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。

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。

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.

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。

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）。

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。

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）。

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）。

公开(公告)号：US06696408B1

公开(公告)日：2004-02-24

申请号：US09606247

申请日：2000-06-29

申请人： A. Grey Craig ,  David Griffen ,  Baldomero M. Olivera ,  Maren Watkins ,  David R. Hillyard ,  Julita Imperial ,  Lourdes J. Cruz ,  John D. Wagstaff ,  Richard T. Layer ,  Robert M. Jones ,  R. Tyler McCabe

发明人： A. Grey Craig ,  David Griffen ,  Baldomero M. Olivera ,  Maren Watkins ,  David R. Hillyard ,  Julita Imperial ,  Lourdes J. Cruz ,  John D. Wagstaff ,  Richard T. Layer ,  Robert M. Jones ,  R. Tyler McCabe

IPC分类号： A01N3718

CPC分类号： C07K7/08 ,  A61K38/00 ,  C07K9/001 ,  C07K14/575

摘要： The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.

公开(公告)号：US06489298B1

公开(公告)日：2002-12-03

申请号：US09605991

申请日：2000-06-29

申请人： A. Grey Craig ,  David Griffen ,  Baldomero M. Olivera ,  Maren Watkins ,  David R. Hillyard ,  Julita Imperial ,  Lourdes J. Cruz ,  John D. Wagstaff ,  Richard T. Layer ,  Robert M. Jones ,  R. Tyler McCabe

发明人： A. Grey Craig ,  David Griffen ,  Baldomero M. Olivera ,  Maren Watkins ,  David R. Hillyard ,  Julita Imperial ,  Lourdes J. Cruz ,  John D. Wagstaff ,  Richard T. Layer ,  Robert M. Jones ,  R. Tyler McCabe

IPC分类号： A61K3800

CPC分类号： C07K7/08 ,  A61K38/00 ,  C07K9/001 ,  C07K14/575

摘要： The present invention is directed to contulakin-G (which is the native glycosylated peptide), a des-glycosylated contulakin-G (termed Thr10-contulakin-G), and derivatives thereof, to a cDNA clone encoding a precursor of this mature peptide and to a precursor peptide. The invention is further directed to the use of this peptide as a therapeutic for anti-seizure, anti-inflammatory, anti-shock, anti-thrombus, hypotensive, analgesia, anti-psychotic, Parkinson's disease, gastrointestinal disorders, depressive states, cognitive dysfunction, anxiety, tardive dyskinesia, drug dependency, panic attack, mania, irritable bowel syndrome, diarrhea, ulcer, GI tumors, Tourette's syndrome, Huntington's chorea, vascular leakage, anti-arteriosclerosis, vascular and vasodilation disorders, as well as neurological, neuropharmalogical and neuropsychopharmacological disorders.

摘要翻译： 本发明涉及到编码该成熟肽的前体的cDNA克隆的contulakin-G（其是天然糖基化肽），去糖基化的连翘蛋白-G（称为Thr10-contulakin-G）及其衍生物，以及 到前体肽。 本发明进一步涉及该肽作为抗癫痫发作，抗炎，抗休克，抗血栓，降血压，止痛，抗精神病，帕金森病，胃肠道疾病，抑郁状态，认知功能障碍 焦虑症，迟发性运动障碍，药物依赖性，恐慌发作，躁狂症，肠易激综合征，腹泻，溃疡，胃肠道肿瘤，杜氏综合征，亨廷顿氏舞蹈病，血管渗漏，抗动脉硬化，血管和血管舒张障碍以及神经系统，神经功能和 神经精神药理学障碍。