CHO-GS悬浮细胞株工业级大量表达细胞系-BioVector NTCC质粒载体菌种细胞基因保藏中心

CHO-GS cell line

The powerful proprietary GS System uses a robust viral

promoter and selection via glutamine metabolism to provide

extremely rapid development of high-yielding, stable,

cGMP-compatible mammalian cell lines. The GS System™ is

successfully used by over 85 global pharmaceutical and biotechnology

companies and is familiar to all worldwide regulatory

authorities who have already approved 5 licensed products

which use the GS System including Zenapax® (Roche)

and Synagis® (Medimmune).

The international use of the GS System by both commercial

organisations and academic institutions has lead to a large

body of published information. New users can draw upon

this material to expand their knowledge and skill base and

improve their use of the GS System.

NTCC has itself created over 250 cell lines using the GS System

™, many of which have been grown at large-scale and produced

product for use in clinical trials and in-market supply.

Other GS System™ users have also accumulated experience

with a diverse range of products where high yields have been

achieved. Many investigators use the GS System™, not only

to develop a manufacturing process, but as a tool to create

recombinant proteins for biological studies. The reliability of

the GS System™, as a consistent means of rapidly generating

high-producing cell lines, speeds time to market.

Principles of the GS System TM

Glutamine synthetase (GS) is the enzyme responsible for

the biosynthesis of glutamine from glutamate and ammonia.

This enzymatic reaction provides the only pathway for glutamine

formation in a mammalian cell.

In the absence of glutamine

in the growth medium, the

GS enzyme is essential for

the survival of mammalian

cells in culture. Some mammalian

cell lines, such as

mouse myeloma lines, do

not express sufficient GS to

survive without added glutamine. With these cell lines, a transfected

GS gene can function as a selectable marker by permitting

growth in a glutamine-free medium. Other cell lines, such

as Chinese hamster ovary (CHO) cell lines, express sufficient

GS to survive without exogenous glutamine. In these cases,

the GS inhibitor, methionine sulphoximine (MSX), can be used

to inhibit endogenous GS activity such that only transfectants

with additional GS activity can survive.

Yield

The high manufacturing cost of protein products,

particularly for therapeutic proteins, means that maximising

volumetric productivity is essential if economic processes

are to be established. Use of the GS System™ reliably results

in high yielding cell lines early in cell construction programmes.

Maximum expression levels attainable depend on

the product but cell lines producing over 5 g/L of recombinant

antibody have been created, with specific production

rates in the range of 15-65 pg/cell/day.

Speed

Speed at the development stage of any biotechnology

project is crucial to success. The GS System™ allows

for rapid selection of high yielding cell lines during the first

screen. Even higher yields are achieved through media and

process optimization. This significantly reduces the time required

to generate a cell line suitable for cGMP manufacture.

Construction of full length antibodies with human constant

regions is rapid and easy using GS constant region

vectors which enable the addition of any variable region in a

single ligation step.

The proprietary CHOK1SV host cell line facilitates the

adaptation to protein-free suspension culture compared to

standard CHOK1 processes.

Regulatory Familiarity The GS System™ is well established

with over 85 companies using the technology worldwide.

Currently there are over 50 products in clinical trials and 5

products in-market that use the GS System.

Evaluation Agreement.

GS Research Evaluation Agreement

A GS REA allows the user to carry out a pre-clinical evaluation

of GS with an unlimited number of products.

Standard GS Package

The current standard package of GS materials to which the

user has access with a GS REA are:

— GS vectors and sequence data

— Vials of GMP host cell bank NS0

— Vials of GMP host cell bank CHOK1SV

— Transfection medium system

— Comprehensive technical operating manuals

— Cell bank characterization reports to support regulatory

submissions

— Access to technical support from the GS experts

— GS newsletters

— Technology updates

Optional GS Packages

GS customers can augment their standard GS REA package

to purchase other proprietary components together with

associated know-how. The current optional packages of GS

materials to which the user has access are:

— pConPlus vectors

— Serum-free medium system

— Protein-free media systems

— Host Cell Protein Western Blotting Assays

— Host Cell Protein ELISA Assays

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