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91. 发明申请

US20100136653A1 CREATION OF DIVERSITY IN POLYPEPTIDES 有权
标题翻译：多糖生物多样性的创造
公开(公告)号：US20100136653A1
公开(公告)日：2010-06-03
申请号：US12703986
申请日：2010-02-11
申请人： Allan Svendsen , Lars Beier
发明人： Allan Svendsen , Lars Beier
IPC分类号： C12N9/10 , C07H21/04
CPC分类号： A21D8/042 , C12N9/1048 , C12N9/2417 , C12N15/1027 , C12N15/1058 , C12N15/1089
摘要： The inventors realized that the diversity generated by conventional methods may be limited by steric hindrance between amino acid residues in the three-dimensional structures of the resulting polypeptides. The steric hindrance may occur between amino acid residues at widely different positions in the amino acid sequences, e.g. between residues in two different domains of the 3D structure, and resulting polypeptides which include such steric hindrance may never be observed in the conventional recombination methods because they may be expressed in poor yields or may have poor activity or stability.The inventors developed a method to identify and alleviate such steric hindrance in the resulting polypeptides. In an alignment of the three-dimensional structures, steric hindrance is indicated when residues from two different structures are located within a certain distance. Pairs of residues at corresponding positions in the amino acid sequences are not considered, and residues close to the surface (high solvent accessibility) are considered to be less prone to steric hindrance.
摘要翻译：发明人意识到，通过常规方法产生的多样性可能受到所得多肽的三维结构中的氨基酸残基之间的空间位阻的限制。空间位阻可以发生在氨基酸序列中广泛不同位置的氨基酸残基之间，例如，在3D结构的两个不同结构域中的残基之间以及包含这种空间位阻的所得多肽在常规重组方法中可能永远不会观察到，因为它们可能以不良产率表达或可能具有差的活性或稳定性。发明人开发了鉴定和减轻所得多肽中这种空间位阻的方法。在三维结构的排列中，当来自两个不同结构的残基位于一定距离内时，指示空间位阻。不考虑氨基酸序列中对应位置的残基对，并且靠近表面的残留物（高溶剂可及性）被认为不太容易产生空间位阻。

92. 发明授权

US09029115B2 Lipase variants for pharmaceutical use 有权
标题翻译：用于药物用途的脂肪酶变体
公开(公告)号：US09029115B2
公开(公告)日：2015-05-12
申请号：US13587043
申请日：2012-08-16
申请人： Allan Svendsen , Michael Skjoet , Deborah Yaver , Lars Lehmann Hylling Christensen , Signe Eskildsen Larsen , Nina Lundin , Michael Lamsa , Peter Colin Gregory
发明人： Allan Svendsen , Michael Skjoet , Deborah Yaver , Lars Lehmann Hylling Christensen , Signe Eskildsen Larsen , Nina Lundin , Michael Lamsa , Peter Colin Gregory
IPC分类号： C12N9/20 , C12N9/14 , C12N9/26 , C12N9/48 , C12Q1/34 , C12Q1/40
CPC分类号： A61K38/465 , A61K38/47 , A61K38/48 , C12N9/20
摘要： The pharmaceutical use of lipases related to the Thermomyces lanuginosus (Humicola lanuginosa) lipase comprising amino acids 1-269 of SEQ ID NO: 2, optionally in combination with a protease and/or an amylase. Examples of medical indications are: Treatment of digestive disorders, pancreatic exocrine insufficiency (PEI), pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II. The lipases of the invention have, e.g., an improved digestion performance in vitro, an improved activity at a pH in the neutral range, an improved stability at low pH, and are stable against protease-degradation, and/or are stable in the presence of pepsin and bile salts. The invention also relates to methods of determining digestion performance in vitro of lipases, as well as to certain novel variants of the lipase of T. lanuginosus.
摘要翻译：与包含SEQ ID NO：2的氨基酸1-269的Thermomyces lanuginosus（Humicola lanuginosa）脂肪酶相关的脂肪酶的药物用途，任选地与蛋白酶和/或淀粉酶组合。医学适应症的例子有：消化系统疾病，胰腺外分泌功能不全（PEI），胰腺炎，囊性纤维化，I型糖尿病和/或II型糖尿病的治疗。本发明的脂肪酶例如在体外具有改善的消化性能，在中性范围内的pH值改善的活性，在低pH下的改进的稳定性，并且对蛋白酶降解是稳定的，和/或在存在下是稳定的的胃蛋白酶和胆汁盐。本发明还涉及确定脂肪酶的体外消化性能的方法以及T.lanuginosus的脂肪酶的某些新颖变体。

93. 发明授权

US08617837B2 Method of hydrolyzing soluble starch with an alpha-amylase variant 有权
标题翻译：用α-淀粉酶变体水解可溶性淀粉的方法
公开(公告)号：US08617837B2
公开(公告)日：2013-12-31
申请号：US13455905
申请日：2012-04-25
申请人： Allan Svendsen , Carsten Andersen , Thomas Thisted , Claus Von Der Osten
发明人： Allan Svendsen , Carsten Andersen , Thomas Thisted , Claus Von Der Osten
IPC分类号： C12Q1/40 , C12N9/28 , C12P21/00 , C07K14/00
CPC分类号： C12N9/2417 , C11D3/386 , C11D3/38618 , C12P7/06 , C12P7/14 , C12P19/14 , C12Y302/01001 , Y02E50/17
摘要： The present invention relates to variants (mutants) of parent Termamyl-like alpha-amylases, which variant has alpha-amylase activity and exhibits altered properties relative to the parent alpha-amylase.
摘要翻译：本发明涉及亲本Termamyl样α-淀粉酶的变体（突变体），该变体具有α-淀粉酶活性并且相对于母体α-淀粉酶具有改变的性质。

94. 发明授权

US08563289B2 Protease variants 有权
标题翻译：蛋白酶变体
公开(公告)号：US08563289B2
公开(公告)日：2013-10-22
申请号：US12758943
申请日：2010-04-13
申请人： Allan Svendsen , Stefan Minning
发明人： Allan Svendsen , Stefan Minning
IPC分类号： C12N9/64 , C07H21/04 , C11D3/386
CPC分类号： C12N9/54 , C07K2299/00
摘要： The present invention relates to methods for producing variants of a parent RP-II protease and the variants having altered properties as compared to the parent RP-II protease.
摘要翻译：本发明涉及用于产生亲本RP-II蛋白酶的变体的方法和与亲本RP-II蛋白酶相比具有改变的性质的变体。

95. 发明授权

US08465957B2 Alpha-amylase variants 有权
标题翻译： α-淀粉酶变体
公开(公告)号：US08465957B2
公开(公告)日：2013-06-18
申请号：US13478512
申请日：2012-05-23
申请人： Allan Svendsen , Soren Kjaerulff , Henrik Bisgaard-Frantzen , Carsten Andersen
发明人： Allan Svendsen , Soren Kjaerulff , Henrik Bisgaard-Frantzen , Carsten Andersen
IPC分类号： C12N9/28
CPC分类号： C12N9/2414 , C07H21/04 , C11D3/38609 , C11D3/38618 , C12N9/2417
摘要： The invention relates to a variant of a parent Termamyl-like alpha-amylase, comprising mutations in two, three, four, five or six regions/positions. The variants have increased stability at high temperatures (relative to the parent). The invention also relates to a DNA construct comprising a DNA sequence encoding an alpha-amylase variant of the invention, a recombinant expression vector which carries a DNA construct of the invention, a cell which is transformed with a DNA construct of the invention, the use of an alpha-amylase variant of the invention for washing and/or dishwashing, textile desizing, starch liquefaction, a detergent additive comprising an alpha-amylase variant of the invention, a manual or automatic dishwashing detergent composition comprising an alpha-amylase variant of the invention, a method for generating a variant of a parent Termamyl-like alpha-amylase, which variant exhibits increased.
摘要翻译：本发明涉及亲本的类戊酰样α-淀粉酶的变体，其包含2,3,4,5或6个/位置的突变。这些变体在高温下（相对于亲本）具有增加的稳定性。本发明还涉及包含编码本发明的α-淀粉酶变体的DNA序列的DNA构建体，携带本发明的DNA构建体的重组表达载体，用本发明的DNA构建体转化的细胞，使用本发明的α-淀粉酶变体用于洗涤和/或餐具洗涤，纺织品退浆，淀粉液化，包含本发明的α-淀粉酶变体的洗涤剂添加剂，手动或自动洗碗洗涤剂组合物，其包含α-淀粉酶变体本发明提供一种产生母体类戊酰样α-淀粉酶的变体的方法，该变体表现出增加。

96. 发明申请

US20120308543A1 Lipase Variants for Pharmaceutical Use 审中-公开
标题翻译：药用脂肪酶变体
公开(公告)号：US20120308543A1
公开(公告)日：2012-12-06
申请号：US13587043
申请日：2012-08-16
申请人： Allan Svendsen , Michael Skjoet , Deborah Yaver , Lars Lehmann Hylling Christensen , Signe Eskildsen Larsen , Nina Lundin , Michael Lamsa , Peter Colin Gregory
发明人： Allan Svendsen , Michael Skjoet , Deborah Yaver , Lars Lehmann Hylling Christensen , Signe Eskildsen Larsen , Nina Lundin , Michael Lamsa , Peter Colin Gregory
IPC分类号： A61K38/54 , A61P3/00 , A61P3/10 , C12N9/20 , A61P1/00
CPC分类号： A61K38/465 , A61K38/47 , A61K38/48 , C12N9/20
摘要： The pharmaceutical use of lipases related to the Thermomyces lanuginosus (Humicola lanuginosa) lipase comprising amino acids 1-269 of SEQ ID NO: 2, optionally in combination with a protease and/or an amylase. Examples of medical indications are: Treatment of digestive disorders, pancreatic exocrine insufficiency (PEI), pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II. The lipases of the invention have, e.g., an improved digestion performance in vitro, an improved activity at a pH in the neutral range, an improved stability at low pH, an are stable against protease-degradation, and/or are stable in the presence of pepsin and bile salts. The invention also relates to methods of determining digestion performance in vitro of lipases, as well as to certain novel variants of the lipase of T. lanuginosus.
摘要翻译：与包含SEQ ID NO：2的氨基酸1-269的Thermomyces lanuginosus（Humicola lanuginosa）脂肪酶相关的脂肪酶的药物用途，任选地与蛋白酶和/或淀粉酶组合。医学适应症的例子有：消化系统疾病，胰腺外分泌功能不全（PEI），胰腺炎，囊性纤维化，I型糖尿病和/或II型糖尿病的治疗。本发明的脂肪酶具有例如体外改进的消化性能，在中性范围内的pH值改善的活性，在低pH下的改进的稳定性，对蛋白酶降解是稳定的，和/或在存在时是稳定的的胃蛋白酶和胆汁盐。本发明还涉及确定脂肪酶的体外消化性能的方法以及T.lanuginosus的脂肪酶的某些新颖变体。

97. 发明授权

US08263382B2 Alpha-amylase mutants 有权
标题翻译： α-淀粉酶突变体
公开(公告)号：US08263382B2
公开(公告)日：2012-09-11
申请号：US13100407
申请日：2011-05-04
申请人： Allan Svendsen , Torben Vedel Borchert , Henrik Bisgard-Frantzen
发明人： Allan Svendsen , Torben Vedel Borchert , Henrik Bisgard-Frantzen
IPC分类号： C12N9/24
CPC分类号： C12N9/2417 , C11D3/386 , C12P19/02 , C12P19/14
摘要： The invention relates to a variant of a parent Termamyl-like alpha-amylase, which variant has alpha-amylase activity and exhibits an alteration in at least one of the following properties relative to the parent alpha-amylase: substrate specificity, substrate binding, substrate cleavage pattern, thermal stability, pH/activity profile, pH/stability profile, stability towards oxidation, Ca2+ dependency and specific activity.
摘要翻译：本发明涉及母体类戊酰样α-淀粉酶的变体，该变体具有α-淀粉酶活性并且相对于母体α-淀粉酶在下列特性中表现出至少一个变化：底物特异性，底物结合，底物裂解模式，热稳定性，pH /活性分布，pH /稳定性分布，对氧化的稳定性，Ca 2+依赖性和比活性。

98. 发明授权

US08124395B2 Alpha-amylase variants 有权
标题翻译： α-淀粉酶变体
公开(公告)号：US08124395B2
公开(公告)日：2012-02-28
申请号：US12952695
申请日：2010-11-23
申请人： Carsten Andersen , Christel Thea Jorgensen , Henrik Bisgard-Frantzen , Allan Svendsen , Soren Kjaerulff
发明人： Carsten Andersen , Christel Thea Jorgensen , Henrik Bisgard-Frantzen , Allan Svendsen , Soren Kjaerulff
IPC分类号： C12N9/00 , C12N9/28 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： C12N9/2417 , C07K2319/00 , C12P19/04 , C12P19/14 , C12Y302/01001 , Y02E50/17 , Y02P20/52
摘要： The invention relates to a variant of a parent Termamyl-like alpha-amylase, which variant exhibits altered properties, in particular reduced capability of cleaving a substrate close to the branching point, and improved substrate specificity and/or improved specific activity relative to the parent alpha-amylase.
摘要翻译：本发明涉及母体类戊酰样α-淀粉酶的变体，该变体表现出改变的性质，特别是降低了切割接近分支点的底物的能力，以及相对于母体改善的底物特异性和/或改善的比活性 α-淀粉酶。

99. 发明申请

US20110287516A1 Alpha-Amylase Variants 审中-公开
标题翻译： α-淀粉酶变体
公开(公告)号：US20110287516A1
公开(公告)日：2011-11-24
申请号：US13038991
申请日：2011-03-02
申请人： Allan Svendsen , Soeren Kjaerulff , Henrik Bisgaard-Frantzen , Carsten Andersen
发明人： Allan Svendsen , Soeren Kjaerulff , Henrik Bisgaard-Frantzen , Carsten Andersen
IPC分类号： C12N9/26
CPC分类号： C12N9/2414 , C07H21/04 , C11D3/38609 , C11D3/38618 , C12N9/2417
摘要： The invention relates to a variant of a parent Termamyl-like alpha-amylase, comprising mutations in two, three, four, five or six regions/positions. The variants have increased stability at high temperatures (relative to the parent). The invention also relates to a DNA construct comprising a DNA sequence encoding an alpha-amylase variant of the invention, a recombinant expression vector which carries a DNA construct of the invention, a cell which is transformed with a DNA construct of the invention, the use of an alpha-amylase variant of the invention for washing and/or dishwashing, textile desizing, starch liquefaction, a detergent additive comprising an alpha-amylase variant of the invention, a manual or automatic dishwashing detergent composition comprising an alpha-amylase variant of the invention, a method for generating a variant of a parent Termamyl-like alpha-amylase, which variant exhibits increased.
摘要翻译：本发明涉及亲本的类戊酰样α-淀粉酶的变体，其包含2,3,4,5或6个/位置的突变。这些变体在高温下（相对于亲本）具有增加的稳定性。本发明还涉及包含编码本发明的α-淀粉酶变体的DNA序列的DNA构建体，携带本发明的DNA构建体的重组表达载体，用本发明的DNA构建体转化的细胞，使用本发明的α-淀粉酶变体用于洗涤和/或餐具洗涤，纺织品退浆，淀粉液化，包含本发明的α-淀粉酶变体的洗涤剂添加剂，手动或自动洗碗洗涤剂组合物，其包含α-淀粉酶变体本发明提供一种产生母体类戊酰样α-淀粉酶的变体的方法，该变体表现出增加。

100. 发明申请

US20110158976A1 Enzymes for pharmaceutical use 审中-公开
标题翻译：药用酶
公开(公告)号：US20110158976A1
公开(公告)日：2011-06-30
申请号：US11597273
申请日：2005-05-24
申请人： Allan Svendsen , Svend Kaasgaard , Kim Borch , Morten Fischer , Dan Pettersson , Peter Colin Gregory
发明人： Allan Svendsen , Svend Kaasgaard , Kim Borch , Morten Fischer , Dan Pettersson , Peter Colin Gregory
IPC分类号： A61K38/48 , C12N9/52 , A61P3/00
CPC分类号： A61K38/482 , A61K38/465 , A61K38/47 , A61K2300/00
摘要： The pharmaceutical use of proteases related to a protease derived from Nocardiopsis sp. NRRL 18262 (SEQ ID NO: 1), optionally in combination with a lipase and/or an amylase. Examples of medical indications are: Treatment of digestive disorders, pancreatic exocrine insufficiency (PEI), pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II.
摘要翻译：与来自诺卡氏菌属的蛋白酶有关的蛋白酶的药物用途 NRRL 18262（SEQ ID NO：1），任选与脂肪酶和/或淀粉酶组合。医学适应症的例子有：消化系统疾病，胰腺外分泌功能不全（PEI），胰腺炎，囊性纤维化，I型糖尿病和/或II型糖尿病的治疗。

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