公开(公告)号：US20230391823A1

公开(公告)日：2023-12-07

申请号：US18454131

申请日：2023-08-23

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Christoph Feistl ,  Thorsten Lemm ,  Marc Pompiati ,  Bernhard Spensberger

IPC: C07K1/34 ,  B01D37/02 ,  B01D39/16 ,  B01D39/18 ,  B01D39/20

CPC classification number: C07K1/34 ,  B01D37/025 ,  B01D39/163 ,  B01D2239/0407 ,  B01D39/2079 ,  B01D2201/085 ,  B01D39/18

Abstract: Herein is reported a method for the purification or production of a therapeutic polypeptide using the same depth filter multiple times, i.e. a depth filter which has been used before and has been regenerated.
Reported herein is a method for purifying or producing a therapeutic polypeptide, characterized in that the method comprises the following steps:



a) filtering an aqueous composition containing said therapeutic polypeptide and impurities through a depth filter, recovering the flow-through and thereby obtaining said purified therapeutic polypeptide,
b) contacting said depth filter with a regeneration solution and thereby regenerating the depth filter, and
c) repeating steps a) and b) one or more times.

公开(公告)号：US20220194980A1

公开(公告)日：2022-06-23

申请号：US17517531

申请日：2021-11-02

Applicant: Genentech, Inc. ,  Hoffmann-La Roche Inc.

Inventor： Michael LEISS ,  Christian Meyer ,  Alexandra Thomas Morris ,  Bernhard Spensberger ,  Yinges Yigzaw ,  Franziska Edelmann ,  Roberto Falkenstein ,  Tobias Graf ,  Jie Gu ,  Jeevan Prabhakar

IPC: C07K1/22 ,  C07K1/34 ,  C07K1/36 ,  A61K39/395 ,  C07K1/20 ,  C07K1/16 ,  B01D15/32 ,  B01D15/38 ,  B01D61/14 ,  B01D15/36 ,  B01D39/20 ,  B01D39/16

Abstract: The present disclosure provides purification platforms comprising a depth filter step and/or a hydrophobic interaction chromatography (HIC) step. Also disclosed herein are methods of using the purification platforms described herein and compositions obtained therefrom, such as pharmaceutical compositions.

公开(公告)号：US11332514B2

公开(公告)日：2022-05-17

申请号：US14920127

申请日：2015-10-22

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Maria Laura Magri ,  Michaela Mehr ,  Klaus Schwendner ,  Bernhard Spensberger

IPC: C07K14/775 ,  C07K1/18 ,  B01D15/36

Abstract: Herein is reported a method for purifying a polypeptide comprising the steps of i) applying a solution comprising the polypeptide to an ion exchange chromatography material, and ii) recovering the polypeptide with a solution comprising a denaturant and thereby purifying the polypeptide, whereby the ion exchange chromatography material comprises a matrix of cross-linked poly (styrene-divinylbenzene) to which ionic ligands have been attached, and wherein the solution comprising the polypeptide applied to the ion exchange chromatography material is free of the denaturant and the polypeptide adsorbed to the ion exchange chromatography material is recovered with a solution comprising a denaturant at a constant conductivity.

公开(公告)号：US10087237B2

公开(公告)日：2018-10-02

申请号：US14934866

申请日：2015-11-06

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Klaus Schwendner ,  Bernhard Spensberger

IPC: C07K1/18 ,  C07K16/00 ,  C07K16/18 ,  C07K16/30 ,  C07K16/28 ,  C07K16/32

Abstract: Herein is reported a method for producing an antibody preparation comprising the steps of a) applying a buffered solution comprising different isoforms of an antibody to a cation exchange chromatography material, b) applying a first solution with a first conductivity to the cation exchange chromatography material, whereby the antibody isoforms remain bound to the cation exchange chromatography material, and c) applying a second solution with a second conductivity to the cation exchange chromatography material and thereby obtaining the antibody preparation, whereby the conductivity of the second solution exceeds the conductivity of the first solution by not more than 10%.

公开(公告)号：US09631007B2

公开(公告)日：2017-04-25

申请号：US14271058

申请日：2014-05-06

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Burkard Kolb ,  Maria Sebald

IPC: C07K16/00 ,  C07K16/06 ,  C07K16/28 ,  C07K16/32 ,  B01D15/36 ,  B01D15/42

CPC classification number: C07K16/00 ,  B01D15/362 ,  B01D15/363 ,  B01D15/426 ,  C07K1/18 ,  C07K16/065 ,  C07K16/2866 ,  C07K16/32 ,  C07K2317/50 ,  G01N30/96

Abstract: A method for the purification of immunoglobulins by ion exchange chromatography is described. The chromatographic method uses a weak ion exchange resin and a single step elution process for the purification of an immunoglobulin. Additionally a method for the determination of the salt concentration for the single step elution of an immunoglobulin from an ion exchange resin is described.

公开(公告)号：US20140163207A1

公开(公告)日：2014-06-12

申请号：US14090927

申请日：2013-11-26

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Wolfgang Koehnlein ,  Wolfgang Kuhne ,  Hartmut Schurig (deceased)

IPC: C07K14/505

CPC classification number: C07K14/505 ,  A61K38/1816 ,  A61K47/60 ,  B01J39/26 ,  C07K1/18 ,  Y02P20/582

Abstract: Herein is reported a method for the purification of a protein comprising erythropoietin and a single poly (ethylene glycol) residue from reaction by-products or not reacted starting material by a cation exchange chromatography method. It has been found that by employing a cation exchange SP Sephacryl™ S 500 HR chromatography material conditioned to a conductivity of 21 mS/cm and a linear gradient elution a fusion protein of erythropoietin and a single poly (ethylene glycol) residue can be obtained in a single step with high purity and yield.

Abstract translation: 本文报道了通过阳离子交换色谱法从反应副产物或未反应的原料纯化包含促红细胞生成素和单一聚（乙二醇）残基的蛋白质的方法。 已经发现，通过使用调节至21mS / cm 2的电导率和线性梯度洗脱的阳离子交换SP Sephacryl TM S 500 HR色谱材料，可以获得促红细胞生成素和单个聚（乙二醇）残基的融合蛋白 纯度高，成品率高的单步。

公开(公告)号：US11993630B2

公开(公告)日：2024-05-28

申请号：US17145653

申请日：2021-01-11

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Bernhard Spensberger

IPC: C07K1/16 ,  B01D15/26 ,  B01D15/36 ,  C07K1/18 ,  C07K14/505

CPC classification number: C07K1/18 ,  B01D15/362 ,  C07K14/505

Abstract: Herein is reported a method for the purification of a protein comprising erythropoietin and a single poly (ethylene glycol) residue from reaction by-products or not reacted starting material by a cation exchange chromatography method. It has been found that by employing a cation exchange Toyopearl® SP-650 chromatography material and employing a second wash step with an increased pH value compared to the first wash step a fusion protein of erythropoietin and a single poly (ethylene glycol) residue can be obtained in a single step with high purity and yield and suitability for large scale applications.

公开(公告)号：US11767342B2

公开(公告)日：2023-09-26

申请号：US16447110

申请日：2019-06-20

Applicant: Hoffmann-La Roche Inc.

Inventor： Thomas Dams ,  Roberto Falkenstein ,  Sebastian Malik ,  Ingrid Grunert ,  Marco Thomann ,  Matthias Freiherr Von Roman ,  Heiko Walch

IPC: C07K1/18 ,  C07K16/18 ,  C12N9/10 ,  C12P21/00 ,  A61K45/06

CPC classification number: C07K1/18 ,  C07K16/18 ,  C12N9/1051 ,  C12N9/1081 ,  C12P21/005 ,  A61K45/06 ,  C12Y204/01038 ,  C12Y204/99003

Abstract: Herein is reported a method for the enzymatic production of an antibody with a modified glycosylation in the Fc-region comprising the steps of incubating the antibody light chain affinity ligand-bound monoclonal antibody with a glycosylation in the Fc-region with a first enzyme for a time sufficient and under conditions suitable to modify the glycosylation of the Fc-region, recovering the antibody from the antibody light chain affinity ligand, incubating the recovered antibody in solution with a second enzyme for a time sufficient and under conditions suitable to modify the glycosylation of the Fc-region to a defined form, separating the antibody with the modified glycosylation in the Fc-region from the second enzyme in a cation exchange chromatography, and thereby producing the antibody with a modified glycosylation in the Fc-region.

公开(公告)号：US20200165297A1

公开(公告)日：2020-05-28

申请号：US16778128

申请日：2020-01-31

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Thorsten Lemm ,  Markus Strasser ,  Hidenari Yamada

IPC: C07K1/18 ,  C07K16/28 ,  C07K16/06

Abstract: Herein is reported a method for the purification of an antibody directly captured from clarified cell culture supernatants using Streamline CST and/or Capto MMC, wherein especially product related (aggregates and fragments) and process related impurities (host cell protein, media components) could efficiently be removed, resulting in a preparation with a purity comparable to classical protein A affinity chromatography.

公开(公告)号：US20190276492A1

公开(公告)日：2019-09-12

申请号：US16258294

申请日：2019-01-25

Applicant: Hoffmann-La Roche Inc.

Inventor： Roberto Falkenstein ,  Hubert Hertenberger ,  Petra Rueger ,  Tilman Schlothauer

IPC: C07K1/22 ,  G01N33/68 ,  B01J39/26 ,  B01J20/32 ,  C07K16/28 ,  B01J20/289 ,  C07K16/06 ,  B01D15/16 ,  B01D15/38

Abstract: Herein is reported the use of an immobilized non-covalent complex of a neonatal Fc receptor (FcRn) and beta-2-microglobulin (b2m) as affinity chromatography ligand in general and, for example, for the determination of the in vivo half-live of an antibody by determining the ratio of the retention times of the antibody and a reference antibody.