Down on the Pharm

So-called pharm animals are being described as "revolutionising" the pharmaceutical industry.

Pharming refers to the use of host animals (and also plants) to express certain qualities (for example, in their milk). Such animals have been described as "animal factories," and their use has attracted a great deal of criticism and debate. As well as concerns over safety (such as the Starlink controversy and the ProdiGene episode), such use of animals has raised ethical questions from various groups, including Animal Liberation (Australia) and the British Union for the Abolition of Vivisection (BUAV).

One such pharm animal is on its way to market. European regulators have recently approved a drug produced in the milk of genetically modified goats.

ATryn is a recombinant form of human antithrombin (ATIII), used in the treatment of hereditary antithrombin deficiency (HAD), where the individual is missing the gene responsible for making the protein, antithrombin. HAD can lead to various problems, including deep-vein thrombosis, because the blood clots too easily. ATryn is lauded as much safer to deliver the missing copy of the gene than other methods, such as through human blood plasma (which carries the risk of vCJD). Antithrombin is administered to HAD patients during times when the usual treatment by warfarin is too risky (such as during childbirth and surgery).

GTC Biotherapeutics, the company responsible for developing the drug, applied for European Market Authorization in January 2004, as discussed in an earlier post, Milking Medicines. However, in February this year, (see previous post, Crying over Spilt Milk), the European Medicines Agency (EMEA) refused the application to license ATryn, calling for more evidence on the benefits of the drug. After reversing this decision and deciding to issue the licence in June, as set out in its positive opinion, the EMEA Committee for Medicinal Products for Human Use (CMPH) has now given approval to the drug (as reported in The Times and a GTC press release).

Tom Newberry, spokesperson for GTC Biotherapeutics, claims the drug could be available in the UK and Europe from mid-2007. The company also has many more transgenic products in various stages of development.

The European approval of the transgenic drug is a boost to other drugs being developed, including the production of polyclonal antibodies in chicken eggs for the treatment of cancer (Origen Therapeutics); the production of high level proteins in insect larvae (Minos Biosystems); and several treatments being developed by Pharming and produced in the milk of transgenic animals. Pharming recently announced its application to the EMEA for marketing authorisation of Rhucin, a drug to be used in the treatment of hereditary angioedema, accepted for review by the EMEA. If approved, Rhucin will receive marketing authorisation in all 25 EU member states.

Crying Over Spilt Milk

The BBC has reported that the application of GTC Biotherapeutics to license Atryn, produced in the milk of transgenic goats, has been refused. The European Medicines Agency (EMEA) has called for more evidence of the benefits of the drug, in order to outweigh the perceived risks associated with the licensing of the medicine. In particular, the EMEA said evidence showing that there was no development of an unfavourable immune response to the drug had not been adequate. The EMEA refusal is noted in a recent press release and its recommendations set out the reasons for refusal in more detail. The BBC report describes this as a major setback for the promises of cheaper living drugs, heralded in the late 1990s but yet to be delivered.

Milking Medicines

GTC Biotherapeutics have applied to the European Medicines Agency (EMEA) to license Atryn, a recombinant form of human antithrombin, extracted from the milk of genetically modified goats. As reported by the BBC, granting of the licence would mean that Atryn will be the world's first medicine to be produced from a genetically modified animal. In Wisconsin, Pharming is working on a herd of transgenic cows that express human lactoferrin in their milk, for which they have just filed a GRAS (Generally Recognized As Safe) notification with the US FDA. In the Netherlands, the same company is milking rabbits for recombinant human C1 inhibitor, for treatment of hereditary angiodema.




"milking a rabbit"

And a mouse?

Last week, Lay Line Genomics (Italy) published a PCT Application, WO/2005/105847, for a non human transgenic animal as a model of neurogenerative diseases and its use for the early diagnosis of such diseases. Such applications are becoming more common, and activities in this area are of particular interest to the Patenting Lives Project. The claims in this application include transgenic members of the genus murine (mouse/rat) and the species mus musculus (house mouse) expressing the antibodies of interest to the application. Anyone producing a mouse expressing the antibodies described in this application would indeed infringe, if this patent were to be granted, because the application specifically claims transgenic animals of the murine genus. Of course, it remains to be seen whether this application will be patentable (resulting in subsequent national patents for which applications will be made throughout the world). One to watch.