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1. 发明授权

US5041424A Epipodophyllotoxin glucoside 4'-phosphate derivatives 失效
标题翻译：鬼臼毒素苷4'-磷酸衍生物
公开(公告)号：US5041424A
公开(公告)日：1991-08-20
申请号：US450718
申请日：1989-12-14
申请人： Mark G. Saulnier , Peter D. Senter , John F. Kadow
发明人： Mark G. Saulnier , Peter D. Senter , John F. Kadow
IPC分类号： C07H17/04 , A61K20060101 , A61K31/365 , A61K31/366 , A61K31/44 , A61K31/66 , A61K31/661 , A61K31/70 , A61K31/7042 , A61K31/7048 , A61P35/00 , A61P35/04 , C07F20060101 , C07H20060101 , C07H3/02 , C07H15/00 , C07H15/24
CPC分类号： C07H17/04 , Y10S514/908
摘要： Phosphate derivatives of 4'-demethylepipodophyllotoxin glucosides are novel antitumor agents and the salts thereof offer the pharmaceutical advantage of high water solubility.
摘要翻译： 4'-去甲表鬼臼毒素葡糖苷的磷酸酯衍生物是新的抗肿瘤剂，其盐提供高水溶性的药物优点。

2. 发明授权

US4904768A Epipodophyllotoxin glucoside 4'-phosphate derivatives 失效
标题翻译：鬼臼毒素苷4'-磷酸衍生物
公开(公告)号：US4904768A
公开(公告)日：1990-02-27
申请号：US199731
申请日：1988-05-27
申请人： Mark G. Saulnier , Peter D. Senter , John F. Kadow
发明人： Mark G. Saulnier , Peter D. Senter , John F. Kadow
IPC分类号： C07H17/04 , A61K20060101 , A61K31/365 , A61K31/366 , A61K31/44 , A61K31/66 , A61K31/661 , A61K31/70 , A61K31/7042 , A61K31/7048 , A61P35/00 , A61P35/04 , C07F20060101 , C07H20060101 , C07H3/02 , C07H15/00 , C07H15/24
CPC分类号： C07H17/04 , Y10S514/908
摘要： Phosphate derivatives of 4'-demethylepipodophyllotoxin glucosides are novel antitumor agents and the salts thereof offer the pharmaceutical advantage of high water solubility.
摘要翻译： 4'-去甲表鬼臼毒素葡糖苷的磷酸酯衍生物是新的抗肿瘤剂，其盐提供高水溶性的药物优点。

3. 再颁专利

USRE35524E Epipodophyllotoxin glucoside 4'-phosphate derivatives 失效
标题翻译：鬼臼毒素苷4'-磷酸衍生物
公开(公告)号：USRE35524E
公开(公告)日：1997-06-03
申请号：US229659
申请日：1994-04-19
申请人： Mark G. Saulnier , Peter D. Senter , John F. Kadow
发明人： Mark G. Saulnier , Peter D. Senter , John F. Kadow
IPC分类号： C07H17/04 , A61K20060101 , A61K31/365 , A61K31/366 , A61K31/44 , A61K31/66 , A61K31/661 , A61K31/70 , A61K31/7042 , A61K31/7048 , A61P35/00 , A61P35/04 , C07F20060101 , C07H20060101 , C07H3/02 , C07H15/00 , C07H15/24 , C07H11/04
CPC分类号： C07H17/04 , Y10S514/908
摘要： Phosphate derivatives of 4'-demethylepipodophyllotoxin glucosides are novel antitumor agents and the salts thereof offer the pharmaceutical advantage of high water solubility.
摘要翻译： 4'-去甲表鬼臼毒素葡糖苷的磷酸酯衍生物是新的抗肿瘤剂，其盐提供高水溶性的药物优点。

4. 发明授权

US4975278A Antibody-enzyme conjugates in combination with prodrugs for the delivery of cytotoxic agents to tumor cells 失效
标题翻译：抗体 - 酶缀合物与用于向肿瘤细胞递送细胞毒性剂的前药组合
公开(公告)号：US4975278A
公开(公告)日：1990-12-04
申请号：US211301
申请日：1988-06-29
申请人： Peter D. Senter , Mark G. Saulnier , Joseph P. Brown , David E. Kerr
发明人： Peter D. Senter , Mark G. Saulnier , Joseph P. Brown , David E. Kerr
IPC分类号： A61K47/48
CPC分类号： B82Y5/00 , A61K47/48761
摘要： This invention relates to a novel method for the delivery of cytotoxic drugs to tumor cells by the administration of a tumor-specific antibody-enzyme conjugate that binds to the tumor cells, and the additional administration of a prodrug that is converted at the tumor site, in the presence of the antibody-bound enzyme, to an active cytotoxic drug. According to preferred embodiments of this invention, antibody-enzyme conjugates containing the enzyme, alkaline phosphatase ("AP"), have been used in conjunction with the novel prodrug, etoposide-4'-phosphate or 7-(2'-aminoethyl phosphate)mitomycin or a combination thereof, to effect killing of tumor cells. According to another embodiment of the invention, an antibody-enzyme conjugate containing the enzyme, penicillin V amidase ("PVA"), has been used in conjunction with a novel prodrug, N-(p-hydroxyphenoxyacetyl)adriamycin to effect killing of tumor cells. Still another embodiment of the invention relates to the use of an antibody-enzyme conjugate containing the enzyme, cytosine deaminase ("CD"), in combination with the prodrug, 5-fluorocytosine, to effect killing of tumor cells. The method, antibody-enzyme conjugates, prodrugs, pharmaceutical compositions and combinations of this invention provide for enhanced selective killing of tumor cells and are thus useful in the treatment of cancers and other tumors.
摘要翻译：本发明涉及通过施用与肿瘤细胞结合的肿瘤特异性抗体 - 酶结合物向肿瘤细胞递送细胞毒性药物的新方法，以及额外施用在肿瘤部位转化的前体药物，在抗体结合酶存在下，与活性细胞毒性药物接触。根据本发明的优选实施方案，含有酶碱性磷酸酶（“AP”）的抗体 - 酶缀合物已经与新的前药，依托泊苷-4'-磷酸或7-（2'-氨基乙基磷酸酯）结合使用，丝裂霉素或其组合，以杀死肿瘤细胞。根据本发明的另一个实施方案，含有酶青霉素V酰胺酶（“PVA”）的抗体 - 酶结合物已经与新的前体药物N-（对羟基苯氧基乙酰基）阿霉素结合使用，以杀死肿瘤细胞。本发明的另一个实施方案涉及含有酶，胞嘧啶脱氨酶（“CD”）与前体药物5-氟胞嘧啶组合的抗体 - 酶偶联物用于杀死肿瘤细胞的用途。本发明的方法，抗体 - 酶缀合物，前药，药物组合物和组合提供增强的肿瘤细胞的选择性杀伤，因此可用于治疗癌症和其它肿瘤。

5. 发明授权

US08906376B2 Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease 有权
标题翻译：药物共轭物及其用于治疗癌症，自身免疫性疾病或传染病的用途
公开(公告)号：US08906376B2
公开(公告)日：2014-12-09
申请号：US12880028
申请日：2010-09-10
申请人： Peter D. Senter , Svetlana O. Doronina , Brian E. Toki
发明人： Peter D. Senter , Svetlana O. Doronina , Brian E. Toki
IPC分类号： A61K47/48 , C07K5/02
CPC分类号： A61K47/48246 , A61K47/64 , A61K47/642 , A61K47/6817 , A61K47/6851 , A61K47/6867 , C07K5/0205
摘要： Drug-Linker-Ligand Conjugates are disclosed in which a Drug is linked to a Ligand via a peptide-based Linker unit. In one embodiment, the Ligand is an Antibody. Drug-Linker compounds and Drug compounds are also disclosed. Methods for treating cancer, an autoimmune disease or an infectious disease using the compounds and compositions of the invention are also disclosed.
摘要翻译：公开了药物 - 接头 - 配体结合物，其中药物通过基于肽的接头单元与配体连接。在一个实施方案中，配体是抗体。还公开了药物连接剂化合物和药物化合物。还公开了使用本发明的化合物和组合物治疗癌症，自身免疫疾病或感染性疾病的方法。

6. 发明授权

US08871720B2 Monomethylvaline compounds having phenylalanine carboxy modifications at the C-terminus 有权
标题翻译：在C末端具有苯丙氨酸羧基修饰的单甲基缬氨酸化合物
公开(公告)号：US08871720B2
公开(公告)日：2014-10-28
申请号：US11994459
申请日：2006-07-07
申请人： Svetlana O. Doronina , Toni Beth Kline , Scott Jeffrey , Peter D. Senter , Damon Meyer
发明人： Svetlana O. Doronina , Toni Beth Kline , Scott Jeffrey , Peter D. Senter , Damon Meyer
IPC分类号： A61K38/04 , C07K7/02 , C07K5/02 , A61K38/00
CPC分类号： A61K47/48415 , A61K38/00 , A61K39/3955 , A61K47/6811 , A61K2039/505 , C07K5/0205 , C07K7/02 , C07K16/2866 , C07K2317/76 , Y02A50/40 , Y02A50/401 , Y02A50/406 , Y02A50/48
摘要： Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) having a carboxylic acid equivalent at the C-terminal phenylalanine were prepared and attached to ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.
摘要翻译：制备具有C-末端苯丙氨酸羧酸当量的MeVal-Val-Dil-Dap-Phe（MMAF）的Auristatin肽类似物，并通过各种接头包括马来酰亚氨基己酰基val-cit-PAB连接到配体上。所得配体药物偶联物在体外和体内都是活性的。

7. 发明申请

US20120027784A1 MONOMETHYLVALINE COMPOUNDS CAPABLE OF CONJUGATION TO LIGANDS 审中-公开
公开(公告)号：US20120027784A1
公开(公告)日：2012-02-02
申请号：US13189452
申请日：2011-07-22
申请人： Svetlana O. Doronina , Peter D. Senter , Brian E. Toki , Allen J. Ebens , Toni Beth Kline , Paul Polakis , Mark X. Sliwkowski , Susan D. Spencer
发明人： Svetlana O. Doronina , Peter D. Senter , Brian E. Toki , Allen J. Ebens , Toni Beth Kline , Paul Polakis , Mark X. Sliwkowski , Susan D. Spencer
IPC分类号： A61K39/395 , A61P35/00 , C07K17/00
CPC分类号： C07K16/32 , A61K38/00 , A61K47/6803 , A61K47/6811 , A61K47/6849 , A61K47/6851 , A61K47/6855 , A61K2039/505 , C07K7/02 , C07K2317/24 , Y02A50/414 , Y02A50/423 , Y02A50/469 , Y10T428/13
摘要： Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.

8. 发明授权

US07964567B2 Monomethylvaline compounds capable of conjugation to ligands 有权
公开(公告)号：US07964567B2
公开(公告)日：2011-06-21
申请号：US11833961
申请日：2007-08-03
申请人： Svetlana O. Doronina , Peter D. Senter , Brian E. Toki , Allen J. Ebens , Toni Beth Kline , Paul Polakis , Mark X. Sliwkowski , Susan D. Spencer
发明人： Svetlana O. Doronina , Peter D. Senter , Brian E. Toki , Allen J. Ebens , Toni Beth Kline , Paul Polakis , Mark X. Sliwkowski , Susan D. Spencer
IPC分类号： A61K38/00 , A61K38/02 , C07K2/00
CPC分类号： C07K16/32 , A61K38/00 , A61K47/6811 , A61K47/6849 , A61K47/6851 , A61K47/6855 , A61K2039/505 , C07K7/02 , C07K2317/24 , Y02A50/414 , Y02A50/423 , Y02A50/469 , Y02A50/491 , Y02A50/492 , Y10T428/13
摘要： Auristatin peptides, including MeVal-Val-Dil-Dap-Norephedrine (MMAE) and MeVal-Val-Dil-Dap-Phe (MMAF), were prepared and attached to Ligands through various linkers, including maleimidocaproyl-val-cit-PAB. The resulting ligand drug conjugates were active in vitro and in vivo.

9. 发明授权

US07659241B2 Drug conjugates and their use for treating cancer, an autoimmune disease or an infectious disease 有权
标题翻译：药物共轭物及其用于治疗癌症，自身免疫性疾病或传染病的用途
公开(公告)号：US07659241B2
公开(公告)日：2010-02-09
申请号：US10522911
申请日：2003-07-31
申请人： Peter D. Senter , Svetlana O. Doronina , Brian E. Toki
发明人： Peter D. Senter , Svetlana O. Doronina , Brian E. Toki
IPC分类号： A61K38/00 , C07K2/00
CPC分类号： A61K47/48246 , A61K47/64 , A61K47/642 , A61K47/6817 , A61K47/6851 , A61K47/6867 , C07K5/0205
摘要： Compounds and compositions are disclosed in which a Drug unit (D) is linked to a Ligand unit (L). In an exemplary embodiment, the compound is of the formula LAa-Ww-Yy-D)p Ia or a pharmaceutically acceptable salt thereof, where A is a stretcher unit, W is an amino acid unit, Y is a spacer unit, D is of the formula and a, w, y, p and R2-R10 are as disclosed in the specification. Methods for treating cancer, autoimmune disease, and infectious disease using the compounds and compositions of the invention are also disclosed.
摘要翻译：公开了化合物和组合物，其中药物单元（D）与配体单元（L）连接。在一个示例性实施方案中，该化合物具有式L Aa-Ww-Yy-D）p Ia或其药学上可接受的盐，其中A是担架单元，W是氨基酸单元，Y是间隔单元，D具有下式：a，w，y，p和R 2 -R 10如说明书中所公开的。还公开了使用本发明的化合物和组合物治疗癌症，自身免疫疾病和感染性疾病的方法。

10. 发明授权

US07098308B2 Pentapeptide compounds and uses related thereto 有权
标题翻译：五肽化合物及其相关用途
公开(公告)号：US07098308B2
公开(公告)日：2006-08-29
申请号：US10979923
申请日：2004-11-01
申请人： Peter D. Senter , Brian E. Toki , Svetlana Doronina
发明人： Peter D. Senter , Brian E. Toki , Svetlana Doronina
IPC分类号： C07K7/00
CPC分类号： C07K5/0202 , A61K38/00 , A61K47/6811 , C07K5/0205
摘要： Pentapeptide compounds are disclosed. The compounds have biological activity, e.g., cytotoxicity. Prodrugs having targeting groups and pentapeptide moieities, as well as precursors thereof are also disclosed. For example, precursors having a reactive linker that can serve as a reaction site for joining to a targeting agent, e.g., an antibody, as disclosed.
摘要翻译：公开了五肽化合物。这些化合物具有生物活性，例如细胞毒性。还公开了具有靶向基团和五肽阴离子的前体药物及其前体物质。例如，具有可用作连接靶向试剂（例如抗体）的反应位点的反应性连接体的前体，如所公开的。

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