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combo SPC validity
What was the SPC?
MSD's SPC/GB08/022 ("the SPC") - a combo SPC covering the anti-retroviral medication used in the treatment of HIV sold as Atripla by BMS and Gilead. Atripla is a fixed-dose combination of three active ingredients which are inhibitors of a viral enzyme known to reverse transcriptase - efavirenz ("EFV"), tenofovir in the form of disoproxil fumarate ("TDF") and emtricitabine ("FTC").
FTC is a NRTI (nucleoside reverse transcriptase inhibitor). EFV is a NNRTI (a non-nucleoside reverse transcriptase inhibitor). Tenofovir, a NtRTI (i.e. a nucleotide RT inhibitor), is a nucleotide analogue.
The rationale of Atripla is that it simplifies HIV-treatment regimens by improving patient compliance (one pill being easier to take than three separate ones).
The SPC described the product as
"A combination of efavirenz, emtricitabine or a pharmaceutically acceptable salt or ester thereof, and tenofovir or a pharmaceutically acceptable prodrug, salt or ester thereof, particularly tenofovir disoproxil, especially tenofovir disoproxil fumarate"The marketing authorization ("MA") for Atripla was granted on 13 December 2007. An MA for EFV was granted in 20 November 1998. This MA was used as the basis to obtain an earlier SPC - SPC/GB00/35 - for EFV, alone ("the EFV mono SPC") which expired on 19 November 2013. The MAs for TDF and FTC were granted on 5 February 2002 and 24 October 2003, respectively.
What was the problem?
Teva argued that the SPC was invalid under Article 3(a) and 3(c) of the SPC Regulation. Article 3(c) demands that the product subject to the SPC be protected by a basic patent in force at the date of the SPC application. Article 3(c) requires that the product not already be subject to an SPC. Teva argued that the SPC was invalid under:
- Article 3(a) as the product was not protected by the basic patent - EP(UK) 0 582 455. Interestingly, MSD amended its patent to include a new claim 17 upon which it relied to protect the product for the purposes of obtaining the SPC, but didn't rely upon it at trial (c.f with the position in Actavis v Boehringer  EWHC 2927 at ). Only claim 16 was relied upon at trial. Claim 16 is in the following terms:
- Article 3(c) as MSD already obtained an SPC for EFV based on the basic patent. Because it was agreed that the basic patent disclosed and claimed EFV specifically and as part of a class of compounds, Teva argued that the Atripla product had already been subject to an SPC (the EFV mono SPC) which compensated MSD for the delay in exploiting the invention.
"A combination of the compound of claim 12 or a pharmaceutically acceptable salt thereof with a nucleoside analog having biological activity against HIV reverse transcriptase."
- Article 3(c) precludes the grant of SPCs for a combination of active ingredients where one of those active ingredients embodies the "core inventive advance" (at  of Actavis v Sanofi) or "sole subject-matter of the invention" (at  of Actavis v Boehringer) of the basic patent and that active ingredient has already been the subject of an SPC based on that patent. This is irrespective of whether the patent contains one of more claims which protect the combination itself.
- But an SPC can be granted if the combination is a distinct invention - it will not matter whether its protected by the same patent or by a different patent. In those circumstances, one of those active ingredients could not be said to be the "sole subject-matter of the invention".
"whether, given the invention of efavirenz [which was accepted by the parties], claim 16 represents a distinct invention such that it could in principle form the subject-matter of a separate patent."What was the answer?
"does not represent a distinct invention. There is nothing in the Patent to suggest that claim 16 represents a distinct invention. Given the need for a simple and transparent system for the grant of SPCs, it seems to me that that should ordinarily be the end of the matter and that it should not be necessary to adduce expert evidence on this question."
"I consider that the evidence establishes that, given efavirenz, it would have been obvious to combine it with a NRTI in vitro because that would have been an obvious thing to try and the skilled person would have had a fair expectation of success. This is for the following combination of reasons."This conclusion pulled support from an earlier finding made by the judge at paragraphs 136-140 where he concluded that it was CGK that combinations of NRTIs and NNRTIs were at least worth considering. This was because emerging research showed that NNRTIs were unlikely to be efficacious alone and given the different mode of action to NRTIs, there were potential advantages in combining the two. The judge held that the skilled person would have considered that there was a reasonable likelihood that a combination of a NRTI and a NNRTI would be either synergistic or additive, in vitro. Further, there was a "reasonable possibility" that the effect would be synergistic, although tests would have to prove this. The SPC was therefore invalid under Article 3(c).