公开(公告)号：US20060172933A1

公开(公告)日：2006-08-03

申请号：US10999761

申请日：2004-11-30

申请人： Kenneth James ,  Balasingham Radhakrishnan ,  Navdeep Malkar ,  Mark Miller ,  Nnochiri Ekwuribe

发明人： Kenneth James ,  Balasingham Radhakrishnan ,  Navdeep Malkar ,  Mark Miller ,  Nnochiri Ekwuribe

IPC分类号： A61K38/17 ,  C07K14/47

CPC分类号： C07K14/58 ,  A61K38/00 ,  A61K47/60 ,  C07K14/72 ,  C07K16/26

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.

摘要翻译： 本发明公开了改良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，结合NPR-A受体的活性，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。 口服，胃肠外，肠内，皮下，肺和静脉内形式的化合物和缀合物可以制备为用于心脏状况的治疗和/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。

公开(公告)号：US20060074009A1

公开(公告)日：2006-04-06

申请号：US11138194

申请日：2005-05-26

申请人： Kenneth James ,  Balasingham Radhakrishnan ,  Navdeep Malkar ,  Mark Miller ,  Nnochiri Ekwuribe

发明人： Kenneth James ,  Balasingham Radhakrishnan ,  Navdeep Malkar ,  Mark Miller ,  Nnochiri Ekwuribe

IPC分类号： A61K38/17 ,  C07K14/47

CPC分类号： C07K14/58 ,  A61K38/00 ,  A61K47/60 ,  C07K14/72 ,  C07K16/26

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.

公开(公告)号：US20060019873A1

公开(公告)日：2006-01-26

申请号：US11184594

申请日：2005-07-19

申请人： Balasingam Radhakrishnan ,  Diti Aggarwal ,  Michelle Ferro ,  Kenneth James ,  Navdeep Malkar ,  Mark Miller ,  Monica Puskas ,  Nnochiri Ekwuribe

发明人： Balasingam Radhakrishnan ,  Diti Aggarwal ,  Michelle Ferro ,  Kenneth James ,  Navdeep Malkar ,  Mark Miller ,  Monica Puskas ,  Nnochiri Ekwuribe

IPC分类号： A61K38/28 ,  C07K14/62

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： An insulin compound coupled to a modifying moiety having a formula: —X—R1—Y-PAG-Z-R  (Formula VI) where, X, Y and Z are independently selected linking groups and each is optionally present, and X, when present, is coupled to the insulin compound by a covalent bond, either R1 or R2 is is a lower alkyl, optionally including a carbonyl group, and when R1 is a lower alkyl, R2 is a capping group, and PAG is a linear or branched carbon chain incorporating one or more alkalene glycol moieties, and optionally incorporating one or more additional moieties selected from the group consisting of —S—, —O—, —N—, and —C(O)—, and where the modifying moiety has a maximum number of 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 heavy atoms.

摘要翻译： 与具有下式的修饰部分偶联的胰岛素化合物：<？in-line-formula description =“In-line formula”end =“lead”→XR 1 -Y-PAG-ZR （式VI）<？in-line-formula description =“In-line Formulas”end =“tail”？>其中，X，Y和Z是独立选择的连接基团，并且每个可选地存在，X如果存在， 通过共价键与胰岛素化合物偶联，R 1或R 2是低级烷基，任选地包括羰基，当R 1 低级烷基是R 2是封端基团，PAG是含有一个或多个二烷基二醇部分的直链或支链碳链，并且任选地加入一个或多个选自以下的另外的部分： 由-S-，-O-，-N-和-C（O） - 组成的组，其中改性部分具有最大数目为3,4,5,6,7,8,9,10， 11，12，13，14，15，16，17，18，19，20，21，22，23，24或25个重原子。

公开(公告)号：US20060019874A1

公开(公告)日：2006-01-26

申请号：US11184668

申请日：2005-07-19

申请人： Balasingam Radhakrishnan ,  Diti Aggarwal ,  Michelle Ferro ,  Kenneth James ,  Navdeep Malkar ,  Mark Miller ,  Monica Puskas ,  Nnochiri Ekwuribe

发明人： Balasingam Radhakrishnan ,  Diti Aggarwal ,  Michelle Ferro ,  Kenneth James ,  Navdeep Malkar ,  Mark Miller ,  Monica Puskas ,  Nnochiri Ekwuribe

IPC分类号： A61K38/28 ,  C07K14/62

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 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与修饰部分如聚乙二醇部分缀合的胰岛素化合物，例如人胰岛素或其类似物。 本发明还包括固体和包含这种复合物的药物组合物，制备这种复合物的方法，以及使用这些复合物治疗胰岛素化合物缺乏症和其它疾病的方法。 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。 本发明还包括用于给药药物的脂肪酸组合物，例如本发明的新型胰岛素化合物缀合物和/或阳离子 - 胰岛素复合物缀合复合物。

公开(公告)号：US20060018874A1

公开(公告)日：2006-01-26

申请号：US11184528

申请日：2005-07-19

申请人： Balasingam Radhakrishnan ,  Diti Aggarwal ,  Michelle Ferro ,  Kenneth James ,  Navdeep Malkar ,  Mark Miller ,  Leo Pavliv ,  Karen Polowy ,  Monica Puskas ,  Nnochiri Ekwuribe

发明人： Balasingam Radhakrishnan ,  Diti Aggarwal ,  Michelle Ferro ,  Kenneth James ,  Navdeep Malkar ,  Mark Miller ,  Leo Pavliv ,  Karen Polowy ,  Monica Puskas ,  Nnochiri Ekwuribe

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： Fatty acid compositions for administration of of pharmaceutical agents, such as proteins and peptides, protein and peptide conjugates, and/or cation-polypeptide conjugate complexes. In particular, the invention provides a solid pharmaceutical composition formulated for oral administration by ingestion, having from about 0.1 to about 75% w/w fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent. Further, the invention provides a liquid pharmaceutical composition formulated for oral administration by ingestion, comprising: from about 0.1 to about 10% w/v fatty acid component, where the fatty acid component comprises saturated or unsaturated C4, C5, C6, C7, C8, C9, C10, C11, or C12 fatty acids and/or salts of such fatty acids; and a therapeutic agent.