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1. 发明申请

WO2005039492A3 IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS 审中-公开
公开(公告)号：WO2005039492A3
公开(公告)日：2005-06-30
申请号：PCT/US2004034625
申请日：2004-10-21
申请人： UNIV JOHNS HOPKINS , DANG LONG , BETTEGOWDA CHETAN , KINZLER KENNETH W , VOGELSTEIN BERT
发明人： DANG LONG , BETTEGOWDA CHETAN , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： A01N63/00 , A61K20060101
CPC分类号： A61K35/742 , A61K31/337 , A61K31/427 , A61K45/06 , Y10S435/842 , A61K2300/00
摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.

2. 发明申请

WO2005035749A3 ANIMAL PRODUCT FREE MEDIA AND PROCESSES FOR OBTAINING A BOTULINUM TOXIN 审中-公开
标题翻译：动物产品免费介质和获得BOTULINUM TOXIN的方法
公开(公告)号：WO2005035749A3
公开(公告)日：2005-06-02
申请号：PCT/US2004027775
申请日：2004-08-25
申请人： ALLERGAN INC , DONOVAN STEPHEN
发明人： DONOVAN STEPHEN
IPC分类号： C12N1/20 , C12N9/64 , C12P21/02
CPC分类号： C12N1/20 , C12N9/52 , C12P21/02 , C12Y304/24069 , Y10S435/842
摘要： Media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions. The growth media can contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferably, the media used are substantially free of animal derived products.
摘要翻译：用于发酵肉毒杆菌的培养基和方法，并获得用于配制肉毒杆菌毒素药物组合物的肉毒杆菌毒素。生长培养基可以使用非动物基产品来显着降低肉类或乳制品副产品的含量，以取代动物来源的产品。优选地，所用介质基本上不含动物衍生产品。

3. 发明申请

WO1996019569A1 ENZYMATIC PRODUCTION OF HALOGENATED CEPHALOSPORIN 审中-公开
标题翻译：致死生物素生物素
公开(公告)号：WO1996019569A1
公开(公告)日：1996-06-27
申请号：PCT/US1995016547
申请日：1995-12-19
申请人： BIOPURE CORPORATION , WONG, Bing, L. , SHEN, Yong-Qiang , CHEN, Yung-Pin
发明人： BIOPURE CORPORATION
IPC分类号： C12N09/08
CPC分类号： C12N9/0065 , C12P35/00 , C12R1/01 , Y10S435/842
摘要： An enzyme preparation that exhibits cephalosporin haloperoxidase activity is isolatable from a microorganism species of the Rathayibacter genus. This enzyme preparation can convert cephalexin to a halogenated cephalosporin antibiotic in a single step. A particular, unique microorganism that can provide the cephalosporin haloperoxidase enzyme preparation is Rathayibacter biopuresis.
摘要翻译：显示头孢菌素卤代过氧化物酶活性的酶制剂可从Rathayibacter属的微生物物种分离。该酶制剂可以在单一步骤中将头孢氨苄转化为卤代头孢菌素抗生素。可以提供头孢菌素卤代过氧化物酶制剂的特殊的独特的微生物是Rathayibacter bioporiesis。

4. 发明申请

WO1994024272A1 PROCESS FOR PURIFYING COLLAGENASE 审中-公开
标题翻译：净化COLLAGENASE的过程
公开(公告)号：WO1994024272A1
公开(公告)日：1994-10-27
申请号：PCT/US1994004083
申请日：1994-04-13
申请人： BAXTER INTERNATIONAL INC.
发明人： BAXTER INTERNATIONAL INC. , LEE, Catherine , HORNACEK, Cynthia , DINH, Tan, Thanh
IPC分类号： C12N09/52
CPC分类号： C12N9/52 , Y10S435/815 , Y10S435/842
摘要： A process for purifying crude collagenase is disclosed. The collagenase purification process includes providing a stabilized crude collagenase solution containing collagenase, pigment, toxins, bacterial materials, and proteolytic enzyme impurities including clostripain, trypsin, and caseinase. The stabilized collagenase solution is applied to hydroxylapatite packing. Pigment and caseinase are eluted with a first solution comprising about 0.05 M to about 0.3 M phosphate buffer, and then collagenase, trypsine, and clostripain are eluted with a second solution comprising about 0.35 M to about 0.5 M phosphate buffer to provide a first collected solution. The first collected solution is then applied to gel filtration packing and collagenase and clostripain are eluted with a neutral pH buffer solution, to provide a second collected solution. The second collected solution is then applied to Reactive Red 120-Agarose packing and collagenase is eluted with a neutral pH buffer solution to provide purified collagenase. The process provides extremely pure collagenase in high yield with reduced consumption of eluting solutions and avoids unpredictable gradient eluting techniques.
摘要翻译：公开了一种纯化粗胶原酶的方法。胶原酶纯化方法包括提供包含胶原酶，颜料，毒素，细菌材料和蛋白水解酶杂质的稳定的粗胶原酶溶液，包括clostripain，胰蛋白酶和酪蛋白酶。将稳定的胶原酶溶液应用于羟基磷灰石包装。用包含约0.05M至约0.3M磷酸盐缓冲液的第一溶液洗脱颜料和酪蛋白酶，然后用包含约0.35M至约0.5M磷酸盐缓冲液的第二溶液洗脱胶原酶，胰蛋白酶和梭菌素，以提供第一收集溶液。然后将第一次收集的溶液施加到凝胶过滤填充物上，并用中性pH缓冲溶液洗脱胶原酶和clostripain，以提供第二个收集的溶液。然后将第二次收集的溶液应用于活性红120-琼脂糖包装，并用中性pH缓冲溶液洗脱胶原酶以提供纯化的胶原酶。该方法以高产率提供极纯的胶原酶，减少洗脱溶液的消耗并避免不可预测的梯度洗脱技术。

5. 发明申请

WO1986001831A1 THERMOSTABLE STARCH CONVERTING ENZYMES 审中-公开
标题翻译：热稳定淀粉转化酶
公开(公告)号：WO1986001831A1
公开(公告)日：1986-03-27
申请号：PCT/US1985001776
申请日：1985-09-13
申请人： MICHIGAN BIOTECHNOLOGY INSTITUTE
发明人： MICHIGAN BIOTECHNOLOGY INSTITUTE , ZEIKUS, Joseph, Gregory , HYUN, Hyung-Hwan
IPC分类号： C12P19/20
CPC分类号： C12Y302/01041 , C12N9/2428 , C12N9/2457 , C12Y302/01003 , Y10S435/842
摘要： A thermostable pullulanase and a thermostable glucoamylase are produced by Clostridium thermohydrosulfuricum. Methods of producing the enzymes and using them to hydrolyze starch are also disclosed.

6. 发明申请

WO2005039492A9 IMPROVED COMBINATION BACTERIOLYTIC THERAPY FOR THE TREATMENT OF TUMORS 审中-公开
标题翻译：改进的联合用于治疗肿瘤的细菌疗法
公开(公告)号：WO2005039492A9
公开(公告)日：2005-06-02
申请号：PCT/US2004034625
申请日：2004-10-21
申请人： UNIV JOHNS HOPKINS , DANG LONG , BETTEGOWDA CHETAN , KINZLER KENNETH W , VOGELSTEIN BERT
发明人： DANG LONG , BETTEGOWDA CHETAN , KINZLER KENNETH W , VOGELSTEIN BERT
IPC分类号： A01N63/00 , A61K20060101 , A61K
CPC分类号： A61K35/742 , A61K31/337 , A61K31/427 , A61K45/06 , Y10S435/842 , A61K2300/00
摘要： Current approaches for treating cancer are limited, in part, by the inability of drugs to affect the poorly vascularized regions of tumors. We have found that spores of anaerobic bacteria in combination with agents which interact with microtubules can cause the destruction of both the vascular and avascular compartments of tumors. Two classes of microtubule inhibitors were found to exert markedly different effects. Some agents that inhibited microtubule synthesis, such as vinorelbine, caused rapid, massive hemorrhagic necrosis when used in combination with spores. In contrast, agents that stabilized microtubules, such as the taxane docetaxel, resulted in slow tumor regressions that killed most neoplastic cells. Remaining cells in the poorly perfused regions of tumors could be eradicated by sponzlated bacteria. Mechanistic studies showed that the microtubule destabilizers, but not the microtubule stabilizers, radically reduced blood flow to tumors, thereby enlarging the hypoxic niche in which spores could germinate. A single intravenous injection of spores plus selected microtubule-interacting agents was able to cause regressions of several tumors in the absence of excessive toxicity.
摘要翻译：目前用于治疗癌症的方法部分地由于药物不能影响肿瘤血管化程度差的区域而受到限制。我们发现厌氧菌的孢子与微管相互作用的药物联合使用会导致肿瘤血管和血管腔的破坏。发现两类微管抑制剂发挥显着不同的作用。一些抑制微管合成的药物，如长春瑞滨，当与孢子结合使用时会引起快速，大量的出血性坏死。相反，稳定微管的药物，如紫杉类多西紫杉醇，则导致缓慢的肿瘤消退，从而杀死大多数肿瘤细胞。肿瘤灌注不足区域的剩余细胞可以被脊椎化细菌消灭。机理研究表明，微管去稳定剂，但不是微管稳定剂，从根本上减少了血液流向肿瘤，从而扩大了孢子可能发芽的缺氧生态位。单次静脉注射孢子加选定的微管相互作用剂能够在没有过度毒性的情况下引起几种肿瘤的消退。

7. 发明申请

WO2005035749A2 ANIMAL PRODUCT FREE MEDIA AND PROCESSES FOR OBTAINING A BOTULINUM TOXIN 审中-公开
标题翻译：动物产品免费媒体和获得肉毒毒素的过程
公开(公告)号：WO2005035749A2
公开(公告)日：2005-04-21
申请号：PCT/US2004/027775
申请日：2004-08-25
申请人： ALLERGAN, INC. , DONOVAN, Stephen
发明人： DONOVAN, Stephen
IPC分类号： C12N9/64
CPC分类号： C12N1/20 , C12N9/52 , C12P21/02 , C12Y304/24069 , Y10S435/842
摘要： Media and processes for the fermentation of Clostridium botulinum and obtaining a botulinum toxin for use in formulating botulinum toxin pharmaceutical compositions. The growth media can contain significantly reduced levels of meat or dairy by-products using non-animal based products to replace the animal-derived products. Preferably, the media used are substantially free of animal derived products.
摘要翻译：用于肉毒梭菌发酵和获得肉毒杆菌毒素以用于配制肉毒杆菌毒素药物组合物的介质和方法。生长培养基可以包含使用非动物基产品替代动物衍生产品的显着降低水平的肉或乳制品副产品。优选地，所使用的培养基基本上不含动物衍生产品。

8. 发明申请

WO0151650A3 METHODS FOR DETERMINING THE PRESENCE OR ABSENCE OF MICROORGANISMS IN LIPID-CONTAINING COMPOSITIONS 审中-公开
标题翻译：用于测定含脂肪组合物中微生物存在或不存在的方法
公开(公告)号：WO0151650A3
公开(公告)日：2002-03-07
申请号：PCT/US0100877
申请日：2001-01-12
申请人： BLUE RIDGE PHARMACEUTICALS INC
发明人： BRINKLEY MICHAEL A
IPC分类号： C12Q1/04 , G01N33/92
CPC分类号： C12Q1/04 , Y10S435/832 , Y10S435/842 , Y10S435/973
摘要： The present invention provides methods of validating the sterility of compositions which contain large quantities of lipids, and especially those lipid compounds which contain quantities of bacteriocidal agents such as antibiotics. The compositions may contain quantities of phospholipids in the form of liposomes, microcrystals, or microdroplets. The methods involve dissolving the lipid composition in a diluent solution, passing the solution through a filtration device, and then incubating microbes which may be captured by the filtration device to determine whether microorganisms are present in the composition.
摘要翻译：本发明提供了验证含有大量脂质的组合物的无菌性的方法，特别是含有大量杀菌剂如抗生素的那些脂质化合物。组合物可以含有大量脂质体，微晶或微滴形式的磷脂。所述方法包括将脂质组合物溶解在稀释溶液中，使溶液通过过滤装置，然后孵育可由过滤装置捕获的微生物以确定微生物是否存在于组合物中。

9. 发明申请

WO1993007284A1 PROCESS FOR THE MANUFACTURE OF ALKALINE EARTH ACETATES 审中-公开
标题翻译：碱性盐水制备方法
公开(公告)号：WO1993007284A1
公开(公告)日：1993-04-15
申请号：PCT/US1992008261
申请日：1992-09-29
申请人： NORTHEASTERN UNIVERSITY
发明人： NORTHEASTERN UNIVERSITY , WISE, Donald, L.
IPC分类号： C12P07/54
CPC分类号： C12P7/54 , C07C51/412 , Y10S435/842 , C07C53/10
摘要： A process for the manufacture of alkaline earth salts of acetic acid. Biomass is fermented under appropriate conditions to produce acetic acid, which is extracted from the fermentation broth with the aid of a basic liquid ion exchanger dissolved in an organic phase. The organic phase containing the product acetic acid is then reacted directly with a basic material such as limestone, and the resulting alkaline earth acetate product is recovered from the aqueous phase.
摘要翻译：一种制造乙酸碱土盐的方法。生物质在合适的条件下发酵以产生乙酸，其借助于溶解在有机相中的碱性液体离子交换剂从发酵液中提取。然后将含有产物乙酸的有机相直接与碱性物质如石灰石反应，并从水相中回收所得的碱土金属乙酸盐产物。

10. 发明申请

WO1986001832A1 THERMOSTABLE 'beta'-AMYLASE 审中-公开
标题翻译：热稳定性β-亚胺酶
公开(公告)号：WO1986001832A1
公开(公告)日：1986-03-27
申请号：PCT/US1985001774
申请日：1985-09-13
申请人： MICHIGAN BIOTECHNOLOGY INSTITUTE
发明人： MICHIGAN BIOTECHNOLOGY INSTITUTE , ZEIKUS, Joseph, Gregory , HYUN, Hyung-Hwan
IPC分类号： C12P19/22
CPC分类号： C12N9/2425 , Y10S435/842
摘要： A thermostable and thermoactive, extracellular beta-amylase is produced by Clostridium thermosulfurogenes. Methods of producing the beta-amylase and using it to convert starch to maltose are also disclosed.

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