12
September 2009
The Importance of Chiral Separations in Single Enantiomer Patent Cases
by CharlotteWeekes LLB, Roiter Zucker Solicitors
cweekes@roiterzucker.co.uk Roiter Zucker acted for the Claimant, Teva in the Generics&others v Lundbeck action
Keywords: Chiral – pharmaceutical – enantiomer – racemate – inventiveness – novelty – patent
The interest in the current state of the art in chiral separations of analytical chemists and other scientists working in the pharmaceutical industry is well known. However, to the pharmaceutical companies themselves the state of the art of chiral separations in years gone by may be just as critical to their business. The field of chiral separations has featured strongly in recent pharmaceutical patent cases and has had a bearing on the outcome regarding the “inventiveness” of chiral drug molecules when patent law is applied. One case found its way to the highest UK court, the House of Lords, and in doing so redefined the scope of patent law.
Patents Act 1977 – a brief introduction
Revocation of a patent is most commonly sought on the following grounds:
a) the invention lacks novelty (anticipation); b) the invention lacks an inventive step (obviousness);
c) the invention is not capable of industrial application;
d) the specification of the patent does not disclose the invention clearly and completely enough for it to be performed by a person skilled in the art (insufficiency)
For an invention to be anticipated there are two requirements:
1) DISCLOSURE – the prior art [1] relied on
must disclose subject matter which, if performed, would necessarily result in an infringement of the patent; and
2) ENABLEMENT - the ordinary skilled person must have been able to perform the invention if he attempted to do so using the disclosed matter and common general knowledge (‘CGK’).
If an invention is obvious to the person skilled in the art (the notional addressee of a patent) it lacks inventive step. The skilled person is a legal fiction. He is deemed to possess the CGK in the field to which the invention relates [2]
but to lack inventive
capacity. He is deemed to have read all publicly available documents, in whatever jurisdiction or language but is not deemed to think laterally or know everything which comprises ‘state of the art’. The addressee may be a skilled team whose combined knowledge allows the instructions in the patent to be carried out [3]
.
To be CGK the information must be generally known and accepted as a good basis for further action by the bulk of those engaged in that art [2]
The cases
Atorvastatin, 2005 [4] (a ‘statin’ for inhibiting cholesterol synthesis)
Although chiral separation of atorvastatin (Fig. 1) was not the issue here, the Judge commented that where a drug is a chiral molecule, the skilled person at the priority date [5] (May 1986) would expect only one of the enantiomers or diastereomers to be responsible for its pharmaceutical activity. This did not mean that chiral drugs had to be administered as single enantiomers but there was undoubtedly a tendency to prefer single enantiomers where resolution of the racemate is practicable.
Escitalopram, 2007 – 2009 [6] (an antidepressant)
This notable case concerned an attempt by three generic manufacturers to revoke Lundbeck’s patent. Escitalopram (Fig. 2a) was first marketed in 2002, the priority date of the patent was June 1988. The revocation arguments were based on the prior art racemate, citalopram, which was synthesized by Lundbeck in 1972 and launched as an antidepressant in 1989.
The argument of lack of novelty advanced by the generic manufacturers was that the claims in Lundbeck’s patent did not exclude (+)-citalopram within the prior disclosed racemic mixture, therefore the racemate would infringe this later patent. The correct approach to a product claim in a patent is that it covers the product wherever found [7]. The generic manufacturers did not suggest that disclosure of a racemate of itself amounted to disclosure of each of the enantiomers, the Judge agreed (previously considered by the European Patent Office [8]). The Judge said “if the claim properly construed, was simply to a product as such then the monopoly would indeed cover that product wherever it might be found”. However, Lundbeck was clearly not laying claim to an unresolved moiety of the racemate - the patent title was “new enantiomers and their isolation” and the specification was clear that the racemate is not new – it related to the isolated product.
Figure 1: atorvastatin, the active pharmaceutical ingredient of the Pfizer product Lipitor®
The obviousness attacks were based largely on what was said to have been CGK and, given that this invention had been made many years ago and the state of the art had advanced considerably since, the Judge
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60
