11 April 2008

The Biogen test revisited

When is a product claim in a patent insufficient? That is the core question in the judgement of April 10 by the UK Court of Appeal in Generics (UK) Limited v Lundbeck A/S in an appeal against the High Court Mr Justice Kitchin’s judgement in 2007.

The key issue is the extent of the monopoly given by a product claim in a patent. Kitchin J had extended the application of the Biogen test for patent insufficiency such that the scope of the monopoly for a product claim could be severely reduced. Lundbeck’s successful appeal, therefore, has significant commercial implications for the pharmaceutical industry as a whole.

The Facts
Three generic pharmaceutical manufacturers sought to revoke’s Lundbeck patent EP (UK) 0,347,066 for an anti depressant drug escitalopram (a single enantiomer of citalopram), claiming pharmaceutical compositions containing escitalopram, and a method of preparing escitalopram. Lundbeck’s patent expired several years ago. Citalopram was marketed as a racemic mixture and Lundbeck found a way to isolate the (+) enantiomer, discovered that this was the effective enantiomer and applied for the patent. The claims in issue were for the (+) enantiomer itself and for a pharmaceutical composition containing it.

The First Instance
The Patents Court concluded that, as was generally believed, a single enantiomer[1]of a known chemical compound was not patentable. Interesting to the pharmaceutical industry, increasingly reliant upon life cycle management, is why precisely this should be the case. The High Court found these claims were invalid for insufficiency. Kitchin J reasoned that since the existence of the (+) enantiomer was known as part of the citalopram mixture and isolation of the separate enantiomers was known to be desirable, Lundbeck’s invention lay solely in the discovery of a way to make it. He concluded that this should not entitle Lundbeck to a monopoly of every way of making it i.e. a product per se claim. He applied the test set out by Lord Hoffmann in the House of Lords case, Biogen v Medeva[2], that for “sufficiency” a disclosure should enable the full extent of the claim and not merely a single example of something within the claim.

The Court of Appeal Decision
The Court unanimously upheld Lundbeck’s appeal and found that the product claims were not invalid for insufficiency. A product claim is sufficiently enabled if the specification discloses one way of making it. In the words of Lord Hoffmann: “in an ordinary product claim, the product is the invention. It is sufficiently enabled if the specification and common general knowledge enables the skilled person to make it. One method is enough.” Lord Hoffmann confirmed that the Biogen test applied to a hybrid or “product-by-process” claim such as that considered by the House of Lords in the Biogen case itself. The test could not be extended to an ordinary product claim in which the product is not defined by a class of processes of manufacture or is not simply a member of a large class. An inventor who finds a way to make a new product is entitled to claim the product however made and however used, even if the desirability of making it was known. The Court of Appeal also upheld Kitchin J in holding that the product claims were novel and inventive.

This decision may in practice put an end to the “Biogen Insufficiency” doctrine, and brings the UK patent courts in line with most other patent jurisdictions worldwide as well as the EPO jurisprudence. As to patent validity it may open up a new trend into a more patentee friendly disposition.

[1] Advances in industrial chemical processes have made it economical for pharmaceutical manufacturers to take drugs that were originally marketed in racemic form and market the individual enantiomers, each of which may have unique properties. For some drugs, such as zopiclone, only one enantiomer (eszopiclone) is active; the FDA has allowed such once-generic drugs to be patented and marketed under another name. In other cases, such as ibuprofen, it is not economically feasible to isolate a single enantiomer from a racemic mixture or to synthesize just the active one, and therefore a racemic mixture is marketed, with an essentially doubled recommended dose (see www.answers.com) . See for background chemistry: “Patents and enantiomers: Generics v Lundbeck” by Brian Whitehead, Stuart Jackson, and Richard Kempner in Journal of Intellectual Property Law & Practice, 2007, Vol. 2, No. 12, p. 808-810

[2] In Biogen v Medeva [1997] R.P.C. 1, Biogen's patent for recombinant DNA coding for a polypeptide having hepatitis B virus (HBV) antigen specificity was held by the House of Lords in 1996 to be insufficiently enabled by its specification, not because of any inability for the described invention to deliver all the promised results, but because the same claimed results could be produced by different means which owe nothing to the teaching of the patent or any principle it disclosed.
Thanks to Simmons & Simmons (London), Howrey (London), Remco de Ranitz (The Hague)

09 April 2008

Dutch court refers Round Up patent dispute to ECJ

In a long standing battle[1] between Monsanto, Argentina and importers of soymeal, the District Court The Hague gave its (interim) judgment on March 19, 2008, referring the case to the ECJ for their interpretation of articles 8 and 9 of the 1998 Council Directive 98/44/EG relating to the protection of biotechnological inventions (Biotechnology Directive).

The facts
Monsanto is the owner of EP patent 0546090, relating to enzymes which, if expressed by a plant, confer resistance to a herbicide. In 1995 Monsanto introduced "Roundup Ready soy plants" soya meal that have had a copy of a gene from the bacterium, Agrobacterium sp. strain CP4, inserted into its genome that allows the transgenic plant to survive after being sprayed by Monsanto's this non-selective herbicide, Roundup. Glyphosate, the active ingredient in Roundup, kills conventional soy plants. The bacterial gene is EPSP (5-enolpyruvyl shikimic acid-3-phosphate) synthase. Regular Soy also has a version of this gene, but the regular version is sensitive to glyphosate, while the CP4 version is not.

The glyphosate works by inhibiting a certain enzyme called EPSPS which is present in the plant. This enzyme is important for the production of aromatic amino acids, these being necessary for the plant growth. The patent describes a class of EPSPS enzymes which are not sensitive to glyphosate, the so-called Class II enzymes. Glyphosate blocks the active centre of Class I EPSPS enzymes whereby the production of aromatic amino acids is disturbed. The plant cannot produce any or at least cannot produce sufficient proteins without these aromatic amino acids and therefore dies off. Plants possessing Class II EPSPS enzymes do not have this problem so they survive the use of glyphosate whilst the weeds around them die.

The Case
The defendants purchased soy beans in Argentina (where there was no patent protection), the beans being grown from plants carrying one of the genes disclosed in the patent. The beans, grown in Argentina, were imported by the defendants into the Netherlands as processed soy meal. Monsanto has no patent protection in Argentina. The patent claims are directed to isolated DNA sequences, a recombinant DNA molecule, a method of producing genetically transformed plants which are tolerant of certain herbicides and a herbicide-tolerant plant cell comprising the previously mentioned DNA molecule. Monsanto maintained that importation of the soybeans infringed its European (Netherlands) patent, the defendants disputed that.
Core of the matter is, briefly, whether according to art.9 of the Directive, the scope of preotection for a biotechnology invention is determined on the basis of the generic information having been incorporated in the product and therein exercising its function. Consequently, protection to the plants may not be extended to the derived products in which the genetic information is residual and does not "exercise its (genetic) function".
Question is whether articles 8 and 9 of the Biotech Directive, implemented in Dutch law as article 53a Dutch Patent Act ("Rijksoctrooiwet", or "ROW") merely explicate the scope of protection awarded to biotechnology inventions, or actually limit the scope of these inventions to actively functioning DNA (sequences).
The Hague District Court judgment
In its interim judgment, the court firstly held that those claims covering an isolated DNA sequence constitute no infringement as the DNA is not present as isolated matter but is incorporated in the soy meal. The court rejected Monsanto’s reasoning that the DNA sequence has been taken out of its natural environment – the bacterial chromosome - and has been encoded in the DNA of the soy plant and, for this reason, the DNA in the soy meal should be regarded as an isolated DNA sequence, or, that it contains this. The average person skilled in the art would understand the term isolated DNA as DNA that has been retrieved from the cell (core) of an organism for further treatment in a manner as is usual in the relevant profession.
Secondly the court rejected an interpretation that the soy meal can be regarded as a “directly obtained product” by application of the claimed methods according to some other claims of the Monsanto patent. Although soy plant and soy bean have been directly obtained by the patented method, the beans are subsequently then separated and subsequently “crushed” the beans are separated, in a number of treatment stages, and worked into different components, finally ending up as soy meal.

Thirdly, the court considered whether any product claims were infringed, which claims relate to a DNA sequence or a DNA molecule. The dispute focused around the question whether the DNA sequence which encodes for the synthesis of a Class II EPSPS enzyme was found in the samples taken from the cargo imported by defendants. Parties then argued on whether any of the DNA sequence was present in the soy meal, so imported. The importers, supported by the Government of Argentina, argued that the DNA sequence was at best present “in fragmented form”, caused by heating during the “crushing process” of the beans.
The major question then became whether, if any of the claims relating to genetic material are infringed, as Monsanto alleges, the soy meal contains at least genomic fragments of the Round Up Ready-DNA sequence?
Questions referred to the ECJ
The court reviewed this question in relation to articles 8 and 9 of the 1998 Council Directive 98/44/EG on the protection of biotechnological inventions “the Biotechnology Directive”).

The first question of the court to the ECJ relates to the scope of art. 9 of the Biotechnology Directive, especially when DNA “performs its function”. Monsanto argued that the DNA found in the imported soybeans may not then and there “performs its function”, but in order to invoke patent protection under art. 9 of the Biotechnology Directive it would suffice for the DNA-sequence to - at any particular moment - have performed its function in the soya plant or that the DNA could again “perform its function” after having been isolated from the soy meal and inserted into living material again. The court wants to know from the ECJ whether this interpretation of Monsanto is correct.

The second question relates to the question whether or not the protection of a biological material by the Biotechnology Directive prevents the national Dutch Patent Act (art 53) from protecting next and above the protection conferred upon DNA as such ("classic product protection")irrespective of whether the DNA sequence it “performs its function”.

The third question is whether in answering the second question it makes any difference that the patent has been granted before the Directive came into force (artt. 27 and 30 TRIPS).

[1] See for an interesting resume of the history of Monsanto’s battle against Argentina patent policy, “Harvesting Royalties for Sowing Dissent? Monsanto's Campaign against Argentina's Patent Policy”, www.grain.org, and http://snipurl.com/23xnu
(with thanks to Erik de Vos, Nauta Dutilh, Amsterdam)