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1. 发明授权

US08518668B2 Method for making maturated insulin polypeptides in a fungal cell 有权
标题翻译：在真菌细胞中制备成熟胰岛素多肽的方法
公开(公告)号：US08518668B2
公开(公告)日：2013-08-27
申请号：US12311431
申请日：2007-09-26
申请人： Per Nørgaard , Asser Sloth Andersen
发明人： Per Nørgaard , Asser Sloth Andersen
IPC分类号： C12N1/15 , C12N15/17 , C12P21/06
CPC分类号： C07K14/62
摘要： The invention is related to a method for making mature human insulin or an analogue thereof by culturing a fungi cell comprising a DNA sequence encoding a precursor for human insulin or an analogue of human insulin which precursor comprises the B-chain of human insulin or an analogue thereof, the A-chain of human insulin or an analogue thereof and a C-peptide linking the B-chain and the A-chain together thereof, wherein the C-peptide comprises at least one Kex2 cleavage site and an amino acid sequence attached at one end to the C-terminal amino acid residue in the B-chain and at the other end to the Kex2 site which amino acid sequence will facilitate a more efficient Kex2 cleavage within the fungi cell. The C-terminal extension of the B-chain may furthermore be capable of subsequently being cleaved off from the C-terminal amino acid residue in the B-chain by means of a carboxypeptidase activity either within the fungi cell or subsequently in the culture medium.
摘要翻译：本发明涉及通过培养包含编码人胰岛素前体的DNA序列或人胰岛素类似物的真菌细胞来制备成熟人胰岛素或其类似物的方法，该前体包含人胰岛素的B链或类似物其中，人胰岛素的A链或其类似物和将β-链和A链连接在一起的C-肽，其中所述C-肽包含至少一个Kex2切割位点和附着于其上的氨基酸序列一端到B链中的C-末端氨基酸残基，另一端连接到Kex2位点，该氨基酸序列将促进真菌细胞内的更有效的Kex2切割。 B链的C-末端延伸还可以随后通过真菌细胞内或随后在培养基中的羧肽酶活性随后从B链中的C末端氨基酸残基断裂。

2. 发明申请

US20090170750A1 Single-Chain Insulin 有权
标题翻译：单链胰岛素
公开(公告)号：US20090170750A1
公开(公告)日：2009-07-02
申请号：US12251901
申请日：2008-10-15
申请人： Thomas Borglum Kjeldsen , Asser Sloth Andersen , Morten Schlein , Anders Robert Sorensen , Peter Madsen
发明人： Thomas Borglum Kjeldsen , Asser Sloth Andersen , Morten Schlein , Anders Robert Sorensen , Peter Madsen
IPC分类号： A61K38/28 , C07K14/62 , C07H21/00 , C12N15/63 , C12N5/10
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 6-11 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6-11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。

3. 发明授权

US06861237B2 Production of heterologous polypeptides in yeast 失效
标题翻译：在酵母中产生异源多肽
公开(公告)号：US06861237B2
公开(公告)日：2005-03-01
申请号：US10002826
申请日：2001-11-30
申请人： Asser Sloth Andersen , Ivan Diers
发明人： Asser Sloth Andersen , Ivan Diers
IPC分类号： C07K14/395 , C07K14/62 , C12P21/02 , C12P21/00 , C12N15/63 , C12N15/81
CPC分类号： C07K14/62 , C07K14/395 , C12P21/02
摘要： A process for producing high amount of proteins or polypeptides in yeast is disclosed. The process makes use of the CIT1 yeast promoter or a functional part or variant thereof. Examples of polypeptides which are expressed in high yields are insulin or insulin analogues or GLP1.
摘要翻译：公开了一种在酵母中产生大量蛋白质或多肽的方法。该方法利用CIT1酵母启动子或其功能部分或变体。以高产量表达的多肽的实例是胰岛素或胰岛素类似物或GLP1。

4. 发明授权

US09732137B2 Semi-recombinant preparation of GLP-1 analogues 有权
公开(公告)号：US09732137B2
公开(公告)日：2017-08-15
申请号：US12810934
申请日：2008-12-22
申请人： Jesper Færgeman Lau , Asser Sloth Andersen , Paw Bloch , Jesper Lau , Patrick William Garibay , Thomas Kruse , Inga Sig Nielsen Nørby , Claus Ulrich Jessen , Caspar Christensen , Jens Christian Norrild
发明人： Jesper Færgeman Lau , Asser Sloth Andersen , Paw Bloch , Jesper Lau , Patrick William Garibay , Thomas Kruse , Inga Sig Nielsen Nørby , Claus Ulrich Jessen , Caspar Christensen , Jens Christian Norrild
IPC分类号： C07K14/605 , C07K1/107 , C07K1/02 , C07K1/06 , C07K1/36 , C07K1/00
CPC分类号： C07K14/605 , C07K1/006 , C07K1/02 , C07K1/061 , C07K1/107 , C07K1/1077
摘要： A semi-recombinant method for the production of GLP-1 analogues and derivatives with non-proteogenic amino acids in the N-terminal part combining the use of recombinant expression techniques and chemical peptide synthesis.

5. 发明授权

US08815541B2 Method for making polypeptides 有权
标题翻译：制备多肽的方法
公开(公告)号：US08815541B2
公开(公告)日：2014-08-26
申请号：US13510363
申请日：2010-11-25
申请人： Asser Sloth Andersen , Inger Lautrup-Larsen , Per Noergaard
发明人： Asser Sloth Andersen , Inger Lautrup-Larsen , Per Noergaard
IPC分类号： C12P21/06 , C07K14/575 , C12P21/02 , C12N15/81 , C12N9/60
CPC分类号： C07K14/575 , C12N9/60 , C12N15/81 , C12P21/02
摘要： The invention provides an improved method for producing polypeptides with a C-terminal glycine in a yeast transformant being characterized in having a non functional KEX1 gene. The method is in particular well suited to produce polypeptides with an aromatic amino acid residue attached to the C-terminal glycine. The yeast strain may have further non-functional protease genes selected from PEP4, YPS1, MKCI, YPS3, YPS5, YPS6, YPS7, PRB1, STE13 and KEX2.
摘要翻译：本发明提供在酵母转化体中产生具有C-末端甘氨酸的多肽的改进方法，其特征在于具有非功能性KEX1基因。该方法特别适用于产生具有连接至C-末端甘氨酸的芳族氨基酸残基的多肽。酵母菌株可以具有选自PEP4，YPS1，MKCI，YPS3，YPS5，YPS6，YPS7，PRB1，STE13和KEX2的其他非功能性蛋白酶基因。

6. 发明申请

US20100317057A1 SEMI-RECOMBINANT PREPARATION OF GLP-1 ANALOGUES 审中-公开
标题翻译： GLP-1类似物的半重复制备
公开(公告)号：US20100317057A1
公开(公告)日：2010-12-16
申请号：US12810934
申请日：2007-12-22
申请人： Jesper Faergeman Lau , Asser Sloth Andersen , Paw Bloch , Jesper Lau , Patrick William Garibay , Thomas Kruse , Inga Sig Nielsen Nørby , Claus Ulrich Jessen , Caspar Christensen , Jens Christian Norrild
发明人： Jesper Faergeman Lau , Asser Sloth Andersen , Paw Bloch , Jesper Lau , Patrick William Garibay , Thomas Kruse , Inga Sig Nielsen Nørby , Claus Ulrich Jessen , Caspar Christensen , Jens Christian Norrild
IPC分类号： C12P21/00
CPC分类号： C07K14/605 , C07K1/006 , C07K1/02 , C07K1/061 , C07K1/107 , C07K1/1077
摘要： A semi-recombinant method for the production of GLP-1 analogues and derivatives with non-proteogenic amino acids in the N-terminal part combining the use of recombinant expression techniques and chemical peptide synthesis.
摘要翻译：在重组表达技术和化学肽合成的N末端部分中用于生产具有非蛋白质氨基酸的GLP-1类似物和衍生物的半重组方法。

7. 发明授权

US5750497A Acylated insulin 失效
标题翻译：酰化胰岛素
公开(公告)号：US5750497A
公开(公告)日：1998-05-12
申请号：US400256
申请日：1995-03-08
申请人： Svend Havelund , John Halstr.o slashed.m , Ib Jonassen , Asser Sloth Andersen , Jan Markussen
发明人： Svend Havelund , John Halstr.o slashed.m , Ib Jonassen , Asser Sloth Andersen , Jan Markussen
IPC分类号： C12N15/09 , A61K38/00 , A61K38/28 , A61P3/08 , A61P3/10 , C07K14/62 , C12N1/19 , C12N1/21 , C12P21/02 , C12R1/19 , C12R1/865
CPC分类号： C07K14/62 , A61K38/00 , Y10S514/866
摘要： The present invention relates to human insulin derivatives having a protracted profile of action in which the A21 and B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; Phe.sup.B1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the E-amino group of Lys.sup.B29 ; (b) any amino acid residue which can be coded by the genetic code except Lys, Arg and Cys, in which case a lipophilic substituent is bound to the E-amino group of Lys.sup.B29 ; or (c) deleted, in which case a lipophilic substituent is bound to the E-amino group of LyS.sup.B29 ; and any Zn.sup.2+ complexes thereof; provided that when the B30 amino acid residue is Thr or Ala, the A21 and B3 amino acid residues are both Asn and Phe.sup.B1 is present, then the insulin derivative is a Zn.sup.2 + complex.
摘要翻译：本发明涉及具有延长的作用曲线的人胰岛素衍生物，其中A21和B3氨基酸残基独立地是可由除Lys，Arg和Cys之外的遗传密码编码的任何氨基酸残基; PheB1可能被删除; B30氨基酸残基是（a）具有10-24个碳原子的非可编码的亲脂性氨基酸，在这种情况下，具有至多5个碳原子的羧酸的酰基与LysB29的E-氨基结合 ; （b）除了Lys，Arg和Cys之外可以通过遗传密码编码的任何氨基酸残基，在这种情况下，亲油性取代基与LysB29的E氨基结合; 或（c）缺失，在这种情况下，亲油取代基与LySB29的E氨基结合; 及其任何Zn2 +配合物; 条件是当B30氨基酸残基是Thr或Ala时，A21和B3氨基酸残基都是Asn和PheB1，则胰岛素衍生物是Zn 2+络合物。

8. 发明授权

US09056921B2 Method for making mature insulin polypeptides 有权
标题翻译：制备成熟胰岛素多肽的方法
公开(公告)号：US09056921B2
公开(公告)日：2015-06-16
申请号：US12063692
申请日：2006-08-15
申请人： Asser Sloth Andersen , Lars Hojlund Christensen
发明人： Asser Sloth Andersen , Lars Hojlund Christensen
IPC分类号： C12N1/19 , C12N15/17 , C12N15/63 , C12N1/16 , C07K14/62
CPC分类号： C07K14/62 , C12N1/16 , C12N15/63
摘要： The invention is related to a method for making human insulin analogs by culturing an fungi cell comprising a DNA vector encoding a precursor for human insulin analog, wherein the said precursor comprises a connecting peptide flanked with cleavage sites at both junctions with the A- and the B-chain of the insulin peptide, respectively said cleavage sites being cleaved within the fungi cell allowing the cell to secrete high amount of correctly processed, mature two chain human insulin analog to the culture media.
摘要翻译：本发明涉及一种通过培养包含编码人胰岛素类似物前体的DNA载体的真菌细胞制备人胰岛素类似物的方法，其中所述前体包含在与A连接的两个连接处具有切割位点的连接肽，胰岛素肽的B链分别表示切割位点在真菌细胞内被切割，允许细胞分泌大量正确加工的，成熟的两链人类胰岛素类似物与培养基。

9. 发明申请

US20120282653A1 METHOD FOR MAKING POLYPEPTIDES 有权
标题翻译：制备多糖的方法
公开(公告)号：US20120282653A1
公开(公告)日：2012-11-08
申请号：US13510363
申请日：2010-11-25
申请人： Asser Sloth Andersen , Inger Lautrup-Larsen , Per Noergaard
发明人： Asser Sloth Andersen , Inger Lautrup-Larsen , Per Noergaard
IPC分类号： C12P21/00
CPC分类号： C07K14/575 , C12N9/60 , C12N15/81 , C12P21/02
摘要： The invention provides an improved method for producing polypeptides with a C-terminal glycine in a yeast transformant being characterized in having a non functional KEX1 gene. The method is in particular well suited to produce polypeptides with an aromatic amino acid residue attached to the C-terminal glycine. The yeast strain may have further non-functional protease genes selected from PEP4, YPS1, MKCI, YPS3, YPS5, YPS6, YPS7, PRB1, STE13 and KEX2.
摘要翻译：本发明提供在酵母转化体中产生具有C-末端甘氨酸的多肽的改进方法，其特征在于具有非功能性KEX1基因。该方法特别适用于产生具有连接至C-末端甘氨酸的芳族氨基酸残基的多肽。酵母菌株可以具有选自PEP4，YPS1，MKCI，YPS3，YPS5，YPS6，YPS7，PRB1，STE13和KEX2的其他非功能性蛋白酶基因。

10. 发明申请

US20110111460A1 Method for Making Mature Insulin Polypeptides 有权
标题翻译：制备成熟胰岛素多肽的方法
公开(公告)号：US20110111460A1
公开(公告)日：2011-05-12
申请号：US12063692
申请日：2006-08-15
申请人： Asser Sloth Andersen , Lars Hojlund Christensen
发明人： Asser Sloth Andersen , Lars Hojlund Christensen
IPC分类号： C12P21/00 , C12N15/17 , C12N15/63 , C12N1/19
CPC分类号： C07K14/62 , C12N1/16 , C12N15/63
摘要： The invention is related to a method for making human insulin analogues by culturing an fungi cell comprising a DNA vector encoding a precursor for human insulin analogue, wherein the said precursor comprises a connecting peptide flanked with cleavage sites at both junctions with the A- and the B-chain of the insulin peptide, respectively said cleavage sites being cleaved within the fungi cell allowing the cell to secrete high amount of correctly processed, mature two chain human insulin analogue to the culture media.
摘要翻译：本发明涉及通过培养包含编码人胰岛素类似物的前体的DNA载体的真菌细胞来制备人胰岛素类似物的方法，其中所述前体包含在与A连接的两个连接处具有切割位点的连接肽，胰岛素肽的B链分别表示切割位点在真菌细胞内切割，使得细胞能够分泌大量正确加工的成熟的两链人胰岛素类似物到培养基中。

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