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1. 发明申请

WO0200263A3 TRIPEPTIDE PRODRUG COMPOUNDS 审中-公开
标题翻译：三磷酸前体化合物
公开(公告)号：WO0200263A3
公开(公告)日：2002-08-15
申请号：PCT/US0140925
申请日：2001-06-11
申请人： CORIXA CORP , BEBBINGTON CHRISTOPHER R , DUBOIS VINCENT , GANGWAR SANJEEV , LOBL THOMAS J , NIEDER MATTHEW H , PICKFORD LESLEY B , TROUET ANDRE , YARRANTON GEOFFREY T
发明人： BEBBINGTON CHRISTOPHER R , DUBOIS VINCENT , GANGWAR SANJEEV , LOBL THOMAS J , NIEDER MATTHEW H , PICKFORD LESLEY B , TROUET ANDRE , YARRANTON GEOFFREY T
IPC分类号： A61K31/704 , A61K38/00 , A61K47/48 , A61P29/00 , A61P31/00 , A61P35/00 , A61P43/00 , C07K5/02 , C07K5/08 , C07K5/083 , C07K5/087 , A61K49/00
CPC分类号： B82Y5/00 , A61K38/00 , A61K47/65 , A61K47/67 , C07K5/0202 , C07K5/0808 , C07K5/081 , C07K5/0812
摘要： The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide of three amino acids, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by a trouase enzyme such as Thimet oligopeptidase. Also disclosed are methods of making and using the prodrug compounds.
摘要翻译：本发明的前药是治疗剂的修饰形式，并且包含治疗剂，三种氨基酸的寡肽，稳定基团和任选的接头基团。该前体药物可通过诸如Thimet寡肽酶之类的休眠酶切割。还公开了制备和使用前药化合物的方法。

2. 发明申请

WO0033888A9 PRODRUG COMPOUNDS AND PROCESS FOR PREPARATION THEREOF 审中-公开
标题翻译： PRODRUG化合物及其制备方法
公开(公告)号：WO0033888A9
公开(公告)日：2001-05-10
申请号：PCT/US9930393
申请日：1999-12-10
申请人： COULTER PHARM INC , LOBL THOMAS J , DUBOIS VINCENT , FERNANDEZ ANNE MARIE , GANGWAR SANJEEV , LEWIS EVAN , NIEDER MATTHEW H , TROUET ANDRE , VISKI PETER , YARRANTON GEOFFREY T
发明人： LOBL THOMAS J , DUBOIS VINCENT , FERNANDEZ ANNE-MARIE , GANGWAR SANJEEV , LEWIS EVAN , NIEDER MATTHEW H , TROUET ANDRE , VISKI PETER , YARRANTON GEOFFREY T
IPC分类号： A61K31/138 , A61K31/165 , A61K31/198 , A61K31/337 , A61K31/407 , A61K31/437 , A61K31/4745 , A61K31/513 , A61K31/519 , A61K31/52 , A61K31/5517 , A61K31/555 , A61K31/7004 , A61K31/7028 , A61K31/7048 , A61K31/7064 , A61K31/7068 , A61K33/24 , A61K47/42 , A61K47/48 , A61P29/00 , A61P35/00 , C07K5/10 , C07K7/00
CPC分类号： A61K47/65
摘要： The prodrug of the invention is a modified form of a therapeutic agent and comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the enzyme trouase. Also disclosed are processes for making the prodrug compounds.
摘要翻译：本发明的前药是治疗剂的修饰形式，并且包含治疗剂，寡肽，稳定基团和任选的连接基团。前药可被酶木瓜酶切割。还公开了制备前药化合物的方法。

3. 发明申请

WO02100353A3 CD10-ACTIVATED PRODRUG COMPOUNDS 审中-公开
标题翻译： CD10活化的PRODRUG化合物
公开(公告)号：WO02100353A3
公开(公告)日：2003-05-22
申请号：PCT/US0221135
申请日：2002-06-11
申请人： MEDAREX INC , BEBBINGTON CHRISTOPHER R , NIEDER MATTHEW H , CARDARELLI PINA M , GANGWAR SANJEEV , PICKFORD LESLEY B , PAN CHIN
发明人： BEBBINGTON CHRISTOPHER R , NIEDER MATTHEW H , CARDARELLI PINA M , GANGWAR SANJEEV , PICKFORD LESLEY B , PAN CHIN
IPC分类号： A61K31/704 , A61K45/00 , A61K47/48 , A61K49/00 , A61P35/00 , A61P35/02 , A61P35/04 , A61P43/00 , C07K5/06 , C07K5/083 , G01N33/68 , A61K38/06 , A61K38/07 , A61K38/08 , C07K1/16 , C07K5/08 , C07K5/10 , C07K7/06 , C12Q1/37
CPC分类号： G01N33/57492 , A61K47/65 , C12Q1/37 , G01N2333/70596 , G01N2500/00
摘要： The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the CD10 enzyme. Methods of treatment using the prodrug and methods of designing a prodrug are also disclosed.
摘要翻译：本发明的化合物是治疗剂的修饰形式。本发明的典型前药化合物包含治疗剂，寡肽，稳定基团和任选的连接基团。前药可被CD10酶切割。还公开了使用前药的治疗方法和设计前药的方法。

4. 发明申请

WO2002100353A2 CD10-ACTIVATED PRODRUG COMPOUNDS 审中-公开
标题翻译： CD10活化的PRODRUG化合物
公开(公告)号：WO2002100353A2
公开(公告)日：2002-12-19
申请号：PCT/US2002/021135
申请日：2002-06-10
申请人： MEDAREX, INC. , BEBBINGTON, Christopher, R. , NIEDER, Matthew, H. , CARDARELLI, Pina, M. , GANGWAR, Sanjeev , PICKFORD, Lesley, B. , PAN, Chin
发明人： BEBBINGTON, Christopher, R. , NIEDER, Matthew, H. , CARDARELLI, Pina, M. , GANGWAR, Sanjeev , PICKFORD, Lesley, B. , PAN, Chin
IPC分类号： A61K
CPC分类号： G01N33/57492 , A61K47/65 , C12Q1/37 , G01N2333/70596 , G01N2500/00
摘要： The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by the CD10 enzyme. Methods of treatment using the prodrug and methods of designing a prodrug are also disclosed.
摘要翻译：本发明的化合物是治疗剂的修饰形式。本发明的典型前药化合物包含治疗剂，寡肽，稳定基团和任选的连接基团。前药可被CD10酶切割。还公开了使用前药的治疗方法和设计前药的方法。

5. 发明申请

WO0033888A3 PRODRUG COMPOUNDS AND PROCESS FOR PREPARATION THEREOF 审中-公开
标题翻译： PRODRUG化合物及其制备方法
公开(公告)号：WO0033888A3
公开(公告)日：2001-11-08
申请号：PCT/US9930393
申请日：1999-12-10
申请人： COULTER PHARM INC , LOBL THOMAS J , DUBOIS VINCENT , FERNANDEZ ANNE MARIE , GANGWAR SANJEEV , LEWIS EVAN , NIEDER MATTHEW H , TROUET ANDRE , VISKI PETER , YARRANTON GEOFFREY T
发明人： LOBL THOMAS J , DUBOIS VINCENT , FERNANDEZ ANNE-MARIE , GANGWAR SANJEEV , LEWIS EVAN , NIEDER MATTHEW H , TROUET ANDRE , VISKI PETER , YARRANTON GEOFFREY T
IPC分类号： A61K31/138 , A61K31/165 , A61K31/198 , A61K31/337 , A61K31/407 , A61K31/437 , A61K31/4745 , A61K31/513 , A61K31/519 , A61K31/52 , A61K31/5517 , A61K31/555 , A61K31/7004 , A61K31/7028 , A61K31/7048 , A61K31/7064 , A61K31/7068 , A61K33/24 , A61K47/42 , A61K47/48 , A61P29/00 , A61P35/00 , C07K5/10 , C07K7/00
CPC分类号： A61K47/65
摘要： The compound of the invention is a prodrug form of a therapeutic agent linked directly or indirectly to an oligopeptide, which in turn, is linked to a stabilizing group. More generally, the present invention may be described as a new prodrug compound of a therapeutic agent, especially prodrugs comprising an antitumor therapeutic agent, displaying improved therapeutic properties relative to the products of the prior art, especially improved therapeutic properties in the treatment of cancerous tumors and/or in the treatment of inflammatory reactions such as rheumatic diseases. Improved therapeutic properties include decreased toxicity and increased efficacy. Particularly desired are prodrugs which display a high specificity of action, a reduced toxicity, an improved stability in the serum and blood, and which do not move into target cells until activated by a target cell associated enzyme. Prodrug compounds of a marker enabling tumors to be characterized (diagnosis, progression of the tumor, assay of the factors secreted by tumor cells, etc.) are also contemplated. The present invention also relates to the pharmaceutical composition comprising the compound according to the invention and optionally a pharmaceutically acceptable adjuvant or vehicle. Further, a method of decreasing toxicity by modifying a therapeutic agent to create a prodrug is disclosed. Several processes for creating a prodrug of the invention are described. Compounds of the invention include the prodrugs, Suc-ssAla-Leu-Ala-Leu-Dox, Suc-ssAla-Leu-Ala-Leu-Dnr, and Glutaryl-ssAla-Leu-Ala-Leu-Dox. Additionally intermediate compounds, important to the process of preparation of the prodrugs of the invention are claimed.
摘要翻译：本发明的化合物是与寡肽直接或间接连接的治疗剂的前药形式，其又与稳定基团连接。更一般地，本发明可以描述为治疗剂的新的前药化合物，特别是包含抗肿瘤治疗剂的前药，相对于现有技术的产品显示出改善的治疗性质，特别是治疗癌性肿瘤的改善的治疗性质和/或治疗诸如风湿性疾病的炎性反应。改进的治疗性质包括毒性降低和功效增加。特别期望的是显示出高度的作用特异性，毒性降低，血清和血液中改善的稳定性，并且不会移动到靶细胞中直到被靶细胞相关的酶活化的前药。还考虑了能够表征肿瘤（诊断，肿瘤进展，肿瘤细胞分泌的因子的测定等）的标记物的前药化合物。本发明还涉及包含根据本发明的化合物和任选的药学上可接受的佐剂或赋形剂的药物组合物。此外，公开了通过修饰治疗剂以产生前药来降低毒性的方法。描述了用于制备本发明的前药的几种方法。本发明的化合物包括前体药物Suc-ssAla-Leu-Ala-Leu-Dox，Suc-ssAla-Leu-Ala-Leu-Dnr和Glutaryl-ssAla-Leu-Ala-Leu-Dox。要求保护本发明前药制备方法重要的中间体化合物。

6. 发明申请

WO0195943A3 PRODRUG COMPOUNDS WITH AN OLIGOPEPTIDE HAVING AN ISOLEUCINE RESIDUE 审中-公开
标题翻译：具有含有残留物的寡核苷酸的PRODRUG化合物
公开(公告)号：WO0195943A3
公开(公告)日：2002-08-29
申请号：PCT/US0118857
申请日：2001-06-11
申请人： CORIXA CORP , PICKFORD LESLEY B , GANGWAR SANJEEV , LOBL THOMAS J , NIEDER MATTHEW H , YARRANTON GEOFFREY T
发明人： PICKFORD LESLEY B , GANGWAR SANJEEV , LOBL THOMAS J , NIEDER MATTHEW H , YARRANTON GEOFFREY T
IPC分类号： A61K38/06 , A61K38/07 , A61K47/48 , A61P29/00 , A61P35/00 , A61P43/00 , C07K5/023 , C07K5/083 , C07K5/10 , C07K5/103 , C07K5/117
CPC分类号： A61K38/06 , A61K38/07 , A61K47/64 , A61K47/65 , C07K5/0808 , C07K5/101 , C07K5/1024
摘要： The compounds of the invention are modified forms of therapeutic agents. A typical prodrug compound of the invention comprises a therapeutic agent, an oligopeptide having an isoleucine residue, a stabilizing group and, optionally, a linker group. The prodrug is cleavable by an enzyme associated with the target cell. Methods of making and using the compounds are also disclosed.
摘要翻译：本发明的化合物是治疗剂的修饰形式。本发明的典型前药化合物包含治疗剂，具有异亮氨酸残基的寡肽，稳定基团和任选的连接基团。前药可通过与靶细胞相关的酶切割。还公开了制备和使用化合物的方法。

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