Delaware District Court Rules Idenix "Sofosbuvir" Patent invalid setting aside $2.54 billion damages award to Idenix

The summary takeaways from the order are -

Claim Constructions

·        "beta-D-2'-methyl-ribofuranosyl nucleoside": "a five member sugar ring with a methyl group in the 2' up position and non-hydrogen substituents at the 2' down and 3' down positions."

·        claim 1 's preamble ("A method for the treatment of a hepatitis C virus infection") and its "effective amount": the Court concluded that claim 1 's preamble is limiting and that the term "effective amount" means "an amount [of the ... ribofuranosyl nucleoside ... ] that is effective to treat HCV"

Combining these two limitations, the claims cover all those nucleosides, but only all those nucleosides, that meet the Structural Limitations - including a methyl group at the 2'-up position - and the Functional Limitations of exhibiting effective anti-HCV activity.

the claims as construed combine Structural Limitations that are satisfied by an enormous number of compounds with Functional Limitations that are satisfied by an unknown, but far smaller, number of undisclosed compounds.

Discussion of facts

-       Idenix contended “Targeting the NS5B polymerase” is the key to a compound demonstrating effectiveness in the treatment of HCV – which is not an explicit claim limitation

-       The court found that “The patent claims are not limited to compounds that are effective in treating HCV due to their acting on the NS5B polymerase. Nor does the patent specification even teach that to identify effective compounds a person of ordinary skill in the art ("POSA") must or even should be looking for compounds that target the NS5B polymerase. Instead, the patent explains that effective compounds can act through "inhibiting HCV polymerase, by inhibiting other enzymes needed in the replication cycle, or by other pathways."

-       the accused embodiment - 2' methyl up 2' fluoro down is not expressly disclosed in the '597 patent. While fluorine is disclosed as a candidate for the 2' up position, it is not disclosed as a candidate for the 2' down position. Notably, fluorine is a halogen, and other halogens are disclosed as candidates for the 2' down position, but, again, fluorine is not.

-       Even the inventor of the '597 patent, Dr. Michael Somadossi, testified that there is no disclosure of the 2' methyl up 2' fluoro down nucleoside in either the May 2000 provisional patent application or the May 2001 patent application.

-       In the Court's view, it is undisputed that the Structural Limitations of the claims are satisfied by billions of compounds. "the structural limitations in the claims encompass nucleosides with a methyl group in the 2' up position, any substituent other than hydrogen at the 2' and 3' down positions, any substituent at other substituent positions on the nucleoside, and any purine or pyrimidine base."

-       While 2’-methyl up was "key" to curing HCV, it was not sufficient, as not all 2'-methyl up compounds are effective against HCV - In other words, it is undisputed that something more (and something more specific) than just 2' methyl up is needed for a compound to be effective in treating HCV. Relatedly, it is undisputed that there are many "inoperable embodiments" that contain 2' methyl up, and otherwise satisfy the claims' Structural Limitations, but do not satisfy the claims' Functional Limitations.

-       not even all of the compounds expressly disclosed in the patent specification are effective to treat HCV. Therefore, it is undisputed that the specification is replete with embodiments that are not within the scope of the claims.

-       a great deal of time and effort (i) would have been required if a POSA wanted to synthesize every compound that met the Refined Structural Limitations of the claims; (ii) may also have been required to synthesize any particular compound that met the Refined Structural Limitations of the claims, including the embodiment that is now called sofosbuvir

-       Idenix's expert, Dr. Meier, acknowledged that not all compounds of interest were commercially available. (See Meier Tr. at 1855) Instead, they needed to be synthesized (before they could be screened for whether they meet the Functional Limitations of the claims)

-       Idenix's Dr. Gosselin agreed with the proposition that "you don't know whether or not a nucleoside will have activity against HCV until you make it and test it."

-       No witness contradicted Gilead's Dr. Secrist's opinion that "an average chemist could make only 2-3 nucleosides a month." A large percentage of the compounds a POSA would want to test were not readily available and needed to be synthesized before they could be studied.

-       synthesis of the embodiment, 2' methyl up 2' fluoro down, was neither routine nor simple but, instead, required extensive experimentation. This conclusion is most vividly demonstrated by the experience, and repeated failures, of Idenix's Dr. Jean-Francois Griffon. Only in March 2005 – two months after the publication of U.S. Patent Application No. 2005/0009737 (DX371), issued to Pharmasset's Jeremy Clark (more on him below), had been distributed at Idenix - did Idenix first succeed in making and testing 2'-methyl up 2'-fluoro down. In short, the undisputed record shows that, between 2002 and 2005, Idenix tried and failed to make and test a 2'-methyl up 2'-fluoro down nucleoside, and only succeeded when Dr. Griffon "us[ed] information from a published Pharmasset patent application."

-       Determining whether a compound meeting the structural limitations also satisfied the functional limitations required screening, which takes substantial time and effort. Dr·De Francesco, Idenix's virology expert, explained, screening is the way you actually cut down the number of compounds, by removing all inactive ones to a few interesting ones. Dr. De Francesco testified that, as of 2000, his lab [had] tested over 100,000 compounds in the HCV polymerase assay and, in only a three-month period in 2000, tested 18,000-20,000 compounds in the HCV replicon assay; such a testimony does not support a finding that screening was not required, nor does it support a finding that anything less than a great deal of screening would have been necessary in order to identify all of the compounds meeting the Refined Structural Limitations. and also satisfying the Functional Limitations.

-       Whether a compound satisfying the structural limitations would also meet the functional limitations could not be predicted nor "visualized". Idenix insisted “that screening was not required to discover active compounds meeting the claims' Functional Limitations.” but the court didn’t agree - Idenix's characterization of screening as merely "confirmatory" is in contravention of both of its experts' testimony and the patent itself.

-       The Court's conclusions are further supported by a comparison between this case and what the Federal Circuit confronted in Wyeth and Cordis Corp. v. Abbott Labs., 720 F.3d 1380 (Fed. Cir. 2013).- The patent at issue claimed methods that involved "administering an antirestenosis effective amount of rapamycin." Id. While the claim was to this genus, the patent disclosed "only one rapamycin species, called sirolimus." The term "rapamycin" was construed to include all compounds containing sirolimus's macrocyclic ring that had "immunosuppressive and antirestenotic effects." The District Court found that practice of the full scope of the claims required undue experimentation and granted summary judgment of invalidity for lack of enablement. Id. On Wyeth's appeal, the Federal Circuit affirmed. The Court observed that, even accepting Wyeth's representations regarding an implicit molecular weight limitation, there were still "at least tens of thousands of candidates" to screen; the specification was "silent about how to structurally modify sirolimus;" it would be necessary to "first synthesize and then screen each candidate" to determine effectiveness; and the record and specification offered no guidance as to which "particular substitutions" at substituent positions might be "prefe~able" or would preserve sirolimuS' effective properties

-       The parallels between Wyeth and the instant case are striking. More particularly, as in Wyeth, the evidence here is that "even minor alterations to the ... [candidate] molecule could impact its ... [treatment] properties." Wyeth, 720 F.3d at 1385. Further, as Idenix's expert, Dr. Gosselin,.testified, "you don't know whether or not a nucleoside will have activity against HCV until you make it and test it."

-       Still further supportfor the Court's conclusion is found in a comparison of the instant case to this Court's recent decisions in the Enzo cases.

-       As with the patent invalidated in Wyeth, Idenix's patent requires a "systematic screening process" to identify the full range of 2'-methyl ribonucleosides falling within the broad structriral and functional scope of the claims Idenix pursued.

-       Gilead met its burden to prove nonenablement by clear and convincing evidence. The trial revealed that there are no genuinely disputed material facts with respect to enablement. Accordingly, Gilead is entitled to judgment as a matter of law that the asserted claims of the '5 97 patent are invalid due to lack of enablement.

Copy of opinon received from https://delawareintellectualproperty.foxrothschild.com/wp-content/uploads/sites/17/2018/02/Gilead-Sciences-Opinion-Feb-16-2018.pdf