Pharma IP & Regulatory Update 2026: Paragraph IV Filings, China RDP, and Case Law: Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc

1. Recent USFDA Paragraph IV Filings (May 2026 Update)

The USFDA’s Paragraph IV database was recently updated to track key Abbreviated New Drug Applications (ANDAs). Broadly, four major drugs and their developers seek lucrative 180-day market exclusivity.

Key Drug Breakdown & Technical Challenges

• Letermovir (Prevymis – Merck)

  • Indication: Prophylaxis of cytomegalovirus (CMV) infection in bone marrow and kidney transplant recipients.

  • Market Dynamics: Nearing the $1 billion mark in annual US revenue. There is currently only one generic filer with a substantially complete ANDA.

  • Technical/IP Barriers: Letermovir is a highly complex zwitterionic compound. Generic applicants must circumvent US Patent No. 10,603,384, which governs solubility and stable formulations for intravenous administration. Currently, only Honour Labs has filed a Drug Master File (DMF).

• Abemaciclib (Verzenio – Eli Lilly)

  • Indication: HR+, HER2-negative advanced or metastatic breast cancers.

  • Market Dynamics: A massive blockbuster is clearing several billion dollars annually. Only one ANDA currently holds a Paragraph IV certificate.

  • Technical/IP Barriers: Exhibits highly pH-dependent solubility (insoluble in neutral environments, highly soluble in acidic environments), creating steep bioequivalence challenges. Generic filers must navigate prior art forms (Crystalline Form I and Form III from WO 2010/075074 A1) and file invalidity arguments against the lone Orange Book listed compound patent. There are 15 DMF filers competing.

• Fluticasone Furoate / Umeclidinium Bromide / Vilanterol Trifenatate (Trelegy Ellipta – GSK)

  • Indication: Maintenance treatment of asthma and COPD.

  • Market Dynamics: Recorded massive US sales approaching $8 billion in 2025. Early generic movers like Transpire Bio are aggressively challenging the patent wall.

  • Technical/IP Barriers: This triple-combination therapy presents significant hurdles for drug-device combinations. Generics must replicate the aerodynamic performance of GSK’s Ellipta dry powder inhaler (DPI) to ensure identical lung deposition, blending three ingredients with diverse physicochemical properties into a uniform powder matrix.

• Semaglutide (Wegovy Tablets – Novo Nordisk)

• Indication: Chronic weight management and cardiovascular risk reduction.

• Market Dynamics: Driven by the booming oral GLP-1 market, Apotex submitted ANDA No. 221238 targeting Novo Nordisk’s extensive patent portfolio stretching to 2039.

• Technical/IP Barriers: Replicating oral delivery requires a complex co-formulation using a massive excess (60% to 95% by weight) of the absorption enhancer SNAC to protect the peptide from enzymatic degradation and allow transcellular passage.

• Why Wegovy and not Rybelsus? Under FDA rules, ANDAs must copy exact strengths. Apotex targeted the 1.5 mg, 4 mg, and 9 mg strengths belonging strictly to Novo Nordisk’s independent oral Wegovy NDA, legally forcing them to use Wegovy as the Reference Listed Drug (RLD).

2. Intellectual Property Case Law Spotlight

Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc.

The Federal Circuit recently affirmed a district court ruling in favour of Mylan regarding Actelion’s hypertension drug, Veletri (epoprostenol). The case provides crucial precedents regarding claim construction and limitations on the doctrine of equivalents.

The Core Dispute

Actelion asserted that Mylan's generic ANDA infringed its patents (US Patent Nos. 8,318,802 and 8,598,227) covering stable, freeze-dried epoprostenol compositions formed from highly basic bulk solutions. The claims required a bulk solution with "a pH of 13 or higher."

Key Legal Takeaways

• Claim Construction of "pH": Actelion argued pH should be measured at the refrigerated manufacturing "operating temperature." However, Mylan's solution only met the pH 13 threshold at 0 °C; at the industry-standard temperature (25 + 2 0C), it fell below the infringement line. Relying on United States Pharmacopoeia (USP) guidelines, the court ruled that pH defaults to standard room temperature unless explicitly stated otherwise. Thus, no literal infringement was found.

• Prosecution History Estoppel: Actelion tried to claim infringement under the Doctrine of Equivalents. However, because Actelion had narrowed its claims during prosecution from "greater than 12" to "13 or higher" to overcome an examiner's obviousness rejection, it was legally barred from recapturing the lower pH ranges.

• The Disclosure-Dedication Rule: The patent specification explicitly disclosed alternative pH ranges of "about 12.5–13.5." Because Actelion chose to disclose those ranges but omitted them from final claims, those alternatives were deemed dedicated to the public, blocking any equivalency claims.

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Contents

Recent Paragraph -IV filings

General information

CVS sues to challenge new Tennessee PBM-pharmacy breakup law

Pillars of exclusivity: Regulatory data protection regime for pharma in China

Intellectual Property

Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc

Recent Paragraph -IV filings 

We follow Paragraph IV filings at the USFDA. The recent list was updated on 11 May, and four ANDAs were listed. 

General information

CVS sues to challenge new Tennessee PBM-pharmacy breakup law

• CVS is suing Tennessee’s pharmacy board over a new law prohibiting pharmacy benefit managers from owning or operating pharmacies in the state.
• The complaint filed Friday argues that Tennesee’s law, which was passed last week despite fervent opposition from major PBMs, constrains out-of-state competition against Tennessee’s independent pharmacies in violation of the Constitution.
• CVS said it will be forced to close 136 retail and specialty pharmacies and halt mail-order services in Tennessee if the law is allowed to go into effect. Currently, companies have until July 2028 to comply.

News here

Pillars of exclusivity: Regulatory data protection regime for pharma in China

Key takeaways

• China’s new Implementation Measures make regulatory data protection a practical and enforceable exclusivity tool, but only if companies actively secure it at the NDA stage and align global filing strategies with China.
• A critical, short transitional window applies to pipeline products already under review, requiring filings by the beginning of June 2026, and failure to act within this deadline will result in a permanent loss of data protection rights.
• The regime also creates concrete opportunities, including extended protection for innovative products and certain new indications, as well as mechanisms to preserve exclusivity through local manufacturing transfers.
• Companies should urgently review pipeline assets, filing timelines, and licensing arrangements to ensure that available exclusivity is captured and not inadvertently forfeited.

News here

Intellectual Property 

Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc 

Executive Summary

This appeal in Actelion Pharmaceuticals Ltd. v. Mylan Pharmaceuticals Inc. arises from a patent infringement suit involving Actelion's hypertension drug Veletri. Actelion owns U.S. Patent Nos. 8,318,802 and 8,598,227, which describe stable, lyophilised (freeze-dried) pharmaceutical compositions of epoprostenol formed from highly basic bulk solutions. Mylan filed an ANDA to market a generic version. Actelion sued, asserting that Mylan’s generic literally or equivalently infringed its patents. 

The United States District Court for the Northern District of West Virginia ruled in favour of Mylan, finding no literal infringement because the claim phrase "a pH of 13 or higher" requires measurement at a standard temperature in the field (25 + 2 °C), a threshold Mylan's bulk solution did not meet. The district court also held that Actelion was legally barred from proving infringement under the doctrine of equivalents. The Federal Circuit affirmed the district court’s final judgment. 

Claim

1. A lyophilized pharmaceutical composition comprising:

(a) a unit dose of 0.5 mg or 1.5 mg of epoprostenol or a salt thereof;

(b) arginine; and

(c) sodium hydroxide,

wherein said lyophilized pharmaceutical composition is (i) formed from a bulk solution having a pH of 13 or higher and (ii) capable of being reconstituted for intravenous administration with an intravenous fluid.

Technical and Operational Background

Epoprostenol acts as a vasodilator but degrades rapidly in water, an unwanted reaction heavily catalysed by hydronium ions or acidic molecules. Historically, the FDA-approved product Flolan (now discontinued) required inconvenient refrigeration and a specialised basic diluent to maintain stability. 

To improve room-temperature stability and eliminate the need for basic diluents, the inventor of the '802 patent designed processes utilising a highly basic bulk solution containing epoprostenol, arginine, and sodium hydroxide. The specification highlights that freeze-dried formulations are most stable when the bulk solution's pH is adjusted to 13 or higher. However, the patent specification does not explicitly define the ambient conditions or testing temperatures under which these pH thresholds were measured. 

Key Legal Analyses and Holdings

1. Literal Infringement and Claim Construction of "pH"

Actelion argued that the phrase "bulk solution having a pH of 13 or higher" refers to the solution’s actual "operating temperature" during refrigerated manufacture. When measured at room temperature, Mylan's solution has a pH above 13. When measured at a standard 25 + 2 °C, Mylan's solution falls well below the 12.98 infringement floor set on remand. 

The Federal Circuit reviewed the intrinsic and extrinsic evidence to uphold the district court’s standard-temperature construction 25 + 2 °C based on the following findings:

1. Intrinsic Evidence: The specification explicitly identifies an alkaline environment as having a "pH > 7," a chemical definition accurate only under standard ambient conditions. Furthermore, the reported experimental comparisons assumed a uniform measurement approach, and their data parameters would "not make sense" under volatile temperature scales. 
2. Extrinsic Evidence: The United States Pharmacopoeia (USP), which both parties' experts have conceded is highly influential in pharmaceutical manufacturing, prescribes a binding industry default that pH measurements are taken at 25 ± 2 °C unless otherwise specified. The experts also agreed that the baseline data charts within the patent’s specification explicitly followed this standard-temperature default. 

Because Mylan’s ANDA product did not meet the pH threshold at standard temperature, the court affirmed the finding of no literal infringement. 

2. Infringement by an Equivalent and Legal Bars

Actelion alternatively argued that Mylan’s refrigerated manufacturing process was equivalent because it performed the same function in the same way to achieve stable epoprostenol. The Federal Circuit rejected this, ruling that Actelion was legally barred by two distinct doctrines: 

• Prosecution History Estoppel: Under the Festo framework, narrowing claim amendments made for patentability reasons presumptively surrender the territory between the original and amended limitations. During prosecution, the examiner issued an obviousness rejection because Actelion failed to show unexpected stability results for bulk solutions with a "pH of greater than 12". Actelion subsequently narrowed its claim from "greater than 12" to "13 or higher". Actelion failed to prove its amendment qualified for the narrow "tangentiality exception," meaning it was legally estopped from recapturing pH values below 13 as equivalents. 
• The Disclosure-Dedication Rule: This rule dictates that when a patent specification explicitly discloses but declines to claim alternative subject matter, it is dedicated to the public. The '802 patent specification explicitly states that the pH of the bulk solution is preferably adjusted to "about 12.5–13.5" or "greater than 12". Because Actelion specifically disclosed these overlapping alternative ranges but chose to strictly claim a boundary of "13 or higher," it dedicated the lower alternatives to the public and could not recapture them via the doctrine of equivalents. 

Conclusion

Finding no literal infringement under the correct claim construction and determining that the doctrine of equivalents was entirely unavailable, the Federal Circuit affirmed the district court's final judgment. 

News here