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1. 发明申请

WO2012020080A3 LIGANDS FOR AFFINITY CHROMATOGRAPHY 审中-公开
公开(公告)号：WO2012020080A3
公开(公告)日：2012-02-16
申请号：PCT/EP2011/063831
申请日：2011-08-11
申请人： GRAFFINITY PHARMACEUTICALS GMBH , BITTERMANN, Holger , BURKERT, Klaus , ARNOLD, Marc , KEIL, Oliver , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SCHWIZER, Daniel , SEKUL, Renate
发明人： BITTERMANN, Holger , BURKERT, Klaus , ARNOLD, Marc , KEIL, Oliver , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SCHWIZER, Daniel , SEKUL, Renate
IPC分类号： C07K1/22 , B01D15/38 , B01J20/286 , B01J20/32
摘要： The present invention relates to the use of a ligand-substituted matrix comprising a support material and at least one ligand covalently bonded to the support material, the being represented by formula (I) wherein L is the linking point on the support material to which the ligand is attached; V is a spacer group; v is 0 or 1; R 1 is hydrogen or C 1 to C 4 alkyl, preferably hydrogen or methyl; and more preferably hydrogen; R 2 is hydrogen or C 1 to C 4 alkyl, preferably hydrogen; Ar 1 is a divalent 5- or 6-membered substituted or unsubstituted aromatic ring; and Ar 2 is 5- or 6-membered aromatic ring which may be unsubstituted or which is (a) attached to a further 5- or 6-membered aromatic ring via a single bond; or (b) fused to a further 5- or 6-membered aromatic or non aromatic ring, as part of a multicyclic ring system; or (c) attached to at least one substituent selected from C 1 to C 4 alkyl; C 2 to C 4 alkenyl; C 2 to C 4 alkynyl; a halogen; C 1 to C 4 haloalkyl; hydroxyl-substituted C 1 to C 4 alkyl; C 1 to C 4 alkoxy; hydroxyl-substituted C 1 to C 4 alkoxy; C 1 to C 4 alkylamino; C 1 to C 4 alkylthio; and combinations thereof, for affinity purification of a protein.

2. 发明申请

WO2012017021A2 LIGANDS FOR ANTIBODY AND Fc-FUSION PROTEIN PURIFICATION BY AFFINITY CHROMATOGRAPHY 审中-公开
标题翻译：亲和层析技术用于抗体和Fc融合蛋白的亲和层析纯化
公开(公告)号：WO2012017021A2
公开(公告)日：2012-02-09
申请号：PCT/EP2011/063392
申请日：2011-08-03
申请人： GRAFFINITY PHARMACEUTICALS GMBH , BITTERMANN, Holger , BURKERT, Klaus , ARNOLD, Marc , KEIL, Oliver , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SCHWIZER, Daniel , SEKUL, Renate
发明人： BITTERMANN, Holger , BURKERT, Klaus , ARNOLD, Marc , KEIL, Oliver , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SCHWIZER, Daniel , SEKUL, Renate
IPC分类号： C07K1/22
CPC分类号： C07K1/22 , B01D15/3804 , B01J20/289 , B01J20/3251 , B01J20/3253 , B01J20/3255 , C07D209/42 , C07D213/82 , C07D217/26 , C07D231/14 , C07D231/56 , C07D235/24 , C07D261/18 , C07D261/20 , C07D271/06 , C07D277/46 , C07D277/56 , C07D277/68 , C07D277/82 , C07D307/87 , C07D403/04 , C07D405/04 , C07D409/04 , C07D413/04 , C07D417/04 , C07D417/14 , C07D471/04 , C07D487/04 , C07D513/04 , C07D519/00 , C07K16/00 , C08B37/0039
摘要： The present invention relates to the use for affinity purification of an antibody or an fragment of an antibody, of a ligand-substituted matrix comprising a support material and at least one ligand covalently bonded to the support material, the ligand being represented by formula (I) wherein Sp is a spacer group; v is 0 or 1; Am is an amide group -NR 1 -C(O)-, and wherein either NR 1 is attached to Ar 1 and C(O)- is attached to Ar 2 , or -C(O)- is attached to Ar 1 and NR 1 is attached to Ar 2 ; and R 1 is hydrogen or C 1 to C 4 alkyl, preferably hydrogen or methyl; and more preferably hydrogen; Ar 1 is a divalent 5- or 6-membered substituted or unsubstituted aromatic ring; Ar 2 is 5- or 6-membered heterocyclic aromatic ring which is (a) attached to a further 5- or 6-membered aromatic ring via a single bond; or (b) fused to a further 5- or 6-membered aromatic ring as part of a multicyclic ring system; or (c) attached to at least one substituent selected from C 1 to C 4 alkyl; C 2 to C 4 alkenyl; C 2 to C 4 alkynyl; a halogen; C 1 to C 4 haloalkyl; hydroxyl-substituted C 1 to C 4 alkyl; C 1 to C 4 alkoxy; hydroxyl-substituted C 1 to C 4 alkoxy; C 1 to C 4 alkylamino; C 1 to C 4 alkylthio; and combinations thereof.
摘要翻译：本发明涉及亲和纯化抗体或抗体片段，包含载体材料和至少一种共价结合于载体材料的配体的配体取代基质的用途，该配体由式（I）表示，其中Sp是间隔基团; v是0或1; Am是酰胺基-NR 1 -C（O） - ，其中或者NR 1与Ar 1和C（O）连接，） - 连接到Ar 2上，或者-C（O） - 连接到Ar 1上并且NR 1连接到Ar 2 ; 和R 1是氢或C 1至C 4烷基，优选氢或甲基; 更优选氢; Ar 1是二价5-或6-元取代或未取代的芳族环; Ar 2是5或6元杂环芳环，其（a）通过单键与另外的5或6元芳环连接; 或（b）作为多环体系的一部分与另一个5或6元芳族环稠合; 或（c）连接至少一个选自C 1至C 4烷基的取代基; C 2至C 4链烯基; C≡C2至C≡4炔基; 卤素; C 1至C 4卤代烷基; 羟基取代的C 1至C 4烷基; C 1〜C 4烷氧基; C 1〜C 4烷氧基; C 1〜C 4烷氧基; 羟基取代的C 1至C 4烷氧基; C 1至C 4烷基氨基; C 1至C 4烷硫基; 和它们的组合。

3. 发明申请

WO2013117707A1 LIGANDS FOR ANTIBODY AND FC-FUSION PROTEIN PURIFICATION BY AFFINITY CHROMOTOGRAPHY IV 审中-公开
标题翻译：抗生素和FC融合蛋白质纯化的配体通过染色体色谱IV
公开(公告)号：WO2013117707A1
公开(公告)日：2013-08-15
申请号：PCT/EP2013/052564
申请日：2013-02-08
申请人： GRAFFINITY PHARMACEUTICALS GMBH , BITTERMANN, Holger , ARNOLD, Marc , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SEKUL, Renate
发明人： BITTERMANN, Holger , ARNOLD, Marc , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SEKUL, Renate
IPC分类号： C07K1/22 , B01D15/38 , C07D317/66
CPC分类号： C07K1/22 , B01D15/3804 , B01D15/3809 , B01J20/289 , B01J20/3204 , B01J20/3208 , B01J20/321 , B01J20/3212 , B01J20/3219 , B01J20/3274 , C07D231/56 , C07D403/12 , C07D405/14 , C07D413/12 , C07D417/04 , C07D417/12 , C07D417/14 , C07D513/04 , C07K16/065 , C07K16/1027 , C07K16/22 , C07K16/2863 , C07K16/2866
摘要： The present invention relates to the use, for affinity purification of an antibody or an fragment of an antibody, of a ligand-substituted matrix comprising a support material and at least one ligand covalently bonded to the support material, the ligand being represented by formula (I) L-(Sp) v -Ar 1 -Am-Ar 2 wherein L is the linking point on the support material to which the ligand is attached; Sp is a spacer group; v is 0 or 1; Am is an amide group -NR 1 -C(O)-, and wherein either NR 1 is attached to Ar 1 and -C(O)- is attached to Ar 2 , or -C(O)- is attached to Ar 1 and NR 1 is attached to Ar 2 ; and R 1 is hydrogen or C 1 to C 4 alkyl, more preferably hydrogen or methyl; and most preferably hydrogen; Ar 1 is a 5-, 6- or 7-membered mononuclear aromatic ring or partially saturated aromatic ring connected to Sp or L via a chemical bond and which is optionally furthermore (a) attached to a further 5- or 6-membered mononuclear aromatic ring via a chemical bond; or (b) fused to a mononuclear or binuclear aromatic ring as part of a multinuclear ring system wherein Ar 1 is directly connected to Am via a chemical bond present on the said 5-, 6- or 7- membered aromatic ring constituting Ar 1 , or indirectly via a chemical bond which is either present at the further 5- or 6-membered aromatic ring attached to Ar 1 , or on the further 5- or 6- membered aromatic ring fused to Ar 1 ; and wherein Ar 1 is either not further substituted or attached to at least one substituent selected from C 1 to C 4 alkyl; C 3 and C 4 cycloalkyl; C 2 to C 4 alkenyl;; C 2 to C 4 alkynyl; a halogen; C 1 to C 4 haloalkyl;;; hydroxyl-substituted C 1 to C 4 alkyl; C 1 to C 4 alkoxy; hydroxyl-substituted C 1 to C 4 alkoxy; halogen-substituted C 1 to C 4 alkoxy; C 1 to C 4 alkylamino; C 1 to C 4 alkylthio; -NO 2 ; =O; =S; =NH; -OH?; and combinations thereof; Ar 2 is a 5- or 6-membered mononuclear aromatic ring which is unsubstituted, or via a chemical bond attached to at least one substituent selected from C 1 to C 6 alkyl; C 3 to C 6 cycloalkyl; C 2 to C 6 alkenyl; C 5 and C 6 cycloalkenyl; C 2 to C 6 alkynyl; a halogen; C 1 to C 6 haloalkyl; hydroxyl-substituted C 1 to C 6 alkyl; C 1 to C 6 alkoxy; hydroxyl-substituted C 1 to C 6 alkoxy; halogen-substituted C 1 to C 6 alkoxy; C 1 to C 6 alkylamino; C 1 to C 6 alkylthio; carbamoyl; methylenedioxy; ethylenedioxy; -OH; SH; a 5- or 6-membered mononuclear aromatic ring; and combinations thereof; and wherein Ar 2 optionally, further to the substituents to which it may be attached via a chemical bond as cited above, is fused to a 5- or 6-membered mononuclear aromatic ring as part of a multinuclear ring system.
摘要翻译：本发明涉及用于亲和纯化抗体或抗体片段的配体取代基质，其包括载体材料和至少一种与载体材料共价结合的配体，所述配体由式（ I）L-（Sp）v -Ar1-Am-Ar2其中L是与配体连接的载体材料上的连接点; Sp是间隔基; v为0或1; Am是酰胺基-NR1-C（O） - ，并且其中NR1与Ar1连接，-C（O） - 连接到Ar2上，或-C（O） - 连接到Ar1上，并且NR1连接到 AR2; 并且R 1是氢或C 1至C 4烷基，更优选氢或甲基; 最优选氢; Ar1是通过化学键连接到Sp或L的5-，6-或7-元单核芳环或部分饱和芳环，并且任选地另外（a）连接到另外的5或6元单核芳环上通过化学键; 或（b）与作为多核环体系的一部分的单核或双核芳环稠合，其中Ar1通过存在于构成Ar1的所述5-，6-或7-元芳族环上的化学键或间接直接与Am直接连接通过化学键，其存在于与Ar 1连接的另外的5或6元芳香环上，或存在于与Ar 1稠合的另外的5或6元芳环上; 并且其中Ar1不被进一步取代或连接至至少一个选自C 1至C 4烷基的取代基; C3和C4环烷基; C2至C4烯基; C2至C4炔基; 卤素 C1至C4卤代烷基; 羟基取代的C1至C4烷基; C1至C4烷氧基; 羟基取代的C1至C4烷氧基; 卤素取代的C1至C4烷氧基; C1至C4烷基氨基; C1〜C4烷硫基; NO 2; = O; = S; = NH; -哦？; 及其组合; Ar2是未取代的或通过连接至至少一个选自C 1至C 6烷基的取代基的化学键的5或6元单环芳环; C3至C6环烷基; C2至C6烯基; C5和C6环烯基; C2〜C6炔基; 卤素 C1至C6卤代烷基; 羟基取代的C1至C6烷基; C1至C6烷氧基; 羟基取代的C1至C6烷氧基; 卤素取代的C1至C6烷氧基; C1至C6烷基氨基; C1至C6烷硫基; 氨基甲酰基; 亚甲二氧基; 亚; -哦; SH; 5-或6-元单核芳环; 及其组合; 并且其中Ar2任选地进一步与其所连接的取代基通过如上所述的化学键连接，作为多核环体系的一部分与5或6元单核芳香环稠合。

4. 发明申请

WO2011104307A2 LIGANDS FOR ANTIBODY PURIFICATION BY AFFINITY CHROMATOGRAPHY 审中-公开
标题翻译：通过亲和色谱法进行抗体纯化的配体
公开(公告)号：WO2011104307A2
公开(公告)日：2011-09-01
申请号：PCT/EP2011/052758
申请日：2011-02-24
申请人： GRAFFINITY PHARMACEUTICALS GMBH , BITTERMANN, Holger , BURKERT, Klaus , KALBFUSS-ZIMMERMANN, Bernd , KEIL, Oliver , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SEKUL, Renate
发明人： BITTERMANN, Holger , BURKERT, Klaus , KALBFUSS-ZIMMERMANN, Bernd , KEIL, Oliver , NEUMANN, Thomas , OTT, Inge , SCHMIDT, Kristina , SEKUL, Renate
IPC分类号： C07K1/22 , B01D15/08 , C07K16/06 , C07C237/10 , C07D207/16 , C07D211/62
CPC分类号： C07C237/22 , B01D15/3804 , B01J20/286 , B01J20/289 , B01J20/3253 , C07B2200/11 , C07D207/16 , C07D211/62 , C07D243/08 , C07D295/104 , C07K1/22 , C07K16/065 , C07K16/22
摘要： The present invention relates to the use, for affinity purification of a protein, of a compound according to the general formula (I), wherein A is selected from the group: -O-;-S-; >CR 7 R 8 ; and NR 9 ; D is a linear or branched Ci to C6 alkyl group, which may comprise a cycloalkyl unit, wherein 1 or more C-atoms which are not connected to each other may be replaced by O or S, and wherein one or more C-atoms in the alkyl group may be substituted by one or more atoms independently from each other selected from the group F, C1, Br, I; L is the linking point via which the compound is attached to a support matrix, L optionally comprising a spacer group -Z-; R 1 , R 2 are identical or different and are independently of each other selected from the group: H; -OH; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit; wherein in the alkyl 1 C-atom may be replaced by -O-, or a terminal C-atom may be replaced by -OH; wherein N may be part of a heterocycle having 3 to 7 members; and wherein one or more C- atoms in the alkyl may be substituted by one or more atoms independently from each other selected from the group F, C1, Br, I; R 3 , R 4 , R 5 and R 6 are identical or different and are independently of each other selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, and wherein in the alkyl 1 C-atom may be replaced by -0-, or a terminal C-atom may be replaced by -OH; and wherein one or more C-atoms in each R 3 , R 4 , R 5 and R 6 may be substituted by one or more atoms independently from each other selected from the group F, C1, Br, I; and - NR 10 R 11 ; R 7 , R 8 are identical or different and are selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, wherein the alkyl group may optionally be substituted; R 9 is selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, and wherein the alkyl group may optionally be substituted; R 10 , R 11 can be identical or different and are independently of each other selected from the group: H; linear and branched C 1 to C 4 alkyl, which may comprise a cycloalkyl unit, and wherein the alkyl group may optionally be substituted. Preferably, the entity to be separated of purified is an antibody, in particular an antibody of the Bevacizumab type or the Ranibizumab type.
摘要翻译：本发明涉及用于亲和纯化蛋白质的根据通式（I）的化合物，其中A选自：-O - ; - S-; > CR7R8; 和NR9; D是直链或支链的C 1 -C 6烷基，其可以包含环烷基单元，其中不彼此连接的一个或多个C原子可以被O或S替代，并且其中一个或多个C原子在烷基可以被一个或多个彼此独立地选自F，C 1，Br，I; L是化合物连接到载体基质上的连接点，L任选地包含间隔基团-Z-; R1，R2相同或不同，彼此独立地选自H： -哦; 直链和支链的C 1 -C 4烷基，其可以包含环烷基单元; 其中在烷基中，C原子可以被-O-取代，或者C末端可被-OH取代; 其中N可以是具有3至7个成员的杂环的一部分; 并且其中所述烷基中的一个或多个C原子可以被一个或多个彼此独立地选自F，C 1，Br，I; R3，R4，R5和R6相同或不同，彼此独立地选自H：直链和支链的C 1 -C 4烷基，其可以包含环烷基单元，并且其中在烷基C 1可以被-O-取代，或者C末端可被-OH取代; 并且其中每个R 3，R 4，R 5和R 6中的一个或多个C原子可以被一个或多个彼此独立地选自F，C 1，Br，I，和 - NR10R11; R 7，R 8相同或不同，选自H; 直链和支链C1至C4烷基，其可以包含环烷基单元，其中烷基可以任选被取代; R9选自H：直链和支链C1至C4烷基，其可以包含环烷基单元，并且其中烷基可以任选被取代; R 10，R 11可以相同或不同，彼此独立地选自H; 直链和支链C 1 -C 4烷基，其可以包含环烷基单元，并且其中烷基可以任选地被取代。优选地，待分离纯化的实体是抗体，特别是贝伐单抗型或拉唑珠单抗型的抗体。

5. 发明申请

WO2014020152A1 LIGANDS FOR APHERESIS AND IMMUNOABSORPTION 审中-公开
标题翻译：用于饲养和免疫的配体
公开(公告)号：WO2014020152A1
公开(公告)日：2014-02-06
申请号：PCT/EP2013/066280
申请日：2013-08-02
申请人： GRAFFINITY PHARMACEUTICALS GMBH
发明人： BITTERMANN, Holger , ARNOLD, Marc , NEUMANN, Thomas
IPC分类号： C07K1/22 , B01D15/38 , B01J20/289
CPC分类号： B01D15/3809 , B01J20/267 , B01J20/289 , B01J20/3204 , B01J20/3208 , B01J20/321 , B01J20/3212 , B01J20/3219 , B01J20/3255 , C07K1/22
摘要： The present invention relates to a method for separating one or more proteins from plasma by immunoadsorption IA, comprising • contacting the plasma with a ligand-substituted matrix; and • removing the plasma from the ligand-substituted matrix; • wherein the ligand-substituted matrix comprises a support material and at least one ligand covalently bonded to the support material.
摘要翻译：本发明涉及通过免疫吸附IA从血浆中分离一种或多种蛋白质的方法，其包括。使等离子体与配体取代的基质接触; 和。从配体取代的基质中除去等离子体; 。其中所述配体取代的基质包含载体材料和共价键合到所述载体材料的至少一种配体。

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