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1. 发明申请

US20200024628A1 MUTANT ENDOGLYCOCERAMIDASES WITH ENHANCED SYNTHETIC ACTIVITY 审中-公开
公开(公告)号：US20200024628A1
公开(公告)日：2020-01-23
申请号：US16415488
申请日：2019-05-17
申请人： Karl F. Johnson , Shawn DeFrees , Stephen Withers , Mark Vaughan
发明人： Karl F. Johnson , Shawn DeFrees , Stephen Withers , Mark Vaughan
IPC分类号： C12P19/26 , C12N9/24
摘要： The present invention relates to a novel endoglycoceramidase whose hydrolytic activity has been substantially reduced or eliminated, such that the enzyme is useful for synthesis of glycolipids from a monosaccharide or oligosaccharide and a ceramide. More specifically, the endoglycoceramidase is a mutant version of a naturally occurring endoglycoceramidase, preferably comprising a mutation within the active site or the nucleophilic site of the enzyme and more preferably comprising a substitution mutation of the Glu residue within the active site or the nucleophilic site. Also disclosed are a method for generating the mutant endoglycoceramidase and a method for enzymatically synthesizing glycolipids using this mutant enzyme.

2. 发明授权

US09493499B2 Process for the production of purified cytidinemonophosphate-sialic acid-polyalkylene oxide (CMP-SA-PEG) as modified nucleotide sugars via anion exchange chromatography 有权
标题翻译：通过阴离子交换色谱法制备纯化的胞苷磷酸唾液酸 - 唾液酸 - 聚环氧烷（CMP-SA-PEG）作为修饰的核苷酸糖的方法
公开(公告)号：US09493499B2
公开(公告)日：2016-11-15
申请号：US12663748
申请日：2008-06-12
申请人： Shawn DeFrees , Caryn Bowe
发明人： Shawn DeFrees , Caryn Bowe
IPC分类号： C07H19/10
CPC分类号： C07H19/10
摘要： The current invention provides methods (e.g., large-scale processes) for the production of nucleotide sugars, which are modified with a polymeric modifying group, such as poly(alkylene oxide) moieties (e.g., poly(ethylene glycol) or poly(propylene glycol)) moieties. A typical process of the invention includes anion exchange chromatography followed by an ultrafiltration procedure, such as tangential flow filtration. The process of the invention provides modified nucleotide sugars in unexpectedly high purity and high overall yields.
摘要翻译：本发明提供用于生产核苷酸糖的方法（例如，大规模方法），其用聚合修饰基团修饰，例如聚（环氧烷）部分（例如聚（乙二醇）或聚（丙二醇））部分。本发明的典型方法包括阴离子交换层析，然后进行超滤方法，例如切向流过滤。本发明的方法提供了出乎意料的高纯度和高总产率的修饰的核苷酸糖。

3. 发明授权

US08853161B2 Glycopegylation methods and proteins/peptides produced by the methods 有权
标题翻译：糖基化方法和蛋白质/肽通过方法生产
公开(公告)号：US08853161B2
公开(公告)日：2014-10-07
申请号：US13246512
申请日：2011-09-27
申请人： Shawn DeFrees , David A. Zopf , Robert J. Bayer , David James Hakes , Caryn Bowe , Xi Chen
发明人： Shawn DeFrees , David A. Zopf , Robert J. Bayer , David James Hakes , Caryn Bowe , Xi Chen
IPC分类号： A61K38/00 , A61P7/00
CPC分类号： A61K47/48215 , A61K38/1793 , A61K38/1816 , A61K38/185 , A61K38/193 , A61K38/212 , A61K38/215 , A61K38/24 , A61K38/36 , A61K38/40 , A61K38/465 , A61K38/47 , A61K38/482 , A61K38/4846 , A61K38/57 , A61K39/3955 , A61K47/549 , A61K47/60 , C07K5/1013 , C07K5/1016 , C07K9/00 , C07K9/008 , C07K14/00 , C07K16/241 , C07K2317/24 , C12N9/6424 , C12N9/6437 , C12N9/644 , C12N9/6459 , C12N9/96 , C12P21/005 , C12Y301/27005 , C12Y302/01045 , C12Y304/21021 , C12Y304/21022 , C12Y304/21068
摘要： The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
摘要翻译：本发明包括用于重组肽分子的方法和组合物，包括向肽添加或缺失一个或多个糖基，和/或向肽中加入修饰基团。

4. 发明授权

US08791066B2 Branched PEG remodeling and glycosylation of glucagon-like peptide-1 [GLP-1] 有权
标题翻译：胰高血糖素样肽-1的分支PEG重构和糖基化[GLP-1]
公开(公告)号：US08791066B2
公开(公告)日：2014-07-29
申请号：US13541185
申请日：2012-07-03
申请人： Shawn DeFrees
发明人： Shawn DeFrees
IPC分类号： A61P3/10 , A61P7/12
CPC分类号： C07K14/605 , A61K38/00
摘要： The present invention provides polypeptides that include an O-linked glycoconjugate in which a species such as a water-soluble polymer, a therapeutic agent of a biomolecule is covalently linked through an intact O-linked glycosyl residue to the polypeptide. The polypeptides of the invention include wild-type peptides and mutant peptides that include an O-linked glycosylation site that is not present in the wild-type peptide. Also provided are methods of making the peptides of the invention and methods, pharmaceutical compositions containing the peptides and methods of treating, ameliorating or preventing diseased in mammals by administering an amount of a peptide of the invention sufficient to achieve the desired response.
摘要翻译：本发明提供了包含O连接的糖缀合物的多肽，其中一种物质如水溶性聚合物，生物分子的治疗剂通过完整的O-连接的糖基残基与多肽共价连接。本发明的多肽包括野生型肽和突变型肽，其包括野生型肽中不存在的O-连接的糖基化位点。还提供了制备本发明的肽和方法的方法，含有肽的药物组合物和通过施用足够达到所需反应的量的本发明的肽来治疗，改善或预防哺乳动物患病的方法。

5. 发明授权

US08633157B2 Glycopegylated erythropoietin 失效
公开(公告)号：US08633157B2
公开(公告)日：2014-01-21
申请号：US11144223
申请日：2005-06-02
申请人： Shawn DeFrees , Robert J. Bayer , David A. Zopf
发明人： Shawn DeFrees , Robert J. Bayer , David A. Zopf
IPC分类号： A61K38/18 , A61P7/06 , C07K14/505
CPC分类号： A61K38/1816
摘要： The present invention provides conjugates between erythropoietin and PEG moieties. The conjugates are linked via an intact glycosyl linking group interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from glycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto a glycosyl residue on the peptide. Also provided are methods for preparing the conjugates, methods for treating various disease conditions with the conjugates, and pharmaceutical formulations including the conjugates.

6. 发明授权

US08076292B2 Factor VIII: remodeling and glycoconjugation of factor VIII 有权
标题翻译：因子VIII：因子VIII的重塑和糖结合
公开(公告)号：US08076292B2
公开(公告)日：2011-12-13
申请号：US11644014
申请日：2006-12-21
申请人： Shawn DeFrees , David A. Zopf , Robert J. Bayer , Caryn Bowe , David James Hakes , Xi Chen
发明人： Shawn DeFrees , David A. Zopf , Robert J. Bayer , Caryn Bowe , David James Hakes , Xi Chen
IPC分类号： A61K38/37
CPC分类号： C07K1/006 , A61K38/00 , A61K47/60 , C07K1/1077 , C07K1/13 , C07K9/00 , C07K14/505 , C07K14/755 , Y02A50/472
摘要： The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
摘要翻译：本发明包括用于重组肽分子的方法和组合物，包括向肽添加或缺失一个或多个糖基，和/或向肽中加入修饰基团。

7. 发明申请

US20100261872A1 Factor VIII: remodeling and glycoconjugation of factor VIII 有权
标题翻译：因子VIII：因子VIII的重塑和糖结合
公开(公告)号：US20100261872A1
公开(公告)日：2010-10-14
申请号：US11644014
申请日：2006-12-21
申请人： Shawn DeFrees , David A. Zopf , Robert J. Bayer , Caryn Bowe , David James Hakes , Xi Chen
发明人： Shawn DeFrees , David A. Zopf , Robert J. Bayer , Caryn Bowe , David James Hakes , Xi Chen
IPC分类号： C07K9/00
CPC分类号： C07K1/006 , A61K38/00 , A61K47/60 , C07K1/1077 , C07K1/13 , C07K9/00 , C07K14/505 , C07K14/755 , Y02A50/472
摘要： The invention includes methods and compositions for remodeling a peptide molecule, including the addition or deletion of one or more glycosyl groups to a peptide, and/or the addition of a modifying group to a peptide.
摘要翻译：本发明包括用于重组肽分子的方法和组合物，包括向肽添加或缺失一个或多个糖基，和/或向肽中加入修饰基团。

8. 发明授权

US07803777B2 Branched water-soluble polymers and their conjugates 有权
标题翻译：支链水溶性聚合物及其共轭物
公开(公告)号：US07803777B2
公开(公告)日：2010-09-28
申请号：US10549445
申请日：2004-03-15
申请人： Shawn DeFrees
发明人： Shawn DeFrees
IPC分类号： A01N43/04 , A61K31/70
CPC分类号： C07H19/20 , A61K38/00 , A61K47/60 , C07C237/12 , C07C271/22 , C07C323/59 , C07K1/13 , C07K5/022 , C07K5/0821 , C07K9/001
摘要： The present invention provides branched water-soluble polymers that allow two or more water-soluble polymers to be conjugated to another species. The branched polymers provide access to therapeutic agents that are conjugated at a single site to two or more water-soluble polymers. The branched polymers are based upon branch points that are simple branched alkyl structures, reactive side-chain amino acids and small peptides of reactive side-chain amino acids, and saccharides. Also provided is a method for preparing mono-disperse poly(ethylene glycol) of a well-defined and determinable molecular weight, and a method for the rational end-functionalization of poly(ethylene glycol). Conjugates of the branched water-soluble polymers with diverse species, e.g., peptides, lipids, glycolipids and small molecules are also provided.
摘要翻译：本发明提供了允许两种或更多种水溶性聚合物与另一种物质结合的支链水溶性聚合物。支链聚合物提供了在单个位点与两个或多个水溶性聚合物共轭的治疗剂。支链聚合物基于分支点，其为简单的支链烷基结构，反应性侧链氨基酸和反应性侧链氨基酸的小肽，以及糖。还提供了制备具有明确且可确定的分子量的单分散聚（乙二醇）的方法，以及聚（乙二醇）的合理末端官能化的方法。还提供了具有不同种类的支链水溶性聚合物的缀合物，例如肽，脂质，糖脂和小分子。

9. 发明申请

US20100009902A1 Glycoconjugation Using Saccharyl Fragments 审中-公开
标题翻译：使用糖基片段糖缀合
公开(公告)号：US20100009902A1
公开(公告)日：2010-01-14
申请号：US11794555
申请日：2006-01-06
申请人： Shawn DeFrees
发明人： Shawn DeFrees
IPC分类号： A61K38/14 , C07H15/00 , C07H19/06 , C12P21/00 , C12N9/96 , A61P37/00
CPC分类号： C07K9/00
摘要： The present invention provides conjugates between a substrate, e.g., peptide, glycopeptide, lipid, etc., and a modified saccharyl fragment bearing a modifying group such as a water-soluble polymer, therapeutic moiety or a biomolecule. The conjugates are linked via the enzymatic conversion of the activated modified saccharyl fragment into a glycosyl linking group that is interposed between and covalently attached to the substrate and the modifying group. The conjugates are formed from substrates by the action of a sugar transferring enzyme, e.g., a glycosyltransferase. For example, when the substrate is a peptide, the enzyme conjugates a modified saccharyl fragment moiety onto either an amino acid or glycosyl residue of the peptide. Also provided are pharmaceutical formulations that include the conjugates. Methods for preparing the conjugates are also within the scope of the invention.
摘要翻译：本发明提供了底物，例如肽，糖肽，脂质等之间的缀合物和带有修饰基团如水溶性聚合物，治疗部分或生物分子的修饰的糖基片段。通过活化的修饰的糖基片段的酶促转化将连接物连接到介于基质和修饰基团之间并共价连接到基质上的糖基连接基团。通过糖转移酶（例如糖基转移酶）的作用，由底物形成缀合物。例如，当底物是肽时，酶将修饰的糖基片段部分缀合到肽的氨基酸或糖基残基上。还提供了包括缀合物的药物制剂。缀合物的制备方法也在本发明的范围内。

10. 发明申请

US20090169509A1 O-linked glycosylation of peptides 有权
标题翻译：肽的O-连接糖基化
公开(公告)号：US20090169509A1
公开(公告)日：2009-07-02
申请号：US10585385
申请日：2005-01-10
申请人： Shawn DeFrees , David A. Zopf , Zhi-Guang Wang , Henrik Clausen
发明人： Shawn DeFrees , David A. Zopf , Zhi-Guang Wang , Henrik Clausen
IPC分类号： A61K38/21 , C07K7/00 , C07K14/00 , C12N15/11 , C12N15/00 , C12N5/06 , C12P21/02 , A61K38/16
CPC分类号： A61K38/193 , C07K1/1077 , C07K9/00 , C07K9/001 , C07K14/535
摘要： The present invention provides polypeptides that include an O-linked glycosylation site that is not present in the wild-type peptide. The polypeptides of the invention include glycoconjugates in which a species such as a water-soluble polymer, a therapeutic agent of a biomolecule is covalently linked through an intact O-linked glycosyl residue to the polypeptide. Also provided are methods of making the peptides of the invention and methods, pharmaceutical compositions containing the peptides and methods of treating, ameliorating or preventing diseased in mammals by administering an amount of a peptide of the invention sufficient to achieve the desired response.
摘要翻译：本发明提供了包含在野生型肽中不存在的O-连接的糖基化位点的多肽。本发明的多肽包括糖缀合物，其中诸如水溶性聚合物的物质，生物分子的治疗剂通过完整的O连接的糖基残基与多肽共价连接。还提供了制备本发明的肽和方法的方法，含有肽的药物组合物和通过施用足够达到所需反应的量的本发明的肽来治疗，改善或预防哺乳动物患病的方法。

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