Amgen Inc. asserted at an analyst meeting in April that it would be able to block biosimilars of Enbrel (etanercept) after a manufacturing patent expired in October 2012. But no one knew it had a crucial patent application pending in the Patent and Trademark Office that could provide 17 years of additional patent protection.

The company’s announcement that the patent had issued on Nov. 22, 11 years after the application was filed, stunned those following the biosimilars field.

The patent may derail the commercialization plans of Merck & Co. Inc. and others who are developing biosimilar versions of the rheumatoid arthritis and psoriasis blockbuster. They now will have to litigate the validity of the patent and could be kept off the market until November 2028 or longer if the patent qualifies for patent-term extension.

The development indicates the risk biosimilar sponsors face from submarine patents that emerge from the patent office years after filing. The risk pertains only to patents filed prior to June 8, 1995 when the patent law was revised so that patent term runs 20 years from the date of the earliest filed application. For applications filed before the revision the patent term is 17 years from the date the patent issues. The Enbrel patent was filed a month before the law changed.

Biosimilar sponsors could see other pre-1995 patents pop up. Michael Siekman, a partner at Wolf, Greenfield & Sacks, said the patent office noted last year that there were about 600 such applications pending. In most instances, he said, companies can figure out that such a pre-1995 application is pending based on the prosecution history of the family of patents. But they will not know the claims of the patent to determine how broad it is.

The change in patent term resulted from the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) negotiated during the Uruguay Round of the General Agreement on Tariffs and Trade. The GATT rules also required applicants to publish the full specification of applications 18 months after filing; applications had not been published before this.

Patent Unlikely To Be Invalidated, Analyst Says

Merck declined to discuss Amgen’s new patent. But others noted its potentially devastating impact for those pursuing Enbrel biosimilars.

“This is huge,” a lawyer who has followed biosimilars for many years said (“Hopes Dashed For Biosimilar Enbrel? The IN VIVO Blog, Nov. 23, 2011).

Sanford C. Bernstein analyst Geoffrey Porges said in a note that the patent would likely block biosimilars for 17 years.

“While nothing is absolute in drug patents, this patent must increase the probability at least that Amgen prevails in keeping biosimilar versions of Enbrel out of the U.S. market through the duration of its exclusivity,” he wrote.

Although the patent is certainly likely to be challenged, he said that “given its specificity, and the clear utility of the fusion protein invention, it is hard to imagine it being completely invalidated or overruled in litigation.”

Amgen also expects the patent will prevent biosimilars from launching. “We don’t envision Enbrel biosimilar competition in the foreseeable future,” a company spokesperson said. “One could rightfully assume” that Enbrel has 17 years of additional patent protection.

Enbrel is one of Amgen’s top products with revenue of $3.5 billion in 2010. Amgen co-promotes the drug with Pfizer Inc. in the U.S. and Canada and pays Pfizer a percentage of its annual gross profits on Enbrel sales. Pfizer has marketing rights to the drug outside North America.

Several companies have been pursuing a biosimilar version of Enbrel. It is among the second wave of biosimilars under development. More complex than the first entrants, they comprise the largest and fastest-growing segment of the global $110 billion biologics market Also see "And Now For The Real Biosimilar Opportunity: Antibodies And Complex Biologics" - Pink Sheet, 27 June, 2011..

Merck had been developing its own biosimilar version of Enbrel but forged ahead when it acquired rights to Hanwah Chemical Corp.’s late stage biosimilar in June Also see "Merck Lands Late-Stage Enbrel Biosimilar In Deal With South Korea's Hanwha" - Pink Sheet, 13 June, 2011..

Amgen Had Long Struggle At Patent Office

Enbrel is a soluble form of a fully human tumor necrosis factor receptor. The new patent, No. 8,063,182, covers unique elements of the specific TNF receptor fusion protein plus the TNF receptor. Amgen said it had a composition of matter patent that was related to the TNF receptor alone which has expired.

Roche filed the ‘182 patent application in May 1995. Immunex Corp. (acquired by Amgen in 2002) licensed it from Roche in 1999 and Amgen obtained an exclusive license in 2004. Amgen did not mention the pending application in its 10-K filing for 2010; it cited a process patent that is to expire on Oct. 23, 2012 and an aqueous formulation patent that is to expire in 2023.

The PTO rejected the’182 patent application in 2007, finding that the patent claims failed to provide a written description of the invention and were obvious over the prior art. The PTO’s Board of Patent Appeals and Interferences reversed the decision in November 2010 and prosecution of the patent was reopened.

At a business review meeting in April, Amgen President and Chief Operating Officer Robert Bradway noted that the company also has a series of manufacturing process patents that expire from 2019 to 2025. “So when we look at the entirety of the Enbrel patent estate, we believe that we will enjoy IP protection well beyond 2012,” he said.

Credit Suisse analyst Ravi Mehrotra pressed the company for more detail on which patents would provide its main defense. “We’re probably not going to tip our hat on strategy,” responded Amgen CEO Kevin Sharer. Amgen executives insisted, however, that there would be no biosimilars of Enbrel Also see "Will A Dividend Keep Investors Happy As Amgen Waits For Its Pipeline To Pan Out?" - Pink Sheet, 21 April, 2011..

Unknown Patent Applications Could Be Factor For Future Biosimilars

Patrick Waller, a partner at Wolf, Greenfield & Sacks, said the Enbrel patent may make a biosimilar company sit up and take greater notice that there may be pending applications. “This just may highlight the risk more painfully,” he stated.

Waller noted that many companies filed continuation and divisional applications prior to the GATT rules in order to have something pending at the patent office. But he said that only in rare circumstances are they sitting at the PTO this long.

There have been several other cases of pre-GATT biopharma patents emerging from the patent office.

Cowan & Company analyst Eric Schmidt said this is the third time he’s seen a patent come out of nowhere. Last year Biogen Inc. asserted an Avonex (interferon beta-1a) patent that issued in 2009 after a 27-year pendency in the patent office.

Biogen then filed suit against Bayer HealthCare Pharmaceuticals Inc., Pfizer Inc., EMD Serono Inc. and Novartis Pharmaceuticals Corp. claiming their multiple sclerosis drugs infringed the patent ([A#00720230016]).

And in the late 1990s Amgen obtained several erythropoietin patents that were based on a patent application filed in 1984 and sued Transkaryotic Therapies Inc. for infringement.

Genentech Inc.also filed a continuation application for its Cabilly III patent in 1995 before the GATT rule went into effect. The patent covers recombinant techniques for manufacturing antibody therapeutics. Earlier this year, Genentech filed suit against Human Genome Sciences Inc.and GlaxoSmithKline PLCAlso see "The Cabilly Saga: New Patent, New Product, New Lawsuits" - Pink Sheet, 18 April, 2011. claiming infringement of the patent.

Amgen’s Stealth Enbrel Patent May Block Biosimilars; Scenario May Apply To Other Biologics

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