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公开(公告)号：US08722620B2
公开(公告)日：2014-05-13
申请号：US12280851
申请日：2007-02-27
申请人： Charlotte Harkjaer Fynbo , Ib Jonassen , Thomas Børglum Kjeldsen , Peter Madsen , Patrick William Garibay , Janos Tibor Kodra , Thomas Hoeg-Jensen , Tina Møller Tagmose
发明人： Charlotte Harkjaer Fynbo , Ib Jonassen , Thomas Børglum Kjeldsen , Peter Madsen , Patrick William Garibay , Janos Tibor Kodra , Thomas Hoeg-Jensen , Tina Møller Tagmose
摘要： The present invention is related to insulin derivatives having a side chain attached to an ε-amino group of a Lys residue present in the A-chain or to an ε-amino group of a Lys residue in the B-chain.
摘要翻译： 本发明涉及具有连接在A链中存在的Lys残基的侧链或B链中的Lys残基的' - 氨基的侧链的胰岛素衍生物。
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公开(公告)号：US20090137454A1
公开(公告)日：2009-05-28
申请号：US12280851
申请日：2007-02-27
申请人： Charlotte Harkjaer Fynbo , Ib Jonassen , Thomas Borglum Kjeldsen , Peter Madsen , Patrick William Garibay , Janos Tibor Kodra , Thomas Hoeg-Jensen , Tina Moller Tagmose
发明人： Charlotte Harkjaer Fynbo , Ib Jonassen , Thomas Borglum Kjeldsen , Peter Madsen , Patrick William Garibay , Janos Tibor Kodra , Thomas Hoeg-Jensen , Tina Moller Tagmose
摘要： The present invention is related to insulin derivatives having a side chain attached to an ε-amino group of a Lys residue present in the A-chain or to an ε-amino group of a Lys residue in the B-chain.
摘要翻译： 本发明涉及具有连接于存在于A链中的Lys残基的ε-氨基侧链或B链中Lys残基的ε-氨基的侧链的胰岛素衍生物。
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公开(公告)号：US20120035104A1
公开(公告)日：2012-02-09
申请号：US13273659
申请日：2011-10-14
申请人： Janos Tibor Kodra , Patrick William Garibay , Thomas Hoeg-Jensen , Ib Jonassen , Peter Madsen , Tina Moeller Tagmose
发明人： Janos Tibor Kodra , Patrick William Garibay , Thomas Hoeg-Jensen , Ib Jonassen , Peter Madsen , Tina Moeller Tagmose
摘要： The present invention relates to insulin derivatives having a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin via an amide bond which side chain comprises at least one aromatic group; at least one free carboxylic acid group or a group which is negatively charged at neutral pH, a fatty acid moiety with 4 to 22 carbon atoms in the carbon chain; and possible linkers which link the individual components in the side chain together via amide bonds.
摘要翻译： 本发明涉及具有侧链连接到B链的N末端氨基酸残基的α-氨基或存在于B链的B链中的Lys残基的' - 氨基的胰岛素衍生物 通过酰胺键的母体胰岛素，该侧链包含至少一个芳族基团; 至少一个游离羧酸基团或在中性pH下带负电荷的基团，碳链中具有4-22个碳原子的脂肪酸部分; 以及通过酰胺键将侧链中各个组分连接在一起的可能接头。
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公开(公告)号：US08933021B2
公开(公告)日：2015-01-13
申请号：US12297911
申请日：2007-05-08
申请人： Frantisek Hubalek , Thomas Hoeg-Jensen , Ib Jonassen , Patrick William Garibay , Palle Jakobsen , Svend Havelund , Janos Tibor Kodra
发明人： Frantisek Hubalek , Thomas Hoeg-Jensen , Ib Jonassen , Patrick William Garibay , Palle Jakobsen , Svend Havelund , Janos Tibor Kodra
摘要： The present invention relates to novel human insulin derivatives which are soluble at physiological pH values and have a prolonged profile of action. The invention also relates to methods of providing such derivatives, to pharmaceutical compositions containing them, to methods of treating diabetes and hyperglycaemia using the insulin derivatives of the invention and to the use of such insulin derivatives in the treatment of diabetes and hyperglycaemia.
摘要翻译： 本发明涉及新的人胰岛素衍生物，其在生理pH值下是可溶的并具有延长的作用特征。 本发明还涉及提供这样的衍生物，含有它们的药物组合物的方法，使用本发明的胰岛素衍生物治疗糖尿病和高血糖的方法以及这种胰岛素衍生物在治疗糖尿病和高血糖中的用途。
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公开(公告)号：US20090239785A1
公开(公告)日：2009-09-24
申请号：US12297911
申请日：2007-05-08
申请人： Frantisek Hubalek , Thomas Hoeg-Jensen , Ib Jonassen , Patrick William Garibay , Palle Jakobsen , Svend Havelund , Janos Tibor Kodra
发明人： Frantisek Hubalek , Thomas Hoeg-Jensen , Ib Jonassen , Patrick William Garibay , Palle Jakobsen , Svend Havelund , Janos Tibor Kodra
摘要： The present invention relates to novel human insulin derivatives which are soluble at physiological pH values and have a prolonged profile of action. The invention also relates to methods of providing such derivatives, to pharmaceutical compositions containing them, to methods of treating diabetes and hyperglycaemia using the insulin derivatives of the invention and to the use of such insulin derivatives in the treatment of diabetes and hyperglycaemia.
摘要翻译： 本发明涉及新的人胰岛素衍生物，其在生理pH值下是可溶的并具有延长的作用特征。 本发明还涉及提供这样的衍生物，含有它们的药物组合物的方法，使用本发明的胰岛素衍生物治疗糖尿病和高血糖的方法以及这种胰岛素衍生物在治疗糖尿病和高血糖中的用途。
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公开(公告)号：US08691759B2
公开(公告)日：2014-04-08
申请号：US12922117
申请日：2009-03-13
申请人： Peter Madsen , Thomas Boerglum Kjeldsen , Thomas Hoeg-Jensen , Palle Jakobsen , Tina Moeller Tagmose , Janos Tibor Kodra , Patrick William Garibay
发明人： Peter Madsen , Thomas Boerglum Kjeldsen , Thomas Hoeg-Jensen , Palle Jakobsen , Tina Moeller Tagmose , Janos Tibor Kodra , Patrick William Garibay
摘要： Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.
摘要翻译： 对蛋白酶具有抗性的新型酰化胰岛素类似物可以有效地被肺或口服给药。 胰岛素类似物含有B25H和A14E或A14H。
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公开(公告)号：US08796205B2
公开(公告)日：2014-08-05
申请号：US12297914
申请日：2007-05-08
摘要： Novel human insulin derivatives are described which are soluble at physiological pH values and have a prolonged profile of action.
摘要翻译： 描述了新的人胰岛素衍生物，其在生理pH值下可溶，并具有延长的作用特征。
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公开(公告)号：US20090105121A1
公开(公告)日：2009-04-23
申请号：US12297914
申请日：2007-05-08
摘要： The present invention relates to novel human insulin derivatives which are soluble at physiological pH values and have a prolonged profile of action.
摘要翻译： 本发明涉及新的人胰岛素衍生物，其在生理pH值下是可溶的并具有延长的作用特征。
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9.发明申请Insulin Derivatives Conjugated with Structurally Well Defined Branched Polymers 审中-公开与结构定义良好的支化聚合物共轭的胰岛素衍生物公开(公告)号：US20090036353A1
公开(公告)日：2009-02-05
申请号：US11814184
申请日：2006-01-26
申请人： Carsten Behrens , Jesper Lau , Janos Tibor Kodra , Mikael Kofod-Hansen , Thomas Hoeg-Jensen , Peter Madsen , Svend Havelund
发明人： Carsten Behrens , Jesper Lau , Janos Tibor Kodra , Mikael Kofod-Hansen , Thomas Hoeg-Jensen , Peter Madsen , Svend Havelund
CPC分类号： B82Y5/00 , A61K47/59 , A61K47/595 , A61K47/60 , A61K47/641 , A61K47/6949
摘要： Insulin conjugated with structurally well defined, bifurcated and trifurcated polymers can be use by pulmonary delivery for systemic absorption through the lungs to reduce or eliminate the need for administering other insulins by injection.
摘要翻译： 与结构良好定义的分叉和三化聚合物结合的胰岛素可以通过肺部递送用于通过肺的全身吸收，以减少或消除通过注射施用其它胰岛素的需要。
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公开(公告)号：US09708383B2
公开(公告)日：2017-07-18
申请号：US13882947
申请日：2011-11-09
申请人： Alice Ravn Madsen , Birgit Wieczorek , Jacob Kofoed , Jesper Lau , Jane Spetzler , Janos Tibor Kodra , Lars Linderoth , Patrick William Garibay , Per Sauerberg , Thomas Kruse
发明人： Alice Ravn Madsen , Birgit Wieczorek , Jacob Kofoed , Jesper Lau , Jane Spetzler , Janos Tibor Kodra , Lars Linderoth , Patrick William Garibay , Per Sauerberg , Thomas Kruse
IPC分类号： A61K38/00 , C07K14/605 , A61K47/48
CPC分类号： C07K14/605 , A61K47/542
摘要： The invention relates to a derivative of a GLP-1 analog, which analog comprises a first K residue at a position corresponding to position 18 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at another position, and a maximum of twelve amino acid changes as compared to GLP-1(7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1, Chem. 2, and Chem. 3: HOOC—(CH2)x—CO—* Chem. 1: HOOC—C6H4—O—(CH2)y—CO—* Chem. 2: R2—C6H4—(CH2)z—CO—*, Chem. 3: in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1-5, and R2 is a group having a molar mass not higher than 150 Da; and the linker comprises *—NH—(CH2)2—(O—(CH2)2)k—O—(CH2)n—CO—*. Chem. 4: wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.
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