Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto

In my experience, since the PTAB—again, that’s the Patent Trial and Appeal Board&mdash;is more concerned about the facts and science of the issues specifically before them in each [inter partes review, IPR] more so than simply applying past precedent, I think it’s very hard to generalize across an entire subset of patents based on just one patent and what happened to it in the IPR. 

It’s true that it appears that method claims haven’t fared as well as formulation claims in IPRs. But it’s important to note that this might just be a function of the patents that have been challenged so far. Method of treatment patents tend to be filed later in time, so petitioners may also be looking at them more often because they have later expiration dates in patent portfolios. And if you have more of a certain type of patent being challenged, of course you’re going to have a higher likelihood of seeing them invalidated, so it may be a product of what we’re seeing challenged.

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Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto, discusses whether the PTAB might invalidate more patents concerning dosing and frequency of biologics, as it did with claims 1 to 5 of AbbVie's '135 patent for Humira. 

Ha Kung Wong: Method of Treatment Patents

Inter partes review (or IPR for short, which people tend to use in the industry) has become an important process for patents throughout the life science industry, but interestingly, so far we haven’t seen as many in the biosimilars space as one might expect. We expected that biosimilar applicants would look to use the IPR pathway to perhaps deal with patents they perceive as vulnerable, as they kind of clear the path to market. But so far, surprisingly, there have been fewer of those than we thought there would be.

In fact, pursuant to some information I saw on 

, we’ve only seen 4 biosimilar-related products have an IPR without a co-pending litigation. So, it doesn’t look like we’re seeing very much path-clearing. And with respect to the 25 or so biosimilar-related litigations that existed as of July 6, 2017, only 3 of them had involved a challenge to one or more patents that had been IPR-ed.

Overall, it appears that whether an IPR is used in a biosimilars context is, at the moment, more related to the parties involved then any type of significant industry-wide trend. For instance, Celltrion, Teva, and Pfizer have been very active with respect to Rituxan and Herceptin. And Coherus has been very active with respect to Humira.

One reason for this may be the issue of standing. Generally speaking, although you don’t need standing to file an IPR, you do need standing to appeal an adverse IPR decision. So some biosimilar companies might not want to risk going through the IPR process without that safety net of having an appeal available, so they wait to have standing prior to filing an IPR, which means they end up waiting for a litigation.

Now, another reason may be the sheer breadth of patents in the biologics space. Unlike small-molecule products that we’re used to, that are covered by the Hatch-Waxman Act, which may be covered by 1 or 2 patents or so, biologic products can have portfolios in the 10s or 100s. This makes it challenging for a biosimilar company to identify the most critical patents, which means it may be less productive to use the IPR process.

And the overarching concern with IPRs, basically in every context, is estoppel. A biosimilar company is unlikely to take their best shot at invalidating a patent in IPR where there is limited discovery, for instance, and the risk being of estopped from raising those arguments, and others that reasonably could have been raised in later district court litigation, may be a concern.

Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto, discusses the use of inter partes review (IPR) in the biosimilars context.

Ha Kung Wong: Inter Partes Review in the Biosimilars Context

Will biosimilar applicants still choose to take part in the BPCIA patent dance in light of the 

One of the primary incentives provided in the [Biologics Price Competition and Innovation Act, BPCIA] to engage in the “patent dance” is that if the applicant completes the dance and the reference product sponsor does not sue that 30-day period, as required by statue, infringement damages for patents that could have been asserted are limited to a reasonable royalty. So the patent dance, which takes about 6 months, in order to narrow down to those 2 lists, is designed in part as a vehicle to provide patent certainty for biosimilar applicants fairly early in the process, rather than allowing a reference product sponsor to bring suits later and potentially complicate the biosimilar launch process.

, we’ve already seen that some biosimilar applicants would prefer to forego the patent dance entirely. Currently, the biosimilars in late-stage development are for blockbuster drugs that have been on the market since the 1990s. And because they’ve been on the market for so long, many are covered by only a handful of unexpired patents. So under those circumstances, biosimilar applicants may not see any incentive to participate in this dance.

With Amgen’s Humira biosimilar, on the other hand, we’ve seen them engage in the BPCIA disclosures and set up this 2-stage litigation. And in that case, Amgen would likely have decided to participate in the patent dance with AbbVie if their application had been accepted by the FDA after the Supreme Court’s ruling with 

The reason why, is because AbbVie has close to 100 patents on Humira, some covering methods of use, some covering formulations, and some covering process technologies. Some of those patents may be more important than others, and Amgen might have likely liked to use the BPCIA to kind of narrow the patents at issue—make sure they know which ones are the most important. Now, in that scenario, both the [Biologics License Application, BLA] holder and the biosimilar gains additional certainty.

Going forward, though, biosimilar applicants will begin targeting newer drugs not long after data exclusivity expires. Under those circumstances, with larger patent portfolios and longer expiration dates, the certainty that the patent dance provides could be valuable to biosimilar applicants.  

And last, keep in mind that whether the biosimilar applicant is looking to get an interchangeable biosimilar may also impact their strategy, as interchangeables carry the additional incentive of potential exclusivity. And the FDA did release a new guidance this year, talking about what they might require to get interchangeable. So that may be the carrot that everyone’s looking for.

Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto, discusses incentives for biosimilar applicants to engage in the BPCIA "patent dance" after the SCOTUS ruling in Sandoz v Amgen.

Ha Kung Wong: The Patent Dance After Sandoz v Amgen

What are some questions that SCOTUS left unresolved in its 

 concerned the interpretation of two procedural provisions of the [Biologics Price Competition and Innovation Act, BPCIA] setting the framework for biosimilar patent litigation. Essentially, the BPCIA (codified at 42 USC s. 262(l)(2)(A)) states that once the FDA accepts an application for a biosimilar drug, that the biosimilar applicant 

shall provide” the brand/reference drug maker, within 20 days, a copy of the application and information about the biosimilar and its manufacturing. Now, this initial disclosure starts an exchange that essentially boils the patent dispute down to 2 lists. Now, the first list is a shortlist of patents to be litigated immediately, and the patents on the second list aren’t litigated until the biosimilar applicant provides notice of commercial marketing to the reference drugmaker. Now, under BPCIA (as codified at 42 USC 262(l)(8)(A)), the biosimilar applicant “shall provide” notice of commercial marketing not less than 180 days before marketing of an FDA-licensed biosimilar.

 holding is fairly clear on the issue of the timing of commercial notice. The Supreme Court held that FDA approval is not required before the 180 day notice. So that issue was, for the most part, resolved.

But the other issue of whether the BPCIA’s requirement that a biosimilar applicant “shall provide” their applications and manufacturing information after the FDA accepts their application—introduces a fair bit of uncertainty into how biosimilars will be launched and what biosimilar patent litigation will actually look like.

The Supreme Court agreed with the Federal Circuit that the initial disclosure requirement of the BPCIA isn’t enforceable by injunction under Federal law. So it’s essentially up to the applicant whether they want to proceed with the two-stage patent litigation procedure set out by the BPCIA. But they remanded the question to the Federal Circuit as to whether an injunction may be available under state law, and specifically whether an injunction for failure to provide the initial disclosures was available under California’s unfair competition law. That’s one question that was deliberately left unanswered by the Court in 

And so, depending on the outcome of remand, we could see that the initial disclosure provision is unenforceable under state and federal law, or that the provision is enforceable on a state-by-state basis. If the initial disclosures under the BPCIA are essentially optional, biosimilar applicants may decide there isn’t enough of an incentive to participate, and may choose to force brand drugmakers to operate in the dark as they assert basically all patents at once after they receive notice of commercial marketing.

Justice Breyer actually issued a short concurrence in that decision, saying that while the court’s interpretation was reasonable, if the FDA promulgated a different interpretation, the Court may be inclined to defer to the FDA’s position. So, whether and how the FDA responds to this, and how that will impact the process, is also an open question.

Ultimately, there remains uncertainty over the initial disclosures, just as a whole. Will there be a state-by-state availability to enforce compliance? Will the FDA act on this? Will Congress act on this? There’s still plenty to be concerned about.

Ha Kung Wong, JD, Partner at Fitzpatrick, Cella, Harper and Scinto, discusses the questions left unresolved by SCOTUS in the Sandoz v Amgen ruling. 

Ha Kung Wong: The Unresolved Questions of Sandoz v Amgen

How will biosimilars impact our healthcare industry?

One of the issues about biosimilars is that they’re taking away the monopoly of a biologic. Now, there is a lot of money that is spent in terms of biologics and in terms of research and development. So they need to get a fair return on their investment. So what we have here is the issue of allowing for innovation, which then will increase consumer welfare—people benefit from these drugs&mdash;and at the same time allow for access to consumers but also allow for innovation of new drugs that will benefit society. One of the things that we see that is different from the generic market in the biosimilar market is that many of the brand-name companies are actually getting into the biosimilar market, so we’ll see competition more like brand-to-brand than we see brand-to-generic.

Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, discusses the impact that biosimilars will have on the healthcare industry. 

Dr Joseph Fuhr: Biosimilars Bring on Brand-to-Brand Competition

How important is interchangeability for biosimilars?

Interchangeability is not important. There are 2 type of biologics: pharmacy, and physician-administered. In physician-administered, interchangeability will not matter, since the physician is picking the drug directly, so (there is) no need to substitute. In a pharmacy scenario, automatic substitution will occur, but are payers willing to pay a price premium for an interchangeable biologic? 

Biosimilars are highly similar, so how much better is an interchangeable biologic? It is highly, highly similar, so if (the) copay is greater for (an) interchangeable, then will patients pay more for it? 

Also, it costs more for an interchangeable study, since you need to do switching studies, which add to cost. So are firms willing to take on this investment with very little gain? There is 1-year exclusivity for interchangeables for each reference product, but other biosimilars will probably be in the market before this occurs. 

Also, some believe they may not be able to apply without some post-market data—which will delay entry&mdash;and not be allowed to apply initially for interchangeability. Also, if they don’t get approved for interchangeability, will this hurt the image of (the) product and (its) market share? There’s too much risk for too little reward to go for interchangeability.

Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, discusses interchangability in biosimilars.

Dr Joseph Fuhr: Interchangeability Poses Too Much Risk, Too Little Reward

What will predict the biosimilar market share? 

Differences in various drug prices concerning various indications will depend on the number of competitors and how the originator responds to competition. If the originator responds aggressively by decreasing its price, market share of biosimilars may be low, but consumers benefit (from) lower prices and greater access. Market share is not the true metric; the real metric is how much prices have decreased in the market since biosimilars’ entry. And this underestimates the benefits, since (the) price of the originators would probably have increased without competition.

Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, discusses biosimilar competition and its effect on market share and price.

Dr Joseph Fuhr: Market Share Is Not the True Metric of Biosimilar Competition

Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, looks to evidence from Europe to predict US biosimilar cost-savings. 

Will biosimilars generate a significant cost savings in the US?

The discount for biosimilars has been around 15% for the first 2 (products), and this is what happened in Europe in the beginning. In the case of Europe, it has generally been tenders which have resulted in decreases, which are equivalent to our exclusive arrangements. (These arrangements) will develop over time in the US. So far, there’s only 1 biosimilar for a given reference product in the generic market. When only 1 competitor exits, price doesn’t decrease that much, so it is an evolving process. In Norway, where they had a 70% discount, there were 2 biosimilar companies and the originator bidding for the tendered contract. More competition will lead to lower prices, but it will take time for the market to evolve.

Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, looks to evidence from Europe to predict US biosimilar cost-savings.

Dr Joseph Fuhr: Competition from Biosimilars Will Lead to Lower Prices Over Time

What will be the immediate economic impact of biosimilars?

In the next few years I see very little economic impact (of biosimilars). There are currently 2 in the market and they are both risk launches. All are involved in various patent disputes and the Supreme Court is looking at 2 issues concerning the 180-day notice of entry and the other concerning whether the patent dance is mandatory. 

As with any new industry, [biosimilars] will take time to develop and so their economic impact will be minimal.

Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, sees a limited economic impact for biosimilars given current patent disputes.

Dr Joseph Fuhr: The Immediate Economic Impact of Biosimilars May be Limited

Joseph P. Fuhr, Jr, PhD, professor emeritus, Widener University, sees value in stakeholder education about biosimilar products.

How important is stakeholder education on biosimilars?

It is important to educate healthcare professionals and patients concerning biosimilars. For me, the most important would be the payers, who have the incentive to inform people about highly similar low-cost alternatives. Payers are the agents of subscribers. Also, physicians need to educate patients. So, consumers should gain through competition from biosimilars. The better educated the physicians are, the more they will be willing to prescribe biosimilars. Unless it is an interchangeable biologic, there will be automatic substitution at the pharmacy level. thus, biosimilars must be directly prescribed by physicians.

However, many biosimilars are physician or hospital-administered, in which case the physician will pick the drug they want. As long as physicians believe the products are highly similar and there are no clinical differences, they can benefit with bundling or value-based pricing by cutting costs and keeping some of the savings.

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