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Does Sandoz have a double-patenting defense to Amgen’s Enbrel® patents?

Zachary Silbersher

In February 2016, Amgen brought suit against Sandoz in connection with its proposed biosimilar for Amgen’s Enbrel® blockbuster.  The case is on a relatively fast track, currently scheduled to go to trial later this year in April.  The case schedule provides that dispositive motions must be filed by the first week of February.  That date is approaching quickly, at which point we will learn more about the defenses on which Sandoz may wish to hang its hat.

We have previously wrote some of those potential defenses here, and we intend to write about the pending Coherus IPRs against Amgen’s two protein patents.  Sandoz’s invalidity defense that the two Enbrel® protein patents are obvious in view of the prior art is, most likely, Sandoz’s strongest tactic to overcoming Amgen’s patent wall to biosimilar entry.  Yet, some investors have inquired about whether Sandoz has a strong obviousness-type double-patenting invalidity defense for the ‘182 patent.

Enbrel is protected by several patents, but the two most important patents are the ‘182 and ‘522 patents.  Rather than being indication or method-of-use patents, these patents protect Enbrel®’s actual protein itself (entanercept).  Even better, the ‘182 and ‘522 patents will not expire until approximately 2028/2029.  Amgen thus stands to gain another 10 to 12 years of monopolistic pricing for Enbrel®.  While it is unusual for compound or protein patents to be the last-expiring patents within a portfolio covering a pharmaceutical drug, in this instance, as we previously wrote here, Amgen potentially profited from a change in the law in 1995.  That change, combined with the fact that the patents lingered within the patent office for close to 15 years, means that Amgen gained a potentially huge windfall for its Enbrel® patent estate.  If the patents do last until 2028/2029, the expiration dates for those patents will be nearly 40 years from their priority date.  For a drug generating approximately $5B annually, that is very material.

The ‘182 patent is directed to a fusion protein, which fuses a fragment of the TNF receptor to the human immunoglobin G antibody (IgG).  More specifically, Enbrel® (entanercept) constitutes a soluble fragment of the 75 kilodalton human tissue TNF receptor that is fused to the hinge, CH2-CH3 region of the heavy chain of IgG. 

The ‘182 patent is itself a divisional of a parent patent, U.S. Patent 5,610,279, which itself is a continuation of U.S. Patent Application No. 07/580013, which was abandoned.  The ‘182 patent was filed in 1995, the ‘279 patent was filed in 1993, and the ‘013 application was filed in 1990.  Yet, the ‘279 patent expired in 2014.  Thus, if there is an obviousness-type double patenting defense between the ‘182 and the ‘279 patents, then that could potentially remove the ‘182 patent (and even potentially the ‘522 patent) from Amgen’s arsenal.

There are many similarities between the ‘279 and ‘182 patents.  Both the ‘279 and ‘182 patents are directed to fusion proteins.  Both combine a fragment TNF receptor to all the domains of the constant region of IgG other than the first domain (i.e., CH2 and CH3).  (More simply, both combine TNFR to the hinge of IgG.)  On its face, there is a strong defense of obviousness-type double patenting. 

There are, however, differences.  The claims of the ‘279 patent are directed to a TNFR fragment with molecular weight 55 kiladaltons, whereas the ‘182 patent claims are directed to a TNFR fragment with 75 kiladaltons.  Is this a patentable distinction?  One data point is that, during prosecution of both the ‘182 and ‘522 patents, in response to restriction requirements, the Applicants argued that the 55 kiladalton and 75 kiladalton embodiments are not distinct inventions, and thus, should be examined together.  On the other hand, the patent office viewed them to be patentably distinct embodiments. 

Another difference is that the claims of the ‘182 patent include limitations that are not required by the claims of the ‘279 patent.  The claims of the ‘182 patent specifically require that the TNFR fragment includes a unique amino acid sequence (SEQ ID NO: 10).  It is most likely beyond dispute that the 55 kiladalton TNFR fragment does not include this unique sequence. 

We will likely get a first glimpse at whether Sandoz considers this a viable defense to the extent it moves for summary judgement on it.  If anything, experts will need to weigh in on whether these differences are obvious variants, i.e., whether one molecular weight fragment is an obvious variant of the other, or whether including SEQ ID NO: 10 for the 75 kiladalton embodiment is a patentable distinction between the two patents.