公开(公告)号：WO2010104949A3

公开(公告)日：2010-09-16

申请号：PCT/US2010/026825

申请日：2010-03-10

Applicant: BIOGEN IDEC MA INC. ,  KALLED, Susan, L. ,  HSU, Yen-Ming

Inventor： KALLED, Susan, L. ,  HSU, Yen-Ming

IPC: C07K16/28 ,  A61K39/395

Abstract: This invention provides antibodies that recognize the B Cell Maturation Antigen (BCMA) and that bind naϊve B cells, plasma cells, and/or memory B cells. The invention further provides methods for depleting naϊve B cells, plasma cells, and memory B cells, and for treating B cell-related disorders, including lymphomas and autoimmune diseases.

公开(公告)号：WO2008118356A2

公开(公告)日：2008-10-02

申请号：PCT/US2008/003735

申请日：2008-03-21

Applicant: BIOGEN IDEC MA INC. ,  UCB PHARMA S.A. ,  BURKLY, Linda C. ,  FERRANT-ORGETTAS, Janine L. ,  GARBER, Ellen A. ,  HSU, Yen-ming ,  SU, Lihe ,  TAYLOR, Frederick R. ,  ADAMS, Ralph ,  BROWN, Derek Thomas ,  POPPLEWELL, Andrew George ,  ROBINSON, Martyn Kim ,  SHOCK, Anthony ,  TYSON, Kerry Louise

Inventor： BURKLY, Linda C. ,  FERRANT-ORGETTAS, Janine L. ,  GARBER, Ellen A. ,  HSU, Yen-ming ,  SU, Lihe ,  TAYLOR, Frederick R. ,  ADAMS, Ralph ,  BROWN, Derek Thomas ,  POPPLEWELL, Andrew George ,  ROBINSON, Martyn Kim ,  SHOCK, Anthony ,  TYSON, Kerry Louise

IPC: C07K16/00

CPC classification number: C07K16/2875 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/40 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/71 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/92

Abstract: This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.

Abstract translation: 本发明提供了特异性结合CD154（CD40L）蛋白的结合蛋白，包括抗体，抗体衍生物和抗体片段。 本发明还提供了嵌合的，人源化的或完全人源的抗体，抗体衍生物或抗体片段，其特异性结合人源化Fab片段的表位，所述人源化Fab片段包含根据SEQ ID NO：1的可变重链序列并且包含可变轻链序列 根据SEQ ID NO：2特异性结合。 相对于第二种抗CD154抗体，本发明的CD154结合蛋白可引起降低的效应子功能。 本发明的CD154结合蛋白可用于诊断和治疗方法，例如用于治疗和预防包括由CD154-CD40相互作用介导的不希望的免疫应答的疾病在内的疾病。

公开(公告)号：WO2004094620A3

公开(公告)日：2006-01-19

申请号：PCT/US2004007692

申请日：2004-03-26

Applicant: BIOGEN IDEC INC ,  AMBROSE CHRISTINE ,  THOMPSON JEFFREY ,  HSU YEN-MING ,  WEN DINGYI ,  SUN YAPING

Inventor： AMBROSE CHRISTINE ,  THOMPSON JEFFREY ,  HSU YEN-MING ,  WEN DINGYI ,  SUN YAPING

IPC: A61K38/00 ,  A61K38/17 ,  A61K39/395 ,  A61P37/00 ,  C07K14/705 ,  C07K14/715 ,  C07K16/00 ,  C07K16/18 ,  C07K19/00 ,  C12N20060101 ,  C12N1/00 ,  C12N15/00 ,  C12N15/12 ,  C12N15/13 ,  C12N15/62 ,  A61K38/18 ,  A61K38/19 ,  C07H21/04 ,  C07K14/475 ,  C07K14/52 ,  C12N5/18 ,  C12P21/00

CPC classification number: C07K14/715 ,  A61K38/00 ,  A61K39/00 ,  A61K2039/505 ,  C07K14/70578 ,  C07K14/7151 ,  C07K16/18 ,  C07K16/2866 ,  C07K2317/52 ,  C07K2317/73 ,  C07K2319/30

Abstract: The disclosure provides a non-naturally occurring BAFF-R glycoprotein having a deletion in the extracellular domain which results in an altered 0-linked glycosylation pattern. The disclosure also provides methods and pharmaceutical compositions for treating B-cell- and T-cell-mediated disorders.

Abstract translation: 本公开提供在细胞外结构域中具有缺失的非天然存在的BAFF-R糖蛋白，其导致改变的O-连接的糖基化模式。 本公开还提供了用于治疗B细胞和T细胞介导的病症的方法和药物组合物。

公开(公告)号：WO0218445A8

公开(公告)日：2002-12-27

申请号：PCT/US0127352

申请日：2001-08-31

Applicant: BIOGEN INC ,  KARPUSAS MICHAEL ,  HSU YEN-MING ,  TAYLOR FREDERICK R ,  ZHENG ZHONGLI

Inventor： KARPUSAS MICHAEL ,  HSU YEN-MING ,  TAYLOR FREDERICK R ,  ZHENG ZHONGLI

IPC: G01N33/48 ,  A61K39/395 ,  A61K45/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P7/00 ,  A61P9/10 ,  A61P11/00 ,  A61P11/02 ,  A61P11/04 ,  A61P11/06 ,  A61P13/12 ,  A61P17/04 ,  A61P17/06 ,  A61P19/08 ,  A61P25/00 ,  A61P25/12 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P31/14 ,  A61P35/00 ,  A61P35/02 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07K14/705 ,  C07K16/28 ,  G01N33/15 ,  G01N33/50 ,  G01N33/68 ,  C07K16/00

CPC classification number: C07K16/2875 ,  A61K2039/505 ,  C07K2299/00 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/55

Abstract: The present invention relates to compositions and crystals of CD154 (CD40L) in complex with an anti-CD154 antibody. In addition, this invention relates to the high resolution structure of a CD154/anti-CD154 antibody complex as obtained by X-ray crystallography. Specifically, this structure provides binding sites defined by the structure coordinates determined herein. This invention also relates to a computer (machine) comprising a machine-readable data storage medium comprising a data storage material encoded with machine-readable data comprising the structure coordinates provided by this invention. The computer has instructions to process said machine-readable data into a three-dimensional representation of a molecular complex of CD154/anti-CD154 antibody based on the structure coordinates provided by this invention. This invention also relates to methods using the structure coordinates of an CD154/anti-CD154 antibody complex to solve the structure of similar or homologous molecular complexes, as well as methods using the structure coordinates of an CD154/anti-CD154 antibody complexto design chemical entities or compounds, including agonists or antagonists of CD154, that specifically bind CD154 and function as CD40:CD154 binding interruptors, as well as to design variants of monoclonal antibody 5c8, or humanized monoclonal antibody 5c8, or antigen binding fragements thereof, having improved properties (such as increased or decreased binding affinity for CD154). This invention also relates to compositions comprising said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8. The invention further relates to uses of said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8 to treat a subject having one or more conditons associated with inappropriate or abnormal CD154 induced activation.

Abstract translation: 本发明涉及与抗CD154抗体复合的CD154（CD40L）的组合物和晶体。 此外，本发明涉及通过X射线晶体学获得的CD154 /抗CD154抗体复合物的高分辨率结构。 具体而言，该结构提供由在此确定的结构坐标定义的结合位点。 本发明还涉及一种包括机器可读数据存储介质的计算机（机器），该机器可读数据存储介质包括用机器可读数据编码的数据存储材料，该机器可读数据包括由本发明提供的结构坐标。 基于本发明提供的结构坐标，计算机具有处理所述机器可读数据为CD154 /抗CD154抗体的分子复合物的三维表示的指令。 本发明还涉及使用CD154 /抗CD154抗体复合物的结构坐标来解决相似或同源分子复合物的结构的方法，以及使用CD154 /抗CD154抗体复合物的结构坐标来设计化学实体的方法 或化合物（包括CD154的激动剂或拮抗剂），其特异性结合CD154并作为CD40：CD154结合阻断剂，以及设计具有改善特性的单克隆抗体5c8或人源化单克隆抗体5c8或其抗原结合片段的变体（ 如对CD154的结合亲和力增加或降低）。 本发明还涉及包含所述化学实体，单克隆抗体5c8或人源化单克隆抗体5c8的化合物或变体的组合物。 本发明进一步涉及单克隆抗体5c8或人源化单克隆抗体5c8的所述化学实体，化合物或变体用于治疗患有一种或多种与不适当或异常CD154诱导活化相关的病症的受试者的用途。

公开(公告)号：WO2002018445A3

公开(公告)日：2002-03-07

申请号：PCT/US2001/027352

申请日：2001-08-31

Applicant: BIOGEN, INC. ,  KARPUSAS, Michael ,  HSU, Yen-Ming ,  TAYLOR, Frederick, R. ,  ZHENG, Zhongli

Inventor： KARPUSAS, Michael ,  HSU, Yen-Ming ,  TAYLOR, Frederick, R. ,  ZHENG, Zhongli

IPC: C07K14/705

Abstract: The present invention relates to compositions and crystals of CD154 (CD40L) in complex with an anti-CD154 antibody. In addition, this invention relates to the high resolution structure of a CD154/anti-CD154 antibody complex as obtained by X-ray crystallography. Specifically, this structure provides binding sites defined by the structure coordinates determined herein. This invention also relates to a computer (machine) comprising a machine-readable data storage medium comprising a data storage material encoded with machine-readable data comprising the structure coordinates provided by this invention. The computer has instructions to process said machine-readable data into a three-dimensional representation of a molecular complex of CD154/anti-CD154 antibody based on the structure coordinates provided by this invention. This invention also relates to methods using the structure coordinates of an CD154/anti-CD154 antibody complex to solve the structure of similar or homologous molecular complexes, as well as methods using the structure coordinates of an CD154/anti-CD154 antibody complexto design chemical entities or compounds, including agonists or antagonists of CD154, that specifically bind CD154 and function as CD40:CD154 binding interruptors, as well as to design variants of monoclonal antibody 5c8, or humanized monoclonal antibody 5c8, or antigen binding fragements thereof, having improved properties (such as increased or decreased binding affinity for CD154). This invention also relates to compositions comprising said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8. The invention further relates to uses of said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8 to treat a subject having one or more conditons associated with inappropriate or abnormal CD154 induced activation.

公开(公告)号：WO0196397A2

公开(公告)日：2001-12-20

申请号：PCT/US0118517

申请日：2001-06-08

Applicant: BIOGEN INC ,  HSU YEN MING ,  GARBER ELLEN

Inventor： HSU YEN-MING ,  GARBER ELLEN

IPC: C12N15/09 ,  A61K31/7052 ,  A61K38/00 ,  A61K48/00 ,  A61P1/04 ,  A61P1/16 ,  A61P3/10 ,  A61P9/10 ,  A61P11/00 ,  A61P11/06 ,  A61P11/08 ,  A61P13/12 ,  A61P17/00 ,  A61P17/06 ,  A61P19/02 ,  A61P19/08 ,  A61P25/00 ,  A61P25/28 ,  A61P27/02 ,  A61P29/00 ,  A61P31/20 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P37/06 ,  A61P37/08 ,  C07K14/705 ,  C12N15/12

CPC classification number: C07K14/70575 ,  A61K38/00 ,  A61K48/00

Abstract: Methods of decreasing (e.g., inhibiting) the expression of wildtype CD154 on the surface of a target cell and methods of treating a patient suffering from or predisposed to a CD154-mediated disease. In these methods, a nucleic acid construct that directs expression of a mutant CD154 lacking at least a portion of the tumor necrosis factor homologous domain ("TNFH") is introduced into a target cell (such as a T helper cell or a cytotoxic T cell). The expressed mutant CD154 binds to wildtype CD154 inside the cell, rendering the wildtype protein unable to reach the cell surface.

Abstract translation: 降低（例如抑制）靶细胞表面上野生型CD154表达的方法和治疗患有或易患CD154介导的疾病的患者的方法。 在这些方法中，将缺乏至少一部分肿瘤坏死因子同源结构域（“TNFH”）的突变体CD154的表达的核酸构建体引入靶细胞（例如T辅助细胞或细胞毒性T细胞 ）。 表达的突变体CD154与细胞内的野生型CD154结合，使野生型蛋白不能到达细胞表面。

公开(公告)号：WO2008118356A3

公开(公告)日：2008-11-20

申请号：PCT/US2008003735

申请日：2008-03-21

Applicant: BIOGEN IDEC INC ,  UCB PHARMA SA ,  BURKLY LINDA C ,  FERRANT-ORGETTAS JANINE L ,  GARBER ELLEN A ,  HSU YEN-MING ,  SU LIHE ,  TAYLOR FREDERICK R ,  ADAMS RALPH ,  BROWN DEREK THOMAS ,  POPPLEWELL ANDREW GEORGE ,  ROBINSON MARTYN KIM ,  SHOCK ANTHONY ,  TYSON KERRY LOUISE

Inventor： BURKLY LINDA C ,  FERRANT-ORGETTAS JANINE L ,  GARBER ELLEN A ,  HSU YEN-MING ,  SU LIHE ,  TAYLOR FREDERICK R ,  ADAMS RALPH ,  BROWN DEREK THOMAS ,  POPPLEWELL ANDREW GEORGE ,  ROBINSON MARTYN KIM ,  SHOCK ANTHONY ,  TYSON KERRY LOUISE

IPC: C07K16/28 ,  A61K39/395 ,  C12N15/13 ,  C12N15/63

CPC classification number: C07K16/2875 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/40 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/71 ,  C07K2317/734 ,  C07K2317/76 ,  C07K2317/92

Abstract: This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.

Abstract translation: 本发明提供特异性结合CD154（CD40L）蛋白的结合蛋白，包括抗体，抗体衍生物和抗体片段。 本发明还提供了嵌合，人源化或完全人抗体，抗体衍生物或抗体片段，其特异性结合包含根据SEQ ID NO：1的可变重链序列的人源化Fab片段的表位，并包含可变轻链序列 根据SEQ ID NO：2特异性结合。 本发明的CD154结合蛋白可以引起相对于第二抗-CD154抗体降低的效应子功能。 本发明的CD154结合蛋白可用于诊断和治疗方法，例如治疗和预防包括由CD154-CD40相互作用介导的不良免疫应答的疾病。

公开(公告)号：WO2007059332A2

公开(公告)日：2007-05-24

申请号：PCT/US2006/044840

申请日：2006-11-17

Applicant: BIOGEN IDEC MA INC. ,  HSU, Yen-Ming ,  SU, Lihe

Inventor： HSU, Yen-Ming ,  SU, Lihe

IPC: G01N33/554

CPC classification number: G01N33/6863 ,  G01N33/86

Abstract: The present invention provides methods of determining platelet aggregation, methods of determining susceptibility to clotting upon administration of a CD40L-binding moiety, and kits related thereto.

Abstract translation: 本发明提供了确定血小板聚集的方法，在给予CD40L结合部分时确定凝血敏感性的方法，以及与其相关的试剂盒。

公开(公告)号：WO2007056288A3

公开(公告)日：2007-05-18

申请号：PCT/US2006/043196

申请日：2006-11-07

Applicant: BIOGEN IDEC MA INC. ,  HSU, Yen-Ming ,  KALLED, Susan, L.

Inventor： HSU, Yen-Ming ,  KALLED, Susan, L.

IPC: C07K16/28 ,  G01N33/53

Abstract: The present disclosure provides compositions and methods relating to the evaluation of BAFF in a biological sample from a subject.

公开(公告)号：WO2004027026A3

公开(公告)日：2005-01-06

申请号：PCT/US0329178

申请日：2003-09-19

Applicant: BIOGEN IDEC INC ,  RENNERT PAUL D ,  FARRINGTON GRAHAM K ,  ELDREDGE JOHN K ,  PELLETIER MARC ,  HSU YEN-MING

Inventor： RENNERT PAUL D ,  FARRINGTON GRAHAM K ,  ELDREDGE JOHN K ,  PELLETIER MARC ,  HSU YEN-MING

IPC: A61K38/00 ,  C07K14/705 ,  A61K38/16 ,  C07K1/16 ,  C07K1/18 ,  C07K1/22 ,  C07K2/00 ,  C12N5/00 ,  C12N7/00 ,  C12N15/09 ,  C12N15/63 ,  C12P21/00

CPC classification number: C07K14/70575 ,  A61K38/00

Abstract: The present invention relates to improved methods for producing biologically active truncated APRIL ligand polypeptides and analogs thereof. The invention further relates to truncated APRIL ligand polypeptides and analogs thereof that retain a high biological activity and may be isolated in high yields, as well as the nucleotide sequences that encode the truncated APRIL ligand polypeptides and analogs thereof. The invention also relates to compositions of the biologically active truncated APRIL ligand polypeptides and analogs thereof. The invention further relates to the use of the biologically active truncated APRIL ligand polypeptides and analogs thereof in promoting cell proliferation.

Abstract translation: 本发明涉及用于生产生物活性截短的APRIL配体多肽及其类似物的改进方法。 本发明进一步涉及截短的APRIL配体多肽及其类似物，其保留高生物活性并且可以以高产量分离，以及编码截短的APRIL配体多肽及其类似物的核苷酸序列。 本发明还涉及生物活性截短的APRIL配体多肽及其类似物的组合物。 本发明还涉及生物活性截短的APRIL配体多肽及其类似物在促进细胞增殖中的用途。