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1. 发明专利

CA2144334A1 OLIGONUCLEOTIDES HAVING UNIVERSAL NUCLEOSIDE SPACERS 未知
公开(公告)号：CA2144334A1
公开(公告)日：1994-03-31
申请号：CA2144334
申请日：1993-09-07
申请人： BERGSTROM DONALD E , ANDREWS PHILIP C , NICHOLS RUTHANN , ZHANG PEIMING
发明人： BERGSTROM DONALD E , ANDREWS PHILIP C , NICHOLS RUTHANN , ZHANG PEIMING
IPC分类号： C12Q1/68 , C07H19/04 , C07H19/044 , C07H19/052 , C07H19/056 , C07H19/24 , C07H21/00
摘要： Oligonucleotides are made having at least ten nucleosides, at least two of which are A, T, G or C and at least one is a universal nucleoside.

2. 发明申请

WO1995013083A1 NOVEL PEPTIDES FOR HEPARIN AND LOW MOLECULAR WEIGHT HEPARIN ANTICOAGULATION REVERSAL 审中-公开
标题翻译： HEPARIN和低分子量HEPARIN抗体逆转的新肽
公开(公告)号：WO1995013083A1
公开(公告)日：1995-05-18
申请号：PCT/US1994012981
申请日：1994-11-10
申请人： UNIVERSITY OF MICHIGAN, THE BOARD OF REGENTS , WAKEFIELD, Thomas, W. , STANLEY, James, C. , ANDREWS, Philip, C.
发明人： UNIVERSITY OF MICHIGAN, THE BOARD OF REGENTS
IPC分类号： A61K37/00
CPC分类号： C07K7/08 , A61K38/00 , C07K14/001 , C07K14/46
摘要： Less toxic agents for reversal of heparin or low molecular weight heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about [+14] to [+18], preferably [+16] to [+18]. In specific embodiments, there are sequences of 29 and 32 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids. The C-terminus and the N-terminus can be modified to mitigate against in vivo degradation by carboxypeptidases and aminopeptidases. Another modification, specifically use of alpha -helix forming amino acids, such as glutamic acid, further promotes anticoagulation reversal.
摘要翻译：用于逆转肝素或低分子量肝素抗凝剂的毒性较小的药物是具有小于正精蛋白的总阳离子电荷的合成鱼精蛋白样聚阳离子肽。在优选的实施方案中，为了易于制造，将n-鱼精蛋白的精氨酸残基替换为赖氨酸残基。选择性带正电的精氨酸残基已被不带电荷的氨基酸残基或其类似物（如甘氨酸或谷氨酰胺）替代，以便将聚阳离子肽上的总阳离子电荷降低至约[+ 14]至[+ 18] ，优选[+ 16]至[+ 18]。在具体实施方案中，存在29和32个氨基酸残基的序列，其中2至4个带正电荷的氨基酸的4至5个簇被2至6个中性氨基酸分开。可以修饰C-末端和N-末端以减轻羧肽酶和氨基肽酶的体内降解。另一个修改，特别是使用α-螺旋形成氨基酸，如谷氨酸，进一步促进抗凝反转。

3. 发明申请

WO1994004176A1 NOVEL PEPTIDES FOR HEPARIN ANTICOAGULATION REVERSAL 审中-公开
标题翻译： HEPARIN抗体逆转的新肽
公开(公告)号：WO1994004176A1
公开(公告)日：1994-03-03
申请号：PCT/US1992006829
申请日：1992-08-14
申请人： UNIVERSITY OF MICHIGAN , WAKEFIELD, Thomas, W. , STANLEY, James, C. , ANDREWS, Philip, C.
发明人： UNIVERSITY OF MICHIGAN
IPC分类号： A61K37/02
CPC分类号： C07K14/46 , A61K38/00 , C07K14/001
摘要： Less toxic agents for reversal of heparin anticoagulation which are synthetic protamine-like polycationic peptides having a total cationic charge which is less than that of n-protamine. In preferred embodiments, arginine residues of n-protamine are replaced with lysine residues for ease of manufacture. Selective positively charged arginine residues have been replaced with an uncharged amino acid residue or its analog, such as glycine or glutamine, in order to reduce the total cationic charge on the polycationic peptide to the range of about +14 to +18, preferably +16. In specific embodiments, there are sequences of 29 amino acid residues wherein 4 to 5 clusters of 2 to 4 positively charged amino acids are separated by 2 to 6 neutral amino acids.
摘要翻译：具有逆转肝素抗凝剂的毒性较小的药物，其是具有小于正精蛋白的总阳离子电荷的合成鱼精蛋白样聚阳离子肽。在优选的实施方案中，为了易于制造，将n-鱼精蛋白的精氨酸残基替换为赖氨酸残基。选择性带正电的精氨酸残基已被不带电荷的氨基酸残基或其类似物如甘氨酸或谷氨酰胺替代，以便将聚阳离子肽上的总阳离子电荷降低至约+14至+18，优选+16 。在具体实施方案中，存在29个氨基酸残基的序列，其中2至4个带正电荷的氨基酸的4至5个簇被2至6个中性氨基酸分离。

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