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Does Uniqure or Spark Therapeutics own the key patents covering FIX-Padua for hemophilia B?

Zachary Silbersher

Uniqure ($QURE) and Spark Therapeutics ($ONCE) are squaring off over who will soon provide the best haemophilia B gene therapy.  Uniqure’s stock recently received a boost from positive data from a phase IIb trial.  Uniqure’s AMT-061 and Spark’s fidanacogene elaparvovec each remain in clinical trials, while the companies jockey for who will reach the market first, and who will be best in class.  Meanwhile, the companies have acknowledged that intellectual property issues may be critical to which drug will come out on top.  Will the patent issues cloud either drug’s commercial performance?

Spark, which has partnered with Pfizer ($PFE) for its factor IX drug, recently stated that the intellectual property issues surrounding the drugs appear to be “somewhat confused.”  The confusion appears to stem from the fact that both drugs utilize the Padua-variant of Factor IX (FIX-Padua), and both appear to have some claims on the intellectual property rights to use it. 

Uniqure has stated that the Padua-variant of Factor IX is “patent-protected.”  Uniqure’s prior gene therapy candidate, AMT-060, previously used the wild-type FIX variant.  That variant, however, lacked sufficient efficacy, which forced Uniqure to switch to the Padua-variant.  To do so, Uniqure announced that it acquired patents that provided protection for the FIX-Padua variant.  The patents were acquired from Paolo Simioni, a hemophilia expert from the University of Padua, Italy.  Among related EU patents and applications, Uniqure acquired U.S. Patent No. 9,249,405.  The assignment of the ‘405 patent to Uniqure has been publicly recorded with the Patent Office.

 Meanwhile, Spark appears to have licensed considerable intellectual property that may potentially cover its hemophilia products.  This includes several patents from the Children’s Hospital of Pennsylvania that relate to different aspects of FIX, such as a patent application for “modified AAV vectors for delivery of factor IX”; a patent relating to “an adjunct therapy to reduce inhibitory antibodies against factor IX administered via gene therapy”; a patent application related to “certain modifications to a FIX gene that enhances secretion of factor IX”; and an application relating to “modified factor IX expression cassettes.”  

Several questions remain, such as, who owns the patent covering the FIX-Padua variant, and can that patent be used to block out its competitor’s drug completely from the market?  On the first question, Uniqure has claimed that its ‘405 patent “broadly covers a hyperactive variant of Factor IX carrying an R338L mutation (often referred to as ‘FIX-Padua’) and its use in gene therapy for the treatment of coagulopathies, including hemophilia B.”  The ‘405 patent itself claims “a modified recombinant FIX (factor IX) polypeptide comprising at least 70% identity to SEQ ID NO: 2 and a leucine in position 338 of SEQ ID NO: 2.” 

Meanwhile, Spark appears to have built up an arsenal of patents that may not necessarily cover the Factor IX variant itself, or as well as the Simioni patent, but may nevertheless cover tangential aspects of FIX gene therapy that Uniqure may stumble upon.  The strength of Spark’s licensed patents will depend upon how integral they are to developing a gene therapy for hemophilia B.  They may not cover Factor IX itself, but may nevertheless cover core technologies that Uniqure’s AMT-061 cannot design around.

Overall, the patent landscape opens up a number of different scenarios.  Technically, both companies may infringe one or more of each other’s patents—thus, creating a scenario where both are entitled to an injunction (or royalties) to each other’s product.  Rather than depriving the public of any gene therapy for hemophilia B, this would more likely sooner result in some sort of cross-license that essentially eviscerates the patent issue.  They key factor in that scenario will be who has the leverage to demand a royalty from the other.

Alternatively, both companies may be able to design around each other’s patents, thus effectively eviscerating any uncertainty regarding patent issues.  This could nevertheless require considerable litigation to untangle and resolve.  That could mean several years before any certainty over the patent issues is reached. 

At a high level, Uniqure’s ‘405 patent appears to be the relative strongest threat, since it purports to cover a key ingredient in Spark’s proposed therapy.  However, several questions remain regarding the strength of this patent.  The first one is the breadth of its coverage.  As discussed above, the ‘405 patent itself claims “a modified recombinant FIX (factor IX) polypeptide comprising at least 70% identity to SEQ ID NO: 2 and a leucine in position 338 of SEQ ID NO: 2.”  There is clearly room here for Spark’s fidanacogene elaparvovec to have designed around.  That is essentially a technical question, which we have not investigated, but would be the first question that needs to be addressed to adequately handicap the relative threat to Spark’s drug by Uniqure’s patents. 

Another question relates to the validity of the ‘405 patent.  Simioni has described his FIX invention as “naturally occurring.”  Because of this, Spark has questioned whether the patent is valid, and whether a naturally-occurring mutation can be patent-protected.  That question is warranted.  Patents covering naturally-occurring phenomena may not comprise “patent eligible” subject matter under Section 101 of the Patent Statute.  The line between eligible and ineligible subject matter for patents within the pharmaceutical space remains a dicey and fine one, which continues to be debated at the Federal Circuit, as illustrated by a recent decision (Vanda Pharmaceuticals, Inc. v. West-Ward Pharmaceuticals.).  A more thorough analysis of this issue is required to adequately assess the strength of Uniqure’s patent position.

The intellectual-property situation between Unique’s and Spark’s pending hemophilia B drugs remains uncertain.  But the company with the right patents may eventually tackle the market, even if not first to market and not best in class.  If either of these drugs is a commercial success, expect considerable patent challenges ahead.