Antibody-drug conjugates (ADCs) are typically composed of a monoclonal antibody attached to a cytotoxic drug via a chemical linker. The antibody is able to identify biomarkers on and attach to cancer cells, allowing targeted delivery of the cytotoxic drug without damaging surrounding, healthy cells. As a result of this targeted treatment, ADCs are associated with improvement in tumor remissions and overall survival, as well as decreased side effects while undergoing treatment.
Although the first ADCs came to market two decades ago, the technology proved difficult to translate into clinical administration. For this reason, while ADCs existed, there were not many products in the market, and thus little litigation surrounding the technology. In recent years, there has been a resurgence in ADC development due to improvements in cytotoxic agents, linker technologies, and the potential to combine ADC treatment with immunotherapy and chemotherapy. There are currently 16 ADC drugs that are U.S. Food and Drug Administration (FDA)-approved and have launched, but the pipeline is robust—there are over 250 ADCs in preclinical development, and nearly another 150 in some stage of clinical development. As the market continues to mature, with more companies and products securing global approvals, there will likely be a concurrent increase in litigation involving ADCs.
Patent Litigation and other Intellectual Property (IP) Issues
The area where there has been the most litigation activity has been surrounding patents for ADCs. This makes sense, as the first step to commercializing a product and making it available to the clinical population is often obtaining patent protection. A previous article in this series highlighted potential strategies for patenting ADC inventions. With increasing numbers of ADC patents granted, it is logical to expect that litigation alleging infringement of these patents will continue to rise.
These litigations could result from patent infringement when one company's claims are infringed by a competitor working on a similar product. Given the current focus on certain diseases, such as cancer, we will likely see numerous companies targeting similar or identical antigens on cells. Consequently, two companies may have claims covering similar types of antibodies in the ADC complex and this could lead to litigation.
Similarly, companies may develop new types of linker systems for their ADCs which are incorporated into competitor products. When this occurs, there may be patent claims from the original developer which are infringed by competitors using a similar linker system.
Given the enormous potential of ADCs, companies may also partner together in the research and development and clinical trials phases to develop technology. Some of these partnerships will terminate, but each company will continue development of new products as well as pursuit of IP covering their work. Later, one company may sue the other for infringing patent claims and the companies will dispute whether the underlying IP was jointly developed during the partnership or afterwards. It's critical for partnerships to clearly agree on ownership of jointly developed IP in order to avoid these scenarios.
Finally, an increase in patent litigation will also lead to increased IPR (Inter Partes Review) filings at the Patent Trial and Appeal Board (PTAB). Any time a patent infringement suit is filed, defendants consider whether or not to challenge the patent at the United States Patent and Trademark Office (USPTO) using an IPR. With the increase in ADC litigations, we will likely see more focus on ADC patents at the PTAB as well.
Other Potential Litigation Issues
Due to the relatively untested waters in the ADC arena, there has not been extensive litigation involving these molecules. However, as the market continues to grow and more patients begin to use ADCs, there will likely be lawsuits involving ADCs in much the same way as any other pharmaceutical product.
For example, drug products are easily susceptible to product liability actions. Pharmaceuticals typically have side effects, and the same is true of ADCs. Where patients experience unexpected side effects or adverse events when using a drug, the manufacturer may be at risk of a lawsuit for negligence, failure to warn, misleading labeling, defective manufacturing, or improper marketing.
ADCs could also become more prominent players in lawsuits regarding Medicare negotiation of pricing for drugs. Under the Inflation Reduction Act (IRA), Medicare has the authority to negotiate prices directly with pharmaceutical and biotechnology companies, but only with respect to certain drugs that do not have generic or biosimilar equivalents and that have been on the market for a set number of years. Drug companies like Merck have filed lawsuits challenging this provision of the IRA as unconstitutional and impermissibly stifling innovation.
ADCs are likely to fall into this category as the market matures, as they are unlikely to have biosimilar equivalents—that is, a product with no relevant differences from an already-approved biotherapeutic (known as a reference product) regarding efficacy, safety, quality, purity, and potency. Because of the vastly complex nature of the monoclonal antibody component of an ADC, experts agree that it is unlikely that any ADC will receive approval through the biosimilar process in the near future. Therefore, ADCs on the market may be subject to price negotiation with Medicare, leading to further future lawsuits over the IRA as it applies to ADCs.
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