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1. 发明公开

EP0698203A4 METHOD FOR SELECTIVE OPENING OF ABNORMAL BRAIN TISSUE CAPILLARIES 失效
标题翻译：方法脑组织毛细血管异常选择性打开
公开(公告)号：EP0698203A4
公开(公告)日：1997-02-26
申请号：EP94915822
申请日：1994-04-19
申请人： BLACK KEITH L
发明人： BLACK KEITH L
IPC分类号： A61K38/17 , A61K38/04 , A61P9/08 , G01N1/00 , A61K38/00
CPC分类号： A61K38/043

2. 发明公开

EP0698203A1 METHOD FOR SELECTIVE OPENING OF ABNORMAL BRAIN TISSUE CAPILLARIES 失效
标题翻译：方法脑组织毛细血管异常选择性打开
公开(公告)号：EP0698203A1
公开(公告)日：1996-02-28
申请号：EP94915822.0
申请日：1994-04-19
申请人： BLACK, Keith L.
发明人： BLACK, Keith L.
IPC分类号： A61K38 , A61P9
CPC分类号： A61K38/043
摘要： A method for selectively opening abnormal brain tissue capillaries of a mammal in order to allow selective passage of both low and high molecular weight neuropharmaceutical agents into abnormal brain tissue. The method utilizes direct infusion of bradykinin into the carotid artery. The dose of bradykinin is maintained at levels which provide opening of abnormal brain tissue capillaries without opening normal brain capillaries. The method is useful for introducing a wide variety of neuropharmaceutical agents selectively to brain tumors and other abnormal brain tissue.

3. 发明授权

EP0698203B1 COMPOSITION COMPRISING BRADYKININ FOR SELECTIVE OPENING OF ABNORMAL BRAIN TISSUE CAPILLARIES 失效
标题翻译：异常的脑组织毛细血管组成含缓激肽选择性打开
公开(公告)号：EP0698203B1
公开(公告)日：2002-07-10
申请号：EP94915822.4
申请日：1994-04-19
申请人： BLACK, Keith L.
发明人： BLACK, Keith L.
IPC分类号： A61K38/08 , A61P9/08
CPC分类号： A61K38/043
摘要： A method for selectively opening abnormal brain tissue capillaries of a mammal in order to allow selective passage of both low and high molecular weight neuropharmaceutical agents into abnormal brain tissue. The method utilizes direct infusion of bradykinin into the carotid artery. The dose of bradykinin is maintained at levels which provide opening of abnormal brain tissue capillaries without opening normal brain capillaries. The method is useful for introducing a wide variety of neuropharmaceutical agents selectively to brain tumors and other abnormal brain tissue.

4. 发明申请

WO2008039974A3 CANCER VACCINES AND VACCINATION METHODS 审中-公开
公开(公告)号：WO2008039974A3
公开(公告)日：2008-07-17
申请号：PCT/US2007079857
申请日：2007-09-28
申请人： CEDARS SINAI MEDICAL CENTER , TORREY PINES INST , YU JOHN S , LIU GENTAO , ZHU HUI PH D , PINILLA CLEMENCIA , BLACK KEITH L
发明人： YU JOHN S , LIU GENTAO , ZHU HUI PH D , PINILLA CLEMENCIA , BLACK KEITH L
IPC分类号： A61K35/12 , A61K35/00 , C12N15/85 , C12N15/86
CPC分类号： A61K39/0011 , A61K2035/124 , A61K2039/5154 , A61K2039/545 , C12N5/0639 , C12N2501/22 , C12N2501/23 , C12N2501/2304 , C12N2501/25 , C12N2501/998 , C12N2506/11
摘要： Methods and compositions for treating cancers (e.g., neural cancers) by dendritic cell vaccination are provided herein.

5. 发明申请

WO2008039969A2 CANCER VACCINES AND VACCINATION METHODS 审中-公开
标题翻译：癌症疫苗和疫苗接种方法
公开(公告)号：WO2008039969A2
公开(公告)日：2008-04-03
申请号：PCT/US2007/079846
申请日：2007-09-28
申请人： CEDARS-SINAI MEDICAL CENTER , YU, John, S. , LIU, Gentao , ZHU, Hui, Ph.D. , BLACK, Keith, L.
发明人： YU, John, S. , LIU, Gentao , ZHU, Hui, Ph.D. , BLACK, Keith, L.
IPC分类号： A61K39/00
CPC分类号： A61K39/0011 , A61K2035/124 , A61K2039/5154 , A61K2039/545 , C12N5/0639 , C12N2501/22 , C12N2501/23 , C12N2501/2304 , C12N2501/25 , C12N2501/998 , C12N2506/11
摘要： Methods and compositions for treating cancers (e.g., neural cancers) by dendritic cell vaccination are provided herein.
摘要翻译：本文提供了通过树突状细胞疫苗接种治疗癌症（如神经癌）的方法和组合物。

6. 发明申请

WO2012139030A1 POLYMALIC ACID BASED NANOCONJUGATES FOR IMAGING 审中-公开
标题翻译：基于聚合酸的纳米颗粒成像
公开(公告)号：WO2012139030A1
公开(公告)日：2012-10-11
申请号：PCT/US2012/032573
申请日：2012-04-06
申请人： CEDARS-SINAI MEDICAL CENTER , BLACK, Keith L. , LJUBIMOVA, Julia Y. , LJUBIMOV, Alexander V. , HOLLER, Eggehard
发明人： BLACK, Keith L. , LJUBIMOVA, Julia Y. , LJUBIMOV, Alexander V. , HOLLER, Eggehard
IPC分类号： A61K49/00 , C07C211/00
CPC分类号： A61K49/16 , A61K47/593 , A61K49/128
摘要： Nanoconjugates include a polymalic-based molecular scaffold with one or more imaging moiety and one or more targeting modules attached to the scaffold. At least one imaging moiety and at least one targeting module is conjugated to the polymalicacid based molecular scaffold. Methods of synthesizing the nanoconjugate involve providing a polymalic acid having a plurality of pendant carboxyi groups. The method reacts a compound containing sulfhydryl groups and amino acid groups through the pendant carboxyi groups to add sulfhydryl groups to the polymalic acid to form an activated polymalic acid. The method reacts at least one imaging moiety containing a sulfhydryl binding group to the activated polymalic acid to form a preconjugate. The method may involve administering to the subject a nanoconjugate that includes a polymalic acid-based molecular scaffold, at least one imaging moiety, and at least one targeting module.
摘要翻译：纳米缀合物包括具有一个或多个成像部分和连接到支架的一个或多个靶向模块的基于聚丙烯的分子支架。至少一个成像部分和至少一个靶向模块与基于聚缩水甘油的分子支架缀合。合成纳米缀合物的方法涉及提供具有多个侧链羧基的聚丙酸。该方法通过侧基羧基将含有巯基和氨基酸的化合物反应，以向聚丙酸中加入巯基以形成活化的聚丙酸。该方法将含有巯基结合基团的至少一个成像部分与活化的聚丙酸反应形成预共轭物。该方法可以包括向受试者施用包括基于聚丙酸的分子支架，至少一个成像部分和至少一个靶向模块的纳米缀合物。

7. 发明申请

WO2010075525A1 METHOD OF USING TUMOR CELL DEBRIS TO REDUCE BRAIN TUMOR RECURRENCE OR GROWTH 审中-公开
标题翻译：使用肿瘤细胞切除术减少脑肿瘤复发或生长的方法
公开(公告)号：WO2010075525A1
公开(公告)日：2010-07-01
申请号：PCT/US2009/069437
申请日：2009-12-23
申请人： CEDARS-SINAI MEDICAL CENTER , MORRIS-IRVIN, Dwain , BLACK, Keith, L.
发明人： MORRIS-IRVIN, Dwain , BLACK, Keith, L.
IPC分类号： A61K35/30 , A61K39/395
CPC分类号： A61K35/30 , A61K39/0011 , A61K2039/55511 , A61K2039/55561 , A61K2039/55572
摘要： The present invention describes compositions comprising tumor cell debris, tumor lysate or tumor antigens and methods of using tumor cell debris, tumor lysate or tumor antigens for stimulating a specific immune response. The compositions may further comprise at least one TLR ligand. The stimulation of the specific immune response may be used to treat tumors, particularly, brain tumors. The treatment method may also reduce the recurrence of a tumor and/or inhibit or slow down the growth of a tumor.
摘要翻译：本发明描述了包含肿瘤细胞碎片，肿瘤裂解物或肿瘤抗原的组合物以及使用肿瘤细胞碎片，肿瘤裂解物或肿瘤抗原刺激特异性免疫应答的方法。组合物还可以包含至少一种TLR配体。特异性免疫应答的刺激可用于治疗肿瘤，特别是脑肿瘤。治疗方法还可以减少肿瘤的复发和/或抑制或减缓肿瘤的生长。

8. 发明申请

WO2005028617A3 ANTISENSE INHIBITION OF LAMININ-8 EXPRESSION TO INHIBIT HUMAN GLIOMAS 审中-公开
公开(公告)号：WO2005028617A3
公开(公告)日：2005-03-31
申请号：PCT/US2004/029956
申请日：2004-09-13
申请人： ARROGENE, INC. , LJUBIMOVA, Julia, Y. , LJUBIMOVA, Alexander, V. , BLACK, Keith, L.
发明人： LJUBIMOVA, Julia, Y. , LJUBIMOVA, Alexander, V. , BLACK, Keith, L.
IPC分类号： C12Q1/68
摘要： Using gene array technology, we observed that an increase of the α4 chain- containing Laminin-8 correlated with poor prognosis for patients with brain gliomas. We established that inhibition of Laminin-8 expression by a new generation of highly specific and stable antisense oligonucleotides (Morpholino TM ) against chains of Laminin-8 could slow or stop the spread of glioma. This was demonstrated in an in vitro model using human glioblastoma multiforme cell lines M059K and U-87MG co-cultured with normal human brain microvascular endothelial cells (HBMVEC). Using Western blot analysis and immunohistochemistry, we confirmed that antisense treatment effectively blocked laminin-8 protein synthesis. Antisense oligonucleotides against both α4 and ß1 chains of laminin-8 blocked significantly the invasion of co-cultures through Matrigel. The results show that Laminin-8 may not only contribute to glioma progression and recurrence as part of the neovascularization process but also by directly increasing the invasive potential of tumor cells.

9. 发明申请

WO2011072240A1 DRUG DELIVERY OF TEMOZOLOMIDE FOR SYSTEMIC BASED TREATMENT OF CANCER 审中-公开
标题翻译：药物输送用于基于系统的癌症治疗的TEMOZOLOMIDE
公开(公告)号：WO2011072240A1
公开(公告)日：2011-06-16
申请号：PCT/US2010/059919
申请日：2010-12-10
申请人： CEDARS-SINAI MEDICAL CENTER , PATIL, Rameshwar , HOLLER, Eggehard , BLACK, Keith L. , LJUBIMOVA, Julia, Y.
发明人： PATIL, Rameshwar , HOLLER, Eggehard , BLACK, Keith L. , LJUBIMOVA, Julia, Y.
IPC分类号： A01N43/52 , A61K31/425
CPC分类号： A61K47/593 , A61K31/4188 , A61K31/425 , A61K47/48061 , A61K47/48215 , A61K47/48246 , A61K47/48338 , A61K47/48384 , A61K47/48561 , A61K47/48584 , A61K47/48623 , A61K47/48669 , A61K47/48692 , A61K47/545 , A61K47/60 , A61K47/64 , A61K47/65 , A61K47/6803 , A61K47/6849 , A61K47/6851 , A61K47/6855 , A61K47/6865 , A61K47/6877 , A61K47/6883 , A61K47/6889 , A61K47/6898 , C07K16/2881 , C07K16/3015 , C07K16/3053 , C07K2317/24 , C07K2317/77
摘要： The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety. The present invention relates to methods of drug delivery for the treatment of a condition or disease, such as cancer. In one embodiment, the invention provides a method of preparing a multifunctional nanoconjugate of temozolomide (TMZ) by conjugating TMZ in its hydrazide form to a polymalic acid platform. In another embodiment, the polymalic acid platform is conjugated to a monoclonal antibody to transferrin receptor, a trileucine (LLL) moiety, and/or a polyethylene glycol (PEG) moiety.
摘要翻译：本发明涉及用于治疗诸如癌症的疾病或疾病的药物递送方法。在一个实施方案中，本发明提供了通过将其酰肼形式的TMZ与聚马来酸平台结合来制备替莫唑胺（TMZ）的多功能纳米缀合物的方法。在另一个实施方案中，聚马来酸平台与转铁蛋白受体的单克隆抗体，三聚亮氨酸（LLL）部分和/或聚乙二醇（PEG）部分缀合。本发明涉及用于治疗诸如癌症的疾病或疾病的药物递送方法。在一个实施方案中，本发明提供了通过将其酰肼形式的TMZ与聚马来酸平台结合来制备替莫唑胺（TMZ）的多功能纳米缀合物的方法。在另一个实施方案中，聚马来酸平台与转铁蛋白受体的单克隆抗体，三聚亮氨酸（LLL）部分和/或聚乙二醇（PEG）部分缀合。

10. 发明申请

WO2010028066A3 CD133 EPITOPES 审中-公开
公开(公告)号：WO2010028066A3
公开(公告)日：2010-03-11
申请号：PCT/US2009/055759
申请日：2009-09-02
申请人： CEDARS-SINAI MEDICAL CENTER , YU, John S. , LIU, Gentao , BLACK, Keith L.
发明人： YU, John S. , LIU, Gentao , BLACK, Keith L.
IPC分类号： C07K14/705 , C07K7/06 , A61K39/00 , A61P35/00
摘要： An immunogen includes an isolated peptide of 800 amino acid residues or fewer having the amino sequence ILSAFSVYV (SEQ ID NO:1) with four or fewer amino acid substitutions, a superagonist variant of SEQ ID NO:1, or an amino acid sequence having the formula: (I/K/T/V/M)-L-(S/L)-(A/E/N/D/Q)-(F/V)-(S/M/V/I)-(V/D/R/G/H)-Y-(V/I/L) (SEQ ID NO:13). The immunogens can be used in compositions and in the treatment of disorders.

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