Arnold J in the Patents Court has found that Novartis' patent, covering its EXELON rivastigmine transdermal patch to treat Alzheimer's disease, is invalid.
To establish infringement by the generic defendants (Focus, Actavis, and Teva), Novartis proposed a broad claim construction, covering any patch which delivered the same starting dose as a defined reference patch. While the Court accepted the broad construction, this led to the conclusion that the patent was invalid because it included added matter over the application as filed and because it was obvious over a prior US patent.
In other European jurisdictions, courts hearing disputes over the equivalent Novartis patents have made divergent findings, particularly with respect to infringement by generics.
The outcome highlights the difficulties patentees face in English courts to put forward a claim construction that is broad enough to cover the allegedly infringing activities, but not so broad as to be invalid on grounds including added matter or obviousness. Where patentees do not get this right, or cannot get this right because of the wording of their application as filed, they risk the alleged infringer successfully running a 'squeeze argument' as the generics did in this case, essentially saying 'if we infringe on that construction, the patent must be invalid'. This case reminds litigants of the possibility of strikingly diverse findings when patent proceedings are heard in different jurisdictions across Europe. Equivalents to Novartis' patent had been litigated in 11 European countries before coming before the English Court. Though most of the proceedings had been interim injunction applications, requiring a lower standard of proof, some courts had found that generics had infringed and others had not on the same facts. In a number of jurisdictions where interim injunctions were awarded, the courts had given little consideration to the patent's validity. Despite the divergent views on infringement, this case indicates that courts in different jurisdictions may be more likely to come to the same conclusion as to the validity of a respective national designation of a European Patent. While the English Court's judgment was the first final decision on validity, the invalidity finding accords with opinions expressed by the European Patent Office (EPO), and courts in The Netherlands and Germany.
- Novartis' patent
- Skilled team and common general knowledge
- Novartis' broad claim construction accepted
- Invalidity for added matter
- Invalidity for obviousness
- Patent not insufficient
- Generics would have infringed
- What next?
1. Novartis' patent
Novartis' patent EP (UK) No. 2 292 219, titled 'Transdermal therapeutic system for the administration of rivastigmine', is a divisional patent derived from International Patent Application No. WO 2007/064407. Prior to introduction of transdermal therapeutic systems, which most commonly come in the form of patches, rivastigmine was administered orally which led to side effects such as nausea, vomiting and diarrhoea. Patients would be prescribed a starting dose of oral rivastigmine which was sub-therapeutic, and then increased to a therapeutically effective dose as they got used to the side effects. According to the patent, the use of a transdermal patch meant that patients could take a much higher starting dose with greater tolerability, so that their treatment was simplified.
2. Skilled team and common general knowledge
The parties agreed that the patent was addressed to a skilled team interested in developing a new formulation for rivastigmine. The team would consist of a formulator skilled in transdermal administration, and a clinician and/or neuroscientist in the field of dementia. There was however, substantial dispute as to the skilled clinician's common general knowledge of how tolerability of rivastigmine could be increased. Arnold J agreed with the generic parties that it was generally accepted at the priority date that rivastigmine should be administered with food, and that it was a reasonable hypothesis that this increased tolerability because it reduced peak plasma concentration of rivastigmine and increased the time at which peak plasma concentration was reached. This was widely stated in reviewed papers put into evidence by the generics.
3. Novartis' broad claim construction accepted
Arnold J accepted Novartis' construction that the single claim of the patent involved three components:
- rivastigmine for use in treating dementia or Alzheimer's;
- rivastigmine administered via a patch; and
- a 'starting dose' of rivastigmine that 'is that of' a reference patch with a structure and composition specified in the final three integers of the claim.
Because of the wording 'the starting dose is that of', the claimed patch could have any structure or composition provided it could deliver the same starting dose as the reference patch. It was not correct, as the generics proposed, to restrict the claim to a rivastigmine patch with the precise structure and composition specified in the final the integers of the claim. These features merely described the reference patch.
4. Invalidity for added matter
The generics' primary objection to validity was that the claim involved added matter. That is, the patent presented the skilled team with information about the invention which was not directly and unambiguously derivable from the international application on which it was based. Although the application disclosed a patch with the same structure and composition as the reference patch claimed in the patent, the application did not suggest that this should be used as a starting dose. In contrast, the patent explicitly disclosed a rivastigmine patch with a starting dose the same as that of the reference patch.
Arnold J accepted the generics' contention that if the claim is construed as Novartis contended, the amendments to the application made during prosecution amounted to disclosure of a new invention altogether. According to the judge, the patent taught the skilled team for the first time that it is the starting dose delivered by the patch that matters, not the structure or composition of the patch, whereas the application presented the structure and composition of the patch as the core of the invention. As a result, the patent was invalid for added matter.
5. Invalidity for obviousness
In their obviousness attack, the generics relied only on United States Patent No. 6 335 031, co-owned by Novartis. There was no dispute that the US patent disclosed the administration of rivastigmine by a transdermal patch with a structure and composition the same as that in the reference patch in the patent in suit. The essential difference was that the US patent did not disclose the use of a starting dose of that released by a reference patch. With regards to inventive step, the key area of disagreement was the starting dose the skilled team would select when administering rivastigmine using patches of the kind disclosed in the US patent.
Although it did not disclose a starting dose, the US patent stated that the size of the patch:
'may be determined by routine bioavailability tests comparing the blood levels of active agents after administration of [rivastigmine] in a composition according to the invention to intact skin and blood levels of [rivastigmine] observed after oral administration of a therapeutically effective dose of the compound [emphasis added]'.
Novartis submitted that this would lead the skilled team to administer as a starting dose, a patch of a dose equivalent to that of the starting dose in the oral rivastigmine regimen, that is the sub-therapeutic dose. This would mean the starting dose would be half that released by the reference patch disclosed in the patent. The generics on the other hand said that this statement in the US patent would lead the skilled team to do exactly what the statement said, and administer what was known to be the lowest therapeutic oral dose of rivastigmine as a starting dose. This would mean the starting dose would be that released by the reference patch disclosed in the patent. Arnold J accepted the generics' position and found the patent obvious in light of the US patent.
6. Patent not insufficient
As Arnold J confirmed, a patent will be insufficient if the skilled person cannot carry out the claimed invention given the description in the specification and the common general knowledge, or if the claims are ambiguous or excessively broad. However neither of these attacks applied to Novartis' patent.
The generics argued that the claim was excessively broad in that if the claim extended to any patch that delivers a starting dose which is that of the reference patch, the claimed benefit of tolerability is not plausibly obtained across the breadth of the claim. However in light of the expert evidence, Arnold J agreed with Novartis that a skilled person would know not to use a formulation that would not have the benefit of enhanced tolerability. The patent was not insufficient merely because it was possible to imagine a way of implementing the claim badly, because in practice this was not something the skilled person would do.
The generics also argued that the claim was ambiguous, because if the claim extends to any patch that delivers a starting dose which is that of the reference patch, the patent did not enable the skilled team to determine whether or not any other patch delivers 'the same' starting dose as the reference patch. Arnold J rejected this argument based on expert evidence that the skilled team would be able to select an appropriate statistical test to determine whether or not the patch delivered the same dose.
7. Generics would have infringed
Having found the patent invalid, Arnold J dealt with infringement briefly, finding that the generics would have infringed had the patent been valid. There was no dispute that the generics' patches were identical to Novartis' Exelon patches, save for the branding, and were in fact made by the same manufacturer. The generic patches would plainly be used for the claimed indication wherein rivastigmine is administered in a dosage regime beginning with the claimed starting dose.
8. What next?
It remains to be seen whether Novartis will appeal the Patent Court's invalidity finding. In the meantime, Novartis' European Patent remains under opposition at the EPO by 13 opponents and the Opposition Division has already issued a provisional opinion that the patent is invalid for added matter and insufficiency. Oral proceedings are scheduled for 15 to 17 December 2015.