Integrated continuous manufacturing of therapeutic protein drug substances

Patent metadata

Field	Value
Publication number	US-12110312-B2
Application number	US-202016908401-A
Country	US
Kind code	B2
Filing date	Jun 22, 2020
Priority date	Mar 8, 2013
Publication date	Oct 8, 2024
Grant date	Oct 8, 2024

Abstract

Provided herein are integrated continuous biomanufacturing processes for producing a therapeutic protein drug substance. Also provided are systems that are capable of continuously producing a therapeutic protein drug substance.

First claim

What is claimed is:

1. A process for manufacturing a recombinant therapeutic protein drug substance, the process comprising:
(a) introducing one or both of liquid culture medium or nutrients into a cell culture disposed in a perfusion bioreactor, wherein cells in the cell culture secrete a recombinant therapeutic protein;
(b) monitoring cell density in the cell culture disposed in the perfusion bioreactor;
(c) continuously flowing the cell culture from the perfusion bioreactor into a cell retention system;
(d) continuously removing a liquid comprising the recombinant therapeutic protein that is substantially free of cells from the cell retention system;
(e) feeding the liquid into a first multi-column chromatography system (MCCS);
(f) capturing the recombinant therapeutic protein in the liquid using the first MCCS; and
(g) purifying and polishing the recombinant therapeutic protein using a second MCCS, wherein the purifying is performed using a resin in the second MCCS that is different in chemical structure compared to the resin in the second MCCS used to perform the polishing.

2. The process of claim 1 , wherein the use of the first MCCS involves column switching.

3. The process of claim 1 , wherein the first MCCS utilizes at least two chromatography columns.

4. The process of claim 1 , wherein the first MCCS utilizes at least one chromatography column and at least one chromatographic membrane.

5. The process of claim 1 , wherein the first MCCS is a periodic counter current chromatography system (PCCS).

6. The process of claim 5 , wherein the PCCS comprises a four-column PCCS.

7. The process of claim 1 , wherein the capturing is performed using affinity chromatography, cation exchange chromatography, anion exchange chromatography, or molecular sieve chromatography.

8. The process of claim 7 , wherein the affinity chromatography is performed with a capture mechanism selected from the group consisting of: protein A-binding capture mechanism, substrate-binding capture mechanism, antibody- or antibody fragment-binding capture mechanism, aptamer-binding capture mechanism, and cofactor-binding capture mechanism.

9. The process of claim 1 , further comprising formulating the recombinant therapeutic protein drug substance into a pharmaceutical composition.

10. The process of claim 1 , wherein the process is performed over a continuous period of at least about 10 days.

11. The process of claim 1 , wherein the process is performed for a continuous period of at least about 30 days.

12. The process of claim 1 , wherein the cell retention system filters the cell culture.

13. The process of claim 1 , wherein the cell retention system is an alternating tangential flow system.

14. The process of claim 1 , wherein the process further comprises performing viral inactivation on the liquid.

Assignees

• Genzyme Corp

Inventors

• Konstantinov Konstantin
• Godawat Rahul
• Warikoo Veena
• Jain Sujit

Classifications

• C12M47/10

  Separation or concentration of fermentation products (bioreactors combined with means for distillation or extraction of liquid fuel C12M43/02) · CPC title

• C12M23/52

  Mobile; Means for transporting the apparatus (transportable laboratories B01L1/52) · CPC title

• B01D15/422

  Displacement mode · CPC title

• B01D15/3814

  of the substrate or cofactor-enzyme type · CPC title

• B01D15/363

  Anion-exchange · CPC title