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1. 发明授权

US09505829B2 Anti-NGF antibodies and their use 有权
标题翻译：抗NGF抗体及其用途
公开(公告)号：US09505829B2
公开(公告)日：2016-11-29
申请号：US13817721
申请日：2011-08-19
申请人： Susan E. Lacy , Jeffrey A. Barbon , Meha Chhaya , Emma Fung , Charles W. Hutchins , Diane M. Lang , Eve H. Barlow , Mary Leddy , Ravi Chari
发明人： Susan E. Lacy , Jeffrey A. Barbon , Meha Chhaya , Emma Fung , Charles W. Hutchins , Diane M. Lang , Eve H. Barlow , Mary Leddy , Ravi Chari
IPC分类号： C07K16/22 , A61K39/395
CPC分类号： C07K16/22 , A61K39/3955 , A61K2039/505 , C07K2317/24 , C07K2317/31 , C07K2317/50 , C07K2317/51 , C07K2317/515 , C07K2317/54 , C07K2317/55 , C07K2317/565 , C07K2317/569 , C07K2317/60 , C07K2317/622 , C07K2317/624 , C07K2317/626 , C07K2317/64 , C07K2317/73 , C07K2317/76 , C07K2317/92 , C07K2317/94 , G01N33/566
摘要： The present disclosure encompasses NGF binding proteins, specifically to antibodies that are chimeric, CDR grafted and canonized antibodies, and methods of making and uses thereof. The antibodies, or antibody portions, of the disclosure are useful for detecting NGF and for inhibiting NGF activity, e.g., in a mammal subject suffering from a disorder in which NGF activity is detrimental.
摘要翻译：本公开内容涵盖NGF结合蛋白，特别是嵌合抗体，CDR移植和标准化抗体的抗体，及其制备和使用方法。本公开的抗体或抗体部分可用于检测NGF和抑制NGF活性，例如在患有NGF活性有害的病症的哺乳动物受试者中。

2. 发明申请

US20140134172A1 ANTI-DLL4/VEGF DUAL VARIABLE DOMAIN IMMUNOGLOBULIN AND USES THEREOF 有权
标题翻译： ANTI-DLL4 / VEGF双变异型域免疫球蛋白及其用途
公开(公告)号：US20140134172A1
公开(公告)日：2014-05-15
申请号：US14068976
申请日：2013-10-31
申请人： Jijie Gu , Dominic J. Ambrosi , Susan E. Lappe , Yingchun Li , Jonathan A. Hickson , Deanna L. Haasch , Supriya Gupta , Ravi Chari , Camellia Zamiri , Louie Naumovski , Xianhua Cao
发明人： Jijie Gu , Dominic J. Ambrosi , Susan E. Lappe , Yingchun Li , Jonathan A. Hickson , Deanna L. Haasch , Supriya Gupta , Ravi Chari , Camellia Zamiri , Louie Naumovski , Xianhua Cao
IPC分类号： C07K16/28 , A61K45/06 , C07K16/22 , A61K39/395
CPC分类号： C07K16/468 , A61K31/337 , A61K31/4745 , A61K31/495 , A61K31/513 , A61K31/525 , A61K31/7068 , A61K39/395 , A61K39/3955 , A61K39/39591 , A61K45/06 , A61K2039/505 , C07K16/22 , C07K16/28 , C07K2317/24 , C07K2317/31 , C07K2317/35 , C07K2317/52 , C07K2317/56 , C07K2317/565 , C07K2317/64 , C07K2317/76 , C07K2317/92 , C07K2317/94 , A61K2300/00
摘要： Disclosed herein are multivalent and multispecific binding proteins, methods of making the binding proteins, and their uses in the diagnosis, monitoring, inhibition, prevention and/or treatment of cancers, tumors, and/or other angiogenesis-dependent diseases characterized by aberrant DLL4 and/or VEGF expression or activity.
摘要翻译：本文公开了多价和多特异性结合蛋白，制备结合蛋白的方法及其在诊断，监测，抑制，预防和/或治疗癌症，肿瘤和/或其它血管发生依赖性疾病中的用途，其特征在于异常DLL4和 /或VEGF表达或活性。

3. 发明申请

US20060009462A1 Prodrugs of CC-1065 analogs 失效
公开(公告)号：US20060009462A1
公开(公告)日：2006-01-12
申请号：US11217351
申请日：2005-09-02
申请人： Robert Yongxin , Ravi Chari
发明人： Robert Yongxin , Ravi Chari
IPC分类号： A61K31/495 , C07D241/04
CPC分类号： C07D307/85 , A61K31/407 , A61K31/4545 , A61K31/495 , A61K31/496 , A61K31/675 , A61K47/545 , A61K47/548 , A61K47/60 , C07D209/42 , C07D209/60 , C07D403/14 , C07D405/12 , C07F9/5728 , C07F9/65583 , Y02A50/423 , Y02A50/491 , Y02P20/55
摘要： Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

4. 发明申请

US20050085513A1 Cytotoxic agents containing novel potent taxanes and their therapeutic use 失效
标题翻译：含有新型有效紫杉烷类及其治疗用途的细胞毒素
公开(公告)号：US20050085513A1
公开(公告)日：2005-04-21
申请号：US10963711
申请日：2004-10-14
申请人： Erkan Baloglu , Michael Miller , Ravi Chari
发明人： Erkan Baloglu , Michael Miller , Ravi Chari
IPC分类号： A61K31/337 , A61P31/04 , A61P31/12 , A61P33/00 , A61P35/00 , A61P37/06 , A61P43/00 , C07D305/14 , C07D407/12 , C07D407/14 , C07D409/12 , A61K31/4025 , A61K31/4433 , C07D45/02
CPC分类号： C07D407/12 , A61K31/337 , C07D305/14 , C07D407/14 , C07D409/12 , Y02A50/423 , Y02A50/491
摘要： Included within the scope of the present invention are potent taxanes and taxanes containing a linking group. Also included is a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for inducing cell death in selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a link, and (B) a pharmaceutically acceptable carrier, diluent or excipient is also included. A method for inducing cell death in selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent is included as well.
摘要翻译：包括在本发明范围内的有效的紫杉烷类和含有连接基团的紫杉烷类。还包括细胞毒性剂，其包含与细胞结合剂连接的一种或多种紫杉烷类。一种用于在所选细胞群体中诱导细胞死亡的治疗组合物，包括：（A）细胞毒性量的一种或多种通过连接体与细胞结合剂共价结合的紫杉烷，和（B）药学上可接受的载体，稀释剂或赋形剂。还包括诱导选择的细胞群体中的细胞死亡的方法，包括使靶细胞或含有靶细胞的组织与有效量的包含与细胞结合剂连接的一种或多种紫杉烷的细胞毒性试剂接触。

5. 发明申请

US20070269447A1 CYTOTOXIC AGENTS COMPRISING NEW MAYTANSINOIDS 有权
公开(公告)号：US20070269447A1
公开(公告)日：2007-11-22
申请号：US11778451
申请日：2007-07-16
申请人： Ravi Chari , Wayne Widdison
发明人： Ravi Chari , Wayne Widdison
IPC分类号： A61K39/00 , A61P35/00
CPC分类号： A61K39/39558 , A61K31/5365 , A61K47/6803 , A61K2039/505 , C07D498/16
摘要： New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

6. 发明申请

US20070264266A1 CYTOTOXIC AGENTS COMPRISING NEW MAYTANSINOIDS 有权
标题翻译：包含新的可待因腺苷的细胞毒性剂
公开(公告)号：US20070264266A1
公开(公告)日：2007-11-15
申请号：US11778437
申请日：2007-07-16
申请人： Ravi Chari , Wayne Widdison
发明人： Ravi Chari , Wayne Widdison
IPC分类号： A61K39/395 , A61P35/04 , C07D491/08 , C07K16/00
CPC分类号： A61K39/39558 , A61K31/5365 , A61K47/6803 , A61K2039/505 , C07D498/16
摘要： New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.
摘要翻译：公开了在带有硫原子的α-碳原子上带有单或二烷基取代的新的含硫醇和二硫化物的美登木素生物碱。还公开了合成这些新的美登木素生物碱的方法和将这些新的美登木素生物素连接到细胞结合剂的方法。美登木素生物碱 - 细胞结合剂缀合物可用作治疗剂，其特异性递送至靶细胞并且是细胞毒性的。与先前描述的试剂相比，这些缀合物在动物肿瘤模型中显示出显着改善的治疗功效。

7. 发明申请

US20070197775A1 Cytotoxic agents comprising taxanes and their therapeutic use 失效
标题翻译：包含紫杉烷及其治疗用途的细胞毒素
公开(公告)号：US20070197775A1
公开(公告)日：2007-08-23
申请号：US11785483
申请日：2007-04-18
申请人： Ravi Chari , Walter Blattler
发明人： Ravi Chari , Walter Blattler
IPC分类号： C07K14/54 , C07K14/56 , C07K16/46
CPC分类号： C07D305/14 , A61K31/337 , A61K47/6803 , A61K47/6849 , A61K47/6851 , A61K47/6881 , A61K2039/505 , C07K16/2863 , C07K16/32 , Y02A50/423 , Y02A50/491
摘要： A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.
摘要翻译：包含与细胞结合剂连接的一种或多种紫杉烷类的细胞毒性剂。一种用于杀死所选细胞群的治疗组合物，其包含：（A）细胞毒性量的一种或多种通过连接基团与细胞结合剂共价结合的紫杉烷，和（B）药学上可接受的载体，稀释剂或赋形剂。一种杀死所选细胞群体的方法，包括使含有目标细胞的靶细胞或组织与有效量的细胞毒性剂接触，所述细胞毒剂包含与细胞结合剂连接的一种或多种紫杉烷类。新型含硫紫杉烷。

8. 发明申请

US20070135346A1 Prodrugs of CC-1065 analogs 失效
标题翻译： CC-1065类似物的前药
公开(公告)号：US20070135346A1
公开(公告)日：2007-06-14
申请号：US11649822
申请日：2007-01-05
申请人： Robert Zhao , Ravi Chari
发明人： Robert Zhao , Ravi Chari
IPC分类号： A61K31/496 , A61K31/4545 , A61K38/16 , C07K14/00 , C07D403/14
CPC分类号： C07D307/85 , A61K31/407 , A61K31/4545 , A61K31/495 , A61K31/496 , A61K31/675 , A61K47/545 , A61K47/548 , A61K47/60 , C07D209/42 , C07D209/60 , C07D403/14 , C07D405/12 , C07F9/5728 , C07F9/65583 , Y02A50/423 , Y02A50/491 , Y02P20/55
摘要： Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.
摘要翻译：具有可切割保护基的抗肿瘤抗生素CC-1065类似物的前药，例如哌嗪基氨基甲酸酯，4-哌啶子基 - 哌啶子基氨基甲酸酯或磷酸酯，其中保护基团赋予增强的水溶性和在前药上的稳定性，其中前药还具有可与细胞结合试剂例如抗体缀合的部分，例如二硫化物。还描述了这种前药缀合物的治疗用途; 这种细胞毒性药物的前药具有治疗用途，因为它们可以将细胞毒性前体药物递送至特定细胞群体，以靶向方式酶促转化为细胞毒性药物。

9. 发明申请

US20050169933A1 Method of targeting specific cell populations using cell-binding agent maytansinoid conjugates linked via a non-cleavable linker, said conjugates, and methods of making said conjugates 有权
标题翻译：使用通过不可切割接头连接的细胞粘附剂美登木素生物碱结合物靶向特定细胞群的方法，所述缀合物和制备所述缀合物的方法
公开(公告)号：US20050169933A1
公开(公告)日：2005-08-04
申请号：US10960602
申请日：2004-10-08
申请人： Rita Steeves , Robert Lutz , Ravi Chari , Hongsheng Xie , Yelena Kovtun
发明人： Rita Steeves , Robert Lutz , Ravi Chari , Hongsheng Xie , Yelena Kovtun
IPC分类号： A61K39/395 , C07K16/46 , C07D491/04
CPC分类号： C07K16/3092 , A61K47/6803 , A61K47/6851 , A61K47/6855 , A61K47/6889 , A61K2039/505 , C07K16/18 , C07K16/32 , C07K2317/24 , C07K2317/92
摘要： The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.
摘要翻译：本发明公开了一种将美登木素生物素靶向选定的细胞群体的方法，所述方法包括将怀疑含有所选细胞群的细胞群体或组织与细胞粘附剂美登木素生物碱缀合物接触，其中一种或多种美登木素生物碱共价连接到细胞结合剂通过不可切割的接头和细胞结合剂结合所选细胞群的细胞。

10. 发明申请

US20050119548A1 Method and apparatus for optical spectroscopic detection of cell and tissue death 审中-公开
标题翻译：光学检测细胞和组织死亡的方法和装置
公开(公告)号：US20050119548A1
公开(公告)日：2005-06-02
申请号：US10955331
申请日：2004-09-30
申请人： Wei-Chiang Lin , Steven Toms , Anita Mahadevan-Jansen , Ravi Chari
发明人： Wei-Chiang Lin , Steven Toms , Anita Mahadevan-Jansen , Ravi Chari
IPC分类号： A61B20060101 , A61B5/00 , A61B6/00
CPC分类号： A61B5/0071 , A61B5/0075 , A61B5/0084 , A61B5/4244
摘要： A method for detecting death process of a cell or tissue of a living subject. In one embodiment, the method includes the steps of illuminating the cell or tissue of the living subject with a coherent light, collecting fluorescent light returned from the illuminated cell or tissue of the living subject, identifying a NAD(P)H peak of a spectrum of the collected fluorescent light with a wavelength, λpeak, and obtaining the intensity of the NAD(P)H peak of the spectrum of the collected fluorescent light substantially corresponding to the wavelength λpeak. These steps are repeated at sequential stages until the intensity of the NAD(P)H peak of the spectrum at a current stage is less than the intensity of the NAD(P)H peak of the spectrum at an earlier stage immediately prior to the current stage so as to detect death process of the cell of the living subject at the current stage using the intensity of the NAD(P)H peak of the spectrum.
摘要翻译：一种用于检测活体受试者的细胞或组织的死亡过程的方法。在一个实施例中，该方法包括以相干光照射活体的细胞或组织的步骤，收集从活体受试者的照射细胞或组织返回的荧光，识别光谱的NAD（P）H峰收集的具有波长λλ峰值的荧光，并且获得基本上对应于波长λ的峰的峰的收集的荧光的光谱的NAD（P）H峰的强度， / SUB>。这些步骤在连续阶段重复，直到当前阶段的光谱的NAD（P）H峰的强度小于在电流之前的较早阶段的光谱的NAD（P）H峰的强度使用光谱的NAD（P）H峰的强度来检测当前阶段的活体的细胞的死亡过程。

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