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1. 发明授权

US07470663B2 Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same 有权
标题翻译：包含聚亚烷基二醇的胰岛素药物 - 低聚物缀合物的混合物，其用途及其制备方法
公开(公告)号：US07470663B2
公开(公告)日：2008-12-30
申请号：US11417586
申请日：2006-05-04
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Balasingam Radhakrishnan , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Balasingam Radhakrishnan , Amy L. Odenbaugh
IPC分类号： A61K38/28 , C07K14/62
CPC分类号： A61K38/28 , A61K45/06 , A61K47/60
摘要： A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.
摘要翻译：公开了混合物的混合物，其中混合物中的每个缀合物包含与包含聚亚烷基二醇部分的低聚物偶联的胰岛素药物。该混合物可以表现出比类似共轭物的多分散混合物更高的体内活性。与类似共轭物的多分散混合物相比，混合物在存活肠内消化的体外模型时也可能更有效。与相似缀合物的多分散混合物相比，混合物还可导致较少的受试者间变异性。

2. 发明授权

US07381702B2 Methods of treating diabetes mellitus 有权
标题翻译：治疗糖尿病的方法
公开(公告)号：US07381702B2
公开(公告)日：2008-06-03
申请号：US11424295
申请日：2006-06-15
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , James Gordon Still , Jennifer Ann Filbey , Aslam M. Ansari , Amy L. Odenbaugh , Balasingam Radhakrishnan
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , James Gordon Still , Jennifer Ann Filbey , Aslam M. Ansari , Amy L. Odenbaugh , Balasingam Radhakrishnan
IPC分类号： A61K38/28 , A61K38/00 , A61K38/02 , C07K2/00
CPC分类号： C07K14/62 , A61K38/28 , A61K47/542 , A61K47/60
摘要： Methods of treating diabetes mellitus in a patient in need of such treatment include administering an effective amount of an insulin drug to the patient in order to treat diabetes mellitus in the patient. Methods according to the present invention may “activate” the liver, potentially restoring normal glucose homeostasis to individuals suffering from diabetes mellitus.
摘要翻译：在需要这种治疗的患者中治疗糖尿病的方法包括向患者施用有效量的胰岛素药物以治疗患者的糖尿病。根据本发明的方法可以“激活”肝脏，潜在地恢复患有糖尿病的个体的正常葡萄糖体内平衡。

3. 发明授权

US07423014B2 Insulin conjugates for treating diabetes mellitus 有权
标题翻译：用于治疗糖尿病的胰岛素结合物
公开(公告)号：US07423014B2
公开(公告)日：2008-09-09
申请号：US11314309
申请日：2005-12-21
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , James Gordon Still , Jennifer Ann Filbey , Aslam M. Ansari , Amy L. Odenbaugh , Balasingam Radhakrishnan
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , James Gordon Still , Jennifer Ann Filbey , Aslam M. Ansari , Amy L. Odenbaugh , Balasingam Radhakrishnan
IPC分类号： A61K38/28 , A61K47/48
CPC分类号： C07K14/62 , A61K38/28 , A61K47/542 , A61K47/60
摘要： Methods of treating diabetes mellitus in a patient in need of such treatment include administering an effective amount of an insulin polypeptide-oligomer conjugate of formula V to the patient in order to treat diabetes mellitus in the patient. Methods according to the present invention may “activate” the liver, potentially restoring normal glucose homeostasis to individuals suffering from diabetes mellitus.
摘要翻译：在需要这种治疗的患者中治疗糖尿病的方法包括向患者施用有效量的式V的胰岛素多肽 - 低聚物缀合物以便治疗患者的糖尿病。根据本发明的方法可以“激活”肝脏，潜在地恢复患有糖尿病的个体的正常葡萄糖体内平衡。

4. 发明授权

US07084114B2 Mixtures of insulin drug-oligomer comprising polyalkylene glycol 有权
标题翻译：包含聚亚烷基二醇的胰岛素药物 - 低聚物的混合物
公开(公告)号：US07084114B2
公开(公告)日：2006-08-01
申请号：US10835018
申请日：2004-04-29
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Balasingam Radhakrishnan , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Balasingam Radhakrishnan , Amy L. Odenbaugh
IPC分类号： A61K38/28 , C07K14/62
CPC分类号： A61K38/28 , A61K45/06 , A61K47/60
摘要： A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.
摘要翻译：公开了混合物的混合物，其中混合物中的每个缀合物包含与包含聚亚烷基二醇部分的低聚物偶联的胰岛素药物。该混合物可以表现出比类似共轭物的多分散混合物更高的体内活性。与类似共轭物的多分散混合物相比，混合物在存活肠内消化的体外模型时也可能更有效。与相似缀合物的多分散混合物相比，混合物还可导致较少的受试者间变异性。

5. 发明授权

US06828297B2 Mixtures of insulin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same 有权
公开(公告)号：US06828297B2
公开(公告)日：2004-12-07
申请号：US09873899
申请日：2001-06-04
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Balasingam Radhakrishnan , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Balasingam Radhakrishnan , Amy L. Odenbaugh
IPC分类号： A61K3828
CPC分类号： A61K38/28 , A61K45/06 , A61K47/60
摘要： A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

6. 发明授权

US06835802B2 Methods of synthesizing substantially monodispersed mixtures of polymers having polyethylene glycol moieties 有权
标题翻译：合成具有聚乙二醇部分的聚合物的基本单分散混合物的方法
公开(公告)号：US06835802B2
公开(公告)日：2004-12-28
申请号：US09873731
申请日：2001-06-04
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
IPC分类号： C08G6534
CPC分类号： C08G65/334 , C08L71/02 , C08L71/00
摘要： Methods of synthesizing a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties include: reacting a substantially monodispersed mixture of compounds having the structure of Formula I: R1(OC2H4)n—O−X+ (I) wherein R1 is H or a lipophilic moiety; n is from 1 to 25; and X+ is a positive ion, with a substantially monodispersed mixture of compounds having the structure of Formula II: R2(OC2H4)m—OMs (II) wherein R2 is H or a lipophilic moiety; and m is from 1 to 25, under conditions sufficient to provide a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties and having the structure of Formula III: R2(OC2H4)m+n—OR1 (III).
摘要翻译：合成包含聚乙二醇部分的基本上单分散的聚合物混合物的方法包括：使具有式I结构的化合物的基本上单分散的混合物：其中R 1为H或亲油部分; n为1至25; 并且X +是正离子，其具有具有式II结构的化合物的基本上单分散的混合物：其中R 2是H或亲脂性部分; 并且m为1至25，在足以提供包含聚乙二醇部分并具有式III结构的聚合物的基本上单分散混合物的条件下：

7. 发明授权

US06713452B2 Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same 失效
标题翻译：包含聚亚烷基二醇的降钙素药物 - 低聚物共轭物的混合物及其制备方法及其制备方法
公开(公告)号：US06713452B2
公开(公告)日：2004-03-30
申请号：US09873777
申请日：2001-06-04
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
IPC分类号： A61K3823
CPC分类号： C07K14/585 , A61K47/60
摘要： A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin.
摘要翻译：公开了混合物的混合物，其中混合物中的每个缀合物包含与包含聚亚烷基二醇部分的低聚物偶联的降钙素药物。该混合物可使受试者中的血清钙水平降低10,15或甚至20％或更多。此外，混合物在存活肠内消化的体外模型时可能比非共轭降钙素更有效。此外，该混合物可能表现出比非共轭降钙素更高的生物利用度。

8. 发明授权

US07084121B2 Mixtures of calcitonin drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same 失效
公开(公告)号：US07084121B2
公开(公告)日：2006-08-01
申请号：US10806523
申请日：2004-03-23
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
IPC分类号： A61K38/23 , C07K14/585
CPC分类号： C07K14/585 , A61K47/60
摘要： A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin.

9. 发明授权

US06828305B2 Mixtures of growth hormone drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same 失效
标题翻译：包含聚亚烷基二醇的生长激素药物 - 低聚物缀合物的混合物及其制备方法及其制备方法
公开(公告)号：US06828305B2
公开(公告)日：2004-12-07
申请号：US09873757
申请日：2001-06-04
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
IPC分类号： A61K3827
CPC分类号： C07K14/61 , A61K38/27 , A61K47/60
摘要： Mixtures of conjugates in which each conjugate in the mixture comprises a growth hormone drug coupled to an oligomer that includes a polyalkylene glycol moiety wherein the mixtures have a molecular weight distribution with a standard deviation of less than about 22 Daltons are disclosed. Methods of treating growth hormone deficiency in a subject in need of such treatment and methods of accelerating the growth rate of an animal arc also disclosed. Processes for synthesizing substantially monodispersed mixtures of conjugates wherein each conjugate comprises a growth hormone drug coupled to an oligomer that comprises a polyethylene glycol moiety are further provided.
摘要翻译：缀合物的混合物，其中混合物中的每个缀合物包含与包含聚亚烷基二醇部分的低聚物偶联的生长激素药物，其中所述混合物具有小于约22道尔顿的标准偏差的分子量分布。还公开了在需要这种治疗的受试者中治疗生长激素缺乏的方法和加速动物弧的生长速率的方法。用于合成基本上单分散的缀合物混合物的方法，其中每个缀合物包含与包含聚乙二醇部分的低聚物偶联的生长激素药物。

10. 发明授权

US07119162B2 Substantially monodispersed mixtures of polymers having polyethylene glycol moieties 有权
标题翻译：具有聚乙二醇部分的聚合物的基本单分散混合物
公开(公告)号：US07119162B2
公开(公告)日：2006-10-10
申请号：US10977973
申请日：2004-10-29
申请人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
发明人： Nnochiri N. Ekwuribe , Christopher H. Price , Aslam M. Ansari , Amy L. Odenbaugh
IPC分类号： C08G65/34
CPC分类号： C08G65/334 , C08L71/02 , C08L71/00
摘要： Methods of synthesizing a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties include: reacting a substantially monodispersed mixture of compounds having the structure of Formula I: R1(OC2H4)n—O−X+ (I) wherein R1 is H or a lipophilic moiety; n is from 1 to 25; and X+ is a positive ion, with a substantially monodispersed mixture of compounds having the structure of Formula II: R2(OC2H4)m—OMs (II) wherein R2 is H or a lipophilic moiety; and m is from 1 to 25, under conditions sufficient to provide a substantially monodispersed mixture of polymers comprising polyethylene glycol moieties and having the structure of Formula III: R2(OC2H4)m+n—OR1 . (III) Substantially monodispersed mixtures of polymers comprising polyethylene glycol moieties are also disclosed.
摘要翻译：合成基本上单分散的包含聚乙二醇部分的聚合物的混合物的方法包括：使具有式I结构的化合物的基本上单分散的混合物：<？in-line-formula description =“In-Line Formulas”end =“lead” （O 2 H 4）（I）<？in-line-formula description =“In-line formula”end =“tail”？>其中R 1是H或亲油部分; n为1至25; 并且X + +是正离子，其具有具有式II结构的化合物的基本上单分散的混合物：<？in-line-formula description =“In-line Formulas”end =“lead”？（II）H 2 -OMs（II）＆lt;＆lt;＆lt;＆lt; 2-in-line-formula description =“In-line Formulas”end =“tail”？>其中R 2是H或亲脂性部分; 且m为1至25，在足以提供包含聚乙二醇部分并且具有式III结构的基本上单分散的聚合物混合物的条件下：<？在线公式描述=“在线公式”末端=“铅（○2 H 4）m + n - 或 - 1个/ SUP>。（III）<？in-line-formula description =“In-line Formulas”end =“tail”？>还公开了包含聚乙二醇部分的聚合物的基本上单分散的混合物。

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