Psychedelics: from fungi and plants to patents

In the past few years there has been a burgeoning interest in the use of psychedelics for the treatment of unmet medical needs in mental health.

Globally, the psychedelics drugs market was estimated to be valued at roughly $5 billion in 2020 and is projected to grow to about $11 billion by 2027.

Accompanying the efforts to commercialise psychedelic technologies has been a steady increase in patent filings as companies and universities seek to protect their investment and maximise commercial opportunities. This article addresses patent issues related to psychedelics.

Background

At the outset, it’s helpful to understand some technical and historical features of psychedelics. The term psychedelics is loosely applied to compounds that are defined based on their pharmacological profiles. Most psychedelic compounds function as serotonin 5-HT2A receptor agonists, although the precise mechanism of action leading to psychoactive effects is not fully understood.

Even medical dictionaries acknowledge this lack of a rigorous definition. “Stedman’s Medical Dictionary” defines psychedelic as: “Pertaining to a ‘rather imprecise’ category of drugs with mainly central nervous system action, and with effects said to be the expansion or heightening of consciousness, eg, lysergic acid diethyl amide (LSD), hashish, mescaline, and psilocybin.”

Psychedelics have diverse chemical structures, falling generally within three families: tryptamines, phenethylamines, or lysergamides. Many psychedelics, including psilocybin, mescaline, ayahuasca, and ibogaine are derived from fungal and plant sources. Others, such as LSD and 3,4-methylenedioxymethamphetamine (MDMA), were chemically synthesised in conventional pharmaceutical research programmes.

In addition to centuries of use by indigenous cultures, psychedelics became the focus of substantial scientific research from the early 20th century through the 1970s. Research was curtailed in the US following their classification as illegal pursuant to Schedule 1 of the Controlled Substances Act of 1970.

Over the past 15 years, psychedelics have experienced a resurgence due to compelling early evidence of substantial efficacy compared to conventional treatments. Investigators at universities and in the private sector have reevaluated psychedelics for treating central nervous system conditions and others, eg, depression, post-traumatic stress disorder (PTSD), obsessive-compulsive disorder, bipolar disorder, anxiety, cluster headaches, and eating disorders.

This research has been further facilitated by an accommodative Food and Drug Administration (FDA) which has granted breakthrough therapy designation to four psychedelic therapies (MDMA, two psilocybin therapies and ketamine), providing for expedited development and review. In 2019, the FDA approved Janssen Pharmaceuticals’ esketamine, the more potent enantiomer of racemic ketamine, for treatment-resistant depression.

The Multidisciplinary Association for Psychedelic Studies’ (MAPS) MDMA therapy for PTSD is in the final innings of its phase three trial, with commercialisation anticipated in 2023. Despite the recent proliferation of companies in the private sector and university research programmes, the industry is in the early stages of development, opening the door for securing IP protection while at the same time presenting some challenges.

Patenting challenges

The legality of psychedelics is irrelevant to patentability in the US. The US Patent and Trademark Office (USPTO) routinely grants patents relating to psychedelics. Patent offices in other jurisdictions, including Canada and Europe, have similar policies.

Nevertheless, there are two significant hurdles to securing patent protection for psychedelic inventions. The first hurdle is that classic psychedelic compounds are known in the art and are not patentable. The problem of seeking patent protection around a known compound is not new. Many applicants in the psychedelics field have relied on anti-generic strategies familiar to practitioners in the life sciences.

For example, applicants have focused on securing claims to specific isolated molecular forms of the compounds; pharmaceutical formulations with potentially superior pharmacokinetics; chemically modified compounds; drug combinations; dosage regimens; and methods of synthesis. Applicants have also focused on new disease indications to secure method of treatment claims.

The second hurdle is the limited availability of prior art databases, which can impose challenges to securing strong patent claims. Because many psychedelic compounds were used in traditional medical or religious practice or were the subject of underground use, published information on these compounds is often sparse.

Taken together with the Schedule 1 status of many psychedelic compounds in the US, which dampened scientific research programmes for nearly 50 years, ferreting out relevant references, particularly non-patent literature references, can be difficult. Failure to identify relevant references can potentially have negative consequences in two ways.

Two examples from the cannabis industry, which also suffers from a lack of extensive prior art databases, illustrate the problem. In Insys Development Company v GW Pharma and Otsuka Pharmaceutical, a US Patent and Trial Appeal Board (PTAB) case, and United Cannabis Corporation v Pure Hemp Collective, a patent infringement case before the Federal Circuit, claims were challenged as obvious over or anticipated by references that were more than 50 years old.

The claims in both cases were characterised as overly broad, and challengers identified older references relevant to patentability that were overlooked by the USPTO during patent prosecution. Similar legal challenges are likely to occur in the rapidly expanding psychedelics industry.

The reassurance provided by strong patent portfolios is important in helping early-stage companies attract much-needed investment. Like the pharmaceutical industry, the psychedelics industry faces high costs (nearly $1 billion when accounting for failed drug candidates) and long lead times (ten to 13 years until commercialisation) in bringing therapeutics to market.

Weak claims may increase investor risk. Concerns that granted claims might be vulnerable to challenge or that pending claims may not mature into commercially valuable claims may factor into investment or licensing decisions.

A potential emerging challenge to patenting psychedelics relates to psychedelic-assisted psychotherapy, a treatment method involving administration of psychedelics in conjunction with psychotherapy.

Such therapy sessions may use particular settings, one or more attending therapists, and last up to eight hours. Research in this area is evolving, but the therapeutic benefit may stem from synergy between the drug and psychotherapy. The USPTO has experience examining combination claims the USPTO database contains about 60 patents having combination claims to psychotherapy) although how this experience will be applied to any particular claim is likely to be fact-specific.

Looking ahead

Many companies and universities are pursuing approaches that potentially afford ways to steer clear of some of the challenges listed above. Some examples include:

1) Development of “third-generation” psychedelics:

Following on the development of novel formulations and delivery methods for classic psychedelics to produce “second generation” therapeutics, some industry players are now modifying the “molecular scaffolds” of known compounds to generate psychedelics with different structural and functional properties.

These “third-generation” psychedelics are more likely to be patentable as new compositions of matter. Such compounds may have superior pharmacokinetics, solubility, and ultimately, improved efficacy. Furthermore, the development of compounds with faster clearance rates may reduce the amount of time needed for each psychedelic psychotherapy session. Presently, such sessions can be costly and are generally not scalable.

2) Development of non-psychoactive “psychedelics”:

Modification of the molecular scaffolds of known compounds or identification of new compounds that retain the beneficial therapeutic effects of known compounds but lack the hallucinogenic effects. This approach is in its infancy, but such compounds may not require psychedelic-assisted psychotherapy for their use and have greater commercial viability.

3) Production methods:

Genetic engineering of fungal and plant sources to develop more efficient ways of producing compounds or compounds with different functional properties.

4) Patient selection:

Using a variety of biomarkers to stratify patient populations into cohorts that are more likely to respond to psychedelics.

The challenges of obtaining patent protection also have prompted some in the field to seek alternative approaches to IP protection in the form of regulatory exclusivity. In the US, the FDA provides up to seven years of regulatory exclusivity depending on the chemical entity and the type of exclusivity sought.

Additionally, orphan drug exclusivity is available for drugs used in treatment of diseases affecting less than 200,000 individuals per year. Regulatory exclusivity varies by jurisdiction, so companies seeking to rely on regulatory exclusivity should consult local experts.

Takeaways

As commercialisation of psychedelics moves forward, those companies with strong IP portfolios will be at a competitive advantage, in terms of attracting investment and forestalling patent challenges, particularly as the field grows more crowded.

Companies should take proactive steps in generating and managing their patent portfolios. Applicants should consider doing a careful analysis of patent and non-patent literature before filing a patent application. Applicants should also consider global strategies, drafting applications with an eye to global coverage. Once an application is filed, applicants should also regularly monitor the literature, paying particular attention to new information relating to the use of compounds in traditional religious practices.

Finally, applicants should make sure that granted claims actually cover what is likely to be a commercial product. Research focus may change over time, so applications should be monitored to ensure that claim amendments are consistent with product development. Lastly, companies should establish multiple layers of IP protection that include regulatory exclusivity if applicable.

Gretchen Temeles is of counsel at Hiller. She can be contacted at:  gt emeles@hillerpc.com

Timothy Schlidt is the co-founder and partner at Palo Santo Ventures. He can be contacted at:  tim@palosanto.vc