After Hep C Patent Battle, Gilead Faces ViiV Suit Over Its New HIV Drug

Complaint says similarities between Gilead's Biktarvy and ViiV's dolutegravir suggest Gilead copied ViiV's drug.

Gilead Sciences Inc. is once again in the middle of a high stakes patent brawl as ViiV Healthcare claims Gilead's new HIV combination therapy Biktarvy (BIC/TAF) is insubstantially different from ViiV's dolutegravir.

ViiV filed a patent infringement suit against Gilead in the US District Court for the District of Delaware on Feb. 7, the day FDA approved Biktarvy. (Also see "Gilead's Biktarvy Approval Heightens HIV Competition With ViiV" - Scrip, 7 Feb, 2018.)

Biktarvy, a daily fixed-dose combination, consists of the novel integrase inhibitor bictegravir, the second-generation nucleotide reverse transcriptase inhibitor TAF (tenofovir alafenamide) and the older nucleoside reverse transcriptase inhibitor emtricitabine. The combo will be a direct competitor to ViiV's Triumeq, which consists of the integrase inhibitor dolutegravir (ViiV's Tivicay), the reverse transcriptase inhibitor abacavir and the nucleoside analogue reverse transcriptase inhibitor lamivudine.

ViiV, which specializes in HIV/AIDS treatments, was formed by GlaxoSmithKline and Pfizer Inc. in 2009 and Shionogi & Co. Ltd. joined the partnership in 2012. The complaint says that in 2001, teams of scientists at GSK and Shionogi began collaborating on a project to develop new and improved integrase strand transfer inhibitors (INSTIs). It says the team identified a novel structural scaffold that presented a foundation for developing a new generation of INSTIs, including dolutegravir.

The GSK and Shionogi team obtained patent No. 8,129,385 covering dolutegravir and other compounds that include dolutegravir's chemical scaffold in March 2012.

The complaint claims that Gilead relied on the dolutegravir (DTG) work performed by GSK and Shionogi in developing Biktarvy (BIC).

"The similarities between BIC and DTG suggest Gilead copied DTG," the complaint asserts. It says BIC has the same molecular scaffold as DTG and claimed in the '385 patent and "is not substantially structurally different" from DTG.

Gilead rejected ViiV's claims. "We remain steadfast in our opinion that Biktarvy does not infringe ViiV's U.S. patent," the company said in a statement. "ViiV's challenge does not impact our ability to make Biktarvy available to patients in the U.S."

Dolutegravir is a blockbuster product. GSK noted in its quarterly earnings call Feb. 7 that the Tivicay/Triumeq franchise generated £3.89bn (more than $5.3bn) in revenue in 2017.

A Similar Battle With Merck

Gilead went through a similar high stakes patent fight with Merck & Co. Inc. over its hepatitis C drugs Sovaldi (sofosbuvir) and Harvoni (ledipasvir/sofosbuvir). Idenix Pharmaceuticals (now Merck) filed a patent infringement suit against Gilead in 2013. Merck claimed that Gilead's predecessor, Pharmasset, failed to develop an active anti-HCV compound until it reviewed Merck's applications.

In December 2016, a Delaware jury found Gilead willfully infringed the patent and awarded Merck $2.45bn in damages. (Also see "Will $2.5Bn Jury Verdict Against Gilead Stand? Future Royalties, Willful Infringement Penalty Uncertain" - Pink Sheet, 16 Dec, 2016.)

Gilead noted in a quarterly SEC filing that the parties filed post-trial motions and briefings, and once the judge rules on them the case will move to the US Court of Appeals for the Federal Circuit.

Gilead said if the jury verdict is upheld on appeal, its estimated potential loss as of Sept. 30, 2017 would include the $2.54bn jury award, which represents 10% of its adjusted revenues from sofosbuvir-containing products from launch through August 2016; approximately $269m, which represents 10% of adjusted revenue from the products from September 2016 through Jan. 25, 2017; pre- and post-judgment interest; and approximately $539m in going forward royalties yet to be assessed by the court.

In a separate case, Gilead filed suit against Merck seeking a declaratory judgement that it does not infringe two other patents. A California jury found Merck's patents are valid and awarded Merck damages of $200m but a judge subsequently found that Merck engaged in misconduct and vanquished the award. (Also see "Brand vs. Brand Patent Battles Heat Up, Focus On Big Drug Classes" - Pink Sheet, 4 Jan, 2017.)

Gilead appealed the invalidity verdict, and Merck appealed the nullification of the verdict. The Federal Circuit heard oral arguments Feb. 5.

A Bridged Ring Too Far?

GSK may have a tougher time making its case. Evercore ISI analyst Umer Raffat said in a Feb. 8 note that after digging into GSK's patent he doesn't think GSK will be successful in its suit against Gilead.

"At the most basic level, as much as there is remarkable structural similarity between GILD's bictegravir vs GSK's dolutegravir, GILD's chemical structure does NOT include a bridged ring – and that's the crux of this case. As a result, we are not worried about this from GLD perspective," Raffat stated.

ViiV's complaint says that the novel structural scaffold of dolutegravir includes a rigid planar three-ring metal chelating region with an oxygen triad and no bulky side chain, to facilitate binding and protect critical moieties.

ViiV says that unlike the first generation INSTIs raltegravir (Merck's Isentress) and elvitegravir (Gilead's Stribild and Vitekta), dolutegravir remains active against a wide variety of mutant strains of the HIV virus and can be administered once daily without a booster.

The complaint says ViiV disclosed dolutegravir's chemical structure to the public at a medical conference in February 2010. It says Gilead was at the conference and presented data on its investigational fixed-dose Quad regimen. The complaint states that Gilead first synthesized Biktarvy after the chemical structure of dolutegravir was publicly disclosed and the '385 patent issued.

In addition to claiming that Biktarvy has the same chemical structure as dolutegravir, the suit says Gilead's reported clinical data for Biktarvy show insubstantial differences from the clinical data reported by ViiV for dolutegravir and that the resistance profile for clinically observed mutations of Biktarvy is "insubstantially different" from that of dolutegravir.

The complaint asserts that Gilead's infringement of the '385 patent was "deliberate, malicious, consciously wrongful, egregious, and/or in bad faith rendering this case exceptional" and permitting ViiV to seek enhanced damages and attorney fees.

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