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

Abstract

Provided are compositions for increasing the half-life of a polypeptide or polypeptides in a canine and methods of their use. The compositions involve variant canine IgG Fc regions.

1 - 43 . (canceled) 
     
     
         44 . A polypeptide comprising a canine IgG Fc region variant, or a canine FcRn-binding region thereof, wherein the canine IgG Fc region variant or the canine FcRn-binding region thereof is different from a wild type canine IgG Fc region or a canine FcRn-binding region thereof by no more than one amino acid, wherein the one amino acid difference is His at a position that corresponds to amino acid position 434 of the wild type canine IgG Fc region, wherein the amino acid position is based on EU numbering, and wherein the polypeptide has increased binding affinity to canine FcRn when compared to a control polypeptide, wherein the control polypeptide is identical to the polypeptide except for having the wild type canine IgG Fc region or a FcRn-binding region thereof in place of the canine IgG Fc region variant or the canine FcRn-binding region thereof. 
     
     
         45 . The polypeptide of  claim 44 , wherein the polypeptide further comprises a binding domain. 
     
     
         46 . The polypeptide of  claim 45 , wherein the binding domain comprises (i) six complementarity determining regions (CDRs) of an immunoglobulin molecule; (ii) a ligand binding domain of a canine receptor protein, (iii) a nanobody or (iv) an extracellular domain of a canine receptor protein. 
     
     
         47 . The polypeptide of  claim 45 , wherein the binding domain specifically binds to an antigen selected from the group consisting of NGF, TrKA, ADAMTS, IL-1, IL-2, IL-4, IL-4R, Angiotensin type 1 (AT1) receptor, Angiotensin type 2 (AT2) receptor, IL-5, IL-12, IL-13, IL-31, IL-33, CD3, CD20, CD47, CD52, and complement system complex. 
     
     
         48 . The polypeptide of  claim 44 , further comprising a protein selected from the group consisting of EPO, CTLA4, LFA3, VEGFR1NEGFR3, IL-1 R, IL-4R, GLP-1 receptor agonist, and Thrombopoietin binding peptide. 
     
     
         49 . The polypeptide of  claim 44 , wherein the polypeptide binds to a canine FcRn at a higher level at pH 5.5 than at pH 7.4. 
     
     
         50 . A pharmaceutical composition comprising (i) the polypeptide of  claim 44 , and (ii) a pharmaceutically acceptable excipient. 
     
     
         51 . A polypeptide comprising a canine IgG Fc region variant, or a canine FcRn-binding region thereof, wherein the canine IgG Fc region variant or the canine FcRn-binding region thereof comprises:
 (i) Met at a position that corresponds to amino acid position 252 of the wild type canine IgG Fc region; and   (ii) His at a position that corresponds to amino acid position 434 of the wild type canine IgG Fc region, wherein the amino acid position is based on EU numbering, and wherein the polypeptide has increased binding affinity to canine FcRn when compared to a control polypeptide, wherein the control polypeptide is identical to the polypeptide except for having the wild type canine IgG Fc region or a FcRn-binding region thereof in place of the canine IgG Fc region variant or the canine FcRn-binding region thereof.   
     
     
         52 . The polypeptide of  claim 51 , wherein the polypeptide further comprises a binding domain. 
     
     
         53 . The polypeptide of  claim 52 , wherein the binding domain comprises (i) six CDRs of an immunoglobulin molecule; (ii) a ligand binding domain of a canine receptor protein, (iii) a nanobody or (iv) an extracellular domain of a canine receptor protein. 
     
     
         54 . The polypeptide of  claim 52 , wherein the binding domain specifically binds to an antigen selected from the group consisting of NGF, TrKA, ADAMTS, IL-1, IL-2, IL-4, IL-4R, AT1 receptor, AT2 receptor, IL-5, IL-12, IL-13, IL-31, IL-33, CD3, CD20, CD47, CD52, and complement system complex. 
     
     
         55 . The polypeptide of  claim 51 , further comprising a protein selected from the group consisting of EPO, CTLA4, LFA3, VEGFR1NEGFR3, IL-1 R, IL-4R, GLP-1 receptor agonist, and Thrombopoietin binding peptide. 
     
     
         56 . The polypeptide of  claim 51 , wherein the polypeptide binds to a canine FcRn at a higher level at pH 5.5 than at pH 7.4. 
     
     
         57 . A pharmaceutical composition comprising (i) the polypeptide of  claim 51 , and (ii) a pharmaceutically acceptable excipient.