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1. 发明申请

US20080317667A1 Compositions and methods for inhibiting growth of smad4-deficient cancers 有权
标题翻译：用于抑制smad4缺陷型癌症生长的组合物和方法
公开(公告)号：US20080317667A1
公开(公告)日：2008-12-25
申请号：US11822859
申请日：2007-07-10
申请人： Shelia M. Violette , Louise A. Koopman
发明人： Shelia M. Violette , Louise A. Koopman
IPC分类号： A61K51/10 , A61K39/395 , A61K38/43 , A61K38/02 , A61K38/04 , A61K38/06 , A61K38/07 , A61K38/08 , A61K38/10 , A61K38/16 , A61P35/00 , A61K31/282 , A61K33/24 , A61K31/519 , A61K31/505 , A61K31/675 , A61K31/704 , A61K31/195 , A61K31/7028 , A61K38/00
CPC分类号： G01N33/5011 , A61K38/1793 , A61K39/39558 , A61K2039/505 , C07K16/2839 , C07K2317/73 , G01N33/5091 , G01N33/574 , G01N33/57407 , A61K2300/00
摘要： The present invention is in the fields of cell biology, immunology and oncology. The invention relates to the discovery that there is a relationship between the expression levels of the tumor suppressor gene smad4 (also known as dpc4) and integrin αvβ6, and the responsiveness of patient populations to αvβ6-active compounds and compositions (e.g., antibodies and other ligands that bind αvβ6), particularly in cancer cells from such patient populations, more particularly on carcinomas such as pancreatic carcinomas. The invention thus provides methods for determining the responsiveness of tumor cells (particularly those from pancreatic tumors) to such αvβ6-active compounds and compositions by examining the expression of αvβ6 and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and small molecule drugs, that bind to integrin αvβ6 on the surfaces of tumor cells and/or that block one or more components of the TGF-β pathway, particularly in smad4-deficient tumor cells.
摘要翻译：本发明涉及细胞生物学，免疫学和肿瘤学领域。本发明涉及以下发现：肿瘤抑制基因smad4（也称为dpc4）和整联蛋白α表达水平的表达水平与患者群体对α-位点活性化合物和组合物的反应性（例如，抗体和其他特别是在来自这些患者群体的癌细胞中，特别是癌症如胰腺癌的结合的αphavβ6的配体）。因此，本发明提供了通过检查肿瘤细胞中alphavbeta6和smad4的表达以及诊断和治疗/预防的方法来确定肿瘤细胞（特别是来自胰腺肿瘤的肿瘤细胞）对这种α2β6活性化合物和组合物的反应性的方法的肿瘤进展，其使用与肿瘤细胞表面上的整联蛋白α1b结合的抗体和小分子药物，和/或阻断TGF-β途径的一个或多个成分，特别是在smad4缺陷型肿瘤细胞中。

2. 发明授权

US07465449B2 Anti-αvβ6 antibodies 有权
标题翻译：抗alphavbeta6抗体
公开(公告)号：US07465449B2
公开(公告)日：2008-12-16
申请号：US10507662
申请日：2003-03-13
申请人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
发明人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
IPC分类号： A61K39/395 , G01N33/53 , C07K16/28
CPC分类号： C07K16/2839 , A61K47/48507 , A61K47/48561 , A61K47/48623 , A61K47/68 , A61K47/6835 , A61K47/6849 , A61K47/6851 , A61K47/6865 , A61K51/1027 , A61K51/1066 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/77 , C07K2317/92 , G01N33/57492 , G01N33/6893 , G01N2333/70546 , G01N2800/085 , G01N2800/205
摘要： Monoclonal antibodies that specifically bind to M.96. Also included are methods of using these antibodies to treat mammals having or at risk of having 006-mediated diseases, or to diagnose % Qmediated diseases.
摘要翻译：特异性结合M.96的单克隆抗体。还包括使用这些抗体治疗具有或具有006介导的疾病的风险的哺乳动物或诊断％Q介导的疾病的方法。

3. 发明授权

US07927590B2 Compositions and methods for inhibiting growth of smad4-deficient cancers 有权
标题翻译：用于抑制smad4缺陷型癌症生长的组合物和方法
公开(公告)号：US07927590B2
公开(公告)日：2011-04-19
申请号：US11822859
申请日：2007-07-10
申请人： Shelia M. Violette , Louise A. Koopman
发明人： Shelia M. Violette , Louise A. Koopman
IPC分类号： A61K39/395
CPC分类号： G01N33/5011 , A61K38/1793 , A61K39/39558 , A61K2039/505 , C07K16/2839 , C07K2317/73 , G01N33/5091 , G01N33/574 , G01N33/57407 , A61K2300/00
摘要： The present invention is in the fields of cell biology, immunology and oncology. The invention relates to the discovery that there is a relationship between the expression levels of the tumor suppressor gene smad4 (also known as dpc4) and integrin αvβ6, and the responsiveness of patient populations to αvβ6-active compounds and compositions (e.g., antibodies and other ligands that bind αvβ6), particularly in cancer cells from such patient populations, more particularly on carcinomas such as pancreatic carcinomas. The invention thus provides methods for determining the responsiveness of tumor cells (particularly those from pancreatic tumors) to such αvβ6-active compounds and compositions by examining the expression of αvβ6 and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and small molecule drugs, that bind to integrin αvβ6 on the surfaces of tumor cells and/or that block one or more components of the TGF-β pathway, particularly in smad4-deficient tumor cells.
摘要翻译：本发明涉及细胞生物学，免疫学和肿瘤学领域。本发明涉及在肿瘤抑制基因smad4（也称为dpc4）和整联蛋白αv＆bgr6之间的表达水平与患者群体对αvβb活性化合物和组合物（例如，，抗体和其他结合αv和bgr的配体; 6），特别是在来自这些患者群体的癌细胞中，更特别地涉及癌如胰腺癌。因此，本发明提供了通过检查肿瘤细胞的αv＆bgr6和smad4的表达以及诊断方法来确定肿瘤细胞（特别是来自胰腺肿瘤的细胞）对这种αvβb-活性化合物和组合物的反应性的方法和使用与肿瘤细胞表面上的整联蛋白αv和bgr结合的配体（包括抗体和小分子药物）治疗/预防肿瘤进展和/或阻断TGF-和bgr的一种或多种成分; 途径，特别是在smad4缺陷型肿瘤细胞中。

4. 发明申请

US20090028853A1 TREATMENT AND PREVENTION OF CHRONIC ASTHMA USING ANTAGONISTS OF INTEGRIN ALPHAvBETA6 审中-公开
标题翻译：治疗和预防使用INTEGRIN ALPHAVBETA6的拮抗剂治疗慢性哮喘
公开(公告)号：US20090028853A1
公开(公告)日：2009-01-29
申请号：US11872876
申请日：2007-10-16
申请人： Dean SHEPPARD , Xiaozhu Huang , Shelia M. VIOLETTE
发明人： Dean SHEPPARD , Xiaozhu Huang , Shelia M. VIOLETTE
IPC分类号： A61K39/395 , A61P11/06 , A61P11/00
CPC分类号： C07K16/2839 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0368 , C07K2317/24 , C07K2317/41 , C07K2317/56 , C07K2317/565
摘要： The present invention relates to methods of asthma treatment and prevention using αvβ6 antagonists, such as αvβ6-binding antibodies. In particular, the invention relates to the discovery of a correlation between reduced expression of αvβ6 and the protection from the increase in airway sensitivity seen in chronic allergen-challenged mice. This protection is associated with protection from the usual allergen-induced increase in airway epithelial mast cells.
摘要翻译：本发明涉及使用alphavbeta6拮抗剂（例如α-位点结合抗体）进行哮喘治疗和预防的方法。特别地，本发明涉及在慢性过敏原挑战的小鼠中观察到的alphavbeta6的表达减少与气道敏感性增加之间的相关性的发现。这种保护与通常的过敏原诱导的气道上皮肥大细胞增加有关。

5. 发明申请

US20120251532A1 ANTI-ALPHA V BETA 6 ANTIBODIES 审中-公开
标题翻译：抗ALPHA V BETA 6抗体
公开(公告)号：US20120251532A1
公开(公告)日：2012-10-04
申请号：US13443261
申请日：2012-04-10
申请人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
发明人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
IPC分类号： A61K39/395 , A61P17/06
CPC分类号： C07K16/2839 , A61K47/48507 , A61K47/48561 , A61K47/48623 , A61K47/68 , A61K47/6835 , A61K47/6849 , A61K47/6851 , A61K47/6865 , A61K51/1027 , A61K51/1066 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/77 , C07K2317/92 , G01N33/57492 , G01N33/6893 , G01N2333/70546 , G01N2800/085 , G01N2800/205
摘要： Monoclonal antibodies that specifically bind to M.96. Also included are methods of using these antibodies to treat mammals having or at risk of having 006-mediated diseases, or to diagnose % Qmediated diseases.
摘要翻译：特异性结合M.96的单克隆抗体。还包括使用这些抗体治疗具有或具有006介导的疾病的风险的哺乳动物或诊断％Q介导的疾病的方法。

6. 发明授权

US08153126B2 Anti-αvβ6 antibodies 有权
标题翻译：抗αv＆bgr; 6抗体
公开(公告)号：US08153126B2
公开(公告)日：2012-04-10
申请号：US12260510
申请日：2008-10-29
申请人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
发明人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
IPC分类号： A61K39/395
CPC分类号： C07K16/2839 , A61K47/48507 , A61K47/48561 , A61K47/48623 , A61K47/68 , A61K47/6835 , A61K47/6849 , A61K47/6851 , A61K47/6865 , A61K51/1027 , A61K51/1066 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/77 , C07K2317/92 , G01N33/57492 , G01N33/6893 , G01N2333/70546 , G01N2800/085 , G01N2800/205
摘要： Monoclonal antibodies that specifically bind to □v□□. Also included are methods of using these antibodies to treat mammals having or at risk of having □v□6-mediated diseases, or to diagnose □V□6-mediated diseases.
摘要翻译：特异性结合□v□□的单克隆抗体。还包括使用这些抗体治疗具有或有V□6介导的疾病或具有□v□6介导的疾病风险的哺乳动物或诊断□V□6介导的疾病的方法。

7. 发明申请

US20110305629A1 Anti-Alpha v Beta 6 Antibodies and Uses Thereof 有权
标题翻译：抗Alpha v Beta 6抗体及其用途
公开(公告)号：US20110305629A1
公开(公告)日：2011-12-15
申请号：US13109168
申请日：2011-05-17
申请人： Shelia M. Violette , Louise A. Koopman , Kenneth J. Simon , Paul H. Weinreb , Herman W.T. van Vlijmen , Jose W. Saldanha , Alexey A. Lugovskoy
发明人： Shelia M. Violette , Louise A. Koopman , Kenneth J. Simon , Paul H. Weinreb , Herman W.T. van Vlijmen , Jose W. Saldanha , Alexey A. Lugovskoy
IPC分类号： A61K39/395 , A61K51/10 , A61P35/04 , A61K51/00 , A61P17/06 , A61P35/00
CPC分类号： C07K16/2839 , A61K2039/505 , A61K2039/545 , C07K16/30 , C07K2317/24 , C07K2317/41 , C07K2317/567 , C07K2317/76 , C07K2317/77 , G01N33/57407 , G01N33/57492 , G01N33/6893 , G01N2333/70546 , G01N2800/085 , G01N2800/12 , G01N2800/20 , G01N2800/347 , Y10S424/80 , Y10S424/801
摘要： The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize αvβ6 integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-αvβ6 antibodies of the invention. The invention also relates to the identification of differential expression of the integrin αvβ6 on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin αvβ6.
摘要翻译：本发明涉及细胞生物学，免疫学和肿瘤学领域。本发明提供识别αv和bgr6整联蛋白的人源化抗体，所述抗体包含非人来源的可变区和至少一部分人源免疫球蛋白。本发明还提供了制备这些抗体的方法，包含它们的药物组合物，以及通过施用本发明的人源化抗αv和bgr6抗体来治疗，诊断和/或预防各种疾病和病症的方法。本发明还涉及确定肿瘤细胞和组织表面的整合素αv和bgr6的差异表达，使用该差异表达来确定肿瘤细胞的转移潜能，以及诊断和治疗/预防肿瘤的方法转移和消除残留的转移性肿瘤细胞，使用结合整联蛋白αv＆bgr的配体，特别是抗体。

8. 发明申请

US20090186036A1 Anti-Alpha V Beta 6 Antibodies 有权
标题翻译：抗Alpha V Beta 6抗体
公开(公告)号：US20090186036A1
公开(公告)日：2009-07-23
申请号：US12260510
申请日：2008-10-29
申请人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
发明人： Shelia M. Violette , Paul H. Weinreb , Kenneth J. Simon , Dean Sheppard , Diane R. Leone
IPC分类号： A61K39/395
CPC分类号： C07K16/2839 , A61K47/48507 , A61K47/48561 , A61K47/48623 , A61K47/68 , A61K47/6835 , A61K47/6849 , A61K47/6851 , A61K47/6865 , A61K51/1027 , A61K51/1066 , A61K2039/505 , C07K2317/24 , C07K2317/56 , C07K2317/565 , C07K2317/73 , C07K2317/76 , C07K2317/77 , C07K2317/92 , G01N33/57492 , G01N33/6893 , G01N2333/70546 , G01N2800/085 , G01N2800/205
摘要： Monoclonal antibodies that specifically bind to M.96. Also included are methods of using these antibodies to treat mammals having or at risk of having O06-mediated diseases, or to diagnose % Qmediated diseases.
摘要翻译：特异性结合M.96的单克隆抗体。还包括使用这些抗体来治疗具有O06介导的疾病或有O06介导的疾病的危险的哺乳动物的方法，或用于诊断％Q介导的疾病。

9. 发明申请

US20120027754A1 Treatment and Prevention of Chronic Asthma Using Antagonists of Integrin AlphavBeta6 审中-公开
标题翻译：使用整合素AlphavBeta6的拮抗剂治疗和预防慢性哮喘
公开(公告)号：US20120027754A1
公开(公告)日：2012-02-02
申请号：US13204382
申请日：2011-08-05
申请人： Dean Sheppard , Xiaozhu Huang , Shelia M. Violette
发明人： Dean Sheppard , Xiaozhu Huang , Shelia M. Violette
IPC分类号： A61K39/395 , A61P11/00 , A61P11/06
CPC分类号： C07K16/2839 , A01K67/0276 , A01K2217/075 , A01K2227/105 , A01K2267/0368 , C07K2317/24 , C07K2317/41 , C07K2317/56 , C07K2317/565
摘要： The present invention relates to methods of asthma treatment and prevention using αvβ6 antagonists, such as αvβ6-binding antibodies. In particular, the invention relates to the discovery of a correlation between reduced expression of αvβ6 and the protection from the increase in airway sensitivity seen in chronic allergen-challenged mice. This protection is associated with protection from the usual allergen-induced increase in airway epithelial mast cells.
摘要翻译：本发明涉及使用αv＆bgr6拮抗剂如αv和bgr-6结合抗体的哮喘治疗和预防方法。特别地，本发明涉及在慢性过敏原挑战小鼠中观察到的αv和bgr6的表达减少与气道敏感性增加之间的相关性的发现。这种保护与通常的过敏原诱导的气道上皮肥大细胞增加有关。

10. 发明申请

US20080286269A1 Anti-alpha(v)beta(6) antibodies and uses thereof 有权
标题翻译：抗α（v）β（6）抗体及其用途
公开(公告)号：US20080286269A1
公开(公告)日：2008-11-20
申请号：US11483190
申请日：2006-07-10
申请人： Shelia M. Violette , Louise A. Koopman , Kenneth J. Simon , Paul H. Weinreb , Herman W.T. van Vlijmen , Jose W. Saldanha , Alexey A. Lugovskoy
发明人： Shelia M. Violette , Louise A. Koopman , Kenneth J. Simon , Paul H. Weinreb , Herman W.T. van Vlijmen , Jose W. Saldanha , Alexey A. Lugovskoy
IPC分类号： A61K39/395 , C07K16/18 , C07H21/00 , A61P43/00 , G01N33/574 , C07K14/00
CPC分类号： C07K16/2839 , A61K2039/505 , A61K2039/545 , C07K16/30 , C07K2317/24 , C07K2317/41 , C07K2317/567 , C07K2317/76 , C07K2317/77 , G01N33/57407 , G01N33/57492 , G01N33/6893 , G01N2333/70546 , G01N2800/085 , G01N2800/12 , G01N2800/20 , G01N2800/347 , Y10S424/80 , Y10S424/801
摘要： The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize αvβ6 integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-αvβ6 antibodies of the invention. The invention also relates to the identification of differential expression of the integrin αvβ6 on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin αvβ6.
摘要翻译：本发明涉及细胞生物学，免疫学和肿瘤学领域。本发明提供识别α6β6E整联蛋白的人源化抗体，所述抗体包含非人来源的可变区和至少一部分人源免疫球蛋白。本发明还提供了制备这种抗体的方法，包含它们的药物组合物，以及通过施用人源化抗α6β6来治疗，诊断和/或预防各种疾病和病症的方法本发明的抗体。本发明还涉及鉴定肿瘤细胞和组织表面上的整联蛋白α-β6-6的差异表达，该差异表达在确定转移性肿瘤细胞的潜力，以及使用与整联蛋白α6β6结合的配体特别是抗体来诊断和治疗/预防肿瘤转移和消除残余转移性肿瘤细胞的方法， SUB>。

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