Jordan M. Engelhardt, Counsel

At the end of 2017, inter partes review (IPR) proceedings for biosimilar products were on the rise.  This was followed by a dip in the number of new filings in FY 2018 and the first half of 2019.  Through Q1 2020, this downward trend has continued.  Specifically, there has been one new biosimilar IPR filing in the nine-month period from the beginning of Q3 2019 through the end of Q1 2020, leading to a total of 102 total biosimilar patent IPRs.  See Fresenius Kabi USA, LLC et al. v. Amgen, Inc. et al., IPR2020-00314 (December 20, 2019).

April 7, 2020 Update: FDA announced on March 31, 2020 that it has created the Coronavirus Treatment Acceleration Program (CTAP), a special emergency program to expedite the development of safe and effective treatments for Covid-19.  Under CTAP, FDA has redeployed medical, operations, policy, and regulatory staff to triage and rapidly respond to inquiries, requests, and submissions relating to Covid-19 therapies.  FDA is now aiming to respond to single patient expanded access requests within three hours; protocol reviews within 24 hours; and requests to develop or evaluate new drug and biologic therapies within a day.  FDA is also aiming to provide “ultra-rapid, interactive” input on most development plans, and to work closely with applicants and other regulatory agencies to expedite quality assessments.

Recently, in Amgen Inc. v. Hospira, Inc., the Federal Circuit clarified the limits of the Safe Harbor defense in cases involving patented manufacturing methods.

In a case brought in the District of Delaware, Amgen alleged that Hospira infringed several patent claims over methods of manufacturing erythropoietin (EPO), a biologic drug used to treat anemia. Following a trial, a jury issued a $70 million verdict for Amgen, which was based in part on the jury’s conclusion that fourteen batches of drug substance for Hospira’s EPO biosimilar product were not covered by the Safe Harbor provision of 35 U.S.C. § 271(e)(1). After the district court denied Hospira’s motion for judgment as a matter of law or alternatively for a new trial, Hospira appealed on a number of issues, including the jury instructions and jury findings on its Safe Harbor defense.

As 2019 draws to a close, a handful of actions regarding biologics are pending in the federal courts.  The current cases are listed below, in order from most-recently-filed to oldest:

In Amgen’s long-running dispute with biosimilar-maker Sandoz over biosimilar versions of Amgen’s filgrastim (Neupogen®) and pegfilgrastim (Neulasta®) biologics, the Federal Circuit earlier this year affirmed summary judgment of no literal infringement and no infringement under the doctrine of equivalents.  Amgen Inc. v. Sandoz Inc., 923 F.3d 1023 (Fed. Cir. May 8, 2019).  In so holding, the panel stated that “the doctrine of equivalents applies only in exceptional cases.”  Amgen petitioned for rehearing en banc, arguing that the Federal Circuit had overstated the law.  According to Amgen’s petition, “[s]uch a rule is contrary to Supreme Court precedent and [Federal Circuit] precedent.”  This week, the Federal Circuit course-corrected, granting Amgen’s petition without explanation for the limited purposes of removing the “exceptional” language from its prior decision. 

On July 23, 2019, Amgen, maker of the cancer treatment drug Neupogen (filgrastim), filed patent infringement claims in the Southern District of California against Tanvex Biopharma over Tanvex’s proposed filgrastim biosimilar.  See Amgen Inc. v. Tanvex BioPharma USA, Inc., 3:19-cv-01374-BEN-MSB.  Amgen asserts a patent that claims methods of refolding recombinant proteins used in the manufacture of Neupogen.

At the end of 2017, inter partes review (IPR) proceedings for biosimilar products were on the rise.  2018 and the first half of 2019, however, have seen a dip in the number of new filings.  And looking back at biosimilar IPRs that have been decided, results have been mixed.  The Patent Trial and Appeal Board has denied institution in about half (47%) of its institution decisions on petitions challenging biologics-related patents.  For those petitions actually reaching a Final Written Decision, the patentability of at least one claim has been upheld in just over half (53%) of the Board’s decisions.  Notwithstanding the mixed results for petitioners and the recent dip in new filings discussed here, IPR remains a key battlefield for biologic innovators and biosimilar makers.

On April 17, 2019, several lawmakers from the Senate and House of Representatives released a bipartisan, bicameral framework for statutory reform of 35 U.S.C. § 101.  The framework was released about two months after the revival of the Senate Judiciary Subcommittee on Intellectual Property.  For the past several years, innovators, the Patent Office, and even judges on the Federal Circuit have raised concerns that Section 101 has become a runaway law for invalidating patents that reflect genuine advances in science and technology.  The revival of the Senate subcommittee and the release of this framework indicate that Capitol Hill has heard, and is moving towards a response to, these concerns. 

Last week, the Federal Circuit issued its long-awaited opinion in Momenta Pharmaceuticals, Inc. v. Bristol-Myers Squibb Co., No. 2017-1694, slip op. (Fed. Cir. Feb. 7, 2019).  While many had hoped the decision would provide clarity on whether a biosimilar maker who has not yet filed an aBLA has standing to appeal a PTAB decision upholding an innovator patent, the Federal Circuit instead dismissed the appeal for lack of standing and mootness based on post-appeal developments making it clear that Momenta had abandoned its efforts to develop the biosimilar in question.  Nevertheless, Momenta is important in that it illustrates the continued risk to biosimilar makers of unappealable IPR decisions when they bring IPRs years before filing an aBLA.

On December 22, 2018, the United States federal government entered a partial shutdown, which now enters its 19th day.  If the shutdown continues through the weekend, it will be the longest federal government shutdown in U.S. history.  While many federal offices and services are completely closed, agencies that impact biologics—including the FDA, the USPTO, and the Federal Judiciary—remain open in various capacities, at least for now.  Nevertheless, if the shutdown continues, the biotech/pharmaceutical industry could begin to feel its effects.

Earlier this month, the President signed into law the Patient Right to Know Drug Prices Act (Public Law 115-263). The Act mainly focuses on eliminating so-called “gag clauses” that prevent pharmacists from telling patients when paying for a drug out of pocket is cheaper than paying through insurance.  In addition, the Act amends the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (Public Law 108-173) to require branded drug companies and biosimilar applicants to disclose settlement agreements relating to the “manufacture, marketing, or sale” of biosimilar products to the Federal Trade Commission (“FTC”) and U.S. Department of Justice (“DOJ”) for evaluation under the antitrust laws. The new legislation brings biosimilar litigation in line with ANDA litigation, for which the same disclosure requirements were already in place. 

Earlier this month, AbbVie filed suit against Sandoz’s proposed biosimilar to AbbVie’s HUMIRA® (adalimumab).  Invoking the Biosimilar Price Competition and Innovation Act (“BPCIA”), AbbVie asserts two patents protecting Humira, a fraction of the 84 patents AbbVie wished to litigate.  Taking full advantage of the pre-litigation “patent dance,” Sandoz limited the number of patents-in-suit to just two.  As this case illustrates, following the patent dance affords biosimilar makers considerable control and power over the scope of biosimilar lawsuits.

On July 20, 2018, FDA approved Pfizer’s biosimilar of Amgen’s Neupogen® (filgrastim).  Pfizer’s product, Nivestym™, is the second biosimilar of Neupogen to be approved after Sandoz’s Zarxio®, the first approved biosimilar in the United States.  Pfizer’s Nivestym gained approval for all eligible Neupogen indications.

On Friday, June 22, 2018, the Supreme Court issued its decision in WesternGeco LLC v. ION Geophysical Corporation, 585 U.S. ___, Slip. Op.  No. 16-1011 (June 22, 2018), reversing the Federal Circuit and holding that WesternGeco’s award for lost foreign profits was a permissible application of the damages provision of the Patent Act, 35 U.S.C. § 284.[1]  Justice Thomas wrote the opinion for a seven-justice majority while Justice Gorsuch wrote a dissent joined by Justice Breyer.

As biosimilar litigation between Amgen, the maker of Enbrel^® (etanercept), and Sandoz, the maker of biosimilar Erelzi^TM (etanercept-szzs) heads toward trial before Judge Claire Cecchi in the District of New Jersey, Sandoz is seeking to stave off Amgen’s infringement claims for three of the patents in suit by pointing to its recent amendment to the Erelzi label, which “carves out” certain treatment indications listed on the Enbrel reference label and, Sandoz argues, moots any claim that Erelzi infringes Amgen’s patents covering the use of etanercept to treat those conditions.

The U.S. Court of Appeals for the Fourth Circuit last month handed manufacturers and wholesalers of off-patent drugs a victory by ruling that Maryland’s anti-price gouging act violates the U.S. Constitution’s dormant commerce clause.  The legislation, like many others, was enacted in the wake of the Martin Shkreli case, where the former Turing Pharmaceutical CEO raised the price of a vital and old prescription drug by 5,000 percent. Although the Circuit sympathized with consumers affected by this type of conduct, it held, in a majority opinion written by Judge Stephanie Thacker, that Maryland overstepped its constitutional limits in seeking to compel manufacturers of off-patent or generic drugs to act in accordance with Maryland law outside of Maryland.

In a highly anticipated ruling, the Supreme Court upheld the constitutionality of inter partes review proceedings.  Justice Thomas, writing for the seven-member majority in Oil States Energy Services, LLC v. Greene’s Energy Group, LLC, held that the Patent Trial and Appeal Board could reconsider and cancel patent claims through inter partes review without violating Article III or the Seventh Amendment of the Constitution.

Biosimilar developers have been aggressive in filing petitions for inter partes reviews (IPRs) of biologics patents before the Patent Trial and Appeal Board (PTAB), many of them preceding the filing of a marketing application.  Such early IPRs are attractive to biosimilar makers, because they provide a chance to challenge innovator patents years before the biosimilar maker files a marketing application with FDA.  Since a petitioner need not have Article III case-or-controversy standing to bring an IPR, the remoteness and uncertainty of future infringement in such circumstances does not preclude these early IPRs.  Under settled precedent, however, a biosimilar maker must have Article III standing to seek a Federal Circuit appeal if the PTAB issues a final decision upholding the challenged patent.  A decision expected from the Federal Circuit this quarter in Momenta Pharmaceuticals, Inc. v. Bristol-Myers Squibb Co., No. 17-1694 (Fed. Cir. argued Dec. 5, 2017) will address how and when a biosimilar maker can establish that standing.