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1. 发明授权

US07605127B2 Truncated hepatocyte growth factor variant protein HGF/NK2 有权
标题翻译：截短肝细胞生长因子变体蛋白HGF / NK2
公开(公告)号：US07605127B2
公开(公告)日：2009-10-20
申请号：US10283769
申请日：2002-10-30
申请人： Andrew M. L. Chan , Jeffrey S. Rubin , Donald P. Bottaro , Stuart A. Aaronson , Stephen J. Stahl , Paul T. Wingfield , Vittoria Cioce
发明人： Andrew M. L. Chan , Jeffrey S. Rubin , Donald P. Bottaro , Stuart A. Aaronson , Stephen J. Stahl , Paul T. Wingfield , Vittoria Cioce
IPC分类号： C07K14/475 , A61K38/18
CPC分类号： A61K38/193 , C07K14/4753 , A61K2300/00
摘要： The present invention relates to a novel truncated form of heptocyte growth factor (HGF) which specifically antagonizes the activity of HGF and to a novel truncated form of HGF that is a partial HGF agonist. In particular, the present invention relates to the purification, molecular cloning, recombinant expression of the truncated HGF variants and related pharmaceutical compositions. The present invention further relates to the utilization of the small HGF variants to either inhibit HGF mitogenesis or stimulate HGF mitogenesis in cells expressing the receptor for HGF.
摘要翻译：本发明涉及特异性拮抗HGF的活性的新型截短形式的肝细胞生长因子（HGF）和作为部分HGF激动剂的新型截短形式的HGF。特别地，本发明涉及截短的HGF变体和相关药物组合物的纯化，分子克隆，重组表达。本发明还涉及小HGF变体在表达HGF受体的细胞中抑制HGF有丝分裂或刺激HGF有丝分裂发生的用途。

2. 发明授权

US5578566A KGF receptor-derived antagonists of KGF binding 失效
标题翻译： KGF受体来源的KGF结合拮抗剂
公开(公告)号：US5578566A
公开(公告)日：1996-11-26
申请号：US59030
申请日：1993-05-04
申请人： Donald P. Bottaro , Jeffrey S. Rubin , Stuart A. Aaronson
发明人： Donald P. Bottaro , Jeffrey S. Rubin , Stuart A. Aaronson
IPC分类号： A61K38/00 , C07K14/71 , C07K5/00 , C07K7/00
CPC分类号： C07K14/71 , A61K38/00
摘要： The invention provides KGFR peptides which inhibit binding between keratinocyte growth factor (KGF) and its receptor. The sequence of the peptides is derived from regions in the receptor which specifically bind the growth factor. Also provided are pharmaceutical compositions and methods of inhibiting the interaction of KGF and the receptor in a patient to treat various carcinomas.
摘要翻译：本发明提供抑制角质形成细胞生长因子（KGF）与其受体之间结合的KGFR肽。肽的序列衍生自特异性结合生长因子的受体中的区域。还提供了药物组合物和抑制患者中KGF和受体相互作用以治疗各种癌症的方法。

3. 发明授权

US06566098B1 DNA encoding truncated hepatocyte growth factor variants 失效
标题翻译：编码截短的肝细胞生长因子变体的DNA
公开(公告)号：US06566098B1
公开(公告)日：2003-05-20
申请号：US08484841
申请日：1995-06-07
申请人： Andrew M. L. Chan , Jeffrey S. Rubin , Donald P. Bottaro , Stuart A. Aaronson
发明人： Andrew M. L. Chan , Jeffrey S. Rubin , Donald P. Bottaro , Stuart A. Aaronson
IPC分类号： C12N1518
CPC分类号： A61K38/193 , C07K14/4753 , A61K2300/00
摘要： The present invention relates to a novel truncated forms of hepatocyte growth factor (HGF) which specifically antagonizes the activity of HGF and to a novel truncated form of HGF that is a partial HGF agonist. In particular, the present invention relates to the purification, molecular cloning, recombinant expression of the truncated HGF variants and related pharmaceutical compositions. The present invention further relates to the utilization of the small HGF variants to either inhibit HGF mitogenesis or stimulate HGF mitogenesis in cells expressing the receptor for HGF.
摘要翻译：本发明涉及特异性拮抗HGF的活性和作为部分HGF激动剂的新型截短形式的HGF的肝细胞生长因子（HGF）的新型截短形式。特别地，本发明涉及截短的HGF变体和相关药物组合物的纯化，分子克隆，重组表达。本发明还涉及小HGF变体在表达HGF受体的细胞中抑制HGF有丝分裂或刺激HGF有丝分裂发生的用途。

4. 发明授权

US5648273A Hepatic growth factor receptor is the MET proto-oncogene 失效
标题翻译：肝细胞生长因子受体是MET原癌基因
公开(公告)号：US5648273A
公开(公告)日：1997-07-15
申请号：US642971
申请日：1991-01-18
申请人： Donald P. Bottaro , Jeffery S. Rubin , Donna Faletto , Andrew M.-L. Chan , George F. Vande Woude , Stuart A. Aaronson
发明人： Donald P. Bottaro , Jeffery S. Rubin , Donna Faletto , Andrew M.-L. Chan , George F. Vande Woude , Stuart A. Aaronson
IPC分类号： C07K17/00 , A61K38/00 , A61K38/18 , A61K38/19 , A61K38/48 , A61K39/395 , A61P35/00 , C07K14/475 , C07K14/52 , C07K14/705 , C07K14/71 , C07K14/82 , C07K16/00 , C07K16/22 , C07K16/24 , C07K16/28 , C07K16/32 , C07K19/00 , C12N5/06 , C12N5/08 , C12N15/09 , C12P21/08 , C12Q1/68 , G01N33/53 , G01N33/566 , G01N33/574 , G01N33/576 , G01N33/68
CPC分类号： G01N33/6872 , A61K38/193 , C07K14/4753 , C07K14/71 , C07K14/82 , C07K16/22 , C07K16/32 , C12Q1/6813 , C12Q1/6886 , G01N33/57446 , C12Q2600/158
摘要： The present invention relates to a complex comprising hepatocyte growth factor (HGF) and met proto-oncogene protein. The present invention also relates to methods for detecting the presence of HGF ligand, met proto-oncogene receptor and methods for isolating either the ligand or receptor or complex comprising both. The present invention further relates to methods of diagnostic proliferative disorders and diseases such as hepatitis or hepatocarcinogenesis by detecting these ligand-receptor pairs.
摘要翻译：本发明涉及包含肝细胞生长因子（HGF）和met原癌基因蛋白的复合物。本发明还涉及用于检测HGF配体，met原癌基因受体的存在的方法和用于分离包含两者的配体或受体或复合物的方法。本发明还涉及通过检测这些配体 - 受体对来诊断增殖性疾病和诸如肝炎或肝癌发生的疾病的方法。

5. 发明授权

US5512434A Expression cloning of a human phosphatase 失效
标题翻译：人磷酸酶的表达克隆
公开(公告)号：US5512434A
公开(公告)日：1996-04-30
申请号：US988273
申请日：1992-12-14
申请人： Stuart A. Aaronson , Donald P. Bottaro , Toshio Ishibashi , Toru Miki
发明人： Stuart A. Aaronson , Donald P. Bottaro , Toshio Ishibashi , Toru Miki
IPC分类号： A61K38/00 , C12N9/16 , C12N15/10 , C12N15/55 , C12Q1/42 , C12Q1/48 , C12Q1/68
CPC分类号： C12N15/1086 , C12N9/16 , A61K38/00
摘要： A method for the identification of related polypeptides, using an function-based selection criterion, is disclosed. A novel human phosphatase, and nucleotide sequences coding therefor, identified by the aforementioned method and designated VHR, is also disclosed.
摘要翻译：公开了使用基于功能的选择标准来鉴定相关多肽的方法。还公开了通过上述方法鉴定并命名为VHR的新型人磷酸酶及其编码的核苷酸序列。

6. 发明授权

US07026291B1 Epithelial cell specific growth factor, keratinocyte growth factor (KGF) 失效
标题翻译：上皮细胞特异性生长因子，角质形成细胞生长因子（KGF）
公开(公告)号：US07026291B1
公开(公告)日：2006-04-11
申请号：US08477983
申请日：1995-06-07
申请人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
发明人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
IPC分类号： A61K38/18 , C07K14/475 , C07K14/50
CPC分类号： G01N33/74 , A61K38/00 , C07K14/50 , C07K16/22 , C07K2317/73 , G01N2333/4742
摘要： Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.
摘要翻译：揭示了显示重组DNA技术的特定方面的发现可以成功地用于产生迄今为止未知的人角质形成细胞生长因子（KGF）蛋白，而不含其他多肽。这些蛋白质可以从自发分泌的细胞或引入细胞的DNA片段以各种功能形式产生。这些形式不同地使得这种新型蛋白质的生物化学和功能研究以及抗体的产生。描述了用于确定KGF蛋白的基因表达水平的方法，例如通过测量细胞中的mRNA水平或通过测量在细胞外或体液中分泌的抗原。

7. 发明授权

US5707805A Assay for detecting keratinocyte growth factor (KGF) and its activity 失效
标题翻译：检测角质形成细胞生长因子（KGF）及其活性
公开(公告)号：US5707805A
公开(公告)日：1998-01-13
申请号：US455641
申请日：1995-05-31
申请人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
发明人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
IPC分类号： A61K39/395 , A61K38/00 , A61K38/18 , A61K38/22 , A61P17/02 , A61P43/00 , C07H21/04 , C07K1/16 , C07K14/00 , C07K14/435 , C07K14/47 , C07K14/475 , C07K14/485 , C07K14/50 , C07K16/00 , C07K16/22 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/08 , C12N5/10 , C12N15/09 , C12N15/12 , C12N15/18 , C12N15/63 , C12N15/70 , C12N15/79 , C12P21/00 , C12P21/02 , C12Q1/68 , C12R1/91 , G01N33/48 , G01N33/50 , G01N33/53
CPC分类号： C12Q1/6876 , C07K14/50 , C07K14/501 , C07K16/22 , C12N15/70 , C12N15/79 , A61K38/00 , C07K2317/73 , C07K2319/00 , C07K2319/02 , C07K2319/75 , C12Q2600/158
摘要： Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.
摘要翻译：揭示了显示重组DNA技术的特定方面的发现可以成功地用于产生迄今为止未知的人角质形成细胞生长因子（KGF）蛋白，而不含其他多肽。这些蛋白质可以从自发分泌的细胞或引入细胞的DNA片段以各种功能形式产生。这些形式不同地使得这种新型蛋白质的生物化学和功能研究以及抗体的产生。描述了用于确定KGF蛋白的基因表达水平的方法，例如通过测量细胞中的mRNA水平或通过测量在细胞外或体液中分泌的抗原。

8. 发明授权

US06709842B1 DNA encoding a growth factor specific for epithelial cells 失效
标题翻译：编码上皮细胞特异性生长因子的DNA
公开(公告)号：US06709842B1
公开(公告)日：2004-03-23
申请号：US08477982
申请日：1995-06-07
申请人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
发明人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
IPC分类号： C12N121
CPC分类号： C12Q1/6876 , A61K38/00 , C07K14/50 , C07K14/501 , C07K16/22 , C07K2317/73 , C07K2319/00 , C07K2319/02 , C07K2319/75 , C12N15/70 , C12N15/79 , C12Q2600/158
摘要： Disccoveries are disclosed that show particular aspects of recombinant DNA technology can be used sucessfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.
摘要翻译：揭示了显示重组DNA技术的特定方面的Disccoveries可被成功地用于产生迄今为止未知的人角质形成细胞生长因子（KGF）蛋白，其不含其他多肽。这些蛋白质可以从自发分泌的细胞或引入细胞的DNA片段以各种功能形式产生。这些形式不同地使得这种新型蛋白质的生物化学和功能研究以及抗体的产生。描述了用于确定KGF蛋白的基因表达水平的方法，例如通过测量细胞中的mRNA水平或通过测量在细胞外或体液中分泌的抗原。

9. 发明授权

US06225088B1 DNA encoding plasminogen-like growth factor (PLGF) and related embodiments 失效
标题翻译：编码纤溶酶原样生长因子（PLGF）的DNA和相关实施方案
公开(公告)号：US06225088B1
公开(公告)日：2001-05-01
申请号：US09170573
申请日：1998-10-13
申请人： Jeffrey S. Rubin , Andrew M. L. Chan , Stuart A. Aaronson
发明人： Jeffrey S. Rubin , Andrew M. L. Chan , Stuart A. Aaronson
IPC分类号： C12N1518
CPC分类号： C07K14/4753 , A61K38/193 , A61K2300/00
摘要： The present invention relates to a potent mitogenic growth factor called plasminogen-like growth factor (PLGF) isolated from conditioned medium of human lung fibroblasts. The protein has an apparent molecular weight under reducing conditioning of 87 kDa and is structurally related to hepatocyte growth factor (HGF); however unlike HGF, which appears to be specific for hepatic cells, PLGF stimulates a wide spectrum of target cells including melanocytes, endothelial cells and epithelial cells but excludes fibroblast cells. The present invention further relates to recombinant cloned DNA fragments and expression cell systems expressing biologically active PLGF. The availability of purified PLGF as well as immunological and molecular probes should facilitate the study of proliferative disorders in which the factor plays an important role.
摘要翻译：本发明涉及从人肺成纤维细胞的条件培养基中分离的称为纤溶酶原样生长因子（PLGF）的有效促有丝分裂生长因子。该蛋白质在87 kDa的还原调节下具有明显的分子量，并且在结构上与肝细胞生长因子（HGF）有关; 然而，不同于似乎对肝细胞特异性的HGF，PLGF刺激大范围的靶细胞，包括黑素细胞，内皮细胞和上皮细胞，但不包括成纤维细胞。本发明还涉及表达生物活性PLGF的重组克隆DNA片段和表达细胞系统。纯化的PLGF以及免疫学和分子探针的可用性应有助于研究增殖性疾病，其中该因子起重要作用。

10. 发明授权

US5731170A DNA encoding a growth factor specific for epithelial cells 失效
标题翻译：编码上皮细胞特异性生长因子的DNA
公开(公告)号：US5731170A
公开(公告)日：1998-03-24
申请号：US480948
申请日：1995-06-07
申请人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
发明人： Jeffrey S. Rubin , Paul W. Finch , Stuart A. Aaronson
IPC分类号： A61K39/395 , A61K38/00 , A61K38/18 , A61K38/22 , A61P17/02 , A61P43/00 , C07H21/04 , C07K1/16 , C07K14/00 , C07K14/435 , C07K14/47 , C07K14/475 , C07K14/485 , C07K14/50 , C07K16/00 , C07K16/22 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/08 , C12N5/10 , C12N15/09 , C12N15/12 , C12N15/18 , C12N15/63 , C12N15/70 , C12N15/79 , C12P21/00 , C12P21/02 , C12Q1/68 , C12R1/91 , G01N33/48 , G01N33/50 , G01N33/53 , C12N15/11
CPC分类号： C12Q1/6876 , C07K14/50 , C07K14/501 , C07K16/22 , C12N15/70 , C12N15/79 , A61K38/00 , C07K2317/73 , C07K2319/00 , C07K2319/02 , C07K2319/75 , C12Q2600/158
摘要： Discoveries are disclosed that show particular aspects of recombinant DNA technology can be used successfully to produce hitherto unknown human keratinocyte growth factor (KGF) protein free of other polypeptides. These proteins can be produced in various functional forms from spontaneously secreting cells or from DNA segments .introduced into cells. These forms variously enable biochemical and functional studies of this novel protein as well as production of antibodies. Means are described for determining the level of expression of genes for the KGF protein, for example, by measuring mRNA levels in cells or by measuring antigen secreted in extracellular or body fluids.
摘要翻译：揭示了显示重组DNA技术的特定方面的发现可以成功地用于产生迄今为止未知的人角质形成细胞生长因子（KGF）蛋白，而不含其他多肽。这些蛋白质可以以各种功能形式从自发分泌的细胞或从DNA片段产生，引入细胞。这些形式不同地使得这种新型蛋白质的生物化学和功能研究以及抗体的产生。描述了用于确定KGF蛋白的基因表达水平的方法，例如通过测量细胞中的mRNA水平或通过测量在细胞外或体液中分泌的抗原。

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