Navigating the complex LNP IP landscape
Rose Hughes
Navigating the complex LNP IP landscape
It is difficult to find a field of patent law in pharma and biotech at the moment that is more complicated and fast-moving than the field of lipid nanoparticles (LNPs). IP strategy for LNPs involves sophisticated science, multiple and overlapping technology platforms, trade secret and ownership disputes and global patent cross-litigation. As we move away from historical disputes surrounding the COVID-19 vaccines, how do companies seeking to develop the next wave of LNP-based products in cell and gene therapy navigate the landscape?
What are LNPs?: Structural formulation and encapsulation challenges
LNPs are sophisticated nanoscale delivery vehicles designed to transport delicate genetic cargo into target cells. Without a protective capsule, nucleic acids like messenger RNA (mRNA) or DNA would be susceptible to degradation by enzymes in the bloodstream. Nucleic acids also need some way to bypass the cell membrane to enter the cell. An LNP both shields its fragile cargo and facilitates its entry into the cellular cytoplasm.
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The remaining three components play equally vital supporting roles for the ionisable lipids. Pegylated lipids are added to control the particle size during formation and provide a hydrophilic shield. This shield is essential for preventing aggregation and reducing clearance by the immune system after administration. Sterols, typically cholesterol, serve as structural helpers that fill gaps within the lipid bilayer to stabilise the particle. Finally, helper phospholipids, such as distearoylphosphatidylcholine, contribute to the overall structural integrity and support cellular uptake.
However, simply combining the four LNP ingredients is not enough to make a functioning LNP. The specific quantitative relationship between them is incredibly important. Innovators must optimise the specific molar ratios of these components to fine-tune the physicochemical properties of LNPs, including their size, stability and surface charge. These properties ultimately dictate the biological performance of the therapy. Efficient and scalable manufacture of LNPs also remains a challenge.
mRNA vaccines: Clinical validation and historical development of LNPs
LNPs forced themselves into the public consciousness during the COVID-19 pandemic. However, the foundational technology actually pre-dated the pandemic by several years. Instead of vaccines, the early LNP products related to the delivery of RNA cargo for silencing of gene expression, with the RNA company Alnylam achieving the historical approval for the first siRNA LNP in 2018 (patisiran, marketed as Onpattro).
When the COVID-19 pandemic struck, the pharmaceutical industry (and governments) then took a gamble by applying LNP technology to vaccines for the first time, in an attempt to overcome the slow manufacturing associated with traditional viral vector-based vaccines. Pfizer and BioNTech collaborated to produce their vaccine, Comirnaty, using their own LNP formulation, whilst Moderna independently developed Spikevax, using another LNP and specific ionisable lipids.
In vivo cell therapy: Commercial acquisitions and clinical pipelines for the next wave of LNP products
As we all know, the LNP-based mRNA vaccines were a success, both clinically and commercially. Building on this, the pharma industry is now aggressively pushing LNP technology beyond infectious diseases and into the realm of complex biotherapeutics, particularly in vivo cell therapy. Unlike traditional ex vivo cell therapy where a patient's cells are extracted and engineered in a laboratory before being reinfused, in vivo cell therapy engineers the cells directly inside the patient's body in the manner of a gene therapy. A targeted LNP delivers the genetic instructions to reprogram circulating cells to attack cancer or autoimmune diseases. This approach is expected to provide huge cost savings by reducing manufacturing and delivery challenges.
For cancer cell therapy, the aim is not a few more months of life expectancy, the aim and expectation is full remission. Similarly, for autoimmune disease cell therapy, the aim and expectation is not a few points improvement in disease severity scales and a hopeful reduction in harmful steroid use, but full remission. However, traditional cell therapy comes with a cost and manufacturing burden that can only enable its use in a small number of the cases and indications, specifically as an end-of-the-line therapy for incurable cancer. In vivo approaches seek to solve that problem.
It is therefore unsurprising that the scientific and commercial interest in this space over the past couple of years has been huge. Large pharmaceutical companies have been aggressively pursuing high value cell and gene therapy acquisitions and collaborations, including in the LNP space. Interestingly, this has been part of a broader shift in strategy from big pharma towards acquiring entire technology platforms capable of generating multiple future products rather than single drug candidates. Key mergers and acquisitions include AbbVie’s 2.1 billion dollar acquisition of Capstan Therapeutics.
The clinical pipeline for LNP-based in vivo CAR-T cell programs is now also rapidly maturing. Capstan initiated a Phase 1 trial for CPTX2309 in June 2025 in SLE and RA patients (NCT06917742). The Capstan platform is based on an ionisable lipid designed to reduce off-target liver accumulation and minimise reactogenicity. The trial is expected to read out in 2026. The first clinical data is now also starting to emerge. The most mature clinical dataset currently belongs to MagicRNA, with its publication of the first clinical data for a mRNA based in vivo CAR T therapy in The New England Journal of Medicine in September 2025. MagicRNA reported results from 5 patients with refractory SLE who received their targeted LNP therapy, known as HN2301. The treatment was administered intravenously without lymphodepletion. Crucially, the treatment achieved complete depletion of the harmful circulating B cells for up to 10 days, which led to a substantial reduction in disease severity scores.
More clinical data has been presented by Vivacta Bio and Grit Biotherapeutics. In a Phase 1 study, 2 patients with relapsed or refractory non-Hodgkin lymphoma received multiple doses of targeted mRNA-LNP without the need for lymphodepleting chemotherapy. Vivacta reported in an oral presentation that the therapy was generally well tolerated and both patients demonstrated high receptor expression on circulating T cells. Durable and repeatable expansion was reported following each subsequent dose.
As is often the case these days, further clinical insights are emerging from investigator initiated studies in China. Starna Therapeutics has reported that a single low-dose infusion of their therapy achieved the complete elimination of circulating B cells within 72 hours in patients with SLE and non-Hodgkin lymphoma (data currently unpublished). Starna Therapeutics is now starting clinical trials in relapsed or refractory non-Hodgkin lymphoma (NCT07245251).
As an aside, it is important to note however that LNPs are not the only game in town when it comes to in vivo cell therapy. The most recent and largest deal in the in vivo cell therapy space (April of this year) was Eli Lilly’s announcement that it will acquire Kelonia Therapeutics for up to seven billion dollars. Unlike the LNP-based deals, the platform developed by Kelonia uses engineered lentiviral particles to transduce T cells in vivo. It remains to be seen whether either LNPs or lentivectors will be the technology of choice for in vivo cell therapy. At the moment, the decision will be a scientific, not a legal one.
Securing IP protection for LNPs
Given the challenges associated with developing LNPs, and the multiple components involved, it is unsurprising that LNP platforms and products are protected by multiple layers of IP, both trade secrets and patents. Patents covering LNPs relate to the types of ionisable lipids, pegylated lipids, helper lipids and additional components in the particles. There are also highly valuable platforms relating to LNP formulations and LNP manufacture. There is further considerable IP relating to optimised LNP cargo formats, such as circularised RNA, and methods and components for targeting LNPs to specific cell types and tissues. Of course, beyond the LNP platform itself, it is also possible and usual to protect the specific cargos. Onpattro, for example, is protected by patents relating to both the sequence of the siRNA cargo (US 8168775 B2) and a method of treatment comprising administering LNPs comprising the siRNA (US 9101643 B2).
Foundational patent litigation and trade secret disputes
Unsurprisingly, the immense commercial value and potential clinical benefits of this technology has inevitably led to an exceptionally complex web of multi-jurisdictional legal disputes. The most high-profile conflicts involved the foundational formulation patents controlled by Arbutus Biopharma and Genevant Sciences. This foundational estate covers the fundamental four-component LNP architecture and its associated manufacturing methods. Arbutus and Genevant initiated global litigation against Moderna, asserting a suite of patents including US 8058069, US 8492359, US 9364435, US 9504651 and US 11141378 against the Spikevax and mRESVIA vaccines (Arbutus v. Moderna). The pair subsequently launched a parallel suit against Pfizer and BioNTech asserting a similar patent family, including US 11298320 and US 11318098, against the Comirnaty vaccine (Arbutus v Pfizer).
Alnylam Pharmaceuticals has pursued a more focused litigation strategy by asserting composition of matter patents directed to specific biodegradable cationic lipids, including US 11246933, US 11590229, US 11612657, US 11633479 and US 11633480. Alnylam alleged that the SM-102 lipid used by Moderna and the ALC-0315 lipid used by Pfizer infringed these specific chemical structures. Notably, the Federal Circuit decision in Alnylam v Moderna illustrated the critical need for precise language when drafting and the impact that description definitions can have in the US (Case No. 23-2357). By including a restrictive boilerplate definition for the term branched alkyl in the description, the Patentee was found to have acted as its own lexicographer, and drastically narrowed their claim scope, providing an easy escape for the Defendant (IPKat). Following this loss, Alnylam has withdrawn its parallel suit against Pfizer and BioNTech.
Moderna, whilst defending against Arbutus and Alnylam, has itself aggressively sued Pfizer and BioNTech across multiple jurisdictions. Moderna asserted patents such as US 10702600, US 10933127 and EP 3718565 which claim the platform tech combining specific mRNA modifications with LNP delivery. In a defensive action, Pfizer and BioNTech successfully invalidated the two key US patents at the Patent Trial and Appeal Board (PTAB), successfully arguing that Moderna had obtained these patents using "unimaginably broad claims" directed at fundamental mRNA concepts that were already known prior to their 2015 priority date (see IPwatchdog). Over the pond, a German court issued a mixed ruling that favoured Moderna, and found infringement of the European patents (case ID: 4b O 62/22). GSK has also now found some patents it thinks are relevant, and has launched infringement proceedings against Pfizer, with Pfizer counterclaiming for revocation of the patents.
Further compounding this complexity, instead of traditional infringement suits, Acuitas has favoured inventorship claims against both Alnylam and CureVac. By arguing their scientists made inventive contributions and should be named as co-inventors, Acuitas is seeking to gain co-ownership rights, which would effectively neutralise the threat these patents pose to themselves and BioNTech.
What happens next?
Recently, the turbulent landscape has begun to calm somewhat. To begin with, a number of the foundational patents are now rapidly approaching their expiry dates. Therefore, whilst their validity makes them still relevant to historical COVID-19 vaccine sales, they are becoming increasingly irrelevant for next-generation LNP products which are many years away from launch. We are also now starting to see settlements between the parties. In March of this year, Arbutus and Genevant announced a massive global settlement with Moderna to resolve their infringement claims and grant a non-exclusive licence.
Additionally, many of the patents currently in dispute have been narrowed specifically to relate to particular vaccine products or the LNP formulations used in these products. Whilst it is not historically possible for the defendants to retroactively modify their LNP formulations and/or the lipids they used for their blockbuster vaccines, companies developing new LNP-based products may do so.
Nonetheless, whilst the vaccine disputes are winding down, legal conflicts are already erupting in relation to the next phase of therapeutics. Interestingly, trade secrets are emerging as a key area of contention alongside traditional infringement proceedings, with even in vivo cell therapy products in the potential firing line. In September 2025, Arcturus Therapeutics initiated a lawsuit against the Defendant AbbVie in the California federal court, following AbbVie's acquisition of Capstan. Arcturus alleges that Capstan Therapeutics hired away a former employee and a consultant to misappropriate trade secrets concerning LNP technology. Arcturus claims that the primary value of the Capstan acquisition lies in these stolen trade secrets relating to the use of delivery vehicles to transport RNA payloads for treating autoimmune diseases. Furthermore, Arcturus asserts that Capstan quickly applied for a related patent naming the former personnel as inventors and incorporating the allegedly stolen proprietary information. It seems therefore that trade secret disputes are not solely the purview of the tech industry. With trade secrets also playing an increasingly important component of IP strategy within biotech, this will be an interesting case to watch.
Final thoughts
The LNP landscape can feel very daunting to navigate. However, developers of new LNP-based products can take heart that the majority of the active disputes relate to IP that is now fairly old, or irrelevant to the next wave of LNP products (absent stolen secrets). Furthermore, the fact that there has been so much litigation in this field probably has as much to do with the commercial success of the vaccines as it has with the underlying IP. The future of IP strategy for LNP will have a very different focus, and must be about building layers of protection for these complex and multi-layered products. Stay tuned for Part 2.
Further reading
- Alnylam v. Moderna and the judicious use of definitions: The European perspective (June 2025)
- Freedom to operate versus patentability in biotech: What the difference is and why it matters (June 2025)
- Why patents matter: Understanding the importance of IP in the pharma industry (July 2025)
- The reproducibility challenge for advanced therapies (T 0827/23) (Aug 2025)