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Demunized serum binding domains and their use to extend serum half-life
专利权人:
Inc.;MacroGenics
发明人:
BONVINI, Ezio,BARAT, Bhaswati,HUANG, Ling,JOHNSON, Leslie S.
申请号:
ES12789439
公开号:
ES2605784T3
申请日:
2012.05.16
申请国别(地区):
ES
年份:
2017
代理人:
摘要:
A polypeptide comprising a portion of a protein that binds to deimmunized serum capable of binding to said whey protein; wherein said portion of protein that binds to deimmunized serum is a variant of a wild-type albumin binding domain (ABD) of a Streptococcal Protein G, said wild-type ABD having the amino acid sequence of SEQ ID NO: 304; wherein said variant ABD has an amino acid sequence that differs from that of SEQ ID NO: 304 in that it comprises: (A) a variation of valine to alanine at position 71 of ABD, wherein said position of variant ABD is position 31 of SEQ ID NO: 304; (B) a variation of leucine to alanine at position 64 of ABD, a variation of isoleucine to alanine at position 65 of ABD, and a variation of valine to alanine at position 71 of ABD, wherein said positions of ABD variant are respectively positions 24, 25, and 31 of SEQ ID NO: 304; or (C) a variation of asparagine to aspartic acid at position 66 ABD, a substitution of threonine to serine at position 70 ABD, and a variation of valine to alanine at position 71 of ABD, in which said ABD positions variant are respectively positions 26, 30, and 31 of SEQ ID NO: 304; wherein said portion of protein that binds to deimmunized serum extends the serum half-life of said polypeptide, relative to the serum half-life of said polypeptide if said portion of said protein that binds to de-immunized serum is lacking.Un polipéptido que comprende una porción de una proteína que se une a suero desinmunizada capaz de unirse a dicha proteína de suero; en el que dicha porción de proteína que se une a suero desinmunizada es una variante de un dominio de unión a albúmina tipo natural (ABD) de una Proteína G de Estreptococos, dicha ABD de tipo natural que tiene la secuencia de aminoácidos de la SEQ ID NO:304; en la que dicha ABD variante tiene una secuencia de aminoácidos que difiere de aquella de la SEQ ID NO:304 en que comprende: (A) una variación de valina a alanina en la posición 71 de ABD, en la que dicha posición d
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