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Court Denies Santaris Bid to End Isis Patent-Infringement Case

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A US District Court last week declined to dismiss a patent-infringement suit filed against Santaris Pharma by Isis Pharmaceuticals after it rejected the defendant's claim that its allegedly infringing activities were protected by a safe harbor provision in the law.

The legal dispute began roughly one year ago when Isis filed suit in the US District Court for the Southern District of California, charging Santaris for infringing patents related to its gapmer technology (GSN 9/29/2011).

The first, No. 6,326,199, is 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 last year.

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.

Isis specifically claimed Santaris uses locked nucleic acid-containing gapmer antisense compounds in cell assays to help identify "potential gene targets and/or to screen the ability of synthesized oligonucleotides to inhibit the production of a specific protein” covered under its intellectual property.

Isis also alleged that Santaris has “attempted to compete directly with [it] by advancing and selling LNA gapmer compounds for a specific mRNA target for which Isis has already invested research time and money as a viable therapeutic target.”

In its lawsuit, Isis cited Santaris' collaborations with Enzon Pharmaceuticals, Shire, Pfizer, and GlaxoSmithKline as situations in which the company has provided partners with gapmer LNAs in violation of the patents.

Earlier this year, Santaris asked the court to dismiss the suit, arguing that its activities are covered by a legal provision that 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” (GSN 2/2/2012).

Known as 35 U.S.C. 271 (e)(1), the provision was extended to the use of patented inventions that are “reasonably related to the development and submission of any information” to the US Food and Drug Administration in a landmark 2005 case between Merck and Integra Lifesciences.

Key to Santaris' argument was its contention that its “entire focus … is to design and develop LNA drug candidates that may be submitted to [the] FDA for regulatory approval.”

At the same time, Santaris claimed that it “only undertakes LNA antisense drug design efforts once there are data showing that modulation of the activity of the proposed target RNA molecules has potential therapeutic value.”

Last week, however, the court rejected this argument, noting that Santaris supported its motion solely with the declaration of its CSO Henrik Orum, who told the court that the company does not begin using the antisense technology at issue until “a therapeutic target has been identified by someone else, and Santaris is sufficiently satisfied that it may achieve a therapeutic effect against a human disease by modulating the identified target with ... antisense drugs.”

Orum's declaration, the court said last week, falls short of the “evidentiary burden placed on an accused infringer claiming exemption from infringement” under 35 U.S.C. 271 (e)(1).

In Merck v. Integra, the court reached its verdict after a “detailed review of the purpose of each of sixteen enumerated categories of accused experiments in light of 'extensive' trial testimony regarding 'how and why all of these experiments were performed,' the type of information generated by each experiment, and the type of information called for the by the specific FDA regulations at issue,” the court said.

This is in “stark contrast” to the record in the current case, it stated, and Orum's declaration only describes “in general terms a process that could fall within the safe harbor.

“But even taking as true everything in the Orum declaration, the court would decline to resolve Santaris’s claim to the safe harbor exemption without a more specific analysis of Santaris’s uses of the allegedly infringing compounds, methods, and processes,” it added.

The court also raised doubts about Santaris' claims that it only uses the patented technology once a therapeutic target has been identified, citing Isis' reference to a press release about one of the allegedly infringing deals between Santaris and Enzon, which stated that Enzon would make milestone payments “upon the successful identification of certain LNA targets.”

Isis also swayed the court with a sworn declaration by Orum during a US Patent and Trademark Office reexamination of a Santaris patent, in which he stated that “the majority of our collaborators have taken broad licenses to our proprietary LNA platform in order to discover, develop, and commercialize new LNA-based drugs against RNA targets associated with disease.”

For these reasons, the court said it denied Santaris' motion for summary judgment dismissing the suit.