The Department of Justice (DOJ) recently filed a brief with the Supreme Court arguing that the Affordable Care Act (ACA) should be found unconstitutional. Although the brief was focused primarily on 3 insurance coverage provisions of the ACA, the DOJ also argued that even the “ACA’s comparatively ‘minor,’ ancillary provisions” are inextricably intertwined and should fall with the unconstitutional provisions. One of the many “minor, ancillary provisions” that would fall under the government’s argument would be the Biosimilar Price Competition and Innovation Act (BPCIA). The BPCIA established a framework for exclusivity for novel biological products and FDA approval of lower-cost “biosimilar” versions of such drugs. It also provided a system for litigation of patent disputes involving those products. It is projected that by 2026 the BPCIA will have saved over $50 billion for patients, health care payers, and providers.

The BPCIA has been far from a perfect system, and arguably it has not achieved its goal of meaningfully reducing the cost of life-saving biological products in the United States. In fact, the United States lags significantly behind the European Union and India in biosimilar approvals and cost savings. And because it is less than ideal from both a patient and business standpoint to toss the BPCIA framework out without a viable system to replace it, now is the time to consider what works well with the BPCIA and what improvements should be made. After all, instead of just blaming the cow, Chicago dealt with the great fire by building one of the world’s greatest skylines.

So, here is what we like about the BPCIA and the 6 things that we would change if we go back to the biosimilars drawing board.

What to Keep: The Approval Standard and the Opportunity for Interchangeability

There are 3 positive aspects of the BPCIA that ultimately should be retained.

: Initially the subject of frustration and derision, the standard for approval of biosimilars is the appropriate standard from a scientific and safety perspective and should be retained. The BPCIA requires that for approval a biosimilar must be demonstrably “highly similar to the reference product, notwithstanding minor differences in clinically inactive components.” There should also be “no clinically meaningful differences in terms of safety, purity, and potency.”

 The statute further provides that this standard can be met through analytical studies, animal studies, and clinical studies, with a focus on the assessment of immunogenicity.

 Companies were initially frustrated because neither the statute nor FDA regulations described the quantum of evidence needed to demonstrate that the “highly similar” standard has been met. But the FDA is becoming more familiar with the types of information it should be seeing from applicants, and therefore, approvals (until very recently) were increasing. In addition, the FDA has established a system of meetings for applicants to discuss their plans for submitting their applications and ways to resolve issues in those applications. Although the regulatory process can still be improved through experience, the statutory standard for approval is the correct one to ensure the safety and efficacy of biosimilars.

 of interchangeability is also a key aspect of the statute that should be retained, although the mechanism needs tweaking, as discussed below. Interchangeability allows a pharmacist to fill a prescription for a higher-cost branded drug with the lower-cost biosimilar version of the same product. This mechanism exists for traditional, small molecule drugs based solely on proof that the active ingredient is the same and that it will result in a similar amount of drug being available in the body as the branded version. No additional clinical trials for efficacy or safety are required. Automatic substitution has resulted in substantial cost savings to consumers and increased market penetration for small molecule products. But biosimilar manufacturers seeking interchangeability in the US market must run complex clinical trials, proving that the drugs will maintain efficacy if patients are switched between the brand and biosimilar products. The complex scientific proof that is required and the high cost of the trials have resulted in no awards of interchangeability in the United States, and the lack of a meaningful opportunity for interchangeability is the primary reason that companies are hesitant to pursue biosimilars.

Because it is unclear whether there will be an interchangeable biosimilar in the near future, the current approach to interchangeability has failed. However, interchangeability is an important statutory incentive for biosimilar applicants, and without it biosimilar applicants must compete with an existing biological product that is sold by a company that often has superior marketing power. The difficulty in attaining interchangeability should not be a reason to abandon it with a new statutory regime; it is incumbent upon the FDA to devise regulations to make it scientifically attainable. We provide a proposal below that provides a further incentive for applicants to seek biosimilar approval.

Notice to sponsor of biosimilar application

: Finally, although the information exchange or “patent dance” provisions of the statute should be eliminated, any new statutory scheme should retain the requirement that the applicant notify the reference sponsor that a biosimilar application has been filed and is under review. Much like in Hatch-Waxman Act cases, such notification would be the trigger for a patent infringement lawsuit and additional exclusivity for the reference product. However, as we discuss further below, significant improvements to this notice requirement are needed.

If the ACA is found unconstitutional in its entirety, we propose that Congress make the following 6 changes to the BPCIA when it is constructing a new pathway for biosimilar approvals and litigation: (1) mandatory biosimilar dispensing for treatment-naïve patients; (2) expansion of the Purple Book; (3) first filer exclusivity; (4) limited period of exclusivity with a potential compulsory license; (5) elimination of the patent dance; and (6) streamlining of the resulting patent litigation.

Default use for treatment-naïve patients

: One of the primary reasons that biosimilars have not taken off in this country is that potential applicants are intimidated by the high costs and risks of the regulatory and litigation processes. Without a meaningful opportunity for interchangeability, the applicant will be forced to compete with the reference sponsor, who will likely be better equipped to market and detail their own product. However, if the statute creates a market for an applicant’s biosimilar product, then there is greater incentive for more companies to undertake the risks associated with filing a biosimilar application. To that end, Congress could mandate that all treatment naïve patients be treated with an approved biosimilar product, if available, unless the treating physician or patient opts out. Although the safety of switching from a reference product to a biosimilar has been debated, it is generally accepted that treatment-naïve patients can be safely started on a biosimilar. And because most biological products treat chronic conditions, this requirement will create a sustained market for the biosimilar applicant and incentivize competition. 

 that setting generic pharmaceuticals as the default option has been shown to increase generic prescribing rates. The same should be expected for biosimilars. This approach would provide patients access to lower-cost treatments, which has been shown to increase medication adherence and thus reduce preventable morbidity and mortality. We would suggest price controls on the applicant in order to receive this benefit; for example, requiring the biosimilar to be priced at a 25% discount from the average sales price of the reference product over the last 5 years. The applicant should also have to maintain that price (absent competition) for at least 2 years.

: In the context of small molecules and Hatch-Waxman, the FDA’s Orange Book has been a useful tool—sponsors have been able to give notice to the public as to what patents purportedly protect their product, and applicants have a better understanding of the patent landscape that could be facing them. On the other hand, the Purple Book for biological products contains very little useful information. In fact, there has been proposed legislation to expand the Purple Book. Those calls should be heeded. As with the Orange Book, sponsors should be required to list in the Purple Book patents covering their approved biological product, and applicants should be required to submit a certification to FDA as to each listed patent that the applicant will not launch its biosimilar product until after the patent expires or that the patent is believed to be invalid and/or will not be infringed by applicant’s biosimilar product if marketed. Unlike the Orange Book, however, the Purple Book should include relevant process patents, because the process for making a biologic product is more often the subject of patent protection. The Purple Book should not include any use codes, and there should be penalties for improper listing of patents in the Purple Book.

: There is currently no exclusivity provided for the first biosimilar applicant to file an application. As a further incentive to encourage filing of biosimilar applications, there should be a 6-month exclusivity period for the first applicant to file a biosimilar application, which would be forfeited if that first filer does not obtain approval within 3.5 years of filing and launch its product within 2 years of approval of its application. This approach would be similar to the first-filer exclusivity period under Hatch-Waxman.

Limited exclusivity and compulsory licensing

: Instead of the current 12 years of exclusivity, Congress should separate the exclusivity period and provide a compulsory licensing period if litigation runs too long. Our proposal would grant a reference drug sponsor a total of 8 years of exclusivity prior to compulsory licensing while allowing biosimilar applicants to challenge patents 5 years into the exclusivity period. Under this approach, the sponsor should be provided a 5-year period of exclusivity during which no biosimilar application may be filed. After that 5-year period, the applicant can file an application referencing that biological product. Like with Hatch-Waxman, the applicant would be required to file with FDA a certification of patent invalidity and/or non-infringement as to every patent listed in the Purple Book, and must inform the sponsor of its application and certifications once FDA begins formal review. If the sponsor files suit in 60 days from receipt of notification from the applicant, then the biosimilar application shall not be approved for 3 years (earlier if the applicant is successful in the litigation). If this sounds like Hatch-Waxman litigation, well it’s very similar. The twist is that if the litigation is still pending after 3 years and the biosimilar application is already approved, the reference sponsor will provide a nonexclusive license to the applicant that will allow the applicant to launch its product and set a standard for damages in the event the launch was improper. Compulsory licensing schemes for pharmaceuticals have been proposed in other countries, such as the United Kingdom, and the international Agreement on Trade-Related Aspects of Intellectual Property Rights already allows for compulsory licensing in some situations.

: One of the most bemoaned aspects of the BPCIA is the so-called patent dance, and with good reason. It is confusing, causes unnecessary delay, and frequently involves gamesmanship. We propose eliminating it in its entirety. Under a new statute, applicants would be required to inform the sponsor of the certifications it provided to the FDA and provide information regarding its application so that the sponsor can determine which patents to assert. Applicants would not be required to provide detailed reasons for their certifications: Lawsuits are inevitable regardless of what is included in the detailed statement, and court-required contentions in patent cases provide advanced notice of the applicant’s patent invalidity arguments well before trial. Applicants would be permitted to restrict review of information to outside counsel eyes only, which would include independent expert review. As stated above, if the sponsor files suit within 60 days of receipt of this information, then they are entitled to another 3 years of exclusivity.

 Finally, the resulting patent litigation can be improved by a statutory requirement limiting the number of patent claims asserted in the litigation. The statute could require the number of asserted claims to be limited by the end of fact discovery, and it could limit either the total number of asserted claims or limit the number of claims per patent family or based on patent subject matter. In addition, patentees could ask the court to increase the number of asserted claims upon a showing of good cause.

In the 10 years since the BPCIA has passed, we have had the opportunity to learn many of the strengths and weaknesses of the act as passed within the Affordable Care Act. If either the Supreme Court or Congress ultimately determines that portions of the ACA are to be repealed, the fundamental premise of the BPCIA should be preserved or reissued in order to improve patient access to lower-cost medical treatments. At the same time, the important lessons learned should also be implemented in the form of the changes we have proposed here. As with the rebuilding of Chicago after the fire, a better version of the BPCIA is possible with careful planning and vision.

1. Regulation of Biological Products. §262(i)(2), 42 USC (2017).

2. Regulation of Biological Products. §262(i)(2)(A)(i)(I)(aa)-(cc), 42 USC (2017).

IP Attorneys Propose a New Biosimilar Pathway in Case of ACA Repeal

Helen H. Ji is an associate intellectual property attorney at 

Helen H. Ji

Kevin M. Nelson is an intellectual property attorney 

Kevin M. Nelson

A number of legal trends have emerged in biologics litigation over the summer. Below we discuss 5 of the most significant.

One Notice Is Sufficient if the Underlying Biologic Remains the Same

Under the Biologics Price Competition and Innovation Act of 2009 (BPCIA), one step of the infamous “patent dance” requires a pharmaceutical company seeking to market a biosimilar product to notify the biologics product reference application holder “not later than 180 days before the date of the first commercial marketing” of the biosimilar. But does an applicant have to renotify the reference product sponsor when it supplements its initial abbreviated biologics license application (aBLA)? That was the issue posed to the United States Court of Appeals for the Federal Circuit in 

Genentech Inc v Immunex Rhode Island Corp.

The court ultimately concluded no additional notice is required.

Immunex (a company acquired by Amgen) filed an aBLA with the FDA and subsequently notified Genentech, the reference drug sponsor for Avastin®, that it intended to market a biosimilar version, Mvasi™. After providing its initial notice, Amgen submitted 4 supplemental applications, which included changes to the manufacturing facility and label. Genentech filed an emergency motion seeking to preclude Amgen from commercially marketing Mvasi™, arguing that Amgen did not provide proper commercial notice because the supplemental applications amending the manufacturing facility and label effectively reset the 180-day period. The district court disagreed, and on appeal, the Federal Circuit affirmed the decision. According to the Federal Circuit, supplemental applications do not require a new notice so long as the biological product that is the subject of the application does not change.

Practically speaking, the Genentech decision is a relief to biosimilars companies that may previously have been fearful that an aBLA cannot be amended during the normal FDA regulatory review process. That said, the court did not provide clear guidance about when the biological product has undergone a change sufficient to require a second notice of commercial marketing. Thus, beyond the facts of 

, the precise contours of when an aBLA supplement may require renewed commercial notice still remain to be seen.

Don’t Invalidate Your Biologics Patents by Licensing Them

It’s well known that biologics patent portfolios are extensive, and that licensing them can be quite lucrative for the patent owner and the licensee manufacturer. But a recent case serves as a stark reminder that companies must nevertheless be cautious when licensing patents, lest they accidentally invalidate their own portfolio through common ownership.

Under the doctrine of statutory double patenting, a patent is invalid if it covers subject matter identical to another patent owned by the same entity. This concept was implicated in 

, where the primary issue was whether, by a transfer of rights from Hoffman-La Roche in the 1990s, Immunex alone owned patents-in-suit covering Enbrel® (etanercept).

 Because Immunex owned other patents that covered the same technology, if Immunex had owned the asserted patents outright, Sandoz may have been able to invalidate the asserted Enbrel® patents on grounds of statutory double patenting.

Considering this among other issues, the Federal Circuit determined that the Roche-Immunex license did not transfer “all substantial rights” to Immunex, thus eliminating a statutory double-patenting defense. The license at issue granted Immunex an irrevocable, exclusive license and control over the prosecution of the pending Enbrel® patent applications. The agreement also granted Immunex the right to sublicense the patents and the first right to sue any potential infringers. Notably, Roche was obligated to cooperate with any prosecution and enforcement of the patents and retained a secondary right to sue if Immunex did not file suit. Roche also retained the ability to object to any sublicenses for the patents.

In its analysis, the majority gave significant weight to Roche’s retention of a secondary right to sue and the ability to prevent Immunex from further licensing the patents. Because these rights are inconsistent with the transfer of all substantial rights for a patent, the court reasoned, Immunex was not an owner. In dissent, Judge Jimmie V. Reyna argued that the license transferred all substantial rights to Immunex, rendering it the sole owner of the asserted patents.

This case shows that companies must be diligent when entering license agreements and appropriately structure such agreements to avoid being considered an owner if the covered matter substantially overlaps with existing portfolio assets. Indeed, in the case of large biologics portfolios, such caution is all the more necessary.

By their nature, biologics portfolios are large; AbbVie’s Humira® (adalimumab) is covered by approximately 247 patent applications that resulted in 132 patents, over 100 of which trace back to just 20 original applications. So, it was no surprise that after AbbVie settled several large-scale litigations relating to Humira® with a variety of biosimilars companies, a group of indirect purchasers sued in federal court alleging that the settlements were antitrust violations.

What was surprising, however, were the plaintiffs’ theories about the case. To be sure, the plaintiffs asserted the typical claim that the settlements were illegal restraints of trade, an argument that failed because the district court concluded that AbbVie’s settlements (which permitted competitors to immediately enter the European market but refrain from entering the US market until 2023) were not unlawfully anticompetitive. However, the plaintiffs also advanced a second, more creative theory: that AbbVie impermissibly monopolized the domestic market for Humira® by obtaining and asserting invalid, unenforceable, or noninfringed patents without regard to the merits of such assertions. This argument likewise failed. The district court found that AbbVie’s conduct was not objectively baseless for multiple reasons, including because the United States Patent and Trademark Office had granted more than half of AbbVie’s patent applications and a substantial majority of the patents challenged in inter partes review proceedings had survived. These successes convinced the district court that AbbVie’s conduct was not unreasonable and shielded AbbVie from antitrust scrutiny.

The plaintiffs filed a notice of appeal this past July, and a decision from the United States Court of Appeals for the Seventh Circuit is expected sometime next year. If this decision stands on appeal, it could potentially encourage biologics companies to create judicially sanctioned dense patent portfolios. In any event, biologics companies should have a focused and well-defined strategy when developing new products to ensure that they can reap the full benefits of patent protection while simultaneously avoiding antitrust exposure.

Federal Circuit Reaffirms That Common, Broad Claim Terms Are Broadly Construed

The Federal Circuit delivered a recent victory to patent owners seeking to give broad scope to the meaning of common terms in patent claims. At issue on appeal were the district court’s constructions of the terms 

 in a patent asserted by Baxalta purportedly covering Genentech’s Hemlibra® (emicizumab).

 Notably, the district court opinion was issued by Federal Circuit Judge Timothy B. Dyk, who was sitting by designation in the District of Delaware.

The district court had concluded that without structural context, the term 

 had multiple, commonly accepted meanings. Choosing between Baxalta’s broad proposal—“molecule having a specific amino acid sequence comprising two heavy chains (H chains) and two light chains (L chains)”—and Genentech’s narrower one—“immunoglobulin molecule, having a specific amino acid sequence that only binds to the antigen that induced its synthesis or very similar antigens, consisting of two identical heavy chains (H chains) and two identical light chains (L chains)”—the district court sided with Genentech. In doing so, it relied primarily on 2 pieces of evidence: (1) the specification’s description of 

 and (2) a claim amendment made during prosecution.

On appeal, the Federal Circuit unanimously reversed the ruling. Placing nearly dispositive weight on the claim language of 

 (which does not itself require 2 identical heavy chains and 2 identical light chains or binding only the antigen that induced its synthesis or similar), the court found no reason to limit the plain meaning of the term. It drew additional support from language in a dependent claim identifying certain subsets of antibodies that fell outside the district court’s construction of the term 

. Although the district court would have reconciled the difference by invalidating the inconsistent claims, the Federal Circuit instead found that they provided significant evidence of the breadth of the term. And contrary to the district court, the Federal Circuit refused to adopt a definition excluding claimed embodiments and disagreed that the prosecution history clearly limited the scope of the claim.

Although claim construction is a patent-specific inquiry, the Federal Circuit’s opinion reaffirms that broad terms will be given broad meaning absent a reason demonstrating that the patentee intended otherwise.

New Regulations for Biologics Are (Possibly) Coming

Earlier this year, the FDA announced that it intended to issue substantive regulations governing biologics to clarify existing requirements and procedures related to BLAs.

 The proposed rules are expected to be released in December 2020. The update would further “promote the goals associated with the FDA’s implementation of the abbreviated licensure pathway created by the” BPCIA. But with the details still in the works, it is unclear what changes the FDA intends to make. Certainly, with a relatively low rate of market penetration and cost savings to would-be biosimilar consumers, there could be much worth considering. Although the FDA has yet to issue any proposed rules, industry stakeholders should continue to monitor the agency’s proposed regulations to determine how the regulations could affect the biologics industry.

In sum, this has certainly been an interesting summer for biologics. From basic statutory interpretation to antitrust issues, the legal and business landscape for biologics continues to evolve at a rapid pace. Companies must remain adaptable and continually take appropriate measures to position themselves for future success.

Genentech Inc v Immunex Rhode Island Corp

In re Humira (Adalimumab) Antitrust Litigation

, Appeal No. 2019-1527 (Fed Cir August 27, 2020).

Biologics Regulation Modernization. Reginfo.gov. Accessed September 2, 2020. https://www.reginfo.gov/public/do/eAgendaViewRule?pubId=202004&RIN=0910-AI14

Intellectual property law attorneys from the Washington, DC, offices of McDermott Will & Emery LLP, discuss 5 of the most significant trends in biologics litigation that have emerged in recent months.

What We Learned About Biologics on Summer Vacation

Christopher M. Bruno is an associate in the Intellectual Property group at McDermott, Will, & Emery LLP, and a former law clerk of the United States Court of Appeals for the Federal Circuit and of the United States District Court for the Central District of California. With a focus on pharmaceutical patent litigation, he has litigated Hatch-Waxman Act cases from pre-complaint investigation through appeal in district courts, the Federal Circuit, the Supreme Court, and the International Trade Commission. Chris was one of the first attorneys with experience litigating the meaning of provisions of the Biologics Price Competition and Innovation Act of 2009, and he continues to play a role in decoding the relatively nascent territory of biosimilar litigation.

Christopher M. Bruno, JD

Corey Greenblatt, MPH, is the manager of policy and advocacy of CreakyJoints and The Global Healthy Living Foundation. The Global Healthy Living Foundation is a 501(c)(3) non-profit organization whose mission is to improve the quality of life for people living with chronic illnesses (such as arthritis, osteoporosis, migraine, diabetes, psoriasis, and cardiovascular disease) by advocating for improved access to health care at the community, state, and federal levels, and amplifying education and awareness efforts within its social media framework. The Global Healthy Living Foundation is the parent organization of CreakyJoints, the digital community and advocacy organization for millions of arthritis patients and caregivers worldwide who seek education, support, advocacy, and patient-centered research through ArthritisPower, the first-ever patient-centered research registry for joint, bone, and inflammatory skin conditions. Visit 

Corey Greenblatt, MPH

Last week the US Food and Drug Administration (FDA) issued a revised draft guidance detailing its policies on mixing, diluting, and repackaging certain types of biological products outside of the scope of an approved biologics license application (BLA).

Diluting or mixing a biological product with other components, or repackaging a biological product by removing it from its approved container-closure system and transferring it to another container-closure system, in the absence of manufacturing controls, is highly likely to affect the safety and/or effectiveness of the biological product. The FDA says even minor manipulations of biologics can result in quality or safety issues due to their unique properties.

There are instances where appropriate to mix or dilute a biological product to meet the needs of specific patients. "For example, for some biological products there is no licensed pediatric strength and/or dosage form, so the product is diluted for use in pediatric patients." While there are exemptions from certain federal regulations for compounded drugs under sections 503A and 503B of the 

, these exemptions do not apply to biological products licensed under sections 351(a) or (k) of the 

In accordance, the FDA says that any biological product that is mixed, diluted, or repackaged outside the scope of an approved BLA is an "unlicensed biological product." It also does not intend to take actions for violations of section 351 of the PHS Act or sections 502(f)(1) or 582 of the FD&C Act if a state-licensed pharmacy, a federal facility, or an outsourcing facility mixes, dilutes, or repackages a biological product" in accordance with the guidance.

The guidance does not apply to investigational new drugs being studied under a new drug application or radioactive biological products.

Biologics Mixing, Diluting, and Repackaging: FDA Draft Guidance

Daniella (Dee) Latham

David T. Rubin, MD, AGAF, is a professor of medicine and section chief of gastroenterology, hepatology, and nutrition at University of Chicago Medicine. He is a fellow of the American Gastroenterological Association (AGA), which represents over 16,000 gastroenterologists worldwide and is dedicated to empowering clinicians and researchers to improve digestive health. He is also chair-elect of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, whose mission is to cure Crohn disease and ulcerative colitis, and to improve the quality of life of children and adults affected by these diseases. AGA is a member of the Biologics Prescribers Collaborative (BPC), an organization comprising medical societies whose members regularly prescribe biologic medicines. BPC strives to ensure that sound policies are in place to promote the safest possible development and use of all biologics, including biosimilars, for all patients.

David T. Rubin, MD, AGAF

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John Bujnoski is Managing Director of Pangea Advisory and Consulting, LLC, a strategic marketing consulting firm focused on the specialty biopharmaceutical and biosimilar market segments. John has extensive global biopharmaceutical industry expertise including extensive knowledge and understanding of the global market environment including pricing, market access, and reimbursement systems.

John Bujnoski

Sarfarzaz K. Niazi

George C. Yu, JD, is a partner in the Intellectual Property group of Schiff Hardin LLP. He is an experienced patent attorney who focuses his practice focuses on patent infringement litigation and counseling and has worked in private practice and in-house positions. George has litigated patents relating to recombinant proteins, monoclonal antibodies, microarray technology, and small molecule therapeutics. George has advised companies developing novel biologics as well as biosimilars on patent strategy.

Authors