Irena Royzman, Ph.D., Partner

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.

The Federal Circuit’s recent decision in Amgen v Sandoz provides a measure of clarity for innovator companies and biosimilar makers eyeing patent litigation. While the Supreme Court of the US held in June that initiating the pre-litigation information exchanges set out in the Biologics Price Competition and Innovation Act (BPCIA) – colloquially referred to as the “patent dance” – cannot be enforced under federal law, the Federal Circuit’s decision goes a step further. It holds that initiation of the exchanges cannot be enforced under state law, either. As a result, innovators seeking to compel disclosures from biosimilar makers have no recourse other than to sue for infringement. For a number of reasons, however, the decision might not prove as impactful in the long run as it may seem.

To continue reading Irena Royzman and Michael Fresco's article from Intellectual Property Magazine, please click here.

2017 has been a record-setting year for biosimilar approvals in Europe. Although the first biosimilars to the European market were approved in 2006 and 2007, the number of approved biosimilars has doubled in the past two years. These approvals have expanded the market into new therapeutic areas and new classes of biologics.

Inter partes review proceedings for biosimilar products are soaring. Biosimilar makers are taking advantage of IPR proceedings to challenge patents protecting some of the world's most important biologic medicines due to the advantages that these proceedings offer: no standing requirement, no presumption of validity, a lower burden of proof and potentially broader claim construction. More than half of the IPR petitions challenging these patents were filed in fiscal 2017. But the results are mixed, with the Patent Trial and Appeal Board denying a high percentage of the petitions. Many of these patents are ultimately litigated in district court under the U.S. biosimilar statute, the Biologics Price Competition and Innovation Act of 2009 (BPCIA). 

In Sandoz v. Amgen, the Supreme Court interpreted the U.S. biosimilars statute, the Biologics Price Competition and Innovation Act (BPCIA), for the first time. The Court held unanimously that provisions of the BPCIA requiring disclosure allowing innovator companies to assess whether their patents are infringed cannot be enforced under federal law. The ruling also allows biosimilar makers to provide notice of commercial marketing long before FDA approval of the biosimilar. The Court’s decision introduces uncertainty into provisions of the BPCIA that many viewed as necessary and enforceable. But, due to the value of certainty for both biosimilar makers and innovators alike in resolving patent disputes for blockbuster biologics, the impact of the Supreme Court’s decision may ultimately be modest.

To read the article by Irena Royzman and Nathan Monroe-Yavneh in Nature Biotechnology, please click here.

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. 

On August 2, AbbVie sued Boehringer in the District of Delaware, alleging infringement of multiple patents related to AbbVie’s blockbuster biologic Humira (adalimumab). Though AbbVie has “more than 100 issued United States patents” that protect Humira and says that Boehringer infringes 74 of them, AbbVie explains that it was only able to assert 8 of the patents against Boehringer in its complaint.  As AbbVie explains, Boehringer was able to limit the scope of litigation to 8 patents by complying with the procedures of the Biologics Price Competition and Innovation Act of 2009 (“BPCIA”).

On Thursday, July 13, 2017, FDA’s Oncological Drugs Advisory Committee (ODAC) unanimously recommended approval of biosimilars of two blockbuster cancer drugs.  The first, Amgen and Allergan’s ABP-215, is a proposed biosimilar of Roche/Genentech’s Avastin (bevacizumab), a monoclonal antibody used in the treatment of a number of different cancers.  The second, Mylan and Biocon’s MYL-1401O, is a proposed biosimilar of Roche/Genentech’s monoclonal antibody Herceptin (trastuzumab), a drug used in the treatment of HER2+ breast and gastric cancer.  If, as expected, the drugs receive final FDA approval, each of these drugs will be the first U.S. biosimilar for its respective reference product. 

This post, Part II, of a three-part series (Part I) on FDA’s interchangeability draft guidance, highlights the key issues that were raised in the stakeholder comments provided to FDA.  FDA received 52 comments in total from a variety of stakeholders, including patients, physicians, insurers, innovators and biosimilar makers.  The stakeholders were divided in their views in a number of areas.  Patient and physician groups and innovators urged FDA to adopt more stringent requirements for interchangeability assessments.  Biosimilar makers and insurers, by contrast, generally pressed for a loosening of the guidance provided by FDA as well as clarification that interchangeable biosimilar products were not more similar to the innovator product than the non-interchangeable ones.  The comments also raised a number of issues not addressed by the guidance, which will be discussed in the third post in this series. 

Approvals of biosimilar products in Europe continue to outpace those in the United States.  28 biosimilars are currently approved in Europe and five in the U.S.  In 2017, the European Medical Agency has approved six biosimilar applications, including applications for biosimilars to two of the best-selling complex biologics, Humira (adalimumab) and MabThera (rituximab).  EMA is likely to approve seven more biosimilar applications in the coming months.  The Food and Drug Administration in turn has approved one biosimilar this year, and has scheduled an advisory committee meeting for later this month for Pfizer’s proposed biosimilar of Amgen’s EPO (epoetin alfa), which the agency previously rejected.  Proposed biosimilars of complex biologics in a number of new classes are pending before both agencies at the same time.

President Donald J. Trump has now been in office for just over one hundred days.  Observers have been quick to mark this milestone and assess the new administration’s performance, especially on headline-grabbing issues like immigration and foreign policy. Amidst the hubbub, however, few have commented on how President Trump’s opening moves could affect the multi-billion-dollar biologics industry.  President Trump’s actions during his first hundred days on issues like trade, judges, and healthcare have the potential to shape the biologics industry for innovators and biosimilar makers alike for years to come.

A number of biosimilar makers have tried to obtain approval for proposed biosimilar versions of Amgen’s Neulasta (pegfilgrastim), a long-acting version of Amgen’s Neupogen (filgrastim), but have encountered hurdles so far both in the U.S. and Europe.

Europe’s biosimilar market continues to develop, with biosimilars in new classes approved and pending in applications before the European Medicines Agency (EMA).  The EMA has approved four additional biosimilars in 2016, including three biosimilars in two new classes: a biosimilar of Amgen’s Enbrel (etanercept) and two biosimilars of Sanofi’s Clexane (enoxaparin sodium).  In addition to the now 22 approved biosimilars, 16 additional biosimilar applications are under evaluation by the EMA with 12 of the 16 falling in four new product classes: biosimilars of Amgen’s Neulasta (pegfilgrastim), Genentech’s Herceptin (trastuzumab), Roche’s MabThera (rituximab) and AbbVie’s Humira (adalimumab).  While Europe’s biosimilar pathway offers important lessons for the U.S., the Food and Drug Administration (FDA) is setting its own path.  Two of the four biosimilars approved in the U.S., Sandoz’s biosimilar of Amgen’s Enbrel and Amgen’s biosimilar of AbbVie’s Humira, were approved in the U.S. without any prior approval in Europe.  The FDA has also rejected applications for proposed biosimilars with authorization and marketing experience in Europe, making clear that approval in Europe will not necessarily result in approval in the U.S.   

This week’s election of Donald Trump as the next President of the United States undoubtedly impacts many sectors of the American economy, and the bio/pharmaceutical industry is no exception.  Two of Trump’s stated policies might bear directly on how biologics will be protected and litigated in this country and abroad: the repeal of the Affordable Care Act of 2010 (ACA), also known as Obamacare, and the repudiation of the Trans-Pacific Partnership (TPP).

The FDA on Friday approved the first U.S. biosimilar of Humira (adalimumab), AbbVie’s best-selling biologic for treatment of inflammatory conditions.  The biosimilar, Amgen’s Amjevita (adalimumab-atto), received approval for all of the indications requested by Amgen:  in adults, moderately to severely active rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, moderately to severely active Crohn’s disease, moderately to severely active ulcerative colitis, and moderate to severe plaque psoriasis, and in patients four years of age and older, moderately to severely active polyarticular juvenile idiopathic arthritis.  Amjevita is the fourth FDA-approved biosimilar in the U.S.  As noted by the FDA, Amjevita has been approved as a biosimilar of Humira, not an interchangeable product.  Amgen also submitted its Humira biosimilar for review by the European Medicines Agency in December 2015, but the EMA has yet to issue a decision.

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.

The Federal Circuit has now issued two decisions interpreting the Biologics Price Competition and Innovation Act of 2009 (BPCIA).  In Amgen v. Sandoz, the first decision to interpret the BPCIA, the majority held that biosimilar makers could opt out of the first step of the BPCIA’s pre-litigation disclosures, the provision requiring biosimilar makers to provide the innovator company with their abbreviated Biologics License Application (aBLA) and other manufacturing information describing the processes used to make the proposed biosimilar.  The court held that the innovator company could sue under the BPCIA in such circumstances and obtain the needed information in discovery.  In its second decision, Amgen v. Apotex, the court further buttressed its reasoning as to why the first step of the BPCIA’s pre-litigation provisions was optional.  Amgen now appeals a discovery ruling in its biosimilar litigation with Hospira holding that Amgen v. Sandoz does not require Hospira to produce manufacturing information for its proposed biosimilar of Amgen’s Epogen (epoetin alfa).   Hospira moved to dismiss the appeal as premature.  The Federal Circuit denied the motion and is allowing the appeal to proceed on the merits while at the same time requiring the parties to further address jurisdictional issues.  

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 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.  

On June 20, 2016, the full Federal Circuit declined to rehear Acorda Therapeutics Inc. v. Mylan Pharms. Inc., 817 F.3d 755 (Fed. Cir. 2016) en banc. Acorda affirmed two District of Delaware decisions finding specific jurisdiction over Mylan Pharms., an out-of-state ANDA filer, based on its plans to sell its proposed generic drugs in Delaware. After the Supreme Court’s decision in Daimler AG v. Bauman, 134 S.Ct. 746 (2014), Mylan has argued that it could only be sued in its home state of West Virginia in ANDA cases since future sales of its proposed generic drugs could not confer specific jurisdiction in Delaware.  The Federal Circuit disagreed.  Under Acorda, plaintiffs in ANDA cases as well as in cases brought under the Biologics Price Competition and Innovation Act (BPCIA) can bring suit in their forum of choice based on future sales of proposed generic or biosimilar products so long as considerations of fairness, such as efficiency or undue burden, do not render jurisdiction in the forum unreasonable.  

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.

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.

On Thursday, FDA released draft guidance clarifying its position on labeling biosimilar products.  While the guidance addresses some of the concerns raised by physicians and innovator companies, FDA’s guidance largely continues to treat biosimilars like generics for purposes of labeling.