Another successful blockbuster: Court of Appeal finds in favour of Gilead’s Sovaldi

Idenix Pharmaceuticals v Gilead Sciences & Others [2016] EWCA Civ 1089

November 2016

The Court of Appeal has dismissed Idenix Pharmaceuticals, Inc’s. (Idenix) appeal against Mr Justice Arnold Judgment revoking Indenix’s patent covering Flaviviridae compounds for treating Hepatitis C.  Kitchin LJ upheld the findings that the Patent was (1) obvious as it was not plausible that substantially all of the compounds covered by claim 1 would have anti-flaviviridae activity; (2) insufficient in that the Patent taken with the common general knowledge (CGK) did not make it plausible that the invention would work across the scope of the claims as well as placing an undue burden on the skilled to perform the invention; and (3) that certain claims added matter.  Furthermore Idenix’s proposed amendments were not allowable.  

Although it was not necessary for the Court of Appeal to consider the novelty aspects of the case, Kitchin LJ did consider the arguments on the assignment of priority in some detail.  He was satisfied that the Judge had correctly decided that the R&D Agreement amounted to a present assignment of the invention such that the PCT applicant was the successor in title to the inventor.  There were a number of issues concerning the agreements (a lack of evidence that the R&D agreement was signed, was a signature required to transfer legal title to the invention) that Kitchin LJ expressed concern over, but declined to reach a conclusion on.  These issues also gave rise to the question as to whether holding equitable title to the invention was sufficient for the purposes of claiming a right to priority.  Kitchin LJ expressed a provisional view that as the Paris Convention did not identify the requirements for the effective transfer of title, this was a matter for national law and that it was the transfer of the substantive right and title to the invention that was important.  However, as it was not necessary to do so, he did not express a final view on this issue.     

Background

UK patent No. 1 523 489 (the Patent) claimed a family of nucleoside analogues with 2'-methyl-up-2'-fluoro-down substituents for treating HCV and other Flaviviridae infections. The application for the Patent, International Patent Application No. WO 2004/002999 (the Application), was filed on 27 June 2003. The Patent was granted on 12 March 2014.

Following grant, Idenix alleged infringement against Gilead Sciences, Inc. and Gilead Sciences Ltd. (collectively Gilead) for the making and selling of the blockbuster drug sofosbuvir (Sovaldi).  Gilead counterclaimed for revocation for lack of novelty over Gilead’s PCT application PCT/US2004/012472 (the Pharmasset PCT), which claimed priority to US 60/474,368 (US’368), obviousness, insufficiency and added matter.

The Appeal

Idenix contended that Arnold J fell into error at almost every stage of his analysis and on every issue.  They took issue with the Judge’s findings that the Pharmasset PCT was entitled to priority, how the Judge approached and assessed the common general knowledge (CGK) and that the Patent lacked an inventive step and was insufficient as well as on the issue of added matter.  Gilead’s Respondent’s Notice argued that Arnold J ought to have found that claim 1 of the Patent as granted was invalid for added matter.

Common General Knowledge

It was an unusual feature of this aspect of the case, that the patentee, was asserting that more information formed part of the CGK than Gilead. In Arnold J’s opinion, this reflected the fact that Idenix was attempting to remedy the deficiencies in the Patent.  In particular, Idenix appealed Arnold J’s finding that it was not part of the CGK that 2'-methyl-up-2'-hydroxy-down nucleoside analogues had the potential to be efficacious in treating HCV.  Idenix had sought to rely on a series of publications in 2002 and 2003 as forming part of the CGK.  However, as Kitchin LJ noted, Idenix’s expert did not mention a number of the publications upon which Gilead’s expert was cross-examined on and upon which Idenix then relied and the Judge had been entitled to have regard to this fact.

Idenix had also sought to rely upon three presentations given at a major conference on Antiviral Research in Savannah, Georgia in 2003 attended by 400 academics and pharmaceuticals.  However, Idenix’s expert had accepted that the conference would not have been attended by all medicinal chemists with an interest in anti-HCV.  Idenix’s expert was sufficiently interested in these presentations (presenting data from a replicon assay demonstrating that 2'-C-Me-Adenosine and 2'-C-Me-Guanosine were potent inhibitors of HCV) and had asked for copies of the authors’ slides.  Arnold J observed that, although Dr Brancale was interested in these presentations, there was no evidence they attracted particular attention.  The evidence fell: “…a long way short of showing that even the general message conveyed by these presentations was CGK by 27 June 2003.”

Kitchin LJ rejected Idenix counsel’s criticisms of the Judge’s approach noting that the presentations were not identified as a highlight of the conference in the July 2003 edition of ISAR News or the newsletter of the International Society for Antiviral Research, nor was there any evidence that the presentations were picked up in any other publication before the priority date.  On that basis, Kitchin LJ was satisfied that Arnold J was correct in holding that Idenix had not established that it was part of the skilled team’s CGK as at 27 June 2003 that 2'-methyl-up-2'-hydroxy-down nucleoside analogues had the potential to be efficacious in treating HCV.   

Inventive Step

Gilead had contended that the claims in issue were invalid for obviousness because they made no technical contribution to the art and that it was not plausible that substantially all of the compounds falling within the scope of these claims would be effective against Flaviviridae.  In the case of a claim to a new class of chemical compounds, the selection of those compounds must not be arbitrary but justified by a technical effect which distinguishes the claimed compounds from many other compounds. 

Kitchin LJ observed that it was important to have in mind the critical question in relation to the compound claims, namely whether it was plausible that substantially all of the compounds covered by those claims would have anti-Flaviviridae activity.  He accepted that all of the claimed compounds have 2'-methyl-up-2'-fluorine-down substituents but, as Arnold J explained, there was nothing in the specification by way of experimental data that suggested that substantially all of these compounds are effective against Flaviviridae.  Further, based on his findings, the CGK provided Idenix with only limited assistance. Finally, he noted that Gilead’s expert accepted that the 2'-methyl-up-2'-hydroxy-down analogues described in the publications and discussed at the Savannah conference were structurally highly related to the analogues claimed in the Patent but he also made it quite clear that any such analogues would have to be tested and that there was no way to predict anti-viral activity in advance of such testing.

On that basis, Kitchin LJ held that Arnold J had been entitled to reach the conclusion he did on the evidence before him as no basis was shown to the court that would me it could interfere with the Judge’s finding that it was not plausible that substantially all of the compounds covered by claim 1 as proposed to be amended would have anti-Flaviviridae activity.

Insufficiency

For the reasons Arnold J had given in relation to obviousness, the disclosure of the Patent, read with the benefit of the CGK, did not make it plausible that the invention would work across the scope of the claims.  Kitchin LJ found this judgment to be inevitable and correct.  Further, Kitchin LJ observed that in particular circumstances it is permissible to limit a claim by adding a functional requirement but it must still be possible to perform the invention across the scope of the claim without undue effort.

In relation to Arnold J’s findings on undue burden, Idenix argued that Arnold J had assessed the issue of enablement by seeking to ascertain whether the skilled person could have made the 2'-methyl-up-2'-fluoro-down nucleoside analogues by a “routine” method.  Kitchin LJ rejected this, holding that Arnold J had followed a detailed assessment of all the material and evidence before him and that he had the correct test in mind, namely whether the disclosure of the Patent enabled the skilled person to make the claimed compounds without undue burden.  A patentee need not describe the ordinary steps which the skilled person would expect to have to take to implement the invention and it was perfectly apt to describe these steps as “routine”.  Further if, on the other hand, the skilled person was required to carry out work which was far from routine then this may be a matter which suggests the disclosure was insufficient.

Arnold J had held that it was not established that a skilled person carrying out a retrosynthetic analysis in June 2003 would have conducted a literature search which would have found that tertiary substrates seldom undergo nucleophilic substitution at all and that, with a few exceptions, nucleophilic substitutions at a tertiary carbon have little or no preparative value.  Idenix also submitted that Arnold J’s refusal to allow the skilled person to read the relevant literature was an illustration of his erroneous approach as, such reading is part of the everyday work of the average medicinal chemist.

Kitchin LJ disagreed, noting that Arnold LJ had focused on the factual evidence in the case before addressing the evidence of the experts.  Secondly, Kitchin LJ recognised that, in assessing insufficiency, the work of one individual chemist may not be representative of that of the ordinary skilled person for one or more of a wide range of reasons.  For example, the patent specification may contain important and useful information of which the chemist was not aware; or the chemist may have missed the obvious; or the chemist may have adopted an eccentric approach.  However, the work of such a chemist may be representative of that of the ordinary skilled person and, if the judge was properly satisfied that was so, it was appropriate to take it into account.

Priority

As part of the novelty attack, Gilead had deployed its own prior art, the Pharmasset PCT filed on 21 April 2004 and claimed priority from US provisional application ‘368, which was filed on 30 May 2003.  It was accepted that if the Pharmasset PCT was entitled to priority then it would anticipate all of the claims of the Patent save for claims 20 and 37.

The invention in ‘368 was made by an employee (Mr Clark) of Pharmasset Inc (“Pharmasset Georgia”), but Pharmasset Limited (“Pharmasset Barbados”) was the applicant for the Pharmasset PCT.  The argument on priority was whether at the date of filing of the Pharmasset PCT, Pharmasset Barbados was Mr Clark’s successor in title.      

Gilead had contended that Pharmasset Barbados was Mr Clark’s successor in title by one of three routes: (1) Mr Clark’s rights to the invention vested in Pharmasset Georgia under the terms of his contract of employment (“the Clark Agreement”).  All such rights were assigned to Pharmasset Barbados by an agreement between Pharmasset Barbados and Pharmasset Georgia (the “R&D Agreement”) which was itself governed by the law of Georgia (“Route 1”); (2) if the R&D Agreement was not effective to transfer legal title to the invention, it was nevertheless effective to transfer the entire beneficial interest in the invention to Pharmasset Barbados (“Route 2”), and that was sufficient for priority purposes and (3) all of Mr Clark’s rights in the invention were assigned directly to Pharmasset Barbados as Pharmasset Georgia’s designee under clause 6.2 of the Clark Agreement (“Route 3”). Route 3 was not elaborated on during oral argument and was not considered further.

Assignment

Kitchin LJ held that Arnold J was right to hold that the language of the R&D Agreement amounted to an immediate assignment of future rights under US Federal patent law, not an agreement to assign those rights.  The R&D Agreement stated that Pharmasset Barbados shall at all times, during or after the term of this Agreement, be the sole owner of all rights relating to or emanating from Intellectual Property, … Improvements, or other matters developed in, or relating to, a Project” (emphasis added).

A further issue in relation to the R&D Agreement was whether it was ever signed. This raised a point of state law, namely whether it was necessary for Pharmasset Georgia to sign the agreement in order to transfer legal title to the invention.  Arnold J held that on the balance of probabilities the R&D Agreement had been signed.  He based this finding on the evidence that the documents were prepared for signature in May 2000, the evidence of a relevant party that he had seen the signed agreement, and other inherent possibilities such as it being unlikely that following an audit request from PWC the agreement would not have been signed.  The Court of Appeal, however, was concerned about this aspect of the case, particularly that the Judge failed to appreciate the significance of evidence that could have been adduced by Gilead but wasn’t.  Kitchin LJ was inclined to find that Gilead had failed to make out its case on signature of the R&D Agreement but declined to decide the point.

Beneficial title

Arnold J found that even if Pharmasset Barbados was the beneficial rather than legal owner of the invention at the date of filing the PCT Application, then this was sufficient to make it the successor in title for the purpose of claiming priority.  Kitchin LJ expressed provisional agreement with Arnold J that it was national law requirements, rather than the Paris Convention that determined the transfer of title to an invention.  However, as it was not necessary to express a final view on the issue and the Court of Appeal was concerned that not all relevant materials and decisions had been drawn to its attention, it declined to do so in this case. 

This update was prepared by HGF Partner Rachel Fetches and IP Solicitor Liz Cooper, who both work in our London Office.  If you would like further advice on this or any other matter please contact Rachel or your usual HGF representative or visit our Contact page to get in touch with your nearest HGF office.