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1. 发明专利

JP2008069155A Erythropoietin conjugate 有权
标题翻译：红细胞凝集素
公开(公告)号：JP2008069155A
公开(公告)日：2008-03-27
申请号：JP2007241171
申请日：2007-09-18
申请人： F Hoffmann La Roche Ag , エフ.ホフマン−ラロシュアーゲーF. Hoffmann−La Roche Aktiengesellschaft
发明人： BURG JOSEF , ENGEL ALFRED , FRANZE REINHARD , HILGER BERND , SCHURIG HARTMUT ERNST , TISCHER WILHELM , WOZNY MANFRED
IPC分类号： C07K14/505 , C12P21/02 , A61K38/27 , A61K47/48 , A61P7/06 , A61P13/12 , A61P31/18 , A61P35/00 , C07K1/113 , C12N15/09 , C12R1/91
CPC分类号： A61K47/62 , A61K47/60
摘要： PROBLEM TO BE SOLVED: To provide an erythropoietin/poly(ethylene)glycol conjugate comprising an erythropoietin glycoprotein having an N-terminal α-amino group and having the in vivo biological activity of causing bone marrow cells to increase the production of reticulocytes and erythrocytes and selected from the group consisting of human erythropoietin and analogues thereof which have the sequence of human erythropoietin modified by the addition of 1-6 glycosylation sites or a rearrangement of at least one glycosylation site. SOLUTION: The glycoprotein is one covalently linked to one poly(ethylene glycol) group represented by the formula: -CO-(CH 2 ) x -(OCH 2 CH 2 ) m -OR [wherein the -CO in the poly(ethylene glycol) group forms an amide bond with the N-terminal α-amino group; R is a lower alkyl; x is 2 or 3; and m is about 450 to about 1,350]. COPYRIGHT: (C)2008,JPO&INPIT
摘要翻译：待解决的问题：提供一种促红细胞生成素/聚（乙二醇）轭合物，其包含具有N-末端α-氨基的促红细胞生成素糖蛋白，并且具有引起骨髓细胞的体内生物活性以增加网织红细胞的产生和选自人红细胞生成素及其类似物的组，其具有通过加入1-6个糖基化位点或至少一个糖基化位点的重排而修饰的促红细胞生成素序列。解决方案：糖蛋白是共价连接到由下式表示的一个聚（乙二醇）基团：-CO-（CH 2 ）其中聚（乙二醇）基团中的-CO与N-末端的α形成酰胺键，氨基; R是低级烷基; x为2或3; m为约450至约1,350]。版权所有（C）2008，JPO＆INPIT

2. 发明专利

JP2013189457A Purification of pegylated polypeptide 有权
标题翻译：聚乙二醇多肽的纯化
公开(公告)号：JP2013189457A
公开(公告)日：2013-09-26
申请号：JP2013113940
申请日：2013-05-30
申请人： F Hoffmann La Roche Ag , エフ.ホフマン−ラロシュアーゲーF. Hoffmann−La Roche Aktiengesellschaft
发明人： BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
IPC分类号： C07K14/505 , C07K1/18
CPC分类号： C07K1/18 , A61K47/60 , C07K14/505
摘要： PROBLEM TO BE SOLVED: To provide a method for purifying mono-PEGylated erythropoietin from a solution containing mono-, poly- and not-PEGylated erythropoietin using an ion-exchange chromatography.SOLUTION: A method for purifying mono-PEGylated erythropoietin comprises the steps of: performing two consecutive cation-exchange chromatography steps; and collecting purified mono-PEGylated erythropoietin in the second cation-exchange chromatography step, wherein the same type of cation exchange material is used in both cation-exchange chromatography steps (a) and (b): (a) a step of purifying mono-, poly- and not-PEGylated erythropoietin; and (b) a step of purifying the purified product with a stepwise increase of ion strength of the through-flowing buffer, and separating mono-PEGylated erythropoietin.
摘要翻译：要解决的问题：提供一种使用离子交换色谱从含有单PEG，聚和非聚乙二醇化促红细胞生成素的溶液中纯化单聚乙二醇化促红细胞生成素的方法。解决方案：纯化单PEG化促红细胞生成素的方法包括以下步骤：：进行两次连续的阳离子交换层析步骤; 和在第二阳离子交换层析步骤中收集纯化的单聚乙二醇化促红细胞生成素，其中在阳离子交换层析步骤（a）和（b）中使用相同类型的阳离子交换材料：（a），聚和非聚乙二醇化促红细胞生成素; 和（b）逐步增加通流缓冲液的离子强度并分离单聚乙二醇化促红细胞生成素的纯化产物的步骤。

3. 发明申请

WO2009010270A8 PURIFICATION OF PEGYLATED POLYPEPTIDES 审中-公开
标题翻译：聚乙二醇的纯化
公开(公告)号：WO2009010270A8
公开(公告)日：2010-04-29
申请号：PCT/EP2008005767
申请日：2008-07-15
申请人： HOFFMANN LA ROCHE , BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
发明人： BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
IPC分类号： C07K1/18 , A61K38/18 , A61K47/48
CPC分类号： C07K1/18 , A61K47/60 , C07K14/505
摘要： The current invention comprises a method for the purification of mono-PEGylated erythropoietin comprising two cation exchange chromatography steps wherein the same type of cation exchange material is used in both cation exchange chromatography steps and a method for producing a mono-PEGylated erythropoietin in substantially homogeneous form.
摘要翻译：本发明包括纯化单聚乙二醇化促红细胞生成素的方法，其包括两个阳离子交换色谱步骤，其中在阳离子交换色谱步骤中使用相同类型的阳离子交换材料和用于以基本均匀的形式生产单聚乙二醇化促红细胞生成素的方法。

4. 发明申请

WO2009010270A3 REINIGUNG PEGYLIERTER POLYPEPTIDE 审中-公开
公开(公告)号：WO2009010270A3
公开(公告)日：2009-04-30
申请号：PCT/EP2008005767
申请日：2008-07-15
申请人： HOFFMANN LA ROCHE , BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
发明人： BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
IPC分类号： C07K1/18 , A61K38/18 , A61K47/48
CPC分类号： C07K1/18 , A61K47/60 , C07K14/505
摘要： The current invention comprises a method for the purification of mono-PEGylated erythropoietin comprising two cation exchange chromatography steps wherein the same type of cation exchange material is used in both cation exchange chromatography steps and a method for producing a mono-PEGylated erythropoietin in substantially homogeneous form.
摘要翻译：本发明包括纯化单聚乙二醇化促红细胞生成素的方法，其包括两个阳离子交换色谱步骤，其中在阳离子交换色谱步骤中使用相同类型的阳离子交换材料和用于以基本均匀的形式生产单聚乙二醇化促红细胞生成素的方法。

5. 发明申请

WO0249673A3 CONJUGATES OF ERYTHROPOIETIN (PEP) WITH POLYETHYLENE GLYCOL (PEG) 审中-公开
标题翻译：聚乙二醇（PEG）与聚乙二醇（PEG）的结合
公开(公告)号：WO0249673A3
公开(公告)日：2003-01-23
申请号：PCT/EP0114434
申请日：2001-12-08
申请人： HOFFMANN LA ROCHE
发明人： BURG JOSEF , ENGEL ALFRED , FRANZE REINHARD , HILGER BERND , SCHURIG HARTMUT ERNST , TISCHER WILHELM , WOZNY MANFRED
IPC分类号： A61K47/48 , A61K38/18 , C07K14/505
CPC分类号： A61K47/62 , A61K47/60
摘要： The present invention refers to conjugates of erythropoietin with poly(ethylene glycol) comprising an erythropoietin glycoprotein having an N-terminal alpha -amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; said glycoprotein being covalently linked to one poly(ethylene glycol) group of the formula -CO-(CH2)x-(OCH2CH2)m-OR with the -CO of the poly(ethylene glycol) group forming an amide bond with said N-terminal alpha -amino group; wherein R is lower alkyl; x is 2 or 3; and m is from about 450 to about 1350.
摘要翻译：本发明涉及促红细胞生成素与聚（乙二醇）的缀合物，其包含具有N-末端α-氨基的促红细胞生成素糖蛋白，具有引起骨髓细胞增加网织红细胞和红细胞产生的体内生物学活性，由人促红细胞生成素及其类似物组成，其具有通过加入1至6个糖基化位点或至少一个糖基化位点的重排而修饰的人促红细胞生成素序列; 所述糖蛋白与式-CO-（CH2）x-（OCH2CH2）m-OR的一个聚（乙二醇）基团共价连接，聚（乙二醇）基团的-CO与所述N- 末端α-氨基; 其中R是低级烷基; x为2或3; m为约450至约1350。

6. 发明申请

WO2009010271A3 CHROMATOGRAPHIC METHODS 审中-公开
标题翻译：色谱方法
公开(公告)号：WO2009010271A3
公开(公告)日：2009-04-02
申请号：PCT/EP2008005768
申请日：2008-07-15
申请人： HOFFMANN LA ROCHE , BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
发明人： BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
IPC分类号： B01D15/36 , B01D15/20 , B01J49/00 , C07K1/18
CPC分类号： B01D15/203 , B01D15/362 , B01J49/53 , B01J49/60 , C07K1/18 , C07K14/505
摘要： The current invention comprises a method for the regeneration of a cation exchange chromatography column.
摘要翻译：本发明包括用于再生阳离子交换色谱柱的方法。

7. 发明申请

WO0102017A3 ERYTHROPOIETIN CONJUGATES WITH POLYETHYLENGLYCOL 审中-公开
标题翻译：聚乙烯吡咯烷酮与聚乙烯醇共聚
公开(公告)号：WO0102017A3
公开(公告)日：2001-08-09
申请号：PCT/EP0006009
申请日：2000-06-28
申请人： HOFFMANN LA ROCHE
发明人： BURG JOSEF , HILGER BERND , JOSEL HANS-PETER
IPC分类号： A61K38/00 , A61K38/22 , A61K47/48 , A61P7/06 , A61P13/12 , A61P31/18 , A61P35/00 , C07K14/505
CPC分类号： C07K14/505 , A61K38/00 , A61K47/60
摘要： Erythropoietin glycoprotein conjugates are disclosed, said conjugates comprise an erythropoietin glycoprotein having at least one free amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have the primary structure of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or by the rearrangement of at least one glycosylation site; said glycoprotein being covalently linked to form one to three lower-alkoxy poly(ethylene glycol) groups, each poly(ethylene glycol) group being covalently linked to the glycoprotein via a linker of the formula -C(O)-X-S-Y- with the C(O) of the linker forming an amide bond with one of said amino groups, wherein X and Y are as defined in the description and claims, the average molecular weight of each poly(ethylene glycol) moiety is from about 20 kilodaltons to about 40 kilodaltons, and the molecular weight of the conjugate is from about 51 kilodaltons to about 175 kilodaltons.
摘要翻译：所述缀合物包含具有至少一个游离氨基并且具有引起骨髓细胞的体内生物学活性以增加网织红细胞和红细胞的产生的促红细胞生成素糖蛋白，并选自由人类红细胞生成素及其类似物组成的组，其具有通过加入1至6个糖基化位点或通过重排至少一个糖基化位点而修饰的促红细胞生成素的一级结构; 所述糖蛋白共价连接以形成一至三个低级烷氧基聚（乙二醇）基团，每个聚（乙二醇）基团通过式-C（O）的连接体与糖蛋白共价连接）-XSY-，其中所述连接体的C（O）与所述氨基之一形成酰胺键，其中X和Y如说明书和权利要求中所定义，每个聚（乙二醇）部分的平均分子量为约20千道尔顿至约40千道尔顿，共轭物的分子量为约51千道尔顿至约175千道尔顿。

8. 发明专利

CA2768325C OPTIMIZING THE PRODUCTION OF ANTIBODIES 未知
公开(公告)号：CA2768325C
公开(公告)日：2019-10-29
申请号：CA2768325
申请日：2010-07-22
申请人： HOFFMANN LA ROCHE
发明人： BURG JOSEF , HILGER BERNHARD , KAISER THORSTEN , KUHNE WOLFGANG , STIENS LARS , WALLERIUS CLAUS , ZETTL FRANK
IPC分类号： C07K16/00 , C07K1/14 , C07K16/32
摘要： A general method is provided for the production of purified antibodies by separation of an antibody molecule from an antibody variant by chromatographic methods, e.g. to enhance therapeutic efficacy, by for example choosing a specific harvesting time point and/or a specific purification scheme. The current invention thus reports a method for producing an antibody composition comprising an antibody molecule and a variant thereof, comprising the following steps: providing a sample comprising the antibody molecule and a variant thereof, determining the presence of the antibody molecule and/or a variant thereof and/or the ratio of the amount of the antibody molecule or variant thereof to the sum of the amounts of the antibody molecule and the variant thereof, in an aliquot of said sample, determining a subsequent harvesting time point and/or antibody purification scheme on basis of the data obtained before, thereby producing an antibody composition comprising the antibody molecule and a variant thereof.

9. 发明专利

HRP20182171T1 POSTUPAK REGENERACIJE KROMATOGRAFSKOG STUPCA 未知
公开(公告)号：HRP20182171T1
公开(公告)日：2019-02-22
申请号：HRP20182171
申请日：2018-12-20
申请人： HOFFMANN LA ROCHE
发明人： BURG JOSEF , REICHERT KLAUS , SCHROTH AXEL , SCHURIG HARTMUT , WESSNER AXEL
IPC分类号： B01D15/36 , B01D15/20 , B01J49/00 , C07K1/18

10. 发明专利

CA2431964C CONJUGATES OF ERYTHROPOIETIN (PEP) WITH POLYETHYLENE GLYCOL (PEG) 未知
公开(公告)号：CA2431964C
公开(公告)日：2013-09-10
申请号：CA2431964
申请日：2001-12-08
申请人： HOFFMANN LA ROCHE
发明人： BURG JOSEF , ENGEL ALFRED , FRANZE REINHARD , HILGER BERND , SCHURIG HARTMUT ERNST , TISCHER WILHELM , WOZNY MANFRED
IPC分类号： C07K17/02 , C12P21/02 , A61K38/18 , A61K47/48 , A61P7/06 , A61P13/12 , A61P31/18 , A61P35/00 , C07K1/113 , C07K14/505
摘要： The present invention refers to conjugates of erythropoietin with poly(ethylene glycol) comprising an erythropoietin glycoprotein having an N-terminal .alpha.-amino group and having the in vivo biological activity of causing bone marrow cells to increase production of reticulocytes and red blood cells and selected from the group consisting of human erythropoietin and analogs thereof which have sequence of human erythropoietin modified by the addition of from 1 to 6 glycosylation sites or a rearrangement of at least one glycosylation site; said glycoprotein being covalently linked to one poly(ethylene glycol) group of the formula -CO-(CH2)x-(OCH2CH2)m-OR with the -CO of the poly(ethylene glycol) group forming an amide bond with said N-terminal .alpha.-amino group; wherein R is lower alkyl; x is 2 or 3; and m is from about 450 to about 1350.

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