On March 6, 2018, the U.S. Food and Drug Administration (“FDA”) authorized, with special controls, the first direct-to-consumer test to detect the presence of genetic mutations in the BRCA1 and BRCA2 genes (“BRCA genes”). The test, offered by the personal genomics company 23andMe, analyzes DNA from a consumer’s self-collected saliva sample for three mutations in the BRCA genes. Mutations in the BRCA genes are associated with an increased risk of developing breast and ovarian cancer in women, and breast and prostate cancer in men. However, the test only detects a small fraction of the more than 1,000 known mutations in the BRCA genes. The three mutations that the test does identify are most prevalent in people of Ashkenazi Jewish descent and are rarely present in individuals of other ethnic groups.
USPTO Adopts Amgen v. Sanofi, Excises “Newly Characterized Antigen” Test from its Written Description Guidance for Antibody Claims
Last month, the USPTO issued a memorandum to its patent examining corps clarifying its guidance concerning the written description requirement for claims drawn to antibodies. In the memorandum, the USPTO adopts the Federal Circuit’s recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit recently denied Amgen’s petition for rehearing and rehearing en banc in Amgen, confirming that Amgen is the law for written description for antibodies.
In a hard-fought patent battle involving “groundbreaking” work by both parties, Chief Judge Stark of the U.S. District Court for the District of Delaware ruled that plaintiff Idenix’s patent for treating Hepatitis C virus (HCV) infection was invalid as a matter of law for lack of enablement. The decision overturns a $2.5 billion award to Idenix, a Merck subsidiary. The opinion provides valuable insight into the court’s thinking on enablement of method of treatment claims encompassing a large genus of therapeutic agents.
2017 was a record-setting year for biosimilar approvals in the U.S. and Europe. In the U.S., five complex antibody products were approved, two of which are in new therapeutic areas for U.S. biosimilars. In Europe, 16 biosimilars were approved. The number of approved biosimilars in Europe has doubled in the past two years. These approvals have expanded European biosimilars into new therapeutic areas and new classes of biologics. In both markets, biosimilars of pegylated biologic products, such as pegfilgrastim, continue to pose challenges for biosimilar makers.
On December 19, 2017, FDA approved Spark Therapeutics’ gene therapy Luxturna (voretigene neparvovec-rzyl), the United States’ first gene therapy approved to treat an inherited genetic disease. This approval follows that of Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ Yescarta (axicabtagene ciloleucel), both gene therapies approved earlier this year to treat certain forms of cancer. Gene therapy has arrived, and although the genetic material central to these new treatments is not expressly listed in the statutory definition of “biological product,” FDA is regulating these products as biologics, giving them twelve-year non-patent exclusivity.
The Federal Circuit’s recent decision in Promega Corp. v. Life Technologies Corp. is a cautionary tale that failure to present evidence of damages closely tied to each alternative basis of liability may result in a hollow victory – infringement with no corresponding damages. The Federal Circuit, on remand from the Supreme Court, affirmed the district court’s rulings in a patent suit against Life Technologies that both overturned the jury’s $52 million infringement verdict in favor of Promega, and denied Promega’s motion for a new trial on damages and infringement. The Federal Circuit held that Promega was not entitled to any damages under the narrow “all-or-nothing” damages strategy that Promega had pursued throughout the litigation, and that Promega had waived any alternative damages arguments.
In July, a split panel of the Federal Circuit upheld the district court’s use of an adverse inference from litigation misconduct to hold a patent unenforceable for inequitable conduct. The Federal Circuit’s decision in the case, Regeneron Pharmaceuticals Inc. v. Merus NV, raises interesting questions about the relationship between attorney misconduct during litigation (which is not supposed to affect the enforceability of a patent) and misconduct during prosecution of the patent (which can). Because the court’s opinion gives no clear answer to these questions, it opens new tactical opportunities for defendants asserting inequitable conduct defenses in patent cases and may incrementally expand the use of a doctrine that the Federal Circuit has famously referred to as a “plague” and repeatedly tried to rein in.
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Following Biosimilar Trial, Jury Awards Amgen $70 Million for Pfizer’s Pre-Approval Infringement of Now-Expired EPO Patent
In one of the first Biologics Price Competition and Innovation Act (BPCIA) litigations to reach trial, a jury on Friday awarded Amgen $70 million in damages for Pfizer’s infringement of one of Amgen’s expired patents protecting Epogen®. The jury found that Pfizer’s subsidiary Hospira, in manufacturing its proposed biosimilar ahead of FDA approval, was not protected by the statutory safe harbor, 35 U.S.C. § 271(e)(1). This action provides an important lesson in the potential value of expired or soon-to-expire patents in BPCIA litigation. Because a biosimilar maker’s pre-approval activity may not be covered by the statutory safe harbor, patents that are expired at the time of approval may still have been infringed.
In Life Technologies Corp. v. Promega, the Supreme Court reversed the Federal Circuit’s interpretation of 35 U.S.C. § 271(f)(1), and held that a single component does not constitute a “substantial portion of the components of a patented invention” under the statute. The Court, however, declined to address how many components are needed to trigger liability.
On Wednesday, February 15, 2017, the Patent Trial and Appeal Board (“PTAB”) ruled in favor of the Broad Institute of MIT and Harvard in a closely watched patent fight with UC Berkeley over the breakthrough CRISPR genome-editing technology. The PTAB concluded that the Broad Institute’s later-filed patents for using CRISPR in eukaryotic cells did not interfere with Berkeley’s earlier-filed patent application that disclosed the use of CRISPR technology in vitro and claimed the use of CRISPR technology in general.
FDA Says BPCIA Poses No Fifth Amendment Taking for Innovator Biologics Submitted Prior to Its Enactment
On the same day that FDA approved the first biosimilar of Humira, the fourth biosimilar to be approved in the U.S., it also denied a citizen petition filed by Abbott Laboratories (now AbbVie) requesting that FDA not accept any filing or approve any application for a biosimilar version of Humira® (adalimubab), AbbVie’s best-selling biologic, or any other product for which a biologics license application (BLA) was submitted to FDA prior to March 23, 2010, the date on which the Biologics Price Competition and Innovation Act (BPCIA) was signed into law. AbbVie argued that to accept or approve any such biosimilar filing would constitute an unconstitutional taking under the Fifth Amendment. AbbVie filed its petition in April 2012, long before any biosimilar was approved in the U.S. and before Amgen filed its biosimilar application for Humira with FDA. All four of the U.S. biosimilars approved to date have relied on BLAs submitted to FDA prior to March 23, 2010.
It has been four years since the first inter partes review proceedings were filed in the United States. The first IPR petition, filed on September 16, 2012 (the first day IPRs became available), made it all the way to the Supreme Court, and the number of IPRs has greatly exceeded expectations, making the Patent Trial and Appeal Board one of the most important and busiest forums for patent validity litigation in the US. IPRs were intended to help high-tech innovators besieged with suits from patent trolls to efficiently and cheaply invalidate dubious patents and focus on innovation. But the impact of these proceedings goes far beyond electrical and computer fields as they have had a major impact on biotech and pharmaceutical patents as well. The PTAB proceedings for U.S. Patent No. 6,331,415 (better known as the “Cabilly II patent”) – one of the most litigated biotech patents in the US – offer key insights into IPRs and why they are widely used across technologies.
Amgen’s Federal Circuit Appeal: the Importance of Manufacturing Information to Biosimilar Litigation
Amgen has filed its appeal brief in Amgen v. Hospira, following the Federal Circuit’s denial of Hospira’s motion to dismiss the appeal for lack of jurisdiction. The appeal presents an important question for biosimilar litigation: where biosimilar applicants fail to provide manufacturing information in the pre-litigation information exchanges of the Biologics Price Competition and Innovation Act (BPCIA), are they required to provide that information in litigation even if it is irrelevant to the asserted patents? The question is particularly important because if the answer is no as the district court held, then innovator companies will be forced to assert manufacturing patents that they do not know to be infringed in order to be able to obtain discovery to evaluate their infringement. Amgen also addresses whether the Federal Circuit has jurisdiction to hear the appeal under either the collateral order doctrine or the All Writs Act.
In UCB, Inc. v. Yeda Research and Development Co., the Federal Circuit affirmed the determination by the District Court for the Eastern District of Virginia that UCB, Inc.’s Cimzia® (certolizumab pegol), a humanized antibody fragment that treats inflammatory conditions such as rheumatoid arthritis and Crohn’s disease, does not infringe a monoclonal antibody patent owned by Yeda Research and Development Co., Ltd.. (Fed. Cir. No. 2015-1957, September 8, 2016). Based on actions taken during prosecution, the Federal Circuit agreed that Yeda was “estopped from including chimeric and humanized antibodies within the scope of the monoclonal antibodies claimed” in its patent.
On August 30 FDA approved Sandoz Inc.’s biosimilar of Enbrel (etanercept), Amgen Inc.’s blockbuster biologic for treatment of moderate to severe rheumatoid arthritis and a number of other autoimmune conditions. The biosimilar, Erelzi (etanercept-szzs), is the third biosimilar approved for marketing in the US under the Biologics Price Competition and Innovation Act of 2009 (BPCIA). Erelzi has been approved for all of Enbrel’s indications and is the first U.S. biosimilar of etanercept.
In July, the Federal Circuit decided Amgen v. Apotex, No. 2016-1308 (Fed, Cir. July 5, 2016), its second decision interpreting the U.S. biosimilar statute, the Biologics Price Competition and Innovation of Act of 2009 (BPCIA). The Federal Circuit affirmed the district court’s preliminary injunction barring Apotex from selling its proposed biosimilar until 180 days after post-licensure notice of first commercial marketing. The Federal Circuit held that 180 days’ notice was mandatory regardless of whether the biosimilar maker provided its regulatory application to the innovator as prescribed at the outset of the BPCIA procedures or not. The decision has impacted other district court litigation, including the Janssen v. Celltrion/Hospira and Amgen v. Hospira cases, since the biosimilar makers in those cases also argued that they did not need to provide 180 days’ notice of commercial marketing after being licensed by FDA.
In Rapid Litig. Mgmt. Ltd v. CellzDirect, Inc., the Federal Circuit reversed a ruling of patent invalidity under Section 101, reviving a biotech patent to a method of preserving hepatocytes, liver cells, for medical use. The Federal Circuit reversed the district court at both steps of the Supreme Court’s framework for patent eligibility set out in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012). In the wake of the Supreme Court’s recent denial of certiorari in Sequenom Inc., v. Ariosa Inc., where Sequenom sought guidance on the proper application of the Mayo two-step test, the Federal Circuit’s decision provides important guidance for how to determine patent eligibility for biotech inventions that build on natural discoveries. It also may help stem what many, including several Federal Circuit judges, have described as a crisis in medical innovation due to how courts and the Patent Office have applied Mayo.
Amgen and Hospira have fired off a dueling letters to the court in their litigation over Amgen's Epogen biosimilar, debating whether the U.S. biosimilar statute, the Biologics Price Competition and Innovation Act of 2009 (BPCIA), contains a private right of action. The letters come in the wake of the Federal Circuit’s Amgen v. Apotex decision, which held that the BPCIA’s 180-day notice of commercial marketing provision is mandatory and enforceable by an injunction.
Federal Circuit Decides Amgen v. Apotex, Holds that 180-Day Notice of Commercial Marketing is Always Mandatory in Biosimilar Litigation
Today, the Federal Circuit decided Amgen v. Apotex, No. 2016-1308 (Fed. Cir. July 5, 2016), its second decision interpreting the U.S. biosimilar statute, the Biologics Price Competition and Innovation of Act of 2009 (BPCIA). The Federal Circuit affirmed the district court’s preliminary injunction barring Apotex from selling its proposed biosimilar on the U.S. market during the 180-day post-approval notice of commercial marketing period. Writing for a unanimous panel that also included Judges Wallach and Bryson, Judge Taranto held that “the commercial marketing provision is mandatory and enforceable by injunction even for an applicant in Apotex’s position.”
Supreme Court Denies Sequenom’s Cert Petition, Leaving the Federal Circuit’s Interpretation of the Mayo/Alice Patent Eligibility Framework Intact For Now
The Supreme Court today denied Sequenom Inc.’s petition for writ of certiorari, in which Sequenom asked the Court to review a decision of the Federal Circuit invalidating its patent on a breakthrough prenatal diagnostic procedure. In denying the petition, the Court has declined to revisit the patent eligibility framework it set out in Mayo Collaborative Servs. v. Prometheus Labs. Inc., 132 S. Ct. 1289 (2012) and reaffirmed in Alice Corp. Pty. Ltd. v. CLS Bank International, 134 S. Ct. 2347 (2014).
Amgen Appeals Ruling on Requirement to Produce Manufacturing Information for a Biosimilar Product under Amgen v. Sandoz
Amgen has appealed a partial denial of its motion to compel in Amgen v. Hospira, which sought discovery of the formulation for the cell culture media that Hospira uses to manufacture its proposed biosimilar of Amgen’s Epogen. Judge Andrews of the District of Delaware granted Amgen’s motion to the extent it sought information relevant to infringement of an asserted patent, but did not agree with Amgen’s broader argument that disclosure of manufacturing information was required under the Federal Circuit’s decision in Amgen v. Sandoz, which held that an innovator company can commence suit when a biosimilar maker fails to provide required information under the statutory process set forth in the Biologics Price Competition and Innovation Act of 2009 (BPCIA) and “access the required information through discovery.” Amgen’s discovery dispute with Hospira represents an important lesson in the aftermath of Amgen v. Sandoz. Innovator companies that assert only a subset of their manufacturing patents, as Amgen did, may only be able to obtain discovery relevant to those patents. As a result, innovator companies may choose to assert all of their manufacturing patents in order to obtain manufacturing information that biosimilar makers fail to provide under the BPCIA.
Today, the Supreme Court deferred a decision on certiorari in Amgen v. Sandoz, inviting the Solicitor General to file a brief expressing the views of the United States. Sandoz petitioned for review of one aspect of the Federal Circuit’s 2015 decision, that court’s first and so far only interpretation of the Biologics Price Competition and Innovation Act of 2009 (BPCIA), and Amgen filed a conditional cross-petition asking for review of another aspect of the decision if Sandoz’s petition were granted. The Supreme Court’s order asks the Solicitor General to comment on both petitions.
Ariosa Diagnostics, Inc., Natera, Inc., and DNA Diagnostics Center, Inc. have filed briefs in opposition to Sequenom’s petition for writ of certiorari to the Supreme Court for review of the Federal Circuit’s decision holding Sequenom’s fetal DNA diagnostic patent ineligible under Section 101 and the test set out in Mayo Collaborative Servs. v. Prometheus Labs. Inc., 132 S. Ct. 1289 (2012).
In the last couple of years, a new gene editing technique called CRISPR has taken biology by storm. Scientists worldwide are using CRISPR to turn off, turn on and alter genes in living cells. CRISPR is so precise that it is expected to turn into a promising therapy for correcting genes in people, thereby curing devastating illnesses. Gene editing startups have burst onto the scene and industry has jumped in to develop this technology for therapeutic use. But CRISPR is now embroiled in a massive patent fight between the research institutions that lay claim to the technology. In January, the Patent Trial and Appeal Board (PTAB) declared an interference, an arcane and largely obsolete proceeding, to decide who was first to invent CRISPR gene editing in eukaryotic cells (using Cas9, a CRISPR associated protein), and thus who may be able to profit from its far-reaching applications.
The biotechnology and life sciences industry has voiced strong support for Sequenom’s recent request that the Supreme Court review the Federal Circuit’s decision holding that Sequenom’s patent on prenatal diagnosis using fetal DNA was invalid under 35 U.S.C. § 101 for claiming ineligible natural phenomena. Twenty-two amici have filed briefs in support of Sequenom’s petition, representing a diverse contingent of stakeholders: biotech and life science companies, innovators in other technological fields, academics, international and domestic professional organizations, and IP licensors. Many elaborate on the arguments raised by Sequenom in its petition, including the potential for a Mayo-induced “crisis of patent law and medical innovation.”
Amgen has fired back in response to Sandoz’s cert petition in Amgen v. Sandoz, arguing that the Supreme Court should not hear the case—but that if it does, it should also review the Federal Circuit’s holding on the Biologics Price Competition and Innovation Act’s (BPCIA’s) “patent dance.” Though Amgen declined to seek cert on the patent dance issue, which it lost at the Federal Circuit, it has now filed a conditional cross-petition on that issue along with its opposition to Sandoz’s petition for review of the Federal Circuit’s holding on the BPCIA’s notice of commercial marketing.
On March 21, 2015, Sequenom filed a petition for writ of certiorari to the Supreme Court in Sequenom, Inc. v. Ariosa Diagnostics, et al. (No. 15-1182). Sequenom seeks Supreme Court review of a Federal Circuit decision holding Sequenom’s patent on a breakthrough non-invasive fetal DNA diagnostic method invalid as directed at patent-ineligible natural phenomena. In its petition, Sequenom calls its case the “ideal vehicle” for the Supreme Court to address mounting concern – acknowledged by the Federal Circuit below – that Mayo Collaborative Servs. v. Prometheus Labs. Inc., 132 S. Ct. 1289 (2012), has been interpreted too broadly, rendering otherwise meritorious inventions patent ineligible. Sequenom argues that the Federal Circuit’s interpretation of Mayo is incorrect and would have sweeping and devastating effects on innovation in biotechnology.
Despite mixed results, biosimilar makers continue to turn to inter partes review (IPR) proceedings in order to challenge innovator patents protecting some of the most important biologics.
Sandoz has filed a petition for a writ of certiorari in Amgen v. Sandoz, the first and, to date, only Federal Circuit decision interpreting the Biologics Price Competition and Innovation Act (BPCIA). Sandoz is challenging the Federal Circuit's ruling that biosimilar applicants must observe a 180-day notice period after their products are approved by the FDA.
AbbVie, Inc., a biopharmaceutical company, has submitted a citizen petition to the FDA regarding determinations of interchangeability under the BPCIA. An interchangeable biological product is biosimilar to a reference product and meets additional, heightened standards for interchangeability. While biosimilars are required to be highly similar to an FDA-approved reference product, an interchangeable biological product is expected to produce the same clinical result as the reference product in any given patient. A determination of interchangeability is significant because an interchangeable biological product may be substituted for a reference product by a pharmacist without requiring permission from the physician who prescribed the reference product. While the FDA approved the first biosimilar biological product in early 2015, it has yet to issue a decision that one biological product is “interchangeable” with another.
In 2015, FDA issued a number of final guidance documents for biosimilars but many fundamental questions remain unsettled, including the requirements for labeling of biosimilars, interchangeability, and naming. There is much ahead for the US biosimilars pathway in 2016.
2015 was a landmark year for biosimilars. It began with the approval of the first US biosimilar, Sandoz’s Zarxio, in March 2015 under the biosimilars pathway. Zarxio entered the US market in September. Many expected the floodgates to open after Zarxio’s approval but Zarxio remains the only approved US biosimilar to this day, although that is expected to change this year. Seven other biosimilar applications were filed in 2014/2015 and are either being reviewed by FDA or have to be refiled. Most of these applications are to complex biologics. 2016 should provide significant insights into how FDA determines biosimilarity and extrapolation for these complex products.
On January 26, 2016, the World Health Organization (WHO) unveiled the final version of its proposal for a worldwide biosimilar naming convention. The WHO proposes to add a “biologic qualifier” (BQ), which consists of four random consonants and an optional two-digit checksum, as an identifier that follows the nonproprietary name of each biologic and biosimilar product. This proposal resembles FDA’s biosimilar naming proposal, which adds four random consonants as a suffix to nonproprietary names. Industry and healthcare stakeholders have criticized FDA’s proposal to use random suffixes, instead of meaningful—and therefore memorable—ones, due to a greater likelihood of reporting and prescription errors with meaningless names. The WHO proposal, which uses a randomly generated separate identifier, is likely to draw similar criticism.
Amgen has decided not to seek Supreme Court review of the Federal Circuit’s Amgen v. Sandoz decision, as the January 14, 2016 deadline to file has now passed without Amgen petitioning for certiorari. In Amgen, the Federal Circuit held that the BPCIA’s “patent dance” patent dispute resolution procedures are essentially optional. With the Federal Circuit having already denied en banc review, Amgen’s decision not to seek cert appears to mean that the patent dance is now optional as a matter of settled law. There is, however, one caveat: if Sandoz seeks cert and the Court accepts, Amgen could file a cross-motion on the patent dance issue.
Earlier this week, the Patent Trial and Appeal Board (PTAB) set the stage for what is expected to be an epic battle over who owns the intellectual property rights to “the biggest biotech discovery of the century.” On January 11, 2016, the PTAB declared an interference to decide who was first to invent the use of the groundbreaking gene-editing technique known as CRISPR in eukaryotic cells. The CRISPR proceeding may be one of the last great biotech interferences. The claims at issue are viewed by many as the “holy grail” for correcting and curing human genetic diseases and interferences will ultimately become obsolete under the America Invents Act.
The Federal Circuit Will Hear Apotex’s Appeal from a Preliminary Injunction Under the BPCIA in Early 2016
In early 2016, the Federal Circuit will hear Apotex’s appeal from a preliminary injunction barring Apotex from selling its proposed Neulasta biosimilar for 180 days after FDA approval. Briefing will be complete on February 12, 2016, and the Federal Circuit agreed to place the case on the oral argument calendar soon thereafter. Apotex had asked for a more expedited schedule but was not able to provide any specific evidence of when its proposed biosimilar product will be approved.
On December 9, a federal district court in Florida issued a preliminary injunction prohibiting Apotex from selling a proposed biosimilar version of Amgen’s cancer drug Neulasta for 180 days after the biosimilar is approved. In the decision, the district court resolved in Amgen’s favor a dispute over the meaning of the Federal Circuit’s recent decision in Amgen v. Sandoz, the first and to date the only appellate decision addressing the Biologics Price Competition and Innovation Act of 2009 (BPCIA).
In Nautilus, Inc. v. Biosig Instruments, Inc., 134 S. Ct. 2120 (2014), the Supreme Court rejected the Federal Circuit’s “insolubly ambiguous” standard for determining whether a patent claim meets the definiteness requirement under 35 U.S.C. §112, ¶ 2, and that “a patent is invalid for indefiniteness if its claims, read in light of the specification delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those skilled in the art about the scope of the invention.” In the ensuing one and a half years, the Federal Circuit and several trial courts have applied the Nautilus standard in the biotechnology and pharmaceutical contexts. We discuss three notable decisions.
In Ariosa Diagnostics Inc. v. Sequenom Inc., 788 F.3d 1371 (Fed. Cir. 2015), a Federal Circuit panel held that Sequenom Inc.’s noninvasive prenatal diagnosis patent claims patent ineligible subject matter under the two-step test of Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012). Sequenom petitioned the court for rehearing en banc, arguing that the panel failed to consider the claimed method as a whole and that its analysis was therefore contrary to Supreme Court precedent. Sequenom’s petition received strong support from amici from numerous organizations, companies and academic groups. There were 12 amicus briefs in total, raising a variety of additional arguments in support of en banc review. On September 3, 2015, the court invited appellees to file a response to the petition for rehearing en banc.
A number of biosimilar makers have turned to inter partes review (IPR) proceedings to challenge innovator patents prior to submitting their biosimilar applications to FDA. IPRs have been attractive to biosimilar makers because in addition to offering procedural and substantive advantages for challenging patents they do not require the filing of a biosimilar application. As a result, they make it possible for biosimilar makers to obtain patent certainty at a time when litigation under the Biologics Price Competition and Innovation Act of 2009 (BPCIA) is premature and, depending on the results of the IPRs, may be avoided entirely. The first such IPRs, however, are yielding mixed results, leaving potential patent disputes for later BPCIA litigation.
In a victory for holders of method patents, the Federal Circuit issued an en banc decision yesterday expanding the scope of direct infringement when multiple parties perform different steps of an invention. In its unanimous Akamai Techs. v. Limelight Networks decision, the appeals court provided a fact-based test for determining when “all method steps can be attributed to a single entity” such that direct infringement can be found under 35 U.S.C. § 271(a). Unlike the earlier panel decision that was overturned, the en banc court held that infringement can, in some circumstances, be attributed to a single entity even when there is an arms-length business relationship between that entity and the other parties that perform steps of the patented method.
The BPCIA created an abbreviated pathway for FDA approval of biological medicinal products that are “biosimilar” to an already FDA-approved product. The FDA recently approved the first U.S. biosimilar – Sandoz’s biosimilar of Amgen’s Neupogen – and is currently reviewing at least four other proposed biosimilars. Many innovators and biosimilars manufacturers are responding to the changing landscape for biologics by developing “biobetters”: new and improved versions of biologic medicinal products. While biobetters require discovery and an original Biologics License Application (BLA) with a full complement of pre-clinical and clinical data for marketing approval, they also offer many advantages. By offering superior and longer-acting medicine, biobetters provide a competitive advantage over biosimilar products. In addition, unlike biosimilars, they generally would be entitled to patent protection and 12 years of non-patent exclusivity under the BPCIA.
The Federal Circuit recently handed down a long-awaited Section 101 decision, one with potentially far-reaching consequences for biotech diagnostic patents. In Ariosa Diagnostics Inc. v. Sequenom Inc., No. 14-1139 (Fed. Cir. June 12, 2015), the Federal Circuit, applying the U.S. Supreme Court’s test for patent eligibility set out in Mayo Collaborative Servs. v. Prometheus Labs. Inc., 132 S. Ct. 1289 (2012), invalidated Sequenom’s breakthrough patent on noninvasive prenatal diagnosis through the amplification and detection of paternally inherited cell-free fetal DNA (“cffDNA”) in the blood of pregnant women. According to the court, “even such valuable contributions can fall short of statutory subject matter” under the test set out in Mayo. In addition to its implications for other biotech patents and investment in diagnostics, the Federal Circuit’s decision illustrates the potentially unintended consequences of Mayo and the need for a legislative solution so that breakthrough manmade inventions remain patent-eligible.
On May 26, 2015, the Supreme Court reversed the Federal Circuit’s decision in Commil USA, LLC v Cisco Systems, Inc. and held that a defendant’s belief regarding patent validity is not a defense to an induced infringement claim. The Supreme Court’s Decision is a big win for the pharmaceutical industry, where method of treatment patents provide important protection for innovative medical therapies. The Federal Circuit’s good-faith belief in invalidity defense gutted liability for inducing infringement of such patents. The Supreme Court’s reversal allows these valuable patents to be enforced against the companies that induce infringement. It also deters “at risk” launches prior to a district court decision on the validity of the patents.
On May 13, the FDA released additional draft question-and-answer guidance on the implementation of the BPCIA. The draft document resurrects a number of the questions from FDA’s original 2012 draft guidance that were omitted from last month’s final version of the 2012 document. As a result, FDA’s final answers to important questions from three years ago may not be forthcoming for some time.
A number of biosimilar makers have turned to inter partes review (IPR) proceedings in order to litigate the validity of patents that cover their proposed products in advance of submitting their regulatory applications to FDA. Since IPRs, unlike district court proceedings, do not require a case or controversy, they allow biosimilar applicants to resolve potential patent disputes long prior to being able to litigate these disputes in district court and to potentially avoid the patent dispute resolution procedures of the Biologics Price Competition and Innovation Act (BPCIA) of 2009 entirely.
Yesterday the Federal Circuit granted Amgen’s motion for an injunction pending appeal in Amgen v. Sandoz, the first appeal to squarely address the patent litigation provisions of the Biologics Price Competition and Innovation Act (BPCIA). While this is an interim decision without a substantive opinion, it indicates that the court is taking Amgen’s arguments seriously.
Amgen v. Sandoz, the first full-fledged dispute under the Biologics Price Reduction and Innovation Act, is headed to the Federal Circuit on an expedited briefing schedule, with oral argument to be held on June 3. The Federal Circuit’s decision is likely to answer basic questions about how the statute operates.
On March 31, the Supreme Court heard oral argument in Commil USA LLC v. Cisco Systems Inc. The Supreme Court considered the Federal Circuit’s holding that a belief in a patent’s invalidity is a defense to inducing infringement under 35 U.S.C. § 271(b). The Justices posed tough questions to both sides. But the ultimate outcome of this case should not impact litigation under the BPCIA where inducing infringement of method of treatment and manufacturing patents offers important protection to innovators since the validity of such patents is typically determined prior to launch of a biosimilar product.
Zarxio is the first biosimilar approved under the 351(k) pathway, but it is not the first “biosimilar” to be approved in the U.S. For a small category of follow-on biologics, there is another pathway for marketing approval -- and it is only available for the next five years.
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