Producing Proteins Using Transgenic Oilbody-Oleosin Technology - Progress has been significant in producing therapeutic proteins in plants. Insulin is an early candidate for commercialization. - BioPh

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Producing Proteins Using Transgenic Oilbody-Oleosin Technology
Progress has been significant in producing therapeutic proteins in plants. Insulin is an early candidate for commercialization.


BioPharm International
Volume 19, Issue 6


Nancy Markley, Ph.D
Securing a safe, economical, and reliable supply of a recombinant therapeutic protein for use in clinical trials and commercialization is an important strategic issue that must be addressed early in the development process. Today, bacteria, yeast, and mammalian cell cultures are routinely used for large-scale commercial production of biopharmaceuticals, but these systems are frequently costly and lack flexibility for scaling up production. Typical unit production costs range from US$100–1,000 per gram of purified protein product, depending on the product, volume, and production system. Capital investment is in the order of several hundred million dollars for a large capacity (100,000 L) facility.1,2




The construction and validation of cGMP compliant facilities requires long lead times, typically three to five years, which creates challenges in matching capacity to demand. As a result, companies must make manufacturing choices and a substantial upfront investment in capacity while their products are still in the test phases. The uncertainty of regulatory approval, and the difficulties in predicting market demand impose a significant business and financial risk. For drug developers, investing large amounts of capital on a drug that is awaiting approval is an expensive and very risky prospect; however, having a drug that is approved without a reliable supply of product can have equally dire consequences.

Transgenic production holds tremendous promise for dealing with the cost, capacity and scale-up limitations faced by traditional systems. Trans-genics can substantially reduce capital investment and lower production costs through economies of scale and more-flexible scale-up. Such advantages could enable the commercialization of proteins that would otherwise be impractical due to cost or capacity constraints, and provide scope for pricing flexibility that could be passed on to patients and health care systems. These benefits could allow companies to expand into new markets, such as follow-on biologics, where price is a barrier to entry.

Transgenic technologies have made significant advances in recent years and several companies have moved products into the clinic and validated their technologies through partnerships with well-established pharmaceutical and biotechnology companies.3,4 Transgenic systems encompass a variety of hosts and tissues from animal, plant, and avian origin. No transgenically derived product has been approved yet. We believe that it is plausible that insulin will be the first. With that in mind, we will discuss our technology based on oilbodies, followed by a description of recombinant protein production systems. We will wrap up with a case study of producing insulin with these technologies.

OILBODY-OLEOSIN TECHNOLOGY

Oilbody-oleosin technology offers several advantages for protein production and purification over traditional cell culture and other transgenic systems. Oilbody-oleosin technology is unique, as it is the only recombinant technology that addresses protein recovery and purification (processes that represent as much as 75% of the cost of production) contemporaneously with bulk protein production. The capital investment in an oilseed processing facility is roughly an order of magnitude lower than that of conventional fermentation facilities.

Beyond economics, oilseeds offer superior inventory management when compared to other transgenic systems. Unlike proteins expressed in milk or leaves, recombinant proteins have been found to be stable in transgenic seeds for several years. Seeds can be stockpiled and safflower, our commercial production crop, can be grown counter-seasonally, allowing maximal flexibility for inventory management. We believe that using safflower will allow us to readily address regulatory issues associated with transgenic crops, because safflower is a small acreage crop that is largely self-pollinating and can easily be geographically segregated from other safflower production and from the main food and feed crops.


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