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1.发明申请Pancreatic cancer associated antigen, antibody thereto, and diagnostic and treatment methods 审中-公开胰腺癌相关抗原，抗体及其诊断和治疗方法公开(公告)号：US20060258841A1
公开(公告)日：2006-11-16
申请号：US10542239
申请日：2004-01-16
申请人： Josef Michl , Stefan Bradu , Raquib Hannan , Matthew Pincus
发明人： Josef Michl , Stefan Bradu , Raquib Hannan , Matthew Pincus
CPC分类号： C07K16/303 , A61K47/6817 , A61K47/6859 , A61K51/1057 , A61K2039/505 , C07K14/47 , C07K2317/24 , C07K2317/734 , G01N33/57438 , G01N2333/705
摘要： The present invention is directed to an antigen found on the surface of rat and human pancreatic cancer cells and provides antibodies of high specificity and selectivity to this antigen as well as hybridomas secreting the subject antibodies. Methods for both the diagnosis and treatment of pancreatic cancer are also provided. This tissue marker of pancreatic adenocarcinoma, an approximately 43.5 kD surface membrane protein designated PaCa-Ag1, is completely unexpressed in normal pancreas but abundantly expressed in pancreatic carcinoma cells. Moreover, a soluble form of PaCa-Ag1 exists, having a molecular weight about 36 to about 38 kD, that is readily identified in sera and other body fluids of pancreatic cancer patients, using a subject antibody.
摘要翻译： 本发明涉及在大鼠和人胰腺癌细胞表面上发现的抗原，并且提供对该抗原以及分泌本发明抗体的杂交瘤具有高特异性和选择性的抗体。 还提供了胰腺癌诊断和治疗方法。 胰腺腺癌组织标志物，一种约43.5 kD的表皮膜蛋白，称为PaCa-Ag1，在正常胰腺中完全未表达，但在胰腺癌细胞中大量表达。 此外，使用受试抗体，存在可溶形式的PaCa-Ag1，其分子量约36至约38kD，其易于在胰腺癌患者的血清和其它体液中鉴定。
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2.发明申请公开(公告)号：US20170065684A9
公开(公告)日：2017-03-09
申请号：US14809666
申请日：2015-07-27
申请人： Matthew Pincus , Josef Michl
发明人： Matthew Pincus , Josef Michl
CPC分类号： A61K38/46 , A61K38/00 , A61K48/00 , C07K14/82 , C07K2319/10 , C12N15/86 , C12N2710/10032 , C12N2710/10043 , C12Y306/05002
摘要： The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.
摘要翻译： 本发明提供了对应于ras-p21的残基96-110和35-47的肽（包括其类似物和衍生物），该肽与其附着有膜穿透前导序列。 本发明的肽，类似物和衍生物可用于治疗癌症，并且已被证明能诱导胰腺癌细胞向非癌细胞的表型逆转。 包含一种或多种受试肽的药物组合物也由本发明提供。 本发明还提供了包含启动子序列和编码目标肽的核苷酸序列的复制无能力腺病毒（AdV）载体。 还提供了通过施用一种或多种受试肽，药物组合物和/或AdV载体治疗癌症的方法。
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公开(公告)号：US20080153754A1
公开(公告)日：2008-06-26
申请号：US11825242
申请日：2007-07-05
申请人： Matthew Pincus , Josef Michl
发明人： Matthew Pincus , Josef Michl
CPC分类号： A61K38/46 , A61K38/00 , A61K48/00 , C07K14/82 , C07K2319/10 , C12N15/86 , C12N2710/10032 , C12N2710/10043 , C12Y306/05002
摘要： The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p2 1, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.
摘要翻译： 本发明提供了对应于ras-p21的残基96-110和35-47的肽（包括其类似物和衍生物），该肽与其连接有膜穿透前导序列。 本发明的肽，类似物和衍生物可用于治疗癌症，并且已被证明能诱导胰腺癌细胞向非癌细胞的表型逆转。 包含一种或多种受试肽的药物组合物也由本发明提供。 本发明还提供了包含启动子序列和编码目标肽的核苷酸序列的复制无能力腺病毒（AdV）载体。 还提供了通过施用一种或多种受试肽，药物组合物和/或AdV载体治疗癌症的方法。
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公开(公告)号：US20060105956A1
公开(公告)日：2006-05-18
申请号：US11142051
申请日：2005-05-31
申请人： Matthew Pincus , Josef Michl
发明人： Matthew Pincus , Josef Michl
CPC分类号： A61K38/46 , A61K38/00 , A61K48/00 , C07K14/82 , C07K2319/10 , C12N15/86 , C12N2710/10032 , C12N2710/10043 , C12Y306/05002
摘要： The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.
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公开(公告)号：US09115213B2
公开(公告)日：2015-08-25
申请号：US13677876
申请日：2012-11-15
申请人： Matthew Pincus , Josef Michl
发明人： Matthew Pincus , Josef Michl
CPC分类号： A61K38/46 , A61K38/00 , A61K48/00 , C07K14/82 , C07K2319/10 , C12N15/86 , C12N2710/10032 , C12N2710/10043 , C12Y306/05002
摘要： The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.
摘要翻译： 本发明提供了对应于ras-p21的残基96-110和35-47的肽（包括其类似物和衍生物），该肽与其附着有膜穿透前导序列。 本发明的肽，类似物和衍生物可用于治疗癌症，并且已被证明能诱导胰腺癌细胞向非癌细胞的表型逆转。 包含一种或多种受试肽的药物组合物也由本发明提供。 本发明还提供了包含启动子序列和编码目标肽的核苷酸序列的复制无能力腺病毒（AdV）载体。 还提供了通过施用一种或多种受试肽，药物组合物和/或AdV载体治疗癌症的方法。
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6.发明申请公开(公告)号：US20090286861A1
公开(公告)日：2009-11-19
申请号：US12488209
申请日：2009-06-19
申请人： Matthew Pincus , Josef Michl
发明人： Matthew Pincus , Josef Michl
IPC分类号： A61K31/7088 , C12N15/63
CPC分类号： A61K38/46 , A61K38/00 , A61K48/00 , C07K14/82 , C07K2319/10 , C12N15/86 , C12N2710/10032 , C12N2710/10043 , C12Y306/05002
摘要： The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.
摘要翻译： 本发明提供了对应于ras-p21的残基96-110和35-47的肽（包括其类似物和衍生物），该肽与其连接有膜穿透前导序列。 本发明的肽，类似物和衍生物可用于治疗癌症，并且已被证明能诱导胰腺癌细胞向非癌细胞的表型逆转。 包含一种或多种受试肽的药物组合物也由本发明提供。 本发明还提供了包含启动子序列和编码目标肽的核苷酸序列的复制无能力腺病毒（AdV）载体。 还提供了通过施用一种或多种受试肽，药物组合物和/或AdV载体治疗癌症的方法。
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公开(公告)号：US20150320841A1
公开(公告)日：2015-11-12
申请号：US14809666
申请日：2015-07-27
申请人： Matthew Pincus , Josef Michl
发明人： Matthew Pincus , Josef Michl
CPC分类号： A61K38/46 , A61K38/00 , A61K48/00 , C07K14/82 , C07K2319/10 , C12N15/86 , C12N2710/10032 , C12N2710/10043 , C12Y306/05002
摘要： The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.
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公开(公告)号：US20130065953A1
公开(公告)日：2013-03-14
申请号：US13677876
申请日：2012-11-15
申请人： Matthew Pincus , Josef Michl
发明人： Matthew Pincus , Josef Michl
IPC分类号： A61K31/711 , A61P35/00 , C12N15/861
CPC分类号： A61K38/46 , A61K38/00 , A61K48/00 , C07K14/82 , C07K2319/10 , C12N15/86 , C12N2710/10032 , C12N2710/10043 , C12Y306/05002
摘要： The present invention provides peptides (including analogs and derivatives thereof) corresponding to residues 96-110 and 35-47 of ras-p21, which peptides have attached thereto a membrane-penetrating leader sequence. The subject peptides, analogs and derivatives thereof are useful in treatment of cancers and have been shown to induce phenotypic reversion of pancreatic cancer cells to non-cancerous cells. Pharmaceutical compositions comprising one or more subject peptides are also provided by the present invention. The present invention further provides replication incompetent Adenovirus (AdV) vectors comprising a promoter sequence and a nucleotide sequence encoding a subject peptide. Methods of treating cancer by administering one or more subject peptides, pharmaceutical compositions, and/or AdV vectors are also provided.
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9.发明申请公开(公告)号：US20050245451A1
公开(公告)日：2005-11-03
申请号：US11019894
申请日：2004-12-21
申请人： Matthew Pincus
发明人： Matthew Pincus
CPC分类号： C07K14/4746 , A61K38/10 , A61K38/1709 , A61K2039/5254 , A61K2039/5256 , C07K2319/03 , C12N2799/022
摘要： The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein, which peptides are lethal to malignant or transformed cells when fused to a membrane-penetrating leader sequence. In order to reduce proteolysis of a subject peptide, one or more D-amino acids may be substituted for the corresponding L-amino acids in the p53 portion and/or the membrane-penetrating leader of a subject peptide. Further, a pseudopeptide bond or a retro-inverso pseudopeptide bond may be substituted for one or more peptide bonds in either or both of the p53 sequence or membrane-penetrating leader sequence in order to render a subject peptide less susceptible to proteolysis. In addition, both the membrane-penetrating leader sequence and the p53 portion of a subject peptide may comprise retro-inverso, and partially modified retro-inverso isomers. Such isomers are less susceptible to proteolysis and therefore have prolonged half-lives. The subject peptides are useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide fused at its carboxy terminal end to a membrane-penetrating leader sequence are also provided as are methods of assessing the level of effectiveness of a subject peptide in killing malignant, transformed, or neoplastic cells in vitro.
摘要翻译： 本发明提供对应于人p53蛋白的全部或部分氨基酸残基12-26的肽，当与透膜前导序列融合时，该肽对恶性或转化细胞致死。 为了减少受试肽的蛋白水解，一个或多个D-氨基酸可以被取代目标肽的p53部分和/或膜穿透前导序列中的相应L-氨基酸。 此外，伪肽键或逆反义假肽键可以取代p53序列或膜穿透前导序列之一或两者中的一个或多个肽键，以使得受试肽对蛋白水解不太敏感。 此外，受试肽的膜穿透前导序列和p53部分都可以包括逆反转和部分修饰的逆反转异构体。 这些异构体不易于蛋白水解，因此具有延长的半衰期。 本发明的肽可用于治疗动物，优选人类的肿瘤疾病。 还提供了包含与药学上可接受的载体混合的受试肽的药物组合物。 还提供了通过将其羧基末端融合的受试肽施用于穿透膜的前导序列来治疗患者的肿瘤性疾病的方法，其中评估主题肽在杀死恶性，转化或肿瘤中的有效性水平的方法 体外细胞。
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10.发明申请公开(公告)号：US20080076713A1
公开(公告)日：2008-03-27
申请号：US11977521
申请日：2007-10-25
申请人： Matthew Pincus
发明人： Matthew Pincus
CPC分类号： C07K14/4746 , A61K38/04 , A61K38/10 , A61K38/1709 , A61K2039/5254 , A61K2039/5256 , C07K2319/03 , C12N2799/022
摘要： The present invention provides peptides corresponding to all or a portion of amino acid residues 12-26 of human p53 protein. When fused to a membrane-penetrating leader sequence, the peptides are either lethal to malignant or transformed cells or else cause reversion to the untransformed morphological phenotype. The subject peptides are thus useful in treating neoplastic disease in an animal, preferably a human. Also provided are pharmaceutical compositions comprising the subject peptides admixed with a pharmaceutical acceptable carrier. Methods of treating neoplastic disease in a patient by administering a subject peptide are also provided.
摘要翻译： 本发明提供对应于人p53蛋白的全部或部分氨基酸残基12-26的肽。 当与膜穿透前导序列融合时，肽对恶性或转化细胞致死，或者导致未转化的形态表型的逆转。 因此，本发明的肽可用于治疗动物，优选人类的肿瘤性疾病。 还提供了包含与药学上可接受的载体混合的受试肽的药物组合物。 还提供了通过施用受试肽治疗患者的肿瘤性疾病的方法。
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