When does the patent for Pertuzumab/Trastuzumab/Hyaluronidase expire?

Introduction to Pertuzumab/Trastuzumab/Hyaluronidase

Pertuzumab, trastuzumab, and recombinant human hyaluronidase (rHuPH20) together form a fixed‐dose combination (FDC) that has transformed the administration of HER2‐targeted therapies for breast cancer. Pertuzumab and trastuzumab are monoclonal antibodies that target different epitopes of the human epidermal growth factor receptor 2 (HER2), thereby blocking cellular mechanisms that drive tumor growth in HER2‐positive cancers. The addition of hyaluronidase facilitates subcutaneous (SC) delivery by temporarily enhancing tissue permeability, which permits the administration of larger volumes of antibody formulations compared to traditional intravenous (IV) infusions. This innovative approach not only improves patient convenience and comfort but also optimizes healthcare resource utilization. Data underpinning the efficacy and safety of this combination have been generated in pivotal studies such as the FeDeriCa trial, which compared SC administration with its IV counterpart.

Clinical Uses and Benefits 
Clinically, this combination is used in both early-stage and metastatic breast cancer to improve survival outcomes in patients who overexpress HER2. The combination leverages the complementary mechanisms of pertuzumab and trastuzumab to enhance anti-tumor activity while offering an improved administration route. Key benefits include reduced administration time and the elimination of long infusion periods, which historically have been associated with IV therapies. Additionally, the SC formulation has been developed to maintain adequate systemic exposure and comparable safety profiles to the IV regimen. These benefits, combined with improved patient quality of life and cost-effectiveness—through potential reductions in hospital resource use—underscore the clinical importance of this therapeutic combination.

Patent Information

Current Patent Status 
The intellectual property landscape for these biologic agents is complex and multifaceted. Each component of the combination—pertuzumab, trastuzumab, and hyaluronidase—has its own patent history and exclusivity window. Over time, companies have pursued additional patents covering new formulations, methods of administration, and fixed-dose combinations. For instance, there are patents protecting the individual molecules of pertuzumab and trastuzumab as well as ancillary patents covering manufacturing processes and the innovative combination’s fixed-dose formulation. Recent patent documents available on platforms such as Synapse describe the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase, emphasizing the importance of integrating efficacy and safety data from recent clinical trials. Although these documents focus on the formulation and method-of-use claims, they often do not explicitly state a final expiration date in the public summary. Instead, the expiration dates must be inferred largely from the known dates associated with the individual antibodies and related formulation protection strategies.

Pertuzumab’s patent protection is a critical piece of this puzzle. According to data derived from synapse sources and reports such as those compiled by GlobalData, the inventorship and patent strategy for pertuzumab have been structured to maintain market exclusivity for several years following approval. Similarly, trastuzumab’s primary patents had already expired in key markets, prompting the emergence of biosimilars. In addition, the recombinant human hyaluronidase, which facilitates the SC delivery, may also be covered by separate patents or part of a broader exclusivity strategy for the combination. Consequently, while the fixed-dose combination is itself subject to specific patent applications and protection claims, its overall life cycle largely depends on the expiries of the constituent molecules—especially pertuzumab.

Expiration Dates 
When we address the question “When does the patent for Pertuzumab/Trastuzumab/Hyaluronidase expire?” it is important to consider that the expiration dates for the individual components differ and that the combination product might be protected by additional formulation patents.

Pertuzumab: 
Pertuzumab, marketed under the brand name Perjeta, is protected by patents that are scheduled to expire at different times in various territories. In Europe, the patent for pertuzumab is reported to expire in May 2023, while in the United States, it is set to expire in June 2024. These dates are based on estimations from the regulatory and patent filings data compiled in public analyses and reflect the strategic management of intellectual property by the innovator. The expiration of pertuzumab’s patent is highly significant because it is the later of the two main antibodies’ patent protections in this combination and represents a key barrier to biosimilar market entry.

Trastuzumab: 
Trastuzumab, known commercially as Herceptin, has a longer history with its core product patents. In the United States, the primary patents for trastuzumab expired in August 2015, while in Europe they expired in June 2019. Despite these expirations, additional patents related to manufacturing processes, formulations, and methods of use have been developed over the life cycle of trastuzumab; however, these secondary patents have not prevented biosimilar versions from entering the market in many regions. For the combination product, trastuzumab’s earlier patent expiration means that its role in determining the overall exclusivity period is now largely superseded by the later-expiring pertuzumab patents, assuming no further new formulation-based exclusive claims are issued.

Hyaluronidase: 
Recombinant human hyaluronidase (rHuPH20) is used here as an enabling component for subcutaneous administration. The patent landscape for hyaluronidase is somewhat separate from the antibodies. Many of the patents covering rHuPH20 have expired or are approaching expiry, but when used in combination with high-value therapeutic antibodies, it may be protected under combination patents or formulation patents that claim the use of hyaluronidase with pertuzumab and trastuzumab for enhanced delivery profiles. While specific publicly disclosed expiration dates for the hyaluronidase component in the fixed-dose combination are not as clearly delineated as for the antibodies, regulatory filings and strategic patent applications suggest that it is covered by the formulation claims which would typically run in parallel with the pertuzumab-related exclusivity period.

Fixed-Dose Combination Patent: 
The patents related to the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase focus on the unique aspects of subcutaneous administration, the dosing method, and the integration of the three agents into a single product. While the detailed expiration dates of these specific combination patents are not explicitly stated in the summarized materials, it is common practice that the combination patent terms will be aligned with or slightly extended compared to the component that has the latest expiration date—in this case, pertuzumab. Therefore, the overall market exclusivity for the fixed-dose combination will likely extend until approximately June 2024 in the United States and May 2023 in Europe, unless additional exclusive protection is granted via term extensions or supplementary protection certificates. This indicates that, from a practical standpoint, the market exclusivity of the combination product is determined primarily by the pertuzumab patent expiration dates, with trastuzumab’s earlier expiration already having opened the door to biosimilars for that component.

As a result, the consolidated view is that for the combination product:
In Europe, the key patent protection linked to pertuzumab expires in May 2023. 
In the United States, the crucial patent protection on pertuzumab expires in June 2024. 

Any combination-specific patents addressing the formulation (the fixed-dose combination of pertuzumab, trastuzumab, and hyaluronidase) are likely designed to preserve exclusivity up to or marginally beyond these dates, ensuring that the innovator maintains market control until the most critical component (pertuzumab) loses its patent protection.

Implications of Patent Expiration

Impact on Biosimilar Development 
The expiration of key patents for the pertuzumab component in the combination has significant implications for biosimilar development. With trastuzumab’s value proposition already challenged by the availability of biosimilars (given its earlier patent expiration in 2015/2019), pertuzumab’s later expiration provides the remaining barrier to widespread biosimilar entry for the combination therapy. Once the patents expire—May 2023 in Europe and June 2024 in the US—biosimilar developers will have a clearer path to develop and launch products that mimic the fixed-dose combination, potentially offering similar clinical benefits at lower costs.

Biosimilar manufacturers must navigate a challenging regulatory environment that requires a demonstration of high similarity in quality, safety, and efficacy. The rigorous comparability exercises mandated by regulatory authorities, as outlined in discussions on biosimilar market entry, will become even more critical in the post-expiration landscape. The fact that the combination product includes an innovative delivery mechanism through hyaluronidase means that biosimilar applicants may also need to address formulation-specific issues, such as ensuring comparable subcutaneous absorption and patient convenience. However, the removal of patent barriers generally leads to increased competition, lower treatment costs, and improved access for patients—benefits that have been observed with other biosimilar competitors in the oncologic and inflammatory disease markets.

Market Competition and Pricing 
Patent expiration is often a turning point in the pharmaceutical market. The entry of biosimilars following the expiration of key patents for pertuzumab (and by extension, the combination product) is expected to drive down prices substantially. Given that trastuzumab-based therapies historically have been among the most expensive treatments—sometimes costing upward of US$70,000 per year—the introduction of biosimilars has already resulted in cost savings of approximately 20–30% for trastuzumab products. As pertuzumab’s patent expires, similar cost savings are anticipated.

The competitive pressures arising from biosimilar entries typically result in a dual effect: while there may be an initial reduction in prices owing to increased competition, the overall market dynamics also stimulate innovation. Innovator companies like Roche, who manage the portfolio for these biologics, often react by developing new formulations or value-added services, such as subcutaneous formulations (e.g., PHESGO), to differentiate their offerings. This “evergreening” strategy may result in diversified product lines that temporarily delay or offset the impact of biosimilar competition. Nonetheless, once the core patent on pertuzumab expires, the market will see a marked shift, culminating in lower treatment costs, improved patient access, and a robust biosimilar market that challenges the pricing power of the original innovator products.

Moreover, market competition following patent expiration is not limited only to pricing dynamics. The potential use of exclusive licensing strategies, formation of patent pools, and competitive tendering processes in various European countries further accentuates the rivalry between originator biologics and biosimilar counterparts. Policy makers and healthcare providers are likely to adopt strategies that favor the prescription of best-value biologics rather than solely relying on established brand names. This, in turn, creates a market environment that encourages cost containment while ensuring that patients still receive clinically effective treatments.

Future Prospects

Research and Development Post-Patent Expiration 
The expiration of key patents for the pertuzumab component of the combination product paves the way for innovative research and new product development. With the core exclusivities waning, both the innovator and biosimilar sectors are expected to intensify their R&D efforts. For the innovator, the loss of market exclusivity often serves as an impetus to develop next-generation biologics or to improve upon existing formulations. In the case of pertuzumab, trastuzumab, and hyaluronidase combination therapy, companies might explore further modifications to enhance efficacy—for example, by investigating bispecific or trifunctional antibodies that overcome known limitations such as resistance or issues related to blood–brain barrier penetration. Additionally, improvements in drug delivery systems and novel dosing strategies could also emerge as part of efforts to extend clinical benefits and maintain a competitive edge despite the biosimilar threat.

For biosimilar developers, the post-patent phase represents an expansive opportunity to capture market share. They will need to focus on developing biosimilar products that not only demonstrate equivalence in terms of safety and efficacy but also replicate the convenience of the subcutaneous delivery system enabled by hyaluronidase. In many cases, the cost savings enabled by biosimilars can stimulate broader patient access, particularly in healthcare systems in low- and middle-income countries where treatment affordability is a critical issue. This increased uptake could result in a shift in research focus toward improving indications, optimizing dosing regimens, and even exploring combination therapies that remain beyond the reach of the original products.

Furthermore, the knowledge accrued from the clinical experience with the current fixed-dose combination will provide valuable data that can be leveraged for future regulatory submissions, postmarketing surveillance studies, and continuous improvements in manufacturing processes. As regulatory authorities gain more experience in evaluating biosimilars in complex therapeutic areas, the pathway for approval may become more streamlined, further encouraging innovation in this space.

Potential Challenges and Opportunities 
Despite the promising outlook, several challenges remain in the wake of patent expiration. One of the primary obstacles for biosimilar entrants will be the need to establish confidence among physicians and patients. Given the complexity of biologics and the inherent difficulties in replicating the exact structure and function of the originator product, concerns about immunogenicity and clinical interchangeability persist. Regulatory frameworks, particularly in the United States and across the European Union, mandate rigorous analytical, preclinical, and clinical evaluations to ensure that biosimilar products do not exhibit clinically meaningful differences from their reference products. Although these requirements are well established, the process remains resource-intensive and time-consuming, which may limit the number of entrants in the immediate aftermath of patent expiration.

Additionally, the “evergreening” strategies employed by innovator companies—such as obtaining secondary patents related to new formulations, manufacturing techniques, or improved administration methods—can extend the effective market exclusivity even after the main antibody patents have expired. For instance, the fixed-dose combination patent embodied in the pertuzumab/trastuzumab/hyaluronidase product may benefit from claims that cover the method of subcutaneous administration or other formulation-specific aspects. Such supplementary patents might temporarily delay the actual commercial impact of the core patent expiries, especially if they are upheld in litigation. Conversely, these strategies may also drive further innovation, compelling both originator and biosimilar companies to enhance their product offerings continually.

Opportunities also arise from the potential to integrate digital quality solutions, improvements in manufacturing controls, and advanced analytics into the development of biosimilar products. With advancements in process analytical technology and real-time quality monitoring (as illustrated by related patent descriptions on pharmaceutical manufacturing monitoring methods), companies can ensure high manufacturing consistency and product integrity. This not only builds confidence in biosimilar products but may also drive overall innovation across the sector through more efficient production processes and enhanced patient safety profiles.

Finally, market dynamics will increasingly be influenced by health economic considerations and evolving payer policies. As biosimilar competition intensifies, healthcare systems are likely to adopt policies based on best-value biologics rather than solely brand loyalty. This shift may drive the development of innovative reimbursement models and bundling practices that reward cost-effectiveness, thus further stimulating innovation in drug delivery, administration, and outcome-based pricing models. The strategic recalibration of portfolios by leading innovators, in response to the evolving competitive landscape, will be critical in determining the long-term success of emerging products in oncology and beyond.

Conclusion 
In summary, the patent protection for the pertuzumab, trastuzumab, and hyaluronidase fixed-dose combination is determined by the distinct patent expirations of its constituent components. Trastuzumab’s primary patents have long expired (August 2015 in the US and June 2019 in Europe), whereas the key patent for pertuzumab is set to expire in May 2023 in Europe and June 2024 in the United States. The combination product itself is further protected by additional patents covering its unique formulation and method-of-use, which are typically aligned with the later-expiring component. Consequently, the overall market exclusivity of the fixed-dose combination product is largely governed by the patency status of pertuzumab. The expiration of these patents opens the door to biosimilar market entry, which is expected to drive down prices, enhance patient access, and foster a more competitive market environment.

From a broader perspective, the loss of patent exclusivity for these biologics presents both challenges and opportunities. Biosimilar developers will face stringent regulatory requirements and the need to gain stakeholder confidence, but they will also benefit from clear market entry paths that could lead to substantial cost savings for patients and healthcare systems. Innovator companies, on the other hand, may leverage evergreening strategies and invest in next-generation therapies to mitigate revenue losses and maintain competitive advantage.

Overall, while the upcoming patent expirations—May 2023 in Europe and June 2024 in the US for pertuzumab, with trastuzumab already off-patent—signal the end of exclusivity for crucial components of the combination product, they also set the stage for the next phase of innovation and market evolution within the biopharmaceutical landscape. This dynamic scenario underscores the importance of proactive strategies in research and development, regulatory adaptation, and market planning in ensuring that both patients and healthcare systems ultimately benefit from enhanced competition, improved access, and sustained innovation in biologic therapies.

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