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1. 发明授权

US09657323B2 Polypeptide cleavage method using OmpT protease variant 有权
公开(公告)号：US09657323B2
公开(公告)日：2017-05-23
申请号：US10573821
申请日：2004-09-29
申请人： Kazuaki Okuno , Masayuki Yabuta
发明人： Kazuaki Okuno , Masayuki Yabuta
IPC分类号： C12N9/52 , C12P21/06 , C07K14/585 , C07K14/63 , C07K14/695
CPC分类号： C12P21/06 , C07K14/585 , C07K14/63 , C07K14/695 , C12N9/52
摘要： A polypeptide cleavage method characterized in that arginine or lysine is at the P1 position of a desired cleavage site in a polypeptide, an amino acid other than aspartic acid, glutamic acid or proline is at the P1′ position, a single basic amino acid or two or three consecutive basic amino acids are situated at any site in the amino acid sequence from the P10 position to the P3 position or from the P3′ position to the P5′ position (with the proviso that a single basic amino acid is not situated at the P6 or P4 position), and OmpT protease or its variant enzyme having a substitution at the 97th amino acid from the N-terminus is used to cleave the desired cleavage site in the polypeptide.

2. 发明授权

US07982018B2 Modified corticotropin releasing factor peptides and uses thereof 失效
标题翻译：修饰的促肾上腺皮质激素释放因子肽及其用途
公开(公告)号：US07982018B2
公开(公告)日：2011-07-19
申请号：US11873291
申请日：2007-10-16
申请人： Thomas R. Ulich , Jean-Philippe Estradier , Karen Thibaudeau
发明人： Thomas R. Ulich , Jean-Philippe Estradier , Karen Thibaudeau
IPC分类号： A61K38/35 , A61K38/38 , C07K14/695 , C07K14/76 , C07K14/765
CPC分类号： C07K14/57509 , A61K38/00 , A61K47/64 , A61K47/643 , A61K47/644 , A61K47/6889
摘要： The present invention relates to compounds comprising modified corticotrophin releasing factor peptide and specifically urocortin and urocortin-related peptides, modified derivatives thereof, and conjugates of such modified peptides and derivatives to serum components, preferably serum proteins or peptides. The compounds and conjugates of the invention comprise a reactive group, which is covalently attached to a modified peptide or derivative, optionally through a linking group. The present invention also provides methods for the covalent attachment of a modified peptide or derivative to a serum protein or peptide to form a conjugate of the invention. The conjugates of the invention preferably exhibit a longer in vivo circulating half-life compared to the corresponding unconjugated peptides. The conjugates of the invention also retain at least some of the biological activity of the unconjugated peptides, and preferably exhibit increased biological activity compared to the unconjugated peptides. The present invention also provides methods for the treatment and prevention of a disease or disorder comprising the administration of one or more of the compounds or conjugates of the invention to a subject in need of such treatment or prevention.
摘要翻译：本发明涉及包含修饰的促肾上腺皮质激素释放因子肽，特别是尿皮质素和尿皮质素相关肽，其修饰的衍生物，以及这些修饰肽和衍生物与血清成分，优选血清蛋白或肽的缀合物的化合物。本发明的化合物和缀合物包含反应性基团，其任选地通过连接基团共价连接到修饰的肽或衍生物上。本发明还提供了将修饰的肽或衍生物共价连接到血清蛋白或肽以形成本发明的缀合物的方法。与相应的未结合的肽相比，本发明的缀合物优选表现出更长的体内循环半衰期。本发明的缀合物还保留非共轭肽的至少一些生物活性，并且与非共轭多肽相比优选表现出增加的生物学活性。本发明还提供了治疗和预防疾病或病症的方法，包括将本发明的一种或多种化合物或缀合物施用于需要这种治疗或预防的受试者。

3. 发明申请

US20050191650A1 Urocortin proteins and uses thereof 有权
标题翻译：尿皮质蛋白及其用途
公开(公告)号：US20050191650A1
公开(公告)日：2005-09-01
申请号：US10973092
申请日：2004-10-25
申请人： Wylie Vale , Teresa Reyes , Paul Sawchenko , Jean Rivier , Kathy Lewis , John Hogenesch , Joan Vaughan , Marilyn Perrin
发明人： Wylie Vale , Teresa Reyes , Paul Sawchenko , Jean Rivier , Kathy Lewis , John Hogenesch , Joan Vaughan , Marilyn Perrin
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61K39/00 , A61P3/00 , A61P5/06 , A61P9/04 , A61P9/10 , A61P25/18 , A61P25/22 , A61P25/24 , A61P25/26 , A61P25/28 , A61P29/00 , C07K14/435 , C07K14/52 , C07K14/575 , C07K16/24 , C12N1/21 , C12N5/10 , C12N15/12 , C12N15/16 , C12P21/08 , C12R1/19 , C12Q1/68 , C07H21/04 , C07K14/695
CPC分类号： C07K14/57509 , A61K38/00 , A61K39/00
摘要： A human urocortin-related peptide with significant sequence homology to the CRF neuropeptide family was identified. A mouse cDNA was isolated from whole brain poly (A+) RNA that encodes a predicted 38 amino acid peptide protein designated herein as urocortin II. Both human URP and mouse Ucn II are structurally related to the other known mammalian family members, CRF and urocortin (Ucn). These peptides are involved in the regulation of the hypothalamic-pituitary-adrenal axis under basal and stress conditions, suggesting a similar role for URP and Ucn II. Synthesized Ucn-II and URP peptide binds with higher affinity to CRF-R2 than to CRF-R1 Ucn II and human URP appear to be involved in the regulation of body temperature and appetite and may play a role in other stress related phenomenon. These findings identify Ucn II and human URP as a new members of the CRF family of neuropeptides, which are expressed centrally and bind to CRF-R2.
摘要翻译：鉴定出与CRF神经肽家族具有显着序列同源性的人尿皮质素相关肽。从编码本文称为尿皮质素II的预测的38个氨基酸的肽蛋白质的全脑poly（A +）RNA中分离出小鼠cDNA。人URP和小鼠Ucn II都与其他已知的哺乳动物家族成员CRF和尿皮质素（Ucn）结构相关。这些肽在基底和应激条件下参与下丘脑 - 垂体 - 肾上腺轴的调节，表明URP和Ucn II具有类似的作用。合成的Ucn-II和URP肽以比CRF-R1 Ucn II更高的亲和力结合，并且人URP似乎参与体温和食欲的调节，并且可能在其他压力相关现象中起作用。这些发现将Ucn II和人类URP鉴定为CRF家族的新成员，它们集中表达并结合CRF-R2。

4. 发明申请

US20050096275A1 Novel corticotropin-releasing hormone analogs 有权
标题翻译：新型促肾上腺皮质激素释放激素类似物
公开(公告)号：US20050096275A1
公开(公告)日：2005-05-05
申请号：US11006296
申请日：2004-12-06
申请人： Edward Wei , Kurt Carlson
发明人： Edward Wei , Kurt Carlson
IPC分类号： A61K38/00 , C07K14/575 , C07K14/695 , A61K38/22
CPC分类号： C07K14/57509 , A61K38/00 , Y10S930/27
摘要： This invention relates to peptide analogs of corticotropin-releasing hormone. Particularly, the invention provides methods for treating proliferative disorders by administering peptide analogs wherein the 38th amino acid from the N-terminus is D-Nle, i.e. [D-Nle38]-CRH peptide.
摘要翻译：本发明涉及促肾上腺皮质激素释放激素的肽类似物。特别地，本发明提供了通过施用肽类似物来治疗增殖性疾病的方法，其中N末端的第38位氨基酸是D-Nle，即[D-Nle < ] -CRH肽。

5. 发明授权

US5726156A Cytokine regulatory agents and methods of use in pathologies and conditions associated with altered cytokine levels 失效
标题翻译：细胞因子调节剂和与改变的细胞因子水平相关的病理学和病症中使用的方法
公开(公告)号：US5726156A
公开(公告)日：1998-03-10
申请号：US527056
申请日：1995-09-12
申请人： Beverly E. Girten , Ali Andalibi , Amaresh Basu , Patrick Fagan , Richard A. Houghten , Costas C. Loullis , Paul Omholt , Ronald R. Tuttle , Mark J. Suto , Patricia A. Weber
发明人： Beverly E. Girten , Ali Andalibi , Amaresh Basu , Patrick Fagan , Richard A. Houghten , Costas C. Loullis , Paul Omholt , Ronald R. Tuttle , Mark J. Suto , Patricia A. Weber
IPC分类号： A61K38/00 , A61K45/00 , A61P3/00 , A61P3/08 , A61P3/10 , A61P9/00 , A61P11/00 , A61P13/02 , A61P15/00 , A61P29/00 , A61P35/00 , A61P37/00 , A61P43/00 , C07K5/087 , C07K5/117 , C07K5/12 , C07K7/06 , C07K7/64 , C07K14/68 , C07K14/695
CPC分类号： C07K14/695 , C07K14/68 , C07K5/0812 , C07K5/1024 , A61K38/00
摘要： The present invention relates to novel peptides that are potent cytokine regulatory agents. In addition, the present invention relates to pharmaceutical compositions comprising a pharmaceutically acceptable carrier and a cytokine regulatory agent. Administration of such a cytokine regulatory agent to a subject can enhance or restrain cytokine activity. Thus, the present invention provides a method of regulating cytokine activity in a subject having a condition characterized by aberrant or altered cytokine activity. The invention also provides methods of treating such conditions, including, for example, disuse deconditioning, diseases mediated by nitric oxide and cytokines, adverse drug reactions, obesity, septic shock, and adverse side effects due to cancer chemotherapy or occurring as in response to organ transplantation.
摘要翻译：本发明涉及有效的细胞因子调节剂的新型肽。此外，本发明涉及包含药学上可接受的载体和细胞因子调节剂的药物组合物。向受试者施用这样的细胞因子调节剂可以增强或抑制细胞因子活性。因此，本发明提供一种调节受试者中细胞因子活性的方法，其特征在于异常或改变的细胞因子活性。本发明还提供了治疗这些病症的方法，包括例如废除解毒，由一氧化氮和细胞因子介导的疾病，药物不良反应，肥胖症，败血性休克以及由于癌症化学疗法或作为对器官的反应而发生的不良副作用移植。

6. 发明授权

US5663292A Cyclic CRF analogs 失效
标题翻译：循环CRF类似物
公开(公告)号：US5663292A
公开(公告)日：1997-09-02
申请号：US353928
申请日：1994-12-12
申请人： Jean E. F. Rivier
发明人： Jean E. F. Rivier
IPC分类号： G01N33/15 , A61K38/00 , A61K38/04 , A61K45/00 , A61P25/00 , A61P29/00 , A61P35/00 , C07K14/575 , G01N33/50 , G01N33/566 , G01N33/68 , G01N33/74 , C07K14/695 , C07K7/64
CPC分类号： G01N33/5008 , C07K14/57509 , G01N33/502 , G01N33/566 , G01N33/68 , G01N33/6842 , G01N33/74 , A61K38/00 , G01N2333/5751 , Y10S514/805 , Y10S930/26
摘要： Improved CRF antagonist peptides have the formula: ##STR1## wherein R.sub.30 is Cys or Glu; R.sub.33 is Cys, Lys or Orn; provided that when R.sub.30 is Cys, R.sub.33 is Cys and when R.sub.30 is Glu, R.sub.33 is Lys or Orn. The N-terminus may be extended by Asp-Leu-Thr. Lys may be substituted for Arg.sup.23 and its side chain connected by a lactam bridge to Glu.sup.20 to form a dicyclic peptide. Specific CRF antagonists disclosed include (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Lys.sup.33 ]rCRF(12-41); (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Glu.sup.30, Orn.sup.33 ]rCRF(12-41), (cyclo 30-33) [D-Phe.sup.12, Nle.sup.21,38, Cys.sup.30,33 ]rCRF (12-41) and (bicyclo 20-23,30-33) [D-Phe.sup.12, Nle.sup.21,38, Lys.sup.23,33, Glu.sup.30 ]-rCRF(12-41).
摘要翻译：改进的CRF拮抗剂肽具有下式：（环30-33）DPheHisLeuLeuArgGluVal LeuGluNleAlaArgAlaGluGlnLeu LeuNleGluIleIleNH2其中R30是Cys或Glu; R33是Cys，Lys或Orn; 条件是当R30为Cys时，R33为Cys，当R30为Glu时，R33为Lys或Orn。 N末端可以被Asp-Leu-Thr延伸。 Lys可被Arg23取代，其侧链通过内酰胺桥连接至Glu20以形成双环肽。公开的具体CRF拮抗剂包括（环30-33）[D-Phe12，Nle21,38，Glu30，Lys33] rCRF（12-41）; （环30-33）[D-Phe12，Nle21,38，Glu30，Orn33] rCRF（12-41），（环30-33）[D-Phe12，Nle21,38，Cys30,33] rCRF（12-41 ）和（双环20-23,30-33）[D-Phe12，Nle21,38，Lys23,33，Glu30] -rCRF（12-41）。

7. 发明授权

US5587462A Brain-derived membrane-associated CRF binding proteins 失效
标题翻译：脑衍生的膜相关CRF结合蛋白
公开(公告)号：US5587462A
公开(公告)日：1996-12-24
申请号：US149091
申请日：1993-11-08
申请人： Dominic P. Behan , Wylie W. Vale, Jr. , Wolfgang H. Fischer , Philip J. Lowry
发明人： Dominic P. Behan , Wylie W. Vale, Jr. , Wolfgang H. Fischer , Philip J. Lowry
IPC分类号： G01N33/53 , C07K7/08 , C07K14/72 , C12N5/10 , C12N15/09 , C12N15/12 , C12P21/02 , C12R1/91 , G01N33/566 , C07K14/705 , C07K14/695
CPC分类号： C07K14/72
摘要： Isolated, substantially pure mammalian brain-derived membrane-associated CRF-binding proteins and biologically active fragments thereof are provided as well as isolated and purified DNA fragments which encode the CRF binding proteins or biologically active fragments thereof or homologs of other mammalian species. By administering an amount of such CRF binding protein or a fragment thereof effective to modulate receptor activation, it is possible to modulate the action of CRF upon (a) the brain and nervous system, (b) the pituitary particularly for production of ACTH, beta endorphin and cortisol, (c) sites of inflammation, (d) the placenta, (e) the adrenal glands, (f) the gonads or (g) the gastrointestinal tract. Administration of an N-terminal fragment of the protein increases the binding site density for CRF and thus modulates its biological effect in vivo.
摘要翻译：提供分离的，基本上纯的哺乳动物脑衍生的膜相关的CRF结合蛋白及其生物活性片段，以及编码CRF结合蛋白或其生物活性片段或其他哺乳动物物种的同系物的分离和纯化的DNA片段。通过施用一定量的有效调节受体激活的CRF结合蛋白或其片段，有可能在（a）脑和神经系统调节CRF的作用，（b）垂体特别是用于产生ACTH，β 内啡肽和皮质醇，（c）炎症部位，（d）胎盘，（e）肾上腺，（f）性腺或（g）胃肠道。施用蛋白质的N-末端片段增加CRF的结合位点密度，从而调节其在体内的生物学效应。

8. 发明授权

US4794104A Pharmaceutical compositions containing ACTH fragments for the therapy of shock conditions and of respiratory and cardiocirculatory insufficiencies 失效
标题翻译：含有ACTH片段的药物组合物用于治疗休克条件和呼吸和心脏循环障碍
公开(公告)号：US4794104A
公开(公告)日：1988-12-27
申请号：US000183
申请日：1987-01-02
申请人： Alfio Bertolini
发明人： Alfio Bertolini
IPC分类号： A61K38/22 , A61K38/00 , A61K38/34 , A61K38/35 , A61P9/00 , A61P11/00 , C07K14/695 , A61K37/40
CPC分类号： A61K38/35 , A61K38/34 , C07K14/695
摘要： The parenteral administration of 80-160 .mu.g per kg body weight of substituted or unsubstituted fragments of ACTH (1-39) having formula ACTH (X-Y) wherein X is an integer from 1 to 5 and Y is an integer from 10 to 39 (provided that, when X is 1, Y is not 24) restores the normal blood pressure and respiratory frequence in a patient in serious shock conditions, particularly in hypovolemic shock.
摘要翻译：胃肠外给药80-160μg/ kg体重的具有式ACTH（XY）的ACTH（1-39）的取代或未取代的片段，其中X是1至5的整数，Y是10至39的整数（条件是，当X为1时，Y不为24）在严重的休克条件下，特别是在低血容量休克中恢复患者的正常血压和呼吸频率。

9. 发明授权

US4732852A Site directed peptidase cleavage 失效
标题翻译：位点定向肽酶裂解
公开(公告)号：US4732852A
公开(公告)日：1988-03-22
申请号：US642755
申请日：1984-08-20
申请人： Stanley N. Cohen , Annie C. Y. Chang
发明人： Stanley N. Cohen , Annie C. Y. Chang
IPC分类号： C07K14/59 , C07K14/695 , C12N15/62 , C12P21/00
CPC分类号： C12N15/62 , C07K14/59 , C07K14/695 , C07K2319/00 , C07K2319/75 , Y10S435/81
摘要： Method for preparing peptides free of undesired amino acids or amino acid sequences employing site specific receptors and proteases to cleave unprotected enzymatically hydrolyzable bonds.
摘要翻译：使用位点特异性受体和蛋白酶制备不含不想要的氨基酸或氨基酸序列的肽以切割未保护的酶促可水解键的方法。

10. 发明授权

US4550099A Peptides with nerve-regenerating properties 失效
标题翻译：具有神经再生特性的肽
公开(公告)号：US4550099A
公开(公告)日：1985-10-29
申请号：US658544
申请日：1984-10-09
申请人： Willem H. Gispen
发明人： Willem H. Gispen
IPC分类号： A61K38/00 , A61P25/00 , A61P25/28 , A61P25/30 , C07K14/00 , C07K14/695 , A61K37/00
CPC分类号： C07K14/6955 , C07K14/695 , A61K38/00
摘要： The present invention relates to the use of the peptides of the general formula:A--B--L--Phe (or L--Ala)--D--Lys--L--Phe--Z--OH, IwhereA represents one of the following groups: H--L--Met, H--L--Met(O), H--L--Met(O.sub.2), desamino-Met, desamino-Met(O) or desamino-Met(O.sub.2),B represents one of the following di-peptide fragments: Glu--His or Ala--Ala, where one amino acid residue of this di-peptide fragment can occur in the D form, andZ is either absent, or represents the amino acid residue Gly, or is the peptide fragment (10-16)--ACTH, where the amino acid L--Lys may be replaced, if desired, by D--Lys at position 11 of the (10-16)--ACTH fragment,and the functional derivatives thereof in promoting axonal regeneration.
摘要翻译：本发明涉及以下通式的肽：ABL-Phe（或L-Ala）-D-Lys-L-Phe-Z-OH，I的用途，其中A代表以下基团之一：HL-Met ，HL-Met（O），HL-Met（O2），desamino-Met，desamino-Met（O）或desamino-Met（O 2），B代表以下二肽片段之一：Glu-His或Ala- Ala，其中该二肽片段的一个氨基酸残基可以以D形式出现，Z不存在，或表示氨基酸残基Gly，或是肽片段（10-16）-ACTH，其中氨基如果需要，酸性L-Lys可以被（10-16）-ACTH片段的第11位的D-Lys和其功能衍生物替代，以促进轴突再生。

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