Keeping pace with the ever-changing life sciences industry, Morrison Foerster stays on top of the trends and political, legal, and economic drivers to support striking the balance between innovative discovery and purposeful business planning to assure our clients continued success. MoFo Life Sciences shares timely legal and business insights and in-depth analyses on trends and the complex technologies at the heart of the global pharmaceutical, biotechnology, diagnostics, medical devices, digital health, and AgTech fields.Learn more about our <a href="https://www.mofo.com/capabilities/life-sciences-healthcare" target="_self">Life Sciences practice</a>.<h2 dir="ltr">ABOUT MORRISON FOERSTER</h2>Morrison Foerster is a leading global law firm that transforms complexity into advantage for its clients. Our clients include some of the largest financial institutions, banks, consulting and accounting firms, and Fortune 100, technology, and life sciences companies. Highlighting the firm’s commitment to client service, leadership in market-changing deals and impact litigation, and values-based culture, Morrison Foerster has been repeatedly recognized as one of the top 10 firms on The American Lawyer’s A-List. Year after year, the firm receives significant recognition from Chambers and The Legal 500 across their various guides, including Global, USA, Asia‑Pacific, Europe, UK, Latin America, and FinTech Legal. Our lawyers passionately care about delivering legal excellence while living our values. Morrison Foerster has a long-standing commitment to creating a culture that respects and celebrates differences, while providing an inclusive environment. The firm has achieved Mansfield Certification Plus since 2018 as a result of successfully reaching at least 30 percent women, communities of color, and LGBTQ+ lawyer representation in a notable number of current leadership roles and committees. The firm also has a long history of commitment to the community and society through providing pro bono legal services, including litigating for civil rights and civil liberties, improving public education and fostering the wellbeing of children, advocating for veterans, promoting international human rights, enforcing the right to asylum, and safeguarding the environment.

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Dr. Meghan Poon counsels clients on patent preparation and prosecution, portfolio strategy, and IP due diligence in the areas of biotechnology and biologics. She has significant experience in diverse technologies including antibodies, cell therapies, gene therapies, diagnostics, and gene-edited plants. She represents clients ranging from large international pharmaceutical companies to midsized companies, startups, and universities.Meghan has filed numerous Patent Term Extension applications to secure additional term for her clients’ patents, which cover FDA-approved products. In addition, Meghan has extensive experience addressing complex obviousness-double patenting and subject matter eligibility issues impacting her clients’ patent portfolios. Meghan also represents clients in both investor-side and target-side due diligence, in deals from seed funding to initial public offerings.Prior to law school, Meghan attended graduate school at the University of California, Los Angeles, where she received a Ph.D. in biological chemistry based on her work on protein-protein and protein-DNA interactions at a molecular level. Meghan is the author of several scientific publications and has presented her research at international conferences.Meghan received her J.D. from the University of Southern California Law School and spent a year as a visiting student at Santa Clara University, where she focused on intellectual property.

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Dr. Meghan Poon counsels clients on patent preparation and prosecution, portfolio strategy, and IP due diligence in the areas of biotechnology and biologics. She has significant experience in diverse technologies including antibodies, cell therapies, gene therapies, diagnostics, and gene-edited plants.

Meghan Poon

Wolfgang advises clients on contentious and non-contentious matters involving their most valuable intellectual property assets in life sciences, digital, and high-tech industries.His subjects of focus include research and development collaborations, complex licensing agreements, and other technology transactions, as well as know-how protection strategies, and employee invention law. He also has substantial experience in litigating patents, trademarks, and other intellectual property assets, often in a multijurisdictional context. In addition, Wolfgang and his team frequently clear trademarks and ad campaigns and prosecute trademark applications.Wolfgang is co-editor of our <a href="https://lifesciences.mofo.com/" dir="ltr" target="_blank">MoFo Life Sciences Blog</a>.Wolfgang is a partner of Morrison Foerster based in our German office in Berlin.<h4 dir="ltr">Representative Transactional Matters</h4><ul dir="ltr"><li>U.S.-based BioTech fund on various research collaborations and other transactions with German start-ups or research institutions.</li><li>Negotiate multimillion-euro strategic partnership between two AgTech leaders concerning the development and commercialization of pest-resistant transgenic traits.</li><li>Craft global multi-million collaboration regarding AI-powered robotic MaaS.</li><li>UK-based digital health company on product roll-out of RPM applications in Germany; coordinate international expansion.</li><li>Advise numerous German start-ups on their U.S. expansion.</li><li>Draft diverse global patent and know-how license agreements in the areas of AgTech and life sciences—including gene licensing and licensing of genome editing technologies (e.g., CRISPR)—and medical devices; draft correlating supply and distribution agreements.</li><li>Structure IP rights in connection with joint ventures and other M&A transactions, including the carve-out of a patent-heavy semiconductor business comprising nine jurisdictions into a German–U.S. joint venture.</li><li dir="ltr">Advise on government-funded, multi-partner R&D projects and/or R&D projects with academic institutions, as well as on employee invention law.</li></ul><h4 dir="ltr">Representative Contentious IP Matters</h4><ul dir="ltr"><li>Lead counsel in an international dispute between software companies on rights and obligations following termination of a multi-million licensing and distribution arrangement; coordinate local counsel.</li><li>Defend Japanese chip manufacturer in high-profile SEP-litigation; advise on global settlement arrangement.</li><li>Represent leading internet retailer in patent infringement and concurrent invalidity proceedings in the context of a multijurisdictional dispute concerning touch-screen technology.</li><li>Represent diverse pharmaceutical and life sciences companies in national and cross-border patent infringement proceedings and other technology-related disputes, including preliminary injunctions as well as pre‑trial discovery and inspection proceedings, concerning, inter alia, drug-coating technologies, toner cartridges, medicinal gases, transgenic plants, and vaccines.</li><li dir="ltr">Conduct trademark, copyright, and false advertising litigation, including, most notably, a high-profile trademark litigation for a German bank, and a nine-country cross-border trademark litigation involving a famous pharmaceutical brand.</li></ul>

Dr. Wolfgang Schönig berät Mandanten zum Schutz des geistigen Eigentums sowohl in streitigen als auch nichtstreitigen Angelegenheiten, mit einem besonderen Fokus auf die IP-rechtliche Beratung von Unternehmen aus den Bereichen Life Sciences, Digitalwirtschaft und High-Tech.Zu seinen Beratungsschwerpunkten gehören Forschungs- und Entwicklungskooperationen, komplexe Lizenzvertragsgestaltungen und andereTechnologie-Transaktionen, sowie Know-how-Schutz-Strategien und das Arbeitnehmererfinderrecht. Er verfügt zudem über umfangreiche Prozesserfahrung zur Durchsetzung von Patenten, Marken- und anderen IP-Rechten, häufig auch in einem grenzüberschreitenden Kontext. Darüber hinaus bewertet Dr. Wolfgang Schönig zusammen mit seinem Team regelmäßig die Rechtskonformität von Werbekampagnen, prüft die Verfügbarkeit von Marken und entwickelt entsprechende Anmeldestrategien.Dr. Wolfgang Schönig ist Co-Editor des Life Sciences Blogs von Morrison Foerster.Er hat seinen Doktortitel an der Heinrich-Heine-Universität Düsseldorf und seinen LL.M. an der Fordham School of Law in New York erworben, jeweils mit Schwerpunkt im gewerblichen Rechtsschutz. Seinen MBA-Abschluss erhielt er von der European University in Barcelona.Dr. Wolfgang Schönig ist Partner des deutschen Büros von Morrison Foerster in Berlin.<h4 dir="ltr">Repräsentative Transaktionen</h4><ul><li dir="ltr">BioTech-Fonds mit Sitz in den USA bei verschiedenen Forschungskooperationen und anderen Transaktionen mit deutschen Start-ups oder Forschungseinrichtungen</li><li dir="ltr">Verhandlung einer hochvolumigen strategischen Partnerschaft zwischen zwei Technologieführern im Bereich Crop Science betreffend der Entwicklung und Kommerzialisierung von bestimmten Resistenzen</li><li dir="ltr">Gestaltung einer globalen Multi-Millionen-Zusammenarbeit für KI-gestützte Roboter</li><li dir="ltr">Ein in Großbritannien ansässiges Unternehmen für digitale Gesundheit bei der Markteinführung von RPM-Anwendungen in Deutschland; Koordination der internationalen Expansion</li><li dir="ltr">Beratung zahlreicher deutscher Start-ups bei deren US-Expansion</li><li dir="ltr">Strukturierung und Verhandlung diverser Patent- und Know-How-Lizenzen in den Bereichen Ag Tech und Life Sciences – einschließlich Fragen zu genome editing wie CRISPR-Medizingeräte, sowie Gestaltung von Softwarelizenzverträgen und Erstellung korrespondierender Liefer- und Vertriebsvereinbarungen</li><li dir="ltr">Strukturierung von IP-Rechten im Zusammenhang mit Joint Ventures und anderen M&A-Transaktionen, darunter die Koordination eines neun Länder umfassenden IP Carve-Outs im Rahmen eines Halbleiter-JVs</li><li dir="ltr">Beratung zu staatlich geförderten Multi-Partner F&E-Projekten und/oder F&E-Projekten mit akademischen Einrichtungen sowie zum Arbeitnehmererfindungsrecht</li></ul><h4 dir="ltr">Repräsentative IP-Streitigkeiten</h4><ul><li dir="ltr">Lead Counsel in einem internationalen Rechtsstreit zwischen Softwareunternehmen über Rechte und Pflichten nach Beendigung einer millionenschweren Lizenz- und Vertriebsvereinbarung; Koordinierung der lokalen Anwälte</li><li dir="ltr">Verteidigung eines japanischen Chipherstellers in einem prominenten Streitfall bezüglich Standardessentieller Patente (SEP); Beratung zu einer globalen Vergleichsregelung</li><li dir="ltr">Verteidigung einer führenden Internetplattform gegen Ansprüche eines Patenttrolls wegen vermeintlicher Verletzung von Patent bezüglich Touchscreen-Technologie sowie korrespondierende US-Streitigkeiten</li><li dir="ltr">Vertretung von Pharma- und Life Science-Unternehmen in nationalen und grenzüberschreitenden Patentverletzungsverfahren und anderen technologiebezogenen Streitigkeiten, einschließlich einstweiliger Verfügungsverfahren und vorprozessualer Beweissicherungs- und Besichtigungsverfahren, unter anderem in Bezug auf Arzneimittelbeschichtungstechnologien, Tonerkartuschen, medizinische Gase, transgene Pflanzen und Impfstoffe</li></ul>

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Wolfgang Schönig is a partner of Morrison Foerster (International) LLP based in our German office in Berlin. His practice specialty is advising on IP aspects relative to transactions in, among others, the life sciences, AgTech and pharmaceuticals industry, as well as legal representation in IP disputes. Wolfgang is specialized in research and development collaborations, complex licensing agreements, technology acquisitions, know-how protection strategies, and employee invention law.

Wolfgang Schönig focuses his practice on IP aspects relative to transactions in the digital, telecoms, high tech, life sciences, and pharmaceuticals industry, as well as legal representation in IP disputes.

Wolfgang Schönig advises clients on IP aspects relating to transactions in, among others, the life sciences, AgTech and pharmaceuticals industry, as well as legal representation in IP disputes. His additional focus areas include research and development collaborations, complex licensing agreements, technology acquisitions, know-how protection strategies, and employee invention law.

Wolfgang Schönig

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On March 16, 2020, FDA issued its Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency (the “Guidance”). The purpose of the Guidance is to expedite the availability of novel coronavirus (SARS-CoV-2) diagnostic tests in view of the current public health emergency. The Guidance contains policies regarding (i) laboratories’ development and use of certain tests prior to or without an Emergency Use Authorization (EUA), (ii) commercial manufacturers’ development and distribution of certain tests prior to an EUA, and (iii) development, use, and distribution of serological tests without an EUA.First, regarding laboratory tests, the Guidance provides two policies: one eventually requires an EUA submission and the other does not. Under the first prong, FDA has indicated that it will not object to a laboratory’s use of SARS-CoV-2 diagnostic tests (i) that occurs after validation and notification to the agency, (ii) for a reasonable time (about 15 business days), (iii) while preparing an EUA request, (iv) provided that the laboratory is certified and meets certain regulatory requirements under Clinical Laboratory Improvement Amendments (CLIA). However, if FDA, upon review of the EUA request, identifies a significant problem that cannot be addressed in a timely manner, the laboratory may have to stop using the test and issue test reports indicating that prior tests may be unreliable.Under the second prong, each state may authorize laboratories within its territory to develop and use SARS-CoV-2 diagnostic tests without notifying FDA of test validation and without engaging in the EUA process.Second, FDA has indicated that it will not object to a commercial manufacturer’s distribution of SARS-CoV-2 diagnostic kits (i) after validation and notification to the agency, (ii) for a reasonable time (about 15 business days), (iii) while preparing an EUA request, (iv) provided that the manufacturer posts instructions for use and data regarding performance of the kit on its website. However, it should be noted that the manufacturer may have to suspend distribution and recall its products if, upon review of the EUA request, FDA identifies a significant problem that cannot be addressed in a timely manner.Third, acknowledging the relative simplicity of serological tests, FDA has indicated that it will not object to a laboratory’s use, and a commercial manufacturer’s distribution of serological tests or kits for SARS-CoV-2 that occur after validation and notification to the agency, provided that certain information listed in section IV(D) of the Guidance is included in the test report (e.g., that the test is not FDA-reviewed).Lastly, it may be worth noting some general points. First, the policies in the Guidance do not apply to at-home testing. Second, where validation is required, FDA recommends the minimum testing described in section V of the Guidance. Finally, FDA recommends including a general statement in the test report that FDA review is pending, whenever that is the case.In sum, the policies set out in the Guidance allow laboratories and commercial manufacturers, under certain conditions, to start using or distributing diagnostic tests or kits for the novel coronavirus prior to or even without an EUA. In addition to the EUA process which is already an expedited authorization process, the new policies will further accelerate distribution and use of the tests.

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FDA’s New Guidance on Use and Distribution of COVID-19 Diagnostic Tests by Laboratories and Commercial Manufacturers

After Striking Deal with the President, the House of Representatives Passes Federal Relief Bill, the Families First Coronavirus Response Act

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On March 16, 2020, FDA issued its Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency (the “Guidance”). The purpose of t

FDA’s New Guidance on Use and Distribution of COVID-19 Diagnostic Tests by Laboratories and Commercial Manufacturers

The Biomedical Advanced Research and Development Authority (<a href="https://www.medicalcountermeasures.gov/" target="_blank">BARDA</a>), part of the U.S Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response, has modified an existing broad agency announcement (BAA) through which it will award government funding to companies seeking to develop products designed to diagnose, prevent or treat coronavirus infections.<a href="https://govcon.mofo.com/health-care/u-s-government-announces-new-federal-funding-opportunities-related-to-covid-19/?utm_source=publications&utm_medium=email" target="_self">Read the full article on our Government Contracts Insights Blog.</a>

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Tina is a partner in Morrison & Foerster’s Government Contracts practice. She represents a wide variety of government contractors including information technology, defense, biotechnology, and pharmace

Tina Reynolds

Tina is co-chair of Morrison Foerster’s Government Contracts & Public Procurement practice. She counsels a wide variety of government contractors on compliance with federal acquisition and ethics regulations. She drafts and negotiates contracts on their behalf and has been involved with numerous internal investigations and compliance reviews, and with bid protest, contract claims, and False Claims Act litigation. She also advises on M&A transactions involving government contractors.

Tina D. Reynolds

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U.S. government announces new federal funding opportunities related to COVID-19

Updated Coronavirus (COVID-19) Guidelines For Employers

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The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S Department of Health and Human Services, Office of the Assistant Secretary f

U.S. government announces new federal funding opportunities related to COVID-19

As industry continues to grapple with and implement the <a href="https://www.govinfo.gov/content/pkg/PLAW-113publ54/pdf/PLAW-113publ54.pdf" target="_blank">Drug Supply Chain Security Act</a> (DSCSA) enacted by Congress in 2013, some of the largest pharmaceutical companies believe they may have a solution to track prescription drugs across the supply chain to prevent the distribution of counterfeit medicines – blockchain.The DSCSA outlines steps to build an electronic, interoperable system to identify and trace, to the packaging level, prescription drugs distributed in the United States as they move throughout the supply chain, and this system must be in place by 2023. The Act includes several different requirements with varying mandatory implementation dates that extend through 2023. Under the Act, FDA is required to establish pilot projects to explore and evaluate methods to enhance the safety and security of the pharmaceutical distribution supply chain.On February 8, 2019, FDA announced the creation of the <a href="https://www.federalregister.gov/documents/2019/02/08/2019-01561/pilot-project-program-under-the-drug-supply-chain-security-act-program-announcement" target="_blank">DSCSA Pilot Project Program</a> to explore issues related to “utilizing the product identifier for product tracing, improving the technical capabilities of the supply chain, identifying the system attributes that are necessary to implement the requirements established under the DSCSA, and any other issues identified by FDA” (84 Fed. Reg. § 2879). Participants in the program were selected by FDA to reflect the diversity of the supply chain. One of the participants in the program is led by blockchain startup MediLedger, and includes a network of 24 companies in the industry, including several major pharmaceutical companies along with other manufacturers, distributors, retailers, and delivery entities. The MediLedger network tested blockchain in the verification of drug returns and recently published its Final Pilot Report in February 2020 detailing the benefits of using blockchain to implement the DSCSA. The MediLedger network believes that blockchain provides a feasible solution to the DSCSA’s track-and-trace requirements and can be used to validate the authenticity of drug identifiers throughout the supply chain in a central point of data sharing while protecting proprietary data.It is still unclear what FDA’s opinion will be on the use of blockchain to implement the DSCSA, and FDA will not release its final program report until all of the projects included in the pilot program are completed. FDA notes that selection of a project into the DSCSA Pilot Project Program is not an endorsement of a particular technology, but other key markers may give us a clue as to FDA’s current thinking. For example, FDA has been supportive of the use of blockchain technology as part of its <a href="https://www.fda.gov/food/conversations-experts-food-topics/deputy-commissioner-champions-more-digital-transparent-food-safety-system" target="_blank">New Era of Smarter Food Safety</a> initiative due to blockchain’s ability to work within decentralized and distributed food systems for full end-to-end traceability. However, based on MediLedger’s report, we know that there are several issues that FDA would need to work through before implementing a blockchain system throughout the industry.  For starters, a new set of standards governing the use of blockchain would need to be developed, including standards for data management among multiple blockchains and non-blockchain networks, recall and alert notification, ensuring authorized trading partner identification, the correction of system records, exception handling, and standards for testing and performance. A governance system would also be necessary, and while the MediLedger network believes that governance should come from the industry itself, FDA may disagree. Additionally, for the system to work, nearly all industry members (manufacturers, wholesalers, dispensers, service providers, etc.) would need to participate in one or more interoperable systems, as the lack of full participation can lead to breaks in the chain of custody, and with higher numbers of interconnected systems, the risk of misaligned and incorrect data increases. Other concerns include the discomfort with blockchain technology, costs for small industry players, international reach, and system security, including permitting only authorized trading partners to access the network. MediLedger’s report also notes that implementation of blockchain is a complex solution and will require a stabilization period, urging a distinction between the implementation date and FDA’s enforcement date of the DSCSA.

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Blockchain and The Drug Supply Chain Security Act (DSCSA)

Blockchain and The Drug Supply Chain Security Act (DSCSA)

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As industry continues to grapple with and implement the Drug Supply Chain Security Act (DSCSA) enacted by Congress in 2013, some of the largest pharmaceutical c

Around the end of 2018, FDA published the “Framework for FDA’s Real-World Evidence Program” (the “Framework”).[1] The Framework is to provide a basis for the agency in evaluating the potential use of real-world evidence (RWE) in regulatory decisions involving drug and biological products.[2] The Framework laid out a “three-part approach” identifying data quality, study design, and regulatory requirements as focal points of the evaluation. In addition, the Framework pointed to the importance of data standards in enabling efficient processing of real-world data (RWD), from which RWE is derived. In 2019, to refine its understanding of these four areas (data quality, study design, regulatory requirements, and data standards) in the context of RWE, FDA coordinated a multifaceted effort including demonstration projects, development of guidance documents, the Sentinel System, and active engagement with sponsors and other stakeholders.In 2019, FDA expanded some of its existing demonstration projects, while funding new ones. In April, Aetion announced that FDA and Brigham and Women’s Hospital/Harvard Medical School will expand the scope of their demonstration project to include predicting seven ongoing randomized control trials (RCTs) with RWE, in addition to the original scope of replicating 30 completed RCTs.[3] In August, a San Francisco-based company Syapse announced that it will work with FDA to assess the potential of RWE especially in the context of precision medicine.[4] While some have criticized these studies,[5] demonstration projects seem to remain a core part of FDA’s Real-World Evidence Program (the “Program”).In May, FDA published a draft guidance entitled “Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics.”[6] The industry reaction was mixed, some cautioning while others encouraging the use of RWE.[7] Notably, some of the pharmaceutical companies asked the agency to consider data from Expanded Access programs as a source of RWD, in response to the draft.[8] While expanding the scope of RWD in such a way may incentivize companies to more actively engage in FDA’s Expanded Access and Right to Try programs,[9] it remains to be seen how the agency’s subsequent treatment of RWE interacts with the level of industry participation in those programs.The Sentinel contract in September marked another step forward in FDA’s endeavor to incorporate RWE into its regulatory practice. According to Jacqueline Corrigan-Curay, FDA’s Director of CDER’s Office of Medical Policy, the contract “will really enable FDA to continue to grow its own RWE capabilities.”[10] The contract will fund up to $220 million for five years starting in 2019, for the next phase of the Sentinel System,[11] which is to become a platform that generates RWE for FDA.[12]Lastly, FDA supported and sponsored workshops to exchange insights with stakeholders. In July, through a public workshop titled “Leveraging Randomized Clinical Trials to Generate Real-World Evidence for Regulatory Purposes,” FDA explored the potential use of RWD not only in single-arm trials but also in randomized clinical trials.[13] Also in July, FDA sponsored a workshop titled “FDA-AACR Real-world Evidence Workshop,” discussing the use of large genomic databases and digital data as RWD, among other things.[14] In October, at a conference entitled “Developing Real-World Data and Evidence to Support Regulatory Decision-Making,” FDA and various stakeholders exchanged thoughts on the key evaluation areas laid out in the Framework.[15] Through these workshops, FDA has shown that it is open to a wide range of creative solutions, while understanding that it may have to take one step at a time.[16]In parallel with its pursuit under the Program, FDA in September announced a Technology Modernization Action Plan.[17] In justifying the timeliness of this plan, FDA explained that a modernized technical infrastructure will be necessary for the agency to accept and process RWD and to derive RWE for its regulatory decision-making, specifically referring to the Framework and the Program. This explanation seems to reach beyond the scope of the Program (and the congressional mandate by the 21st Century Cures Act), which simply sets out to evaluate the potential use of RWE.[18]Finally, it is worth noting how RWE continued to play a role in supporting drug approvals in 2019, especially in the context of cancer and rare diseases. For instance, FDA’s Oncology Drugs Advisory Committee last month unanimously recommended accelerated approval of a drug (tazemetostat) for a rare form of cancer,[19] where the approval was supported in part by a Natural History Study.[20] Further, FDA in April approved a new indication of a drug (palbociclib) primarily based on RWD such as electronic health records and post-marketing reports.[21] The approval is one of the rare cases where FDA accepted RWE to support an effectiveness decision (rather than a safety evaluation), and will serve as a precedent for future drug approvals. Given FDA’s willingness apparent in the Framework to further explore the use of RWE in effectiveness decisions, it seems likely that RWE will play a bigger role in drug approval processes in 2020.In short, FDA in 2019 tapped into multiple channels to gather input from stakeholders and also to broaden its own experience with RWD and RWE. Although the exact outcome of these endeavors remains to be seen in 2020, the agency appears to be slowly but surely getting ready to incorporate more RWE into its regulatory decisions. [1] Framework for FDA’s Real-World Evidence Program, FDA (December 2018)[2] <a target="_blank" href="https://www.fda.gov/drugs/webinar-framework-fdas-real-world-evidence-program-mar-15-2019">Webinar: Framework for FDA’s Real-World Evidence Program, FDA (March 2019)</a>[3] <a target="_blank" href="https://www.prnewswire.com/news-releases/fda-expands-real-world-evidence-partnership-with-brigham-and-womens-hospital-and-aetion-300829517.html">FDA Expands Real-World Evidence Partnership with Brigham and Women’s Hospital and Aetion, PR Newswire</a>[4] <a target="_blank" href="https://www.syapse.com/news/press-releases/syapse-fda-research-collaboration">Syapse Announces Research Collaboration with the FDA Focused on the Regulatory Use of Real-World Evidence (August 2019)</a>[5] <a target="_blank" href="https://www.statnews.com/2019/07/03/replicate-clinical-trials-real-world-evidence">Attempt to Replicate Clinical Trials with Real-World Data Generates Real-World Criticism, Too, Matthew Herper (July 2019)</a>[6] <a target="_blank" href="https://www.fda.gov/media/124795/download">Draft Guidance: Submitting Documents Using Real-World Data and Real-World Evidence to FDA for Drugs and Biologics, FDA (May 2019)</a>[7] <a target="_blank" href="https://www.policymed.com/2019/09/industry-reaction-mixed-to-fda-draft-guidance-on-real-world-data-and-evidence.html">Industry Reaction Mixed to FDA Draft Guidance on Real World Data and Evidence, Thomas Sullivan (September 2019)</a>[8] Gilead and Novartis Seek to Expand What FDA Considers as Real-World Data and Real-World Evidence, Zachary Brennan (July 2019)[9] Public Meeting Report: Leveraging Real World Treatment Experience from Expanded Access Protocols, Silver Spring (November 2018); Pre-Approval Access and Real-World Evidence: A Win-Win Proposition, Jane Reese-Coulbourne (November 2017); Working Group on Compassionate Use & Preapproval Access Frequently Asked Questions (“If companies see expanded access programs as a source of valuable RWE, they may become more willing to run expanded access programs alongside their clinical trials.”)[10] <a target="_blank" href="https://healthpolicy.duke.edu/events/developing-real-world-data-and-evidence-support-regulatory-decision-making">Developing Real-World Data and Evidence to Support Regulatory Decision-Making, FDA & Duke-Margolis Center for Health Policy (October 2019)</a>[11] <a target="_blank" href="https://www.populationmedicine.org/pressrelease/Sentinel">Harvard Pilgrim Health Care Institute Funded up to $220 Million for The Next Phase of FDA Sentinel System, Harvard Department of Population Medicine (September 2019)</a>[12] <a target="_blank" href="https://www.fda.gov/media/120333/download">Sentinel System: Five-Year Strategy 2019-2023, FDA (January 2019)</a>[13] Leveraging Randomized Clinical Trials to Generate Real-World Evidence for Regulatory Purposes, FDA & Duke-Margolis Center for Health Policy (July 2019), <a target="_blank" href="https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/leveraging-randomized-clinical-trials-generate-real-world-evidence-regulatory-purposes">https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/leveraging-randomized-clinical-trials-generate-real-world-evidence-regulatory-purposes</a>; <a target="_blank" href="https://healthpolicy.duke.edu/events/leveraging-randomized-clinical-trials-generate-real-world-evidence-regulatory-purposes">https://healthpolicy.duke.edu/events/leveraging-randomized-clinical-trials-generate-real-world-evidence-regulatory-purposes</a>[14] FDA-AACR Workshop: Real-world Evidence, FDA & AACR (July 2019), <a target="_blank" href="https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/fda-aacr-workshop-real-world-evidence-07192019-07192019">https://www.fda.gov/news-events/fda-meetings-conferences-and-workshops/fda-aacr-workshop-real-world-evidence-07192019-07192019</a>; <a target="_blank" href="https://www.fda.gov/media/128598/download">https://www.fda.gov/media/128598/download</a>[15] <a target="_blank" href="https://healthpolicy.duke.edu/events/developing-real-world-data-and-evidence-support-regulatory-decision-making">Developing Real-World Data and Evidence to Support Regulatory Decision-Making, FDA & Duke-Margolis Center for Health Policy (October 2019)</a>[16] <a target="_blank" href="https://healthpolicy.duke.edu/events/developing-real-world-data-and-evidence-support-regulatory-decision-making">E.g., Developing Real-World Data and Evidence to Support Regulatory Decision-Making, FDA & Duke-Margolis Center for Health Policy (October 2019)</a> (“We know that today data (does) not just seamlessly flow from the EHR or claims data for use in research. Today we’re going to hear maybe how we might get one step closer to that: whether that will require re-imagination of the EHR and the clinical work flow to capture data that is relevant to both quality practice and research … or maybe it’s more relying on natural language processing and artificial intelligence.”)[17] <a target="_blank" href="https://www.fda.gov/media/130883/download">FDA’s Technology Modernization Action Plan, FDA (September 2019)</a>[18] <a target="_blank" href="https://www.fda.gov/drugs/webinar-framework-fdas-real-world-evidence-program-mar-15-2019">Webinar: Framework for FDA’s Real-World Evidence Program, FDA (March 2019)</a>[19] <a target="_blank" href="https://medcitynews.com/2019/12/fda-panel-recommends-approval-of-epizyme-drug-for-rare-cancer/?rf=1">FDA Panel Recommends Approval of Epizyme Drug for Rare Cancer, Alaric Dearment (December 2019)</a>[20] NDA211723: Tazemetostat for the Treatment of Patients with Metastatic or Locally Advanced Epithelioid Sarcoma Who Are Not Eligible for Curative Surgery, Epizyme (December 2019)[21] <a target="_blank" href=" https://www.pfizer.com/news/press-release/press-release-detail/u_s_fda_approves_ibrance_palbociclib_for_the_treatment_of_men_with_hr_her2_metastatic_breast_cancer">U.S. FDA Approves Ibrance® (Palbociclib) for the Treatment of Men with HR+, HER2- Metastatic Breast Cancer (April 2019)</a>

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FDA and Real-World Evidence in 2019

mofolifesciences-intellectual-property

Around the end of 2018, FDA published the “Framework for FDA’s Real-World Evidence Program” (the “Framework”).[1] The Framework is to provide a basis for the ag

FDA and Real-World Evidence in 2019

Our earlier posts (<a href="http://lifesciences.mofo.com/topics/2019-FDA-enforcement-related-litigation-trends.html" title="2019 FDA Enforcement and Related Litigation Trends (Part 1)" target="_blank">part 1</a> and <a href="http://lifesciences.mofo.com/topics/2019-FDA-enforcement-related-litigation-trends-part-2.html" title="2019 FDA Enforcement and Related Litigation Trends (Part 2)" target="_blank">part 2</a>) looked at a few overall trends at FDA as well as the impact of consent decrees issued in 2019. Today we will highlight some enforcement trends at the Department of Justice.Department of Justice Enforcement TrendsIn 2019, the Department of Justice (DOJ) increased its enforcement on opioid manufacturers, distributors, and pharmacies.  On February 8, 2019, the DOJ announced the issuance of a temporary restraining order to stop two Tennessee pharmacies, their owner, and three pharmacists from dispensing controlled substance medications, including opioids.  The complaint alleged that the pharmacies and pharmacists were dispensing and billing Medicare for prescriptions in violation of the Controlled Substances Act and False Claims Act, and that the unlawful dispensing of opioids was tied to the deaths of at least two people and numerous other serious overdoses.  Specifically, the complaint alleges that defendants dispensed controlled substances while ignoring signs of abuse, and falsely billed Medicare for illegally dispensed prescriptions.On April 9, 2019, a grand jury in Virginia indicted Indivior Inc. (formerly known as Reckitt Benckiser Pharmaceuticals Inc.) for engaging in an illicit nationwide scheme to increase prescriptions of an opioid drug used in the treatment of opioid addiction.  The indictment alleges that Indivior promoted its drug without regard for safety concerns and risk of abuse.  Principal Deputy Associate Attorney General Jesse Panuccio noted that “The Department of Justice intends to hold accountable those who are in position to know the harm opioid abuse inflicts, but instead choose to profit illegally from the pain of others.  Manufacturers, distributors, pharmacies, and doctors should all be on notice that they must follow the law and act responsibly.”  On July 11, 2019, Reckitt Benckiser Group agreed to pay $1.4 billion to resolve these claims, including $647 million in forfeiture of proceeds, $700 million for false claims to government healthcare programs, and $50 million to resolve claims with the FTC for unfair methods of competition.  Acting Commissioner Sharpless stated, “Opioid addiction and abuse is an immense public health crisis and taking steps to address it is one of the FDA’s highest priorities . . . .  We also are particularly concerned with schemes to game the drug approval process to prevent generic competition for important medicines.  The FDA, including criminal investigators in our Office of Regulatory Affairs and the lawyers in our Office of Chief Counsel, will continue to work with the Department of Justice to investigate and hold accountable those who devise and participate in schemes to the detriment of the public health.” The DOJ also brought several actions against companies offering copay support to patients through donations to independent charitable foundations.  The focus on independent charitable foundations may be related to the government’s general concern for drug pricing, as press releases related to settlements for independent charitable foundation cases frequently noted that these copay foundations were seen as schemes to support elevated drug prices.  For example, on April 4, 2019, the U.S. Attorney’s Office announced that three pharmaceutical companies – Jazz Pharmaceuticals, Lundbeck, and Alexion Pharmaceuticals – agreed to pay a total of $122.6 million to resolve allegations that they paid kickbacks to Medicare and Civilian Health and Medical Program patients through purportedly independent charitable foundations, violating the False Claims Act.  While announcing the settlement, United States Attorney Andrew E. Lelling stated, “We are committed to ensuring that pharmaceutical companies do not use third-party foundations to pay kickbacks masking the high prices those companies charge for their drugs . . . .  This misconduct is widespread, and enforcement will continue until pharmaceutical companies stop circumventing the anti-kickback laws to artificially bolster high drug prices, all at the expense of American taxpayers.”Paid physician speaker programs and other payments to physicians also continued as a focus for the DOJ in 2019 through Anti-Kickback Statute and False Claims Act claims.  For example, on September 26, 2019, the DOJ announced that Avanir Pharmaceuticals agreed to pay $95,972,017 to resolve allegations under the False Claims Act arising from the company providing remuneration in the form of money, honoraria, travel, and food to certain physicians to induce them to write prescriptions for Nuedexta, and specifically, payment to healthcare professionals for speaker programs based on their willingness to prescribe the product.  Enforcement for these types of programs has been prevalent over the past couple of years, and there have been no signals that we should expect anything different in 2020. ConclusionOverall, it has been a year of continuing trends, with a few new areas of focus dispersed throughout the year for FDA.  We look forward to seeing what 2020 brings, especially under the new leadership and priorities of Commissioner Stephen Hahn.

2019 FDA Enforcement and Related Litigation Trends (Part 3)

Our earlier posts (part 1 and part 2) looked at a few overall trends at FDA as well as the impact of consent decrees issued in 2019. Today we will highlight som

2019 FDA Enforcement and Related Litigation Trends (Part 3)

<a href="http://lifesciences.mofo.com/topics/2019-FDA-enforcement-related-litigation-trends.html" title="2019 FDA Enforcement and Related Litigation Trends (Part 1)" target="_blank">Yesterday</a>, we covered some 2019 stats regarding FDA’s inspections and Warning Letters, and discussed a few specific trends we saw last year. In Part Two of our series, we look at the specifics of FDA’s 2019 consent decrees. FDA Consent DecreesFDA published press releases about six consent decrees in 2019.  As discusssed in Part One, compounding facilities were a focus of FDA enforcement in 2019, and this focus included entering consent decrees, with four of the six consent decrees in 2019 entered against compounding facilities.On February 6, 2019, the U.S. District Court for the Western District of Pennsylvania entered a consent decree between the United States and Ranier’s Rx Laboratory Inc., and owner Francis H. Ranier for manufacturing purportedly sterile drug products in insanitary conditions.  When announcing the consent decree, then-Commissioner Gottlieb stated, “We continue to see concerning activity when it comes to some compounded drugs, including problems related to the conditions under which compounded sterile medicines are made, which can raise significant risks to patients.  This is an area of intense focus for FDA.  We’re committed to making sure that compounded drugs are made under appropriate production standards and, when necessary, taking enforcement actions against compounders who fail to produce sterile drugs in compliance with the law.”   On March 12, 2019, the U.S. District Court for the Northern District of Texas entered a consent decree against Guardian Pharmacy Services and owner Jack Munn.  When announcing the consent decree, Commissioner Gottlieb again confirmed FDA’s enforcement focus on compounding facilities, stating, “Although compounded drugs can serve an important role for certain patients whose medical needs cannot be met by an FDA approved drug product, compounded drugs can also pose unique risks.  They’re not FDA approved and do not undergo premarket review for safety, effectiveness or quality.  All drug compounders must comply with certain requirements, which can include current good manufacturing practice requirements, to avoid product quality problems and potential patient harm.”  According to the complaint, Guardian manufactured and distributed purportedly sterile drug products that were manufactured under insanitary conditions.  Additionally, Guardian’s labels were false or misleading and did not include adequate directions for patient use. On May 22, 2019, the U.S. District Court for the Southern District of Texas entered a consent decree against Pharm D Solutions, LLC, and owners Luis R. De Leon and Juan C. De Leon.  When announcing the consent decree, Acting Commissioner Sharpless stated, “We understand that compounded drugs can be important for patients whose medical needs cannot be met by FDA-approved drug products, and we’re continuing efforts to advance policies to help further improve the quality of compounded products. . . .  These drugs are not approved by the FDA and have not been evaluated for safety or efficacy, so when they’re not appropriately compounded, they have the potential to cause patients harm.  We’ll continue taking enforcement actions, like the one we’re taking today, to ensure that these companies and products do not put patient health at risk.”  According to the complaint, Pharm D Solutions manufactured and distributed drugs that were made under insanitary conditions, had strengths different from what they were represented to possess, and did not include adequate directions for use. Also on May 22, 2019, the U.S. District Court for the Northern District of Illinois entered a consent decree against PharMedium Services and president and vice president Scott Aladeen and Warren Horton for violations at multiple facilities including manufacturing drugs under insanitary conditions and failing to include adequate directions for use.  When announcing the consent decree, Acting Commissioner Sharpless stated, “We will continue to take appropriate actions when compounding pharmacies and outsourcing facilities produce drugs under substandard conditions or use inappropriate practices that could lead to serious harm to patients.”The other two consent decrees were entered on July 18, 2019 and September 3, 2019, respectively, against an Arkansas food and medical product grocery warehouse, J and L Grocery, LLC, for insanitary conditions, and Tennessee drug, dietary supplement, and device distributors Basic Reset and Biogenyx, for distributing unapproved drugs and devices, failing to comply with CGMPs for dietary supplements, and distributing dietary supplements with incomplete labeling. Check back tomorrow for Part Three of our series, where we’ll take a look at some of the Department of Justice enforcement trends in 2019.

2019 FDA Enforcement and Related Litigation Trends (Part 2)

Yesterday, we covered some 2019 stats regarding FDA’s inspections and Warning Letters, and discussed a few specific trends we saw last year. In Part Two of our 

2019 FDA Enforcement and Related Litigation Trends (Part 2)

The year 2019 was one of uncertainty for FDA, as former Commissioner Scott Gottlieb announced his departure in March, ultimately stepping down in April.  For the bulk of the year, FDA was led by Acting Commissioner, Ned Sharpless, until Brett Giroir took over in November, and ultimately, Stephen Hahn was sworn in as the 24th Commissioner of Food and Drugs on December 17, 2019.  In this three-part series, we’ll take a look back at FDA’s enforcement actions over the past year, discuss trends and focuses, and look forward to what we might be able to expect from FDA in 2020. The BasicsFDA conducted a total of 18,034 inspections in FY 2019, 14,377 of those being domestic inspections.  This is a decrease from FY 2018, when there were 21,343 inspections, with 17,330 being domestic inspections. The following shows the breakdown of the different kinds of firms undergoing inspections:As has been the case in previous years, the majority of inspections resulted in a classification of No Action Indicated (NAI). FDA issued a total of 15,015 Warning Letters in FY 2019, which is a slight increase over 2018, but still below the total for 2017.In FY 2019, 14,929 Warning Letters were sent to domestic firms, and 88 were sent to foreign firms.  In FY 2018, 14,358 Warning Letters were sent to domestic firms, and 131 Warning Letters were sent to foreign firms.  The following shows the Warning Letters sent broken down by product type, comparing 2019 to 2018:FDA continued its trend of increasing the number of import alerts, publishing 98 import alerts in 2019, a significant increase over 2018, when 23 import alerts were published, and 2017, when 10 import alerts were published.  The increased number of import alerts corresponds with a decreased number of injunctions and seizures – while in 2017 there were 10 injunctions and two seizures, and in 2018 there were seven injunctions and one seizure, in 2019, there was one injunction and zero seizures – showing FDA’s preference for earlier preventive measures over later involvement.  Specific Trends in 2019Enforcement Specific to Drug Manufacturers An analysis of 483s provided to drug manufacturers in FY 2019 shows that manufacturers continue to struggle with the same themes.  §211.22(d), “Procedures applicable to the quality unit shall be in writing and shall be followed,” was the most frequently cited regulation in 483s sent to drug manufacturers in FY 2019; it was the second most frequently cited regulation in FY 2018.  The frequency of the appearance of this regulation may be explained by FDA’s focus on over-the-counter manufacturers, which often lack formalized quality units.  While the frequency of §211.113(b), “Control of microbiological contamination” dropped consistently from FY 2015 through FY 2018, it increased significantly in FY 2019.  Additionally, §211.160(b), “Lab controls should include scientifically sound specifications” fell from first place in FY 2018 to fourth place in FY 2019. A total of 81 Warning Letters were issued to finished product manufacturers in FY 2019, the highest number since FY 2015.  Warning Letters issued to API manufacturers, however, continued to drop after peaking in FY 2017.  The highest number of Warning Letters were issued to domestic firms, followed by firms in India and China.  The most frequently cited regulation in the Warning Letters issued to drug manufacturers was §211.22, “Responsibilities of the quality control unit” (41 Warning Letters), followed by §211.100, “Written procedures; deviations” (31 Warning Letters).  As mentioned above, FDA continued to focus on over-the-counter drug manufacturers, and Warning Letters to these firms in FY 2019 focused on four main themes: documented adherence to relevant regulations and standards; establishment and suitability of analytical and microbial testing and validation methods; nonconformance management; and the roles, responsibilities, and authority of the quality unit. Homeopathic MedicineOn October 24, 2019, Acting Commissioner Ned Sharpless announced that the Agency was withdrawing Compliance Policy Guide (CPG) 400.400, entitled “Conditions Under Which Homeopathic Drugs May Be Marketed.”  In his announcement Sharpless noted that, “Since the issuance of CPG 400.400 in 1988, the FDA has encountered multiple situations in which homeopathic drug products posed a significant risk to patients, even though the products, as labeled, appeared to meet the conditions described in CPG 400.400.  However, CPG 400.400 is inconsistent with our risk-based approach to regulatory and enforcement action generally and therefore does not reflect our current thinking.”  By withdrawing CPG 400.400, FDA ended its previous exercise of enforcement discretion for the marketing of homeopathic drugs without FDA approval.  In the announcement, Sharpless also noted that FDA had issued more than ten Warning Letters to companies for violations concerning homeopathic products, including to four companies that had manufactured and packaged eye drops in non-sterile conditions.  With the withdrawal of CPG 400.400, FDA also revised its 2017 draft guidance to expand upon the details of FDA’s risk-based enforcement policy, and asked for public input on the revised draft.  The comment period closes on January 23, 2020, and as such, it is likely that we will see continuing trends of enforcement against unproved homeopathic drugs in 2020. Stem CellsAs we head into the last year of FDA’s three-year period of enforcement discretion towards certain regenerative medicine products, which ends in November 2020, it is important to look back at FDA’s related activities in 2019.  Early in the year, on January 15, 2019, Commissioner Gottlieb reinforced the Agency’s focus on stem cell and gene therapies in a statement that noted that FDA anticipates that by 2020, it will receive more than 200 investigational new drug applications per year, building on the more than 800 active investigational new drug applications already on file with FDA.  On April 3, 2019, then-Commissioner Gottlieb released another statement, this one focused on firms illegally manufacturing, selling, and promoting stem cell therapy products.  He noted specifically that contrary to certain industry belief, products originating from the same person they are given back to are still subject to FDA regulation.  In his statement, Commissioner Gottlieb stated that as the Agency comes to the end of the period of enforcement discretion, it may “take additional steps to delineate an efficient development path for promising products that pose lower risk to patients and that are being developed by sponsors who’ve engaged the regulatory process in a responsible manner by filing INDs,” but for products with significant potential risks and that are being developed by sponsors who have not engaged in the regulatory process, the FDA plans to step up its oversight.  The same day, FDA issued twenty-one enforcement letters to manufacturers and health care providers offering unapproved stem cell products.  As we approach November 2020, we expect to see this enforcement trend to continue. CompoundingIn 2019, FDA continued to focus on improving the quality of compounded drugs.  Days before stepping down, Commissioner Gottlieb released a statement on new 2019 efforts to improve the quality of compounded drugs, in which he shared FDA’s 2019 compounding priorities.  Commissioner Gottlieb noted that the Agency would focus on compliance with good manufacturing practice requirements by outsourcing facilities, helping compounders identify insanitary conditions, and performing risk-based inspection and other enforcement efforts to identify compounders producing drugs under substandard conditions.  Additionally, Commissioner Gottlieb stated that the Agency would focus on the inappropriate use of bulk drug substances in compounding, including developing the 503A and 503B lists of appropriate bulk drug substances, and compounding performed by hospitals and health systems.  As noted below, FDA’s stated priority of enforcement against inappropriate compounding conditions held true, with at least four permanent injunctions entered against compounding companies operating under conditions identified as risks to public health and safety in 2019. Dietary SupplementsOn February 11, 2019, Commissioner Gottlieb released “a plan for policy advancements with the goal of implementing one of the most significant modernizations of dietary supplement regulation and oversight in more than 25 years.”  Commissioner Gottlieb noted that while scientific advancement has led to new opportunities for consumers to improve their health, there has also been an increase in the number of adulterated and misbranded products “including those spiked with drug ingredients not declared on their labels, misleading claims, and other risks.”  On the same day, FDA issued twelve Warning Letters and five online advisory letters to companies illegally marketing unapproved drugs claiming to prevent, treat, or cure Alzheimer’s disease and other serious health conditions.  In his statement, Commissioner Gottlieb also highlighted actions taken against dietary supplement manufacturers claiming to prevent, treat, or cure other serious conditions such as cancer and opioid addiction.  One month later, on March 11, 2019, FDA issued a Warning Letter to Nutra Pharma Corp., noting its distribution of new unapproved drugs claiming treatment of cancer, arthritis, and opioid addiction. Throughout 2019, FDA took a particular interest in athletic performance enhancing dietary supplements and probiotic dietary supplements.  For example, on March 13, 2019, six people and two Florida corporations were charged in an indictment for their roles in a scheme to distribute hundreds of thousands illegal products, including anabolic steroids, claiming that the products were high-quality, legal dietary supplements.  Additionally, at the May 14, 2019 Dietary Supplement Regulatory Summit, FDA speakers focused on probiotic labeling, specifically, controversy over the listing of the quantity of colony-forming-units (CFUs) to indicate strength and effectiveness. On May 16, 2019, Steven Tave, FDA Director of the Office of Dietary Supplement Programs, highlighted significant non-compliance by the supplement industry with the FDA’s requirement for Premarket Notification for New Dietary Ingredients (NDIs), estimating that the number of premarket notifications for supplements containing new dietary ingredients submitted is less than 25% of where the Agency expects it should be.  It appears as though FDA will continue more aggressively enforcing the NDI notification requirement in 2020. Electronic Nicotine Delivery SystemsThroughout 2019, FDA stepped up its highly publicized enforcement of Electronic Nicotine Delivery Systems (ENDS) manufacturers and distributors, especially related to marketing practices directed towards children.  On September 9, 2019, FDA issued a Warning Letter to JUUL Labs Inc. for selling and distributing modified-risk tobacco products without an FDA order that permits such sale or distribution.  The Warning Letter highlighted FDA’s concern about JUUL’s claims that their products are safer than cigarettes, and that these claims were made directly to children in school: “Our concern is amplified by the epidemic rate of increase in youth use of ENDS products, including JUUL’s products, and evidence that ENDS products contribute to youth use of, and addiction to, nicotine, to which youth are especially vulnerable.”  Just a few days ago, FDA released its “Enforcement Priorities for Electronic Nicotine Delivery Systems (ENDS) and Other Deemed Products on the Market Without Premarket Authorization” guidance document, indicating that FDA intends to prioritize enforcement against flavored, cartridge-based ENDS products, and products that are either targeted to minors or for which the manufacturer has failed to take adequate measures to prevent minors’ access to the products.  With the release of this document, it is clear that FDA will continue to take enforcement actions against ENDS manufacturers and distributors in 2020. Come back tomorrow for Part Two of our 2019 FDA recap, where we will review last year’s six Consent Decrees.

2019 FDA Enforcement and Related Litigation Trends (Part 1)

The year 2019 was one of uncertainty for FDA, as former Commissioner Scott Gottlieb announced his departure in March, ultimately stepping down in April.  For th

2019 FDA Enforcement and Related Litigation Trends (Part 1)

On November 15, Pfizer’s adalimumab product became the 25th biosimilar approved by FDA under the Biologics Price Competition and Innovation Act (BPCIA).  The road to the 25th approval has been long and has involved some of the biggest companies and medications in the pharmaceutical industry.  In this post, we take a brief look at how we got here, where things stand for the 25 approved biosimilars, and where we are headed next.<a target="_blank" href="https://www.mofo.com/resources/insights/191121-fda-approves-biosimilar.html?utm_source=publication&utm_medium=email"> Read the client alert</a>

FDA Approves 25th Biosimilar

On November 15, Pfizer’s adalimumab product became the 25th biosimilar approved by FDA under the Biologics Price Competition and Innovation Act (BPCIA).  The ro

FDA Approves 25th Biosimilar

On September 23, 2019, China National Intellectual Property Administration (“CNIPA”) announced its proposed amendments to China’s Guideline on Patent Examination (the “Guideline”), which is the counterpart of the Manual of Patent Examining Procedure in the U.S.  The proposed amendments will become effective November 1, 2019.The current Guideline explicitly provides that “human embryonic stem cells and the methods of preparing them are patent-ineligible inventions in accordance with Article 5(1) of the Patent Law.” The Guideline, as amended, has removed this categorical exclusion, and instructs patent examiners in China that they cannot refuse to grant patent rights by reason of “contravening social morality” with respect to inventions on “isolating or obtaining stem cells using human embryos within fourteen (14) days after fertilization that have not been developed in vivo.” Article 5(1) of China’s Patent Law provides that “[n]o patent shall be granted for an invention that contravenes any law or social morality or that is detrimental to public interests.” This provision is in accordance with Article 27.2 of the Agreement on Trade-Related Aspects of Intellectual Property Rights, which permits WTO members to “exclude from patentability inventions, the prevention within their territory of the commercial exploitation of which is necessary to protect ordre public or morality, including to protect human, animal or plant life or health or to avoid serious prejudice to the environment, provided that such exclusion is not made merely because the exploitation is prohibited by their law.”  Similar exclusions based on ordre public or morality can be found in Article 53(a) of the European Patent Convention.Whether an invention contravenes social morality is subject to preliminary examination under China’s Patent Law.  This means that patent examiners in China can reject an application based on contravention of social morality even before substantive examination.  This is particularly important in cases where substantive examination is not provided under the Patent Law, i.e., utility model patents and design patents in China.  Although these types of patent applications are not substantively examined, they can nevertheless be rejected based on Article 5(1) of the Chinese Patent Law.  For example, obscene designs are not patent-eligible in China.Article 5(1) also provides a basis for rejecting a Chinese patent application during substantive examination, and for invalidating a Chinese patent claim.  Therefore, passing the preliminary examination or even obtaining an issued patent is no guarantee that CNIPA will not come back to reject a patent application or invalidate an issued patent for contravention of social morality.An obvious example of inventions contravening social morality in the life sciences industry is methods of human cloning.  Other inventions explicitly prohibited from being patent-eligible under the Guideline for contravention of social morality include “human bodies, regardless of the stages of formation and development, including human germ cells, oosperms, embryos and entire human bodies.”  To accommodate the proposed amendment related to human embryonic stem cells, the Guideline, as amended, states explicitly that “human embryonic stem cells are not human bodies at any stage of formation or development.”Unlike in the United States, where patent eligibility or the lack thereof is frequently the subject of heated legal battles and often subject to judicially crafted tests, China’s primary approach to this issue has been administrative.  Even though the Guideline supposedly only binds patent examiners, we can expect that the Patent Reexamination Board of CNIPA (“PRB”), which is the venue where patents can be invalidated in China, will take a position consistent with the Guideline.  PRB decisions of validity or invalidity are of course, subject to judicial appeal and review, but when it comes to issues related to contravention of social morality, it is also unlikely that Chinese courts will take a different position from that of the Guideline.

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China Patent Eligibility Update: Human Embryonic Stem Cells

China Patent Eligibility Update: Human Embryonic Stem Cells

mofolifesciences-asia

On September 23, 2019, China National Intellectual Property Administration (“CNIPA”) announced its proposed amendments to China’s Guideline on Patent Examinatio

In a recent decision, Ajinomoto v. ITC, the Federal Circuit addressed the issues of doctrine of equivalents and prosecution history estoppel as applied to patent claims reciting specific amino acid sequence of a biologic. On appeal, the Federal Circuit affirmed the decision by the United States International Trade Commission that a protein having 85% to 95% identity infringed a claim reciting specific amino acid sequences under the doctrine of equivalents.The doctrine of equivalents is used to find infringement of products or processes that do not fall within the literal scope of patent claims. The function-way-result test is frequently used to determine equivalents.[1] Prosecution history estoppel limits the reach of equivalents based on claim amendments during prosecution of a patent. Specifically, a narrowing amendment gives rise to the presumption that the territory between the original claim and the amended claim has been surrendered. This presumption can be rebutted, however, if 1) the equivalent was unforeseeable at the time of amendment; 2) the rationale underlying the amendment bears no more than a tangential relationship to the equivalent in question; or 3) there is some other reason suggesting that the patentee could not reasonably be expected to have claimed the equivalent. [2]The Ajinomoto case involved an unusual file history. During prosecution of the asserted patent, Ajinomoto presented a claim that recited two alternatives for the claimed protein:(A) a protein that comprises the amino acid sequence of SEQ ID NO:2; or(B) a protein that comprises an amino acid sequence including deletion, substitution, insertion, or addition of one or several amino acids in the amino acid sequence shown in SEQ ID NO:2.SEQ ID NO:2 corresponds to the amino acid sequence of the E. Coli YddG protein. Facing anticipatory prior art which disclosed an E. Coli protein with a similar sequence, Ajinomoto kept alternative (A) and replaced alternative (B) with “a protein which comprises an amino acid sequence that is encoded by a nucleotide sequence that hybridizes with the nucleotide sequence of SEQ ID NO:1 under stringent conditions.” Ultimately, claims 9 and 15 issued, each reciting one of the alternatives. The asserted claim (claim 20) depends from both claims and recites:A method for producing an aromatic L-amino acid, which comprises cultivating the bacterium according to any one of claims 9-12, 13, 14, 15-18, or 19.The accused bacterial strain expressed a codon-randomized non-E. Coli YddG gene that codes for a protein having 85% – 95% identity with the amino acid sequence of SEQ ID NO:2.[3] The issue before the Court was whether the accused bacterial strain met the protein limitation (A) under the doctrine of equivalents.Although a narrowing claim amendment was made during prosecution, the Court held that prosecution history estoppel did not preclude a finding of equivalents. The Court reasoned that prosecution history applies under unusual circumstances, because the infringement determination rested on finding equivalents of the protein limitation (A), which was not altered during prosecution.[4] The Court found that the amendment to the claim limitation (B) bore no more than a tangential relationship to the accused product because “the objectively evident rationale for the amendment was to limit the set of proteins within the claim’s scope so that it no longer included the prior art E. Coli YfiK protein and, more generally, no longer allowed as wide a range of amino acid alterations. The reason for the amendment had nothing to do with choosing among several DNA sequences in the redundant genetic code that correspond to the same protein.”[5]The Federal Circuit then applied the function-way-result test set forth by the Supreme Court in Graver Tank to determine equivalents.[6] The Federal Circuit found that the accused equivalent performed the same function, namely exporting aromatic L-amino acids out of bacterial cells. The Court found that the accused equivalent performed the function in the same way because the equivalent had 85 – 95% identity with the sequence recited in the claim. The Court further determined that the recited protein and the accused equivalent produced the same result of increasing the ability of the bacteria to produce and accumulate L-tryptophan. The Court consequently concluded that the accused strain infringed the asserted claim under the doctrine of equivalents.Judge Dyk, in dissent, disagreed with the majority’s prosecution history estoppel analysis. In Judge Dyk’s view, the equivalent was directly related to the reason for the claim amendment, namely to exclude those proteins made by an encoding nucleotide that does not hybridize with SEQ ID NO:1.[7]The Ajinomoto decision sheds light on how patents reciting specific sequences of a biologic are analyzed under the existing prosecution history estoppel and doctrine of equivalents frameworks. However, many questions remain unanswered. For example, as noted by the decision, this was an unusual case where the amendment that may have given rise to prosecution history estoppel was not made with respect to the particular limitation at issue. It is unclear whether similar reasoning would apply if the original claim did not list the protein and its variants as alternatives on separate tracks and/or if the narrowing amendment were made to the limitation at issue.The doctrine of equivalents and prosecution history estoppel involve fact-intensive inquiries and detailed analysis of the prosecution history of a patent. Practitioners analyzing infringement of biologics on a patent should go beyond the claimed sequences and consider whether related proteins or nucleic acids may be infringing under the doctrine of equivalents, even if the claims are narrowed during prosecution. In addition, patent applicants should consider the option of starting prosecution with narrow claims when prosecuting a biologics patent application to limit potential prosecution history estoppel arguments down the line during litigation.[1]Graver Tank v. Linde Air Products, 339 U.S. 605, 608 (1950).[2] Festo v. Shoketsu Kinzoku Kogyo Kabushiki, 535 U.S. 722, 740 (2002).[3] Although it is unclear from the opinion, it appears that the Court may be referring to 85% identity with respect to predicted secondary structure based upon the reference cited in the opinion.  [4] Ajinomoto V. ITC, Federal Circuit (2018-1590, 2018-1629), slip opinion at p. 18.[5] Slip opinion at p. 21.[6] Graver Tank at 608.[7] Slip opinion Dissent at p. 7.

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Janet focuses her practice on worldwide patent procurement, patent portfolio management, and strategic planning for life sciences companies. Janet’s clients range from large multinational biopharmaceu

Janet Xiao Ph.D.

Janet focuses her practice on worldwide patent procurement, patent portfolio management, and strategic planning for life sciences companies. Janet’s clients range from large multinational biopharmaceutical companies, such as Celgene and Genentech, to emerging startup companies around the world.

Janet Xiao

Dr. Meghan Poon counsels clients on patent preparation and prosecution, portfolio strategy, and IP due diligence in the areas of biotechnology and biologics. She has significant experience in diverse technologies including antibodies, cell therapies, gene therapies, diagnostics, and gene-edited plants. 

Analyzing Biologics Under the Doctrine of Equivalents and Prosecution History Estoppel

In a recent decision, Ajinomoto v. ITC, the Federal Circuit addressed the issues of doctrine of equivalents and prosecution history estoppel as applied to paten

Analyzing Biologics Under the Doctrine of Equivalents and Prosecution History Estoppel