Sandoz’s aBLA for HUMIRA® has been accepted by FDA -- what happens next?

Zachary Silbersher

Sandoz, the generic arm of Novartis, has announced that its abbreviated Biologic License Application (aBLA) for a Humira® biosimilar has been accepted by FDA.  Sandoz’s proposed biosimilar is the third aBLA filed for Humira®, behind Amgen’s Amjevita, approved in September 2016, and Boehringer-Ingelheim’s Cyletzo, approved in August 2017.  Following Amgen’s aBLA, AbbVie brought suit against Amgen under the Biologics Price Competition and Innovation Act (BPCIA) for alleged infringement of 10 patents covering Humira®.  The case settled in late September 2017, with Amgen agreeing to delay entry of its biosimilar until early 2023.  Meanwhile, Amgen brought suit against Boehringer-Ingelheim in August 2017, and the suit remains pending.  (The suit will be the subject of a future post.)

Now that Sandoz’s aBLA has been accepted for review by FDA, what happens next on the patent front?  Acceptance of an aBLA by FDA triggers a series of potential exchanges under the BPCIA, informally known as the “patent dance.”  The first step in those exchanges is for the biosimilar applicant (Sandoz, in this case) to provide to the sponsor (AbbVie) with its confidential aBLA application as well as information describing the manufacturing process for its proposed biosimilar.

Will Sandoz engage in the patent dance with AbbVie?  Sandoz has filed two prior biosimilar applications, including one for Neupogen® and another for Enbrel®.  The Neupogen biosmilar application led to one of the first biosimilar cases under the BPCIA.  Sandoz refused to engage in the patent dance in that case, and the case went up to the Supreme Court, which confirmed that the patent dance is optional under the statute.  In other words, the biosimilar applicant is not obliged to disclose its aBLA or manufacturing process in advance of litigation.  In that case, the only remedy available to the sponsor is to commence immediate litigation for patent infringement. 

In its second case involving Enbrel®, Sandoz appears to have disclosed limited information about its aBLA and manufacturing process, but did not fully engage in the patent dance.  Instead, Sandoz essentially asked Amgen to sue on its patents as soon as possible.  Thus, if the past is any guide, Sandoz is unlikely to seriously engage in the patent dance with AbbVie.  And it can take more comfort that avoiding the patent dance is not a violation of the BPCIA given the Supreme Court’s precedent earlier this year. 

Yet, Humira® is different from Enbrel® in one important respect.  Enbrel® was only covered by a small number of patents (approximately six or eight patents.)  By contrast, AbbVie continues to maintain that it has over 100 patents covering Humira®.  In its recent case against Boehringer-Ingelheim, during the patent dance, AbbVie threw down upwards of 74 patents as potentially infringed by BI’s proposed biosimiar. 

If Sandoz fails to engage in the patent dance, that will yield two consequences.  First, any patent litigation will be commenced rather quickly.  Rather than seven to nine months for the patent dance to play out, AbbVie may be forced to commence suit much earlier, perhaps within one or two months.  The timing will depend on what, if anything, Sandoz chooses to disclose. 

Second, if Sandoz does not disclose its aBLA or manufacturing process, then AbbVie will effectively have to sue blind.  In other words, without actually seeing Sandoz’s proposed biosimilar, AbbVie cannot assess in advance which patents are likely infringed.  It remains to be seen how AbbVie will handle this.  But most likely, it will simply commence suit and assert all of its patents, or anywhere between 75 and 100 patents.  After the case is commenced, the Judge will likely lean on Sandoz to immediately produce its aBLA and manufacturing process, while also leaning on AbbVie to widdle down its asserted patents to a reasonable number after reviewing that information.  That, in effect, will constitute a modified version of the “patent dance,” but only after the case commenced, rather than before.  Indeed, now that the Supreme Court has blessed the tactic of avoiding the patent dance altogether, AbbVie’s upcoming case against Sandoze may create a template for how court’s manage an unwieldy assertion of patents when the biosimilar refrains from the patent dance.

Admittedly, the intention behind the “patent dance” was purported efficiency.  The biosimilar applicant is supposed to disclose its confidential aBLA and manufacturing process before litigation so that the sponsor could see the product, and determine in advance the most suitable patents on which to bring suit.  However, the “patent dance” can take upwards of seven to nine months.  For some biosimilar applicants, time is money, and getting into litigation quickly is preferred.  If Sandoz can get the case going faster, without getting bogged down in the “patent dance,” that could, in theory, be a tactical success.  Future biosimilar applicants may follow suit.

Meanwhile, Sandoz has already been pre-emptively attacking AbbVie’s patents.  Over the past several months, Sandoz has been quietly filing petitions for inter partes review (IPRs) against patents covering Humira®.  By our count, since July 2017, Sandoz has filed eight IPRs against eight different Humira® patents.  Presumably, the patents that Sandoz is attacking represent those that Sandoz likely had the most difficulty designing around.  Indeed, as we previously discussed a few years ago in our preliminary Humira® report, a biosimilar applicant is likely to face numerous patents owned by the sponsor that will be difficult to design around.  This is because the biosimilar applicant is obliged to copy many aspects of the sponsor’s drug, such as route of administration, dosage form and strength.  If those aspects of the drug are covered by patents, then designing around them will inevitably prove difficult.

So, which patents did Sandoz attack with IPRs?  Among its eight IPRs, seven of the IPRs attack patents covering major indications for Humira®.  For instance, Sandoz attacked patents that use the Humira® protein to treat ulcerative colitis, plaque psoriasis, Crohn’s disease, inflammatory bowel disease, and psoriatic arthritis.  These are admittedly very hard to design around.  Earlier IPRs filed by other biosimilar applicants for Humira®, including Coherus Biosciences and Boehringer-Ingelheim, also attacked indication patents Humira®, namely, those for rheumatoid arthritis.  RA is one of the drug’s largest indications by revenue.  The eighth patent that Sandoz attacked is U.S. Patent No. 8,802,100, which is a formulation patent.

Even if Sandoz succeeds on all of these IPRs, what use will it be?  AbbVie claims to have so many other patents at its disposal, even knocking out eight patents among 100 may prove futile. One answer is that Sandoz most likely filed these IPRs for settlement leverage more than anything else.  Indeed, whereas Coherus and Boehringer filed multiple IPRs against some of the same patents, which suggests a genuine desire to knock out that patent, Sandoz has instead chosen a volume approach, targeting multiple patents, but only filing one IPR against each.  Another answer is that, several of AbbVie’s Humira® patents can, most likely, be designed around.  Many of them cover devices, formulations or manufacturing elements that are likely not infringed.  The indication patents, namely the ones that Sandoz, Coherus and BI have focused on through IPRs, are the hardest to circumvent.

Against the background of this upcoming lawsuit is AbbVie’s settlement with Amgen.  That settlement most likely cemented the earliest entry date that AbbVie will agree to with other biosimilars.  By giving Amgen entry in 2023, it is unlikely that AbbVie can or will agree to an earlier date for anyone else.  Every respective biosimilar applicant moving in on Humira® will face the same wall of patents that Amgen did, and any litigation itself through appeals could take so many years, that 2023 could be close to the earliest possible date to enter without risk.  By filing so many unique IPRs against indication patents, Sandoz’s may potentially building a threatthat invalidating those patents just makes it easier for the next guy (i.e., the next biosimilar applicant for Humira®, of which there will be others.)  If there is a settlement, then Sandoz will presumably agree to drop those IPRs.  That’s leverage, and if it buys an entry date that is a few months earlier, it’s worth it.