Target Product Selection - Where Can Molecular Pharming Make the Difference?

Abstract

Four major developments have taken place in the world of Molecular Pharming recently. In the USA, the DARPA initiative challenged plant biotechnology companies to develop strategies for the large-scale manufacture of influenza vaccines, resulting in a successful Phase I clinical trial; in Europe the Pharma-Planta academic consortium gained regulatory approval for a plant-derived monoclonal antibody and completed a first-in-human phase I clinical trial; the Dutch pharmaceutical company Synthon acquired the assets of Biolex Therapeutics, an established Molecular Pharming company with several clinical candidates produced in their proprietary LEX system based on aquatic plants; and finally, the Israeli biotechnology company Protalix Biotherapeutics won FDA approval for the commercial release of a recombinant form of the enzyme glucocerebrosidase produced in carrot cells, the first plant biotechnology-derived biopharmaceutical in the world approved for the market. Commercial momentum is gathering pace with additional candidates now undergoing or awaiting approval for phase III clinical trials. Filling the product pipeline is vital to establish commercial sustainability, and the selection of appropriate target products for Molecular Pharming will be a critical factor. An interesting feature of the four stories outlined above is that they span the use of very different platform technologies addressing different types of molecules which aim to satisfy distinct market demands. In each case, Molecular Pharming was an economically and technically suitable approach, but this decisionmaking process is not necessarily straightforward. Although the various technologies available to Molecular Pharming are broad ranging and flexible, competing technologies are better established, so there needs to be a compelling reason to move into plants. It is most unlikely that plant biotechnology will be the answer for the whole biologics field. In this article, we discuss the current plant biotechnology approaches that appear to hold the greatest promise and in doing so attempt to define the product areas that are most likely to benefit from different Molecular Pharming technologies.

Molecular Farming in Plants: The Long Road to the Market

“…The CONCERT TM platform based on tobacco BY-2 cells is one example of the former approach, and this was used by Dow AgroSciences to produce a poultry vaccine which was approved by the USDA in 2006 ). The Israeli company Protalix BioTherapeutics followed the same route to develop the ProCellEx platform based on carrot cells, which is thus far the only plant-based platform used to manufacture biopharmaceuticals approved for human use (Aviezer et al 2009a, b;Paul et al 2013). Other biopharmaceutical products manufactured using plant cell/tissue platforms are also close to approval (Tiwari et al 2009, Xu et al 2011.…”

“…Many of the original molecular farming SMEs collapsed, and the large industry players gradually lost interest. The more recent revival of molecular farming reflects two major advances-first, the focus on specific platforms, which paved the way for specific regulatory guidelines, and second, the focus on niche products that can be produced more successfully in plants than by bacteria or microbes (Paul et al 2013). …”

An in silico overview on the usefulness of tags and linkers in plant molecular pharming

“…Genetically engineered plants have emerged as one of most attractive platforms for producing therapeutic recombinant proteins such as antibodies, vaccines, enzymes, and other pharmaceutical entities, such as human alpha-1-antitrypsin or human serum albumin, necessary for the improvement of veterinary and human healthcare systems throughout the world (He et al, 2011;Ou et al, 2014;Paul, Teh, Twyman, & Ma, 2013;Zhang et al, 2012). Plants offer scalability, low cost and safety, as they are devoid of mammalian pathogens.…”

Plant Molecular Farming: Much More than Medicines

“…The first examples of molecular farming involved the production of an antibody and human serum albumin in transgenic plants and plant cell suspension cultures (1,2). This led to the rapid exploration of many different plant species as hosts for the production of recombinant pharmaceutical proteins, a field sometimes described as molecular pharming (3,4). Many proof-of-principle studies were published in the following years, but the breakthrough to commercial success only came once a defined regulatory framework was accepted for plant-derived biologics, culminating in 2012 with the approval of taliglucerase alfa, a recombinant form of human glucocerebrosidase developed by Protalix Biotherapeutics for the treatment of the lysosomal storage disorder Gaucher's disease (5).…”

“…Other companies have since taken up this mantle, including those with a clinical development program, in the realization that nonpharmaceutical products can reach the market more quickly because of the much lower regulatory burden. The product portfolio ranges from technical enzymes and research-grade reagents to cosmetic products (3,7). There are more nonpharmaceutical products already on the market than there are pharmaceutical proteins undergoing clinical development ( Table 1).…”