公开(公告)号：US20150086570A1

公开(公告)日：2015-03-26

申请号：US14387762

申请日：2013-03-15

Applicant: Biogen Idec MA Inc. ,  The Regents of the University of California

Inventor： Shelia M. Violette ,  Dean Sheppard

IPC: C12Q1/68

CPC classification number: C12Q1/6876 ,  C12Q1/6883 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/6893 ,  G01N2333/495 ,  G01N2333/70546 ,  G01N2800/52

Abstract: The present invention relates to biomarkers for use in determining the sensitivity of patients to therapy with αvβ6 integrin inhibition or therapy with TGF-β pathway inhibitors. The biomarker profiles disclosed herein provide individualized gene and protein profiles which will aid in treating diseases and disorders which are amenable to treatment with therapies designed against αvβ6-integrin and/or TGF-β pathway inhibitors.

Abstract translation: 本发明涉及用于确定患者用αv＆bgr6整联蛋白抑制或TGF-β1治疗的敏感性的生物标志物; 通路抑制剂。 本文公开的生物标志物概况提供个体化的基因和蛋白质谱，其将有助于治疗适于用针对αv＆bgr6-整联蛋白和/或TGF-β1设计的治疗方法治疗的疾病和病症; 通路抑制剂。

公开(公告)号：US20150140609A1

公开(公告)日：2015-05-21

申请号：US14444701

申请日：2014-07-28

Applicant: BIOGEN IDEC MA INC. ,  THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

Inventor： Shelia M. Violette ,  Paul H. Weinreb ,  Kenneth J. Simon ,  Dean Sheppard ,  Diane R. Leone

IPC: C07K16/28

CPC classification number: 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

Abstract: 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 % Q mediated diseases.

Abstract translation: 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。

公开(公告)号：US20140294809A1

公开(公告)日：2014-10-02

申请号：US14161207

申请日：2014-01-22

Applicant: BIOGEN IDEC MA INC.

Inventor： Shelia M. Violette ,  Louise A. Koopman ,  Kenneth J. Simon ,  Paul H. Weinreb ,  Herman W.T. Van Vlijmen ,  Jose W. Saldanha ,  Alexey A. Lugovskoy

IPC: C07K16/28

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：USRE44681E1

公开(公告)日：2013-12-31

申请号：US13863646

申请日：2013-04-16

Applicant: Biogen Idec MA Inc.

Inventor： Shelia M. Violette ,  Louise A. Koopman

IPC: A61K39/395 ,  C07K16/00

CPC classification number: G01N33/5011 ,  A61K38/1793 ,  A61K39/39558 ,  A61K2039/505 ,  C07K16/2839 ,  C07K2317/73 ,  G01N33/5091 ,  G01N33/574 ,  G01N33/57407 ,  A61K2300/00

Abstract: 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 ανβ6, and the responsiveness of patient populations to ανβ6-active compounds and compositions (e.g., antibodies and other ligands that bind ανβ6), 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 ανβ6-active compounds and compositions by examining the expression of ≢νβ6 and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and molecule drugs, that bind to integrin ανβ6 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.

Abstract translation: 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alphaneta6的表达水平之间存在关系，以及患者群体对α6β6活性化合物和组合物（例如，抗体和其他 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的配体。 因此，本发明提供了通过检查肿瘤细胞的alphav nubeta6和smad4的表达以及诊断和治疗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α6β6活性化合物和组合物的反应性的方法 /使用与肿瘤细胞表面上的整联蛋白α2β6结合的配体（包括抗体和分子药物）预防肿瘤进展和/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。