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1. 发明申请

WO2008060780A2 GLYCEROL LINKED PEGYLATED SUGARS AND GLYCOPEPTIDES 审中-公开
标题翻译：甘油连接的聚乙二醇和糖蛋白
公开(公告)号：WO2008060780A2
公开(公告)日：2008-05-22
申请号：PCT/US2007/080471
申请日：2007-10-04
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn , ZENG, Xiao
发明人： DEFREES, Shawn , ZENG, Xiao
IPC分类号： C07K14/00 , C07K14/755 , C07K14/51 , C07K14/745 , C07K14/52 , C07K16/00 , C07K14/54
CPC分类号： C12N9/96 , A61K38/4846 , A61K47/549 , A61K47/60 , C12N9/6437 , C12Y304/21021 , C12Y304/21022
摘要： The present invention provides conjugates between peptides and PEG moieties through glycerol linkers.
摘要翻译：本发明通过甘油接头提供肽和PEG部分之间的缀合物。

2. 发明申请

WO2008151258A2 O-LINKED GLYCOSYLATION USING N-ACETYLGLUCOSAMINYL TRANSFERASES 审中-公开
标题翻译：使用N-乙酰氨基葡萄糖转移的O-连接的糖蛋白
公开(公告)号：WO2008151258A2
公开(公告)日：2008-12-11
申请号：PCT/US2008/065825
申请日：2008-06-04
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn
发明人： DEFREES, Shawn
IPC分类号： G01N33/53
CPC分类号： C07K14/51 , A61K47/60 , C07K14/535 , C07K14/56 , C07K14/61 , C07K2319/00
摘要： The present invention provides covalent conjugates between a polypeptide and a modifying group, such as a water-soluble polymer (e.g., PEG). The amino acid sequence of the polypeptide includes one or more O-linked glycosylation sequence, each being a substrate for a GIcNAc transferase. The modifying group is covalently linked to the polypeptide via a glycosyl-linking group interposed between and covalently linked to both the polypeptide and the modifying group. In one embodiment, a glucosamine linking group is directly attached to an amino acid residue of the O-linked glycosylation sequence. The invention further provides methods of making polypeptide conjugates. The present invention also provides non-naturally ocurring polypeptides that include at leats one O-linked linked glycosylation sequence of the invention, wherein each glycosylation sequence is a substrate for a GIcNAc transferase. The invention further provides pharmaceutical compositions that include a polypeptide conjugate of the invention.
摘要翻译：本发明提供多肽和修饰基团之间的共价缀合物，例如水溶性聚合物（例如PEG）。多肽的氨基酸序列包括一个或多个O-连接的糖基化序列，各自为GlcNAc转移酶的底物。修饰基团通过插入在多肽和修饰基团之间并且共价连接的糖基连接基团与多肽共价连接。在一个实施方案中，葡糖胺连接基团直接连接到O-连接的糖基化序列的氨基酸残基。本发明进一步提供了制备多肽缀合物的方法。本发明还提供了非天然的多肽，其包括在本发明的一个O-连接的糖基化序列中，其中每个糖基化序列是GlcNAc转移酶的底物。本发明进一步提供包含本发明的多肽缀合物的药物组合物。

3. 发明申请

WO2006020372A2 ENZYMATIC MODIFICATION OF GLYCOPEPTIDES 审中-公开
标题翻译：糖化酶的酶学修饰
公开(公告)号：WO2006020372A2
公开(公告)日：2006-02-23
申请号：PCT/US2005/026377
申请日：2005-07-25
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn
发明人： DEFREES, Shawn
IPC分类号： C12P21/06
CPC分类号： C12P21/005
摘要： The present invention provides glycoconjugates that are formed through the enzymatically-mediated coupling of a glycosyl moiety, e.g., on a peptide or lipid, and a modifying group that includes an acyl group. The conjugates include the modifying group tethered to the glycosyl moiety through a linking moiety that includes an acyl residue. Also provided are methods for preparing the conjugates of the invention.
摘要翻译：本发明提供了通过酶促介导的糖基部分（例如肽或脂质）和包含酰基的修饰基团的酶促介导的偶联形成的糖缀合物。缀合物包括通过包含酰基残基的连接部分连接到糖基部分的修饰基团。还提供了制备本发明的缀合物的方法。

4. 发明申请

WO2005089102A2 METHODS OF REFOLDING MAMMALIAN GLYCOSYLTRANSFERASES 审中-公开
标题翻译：重建马马里甘草酸酯的方法
公开(公告)号：WO2005089102A2
公开(公告)日：2005-09-29
申请号：PCT/US2005/003856
申请日：2005-02-04
申请人： NEOSE TECHNOLOGIES, INC. , SARIBAS, Sami , HAKES, David , WILLETT, Scott , JOHNSON, Karl, F. , BEZILA, Daniel James , DEFREES, Shawn
发明人： SARIBAS, Sami , HAKES, David , WILLETT, Scott , JOHNSON, Karl, F. , BEZILA, Daniel James , DEFREES, Shawn
IPC分类号： C12N9/10
CPC分类号： C12N9/1081 , C12N9/1048
摘要： The present invention provides methods of refolding mammalian glycosyltransferases that have been produced in bacterial cells, and methods to use such refolded glycosyltransferases, including glycosyltransferase mutants that have enhanced ability to be refolded. The invention also provides methods of refolding more than one glycosyltransferase in a single vessel, methods to use such refolded glycosyltransferases, and reaction mixtures comprising the refolded glycosyltransferases.
摘要翻译：本发明提供了在细菌细胞中产生的哺乳动物糖基转移酶重折叠的方法，以及使用这种重折叠的糖基转移酶（包括具有增强的重折叠能力的糖基转移酶突变体）的方法。本发明还提供了在单个容器中重折叠多于一种糖基转移酶的方法，使用这种重折叠的糖基转移酶的方法和包含重折叠的糖基转移酶的反应混合物。

5. 发明申请

WO2005072371A3 BRANCHED POLYMERIC SUGARS AND NUCLEOTIDES THEREOF 审中-公开
公开(公告)号：WO2005072371A3
公开(公告)日：2005-08-11
申请号：PCT/US2005/002522
申请日：2005-01-26
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn , BOWE, Caryn
发明人： DEFREES, Shawn , BOWE, Caryn
IPC分类号： C07H21/02
摘要： The present invention provides sugars, nucleotide sugars, activated sugars that include one or more polymeric modifying moiety within their structure. The invention is exemplified by reference to linear and branched polymers, such as the water-soluble polymer poly(ethylene glycol).

6. 发明申请

WO2005055946A2 GLYCOPEGYLATED GRANULOCYTE COLONY STIMULATING FACTOR 审中-公开
公开(公告)号：WO2005055946A2
公开(公告)日：2005-06-23
申请号：PCT/US2004/041004
申请日：2004-12-03
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn , CLAUSEN, Henrik , ZOPF, David, A. , WANG, Zhi-Guang , SCHWARTZ, Marc , WU, Bingyuan
发明人： DEFREES, Shawn , CLAUSEN, Henrik , ZOPF, David, A. , WANG, Zhi-Guang , SCHWARTZ, Marc , WU, Bingyuan
IPC分类号： A61K
CPC分类号： A61K38/193 , A61K47/60 , C07K14/535
摘要： The present invention provides conjugates between Granulocyte Colony Stimulating Factor and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.
摘要翻译：本发明提供粒细胞集落刺激因子和PEG部分之间的缀合物。缀合物经由完整的糖基连接基团连接，该基团介于并共价连接到肽和修饰基团之间。通过糖基转移酶的作用，缀合物由糖基化和未糖基化的肽形成。糖基转移酶将修饰的糖部分连接到肽上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。

7. 发明申请

WO2008073620A2 MANUFACTURING PROCESS FOR THE PRODUCTION OF POLYPEPTIDES EXPRESSED IN INSECT CELL-LINES 审中-公开
标题翻译：用于生产在细胞细胞中表达的多肽的制造方法
公开(公告)号：WO2008073620A2
公开(公告)日：2008-06-19
申请号：PCT/US2007/083538
申请日：2007-11-02
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn , KINEALY, Kyle , HERZER, Sibylle
发明人： DEFREES, Shawn , KINEALY, Kyle , HERZER, Sibylle
IPC分类号： C12P21/06
CPC分类号： C12P21/02 , C07K1/165 , C07K1/18 , C07K1/20 , C07K1/36 , C12P21/005
摘要： The present invention provides a manufacturing method for polypeptides that are produced in insect cells using a baculoviral expression system. In one example, the insect cell culture is supplemented with a lipid mixture immediately prior to infection (e.g., one hour prior to infection). The polypeptides are isolated from the insect cell culture using a method that employs anion exchange or mixed-mode chromatography early in the purification process. This process step is useful to remove insect-cell derived endoglycanases and proteases and thus reduces the loss of desired polypeptide due to enzymatic degradation. In another example, mixed-mode chromatography is combined with dye-ligand affinity chromatography in a continuous-flow manner to allow for rapid processing of the insect-cell culture liquid and capture of the polypeptide. In yet another example, a polypeptide is isolated from an insect cell culture liquid using a process that combines hollow fiber filtration, mixed-mode chromatography and dye-ligand affinity in a single unit operation producing a polypeptide solution that is essentially free of endoglycanase and proteolytic activities. In a further example, the isolated polypeptides are glycopeptides having an insect specific glycosylation pattern, which are optionally conjugated to a modifying group, such as a polymer (e.g., PEG) using a glycosyltransferase and a modified nucleotide sugar.
摘要翻译：本发明提供了使用杆状病毒表达系统在昆虫细胞中产生的多肽的制备方法。在一个实例中，昆虫细胞培养物在感染之前（例如感染前一小时）补充有脂质混合物。使用在纯化过程早期使用阴离子交换或混合模式色谱法的方法从昆虫细胞培养物中分离多肽。该方法步骤可用于除去昆虫细胞来源的聚糖内切酶和蛋白酶，从而减少由于酶降解导致的期望多肽的损失。在另一个实例中，混合模式色谱法以连续流动方式与染料 - 配体亲和层析组合，以允许昆虫细胞培养液的快速加工和捕获多肽。在另一个实例中，使用在单个单元操作中组合中空纤维过滤，混合模式层析和染料 - 配体亲和力的方法从昆虫细胞培养液中分离多肽，产生基本上不含内聚糖和多肽的多肽溶液和蛋白水解活动。在另一个实例中，分离的多肽是具有昆虫特异性糖基化图案的糖肽，其可任选地使用糖基转移酶和修饰的核苷酸糖缀合至修饰基团，例如聚合物（例如PEG）。

8. 发明申请

WO2006066258A2 LIPOCONJUGATION OF PEPTIDES 审中-公开
标题翻译：脂多糖的共轭
公开(公告)号：WO2006066258A2
公开(公告)日：2006-06-22
申请号：PCT/US2005/046198
申请日：2005-12-19
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn
发明人： DEFREES, Shawn
IPC分类号： C07K14/47 , C07K14/775
CPC分类号： C07K9/003 , A61K47/543 , A61K47/60 , C07K1/1077
摘要： The present invention provides peptide conjugates that are formed between a modified lipid and a glycosyl residue and/or an amino acid residue on a peptide. The modified lipid includes a modifying group and a lipid linking group. Exemplary lipid linking groups include myristoyl, palmitoyl, and isoprenyl moieties.
摘要翻译：本发明提供了在修饰的脂质与糖基残基和/或肽上的氨基酸残基之间形成的肽缀合物。修饰的脂质包括修饰基团和脂质连接基团。示例性的脂质连接基团包括肉豆蔻酰基，棕榈酰基和异戊二烯基部分。

9. 发明申请

WO2005070138A2 O-LINKED GLYCOSYLATION OF PEPTIDES 审中-公开
标题翻译：肽连接的糖蛋白
公开(公告)号：WO2005070138A2
公开(公告)日：2005-08-04
申请号：PCT/US2005/000799
申请日：2005-01-10
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn , ZOPF, David, A. , WANG, Zhi-Guang , CLAUSEN, Henrik
发明人： DEFREES, Shawn , ZOPF, David, A. , WANG, Zhi-Guang , CLAUSEN, Henrik
IPC分类号： A61K38/14 , A61K38/19 , C07K1/107 , C07K9/00 , C07K14/535
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。

10. 发明申请

WO2005056760A2 GLYCOPEGYLATED FOLLICLE STIMULATING HORMONE 审中-公开
公开(公告)号：WO2005056760A2
公开(公告)日：2005-06-23
申请号：PCT/US2004/040709
申请日：2004-12-03
申请人： NEOSE TECHNOLOGIES, INC. , DEFREES, Shawn , BAYER, Robert, J.
发明人： DEFREES, Shawn , BAYER, Robert, J.
IPC分类号： C12N
CPC分类号： C07K14/59 , A61K38/17 , Y02A50/471
摘要： The present invention provides conjugates between follicle stimulating hormone and PEG moieties. The conjugates are linked via an intact glycosyl linking group that is interposed between and covalently attached to the peptide and the modifying group. The conjugates are formed from both glycosylated and unglycosylated peptides by the action of a glycosyltransferase. The glycosyltransferase ligates a modified sugar moiety onto either an amino acid or glycosyl residue on the peptide. Also provided are pharmaceutical formulations including the conjugates. Methods for preparing the conjugates are also within the scope of the invention.
摘要翻译：本发明提供了促卵泡激素和PEG部分之间的缀合物。偶联物通过介于肽和修饰基团之间并共价连接的完整糖基连接基团连接。通过糖基转移酶的作用从糖基化和非糖基化肽两者形成缀合物。糖基转移酶将修饰的糖部分连接到肽上的氨基酸或糖基残基上。还提供了包含缀合物的药物制剂。制备缀合物的方法也在本发明的范围内。

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