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1. 发明申请

WO2009108261A3 COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS 审中-公开
公开(公告)号：WO2009108261A3
公开(公告)日：2009-09-03
申请号：PCT/US2009/000438
申请日：2009-01-23
申请人： DANA FARBER CANCER INSTITUTE , WALENSKY, Loren, D. , BIRD, Gregory, H.
发明人： WALENSKY, Loren, D. , BIRD, Gregory, H.
IPC分类号： C07K14/16
摘要： The invention provides compositions, kits and methods utilizing polypeptides having a viral alpha-helix heptad repeat domain in a stabilized α-helical structure (herein also referred to as SAH). The compositions are useful for treating and/or preventing viral infections. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled alpha helical peptides display excellent proteolytic, acid, and thermal stability, restore the native alpha- helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.

2. 发明申请

WO2010148335A2 STRUCTURED VIRAL PEPTIDE COMPOSITIONS AND METHODS OF USE 审中-公开
标题翻译：结构病毒组合物及其使用方法
公开(公告)号：WO2010148335A2
公开(公告)日：2010-12-23
申请号：PCT/US2010039223
申请日：2010-06-18
申请人： DANA FARBER CANCER INST INC , WALENSKY LOREN D , BIRD GREGORY
发明人： WALENSKY LOREN D , BIRD GREGORY
IPC分类号： A61K39/42
CPC分类号： C07K16/1045 , A61K39/12 , A61K39/21 , C07K16/1063 , C07K2317/34 , C07K2317/76 , C12N2740/16034 , C12N2740/16122 , C12N2740/16134
摘要： The invention provides structurally constrained viral peptides for use as therapeutic and vaccination agents, and for the production of antibodies for use in a number of applications including as therapeutic agents. The invention further provides methods and kits for use of the structurally constrained peptides and antibodies of the instant invention. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.
摘要翻译：本发明提供用作治疗和接种试剂的结构受限的病毒肽，以及用于许多应用的抗体的生产，包括作为治疗剂。本发明还提供了用于本发明的结构受限的肽和抗体的方法和试剂盒。本发明至少部分地基于本文提供的结果，证明病毒性碳氢化合物钉合螺旋肽显示优异的蛋白水解，酸和热稳定性，恢复肽的天然螺旋结构，在干扰病毒融合方面是高度有效的过程，并且与相应的未修饰的肽相比具有优异的药代动力学性质。

3. 发明申请

WO2010042225A2 CHEMICAL MODULATORS OF PRO-APOPTOTIC BAX AND BCL-2 POLYPEPTIDES 审中-公开
标题翻译：化合物BAX和BCL-2多肽的化学调节剂
公开(公告)号：WO2010042225A2
公开(公告)日：2010-04-15
申请号：PCT/US2009/005568
申请日：2009-10-09
申请人： DANA FARBER CANCER INSTITUTE , WALENSKY, Loren, D. , GAVATHIOTIS, Evripidis
发明人： WALENSKY, Loren, D. , GAVATHIOTIS, Evripidis
IPC分类号： G01N33/68 , C07K14/435 , A61K38/17 , A61P35/00
CPC分类号： G06F19/12 , A61K38/00 , C07K14/4747 , C40B30/02
摘要： The invention provides a method for identifying a compound which modulates the activity of a BCL-2 family polypeptide, the method comprising: a) contacting said BCL-2 family polypeptide with a compound under conditions suitable for modulation of the activity of said BCL-2 family polypeptide; and b) detecting modulation of the activity of said BCL-2 family polypeptide by the compound, wherein the compound interacts with a binding site comprising one or more of an αl helix, α2 helix, a loop between αl-α2, α.6 helix, and select residues of α4, α.5, and α.8 helices in said BCL-2 family polypeptide; wherein the interaction of the compound with the binding site occurs at a horizontal hydrophobic groove with or without a perimeter of charged and hydrophilic residues, a superior juxta-loop, an inferior juxta-loop, or combination thereof.
摘要翻译：本发明提供了鉴定调节BCL-2家族多肽活性的化合物的方法，该方法包括：a）在适于调节所述BCL-2活性的条件下，使所述BCL-2家族多肽与化合物接触家庭多肽; 和b）检测所述化合物对所述BCL-2家族多肽的活性的调节，其中所述化合物与包含一个或多个al螺旋，a2螺旋，al-a2，a.6螺旋之间的环的结合位点相互作用并选择所述BCL-2家族多肽中a4，a.5和a.8螺旋的残基; 其中所述化合物与结合位点的相互作用发生在具有或不具有带电和亲水残基的周边的水平疏水沟槽，优异的柔性环，较低的柔性环或其组合。

4. 发明申请

WO2009108261A2 COMPOSITIONS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS 审中-公开
标题翻译：用于治疗病毒感染的组合物和方法
公开(公告)号：WO2009108261A2
公开(公告)日：2009-09-03
申请号：PCT/US2009000438
申请日：2009-01-23
申请人： DANA FARBER CANCER INST INC , WALENSKY LOREN D , BIRD GREGORY H
发明人： WALENSKY LOREN D , BIRD GREGORY H
IPC分类号： C07K14/005
CPC分类号： C07K14/005 , A61K38/162 , A61K39/145 , A61K39/155 , A61K39/21 , C07K16/1063 , C07K2317/76 , C12N2740/15022 , C12N2740/15034 , C12N2740/15071 , C12N2740/16122 , C12N2740/16134 , C12N2740/16171 , C12N2740/16222 , C12N2740/16234 , C12N2740/16271 , C12N2760/14022 , C12N2760/14034 , C12N2760/14071 , C12N2760/16022 , C12N2760/16034 , C12N2760/16071 , C12N2760/18022 , C12N2760/18034 , C12N2760/18071 , C12N2760/18522 , C12N2760/18534 , C12N2760/18571 , C12N2760/18622 , C12N2760/18634 , C12N2760/18671
摘要： The invention provides compositions, kits and methods utilizing polypeptides having a viral alpha-helix heptad repeat domain in a stabilized a-helical structure (herein also referred to as SAH). The compositions are useful for treating and/or preventing viral infections. The invention is based, at least in part, on the result provided herein demonstrating that viral hydrocarbon stapled alpha helical peptides display excellent proteolytic, acid, and thermal stability, restore the native alpha- helical structure of the peptide, are highly effective in interfering with the viral fusogenic process, and possess superior pharmacokinetic properties compared to the corresponding unmodified peptides.
摘要翻译：本发明提供使用在稳定的α-螺旋结构（本文中也称为SAH）中具有病毒α-螺旋七肽重复结构域的多肽的组合物，试剂盒和方法。该组合物可用于治疗和/或预防病毒感染。本发明至少部分地基于本文提供的结果，证明病毒性碳氢化合物吻合的α螺旋肽显示优异的蛋白水解，酸和热稳定性，恢复肽的天然α-螺旋结构，在干扰病毒融合过程，并且与相应的未修饰的肽相比具有优异的药代动力学性质。

5. 发明申请

WO2005044839A2 STABILIZED ALPHA HELICAL PEPTIDES AND USES THEREOF 审中-公开
标题翻译：稳定的α螺旋肽及其用途
公开(公告)号：WO2005044839A2
公开(公告)日：2005-05-19
申请号：PCT/US2004/038403
申请日：2004-11-05
申请人： DANA-FARBER CANCER INSTITUTE, INC. , WALENSKY, Loren, D. , KORSMEYER, Stanley, J. , VERDINE, Gregory
发明人： WALENSKY, Loren, D. , KORSMEYER, Stanley, J. , VERDINE, Gregory
IPC分类号： C07K
CPC分类号： C07K7/08 , A61K38/00 , C07K1/113 , C07K1/1136 , C07K7/64 , C07K14/001 , C07K14/435 , C07K14/4747
摘要： Novel polypeptides and methods of making and using the same are described herein. The polypeptides include cross-linking (“hydrocarbon stapling”) moieties to provide a tether between two amino acid moieties, which constrains the secondary structure of the polypeptide. The polypeptides described herein can be used to treat diseases characterized by excessive or inadequate cellular death.
摘要翻译：本文描述了新多肽及其制备和使用方法。多肽包括交联（“碳氢化合物钉”）部分以在两个氨基酸部分之间提供束缚，这限制了多肽的二级结构。本文所述的多肽可用于治疗以过度或不足细胞死亡为特征的疾病。

6. 发明申请

WO2012142604A3 TARGETING DEREGULATED WNT SIGNALING IN CANCER USING STABILIZED ALPHA-HELICES OF BCL-9 审中-公开
标题翻译：使用稳定的BCL-9的ALPHA-HELIC来定位在癌症中的DEREGULATED WNT信号
公开(公告)号：WO2012142604A3
公开(公告)日：2012-12-27
申请号：PCT/US2012033822
申请日：2012-04-16
申请人： DANA FARBER CANCER INST INC , WALENSKY LOREN D , CARRASCO RUBEN , BIRD GREGORY H
发明人： WALENSKY LOREN D , CARRASCO RUBEN , BIRD GREGORY H
IPC分类号： C07K14/47 , A61K38/17 , A61P35/00
CPC分类号： C07K14/47 , A61K38/00 , A61K38/1709 , A61K45/06 , C07K14/82 , G01N33/53
摘要： The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to ß-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/ß-catenin interaction, and thereby interfering with deregulated Wnt/ß-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.
摘要翻译：本发明通过用于治疗剂的BCL9 HD2螺旋的烃装订来提供结构受限的肽。本发明还提供了用于本发明的结构受限肽的方法和试剂盒。本发明至少部分地基于本文提供的结果，表明烃类钉合螺旋肽显示出优异的蛋白水解，酸和热稳定性，恢复肽的天然螺旋结构，与相应的未修饰的肽相比具有优异的药代动力学性质，并且在体外，纤维素和体内结合ß-连环蛋白非常有效，破坏了BCL-9 /β-连环蛋白相互作用，从而干扰放线性的Wnt /β-catenin信号传导在各种各样的治疗益处人类疾病包括人类癌症。

7. 发明申请

WO2012142604A2 TARGETING DEREGULATED WNT SIGNALING IN CANCER USING STABILIZED ALPHA-HELICES OF BCL-9 审中-公开
标题翻译：用BCL-9稳定的α螺旋靶向固定的WNT信号传导
公开(公告)号：WO2012142604A2
公开(公告)日：2012-10-18
申请号：PCT/US2012/033822
申请日：2012-04-16
申请人： DANA-FARBER CANCER INSTITUTE, INC. , WALENSKY, Loren, D. , CARRASCO, Ruben , BIRD, Gregory, H.
发明人： WALENSKY, Loren, D. , CARRASCO, Ruben , BIRD, Gregory, H.
IPC分类号： C07K14/47 , A61K38/17 , A61P35/00
CPC分类号： C07K14/47 , A61K38/00 , A61K38/1709 , A61K45/06 , C07K14/82 , G01N33/53
摘要： The invention provides structurally-constrained peptides by hydrocarbon stapling of a BCL9 HD2 helix for use as a therapeutic agent. The invention further provides methods and kits for use of the structurally-constrained peptide of the instant invention. The invention is based, at least in part, on the results provided herein demonstrating that hydrocarbon stapled helical peptides display excellent proteolytic, acid, and thermal stability, restore the native helical structure of the peptide, possess superior pharmacokinetic properties compared to the corresponding unmodified peptides, and are highly effective in binding to β-catenin in vitro, in cellulo, and in vivo, disrupting the BCL-9/β-catenin interaction, and thereby interfering with deregulated Wnt/β-catenin signaling for therapeutic benefit in a variety of human diseases including human cancer.
摘要翻译：本发明通过用作治疗剂的BCL9HD2螺旋的烃吻合提供了结构约束的肽。本发明还提供了用于使用本发明的结构约束肽的方法和试剂盒。本发明至少部分基于本文提供的结果，表明烃吻合的螺旋肽显示优异的蛋白水解，酸和热稳定性，恢复肽的天然螺旋结构，与相应的未修饰的肽相比具有优良的药代动力学性质，并且在体外，纤维素和体内高度有效地结合β-连环蛋白，破坏BCL-9 /β-连环蛋白相互作用，从而干扰解除调节的Wnt /β-连环蛋白信号传导以在多种治疗中获益包括人类癌症在内的人类疾病。

8. 发明申请

WO2012065181A3 CANCER THERAPIES AND DIAGNOSTICS 审中-公开
标题翻译：癌症治疗和诊断
公开(公告)号：WO2012065181A3
公开(公告)日：2012-09-27
申请号：PCT/US2011060647
申请日：2011-11-14
申请人： DANA FARBER CANCER INST INC , SALK INST FOR BIOLOG STUDIES INTELLECTUAL PROPERTY AND TECHNOLOGY TRANSFER , WALENSKY LOREN D , BERNAL FEDERICO , WAHL GEOFFREY , WADE MARK
发明人： WALENSKY LOREN D , BERNAL FEDERICO , WAHL GEOFFREY , WADE MARK
IPC分类号： A61K38/10
CPC分类号： C07K4/12 , A61K38/1709
摘要： Compositions and methods for increasing p53-dependent transcriptional activity in a cell.
摘要翻译：用于增加细胞中p53依赖性转录活性的组合物和方法。

9. 发明申请

WO2012006598A3 STABILIZED INSULINOTROPIC PEPTIDES AND METHODS OF USE 审中-公开
标题翻译：稳定的胰岛素样肽和使用方法
公开(公告)号：WO2012006598A3
公开(公告)日：2012-07-05
申请号：PCT/US2011043465
申请日：2011-07-08
申请人： DANA FARBER CANCER INST INC , WALENSKY LOREN D , BIRD GREGORY
发明人： WALENSKY LOREN D , BIRD GREGORY
IPC分类号： C07K14/605 , A61K38/22 , A61K38/26 , A61P3/10 , C07K14/575 , C07K14/62
CPC分类号： C07K14/605 , A61K38/00 , C07K14/575 , C07K14/57563
摘要： The present invention provides stably crosslinked insulionotropic polypeptides having superior and unexpected benefits in the treatment of conditions involving abnormal glucose homeostasis, e.g., type 2 diabetes and conditions relating to type 2 diabetes. Such benefits include, but are not limited to, extended polypeptide half-life, enhanced alpha-helicity, improved thermal stability and protease resistance, increased functional activity and pharmacologic properties, improved bioavailability when administered by any route, and improved bioavailability and gastrointestinal absorption when delivered orally, as compared to the corresponding unmodified polypeptides. The invention also provides compositions for administering the polypeptides of the invention, as well as methods for preparing and evaluating the polypeptides of the invention.
摘要翻译：本发明提供稳定交联的胰岛素样多肽，其在治疗涉及异常葡萄糖体内平衡的病症例如2型糖尿病和与2型糖尿病相关的病症中具有优越和出乎意料的益处。这些益处包括但不限于延长的多肽半衰期，增强的α-螺旋性，改进的热稳定性和蛋白酶抗性，增加的功能活性和药理学性质，当通过任何途径施用时改善的生物利用度，以及改善的生物利用度和胃肠吸收与相应的未修饰多肽相比，口服递送。本发明还提供了用于施用本发明多肽的组合物，以及用于制备和评估本发明多肽的方法。

10. 发明申请

WO2010068684A3 METHODS AND COMPOSITIONS FOR SPECIFIC MODULATION OF MCL-1 审中-公开
标题翻译：用于MCL-1的特异性调节的方法和组合物
公开(公告)号：WO2010068684A3
公开(公告)日：2010-10-14
申请号：PCT/US2009067363
申请日：2009-12-09
申请人： DANA FARBER CANCER INST INC , WALENSKY LOREN D , STEWART MICHELLE L
发明人： WALENSKY LOREN D , STEWART MICHELLE L
IPC分类号： C07K14/47 , A61K38/17 , A61P35/00
CPC分类号： C07K14/47 , A61K31/00 , A61K38/00 , A61K38/08 , A61K38/10 , A61K38/1709 , C07K7/06 , C07K7/08 , C07K14/4747 , G01N33/5011 , G01N33/57484 , A61K2300/00
摘要： A series of stapled BCL-2 family peptide helices were identified as able to target the survival protein MCL-I with high affinity and a subset with unprecedented selectivity. Agents and methods for selective pharmacologic neutralization of MCL-I are provided for drug discovery and therapeutic uses, including use in overcoming the apoptotic resistance of cancer and other diseases associated with impaired cell death.
摘要翻译：一系列钉合的BCL-2家族肽螺旋被鉴定为能够以高亲和力和具有前所未有的选择性的子集靶向存活蛋白MCL-1。用于MCL-1选择性药理中和的药剂和方法用于药物发现和治疗用途，包括用于克服癌症和与细胞死亡受损相关的其他疾病的凋亡抗性。

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