Biologics are one of the fastest-growing areas of pharmaceutical development, and more companies are conducting initial clinical work outside the United States. Jurisdictions such as China, Australia, and countries across Latin America offer compelling advantages for first-in-human studies, including faster enrollment, lower trial costs, and, in some cases, more accommodating regulatory frameworks for early-phase investigations. Yet companies pursuing this strategy to obtain U.S. marketing approval face layered regulatory, manufacturing, data-integrity, and, in some cases, geopolitical challenges with significant and often underappreciated implications for patent protection. Initiating Phase I trials abroad affects patent prosecution timelines, creates prior-art risks through foreign clinical trial registrations and disclosures, complicates protection of proprietary manufacturing know-how shared with overseas contractors, and requires coordination of intellectual property (IP) milestones with a U.S. Food and Drug Administration (FDA) regulatory calendar not designed for a foreign-first development model. While many of the following risks are not exclusive to foreign trials, the risks greatly increase when conducting regulatory activities outside the U.S. under foreign legal regimes as described in further detail in this article.

This article examines intellectual property issues biotech companies should anticipate when conducting early-stage biologics trials outside the United States and offers practical guidance for structuring a patent filing strategy that preserves and strengthens market exclusivity on the path to U.S. approval.

Intellectual Property Strategy: Using Patent Filings to Mitigate Regulatory Risks

A thoughtful patent filing strategy is a critical risk-mitigation tool that directly addresses the regulatory challenges described above. Patent prosecution timelines and regulatory milestones must be coordinated carefully; misalignment can forfeit patent rights and diminish market exclusivity.

A. Understand the Risks Associated with Clinical Trial Disclosures

Under U.S. patent law, a public disclosure can constitute prior art that bars or limits patent protection. In the life sciences, “public disclosure” includes clinical trial registrations, whether on ClinicalTrials.gov, China’s Chinese Clinical Trial Registry (ChiCTR), or comparable foreign registries, and regulatory filings that become publicly accessible. Companies initiating Phase I trials in foreign jurisdictions should take special care because foreign regulatory agencies may require disclosures that become public in some form, creating a risk that the trial itself undermines the exclusivity needed to commercialize the therapy in the United States. Foreign registry disclosure requirements are often less transparent or predictable than U.S. requirements, making prior-art risk harder to assess and manage.

Failure to file patent applications before such a disclosure can result in a permanent and irrevocable loss of patent rights, potentially eliminating the company’s ability to exclude competitors from the U.S. market for the therapy altogether.

To mitigate this risk, companies should consider filing provisional or non-provisional patent applications covering the composition, methods of treatment for indications expected to appear on regulatory labels, Phase I dosing regimens, and manufacturing processes before disclosing the trial design to foreign entities, and certainly before public disclosure. In addition to covering the therapeutic product itself in these filings, companies should consider including the clinical methodology and any novel manufacturing features that may be disclosed in connection with the trial.

B. Consider Filing on Patent-Eligible Manufacturing Techniques Before Engaging a Contract Research Organization (CRO) or Contract Manufacturing Organization (CMO)

Companies may be able to obtain patent protection for their manufacturing processes, including cell isolation and activation techniques; genetic modification methods, (e.g., viral vector transduction, electroporation, and CRISPR-based gene editing); expansion protocols; formulation strategies; cryopreservation methods; and quality-control assays, provided they are novel and non-obvious.

However, engaging a CRO or CMO, often an early necessity for companies conducting foreign Phase I trials, creates risks to the company’s ability to secure and maintain patent protection for these manufacturing innovations. Disclosing proprietary manufacturing know-how to a third-party contractor, even under an NDA, increases the risk of inadvertent disclosure and inventorship disputes.  A contractor’s independent patent filing on the originator company’s innovations could also prevent the company from practicing its own manufacturing process, forcing costly redesign or licensing negotiations and potentially delaying commercialization.

Companies should therefore consider filing patent applications covering novel manufacturing methods and process innovations before sharing technical details with any third-party manufacturer or service provider, regardless of jurisdiction. This risk is heightened in countries with less-developed IP enforcement mechanisms or where CRO/CMO relationships may be subject to government-directed technology-transfer requirements.

C. Coordinate IP and Regulatory Timelines

Patent prosecution timelines and FDA regulatory milestones should be managed in tandem. Without coordination, a company may reach a critical regulatory juncture without adequate patent protection in place. Alignment strengthens the company’s market-exclusivity position by extending patent term. A gap in patent coverage can leave the product exposed to generic or biosimilar competition from the date of launch, dramatically reducing the company’s return on its development investment.

Companies should work with patent counsel to develop prosecution strategies that account for typical examination timelines at the U.S. Patent and Trademark Office and, where appropriate, use accelerated examination procedures to align patent prosecution with the regulatory development calendar. Foreign-first development timelines frequently diverge from the assumptions underlying standard U.S. patent prosecution pacing, requiring earlier and more deliberate coordination.

Companies may benefit from establishing an IP review checkpoint at each major development milestone: pre-CRO/CMO engagement, pre-investigational new drug (IND) filing, pre-clinical trial registration, and pre-biologics license application (BLA) submission, to ensure that patentable innovations are identified and captured in filed applications before they are publicly disclosed or shared with third parties. This structured approach to IP diligence reduces the risk of inadvertent forfeiture and aligns the company’s patent portfolio with its regulatory development strategy at every stage of the product’s journey toward U.S. market approval.