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1. 发明申请

WO1998015835A1 METHOD OF EARLY LUNG CANCER DETECTION VIA SPUTUM INDUCTION AND ANALYSIS OF SPUTUM TO DETECT CANCER ASSOCIATED SUBSTANCES 审中-公开
标题翻译：早期肺癌检测方法通过SPUTUM诱导和SPUTUM分析检测癌症相关物质
公开(公告)号：WO1998015835A1
公开(公告)日：1998-04-16
申请号：PCT/US1997018137
申请日：1997-10-08
申请人： INSPIRE PHARMACEUTICALS, INC. , LACROIX, Karol, K. , SHAFFER, Christy, L. , JACOBUS, Karla, M. , RIDEOUT, Janet, L. , DRUTZ, David, J. , PENDERGAST, William , YERXA, Benjamin, R.
发明人： INSPIRE PHARMACEUTICALS, INC.
IPC分类号： G01N33/574
CPC分类号： G01N33/57423
摘要： A method of early detection of lung cancer is disclosed. The method comprises using uridine 5'-triphosphate (UTP) or related compounds to induce a sputum sample from the lungs of a subject, then using labeled reagents to detect substances in the sputum whose presence is associated with the development of lung cancer. Methods to detect cancer-associated substances in the sputum include monoclonal antibody immunostaining to detect cancer associated cellular antigens, or PCR analysis to amplify and detect cancer associated gene mutations. The UTP sputum induction agent is administered to subject by means of a liquid solution, a liquid suspension in nebulized form or by means of a dry power inhalant.
摘要翻译：公开了早期检测肺癌的方法。该方法包括使用尿苷5'-三磷酸（UTP）或相关化合物从受试者的肺中诱导痰样品，然后使用标记的试剂检测痰中与肺癌发展相关的物质。检测痰中癌症相关物质的方法包括单克隆抗体免疫染色以检测癌症相关细胞抗原，或PCR分析来扩增和检测癌症相关基因突变。通过液体溶液，雾化形式的液体悬浮液或通过干力吸入剂将UTP痰诱导剂施用于受试者。

2. 发明申请

WO1998003177A1 METHOD OF TREATING SINUSITIS WITH URIDINE TRIPHOSPHATES AND RELATED COMPOUNDS 审中-公开
标题翻译：用尿苷磷酸酯和相关化合物处理辛烷肟的方法
公开(公告)号：WO1998003177A1
公开(公告)日：1998-01-29
申请号：PCT/US1997011795
申请日：1997-07-03
申请人： INSPIRE PHARMACEUTICALS, INC. , JABOBUS, Karla , RIDEOUT, Janet , YERXA, Ben , PENDERGAST, William , SIDDIQI, Suhaib , DRUTZ, David, J.
发明人： INSPIRE PHARMACEUTICALS, INC.
IPC分类号： A61K31/52
CPC分类号： A61K31/7048 , A61K31/7068 , A61K31/7072 , A61K31/7076 , C07H19/10 , C07H19/20
摘要： The invention is the method of treating sinusitis using nucleoside phosphates selected from UTP, ATP, CTP or derivative thereof, or using dinucleoside tetraphosphates of adenosine or uridine.
摘要翻译：本发明是使用选自UTP，ATP，CTP或其衍生物的核苷磷酸盐或使用腺苷或尿苷的二核苷四磷酸治疗鼻窦炎的方法。

3. 发明申请

WO9735591B1 METHOD OF TREATING CILIARY DYSKINESIA WITH URIDINE TRIPHOSPHATES AND RELATED COMPOUNDS 审中-公开
标题翻译：用尿苷磷酸酯及相关化合物处理胆固醇的方法
公开(公告)号：WO9735591B1
公开(公告)日：2001-04-26
申请号：PCT/US9705101
申请日：1997-03-27
申请人： INSPIRE PHARMACEUTICALS INC , JACOBUS KARLA M , YERXA BENJAMIN R , PENDERGAST WILLIAM , BOUCHER RICHARD C JR , RIDEOUT JANET L , DRUTZ DAVID J , JAMES MICHAEL K , STUTTS MONROE JACKSON , GEARY CARY , LAZAROWSKI EDWARDO R
发明人： JACOBUS KARLA M , YERXA BENJAMIN R , PENDERGAST WILLIAM , BOUCHER RICHARD C JR , RIDEOUT JANET L , DRUTZ DAVID J , JAMES MICHAEL K , STUTTS MONROE JACKSON , GEARY CARY , LAZAROWSKI EDWARDO R
IPC分类号： C07H19/10 , A61K9/06 , A61K9/08 , A61K9/10 , A61K9/12 , A61K9/70 , A61K31/00 , A61K31/505 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/706 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61P11/00 , A61P13/00 , A61P15/00 , A61P27/00 , A61P27/02 , A61P27/16 , A61P37/00 , A61P37/04 , C07H19/20 , C07H21/02
CPC分类号： A61K31/7076 , A61K31/7072
摘要： A method of stimulating ciliary beat frequency in a subject in need of such treatment is disclosed. The method comprises administering to the airways, ears, eyes, or genito-urinary tract of the subject a triphosphate nucleotide such as uridine 5'-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to stimulate ciliary beat frequency. This method is useful for treating patients afflicted with ciliary dyskinesia, Kartagener's syndrome, or any other disease involving dysfunction of ciliary movement, such as male infertility caused by impairment of propulsion of the spermatozoa or immune deficiency caused by impairment of ciliary movement in neutrophils or macrophages. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal spray or nasal or eye drops), oral, inhaled by nebulization, topical, injected, suppository, intra-operative by instillation or application, or ex vivo direct application to spermatozoa.
摘要翻译：公开了一种在需要这种治疗的受试者中刺激睫状肌搏动频率的方法。该方法包括向受试者的气道，耳朵，眼睛或生殖泌尿道施用有效刺激的量的三磷酸核苷酸，例如尿苷5'-三磷酸（UTP），UTP类似物或任何其它类似物睫毛拍频。该方法可用于治疗患有睫状肌运动障碍，Kartagener综合征或涉及睫状肌运动功能障碍的任何其他疾病，例如由嗜中性粒细胞或巨噬细胞的睫状肌运动损伤引起的精子推进或免疫缺陷引起的男性不育症。还公开了药物制剂及其制备方法。给药方法包括任何液体悬浮液（包括鼻喷雾或鼻腔或滴眼液），口服，通过雾化吸入，局部注射，注射，栓剂，通过滴注或施用手术，或离体直接施用于精子。

4. 发明申请

WO9932085A2 NOVEL PHARMACEUTICAL COMPOSITIONS OF URIDINE TRIPHOSPHATE 审中-公开
标题翻译：尿苷三磷酸的新型药物组合物
公开(公告)号：WO9932085A2
公开(公告)日：1999-07-01
申请号：PCT/US9827409
申请日：1998-12-23
申请人： INSPIRE PHARMACEUTICALS INC , LACROIX KAROL K , SHAFFER CHRISTY L , JACOBUS KARLA M , RIDEOUT JANET L , DRUTZ DAVID J , EVANS RICHARD M , PENDERGAST WILLIAM
发明人： LACROIX KAROL K , SHAFFER CHRISTY L , JACOBUS KARLA M , RIDEOUT JANET L , DRUTZ DAVID J , EVANS RICHARD M , PENDERGAST WILLIAM
IPC分类号： A61K9/00 , A61K9/08 , A61K9/72 , A61K31/70 , A61K31/7072 , A61K47/02 , A61P43/00
CPC分类号： A61K9/0078 , A61K9/08 , A61K31/7072 , A61K47/02
摘要： Novel pharmaceutical compositions of uridine 5'-triphosphate (UTP) for use in promoting increased mucociliary clearance of retained mucous secretions of the human airways, middle/inner ears or sinuses are disclosed. Novel Formulation (I) comprises UTP and aqueous solution having a therapeutic concentration between 5 and 45 mg/mL, a controlled tonicity within the range of 250 to 100 mOsM, a pH between 7.0 and 7.5, and is sterile. The pH-adjusted composition is capable of long-term storage in the refrigerated state with a shelf life of up to 30 months. Formulation (I) may be delivered therapeutically either in a nebulized form or in a liquid form. Novel Formulation (II) comprises UTP in an aqueous solution having a therapeutic concentration approaching the limit of UTP's solubility at ambient temperature or in a suspension which exceeds drug solubility. This high concentration allows delivery of a therapeutic amount of UTP in very small volumes (50 to 100 mu L) suitable for administration via portable hand-held devices such as metered dose inhalers. Formulation (II) has extended shelf life without the need for refrigeration after being dispensed to the patient.
摘要翻译：公开了用于促进对人气道，中耳/内耳或窦的保留的粘液分泌物的增加的粘膜纤毛清除的尿苷5'-三磷酸（UTP）的新型药物组合物。新配方（I）包括UTP和治疗浓度为5至45mg / mL的水溶液，控制张力在250至100mOsM范围内，pH在7.0至7.5之间，并且是无菌的。经pH调节的组合物能够在冷藏状态下长期储存，保质期长达30个月。制剂（I）可以以雾化形式或液体形式递送。新型制剂（II）在具有接近UTP在环境温度下的溶解度或超过药物溶解度的悬浮液中的治疗浓度的水溶液中包含UTP。这种高浓度允许以非常小的体积（50至100μL）递送治疗量的UTP，其适用于经由便携式手持式装置例如计量吸入器的给药。制剂（II）延长了保质期，而不需要在分配给患者后进行制冷。

5. 发明申请

WO03070192A9 COMPOSITIONS AND METHODS FOR SURROGATE ANTIBODY MODULATION OF AN IMMUNE RESPONSE AND TRANSPORT 审中-公开
标题翻译：用于免疫反应和运输的抗体调节的组合物和方法
公开(公告)号：WO03070192A9
公开(公告)日：2003-11-20
申请号：PCT/US0305000
申请日：2003-02-19
申请人： SYNTHERICA CORP , FRIEDMAN STEPHEN B , DRUTZ DAVID J
发明人： FRIEDMAN STEPHEN B , DRUTZ DAVID J
IPC分类号： C12N15/09 , A61K31/739 , A61K38/00 , A61K39/395 , A61K45/00 , A61P1/02 , A61P1/04 , A61P3/10 , A61P11/06 , A61P17/06 , A61P19/02 , A61P21/04 , A61P25/00 , A61P29/00 , A61P31/04 , A61P31/10 , A61P31/12 , A61P31/18 , A61P33/00 , A61P35/00 , A61P37/06 , A61P37/08 , C07K14/52 , C07K16/00 , C07K16/08 , C07K16/12 , C07K16/28 , C07K16/30 , C07K16/42 , C07K16/44 , C07K16/46 , C07K19/00 , C12P21/08 , A61K
CPC分类号： C07K16/44 , A61K2039/505 , C07K16/00 , C07K16/283 , C07K16/4283 , C07K2317/31
摘要： Methods and compositions for the modulation of an immune response are provided. Compositions comprise a bi-functional surrogate antibody molecule that interacts with a ligand of interest, wherein the bi-functional surrogate antibody further has attached thereto an immunomodulatory agent and/or a transporting agent. The compositions of the invention find use in a method for delivering an immunomodulatory agent to a ligand of interest. Further provided are methods for modulating an immune response in a subject against a ligand of interest. The method comprises administering a therapeutically effective amount of a bi-functional surrogate antibody of the invention. The methods of the invention also find use in improving the clinical outcome of a subject in need of a modulation in the immune response. Methods are further provided for the treatment or prevention of a variety of conditions and/or disorders including cancer, autoimmune diseases, allergies, prions, and various diseases or conditions of bacterial, parasitic, yeast or viral etiology.
摘要翻译：提供了用于调节免疫应答的方法和组合物。组合物包含与感兴趣的配体相互作用的双功能替代抗体分子，其中双功能替代抗体还具有与其连接的免疫调节剂和/或转运剂。本发明的组合物可用于将免疫调节剂递送至感兴趣的配体的方法中。进一步提供了用于调节受试者针对感兴趣配体的免疫应答的方法。该方法包括施用治疗有效量的本发明的双功能替代抗体。本发明的方法也可用于改善需要调节免疫应答的受试者的临床结果。还提供了用于治疗或预防各种病症和/或病症的方法，所述病症和/或病症包括癌症，自身免疫性疾病，变态反应，朊病毒以及细菌，寄生虫，酵母或病毒病原学的各种疾病或病症。

6. 发明申请

WO1997029756A1 METHOD OF TREATING OTITIS MEDIA WITH URIDINE TRIPHOSPHATES AND RELATED COMPOUNDS 审中-公开
标题翻译：用尿苷磷酸酯及相关化合物处理脂肪介质的方法
公开(公告)号：WO1997029756A1
公开(公告)日：1997-08-21
申请号：PCT/US1997002299
申请日：1997-02-14
申请人： INSPIRE PHARMACEUTICALS, INC. , DRUTZ, David, J. , RIDEOUT, Janet, L. , JACOBUS, Karla, M.
发明人： INSPIRE PHARMACEUTICALS, INC.
IPC分类号： A61K31/70
CPC分类号： A61K31/7076 , A61K31/7072
摘要： A method of promoting drainage of congested middle ear fluid in a subject in need of such treatment is disclosed. The method comprises administering to the middle ear of the subject a uridine triphosphate such as uridine 5'-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to promote drainage of congested middle ear fluid by hydrating mucous secretions in the middle ear or by stimulating ciliary beat frequency in the middle ear or eustachian tube. The method is useful for treating patients afflicted with otitis media and other middle ear diseases, otitis externa, and inner ear diseases including Ménière's Disease. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal drops or spray), oral, inhaled by nebulization, topical, injected or suppository form.
摘要翻译：公开了一种在需要这种治疗的受试者中促进拥挤的中耳液的引流的方法。该方法包括向受试者的中耳施用尿苷三磷酸，例如尿苷5'-三磷酸（UTP），UTP的类似物或任何其它类似物，其量可有效地促进通过保湿粘液促进拥挤的中耳液的引流中耳分泌物或通过刺激中耳或咽鼓管中的睫状肌搏动频率。该方法可用于治疗患有中耳炎和其他中耳疾病，外耳炎和内耳疾病（包括梅尼埃病）的患者。还公开了药物制剂及其制备方法。给药方法包括任何液体悬浮液（包括滴鼻剂或喷雾剂），口服，通过雾化，局部，注射或栓剂形式吸入。

7. 发明申请

WO2003070192A3 COMPOSITIONS AND METHODS FOR SURROGATE ANTIBODY MODULATION OF AN IMMUNE RESPONSE AND TRANSPORT 审中-公开
公开(公告)号：WO2003070192A3
公开(公告)日：2003-08-28
申请号：PCT/US2003/005000
申请日：2003-02-19
申请人： SYNTHERICA CORPORATION , FRIEDMAN, Stephen, B. , DRUTZ, David, J.
发明人： FRIEDMAN, Stephen, B. , DRUTZ, David, J.
IPC分类号： C07H21/00
摘要： Methods and compositions for the modulation of an immune response are provided. Compositions comprise a bi-functional surrogate antibody molecule that interacts with a ligand of interest, wherein the bi-functional surrogate antibody further has attached thereto an immunomodulatory agent and/or a transporting agent. The compositions of the invention find use in a method for delivering an immunomodulatory agent to a ligand of interest. Further provided are methods for modulating an immune response in a subject against a ligand of interest. The method comprises administering a therapeutically effective amount of a bi-functional surrogate antibody of the invention. The methods of the invention also find use in improving the clinical outcome of a subject in need of a modulation in the immune response. Methods are further provided for the treatment or prevention of a variety of conditions and/or disorders including cancer, autoimmune diseases, allergies, prions, and various diseases or conditions of bacterial, parasitic, yeast or viral etiology.

8. 发明申请

WO0030629A3 METHOD OF PROMOTING CERVICAL AND VAGINAL SECRETIONS 审中-公开
标题翻译：促进宫颈和阴道分泌的方法
公开(公告)号：WO0030629A3
公开(公告)日：2001-06-07
申请号：PCT/US9927634
申请日：1999-11-19
申请人： INSPIRE PHARMACEUTICALS INC , PENDERGAST WILLIAM , SHAVER SAMMY R , DRUTZ DAVID J , RIDEOUT JANET L
发明人： PENDERGAST WILLIAM , SHAVER SAMMY R , DRUTZ DAVID J , RIDEOUT JANET L
IPC分类号： C07H19/10 , A61K31/00 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/708 , A61K31/7084 , A61P15/02 , C07H19/20 , C07H19/207 , C07H21/00
CPC分类号： C07H21/00 , A61K31/00
摘要： The present invention provides a method of stimulating cervical and vaginal secretions in a mammal by treatment with P2Y2, and/or P2Y4 purinergic receptor agonists. Treatment of vaginal dryness associated with menopause, chemotherapy, and various disease states as well as the treatment of vulvar pain is discussed. Suitable purinergic receptor agonists include nucleotide triphosphates such as uridine 5-triphosphate, cytidine 5'-triphosphate and adenosine 5'-triphosphate; dinucleotide polyphosphates such as P , P -di(uridine-5') tetraphosphate; and their analogs. These purinergic receptor agonists are useful in stimulating cervical and vaginal secretions and treating vaginal dryness in mammals.
摘要翻译：本发明提供了通过用P2Y2和/或P2Y4嘌呤能受体激动剂治疗来刺激哺乳动物的宫颈和阴道分泌物的方法。讨论了与绝经，化疗和各种疾病状态相关的阴道干燥的治疗以及外阴疼痛的治疗。合适的嘌呤能受体激动剂包括三磷酸核苷酸，如五磷酸尿苷，胞苷5'-三磷酸和腺苷5'-三磷酸; 二磷酸二核苷酸如P 1，P 4 - 二（尿苷-5'）四磷酸; 及其类似物。这些嘌呤能受体激动剂可用于刺激宫颈和阴道分泌物并治疗哺乳动物的阴道干燥。

10. 发明申请

WO9735591A2 METHOD OF TREATING CILIARY DYSKINESIA WITH URIDINE TRIPHOSPHATES AND RELATED COMPOUNDS 审中-公开
标题翻译：用尿苷磷酸酯及相关化合物处理胆固醇的方法
公开(公告)号：WO9735591A2
公开(公告)日：1997-10-02
申请号：PCT/US9705101
申请日：1997-03-27
申请人： INSPIRE PHARMACEUTICALS INC , JACOBUS KARLA M , YERXA BEN , PENDERGAST WILLIAM , BOUCHER RICARD C JR , RIDEOUT JANET L , DRUTZ DAVID J , JAMES MICHAEL K , STUTTS MONROE JACKSON , GEARY CARY , LAZAROWSKI EDWARDO R
发明人： JACOBUS KARLA M , YERXA BEN , PENDERGAST WILLIAM , BOUCHER RICARD C JR , RIDEOUT JANET L , DRUTZ DAVID J , JAMES MICHAEL K , STUTTS MONROE JACKSON , GEARY CARY , LAZAROWSKI EDWARDO R
IPC分类号： C07H19/10 , A61K9/06 , A61K9/08 , A61K9/10 , A61K9/12 , A61K9/70 , A61K31/00 , A61K31/505 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/706 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/7084 , A61P11/00 , A61P13/00 , A61P15/00 , A61P27/00 , A61P27/02 , A61P27/16 , A61P37/00 , A61P37/04 , C07H19/20 , C07H21/02
CPC分类号： A61K31/7076 , A61K31/7072
摘要： A method of stimulating ciliary beat frequency in a subject in need of such treatment is disclosed. The method comprises administering to the airways, ears, eyes, or genito-urinary tract of the subject a triphosphate nucleotide such as uridine 5'-triphosphate (UTP), an analog of UTP, or any other analog, in an amount effective to stimulate ciliary beat frequency. This method is useful for treating patients afflicted with ciliary dyskinesia, Kartagener's syndrome, or any other disease involving dysfunction of ciliary movement, such as male infertility caused by impairment of propulsion of the spermatozoa or immune deficiency caused by impairment of ciliary movement in neutrophils or macrophages. Pharmaceutical formulations and methods of making the same are also disclosed. Methods of administering the same would include any liquid suspension (including nasal spray or nasal or eye drops), oral, inhaled by nebulization, topical, injected, suppository, intra-operative by instillation or application, or ex vivo direct application to spermatozoa.
摘要翻译：公开了一种在需要这种治疗的受试者中刺激睫状肌搏动频率的方法。该方法包括向受试者的气道，耳朵，眼睛或生殖泌尿道施用有效刺激的量的三磷酸核苷酸，例如尿苷5'-三磷酸（UTP），UTP类似物或任何其他类似物睫毛拍频。该方法可用于治疗患有睫状肌运动障碍，Kartagener综合征或涉及睫状肌运动功能障碍的任何其他疾病，例如由嗜中性粒细胞或巨噬细胞的睫状肌运动损伤引起的精子推进或免疫缺陷引起的男性不育症。还公开了药物制剂及其制备方法。给药方法包括任何液体悬浮液（包括鼻喷雾或鼻腔或滴眼液），口服，通过雾化吸入，局部注射，注射，栓剂，通过滴注或施用手术，或离体直接施用于精子。

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