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1. 发明授权

EP2797605B1 TARGETED SELF-ASSEMBLY 0F FUNCTIONALIZED CARBON NANOTUBES ON TUMORS 有权
标题翻译：目标自组装0F功能化碳纳米管在肿瘤上的应用
公开(公告)号：EP2797605B1
公开(公告)日：2017-07-05
申请号：EP12862274.3
申请日：2012-12-28
申请人： Sloan Kettering Institute For Cancer Research , Scheinberg, David, A. , McDevitt, Michael, R. , Villa, Carlos, H. , Mulvey, J., Justin
发明人： SCHEINBERG, David, A. , MCDEVITT, Michael, R. , VILLA, Carlos, H. , MULVEY, J., Justin
IPC分类号： A61K31/713 , C12N15/113 , B82Y5/00 , A61P35/00 , G01N33/574 , B82Y30/00
CPC分类号： C12N15/113 , A61K47/6849 , A61K51/1027 , A61K51/1093 , A61K51/1203 , A61K51/1248 , B82Y5/00 , C07K16/2803 , C07K16/2887 , C07K16/30 , C07K2317/92 , C12N15/111 , C12N2310/113 , C12N2310/3233 , C12N2310/351 , C12N2320/32 , Y10S977/75 , Y10S977/842 , Y10S977/906
摘要： Provided herein are methods for delivering a molecule in situ to a cell and for treating a cancer via the in situ delivery. The methods comprise contacting or administering to the cell, as two separate components, a morpholino oligonucleotide comprising a targeting moiety followed by a single wall nanotube construct comprising second morpholino oligonucleotides complementary to the first morpholino oligonucleotides and one or both of a therapeutic or diagnostic payload molecule linked to the single wall nanotube construct. Upon self-assembly of a single wall nanotube complex via hybridization of the first morpholino and second complementary morpholino oligonucleotides at the cell, the payload molecule is delivered. Also provided is the two component self-assembly single wall nanotube system and the single wall nanotube construct comprising the second component.
摘要翻译：本文提供用于将分子原位递送至细胞并通过原位递送来治疗癌症的方法。所述方法包括将作为两个单独组分的细胞作为两个单独组分接触或施用包含靶向部分的吗啉代寡核苷酸，接着是单壁纳米管构建体，所述单壁纳米管构建体包含与第一吗啉代寡核苷酸互补的第二吗啉代寡核苷酸以及治疗性或诊断性有效负载分子与单壁纳米管构建体相连接。在通过细胞处的第一吗啉代和第二互补吗啉代寡核苷酸的杂交自组装单壁纳米管复合物后，递送有效负载分子。还提供了双组分自组装单壁纳米管系统和包含第二组分的单壁纳米管构建体。

2. 发明公开

EP1227849A2 ACTINIUM-225 COMPLEXES AND CONJUGATES FOR RADIOIMMUNOTHERAPY 审中-公开
标题翻译：锕-225情结与偶联物RADIO免疫治疗
公开(公告)号：EP1227849A2
公开(公告)日：2002-08-07
申请号：EP01922246.2
申请日：2001-02-23
申请人： Ma, Dangshe , McDevitt, Michael R. , Scheinberg, David A. , Simon, Jaime , Kiefer, Garry E. , Franck, R. Keith , Gulyas, Gyongyi
发明人： Ma, Dangshe , McDevitt, Michael R. , Scheinberg, David A. , Simon, Jaime , Kiefer, Garry E. , Franck, R. Keith , Gulyas, Gyongyi
IPC分类号： A61K51/04 , A61K51/10
CPC分类号： A61K51/1093 , A61K51/0482 , A61K51/0497 , A61K51/1027
摘要： Actinium-225 (225Ac) complexes with functionalized chelants of the formula (I) wherein: each Q is independently hydrogen or (CHR5)pCO2R; Q1 is hydrogen or (CHR5)wCO2R; each R independently is hydrogen, benzyl or C1-C4 alkyl; with the proviso that at least two of the sum of Q and Q1 must be other than hydrogen; each R5 independently is hydrogen; C¿1?-C4 alkyl or (C1-C2 alkyl)phenyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p is 1 or 2; r is 0 or 1; w is 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon to carbon bond, and the sum of r and w is 0 or 1; L is a linker/spacer group covalently bonded to, and replaces one hydrogen atom of one of the carbon atoms to which it is joined, said linker/spacer group being represented by the formula (1) wherein s is an integer of 0 or 1; t is an integer of 0 to 20 inclusive; R?1¿ is an electrophilic or nucleophilic moiety which allows for covalent attachment to an antibody or fragment thereof, or synthetic linker which can be attached to an antibody or fragment thereof, or precursor thereof; and Cyc represents a cyclic aliphatic moiety, aromatic moiety, aliphatic heterocyclic moiety, or aromatic heterocyclic moiety, each of said moieties optionally substituted with one or more groups which do not interfere with binding to an antibody or antibody fragment; with the proviso that when s, t, m, r, and n are 0, then R1 is other than carboxyl; their pharmaceutically acceptable salts, their conjugates and the use thereof for radioimmunotherapy is disclosed.

3. 发明公开

EP2797605A4 TARGETED SELF-ASSEMBLY 0F FUNCTIONALIZED CARBON NANOTUBES ON TUMORS 有权
标题翻译：靶向自行安排官能化碳纳米管对肿瘤
公开(公告)号：EP2797605A4
公开(公告)日：2015-07-08
申请号：EP12862274
申请日：2012-12-28
申请人： SLOAN KETTERING INST CANCER , SCHEINBERG DAVID A , MCDEVITT MICHAEL R , VILLA CARLOS H , MULVEY J JUSTIN
发明人： SCHEINBERG DAVID A , MCDEVITT MICHAEL R , VILLA CARLOS H , MULVEY J JUSTIN
IPC分类号： A61K31/713 , A61P35/00 , B82Y5/00 , B82Y30/00 , C12N15/113 , G01N33/574
CPC分类号： C12N15/113 , A61K47/6849 , A61K51/1027 , A61K51/1093 , A61K51/1203 , A61K51/1248 , B82Y5/00 , C07K16/2803 , C07K16/2887 , C07K16/30 , C07K2317/92 , C12N15/111 , C12N2310/113 , C12N2310/3233 , C12N2310/351 , C12N2320/32 , Y10S977/75 , Y10S977/842 , Y10S977/906
摘要： Provided herein are methods for delivering a molecule in situ to a cell and for treating a cancer via the in situ delivery. The methods comprise contacting or administering to the cell, as two separate components, a morpholino oligonucleotide comprising a targeting moiety followed by a single wall nanotube construct comprising second morpholino oligonucleotides complementary to the first morpholino oligonucleotides and one or both of a therapeutic or diagnostic payload molecule linked to the single wall nanotube construct. Upon self-assembly of a single wall nanotube complex via hybridization of the first morpholino and second complementary morpholino oligonucleotides at the cell, the payload molecule is delivered. Also provided is the two component self-assembly single wall nanotube system and the single wall nanotube construct comprising the second component.

4. 发明公开

EP2797605A2 TARGETED SELF-ASSEMBLY 0F FUNCTIONALIZED CARBON NANOTUBES ON TUMORS 有权
标题翻译：靶向自行安排官能化碳纳米管对肿瘤
公开(公告)号：EP2797605A2
公开(公告)日：2014-11-05
申请号：EP12862274.3
申请日：2012-12-28
申请人： Sloan Kettering Institute For Cancer Research , Scheinberg, David, A. , McDevitt, Michael, R. , Villa, Carlos, H. , Mulvey, J., Justin
发明人： SCHEINBERG, David, A. , MCDEVITT, Michael, R. , VILLA, Carlos, H. , MULVEY, J., Justin
IPC分类号： A61K31/713 , C12N15/113 , B82Y5/00 , A61P35/00 , G01N33/574 , B82Y30/00
CPC分类号： C12N15/113 , A61K47/6849 , A61K51/1027 , A61K51/1093 , A61K51/1203 , A61K51/1248 , B82Y5/00 , C07K16/2803 , C07K16/2887 , C07K16/30 , C07K2317/92 , C12N15/111 , C12N2310/113 , C12N2310/3233 , C12N2310/351 , C12N2320/32 , Y10S977/75 , Y10S977/842 , Y10S977/906
摘要： Provided herein are methods for delivering a molecule in situ to a cell and for treating a cancer via the in situ delivery. The methods comprise contacting or administering to the cell, as two separate components, a morpholino oligonucleotide comprising a targeting moiety followed by a single wall nanotube construct comprising second morpholino oligonucleotides complementary to the first morpholino oligonucleotides and one or both of a therapeutic or diagnostic payload molecule linked to the single wall nanotube construct. Upon self-assembly of a single wall nanotube complex via hybridization of the first morpholino and second complementary morpholino oligonucleotides at the cell, the payload molecule is delivered. Also provided is the two component self-assembly single wall nanotube system and the single wall nanotube construct comprising the second component.

5. 发明申请

WO2007120673A3 IMMUNOGENIC WT-1 PEPTIDES AND METHODS OF USE THEREOF 审中-公开
标题翻译：免疫球蛋白WT-1肽及其使用方法
公开(公告)号：WO2007120673A3
公开(公告)日：2008-11-06
申请号：PCT/US2007008853
申请日：2007-04-10
申请人： SLOAN KETTERING INST CANCER , SCHEINBERG DAVID A , MAY RENA
发明人： SCHEINBERG DAVID A , MAY RENA
IPC分类号： A61K39/00 , A61K38/16 , A61K38/17 , C07K14/00 , C07K14/47 , C12N1/00 , C12N5/10 , C12N15/11
CPC分类号： C07K7/08 , A61K38/10 , A61K38/1764 , A61K38/177 , A61K39/00 , A61K39/0011 , A61K2039/5154 , A61K2039/53 , A61K2039/57 , C07K14/4703 , C07K14/4748
摘要： This invention provides peptides, immunogenic compositions and vaccines comprising same, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising same.
摘要翻译：本发明提供了包含其的肽，免疫原性组合物和疫苗，以及包含其的表达WT1的癌症的治疗，降低发生率和诱导免疫应答的方法。

6. 发明申请

WO2005044995A3 USES OF HUMAN PEPTIDE DEFORMYLASE 审中-公开
公开(公告)号：WO2005044995A3
公开(公告)日：2005-05-19
申请号：PCT/US2004/036866
申请日：2004-11-04
申请人： SLOAN-KETTERING INSTITUTE FOR CANCER RESEARCH , SCHEINBERG, David, A. , LEE, Mona, D. , SIROTNAK, Francis, M. , ANTCZAK, Christophe , BORNMANN, William, G.
发明人： SCHEINBERG, David, A. , LEE, Mona, D. , SIROTNAK, Francis, M. , ANTCZAK, Christophe , BORNMANN, William, G.
IPC分类号： C07K2/00 , A61K38/00
摘要： This invention provides a substance derived naturally or manufactured through chemical or genetic engineering that is capable of inhibiting the removal of N-formyl group from peptides by peptide deformylase. This invention also provides a nucleic acid molecule encoding the above fragment of human peptide deformylase or its functional equivalent. This invention provides methods of identifying (1) a compound that inhibits peptide deformylase or its functional equivalent, and (2) a compound that inhibits tumor growth. The invention further provides a method of identifying a compound that inhibits tumor growth comprising comparison of the inhibitory concentration or binding affinity of the compound to a bacterial peptide deformylase with a human peptide deformylase, and this inhibitory concentration or binding of the compound to human peptide deformylase indicates a better inhibition of tumor growth. This invention provides a composition comprising an effective amount of the compound identified by the above methods and a suitable carrier.

7. 发明申请

WO2012135854A3 T CELL RECEPTOR-LIKE ANTIBODIES SPECIFIC FOR A WT1 PEPTIDE PRESENTED BY HLA-A2 审中-公开
标题翻译： T细胞受体 - HLA-A2提供的WT1肽特异性抗体
公开(公告)号：WO2012135854A3
公开(公告)日：2013-03-14
申请号：PCT/US2012031892
申请日：2012-04-02
申请人： SLOAN KETTERING INST CANCER , SCHEINBERG DAVID A , DAO TAO , LIU CHENG , YAN SU
发明人： SCHEINBERG DAVID A , DAO TAO , LIU CHENG , YAN SU
IPC分类号： C07K16/28 , A61K47/48 , G01N33/574
CPC分类号： C07K16/32 , A61K47/6849 , A61K47/6851 , A61K2039/505 , C07K16/18 , C07K16/2833 , C07K2317/21 , C07K2317/34 , C07K2317/56 , C07K2317/565 , C07K2317/567 , C07K2317/622 , C07K2317/732 , G01N33/5748
摘要： The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid/myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1/A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and/or expression levels.
摘要翻译：本发明提供特异性结合Wilms肿瘤蛋白（WT1）的抗原结合蛋白，包括针对WT1的人源化，嵌合和完全人抗体，抗体片段，嵌合抗原受体（CAR），融合蛋白及其缀合物。抗原结合蛋白和抗体结合HLA-A0201限制性WT1肽。这样的抗体，片段，融合蛋白及其结合物可用于治疗WT1相关的癌症，包括例如乳腺癌，卵巢癌，前列腺癌，慢性骨髓性白血病，多发性骨髓瘤，急性淋巴细胞性白血病（ALL），急性骨髓/ 骨髓性白血病（AML）和骨髓增生异常综合征（MDS）。在更具体的实施方案中，抗WT1 / A抗体可以包含设计用于改善蛋白质稳定性，抗体结合和/或表达水平的一个或多个框架区氨基酸取代。

8. 发明申请

WO2011060435A1 COMPOSITIONS AND METHODS FOR TREATING CANCER AND OTHER DISEASES 审中-公开
标题翻译：用于治疗癌症和其他疾病的组合物和方法
公开(公告)号：WO2011060435A1
公开(公告)日：2011-05-19
申请号：PCT/US2010/056881
申请日：2010-11-16
申请人： MEMORIAL SLOAN KETTERING CANCER CENTER , SCHEINBERG, David A. , MALLIKARATCHY, Prabodhika
发明人： SCHEINBERG, David A. , MALLIKARATCHY, Prabodhika
IPC分类号： A61K48/00 , C07H21/02
CPC分类号： C12N15/115 , A61K31/711 , C07K16/18 , C12N15/113 , C12N2310/14 , C12N2310/16
摘要： Aptamers and improved aptamers are provided with enhanced efficacy for binding to target molecules in vivo or for treating cancer or other diseases. Such improvements in aptamers are provided that enhance in vivo efficacy such as binding to the target molecule or enhancing anti-cancer activity. Such improvements also include stability to serum nucleases, reduced binding to a soluble form of the target molecule, increased avidity, affinity or specificity to the target molecule on a cell surface, increased lifetime in circulation, or any combination of the foregoing. Improvements are provided by truncation, multimerization, including at least one non-natural nucleic acid, adding a 3' or 5' polyethylene glycol, or any combination thereof. Aptamers for treatment of autoimmune diseases are also provided.
摘要翻译：提供适配体和改良的适配体具有在体内与靶分子结合或用于治疗癌症或其它疾病的增强的功效。提供了适配体的这种改善，其提高体内功效，例如结合靶分子或增强抗癌活性。这些改善还包括对血清核酸酶的稳定性，与可溶形式的靶分子的结合减少，对细胞表面上的靶分子的亲合力，亲合力或特异性的增加，循环中的寿命增加或前述的任何组合。通过截短，多聚化，包括至少一种非天然核酸，加入3'或5'聚乙二醇或其任何组合来提供改进。还提供了治疗自身免疫性疾病的适配者。

9. 发明申请

WO2005044995A2 USES OF HUMAN PEPTIDE DEFORMYLASE 审中-公开
标题翻译：使用人类胃蛋白酶
公开(公告)号：WO2005044995A2
公开(公告)日：2005-05-19
申请号：PCT/US2004036866
申请日：2004-11-04
申请人： SLOAN KETTERING INST CANCER , SCHEINBERG DAVID A , LEE MONA D , SIROTNAK FRANCIS M , ANTCZAK CHRISTOPHE , BORNMANN WILLIAM G
发明人： SCHEINBERG DAVID A , LEE MONA D , SIROTNAK FRANCIS M , ANTCZAK CHRISTOPHE , BORNMANN WILLIAM G
IPC分类号： C12N20060101 , C12N
CPC分类号： C12N9/80 , A61K38/00 , C12N15/1137 , C12N2310/14 , C12Y305/01088
摘要： This invention provides a substance derived naturally or manufactured through chemical or genetic engineering that is capable of inhibiting the removal of N-formyl group from peptides by peptide deformylase. This invention also provides a nucleic acid molecule encoding the above fragment of human peptide deformylase or its functional equivalent. This invention provides methods of identifying (1) a compound that inhibits peptide deformylase or its functional equivalent, and (2) a compound that inhibits tumor growth. The invention further provides a method of identifying a compound that inhibits tumor growth comprising comparison of the inhibitory concentration or binding affinity of the compound to a bacterial peptide deformylase with a human peptide deformylase, and this inhibitory concentration or binding of the compound to human peptide deformylase indicates a better inhibition of tumor growth. This invention provides a composition comprising an effective amount of the compound identified by the above methods and a suitable carrier.
摘要翻译：本发明提供了一种天然产生的或通过化学或遗传工程制造的物质，其能够通过肽去甲酰化酶抑制从肽中去除N-甲酰基。本发明还提供了编码人肽脱甲酰酶的上述片段或其功能等同物的核酸分子。本发明提供鉴定（1）抑制肽脱甲酰酶或其功能等价物的化合物的方法，和（2）抑制肿瘤生长的化合物。本发明还提供了鉴定抑制肿瘤生长的化合物的方法，其包括将化合物与细菌肽变性酶与人肽脱甲酰酶的抑制浓度或结合亲和性与人肽变性酶的抑制浓度或结合作用表明更好地抑制肿瘤生长。本发明提供了包含有效量的通过上述方法鉴定的化合物和合适的载体的组合物。

10. 发明申请

WO0166155A3 ACTINIUM-225 COMPLEXES AND CONJUGATES FOR RADIOIMMUNOTHERAPY 审中-公开
标题翻译： ACTINIUM-225配合物和缀合物用于放射性免疫治疗
公开(公告)号：WO0166155A3
公开(公告)日：2002-06-06
申请号：PCT/US0105927
申请日：2001-02-23
申请人： MA DANGSHE , MCDEVITT MICHAEL R , SCHEINBERG DAVID A , SIMON JAIME , KIEFER GARRY E , FRANK R KEITH , GULYAS GYONGYI
发明人： MA DANGSHE , MCDEVITT MICHAEL R , SCHEINBERG DAVID A , SIMON JAIME , KIEFER GARRY E , FRANK R KEITH , GULYAS GYONGYI
IPC分类号： A61K51/04 , A61K51/10
CPC分类号： A61K51/1093 , A61K51/0482 , A61K51/0497 , A61K51/1027
摘要： Actinium-225 ( Ac) complexes with functionalized chelants of the formula (I) wherein: each Q is independently hydrogen or (CHR )pCO2R; Q is hydrogen or (CHR )wCO2R; each R independently is hydrogen, benzyl or C1-C4 alkyl; with the proviso that at least two of the sum of Q and Q must be other than hydrogen; each R independently is hydrogen; C1-C4 alkyl or (C1-C2 alkyl)phenyl; X and Y are each independently hydrogen or may be taken with an adjacent X and Y to form an additional carbon-carbon bond; n is 0 or 1; m is an integer from 0 to 10 inclusive; p is 1 or 2; r is 0 or 1; w is 0 or 1; with the proviso that n is only 1 when X and/or Y form an additional carbon to carbon bond, and the sum of r and w is 0 or 1; L is a linker/spacer group covalently bonded to, and replaces one hydrogen atom of one of the carbon atoms to which it is joined, said linker/spacer group being represented by the formula (1) wherein s is an integer of 0 or 1; t is an integer of 0 to 20 inclusive; R is an electrophilic or nucleophilic moiety which allows for covalent attachment to an antibody or fragment thereof, or synthetic linker which can be attached to an antibody or fragment thereof, or precursor thereof; and Cyc represents a cyclic aliphatic moiety, aromatic moiety, aliphatic heterocyclic moiety, or aromatic heterocyclic moiety, each of said moieties optionally substituted with one or more groups which do not interfere with binding to an antibody or antibody fragment; with the proviso that when s, t, m, r, and n are 0, then R is other than carboxyl; their pharmaceutically acceptable salts, their conjugates and the use thereof for radioimmunotherapy is disclosed.
摘要翻译：吖啶-225（225Ac）与式（I）的官能化螯合剂络合，其中：每个Q独立地为氢或（CHR 5）pCO 2 R; Q 1是氢或（CHR 5）wCO 2 R; 每个R独立地为氢，苄基或C 1 -C 4烷基; 条件是Q和Q 1的总和中的至少两个必须不是氢; 每个R 5独立地为氢; C1-C4烷基或（C1-C2烷基）苯基; X和Y各自独立地为氢或可以与相邻的X和Y一起形成额外的碳 - 碳键; n是0或1; m是从0到10的整数，包括0和10; p是1或2; r是0或1; w是0或1; 条件是当X和/或Y形成另外的碳 - 碳键时，n仅为1，并且r和w之和为0或1; L是与其所连接的碳原子中的一个碳原子共价键合并且取代其中一个碳原子的一个氢原子的连接基团/间隔基团，所述连接基团/间隔基团由式（1）表示，其中s是0或1的整数 ; t是0〜20的整数， R 1是允许共价连接至抗体或其片段或可以连接至抗体或其片段或其前体的合成连接体的亲电或亲核部分; 并且Cyc表示环状脂族部分，芳族部分，脂族杂环部分或芳族杂环部分，所述部分中的每一个任选地被一个或多个不干扰与抗体或抗体片段结合的基团取代; 条件是当s，t，m，r和n为0时，则R 1不是羧基; 其药学上可接受的盐，它们的缀合物及其用于放射免疫疗法的用途。

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