In 1910, German scientist Paul Ehrlich introduced a groundbreaking concept to the world: chemical compounds could be engineered to interact with unique receptors on disease-causing cells while avoiding interaction with healthy cells.

Over a century later, Antibody Drug Conjugates (ADCs) – which are a species of Ehrlich’s “magic bullet” concept – have been developed by many of the world’s leading global pharmaceutical companies primarily to treat cancer.

This article provides an overview of (1) ADC technology; (2) the ADC competitive landscape; and (3) key patent strategies for operating in this space.

ADC Technology

ADCs are comprised of three major components that each play a crucial role in the mechanisms of action and therapeutic effects of ADCs.

They include (1) a monoclonal antibody that selectively binds to target antigens located on specific cancer cells; (2) a cytotoxic payload that is configured to kill the targeted cancer cells; and (3) a linker that connects the payload to the antibody and controls the release of the payload.

While simply explained here, ADCs are incredibly complex molecules which can be engineered in a multitude of ways to result in conjugates tailored to address a wide range of indications. These diversities also make ADCs a ripe area for innovation.

ADC Competitive Landscape

Many of the world’s leading pharmaceutical companies are active in the ADC space. For example, as summarized below, Pfizer, Astra-Zeneca, GSK, Daiichi Sankyo, Gilead and Roche, and other companies, have assets that have received marketing authorization from the U.S. Food and Drug Administration (FDA).

Of the above products, Adcetris, Kadcyla, Enhertu, Padcev, Polivy, and Trodelvy have reportedly each reached or are expected to obtain over $1 billion in annual global sales.

The ADC space has seen significant deal activity over the past several years with Abbvie, Amgen, AstraZeneca, BioNTech, BMS, Eli Lilly, Genmab, Gilead, GSK, Ipsen, Johnson & Johnson, Merck, Pfizer, Roche, and Vertex, each inking major ADC-related deals (including 9, 10 and 11-figure deals) through acquisition and/or collaboration.

Notable acquisitions include Gilead’s 2020 acquisition of ImmunoMedics (valued at ~$21 billion); Pfizer’s 2023 acquisition of Seagen (valued at ~$43 billion); AbbVie’s 2023 acquisition of ImmunoGen (valued at ~$10 billion); and Johnson & Johnson’s 2024 acquisition of Ambrx Biopharma (valued at ~$2 billion). Those and other acquisitions are summarized as follows:

In addition, many other ADC-related deals have been secured over the past several years by companies not mentioned above.

This all makes for a robust and dynamic space that will continue to evolve as existing and new market players increasingly pursue ADC-based medicines and enter the market.

As this activity continues, so will related innovations, and  companies operating in this space must take steps to smartly navigate third party patent rights while building their own patent portfolios.

Key ADC Patent Strategies

Freedom to Operate

ADC innovators, including pioneers and newer entrants, have developed significant ADC-related patent portfolios, with such filings having significantly increased over the past few decades.

Such patents and applications include claims directed to antibodies, linkers, cytotoxic payloads, manufacturing methods, methods of treatment, and other ADC-related subject matter. 

Given this complex patent landscape, companies developing ADCs must take careful consideration that their ADC candidates do not risk infringing existing IP. Conducting this freedom to operate (FTO) analysis at the outset is critical to avoid expending significant resources for regulatory and other efforts only to later discover that the ADC candidates may be infringing.

The FTO analysis should take a number of considerations into account including (1) the ADC structures and formulations at issue; (2) the patent landscape and infringement risks; (3) timing for commercialization; (4) timing for patent expiration; (5) market and manufacturing locations; (6) scope of applicable pre-commercialization safe harbors; (7) licensing options; (8) potential design-arounds; (9) internal innovation; and other factors.

Notably, patents relating to several of the most profitable ADCs – including Kadcyla, Adcetris, and Trodelvy – face expiration in the coming years. This is something companies should potentially consider taking advantage of in their programs, while understanding that related follow-on patents may also be highly relevant.

Innovation

If a company determines from its FTO analysis that its desired ADCs may infringe third-party patents, there are several options to consider.

First, the company should, if possible, develop its own novel technology directed to, for example, the aspects of the ADCs that may be covered by third-party patents. This is an ideal scenario potentially yielding the two-fold benefit of avoiding infringement and building IP assets in the process, which may be used both to shield the invention and as a source of revenue through licensing.

Protection could be sought for novel monoclonal antibodies (e.g., antibodies exhibiting unique binding properties, broader target selection, or enhanced tumor-targeting abilities); cytotoxic payloads (e.g.,cytotoxic agents, derivatives, or modifications thereof that have increased potency); linkers (e.g., linkers that exhibit promising stability, cleavability, and biocompatibility; methods of treatment (e.g., for new indications); combination therapies and formulations (e.g., formulations to treat various indications); and conjugation methods (e.g., methods that improve site-specific conjugation and stability). Ideally, the patent portfolio should protect the company’s foundational technology –especially its market differentiators.

Regarding conjugation methods, since ADC manufacturing can be quite complex, companies may also consider holding those and other internal processes as trade secrets in lieu of filing for patent protection. This approach should be carefully considered in consultation with patent counsel. 

Furthermore, a company may also determine that using third-party patented technology in its ADCs could be desirable. In that circumstance, the company may seek to license the technology from the patent holder which, on the one hand, could be a good collaboration opportunity, but on the other hand could also be overly expensive or not possible (e.g., in a direct competitor situation).

Moreover, in the event a company believes that the patent in question is not valid, the company could challenge the patent by filing a petition for post grant review (PGR) or inter partes review (IPR) with the USPTO Patent Trial and Appeal Board to attempt to cancel the subject patent. Opinions of counsel for invalidity and/or non-infringement may also be obtained to mitigate against claims of willful infringement and be useful when mounting a defense to infringement allegations.

The above is exemplary, and a company would have many approaches to consider when formulating a winning IP strategy based on its particular circumstance.

Conclusion

The ADC therapeutics space is surging and could have a major, long-term impact on cancer care. With respect to IP, market players should proceed judiciously in both establishing freedom to operate and building homegrown patent portfolios. In all cases, companies should consult with their well-informed patent counsel in developing and implementing a proper IP strategy that positions them for success.

End note: Reports by Alira Health and Veranova®, as well as other numerous publicly available resources, were helpful in providing the market-related information set forth in this post.

Disclaimer: The information contained in this posting does not, and is not intended to, constitute legal advice or express any opinion to be relied upon legally, for investment purposes or otherwise. If you would like to obtain legal advice relating to the subject matter addressed in this posting, please consult with your attorney. The information in this post is also based upon publicly available information, presents opinions, and does not represent in any way whatsoever the opinions or official positions of the entities or individuals referenced herein.