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1. 发明申请

WO2008073615A3 N-GLYCOSYLATION MUTANT OF MELANOMA DIFFERENTIATION ASSOCIATED GENE-7 审中-公开
公开(公告)号：WO2008073615A3
公开(公告)日：2008-06-19
申请号：PCT/US2007/083491
申请日：2007-11-02
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , GOPALKRISHNAN, Rahul, V. , SAUANE, Moira , FISHER, Paul, B.
发明人： GOPALKRISHNAN, Rahul, V. , SAUANE, Moira , FISHER, Paul, B.
IPC分类号： C07H21/04 , C07H21/02 , C12N15/11 , C07K14/00 , A61K39/00
摘要： The present invention relates to MDA-7 variant proteins which are deficient in or lack glycosylation. It is based, at least in part, on the results of experiments which have demonstrated that such variants are functionally equivalent to wild-type MDA-7 protein. Such proteins may be more easily produced large-scale than the wild-type protein, and may be found to be less immunogenic (thereby facilitating treatment, especially repeated treatments). Accordingly, the present invention provides for such proteins ("Gly(def)MDA-7 proteins"), nucleic acids encoding them ("Gly(def)mda-7 nucleic acids), pharmaceutical compositions comprising such proteins or nucleic acids, and related methods of treatment.

2. 发明申请

WO2004005481A2 METHODS FOR IDENTIFYING MODULATORS OF MDA-7 MEDIATED APOPTOSIS 审中-公开
标题翻译：鉴定MDA-7介导的细胞凋亡的调节剂的方法
公开(公告)号：WO2004005481A2
公开(公告)日：2004-01-15
申请号：PCT/US2003/021237
申请日：2003-07-03
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B. , SARKAR, Devanand , GOPALKRISHNAN, Rahul, V. , SAUANE, Moira
发明人： FISHER, Paul, B. , SARKAR, Devanand , GOPALKRISHNAN, Rahul, V. , SAUANE, Moira
IPC分类号： C12N
CPC分类号： G01N33/5011 , C07K14/54 , G01N33/5041 , G01N2510/00
摘要： The present invention relates to the discoveries that apoptotic effects of the melanoma differentiation associated gene mda -7 (also known as interleukin-24, "IL-24") on malignant cells occur via the p38 MAPK pathway and members of the Growth Arrest and DNA Damage ("GADD") gene family but are substantially independent of the JAK/STAT pathway. Accordingly, the invention provides for methods for identifying apoptosis-modulating agents using assay methods which determine the ability of a test agent to increase or decrease expression of constituents of the mda -7 apoptosis pathway, preferably in a JAK/STAT substantially independent manner. Such agents may be small molecules or may be fragments, variants and/or derivatives of native MDA-7.
摘要翻译：本发明涉及发现黑色素瘤分化相关基因mda-7（也称为白细胞介素-24，“IL-24”）的凋亡作用对恶性细胞经由p38MAPK途径和生长停滞和DNA损伤（“GADD”）基因家族成员发生，但基本上与JAK / STAT途径无关。因此，本发明提供了使用测定方法鉴定凋亡调节剂的方法，所述测定方法确定测试剂增加或减少mda-7凋亡途径成分表达的能力，优选在JAK / STAT基本上独立的方式。这样的药剂可以是小分子或可以是天然MDA-7的片段，变体和/或衍生物。

3. 发明申请

WO2003022212A2 ANTI-TUMOR EFFECTS OF PROSTATE CARCINOMA TUMOR ANTIGEN-1 审中-公开
标题翻译：前列腺癌肿瘤抗原的抗肿瘤作用1
公开(公告)号：WO2003022212A2
公开(公告)日：2003-03-20
申请号：PCT/US2002/028587
申请日：2002-09-06
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B. , GOPALKRISHNAN, Rahul, V.
发明人： FISHER, Paul, B. , GOPALKRISHNAN, Rahul, V.
IPC分类号： A61K
CPC分类号： A61K38/19 , A01K2217/05 , A61K48/00 , C12N2799/021 , A61K2300/00
摘要： The present invention relates to methods of inhibiting the proliferation and/or metastasis of a cancer cell by administering, to the cancer cell, a molecule which increases, in the cell or at the cell surface, the amount of a Bivalent Prostate Carcinoma Tumor Antigen-1 ("B-PCTA-1") protein (referred to as "bivalent" because it comprises both carbohydrate recognition domains ("CRDs")). It is based, at least in part, on the discovery that increased expression of the full-length open reading frame of the PCTA-1 gene suppressed proliferation of tumor cells in soft agar (a characteristic associated with malignancy and tumor metastasis), whereas increased expression of a PCTA-1 gene lacking the second CRD-encoding region had the opposite effect, increasing the anchorage-independent proliferation of the tumor cells.
摘要翻译：本发明涉及通过向癌细胞施用在细胞中或在细胞表面增加二价前列腺癌肿瘤抗原基因的量的分子来抑制癌细胞的增殖和/或转移的方法， 1（“B-PCTA-1”）蛋白（称为“二价”，因为它包含碳水化合物识别结构域（“CRD”））。至少部分是基于PCTA-1基因全长开放阅读框的增加表达抑制软琼脂中肿瘤细胞增殖（与恶性肿瘤和肿瘤转移相关的特征）的发现，而增加缺乏第二CRD编码区的PCTA-1基因的表达具有相反的作用，增加了肿瘤细胞的锚定依赖性增殖。

4. 发明申请

WO2003022212A3 ANTI-TUMOR EFFECTS OF PROSTATE CARCINOMA TUMOR ANTIGEN-1 审中-公开
公开(公告)号：WO2003022212A3
公开(公告)日：2003-03-20
申请号：PCT/US2002/028587
申请日：2002-09-06
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B. , GOPALKRISHNAN, Rahul, V.
发明人： FISHER, Paul, B. , GOPALKRISHNAN, Rahul, V.
IPC分类号： A61K48/00
摘要： The present invention relates to methods of inhibiting the proliferation and/or metastasis of a cancer cell by administering, to the cancer cell, a molecule which increases, in the cell or at the cell surface, the amount of a Bivalent Prostate Carcinoma Tumor Antigen-1 ("B-PCTA-1") protein (referred to as "bivalent" because it comprises both carbohydrate recognition domains ("CRDs")). It is based, at least in part, on the discovery that increased expression of the full-length open reading frame of the PCTA-1 gene suppressed proliferation of tumor cells in soft agar (a characteristic associated with malignancy and tumor metastasis), whereas increased expression of a PCTA-1 gene lacking the second CRD-encoding region had the opposite effect, increasing the anchorage-independent proliferation of the tumor cells.

5. 发明申请

WO2004016732A2 ASTROCYTE MODULATED GENES AND USES THEREOF 审中-公开
标题翻译： ASTROCYTE MODULATED GENES AND ANDESES THEREOF
公开(公告)号：WO2004016732A2
公开(公告)日：2004-02-26
申请号：PCT/US2003/011887
申请日：2003-04-17
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B. , SU, Zao-Zhong , KANG, Dong-Chul
发明人： FISHER, Paul, B. , SU, Zao-Zhong , KANG, Dong-Chul
IPC分类号： C12N
CPC分类号： C07K14/47
摘要： The present invention relates to Astrocyte Modulated Genes ( AMGs ). AMGs are genes whose expression are modulated in human astrocytes grown in primary cell culture following the exposure of these cells to either the human immunodeficiency virus HIV-1 or to the HIV-1 protein gp120. AMGs comprise both Astrocyte Enhanced Genes ( AEGs ) and Astrocyte Suppressed Genes ( ASGs ). Thus, the present invention further relates to Astrocyte Enhanced Genes ( AEGs ), the expression of which are up-regulated in human astrocytes grown in primary cell culture that are exposed to either the human immunodeficiency virus HIV-1 or to the HIV-1 protein gpl20, and to Astrocyte Suppressed Genes ( ASGs ), the expression of which are downregulated in human astrocytes grown in primary cell culture that are exposed to either the human immunodeficiency virus HIV-1 or to the HIV-1 protein gp 120. Because they may playa role in HIV-associated dementia ("HAD"), AMGs may be used as markers in methods for screening for drugs that treat or prevent HAD.
摘要翻译：本发明涉及星形胶质细胞调节基因（AMG）。 AMG是在将这些细胞暴露于人类免疫缺陷病毒HIV-1或HIV-1蛋白gp120后在原代细胞培养物中生长的人星形胶质细胞中表达的基因。 AMGs包括星形胶质细胞增强基因（AEG）和星形胶质细胞抑制基因（ASGs）。因此，本发明还涉及星形胶质细胞增强型基因（AEG），其表达在暴露于人类免疫缺陷病毒HIV-1或HIV-1蛋白的原代细胞培养物中生长的人星形胶质细胞中上调 gpl20和Astrocyte Suppressed Genes（ASG），其表达在暴露于人类免疫缺陷病毒HIV-1或HIV-1蛋白gp 120的原代细胞培养物中生长的人类星形胶质细胞中下调。因为它们可能在艾滋病相关性痴呆（“HAD”）中发挥作用，AMG可用作筛选治疗或预防HAD的药物的方法中的标记。

6. 发明申请

WO2003016499A3 COMBINATORIAL METHODS FOR INDUCING CANCER CELL DEATH 审中-公开
公开(公告)号：WO2003016499A3
公开(公告)日：2003-02-27
申请号：PCT/US2002/026454
申请日：2002-08-19
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B.
发明人： FISHER, Paul, B.
IPC分类号： C12N15/63
摘要： The present invention relates to methods and compositions for inhibiting proliferation and inducing cell death in a population of cancer cells by (i) increasing the amount of the differentiation associated protein MDA -7, and (ii) decreasing RAS activity within the population. It is based, at least in part, on the discovery that decreasing expression of a mutated, activated K- ras gene, together with introducing an expressible mda -7 gene, in pancreatic cancer cells had a synergistic growth-inhibitory and anti-survival effect, and abolished tumorigenicity of the cells in athymic nude mice. The methods of the invention may be directed to the therapy of pancreatic cancer and other malignancies.

7. 发明申请

WO2008063773A2 COMBINATORIAL TREATMENT WITH EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITOR MOLECULES AND MELANOMA DIFFERENTIATION ASSOCIATED GENE-7 审中-公开
标题翻译：表皮生长因子受体抑制剂分子与黑色素瘤分化相关基因7的组合治疗
公开(公告)号：WO2008063773A2
公开(公告)日：2008-05-29
申请号：PCT/US2007/080962
申请日：2007-10-10
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , SETTLEMAN, Jeffrey , FISHER, Paul, B. , EMDAD, Luni
发明人： SETTLEMAN, Jeffrey , FISHER, Paul, B. , EMDAD, Luni
IPC分类号： A61K48/00
CPC分类号： A61K31/7088 , A61K38/179 , A61K38/20 , A61K45/06 , A61K48/00 , C12N15/86 , C12N2710/10343 , A61K2300/00
摘要： The present invention relates to methods of treating a cancer associated with aberrant EGFR-activity comprising administering, to a subject in need of such treatment, an effective amount of a combination of an EGFR inhibitor and a MD A-7 molecule. The combined use of these agents allows effective therapy of cancers that may be relatively resistant to either agent alone.
摘要翻译：本发明涉及治疗与异常EGFR活性相关的癌症的方法，其包括向需要这种治疗的受试者施用有效量的EGFR抑制剂和MDA的组合 -7分子。这些药物的联合使用可以有效治疗对任何一种药物都有相对抗性的癌症。

8. 发明申请

WO2006076408A1 CANCER-TARGETED VIRAL VECTORS 审中-公开
标题翻译：癌症靶向病毒载体
公开(公告)号：WO2006076408A1
公开(公告)日：2006-07-20
申请号：PCT/US2006/000941
申请日：2006-01-11
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B. , SARKAR, Devanand
发明人： FISHER, Paul, B. , SARKAR, Devanand
IPC分类号： C12N15/00 , A01N63/00
CPC分类号： C12N15/86 , A61K35/761 , A61K38/217 , A61K48/0058 , A61K48/0091 , C12N2710/10332 , C12N2710/10343 , C12N2710/10345 , C12N2800/70 , C12N2810/40 , C12N2810/405 , C12N2830/008 , C12N2830/85 , A61K2300/00
摘要： The present invention relates to viral vectors that are targeted to cancer cells. The viral vectors of the invention are adenoviruses having a PEG-3 promoter driving the expression of the viral genes ElA and ElB. The PEG-3 promoter exhibits increased activity in malignant cells. Adenoviruses of the invention show increased replication in malignant cells, thereby producing a cytopathic effect. The viral vectors of the invention may comprise additional genes of interest, and/or may have altered capsid proteins that may enhance infection of and/or target infection to cancer cells. Additional cell types derived from diseased states in which the PEG-3 promoter is selectively active are also therapeutic targets of the viral vectors of the instant invention including those generating allergic, autoimmune and inflammatory responses.
摘要翻译：本发明涉及靶向癌细胞的病毒载体。本发明的病毒载体是具有驱动病毒基因E1A和E1B表达的PEG-3启动子的腺病毒。 PEG-3启动子在恶性细胞中表现出增加的活性。本发明的腺病毒在恶性细胞中显示增加的复制，从而产生细胞病变效应。本发明的病毒载体可以包含另外的感兴趣的基因，和/或可以具有改变的衣壳蛋白，其可增强对癌细胞的感染和/或靶向感染。衍生自其中PEG-3启动子选择性活性的患病状态的另外的细胞类型也是本发明的病毒载体的治疗靶标，包括产生过敏性，自身免疫性和炎性反应的那些。

9. 发明申请

WO2006047311A2 CLONING OF THE RETINOIC ACID INDUCIBLE GENE-1 PROMOTER AND USES THEREOF 审中-公开
标题翻译：视黄酸可诱导的基因-1启动子的克隆及其用途
公开(公告)号：WO2006047311A2
公开(公告)日：2006-05-04
申请号：PCT/US2005/037950
申请日：2005-10-19
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B. , SU, Zao-zhong
发明人： FISHER, Paul, B. , SU, Zao-zhong
IPC分类号： C07K14/72
CPC分类号： C07K14/47
摘要： The present invention relates to the human Retinoic Acid Inducible Gene-1 (hereafter, "RIG-1") promoter. The present invention provides for the promoter itself which is inducible by interferon, virus infection, retinoic acid and double-stranded RNA. A further embodiment includes expression constructs comprising the RIG-1 promoter operatively linked to a gene of interest, which may be a reporter gene or a therapeutic gene. It also provides for cells and non-human transgenic animals comprising such expression constructs. In addition, the present invention provides for methods of screening agents for anti-viral activity using RIG-1 promoter activation or inhibition as the basis of the screening system.
摘要翻译：本发明涉及人视黄酸可诱导基因-1（以下称为“RIG-1”）启动子。本发明提供了可由干扰素，病毒感染，视黄酸和双链RNA诱导的启动子本身。另一个实施方案包括表达构建体，其包含可操作地连接至感兴趣基因的RIG-1启动子，其可以是报道基因或治疗基因。它还提供了包含此类表达构建体的细胞和非人转基因动物。此外，本发明提供了使用RIG-1启动子活化或抑制作为筛选系统的基础筛选抗病毒活性剂的方法。

10. 发明申请

WO2009140572A3 COMBINATORIAL TREATMENT WITH GLUCOSE REGULATED PROTEIN-170 AND MELANOMA DIFFERENTIATION ASSOCIATED GENE-7 审中-公开
公开(公告)号：WO2009140572A3
公开(公告)日：2009-11-19
申请号：PCT/US2009/044092
申请日：2009-05-15
申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK , FISHER, Paul, B. , WANG, Xiang-Yang
发明人： FISHER, Paul, B. , WANG, Xiang-Yang
IPC分类号： C12N5/00 , A61K31/70
摘要： The present invention relates to methods of treating cancer comprising administering, to a subject in need of such treatment, an effective amount of a combination of a GRP-170 and a MDA-7 molecule. The combined use of these agents allows effective therapy of cancers that may be relatively resistant to either agent alone.

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