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Amgen asks the full Federal Circuit to reconsider its PCSK9 loss

Zachary Silbersher

Earlier this year, in October, the Federal Circuit vacated Amgen’s hard-earned injunction against Praluent®, the only other PCSK9 drug competing with its own, Repatha®.  The case has been remanded to the District Court of Delaware for a new trial on the validity of Amgen’s patents.  Before that could happen, however, earlier this week Amgen petitioned the Federal Circuit for en banc review of its October 5, 2017 decision that cut against Amgen. 

At the outset, it is not surprising that Amgen has petitioned for en banc review.  Any en banc petition is always a wild-card, but this case justifies a petition for two reasons.  First, it squarely impacts the revenue of a drug that could yet become a blockbuster for Amgen.  Second, and perhaps more importantly, the Court’s October decision basically established much clearer guidelines for patenting antibodies.  As discussed in more detail here, the short of it is that lots of existing antibody patents procured by other biotech firms and relied upon in the course of investing in a new drug, may, as it turns out, be invalid.  Given the rising prevalence of biologics in comparison to small-molecule drugs, the Court may just deem it worthwhile to visit this question with the full weight of the entire Federal Circuit.

Amgen’s first argument is that the Federal Circuit has overturned precedent upholding that “newly characterized antigen” test.  The test has its roots in PTO training materials as well as the MPEP, and it has support in subsequent caselaw from the Federal Circuit.  Thus, the thrust of Amgen’s argument is that biotech firms have relied on the test in the course of investing in new antibodies and procuring patents to protect them from competition.  Yet, the Federal Circuit has now turned its back on biotech, and pulled the rug out from under them.  The test is fairly simple:  if you can adequately characterize a new antigen, then you can patent all antibodies that bind to that antigen.  Amgen argues that, in reliance on that test, that’s what it did.  So what happened to its injunction against Praluent?

That is a compelling story, but it may not necessarily hold up.  Before Amgen’s recent tassle with Regeneron, the Federal Circuit most recently discussed the “newly characterized antigen” test in 2011.  In doing so, the Court did not necessarily endorse the test, but rather questioned its propriety.  See Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011).  The Court stated that it is routine and conventional to produce antibodies for some antigens.  For instance, it may be routine to produce antibodies for a known protein “simply by injecting that protein into a host animal that is a different species . . . [and] [t]he host generates antibodies to the foreign protein.”  636 F.3d at 1351 n.4.  Yet, the Court noted the same may not be true for human antibodies, on both ethical as well as scientific grounds.  Thus, Amgen’s contention that the Court’s October decision has upset firmly rooted precedent on the “newly characterized antigen” test is not necessarily, itself, firmly rooted.

In its en banc petition, Amgen makes an interesting retort.  If the Federal Circuit’s rejection of the “newly characterized antigen” test is left to stand, then other biotech firms can theoretically take the guidance in Amgen’s patents, use that guidance to develop proteins that bind to the PCSK9 “sweet spot,” and then use those later-developed proteins against Amgen to invalidate its patents.  The current law, Amgen argues, creates a scenario where filing a patent could actually create more competition, rather than less.

Amgen’s identification of injustices is compelling from the perspective of patents.  Yet, the practical realities, at least of this case, do not necessarily support those injustices.  There is no strong suggestion that Regeneron and Sanofi took Amgen’s patents, and leveraged them to come up with their own protein.  Rather, its appears they developed their own protein, on their own, before Amgen’s patents were filed.  Further, the step between knowing the “sweet spot” on PCSK9 and developing a corresponding antibody that binds does not, in fact, appear to be a routine one. 

Indeed, that is precisely the point.  Had the Federal Circuit found that jumping from the PCSK9 antigen to a binding protein was itself routine and conventional, then it likely would not have vacated the injunction.  The Court stated, “But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies.”  (p. 17).  This is why the Court in Centocor suggested that the “newly characterized antigen” test probably only makes sense where going from the antigen to the antibody is, indeed, routine.

Amgen also claims that without genus claims, patent protection for antibodies may be worthless.  That may be true.  But Amgen’s follow on point, that no one would bother investing in antibodies, is questionable.  Indeed, the flip side of Amgen’s argument may also be true.  If broad antibody patents are allowed to stand, that might do more to discourage biotech investment, because no one will want to pour billions into a drug, only to be sandbagged with an injunction by broadly drafted patents.  Indeed, just as weak patent protection discourages investment, overly-rigorous patent protection ironically may do the same.  It is finding the right balance that, presumably, should matter.

Amgen’s second argument is that the Court reversed even more established law regarding the use of post-priority date evidence in assessing enablement and written description.  To briefly recap, Amgen’s patents do not describe their PCSK9 protein by what it is, i.e., the amino-acid sequence, but rather by what it does.  The patents essentially claim any protein that binds to specific residues of PCSK9.  By having purportedly characterized the “sweet spot” of the antigen, Amgen has essentially claimed a patent on any protein that binds in that sweet spot.  Yet, the patents themselves only described two purported examples of proteins that do so, even though Regeneron claimed millions could theoretically do so. 

During the trial, Regeneron asked the Court permission to show its own Praluent® protein to the jury.  It endeavored to demonstrate that its own protein was considerably different than the two representative example proteins disclosed in Amgen’s patents (there was purportedly only 26% overlap.)  The Court denied that request, and held that because Regeneron’s protein post-dated the priority date for Amgen’s patents, it must be excluded from evidence on the ground that a patent’s enablement and written description are typically assessed as of a patent’s filing (priority) date.

The Federal Circuit disagreed, and remanded to allow Regeneron to show their protein to the jury.  The Court reasoned that it is permissible to use post-priority date evidence to show that a patent’s disclosed species are not representative of a genus.  Amgen now declares this was an unwise reversal of long-established precedent.  On this point, Amgen is correct, in some regard.  The Federal Circuit has long recognized that enablement and written description are assessed as of a patent’s priority date, and post-filing evidence is typically barred from consideration. 

But there is a nuance to that rule that Amgen may be conveniently overlooking.  The Court ruled that post-priority date evidence is permitted to show that the disclosed species for a claimed genus are not representative of that genus.  If the evidence preceded the priority date, then it would anticipate the claims.  Put another way, as argued by Regeneron’s counsel during rebuttal oral argument on appeal, it makes sense that an inventor cannot come up with post-priority date evidence to show she was allegedly in possession of an invention as of the priority date.  But it does not necessarily make sense that a post-priority date evidence that falls within the scope of the claims, but nonetheless shows that the disclosed species are not representative of the claimed genus, is not relevant to enablement or written description.

At the heart of this matter is a simple, age-old question about, what is patent protection really for?  There are millions of antibodies that purportedly bind to the sweet spot of PCSK9.  Just knowing the sweet spot is not enough to routinely develop one of those antibodies.  Amgen discovered some of them.  But so did Regeneron.  Both companies spent billions of dollars to do so.  Should Amgen be allowed to corner the market on all antibodies that bind to that sweet spot, even though it only actually discovered two of them?  The consequences of that decision could clearly reverberate throughout the biotech industry.  The answer hangs in the balance of the Federal Circuit’s decision on Amgen’s en banc petition.