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1. 发明授权

US06693073B2 Pulmonary delivery of active agents 有权
标题翻译：肺部递送活性剂
公开(公告)号：US06693073B2
公开(公告)日：2004-02-17
申请号：US10172582
申请日：2002-06-14
申请人： Sam J. Milstein , John E. Smart , Donald J. Sarubbi , Monica Leipold , Elizabeth Flanders , Doris O'Toole , Andrea Leone-Bay , David Gschneidner
发明人： Sam J. Milstein , John E. Smart , Donald J. Sarubbi , Monica Leipold , Elizabeth Flanders , Doris O'Toole , Andrea Leone-Bay , David Gschneidner
IPC分类号： A61K3828
CPC分类号： C07C235/64 , A61K9/0073 , A61K31/16 , A61K31/727 , A61K38/00 , A61K38/1709 , A61K38/1816 , A61K38/27 , A61K38/28 , A61K38/29 , A61K38/30 , A61K47/183
摘要： The present invention provides methods for administering an active agent to an animal in need of the agent by the pulmonary route. This method comprises administering via the pulmonary route, a composition comprising (a) an active agent and (b)(i) an acylated amino acid, (ii) a sulfonated amino acid, or (iii) a combination of (i) and (ii). Administration of the compositions of the present invention provide improved pulmonary delivery and greater bioavailability of the active agent than administration of the active agent alone. As a result, lesser amounts of the active agent may be administered to obtain a desired result when contained in the composition of the present invention than when administered alone.
摘要翻译：本发明提供了通过肺部途径向需要该药物的动物施用活性剂的方法。该方法包括通过肺部途径施用包含（a）活性剂和（b）（i）酰化氨基酸，（ii）磺化氨基酸或（iii）（i）和（i） ii）。施用本发明的组合物比单独施用活性剂提供了改善的肺输送和活性剂的更大的生物利用度。结果，当与本发明的组合物相比时，可以施用较少量的活性剂以获得期望的结果。

2. 发明授权

US06399569B1 Morphogen treatments for limiting proliferation of epithelial cells 失效
标题翻译：用于限制上皮细胞增殖的形态治疗
公开(公告)号：US06399569B1
公开(公告)日：2002-06-04
申请号：US08461113
申请日：1995-06-05
申请人： Charles M. Cohen , Marc F. Charette , Thangavel Kuberasampath , David C. Rueger , Hermann Oppermann , Roy H. L. Pang , Engin Ozkaynak , John E. Smart
发明人： Charles M. Cohen , Marc F. Charette , Thangavel Kuberasampath , David C. Rueger , Hermann Oppermann , Roy H. L. Pang , Engin Ozkaynak , John E. Smart
IPC分类号： A61K3818
CPC分类号： G01N33/6872 , A61F2310/00365 , A61K38/17 , A61K38/1703 , A61K38/1875 , A61L27/227 , A61L27/24 , C07K14/495 , C07K14/51 , C07K16/22 , G01N2500/10 , G01N2800/06 , A61K2300/00
摘要： Disclosed are methods and compositions for maintaining the integrity of the gastrointestinal tract luminal lining in a mammal, including (1) limiting epithelial cell proliferation, (2) inhibiting ulcerative lesion formation, (3) inhibiting inflammation normally associated with ulcerative diseases, and (4) stimulating the repair of ulcerative lesions and the regeneration of the luminal tissue. The methods and compositions include a therapeutically effective amount of a morphogen as defined herein.
摘要翻译：公开了用于维持哺乳动物胃肠道腔内衬的完整性的方法和组合物，包括（1）限制上皮细胞增殖，（2）抑制溃疡性病变形成，（3）抑制通常与溃疡性疾病相关的炎症，和（4 ）刺激溃疡性病变的修复和管腔组织的再生。方法和组合物包括治疗有效量的如本文所定义的形态发生素。

3. 发明授权

US6090776A Morphogen treatment of organ implants 失效
标题翻译：器官植入物的形态治疗
公开(公告)号：US6090776A
公开(公告)日：2000-07-18
申请号：US480515
申请日：1995-06-07
申请人： Thangavel Kuberasampath , Roy H. L. Pang , Hermann Oppermann , David C. Rueger , Charles M. Cohen , John E. Smart
发明人： Thangavel Kuberasampath , Roy H. L. Pang , Hermann Oppermann , David C. Rueger , Charles M. Cohen , John E. Smart
IPC分类号： A01N1/02 , A61K6/00 , A61L27/22 , A61L27/24 , A61L27/36 , A61K38/16 , A61K38/17 , A61K38/18
CPC分类号： A61L27/3687 , A01N1/0226 , A61L27/227 , A61L27/24 , A61L27/3604 , G01N2500/10
摘要： The present invention is directed to methods and compositions for enhancing viability of organs and living tissues to be transplanted in a mammal. The methods and compositions provide a therapeutically effective concentration of a morphogen or morphogen-stimulating agent to the tissue or organ to be transplanted, sufficient to substantially protect the tissue or organ from tissue damage.
摘要翻译：本发明涉及用于增强要移植到哺乳动物中的器官和活组织活力的方法和组合物。所述方法和组合物向要移植的组织或器官提供治疗有效浓度的形态发生剂或形态发生剂刺激剂，足以基本上保护组织或器官免受组织损伤。

4. 发明授权

US5162503A Purification of interleukin-2 by receptor-affinity chromatography 失效
标题翻译：通过受体亲和色谱法纯化白介素-2
公开(公告)号：US5162503A
公开(公告)日：1992-11-10
申请号：US51967
申请日：1987-05-19
申请人： Pascal Bailon , John E. Smart , David V. Weber
发明人： Pascal Bailon , John E. Smart , David V. Weber
IPC分类号： B01J20/26 , B01J20/24 , C07K1/22 , C07K14/00 , C07K14/52 , C07K14/54 , C07K14/55 , C07K14/705 , C07K14/715 , C07K17/02 , C07K17/14 , C12P21/00 , C12P21/02 , G01N33/53
CPC分类号： C07K14/55 , Y10S530/81 , Y10S530/811 , Y10S530/812 , Y10S530/813 , Y10S530/814
摘要： Methods are provided for the purification of interleukin-2 (IL-2) from a wide variety of sources, including synthetic mixtures, culture medium conditioned by natural IL-2 producing cells, and mammalian and bacterial recombinant IL-2 expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 can be produced in a single step from bacterial extracts or conditioned medium. The IL-2 thus purified is largely free of aggregated forms, which are often present when other purification methods are used.
摘要翻译：提供了从各种来源（包括合成混合物，由天然IL-2产生细胞调节的培养基）和哺乳动物和细菌重组IL-2表达系统纯化白细胞介素-2（IL-2）的方法。本发明的方法使用其中可溶性IL-2受体已经固定在固体支持物上的IL-2受体亲和吸附剂。通过使用这些亲和吸附剂，可以从细菌提取物或条件培养基中单步制备高纯度的IL-2。如此纯化的IL-2基本上没有聚集形式，当使用其它纯化方法时，它们通常存在。

5. 发明授权

US5149788A Purification of chimeric proteins containing an IL-2 moiety by receptor-affinity chromatography 失效
标题翻译：通过受体亲和层析纯化含有IL-2部分的嵌合蛋白
公开(公告)号：US5149788A
公开(公告)日：1992-09-22
申请号：US261198
申请日：1988-10-24
申请人： Pascal Bailon , John E. Smart , David V. Weber
发明人： Pascal Bailon , John E. Smart , David V. Weber
IPC分类号： C07K14/55
CPC分类号： C07K14/55 , Y10S530/81 , Y10S530/811 , Y10S530/812 , Y10S530/813 , Y10S530/814
摘要： Methods are provided for the purification of interleukin-2 (IL-2) and chimeric proteins containing an IL-2 moiety from a wide variety of sources, including synthetic mixtures, cell culture conditioned medium and mammalian and bacterial recombinant expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 and chimeric proteins containing an IL-2 moiety can be produced in a single step from bacterial extracts or conditioned medium. The proteins thus purified are largely free of aggregated forms, which are often present when other purification methods are used.
摘要翻译：提供了用于从多种来源（包括合成混合物，细胞培养条件培养基和哺乳动物和细菌重组表达系统）纯化白细胞介素-2（IL-2）和含有IL-2部分的嵌合蛋白的方法。本发明的方法使用其中可溶性IL-2受体已经固定在固体支持物上的IL-2受体亲和吸附剂。通过使用这些亲和吸附剂，可以从细菌提取物或条件培养基中单步制备高纯度的IL-2和含有IL-2部分的嵌合蛋白质。如此纯化的蛋白质基本上不含聚集形式，当使用其它纯化方法时，它们通常存在。

6. 发明授权

US07060680B2 Morphogen treatments for limiting proliferation of epithelial cells 失效
公开(公告)号：US07060680B2
公开(公告)日：2006-06-13
申请号：US10050050
申请日：2002-01-15
申请人： Charles M. Cohen , Marc F. Charette , Thangavel Kuberasampath , David C. Rueger , Hermann Oppermann , Roy H. L. Pang , Engin Ozkaynak , John E. Smart
发明人： Charles M. Cohen , Marc F. Charette , Thangavel Kuberasampath , David C. Rueger , Hermann Oppermann , Roy H. L. Pang , Engin Ozkaynak , John E. Smart
IPC分类号： A61K38/18 , C07K14/51
CPC分类号： G01N33/6872 , A61F2310/00365 , A61K38/17 , A61K38/1703 , A61K38/1875 , A61L27/227 , A61L27/24 , C07K14/495 , C07K14/51 , C07K16/22 , G01N2500/10 , G01N2800/06 , A61K2300/00
摘要： Disclosed are methods and compositions for maintaining the integrity of the gastrointestinal tract luminal lining in a mammal, including (1) limiting epithelial cell proliferation, (2) inhibiting ulcerative lesion formation, (3) inhibiting inflammation normally associated with ulcerative diseases, and (4) stimulating the repair of ulcerative lesions and the regeneration of the luminal tissue. The methods and compositions include a therapeutically effective amount of a morphogen as defined herein.

7. 发明授权

US06440929B1 Pulmonary delivery of active agents 有权
标题翻译：肺部递送活性剂
公开(公告)号：US06440929B1
公开(公告)日：2002-08-27
申请号：US09744777
申请日：2001-04-26
申请人： Sam J. Milstein , John E. Smart , Donald J. Sarubbi , Monica Leipold , Elizabeth Flanders , Doris O'Toole , Andrea Leone-Bay , David Gschneidner
发明人： Sam J. Milstein , John E. Smart , Donald J. Sarubbi , Monica Leipold , Elizabeth Flanders , Doris O'Toole , Andrea Leone-Bay , David Gschneidner
IPC分类号： A61K3800
CPC分类号： C07C235/64 , A61K9/0073 , A61K31/16 , A61K31/727 , A61K38/00 , A61K38/1709 , A61K38/1816 , A61K38/27 , A61K38/28 , A61K38/29 , A61K38/30 , A61K47/183
摘要： The present invention relates to pulmonary delivery of active agents. Acylated or sufonated amino acids are used as carriers to facilitate pulmonary delivery of active agents to a target.
摘要翻译：本发明涉及活性剂的肺部递送。使用酰化或辅助氨基酸作为载体以促进活性剂向目标物的肺部递送。

8. 发明授权

US5994131A Morphogenic protein screening method 失效
标题翻译：形态蛋白筛选方法
公开(公告)号：US5994131A
公开(公告)日：1999-11-30
申请号：US912088
申请日：1997-08-15
申请人： John E. Smart , Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang , Charles M. Cohen
发明人： John E. Smart , Hermann Oppermann , Engin Ozkaynak , Thangavel Kuberasampath , David C. Rueger , Roy H. L. Pang , Charles M. Cohen
IPC分类号： A01N1/02 , A61F2/00 , A61K6/00 , A61K38/00 , A61K38/17 , A61K38/18 , A61L27/22 , A61L27/24 , C07K14/495 , C07K14/51 , C07K14/625 , C07K16/22 , C12Q1/68 , G01N33/50 , G01N33/74 , C12N5/06 , C12N5/08
CPC分类号： G01N33/74 , A61K38/17 , A61K38/1703 , A61K38/1875 , A61L27/227 , A61L27/24 , C07K14/495 , C07K14/51 , C07K14/625 , C07K16/22 , C12Q1/6881 , G01N33/5008 , G01N33/5023 , G01N33/5044 , A61F2310/00365 , C12Q2600/136 , C12Q2600/158 , G01N2333/495 , G01N2333/51 , G01N2500/02 , G01N2500/10 , G01N2510/00
摘要： Disclosed is a method of screening candidate compounds for the ability to modulate the level of morphogenic protein in mammalian system. The method includes determining a parameter indicative of the level of production of a morphogenic in a cell culture known to produce the morphogen, incubating a candidate compound with the culture for a time sufficient to allow the compound to affect the production of the morphogenic protein, and then assaying the culture again to detect a change in the level of morphogenic protein production.
摘要翻译：公开了一种筛选候选化合物以调节哺乳动物系统中形态发生蛋白水平的能力的方法。所述方法包括确定指示已知产生形态发生的细胞培养物中形态发生水平的参数的参数，将候选化合物与培养物孵育足以允许化合物影响形态发生蛋白质的产生的时间，以及然后再次测定培养物以检测形态发生蛋白质生产水平的变化。

9. 发明授权

US5861479A Morphogen cell surface receptor 失效
标题翻译：形态细胞表面受体
公开(公告)号：US5861479A
公开(公告)日：1999-01-19
申请号：US459009
申请日：1995-06-02
申请人： Donald F. Jin , Hermann Oppermann , Thangavel Kuberasampath , John E. Smart
发明人： Donald F. Jin , Hermann Oppermann , Thangavel Kuberasampath , John E. Smart
IPC分类号： C07K14/705 , A61K38/00 , A61K38/24 , C12Q1/68 , G01N33/574
CPC分类号： C07K14/705 , Y10S435/81 , Y10S435/975
摘要： Disclosed are (1) nucleic acid sequences, amino acid sequences, homologies, structural features and various other data characterizing a morphogen cell surface receptor; (2) methods for producing receptor proteins, including fragments thereof, using recombinant DNA technology; (3) methods for identifying novel morphogen receptors and their encoding DNAs; (4) methods for identifying compounds capable of modulating endogenous morphogen receptor levels; and (5) methods for identifying morphogen receptor binding analogs useful in the design of morphogen agonists and antagonists for therapeutic, diagnostic and experimental uses.
摘要翻译：公开了（1）表征形态发生细胞表面受体的核酸序列，氨基酸序列，同源性，结构特征和各种其他数据; （2）使用重组DNA技术生产受体蛋白，包括其片段的方法; （3）鉴定新型形态发生受体及其编码DNA的方法; （4）鉴定能够调节内源性形态发生物受体水平的化合物的方法; 以及（5）用于鉴定形态发生受体结合类似物的方法，其可用于设计用于治疗，诊断和实验用途的形态发生激动剂和拮抗剂。

10. 发明授权

US5460224A Well purge and sample apparatus and method 失效
标题翻译：良好的吹扫和取样装置和方法
公开(公告)号：US5460224A
公开(公告)日：1995-10-24
申请号：US112829
申请日：1993-08-26
申请人： Ronald Schalla , Ronald M. Smith , Stephen H. Hall , John E. Smart , Gregg S. Gustafson
发明人： Ronald Schalla , Ronald M. Smith , Stephen H. Hall , John E. Smart , Gregg S. Gustafson
IPC分类号： E21B43/12 , E21B49/08
CPC分类号： E21B49/084 , E21B43/121 , E21B49/082
摘要： The present invention specifically permits purging and/or sampling of a well but only removing, at most, about 25% of the fluid volume compared to conventional methods and, at a minimum, removing none of the fluid volume from the well.The invention is an isolation assembly with a packer, pump and exhaust, that is inserted into the well. The isolation assembly is designed so that only a volume of fluid between the outside diameter of the isolation assembly and the inside diameter of the well over a fluid column height from the bottom of the well to the top of the active portion (lower annulus) is removed. The packer is positioned above the active portion thereby sealing the well and preventing any mixing or contamination of inlet fluid with fluid above the packer. Ports in the wall of the isolation assembly permit purging and sampling of the lower annulus along the height of the active portion.
摘要翻译：本发明具体允许清洗和/或取样一个井，但与常规方法相比只能去除至多约25％的流体体积，并且至少从井中不去除流体体积。本发明是一种具有封隔器，泵和排气的隔离组件，其被插入井中。隔离组件被设计成使得在隔离组件的外径和从井的底部到活动部分（下环空间）的顶部之间的流体柱高度的井的内径之间仅有一定体积的流体是删除。封隔器位于有效部分上方，从而密封井，并防止入口流体与封隔器上方的流体混合或污染。隔离组件的壁中的端口允许沿着有效部分的高度清洗和取样下环。

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