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1. 发明申请

WO2004083234A2 INSULIN POLYPEPTIDE-OLIGOMER CONJUGATES, PROINSULIN POLYPEPTIDE-OLIGOMER CONJUGATES AND METHODS OF SYNTHESIZING SAME 审中-公开
标题翻译：胰岛素多肽 - 寡聚体，蛋白多肽 - 低聚物结合体及其合成方法
公开(公告)号：WO2004083234A2
公开(公告)日：2004-09-30
申请号：PCT/US2004/007310
申请日：2004-03-11
申请人： NOBEX CORPORATION , EKWURIBE, Nnochiri N. , RADHAKRISHNAN, Balasingam , SOLTERO, Richard , PUSKAS, Monica , SANGAL, Diti
发明人： EKWURIBE, Nnochiri N. , RADHAKRISHNAN, Balasingam , SOLTERO, Richard , PUSKAS, Monica , SANGAL, Diti
IPC分类号： C07K
CPC分类号： C07K14/62 , A61K47/60
摘要： Methods for synthesizing proinsulin polypeptides are described that include contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also provided as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates and other pro-polypeptide-oligomer conjugates are also provided.
摘要翻译：描述了用于合成胰岛素原多肽的方法，其包括通过能够被切割的肽键将包含与一个或多个肽偶联的胰岛素原多肽与足够使寡聚物与胰岛素原多肽的胰岛素多肽部分，并提供胰岛素原多肽 - 低聚物缀合物，并切割来自胰岛素原多肽 - 低聚物缀合物的一种或多种肽，以提供胰岛素多肽 - 低聚物缀合物。还提供了合成胰岛素原多肽 - 低聚物缀合物的方法，胰岛素原多肽 - 低聚物缀合物。还提供了合成C-肽多肽 - 低聚物缀合物和其它前 - 多肽 - 低聚物缀合物的方法。

2. 发明申请

WO2004043347A2 CALCITONIN DRUG-OLIGOMER CONJUGATES, AND USES THEREOF 审中-公开
标题翻译：降钙素药物 - 低聚物缀合物及其用途
公开(公告)号：WO2004043347A2
公开(公告)日：2004-05-27
申请号：PCT/US2003/033618
申请日：2003-10-24
申请人： NOBEX CORPORATION , EKWURIBE, Nnochiri, N. , RADHAKRISHNAN, Balasingam
发明人： EKWURIBE, Nnochiri, N. , RADHAKRISHNAN, Balasingam
IPC分类号： A61K
CPC分类号： C07K14/585 , A61K47/60
摘要： Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed.
摘要翻译：包括降钙素药物的降钙素药物 - 寡聚物缀合物被偶联到包含由4和10个聚亚烷基二醇亚单元组成的单个聚亚烷基二醇部分的寡聚物上。还公开了包含这种缀合物的药物组合物和通过施用这样的缀合物来治疗骨疾病的方法。

3. 发明申请

WO2005116655A3 NATRIURETIC COMPOUNDS, CONJUGATES, AND USES THEREOF 审中-公开
公开(公告)号：WO2005116655A3
公开(公告)日：2005-12-08
申请号：PCT/US2005/019249
申请日：2005-05-26
申请人： NOBEX CORPORATION , JAMES, Kenneth, D. , RADHAKRISHNAN, Balasingam , MALKAR, Navdeep, B. , MILLER, Mark, A. , EKWURIBE, Nnochiri, N.
发明人： JAMES, Kenneth, D. , RADHAKRISHNAN, Balasingam , MALKAR, Navdeep, B. , MILLER, Mark, A. , EKWURIBE, Nnochiri, N.
IPC分类号： A61K38/00
摘要： Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, enteral, subcutaneous, pulmonary, and intravenous forms of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the natriuretic compound are also disclosed, having an amino acid sequence that is other than the native sequence.

4. 发明申请

WO2002065985A3 METHODS OF TREATING DIABETES MELLITUS 审中-公开
公开(公告)号：WO2002065985A3
公开(公告)日：2002-08-29
申请号：PCT/US2002/004440
申请日：2002-02-14
申请人： NOBEX CORPORATION , EKWURIBE, Nnochiri, N. , PRICE, Christopher, H. , STILL, James, Gordon , FILBEY, Jennifer, Ann , RADHAKRISHNAN, Balasingam , ANSARI, Aslam, M. , ODENBAUGH, Amy, L.
发明人： EKWURIBE, Nnochiri, N. , PRICE, Christopher, H. , STILL, James, Gordon , FILBEY, Jennifer, Ann , RADHAKRISHNAN, Balasingam , ANSARI, Aslam, M. , ODENBAUGH, Amy, L.
IPC分类号： A61K38/28
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.

5. 发明申请

WO2002098232A1 MIXTURES OF INSULIN DRUG-OLIGOMER CONJUGATES COMPRISING POLYALKYLENE GLYCOL, USES THEREOF, AND METHODS OF MAKING SAME 审中-公开
标题翻译：包含聚乙烯甘露糖的胰岛素药物 - 低聚物混合物的混合物及其制备方法
公开(公告)号：WO2002098232A1
公开(公告)日：2002-12-12
申请号：PCT/US2002/017574
申请日：2002-06-04
申请人： NOBEX CORPORATION , EKWURIBE, Nnochiri, N. , PRICE, Christopher, H. , ANSARI, Aslam, M. , ODENBAUGH, Amy, L. , RADHAKRISHNAN, Balasingam
发明人： EKWURIBE, Nnochiri, N. , PRICE, Christopher, H. , ANSARI, Aslam, M. , ODENBAUGH, Amy, L. , RADHAKRISHNAN, Balasingam
IPC分类号： A01N61/00
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。

6. 发明申请

WO2006014673A2 INSULIN-OLIGOMER CONJUGATES, FORMULATIONS AND USES THEREOF 审中-公开
标题翻译：胰岛素 - 低聚物共轭物，制剂及其用途
公开(公告)号：WO2006014673A2
公开(公告)日：2006-02-09
申请号：PCT/US2005/025644
申请日：2005-07-19
申请人： NOBEX CORPORATION , RADHAKRISHNAN, Balasingam , AGGARWAL, Diti , FERRO, Michelle , JAMES, Kenneth, D. , MALKAR, Navdeep, B. , MILLER, Mark, A. , PAVLIV, Leo , POLOWY, Karen , PUSKAS, Karen , EKWURIBE, NnochiriI, N.
发明人： RADHAKRISHNAN, Balasingam , AGGARWAL, Diti , FERRO, Michelle , JAMES, Kenneth, D. , MALKAR, Navdeep, B. , MILLER, Mark, A. , PAVLIV, Leo , POLOWY, Karen , PUSKAS, Karen , EKWURIBE, NnochiriI, N.
IPC分类号： A61K38/28 , A61K38/21 , A61K39/395 , A61K38/22 , A61K38/18
CPC分类号： C07K14/62 , A61K9/0095 , A61K9/2013 , A61K9/2018 , A61K33/30 , A61K38/00 , A61K38/28 , A61K45/06 , A61K47/60 , A61K47/69 , A61K2300/00
摘要： The invention provides a complex including a cation and an insulin compound conjugate. The insulin compound conjugate includes insulin compound, such as human insulin or an analog thereof, conjugated to a modifying moiety, such as a polyethylene glycol moiety. The invention also includes solids and pharmaceutical compositions including such complexes, methods of making such complexes, and methods of using such complexes in the treatment of insulin compound deficiencies and other ailments. Further, the invention includes novel insulin compound conjugates and modifying moieties for use in making novel insulin compound conjugates. The invention also includes fatty acid compositions for administration of of pharmaceutical agents, such as the novel insulin compound conjugates, and/or the cation-insulin compound conjugate complexes of the invention.
摘要翻译：本发明提供了包含阳离子和胰岛素化合物缀合物的复合物。胰岛素化合物缀合物包括缀合至修饰部分例如聚乙二醇部分的胰岛素化合物，例如人胰岛素或其类似物。本发明还包括包含这种复合物的固体和药物组合物，制备这种复合物的方法，以及使用这种复合物治疗胰岛素化合物缺陷和其他疾病的方法。此外，本发明包括用于制备新型胰岛素化合物缀合物的新型胰岛素化合物缀合物和修饰部分。本发明还包括用于施用药剂的脂肪酸组合物，例如本发明的新型胰岛素化合物缀合物和/或阳离子 - 胰岛素化合物缀合物复合物。

7. 发明申请

WO2004047871A2 MODIFIED NATURETIC COMPOUNDS, CONJUGATES, AND USES THEREOF 审中-公开
标题翻译：改性天然化合物，结合物及其用途
公开(公告)号：WO2004047871A2
公开(公告)日：2004-06-10
申请号：PCT/US2003/037996
申请日：2003-11-12
申请人： NOBEX CORPORATION
发明人： JAMES, Kenneth, D. , RADHAKRISHNAN, Balasingam , MALKAR, Navdeep, B. , MILLER, Mark, A. , EKWURIBE, Nnochiri, N.
IPC分类号： A61K47/48
CPC分类号： C08G65/329 , A61K47/60 , C07K14/58 , C07K14/72 , C08L2203/02
摘要： Modified natriuretic compounds and conjugates thereof are disclosed in the present invention. In particular, conjugated forms of hBNP are provided that include at least one modifying moiety attached thereto. The modified natriuretic compound conjugates retain activity for stimulating cGMP production, binding to NPR-A receptor, and in some embodiments an improved half-life in circulation as compared to unmodified counterpart natriuretic compounds. Oral, parenteral, subcutaneous, and intravenous forms to of the compounds and conjugates may be prepared as treatments and/or therapies for heart conditions particularly congestive heart failure. Modifying moieties comprising oligomeric structures having a variety of lengths and configurations are also disclosed. Analogs of the natriuretic compound are also disclosed, having an amino acid sequence that is other than the native sequence.
摘要翻译：本发明公开了改进的利尿钠化合物及其缀合物。特别地，提供了缀合形式的hBNP，其包括与其连接的至少一个修饰部分。修饰的利尿钠化合物缀合物保留刺激cGMP产生，与NPR-A受体结合的活性，并且在一些实施方案中，与未修饰的对应利钠化合物相比，循环中的半衰期改善。可以制备化合物和缀合物的口服，肠胃外，皮下和静脉内形式作为心脏状况的治疗和/或治疗，特别是充血性心力衰竭。还公开了包含具有各种长度和构型的寡聚结构的修饰部分。还公开了利尿钠化合物的类似物，其具有不同于天然序列的氨基酸序列。

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