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1. 发明授权

US08481580B2 Lisofylline analogs and methods for use 有权
公开(公告)号：US08481580B2
公开(公告)日：2013-07-09
申请号：US12036646
申请日：2008-02-25
申请人： Timothy L. Macdonald , Jerry L. Nadler , Peng Cui
发明人： Timothy L. Macdonald , Jerry L. Nadler , Peng Cui
IPC分类号： A61P9/10 , A61P19/02 , A61P25/28 , A61K31/41 , C07D249/12
CPC分类号： A61K31/538 , A61K31/404 , A61K31/405 , A61K31/4196 , A61K31/495 , A61K31/502 , A61K31/53 , C07C215/68 , C07C219/32 , C07D209/08 , C07D209/80 , C07D221/08 , C07D223/22 , C07D241/08 , C07D241/18 , C07D249/12 , C07D253/04 , C07D265/26 , C07D265/36 , C07D265/38 , C07D275/04 , C07D279/22 , C07D487/04
摘要： The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.

2. 发明申请

US20100105690A1 LISOFYLLINE ANALOGS AND METHODS FOR USE 审中-公开
标题翻译： LISOFYLLINE模拟和使用方法
公开(公告)号：US20100105690A1
公开(公告)日：2010-04-29
申请号：US12550124
申请日：2009-08-28
申请人： Timothy L. Macdonald , Jerry L. Nadler , Peng Cui
发明人： Timothy L. Macdonald , Jerry L. Nadler , Peng Cui
IPC分类号： A61K31/502 , C07D237/30
CPC分类号： C07D237/32 , A61K31/502
摘要： Analogs of a Lisofylline (LSF), and synthetic methods for the preparation of such analogs are provided. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic β-cells.
摘要翻译：提供了莱索菲线（LSF）的类似物，以及制备此类类似物的合成方法。提供的LSF的类似物具有保护细胞活力的能力，特别是保护胰腺细胞的能力。

3. 发明授权

US08871764B2 Lisofylline analogs and methods for use 有权
标题翻译：利福罗线类似物和使用方法
公开(公告)号：US08871764B2
公开(公告)日：2014-10-28
申请号：US13477613
申请日：2012-05-22
申请人： Timothy L. MacDonald , Jerry L. Nadler , Peng Cui
发明人： Timothy L. MacDonald , Jerry L. Nadler , Peng Cui
IPC分类号： C07D237/32 , A61K31/502 , A61P3/10
CPC分类号： A61K31/502 , C07D237/32
摘要： Analogs of a Lisofylline (LSF), and synthetic methods for the preparation of such analogs are provided. The analogs of LSF provided have the ability to protect cell viability, particularly the ability to protect pancreatic β-cells.
摘要翻译：提供了莱索菲线（LSF）的类似物，以及制备此类类似物的合成方法。提供的LSF的类似物具有保护细胞活力的能力，特别是保护胰腺细胞的能力。

4. 发明申请

US20080146544A1 LISOFYLLINE ANALOGS AND METHODS FOR USE 有权
标题翻译： LISOFYLLINE模拟和使用方法
公开(公告)号：US20080146544A1
公开(公告)日：2008-06-19
申请号：US12036646
申请日：2008-02-25
申请人： Timothy L. MacDonald , Jerry L. Nadler , Peng Cui
发明人： Timothy L. MacDonald , Jerry L. Nadler , Peng Cui
IPC分类号： A61K31/517 , A61K31/5415 , A61K31/538 , A61K31/53 , A61K31/502 , A61K31/473 , A61K31/425 , A61K31/4196 , A61K31/495
CPC分类号： A61K31/538 , A61K31/404 , A61K31/405 , A61K31/4196 , A61K31/495 , A61K31/502 , A61K31/53 , C07C215/68 , C07C219/32 , C07D209/08 , C07D209/80 , C07D221/08 , C07D223/22 , C07D241/08 , C07D241/18 , C07D249/12 , C07D253/04 , C07D265/26 , C07D265/36 , C07D265/38 , C07D275/04 , C07D279/22 , C07D487/04
摘要： The present invention provides analogs of a Lysofylline (LSF), and synthetic methods for the preparation of such analogs. The have the active side chain moiety (5-R-hydroxyhexyl) of LSF and can have greater potency and oral bioavailability than LSF.
摘要翻译：本发明提供了类似物溶血素（LSF）的类似物，以及制备这类类似物的合成方法。具有LSF的活性侧链部分（5-R-羟基己基），并且可以具有比LSF更大的效力和口服生物利用度。

5. 发明申请

US20090269313A1 ENCAPSULATION SYSTEM 审中-公开
标题翻译：封装系统
公开(公告)号：US20090269313A1
公开(公告)日：2009-10-29
申请号：US12373870
申请日：2007-07-19
申请人： Jerry L. Nadler
发明人： Jerry L. Nadler
IPC分类号： A61K35/12 , A61P3/10
CPC分类号： A61K35/39
摘要： An encapsulation system for use in the treatment of diabetes (Types 1 or 2, and LADA) are provided. The system has (1) a delivery vehicle comprising a selectively permeable membrane that allows passage of glucose, insulin and other nutrients through the membrane, but prevents large molecules such as antibodies or inflammatory cells from passing through the membrane; (2) a population of islet cells or insulin producing cells encapsulated by said membrane; and (3) a biological response modifier that may be in contact with the membrane or encapsulated by the membrane. Generally, the biological response modifier is a compound, including resolved enantiomers, diastereomers, tautomers, salts and solvates thereof, having the following formula: wherein: X, Y and Z are independently selected from a member of the group consisting of C(R3), N, N(R3) and S; R1 is selected from a member of the group consisting of hydrogen, methyl, C(5-9)alkyl, C(5-9)alkenyl, C(5-9)alkynyl, C(5-9)hydroxyalkyl, C(3-8)alkoxyl, C(5-9)alkoxyalkyl, the R1 being optionally substituted; R2 and R3 are independently selected from a member of the group consisting of hydrogen, halo, oxo, C(1-20)alkyl, C(1-20)hydroxyalkyl, C(1-20)thioalkyl, C(1-20)alkylamino, C(1-20)alkylaminoalkyl, C(1-20)aminoalkyl, C(1-20)aminoalkoxyalkenyl, C(1-20)aminoalkoxyalkynyl, C(1-20)diaminoalkyl, C(1-20)triaminoalkyl, C(1-20)tetraaminoalkyl, C(5-15)aminotrialkoxyamino, C(1-20)alkylamido, C(1-20)alkylamidoalkyl, C(1-20)amidoalkyl, C(1-20)acetamidoalkyl, C(1-20)alkenyl, C(1-20)alkynyl, C(3-8)alkoxyl, C(1-11)alkoxyalkyl, and C(1-20)dialkoxyalkyl.
摘要翻译：提供了一种用于治疗糖尿病的包封系统（1型或2型和LADA型）。该系统具有（1）包含选择性渗透膜的输送载体，其允许葡萄糖，胰岛素和其它营养物通过膜，但是阻止大分子例如抗体或炎性细胞通过膜; （2）由所述膜包封的胰岛细胞群体或产生胰岛素的细胞群; 和（3）可以与膜接触或被膜包封的生物反应调节剂。通常，生物反应调节剂是具有下列结构式的拆分的对映异构体，非对映异构体，互变异构体，盐和溶剂化物的化合物：其中：X，Y和Z独立地选自C（R3），N，N（R3）和S; R 1选自氢，甲基，C（5-9）烷基，C（5-9）烯基，C（5-9）炔基，C（5-9）羟基烷基，C（3） -8）烷氧基，C（5-9）烷氧基烷基，R1任选被取代; R 2和R 3独立地选自氢，卤素，氧代，C（1-20）烷基，C（1-20）羟基烷基，C（1-20）硫代烷基，C（1-20）烷基氨基，C（1-20）烷基氨基烷基，C（1-20）氨基烷基，C（1-20）氨基烷氧基烯基，C（1-20）氨基烷氧基炔基，C（1-20）二氨基烷基，C（1-20） C 1-20 1-20烷基氨基烷基，C（1-20）烷基氨基烷基，C（1-20）氨基烷基，C（1-20）乙酰氨基烷基，C（1-20） 1-20）烯基，C（1-20）炔基，C（3-8）烷氧基，C（1-11）烷氧基烷基和C（1-20）二烷氧基烷基。

6. 发明授权

US06486181B1 Human leukocutye 12-lipoxygenase and its role in the pathogenesis of disease states 失效
标题翻译：人类白细胞12-脂肪氧合酶及其在疾病发病机理中的作用
公开(公告)号：US06486181B1
公开(公告)日：2002-11-26
申请号：US09691845
申请日：2000-10-18
申请人： Jerry L. Nadler , Rama Natarajan
发明人： Jerry L. Nadler , Rama Natarajan
IPC分类号： A61K3144
CPC分类号： A61K31/00 , A61K31/045 , A61K31/05 , A61K31/155 , A61K31/195 , A61K31/20 , A61K31/35 , A61K31/352 , A61K31/44 , A61K31/4439 , A61K31/575 , C12N9/0069 , C12N15/113 , C12Q1/26 , C12Y113/11012 , C12Y113/11031 , G01N33/573 , G01N33/6893 , G01N2333/90241 , G01N2800/042
摘要： The present invention relates to a method for inhibiting the etiology of disease in patients having a disease state caused by an excess of 12-lipoxygenase or its products. In particular, the invention provides for administration of a human leukocyte 12-lipoxygenase pathway inhibitor to inhibit disease etiology, to inhibit the proliferation of breast cancer and to increase insulin receptor phosphorylation in a patient having Type II diabetics.
摘要翻译：本发明涉及一种抑制患有由过量的12-脂肪氧合酶或其产物引起的疾病状态的患者的疾病病因的方法。特别地，本发明提供了用于抑制疾病病因的人白细胞12-脂肪氧合酶途径抑制剂，抑制乳腺癌的增殖并增加患有II型糖尿病患者的胰岛素受体磷酸化。

7. 发明授权

US06485976B1 Use of adeno-associated virus (AAV) to deliver genes 有权
标题翻译：使用腺相关病毒（AAV）传递基因
公开(公告)号：US06485976B1
公开(公告)日：2002-11-26
申请号：US09559915
申请日：2000-04-28
申请人： Jerry L. Nadler , David Bleich , Konkal-Matt R. Prasad
发明人： Jerry L. Nadler , David Bleich , Konkal-Matt R. Prasad
IPC分类号： C12N1563
CPC分类号： C12N15/86 , A61K38/44 , A61K48/00 , C12N2750/14143
摘要： This invention pertains to a method of protecting pancreatic &bgr;-cells from immune system-mediated cell damage through transduction of the cells with an adeno-associated viral vector encoding cytoprotective genes. These protected cells are suitable for transplantation into mammals and will be protected from rejection by the host. The method also may be used to protect pancreatic islet &bgr;-cells in situ for the primary prevention of immune-mediated destruction which leads to Type 1 diabetes. Pancreatic &bgr;-cells may be transduced with AAV vectors according to the invention for in vivo or ex vivo gene therapy.
摘要翻译：本发明涉及通过用编码细胞保护基因的腺相关病毒载体转导细胞来保护胰腺β-细胞免受免疫系统介导的细胞损伤的方法。这些受保护的细胞适合于移植到哺乳动物中，并且将被保护免受宿主的排斥。该方法还可用于原位保护胰岛β细胞，以初步预防免疫介导的破坏，导致1型糖尿病。胰腺β细胞可以用根据本发明的用于体内或体外基因治疗的AAV载体转导。

8. 发明授权

US06191169B1 Human leukocyte 12-lipoxygenase and its role in the pathogenesis of disease states 失效
标题翻译：人类白细胞12-脂肪氧合酶及其在疾病发病机理中的作用
公开(公告)号：US06191169B1
公开(公告)日：2001-02-20
申请号：US08945744
申请日：1997-11-03
申请人： Jerry L. Nadler , Rama Natarajan
发明人： Jerry L. Nadler , Rama Natarajan
IPC分类号： A61K31195
CPC分类号： A61K31/045 , A61K31/00 , A61K31/05 , A61K31/155 , A61K31/195 , A61K31/20 , A61K31/35 , A61K31/352 , A61K31/44 , A61K31/4439 , A61K31/575 , C12N9/0069 , C12N15/113 , C12Q1/26 , C12Y113/11012 , C12Y113/11031 , G01N33/573 , G01N33/6893 , G01N2333/90241 , G01N2800/042 , Y10S514/866
摘要： The present invention relates to a method for inhibiting the etiology of disease in patients having a disease state caused by an excess of 12-lipoxygenase or its products. In particular, the invention provides for administration of a human leukocyte 12-lipoxygenase pathway inhibitor to inhibit disease etiology, to inhibit the proliferation of breast cancer and to increase insulin receptor phosphorylation in a patient having Type II diabetics.
摘要翻译：本发明涉及一种抑制患有由过量的12-脂肪氧合酶或其产物引起的疾病状态的患者的疾病病因的方法。特别地，本发明提供了用于抑制疾病病因的人白细胞12-脂肪氧合酶途径抑制剂，抑制乳腺癌的增殖并增加患有II型糖尿病患者的胰岛素受体磷酸化。

9. 发明申请

US20110052625A1 COMPOSITIONS AND METHODS FOR TREATING DIABETES USING LISOFYLLINE ANALOGS AND ISLET NEOGENESIS ASSOCIATED PEPTIDE 审中-公开
标题翻译：用类似的方法治疗糖尿病的组合物和方法和血小板生成相关肽
公开(公告)号：US20110052625A1
公开(公告)日：2011-03-03
申请号：US12865062
申请日：2009-02-02
申请人： Mary Ann Latona Nadler , Jerry L. Nadler
发明人： Mary Ann Latona Nadler , Jerry L. Nadler
IPC分类号： A61K38/10 , A61P3/10
CPC分类号： A61K38/10 , A61K31/502 , A61K31/522 , A61K31/5377 , A61K31/695 , A61K38/1709 , A61K2300/00
摘要： Pharmaceutical compositions and methods are provided for treating diabetes and/or restoring β-cell mass and function in a mammal in need thereof. Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by immune damage to pancreatic beta-cells. Lisofylline analogs (LSF analogs) are immunomodulators that reduce interlukin 12 signaling and reduce the onset of T1DM in non-obese diabetic (NOD) mice. A combination therapy with both LSF analog (pretreatment) and INGAP provides protection from autoimmune destruction. The concomitant or combination of an LSF analog and INGAP after pre-treatment with an LSF analog is an effective therapy for a disease or condition resulting from the loss of pancreatic islet cells or insulin production in a mammal.
摘要翻译：提供药物组合物和方法用于治疗有需要的哺乳动物的糖尿病和/或恢复和/或细胞质量和功能。 1型糖尿病（T1DM）是以胰腺β细胞免疫损伤为特征的自身免疫性疾病。赖索丝线类似物（LSF类似物）是免疫调节剂，其减少非肥胖性糖尿病（NOD）小鼠中的IL-12信号并减少T1DM的发生。使用LSF类似物（预处理）和INGAP的联合治疗可以防止自身免疫破坏。与LSF类似物预处理后的LSF类似物和INGAP的伴随或组合是由哺乳动物胰岛细胞或胰岛素产生丧失导致的疾病或病症的有效治疗方法。

10. 发明授权

US06316458B1 Method of enhancing insulin action 有权
标题翻译：增强胰岛素作用的方法
公开(公告)号：US06316458B1
公开(公告)日：2001-11-13
申请号：US09557318
申请日：2000-04-25
申请人： Jerry L. Nadler , Thomas W. Balon , Yoko Yamaguchi
发明人： Jerry L. Nadler , Thomas W. Balon , Yoko Yamaguchi
IPC分类号： A01N4390
CPC分类号： A61K31/522
摘要： A category of hydroxyalkyl-substituted xanthines are useful in treating patients suffering from disorders associated with impaired glucose metabolism or impaired insulin function. Use of these compounds, for example, restores insulin responsiveness in otherwise insulin-resistant Type 2 diabetic patients, thus reducing elevated blood glucose levels. The subject compounds also act to restore certain defects of lipid metabolism and to enhance the effects of insulin in general. Insulin-enhancing compositions and methods of treating disorders of glucose metabolism are provided.
摘要翻译：一类羟烷基取代的黄嘌呤可用于治疗患有与葡萄糖代谢受损或胰岛素功能受损相关的疾病的患者。例如，使用这些化合物可恢复胰岛素抵抗2型糖尿病患者的胰岛素反应性，从而降低血糖水平升高。主题化合物还起到恢复脂质代谢的某些缺陷并增强胰岛素的作用的作用。提供胰岛素增强组合物和治疗葡萄糖代谢紊乱的方法。

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