# US 11,078,512 B2 · Compositions for cell bioproduction and methods of using the same

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- Number: US 11,078,512 B2
- Document ID: US11078512B2
- Status: Granted
- Kind: B2
- Application number: 16/782,195
- Filed: 2020-02-05
- Published: 2020-06-04
- Granted: 2021-08-03
- Earliest claimed: 2015-02-11
- Assignees: Bristol-Myers Squibb Company
- Applicants: Bristol-Myers Squibb Company
- Inventors: Jun Tian; Jianlin Xu; Qin He
- Web page: https://patentgrep.com/patent/US11078512B2

## CPC

- C12P 21/02: having a known sequence of two or more amino acids, e.g. glutathione
- C12N 5/0018: {Culture media for cell or tissue culture (media for specific animal cell type C12N5/06)}
- C12Q 1/04: Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor {(C12Q1/6897 takes precedence)}
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

The present invention relates to new methods and processes for culturing mammalian cells with the addition of phenolic antioxidants. Performance of the cell culturing methods and processes in their various aspects result in a higher viable cell density and higher protein titer.

## Claims

### Claim 1

A cell culture process for the production of protein, comprising:
a) culturing CHO cells in a basal media which produce a protein of interest in cell culture under conditions that allow for protein production; and
b) feeding the cell culture with a feed media, wherein 1 mM rosmarinic acid is added to the feed media,
wherein viable cell density is increased compared to the same cell culture without supplementation of rosmarinic acid.

### Claim 2 (depends on 1)

The process according to claim 1, wherein the feed media is added to the cell culture on a daily basis.

### Claim 3 (depends on 1)

The process according to claim 1, further comprising adding rosmarinic acid to the basal media.

### Claim 4 (depends on 3)

The process according to claim 3, wherein 0.1 mM rosmarinic acid is added to the basal media.

### Claim 5 (depends on 1)

The process according to claim 1, wherein protein titer is increased compared to the same cell culture without supplementation of rosmarinic acid.
