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1. 发明授权

US06737409B2 Dolastatin 10 derivatives 失效
标题翻译： Dolastatin 10衍生物
公开(公告)号：US06737409B2
公开(公告)日：2004-05-18
申请号：US10195698
申请日：2002-07-15
申请人： Toshihiko Fujii , Takehiro Okada , Mikio Taniguchi , Fumio Watanabe
发明人： Toshihiko Fujii , Takehiro Okada , Mikio Taniguchi , Fumio Watanabe
IPC分类号： A61K3807
CPC分类号： A61K38/05 , C07K5/0205
摘要： Novel anti-tumor compounds of formula, are disclosed. Also disclosed are pharmaceutical compositions comprising compounds of formula (I), the use of compounds of formula (I) for the treatment of cancer, and processes for the preparation of compounds (I).
摘要翻译：公开了新型抗肿瘤化合物。还公开了包含式（I）化合物，式（I）化合物用于治疗癌症的药物组合物，以及化合物（I）的制备方法。

2. 发明授权

US06727227B1 Tetrapetide revealing geroprotective effect, pharmacological substance on its basis, and the method of its application 失效
标题翻译：四肽具有显着的保护作用，其药理学物质及其应用的方法
公开(公告)号：US06727227B1
公开(公告)日：2004-04-27
申请号：US09959852
申请日：2002-03-06
申请人： Vladimir K. Khavinson
发明人： Vladimir K. Khavinson
IPC分类号： A61K3807
CPC分类号： C07K5/1008 , A61K38/00
摘要： Tetrapeptide L-alanyl-L-glutamyl-L-aspartyl-glycine (SEQ ID NO: 1) of the general formula L-Ala-L-Glu-L-Asp-Gly (SEQ ID NO: 1) is proposed as a biologically active compound with a geroprotective effect. The use of L-Ala-L-Glu-L-Asp-Gly (SEQ ID NO: 1) tetrapeptide in medicine is proposed for preparing a substance displaying a geroprotective effect. There is proposed a pharmacological substance, which contains as its active base an effective amount of tetrapeptide of the formula L-alanyl-L-glutamyl-L-aspartyl-glycine (L-Ala-L-Glu-L-Asp-Gly) (SEQ ID NO: 1) or its salts of the amino group (acetate, hydrochloride, oxalate) and of carboxyl groups (the salts of metals-Sodium, Potassium, Calcium, Lithium, Zinc, Magnesium, and also the salts of organic and inorganic cations-ammonium and triethylammonium). The substance is proposed for parenteral, intranasal, oral administration, and local application. With respect to the invention, the method of premature ageing prevention involves prophylactic and/or therapeutic administration to a patient of the pharmacological substance in doses of 0.01 to 100 &mgr;g/kg of the body weight at least once a day for a period necessary for the achievement of a therapeutic effect.
摘要翻译：提出了通式L-Ala-L-Glu-L-Asp-Gly（SEQ ID NO：1）的四肽L-丙氨酰-L-谷氨酰-L-天冬氨酰 - 甘氨酸（SEQ ID NO：1）作为生物学具有保护作用的活性化合物。提出在药物中使用L-Ala-L-Glu-L-Asp-Gly（SEQ ID NO：1）四肽来制备显示保护作用的物质。提出了一种药理学物质，其含有有效量的式L-丙氨酰-L-谷氨酰基-L-天冬氨酰甘氨酸（L-Ala-L-Glu-L-Asp-Gly）的四肽 SEQ ID NO：1）或其氨基（乙酸盐，盐酸盐，草酸盐）和羧基的盐（金属盐，钠，钾，钙，锂，锌，镁以及有机和无机盐）阳离子 - 铵和三乙基铵）。该物质被提出用于胃肠外，鼻内，口服和局部应用。关于本发明，预防性老化的方法涉及对药物物质的患者的预防和/或治疗性给药，其剂量为0.01至100μg/ kg体重，每天至少一次，持续一段时间达到治疗效果。

3. 发明授权

US06699466B1 IL-16 antagonist peptides and DNA encoding the peptides 有权
标题翻译： IL-16拮抗剂肽和编码肽的DNA
公开(公告)号：US06699466B1
公开(公告)日：2004-03-02
申请号：US09368630
申请日：1999-08-05
申请人： David M. Center , William W. Cruikshank , Hardy Kornfeld
发明人： David M. Center , William W. Cruikshank , Hardy Kornfeld
IPC分类号： A61K3807
CPC分类号： A61K38/13 , A61K31/00 , A61K38/00 , A61K39/395 , A61K45/06 , C07K14/5446 , A61K2300/00
摘要： The present invention has found that a series of peptides having sequences that substantially correspond to specific regions of the C-terminus of IL-16 can inhibit the activity of IL-16. The present invention has demonstrated that such IL-16-inhibiting peptides can be as short as 4 amino acids in length. Based on these discoveries, the present invention provides IL-16 antagonist peptides and the use thereof for the treatment of IL-16-mediated disorders such as certain inflammatory diseases.
摘要翻译：本发明已经发现，具有基本上对应于IL-16的C末端的特定区域的序列的一系列肽可以抑制IL-16的活性。本发明已经证明这样的IL-16抑制肽的长度可以短至4个氨基酸。基于这些发现，本发明提供IL-16拮抗剂肽及其用于治疗IL-16介导的病症如某些炎性疾病的用途。

4. 发明授权

US06608025B1 Human NESP55 polypeptides, polynucleotides and uses thereof 有权
标题翻译：人NESP55多肽，多核苷酸及其用途
公开(公告)号：US06608025B1
公开(公告)日：2003-08-19
申请号：US09468554
申请日：1999-12-21
申请人： Douglas Fraser , Steven St. Gallay
发明人： Douglas Fraser , Steven St. Gallay
IPC分类号： A61K3807
CPC分类号： C07K14/575
摘要： A substantially pure polypeptide (human NESP55) comprising the amino acid sequence (SEQ ID NO: 2) IRLEVPKRMDRRSRAQQWRRARHNYNDLCPPIGRRAATALLWLSCSIALL RALATSNARAQQRAAAQQRRSFLNAHHRSGAQVFPESPESESDHEHEEAD LELSLPECLEYEEEFDYETESETESEIESETDFETEPETAPTTEPETEPE DDRGPVVPKHSTFGQSLTQRLHALKLRSPDASPSRAPPSTQEPQSPREGE ELKPEDKDPRRDPEESKEPKEEKQRRRCKPKKPTRRDASPESPSKKGPIP IRRH or a variant, fragment, fusion or derivative thereof, or a fusion of a said variant or fragment or derivative, wherein the polypeptide variant has an amino acid sequence which has at least 90% identity with the amino acid sequence given above. NESP55 or fragments thereof may be useful in medicine for the treatment of obesity.
摘要翻译：包含氨基酸序列或其变体，片段，融合物或衍生物或所述变体或片段或衍生物的融合物的基本上纯的多肽（人NESP55），其中所述多肽变体具有氨基酸序列，其具有至少90％与上述氨基酸序列的同一性.NESP55或其片段可用于治疗肥胖症的药物中。

5. 发明授权

US06288037B1 Substrates and inhibitors for cysteine protease ICH-1 失效
标题翻译：半胱氨酸蛋白酶ICH-1的底物和抑制剂
公开(公告)号：US06288037B1
公开(公告)日：2001-09-11
申请号：US08665643
申请日：1996-06-18
申请人： Robert V. Talanian , Tariq Ghayur , John C. Hodges
发明人： Robert V. Talanian , Tariq Ghayur , John C. Hodges
IPC分类号： A61K3807
CPC分类号： C07K5/101 , A61K38/00 , C07K14/81
摘要： Substrates and inhibitors for the cysteine protease Ich-1 are disclosed. These compounds are designed based on an optimal minimal substrate for Ich-1 and include reversible inhibitors, irreversible inhibitors, selectively reversible inhibitors, chromogenic substrates, fluorogenic substrates and radiolabeled substrates/inhibitors. Pharmaceutical compositions comprising the compounds of the invention are also provided. Methods for inhibiting the proteolytic activity of Ich-1, methods for detecting the presence of Ich-1 and methods for isolating Ich-1 using the compounds of the invention are also disclosed.
摘要翻译：公开了半胱氨酸蛋白酶Ich-1的底物和抑制剂。这些化合物是基于Ich-1的最佳最小底物设计的，包括可逆抑制剂，不可逆抑制剂，选择性可逆抑制剂，显色底物，荧光底物和放射性标记底物/抑制剂。还提供了包含本发明化合物的药物组合物。还公开了用于抑制Ich-1的蛋白水解活性的方法，用于检测Ich-1的存在的方法和使用本发明的化合物分离Ich-1的方法。

6. 发明授权

US06689752B2 Modulators of &bgr;-amyloid peptide aggregation comprising D-amino acids 失效
标题翻译：包含D-氨基酸的β-淀粉样肽聚集体的调节剂
公开(公告)号：US06689752B2
公开(公告)日：2004-02-10
申请号：US09895443
申请日：2001-06-29
申请人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
发明人： Mark A. Findeis , Malcolm L. Gefter , Gary Musso , Ethan R. Signer , James Wakefield , Susan Molineaux , Joseph Chin , Jung-Ja Lee , Michael Kelley , Sonja Komar-Panicucci , Christopher C. Arico-Muendel , Kathryn Phillips , Neil J. Hayward
IPC分类号： A61K3807
CPC分类号： C07K5/101 , A61K38/00 , C07K5/1027 , C07K7/06 , C07K14/4711 , G01N33/6896 , G01N2333/4709 , G01N2800/2821
摘要： Compounds that modulate natural &bgr; amyloid peptide aggregation are provided. The modulators of the invention comprise a peptide, preferably based on a &bgr; amyloid peptide, that is comprised entirely of D-amino acids. Preferably, the peptide comprises 3-5 D-amino acid residues and includes at least two D-amino acid residues independently selected from the group consisting of D-leucine, D-phenylalanine and D-valine. In a particularly preferred embodiment, the peptide is a retro-inverso isomer of a &bgr; amyloid peptide, preferably a retro-inverso isomer of A&bgr;17-21. In certain embodiments, the peptide is modified at the amino-terminus, the carboxy-terminus, or both. Preferred amino-terminal modifying groups include cyclic, heterocyclic, polycyclic and branched alkyl groups. Preferred carboxy-terminal modifying groups include an amide group, an alkyl amide group, an aryl amide group or a hydroxy group. Pharmaceutical compositions comprising the compounds of the invention, and diagnostic and treatment methods for amyloidogenic diseases using the compounds of the invention, are also disclosed.
摘要翻译：提供调节天然β淀粉样肽聚集的化合物。本发明的调节剂包含优选基于β-淀粉样肽的肽，其完全由D-氨基酸组成。优选地，肽包含3-5个D-氨基酸残基，并且包括独立地选自D-亮氨酸，D-苯丙氨酸和D-缬氨酸的至少两个D-氨基酸残基。在特别优选的实施方案中，肽是β淀粉样肽的逆反异构体，优选Abeta17-21的逆反异构体。在某些实施方案中，肽在氨基末端，羧基末端或两者都被修饰。优选的氨基末端修饰基团包括环状，杂环，多环和支链烷基。优选的羧基末端修饰基团包括酰胺基，烷基酰胺基，芳基酰胺基或羟基。还公开了包含本发明化合物的药物组合物，以及使用本发明化合物的淀粉样变性疾病的诊断和治疗方法。

7. 发明授权

US06656905B1 Cyclic tetrapeptide compound and use thereof 失效
标题翻译：环状四肽化合物及其用途
公开(公告)号：US06656905B1
公开(公告)日：2003-12-02
申请号：US09806500
申请日：2001-05-04
申请人： Hiroaki Mori , Kazutoshi Sakamoto , Yasuhisa Tsurumi , Shigehiro Takase , Motohiro Hino
发明人： Hiroaki Mori , Kazutoshi Sakamoto , Yasuhisa Tsurumi , Shigehiro Takase , Motohiro Hino
IPC分类号： A61K3807
CPC分类号： A61K38/12 , C07K5/126
摘要： A cyclic tetrapeptide compound and use thereof. Especially, a compound WF27082, a process for production of the compound by culturing, in a nutrient medium, a WF27082-producing strain belonging to Acremonium and recovering the compound from a culture broth, a pharmaceutical composition containing the compound as an active ingredient, in association with a pharmaceutically acceptable, substantially non-toxic carrier or excipient, the compound for use as a medicament, a use of the compound for manufacture of a medicament for inhibiting histone deacetylase, a use of the compound for manufacture of a medicament for treating or preventing inflammatory disorders, diabetes, diabetic complications, homozygous thalassemia, fibrosis, cirrhosis, acute promyelocytic leukaemia (APL), protozoal infections, organ transplant rejections, autoimmune diseases, or tumors, a use of histone deacetylase inhibitors as an immunosuppressant or an antitumor agent, and a use of histone deacetylase inhibitors for manufacture of a medicament for treating or preventing organ transplant rejections, autoimmune diseases or tumors are described.
摘要翻译：一种环状四肽化合物及其用途。特别地，化合物WF27082是通过在营养培养基中培养属于顶孢菌属的WF27082产生菌株并从培养液中回收化合物，将含有该化合物作为活性成分的药物组合物生产化合物的方法，与药学上可接受的，基本上无毒的载体或赋形剂的相关联，用作药物的化合物，该化合物用于制备用于抑制组蛋白脱乙酰酶的药物的用途，该化合物用于制备用于治疗或预防炎性疾病，糖尿病，糖尿病并发症，纯合地中海贫血，纤维化，肝硬化，急性早幼粒细胞白血病（APL），原生动物感染，器官移植排斥，自身免疫疾病或肿瘤，组蛋白脱乙酰酶抑制剂作为免疫抑制剂或抗肿瘤剂的用途，以及使用组蛋白脱乙酰酶抑制剂来制造用于治疗或预防的药物描述器官移植排斥，自身免疫性疾病或肿瘤。

8. 再颁专利

USRE38313E1 Soluble polypeptide fractions of the LAG-3 protein, production method, therapeutic composition, anti-idiotype antibodies 有权
$Soluble polypeptide fractions of the LAG-3 protein, production method, therapeutic composition, anti-idiotype antibodies$
标题翻译： LAG-3蛋白的可溶性多肽级分，制备方法，治疗组合物，抗独特型抗体
公开(公告)号：USRE38313E1
公开(公告)日：2003-11-11
申请号：US09931103
申请日：2001-08-17
申请人： Florence Faure , Thierry Hercend , Bertrand Huard , Frédéric Triebel
发明人： Florence Faure , Thierry Hercend , Bertrand Huard , Frédéric Triebel
IPC分类号： A61K3807
CPC分类号： C07K19/00 , A61K38/00 , C07K14/70503 , C07K16/2803 , C07K2319/00
摘要： Soluble polypeptide fraction consisting of all or part one of at least one of the four immunoglobulin-type extracellular LAG-3 protein domains (amino acids 1-159, 160-230 239, 240-330 and 331-412 of the SEQ ID NO:1 sequence) or consisting of one peptide sequence derived from these domains by replacement, addition or deletion of one or more amino acids. The fraction of the invention has a specificity at least equal to that of LAG-3 in relation to its ligand.

9. 发明授权

US06337319B1 &mgr;-Selective opioid peptides 失效
标题翻译： mu-选择性阿片肽
公开(公告)号：US06337319B1
公开(公告)日：2002-01-08
申请号：US08718585
申请日：1996-10-02
申请人： Wuyi Wang
发明人： Wuyi Wang
IPC分类号： A61K3807
CPC分类号： C07K5/1027 , A61K38/00 , C07K5/1016
摘要： This invention relates to novel opioid peptides for the treatment of pain as well as a method for the preparation thereof and pharmaceutically acceptable compositions comprising these peptides. The invention also relates to methods for controlling pain in patients using compositions of the invention and the use of said compounds in the preparation of formulations effective in pain treatment. The peptides of this invention have a high degree of selectivity for the &mgr;-opioid receptor. The peptides of the present invention are particularly well-suited as analgesic agents acting substantially on peripheral &mgr;-opioid receptors. Because these peptides act peripherally, they substantially avoid producing side effects normally associated with central analgesic action.
摘要翻译：本发明涉及用于治疗疼痛的新型阿片类肽以及其制备方法和包含这些肽的药学上可接受的组合物。本发明还涉及使用本发明组合物治疗患者疼痛的方法以及所述化合物在制备有效治疗疼痛的配方中的用途。本发明的肽对μ-阿片受体具有高度的选择性。本发明的肽特别适合作为基本上作用于外周mu-阿片受体的止痛剂。因为这些肽在外周作用，它们基本上避免产生通常与中枢镇痛作用相关的副作用。

10. 发明授权

US06638912B2 Peptide compositions mimicking TGF-&bgr; activity 失效
标题翻译：模拟TGF-β活性的肽组合物
公开(公告)号：US06638912B2
公开(公告)日：2003-10-28
申请号：US09113696
申请日：1998-07-10
申请人： Rajendra S. Bhatnagar , Jing Jing Qian , Craig Gough
发明人： Rajendra S. Bhatnagar , Jing Jing Qian , Craig Gough
IPC分类号： A61K3807
CPC分类号： A61L27/227 , A61K38/00 , C07K7/06 , C07K14/495 , C07K14/78
摘要： Compositions suitable for pharmaceutical administration are provided in which one compound is a small peptide mimic of TGF-&bgr;. More preferably, pharmaceutical compositions of the present invention are formulated as combinations of two components, wherein one component includes a peptide mimic for TGF-&bgr; and the other component is structurally or biologically analogous to a small region of collagen and mimics the conformation recognized by collagen binding species. A particularly preferred combination is A-N-V-A-E-N-A (SEQ ID NO:1) and G-T-P-G-P-Q-G-I-A-G-Q-R-G-V-V (SEQ ID NO:17).
摘要翻译：提供了适合于药物给药的组合物，其中一种化合物是TGF-β的小肽模拟物。更优选地，将本发明的药物组合物配制成两种组分的组合，其中一种组分包括TGF-β的肽模拟物，另一种组分在结构上或生物学上类似于胶原蛋白的小区域并且模拟胶原识别的构象结合物种。特别优选的组合是A-N-V-A-E-N-A（SEQ ID NO：1）和G-T-P-G-P-Q-G-I-A-G-Q-R-G-V-V（SEQ ID NO：17）。

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