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1. 发明授权

US06727226B2 Mu-conopeptides 有权
公开(公告)号：US06727226B2
公开(公告)日：2004-04-27
申请号：US09910009
申请日：2001-07-23
申请人： Baldomero M. Olivera , J. Michael McIntosh , James E. Garrett , Lourdes J. Cruz , Robert M. Jones , G. Edward Cartier , John D. Wagstaff
发明人： Baldomero M. Olivera , J. Michael McIntosh , James E. Garrett , Lourdes J. Cruz , Robert M. Jones , G. Edward Cartier , John D. Wagstaff
IPC分类号： C07K708
CPC分类号： C07K14/43504 , A61K38/00
摘要： The present invention is to &mgr;-conopeptides, derivatives or pharmaceutically acceptable salts thereof. The present invention is further directed to the use of this peptide, derivatives thereof and pharmaceutically acceptable salts thereof for the treatment of disorders associated with voltage-gated sodium channels. Thus, the &mgr;-conopeptides or derivatives are useful as neuromuscular blocking agents, local anesthetic agents, analgesic agents and neuroprotective agents. The &mgr;-conopeptides are also useful for treating neuromuscular disorders. The invention is further directed to nucleic acid sequences encoding the &mgr;-conopeptides and encoding propeptides, as well as the propeptides.

2. 发明授权

US06767896B1 Conotoxin peptides 失效
标题翻译：芋螺毒素肽
公开(公告)号：US06767896B1
公开(公告)日：2004-07-27
申请号：US09580201
申请日：2000-05-26
申请人： J. Michael McIntosh , Baldomero M. Olivera , Lourdes J. Cruz , Gloria P. Corpuz , Robert M. Jones , James E. Garrett
发明人： J. Michael McIntosh , Baldomero M. Olivera , Lourdes J. Cruz , Gloria P. Corpuz , Robert M. Jones , James E. Garrett
IPC分类号： A61K3808
CPC分类号： C07K14/43504 , A61K38/00 , Y10S530/857
摘要： The invention relates to relatively short conotoxin peptides, about 10-20 residues in length as described herein, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds. These conotoxin peptides have analgesic activity and are thus useful for treating or preventing pain.
摘要翻译：本发明涉及相对较短的荚毒素肽，如本文所述，其长度约为10-20个残基，其可以在锥形蜗牛的毒液中以微量天然存在或类似于天然可得的肽，并且其优选包括两个二硫键。这些芋螺毒素肽具有止痛活性，因此可用于治疗或预防疼痛。

3. 发明授权

US07368432B2 Conotoxin peptides 失效
标题翻译：芋螺毒素肽
公开(公告)号：US07368432B2
公开(公告)日：2008-05-06
申请号：US10893300
申请日：2004-07-19
申请人： J. Michael McIntosh , Baldomero M. Olivera , Lourdes J. Cruz , Gloria P. Corpuz , Robert M. Jones , James E. Garrett
发明人： J. Michael McIntosh , Baldomero M. Olivera , Lourdes J. Cruz , Gloria P. Corpuz , Robert M. Jones , James E. Garrett
IPC分类号： A61K38/08 , A61K38/17 , C07K7/06 , C07K14/435
CPC分类号： C07K14/43504 , A61K38/00 , Y10S530/857
摘要： The invention relates to relatively short conotoxin peptides, about 10-20 residues in length as described herein, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds. These conotoxin peptides have analgesic activity and are thus useful for treating or preventing pain.
摘要翻译：本发明涉及相对较短的荚毒素肽，如本文所述，其长度约为10-20个残基，其可以在锥形蜗牛的毒液中以微量天然存在或类似于天然可得的肽，并且其优选包括两个二硫键。这些芋螺毒素肽具有止痛活性，因此可用于治疗或预防疼痛。

4. 发明授权

US06762165B2 O-superfamily conotoxin peptides 有权
标题翻译： O超家族荚果毒素肽
公开(公告)号：US06762165B2
公开(公告)日：2004-07-13
申请号：US09749637
申请日：2000-12-28
申请人： Baldomero M. Olivera , G. Edward Cartier , Maren Watkins , David R. Hillyard , J. Michael McIntosh , Richard T. Layer , Robert M. Jones
发明人： Baldomero M. Olivera , G. Edward Cartier , Maren Watkins , David R. Hillyard , J. Michael McIntosh , Richard T. Layer , Robert M. Jones
IPC分类号： C07K14435
CPC分类号： C07K14/43504 , A61K38/00
摘要： The invention relates to relatively short peptides (termed O-Superfamily conotoxins herein), about 20-40 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogous to the naturally available peptides, and which preferably include two disulfide bonds.
摘要翻译：本发明涉及相对较短的肽（本文中称为O超家族芋螺毒素），长度约20-40个残基，其在锥形蜗牛的毒液中天然可以微量天然存在或类似于天然可得的肽，并且其优选包括两个二硫键。

5. 发明授权

US5889147A Bromo-tryptophan conopeptides 失效
标题翻译：溴色氨酸多肽
公开(公告)号：US5889147A
公开(公告)日：1999-03-30
申请号：US785534
申请日：1997-01-17
申请人： Lourdes J. Cruz , Baldomero M. Olivera , J. Michael McIntosh , Elsie Jimenez , A. Grey Craig , Jean A. Rivier , David Julius , Laura England
发明人： Lourdes J. Cruz , Baldomero M. Olivera , J. Michael McIntosh , Elsie Jimenez , A. Grey Craig , Jean A. Rivier , David Julius , Laura England
IPC分类号： A61K38/00 , C07K5/10 , C07K5/117 , C07K7/06 , C07K14/435 , A61K38/08 , A61K38/10 , A61K38/16 , C07K7/04
CPC分类号： C07K7/06 , C07K14/43504 , C07K5/1024 , C07K5/1027 , A61K38/00
摘要： The present invention is directed to conopeptides having 6-45 amino acids, including one or more bromo-tryptophan residues. More specifically, the present invention is directed to conopeptides having the general formula: R-(Cys).sub.n -R.sup.1 -B-R.sup.2 -Cys-R.sup.3, wherein R is a peptide chain of 0-24 amino acids, R.sup.1 is a peptide chain of 0 to 31 amino acids, R.sup.2 is a peptide chain of 0-29 amino acids, R.sup.3 is a peptide chain of 0 to 26 amino acids, B is 6-bromo-tryptophan, n is 0 or 1 and the total length of the conopeptide is from about 6 to about 45 amino acids. The invention also includes pharmaceutically acceptable salts of the conopeptides. These bromo-tryptophan containing conopeptides invention are useful as antihelminthic agents, anti-vomiting agents, sleep-inducing agents, adjuncts to anesthesia, anticonvulsant or neuroprotective agents.
摘要翻译：本发明涉及具有6-45个氨基酸的肽，包括一个或多个溴 - 色氨酸残基。更具体地，本发明涉及具有以下通式的肽：R-（Cys）n -R 1 -B-R 2 -Cys-R 3，其中R是0-24个氨基酸的肽链，R 1是肽链 0至31个氨基酸，R2为0-29个氨基酸的肽链，R3为0至26个氨基酸的肽链，B为6-溴色氨酸，n为0或1，总长度为肽是约6至约45个氨基酸。本发明还包括肽的药学上可接受的盐。这些含有溴代色氨酸的多肽本发明可用作抗凝血剂，抗呕吐剂，睡眠诱导剂，麻醉剂，抗惊厥药或神经保护剂。

6. 发明授权

US5633347A Conotoxin peptides 失效
标题翻译：芋螺毒素肽
公开(公告)号：US5633347A
公开(公告)日：1997-05-27
申请号：US480750
申请日：1995-06-07
申请人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfino O. Santos
发明人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfino O. Santos
IPC分类号： A61K38/00 , A61K39/00 , C07K14/435
CPC分类号： C07K14/435 , C07K14/43504 , A61K38/00 , A61K39/00 , Y10S530/857
摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha.3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa- Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha.4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa- Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa- Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO:3).
摘要翻译：本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。该核心序列称为α3/5核心，并表示为Cys-Cys-Xaa-Xaa-Xaa- Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1）。 α-类毒素样肽通常共有称为α4/7核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa- Xaa-Xaa-Xaa-Xaa-Xaa-Xaa -Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为κ7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa- Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）。

7. 发明授权

US5595972A Conotoxin peptides 失效
标题翻译：芋螺毒素肽
公开(公告)号：US5595972A
公开(公告)日：1997-01-21
申请号：US487174
申请日：1995-06-07
申请人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfino D. Santos
发明人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfino D. Santos
IPC分类号： A61K38/00 , A61K38/17 , A61K39/00 , A61K49/00 , A61P35/00 , C07K14/435 , A61K38/10
CPC分类号： C07K14/435 , A61K38/17 , C07K14/43504 , A61K39/00 , Y10S436/813
摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha.3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha.4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO:3) .alpha.-conotoxins MII (SEQ ID NO:54) and U002 (SEQ ID NO:10) preferentially bind to neuronal nicotinic acetylcholine receptors, rather than neuromuscular receptors. These latter two conotoxins can be used to diagnose and treat small-cell lung carcinomas, which have cholinergic nicotinic receptors.
摘要翻译：本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。该核心序列称为α3/ 5核，并表示为Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1）。 α-类毒素样肽通常共有称为α4/7核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa -Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为kappa 7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）α-毒素MII（SEQ ID NO：54）和U002（SEQ ID NO：10）优先结合神经元烟碱乙酰胆碱受体，而不是神经肌肉受体。后两种芋螺毒素可用于诊断和治疗具有胆碱能烟碱受体的小细胞肺癌。

8. 发明授权

US5589340A Process and primers for identifying nucleic acids encoding A-lineage conotoxin peptides 失效
标题翻译：用于鉴定编码A谱系芋螺毒素肽的核酸的方法和引物
公开(公告)号：US5589340A
公开(公告)日：1996-12-31
申请号：US477383
申请日：1995-06-07
申请人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfino D. Santos
发明人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfino D. Santos
IPC分类号： A61K38/00 , A61K39/00 , C07K14/435 , C12Q1/68 , C07H21/04 , C12P19/34
CPC分类号： C07K14/435 , C07K14/43504 , A61K38/00 , A61K39/00
摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha. 3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha. 4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO: 3).
摘要翻译：本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。该核心序列称为α+ E，fra 3/5 + EE核心，并表示为Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1 ）。 α-类毒素样肽通常共有称为α+ E，f 4/7 + EE核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa -Xaa-Xaa-Xaa-Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为kappa 7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）。

9. 发明授权

US5514774A Conotoxin peptides 失效
标题翻译：芋螺毒素肽
公开(公告)号：US5514774A
公开(公告)日：1996-05-07
申请号：US137800
申请日：1993-10-19
申请人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfina D. Santos
发明人： Baldomero M. Olivera , Lourdes J. Cruz , David R. Hillyard , J. Michael McIntosh , Ameurfina D. Santos
IPC分类号： C12N15/09 , A61K38/00 , A61K39/00 , C07K7/06 , C07K7/08 , C07K14/435 , C12N15/12 , C07K7/00 , A61K38/04
CPC分类号： C07K14/43504 , C07K14/435 , A61K38/00 , A61K39/00
摘要： The invention is directed to A-lineage conotoxin peptides, which are conotoxin peptides that have strong homology in the signal sequence and the 3'-untranslated region of the genes coding for these peptides to the sequences in the .alpha.-conotoxin peptides. The A-lineage conotoxin peptides include the .alpha.-conotoxin peptides, the .alpha.-conotoxin-like peptides and the .kappa.-conotoxin peptides, described further below. The .alpha.-conotoxin-peptides generally share a "core" sequence motif. This core sequence is termed the .alpha.3/5 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:1). The .alpha.-conotoxin-like peptides generally share a core sequence termed the .alpha.4/7 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys (SEQ ID NO:2). The .kappa.-conotoxin peptides generally have a core sequence termed the .kappa.7/2/1/3 core and is represented as Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys-Xaa-Cys-Xaa-Xaa-Xaa-Cys (SEQ ID NO:3).
摘要翻译：本发明涉及A系血凝素毒素肽，其是在编码这些肽的基因的信号序列和3'非翻译区与α-毒素肽序列中具有强同源性的芋螺毒素肽。 A系血凝素毒素肽包括下文进一步描述的α-毒素肽，α-毒素样肽和κ-毒素肽。 α-毒素 - 肽通常共有“核心”序列基序。该核心序列称为α3/ 5核，并表示为Cys-Cys-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Cys（SEQ ID NO：1）。 α-类毒素样肽通常共有称为α4/7核心的核心序列，并表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa -Cys（SEQ ID NO：2）。 κ-毒素肽通常具有称为kappa 7/2/1/3核心的核心序列，并且表示为Cys-Cys-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Xaa-Cys-Xaa-Xaa-Cys -Xaa-Cys-Xaa-Xaa-Xaa-Cys（SEQ ID NO：3）。

10. 发明授权

US06265541B1 Uses of &agr;-conotoxin peptides 有权
标题翻译： α-芋螺毒素肽的使用
公开(公告)号：US06265541B1
公开(公告)日：2001-07-24
申请号：US09219446
申请日：1998-12-23
申请人： Baldomero M. Olivera , J. Michael McIntosh , Doju Yoshikami , G. Edward Cartier , Siqin Luo
发明人： Baldomero M. Olivera , J. Michael McIntosh , Doju Yoshikami , G. Edward Cartier , Siqin Luo
IPC分类号： C07K1400
CPC分类号： A61K38/17 , A61K38/08 , C07K14/43504
摘要： The present invention relates to the use of &agr;-conotoxin peptides having the general formula Xaa1-Xaa2-Cys-Cys-Xaa3-Xaa4-Pro-Xaa5-Cys-Xaa6-Cys (SEQ ID NO: 1) for treating disorders regulated at neuronal nicotinic acetylcholine receptors. Such disorders include, but are not limited to, cardiovascular disorders, gastric motility disorders, urinary incontinence, nicotine addiction, mood disorders (such as bipolar disorder, unipolar depression, dysthymia and seasonal effective disorder) and small cell lung carcinoma, as well as the localization of small cell lung carcinoma. In this formula, Xaa1 is des-Xaa1, Tyr, mono-iodo-Tyr or di-iodo-Tyr, Xaa2 is any amino acid, Xaa3 is any amino acid, Xaa4 is any amino acid, Xaa5 is any amino acid and Xaa6 represents a peptide of 3-7 amino acids. Disulfide linkages exist between the first and third cysteines and the second and fourth cysteines. Pro may be replaced with hydroxy-Pro. The C-terminus may contain a hydroxyl or an amide group, preferably an amide group.
摘要翻译：本发明涉及具有用于治疗在神经元烟碱乙酰胆碱受体调节的病症的通式的α-芋螺毒素肽的用途。这些病症包括但不限于心血管疾病，胃动力障碍，尿失禁，尼古丁成瘾，情绪障碍（例如双相情感障碍，单极抑郁，精神抑郁和季节性有效障碍）和小细胞肺癌，以及小细胞肺癌的定位。在该式中，Xaa1是des-Xaa1，Tyr，单碘-Tyr或二碘-Tyr，Xaa2是任何氨基酸，Xaa3是任何氨基酸，Xaa4是任何氨基酸，Xaa5是任何氨基酸，Xaa6表示 3-7个氨基酸的肽。第一和第三半胱氨酸与第二和第四半胱氨酸之间存在二硫键。 Pro可以用羟基替代。 C末端可以含有羟基或酰胺基，优选酰胺基。

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