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1. 发明公开

EP3033150A1 ADMINISTRATION OF KARENITECIN FOR THE TREATMENT OF ADVANCED OVARIAN CANCER, INCLUDING CHEMOTHERAPY-RESISTANT AND/OR THE MUCINOUS ADENOCARCINOMA SUB-TYPES 审中-公开
标题翻译： Karenitecin用于治疗晚期卵巢癌，与化疗耐药性亚型和/或亚型粘液腺癌管理
公开(公告)号：EP3033150A1
公开(公告)日：2016-06-22
申请号：EP14836702.2
申请日：2014-08-10
申请人： BIONUMERIK PHARMACEUTICALS, INC.
发明人： HAUSHEER, Frederick H.
IPC分类号： A61P35/00
CPC分类号： A61K31/4745 , A61K31/185 , A61K45/06 , A61K2300/00
摘要： The present invention discloses and claims methods and compositions for the treatment of platinum and/or taxane cancer treating agent-resistanf-refractory sub-populations and/or the mucinous adenocarcinoma sub-type of ovarian cancer subjects with the silicon-containing highly lipophilic camptothecin derivative (HLCD), Karenitecin (also known as BNP1350; cositecan; 7-[(2'-trimethylsilyl) ethyl]-20(S) camptothecin). The administration of Karenitecin by intravenous (i.v.) and/or oral methodologies are also disclosed and claimed.
摘要翻译：本发明盘松动和权利要求的新的药物组合物，方法，以及用于试剂盒的同期，非均相-orriented，多靶向治疗修饰和/或细胞代谢异常或其它不希望的生理状况，包括癌症，其中正常细胞生物化学的调制功能和/或各种蛋白质/酶的表达水平（即，目标分子）是异常的，必须被修改和/或为了治疗代谢异常论文或其他不期望的生理条件下，包括癌症调制。上述目标分子，通过非限制性实施例的方式，包括：间变性淋巴瘤激酶（ALK），间充质上皮转化（MET）激酶，受体酪氨酸激酶（ROS1），表皮生长因子受体（EGFR），过氧化物酶（的Prx），切除修复交叉互补蛋白1（ERCC1），胰岛素生长因子1受体（IGF1R），核糖核苷酸还原酶（RNR），微管蛋白，法尼基转移酶，和各种其它的类蛋白质/酶。此外，本发明盘松动和权利要求的方法和用于：（a）的受试者进行治疗的选择包; （B）的最有效的药剂（或多个）的确定，以在联合施用与施用含硫，氨基本发明的酸 - 特异性小分子; （C）的药用剂施用的剂量; （D）的长度和/或治疗周期的数目的确定; （E）所使用的特定药剂（S）和在治疗过程中，给药剂量的调整; 和/或（f）确定该特定疾病的潜在治疗响应从一个或多个类型的选择用于施用至患有该药剂（S）：（ⅰ）癌症或（ii）的代谢异常或其它不希望的生理定量条件由确定性采矿上述目标分子的任何组合的异常生化活性和/或异常表达的水平; 通过使用定量测量的方法论，包括但不限于：荧光原位杂交（FISH），核酸微阵列分析，免疫组织化学（IHC），放射免疫测定（RIA），免疫荧光定量和/或自动化定量分析; ELISA和流动cytometry-基础的分析; PCR加上MS途径; 质谱基于光谱的方法; 和X射线晶体学，以及其他相关的分析方法。

2. 发明授权

EP1991237B1 CHEMOPROTECTIVE METHODS AND COMPOSITIONS 有权转让
标题翻译：化学保护方法和组合物
公开(公告)号：EP1991237B1
公开(公告)日：2015-02-25
申请号：EP06848549.9
申请日：2006-12-13
申请人： BIONUMERIK PHARMACEUTICALS, INC.
发明人： HAUSHEER, Frederick, H.
IPC分类号： A61P39/00 , A61K31/185 , A61K31/337
CPC分类号： A61K31/185 , A61K31/255

3. 发明公开

EP1694242A4 PHARMACEUTICAL FORMULATIONS OF CAMPTOTHECINS AND PROCESS FOR MAKING SAME 有权
标题翻译： CAMPOTHECINEN和方法的药物制剂
公开(公告)号：EP1694242A4
公开(公告)日：2011-11-02
申请号：EP04800502
申请日：2004-11-01
申请人： BIONUMERIK PHARMACEUTICALS INC
发明人： HAUSHEER FREDERICK H , WANG JIANYAN , KOCHAT HARRY
IPC分类号： A61K9/08 , A61F2/00 , A61K9/00 , A61K31/4745 , A61K47/10 , A61K47/12 , A61K47/18 , A61K47/22 , A61K47/26
CPC分类号： A61K31/4745 , A61K9/0019 , A61K9/08 , A61K47/10 , A61K47/12 , A61K47/18 , A61K47/22 , A61K47/26

4. 发明公开

EP2249826A1 COMPOSITIONS AND METHODS OF USE OF COMPOUNDS TO INCREASE CANCER PATIENT SURVIVAL TIME 有权转让
标题翻译：组合物及其化合物的癌症患者生存时间的延长使用方法
公开(公告)号：EP2249826A1
公开(公告)日：2010-11-17
申请号：EP08794507.7
申请日：2008-07-15
申请人： BIONUMERIK PHARMACEUTICALS, INC.
发明人： HAUSHEER, Frederick, H.
IPC分类号： A61K31/255
CPC分类号： A61K31/255
摘要： The present invention discloses and claims compositions, methods of treatment, and kits which cause an increase in time of survival in cancer patients, wherein the cancer either: (i) overexpresses thioredoxin or glutaredoxin and/or (ii) exhibits evidence of thioredoxin- or glutaredoxin-mediated resistance to one or more chemotherapeutic interventions. The present invention also discloses and claims methods and kits for the administration of said compositions to properly treat cancer patients. Additionally, the present invention discloses and claims methods and kits for quantitatively determining the level of expression of thioredoxin or glutaredoxin in the cancer cells of a cancer patient, methods of using those determined levels in the initial diagnosis and/or planning of subsequent treatment methodologies for said cancer patient, as well as ascertaining the potential growth 'aggressiveness' of the particular cancer and treatment responsiveness of the particular type of cancer. Further, the present invention discloses and claims novel pharmaceutical compositions, methods, and kits used for the treatment of patients with medical conditions and disease where there is the overexpression of thioredoxin and/or glutaredoxin, and wherein this overexpression is associated with deleterious physiological effects in the patients.

5. 发明公开

EP2197279A4 C10-SUBSTITUTED CAMPTOTHECIN ANALOGS 有权
标题翻译： C10-SUBSTITUIERTE CAMPTOTHECIN-ANALOGE
公开(公告)号：EP2197279A4
公开(公告)日：2010-10-13
申请号：EP07852779
申请日：2007-10-16
申请人： BIONUMERIK PHARMACEUTICALS INC
发明人： NARKUNAN KESAVARAM , CHEN XINGHAI , KOCHAT HARRY , HAUSHEER FREDERICK
IPC分类号： A01N43/42 , A61K31/44 , A61P35/00
CPC分类号： A61K31/44

6. 发明公开

EP2197279A1 C10-SUBSTITUTED CAMPTOTHECIN ANALOGS 有权
标题翻译： C10-取代的喜树碱类似物
公开(公告)号：EP2197279A1
公开(公告)日：2010-06-23
申请号：EP07852779.3
申请日：2007-10-16
申请人： BIONUMERIK PHARMACEUTICALS, INC.
发明人： NARKUNAN, Kesavaram , CHEN, Xinghai , KOCHAT, Harry , HAUSHEER, Frederick
IPC分类号： A01N43/42 , A61K31/44
CPC分类号： A61K31/44
摘要： The novel C10-modified camptothecin analogs, and pharmaceutically-acceptable salts thereof, of the present invention: (i) possess potent antitumor activity (i.e., in nanomolar or subnanomolar concentrations) for inhibiting the growth of human and animal tumor cells in vitro; (ii) are potent inhibition of Topoisomerase I; (iii) lack of susceptibility to MDR/MRP drug resistance; (iv) require no metabolic drug activation: (v) lack glucuronidation of the A-ring or B-ring; (vi) reduce drug-binding affinity to plasma proteins; (vii) maintain lactone stability; (viii) maintain drug potency; and (ix) possess a low molecular weight (e.g., MW

7. 发明公开

EP1896491A4 MONOAZOLE LIGAND PLATINUM ANALOGS 有权
标题翻译： PLATINANALOGA MIT MONOAZOLLIGAND
公开(公告)号：EP1896491A4
公开(公告)日：2009-12-09
申请号：EP06719723
申请日：2006-01-26
申请人： BIONUMERIK PHARMACEUTICALS INC
发明人： XIAO ZEJUN , KOCHAT HARRY , HAUSHEER FREDERICK
IPC分类号： C07D237/30 , A61K31/7135 , A61P35/00 , C07D237/32 , C07D249/18 , C07D257/04
CPC分类号： C07F15/0093

8. 发明公开

EP1896492A2 PLATINUM COMPLEXES WITH MONONITRILE-CONTAINING LIGANDS 有权
标题翻译：与MONONITRILHALTIGEN配体铂络合物
公开(公告)号：EP1896492A2
公开(公告)日：2008-03-12
申请号：EP06733954.9
申请日：2006-01-26
申请人： BIONUMERIK PHARMACEUTICALS, INC.
发明人： XIAO, Zejun , HAUSHEER, Frederick, H. , PETLURU, Pavankumar
IPC分类号： C07F15/00 , A61K31/28
CPC分类号： C07F15/0093
摘要： Disclosed herein are novel platinum-based complexes possessing one nitrile substituent group (mononitrile) covalently-bonded to the platinum, one or more nitrogen donor ligands capable of forming hydrogen bonds with the bases in DNA or RNA and leaving groups (i.e., L1 and L2 )which can be hydrolyzed in vivo to active species, which can then form coordinate adducts with DNA or RNA at the Guanine or Adenine bases thereof. Also disclosed herein are the reaction schemes for the synthesis of said platinum complexes, as well as methods of treatment of various types of cancer by the administration of a pharmaceutically-effective dose of said novel platinum complexes.

9. 发明公开

EP1896491A2 MONOAZOLE LIGAND PLATINUM ANALOGS 有权
标题翻译：单偶氮配体铂类似物
公开(公告)号：EP1896491A2
公开(公告)日：2008-03-12
申请号：EP06719723.6
申请日：2006-01-26
申请人： BIONUMERIK PHARMACEUTICALS, INC.
发明人： XIAO, Zejun , KOCHAT, Harry , HAUSHEER, Frederick
IPC分类号： C07F15/00 , A61K31/555
CPC分类号： C07F15/0093
摘要： Disclosed herein are novel platinum-based analogs with a single substituted azole ligand: RN=NR7, wherein the RN=NR7 functional group is covalently bonded to the platinum through nitrogen of NR7. The analogs also have nitrogen donor ligands capable of forming hydrogen bonds with the bases in DNA or RNA, and one or more leaving groups which can be displaced by water, hydroxide ions or other nucleophiles, which is thought to form active species in vivo, and then, form cross-linked complexes between nucleic acid strands, principally between purines in DNA (or RNA), i.e., at the Guanine or Adenine bases, thereof. These platinum analogs may also be more easily transported into tumor cells, due to their increased lipophilicity and are likely to be useful as anti¬ neoplastic agents, and in modulating or interfering with the synthesis or replication or transcription of DNA or translation or function of RNA in vitro or in vivo, as they are potentially capable of forming a platinum coordinate complex with an intact or nascent DNA or RNA and thereby interfering with cellular synthesis, transcription or replication of nucleic acid polynucleotides.
摘要翻译：本文公开了具有单个取代的吡咯配体的新型铂基类似物：RN = NR7，其中RN = NR7官能团通过NR7的氮共价键合至铂。类似物还具有能够与DNA或RNA中的碱基形成氢键的氮供体配体和可以被水，氢氧根离子或其他亲核试剂取代的一个或多个离去基团，其被认为在体内形成活性物质，并且然后在核酸链之间形成交联复合物，主要是在DNA（或RNA）中的嘌呤，即在其鸟嘌呤或腺嘌呤碱基之间。由于其亲脂性增加，这些铂类似物也可以更容易地转运到肿瘤细胞中，并且可能用作抗肿瘤剂，并且调节或干扰DNA的合成或复制或转录或RNA的翻译或功能因为它们可能能够与完整或新生的DNA或RNA形成铂配位络合物，从而干扰核酸多核苷酸的细胞合成，转录或复制。

10. 发明授权

EP1301477B1 PROCEDE DE PREPARATION DU 2,2'-DITHIOBIS(ETHANESULFONATE) DE DISODIUM 有权
标题翻译：用于生产DISODIUM 2,2'-二硫代双（乙磺酸）
公开(公告)号：EP1301477B1
公开(公告)日：2004-09-29
申请号：EP01954111.9
申请日：2001-07-17
申请人： BIONUMERIK PHARMACEUTICALS, INC.
发明人： CAZAUX, Jean-Bernard , MANGINOT, Eric , VEYRAT, Marc
IPC分类号： C07C319/24 , C07C319/02 , C07C323/66
CPC分类号： C07C319/02 , C07C319/24 , C07C323/66
摘要： The invention concerns a novel method for industrial preparation of disodium 2,2'-dithiobis(alkylsulphonates), and in particular disodium 2,2'-dithiobis(ethanesulphate) (dimesna). Said novel method is summarised by the reaction diagram (A). In diagram (A), Hal represents a halogen atom, and preferably a bromine atom; M represents a sodium or potassium atom; and n represents an integer ranging between 0 and 2.

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