公开(公告)号：US20140011259A1

公开(公告)日：2014-01-09

申请号：US13936300

申请日：2013-07-08

Applicant: Novozymes A/S

Inventor： Erwin Ludo Roggen ,  Steffen Ernst ,  Allan Svendsen ,  Esben Peter Friis ,  Claus Von Der Osten

IPC: C12N9/54

CPC classification number: C12N9/54 ,  A21D2/267 ,  A21D8/042 ,  A61K39/00 ,  C07K1/047 ,  C07K5/1008 ,  C07K5/101 ,  C07K5/1013 ,  C07K5/1019 ,  C07K5/1021 ,  C07K14/001 ,  C07K16/40 ,  C07K16/4283 ,  C11D3/38627 ,  C11D3/38645 ,  C12N9/0061 ,  C12N9/20 ,  C12Y110/03002 ,  C12Y304/21062 ,  Y10S435/911

Abstract: The present invention relates to a method of selecting a protein variant having modified immunogenicity as compared to the parent protein comprising the steps obtaining antibody binding peptide sequences, using the sequences to localise epitope sequences on the 3-dimensional structure of parent protein, defining an epitope area including amino acids situated within 5 Å from the epitope amino acids constituting the epitope sequence, changing one or more of the amino acids defining the epitope area of the parent protein by genetical engineering mutations of a DNA sequence encoding the parent protein, introducing the mutated DNA sequence into a suitable host, culturing said host and expressing the protein variant, and evaluating the immunogenicity of the protein variant using the parent protein as reference. The invention further relates to the protein variant and use thereof, as well as to a method for producing said protein variant.

Abstract translation: 本发明涉及选择与亲本蛋白相比具有改良的免疫原性的蛋白质变体的方法，其包括获得抗体结合肽序列的步骤，使用该序列来定位母体蛋白的3维结构上的表位序列，限定表位 包括位于构成表位序列的表位氨基酸5埃范围内的氨基酸，通过编码母体蛋白质的DNA序列的遗传工程突变改变限定母体蛋白表位区域的一个或多个氨基酸，引入突变的 DNA序列转化为合适的宿主，培养所述宿主并表达蛋白质变体，并使用亲本蛋白作为参考来评估蛋白质变体的免疫原性。 本发明还涉及蛋白质变体及其用途，以及生产所述蛋白质变体的方法。

公开(公告)号：US20150037872A1

公开(公告)日：2015-02-05

申请号：US14514652

申请日：2014-10-15

Applicant: Novozymes A/S

Inventor： Erwin Ludo Roggen ,  Steffen Ernst ,  Allan Svendsen ,  Esben Peter Friis ,  Claus Von Der Osten

IPC: C12N9/54

CPC classification number: C12N9/54 ,  A21D2/267 ,  A21D8/042 ,  A61K39/00 ,  C07K1/047 ,  C07K5/1008 ,  C07K5/101 ,  C07K5/1013 ,  C07K5/1019 ,  C07K5/1021 ,  C07K14/001 ,  C07K16/40 ,  C07K16/4283 ,  C11D3/38627 ,  C11D3/38645 ,  C12N9/0061 ,  C12N9/20 ,  C12Y110/03002 ,  C12Y304/21062 ,  Y10S435/911

Abstract: The present invention relates to a method of selecting a protein variant having modified immunogenicity as compared to the parent protein comprising the steps obtaining antibody binding peptide sequences, using the sequences to localise epitope sequences on the 3-dimensional structure of parent protein, defining an epitope area including amino acids situated within 5 Å from the epitope amino acids constituting the epitope sequence, changing one or more of the amino acids defining the epitope area of the parent protein by genetical engineering mutations of a DNA sequence encoding the parent protein, introducing the mutated DNA sequence into a suitable host, culturing said host and expressing the protein variant, and evaluating the immunogenicity of the protein variant using the parent protein as reference. The invention further relates to the protein variant and use thereof, as well as to a method for producing said protein variant.

Abstract translation: 本发明涉及选择与亲本蛋白相比具有改良的免疫原性的蛋白质变体的方法，其包括获得抗体结合肽序列的步骤，使用该序列来定位母体蛋白的3维结构上的表位序列，限定表位 包括位于构成表位序列的表位氨基酸5埃范围内的氨基酸，通过编码母体蛋白质的DNA序列的遗传工程突变改变限定母体蛋白表位区域的一个或多个氨基酸，引入突变的 DNA序列转化为合适的宿主，培养所述宿主并表达蛋白质变体，并使用亲本蛋白作为参考来评估蛋白质变体的免疫原性。 本发明还涉及蛋白质变体及其用途，以及生产所述蛋白质变体的方法。