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1. 发明申请

WO2011161125A1 INSULIN DERIVATIVES CONTAINING ADDITIONAL DISULFIDE BONDS 审中-公开
标题翻译：含胰岛素的胰岛素衍生物
公开(公告)号：WO2011161125A1
公开(公告)日：2011-12-29
申请号：PCT/EP2011/060383
申请日：2011-06-21
申请人： NOVO NORDISK A/S , MADSEN, Peter , HUBALEK, Frantisek , KJELDSEN, Thomas, Børglum , LUDVIGSEN, Svend
发明人： MADSEN, Peter , HUBALEK, Frantisek , KJELDSEN, Thomas, Børglum , LUDVIGSEN, Svend
IPC分类号： C07K14/62
CPC分类号： C07K14/62
摘要： The present invention is related to insulin derivatives containing additional disulfide bonds and methods of making such.
摘要翻译：本发明涉及含有二硫键的胰岛素衍生物及其制备方法。

2. 发明申请

WO2007104734A1 ACYLATED SINGLE CHAIN INSULIN 审中-公开
标题翻译：单链单链胰岛素
公开(公告)号：WO2007104734A1
公开(公告)日：2007-09-20
申请号：PCT/EP2007/052286
申请日：2007-03-12
申请人： NOVO NORDISK A/S , MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
发明人： MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
IPC分类号： C07K14/62 , A61K38/28
CPC分类号： C07K14/62 , A61K38/00
摘要： The invention is related to an acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein a lysine residue being substituted for the natural amino acid residue in at least one of the positions A8, A9 or A10 in the human insulin A-chain is chemically modified by acylation.
摘要翻译：本发明涉及包含通过连接肽连接的人胰岛素的B-和A链的酰化单链胰岛素，其中赖氨酸残基被至少一个取代了天然氨基酸残基的人胰岛素A链中的位置A8，A9或A10通过酰化被化学修饰。

3. 发明申请

WO2007096431A1 INSULIN DERIVATIVES 审中-公开
标题翻译：胰岛素衍生物
公开(公告)号：WO2007096431A1
公开(公告)日：2007-08-30
申请号：PCT/EP2007/051835
申请日：2007-02-27
申请人： NOVO NORDISK A/S , FYNBO, Charlotte, Harkjaer , JONASSEN, Ib , KJELDSEN, Thomas, Børglum , MADSEN, Peter , GARIBAY, Patrick, William , KODRA, Janos, Tibor , HOEG-JENSEN, Thomas , TAGMOSE, Tina, Møller
发明人： FYNBO, Charlotte, Harkjaer , JONASSEN, Ib , KJELDSEN, Thomas, Børglum , MADSEN, Peter , GARIBAY, Patrick, William , KODRA, Janos, Tibor , HOEG-JENSEN, Thomas , TAGMOSE, Tina, Møller
IPC分类号： C07K14/62 , A61K38/28
CPC分类号： C07K14/62 , A61K38/00
摘要： The present invention is related to insulin derivatives having a side chain attached to an ε-amino group of a Lys residue present in the A-chain or to an ε -amino group of a Lys residue in the B-chain.
摘要翻译：本发明涉及具有连接在A链中存在的Lys残基的e-氨基的侧链或B链中的Lys残基的e-氨基的胰岛素衍生物。

4. 发明申请

WO2005054291A1 SINGLE-CHAIN INSULIN 审中-公开
标题翻译：单链胰岛素
公开(公告)号：WO2005054291A1
公开(公告)日：2005-06-16
申请号：PCT/DK2004/000843
申请日：2004-12-03
申请人： NOVO NORDISK A/S , KJELDSEN, Thomas, Børglum , ANDERSEN, Asser, Sloth , SCHLEIN, Morten , SØRENSEN, Anders, Robert , MADSEN, Peter
发明人： KJELDSEN, Thomas, Børglum , ANDERSEN, Asser, Sloth , SCHLEIN, Morten , SØRENSEN, Anders, Robert , MADSEN, Peter
IPC分类号： C07K14/62
CPC分类号： C07K14/62 , A61K38/00
摘要： The present invention is related to single-chain insulin having insulin activity comprising a B- and an A-chain or a modified B- and A-chain connected by a connecting peptide of from 5-11 amino acids. The single-chain insulins will have biological insulin activity and an IGF-1 receptor affinity similar to or lower than that of human insulin and a high physical stability. The single-chain insulin may contain at least one basic amino acid residues in the connecting peptide. The single-chain insulins may also be acylated in one or more Lys residues.
摘要翻译：本发明涉及具有胰岛素活性的单链胰岛素，其包含通过5-11个氨基酸的连接肽连接的B和A链或经修饰的B和A链。单链胰岛素将具有与人胰岛素相似或更低的生物胰岛素活性和IGF-1受体亲和力，并具有高的物理稳定性。单链胰岛素可以在连接肽中含有至少一个碱性氨基酸残基。单链胰岛素也可以在一个或多个Lys残基中酰化。

5. 发明申请

WO2007104738A2 ACYLATED SINGLE CHAIN INSULIN 审中-公开
标题翻译：单级单链胰岛素
公开(公告)号：WO2007104738A2
公开(公告)日：2007-09-20
申请号：PCT/EP2007/052294
申请日：2007-03-12
申请人： NOVO NORDISK A/S , MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
发明人： MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
IPC分类号： C07K14/43
CPC分类号： C12N15/62
摘要： The invention is related to an acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein a lysine residue being substituted for the natural amino acid residue in one of the positions A12-A23 in the human insulin A-chain has been chemically modified by acylation.
摘要翻译：本发明涉及包含人胰岛素的B链和A链的酰化单链胰岛素或其连接肽连接的类似物，其中赖氨酸残基取代其中一个的天然氨基酸残基人胰岛素A链中的位置A12-A23已通过酰化化学修饰。

6. 发明申请

WO2007104737A1 ACYLATED SINGLE CHAIN INSULIN 审中-公开
标题翻译：单级单链胰岛素
公开(公告)号：WO2007104737A1
公开(公告)日：2007-09-20
申请号：PCT/EP2007/052289
申请日：2007-03-12
申请人： NOVO NORDISK A/S , MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
发明人： MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
IPC分类号： A61K38/28 , C07K14/62
CPC分类号： C07K14/62 , A61K38/00
摘要： The invention is related to an acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein a lysine residue being substituted for the natural amino acid residue in at least one of the positions B20, B21 or B22 in the human insulin B-chain is chemically modified by acylation.
摘要翻译：本发明涉及包含通过连接肽连接的人胰岛素的B链和A链的酰化单链胰岛素，其中赖氨酸残基被至少一个取代了天然氨基酸残基的人胰岛素B链中的位置B20，B21或B22通过酰化进行化学修饰。

7. 发明申请

WO2007104736A2 ACYLATED SINGLE CHAIN INSULIN 审中-公开
标题翻译：酰化单链胰岛素
公开(公告)号：WO2007104736A2
公开(公告)日：2007-09-20
申请号：PCT/EP2007/052288
申请日：2007-03-12
申请人： NOVO NORDISK A/S , MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
发明人： MADSEN, Peter , KJELDSEN, Thomas, Børglum , TAGMOSE, Tina, Møller
IPC分类号： C07K14/62 , A61K38/28
CPC分类号： C07K14/62
摘要： The invention is related to acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein the natural amino acid residue in position B1 or a lysine residue being substituted for the natural amino acid residue in one of the positions B1, B2, B3 or B4 in the human insulin B-chain has been chemically modified by acylation.
摘要翻译：本发明涉及酰化的单链胰岛素，其包含通过连接肽连接的人胰岛素或其类似物的B链和A链，其中B1位的天然氨基酸残基或取代人胰岛素B链中位置B1，B2，B3或B4之一的天然氨基酸残基的赖氨酸残基已通过酰化化学修饰。

8. 发明申请

WO2006097521A1 PEGYLATED SINGLE-CHAIN INSULIN 审中-公开
标题翻译：聚乙二醇单链胰岛素
公开(公告)号：WO2006097521A1
公开(公告)日：2006-09-21
申请号：PCT/EP2006/060816
申请日：2006-03-17
申请人： NOVO NORDISK A/S , MADSEN, Peter , KJELDSEN, Thomas, Børglum
发明人： MADSEN, Peter , KJELDSEN, Thomas, Børglum
IPC分类号： C07K14/62 , A61K47/48
CPC分类号： C07K14/62 , A61K38/00 , A61K47/60
摘要： The present invention is related to a single-chain insulin comprising the B- and the A-chain of human insulin or analogues thereof connected by a connecting peptide having from 3-35 amino acid residues, wherein the single-chain insulin comprises at least one PEG group attached to at least one lysine residue in the single-chain insulin molecule and/or to the B1 N terminal amino acid residue. The PEGylated single-chain insulins may comprise up to 4 PEG groups which may be the same or different.
摘要翻译：本发明涉及包含通过具有3-35个氨基酸残基的连接肽连接的人胰岛素的B链和A链的单链胰岛素或其类似物，其中所述单链胰岛素包含至少一个 PEG基团连接至单链胰岛素分子中至少一个赖氨酸残基和/或连接至B1N末端氨基酸残基。 PEG化的单链胰岛素可以包含最多4个可以相同或不同的PEG基团。

9. 发明申请

WO2009021955A1 RAPID ACTING INSULIN ANALOGUES 审中-公开
标题翻译：快速行动胰岛素类似物
公开(公告)号：WO2009021955A1
公开(公告)日：2009-02-19
申请号：PCT/EP2008/060596
申请日：2008-08-12
申请人： NOVO NORDISK A/S , OLSEN, Helle, Birk , KJELDSEN, Thomas, Børglum , BALSCHMIDT, Per , GLENDORF, Tine , HAVELUND, Svend
发明人： OLSEN, Helle, Birk , KJELDSEN, Thomas, Børglum , BALSCHMIDT, Per , GLENDORF, Tine , HAVELUND, Svend
IPC分类号： C07K14/62 , A61K38/28
CPC分类号： C07K14/62 , A61K38/00
摘要： The invention is related to fast acting insulin analogues which can form soluble mix- tures (pre-mixed or self-mixed) with long acting insulin analogues. The fast action is achieved through monomerizing substitutions/deletions in the C-terminus of the B-chain of human insulin and the mixability with long acting insulin analogues is achieved through a substitution of the Zn-binding His in position B10 of human insulin with a Gln amino acid residue. In one embodiment the invention is related to fast acting insulin analogues in which at least one of the natural amino acid residues in position B22-B30 in the human B-chain has been substituted with another amino acid residue having the effect of promoting formation of the monomeric form of insulin, the His amino acid residue in position 10 in the B-chain is substituted with a Gln and wherein further one or more of the amino acid residues in position B22-B30 optionally have been deleted.
摘要翻译：本发明涉及可与长效胰岛素类似物形成可溶性混合物（预混合或自混合）的快速作用胰岛素类似物。快速作用通过在人胰岛素的B链的C末端进行单体取代/缺失实现，并且通过用人胰岛素B10位置上的Zn结合His取代长效胰岛素类似物的混合性来实现 Gln氨基酸残基。在一个实施方案中，本发明涉及快速作用的胰岛素类似物，其中人B链中位置B22-B30中的至少一个天然氨基酸残基已经被另一个氨基酸残基取代，其具有促进形成单体形式的胰岛素，B链中10位的His氨基酸残基被Gln取代，并且其中一个或多个位置B22-B30的氨基酸残基可任选地被缺失。

10. 发明申请

WO2005047508A1 PROCESSES FOR MAKING ACYLATED INSULIN 审中-公开
标题翻译：制备精制胰岛素的方法
公开(公告)号：WO2005047508A1
公开(公告)日：2005-05-26
申请号：PCT/DK2004/000782
申请日：2004-11-11
申请人： NOVO NORDISK A/S , KJELDSEN, Thomas, Børglum , MARKUSSEN, Jan
发明人： KJELDSEN, Thomas, Børglum , MARKUSSEN, Jan
IPC分类号： C12N15/17
CPC分类号： C12P21/06 , C07K14/62
摘要： A method is provided which allows high yields of acylated insulin. The method comprises expressing a singe-chain insulin precursor, preferably in yeast, cleaving the single-chain insulin precursor with a suitable protease which will open the peptide bond between the C-terminal amino group in the B-chain and a connecting peptide connecting the B chain with the A-chain, acylating the two-chain insulin intermediate in the e-amino group in LysB29 and subjecting the acylated two-chain insulin intermediate to a proteolytic enzyme which will cleave of the N-terminal extension on the B- and A-chains on the precursor molecule.
摘要翻译：提供了一种允许高产量的酰化胰岛素的方法。所述方法包括将优选在酵母中的单链胰岛素前体表达，用合适的蛋白酶切割单链胰岛素前体，所述蛋白酶将打开B链中的C末端氨基与连接肽之间的连接肽 B链与A链反应，在LysB29的e氨基中酰化双链胰岛素中间体，并使酰化的双链胰岛素中间体进入蛋白水解酶，其将在B-上切割N末端延伸，前体分子上的A链。

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