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1. 发明授权

US5935936A Compositions comprising cationic amphiphiles and co-lipids for intracellular delivery of therapeutic molecules 失效
标题翻译：包含阳离子两亲物和用于细胞内递送治疗性分子的共 - 脂质的组合物
公开(公告)号：US5935936A
公开(公告)日：1999-08-10
申请号：US657238
申请日：1996-06-03
申请人： Allen J. Fasbender , Michael J. Welsh , Craig S. Siegel , Edward R. Lee , Chau-Dung Chang , John Marshall , Seng H. Cheng , David J. Harris , Simon J. Eastman , Shirley C. Hubbard , Mathieu B. Lane , Eric A. Rowe , Ronald K. Scheule , Nelson S. Yew
发明人： Allen J. Fasbender , Michael J. Welsh , Craig S. Siegel , Edward R. Lee , Chau-Dung Chang , John Marshall , Seng H. Cheng , David J. Harris , Simon J. Eastman , Shirley C. Hubbard , Mathieu B. Lane , Eric A. Rowe , Ronald K. Scheule , Nelson S. Yew
IPC分类号： A61K47/28 , A61K9/127 , A61K31/70 , A61K31/7088 , A61K48/00 , C07K14/47 , C12N15/88 , A01N43/04
CPC分类号： C12N15/88 , A61K9/1272 , C07K14/4712
摘要： Novel compositions are provided. Typically, the compositions comprise one or more neutral co-lipids and also a cationic amphiphile. Therapeutic compositions are prepared according to the practice of the invention by contacting a therapeutically active molecule with a dispersion of neutral co-lipid(s) and amphiphile(s).
摘要翻译：提供了新的组合物。通常，组合物包含一种或多种中性助脂和阳离子两亲物。通过使治疗活性分子与中性助脂质和两亲物的分散体接触，根据本发明的实践制备治疗组合物。

2. 发明授权

US5962429A Complexes of adenovirus with cationic molecules 失效
标题翻译：腺病毒与阳离子分子的复合物
公开(公告)号：US5962429A
公开(公告)日：1999-10-05
申请号：US755035
申请日：1996-11-22
申请人： Michael J. Welsh , Allen J. Fasbender
发明人： Michael J. Welsh , Allen J. Fasbender
IPC分类号： A61K48/00 , C12N15/861
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/10343 , C12N2810/10 , C12N2810/40
摘要： The present invention provides noncovalent complexes of cationic molecules and adenoviral vectors containing a transgene. The complexes of the invention exhibit increased efficiency of gene transfer to a target cell relative to adenoviral vectors alone. Methods of making and using the complexes are also provided. A method of delivering cystic fibrosis transmembrane conductance regulator to a CF patient utilizing a complex of cationic molecules and adenoviral vectors containing a transgene encoding a CFTR protein is provided.
摘要翻译：本发明提供阳离子分子的非共价络合物和含有转基因的腺病毒载体。相对于单独的腺病毒载体，本发明的复合物显示提高了靶细胞转移的效率。还提供了制备和使用络合物的方法。提供了使用阳离子分子的复合物和含有编码CFTR蛋白的转基因的腺病毒载体将囊性纤维化跨膜传导调节剂递送至CF患者的方法。

3. 发明申请

US20120030782A1 Compositions and Methods for Generating Transgenic Animals 审中-公开
标题翻译：用于产生转基因动物的组合物和方法
公开(公告)号：US20120030782A1
公开(公告)日：2012-02-02
申请号：US13252638
申请日：2011-10-04
申请人： Lisa S. D. Emmett , Theresa Gratsch , K. Sue O'Shea , J. Matthew Velkey , Michael J. Welsh , William Wu
发明人： Lisa S. D. Emmett , Theresa Gratsch , K. Sue O'Shea , J. Matthew Velkey , Michael J. Welsh , William Wu
IPC分类号： A01K67/027 , C12N5/10 , C12N15/85
CPC分类号： A01K67/0275 , A01K2217/058 , A01K2227/105 , A01K2267/03 , C12N15/873
摘要： The present invention provides methods of altering gene expression of embryos to provide compositions and methods for efficient generation of transgenic animals. In particular, the present invention provides compositions and methods for generating germline transgenic animals by direct injection of nucleic acid molecules into animals.
摘要翻译：本发明提供了改变胚胎基因表达以提供用于有效产生转基因动物的组合物和方法的方法。特别地，本发明提供了通过将核酸分子直接注入动物来产生种系转基因动物的组合物和方法。

4. 发明授权

US07407801B2 Truncated CMV promoters and vectors containing same 有权
标题翻译：截短的CMV启动子和含有其的载体
公开(公告)号：US07407801B2
公开(公告)日：2008-08-05
申请号：US11005410
申请日：2004-12-06
申请人： Lynda S. Ostedgaard , Michael J. Welsh , Mark F. Stinski , John A. Chiorini
发明人： Lynda S. Ostedgaard , Michael J. Welsh , Mark F. Stinski , John A. Chiorini
IPC分类号： C12N15/70 , C12N15/74 , C12N15/85 , C12N15/86 , C12N15/864 , A61K48/00
CPC分类号： C12N15/86 , A61K38/1709 , A61K48/00 , A61K48/0066 , C12N7/00 , C12N15/85 , C12N2750/14111 , C12N2750/14143 , C12N2750/14171 , C12N2830/00 , C12N2830/60
摘要： The present invention relates to nucleic acid molecules comprising certain truncated forms of the human cytomegalovirus (CMV) immediate-early enhancer-promoter, either alone or operably linked to transgenes of interest, including those encoding partially-deleted CFTR proteins. This invention further relates to vectors comprising these nucleic acid molecules and host cells transformed by such vectors. The nucleic acid molecules, vectors and transformed host cells of the present invention are useful for treating a variety of genetic, metabolic and acquired diseases, including inter alia cystic fibrosis (CF) airway disease.
摘要翻译：本发明涉及包含某些截短形式的人巨细胞病毒（CMV）立即早期增强子启动子的核酸分子，其单独或可操作地连接到感兴趣的转基因，包括编码部分缺失的CFTR蛋白的转基因。本发明还涉及包含这些核酸分子的载体和由这些载体转化的宿主细胞。本发明的核酸分子，载体和转化的宿主细胞可用于治疗各种遗传，代谢和获得性疾病，包括尤其是囊性纤维化（CF）气道疾病。

5. 发明授权

US06716819B2 Use of xylitol to reduce ionic strength and activate endogenous antimicrobials for prevention and treatment of infections 有权
标题翻译：使用木糖醇降低离子强度并激活内源性抗菌药物以预防和治疗感染
公开(公告)号：US06716819B2
公开(公告)日：2004-04-06
申请号：US09861841
申请日：2001-05-21
申请人： Michael J. Welsh , Joseph Zabner
发明人： Michael J. Welsh , Joseph Zabner
IPC分类号： A61K3170
CPC分类号： A61K31/045 , A61K9/0075 , A61K31/047
摘要： A method for killing infectious microbial cells by exposing the microbial cells to endogenous antimicrobial compounds. Activation of the antimicrobials is achieved by addition of low permeability, non-ionic osmolytes to lower ionic strength in body fluids where the antimicrobials have been previously suppressed by alteration of ionic transport (increase in salt concentration). The method can be used to treat cystic fibrosis. Cystic fibrosis causes elevated salt concentrations in the airway surface liquid (ASL) occur due to the impaired chloride transport across the epithelia. Xylitol has been found to be an effective low permeability, non-ionic osmolyte for use in the present invention.
摘要翻译：通过将微生物细胞暴露于内源性抗微生物化合物来杀死感染性微生物细胞的方法。抗微生物剂的活化通过加入低渗透性非离子渗透剂来降低体液中的离子强度来实现，其中通过离子迁移的改变（盐浓度的增加）预先抑制了抗微生物剂。该方法可用于治疗囊性纤维化。囊性纤维化导致气道表面液体（ASL）中的盐浓度升高是由于氯化物通过上皮细胞运输受损。已经发现木糖醇是用于本发明的有效的低渗透性，非离子渗透液。

6. 发明授权

US5234922A Use of sulfonylureas and other potassium channel regulators to treat secretory diarrhea 失效
标题翻译：使用磺酰脲和其他钾通道调节剂治疗分泌性腹泻
公开(公告)号：US5234922A
公开(公告)日：1993-08-10
申请号：US952279
申请日：1992-09-28
申请人： Michael J. Welsh , David N. Sheppard
发明人： Michael J. Welsh , David N. Sheppard
IPC分类号： A61K31/40 , A61K31/505 , A61K31/54 , A61K31/64
CPC分类号： A61K31/64 , A61K31/40 , A61K31/505 , A61K31/54
摘要： Methods for the treatment of secretory diarrhea comprised of administering to a patient in need thereof, an effective amount of a CFTR chloride channel blocker or a potassium channel opener are disclosed. The CFTR chloride channel blocker is a sulfonylurea of the group consisting of tolbutamide, glibenclamide, and related analogs. The potassium channel opener is selected from the group consisting of diazoxide, lemakalim, and minoxidil sulfate.
摘要翻译：公开了治疗分泌性腹泻的方法，其包括向有需要的患者施用有效量的CFTR氯化物通道阻断剂或钾通道开放剂。 CFTR氯化物通道阻断剂是由丁酰胺，格列本脲和相关类似物组成的组的磺酰脲。钾通道开放剂选自二氮嗪，雷马卡林和硫酸米诺地尔组成。

7. 发明授权

US08343911B2 Methods of inhibiting and treating bacterial biofilms by metal chelators 有权
标题翻译：金属螯合剂抑制和治疗细菌生物膜的方法
公开(公告)号：US08343911B2
公开(公告)日：2013-01-01
申请号：US12288449
申请日：2008-10-20
申请人： Pradeep K. Singh , Michael J. Welsh , E. Peter Greenberg
发明人： Pradeep K. Singh , Michael J. Welsh , E. Peter Greenberg
IPC分类号： A61K38/00 , A61K38/40
CPC分类号： A61K38/40 , A01N61/00 , A01N63/02 , A23B4/20 , A23B4/22 , A23L3/34635 , A23L3/3526 , A23L3/3571 , A61L2/0082 , A61L2/16 , A61L2/186 , A61L2202/24
摘要： The invention presented herein provides methods and compositions for the prevention and treatment of bacterial infections. The methods are based on the discovery that depletion of bioavailable iron stimulates surface motility in bacteria thus inhibiting the ability of a bacterial population to develop into a biofilm.
摘要翻译：本发明提供了用于预防和治疗细菌感染的方法和组合物。这些方法是基于发现生物可利用的铁的消耗刺激细菌中的表面运动，从而抑制细菌群体发展成生物膜的能力。

8. 发明申请

US20120142583A1 Methods of inhibiting and treating bacterial biofilms by metal chelators 有权
标题翻译：金属螯合剂抑制和治疗细菌生物膜的方法
公开(公告)号：US20120142583A1
公开(公告)日：2012-06-07
申请号：US12288449
申请日：2008-10-20
申请人： Pradeep K. Singh , Michael J. Welsh , Everett P. Greenberg
发明人： Pradeep K. Singh , Michael J. Welsh , Everett P. Greenberg
IPC分类号： A61K38/40 , A61P31/04 , A61K38/38
CPC分类号： A61K38/40 , A01N61/00 , A01N63/02 , A23B4/20 , A23B4/22 , A23L3/34635 , A23L3/3526 , A23L3/3571 , A61L2/0082 , A61L2/16 , A61L2/186 , A61L2202/24
摘要： The invention presented herein provides methods and compositions for the prevention and treatment of bacterial infections. The methods are based on the discovery that depletion of bioavailable iron stimulates surface motility in bacteria thus inhibiting the ability of a bacterial population to develop into a biofilm.
摘要翻译：本发明提供了用于预防和治疗细菌感染的方法和组合物。这些方法是基于发现生物可利用的铁的消耗刺激细菌中的表面运动，从而抑制细菌群体发展成生物膜的能力。

9. 发明申请

US20100005535A1 Compositions And Methods For Generating Transgenic Animals 审中-公开
标题翻译：用于产生转基因动物的组合物和方法
公开(公告)号：US20100005535A1
公开(公告)日：2010-01-07
申请号：US11939434
申请日：2007-11-13
申请人： Lisa S. D. Emmett , Theresa Gratsch , K. Sue O'Shea , J. Matthew Velkey , Michael J. Welsh , William Wu
发明人： Lisa S. D. Emmett , Theresa Gratsch , K. Sue O'Shea , J. Matthew Velkey , Michael J. Welsh , William Wu
IPC分类号： C12N15/87 , A01K67/027 , C12N5/06
CPC分类号： A01K67/0275 , A01K2217/058 , A01K2227/105 , A01K2267/03 , C12N15/873
摘要： The present invention provides methods of altering gene expression of embryos to provide compositions and methods for efficient generation of transgenic animals. In particular, the present invention provides compositions and methods for generating germ-line transgenic animals by direct injection of nucleic acid molecules into animals.
摘要翻译：本发明提供了改变胚胎基因表达以提供用于有效产生转基因动物的组合物和方法的方法。特别地，本发明提供了通过将核酸分子直接注入动物来产生生殖系转基因动物的组合物和方法。

10. 发明授权

US06635432B1 Peptide potentiation of acid-sensory ion channel in pain 失效
标题翻译：疼痛中酸感觉离子通道的肽增强作用
公开(公告)号：US06635432B1
公开(公告)日：2003-10-21
申请号：US09557506
申请日：2000-04-25
申请人： Michael J. Welsh , Candice C. Askwith
发明人： Michael J. Welsh , Candice C. Askwith
IPC分类号： G01N33566
CPC分类号： G01N33/9406 , C07K5/1016
摘要： An assay for determining agonists, antagonists, or modulators for acid-sensing ion channels. The assay is especially useful for screening analgesics. The screening assay can be provided in a kit form. The assay comprises administering the composition to be screened to cells expressing acid-gated channels and then determining whether the composition inhibits, enhances, or has no effect on the channels when acid is introduced. The determination can be performed by analyzing whether a current is sustained by the cells in the presence of the composition and the acid. This current can be compared to that sustained by the FMRFamide and related peptides.
摘要翻译：用于测定酸感应离子通道的激动剂，拮抗剂或调节剂的测定法。该测定法特别适用于筛选镇痛药。筛选测定可以以试剂盒形式提供。测定包括将待筛选的组合物施用于表达酸门控通道的细胞，然后确定当引入酸时，组合物是否抑制，增强或不影响通道。可以通过分析在组合物和酸的存在下细胞是否持续电流来进行测定。该电流可以与FMRFamide和相关肽所持续的电流进行比较。

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