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1. 发明授权

US08314091B2 N-benzyl,N'-arylcarbonylpiperazine derivatives 有权
标题翻译： N-苄基，N'-芳基羰基哌嗪衍生物
公开(公告)号：US08314091B2
公开(公告)日：2012-11-20
申请号：US12194146
申请日：2008-08-19
申请人： Koc-Kan Ho , Andrew Laird Roughton , Irina Neagu , Jui-Hsiang Chan , Nasrin Ansari , Michelle Lee Morris , Yajing Rong , Michael Ohlmeyer , Andrew John Cooke , Andrew Stanley Edwards , David Jonathan Bennett
发明人： Koc-Kan Ho , Andrew Laird Roughton , Irina Neagu , Jui-Hsiang Chan , Nasrin Ansari , Michelle Lee Morris , Yajing Rong , Michael Ohlmeyer , Andrew John Cooke , Andrew Stanley Edwards , David Jonathan Bennett
IPC分类号： A01N43/62 , A01N43/58 , A01N43/60 , A61K31/55 , A61K31/535 , A61K31/50 , A61K31/495 , A61K31/497 , A61K31/4965 , C07D243/00 , C07D487/22 , C07D491/00 , C07D498/00 , C07D243/08 , C07D413/00 , C07D239/02 , C07D241/36 , C07D271/00 , C07D487/00 , C07D495/00 , C07D497/00 , C07D513/00 , C07D417/00 , C07D419/00 , C07D241/02 , C07D403/00 , C07D411/00 , C07D295/00
CPC分类号： C07D295/192 , C07D241/04 , C07D243/08 , C07D401/06 , C07D401/12 , C07D403/06 , C07D405/12 , C07D409/12 , C07D413/12 , C07D417/12
摘要： The present invention relates to N-benzyl,N′-arylcarbonylpiperazine derivatives having the general formula I to pharmaceutical compositions comprising the same, and to the use of a these N-benzyl,N′-arylcarbonylpiperazine derivatives for the manufacture of a medicament for treating or preventing atherosclerosis and related disorders associated with cholesterol and bile acids transport and metabolism.
摘要翻译：本发明涉及具有通式I的N-苄基，N'-芳基羰基哌嗪衍生物，其包含其的药物组合物，以及这些N-苄基，N'-芳基羰基哌嗪衍生物在制备用于治疗或预防与胆固醇和胆汁酸运输和代谢相关的动脉粥样硬化和相关疾病。

2. 发明授权

US08258293B2 Tetrahydroquinoline derivatives 有权
公开(公告)号：US08258293B2
公开(公告)日：2012-09-04
申请号：US13268214
申请日：2011-10-07
申请人： Nicole Corine Renee Van Straten , Rudolf Gijsbertus Van Someren , Jurgen Schulz
发明人： Nicole Corine Renee Van Straten , Rudolf Gijsbertus Van Someren , Jurgen Schulz
IPC分类号： C07D215/08 , C07D215/12 , C07D215/20 , C07D215/38 , C07D215/48 , C07D401/12 , C07D405/12 , C07D405/14 , C07D409/12 , C07D413/12 , C07D417/12
CPC分类号： C07D215/38 , A61K31/47 , A61K31/4709 , C07D215/08 , C07D215/20 , C07D215/48
摘要： The present invention relates to tetrahydroquinoline derivatives having general formula I: or a pharmaceutically acceptable salt thereof, wherein R1 is formyl, (1-6C)alkylcarbonyl or (1-6C)alkylsulfonyl; R2 and R3 are H or (1-4C)alkyl; R4 is phenyl; R5 is (1-4C)alkyl; Y—X is C(O)—O, S(O)2-O, NHC(O)—O, NHC(S)—O, OC(O)—O, bond-O, C(O)—NH, S(O)2-NH, NHC(O)—NH, NHC(S)—NH, OC(O)—NH, bond-NH, NH—C(O), O—C(O), NH—S(O)2, or O—S(O)2 or Y—X is a bond; R6 is H, trifluoromethyl, (1-6C)alkyl, 1- or 2-adamantyl(1-4C)alkyl, (2-6C)alkenyl, (2-6C)alkynyl, (3-9C)heteroaryl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, (1-4C)alkylthio(1-4C)alkyl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, R8,R9-aminocarbonyl(1-4C)alkyl, R8,R9-amino(1-4C)alkyl, R8-oxycarbonyl(1-4C)alkyl, R8-oxy(1-4C)alkyl, R8-carbonyl(1-4C)alkyl or (6-10C)aryl; R7 is H, (1-4C)alkyl, (1-4C)alkoxy, halogen, trifluoromethyl, cyano, nitro, hydroxyl; and R8 and/or R9 is H, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (6-10C)aryl, (3-9C)heteroaryl, (6-10C)aryl(1-4C)alkyl, (3-9C)heteroaryl(1-4C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl, (2-6C)heterocycloalkyl(1-4C)alkyl, (1-4C)(di)alkylamino(1-4C)alkyl, (1-4C)alkoxy(1-4C)alkyl, (1-4C)alkylthio(1-4C)alkyl, (1-4C)alkylcarbonylamino(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonylamino(1-4C)alkyl, (3-6C)cycloalkyl, (2-6C)heterocycloalkyl, or R8 and R9 may be joined in a (2-6C)heterocycloalkyl ring. The present invention also relates to pharmaceutical compositions comprising said derivatives and the use of these derivatives to control fertility.

3. 发明授权

US08143246B2 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives 失效
标题翻译： 1-（4-（吡啶-2-基）苄基）咪唑烷-2,4-二酮衍生物
公开(公告)号：US08143246B2
公开(公告)日：2012-03-27
申请号：US12628538
申请日：2010-02-15
申请人： Marcelis van der Stelt , Joseph Maria Gerardus Barbara Cals , Johannes Petrus Gerardus Klomp
发明人： Marcelis van der Stelt , Joseph Maria Gerardus Barbara Cals , Johannes Petrus Gerardus Klomp
IPC分类号： C07D417/14 , C07D401/14 , C07D413/14 , C07D405/14 , A61K31/445 , A61K31/541
CPC分类号： C07D401/10 , C07D401/14 , C07D405/14
摘要： The invention relates to 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivative having the general Formula I wherein R1 is H, (C1-6)alkyl (optionally substituted with oxo, (C1-3)alkyloxy, (C1-3)alkyloxycarbonyl, halogen or CN), (C3-6)cycloalkyl or (C3-6)cycloalkyl(C1-3)alkyl, each cycloalkyl ring optionally comprising a heteroatom selected from O and S; R2 and R3 are independently H or (C1-3)alkyl; or R2 and R3 form together with the carbon atom to which they are bound a (C3-5)cycloalkyl group; R4 is H or 1 to 3 F substituents; R5 is H or 1 to 4 F substituents; R6 and R7 are independently H or F; X represents R8, OR8, NR8R9, R8 is (C5-7)cycloalkyl optionally comprising a heteroatom selected from O, S, SO and SO2; R9 is H or (C1-4)alkyl; R10 represents 1-3 substituents independently selected from H, (C1-3)alkyl, halogen, oxo, CN and CF3; Y is CF2, O, S, SO or SO2; or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of said 1-(4-(pyridin-2-yl)benzyl)imidazolidine-2,4-dione derivatives in the treatment of pain such as for example peri-operative pain, chronic pain, neuropathic pain, cancer pain and pain and spasticity associated with multiple sclerosis.
摘要翻译：本发明涉及具有通式I的1-（4-（吡啶-2-基）苄基）咪唑烷-2,4-二酮衍生物，其中R 1是H，（C 1-6）烷基（任选被氧代取代，（C 1 -3）烷氧基，（C1-3）烷氧基羰基，卤素或CN），（C3-6）环烷基或（C3-6）环烷基（C1-3）烷基，每个环烷基环任选地包含选自O和S的杂原子; R2和R3独立地是H或（C1-3）烷基; 或者R 2和R 3与它们所连接的碳原子一起形成（C 3-5）环烷基; R4为H或1〜3F取代基; R5为H或1〜4F取代基; R6和R7独立地为H或F; X代表R8，OR8，NR8R9，R8是任选地含有选自O，S，SO和SO 2的杂原子的（C5-7）环烷基; R 9为H或（C 1-4）烷基; R 10表示1-3个独立地选自H，（C 1-3）烷基，卤素，氧代，CN和CF 3的取代基; Y为CF 2，O，S，SO或SO 2; 或其药学上可接受的盐用于包含其的药物组合物，以及所述1-（4-（吡啶-2-基）苄基）咪唑烷-2,4-二酮衍生物在治疗疼痛中的用途，例如例如围手术期疼痛，慢性疼痛，神经性疼痛，癌症疼痛和与多发性硬化相关的疼痛和痉挛状态。

4. 发明授权

US09505802B2 Method for protein isolation in anoxic conditions 有权
标题翻译：缺氧条件下蛋白质分离的方法
公开(公告)号：US09505802B2
公开(公告)日：2016-11-29
申请号：US14325822
申请日：2014-07-08
申请人： MSD OSS B.V.
发明人： Peter Van Der Meijden , Gijsbert Willem Karel Van Dedem , Michel Hendrikus Maria Eppink , Roeland Wilhelmus Wassenaar
IPC分类号： C07K1/14 , C07K1/113 , C07K1/36 , C07K14/62
CPC分类号： C07K1/14 , C07K1/113 , C07K1/36 , C07K14/62
摘要： The present invention relates to a method for the isolation of proteins that comprise disulfide-bonds in their native conformation. Essentially, a method of the present makes the use of reducing agents such as β-mercaptoethanol or dithiothreitol in protein isolation methods obsolete. A method of the present invention is particularly suitable for the isolation of precursor proteins such as proinsulin from recombinant cells.
摘要翻译：本发明涉及一种分离其天然构象中包含二硫键的蛋白质的方法。基本上，本发明的方法使蛋白质分离方法中使用诸如β-巯基乙醇或二硫苏糖醇的还原剂过时。本发明的方法特别适用于从重组细胞中分离前体蛋白如胰岛素原。

5. 发明申请

US20130131029A1 ANTISOLVENT SOLIDIFICATION PROCESS 审中-公开
标题翻译：抗菌固化工艺
公开(公告)号：US20130131029A1
公开(公告)日：2013-05-23
申请号：US13737061
申请日：2013-01-09
申请人： MSD Oss B.V.
发明人： Wridzer Jan Willem Bakker , Robert Michael Geertman , Marianne Frederika Reedijk , Jozef Johannes Maria Baltussen , Gerrald Bargeman , Cornelis Elizabeth Johannus Van Lare
IPC分类号： B01D9/00 , A61K9/14 , C07J1/00 , C01D3/24 , C07J7/00
CPC分类号： B01D9/0063 , A61K9/14 , A61K9/1688 , A61K31/57 , B01D9/005 , C01D3/24 , C07J1/00 , C07J7/0005 , C07J7/0045
摘要： The present invention relates to a antisolvent solidification process wherein a liquid medium comprising at least one organic or inorganic compound which is to be solidified is forced through a membrane into one or more antisolvents, or wherein one or more antisolvents are forced through a membrane into a liquid medium comprising at least one organic or inorganic compound which is to be solidified, yielding a composition comprising solid particles comprising said organic and/or inorganic compound(s).
摘要翻译：本发明涉及一种抗溶剂固化方法，其中包含至少一种待固化的有机或无机化合物的液体介质被迫通过膜进入一种或多种抗溶剂，或其中一种或多种抗溶剂被迫通过膜进入包含至少一种待固化的有机或无机化合物的液体介质，产生包含所述有机和/或无机化合物的固体颗粒的组合物。

6. 发明授权

US08357679B2 Hexafluoroisopropanol derivatives 有权
标题翻译：六氟异丙醇衍生物
公开(公告)号：US08357679B2
公开(公告)日：2013-01-22
申请号：US12465134
申请日：2009-05-13
申请人： Andrew John Cooke , Andrew Stanley Edwards , Fiona Elizabeth Andrews , David Jonathan Bennett , Olaf Nimz , Emma Louise Carswell
发明人： Andrew John Cooke , Andrew Stanley Edwards , Fiona Elizabeth Andrews , David Jonathan Bennett , Olaf Nimz , Emma Louise Carswell
IPC分类号： A61K31/50 , A61K31/55 , A61K31/4965 , A61K31/497 , A61K31/51 , A01N43/54 , C07D239/02 , C07D243/00 , C07D403/00 , C07D241/04 , C07D295/00
CPC分类号： C07D295/192 , C07D243/08
摘要： The present invention relates to hexafluoroisopropanol derivatives having the general formula I to pharmaceutical compositions comprising the same and to the use of these hexafluoroisopropanol derivatives in the treatment of atherosclerosis.
摘要翻译：本发明涉及具有通式I的六氟异丙醇衍生物，其含有该组合物的药物组合物以及这些六氟异丙醇衍生物用于治疗动脉粥样硬化的用途。

7. 发明授权

US08354509B2 Antibodies to human programmed death receptor PD-1 有权
标题翻译：人类程序性死亡受体PD-1的抗体
公开(公告)号：US08354509B2
公开(公告)日：2013-01-15
申请号：US12663950
申请日：2008-06-13
申请人： Gregory John Carven , Hans van Eenennaam , Gradus Johannes Dulos
发明人： Gregory John Carven , Hans van Eenennaam , Gradus Johannes Dulos
IPC分类号： C07K16/00
CPC分类号： C07K16/2803 , C07K16/2818 , C07K2317/24 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/57488 , G01N33/6869 , G01N2333/55 , G01N2800/52
摘要： Antibodies which block the binding of human Programmed Death Receptor 1 (hPD-1) to its ligands (hPD-L1 or hPD-L2) and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune response through the PD-I pathway is also disclosed.
摘要翻译：公开了阻断人程序死亡受体1（hPD-1）与其配体（hPD-L1或hPD-L2）及其可变区序列的结合的抗体。还公开了通过PD-1途径增加免疫应答的活性（或降低调节）的方法。

8. 发明授权

US08129397B2 Substituted thieno[2,3-d]pyrimidines as AMPA modulators 有权
标题翻译：取代噻吩并[2,3-d]嘧啶作为AMPA调节剂
公开(公告)号：US08129397B2
公开(公告)日：2012-03-06
申请号：US12269306
申请日：2008-11-12
申请人： Michael Gerard Gallagher , Craig C. Jamieson , Amanda Jane Lyons , John Kinnaird Ferguson Maclean , Elizabeth Margaret Moir
发明人： Michael Gerard Gallagher , Craig C. Jamieson , Amanda Jane Lyons , John Kinnaird Ferguson Maclean , Elizabeth Margaret Moir
IPC分类号： C07D495/04 , A61K31/519 , A61P25/24 , A61P25/28 , A61P25/22 , A61P25/18 , A61P25/16
CPC分类号： C07D495/04
摘要： The present invention relates to a heterocyclic derivative according to formula I wherein the variables are defined as in the specification, or to a pharmaceutically acceptable salt or solvate thereof. The present invention also relates to a pharmaceutical composition comprising said heterocyclic derivatives and to their use in therapy, for instance in the treatment or prevention of psychiatric diseases where an enhancement of synaptic responses mediated by AMPA receptors is required, including schizophrenia, depression and learning and memory disorders such as Alzheimer's disease.
摘要翻译：本发明涉及式I的杂环衍生物，其中变量如说明书中所定义，或其药学上可接受的盐或溶剂合物。本发明还涉及包含所述杂环衍生物的药物组合物及其在治疗中的用途，例如用于治疗或预防精神疾病，其中需要由AMPA受体介导的突触应答的增强，包括精神分裂症，抑郁和学习，以及记忆障碍如阿尔茨海默病。

9. 发明授权

US08802395B2 Method for protein isolation in anoxic conditions 有权
标题翻译：缺氧条件下蛋白质分离的方法
公开(公告)号：US08802395B2
公开(公告)日：2014-08-12
申请号：US13467305
申请日：2012-05-09
申请人： Peter Van Der Meijden , Gijsbert Willem Karel Van Dedem , Michel Hendrikus Maria Eppink , Roeland Wilhelmus Wassenaar
发明人： Peter Van Der Meijden , Gijsbert Willem Karel Van Dedem , Michel Hendrikus Maria Eppink , Roeland Wilhelmus Wassenaar
IPC分类号： C12P21/02
CPC分类号： C07K1/14 , C07K1/113 , C07K1/36 , C07K14/62
摘要： The present invention relates to a method for the isolation of proteins that comprise disulfide bonds in their native conformation. Essentially, a method of the present invention makes use of reducing agents such as β-mercaptoethanol or dithiothreitol in protein isolation methods obsolete. A method of the present invention is particularly suitable for the isolation of precursor proteins such as proinsulin from recombinant cells.
摘要翻译：本发明涉及一种分离其天然构象中包含二硫键的蛋白质的方法。基本上，本发明的方法在蛋白质分离方法中使用诸如“巯基乙醇”或“二硫苏糖醇”等还原剂已被淘汰。本发明的方法特别适用于从重组细胞中分离前体蛋白如胰岛素原。

10. 发明申请

US20130108651A1 ANTIBODIES TO HUMAN PROGRAMMED DEATH RECEPTOR PD-1 有权
公开(公告)号：US20130108651A1
公开(公告)日：2013-05-02
申请号：US13719763
申请日：2012-12-19
申请人： MSD OSS B.V.
发明人： Gregory John Carven , Hans Van Eenenneem , Gradus Johannes Dulos
IPC分类号： C07K16/28
CPC分类号： C07K16/2803 , C07K16/2818 , C07K2317/24 , C07K2317/565 , C07K2317/76 , C07K2317/92 , G01N33/57488 , G01N33/6869 , G01N2333/55 , G01N2800/52
摘要： Antibodies which block binding of hPD-1 to hPD-L1 or hPD-L2 and their variable region sequences are disclosed. A method of increasing the activity (or reducing downmodulation) of an immune cell through the PD-1 pathway is also disclosed.

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