13;be) a S426Q amino acid substitution in SEQ ID NO: 13;bf) a S426H amino acid substitution in SEQ ID NO: 13;bg) S252Q and S428F amino acid substitutions in SEQ ID NO: 13;bh) a S252Q amino acid substitution in SEQ ID NO: 13;bi) S252H, Q311Y, and S426Q amino acid substitutions in SEQ ID NO: 13;bj) S252H and Q311Y amino acid substitutions in SEQ ID NO: 13;bk) a S252H amino acid substitution in SEQ ID NO: 13;bl) Q311Y and S426H amino acid substitutions in SEQ ID NO: 13;bm) a Q311Y amino acid substitutions in SEQ ID NO: 13;bn) a L309I amino acid substitutions in SEQ ID NO: 13;bo) a K317F amino acid substitutions in SEQ ID NO: 13;bp) a S408N amino acid substitutions in SEQ ID NO: 13;bq) a S428W amino acid substitutions in SEQ ID NO: 13;br) a Q311W amino acid substitutions in SEQ ID NO: 13;Attorney Reference No. 2920951-551977 bs) S428W and S434Q amino acid substitutions in SEQ ID NO: 13;bt) S252Y and T256D amino acid substitutions in SEQ ID NO: 13;bu) S252H, S408N, and S426Q amino acid substitutions in SEQ ID NO: 13;bv) S252H and S434Q amino acid substitutions in SEQ ID NO: 13;bw) a S252Y amino acid substitution in SEQ ID NO: 13; orbx) S252H, S408N, and S434H amino acid substitutions in SEQ ID NO: 13by) 439K amino acid substitutions in SEQ ID NO: 2;bz) 252Y, 408N, and 439K amino acid substitutions in SEQ ID NO: 2;ca) 252Y, 408N, 426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cb) P307T, G309E, K338R, and 439K amino acid substitutions in SEQ ID NO: 2;cc) L252Y, S408N, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cd) L252Y, S408N, and 439K amino acid substitutions in SEQ ID NO: 2;ce) L252Y, A287Q, S408N, and 439K amino acid substitutions in SEQ ID NO: 2;cf) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 2;eg) A287W, E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; ch) A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; ci) L252H, E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;cj) G309E, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;ck) V279R, A287W, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; cl) A287Q, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; cm) E380S, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; cn) A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;co) G309E, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cp) L252H, V279R, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2; eq) L252H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;er) G309E, M428H, and 439K amino acid substitutions in SEQ ID NO: 2;cs) E380S, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;Attorney Reference No. 2920951-551977 ct) L252H, E380S, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cu) A287W, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 2; cv) L252H, S408N, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cw) T250M, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2; ex) E308S M428H, and 439K amino acid substitutions in SEQ ID NO: 2;cy) E380H, A426Q, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;cz) P307H, G309E, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;da) L252H, E380S, A431G, and 439K amino acid substitutions in SEQ ID NO: 2;db) L252H, L306V, P307T, and 439K amino acid substitutions in SEQ ID NO: 2;de) T250H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;dd) P307H, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;de) E380H, A426Q, and 439K amino acid substitutions in SEQ ID NO: 2;df) M428H, T437R, and 439K amino acid substitutions in SEQ ID NO: 2;dg) A287W, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2; dh) A426Q, M428H, and 439K amino acid substitutions in SEQ ID NO: 2;di) L252H, P307T, G309E, and 439K amino acid substitutions in SEQ ID NO: 2;dj) Q311Y, S408N, A426Q, T437R (YRQN), and 439K amino acid substitutions in SEQ ID NO: 2;dk) Q311Y, A426Q, T437R (YRQ), and 439K amino acid substitutions in SEQ ID NO: 2; dl) A287W, Q311Y, S408N, A426Q (YWQN), and 439K amino acid substitutions in SEQ ID NO: 2;dm) L252Y, T256D, and 439K amino acid substitutions in SEQ ID NO: 2;dn) A287W, Q311Y, S408N, T437R (YWRN), and 439K amino acid substitutions in SEQ ID NO: 2;do) A287W, Q311Y, S408N (YWN), and 439K amino acid substitutions in SEQ ID NO: 2; dp) Q311Y, S408N, T437R (YRN), and 439K amino acid substitutions in SEQ ID NO: 2; or dq) Q311Y, S408N (OYON), and 439K amino acid substitutions in SEQ ID NO: 2.Attorney Reference No. 2920951-551977 11. The polypeptide of any one of claims 7 - 10, wherein the variant IgG Fc polypeptide binds to FcRn with an affinity greater 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 from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.2, a pH of about 5.5, a pH of about 6.0, a pH of about 6.2, or a pH of about 6.5.

12. The polypeptide of any one of claims 7 - 10, wherein the variant IgG Fc polypeptide binds to FcRn with a dissociation constant (Kd) of less than 5 x 10'6M, less than 1 x 10'6M, less than 5 x 10'7M, less than 1 x 10'7M, less than 5 x 10'8M, less than 1 x 10'8M, less than 5 x 10'9M, less than 1 x 10'9M, less than 5 x 1010M, less than 1 x 1010M, less than 5 x 1011M, less than 1 x 1011M, less than 5 x 1012M, or less than 1 x 1012M, as measured by biolayer interferometry, surface plasmon resonance, or any protein-protein interaction tool at a pH in the range of from about 5.0 to about 6.5, such as at a pH of about 5.0, a pH of about 5.5, a pH of about 6.0, or a pH of about 6.5.

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

14. The polypeptide of claim 13, 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.

15. The polypeptide of any one of claims 1 - 14, wherein the polypeptide is an antibody, an antibody fragment, or a fusion polypeptide.

16. The polypeptide of any one of claims 1 - 15, wherein the polypeptide comprises at least one therapeutic polypeptide selected from a late embryogenesis abundant (LEA) protein polypeptide (e.g., an LEA-3 polypeptide), an NGF polypeptide, a receptor of an NGF polypeptide (e.g., an ECD of a receptor of an NGF polypeptide), a TrkA polypeptide (e.g., an ECD of a TrkA polypeptide), an LNGFR polypeptide (e.g., an ECD of a LNGFR polypeptide), a TNFa polypeptide, a receptor of a TNFa polypeptide, a TNFR polypeptide (e.g., an ECD of a TNFR polypeptide), a TNFR1 polypeptide (e.g., an ECD of a TNFR1 polypeptide), a TNFR2 polypeptide (e.g., an ECD of a TNFR2 polypeptide), an IL5 polypeptide, a receptor of an IL5Attorney Reference No. 2920951-551977 polypeptide, an IL5R polypeptide (e.g., an ECD of an IL5R polypeptide), an IL5Ra polypeptide (e.g., an ECD of an IL5Ra polypeptide), an IL6 polypeptide, a receptor of an IL6 polypeptide, an IL6R polypeptide (e.g., an ECD of an IL6R polypeptide), an IL 17 polypeptide, a receptor of 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 (e.g., an ECD of an IL17RB polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an IL23 polypeptide, a receptor of an IL23 polypeptide, an IL23R polypeptide (e.g., an ECD of an IL23R polypeptide), an IL12R 1 polypeptide (e.g., an ECD of an IL12Rpi polypeptide), a PDL1 polypeptide, a receptor of a PDL1 polypeptide, a PDL2 polypeptide, a receptor of a PDL2 polypeptide, a PD1 polypeptide (e.g., an ECD of a PD1 polypeptide), an 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), a receptor of 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), a collagen polypeptide (e.g., an ECD of a collagen polypeptide), a laminin polypeptide (e.g., an ECD of a laminin polypeptide), a CD80 polypeptide, a receptor of a CD80 polypeptide, a CD86 polypeptide, a receptor of a CD86 polypeptide, a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a B7-H3 polypeptide, a receptor of a B7-H3 polypeptide (e.g., an ECD of receptor of a B7-H3 polypeptide), a LAG-3 polypeptide (e.g., an ECD of a LAG-3 polypeptide), an IL31 polypeptide, a receptor of an IL31 polypeptide, an IL31RA polypeptide (e.g., an ECD of an IL31RA polypeptide), an OSMR polypeptide (e.g., an ECD of an OSMR polypeptide), an IL4 polypeptide, a receptor of an IL4R polypeptide, an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL 13 polypeptide, a receptor of an IL 13 polypeptide, an IL13RA1 polypeptide (e.g., an ECD of an IL13RA1 polypeptide), an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13Ra2 polypeptide (e.g., an ECD of an IL13Ra2 polypeptide), an IL22 polypeptide, a receptor of an IL22 polypeptide (e.g., an ECD of an IL22 polypeptide), an IL22Ral polypeptide (e.g., an ECD of an IL22Ral polypeptide), an IL10RP2 polypeptide (e.g., an ECD of an IL10Rβ2 polypeptide), an IL33 polypeptide, a receptor of an IL33 polypeptide, an IL1RL1 polypeptide (e.g., an ECD of an IL1RL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a TGFa polypeptide, a receptor of a TGFa polypeptide, an EGFR polypeptide (e.g., an ECD of an EGFR polypeptide), an MMP9 polypeptide, an 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,Attorney Reference No. 2920951-551977 FGF22, or FGF23 polypeptide), a receptor of an FGF polypeptide, an FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3, FGFR4, or FGFRL1 polypeptide), an ECD of an FGFR polypeptide (e.g., an ECD of an FGFR1, an FGFR2, an FGFR3, an FGFR4, or an FGFRL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V, or VI polypeptide), a receptor of a neuregulin polypeptide, a HER polypeptide (e.g., HER1, HER2, HER3, or HER4 polypeptide), an ECD of a HER polypeptide (e.g., an ECD of a HER1, a HER2, a HER3, or a HER4 polypeptide), an EpCAM polypeptide (e.g., an ECD of 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 CD 19 polypeptide, a CGRP polypeptide (e.g., an a-CGRP polypeptide or a P-CGRP polypeptide), a receptor of a CGRP polypeptide, a receptor of an a-CGRP polypeptide, a receptor of a P-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 an IGF-2 polypeptide), a receptor of an IGF polypeptide (e.g., a receptor of an IGF-1 or an IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or an IGFR2 polypeptide), an ECD of an IGFR polypeptide (e.g., an ECD of an IGFR1 or an IGFR2 polypeptide), an IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, or IGFBP6 polypeptide), a VEGF polypeptide (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptide), a receptor of a VEGF polypeptide (e.g., a receptor of a VEGF-A, a VEGF-B, a VEGF-C, a VEGF-D, or a PGF polypeptide), a VEGFR polypeptide (e.g., a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an ECD of a VEGFR polypeptide (e.g., an ECD of a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an FLT1 receptor polypeptide (e.g., an ECD of an FLT1 receptor polypeptide), an IL36 polypeptide (e.g., IL36A, IL36B, or IL36G polypeptide), a receptor of an IL36 polypeptide (e.g., a receptor of an IL36A, an IL36B, or an 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 (an ECD of an IL1RL1 polypeptide), an IL18R1 polypeptide (an ECD of an IL18R1 polypeptide), a bacterial toxin polypeptide, an exotoxin polypeptide, an endotoxin polypeptide, a Botulinum neurotoxin polypeptide, a Tetanus toxin polypeptide, a Staphylococcal toxin polypeptide, a CD52 polypeptide (e.g., an ECD of a CD52 polypeptide), a ligand of a CD52 polypeptide, a SIGLEC10 polypeptide, a PCSK9 polypeptide, a receptor of a PCSK9 polypeptide, an LDLR polypeptide (e.g., an ECD of an LDLR polypeptide), a CEA polypeptide (e.g., CD66a, CD66b,Attorney Reference No. 2920951-551977 CD66c, CD66d, CD66e, or CD66f polypeptide), an ECD of a CEA polypeptide (e.g., an ECD of a CD66a, a CD66b, a CD66c, a CD66d, a CD66e, or a CD66f polypeptide), a BAFF polypeptide, a receptor of a BAFF polypeptide, a TRAF polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptide), a receptor of a TRAF polypeptide (e.g., a receptor of a TRAF1, a TRAF2, a TRAF3, a TRAF4, a TRAF5 polypeptide), a BCMA polypeptide, an ECD of a BCMA polypeptide, a SOST polypeptide, a receptor of a SOST polypeptide, an LRP polypeptide (e.g., an LRP5 or an LRP6 polypeptide), an ECD of an LRP polypeptide (e.g., an ECD of an LRP5 or an LRP6 polypeptide), a DLL polypeptide (e.g., a DLL4 polypeptide), a receptor of a DLL polypeptide, a Jagged polypeptide (e.g., JAG1 or JAG polypeptide), a receptor of a Jagged polypeptide (e.g., a receptor of a JAG1 or a JAG polypeptide), a NOTCH polypeptide (e.g., NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptide), a ligand of a NOTCH polypeptide (e.g., a ligand of a NOTCH1, a NOTCH2, a NOTCH3, or a NOTCH4 polypeptide), a VWF polypeptide, a receptor of a VWF polypeptide, a Factor VIII polypeptide, a receptor of a Factor VIII polypeptide, a platelet GPlb receptor polypeptide (e.g., an ECD of a platelet GPlb receptor polypeptide), an integrin anb03 polypeptide (e.g., an ECD of an integrin anb03 polypeptide), an IL2 polypeptide, a receptor of an IL2 polypeptide, an IL2R polypeptide (e.g., an IL2Ra, an IL2R0, or an IL2Ry polypeptide), an ECD of an IL2R polypeptide (e.g., an ECD of an IL2Ra, an IL2R0, or an IL2Ry polypeptide), a TGF0 polypeptide, a receptor of a TGF0 polypeptide, a Decorin polypeptide, an EIF3I polypeptide, a LTBP1 polypeptide, a TGF0R1 polypeptide (e.g., an ECD of a TGF0R1 polypeptide), a YWHAE polypeptide, an IgE polypeptide, a receptor or an IgE polypeptide, an Fc receptor polypeptide (e.g., an FCERI or an FCERII polypeptide), an ECD of an Fc receptor polypeptide (e.g., an ECD of an FCERI or an FCERII polypeptide), a KLK polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, or KLK15 polypeptide), a Rankl polypeptide, a receptor of a Rankl polypeptide, a RANK polypeptide (e.g., an ECD of a RANK polypeptide), a TSLP polypeptide, a receptor of a TSLP polypeptide, a CRLF2 polypeptide (e.g., an ECD of a CRLF2 polypeptide), an IL7Ra polypeptide (e.g., an ECD of an IL7Ra polypeptide), an SIP polypeptide, a CD3 polypeptide (e.g., a CD3y polypeptide, a CD38 polypeptide, or a CD3E polypeptide), an ECD of a CD3 polypeptide (e.g., an ECD of a CD3y polypeptide, a CD38 polypeptide, or a CD3E polypeptide), a CD80 polypeptide, a receptor of 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 of a GNRH polypeptide, a GnRHR polypeptide (e.g., an ECD of a GnRHR polypeptide), an ICAM polypeptide (e.g., ICAM-1, ICAM-2,Attorney Reference No. 2920951-551977 ICAM-3, ICAM-4, or ICAM-5 polypeptide), a receptor of an ICAM polypeptide (e.g., a receptor of an ICAM-1, an ICAM-2, an ICAM-3, an ICAM-4, or an ICAM-5 polypeptide), a JAM-A polypeptide, a receptor of a JAM-A polypeptide, an LFA-1 polypeptide (e.g., an ECD of an LFA-1 polypeptide), a Nav1.7 polypeptide, a C5 polypeptide (e.g., a C5a or a C5b polypeptide), a receptor of a C5 polypeptide (e.g., a receptor of a C5a or a 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 IL 17 polypeptide, a receptor of an IL 17 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.

17. The polypeptide of claim 16, wherein the therapeutic polypeptide is a canine polypeptide, a feline polypeptide, or an equine polypeptide.

18. The polypeptide of any one of claims 1 - 17, wherein the polypeptide comprises an antibody or antibody fragment that binds at least one target polypeptide selected from a late embryogenesis abundant (LEA) protein polypeptide (e.g., an LEA-3 polypeptide), an NGF polypeptide, a receptor of an NGF polypeptide (e.g., an ECD of a receptor of an NGF polypeptide), a TrkA polypeptide (e.g., an ECD of a TrkA polypeptide), an LNGFR polypeptide (e.g., an ECD of a LNGFR polypeptide), a TNFa polypeptide, a receptor of a TNFa polypeptide, a TNFR polypeptide (e.g., an ECD of a TNFR polypeptide), a TNFR1 polypeptide (e.g., an ECD of a TNFR1 polypeptide), a TNFR2 polypeptide (e.g., an ECD of a TNFR2 polypeptide), an IL5 polypeptide, a receptor of an IL5 polypeptide, an IL5R polypeptide (e.g., an ECD of an IL5R polypeptide), an IL5Ra polypeptide (e.g., an ECD of an IL5Ra polypeptide), an IL6 polypeptide, a receptor of an IL6 polypeptide, an IL6R polypeptide (e.g., an ECD of an IL6R polypeptide), an IL 17 polypeptide, a receptor of an IL 17 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 (e.g., an ECD of an IL17RB polypeptide), an IL17RC polypeptide (e.g., an ECD of an IL17RC polypeptide), an IL23 polypeptide, a receptor of an IL23 polypeptide, an IL23R polypeptide (e.g., an ECD of an IL23R polypeptide), an IL12Rpi polypeptide (e.g., an ECD of an IL12Rpi polypeptide), a PDL1 polypeptide, a receptor of a PDL1 polypeptide, a PDL2 polypeptide, a receptor of a PDL2 polypeptide, a PD1 polypeptide (e.g., an ECD of a PD1 polypeptide), an 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,Attorney Reference No. 2920951-551977 or ITGB8 polypeptide), a receptor of 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), a collagen polypeptide (e.g., an ECD of a collagen polypeptide), a laminin polypeptide (e.g., an ECD of a laminin polypeptide), a CD80 polypeptide, a receptor of a CD80 polypeptide, a CD86 polypeptide, a receptor of a CD86 polypeptide, a CTLA-4 polypeptide (e.g., an ECD of a CTLA-4 polypeptide), a B7-H3 polypeptide, a receptor of a B7-H3 polypeptide (e.g., an ECD of receptor of a B7-H3 polypeptide), a LAG-3 polypeptide (e.g., an ECD of a LAG-3 polypeptide), an IL31 polypeptide, a receptor of an IL31 polypeptide, an IL31RA polypeptide (e.g., an ECD of an IL31RA polypeptide), an OSMR polypeptide (e.g., an ECD of an OSMR polypeptide), an IL4 polypeptide, a receptor of an IL4R polypeptide, an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13 polypeptide, a receptor of an IL13 polypeptide, an IL13RA1 polypeptide (e.g., an ECD of an IL13RA1 polypeptide), an IL4R polypeptide (e.g., an ECD of an IL4R polypeptide), an IL13Ra2 polypeptide (e.g., an ECD of an IL13Ra2 polypeptide), an IL22 polypeptide, a receptor of an IL22 polypeptide (e.g., an ECD of an IL22 polypeptide), an IL22Ral polypeptide (e.g., an ECD of an IL22Ral polypeptide), an IL10RP2 polypeptide (e.g., an ECD of an IL10Rβ2 polypeptide), an IL33 polypeptide, a receptor of an IL33 polypeptide, an IL1RL1 polypeptide (e.g., an ED of an IL1RL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a TGFa polypeptide, a receptor of a TGFa polypeptide, an EGFR polypeptide (e.g., an ECD of an EGFR polypeptide), an MMP9 polypeptide, an 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 of an FGF polypeptide, an FGFR polypeptide (e.g., FGFR1, FGFR2, FGFR3, FGFR4, or FGFRL1 polypeptide), an ECD of an FGFR polypeptide (e.g., an ECD of an FGFR1, an FGFR2, an FGFR3, an FGFR4, or an FGFRL1 polypeptide), an EGF polypeptide, a receptor of an EGF polypeptide, a neuregulin polypeptide (e.g., a neuregulin isoform I, II, III, IV, V, or VI polypeptide), a receptor of a neuregulin polypeptide, a HER polypeptide (e.g., HER1, HER2, HER3, or HER4 polypeptide), an ECD of a HER polypeptide (e.g., an ECD of a HER1, a HER2, a HER3, or a HER4 polypeptide), an EpCAM polypeptide (e.g., an ECD of 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 a-CGRP polypeptide or a 0-CGRP polypeptide), a receptor of a CGRP polypeptide, a receptor of an a-CGRP polypeptide, a receptor of a -CGRP polypeptide, a CALCRL polypeptide (e.g., an ECD of a CALCRL polypeptide), a RAMP polypeptide (e.g.,Attorney Reference No. 2920951-551977 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 an IGF-2 polypeptide), a receptor of an IGF polypeptide (e.g., a receptor of an IGF-1 or an IGF-2 polypeptide), an IGFR polypeptide (e.g., an IGFR1 or an IGFR2 polypeptide), an ECD of an IGFR polypeptide (e.g., an ECD of an IGFR1 or an IGFR2 polypeptide), an IGFBP polypeptide (e.g., IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, or IGFBP6 polypeptide), a VEGF polypeptide (e.g., VEGF-A, VEGF-B, VEGF-C, VEGF-D, or PGF polypeptide), a receptor of a VEGF polypeptide (e.g., a receptor of a VEGF-A, a VEGF-B, a VEGF-C, a VEGF-D, or a PGF polypeptide), a VEGFR polypeptide (e.g., a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an ECD of a VEGFR polypeptide (e.g., an ECD of a VEGFR1, a VEGFR2, or a VEGFR3 polypeptide), an FLT1 receptor polypeptide (e.g., an ECD of an FLT1 receptor polypeptide), an IL36 polypeptide (e.g., IL36A, IL36B, or IL36G polypeptide), a receptor of an IL36 polypeptide (e.g., a receptor of an IL36A, an IL36B, or an 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 (an ECD of an IL1RL1 polypeptide), an IL18R1 polypeptide (an ECD of an IL18R1 polypeptide), a bacterial toxin polypeptide, an exotoxin polypeptide, an endotoxin polypeptide, a Botulinum neurotoxin polypeptide, a Tetanus toxin polypeptide, a Staphylococcal toxin polypeptide, a CD52 polypeptide (e.g., an ECD of a CD52 polypeptide), a ligand of a CD52 polypeptide, a SIGLEC10 polypeptide, a PCSK9 polypeptide, a receptor of a PCSK9 polypeptide, an LDLR polypeptide (e.g., an ECD of an LDLR polypeptide), a CEA polypeptide (e.g., CD66a, CD66b, CD66c, CD66d, CD66e, or CD66f polypeptide), an ECD of a CEA polypeptide (e.g., an ECD of a CD66a, a CD66b, a CD66c, a CD66d, a CD66e, or a CD66f polypeptide), a BAFF polypeptide, a receptor of a BAFF polypeptide, a TRAF polypeptide (e.g., TRAF1, TRAF2, TRAF3, TRAF4, TRAF5, TRAF6, TRAF7 polypeptide), a receptor of a TRAF polypeptide (e.g., a receptor of a TRAF1, a TRAF2, a TRAF3, a TRAF4, a TRAF5 polypeptide), a BCMA polypeptide, an ECD of a BCMA polypeptide, a SOST polypeptide, a receptor of a SOST polypeptide, an LRP polypeptide (e.g., an LRP5 or an LRP6 polypeptide), an ECD of an LRP polypeptide (e.g., an ECD of an LRP5 or an LRP6 polypeptide), a DLL polypeptide (e.g., a DLL4 polypeptide), a receptor of a DLL polypeptide, a Jagged polypeptide (e.g., JAG1 or JAG polypeptide), a receptor of a Jagged polypeptide (e.g., a receptor of a JAG1 or a JAG polypeptide), a NOTCH polypeptide (e.g., NOTCH1, NOTCH2, NOTCH3, or NOTCH4 polypeptide), a ligand of a NOTCH polypeptide (e.g., a ligand of a NOTCH1, a NOTCH2, a NOTCH3, or a NOTCH4 polypeptide), a VWF polypeptide, a receptor of a VWFAttorney Reference No. 2920951-551977 polypeptide, a Factor VIII polypeptide, a receptor of a Factor VIII polypeptide, a platelet GPlb receptor polypeptide (e.g., an ECD of a platelet GPlb receptor polypeptide), an integrin anb03 polypeptide (e.g., an ECD of an integrin anb03 polypeptide), an IL2 polypeptide, a receptor of an IL2 polypeptide, an IL2R polypeptide (e.g., an IL2Ra, an IL2R0, or an IL2Ry polypeptide), an ECD of an IL2R polypeptide (e.g., an ECD of an IL2Ra, an IL2R0, or an IL2Ry polypeptide), a TGF0 polypeptide, a receptor of a TGF0 polypeptide, a Decorin polypeptide, an EIF3I polypeptide, a LTBP1 polypeptide, a TGF0R1 polypeptide (e.g., an ECD of a TGF0R1 polypeptide), a YWHAE polypeptide, an IgE polypeptide, a receptor or an IgE polypeptide, an Fc receptor polypeptide (e.g., an FCERI or an FCERII polypeptide), an ECD of an Fc receptor polypeptide (e.g., an ECD of an FCERI or an FCERII polypeptide), a KLK polypeptide (e.g., KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, or KLK15 polypeptide), a Rankl polypeptide, a receptor of a Rankl polypeptide, a RANK polypeptide (e.g., an ECD of a RANK polypeptide), a TSLP polypeptide, a receptor of a TSLP polypeptide, a CRLF2 polypeptide (e.g., an ECD of a CRLF2 polypeptide), an IL7Ra polypeptide (e.g., an ECD of an IL7Ra polypeptide), an SIP polypeptide, a CD3 polypeptide (e.g., a CD3y polypeptide, a CD38 polypeptide, or a CD3E polypeptide), an ECD of a CD3 polypeptide (e.g., an ECD of a CD3y polypeptide, a CD38 polypeptide, or a CD3E polypeptide), a CD80 polypeptide, a receptor of 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 of a GNRH polypeptide, a GnRHR polypeptide (e.g., an ECD of a GnRHR polypeptide), an ICAM polypeptide (e.g., ICAM-1, ICAM-2, ICAM-3, ICAM-4, or ICAM-5 polypeptide), a receptor of an ICAM polypeptide (e.g., a receptor of an ICAM-1, an ICAM-2, an ICAM-3, an ICAM-4, or an ICAM-5 polypeptide), a JAM-A polypeptide, a receptor of a JAM-A polypeptide, an LFA-1 polypeptide (e.g., an ECD of an LFA-1 polypeptide), a Nav1.7 polypeptide, a C5 polypeptide (e.g., a C5a or a C5b polypeptide), a receptor of a C5 polypeptide (e.g., a receptor of a C5a or a 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 IL 17 polypeptide, a receptor of an IL 17 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.

19. The polypeptide of claim 18, wherein the target polypeptide is a canine polypeptide, a feline polypeptide, or an equine polypeptide.Attorney Reference No. 2920951-551977 20. The polypeptide of any one of claims 1 - 19, wherein the polypeptide comprises an antibody or antibody fragment that binds canine and / or feline neuron growth factor (NGF).

21. The polypeptide of any one of claims 1 - 19, wherein the polypeptide comprises an antibody or antibody fragment that binds canine and / or feline tumor necrosis factor alpha (TNFa).

22. The polypeptide of any one of claims 1 -21, wherein the variant IgG Fc polypeptide has altered binding affinity to Protein A, Clq, CD 16, CD32, or CD64 relative to the wild-type IgG Fc polypeptide.

23. The polypeptide of claim 9, wherein the variant IgG Fc polypeptide comprises 287W, 311Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;24. The polypeptide of claim 23, wherein the variant IgG Fc polypeptide comprises 287W, 311Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2.

25. The polypeptide of claim 9, wherein the variant IgG Fc polypeptide comprises 252Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

26. The polypeptide of claim 25, wherein the variant IgG Fc polypeptide comprises 252Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2.

27. The polypeptide of claim 9, wherein the variant IgG polypeptide comprises 287R, 311 Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

28. The polypeptide of claim 27, wherein the variant IgG polypeptide comprises 287R, 311Y, 408N, and 426Q amino acid substitutions in SEQ ID NO: 2.

29. The polypeptide of claim 9, wherein the variant IgG Fc polypeptide comprises 287W, 311Y, 408N, 426Q, and K439 amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4;30. The polypeptide of claim 29, wherein the variant IgG Fc polypeptide comprises 287W, 311Y, 408N, 426Q, and K439 amino acid substitutions in SEQ ID NO: 2.Attorney Reference No. 2920951-551977 31. The polypeptide of claim 9, wherein the variant IgG Fc polypeptide comprises 252Y, 408N, 426Q and K439 amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

32. The polypeptide of claim 31, wherein the variant IgG Fc polypeptide comprises 252Y, 408N, 426Q and K439 amino acid substitutions in SEQ ID NO: 2.

33. The polypeptide of claim 9, wherein the variant IgG polypeptide comprises 287R, 311Y, 408N, 426Q, and K439 amino acid substitutions in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, or SEQ ID NO: 4.

34. The polypeptide of claim 33, wherein the variant IgG polypeptide comprises 287R, 311Y, 408N, 426Q, and K439 amino acid substitutions in SEQ ID NO: 2.

35. A polypeptide comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 311Y amino substitution; and(ii) one or more amino acid substitutions selected from 252H, 287R, 287W, 408N, 426H, 426Q, 428F, 434H,437R, and 439K.

36. A polypeptide comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 434H amino substitution; and(ii) one or more amino acid substitutions selected from 252H, 311Y, 408N 428F, and 439K.

37. A polypeptide comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises:(i) a 252H, 252Q,or an 252Y amino substitution; and(ii) one or more amino acid substitutions selected from a 287Q, 254T 256D, 256E, 279R, 306V, 307T, 309E, 311Y, 380S, 408N, 426Q, 428F, 431G, 434H, 434Q, 437R, and 439K.

38. The polypeptide of any one of claims 7- 10 and 23 - 37, wherein the variant IgG Fc polypeptide is capable of binding to a neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type IgG Fc polypeptide.Attorney Reference No. 2920951-551977 39. The polypeptide of any one of claims 7 - 10 and 23 - 38, wherein the variant IgG Fc polypeptide has increased serum half-life relative to a polypeptide comprising a wild-type IgG Fc polypeptide and optionally wherein the serum half-life of the IgG Fc polypeptide is from 1.5 to 5 times, 1.5 to 4 times, 1.5 -3 times, 2 - 5 times, 2 to 4 times, more than 1.5 times, more than 2 times, more than 2.5 times, or more than 3 times greater than the corresponding wild-type IgG Fc polypeptide or non-mutated IgG Fc polypeptide.

40. An isolated nucleic acid encoding a polypeptide of any one of claims 1 - 39.

41. A host cell comprising the nucleic acid of claim 40.

42. A host cell that expresses the polypeptide of any one of claims 1 - 39.

43. A method of producing a polypeptide comprising culturing the host cell of claim 41 or of claim 42 and isolating the polypeptide.

44. A pharmaceutical composition comprising a polypeptide of any one of claims 1 -39 and a pharmaceutically acceptable carrier.

45. A method of delivering a polypeptide to a companion animal species comprising administering the polypeptide of any one of claims 1 - 39 or the pharmaceutical composition of claim 44.

46. The method of claim 45, wherein the companion animal is treated parenterally.

47. A method of delivering a polypeptide to a companion animal species comprising administering the polypeptide of any one of claims 1 - 39 or the pharmaceutical composition of claim 44 by an intramuscular route, an intraperitoneal route, an intracerebrospinal route, a subcutaneous route, an intra-arterial route, an intrasynovial route, an intrathecal route, or an inhalation route.

48. The method of any one of claims 45 - 47, wherein the companion animal species is canine, equine, or feline.

49. The method of claim 48, wherein the companion animal species is canine.

50. The method of claim 48, wherein the companion animal species is feline.

51. Use of the polypeptide of anyone of claims 1 - 39 to treat an animal in need thereof.Attorney Reference No. 2920951-551977 52. Use of claim 51 wherein said animal is a comparison animal selected from canine or feline.

53. A polypeptide comprising a variant IgG Fc polypeptide comprising at least one amino acid substitution relative to a wild-type IgG Fc polypeptide, wherein the substitution according to the EU consensus numbering comprises one or more of the following:i. a threonine at position 436;ii. an arginine at position 437;iii. an arginine or leucine at position 438;iv. a lysine at position 439;v. a glutamate at position 440;vi. a threonine, histidine, phenylalanine, tyrosine, methionine, valine, glutamine, arginine, or asparagine at position 252;vii. an alanine or isoleucine at position 259;viii. a phenylalanine, tyrosine, alanine, serine, or histidine at position 434; and wherein the variant IgG Fc polypeptide is capable of binding to a neonatal Fc receptor (FcRn) with an increased affinity relative to the wild-type IgG Fc polypeptide.

54. An IgG Fc polypeptide comprising at least 90% identity, at least 95% identity, at least 97% identity, at least 99% identity, or 100% identity to an amino acid sequence of SEQ ID NO: 300, SEQ ID NO: 301, SEQ ID NO: 302, SEQ ID NO: 303, SEQ ID NO: 304, SEQ ID NO: 305, SEQ ID NO: 306, SEQ ID NO: 307, SEQ ID NO: 308, SEQ ID NO: 309, SEQ ID NO: 310, SEQ ID NO: 311, SEQ ID NO: 312, SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, SEQ ID NO: 316, or SEQ ID NO: 317.

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