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1. 发明申请

US20040241806A1 G-CSF polypeptides and conjugates 审中-公开
标题翻译： G-CSF多肽和缀合物
公开(公告)号：US20040241806A1
公开(公告)日：2004-12-02
申请号：US10705745
申请日：2003-11-10
申请人： Maxygen Holdings, Ltd.
发明人： Torben Lauesgaard Nissen , Kim Vilbour Andersen , Christian Karsten Hansen , Jan Moller Mikkelsen , Hans Thalsgard Schambye
IPC分类号： C07K014/53 , C07H021/04 , C12P021/02
CPC分类号： A61K9/0019 , A61K38/00 , A61K47/42 , C07K14/535
摘要： The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and/or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g., be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g., be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate has one or more improved properties such as increased biological half-life and reduced side effects.
摘要翻译：本发明涉及多肽缀合物，其包含显示G-CSF活性的多肽，并且具有不同于至少一个指定的引入和/或去除的氨基酸残基中的人G-CSF的氨基酸序列的氨基酸序列，所述氨基酸残基包含用于非多肽部分，并且具有连接到多肽的连接基团的至少一个非多肽部分。连接基团可以例如是赖氨酸，半胱氨酸，天冬氨酸或谷氨酸残基或糖基化位点，并且非多肽部分可以例如是聚合物，例如聚乙二醇或低聚糖。缀合物具有一个或多个改进的性质，例如增加的生物半衰期和减少的副作用。

2. 发明申请

US20030133907A1 Interferon gamma polypeptide variants 失效
标题翻译：干扰素γ多肽变体
公开(公告)号：US20030133907A1
公开(公告)日：2003-07-17
申请号：US10195707
申请日：2002-07-15
申请人： MaXygen Holdings, Ltd
发明人： Bart Van Den Hazel , Anne Dam Jensen , Frank Bech Nygaard , Kim Vilbour Andersen
IPC分类号： A61K038/21 , C07H021/04 , C12P021/04 , C12N005/06 , C07K014/57
CPC分类号： C07K14/57 , A61K38/00
摘要： When interferon gamma (IFNG) is produced in mammalian cell lines a heterogenous population of IFNG polypeptides is obtained due to C-terminal processing of the IFNG polypeptide. Clearly, this constitutes a severe problem in that valuable polypeptide material is lost and, further, it is necessary to carry out time-consuming and cumbersome purification in order to obtain a homogenous population of active IFNG polypeptides having the desired length. It has now been found that an IFNG fragment containing 132 amino acid residues (truncated at the nucleotide level by introducing a stop-codon after the codon encoding amino acid residue no. 132) does not undergo C-terminal truncation or, at least, is not significantly C-terminally truncated. Furthermore, as the IFNG fragment containing 132 amino acid residues is active, this opens up the possibility of producing a homogenous active IFNG polypeptide in eukaryotic host cells, such as CHO cells. More particularly, the present invention relates to an IFNG polypeptide variant exhibiting IFNG activity and having the amino acid sequence shown in SEQ ID NO:12. In a highly preferred embodiment of the invention, the variant comprises at least one further modification, such as 1-10 further modifications, relative to the amino acid sequence shown in SEQ ID NO:12. A particular preferred further modification is E38NnullS40T.
摘要翻译：当在哺乳动物细胞系中产生干扰素γ（IFNG）时，由于IFNG多肽的C末端加工，获得IFNG多肽的异源群体。显然，这构成了一个严重的问题，即有价值的多肽材料丢失，而且还需要进行耗时且繁琐的纯化，以获得具有所需长度的活性IFNG多肽的均质群体。现在已经发现，含有132个氨基酸残基的IFNG片段（在编码氨基酸残基132号的密码子后通过引入终止密码子在核苷酸水平被截短）不经历C-末端截短，或至少是不显着C末端截断。此外，由于含有132个氨基酸残基的IFNG片段是有活性的，因此可以在真核宿主细胞如CHO细胞中产生均一的活性IFNG多肽。更具体地，本发明涉及表现出IFNG活性且具有SEQ ID NO：12所示氨基酸序列的IFNG多肽变体。在本发明的一个非常优选的实施方案中，相对于SEQ ID NO：12所示的氨基酸序列，变体包含至少一个其它修饰，例如1-10个其它修饰。特别优选的进一步修改是E38N + S40T。

3. 发明申请

US20030158375A1 G-CSF polypeptides and conjugates 审中-公开
标题翻译： G-CSF多肽和缀合物
公开(公告)号：US20030158375A1
公开(公告)日：2003-08-21
申请号：US10318966
申请日：2002-12-13
申请人： Maxygen Holdings, Ltd.
发明人： Torben Lauesgaard Nissen , Kim Vilbour Andersen , Christian Karsten Hansen , Jan Moller Mikkelsen , Hans Thalsgaard Schambye
IPC分类号： C12Q001/68 , A61K039/395 , C07K002/00 , C07K004/00 , C07K005/00 , C07K007/00 , C07K014/00 , C07K016/00 , C07K017/00 , A61K038/00 , C07K001/00
CPC分类号： C07K14/535 , A61K9/0019 , A61K38/00 , A61K47/42 , A61K47/60 , A61K47/61 , C07K14/53
摘要： The invention relates to polypeptide conjugates comprising a polypeptide exhibiting G-CSF activity and having an amino acid sequence that differs from the amino acid sequence of human G-CSF in at least one specified introduced and/or removed amino acid residue comprising an attachment group for a non-polypeptide moiety, and having at least one non-polypeptide moiety attached to an attachment group of the polypeptide. The attachment group may e.g. be a lysine, cysteine, aspartic acid or glutamic acid residue or a glycosylation site, and the non-polypeptide moiety may e.g. be a polymer such as polyethylene glycol or an oligosaccharide. The conjugate, which has a reduced in vitro bioactivity compared to hG-CSF, has one or more improved properties such as increased biological half-life and increased stimulation of neutrophils.
摘要翻译：本发明涉及多肽缀合物，其包含显示G-CSF活性的多肽，并且具有不同于至少一个指定的引入和/或去除的氨基酸残基中的人G-CSF的氨基酸序列的氨基酸序列，所述氨基酸残基包含用于非多肽部分，并且具有连接到多肽的连接基团的至少一个非多肽部分。附件组可以例如。是赖氨酸，半胱氨酸，天冬氨酸或谷氨酸残基或糖基化位点，并且非多肽部分可以是例如。作为聚合物如聚乙二醇或寡糖。与hG-CSF相比，具有降低的体外生物活性的缀合物具有一种或多种改进的性质，例如增加的生物半衰期和增加的嗜中性粒细胞的刺激。

4. 发明申请

US20030153046A1 Interferon gamma conjugates 失效
标题翻译：干扰素γ偶联物
公开(公告)号：US20030153046A1
公开(公告)日：2003-08-14
申请号：US10369495
申请日：2003-02-19
申请人： MaXygen Holdings, Ltd.
发明人： Anne Dam Jensen , Kim Vilbour Andersen , Christian Karsten Hansen
IPC分类号： A61K038/17 , C12P021/02 , C12N005/06 , C07K014/47
CPC分类号： A61K47/60
摘要： A conjugate exhibiting interferon gamma activity and comprising at least one first non-polypeptide moiety covalently linked to an IFG polypeptide, the polypeptide comprising an amino acid sequence that differs from that of a parent IFNG polypeptide in at least one introduced and/or at least one removed amino acid residue comprising an attachment group for the non-polypeptide moiety. The conjugate may be used for treatment of various diseases.
摘要翻译：一种显示干扰素γ活性并包含与IFG多肽共价连接的至少一个第一非多肽部分的缀合物，所述多肽包含与至少一个引入的和/或至少一个的IFIF多肽的母体IFNG多肽不同的氨基酸序列去除的氨基酸残基包含非多肽部分的连接基团。缀合物可用于治疗各种疾病。

5. 发明申请

US20030118612A1 G-CSF conjugates 失效
公开(公告)号：US20030118612A1
公开(公告)日：2003-06-26
申请号：US10192294
申请日：2002-07-10
申请人： Maxygen Holdings Ltd.
发明人： Torben Lauesgaard Nissen , Kim Vilbour Andersen , Christian Karsten Hansen , Jan Moller Mikkelsen , Hans Thalsgaard Schambye
IPC分类号： C07H021/04 , A61K045/00 , A61K047/00 , C07K001/00 , C07K014/00 , C07K017/00
CPC分类号： C07K14/535 , A61K9/0019 , A61K38/00 , A61K47/42 , C07K14/53
摘要： Polypeptide conjugates with G-CSF activity comprising a polypeptide having at least one introduced lysine residue and at least one removed lysine residue compared to the sequence of human G-CSF, and which are conjugated to 2-6 polyethylene glycol moieties. The conjugates have a low in vitro bioactivity, a long in vivo half-life, a reduced receptor-mediated clearance, and provide a more rapid stimulation of production of white blood cells and neutrophils than non-conjugated recombinant human G-CSF.

6. 发明申请

US20040013644A1 Interferon beta-like molecules 失效
标题翻译：干扰素β样分子
公开(公告)号：US20040013644A1
公开(公告)日：2004-01-22
申请号：US10609296
申请日：2003-06-27
申请人： Maxygen ApS , Maxygen Holdings Ltd.
发明人： Poul Baad Rasmussen , Joern Drustrup , Grethe Rasmussen , Anders Hjelholt Pedersen , Hans Thalsgard Schambye , Kim Vilbour Andersen , Claus Bornaes
IPC分类号： A61K038/21 , C07K014/565
CPC分类号： A61K9/0019 , A61K9/0073 , A61K31/724 , A61K38/21 , A61K38/215 , A61K47/40 , A61K47/60 , A61K47/6951 , B82Y5/00 , C07K14/565 , A61K2300/00
摘要： The invention relates to a conjugate exhibiting interferon null (IFNB) activity and comprising at least one first non-polypeptide moiety covalently attached to an IFNB polypeptide, the amino acid sequence of which differs from that of wildtype human IFNB in at least one introduced and at least one removed amino acid residue comprising an attachment group for said first non-polypeptide moiety. The first non-polypeptide moiety is e.g. a polymer molecule or a sugar moiety. The conjugate finds particular use in therapy. The invention also relates to a glycosylated variant of a parent IFNB polypeptide comprising at least one in vivo glycosylation site, wherein an amino acid residue of said parent polypeptide located close to said glycosylation site has been modified to obtain the variant polypeptide having an increased glycosylation as compared to the glycosylation of the parent polypeptide.
摘要翻译：本发明涉及一种表现出干扰素β（IFNB）活性的缀合物，其包含共价连接到IFNB多肽的至少一个第一非多肽部分，所述第一非多肽部分与至少一个引入的和在至少一个除去的氨基酸残基，其包含所述第一非多肽部分的连接基团。第一非多肽部分是例如。聚合物分子或糖部分。该缀合物在治疗中特别有用。本发明还涉及包含至少一个体内糖基化位点的母体IFNB多肽的糖基化变体，其中位于所述糖基化位点附近的所述亲本多肽的氨基酸残基已被修饰以获得具有增加的糖基化的变体多肽作为与母体多肽的糖基化相比。

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