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公开(公告)号：US20070009478A1
公开(公告)日：2007-01-11
申请号：US11420546
申请日：2006-05-26
申请人： Carsten Germansen , Bobby Soni , Grethe Rasmussen
发明人： Carsten Germansen , Bobby Soni , Grethe Rasmussen
IPC分类号： A61K38/19 , C07K14/535
CPC分类号： C07K14/535 , A61K38/193 , A61K47/60 , C12P21/02
摘要： A method for increasing the stability and uniformity of a PEGylated G-CSF polypeptide having at least one PEG moiety attached to the epsilon amino group of a lysine residue or the N-terminal amino group and at least one PEG moiety attached to a hydroxyl group, comprising subjecting the polypeptide to an elevated pH of above 8.0 for a period of time suitable to remove PEG moieties attached to a hydroxyl group, and reducing the pH to about 8.0 or lower; as well as PEGylated G-CSF polypeptides and compositions produced according to the method and methods for increasing neutrophil levels in a patient using the PEGylated G-CSF polypeptides and compositions.
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公开(公告)号：US20060286068A1
公开(公告)日：2006-12-21
申请号：US11463861
申请日：2006-08-10
申请人： Torben Nissen , Kim Andersen , Christian Hansen , Jan Mikkelsen , Hans Schambye
发明人： Torben Nissen , Kim Andersen , Christian Hansen , Jan Mikkelsen , Hans Schambye
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.
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公开(公告)号：US20060276377A1
公开(公告)日：2006-12-07
申请号：US11381718
申请日：2006-05-04
申请人： Jesper Haaning , Kim Andersen
发明人： Jesper Haaning , Kim Andersen
IPC分类号： A61K38/37 , C07K14/745 , A61K38/16 , C07H21/04 , C12P21/04
CPC分类号： C12N9/6437 , A61K38/00 , C12Y304/21021
摘要： The present invention relates to novel polypeptide variants of factor VII (FVII) or factor VIIa (FVIIa) polypeptides, where said variants comprise an amino acid substitution in position 10 and 32 and where said variants further comprise a sugar moiety covalently attached to an introduced in vivo N-glycosylation site located outside of the Gla domain. Such polypeptide variants are useful in therapy, in particular for the treatment of a variety of coagulation-related disorders, such as trauma.
摘要翻译： 本发明涉及因子VII（FVII）或因子VIIa（FVIIa）多肽的新型多肽变体，其中所述变体包含位置10和32的氨基酸取代，并且其中所述变体还包含共价连接到引入 位于Gla结构域之外的体内N-糖基化位点。 这样的多肽变体可用于治疗，特别是用于治疗各种凝血相关疾病如创伤。
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公开(公告)号：US20060270829A1
公开(公告)日：2006-11-30
申请号：US11462335
申请日：2006-08-03
申请人： Torben Nissen , Kim Andersen , Christian Hansen , Jan Mikkelsen , Hans Schambye
发明人： Torben Nissen , Kim Andersen , Christian Hansen , Jan Mikkelsen , Hans Schambye
IPC分类号： A61K31/70 , C07K14/00 , A01N43/04 , C07K16/00 , A61K38/00 , C07K17/00 , C07K2/00 , C07K4/00 , C07K5/00 , C07K7/00
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。
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公开(公告)号：US20060270002A1
公开(公告)日：2006-11-30
申请号：US11381717
申请日：2006-05-04
申请人： Jesper Haaning , Kim Andersen
发明人： Jesper Haaning , Kim Andersen
IPC分类号： A61K38/37 , C07K14/765 , C07H21/04 , C12P21/04
CPC分类号： C12N9/6437 , A61K38/00 , C12Y304/21021
摘要： The present invention relates to novel polypeptide variants of factor VII (FVII) or factor VIIa (FVIIa) polypeptides, where said variants comprise an amino acid substitution in position 10 and 32 and where said variants further comprise a sugar moiety covalently attached to an introduced in vivo N-glycosylation site located outside of the Gla domain. Such polypeptide variants are useful in therapy, in particular for the treatment of a variety of coagulation-related disorders, such as trauma.
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公开(公告)号：US20060270000A1
公开(公告)日：2006-11-30
申请号：US11381705
申请日：2006-05-04
申请人： Jesper Haaning , Kim Andersen
发明人： Jesper Haaning , Kim Andersen
IPC分类号： A61K38/38 , C07K14/745 , C07H21/04 , C12P21/04
CPC分类号： C12N9/6437 , A61K38/00 , C12Y304/21021
摘要： The present invention relates to novel polypeptide variants of factor VII (FVII) or factor VIIa (FVIIa) polypeptides, where said variants comprise an amino acid substitution in position 10 and 32 and where said variants further comprise a sugar moiety covalently attached to an introduced in vivo N-glycosylation site located outside of the Gla domain. Such polypeptide variants are useful in therapy, in particular for the treatment of a variety of coagulation-related disorders, such as trauma.
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公开(公告)号：US20060258585A1
公开(公告)日：2006-11-16
申请号：US11396314
申请日：2006-03-30
申请人： Anders Pedersen , Kim Andersen , Claus Bornaes
发明人： Anders Pedersen , Kim Andersen , Claus Bornaes
IPC分类号： A61K38/37 , C07K14/745
CPC分类号： C07K14/745 , A61K38/00 , A61K47/60 , A61K47/62 , C12N9/6437 , C12Y304/21021 , Y10S514/802
摘要： Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.
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公开(公告)号：US20060252128A1
公开(公告)日：2006-11-09
申请号：US11379664
申请日：2006-04-21
申请人： Jesper Haaning , Kim Andersen , Claus Bornaes
发明人： Jesper Haaning , Kim Andersen , Claus Bornaes
CPC分类号： C12N9/6437 , A61K38/4846 , C12N9/647 , C12Y304/21021
摘要： Gla domain variants of human Factor VII or human Factor VIIa, comprising 1-15 amino acid modifications relative to human Factor VII or human Factor VIIa, wherein a hydrophobic amino acid residue has been introduced by substitution in position 34; or having an amino acid substitution in position 36; and use of the variants for the treatment of intracerebral haemorrhage (ICH) or trauma.
摘要翻译： 人因子VII或人因子VIIa的Gla结构域变体，其相对于人因子VII或人因子VIIa包含1-15个氨基酸修饰，其中通过在位置34取代引入疏水性氨基酸残基; 或在36位具有氨基酸取代; 并使用变体治疗脑内出血（ICH）或创伤。
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公开(公告)号：US20060252127A1
公开(公告)日：2006-11-09
申请号：US11379189
申请日：2006-04-18
申请人： Anders Pedersen , Kim Andersen , Claus Bornaes
发明人： Anders Pedersen , Kim Andersen , Claus Bornaes
IPC分类号： A61K38/37 , C07H21/04 , C12P21/04 , C07K14/745
CPC分类号： C07K14/745 , A61K38/00 , A61K47/60 , A61K47/62 , C12N9/6437 , C12Y304/21021 , Y10S514/802
摘要： Conjugates of Factor VII (FVII) and Factor VIIa (FVIIA) are provided, as are methods for preparing them. Methods for producing novel polypeptides contributing to the production of such conjugates are provided. Methods of treatment by administering a FVII or FVIIa conjugate are provided.
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公开(公告)号：US20060241041A1
公开(公告)日：2006-10-26
申请号：US11424035
申请日：2006-06-14
申请人： Jesper Haaning , Kim Andersen , Claus Bornaes
发明人： Jesper Haaning , Kim Andersen , Claus Bornaes
CPC分类号： C12N9/6437 , A61K38/4846 , C12N9/647 , C12Y304/21021
摘要： Gla domain variants of human Factor VII or human Factor VIIa, comprising 1-15 amino acid modifications relative to human Factor VII or human Factor VIIa, wherein a hydrophobic amino acid residue has been introduced by substitution in position 34; or having an amino acid substitution in position 36; and use of the variants for the treatment of intracerebral haemorrhage (ICH) or trauma.
摘要翻译： 人因子VII或人因子VIIa的Gla结构域变体，其相对于人因子VII或人因子VIIa包含1-15个氨基酸修饰，其中通过在位置34取代引入疏水性氨基酸残基; 或在36位具有氨基酸取代; 并使用变体治疗脑内出血（ICH）或创伤。
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