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1. 发明授权

US07202256B2 Proline CCI-779, production of and uses therefor, and two-step enzymatic synthesis of proline CCI-779 and CCI-779 失效
标题翻译：脯氨酸CCI-779，其生产和用途，以及脯氨酸CCI-779和CCI-779的两步酶合成
公开(公告)号：US07202256B2
公开(公告)日：2007-04-10
申请号：US11103779
申请日：2005-04-12
申请人： Jianxin Gu , Mark E. Ruppen , Panolil Raveendranath , Warren Chew , Chia-Cheng Shaw
发明人： Jianxin Gu , Mark E. Ruppen , Panolil Raveendranath , Warren Chew , Chia-Cheng Shaw
IPC分类号： C07D498/18 , C07D498/22 , A61K31/435 , A61K31/436
CPC分类号： C07D498/08
摘要： Methods for the synthesis of CCI-779 and proline-CCI-779 are described, including a method involving lipase-catalyzed acetylation of 42-hydroxy of rapamycin with a vinyl ester of 2,2-bis(hydroxymethyl) propionic acid in an organic solvent followed by deprotection. Also provided are products containing proline-CCI-779 and uses thereof.
摘要翻译：描述了合成CCI-779和脯氨酸-CCI-779的方法，包括在有机溶剂中使用2,2-双（羟甲基）丙酸的乙烯基酯将雷帕霉素的42-羟基脂肪酶催化的乙酰化的方法然后脱保护。还提供含有脯氨酸CCI-779的产品及其用途。

2. 发明申请

US20090029426A1 PROCESS FOR PREPARING RAPAMYCIN 42-ESTERS AND FK-506 32-ESTERS WITH DICARBOXYLIC ACID, PRECURSORS FOR RAPAMYCIN CONJUGATES AND ANTIBODIES 失效
标题翻译：制备RAPAMYCIN 42-ESTERS和FK-506 32-二酯与二羧酸的方法，RAPAMYCIN结合物和抗体的前体
公开(公告)号：US20090029426A1
公开(公告)日：2009-01-29
申请号：US12240230
申请日：2008-09-29
申请人： Jianxin Gu , Ping Cai , Mark E. Ruppen
发明人： Jianxin Gu , Ping Cai , Mark E. Ruppen
IPC分类号： C12P17/16 , C07D267/22 , C07K16/44
CPC分类号： C07D498/18 , C12P17/188
摘要： Methods for the synthesis of regiospecific rapamycin 42-hemiesters and regiospecific FK506 32-esters with dicarboxylic acids is described. The methods involve catalyzing the reaction between a rapamycin or a FK-506 and a dicarboxylic anhydride or a bifunctional activated ester of dicarboxylic acid with a lipase.
摘要翻译：描述了用二羧酸合成区域特异性雷帕霉素42-半酯和区域特异性FK50632-酯的方法。所述方法包括催化雷帕霉素或FK-506与二羧酸酐或二酸的双功能活化酯与脂肪酶之间的反应。

3. 发明授权

US07445916B2 Process for preparing rapamycin 42-esters and FK-506 32-esters with dicarboxylic acid, precursors for rapamycin conjugates and antibodies 有权
标题翻译：用二羧酸制备雷帕霉素42-酯和FK-50632-酯的方法，雷帕霉素缀合物和抗体的前体
公开(公告)号：US07445916B2
公开(公告)日：2008-11-04
申请号：US11104349
申请日：2005-04-12
申请人： Jianxin Gu , Ping Cai , Mark E. Ruppen
发明人： Jianxin Gu , Ping Cai , Mark E. Ruppen
IPC分类号： C12P17/16 , C12P17/18
CPC分类号： C07D498/18 , C12P17/188
摘要： Methods for the synthesis of regiospecific rapamycin 42-hemiesters and regiospecific FK506 32-esters with dicarboxylic acids is described. The methods involve catalyzing the reaction between a rapamycin or a FK-506 and a dicarboxylic anhydride or a bifunctional activated ester of dicarboxylic acid with a lipase.
摘要翻译：描述了用二羧酸合成区域特异性雷帕霉素42-半酯和区域特异性FK50632-酯的方法。所述方法包括催化雷帕霉素或FK-506与二羧酸酐或二酸的双功能活化酯与脂肪酶之间的反应。

4. 发明授权

US07268144B2 Regiospecific synthesis of rapamycin 42-ester derivatives 失效
标题翻译：雷帕霉素42-酯衍生物的区域特异性合成
公开(公告)号：US07268144B2
公开(公告)日：2007-09-11
申请号：US11103799
申请日：2005-04-12
申请人： Jianxin Gu , Ping Cai , Mark E. Ruppen
发明人： Jianxin Gu , Ping Cai , Mark E. Ruppen
IPC分类号： C07D498/18 , A61K31/395
CPC分类号： C07D498/18 , C12P17/188
摘要： A method for the regiospecific synthesis of rapamycin 42-ester derivatives is described. The method involves lipase-catalyzed acetylation of 42-hydroxy of rapamycin with an acyl donor such as a vinyl ester, an isopropenyl ester or an anhydride in a suitable organic solvent.
摘要翻译：描述了雷帕霉素42-酯衍生物的区域特异性合成的方法。该方法包括在合适的有机溶剂中用酰基供体如乙烯基酯，异丙烯基酯或酸酐对雷帕霉素的42-羟基进行脂肪酶催化的乙酰化。

5. 发明授权

US07625726B2 Process for preparing rapamycin 42-esters and FK-506 32-esters with dicarboxylic acid, precursors for rapamycin conjugates and antibodies 失效
标题翻译：用二羧酸制备雷帕霉素42-酯和FK-50632-酯的方法，雷帕霉素缀合物和抗体的前体
公开(公告)号：US07625726B2
公开(公告)日：2009-12-01
申请号：US12240230
申请日：2008-09-29
申请人： Jianxin Gu , Ping Cai , Mark E. Ruppen
发明人： Jianxin Gu , Ping Cai , Mark E. Ruppen
IPC分类号： C12P17/16 , C12P17/18
CPC分类号： C07D498/18 , C12P17/188
摘要： Methods for the synthesis of regiospecific rapamycin 42-hemiesters and regiospecific FK506 32-esters with dicarboxylic acids is described. The methods involve catalyzing the reaction between a rapamycin or a FK-506 and a dicarboxylic anhydride or a bifunctional activated ester of dicarboxylic acid with a lipase.
摘要翻译：描述了用二羧酸合成区域特异性雷帕霉素42-半酯和区域特异性FK50632-酯的方法。所述方法包括催化雷帕霉素或FK-506与二羧酸酐或二酸的双功能活化酯与脂肪酶之间的反应。

6. 发明授权

US07396660B2 Cloning genes from Streptomyces cyaneogriseus subsp. Noncyanogenus for biosynthesis of antibiotics and methods of use 失效
标题翻译：从链霉菌（Cytotomyces cyaneogriseus）亚种克隆基因非生物素用于生物合成抗生素及使用方法
公开(公告)号：US07396660B2
公开(公告)日：2008-07-08
申请号：US10844716
申请日：2004-05-13
申请人： Chengjin Huang , Deborah T. Chaleff , Mark E. Ruppen , Jerome Stephens
发明人： Chengjin Huang , Deborah T. Chaleff , Mark E. Ruppen , Jerome Stephens
IPC分类号： C12P19/44 , C12N15/52 , C12N15/70 , C12N15/76
CPC分类号： C12N9/0004 , C12N9/1007 , C12N9/16 , C12N15/52 , C12P17/181
摘要： The present invention relates to the complete biosynthetic pathway for the formation of the LL-F28249 compounds and, most importantly, the major component LL-F28249α. The purified and isolated nucleic acid molecule encoding the proteins of the biosynthetic pathway, which is isolated from a wild-type or mutant Streptomyces, is fully described in FIG. 6 to FIG. 6-39 and SEQ ID NO:1. The DNA gene cluster and its expression in a suitable host enable the efficient production of the highly active natural metabolites and semisynthetic derivatives. The invention further concerns plasmids, vectors and host cells that contain and express the novel nucleic acid molecule. Of particular interest, the entire biosynthetic pathway fits compactly in three plasmids, Cos11, Cos36 and Cos40. The invention also concerns the purified and isolated biosynthesis proteins that are encoded by the whole DNA gene cluster. Additionally, the invention involves a new efficient, biochemical method of preparing moxidectin.
摘要翻译：本发明涉及用于形成LL-F28249化合物的完整生物合成途径，最重要的是涉及主要成分LL-F28249α。编码从野生型或突变链霉菌分离的生物合成途径的蛋白质的纯化和分离的核酸分子在图1中完全描述。参照图6〜 6-39和SEQ ID NO：1。 DNA基因簇及其在合适的宿主中的表达使得能够高效生产高活性的天然代谢物和半合成衍生物。本发明还涉及含有和表达新型核酸分子的质粒，载体和宿主细胞。特别令人感兴趣的是，整个生物合成途径紧密地适应于三种质粒Cos11，Cos36和Cos40。本发明还涉及由整个DNA基因簇编码的纯化和分离的生物合成蛋白。此外，本发明涉及制备莫昔克丁的新的有效的生物化学方法。

7. 发明授权

US08481692B2 Compositions relating to a mutant Clostridium difficile toxin and methods thereof 有权
公开(公告)号：US08481692B2
公开(公告)日：2013-07-09
申请号：US13451631
申请日：2012-04-20
申请人： Maninder K. Sidhu , Annaliesa Sybil Anderson , Robert G. K. Donald , Kathrin Ute Jansen , Narender K. Kalyan , Justin Keith Moran , Mark E. Ruppen , Michael James Flint
发明人： Maninder K. Sidhu , Annaliesa Sybil Anderson , Robert G. K. Donald , Kathrin Ute Jansen , Narender K. Kalyan , Justin Keith Moran , Mark E. Ruppen , Michael James Flint
IPC分类号： A61K39/08 , C07K14/00
CPC分类号： C07K14/33 , A61K39/08 , C07K16/1282 , C07K2317/33 , C07K2317/76 , C07K2317/92 , C12N9/1051 , C12N9/99 , C12N15/74
摘要： In one aspect, the invention relates to an immunogenic composition that includes a mutant Clostridium difficile toxin A and/or a mutant Clostridium difficile toxin B. Each mutant toxin includes a glucosyltransferase domain having at least one mutation and a cysteine protease domain having at least one mutation, relative to the corresponding wild-type C. difficile toxin. The mutant toxins may further include at least one amino acid that is chemically crosslinked. In another aspect, the invention relates to antibodies or binding fragments thereof that binds to said immunogenic compositions. In further aspects, the invention relates to isolated nucleotide sequences that encode any of the foregoing, and methods of use of any of the foregoing compositions.

8. 发明申请

US20090176969A1 CLONING GENES FROM STREPTOMYCES CYANEOGRISEUS SUBSP. NONCYANOGENUS FOR BIOSYNTHESIS OF ANTIBIOTICS AND METHODS OF USE 审中-公开
标题翻译：克隆基因来自结构域CYANEOGRISEUS SUBSP。用于抗生素生产的非亚麻酸和使用方法
公开(公告)号：US20090176969A1
公开(公告)日：2009-07-09
申请号：US12053013
申请日：2008-03-21
申请人： Chengjin Huang , Deborah T. Chaleff , Mark E. Ruppen , Jerome Stephens
发明人： Chengjin Huang , Deborah T. Chaleff , Mark E. Ruppen , Jerome Stephens
IPC分类号： C07K14/195 , C12N15/31 , C12N15/70 , C12N1/21 , C12P21/02 , C12N15/75 , C12N15/76 , C12N15/77
CPC分类号： C12N9/0004 , C12N9/1007 , C12N9/16 , C12N15/52 , C12P17/181
摘要： The present invention relates to the complete biosynthetic pathway for the formation of the LL-F28249 compounds and, most importantly, the major component LL-F28249α. The purified and isolated nucleic acid molecule encoding the proteins of the biosynthetic pathway, which is isolated from a wild-type or mutant Streptomyces, is fully described in FIG. 6 to FIG. 6-39 and SEQ ID NO:1. The DNA gene cluster and its expression in a suitable host enable the efficient production of the highly active natural metabolites and semisynthetic derivatives. The invention further concerns plasmids, vectors and host cells that contain and express the novel nucleic acid molecule. Of particular interest, the entire biosynthetic pathway fits compactly in three plasmids, Cos11, Cos36 and Cos40. The invention also concerns the purified and isolated biosynthesis proteins that are encoded by the whole DNA gene cluster. Additionally, the invention involves a new efficient, biochemical method of preparing moxidectin.
摘要翻译：本发明涉及用于形成LL-F28249化合物的完整生物合成途径，最重要的是涉及主要成分LL-F28249α。编码从野生型或突变链霉菌分离的生物合成途径的蛋白质的纯化和分离的核酸分子在图1中完全描述。参照图6〜 6-39和SEQ ID NO：1。 DNA基因簇及其在合适的宿主中的表达使得能够高效生产高活性的天然代谢物和半合成衍生物。本发明还涉及含有和表达新型核酸分子的质粒，载体和宿主细胞。特别令人感兴趣的是，整个生物合成途径紧密地适应于三种质粒Cos11，Cos36和Cos40。本发明还涉及由整个DNA基因簇编码的纯化和分离的生物合成蛋白。此外，本发明涉及制备莫昔克丁的新的有效的生物化学方法。

9. 发明授权

US5888798A Chondroitinase I and chondroitinase II producing mutants of P. vulgaris 失效
标题翻译：软骨素酶I和软骨素酶II产生普通寻常型突变体
公开(公告)号：US5888798A
公开(公告)日：1999-03-30
申请号：US476261
申请日：1995-06-07
申请人： Jason Arnold Lotvin , Kiran M. Khandke , Mark E. Ruppen
发明人： Jason Arnold Lotvin , Kiran M. Khandke , Mark E. Ruppen
IPC分类号： C12N15/09 , C12N1/21 , C12N9/88 , C12Q1/527 , C12R1/19 , C12R1/37 , C12N1/20
CPC分类号： C12R1/37 , C12N9/88 , Y10S435/873
摘要： Mutant Proteus vulgaris strains are provided that, when grown in the absence of an exogenous chondroitinase I and II inducer, produce P. vulgans chondroitinase I and chondroitinase II proteins. The mutants typically produce chondroitinase I and II proteins in the absence of exogenous inducers and in amounts in excess of those produced by wild-type P. vulgaris strains induced with such inducers. Two classes of such mutants, Classes 1 and 2, are disclosed. Class 1 and class 2 mutants differ in the relative amounts of chondroitinases I and II produced when cells are grown in casamino acids--supplemented minimal medium. Additional phenotypic variants that release chondroitinase I protein into the culture medium are provided as well. Also contemplated is a method for producing P. vulgaris chondroitinase I and II proteins. The mutant cells described above are cultured in the absence of a conventional exogenous chondroitinase I and II inducer, after which the cells are harvested and chondroitinase I and II are recovered from the harvested cells. A method for in situ detection of chondroitinase I and II production by bacterial colonies is also provided.
摘要翻译：提供突变型普通变形杆菌，当在不存在外源性软骨素酶I和II诱导物的情况下生长时，产生P. vulgans软骨素酶I和软骨素II蛋白。突变体通常在没有外源性诱导物的情况下产生软骨素酶I和II蛋白，并且其量超过由这种诱导物诱导的野生型寻常型菌株产生的那些。披露了两类这类突变体，1类和2类。 1类和2类突变体在细胞生长在补充有酪氨酸氨酸的基本培养基中时产生的软骨素酶I和II的相对量不同。还提供将软骨素酶蛋白质释放到培养基中的其他表型变体。还考虑了用于产生寻常性软骨素酶I和II蛋白质的方法。在不存在常规外源性软骨素酶I和II诱导剂的情况下培养上述突变细胞，之后收获细胞，从收获的细胞中回收软骨素酶I和II。还提供了通过细菌菌落原位检测软骨素酶I和II产生的方法。

10. 发明授权

US5124479A Process for the preparation of hydroxyterephthalic acid 失效
标题翻译：羟基对苯二甲酸的制备方法
公开(公告)号：US5124479A
公开(公告)日：1992-06-23
申请号：US583493
申请日：1990-09-17
申请人： Mark E. Ruppen , Scott Hagedorn
发明人： Mark E. Ruppen , Scott Hagedorn
IPC分类号： C07C62/32
CPC分类号： C07C62/32
摘要： 1,2-Dihydroxycyclohexa-3,5-diene-1,4-dicarboxylic acid and its salts, which are novel intermediates yielding hydroxyterephthalic acid upon dehydration, can be prepared by culturing terephthalic acid and a carbon/energy source with a microorganism capable of oxidizing terephthalic acid but incapable of degradation of 1,2-dihydroxycyclohexa-3,5-diene-1,4-dicarboxylic acid thereby formed.
摘要翻译：作为在脱水时产生羟基对苯二甲酸的新中间体的1,2-二羟基环己-3,5-二烯-1,4-二羧酸及其盐可以通过用能够生产羟基对苯二甲酸的微生物培养对苯二甲酸和碳/能源来制备氧化对苯二甲酸，但不能由此形成1,2-二羟基环己-3,5-二烯-1,4-二羧酸的降解。

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