PTAB Reforms Shift the Battleground: Why Ex Parte Reexaminations Are Gaining Ground as IPRs Fade

By Jake Rosvold & Aydin H. Harston on January 27, 2026

Posted in Legal

In the evolving biosimilar landscape, patent challenges remain a critical strategy to clear the path for market entry. Recent reforms at the Patent Trial and Appeal Board (PTAB) under Director John Squires have significantly altered the inter partes reviews (IPRs) landscape, leading to a steep decline in institution rates. While this shift may initially appear as a hurdle for biosimilar developers seeking to challenge blocking patents, it opens the door to underutilized alternatives like ex parte reexaminations and it increases the criticality of filing post-grant review (PGR) petitions when the opportunity arises (i.e., within 9-months of patent grant). Here we explore these changes, their impact on biosimilars specifically, and why reexams could emerge as a strategic tool in biosimilars manufacturers’ toolboxes.

PTAB Reforms and the Decline in IPR Institutions

Director Squires implemented procedural changes aimed at enhancing efficiency of PTAB proceedings. These changes include centralization of institution decisions under his direct oversight (effective October 2025), proposed rules addressing serial petitions, and real-party-in-interest requirements [1]. These reforms have dramatically decreased IPR institution rates initially. IPR filings declined to 60.4% of total PTAB petitions in 2025 (down from 73% in 2024), procedural denials surged 630% (i.e., to a record 607), and institution rates plummeted from 65-82% in the first quarter to 15-34% by the third quarter [2]. See FIG. 1 (illustrating drop in instituted IPRs); see also FIG. 2 (illustrating slight increase in instituted PGRs). A full review of fiscal year 2025 trial statistics at the PTAB can be found on our PTAB Law Blog.

FIG. 1: Demonstration of IPR filings and institution rates from September 2024 through January 2026. Data for January 2026 were collected through January 25, 2026. The blue bars depict the number of IPR filings for each month; the red line depicts the institution rate (%), where the institution rate is calculated from the number of petitions instituted divided by the total number of decisions made (instituted and denied), excluding settlements, terminations, pending petitions, etc. The trend line shows a downward trend of IPR institution rates. Appended notes depict important dates. Data collected January 25, 2026, and are available at https://data.uspto.gov/ptab/trials/proceedings.

FIG. 2: Demonstration of PGR filings and institution rates from September 2024 through January 2026. Data for January 2026 were collected through January 25, 2026. The yellow bars depict the number of PGR filings for each month; the blue line depicts the institution rate (%), where the institution rate is calculated from the number of petitions instituted divided by the total number of decisions made (instituted and denied), excluding pending petitions. The trend line shows a slightly upward trend of PGR institution rates. Appended notes depict important dates. Data collected January 25, 2026, and are available at https://data.uspto.gov/ptab/trials/proceedings.

Historically, IPRs have been a favored tool for biosimilar applicants under the Biologics Price Competition and Innovation Act (BPCIA), allowing challengers to invalidate key patents efficiently [3, 5]. However, with stricter scrutiny, denials have increased, which may potentially prolong patent disputes and delay biosimilar launches. Recent analysis suggests that IPR institution rates may be climbing off the recent lows, but the rate remains well below the historical average of roughly 67% [7].

Ex Parte Reexaminations: An Underutilized Avenue for Biosimilar Challengers

Amid these PTAB changes, ex parte reexaminations stand out as a promising, yet underutilized, alternative to IPRs. Unlike IPRs, which involve adversarial proceedings (albeit with historically high invalidation rates averaging around 60-70%), ex parte reexams are conducted between the patent owner and an examiner, after the reexamination request is filed by a requester. While the USPTO grants 95% of ex parte reexam requests (vs. 63% institution for IPRs), reexams have lower claim cancellation rates (only 14%) [4]. Approximately 62% of patents that undergo reexamination end up with modified or canceled claims [4]. Filings for ex parte reexams surged 66.1% to 726 in 2025, likely driven by the IPR institution declines [2]. See FIG. 3:

FIG. 3: Demonstration of ex parte reexamination filings from September 2024 through January 2026. Data for January 2026 were collected through January 25, 2026. The green bars depict the number of ex parte reexamination filings for each month. The trend line shows an upward trend of ex parte reexamination filings. Appended notes depict important dates. Data collected January 25, 2026, and are available at https://portal.unifiedpatents.com/exparte/analytics.

For biosimilars developers, an ex parte reexam provides several advantages. The process is cost-effective (i.e., filing fees are around $6,000 vs. $40,000+ for IPRs), anonymous (i.e., no real-party-of-interest disclosure), and flexible, which allows challenges based on printed publications without estoppel risks in subsequent litigation [4]. In biologic patent disputes, where complex formulations and methods are common, ex parte reexams can target narrow invalidity grounds effectively. Another key benefit is that challenges based on double patenting are allowed, which can be critical for challenging patents that extend pharmaceutical exclusivity. However, drawbacks include inability to assert enablement (35 U.S.C. § 112) and eligibility (35 U.S.C. § 101) challenges, and no direct interaction with the examiner after filing the request. Meanwhile, patentees can conduct examiner interviews, submit expert declarations, amend claims, and argue iteratively.

Proposed ‘one-and-done’ rules could bar subsequent PTAB challenges if a patent is upheld in reexam or court, potentially bulletproofing it from further challenges [6]. We are closely monitoring developments in regard to this proposal and will continue to provide updates.

The uptick of ex parte reexams could represent an adaptation to patent challenge strategy. Biosimilar applicants can use them strategically to cancel key claims of blocking patents while minimizing costs and avoiding the uncertainty around IPR institutions. This underutilized tool provides an alternative avenue for challengers to clear patent thickets blocking biosimilar entry.

Impact on the Biosimilars Patent Landscape

Over the years, the biosimilars market has seen robust growth, with PTAB challenges playing a pivotal role in facilitating competition. For example, in pharmaceutical disputes, IPRs historically achieved high institution rates (around 73%) and contributed to settlements that enabled earlier market entry [3]. Under the new regime, lower IPR institution rates shift most patent challenges to district courts, rather than faster and cheaper resolutions at the PTAB, unless PGRs and ex parte reexaminations can fill the void. District court litigations can favor patentees, where patents enjoy a presumption of validity and the standard for proving invalidity is clear and convincing evidence as opposed to the PTAB’s lower standard of a preponderance of the evidence and no presumption of validity.

For biosimilar developers, and for challengers in general, the procedural changes signal a directive from the USPTO to severely limit duplicative or late challenges, favoring recently granted patents. Medical and pharmaceutical petitions, including those for biologics, remained relatively steady at 12.7% of PTAB activity in 2025, indicating sustained interest despite the uncertainty [2]. Challengers may need to adapt strategies, such as focusing on stronger prior art (e.g., airtight, single grounds) to avoid denial or considering the procedural factors likely to impact institution, such as parallel litigation or real-party-in-interest disclosures.

Looking Ahead

While declining IPR institutions may reshape biosimilar strategies, the situation is likely to lead to a rise in ex parte reexaminations as well as PGRs (when available). Ex parte reexaminations offer an efficient, low-risk alternative that biosimilar developers should consider, particularly when double patenting-based challenges are available. These proceedings remain viable under the new regime, and provide alternative pathways to clear patents blocking biosimilar entry.

References

1. USPTO Proposes New Institution Rules and Director Takes Over Merits-Based Institution Decisions, Morgan Lewis. (available at https://www.morganlewis.com/pubs/2025/10/uspto-proposes-new-institution-rules-and-director-takes-over-merits-based-institution-decisions).

2. Patent Dispute Report: 2025 in Review, Unified Patents. (available at https://www.unifiedpatents.com/insights/2026/1/13/patent-dispute-report-2025-in-review).

3. Biosimilar Patent Dance: Leveraging PTAB Challenges for Strategic Advantage, Drug Patent Watch. (available at https://www.drugpatentwatch.com/blog/biosimilar-patent-dance-leveraging-ptab-challenges-for-strategic-advantage/?srsltid=AfmBOopbJSNMW1vtWQXpBWyZmCaOvOLuVZMIDMiZDg53ErL0y3ZRinAs).

4. Ex Parte Reexamination Process, Adibi IP. (available at https://adibiip.com/ex-parte-reexamination-process/).

5. Cracking the Biosimilar Code: A Deep Dive into Effective IP Strategies, Drug Patent Watch. (available at https://www.drugpatentwatch.com/blog/cracking-the-biosimilar-code-a-deep-dive-into-effective-ip-strategies).

6. The Slow Death of AIA Trials: A Look into the USPTO’s ‘One-and-Done’ Rule Package, IPWatchdog. (available at https://ipwatchdog.com/2025/12/09/slow-death-aia-trials-one-and-done/).

7. The Thaw Begins?: What’s Driving IPR Institutions Under Director Squires, Patently-O. (available at https://patentlyo.com/patent/2026/01/driving-institutions-director.html).

Disclaimer: The information contained in this posting does not, and is not intended to, constitute legal advice or express any opinion to be relied upon legally, for investment purposes or otherwise. If you would like to obtain legal advice relating to the subject matter addressed in this posting, please consult with us or your attorney. The information in this post is also based upon publicly available information, presents opinions, and does not represent in any way whatsoever the opinions or official positions of the entities or individuals referenced herein.

How the U.S. Compares to Europe on Biosimilar Approvals and Products In the Pipeline – Updated January 22, 2026

By Alex Shaver & Aydin H. Harston on January 22, 2026

Posted in Regulatory

Many Prolia®/Xgeva® (denosumab) biosimilars approved in 2025 by FDA and EMA.
FDA grants first interchangeable status for rapid acting insulin aspart, Kristy^TM.
EMA sets record with 44 biosimilar authorizations in 2025.

Biosimilars continue to make a significant impact on global healthcare. These products are highly similar to an already-approved reference product, offering a more affordable treatment option without compromising on safety or efficacy. Regulatory bodies like the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) play a critical role in shaping their market introduction. While both agencies share similar goals of ensuring patient safety and promoting access to high-quality therapeutics, their regulatory pathways and approval trends show notable differences.

One such difference is that the EMA has historically been quicker than the FDA in approving biosimilars. Since 2005, the biosimilar regulatory framework in Europe has been implemented through the Committee for Medicinal Products for Human Use (CHMP) under the EMA. The CHMP provides initial assessments for marketing authorization of new medicines that are ultimately approved centrally by the EMA. Since Sandoz’s somatotropin biosimilar, Omnitrope®, was first authorized on April 12, 2006, an additional 161 applications have been approved in Europe. Twenty of the authorizations have been withdrawn post-approval (Table 1). On average, the EMA takes about 1-2 years from submission of a biosimilar application to approval.

In contrast, the FDA’s biosimilar approval process has been relatively slow, with initial approval times averaging 3-4 years for the first generation of biosimilars. This delay in approval is partly due to the FDA’s more rigorous evaluation of biosimilars and the additional data required to achieve interchangeability designation. Additionally, the U.S. did not implement a regulatory framework for biosimilar evaluation until after enactment of the Biologics Price Competition and Innovation Act (BPCIA) of 2009. As the EMA had already approved over a dozen biosimilars by this time, Europe had a significant head start on both the number of approved biosimilars and the regulatory process for approving more. Sandoz’s filgrastim biosimilar, Zarxio®, received the first U.S. approval in 2015, whereas nine filgrastim biosimilars have been approved in Europe dating back to multiple authorizations in 2008. Despite the FDA’s relatively slower biosimilar approval pace, the U.S. biosimilar market has managed to grow continuously over the past decade. Subsequent to Zarxio®’s approval, 89 other biosimilar drugs have gained U.S. approval to date including 25 interchangeable products (Table 2).

As illustrated in the following graph, the EU’s significant head start and higher approval rate led to an imbalance in the number of biosimilar drugs available in the respective markets, and this imbalance was amplified in the past year. In 2025 alone, the EMA authorized a record 44 biosimilars, far outpacing the 26 approvals granted by the FDA. However, in October 2025, the FDA released updated guidance for biosimilars that aims to reduce unnecessary clinical testing and accelerate biosimilar development, so it’s possible the FDA may keep pace with EMA approvals in the future.

For biosimilar approvals, 2025 was the year of denosumab. In the U.S., eight biosimilars were approved for both Prolia® (60 mg pre-filled syringe) and Xgeva® (120 mg vial). In the EU, 12 biosimilars were approved for each product, making denosumab the antibody with the most biosimilars approved to date. Additional highlights for the year 2025 include the FDA’s approval of Omylco® (omalizumab), the first biosimilar of Xolair®, which achieved interchangeability designation, and Kristy^TM, the first, and thus far only, rapid-acting insulin aspart biosimilar to achieve interchangeability status with the reference product NovoLog®.

Looking forward, there are currently only 14 biosimilar applications under review by the EMA for marketing authorization (Table 3). However, as an increasing number of patents expire on biologic drugs, this number is expected to increase. Additionally, the number of abbreviated biologics license applications at the FDA is expected to increase as the primary patents for some blockbuster drugs, such as Keytruda®, expire soon in the U.S. (Table 4).

Table 1. European Medicines Agency List of Approved Biosimilar Drugs.

Biosimilar Proprietary Name	Drug Product	Owner	Status^‡	Authorization/ Withdrawal Date
Abasaglar (previously Abasria)	Insulin Glargine	Eli Lilly Regional Operations GmbH	Authorized	9/9/2014
Abevmy	Bevacizumab	Mylan IRE Healthcare Limited	Authorized	4/21/2021
Abseamed	Epoetin Alfa	Medice Arzneimittel Pütter GmbH & Co. Kg	Authorized	8/28/2007
Absimky	Ustekinumab	Accord Healthcare Ltd	Authorized Withdrawn	12/12/2024 12/15/2025
Accofil	Filgrastim	Accord Healthcare Ltd	Authorized	9/18/2014
Admelog	Insulin lispro	Sanofi	Authorized	5/19/2017
Afiveg	Aflibercept	STADA Arzneimittel AG	Authorized	8/18/2025
Afqlir	Aflibercept	Sandoz	Authorized	11/13/2024
Ahzantive	Aflibercept	Formycon AG	Authorized	1/13/2025
Alpheon	Recombinant Human Interferon Alfa-2a	Biopartners GmbH	Refused	–
Alymsys	Bevacizumab	Mabxience Research SL	Authorized	3/26/2021
Amgevita	Adalimumab	Amgen Europe	Authorized	3/22/2017
Amsparity	Adalimumab	Pfizer Europe MA EEIG	Authorized	2/13/2020
Avtozma	Tocilizumab	Celltrion	Authorized	2/14/2025
Avzivi	Bevacizumab	FGK Representative Service GmbH	Authorized	7/26/2024
Aybintio	Bevacizumab	Samsung Bioepis NL B.V.	Authorized	8/20/2020
Baiama	Aflibercept	Formycon AG	Authorized	1/13/2025
Bekemv	Eculizumab	Amgen Technology UC	Authorized	4/19/2023
Bemfola	Follitropin Alfa	Gedeon Richter Plc.	Authorized	3/27/2014
Benepali	Etanercept	Samsung Bioepis Uk Limited (Sbuk)	Authorized	1/14/2016
Bildyos	Denosumab	Sciencepharma	Authorized	9/17/2025
Bilprevda	Denosumab	Sciencepharma	Authorized	9/17/2025
Binocrit	Epoetin Alfa	Sandoz GmbH	Authorized	8/28/2007
Biograstim	Filgrastim	Abz-Pharma GmbH	Authorized Withdrawn	9/15/2008 9/23/2015
Blitzima	Rituximab	Celltrion	Authorized	7/13/2017
Boomyntra	Denosumab	Fresenius Kabi Deutschland GmbH	Authorized	7/17/2025
Byooviz	Ranibizumab	Samsung Bioepis	Authorized	8/18/2021
Conexxence	Denosumab	Fresenius Kabi Deutschland GmbH	Authorized	7/18/2025
Cyltezo	Adalimumab	Boehringer Ingelheim International GmbH	Authorized Withdrawn	11/10/2017 1/15/2019
Dazublys	Trastuzumab	CuraTeQ Biologics	Authorized	6/30/2025
Degevma	Denosumab	Teva GmbH	Authorized	11/17/2025
Denbrayce	Denosumab	Mabxience Research SL	Authorized	6/26/2025
Denosumab Intas	Denosumab	Intas	Authorized	11/17/2025
Dyrupeg	Pegfilgrastim	CuraTeQ Boilogice	Authorized	3/28/2025
Eiyzey	Aflibercept	Zaklady Farmaceutyczne Polpharma	Authorized	8/14/2025
Eksunbi	Ustekinumab	Samsung Bioepis NL B.V.	Authorized Withdrawn	9/12/2024 8/19/2025
Enwylma	Denosumab	Zentiva k.s.	Authorized	6/26/2025
Epoetin Alfa Hexal	Epoetin Alfa	Hexal Ag	Authorized	8/28/2007
Epysqli	Eculizumab	Samsung Bioepis NL B.V.	Authorized	5/26/2023
Equidacent	Bevacizumab	Centus Biotherapeutics Europe Limited	Authorized Withdrawn	9/25/2020 10/11/2021
Erelzi	Etanercept	Sandoz GmbH	Authorized	6/23/2017
Evfraxy	Denosumab	Biosimilar Collaborations Ireland Limited	Authorized	6/30/2025
Eydenzelt	Aflibercept	Celltrion	Authorized	2/12/2025
Eyluxvi	Aflibercept	Biolitec pharma Limited	Authorized	9/15/2025
Filgrastim Hexal	Filgrastim	Hexal Ag	Authorized	6/2/2009
Filgrastim ratiopharm	Filgrastim	Ratiopharm GmbH	Authorized Withdrawn	9/15/2008 4/20/2011
Flixabi	Infliximab	Samsung Bioepis Uk Limited (SBUK)	Authorized	5/26/2016
Fulphila	Pegfilgrastim	Mylan S.A.S.	Authorized	11/20/2018
Fymskina	Ustekinumab	Formycon AG	Authorized	9/25/2024
Gobivaz	Golimumab	Advanz Pharma Limited	Authorized	11/17/2025
Grastofil	Filgrastim	Apotex Europe Bv	Authorized Withdrawn	10/18/2013 1/13/2025
Grasustek	Pegfilgrastim	Juta Pharma GmbH	Authorized	4/26/2019
Halimatoz	Adalimumab	Sandoz GmbH	Authorized Withdrawn	7/26/2018 12/18/2020
Hefiya	Adalimumab	Sandoz GmbH	Authorized	7/26/2018
Herwenda	Trastuzumab	Sandoz GmbH	Authorized	11/15/2023
Herzuma	Trastuzumab	Celltrion Healthcare Hungary Kft.	Authorized	2/9/2018
Hukyndra	Adalimumab	Stada Arzneimittel AG	Authorized	11/15/2021
Hulio	Adalimumab	Mylan S.A.S.	Authorized	9/19/2018
Hyrimoz	Adalimumab	Sandoz GmbH	Authorized	7/26/2018
Idacio	Adalimumab	Fresenius Kabi Deutschland GmbH	Authorized	4/2/2019
Imraldi	Adalimumab	Samsung Bioepis UK Limited (SBUK)	Authorized	8/24/2017
Imuldosa	Ustekinumab	Accord Healthcare S.L.U.	Authorized	12/12/2024
Inflectra	Infliximab	Hospira Uk Limited	Authorized	9/10/2013
Inhixa	Enoxaparin Sodium	Techdow Europe Ab	Authorized	9/15/2016
Inpremzia	Insulin human	Baxter Holding B.V.	Authorized Withdrawn	4/25/2022 4/20/2023
Insulin aspart Sanofi	Insulin aspartate	Sanofi	Authorized	7/26/2020
Insulin lispro Sanofi	Insulin lispro	Sanofi	Authorized	7/19/2017
Ituxredi	Rituximab	Reddy Holding	Authorized	9/19/2024
Izamby	Denosumab	Mabxience Research SL	Authorized	6/26/2025
Jubbonti	Denosumab	Sandoz GmbH	Authorized	5/16/2024
Jubereq	Denosumab	Accord Healthcare S.L.U.	Authorized	5/26/2025
Junod	Denosumab	Gedeon Richter Plc.	Authorized	6/23/2025
Kanjinti	Trastuzumab	Amgen/Allergan	Authorized	5/16/2018
Kauliv	Teriparatide	Strides Pharma Limited	Authorized	1/12/2023
Kefdensis	Denosumab	Stada Arzneimittel AG	Authorized	11/17/2025
Kirsty (previously Kixelle)	Insulin aspart	Mylan	Authorized	2/8/2021
Kromeya	Adalimumab	Fresenius Kabi Deutschland GmbH	Authorized Withdrawn	4/2/2019 12/17/2019
Lextemy	Bevacizumab	Mylan IRE Healthcare Limited	Authorized Withdrawn	4/21/2021 6/21/2021
Libmyris	Adalimumab	Stada Arzneimittel AG	Authorized	11/12/2021
Livogiva	Teriparatide	Theramex Ireland Limited	Authorized	8/27/2020
Lusduna	Insulin Glargine	Merck Sharp & Dohme Limited	Authorized Withdrawn	4/1/2017 10/29/2018
Lyumjev	Insulin lispro	Eli Lilly Nederland B.V.	Authorized	3/24/2020
Movymia	Teriparatide	Stada Arzneimittel Ag	Authorized	1/11/2017
Mvasi	Bevacizumab	Amgen Europe B.V.	Authorized	1/15/2018
Mynzepli	Aflibercept	Advanz Pharma Limited	Authorized	8/18/2025
Nepexto	Etanercept	Mylan and Lupin	Authorized	6/4/2020
Nivestim	Filgrastim	Hospira Uk Ltd	Authorized	6/8/2010
Nyvepria	Pegfilgrastim	Pfizer Europe MA EEIG	Authorized	11/18/2020
Obodence	Denosumab	Samsung Bioepis	Authorized	2/12/2025
Ogivri	Trastuzumab	Viatris	Authorized	12/12/2018
Omlyclo	Omalizumab	Celltrion Healthcare Hungary Kft,	Authorized	5/16/2024
Omnitrope	Somatropin	Sandoz GmbH	Authorized	4/12/2006
Onbevzi	Bevacizumab	Samsung Bioepis Co., Ltd.	Authorized Withdrawn	1/13/2021 10/24/2024
Ontruzant	Trastuzumab	Samsung Bioepis Co., Ltd.	Authorized	11/17/2017
Opuviz	Aflibercept	Samsung Bioepis NL B.V.	Authorized	9/19/2024
Osenvelt	Denosumab	Celltrion	Authorized	2/14/2025
Osvyrti	Denosumab	Accord Healthcare S.L.U.	Authorized	5/26/2025
Otulfi	Ustekinumab	Fresenius Kabi Deutschland GmbH	Authorized	9/25/2024
Ovaleap	Follitropin Alfa	Teva Pharma B.V.	Authorized	9/27/2013
Oyavas	Bevacizumab	STADA Arzneimittel AG	Authorized	3/26/2021
Pavblu	Aflibercept	Amgen	Authorized	4/04/2025
Pegfilgrastim Mundipharma (Cegfila)	Pegfilgrastim	Mundipharma Biologics S.L.	Authorized	12/19/2019
Pelgraz	Pegfilgrastim	Accord Healthcare Limited	Authorized	9/25/2018
Pelmeg	Pegfilgrastim	Cinfa Biotech S.L.	Authorized	11/20/2018
Ponlimsi	Denosumab	Teva GMBH	Authorized	11/17/2025
Pyzchiva	Ustekinumab	Samsung Bioepis NL B.V.	Authorized	4/19/2024
Qoyvolma	Ustekinumab	Celltrion Healthcare Hungary Kft.	Authroized	6/02/2025
Qutavina	Teriparatide	EuroGenerics Holdings BV	Authorized Withdrawn	8/31/2020 11/26/2020
Ranibizumab Midas (Epruvy)	Ranibizumab	Midas Pharma GmbH	Authorized	9/19/2024
Ranivisio	Ranibizumab	Midas Pharma GmbH	Authorized	8/25/2022
Ratiograstim	Filgrastim	Ratiopharm GmbH	Authorized	9/15/2008
Remsima	Infliximab	Celltrion Healthcare Hungary Kft.	Authorized	9/10/2013
Retacrit	Epoetin Zeta	Hospira Uk Limited	Authorized	12/18/2007
Rimmyrah	Ranibizumab	Qilu Pharma Spain S.L.	Authorized	1/05/2024
Ritemvia	Rituximab	Celltrion	Authorized Withdrawn	7/13/2017 6/21/2021
Rituzena (previously Tuxella)	Rituximab	Celltrion	Authorized Withdrawn	7/13/2017 4/12/2019
Rixathon	Rituximab	Sandoz GmbH	Authorized	6/15/2017
Riximyo	Rituximab	Sandoz GmbH	Authorized	6/15/2017
Rolcya	Denosumab	Sandoz GmbH	Authorized	7/17/2025
Ruxience	Rituximab	Pfizer Europe MA EEIG	Authorized	4/1/2020
Semglee	Insulin glargine	Mylan S.A.S.	Authorized	3/27/2018
Silapo	Epoetin Zeta	Stada Arzneimittel Ag	Authorized	12/18/2007
Skojoy	Aflibercept	Amgen	Withdrawn	3/04/2025
Solumarv	Insulin Human	Marvel Lifesciences Ltd	Refused	–
Solymbic	Adalimumab	Amgen Europe	Authorized Withdrawn	3/22/2017 6/15/2018
Sondelbay	Teriparatide	Accord Healthcare S.L.U.	Authorized	3/24/2022
Steqeyma	Ustekinumab	Celltrion Healthcare Hungary Kft.	Authorized	8/22/2024
Stimufend	Pegfilgrastim	Fresenius Kabi Deutschland GmbH	Authorized	3/28/2022
Stoboclo	Denosumab	Celltrion	Authorized	2/14/2025
Terrosa	Teriparatide	Gedeon Richter Plc.	Authorized	1/4/2017
Tevagrastim	Filgrastim	Teva GmbH	Authorized	9/15/2008
Thorinane	Enoxaparin Sodium	Pharmathen S.A.	Authorized Withdrawn	9/15/2016 10/24/2019
Tocilizumab STADA (previously Tofidence)	Tocilizumab	STADA Arzneimittel AG	Authorized	6/20/2024
Trazimera	Trastuzumab	Pfizer	Authorized	7/26/2018
Truvelog Mix 30	Insulin aspart	Sanofi Winthrop Industrie	Authorized	4/25/2022
Truxima	Rituximab	Celltrion Healthcare Hungary Kft.	Authorized	2/17/2017
Tuznue	Trastuzumab	Prestige Biopharma Belgium	Authorized	9/19/2024
Tyenne	Tocilizumab	Fresenius Kabi Deutschland GmbH	Authorized	9/15/2023
Tyruko	Natalizumab	Sandoz GmbH	Authorized	9/22/2023
Udenyca	Pegfilgrastim	Coherus/ERA Consulting GmbH	Authorized Withdrawn	9/25/2018 2/4/2021
Usgena	Ustekinumab	Stada Arzneimittel AG	Authorized	11/17/2025
Usrenty	Ustekinumab	Biosimilar Collaborations Ireland Limited	Authorized	9/17/2025
Usymro	Ustekinumab	Gedeon Richter Plc.	Authorized	8/14/2025
Uzpruvo	Ustekinumab	Stada Arzneimittel	Authorized	1/05/2024
Vegzelma	Bevacizumab	Celltrion Healthcare	Authorized	8/17/2022
Vevzuo	Denosumab	Biosimilar Collaborations Ireland Limited	Authorized	6/25/2025
Vgenfli	Aflibercept	Zaklady Farmaceutyczne Polpharma	Authorized	8/14/2025
Vivlipeg	Pegfilgrastim	Biosimilar Collaborations Ireland Limited	Authorized	8/18/2025
Wezenla	Ustekinumab	Amgen Technology UC	Authorized	6/20/2024
Wyost	Denosumab	Sandoz GmbH	Authorized	5/17/2024
Xbryk	Denosumab	Samsung Bioepis	Authorized	2/15/2025
Ximluci	Ranibizumab	STADA Arzneimittel AG	Authorized	3/26/2022
Yaxwer	Denosumab	Gedeon Richter Plc.	Authorized	6/23/2025
Yesafili	Aflibercept	Biosimilar Collaborations Ireland Limited	Authorized	7/20/2023
Yesintek	Ustekinumab	Biocon	Authorized	2/14/2025
Yuflyma	Adalimumab	Celltrion Healthcare Hungary Kft.	Authorized	2/11/2021
Valtropin	Somatropin	Biopartners GmbH	Authorized Withdrawn	4/24/2006 5/10/2012
Zadenvi	Denosumab	Zentiva k.s.	Authorized	6/26/2025
Zarzio	Filgrastim	Sandoz GmbH	Authorized	2/6/2009
Zefylti	Filgrastim	CuraTeQ Biologics	Authorized	2/12/2025
Zercepac	Trastuzumab	Accord Healthcare S.L.U.	Authorized	7/28/2020
Zessly	Infliximab	Sandoz GmbH	Authorized	5/18/2018
Ziextenzo	Pegfilgrastim	Sandoz GmbH	Authorized	11/22/2018
Zirabev	Bevacizumab	Pfizer	Authorized	2/14/2019
Zvogra	Denosumab	Stada Arzneimittel AG	Authorized	11/17/2025

Table 2. U.S. Food and Drug Administration List of Approved Biosimilar Drugs.

No.	Drug Product	Company	Reference Product and Sponsor	Marketing Status	FDA Approval Date
90	Boncresa® (denosumab-mobz)	Amneal Pharmaceuticals	Amgen Prolia®	Not Available	12/22/2025
89	Oziltus® (denosumab-mobz)	Amneal Pharmaceuticals	Amgen Xgeva®	Not Available	12/22/2025
88	Nufymco® (ranibizumab-leyk)	Formycon	Genentech Lucentis®	Not Available	12/18/2025
87	Armlupeg (pegfilgrastim-unne)	Lupin	Amgen Neulasta®	Not Available	11/28/2025
86	Poherdy® (pertuzumab-dpzb)	Shanghai Henlius Biotech	Genentech Perjeta®	Not Available	11/13/2025
85	Osvyrti® (denosumab-desu)	Accord Biopharma	Amgen Prolia®	Not Available	10/29/2025
84	Jubereq® (denosumab-desu)	Accord Biopharma	Amgen Xgeva®	Not Available	10/29/2025
83	Eydenzelt® (aflibercept-boav)	Celltrion	Regeneron Eylea®	Not Available Launch Expected December 2027	10/02/2025
82	Enoby (denosumab-qbde)	Hikma Pharmaceuticals	Amgen Prolia®	Launched January 2026	9/26/2025
81	Xtrenbo (denosumab-qbde)	Hikma Pharmaceuticals	Amgen Xgeva®	Launched January 2026	9/26/2025
80	Aukelso (denosumab-kyqq)	Biocon Biologics	Amgen Prolia®	Launched October 2025	9/16/2025
79	Bosaya (denosumab-kyqq)	Biocon Biologics	Amgen Xgeva®	Launched October 2025	9/16/2025
78	Bidyos® (denosumab-nxxp)	Shanghai Henlius Biotech	Amgen Prolia®	Not Available	8/29/2025
77	Bilprevda® (denosumab-nxxp)	Shanghai Henlius Biotech	Amgen Xgeva®	Not Available	8/29/2025
76	Kristy^TM (insulin aspart-xjhz)	Biocon Biologics	Novo Nordisk Novolog®	Not Available	7/15/2025
75	Starjemza^TM (ustekinumab-hmny)	Bio-thera Solutions	Janssen Stelara®	Launched November 2025	5/22/2025
74	Jobevne^TM (bevacizumab-nwgd)	Biocon Biologics	Genentech Avastin®	Available	4/09/2025
73	Bomyntra® (denosumab-bnht)	Fresenius Kabi	Amgen Xgeva®	Launched July 2025	3/25/2025
72	Conexxence® (denosumab-dbnht)	Fresenius Kabi	Amgen Prolia®	Launched July 2025	3/25/2025
71	Omlyclo® (omalizumab-igec)	Celltrion	Genentech Xolair®	Not Available Launch Expected September 2026	3/07/2025
70	Stoboclo® (denosumab-bmwo)	Celltrion	Amgen Prolia®	Launched July 2025	2/28/2025
69	Osenvelt® (denosumab-bmwo)	Celltrion	Amgen Xgeva®	Launched July 2025	2/28/2025
68	Merilog^TM (insulin aspart-szjj)	Sanofi-Aventis	Novo Nordisk Novolog®	Not Available	2/14/2025
67	Xbryk^TM (denosumab-dssb)	Samsung Bioepis	Amgen Xgeva®	Not Available	2/13/2025
66	Ospomyv^TM (denosumab-dssb)	Samsung Bioepis	Amgen Prolia®	Not Available	2/13/2025
65	Avtozma® (tocilizumab-anoh)	Celltrion	Genentech Actemra®	Launched October 2025	1/30/2025
64	Steqeyma® (Ustekinumab-stba)	Celltrion	Janssen Stelara®	Launched March 2025	12/17/2024
63	Yesintek^TM (ustekinumab-kfce)	Biocon Biologics Inc.	Janssen Stelara®	Launched February 2025	11/29/2024
62	Imuldosa® (ustekinumab-srlf)	Accord Biopharma	Janssen Stelara®	Launched August 2025	10/10/2024
61	Otulfi® (ustekinumab-aauz)	Fresenius Kabi	Janssen Stelara®	Launched March 2025	9/27/2024
60	Pavblu® (aflibercept-ayyh)	Amgen	Regeneron Eylea®	Launched October 2024	8/23/2024
59	Enzeevu^TM (aflibercept-abzv)	Sandoz	Regeneron Eylea®	Not Available	8/09/2024
58	Epysqli® (eculizumab-aagh)	Samsung Bioepis	Alexion Soliris®	Launched April 2025	7/19/2024
57	Ahzantive® (aflibercept-mrbb)	Formycon AG	Regeneron Eylea®	Not Available	6/28/2024
56	Nypozi® (filgrastim-txid)	Tanvex Biopharma	Amgen Neupogen®	Not Available	6/28/2024
55	Pyzchiva® (ustekinumab-ttwe)	Samsung Bioepis	Janssen Stelara®	Launched February 2025	6/28/2024
54	Bkemv® (eculizumab-aeeb)	Amgen	Alexion Soliris®	Launched March 2025	5/28/2024
53	Yesafili^TM (aflibercept-jbvf)	Biocon Biologics	Regeneron Eylea®	Not Available Launch Expected July 2026	5/20/2024
52	Opuviz^TM (aflibercept-yszy)	Samsung Bioepis	Regeneron Eylea®	Not Available Launch Delayed to 2026	5/20/2024
51	Hercessi® (trastuzumab-strf)	Accord Biopharma	Genentech Herceptin®	Launched November 2024	4/25/2024
50	Selarsdi® (ustekinumab-aekn)	Alvotech	Janssen Stelara®	Launched February 2025	4/16/2024
49	Tyenne® (tocilizumab-aazg)	Fresenius Kabi	Genentech Actemra®	Launched April 2024	3/05/2024
48	Jubbonti® (denosumab-bbdz)	Sandoz	Amgen Prolia®	Launched June 2025	3/05/2024
47	Wyost® (denosumab-bbdz)	Sandoz	Amgen Xgeva®	Launched June 2025	3/05/2024
46	Simlandi® (adalimumab-ryvk)	Alvotech	AbbVie Humira®	Launched May 2024	2/23/2024
45	Avzivi® (bevacizumab-tnjn)	Bio-thera Solutions	Genentech Avastin®	Not Available	12/06/2023
44	Wezlana^TM (ustekinumab-auub)	Amgen	Janssen Stelara®	Launched January 2025	10/31/2023
43	Tofidence® (tocilizumab-bavi)	Biogen	Genentech Actemra®	Launched May 2024	9/29/2023
42	Tyruko® (natalizumab-sztn)	Sandoz	Biogen Tysabri®	Launched February 2024	8/24/2023
41	Yuflyma® (adalimumab-aaty)	Celltrion	AbbVie Humira®	Launched July 2023	5/23/2023
40	Idacio® (adalimumab-aacf)	Fresenius Kabi	AbbVie Humira®	Launched July 2023	12/13/2022
39	Vegzelma® (bevacizumab-adcd)	Celltrion	Genentech Avastin®	Launched April 2023	9/27/2022
38	Stimufend® (pegfilgrastim-fpgk)	Fresenius Kabi	Amgen Neulasta®	Launched February 2023	9/01/2022
37	Cimerli® (ranibizumab-eqrn)	Sandoz	Genentech Lucentis®	Launched October 2022	8/02/2022
36	Fylnetra® (pegfilgrastim-pbbk)	Kashiv Biosciences	Amgen Neulasta®	Launched May 2023	5/26/2022
35	Alymsys® (bevacizumab-maly)	Amneal	Genentech Avastin®	Launched October 2022	4/13/2022
34	Releuko® (filgrastim-ayow)	Kashiv Biosciences & Amneal Pharmaceuticals	Amgen Neupogen®	Launched November 2022	2/28/2022
33	Yusimry® (adalimumab-aqvh)	Coherus	AbbVie Humira®	Launched July 2023	12/20/2021
32	Rezvoglar® (insulin glargine-aglr)	Eli Lilly	Sanofi Lantus®	Launched April 2023	12/20/2021
31	Byooviz® (ranibizumab-nuna)	Samsung Bioepis and Biogen	Genentech Lucentis®	Launched July 2022	9/17/2021
30	Semglee® (insulin glargine-yfqn) INTERCHANGEABLE	Viatris and Biocon Biologics	Sanofi Lantus®	Launched November 2021	7/28/2021
29	Riabni^TM (rituximab-arrx)	Amgen	Biogen and Genentech Rituxan®	Launched January 2021	12/17/2020
28	Hulio (adalimumab-fkjp)	Mylan	AbbVie Humira®	Launched July 2023	7/6/2020
27	Nyvepria® (pegfilgrastim-apgf)	Pfizer	Amgen Neulasta®	Launched January 2021	6/10/2020
26	Avsola® (infliximab-axxq)	Amgen	Janssen Remicade®	Launched July 2020	12/6/2019
25	Abrilada^TM (adalimumab-afzb)	Pfizer	AbbVie Humira®	Launched November 2023	11/15/2019
24	Ziextenzo® (pegfilgrastim-bmez)	Sandoz	Amgen Neulasta®	Launched November 2019	11/4/2019
23	Hadlima^TM (adalimumab-bwwd)	Samsung Bioepis	AbbVie Humira®	Launched July 2023	7/23/2019
22	Ruxience® (rituximab-pvvr)	Pfizer	Biogen and Genentech Rituxan®	Launched January 2020	7/23/2019
21	Zirabev^TM (bevacizumab-bvzr)	Pfizer	Genentech/Roche Avastin®	Launched December 2019	6/28/2019
20	Kanjinti® (trastuzumab-anns)	Amgen	Roche/Genentech Herceptin®	Launched July 2019	6/13/2019
19	Eticovo® (etanercept-ykro)	Samsung Bioepis	Amgen Enbrel®	Not available	4/25/2019
18	Trazimera® (trastuzumab-qyyp)	Pfizer	Roche/Genentech Herceptin®	Launched February 2020	3/11/2019
17	Ontruzant® (trastuzumab-dttb)	Samsung Bioepis	Roche/Genentech Herceptin®	Launched April 2020	1/18/2019
16	Herzuma® (trastuzumab-pkrb)	Celltrion and Teva	Roche/Genentech Herceptin®	Launched March 2020	12/14/2018
15	Truxima® (rituximab-abbs)	Celltrion and Teva	Biogen and Genentech Rituxan®	Launched November 2019	11/28/2018
14	Udenyca® (pegfilgrastim-cbqv)	Coherus BioSciences	Amgen Neulasta®	Launched January 2019	11/2/2018
13	Hyrimoz® (adalimumab-adaz)	Sandoz	AbbVie Humira®	Launched July 2023	10/30/2018
12	Nivestym® (filgrastim-aafi)	Pfizer	Amgen Neupogen®	Launched October 2018	7/20/2018
11	Fulphila® (pegfilgrastim-jmdb)	Mylan/Biocon	Amgen Neulasta®	Launched July 2018	6/4/2018
10	Retacrit® (epoetin alfa-epbx)	Pfizer	Janssen Procrit®	Launched November 2018	5/15/2018
9	Ixifi® (infliximab-qbtx)	Pfizer	Janssen Remicade®	Not Available	12/13/2017
8	Ogivri® (trastuzumab-dkst)	Mylan/Biocon	Roche/Genentech Herceptin®	Launched December 2019	12/01/2017
7	Mvasi® (bevacizumab-awwb)	Amgen Allergan	Genentech/Roche Avastin®	Launched July 2019	9/14/2017
6	Cyltezo® (adalimumab-adbm) INTERCHANGEABLE	Boehringer Ingelheim International GmbH	AbbVie Humira®	Launched July 2023	8/25/2017
5	Renflexis® (infliximab-abda)	Samsung Bioepis	Janssen Remicade®	Launched July 2017	4/21/2017
4	Amjevita® (adalimumab-atto)	Amgen	AbbVie Humira®	Launched January 2023	9/23/2016
3	Erelzi ® (etanercept-szzs)	Sandoz	Amgen Enbrel® (etanercept)	Not Available	8/30/2016
2	Inflectra® (infliximab-dyyb)	Celltrion/Pfizer	Janssen Remicade®	Launched November 2016	4/05/2016
1	Zarxio® (filgrastim-sndz)	Sandoz	Amgen Neupogen®	Launched September 2015	03/06/2015

Table 3. European Medicines Agency List of Biosimilars Under Evaluation for Marketing Approval (Source: EMA list of applications for new human medicines compiled on January 16, 2026, and published on January 20, 2026).

Drug Product	Reference Product Proprietary Name	Reference Product Sponsor	Number of Applications
Bevacizumab	Avastin®	Genentech	1
Denosumab	Prolia®	Amgen	1
Etanercept	Enbrel®	Amgen	1
Insulin aspart			3
Insulin lispro			1
Omalizumab	Xolair®	Genentech	1
Pegfilgrastim			1
Pertuzumab	Perjeta®	Roche/Genentech	2
Ranibizumab	Lucentis®	Genentech	1
Teriparatide	Forteo®/Forsteo®	Eli Lilly	1
Tocilizumab	Actemra®	Genentech	1

Table 4. Biologics having already expired or nearing primary patent expiry in the U.S. and biologics that have biosimilars in the regulatory pipeline.

Drug Product	Primary U.S. Patent Expiry*
OnabotulinumtoxinA (Botox®)	Primary patents long-expired, various use patents pending
Insulin products (various)	Primary patents long-expired
Filgrastim (Neupogen®)	2013
Epoetin alfa (Epogen®)	2013
Pegfilgrastim (Neulasta®)	2015
Adalimumab (Humira®)	2016
Rituximab (Rituxan®)	2018
Cetuximab (Erbitux®)	2018
Omalizumab (Xolair®)	2018
Infliximab (Remicade®)	2018
Teriparatide (Forteo®)	2019
Bevacizumab (Avastin®)	2019
Trastuzumab (Herceptin®)	2019
Tocilizumab (Acetmra®)	2019
Abatacept (Orencia®)	2019
Ranibizumab (Lucentis®)	2020
Panitumumab (Vectibix®)	2020
Eculizumab (Soliris®)	2021
Aflibercept (Eylea®)	2023
Denosumab (Prolia® and Xgeva®)	2023
Palivizumab (Synagis®)	2023
Ustekinumab (Stelara®)	2023
Certolizumab pegol (Cimzia®)	2024
Golimumab (Simponi®)	2024
Darbepoetin alfa (Aranesp®)	2024
Pertuzumab (Perjeta®)	2024
Canakinumab (Ilaris®)	2024
Benralizumab (Fasenra®)	2024
Ipilimumab (Yervoy®)	2025
Natalizumab (Tysabri®)	2027
Etanercept (Enbrel®)	2028
Pembrolizumab (Keytruda®)	2028
Ocrelizumab (Ocrevus®)	2028
Nivolumab (Opdivo®)	2028
Tezepelumab (Tezspire®)	2028
Daratumumab (Daralex®)	2029
Secukinumab (Cosentyx®)	2029
Anifrolumab (Saphnelo®)	2029
Vedolizumab (Entyvio®)	2031
Tremelimumab (Imjudo®)	2031
Nirsevimab (Beyfortus®)	2035
Ravulizumab (Ultomiris®)	2035

*Expiration dates are estimated and subject to change, for example, if pending patent term extension applications are granted.

Supreme Court to Address ‘Skinny Label’ Patent Disputes

By Anh-Thu Lam & Aydin H. Harston on January 20, 2026

Posted in Legal

Introduction

On January 16, 2026, the U.S. Supreme Court agreed to hear Hikma Pharmaceuticals USA, Inc. v. Amarin Pharma, Inc., a patent dispute that could reshape the landscape of generic drug competition and patent enforcement.

This case centers on a contentious question: If a generic drug is labeled only for non-infringing uses (a so-called ‘skinny label’), can a generic company still be liable for inducing patent infringement of the branded innovator’s remaining patented uses, even when the FDA-approved label omits the patented use? The Supreme Court’s decision to grant review signals the importance of this issue for both branded and generic manufacturers.

What Is a Skinny Label?

Under the Hatch-Waxman Act, generic drug applicants can seek FDA approval only for indications no longer protected by patents. This “section viii carve-out” process creates a skinny label – a label that omits patented uses so that generics may enter the market before all patents covering the reference product expire. The goal of this framework is to balance affordable competition with innovation incentives.

In practice, a skinny label works like this:

A branded drug is approved for multiple indications.
Some of those indications are covered by patents that expire later than other indications.
A generic applicant carves out one or more patented indications from its label.
The generic launches with a label limited to expired indications.

Generic manufacturers have historically relied on this pathway to avoid patent infringement liability and bring generic products to market sooner. But the Hikma case raises the question of whether the protection from infringement liability has been nullified by the Federal Circuit’s decision.

The Hikma/Amarin Dispute

The dispute involves Amarin’s cardiovascular drug Vascepa^®and a generic version marketed by Hikma. Vascepa^® received FDA approval for an initial indication (severe hypertriglyceridemia) and later for a cardiovascular risk reduction indication – the latter still patent protected. Hikma’s generic was approved only for the off-patent hypertriglyceridemia indication, omitting the cardiovascular use from its skinny label, as permitted by the FDA. In 2020, Amarin filed suit alleging that Hikma’s marketing materials (e.g., press releases, public statements) encouraged physicians to prescribe the generic for the patented cardiovascular use, constituting induced infringement. A federal district court initially dismissed the infringement claims as insufficiently pled, but the U.S. Court of Appeals for the Federal Circuit reversed in 2024, finding Amarin’s allegation plausible when considering Hikma’s combined label and public statements. Hikma then petitioned the Supreme Court, arguing that the Federal Circuit’s approach effectively nullifies the statutory Section viii carve-out process and threatens generic competition.

The critical facts included that Hikma’s product had already been launched, as opposed to being a Hatch-Waxman case or merely a section viii case that did not involve ongoing, alleged induced infringement. Further, while Hikma’s press release stated that its “product is not approved for any other indication for the reference listed drug VASCEPA®” and its website provided a disclaimer that “Hikma’s generic version is indicated for fewer than all approved indications of the Reference Listed Drug,” some of Hikma’s press releases referred to the product as either a “generic version of VASCEPA®” or “generic VASCEPA®” and did not include AB-rating disclaimers (indicating that “a generic drug is therapeutically equivalent to a branded drug when the generic drug is used as labeled. It does not reflect a decision of therapeutic equivalence for off-label use.”). Further, Hikma’s press releases referred to VASCEPA’s entire revenue for all uses, including the CV indication, which the Federal Circuit considered as a factor indicating potential for encouraging use for all of VASCEPA’s indications.

Legal Questions Before the Supreme Court

This Hikma case presents the Supreme Court with a series of legal questions arising from the Federal Circuit’s decision. First, it must consider whether the use of a skinny label alone is sufficient to shield a generic manufacturer from liability for induced infringement. Although it has traditionally been presumed that carving out patented uses from a generic label avoids infringement, the Federal Circuit suggested that other public-facing conduct – such as marketing material, press releases, and representations of therapeutic equivalence to the branded drug – may still give rise to liability. Second, the Court must assess the role that that marketing and other non-label communications play in the inducement analysis, particularly where those communications are consistent with FDA approval but may nonetheless encourage infringing use. Finally, the case presents an opportunity to clarify the proper standard for induced infringement in the skinny-label context, including whether traditional inducement principles should apply or whether a modified standard is warranted when FDA-mandated labeling constraints are involved.

Practical Implications for Industry Stakeholders

Beyond doctrinal questions, the Court’s resolution is likely to have practical consequences for a range of stakeholders, shaping not only liability for skinny-label generics but also how both branded and generic companies assess risk, structure litigation strategies, and communicate about approved products, with downstream effects for the healthcare system more broadly.

Against the backdrop of heightened uncertainty, stakeholders should be thinking proactively about how to adapt their strategies in anticipation of a shifting legal landscape. Regardless of how the Court ultimately rules, the Hikma case underscores the need for careful planning and risk management when navigating skinny labels and post-approval conduct – making forward-looking strategic preparation essential. For branded manufacturers, enforcement strategies should incorporate inducement theories post-launch – but be wary of over-extension that could invite political scrutiny or antitrust issues. For generics, all product communications should be audited against potential inducement risk, including careful review of press releases, marketing content, and physician messaging for skinny labeled products.

A Landmark Case and Legislative Development

This is the first time in years that the Supreme Court has heard a patent dispute, and is set to provide a landmark decision for skinny labels. The decision will reset the balance of generic competition and patent protection– and how courts will interpret that balance in an era where marketing and product communications are increasingly scrutinized. At the same time, Congress is considering the Skinny Labels, Big Savings Act, billed as a bipartisan bill to help lower prescription drug costs by protecting generic drug makers from abusive lawsuits and preserving patient access to affordable medications. The bill specifically lists the following as actions that are not considered infringement of a method of use claim in a patent under the Federal Food, Drug, and Cosmetic Act:

submitting or seeking approval of a skinny label for a generic or biosimilar drug;
promoting or commercially marketing a drug with skinny labeling approved by the FDA; or
describing a drug product approved by the FDA as a generic of, or therapeutically equivalent to, the branded drug.

Looking Ahead

We will continue to monitor further developments relating to skinny labels and provide insight and updates as they become available.

FDA Proposes Sweeping Changes to Accelerate Biosimilar Development

By Michael Ellenberger & Aydin H. Harston on November 7, 2025

Posted in News

On October 29, 2025, the U.S. Food and Drug Administration (FDA), in coordination with the Department of Health and Human Services (HHS) and the Centers for Medicare and Medicaid Services (CMS), announced a new strategy aimed at dramatically reducing the cost and timeline of biosimilar development (U.S. Food and Drug Administration,FDA Moves to Accelerate Biosimilar Development and Lower Drug Costs, Oct. 29, 2025). The proposed reforms, introduced through a new draft guidance,[1] would eliminate many comparative clinical efficacy studies, previously required for biosimilar approval, and thereby simplify the process for obtaining an interchangeability designation.

A Shift Away from Comparative Clinical Trials

Under the draft guidance, developers of new biosimilar compounds will generally no longer be required to conduct human comparative efficacy studies when analytical testing can sufficiently demonstrate biosimilarity (U.S. Food and Drug Administration, Scientific Considerations in Demonstrating Biosimilarity, Draft Guidance, 2025). These previously required studies typically last one to three years and may cost more than $20 million per product. However, in the draft guidance, the FDA asserts that such trials add “little scientific value” relative to advanced analytical assessments of molecular structure and function. (U.S. Food and Drug Administration, Fact Sheet: Bringing Lower-Cost Biosimilar Drugs to American Patients, Oct. 29, 2025). In its statement of the problems being addressed, HHS pointed to the much higher rate of biosimilars approval in Europe, which we have highlighted on our blog.

FDA Commissioner Marty Makary, M.D., stated that the agency’s goal is to “cut the development time of biosimilars … in half while lowering drug prices” (Pharmacy Times, FDA, HHS Move to Accelerate Biosimilar Approvals, Oct. 29, 2025). According to the agency’s accompanying fact sheet, the shift could save developers tens of millions in research costs and shorten the approval window from the current five-to-eight-year average to as few as two to four years (U.S. Food and Drug Administration, Fact Sheet: Bringing Lower-Cost Biosimilar Drugs to American Patients, Oct. 29, 2025).

The FDA also announced that it “now generally does not recommend switching studies,” which test the safety of alternating between reference and biosimilar products, in order to support interchangeability. The agency emphasized that these additional studies are unnecessary given the maturity of analytical science and the extensive postmarket data confirming biosimilar safety and efficacy (U.S. Food and Drug Administration, FDA Moves to Accelerate Biosimilar Development and Lower Drug Costs, Oct. 29, 2025).

Implications for Market Competition

Biologics represent just five percent of prescriptions in the United States but account for more than half of all drug spending (U.S. Food and Drug Administration, Fact Sheet: Bringing Lower-Cost Biosimilar Drugs to American Patients, Oct. 29, 2025). Despite approval of 76 biosimilars since 2015, market penetration in the U.S. remains under 20 percent. Myriad factors, including high development costs, complex patent litigation, and payer coverage challenges have slowed biosimilar entry and adoption.

Thus, by eliminating unnecessary clinical requirements and easing interchangeability, the FDA aims to promote greater price competition and enable pharmacists to substitute biosimilars without prescriber intervention, which was previously limited to interchangeable products (Pharmacy Times, FDA, HHS Move to Accelerate Biosimilar Approvals, Oct. 29, 2025). The agency anticipates that this change will lead to substantial cost savings for patients and payers, perhaps mirroring the effects of the Hatch-Waxman framework that transformed the generic drug market in the 1980s.

Patent and Regulatory Considerations

The FDA’s proposal also intersects with key issues under the Biologics Price Competition and Innovation Act (BPCIA). While the regulatory burden for demonstrating biosimilarity may ease, patent litigation under the “patent dance” framework would not change. As noted by the New York Times, many approved biosimilars have faced years of delay in reaching the market due to patent settlements and injunctions that prevent commercial launch even after FDA approval (The New York Times, F.D.A. Moves to Speed Approvals for Cheaper Copycat Drugs, Oct. 29, 2025).

Reducing development costs may incentivize more manufacturers to initiate biosimilar programs earlier in a biologic product’s patent term, increasing the number of applicants poised to challenge patents. Conversely, by lowering the barriers to market entry, the FDA’s action could also intensify earlier patent challenges, design around efforts, and freedom-to-operate analyses, spurring companies to engage in more proactive intellectual property due diligence.

Moreover, elimination of switching studies for interchangeability may have pronounced downstream effects on interchangeability-related exclusivity. Under the BPCIA, the first biosimilar approved as interchangeable with a given reference product enjoys a one-year marketing exclusivity period, during which the FDA may not make effective the approval of another interchangeable product referencing the same biologic (see 42 U.S.C. § 262(k)(6)). While the proposed guidance does not alter this exclusivity, with interchangeability now more easily attainable, the lowered evidentiary burden for achieving interchangeability (of allowing developers to rely primarily on analytical and functional comparability data instead of costly switching studies) may drive more applicants to be able to secure interchangeability designations earlier, potentially clustering approvals and narrowing the first mover’s practical commercial advantage.

The Path Ahead

Although the reforms represent a substantial regulatory shift, some analysts caution that they do not fully address other structural barriers, including payer contracting practices and the persistence of “patent thickets” around blockbuster biologics (The New York Times, F.D.A. Moves to Speed Approvals for Cheaper Copycat Drugs, Oct. 29, 2025). Still, the changes mark the most consequential FDA policy development for biosimilars in a decade.

If adopted, the guidance could accelerate biosimilar development timelines, attract new entrants into the market, and potentially increase the number of lower-cost biologic therapies – while also intensifying the strategic interplay between regulatory approval and patent enforcement. For manufacturers and investors alike, navigating this evolving landscape will require close coordination among regulatory, IP, and market access teams to ensure that the promise of biosimilars translates into practical patient savings. We will continue to monitor further developments on these proposed changes and provide insight and updates as they become available.

[1] Draft Guidance is available at https://www.fda.gov/media/189366/download.

Breaking the Patent Thicket: Why the Proposed ETHIC Act Could Have Big Implications on Pharma Patent Law

By Adam Nicolais & Jennifer P. Nock on August 19, 2025

Posted in News

On July 15, 2025, U.S. Senators Peter Welch (D‑VT), Josh Hawley (R‑MO), and Amy Klobuchar (D‑MN) introduced the ETHIC Act—the Eliminating Thickets to Increase Competition Act (S. 2276)—in the U.S. Senate.[1] The bill is designed to limit the number of drug patents that may be asserted by patent holders (often branded drug companies) in patent infringement actions, with the goal of increasing competition and lowering drug prices by easing the ability for generic and biosimilar drug makers to enter the market.

What Is the ETHIC Act?

The proposed bill seeks to add an amendment to 35 U.S.C. § 271(e)—the statute in play in Hatch-Waxman and biosimilar patent litigation cases—that makes it an “artificial act of infringement” to file a generic drug application (i.e., ANDA or 505(b)(2)) or biosimilar drug application (i.e., aBLA) with the FDA on a drug claimed in a patent. The bill would only apply to patents asserted against generic and biosimilar drug companies, and thus would not impact other industries.

The proposed bill states:

A person who brings an action for infringement of a patent under [35 U.S.C. § 271(e)] against a party described in subparagraph (B) [e.g. a generic or biosimilar drug applicant] may assert in the action not more than one patent per Patent Group.”[2]

The bill was read twice and referred to the Committee on the Judiciary.[3] A related identical bill was previously introduced into the House of Representatives on May 8, 2025, also read twice, and referred to the House Committee on the Judiciary.[4]

What Are Patent Thickets?

A “patent thicket” is the term generally applied to groups of overlapping patents that cover a single product. The various patent claims in a thicket may cover different aspects of the product, or they may target the same aspect of the product with similar but non-identical claims. Often, a single drug may be protected by two, three, or even dozens of patents covering a drug molecule, drug formulation, manufacturing process, or drug delivery methods. Such “patent thickets” can sometimes be used to extend patent exclusivity well beyond the original patent’s expiration, which can block and delay generic drugs and biosimilars from entering the market. Further, “patent thickets” can increase the complexity and cost of pharmaceutical patent litigation, as NDA and BLA drug holders (i.e., branded drug companies) often assert infringement or several (or even dozens) of patents against generic and biosimilar drug applicants.

As defined in the proposed ETHIC act, a “Patent Group” means two or more commonly-owned patents or applications that are related by way of terminal disclaimers under 35 U.S.C. § 253.[5] Each patent or application that is identified on, or is subject to, a terminal disclaimer for a commonly-owned patent is part of the same “Patent Group.” Terminal disclaimers typically are filed by applicants during patent prosecution to overcome obviousness-type double patenting (OTDP) rejections made by the USPTO.

Why it Matters.

If the bill passes, branded drug companies would be limited to asserting infringement of just one patent in a terminally disclaimed Patent Group against a given defendant. This would mean that, if the asserted patent in a Patent Group is invalidated or found not infringed by a court, the patentee could not assert a new or different patent from the same Patent Group against that defendant. This could potentially pave the way for quicker and cheaper access for generic and biosimilar drug companies to launch their products on the market.

Branded and generic drug companies should keep an eye on the bill’s progress. If passed, it could have significant impacts on patent litigators’ strategies and decision making before a complaint is filed in deciding which patent is “strongest” to assert. The bill also gives attorneys prosecuting patents directed to pharmaceutical and biotech inventions another reason to carefully consider whether to file a terminal disclaimer to overcome an OTDP rejection. As the ETHIC act is currently drafted, patent prosecutors could avoid potentially creating a “Patent Group” by making non-obviousness arguments over commonly owned patents rather than taking the more expeditious route of filing a terminal disclaimer.

Disclaimer: The information contained in this posting does not, and is not intended to, constitute legal advice or express any opinion to be relied upon legally or otherwise. If you would like to obtain legal advice relating to the subject matter addressed in this posting, please consult with us or your attorney. The information in this post is also based upon publicly available information, presents opinions, and does not represent in any way whatsoever the opinions or official positions of the entities or individuals referenced herein.

[1] S. 2276- ETHIC Act (119^th Congress, 1^st session, Introduced Jul. 15, 2015), available at https://www.congress.gov/bill/119th-congress/senate-bill/2276/text

[2] Id.

[3] Id.

[4] H.R. 3269- ETHIC ACT (119^th Congress, 1^st session, Introduced May 8, 2025), available at https://www.congress.gov/bill/119th-congress/house-bill/3269/text

[5] See supra n.1.

One is the Loneliest Number: Can Single-Patient Case Studies Provide an Enabling Basis for Patent Claims?

By Gregory DeLassus & Aydin H. Harston on July 30, 2025

Posted in Legal

The U.S. Court of Appeals for the Federal Circuit recently issued a non-precedential Rule 36 afﬁrmance of the Patent Trial and Appeal Board (PTAB) in In re Adhami, No. 2024-1218, 2025 WL 1949797 (Fed. Cir. July 16, 2025).[1] This appeal concerned the question of when and how a single-patient study can provide sufﬁcient data to provide an enabling disclosure to support patent claims.

N=1 clinical trials are a common phenomenon. The U.S. Food and Drug Administration will frequently grant “compassionate use” dispensations to individual patients whose illness is so severe that they are willing to try an experimental drug. Because these dispensations are granted on a case-by-case basis, the patient population enrolled in such compassionate use studies is necessarily small—typically a single patient. Where an encouraging, novel result emerges from such a trial, the investigator might naturally wonder whether this compassionate use result can be applied to other patients. If it seems likely that what worked for one patient might work for another, then the next logical question to ask is whether this novel and interesting new treatment is patentable.

Dr. Eftim Adhami asked the same question after he observed a curious incident in which a 27-year-old male arrived at an emergency room where Dr. Adhami worked. The patient was in coma with a blood ethanol concentration of 700 mg/dL. Not much was known about the unconscious patient at the time, but when he emerged from his coma 10 days later, friends showed up and explained that the patient did not typically drink alcohol—so, he did not have tolerance to alcohol—but that he had drunk a lot on the day of his hospital admission during a drinking competition in a party.

Meanwhile, hospital records showed that he was HIV+. Blood tests showed an HIV viral load of 60,000 vg/mL at the time. He did not have any more records until this admission and he never took antiretroviral therapy.

During the ICU stay, he was maintained in coma with propofol infusions, opioids, and muscle paralyzers. Fluids were administered intravenously, mostly as Ringer’s lactate and dextrose 5% in water. To avoid precipitous alcohol withdrawal, the patient was treated with ethanol infusion to decrease the concentration slowly over days. The day after admission, his blood alcohol concentration was 300 mg/dL.

The patient recovered uneventfully after 10 days, after which he was extubated. The patient saw an internist at the same hospital two years later and records of that encounter showed normal blood tests, including absolute CD4+ numbers. More remarkably, his HIV viral load at this time was undetectable—despite the fact that the patient had never started any antiretroviral medication.

Based on this singular incident, Dr. Adhami ﬁled a patent application (U.S. Publication No. 2017/0281676) claiming a novel method for treating HIV using a combination of anesthesia and the administration of certain chemicals, including ethanol, isopropyl alcohol, methanol, and ethylene glycol. The method involved placing the patient under general anesthesia and administering these chemicals to achieve a therapeutic effect. The application explained Dr. Adhami’s theory that the alcohol (or other disinfectant) kills the virus, while the anesthesia and other chemicals slow metabolism enough to prevent off-target damage to the patient’s own organs. The claims were rejected by the Examiner on the grounds of failing to meet the enablement and written description requirements.

The legal issues in this case revolved around whether the patent application met the requirements of enablement and written description under 35 U.S.C. § 112(a). The Examiner argued that the speciﬁcation did not adequately describe how the claimed method could achieve the intended therapeutic effect, nor did it provide sufﬁcient guidance for a person skilled in the art to practice the invention without undue experimentation.

The PTAB reversed the written description rejection, but afﬁrmed the enablement rejection. The PTAB found that the application did not satisfy the enablement requirement because it lacked sufﬁcient evidence to demonstrate that the claimed method could effectively treat HIV in humans. In particular, the PTAB noted that the “Speciﬁcation proposes that treatment with ethanol reduces the viral load in a patient to zero (‘to provide a permanent destruction of HIV or other viruses with a single treatment procedure’ (Spec. ¶ 11)).” This meant that the application needed data to make plausible not merely that the claimed invention should improve viral load, but that it could reliably eliminate the virus entirely, and in a human body—not just a test tube.

The PTAB also noted that the speciﬁcation provided only the anecdotal example of the single, 27-year-old patient, without considering other factors that could have contributed to this outcome. Moreover, the PTAB highlighted the unpredictability of using the claimed chemicals for treating HIV, and cited several existing studies in which alcohol consumption increased HIV viral loads.

This is not to say that enablement cannot be acknowledged based on an N=1 case study (see, e.g., U.S. Application No. 12/744,131). One can take away several practice points from Adhami that one should consider when pursuing an invention discovered in this sort of N=1 study:

The title of Adhami’s application was “HIV-Cure,” which sets a high bar for the amount of proof necessary to establish enablement across the entire scope of the claims. It is important not to “oversell” the utility that the invention is disclosed as providing.
There were known reports in the published literature that alcohol exacerbates HIV infection, so Adhami’s claims were running counter to the weight of evidence. That makes a plausible basis to argue non-obviousness, but it also means that the argument for enablement needs to be able to speak to these known facts in the literature. An inventor pursuing an invention based on an N=1 study would do well to search the literature for such counter-examples before ﬁling, and include explanations to account for these counter-examples in the application.
Finally, Dr. Adhami provided an expert declaration averring that the claims “relied on ‘reputable studies and medical journals with an ample amount of laboratory and human data’,” but the PTAB noted that no studies, journals, or data were speciﬁcally named or provided in the declaration. When providing a declaration to supplement the evidentiary record, it pays to be speciﬁc about the sources of the data and the names of the expert, in order for the fact-ﬁnder to be able to accord credible weight to the assertions in the declaration.

[1] Appeal from Ex parte Adhami, Appeal 2023-002654, 2023 WL 4842063 (Patent Tr. & App. Bd.).

Beyond Guinea Pigs: Patent Risks and Opportunities in AI-Enabled Drug Development

By Michael Ellenberger & Aydin H. Harston on July 23, 2025

Posted in Regulatory

Introduction

On April 10, 2025, the U.S. Food and Drug Administration (FDA) announced a landmark initiative to phase out animal testing in drug development, signaling a major shift toward human-relevant, science-driven alternatives. This initiative formalizes the agency’s long-building effort to incorporate New Approach Methodologies (NAMs) into regulatory review and follows the release of draft guidance in January 2025 on using artificial intelligence (AI) to support regulatory decisions.[1] In parallel, the National Institutes of Health (NIH) announced the creation of a new internal office to prioritize human-based research[2] and, weeks later, announced an end to funding for animal-only studies.[3] Collectively, these developments signal a coordinated policy shift by HHS agencies that will reshape not only scientific workflows but also the strategic IP landscape. As human-relevant technologies increasingly underpin safety and efficacy claims, innovators face new opportunities – and risks – in patenting platforms, data models, and trial designs that meet evolving regulatory standards.

Regulatory and Legislative Context

The FDA Modernization Act 2.0, enacted in December 2022, amended the Federal Food, Drug, and Cosmetic (FD&C) Act to eliminate the requirement for animal testing prior to clinical trials and authorized the use of validated, scientifically sound alternatives.[4] The Act, passed with bipartisan support, reflected growing consensus that non-animal models can outperform animal testing, particularly in early development.

Since then, FDA centers such as the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) have expanded their internal capabilities to evaluate NAM data. The April 2025 roadmap, issued under Commissioner Martin Makary, introduces a pilot program and outlines a phased strategy to reduce reliance on animal studies.[5] NIH’s simultaneous announcement established the Office of Research, Innovation, and Application (ORIVA) to coordinate research funding, training, and infrastructure to support non-animal technologies across NIH’s broad research portfolio.[6]

Key Elements of the FDA’s Plan

The FDA’s pilot program invites selected developers of monoclonal antibodies and similar biologics to submit safety data that exclude animal testing. CDER and CBER will jointly administer the pilot, which will help inform future guidance on incorporating NAMs into regulatory submissions.[7] The pilot, scheduled to launch within 12 months, will evaluate:

AI-based computational toxicology and pharmacokinetics
High-throughput in vitro assays using human cell lines
Organoids and organ-on-a-chip systems
Human microdosing data and real-world evidence

Although not mandatory, the FDA is encouraging sponsors to submit alternative data when scientifically justified. While the pilot focuses initially on antibodies, the agency stated this is “the beginning of a broader effort” that will eventually extend to additional biologics and small molecules. Its stated long-term goal is to make animal studies “the exception rather than the norm” for preclinical safety testing within 3–5 years.[8] This shift reflects both ethical and scientific considerations. Studies cited by the FDA show that most drugs passing animal studies fail in human trials due to unanticipated safety or efficacy issues.[9] NAMs may offer more predictive, efficient, and cost-effective models.

While some stakeholders remain cautious, many biotech and platform companies have publicly embraced the shift, viewing the FDA’s new framework as both scientifically valid, and commercial enabling. Organ-on-chip innovator Emulate publicly endorsed the FDA’s April 2025 roadmap, highlighting the agency’s recognition of validated microphysiological systems as viable alternatives to animal models. The company emphasized that this regulatory shift reinforces the utility of its platform and supports broader adoption across pharmaceutical R&D pipelines.[10] As the rollout continues, it will be imperative to monitor industry adaptation and response.

NIH Confirms Strategic Pivot to Human-Based Research

While the FDA’s roadmap modernizes regulatory review, the NIH’s new ORIVA office will drive structural change across biomedical research. Announced on April 29, 2025, ORIVA will coordinate efforts to validate and scale non-animal research technologies.[11] The NIH also intends to expand training, mitigate reviewer bias, and integrate evaluation criteria for NAMs into its grant-making processes.[12] The office will train reviewers to better assess the scientific merit and translational potential of NAM-based proposals. Together, the FDA and NIH initiatives signal a unified HHS vision: regulatory reform alongside systemic changes in federally funded research.

At a July 2025 workshop co-hosted by the FDA and NIH, NIH officials confirmed that future grant opportunities will no longer permit proposals that rely exclusively on animal studies.[13] Instead, all new NIH-funded research must at minimum incorporate consideration of NAMs including computer modeling, artificial intelligence, and organ-on-chip platforms. While the guidance stops short of a full mandate, the NIH’s formal policy shift clearly aligns with the broader federal transition away from animal-based testing, and towards next-generation models, including AI.

AI, In Silico Models, and Regulatory Acceptance

In addition to the NAMs described above, the FDA is actively integrating AI elsewhere into its regulatory framework. In January 2025, the agency released draft guidance introducing a risk-based approach for evaluating AI tools based on their influence on decisions and associated risks to patients.[14] Sponsors must disclose model architecture, training data, and governance protocols, especially for high-impact applications. Notably, the FDA has already accepted certain in silico platforms, such as the UVA/Padova Type 1 Diabetes Simulator, in regulatory submissions.[15] The agency has also deployed internal AI tools like “Elsa” to streamline reviews – demonstrating that AI-driven platforms are not merely permissible, but increasingly central to regulatory science.

Implications for Patent and IP Strategy

As AI tools become foundational to NAM-driven drug development, patent strategy must evolve to address novel risks. One key concern is the emergence of AI-generated prior art. Machine learning models deployed in target identification, compound screening, or toxicology prediction may produce outputs that enter the public domain via academic publication, data repositories, or regulatory submissions. These outputs, even if unintentionally shared, could later be cited to challenge novelty or render claims obvious.[16]

To mitigate this, early-stage innovators may consider front-loading patent filings for novel algorithms, data processing workflows, and NAM-integrated systems before widespread deployment or disclosure. Claims that capture specific implementations – such as model validation pipelines, bias mitigation protocols, or multi-modal integration of biospecimen data – may be particularly valuable.

Further complexity arises around patent eligibility. The USPTO continues to scrutinize AI-related inventions under the Alice/Mayo framework, often rejecting abstract model claims absent a clear technical improvement. However, NAM systems that demonstrate real-world utility – for instance, by stratifying patients or altering trial protocols – may satisfy eligibility requirements when claim language emphasizes technical architecture and regulatory relevance.[17]

Meanwhile, the FDA’s draft guidance encourages methodological transparency for AI used in regulatory submissions, including documentation of model design, data provenance, and performance characteristics. While this enhances regulatory trust, it also narrows the path for trade secret protection and underscores the importance of compartmentalized IP strategies. Where possible, sponsors should implement modular documentation systems that isolate proprietary elements from disclosed content – and consider filing claims to tools that enable such separation.[18]

Conclusion

The 2025 initiatives from the FDA and NIH mark a fundamental shift in drug development and biomedical research. NAMs and AI are no longer on the periphery – they are integral to regulatory science. Sponsors should act now to engage with regulators, participate in pilot programs, and secure innovation through thoughtful IP and data governance strategies.

[1] From Algorithms to Approvals: Navigating AI in Drug and Biological Product Regulation (Biosimilars IP, Feb. 2025).

[2] NIH, NIH News Release, NIH to prioritize human-based research technologies (Apr. 29, 2025), https://www.nih.gov/news-events/news-releases/nih-prioritize-human-based-research-technologies.

[3] Brian Buntz, NIH announces end to funding for animal-only studies, Drug Discovery & Development (July 7, 2025), https://www.drugdiscoverytrends.com/nih-announces-end-to-funding-for-animal-only-studies/.

[4] FDA Modernization Act 2.0, Pub. L. No. 117-328, § 3209 (2022).

[5] U.S. Food and Drug Administration. (2025, April 10). FDA Announces Initiative to Modernize Drug Development Through Alternative Testing Methods. Retrieved from fda.gov.

[6] NIH, NIH News Release, NIH to prioritize human-based research technologies (Apr. 29, 2025), https://www.nih.gov/news-events/news-releases/nih-prioritize-human-based-research-technologies.

[7] U.S. Food and Drug Administration. (2025, April 10). FDA Announces Initiative to Modernize Drug Development Through Alternative Testing Methods. Retrieved from fda.gov.

[8] Roadmap to Reducing Animal Testing in Preclinical Safety Studies; available at https://www.fda.gov/media/186092/download?attachment.

[9] Dowden, H., & Munro, J. (2019). Trends in clinical success rates and therapeutic focus. Nature Reviews Drug Discovery, 18(7), 495-496.

[10] Emulate Applauds FDA’s Roadmap to Reduce Animal Testing and Embrace Organ‑Chip Technologies. Emulate, April 2025, https://emulatebio.com/press/emulate-applauds-fdas-roadmap-to-reduce-animal-testing-and-embrace-organ-chip-technologies/.

[11] NIH, NIH News Release, NIH to prioritize human-based research technologies (Apr. 29, 2025), https://www.nih.gov/news-events/news-releases/nih-prioritize-human-based-research-technologies

[12] Id.

[13] Brian Buntz, NIH announces end to funding for animal-only studies, Drug Discovery & Development (July 7, 2025), https://www.drugdiscoverytrends.com/nih-announces-end-to-funding-for-animal-only-studies/.

[14] From Algorithms to Approvals: Navigating AI in Drug and Biological Product Regulation (Biosimilars IP, Feb. 2025).

[15] Cobelli C, Kovatchev B. Developing the UVA/Padova Type 1 Diabetes Simulator: Modeling, Validation, Refinements, and Utility. J Diabetes Sci Technol. 2023;17(6):1493-1505.

[16] See, e.g., Dennis Crouch, “Discerning Signal from Noise: Navigating the Flood of AI‑Generated Prior Art,” Patently‑O, April 30, 2024, https://patentlyo.com/patent/2024/04/discerning-navigating-generated.html.

[17] Alison Frankel, “Navigating Patent Eligibility for AI Inventions After USPTO’s Guidance Update,” Reuters Legal, Oct. 8, 2024, https://www.reuters.com/legal/legalindustry/navigating-patent-eligibility-ai-inventions-after-usptos-ai-guidance-update-2024-10-08.

[18] Darren Smyth, “IP Implications of FDA Guidance for Use of AI in Drug Development,” IPKat, June 2025, https://ipkitten.blogspot.com/2025/06/ip-implications-of-fda-guidance-for-use.html

District Circuit Denies Novartis’s Request for Injunctive Relief Against MSN’s Generic Version of Entresto®

By Alex Shaver & Jennifer P. Nock on July 18, 2025

Posted in Legal

The District Court for the District of Delaware recently rejected Novartis’s effort to block MSN Pharmaceuticals from launching a generic version of Entresto® (sacubitril/valsartan), its top-selling heart failure medication. The decision, issued on July 11, 2025, potentially clears the path for generic entry before expiration of U.S. Patent No. 11,096,918 (“the ’918 patent”) on November 9, 2026. However, on July 15, 2025, the Court of Appeals for the Federal Circuit issued a temporary injunction blocking MSN’s launch and ordered expedited briefing on whether the circuit court should issue an injunction pending appeal.

While not specific to biosimilars, this case highlights the importance of data reliability in patent litigation and raises interesting issues involving a plaintiff’s discovery obligations in a multi-defendant litigation.

Background

Novartis’s Entresto®, approved by the FDA in 2015, combines valsartan, an angiotensin receptor blocker, and sacubitril, a neutral endopeptidase inhibitor. On October 24, 2022, Novartis filed C.A. No. 22-1395 against MSN, alleging infringement of the ’918 patent, which claims an amorphous solid form of a compound comprising sacubitril, valsartan, and sodium cations (“amorphous TVS”). The only independent claim of the ’918 patent recites:

1. An amorphous solid form of a compound comprising anionic (S)-N-valeryl-N-{[2’-(1H-tetrazole-5-yl)-biphenyl-4-yl]-methyl}-valine [valsartan], anionic (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methyl-pentanoic acid ethyl ester [sacubitril], and sodium cations in a 1:1:3 molar ratio.

Following a bench trial in December 2024, Judge Andrews found that Novartis has not proven that MSN infringes the ’918 patent.[1] Prior to the trial, the court construed the term “amorphous solid form of a compound” in the ’918 patent to mean “a solid form of a compound in which the amorphous form of the compound predominates. An amorphous solid form is mutually exclusive from a crystalline solid form, but not necessarily mutually exclusive from a partially crystalline solid form.”[2] At trial, the question of infringement revolved around whether Novartis could prove that MSN’s generic product is predominantly amorphous TVS (an amorphous complex with chemical interactions among the compounds) rather than a physical mixture of amorphous valsartan and amorphous sacubitril sodium with no significant chemical interactions among the compounds.[3]

The Court’s Decision

To demonstrate that MSN infringes the ’918 patent, Novartis compared a Raman spectrum from MSN’s abbreviated new drug application (ANDA) to a reference Raman spectrum. Raman spectroscopy is a method that produces a unique spectrum for different compounds or mixtures of compounds. Specifically of interest here, Raman spectroscopy is capable of differentiating a physical mixture of two compounds (in which no interaction occurs between the compounds) versus an amorphous complex (e.g., amorphous TVS).

Novartis’s expert made a “mathematically-created” reference spectrum for an amorphous physical mixture (which is different from the claimed “amorphous TVS” complex) by adding together the Raman spectra of separate amorphous valsartan disodium and amorphous sacubitril sodium samples. The district court found this spectrum reliable.[4] Novartis’s expert also created a “glassy solid” sample, which Novartis argued was amorphous TVS, to compare with MSN’s ANDA spectrum. The district court found the Raman spectrum collected for this glassy solid was not reliable, and thus Novartis failed to show by a preponderance of the evidence that the resulting reference Raman spectrum corresponds to amorphous TVS.[5] Specifically, the court found the Raman spectrum for Novartis’s glassy solid sample was suspiciously similar to the spectrum for the physical mixture; the differences in the spectra appeared to be only a systematic shift of all peaks, rather than different peaks as would be expected for different samples.

Novartis argued that the Raman spectrum of the glassy solid “is different from the Raman spectrum of a[] physical mixture”, pointing to peak shifts when comparing the glassy solid spectrum to the mathematically-created spectrum of a physical mixture of sacubitril and valsartan.[6] Novartis further argued that the peak shifts indicate that the glassy solid sample is amorphous TVS.

MSN disagreed, pointing out that the entire Raman spectrum for the glassy solid “is shifted…to the right of the Raman spectrum of the physical mixture”.[7] MSN’s expert testified that “the type of systematic shift observed…is simply impossible”,[8] thus casting doubt on the reliability of the glassy solid Raman spectrum.

Further compounding this issue, the court took an adverse inference against Novartis for failing to produce the glassy solid sample during discovery. Novartis argued, in part, that an adverse inference is not applicable because MSN did not request production of the sample. However, Noratech was MSN’s co-defendant at the time of discovery and did request production of the sample. The court found that this “discovery [was] common to both Defendants,” that MSN and Noratech shared an expert witness for this issue, and that “MSN wished to test [Novartis’s] glassy solid, the material against which its ANDA was compared.”[9] The court found Novartis had the sample, knew it fell within the scope of requested discovery, and did not provide it. Thus, the court assumed that, “had Novartis produced the glassy solid sample to Defendants, it would have been unfavorable to Novartis’ case.”[10]

Novartis presented additional evidence to demonstrate that the glassy solid was amorphous TVS. However, because Novartis used Raman spectra to show infringement by MSN’s ANDA, the additional evidence was not directly considered when determining infringement. In the end, the “unreliability of Novartis’ reference Raman spectrum” lead the court “to conclude that Novartis did not meet its burden to show MSN’s ANDA infringes by a preponderance of evidence.”[11]

Implications

As a result of the decision, Novartis is denied injunctive relief based on the ’918 patent, and MSN’s generic version of Entresto® could soon receive final FDA approval.[12] MSN has previously indicated that it is poised to launch its product as soon as it is approved.[13] However, Novartis has appealed the District Court’s decision, and the Federal Circuit has issued a temporary stay preventing launch of the generic. Both Novartis and MSN have until July 21 to file briefs, at which time the Federal Circuit will determine whether a lengthier pause is warranted.

[1] In re Entresto (Sacubitril/Valsartan) Pat. Litig., No. 22-cv-1395-RGA, 2025 WL 1911823 (D. Del. July 11, 2025).

[2] Id. at *2.

[3] See id. at *3.

[4] Id. at *3.

[5] Id. at *4.

[6] Id. at *8.

[7] Id. at *10.

[8] Id. at *13.

[9] Id. at *21.

[10] Id. at *22.

[11] Id. at *22.

[12] The district court previously issued an order under 35 U.S.C. § 271(e)(4)(A) resetting the date of approval of MSN’s ANDA to July 16, 2025, after the expiration of the pediatric exclusivity period for U.S. Patent No. 8,101,659. See MSN’s Emergency Motion to Stay, Novartis Pharms. Corp. v. MSN Pharms. Inc., No. 19-cv-2053, Dkt. 511 (D. Del., filed April 2, 2025).

[13] See id. at 3.

Biosimilars Boom: 2025’s Fast Track Approvals Look to Reshape Healthcare

By Aydin H. Harston & Michael Ellenberger on July 16, 2025

Posted in Regulatory

With healthcare costs rising and biologics driving a large portion of drug spend, the next wave of biosimilar launches promises to reshape the U.S. pharmaceutical market in profound ways, including reduced prices for close analogs of existing reference blockbuster branded products. This post provides a roadmap into this evolution, focusing on potential biosimilar approvals and launches through 2029 in view of a changing regulatory scheme, as well as the cost implications of the changing landscape.

Primer – What are Biosimilars?

Biosimilars are biologic therapeutic products that are highly similar to an already approved (so-called “reference”) biologic, with no clinically meaningful differences with regards to safety, purity, and potency. In the United States, biosimilars are approved under the Public Health Service (PHS) Act via the abbreviated 351(k) Biologics License Application (BLA) pathway. Under this framework, the review standard focuses on a “totality of evidence” model, allowing extrapolation of indications if similarity is established. Importantly, biosimilars may also seek “interchangeable” designation, which (until recently) required additional switching studies to support automatic substitution at the pharmacy level. However, as of June 2024, the FDA issued draft guidance eliminating the need for switching studies, permitting interchangeability designations based on comparative analytical and clinical data alone, aligning the U.S. more closely with European Medicines Agency (EMA) and World Health Organization (WHO) frameworks.

2025 Off to a Fast Start: 12 Biosimilar Approvals and Counting

Within the first half of 2025, the FDA had already approved twelve biosimilars across immunology, oncology, and endocrinology. The approved biosimilars reference Stelara (ustekinumab), Prolia/Xgeva (denosumab), Actemra (tocilizumab), and Xolair (omalizumab), among others.[1]

As of 2025, the following biosimilars have been approved:[2]

Biosimilar Name	Approval Date	Reference Product	More Information
Kirsty (insulin aspart-xjhz)	Jul-25	Novolog (insulin aspart)	Kirsty Information
Starjemza (ustekinumab-hmny)	May-25	Stelara (ustekinumab)	Starjemza Information
Jobevne (bevacizumab-nwgd)	Apr-25	Avastin (bevacizumab)	Jobevne Information
Bomyntra (denosumab-bnht)	Mar-25	Xgeva (denosumab)	Bomyntra Information
Conexxence (denosumab-bnht)	Mar-25	Prolia (denosumab)	Conexxence Information
Omlyclo (omalizumab-igec)	Mar-25	Xolair (omalizumab)	Omlyclo Information
Osenvelt (denosumab-bmwo)	Feb-25	Prolia (denosumab)	Osenvelt Information
Stoboclo (denosumab-bmwo)	Feb-25	Prolia (denosumab)	Stoboclo Information
Merilog (insulin aspart-szjj)	Feb-25	Novolog (insulin aspart)	Merilog Information
Ospomyv (denosumab-dssb)	Feb-25	Prolia (denosumab)	Ospomyv Information
Xbryk (denosumab-dssb)	Feb-25	Xgeva (denosumab)	Xbryk Information
Avtozma (tocilizumab-anoh)	Jan-25	Actemra (tocilizumab)	Avtozma Information

What stands out is the pace: these approvals occurred faster than during prior years, suggesting regulators and developers alike are adapting to biosimilar pathways with more confidence and coordination.

A Turning Point in FDA Interchangeability Policy

As noted above, perhaps the most consequential change to the field is regulatory: in June 2024, the FDA issued draft guidance eliminating the requirement for switching studies in order to obtain interchangeability designation.[3] Manufacturers can now rely on comparative analytical and clinical data instead of conducting costly and time-consuming trials.[4] The removal of switching studies is predicted to cut biosimilar development costs from $100-$300 million to $75-250 million and timelines from 7-8 years down to 6.5-7.5 years, with further reductions to $50-75 million and 5-6 years if Phase 3 studies are also eliminated.[5]

This change is already affecting how biosimilar developers approach product development. For example, Formycon,[6] Sandoz,[7] and Bio-Thera[8] all cancelled or modified Phase 3 trials for their Keytruda (pembrolizumab) biosimilars, aiming instead for FDA submission based on Phase 1 data and analytics. This could signal an accelerated path to market for other oncology biosimilars in development and a major reduction in overall biosimilar development costs.

Pipeline Highlights by Therapeutic Class

During the next half-decade, a significant number of biosimilars are expected to enter the market across a myriad of therapeutic classes. Some of the most prominent candidates in development include:

Immunology

Simponi (golimumab) biosimilars from Bio-Thera (BAT2506)[9] and Alvotech/Teva (AVT05) are progressing, with launches expected in 2025-2027.[10]
Entyvio (vedolizumab) biosimilars from Polpharma and Alvotech are in Phase 3, with expected launches around 2028-2032, pending IV and SC formulation development.[11]
Cosentyx (secukinumab) biosimilars are in Phase 3 trials by Celltrion (CT-P55) and Bio-Thera (BAT2306), with exclusivity set to expire in 2029.[12]

Oncology

Pembrolizumab (Keytruda) biosimilars are being pursued by at least seven developers, including Samsung Bioepis, Sandoz, Celltrion, Bio-Thera, and Amgen.[13] Launches could begin around 2028-2029, but may accelerate due to the regulatory flexibility described herein.
Other oncology biosimilars in active development include agents referencing Opdivo (nivolumab), Herceptin (trastuzumab), and Perjeta (pertuzumab).[14]

Endocrinology & Pulmonology

A biosimilar for Trulicity (dulaglutide) from Boan Biotech, already approved in China, is in early development, with exclusivity set to expire in late 2027.[15]
Nucala (mepolizumab) biosimilars are entering early-phase trials, targeting a post-2027 window.[16]

Ophthalmology

Ongoing development of additional biosimilars for Eylea (aflibercept) and Lucentis (ranibizumab).[17]

Cost Implications and Market Forces

In spring 2025, though approximately 73 biosimilars have been approved, only 48 have launched.[18] That means 34% of approvals remain uncommercialized (often due to market barriers such as patent disputes or pricing challenges), a key reminder that FDA approval does not guarantee immediate or near-term market entry. Q1 2025 alone saw 10 new biosimilar approvals, including multiple entrants for Stelara, Prolia/Xgeva, and Actemra, and 7 biosimilar launches, including Wezlana (Amgen), Selarsdi (Alvotech/Teva), and Steqeyma (Celltrion) for Stelara.[19]

Image source: BiologicsHQ. “SB Biosimilar Market Report Q2 2025.” BiologicsHQ, Apr. 2025, biologicshq.com/wp-content/uploads/2025/04/SB-Biosimilar-Market-Report-Q2-2025.pdf.

Biosimilar competition is driving significant price reductions in 2025. Oncology biosimilars, such as trastuzumab, bevacizumab, and rituximab, show average sales price (ASP) discounts of 50-70%.[20] Denosumab biosimilars launched with wholesale acquisition cost (WAC) discounts exceeding 80% versus Prolia and Xgeva, while tocilizumab biosimilars vary, with Tofidence priced 0.3% below the reference ASP and Tyenne 29% lower.[21] In immunology, infliximab and adalimumab biosimilars offer WAC reductions of 20–60%, with unbranded variants leading the trend. Pegfilgrastim’s ASP dropped 95% since biosimilar entry, and rituximab and trastuzumab fell 33% and 24%, respectively.[22] These trends signal deeper savings as more biosimilars enter pharmacy-benefit areas like endocrinology and ophthalmology.

Bottom Line: A Market About to Tip

Between newly approved agents, relaxed FDA requirements, and a maturing biosimilar developer ecosystem, the U.S. pipeline for 2025-2029 is poised to deliver wider biosimilar adoption, faster launches, and lower prices. Key therapeutic areas to watch include immunology, oncology, and endocrinology, with Cosentyx, Entyvio, Keytruda, and Trulicity representing pivotal inflection points in the next phase of biosimilar growth.

[1] IPD Analytics. “Biosimilar Pipeline 2H 2025.” IPD Analytics, July 2025, www.ipdanalytics.com/sample-reports-1/biosimilar-pipeline-2h-2025.

[2] FDA Biosimilar Product Information – Approved Biosimilar Products. Accessed July 15, 2025, https://www.fda.gov/drugs/biosimilars/biosimilar-product-information.

[3] U.S. Food and Drug Administration. “FDA Updates Guidance on Interchangeability.” FDA.gov, 20 June 2024, www.fda.gov/drugs/drug-safety-and-availability/fda-updates-guidance-interchangeability.

[4] IPD Analytics. “Biosimilar Pipeline 2H 2025.” IPD Analytics, July 2025, www.ipdanalytics.com/sample-reports-1/biosimilar-pipeline-2h-2025.

[5] Id.

[6] Pearce IP. “Formycon to Terminate Ph 3 Trial and Pursue US-Approval of Pembrolizumab Biosimilar Based on Ph 1/Analytical Data.” Pearce IP, 17 Feb. 2025, www.pearceip.law/2025/02/17/formycon-to-terminate-ph-3-trial-and-pursue-us-approval-of-pembrolizumab-biosimilar-based-on-ph-1-analytical-data/.

[7] Pearce IP. “Sandoz to ‘Minimise’ Phase 3 Biosimilar Pembrolizumab Trial Due to Regulatory Streamlining.” Pearce IP, 30 Apr. 2025, www.pearceip.law/2025/04/30/sandoz-to-minimise-phase-3-biosimilar-pembrolizumab-trial-due-to-regulatory-streamlining/.

[8] Bio-Thera Solutions. “Bio-Thera Solutions Initiates Integrated Phase I/Phase III Clinical Trial for BAT3306, a Proposed Biosimilar of Keytruda® (Pembrolizumab).” PR Newswire, 25 July 2024, www.prnewswire.com/news-releases/bio-thera-solutions-initiates-integrated-phase-i–phase-iii-clinical-trial-for-bat3306-a-proposed-biosimilar-of-keytruda-pembrolizumab-302206502.html.

[9] Bio-Thera Solutions. “Bio-Thera Solutions Announces Exclusive Commercialization and License Agreement with Intas Pharmaceuticals for BAT2506, a Proposed Biosimilar Referencing Simponi® (Golimumab), in the United States of America.” Bio-Thera Solutions, 10 Feb. 2025, www.bio-thera.com/plus/view.php?aid=1130.

[10] Alvotech and Teva Pharmaceuticals. “Alvotech and Teva Announce Filing Acceptance of U.S. Biologics License Applications for AVT05, a Proposed Biosimilar to Simponi® and Simponi Aria® (Golimumab).” Alvotech, 27 Jan. 2025, investors.alvotech.com/news-releases/news-release-details/alvotech-and-teva-announce-filing-acceptance-us-biologic/

[11] IPD Analytics. “Biosimilar Pipeline 2H 2025.” IPD Analytics, July 2025, www.ipdanalytics.com/sample-reports-1/biosimilar-pipeline-2h-2025.

[12] Id.

[13] Id.

[14] Id.

[15] Boan Biotech. “Boan’s Dulaglutide Cleared by FDA for Clinical Trials.” Boan Biotech, 5 Aug. 2024, www.boan-bio.com/en/phone/info.php?id=317.

[16] IPD Analytics. “Biosimilar Pipeline 2H 2025.” IPD Analytics, July 2025, www.ipdanalytics.com/sample-reports-1/biosimilar-pipeline-2h-2025.

[17] Id.; Biosimilars for both products are already on the market.

[18] BiologicsHQ. “SB Biosimilar Market Report Q2 2025.” BiologicsHQ, Apr. 2025, biologicshq.com/wp-content/uploads/2025/04/SB-Biosimilar-Market-Report-Q2-2025.pdf.

[19] Id.

[20] Id.

[21] Id.

[22] IPD Analytics. “Biosimilar Pipeline 2H 2025.” IPD Analytics, July 2025, www.ipdanalytics.com/sample-reports-1/biosimilar-pipeline-2h-2025.

Jazz Pharma. v. Avadel CNS Pharma: Federal Circuit Applies a Fact-Specific Approach to the Patent Infringement Safe Harbor

By Gregory DeLassus & Jennifer P. Nock on May 12, 2025

Posted in Legal

In a precedential ruling, the U.S. Court of Appeals for the Federal Circuit in Jazz Pharma. v. Avadel CNS Pharma., 2025 WL 1298920, — F.4^th — (Fed. Cir. May 6, 2025), addressed the scope of the 35 U.S.C. § 271(e)(1) “safe harbor” provisions for certain clinical trials and regulatory filings. Although the case arose under the Hatch-Waxman Act, the same safe harbor provision applies to biologics.[1]

Background

Jazz Pharmaceuticals markets XYREM and XYWAV (sodium oxybate) for narcolepsy and related conditions. Avadel CNS Pharmaceuticals developed LUMRYZ, a competing sodium oxybate product approved under the FDA’s 505(b)(2) pathway.

The dispute centers on Jazz’s U.S. Patent No. 11,147,782, which cover sustained-release formulations. Notably, while this patent was held to cover LUMRYZ, it does not cover either XYREM or XYWAV, and is thus not listed in the FDA’s listing of “Approved Drug Products with Therapeutic Equivalence Evaluations” (a.k.a., “Orange Book”).[2]

Avadel stipulated that LUMRYZ would infringe claim 24 of the ’782 patent if it were not found invalid. After a jury found that claim 24 was not invalid, the U.S. District Court for the District of Delaware issued an injunction that barred Avadel from engaging in certain clinical trials and regulatory activities for LUMRYZ, specifically: (1) offering open-label extensions to clinical trial participants, (2) applying for FDA approval and marketing LUMRYZ for new indications, including idiopathic hypersomnia (an indication for which Avadel had begun clinical trials), and (3) initiating new clinical trials or studies after the effective date of the injunction.[3]

Avadel appealed, arguing that the injunction was overly broad, particularly in restricting activities protected under the “safe harbor” provision of 35 U.S.C. § 271(e)(1). This provision shields certain activities related to regulatory approval from patent infringement liability by providing that:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention (other than [certain animal drugs and veterinary biological products]) solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

35 U.S.C. § 271(e)(1).

The Federal Circuit reversed in part and remanded in part, holding that injunction prohibiting new clinical trials and open-label extensions was “overbroad as a matter of law.”[4] The court emphasized that the safe harbor applies broadly to “all uses of patented inventions that are reasonably related to the development and submission of any information under the FDCA,” even if the commercial product has been held to infringe a valid patent.[5] At the same time, the court underscored the fact-specific nature of the safe harbor inquiry, pointing out that Jazz may in the future bring patent infringement claims based on specific clinical trial-related activities that it believes fall outside of the § 271(e)(1) safe harbor.[6]

Key points from the ruling include:

Future Clinical Trials: The Federal Circuit reversed the injunction’s prohibition on initiation of new clinical trials, holding that “the plain language and purposes” of § 271(e)(1) exempts from infringement such clinical trial activities.[7] The court noted that in enacting the Hatch-Waxman Act’s safe harbor provision, Congress expressed its intent that “experimentation with a patented drug, when the purpose is to prepare for commercial activity which will begin after a valid patent expires, is not a patent infringement.”[8]
Safe Harbor as an Affirmative Defense: The Federal Circuit rejected Jazz’s argument that Avadel had waived the protection of the safe harbor by not pleading it as an affirmative defense. The court found that the “forward-looking injunction” against future clinical trial activities turned entirely on a question of law and was facially in violation of § 271(e)(3), which expressly prohibits injunctions against activity that falls within the safe harbor.[9] Because Avadel had not been accused of specific infringing acts involving its future clinical trials, it would be premature to require it to plead (much less develop facts to support) a safe-harbor defense. The court noted, however, that Jazz could in the future challenge specific activities by Avadel that it believes fall outside of the safe harbor, and that it then would be “incumbent upon Avadel to plead its entitlement to safe-harbor protection” as an affirmative defense.[10]
Open Label Extensions: An open label extension (“OLE”) “allows clinical trial participants to receive a trial drug past the formal completion of the trial, both to gather additional safety data for submission to the FDA and to maintain continuity of patient treatment.”[11] Although the parties presented extensive arguments on appeal about whether Avadel’s use of OLEs was protected by the safe harbor, the Federal Circuit noted those issues had not been decided by the district court and reversed the injunction prohibiting Avadel from offering OLEs. The court held that specific OLE activity must first be accused of infringement and held outside the protection of § 271(e)(1) before an injunction may issue. “Only if and when that activity is adjudicated to fall outside the protection of the safe harbor, and only if and when the district court finds the eBay factors to favor an injunction, may it be permanently enjoined.”[12]
Applying for FDA Approval for New Indications: The court vacated and remanded the portion of the injunction barring Avadel from seeking FDA approval for new indications. The court noted that merely filing an application seeking FDA approval is not an infringing act under § 271(a)-(c). While an injunction may extend to certain non-infringing acts, it may do so only if the injunction is “necessary” to prevent future infringement.[13] While the Federal Circuit noted several reasons that enjoining the filing of an FDA application does not seem necessary to prevent actual infringement, it remanded to the district court for further consideration.[14]
Can there be an act of infringement under § 271(e)(2)(A) without an Orange Book listing? The court identified an apparent issue of first impression as to whether Avadel’s submission of a 505(b)(2) application for a new indication would be a technical act of infringement under § 271(e)(2)(A) even though the asserted patent is not listed in the Orange Book.[15] The appeals court noted that if such a submission is an infringing act under § 271(e)(2)(A), then the district court’s injunction against seeking approval for new indications exceeds the scope of its statutory powers under § 271(e)(4). However, the court remanded to the district court to decide this issue in the first instance.

The Federal Circuit’s decision reinforces the balance struck by Congress between patent protection and fostering generic or follow-on drug development. It underscores that clinical and regulatory activities, even for infringing products, are protected if they are solely for uses reasonably related to development and submission of information under the FDCA.

[1] See, e.g., Amgen Inc. v. Hospira, Inc., 944 F.3d 1327 (Fed. Cir. 2019).

[2] Jazz Pharma. v. Avadel CNS Pharma., 2025 WL 1298920, at *2 (Fed. Cir. May 6, 2025). Notably, the district court did not enjoin Avadel from making, using, or selling LUMRYZ for its FDA-approved indication (treatment of narcolepsy). The district court found the potential harms to the public from such an injunction outweighed any irreparable harm to Jazz. Id. at *3, n. 5. Jazz did not appeal that issue.

[3] Id. at *4.

[4] Id. at *5; see id. at *7.

[5] Id. at *5 (quoting Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193, 202 (2005)). The “FDCA” is the Federal, Food, Drug and Cosmetics Act, codified in Title 21, Chapter 9 of the United States Code.

[6] See id. at *7 (finding “no support in the record to sustain a determination one way or the other on whether the safe-harbor provision applies to those [future] activities” not yet accused of infringement).

[7] Id. at *5.

[8] Id. at *5 (quoting H.R. Rep. No. 98-857, pt. 1, at 45-46 (1984), as reprinted in 1984 U.S.C.C.A.N. 2647).

[9] Id. at *6.

[10] Id. at *7.

[11] Id. at *3 (quoting J.A. 7511-12).

[12] Id. at *7.

[13] Id. at *10.

[14] See id. at *11. The Federal Circuit instructed the district court to first consider whether its injunction against filing a 505(b)(2) application for new indications would be prohibited by § 271(e)(4).

[15] Id. at *9-*10. This issue does not apply to biosimilars. Under the BPCIA, the technical act of infringement involved in filing an application for FDA approval refers to those patents identified in the lists provided under 42 U.S.C. § 262(l)(3) or (l)(7).

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Jazz Pharma. v. Avadel CNS Pharma: Federal Circuit Applies a Fact-Specific Approach to the Patent Infringement Safe Harbor

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