Process system for bioreactor-based clean meat production

Patent metadata

Field	Value
Publication number	US-2023303956-A1
Application number	US-202118042040-A
Country	US
Kind code	A1
Filing date	Aug 19, 2021
Priority date	Aug 21, 2020
Publication date	Sep 28, 2023
Grant date	—

Abstract

The present invention is for a closed environment process for the growth and differentiation of cells and the culturing of cells to confluency for the production of tissue. The tissue may be a clean meat product.

First claim

We claim:

1 . A closed environment process for the culture of cells to confluency to form tissue, said process comprising:
a) providing, a system comprising: i) a cell growth and expansion reactor; ii) one or more tissue formation reactors; and, iii) a cell retention device; b) i) seeding said cell growth and expansion reactor and expanding the cell density within the cell growth and expansion reactor to a desired cell density, ii) once a desired cell density is obtained, processing the cells through the cell retention device thereby transferring the cells to the one or more tissue formation reactors and removing the growth media; and, iii) converting the bioreactor to a differentiation media reservoir for feeding the tissue growing reactors, and; c) i) differentiating and growing said cells in said one or more tissue formation reactors until a desired level of confluency is reached and tissue formed, and ii) harvesting the tissue from said one or more tissue formation reactors.

2 . The process of claim 1 , wherein said process system is semi-continuous or continuous.

3 . The process of claim 1 , wherein the size of said cell growth and expansion reactor is from 0.5 liter to 20,000 liters.

4 . The process of claim 3 , wherein said the size of said cell growth and expansion reactor is from 0.5 liters to 2000 liters.

5 . The process of claim 1 , further comprising a manifold system to integrate said tissue formation reactors if said process system has two or more of said tissue formation reactors.

6 . The process of claim 1 , further comprising one or more monitoring systems for i) dissolved oxygen, ii) pH, iii) carbon dioxide, iv) cell waste, v) one or more cell metabolites, vi) temperature, vii) flow rate, viii) cell density and ix) cell viability.

7 . The process of claim 1 , further comprising, wherein the cell retention device can be bypassed.

8 . The process of claim 1 , wherein said one or more tissue formation reactors are hollow fiber reactors.

9 . The process of claim 1 , wherein, tissue can be sterilely harvested from one or more of the one or more tissue formation reactors while maintaining the sterility of the remainder of the system.

10 . The process of claim 1 , wherein the cells in the bioreactor are adapted to suspension growth, aggregate growth or microcarrier growth.

11 . The process of claim 1 , wherein said one or more tissue formation reactors comprise scaffolding for cell attachment.

12 . A closed environment process for the culture of cells to confluency to form tissue, said process comprising:
a) providing: i) a cell growth and expansion reactor, ii) one or more tissue formation reactors; iii) a cell retention device; b) i) seeding said cell growth and expansion reactor and expanding the cell density within the cell growth and expansion reactor, ii) once a desired cell density is obtained, iii) processing the cells through the cell retention device thereby transferring a portion of the cells to the one or more tissue formation reactors and returning a portion of the cells to the bioreactor; and, iv) continuing to transfer cells from the cell growth and expansion reactor to the one or more tissue formation reactors as adequate cell density become available in the cell growth and expansion reactor; and, c) i) differentiating and growing said cells in said one or more tissue formation reactors until a desired level of confluency is reached and tissue formed, and ii) harvesting the tissue from said one or more tissue formation reactors.

13 . The process of claim 12 , further comprising a first reservoir holding cell growth media and a second reservoir holding differentiation media, said cell growth media being delivered to the cell growth and expansion reactor and said differentiation media being delivered to the one or more tissue formation reactors after transferring said cells to the one or more tissue formation reactors.

12 . he process of claim 12 , wherein said process system is semi-continuous or continuous.

15 . The process of claim 12 , wherein the size of said cell growth and expansion reactor is from 0.5 liters to 20,000 liters.

16 . The process of claim 15 , wherein the size of said cell growth and expansion reactor is from 0.5 liter to 2000 liters.

17 . The process of claim 12 , further comprising a manifold system to integrate said tissue formation reactors if said process system has two or more of said tissue formation reactors.

18 . The process of claim 12 , further comprising one or more monitoring systems for i) dissolved oxygen, ii) pH, iii) carbon dioxide, iv) cell waste, v) one or more cell metabolites, vi) temperature, vii) flow rate, viii) cell density and ix) cell viability.

19 . The process of claim 12 , further comprising, wherein the cell retention device can be bypassed.

20 . The process of claim 12 , wherein said one or more tissue formation reactors are hollow fiber reactors.

21 . The process of claim 12 , wherein, tissue can be sterilely harvested from one or more of the one or more tissue formation reactors while maintaining the sterility of the remainder of the system.

22 . The process of claim 12 , wherein the cells in the bioreactor are adapted to suspension growth, aggregate growth or microcarrier growth.

23 . The process of claim 12 , wherein said one or more tissue formation reactors comprise scaffolding for cell attachment.

24 . The process of claim 12 , further comprising a separate reservoir for differentiation media that is fluidly connected to said tissue formation reactors.

Assignees

• Merck Patent Gmbh

Inventors

• Weissenbach Jean-Louis
• Sylvia Ryan
• Von Der Brelie Almut
• Brandl Melanie
• Fesenfeld Michaela

Classifications

• C12M21/08 Primary

  for producing artificial tissue or for ex-vivo cultivation of tissue (prostheses A61F2/00, grafts A61L27/00) · CPC title

• C12M23/58 Primary

  Reaction vessels connected in series or in parallel (combinations of bioreactors with other apparatus, C12M43/00) · CPC title

• C12M23/40

  Manifolds; Distribution pieces (fluid transfer means B01L3/563) · CPC title

• C12M25/10

  Hollow fibers or tubes (hollow fiber modules in general B01D63/02) · CPC title

• A23L13/00

  Meat products; Meat meal; Preparation or treatment thereof · CPC title