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1. 发明授权

US06677377B2 Structure based discovery of inhibitors of matriptase for the treatment of cancer and other conditions 失效
标题翻译：基于结构发现的matriptase抑制剂用于治疗癌症和其他病症
公开(公告)号：US06677377B2
公开(公告)日：2004-01-13
申请号：US09885295
申请日：2001-06-21
申请人： Chen-Yong Lin , Robert B. Dickson , Shaomeng Wang , Istvan Enyedy , Sheau-Ling Lee
发明人： Chen-Yong Lin , Robert B. Dickson , Shaomeng Wang , Istvan Enyedy , Sheau-Ling Lee
IPC分类号： A61K31155
CPC分类号： A61K31/655 , A61K31/155 , A61K31/341 , A61K31/404 , A61K31/505 , A61K49/0002 , G01N33/574 , G01N2333/96486
摘要： The present invention relates to a method of inhibiting carcinoma progression wherein matriptase plays a role in a subject in need of such inhibition including administering to a subject an effective amount of a compound comprising two positively charged groups, which are the same or different. The groups are linked by a chemical group having a length of between 5 and 30 A, and preferably between 15 and 24 A. Diagnostic methods based on matriptase action and therapeutic methods involving inhibition of matriptase activity are provided.
摘要翻译：本发明涉及一种抑制癌症进展的方法，其中底物酶在需要这种抑制的受试者中起作用，包括向受试者施用有效量的包含相同或不同的两个带正电基团的化合物。这些基团通过长度为5至30A，优选15至24A的化学基团连接。提供了基于片段酶作用的诊断方法和涉及抑制matriptase活性的治疗方法。

2. 发明申请

US20080248566A1 MATRIPTASE, A SERINE PROTEASE AND ITS APPLICATIONS 有权
标题翻译： MATRIPTASE，丝氨酸蛋白酶及其应用
公开(公告)号：US20080248566A1
公开(公告)日：2008-10-09
申请号：US12040467
申请日：2008-02-29
申请人： Robert B. Dickson , Chen-Yong Lin , Michael Johnson , Shaomeng Wang , Istvan Enyedy
发明人： Robert B. Dickson , Chen-Yong Lin , Michael Johnson , Shaomeng Wang , Istvan Enyedy
IPC分类号： C12N5/06 , C12N15/11 , C12N15/00
CPC分类号： A61K49/0039 , A61K38/00 , A61K49/0056 , A61K49/0058 , A61K51/10 , C12Q1/37 , G01N33/573 , G01N2333/96433 , G01N2500/20
摘要： The invention is directed to a method of detecting a malignancy or a pre-malignant lesion in breast or other tissue, or a pathologic condition, by detecting the presence of single-chain or two-chain forms of matriptase in the tissue. The invention is further directed to a method of treating malignancies, which have the phenotype of matriptase production by administering a tumor formation inhibiting effective amount of concentrate of Bowman-Birk inhibitor (BBIC), or other matriptase inhibitor. The invention also is directed to nucleic acids encoding a matriptase protein or fragments thereof, and their use for structure elucidation and modeling to identify other inhibitors of matriptase, as well as to methods of identifying matriptase modulating agents, including activators and inhibitors.
摘要翻译：本发明涉及通过检测组织中单链或双链形式的matriptase的存在来检测乳腺或其他组织或病理状况中的恶性肿瘤或恶性前病变的方法。本发明进一步涉及通过施用抑制有效量的Bowman-Birk抑制剂（BBIC）浓缩物或其它片剂酶抑制剂的肿瘤形成来治疗恶性肿瘤的方法，所述恶性肿瘤具有基质酶产生的表型。本发明还涉及编码matriptase蛋白质或其片段的核酸，以及其用于结构阐明和建模以鉴定其它抑制剂的用途，以及鉴定片段酶调节剂（包括活化剂和抑制剂）的方法。

3. 发明授权

US07960163B2 Matriptase, a serine protease and its applications 有权
标题翻译： Matriptase，丝氨酸蛋白酶及其应用
公开(公告)号：US07960163B2
公开(公告)日：2011-06-14
申请号：US12040467
申请日：2008-02-29
申请人： Robert B. Dickson , Chen-Yong Lin , Michael Johnson , Shaomeng Wang , Istvan Enyedy
发明人： Robert B. Dickson , Chen-Yong Lin , Michael Johnson , Shaomeng Wang , Istvan Enyedy
IPC分类号： C12N9/00 , C12N9/50 , C12N1/20 , C12N15/00 , C07H21/04
CPC分类号： A61K49/0039 , A61K38/00 , A61K49/0056 , A61K49/0058 , A61K51/10 , C12Q1/37 , G01N33/573 , G01N2333/96433 , G01N2500/20
摘要： The invention is directed to a method of detecting a malignancy or a pre-malignant lesion in breast or other tissue, or a pathologic condition, by detecting the presence of single-chain or two-chain forms of matriptase in the tissue. The invention is further directed to a method of treating malignancies, which have the phenotype of matriptase production by administering a tumor formation inhibiting effective amount of concentrate of Bowman-Birk inhibitor (BBIC), or other matriptase inhibitor. The invention also is directed to nucleic acids encoding a matriptase protein or fragments thereof, and their use for structure elucidation and modeling to identify other inhibitors of matriptase, as well as to methods of identifying matriptase modulating agents, including activators and inhibitors.
摘要翻译：本发明涉及通过检测组织中单链或双链形式的matriptase的存在来检测乳腺或其他组织或病理状况中的恶性肿瘤或恶性前病变的方法。本发明进一步涉及通过施用抑制有效量的Bowman-Birk抑制剂（BBIC）浓缩物或其它片剂酶抑制剂的肿瘤形成来治疗恶性肿瘤的方法，所述恶性肿瘤具有基质酶产生的表型。本发明还涉及编码matriptase蛋白质或其片段的核酸，以及其用于结构阐明和建模以鉴定其它抑制剂的用途，以及鉴定片段酶调节剂（包括活化剂和抑制剂）的方法。

4. 发明授权

US07355015B1 Matriptase, a serine protease and its applications 有权
标题翻译： Matriptase，丝氨酸蛋白酶及其应用
公开(公告)号：US07355015B1
公开(公告)日：2008-04-08
申请号：US09936333
申请日：2000-03-10
申请人： Robert B. Dickson , Chen-Yong Lin , Michael Johnson , Shaomeng Wang , Istvan Enyedy
发明人： Robert B. Dickson , Chen-Yong Lin , Michael Johnson , Shaomeng Wang , Istvan Enyedy
IPC分类号： C07K16/00 , C07K16/40 , A61K38/43
CPC分类号： A61K49/0039 , A61K38/00 , A61K49/0056 , A61K49/0058 , A61K51/10 , C12Q1/37 , G01N33/573 , G01N2333/96433 , G01N2500/20
摘要： The invention is directed to a method of detecting a malignancy or a pre-malignant lesion in breast or other tissue, or a pathologic condition, by detecting the presence of single-chain or two-chain forms of matriptase in the tissue. The invention is further directed to a method of treating malignancies, which have the phenotype of matriptase production by administering a tumor formation inhibiting effective amount of concentrate of Bowman-Birk inhibitor (BBIC), or other matriptase inhibitor. The invention also is directed to nucleic acids encoding a matriptase protein or fragments thereof, and their use for structure elucidation and modeling to identify other inhibitors of matriptase, as well as to methods of identifying matriptase modulating agents, including activators and inhibitors.
摘要翻译：本发明涉及通过检测组织中单链或双链形式的matriptase的存在来检测乳腺或其他组织或病理状况中的恶性肿瘤或恶性前病变的方法。本发明进一步涉及通过施用抑制有效量的Bowman-Birk抑制剂（BBIC）浓缩物或其它片剂酶抑制剂的肿瘤形成来治疗恶性肿瘤的方法，所述恶性肿瘤具有基质酶产生的表型。本发明还涉及编码matriptase蛋白质或其片段的核酸，以及其用于结构阐明和建模以鉴定其它抑制剂的用途，以及鉴定片段酶调节剂（包括活化剂和抑制剂）的方法。

5. 发明授权

US6077938A Monoclonal antibody to an 80 kda protease 失效
标题翻译： 80 kda蛋白酶的单克隆抗体
公开(公告)号：US6077938A
公开(公告)日：2000-06-20
申请号：US957816
申请日：1997-10-27
申请人： Robert B. Dickson , Chen-Yong Lin
发明人： Robert B. Dickson , Chen-Yong Lin
IPC分类号： C07K16/40 , C07K16/00
CPC分类号： C07K16/40
摘要： Compositions of the instant invention comprise a monoclonal antibody designated as 21-9 which binds selectively with an 80 kDa matrix-degrading proteinase having an average molecular weight of about 80 kDa, which is active in the presence of Ca.sup.2, Mg.sup.2+ and Mn.sup.2+.
摘要翻译：本发明的组合物包含命名为21-9的单克隆抗体，其与平均分子量约80kDa的80kDa的基质降解蛋白酶选择性结合，其在Ca2，Mg2 +和Mn2 +的存在下是有活性的。

6. 发明授权

US07371776B2 Methods and compositions for treating cancer 失效
标题翻译：治疗癌症的方法和组合物
公开(公告)号：US07371776B2
公开(公告)日：2008-05-13
申请号：US11045947
申请日：2005-01-29
申请人： Danica Ramljak , Leo J. Romanczyk, Jr. , Robert B. Dickson
发明人： Danica Ramljak , Leo J. Romanczyk, Jr. , Robert B. Dickson
IPC分类号： A61K31/35
CPC分类号： A61K31/353 , A61K31/7048
摘要： This invention relates to methods of inducing dephosphorylation of a hyperphosphorylated cell cycle regulatory protein in a tumor cell in which hyperphosphorylation of said protein contributed to cell transformation, the method comprising contacting the tumor cell with a procyanidin oligomer of five monomeric units connected via a C-4→C-8 linkage. Examples of such compounds are [EC-(4β→8)]4-EC, and [EC-(4β→8)]3-EC-(4β→8)-C, wherein EC is epicatcchin and C is catechin.
摘要翻译：本发明涉及在肿瘤细胞中诱导过磷酸化细胞周期调节蛋白的去磷酸化的方法，其中所述蛋白质的高度磷酸化有助于细胞转化，所述方法包括使肿瘤细胞与五个单体单元的原花青素低聚物接触， 4-> C-8连接。这些化合物的实例是[EC-（4beta-> 8）] 4 -EC，和[EC-（4beta-> 8）] 3 -EC-（4beta - > 8）-C，其中EC是epicatcchin，C是儿茶素。

7. 发明授权

US06316189B1 Evaluation of changes in breast cells using nipple aspirate fluid 失效
标题翻译：使用乳头抽吸液评估乳腺细胞的变化
公开(公告)号：US06316189B1
公开(公告)日：2001-11-13
申请号：US09176928
申请日：1998-10-23
申请人： Bassem R. Haddad , Robert B. Dickson , Stephen J. McCormack
发明人： Bassem R. Haddad , Robert B. Dickson , Stephen J. McCormack
IPC分类号： C12Q168
CPC分类号： C12Q1/6841 , C12Q1/6806 , C12Q1/6886
摘要： This invention provides a method for studying chromosomal gains and losses in cells from nipple aspirate fluid comprising the steps of: (1) aspirating fluid from breasts; (2) placing the samples of fluid obtained in step 1 onto dishes containing conditioned medium composed of a mixture of (a) supernatant from immortalized mammary epithelial cells and (b) mammary epithelial growth medium; (3) incubating the product of step 2 in a humidified incubator; (4) replenishing the medium in the dishes prepared in step 2 at regular intervals to maintain cell growth; (5) isolating the cells from the cultures; (6) preparing DNA from these cells; (7) amplifying the DNA; (8) labeling an aliquot of the amplified DNA; and (9) evaluating the labeled DNA for evidence of chromosomal gains or losses.
摘要翻译：本发明提供一种用于研究来自乳头抽吸液的细胞染色体增益和损失的方法，包括以下步骤：（1）从乳汁吸出液体; （2）将步骤1中获得的液体样品放入含有由（a）来自永生化乳腺上皮细胞的上清液和（b）乳腺上皮生长培养基的混合物组成的条件培养基的培养皿中; （3）将步骤2的产物在加湿培养箱中孵育; （4）定期补充步骤2中制备的培养皿中的培养基以维持细胞生长; （5）从培养物中分离细胞; （6）从这些细胞制备DNA; （7）扩增DNA; （8）标记扩增的DNA的等分试样; 和（9）评估标记的DNA作为染色体获益或损失的证据。

8. 发明授权

US5482848A Matrix-degrading metalloproteinase 失效
标题翻译：基质降解金属蛋白酶
公开(公告)号：US5482848A
公开(公告)日：1996-01-09
申请号：US199792
申请日：1994-02-22
申请人： Robert B. Dickson , Yuenian E. Shi
发明人： Robert B. Dickson , Yuenian E. Shi
IPC分类号： C12N9/64 , C12Q1/37 , G01N33/573 , G01N33/574 , C12N9/50 , C12N9/96
CPC分类号： C12N9/6491 , C12Q1/37 , G01N33/573 , G01N33/57415 , G01N2333/96486
摘要： An 80 kDa metaloproteinase is found in hormone-dependent human breast cancer cells. The enzyme is active in the presence of calcium, manganese, or magnesium ions. The 80 kDa proteinase is useful for evaluating therapeutic progress and in formulating plans for treatment.
摘要翻译：在激素依赖型人乳腺癌细胞中发现80kDa的金属蛋白酶。该酶在钙，锰或镁离子的存在下是有活性的。 80 kDa蛋白酶可用于评估治疗进展和制定治疗计划。

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