Speed. Stability. Reproducibility. Success.

With our reputation for satisfaction and customer service – recently highlighted in the July 2007 BioInformatics, LLC report, “Customer Satisfaction & Loyalty in the Life Sciences: Boosting Profit Through Exceptional Service & Support” as a Top 5 supplier – we have a broad selection of Upstream products to fit the needs of its biopharmaceutical customers.

EX-CYTE growth enhancement media supplements

EX-CYTE supplement is an ideal enhancer for reduced-serum cell culture as it supplies critical growth factors and eliminates the need for full-serum supplementation. When used in conjunction with Millipore’s other critical media supplements, EX-CYTE supplement can significantly improve the cell culture manufacturing process.

EX-CYTE supplement is a water-soluble concentrate of cholesterol, lipoproteins and fatty acids that provide a balanced profile of metabolic factors proven to enhance cell growth and protein production in a variety of mammalian cells including: hybridomas, myelomas, CHO and HEK293 cells.

EX-CYTE supplement is manufactured under cGMP guidelines in large batch sizes, and tested for consistency, microbial content, clearance of bovine viruses (9 CFR 113), mycoplasma and endotoxins. Heat pasteurized, organic solvent and detergent free, EX-CYTE supplement is made from US-sourced materials.

Probumin bovine serum albumin (BSA)

Albumin is one of the most extensively utilized proteins in the medical industry. Its availability, inherent stability, and ligand binding ability, makes albumin an essential component in the production of many therapeutic drugs and diagnostic tests.

Millipore, with over five decades of protein fractionation expertise, is the world’s largest and most experienced manufacturer of high quality albumins for the diagnostic and cell culture market.

From albumins for nutrient-rich cell culture to the highly purified albumins for diagnostic applications, each of the Probumin BSA products have been designed to meet a specific need. Our fractionation technology, ISO certified facilities, US-sourced materials and proactive regulatory procedures enable us to deliver products with the highest quality, performance and safety every time.

Incelligent recombinant human insulin

Millipore is the leading provider of recombinant human insulin for cell culture applications to the biotech industry. Millipore’s insulin products are used in more cell culture applications and in large scale industrial processes than any insulin product available. A number of key pharmaceuticals on the market today use Incelligent insulin in their manufacturing processes.

Identical in structure and function to the native human sequence. A hormone consisting of two polypeptide chains, rHu Insulin’s Achain (21 amino acids) and B-chain (30 amino acids) are covalently connected by disulfide bonds between cysteine residues. Our genetically engineered human insulin is a full sequence molecule produced by recombinant DNA technology in baker’s yeast, Saccharomyces cerevisiae. It is a white crystalline powder with a potency of = 27.5 IU/mg (dry basis).

LucraTone hydrolysates, peptones and yeast extracts

LucraTone supplements are a full range of plant hydrolysates, yeast extracts and peptones. These supplements provide a highly pure source of soluble amino acids, peptides, vitamins and essential elements for cell culture and fermentation processes.

LucraTone supplements are manufactured in ISO certified manufacturing plants, require ambient conditions for storage and shipping and are available in large bulk batch sizes. As one of the leading suppliers of supplements to the bioprocessing industry, Millipore (formerly Celliance) continues to expand its leadership by offering more solutions to the industry’s needs.

UCOE Expression Technology – Protein production solutions

Millipore's UCOE Technology
(Ubiquitous Chromatin Opening Element)
Winner of 2007 Frost & Sullivan Technology Innovation Award

UCOE (Ubiquitous Chromatin Opening Element) expression technology gives major improvements in gene expression in stably-transfected mammalian cells through effects on the structure of chromatin. UCOE expression technology prevents transgene silencing and gives consistent, stable and high-level gene expression irrespective of the chromosomal integration site. UCOE expression elements are small DNA elements (isolated from the area around house-keeping genes, which need to be active most of the time) that create a transcriptionally active, open chromatin environment around an integrated transgene, maximizing its potential to be transcribed into protein, irrespective of the position of the transgene in the chromosome.

Advantages

Over 50% of UCOE-derived clones have higher expression than the best non-UCOE-derived clones
UCOE-derived vectors produce substantially more expressing clones than non-UCOE-derived vectors
Cell lines stable over 130 generations
High-yielding cell lines can be derived in less than 60 days, without amplification
Small (4-8kb) DNA elements, capable of making two protein chains per plasmid, e.g., antibodies
Express Antibodies, Receptors, Enzymes, Cytokines, etc.
Integrates with industry standard platforms, e.g, CHO cells, CMV promoters, plasmids, transfection agents, media, etc.

Successful Integration

The successful integration of a transgene into mammalian cells is largely dependent upon the chromatin structure around the integration site. Most mammalian chromatin exists in the closed (heterochromatin) form, which is transcriptionally silent. With conventional vectors, most integrations suffer from position effects and chromatin shutdown, which leads to gene-silencing and unproductive integration events. As a result, pools of stably-transfected cells generally show low productivity and stability, as only a few cells might be good producers, and gene silencing and overgrowth of non-producers rapidly diminish the overall productivity of the pool. This also makes it very difficult and time consuming to find high-expressing stable clones needed for large-scale manufacturing.

Benefits Of UCOE Expression Technology

The productivity and stability of individual cells allows pools to be a source for rapidly generating gram quantities of proteins in 3 – 4 weeks. This has potential advantages over transient transfection, minimizing the quantities of DNA and costly transfection agent, as well as allowing aliquots of the pool to be stored for future use if the protein is required at a later stage.

3x107 CHO-S cells were transfected with 90µg of an antibody expression plasmid either with or without a UCOE, drug selection was applied and once sufficient cell number was generated cells were seeded at a cell density that would allow growth to 10L. On day 16 a small non-feed addition was made to a proportion of the cultures (+opti). A fraction of the cells were grown and the data shown

Because the majority of cells are stable high-expressors, it is much easier and faster to find high-yielding clones with the productivity and stability required for manufacturing, as opposed to the "needle-in-a-haystack" approach using conventional vectors.

Vectors encoding heavy and light chains (separate plasmids) were cotransfected into CHO-S cells followed by drug selection and screening of 96 randomly selected clones.

Licensing opportunities

UCOE technology is under license to a number of pharmaceutical and biotechnology companies across North America, Europe and Japan and is covered by 55 issued and pending patents worldwide. Non-exclusive licenses are available for use of the UCOE technology for research or manufacturing purposes.

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