发明名称 |
MODIFIZIERTER GRANULOZYTEN STIMULIERENDER FACTOR (G-CSF) MIT VERRINGERTER IMMUNOGENITÄT |
摘要 |
A method of preparing a modified granulocyte colony stimulating factor (G-CSF) protein having reduced immunogenicity relative to human G-CSF comprises the steps of (i) identifying one or more potential T-cell epitopes within the amino acid sequence of human G-CSF (SEQ ID NO: 1 ); (ii) designing at least one sequence variant of at least one potential T-cell epitope identified in step (i), wherein the sequence variant eliminates or substantially reduces the MHC class II binding activity of the potential T-cell epitope; (iii) preparing, by recombinant DNA techniques, at least one modified G-CSF protein including a sequence variant designed in step (ii); (iv) evaluating at least one modified G-CSF protein prepared in step (iii) for G-CSF activity and immunogenicity; and (v) selecting a modified G-CSF protein evaluated in step (iv) that has substantially the same therapeutic G-CSF biological activity as, but substantially less immunogenicity than, human G-CSF. |
申请公布号 |
DE60227367(D1) |
申请公布日期 |
2008.08.14 |
申请号 |
DE2002627367 |
申请日期 |
2002.02.05 |
申请人 |
MERCK PATENT GMBH |
发明人 |
CARR, FRANCIS J.;CARTER, GRAHAM;JONES, TIM;WILLIAMS, STEPHEN |
分类号 |
C07K14/535;C12N15/09;A61K9/70;A61K38/00;A61K38/11;A61K38/18;A61K47/02;A61K47/12;A61K48/00;A61P37/02;C07K7/06;C07K7/08;C07K14/54;C07K16/18;C07K16/28;C07K16/30;C07K16/46;C12N15/27;C12P21/02;G06F19/16;G06F19/18 |
主分类号 |
C07K14/535 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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