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1. 发明申请

WO2004022054A1 PYRAZOLOPYRIDINES AND METHODS OF MAKING AND USING THE SAME 审中-公开
标题翻译：吡咯并吡啶类及其制备方法和使用方法
公开(公告)号：WO2004022054A1
公开(公告)日：2004-03-18
申请号：PCT/US2003/027722
申请日：2003-09-05
申请人： BIOGEN, INC. , LEE, Wen-Cherng , CARTER, Mary, Beth , SUN, Lihong , LYNE, Paul , CHUAQUI, Claudio , ZHENG, Zhongli , SINGH, Juswinder , BORIACK-SJODIN, Paula
发明人： LEE, Wen-Cherng , CARTER, Mary, Beth , SUN, Lihong , LYNE, Paul , CHUAQUI, Claudio , ZHENG, Zhongli , SINGH, Juswinder , BORIACK-SJODIN, Paula
IPC分类号： A61K31/415
CPC分类号： C07D487/04 , C07D471/04
摘要： Compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I:
摘要翻译：式I化合物对Alk 5和/或Alk 4具有出人意料的高亲和力，并且可用作其拮抗剂，用于预防和/或治疗包括纤维化疾病在内的许多疾病。在一个实施方案中，本发明的特征在于式I的化合物：

2. 发明申请

WO2003087304A3 TRI-SUBSTITUTED HETEROARYLS AND METHODS OF MAKING AND USING THE SAME 审中-公开
公开(公告)号：WO2003087304A3
公开(公告)日：2003-10-23
申请号：PCT/US2003/010440
申请日：2003-04-04
申请人： BIOGEN, INC. , LEE, Wen-Cherng , SUN, Lihong , SHAN, Feng , CHUAQUI, Claudio , ZHENG, Zhongli , PETTER, Russell, C.
发明人： LEE, Wen-Cherng , SUN, Lihong , SHAN, Feng , CHUAQUI, Claudio , ZHENG, Zhongli , PETTER, Russell, C.
IPC分类号： A61K31/36
摘要： Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (I).

3. 发明申请

WO2003087304A2 TRI-SUBSTITUTED HETEROARYLS AND METHODS OF MAKING AND USING THE SAME 审中-公开
标题翻译：三取代异构体及其制备方法和使用方法
公开(公告)号：WO2003087304A2
公开(公告)日：2003-10-23
申请号：PCT/US2003/010440
申请日：2003-04-04
申请人： BIOGEN, INC. , LEE, Wen-Cherng , SUN, Lihong , SHAN, Feng , CHUAQUI, Claudio , ZHENG, Zhongli , PETTER, Russell, C.
发明人： LEE, Wen-Cherng , SUN, Lihong , SHAN, Feng , CHUAQUI, Claudio , ZHENG, Zhongli , PETTER, Russell, C.
IPC分类号： C12N
CPC分类号： C07D471/04 , C07D401/04 , C07D401/14 , C07D405/14 , C07D413/14 , C07D417/14 , C07D453/00 , C07D487/08
摘要： Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (I).
摘要翻译：式（I）化合物对Alk 5和/或Alk 4具有出人意料的高亲和力，并且可用作其拮抗剂，用于预防和/或治疗包括纤维化疾病在内的许多疾病。在一个实施方案中，本发明的特征在于通式（I）的化合物。

4. 发明申请

WO2002018445A2 CO-CRYSTAL STRUCTURE OF MONOCLONAL ANTIBODY 5C8 AND CD154, AND USE THEREOF IN DRUG DESIGN 审中-公开
标题翻译：单克隆抗体5C8和CD154的CO结晶结构及其在药物设计中的应用
公开(公告)号：WO2002018445A2
公开(公告)日：2002-03-07
申请号：PCT/US2001/027352
申请日：2001-08-31
申请人： BIOGEN, INC. , KARPUSAS, Michael , HSU, Yen-Ming , TAYLOR, Frederick, R. , ZHENG, Zhongli
发明人： KARPUSAS, Michael , HSU, Yen-Ming , TAYLOR, Frederick, R. , ZHENG, Zhongli
IPC分类号： C07K16/00
CPC分类号： C07K16/2875 , A61K2039/505 , C07K2299/00 , C07K2317/24 , C07K2317/34 , C07K2317/55
摘要： 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.
摘要翻译：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。具体地，该结构提供了由本文确定的结构坐标限定的结合位点。本发明还涉及一种计算机（机器），其包括机器可读数据存储介质，其包括用包括由本发明提供的结构坐标的机器可读数据编码的数据存储材料。计算机具有基于本发明提供的结构坐标将所述机读数据处理成CD154 /抗-CD154抗体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类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设计化学实体的方法或包含CD154的特异性结合CD154和作为CD40：CD154结合中断的功能的CD154的激动剂或拮抗剂的化合物，以及设计具有改善性质的单克隆抗体5c8或其抗原结合残基的变体，例如增加或降低对CD154的结合亲和力）。本发明还涉及包含单克隆抗体5c8或人源化单克隆抗体5c8的所述化学实体，化合物或变体的组合物。本发明还涉及所述化学实体，单克隆抗体5c8或人源化单克隆抗体5c8的化合物或变体的用途来治疗具有与不适当或异常CD154诱导的活化相关的一个或多个条件的受试者。

5. 发明申请

WO2002018445A3 CO-CRYSTAL STRUCTURE OF MONOCLONAL ANTIBODY 5C8 AND CD154, AND USE THEREOF IN DRUG DESIGN 审中-公开
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
申请人： BIOGEN, INC. , KARPUSAS, Michael , HSU, Yen-Ming , TAYLOR, Frederick, R. , ZHENG, Zhongli
发明人： KARPUSAS, Michael , HSU, Yen-Ming , TAYLOR, Frederick, R. , ZHENG, Zhongli
IPC分类号： C07K14/705
摘要： 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.

6. 发明申请

WO2004085618A2 METHOD OF SCREENING FOR TARGET LIGANDS 审中-公开
标题翻译：目标配对方法
公开(公告)号：WO2004085618A2
公开(公告)日：2004-10-07
申请号：PCT/US2004/008805
申请日：2004-03-22
申请人： NEOGENESIS PHARMACEUTICALS, INC. , NASH, Huw, M. , MASON, Keith , MOALLEMI, Ciamac , WINTNER, Edward , FLYNN, Daniel , KELLY, Michael , ADAMS, Steve , ZHENG, Zhongli , MAKARA, Greg
发明人： NASH, Huw, M. , MASON, Keith , MOALLEMI, Ciamac , WINTNER, Edward , FLYNN, Daniel , KELLY, Michael , ADAMS, Steve , ZHENG, Zhongli , MAKARA, Greg
IPC分类号： C12N
CPC分类号： C12Q1/485 , C12N9/12 , G01N30/72 , G01N33/6845 , G01N2500/04 , B01D15/34
摘要： A general system for screening targets (e.g., biomolecules) is described. The screening can be used to discover compounds that bind to a naturally occurring low activity or inactive state of a target and act as inhibitors of the target function as seen in subsequent biological assays.
摘要翻译：描述了用于筛选靶标的一般系统（例如，生物分子）。筛选可以用于发现结合靶的天然存在的低活性或非活性状态的化合物，并且作为靶功能的抑制剂，如随后的生物测定中所见。

7. 发明公开

EP1314037A2 METHODS OF DESIGNING AND PRODUCING COMPOUNDS HAVING IMPROVED BINDING AFFINITY FOR CD154 OR OTHER TRIMERIC PROTEINS 审中-公开
标题翻译：对于具有亲和力提高产品的生产方法进行结合CD154或其他TRIMER蛋白
公开(公告)号：EP1314037A2
公开(公告)日：2003-05-28
申请号：EP01966535.5
申请日：2001-08-31
申请人： BIOGEN, INC.
发明人： ZHENG, Zhongli , TAYLOR, Frederick, R. , BENJAMIN, Christopher, D. , HSU, Yen-Ming
IPC分类号： G01N33/554 , G01N33/536 , C07K16/28 , A61K39/395 , A61P37/00
CPC分类号： C07K16/2875 , A61K38/00 , A61K2039/505 , C07K14/70575 , C07K2319/00 , G01N33/56972 , G01N2333/70575 , G01N2333/70578 , G01N2500/10 , G01N2500/20
摘要： The present invention relates to methods for designing and producing novel CD40:CD154 binding interruptor compounds and methods using these compounds to treat conditions associated with inappropriate CD154 activation in a subject. This invention also relates to novel methods for screening candidate compounds for the properties of specifically binding CD154 and interrupting CD40:CD154 interaction. This invention further relates to methods of improving the binding affinity, or the ability to block CD40/CD154 interaction, of a synthetic molecule for a trimeric protein, such as CD154. These methods comprise converting a first synthetic molecule that cannot promote lattice or aggregate formation of its target trimeric protein to a second synthetic molecule that can promote lattice or aggregate formation of its target trimeric protein. This invention also relates to a two-dimensional lattice or aggregate comprising a plurality of trimeric CD154 on a cell surface or in solution, wherein the lattice or aggregate is formed by bivalent anti-CD154 antibodies associated with trimeric CD154 molecules.

8. 发明公开

EP1253923A1 PHARMACEUTICAL COMPOSITIONS CONTAINING ANTI-BETA 1 INTEGRIN COMPOUNDS AND USES 审中-公开
标题翻译：药物组合物含有抗β1整合化合物及其使用
公开(公告)号：EP1253923A1
公开(公告)日：2002-11-06
申请号：EP01905160.6
申请日：2001-01-26
申请人： BIOGEN, INC.
发明人： ZHENG, Zhongli , CUERVO, Julio, H. , LIN, KoChung , ATEEQ, Humayun, Saleem
IPC分类号： A61K31/401 , A61K31/4025 , A61K31/445 , C07K5/06 , A61P11/06 , A61P17/00 , A61P19/02 , A61P19/04 , A61P37/00
CPC分类号： C07K5/06165 , A61K31/401 , A61K31/4025 , A61K31/445 , A61K38/00 , C07K5/06139 , C07K5/06173
摘要： Organic Anti-Beta 1 integrin compounds useful for inhibiting cell-adhesion.

9. 发明公开

EP1328548A2 CO-CRYSTAL STRUCTURE OF MONOCLONAL ANTIBODY 5C8 AND CD154, AND USE THEREOF IN DRUG DESIGN 审中-公开
标题翻译： KOKRISTALLSTRUKTUR单克隆抗体5C8和CD154，其使用毒品草案
公开(公告)号：EP1328548A2
公开(公告)日：2003-07-23
申请号：EP01968425.7
申请日：2001-08-31
申请人： BIOGEN, INC.
发明人： KARPUSAS, Michael , HSU, Yen-Ming , TAYLOR, Frederick, R. , ZHENG, Zhongli
IPC分类号： C07K14/705 , C07K16/28 , G06F19/00 , G01N33/53 , A61K39/395 , A61P37/00
CPC分类号： C07K16/2875 , A61K2039/505 , C07K2299/00 , C07K2317/24 , C07K2317/34 , C07K2317/55
摘要： 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 complex to design chemical entities or compounds, including agonists or antagonists of CD154, that specifically bind CD154 and function as CD40:CD154 binding interrupters, as well as to design variants of monoclonal antibody 5c8, or humanized monoclonal antibody 5c8, or antigen binding fragments 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 conditions associated with inappropriate or abnormal CD154 induced activation.

10. 发明公开

EP1499308A2 TRI-SUBSTITUTED HETEROARYLS AND METHODS OF MAKING AND USING THE SAME 审中-公开
标题翻译：三取代杂及其制造方法和使用
公开(公告)号：EP1499308A2
公开(公告)日：2005-01-26
申请号：EP03726198.9
申请日：2003-04-04
申请人： BIOGEN, INC.
发明人： LEE, Wen-Cherng , SUN, Lihong , SHAN, Feng , CHUAQUI, Claudio , ZHENG, Zhongli , PETTER, Russell, C.
IPC分类号： A61K31/36 , A61K31/395 , A61K31/41 , A61K31/435 , A61K31/517 , C07D401/04 , C07D401/14 , C07D405/04 , C07D405/14 , C07D409/04 , C07D409/14
CPC分类号： C07D471/04 , C07D401/04 , C07D401/14 , C07D405/14 , C07D413/14 , C07D417/14 , C07D453/00 , C07D487/08
摘要： Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (I).

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