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 The proposed reforms, introduced through a new draft guidance,[1] would eliminate many comparative clinical efficacy studies, previously required for biosimilar approval, and thereby simplify the process for obtaining an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Under the draft guidance, developers of new biosimilar compounds will generally no longer be required to conduct human comparative efficacy studies when analytical testing can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demonstrate biosimilarity (U.S. Food and Drug Administration, Scientific Considerations in Demonstrating Biosimilarity, Draft Guidance, 2025).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 However, in the draft guidance, the FDA asserts that such trials add “little scientific value” relative to advanced analytical assessments of molecular structure and function.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.

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.

[1] Draft Guidance is available at https://www.fda.gov/media/189366/download.

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 (119th Congress, 1st 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 (119th Congress, 1st session, Introduced May 8, 2025), available at https://www.congress.gov/bill/119th-congress/house-bill/3269/text

[5] See supra n.1.

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:

  1. 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.
  2. 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.
  3. 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.

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

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.

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.

[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

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.

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.

[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.

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

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.

[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.

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.4th — (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.

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.

[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).

  • FDA approves Omylco® (omalizumab), first biosimilar of Xolair®.
  • After Q1, FDA and EMA on track for a record number of biosimilar authorizations in 2025.

Biosimilars, once a niche segment in the pharmaceutical industry, are now making 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. As biosimilars gain traction worldwide, 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 124 applications have been approved in Europe. Sixteen 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, 73 other biosimilar drugs have gained U.S. approval to date including 17 interchangeable products (Table 2).

As illustrated in the following graph, while 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, the FDA has increased the rate of approval in recent years. In 2024 alone, the FDA approved 19 biosimilars, the most approvals in a single year by either regulatory body to date.

In the first four months of 2025, Europe and the U.S. are nearly equivalent in the number of biosimilar approvals, having authorized 12 and 10 biosimilars, respectively. Of note, these approval numbers include both 60 mg pre-filled syringe (Connexance, Stoboclo, and Ospomyv/Obodence; referencing Prolia®) and 120 mg vial (Bomyntra, Osenvelt, and Xbryk; referencing Xgeva®) forms of denosumab. Should the high rate of approvals be maintained throughout the year, both the EMA and FDA are on track to surpass the record 19 approvals seen in 2024. Notably, the EMA has also issued favorable opinions for the approval of Jubereq and Osvyrti (denosumab) and Quyvolma (ustekinumab), though final marketing authorization is still pending. In the U.S., the FDA recently approved Omylco® (omalizumab), the first biosimilar of Xolair®, which also achieved interchangeability designation with the reference product.

Looking forward, there are currently 36 biosimilar applications under review by the EMA for marketing authorization (Table 3).  As an increasing number of patents expire on blockbuster biologic drugs, the number of abbreviated biologics license applications is also increasing. Biosimilars for more than 31 different original biologics are currently navigating biosimilar pathways or are in late stage development in the U.S. (Table 4).  

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

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

Table 3. European Medicines Agency List of Biosimilars Under Evaluation for Marketing Approval (Source: EMA list of applications for new human medicines compiled on April 8, 2025, and published on April 16, 2025).

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

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

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.

Summary of the Budapest Treaty for Biological Deposits

The Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purposes of Patent Procedure is an international agreement to establish a uniform system for depositing microorganisms and other biological material to meet patent disclosure requirements. The agreement was first ratified in 1977, and was later modified in 1980. In other words, this is an international agreement regarding biotech patent law that predates PCR (invented 1983), Western blotting (invented 1981), massively parallel signature sequencing (MPSS, invented 1992), and a host of other molecular biological techniques that are the commonplace workhorses of biotech today.

The treaty was intended to address the challenge—as it existed at the time—of adequately describing transgenic organisms in patent applications, back in the day when it was impractical or even impossible to describe a transgenic organism in precise terms that would enable others to replicate the organism and practice the invention. The treaty allows applicants to deposit biological material with a recognized institution instead of providing a detailed description, so as to ensure accessibility to others in the art for purposes of satisfying patent law enablement requirements. The treaty provides for:

  1. International Depositary Authorities (IDAs), i.e., cell banks, tissue banks, and seed banks designated by treaty signatory governments to store biological material. IDAs are required under the treaty to meet standards for secure storage, impartiality, and accessibility;
  2. Single Deposit Recognition, i.e., a standard whereby a deposit made with any IDA is recognized by all contracting states for patent purposes, eliminating the need for multiple deposits in different countries; and
  3. Requirements, specifying timing and quantities by which the material must be deposited, the terms on which deposited material is available to interested parties, and the terms under which applicants must replace or replenish a deposit with the same material if a deposit becomes non-viable or depleted.

Those requirements—especially the requirements to make available and to replenish—can be noisome to businesses. For example, although some depository institutions have a box on their depository paperwork that the depositor can check requesting that the IDA notify the depositor every time that a withdrawal is made, there is no mechanism to enforce this notice provision, and no easy way for the depositor to know that it has been violated until after the harm (i.e., the unreported dissemination of the depositor’s patented materials) has already occurred. Moreover, the need to replenish the supply as (often unauthorized) withdrawals deplete the deposited supply can be a costly and time-consuming nuisance for the depositor. However, if a patent is granted on the basis of a Budapest treaty declaration having been given to the patent office, then failure to comply with these requirements could later prejudice the validity of the patent. 37 C.F.R. § 1.805.

Tips

For these reasons, many patent applicants prefer not to give a Budapest treaty declaration during patent prosecution. To avoid the need for a Budapest Treaty deposit during patent prosecution, consider the following three tips:

  1. Provide a Comprehensive Written Description: The Budapest treaty was negotiated back in a time when it was difficult or even impossible to know the genetic sequences of the organism or germ plasm being deposited. Today, however, whole genome sequencing often can be done fairly inexpensively. If the material for which patent protection is being sought (e.g., seeds, bacteria, plasmids) can be fully described (e.g., through genetic sequences, chemical composition, etc.) then this information can be included in the application in lieu of a deposit.
  2. Distribute the Materials Yourself: The logic behind the Budapest treaty is that sometimes one needs access to a particular biological material (e.g., a transgenic bacterium) to practice the claimed invention. But the IDAs are not the only plausible source of the material. If the material is accessible to the public through a known commercial vendor, this is also the sort of availability that can enable practice of the invention.
  3. Demonstrate That the Materials Are Already Available to the Public Elsewhere: It is commonplace in the “materials & methods” sections of scientific publications to see a line to the effect of “E. coli strain DX5K9 was a kind gift of _____ of ____ University….” If one can point to scientific publications showing that the material for use in the invention to be patented is already in circulation among scientists in the relevant field, this is also the sort of availability that can enable practice of the invention.

These strategies depend on the invention’s specifics and jurisdiction requirements. Consulting a patent attorney is advisable to assess whether a deposit can be avoided while meeting disclosure obligations.

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.

On March 13, 2025, the U.S. Court of Appeals for the Federal Circuit affirmed a five-year patent term extension (“PTE”) for Merck’s sugammadex patent, holding that the district court had correctly calculated PTE based on the issue date of the original patent rather than the issue date of the reissued patent.[1]

Background

The case originated as a series of Hatch-Waxman litigations related to Merck’s Bridion®, a drug with the active ingredient sugammadex which is administered as an intravenous injection to reverse neuromuscular blockade, a form of paralysis induced by rocuronium bromide and vecuronium bromide in certain types of surgery.[2]

Merck originally obtained U.S. Patent No. 6,670,340 (“the ’340 patent”), which is directed to a class of 6-mercapto-cyclodextrin derivatives and issued on December 30, 2003, and applied to the Food and Drug Administration (“FDA”) for approval of a species within that class, sugammadex, shortly after on April 13, 2004.[3] Years later, while regulatory review was ongoing, Merck filed a reissue application for the ’340 patent that included both the original claims and narrower claims specifically directed to sugammadex, which was granted and issued as U.S. Patent No. RE44,733 (“the RE’733 patent”) on January 28, 2014.[4] The FDA approved sugammadex on December 15, 2015.

On February 10, 2016, Merck filed a PTE application for the RE’733 patent seeking PTE under 35 U.S.C. § 156 based on the original ’340 patent’s issue date (capped at five years under § 156(g)(6)(A)).[5] On February 4, 2020, the U.S. Patent and Trademark Office (“PTO”) granted a five-year PTE based on the ’340 patent’s issue date, extending the RE’733 patent’s expiration date from January 27, 2021, to January 27, 2026.[6]

In early 2020, Merck filed Hatch-Waxman lawsuits in the U.S. District Court for the District of New Jersey against several companies (collectively, “Aurobindo”) that had filed Abbreviated New Drug Applications (“ANDAs”) for generic versions of Bridion® and which had submitted Paragraph IV certifications as to the RE’733 patent.[7] The cases were consolidated.

At trial, Aurobindo argued that based on the plain text of § 156(c), which provides that the length of patent term extension is “the time equal to the regulatory review period… occur[ring] after the date the patent is issued,” the PTO should have calculated the RE’733 patent’s PTE based on the reissued patent’s issue date, rather than the original patent’s issue date.[8] Thus, the RE’733 patent was entitled not to a five-year PTE, but only to a 686-day PTE based on the period of regulatory review that had taken place after the RE’733 patent’s January 28, 2014 issue date, corresponding to an expiration date of December 14, 2022.[9]  Thus, Aurobindo sought to reduce the granted PTE by 1,140 days.

The district court rejected Aurobindo’s construction, and concluded that, when calculating PTE for a reissued patent, the PTO is statutorily required to base its calculation on the original patent’s issue date rather than the reissue patent’s issue date.[10] It thus held that the RE’733 patent was entitled to its full five-year PTE.[11]

Aurobindo appealed the decision. Notably, the PTO filed an amicus brief in support of Merck and took part in the oral argument on February 4, 2025.

The Federal Circuit’s Affirmance

On appeal, the Federal Circuit affirmed the district court’s holding, explaining that

[I]n the context of reissued patents, the reference to “the patent” in subsection 156(c) is to the original patent. Here, the ’340 patent included claims directed to the active ingredient for a drug product . . . . Under these circumstances, the RE’733 patent was entitled to a five-year PTE based on the ’340 patent’s issue date, since regulatory review effectively prevented the patent owner from enforcing the patent during that period.[12]

Central to the Federal Circuit’s decision was the statutory interpretation of 35 U.S.C. § 156(c). In this respect, the Federal Circuit found that “the language of subsection 156(c) standing alone is ambiguous.”[13] Looking to the statutory text and the broader context of the statute, the Federal Circuit explained that Congressional intent made clear the purpose of this section of the Hatch-Waxman Act: “to compensate the pharmaceutical companies for the effective truncation of their patent terms while waiting for regulatory approval of new drug applications.”[14] It emphasized that “[t]he statute contemplates a patentee receiving time lost in its patent term by reason of FDA delay, and the statute should be liberally interpreted to achieve this end,” and observed that Aurobindo’s construction of the statute, which would “den[y] Merck compensation for all but a small period of the delay,” was at odds with the purpose of the statute.[15]

The Federal Circuit thus concluded that “[a] reissued patent is entitled to PTE based on the original patent’s issue date where, as here, the original patent included the same claims directed to a drug product subject to FDA review.”[16] It added as a final note that the PTO’s revised Manual of Patent Examining Procedure, which instructs patent examiners to calculate the amount of PTE to which reissued patents are entitled based on the original patent’s issue date so long as both patents claimed or claim the approved product, “substantially tracks with our analysis as applied in this case.”[17]

Implications for PTE Based on Regulatory Review Period

In light of the Federal Circuit’s holding, the status quo with respect to how the USPTO calculates PTE based on the FDA’s regulatory review period remains unchanged. As the PTO suggested during oral argument, calculating PTE based on reissue date rather than the original patent’s issue date could lead to gamesmanship to maximize PTE by “either not filing the reissue or, at the [PTO], taking certain steps to delay your reissue application, until you get PTE on the original patent.” However, the affirmance avoids the need for such measures—patent owners can continue to file reissue patents without opening themselves up to the possibility of cutting off PTE (provided that both the reissued and original patents include the same claims directed to the approved drug product).

[1] Merck Sharp & Dohme B.V. v. Aurobindo Pharma USA, Inc., No. 23-2254 (Fed. Cir. Mar. 13, 2025) (available at https://www.cafc.uscourts.gov/opinions-orders/23-2254.OPINION.3-13-2025_2481365.pdf).

[2] Id. at 5-6.

[3] Id. at 5.

[4] Id. at 6.

[5] Id. at 6-7; 35 U.S.C. §§ 156(c), 156(g).

[6] Merck at 7.

[7] Id. at 7-8.

[8] Id. at 8.

[9] Id.

[10] Id. at 8-9.

[11] Id. at 9.

[12] Id. at 4.

[13] Id. at 10.

[14] Id. at 10-12.

[15] Id. at 13.

[16] Id. at 14-15.

[17] Id. at 16-17.