Isis Pharmaceuticals this month took issue with Santaris Pharma's latest attempt to use a safe harbor provision in US law to fend off patent infringement charges in the companies' ongoing legal war, arguing in a court filing that the legal protection only covers the development of specific drug candidates and not platform technologies.
"Santaris unlawfully … [sold] Isis' platform technology for use as a tool in drug discovery that had not commenced," Isis said in the filing. Further, Santaris' argument that its activities are protected because they may lead to "some future regulatory submission" overreaches the law, turning "safe harbor into a safe ocean subject to abuse."
A court ruling in Santaris' favor, Isis added, would turn "research tool patent rights into unenforceable pieces of paper." As such, Isis requested that a Santaris request for dismissal of the case be denied and that the suit proceed to trial.
The dispute began in 2011 when Isis sued Santaris for infringing two of its US patents by providing antisense drug candidates and drug discovery services to five pharmaceutical partners: Enzon, GlaxoSmithKline, Wyeth (now a part of Pfizer), Shire, and Pfizer.
The first patent is No. 6,326,199, entitled “Gapped 2' Modified Oligonucleotides” and claims oligos and macromolecules that have increased nuclease resistance, substituent groups for increasing binding affinity to complementary strands, and sub-sequences of 2'-deoxy-erythro-pentofuranosyl nucleotides that activate RNase H enzyme. The patent expired in 2011.
The second, No. 6,066,500, is entitled “Antisense Modulation of Beta Catenin Expression” and claims the use of antisense compounds “targeted to nucleic acids encoding beta catenin,” as well as methods of using these agents to treat diseases associated with the protein.
To fend off the lawsuit, Santaris in 2012 asked the court to find that its allegedly infringing activities were protected by a legal statute known as 35 U.S.C. 271 (e)(1), which allows companies to “make, use, offer to sell, or sell ... a patented invention … solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.”
The safe harbor of 35 U.S.C. 271 (e)(1) was established in the landmark 2005 US Supreme Court ruling in a case between Merck KGaA and Integra Life Sciences.
However, the court denied Santaris' bid, stating that the company supported its request for dismissal solely on the testimony of its CSO Henrik Orum, which fell short of the “evidentiary burden placed on an accused infringer claiming exemption from infringement” under 35 U.S.C. 271 (e)(1).
In December Santaris again petitioned the court for a ruling that it was protected by the safe harbor provision, including specific details about the corporate arrangements at issue to highlight their focus on generating FDA-approved drugs, although much of the information was redacted.
Each of the allegedly infringing collaborations, Santaris said at the time, contemplated that the pharmaceutical partner would "select specific RNA targets that were each related to a human disease," and that for each target, Santaris would design in its native Denmark a library of antisense compounds directed to it. Because further work on the molecules was to be conducted by Santaris' partners in order to develop them into potential drugs, the safe harbor provision should apply, the company told the court.
But this month, Isis charged that Santaris' reading of 35 U.S.C. 271 (e)(1) overstepped the boundaries of the legal provision.
At the time Santaris signed its deals with its partners, "the structure of any Santaris compound for any target was not known, and remained to be 'discovered' through basic research," Isis argued. "Santaris at the time of sale did not sell 'specific drug candidates itself,' but was selling patented platform technology before 'basic scientific research' commenced."
This, Isis stated, "contrasts sharply" with the Supreme Court's ruling in Merck v. Integra, which protects activities performed in the "subsequent drug-development state for a few investigational lead drug candidates." Nowhere in that ruling does "stating a goal of some future regulatory submission equate with automatic safe harbor protection."
Citing the Merck v. Integra case directly, Isis said that safe harbor applies when a party could have reasonably “recognized” the “particular biological process” and “particular physiological effect” of a promising candidate drug, adding that that case centered on three compounds under development at the time.
No potential drug compound had been discovered at the time Santaris inked its deals, Isis noted.
"In addition, the experiments themselves must be of the type that contribute 'relatively directly' to the generation of data for 'the processes by which FDA would decide to approve the product in question,'" Isis added, quoting from jury instruction in the Merck v. Integra litigation.
"Early-stage screening of multiple libraries of compounds fails this FDA process requirement," Isis said.