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1. 发明授权

US09018161B2 Protease resistant insulin analogues 有权
标题翻译：蛋白酶抗性胰岛素类似物
公开(公告)号：US09018161B2
公开(公告)日：2015-04-28
申请号：US12442190
申请日：2007-09-20
申请人： Peter Kresten Nielsen , Frantisek Hubalek , Inger Lautrup-Larsen , Svend Ludvigsen , Ulla Ribel-Madsen , Per Balschmidt , Per Nørgaard , Svend Havelund
发明人： Peter Kresten Nielsen , Frantisek Hubalek , Inger Lautrup-Larsen , Svend Ludvigsen , Ulla Ribel-Madsen , Per Balschmidt , Per Nørgaard , Svend Havelund
IPC分类号： A61K38/28 , C07K14/62 , A61K38/00
CPC分类号： C07K14/62 , A61K38/00
摘要： The present invention relates to novel insulin analogues exhibiting resistance towards protease, wherein at least two amino acids are substituted and/or deleted relative to the parent insulin molecule. A method for the preparation of such insulin analogues, insulin preparations containing the insulin analogues of the invention and a method of treating diabetes mellitus using these insulin analogues is also provided.
摘要翻译：本发明涉及对蛋白酶表现出抗性的新型胰岛素类似物，其中至少两个氨基酸相对于母体胰岛素分子被取代和/或缺失。还提供了制备这种胰岛素类似物的方法，含有本发明的胰岛素类似物的胰岛素制剂和使用这些胰岛素类似物治疗糖尿病的方法。

2. 发明申请

US20100173357A1 METHOD OF MAKING ACTIVATED CARBOXYPEPTIDASES 有权
标题翻译：制备活性羧基纤维素的方法
公开(公告)号：US20100173357A1
公开(公告)日：2010-07-08
申请号：US12312663
申请日：2007-11-21
申请人： Per Nørgaard
发明人： Per Nørgaard
IPC分类号： C12P21/06
CPC分类号： C12N9/48 , C07K14/62 , C07K2319/50 , C12N15/80
摘要： The invention is related to a method for making an activated carboxypeptidase in a fungi cell comprising introducing a DNA sequence encoding a proform of the carboxypeptidase wherein a Kex2 site has been introduced in the prosequence of the carboxypeptidase, culturing the fungi cell under conditions suitable for expression of the procarboxypeptidase and cleaving off the prosequence within the cell to liberate the free active form of the carboxypeptidase. The invention is also related to methods for making mature human insulin and human insulin analogues by use of the activated carboxypeptidase enzyme.
摘要翻译：本发明涉及一种在真菌细胞中制备活化的羧肽酶的方法，包括引入编码羧肽酶形式的DNA序列，其中在羧肽酶的前导序列中引入Kex2位点，在适合于表达的条件下培养真菌细胞的前羧肽酶并切断细胞内的原序以释放羧肽酶的游离活性形式。本发明还涉及通过使用活化的羧肽酶制备成熟人胰岛素和人胰岛素类似物的方法。

3. 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。

4. 发明授权

US08153395B2 Method of making activated carboxypeptidases 有权
标题翻译：活化羧肽酶的制备方法
公开(公告)号：US08153395B2
公开(公告)日：2012-04-10
申请号：US12312663
申请日：2007-11-21
申请人： Per Nørgaard
发明人： Per Nørgaard
IPC分类号： C12P21/06
CPC分类号： C12N9/48 , C07K14/62 , C07K2319/50 , C12N15/80
摘要： The invention is related to a method for making an activated carboxypeptidase in a fungi cell comprising introducing a DNA sequence encoding a proform of the carboxypeptidase wherein a Kex2 site has been introduced in the prosequence of the carboxypeptidase, culturing the fungi cell under conditions suitable for expression of the procarboxypeptidase and cleaving off the prosequence within the cell to liberate the free active form of the carboxypeptidase. The invention is also related to methods for making mature human insulin and human insulin analogues by use of the activated carboxypeptidase enzyme.
摘要翻译：本发明涉及一种在真菌细胞中制备活化的羧肽酶的方法，包括引入编码羧肽酶形式的DNA序列，其中在羧肽酶的前导序列中引入Kex2位点，在适合于表达的条件下培养真菌细胞的前羧肽酶并切断细胞内的原序以释放羧肽酶的游离活性形式。本发明还涉及通过使用活化的羧肽酶制备成熟人胰岛素和人胰岛素类似物的方法。

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