Cell Culture

Novozymes GroPep growth factors are manufactured exclusively for the industrial cell culture market. Unlike competitors, our product specifications are determined only by the requirements of the bioprocessing industry and have not changed since our first sales in
1993.

We are the original manufacturer of our products. Produced under GMP, our products are animal component free and long-term continuity of supply is ensured by a comprehensive risk management plan approved by major customers.

The excellence of our products is matched by the service and support of our distributor - SAFC Biosciences.

For information, product-related or general enquiries, please contact:

cellculture@novozymes.com.au
 

LONG®R³IGF-I - Your insulin alternative
LONG®R³IGF-I Technical Resources
LONG®EGF and LONG®TGF-α

Growth Factors & Cell Culture

Cell Culture techniques have been used in biological sciences for more than 50 years and have been applied to production systems for at least half of that time. The basic technique involves the in vitro culture of cells using a basal medium containing a source of nutrients such as glucose and amino acids, essential minerals, growth factors, proteins such as albumin and transferrin and a range of other agents specific to particular cell types. The traditional source of all of these factors was fetal bovine serum. Due primarily to regulatory issues, the use of culture media in which components are fully defined is now essential in the biopharmaceutical industry. Novozymes GroPep supplies growth factor supplements to the biopharmaceutical industry for use in a range of cell types for the production of recombinant proteins and monoclonal antibodies, vaccines and gene therapy vectors. Novozymes GroPep markets three recombinant growth factors LONG®R³IGF-I, LONG®EGF and LONG®TGF-α through a commercial agreement with SAFC Biosciences

Mammalian Cell Culture

Mammalian cells are widely used to manufacture recombinant proteins for the biopharmaceutical industry. Growth factors are an essential input to this method of biopharmaceutical production. Early cell culture media used animal serum as the source of growth factors. For both cost and safety reasons there has been a trend away from the use of serum and other animal-derived products and towards serum-free media (“SFM”). When serum dependent cells are adapted to grow in SFM they become more susceptible to stresses that cause cell death (1). Under bioreactor conditions, the most significant mechanism driving loss of cell viability is an increase in apoptosis (2). In order to maintain the growth of cells in the absence of serum, optimization of media with various growth factor supplements, including recombinant insulin, has traditionally been used. Several observations have led to the widespread belief that in cell culture the potency of insulin can be attributed to signaling through the Type I IGF receptor rather than via its own insulin receptor: The standard industry cell line, Chinese Hamster Ovary (CHO) cells, and most other cell lines have very few insulin receptors on their surface (3). Insulin is required at supra-physiological concentrations to support cell growth under serum free culture conditions and this concentration (2 - 10 mg/l) is much greater than would be required to induce activation of its own receptor (4). Therefore it is unlikely that that the effects of insulin are mediated solely by the insulin receptor (3) and it can be concluded that activation of the Type I IGF receptor is the mechanism by which insulin is acting in serum free cell culture.

Supplementation with LONG®R³IGF-I

A more effective means of media optimization is to supplement with an IGF analogue that acts directly on the Type I IGF receptor. LONG®R³IGF-I has been developed specifically to supplement mammalian cell culture and support the survival and proliferation of cells. It is engineered to have a higher biological potency than native IGF-I or IGF-II (3) and has several advantages over recombinant insulin, potency being among them. Our research has shown that supplementation of cell cultures with LONG®R³IGF-I at a much lower concentration results in equivalent or better productivity than supplementation with high concentrations of insulin. LONG®R³IGF-I is better able to stimulate the Type I IGF receptor and thus induce a higher level of activation of intracellular signaling molecules which are responsible for promoting cell survival by inhibition of apoptosis (4). LONG®R³IGF-I is used in the production of 7 FDA/EMEA approved biopharmaceutical drugs, which together achieved sales in excess of USD$3.2 billion for financial year 2004/2005. It is also being used by more than 100 companies in products at various stages of development. SAFC Biosciences has the exclusive right to market and distribute LONG®R³IGF-I for industrial cell culture applications. SAFC can assist with media optimization incorporating LONG®R³IGF-I. For ordering information regarding LONG®R³IGF-I, visit the SAFC Biosciences website. SAFC Biosciences website: www.SAFCBiosciences.com

References

1. Goswami, J., et al. Apoptosis in batch cultures of Chinese Hamster Ovary cells. Biotech. Bioeng. 1999, 62, 632-640. 2. Dickson, A.J. Apoptosis regulation and its applications to biotechnology. Trends Biotech. 1998, 16, 339-342 3. Yandell C., et al. An analogue of IGF-I. BioProcess International 2004, 2, 56-64 4. Morris, A.E. and Schmid, J. Effects of insulin and LongR(3) on serum free Chinese hamster Ovary cell cultures expressing two recombinant proteins. Biotechnol. Prog. 2000, 16, 693-697. LONG is a trade mark owned by Novozymes GroPep Limited

LONG®R³IGF-I is covered by the following patents assigned to Novozymes GroPep:

US patents 5,164,370 and 5,330,971; European patents 346,429 and 429,586; Japanese patents 2,507,106 and 2,682,738; Australian patents 612,776 and 633,099; Canadian patents 1,341,204 and 2,033,176.

For more information, please contact:

cellculture@novozymes.com.au