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Psychedelic Patents

Has Flourish Mushroom Labs Revolutionized the Field of Psychedelics?

Yield Growth (now Better Plant Sciences Inc., CSE:PLNT) subsidiary Flourish Mushroom Labs appears to have discovered a fundamentally new use for the active compounds in magic mushrooms, i.e. psilocin and its prodrug psilocybin.

On December 10, 2019, Yield Growth Corporation announced that its subsidiary Flourish Mushroom Labs filed a U.S. provisional patent application relating to “methods of using serotonin antagonists, in particular, psychedelic mushroom actives, for weight loss.

This development is exciting for at least two reasons:

  1. Using active compounds from magic mushrooms as serotonin-2a (i.e., 5HT-2a antagonists) represents an entire new area in psychedelic research.
  2. This departure from the accepted knowledge about psilocybin/psilocin suggests that Flourish Mushroom’s new use of these compounds as 5HT-2a antagonists will likely result in patentable subject matter.  (Inventions that represent a major departure from accepted knowledge are usually considered “non-obvious” during examination at the patent office.)

According to the press release, the Flourish Mushroom Labs patent application pertains to administering psilocin and/or psilocybin to provide an overall weight loss in individuals.  The weight loss is achieved by reducing food cravings, counteracting compulsive overeating, and aiding in improving quality of diet by altering food choices. The application also attempts to claim methods of administering “microdoses” of psilocin/psilocybin to provide weight loss by “increasing metabolism, which, combined with a decrease in food cravings or compulsive overeating, or altering food choices to less calorie dense foods, could result in substantial and beneficial weight loss.” Yield Growth also claims that “the Flourish Mushroom Labs pending patent also covers the use of psilocin/psilocybin in treatment or regulation of diabetes, and regulation of blood glucose and to reduce susceptibility to cardiovascular disease, high blood pressure, diabetes mellitus and other illnesses associated with obesity.”

Yield Growth’s New Approach to Psychedelics as Serotonin Receptor Antagonists.

According to Yield Growth’s press release about Flourish Mushroom Labs Provisional Patent Application, “Psilocin/psilocybin is known as 5-HT2A agonists or partial agonists.”

Psilocin is a known 5HT-2A agonist.  Psilocybin is recognized as an inactive prodrug of psilocin, i.e., neither an agonist or an antagonist.

Yield Growth’s description of Flourish Mushroom’s patent application is as follows: “U.S. PATENT TO USE SEROTONIN ANTAGONISTS FROM PSYCHEDELIC MUSHROOMS FOR WEIGHT LOSS.”

Although neither Yield Growth’s website nor the press release provides detailed information about the technology, the use fo psilocybin/psilocin as a 5HT-2A antagonist represents a significant departure from previous approaches.  To date, all other research has focused on using psilocybin as a prodrug of psilocin, thereby providing psilocin as a 5HT-2A agonist with an increasing number of applications.

This development highlights the tremendous opportunities for making new fundamental breakthroughs in the space.  It will be fascinating to follow Yield Growth and Flourish Mushrooms as they develop this new technology, which seems to defy accepted wisdom about psilocin’s method of action.

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Psychedelic Patents

Silo Wellness Announces Patent Pending Psilocybin Formulation

Silo Wellness just announced the world’s first metered-dose magic mushroom nasal spray. The nasal spray formulation was designed to provide users with rapidly absorbed and predictable doses of “full spectrum” magic mushroom compositions.  According to Silo Wellness founder, Mike Arnold, the new formulations were made to address an unmet need for precision dosing: “This is a business problem in need of a solution.  I reached out to my long-time colleague from the marijuana space, brilliant inventor Michael Hartman, and we agreed that we need to be able to give patients predictable dosing so they can self-titrate into the desired levels of sub-psychedelic or psychedelic treatment.”  

The inherent chemical variability of naturally occurring magic mushrooms has been a longstanding unmet need for people wishing to consume precise and reliable amounts of full spectrum psilocybin composition.  See State of the Art for Microdosing Psychedelics. To date, the existing options have been either (a) consume mushroom fruiting bodies or (b) consume a single purified chemical. The former fails to provide precise or reliable doses of known ingredients; the latter fails to provide the synergistic benefits of full spectrum mushroom compositions.  See Entourage Effect.  We have previously pointed out that the future of the magic mushroom industry will be formulated tryptamines.  Paul Stamets recently expressed a similar view regarding the benefits of “standardized” doses on the Joe Rogan Podcast #1385.

Silo Wellness’s Patent Strategy

Silo Wellness is also clear about its aggressive intellectual property strategy, which has become in important consideration for investors in the psychedelic space.  Silo Wellness’s webpage emphasizes its “Provisional Application for a Patent for metered dosing formulations” and directs readers to an entire page dedicated to Intellectual Property.  On its intellectual property page, Silo Wellness explains: “We have filed [in July 2019] a provisional application for a patent to cover metered dosing formulations of plant and fungal compounds for oral, nasal, sublingual, and topical use. We are developing solutions for metered dosing for mushrooms, Ayahuasca/DMT, and peyote/mescaline.”  The intellectual property was apparently developed by Michael Hartman, who has developed extensive metered-dose inhaler IP for other pharmaceutical companies. Examples of Mr. Hartman’s metered dose technology can be found here and here.

Silo Wellness further highlights it’s IP-guided strategy by describing its dual focus on technology and IP:  “The problems we are attempting to address through protectible IP (patent and trade secrets) are as follows: 1. How to deliver a predictable and safe experience; and 2. How to make them palatable.

Foreshadowing a Patent Licensing Strategy?

According to their webpage, Silo Wellness “intend[s] to be directly involved through ownership interests, product licensing agreements, and management contracts in the cultivation, manufacturing, and therapy dosing in this emerging space.”  Silo Wellness’s description of their Nasal Spray formulation also includes a section about “Licensing the Technology for Manufacturing,” where the company invites discussions about licensing their IP.

“If you have a lab in Jamaica or are otherwise interested in licensing our technology in advance of legalization in your home jurisdiction, please contact our team for available territories.”

Although Silo Wellness frequently mentions its intellectual property and licensing strategy, there is no information about the scope or contents of its patent portfolio.  The webpage states that their provisional patent application was filed in July of 2019, suggesting that the content of that patent disclosure will not publish until about January of 2021 (18 months from the earliest priority). Presumably, the IP is centered around “metered dosing formulations,” leveraging Mr. Hartman’s expertise with metered dose inhalers.  However, it is not clear what chemical compositions will be used in the metered dose inhalers or whether those compositions are subject to patent protection by Silo Wellness or another entity, like Paul Stamets who holds multiple earlier-filed patent applications on magic mushroom compositions.

Conclusions – The Patent Race has Begun

On August 28, 2018, the Waking Times published an article explaining that “The Race to Patent Magic Mushrooms Heats Up.”  Since that time, there have been murmurings about different entities filing patent applications on magic mushroom formulations or related technology.  But, with their heavy emphasis on patent strategy, Silo Wellness has confirmed earlier suspicions that the patent race has begun in the psychedelics industry.  Here, Mike Arnold refers to the “Shroom Boom” as the “New Cannabis Green Rush,” adding that the peer-reviewed studies are even stronger.  However, Mr. Arnold further notes: “When everyone is running in one direction, that’s the last place an entrepreneur or investor wants to be. If you were on time for cannabis, you were already too late.”  Given that patents are awarded to the first inventor to file, do these signs of the psychedelic patent race indicate that it’s already too late to make a meaningful IP play in the space?

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Psychedelic Patents

Compass Pathways’ Patents

In late April of 2019, both the United States Patent and Trademark Office (“USPTO”) and the World Intellectual Property Office (“WIPO”) published Compass Pathways’s Patent Applications directed to psilocybin technology.  These applications were previously unavailable for public inspection, which led some journalists to speculate that Compass Pathways was creating a “magic mushroom monopoly.”

Now that Compass’s patent applications have published, it seems clear that they have no intentions of creating an expansive patent portfolio or stifling R&D by other entities.  To the contrary, their patent claims are extremely narrow, bordering on insignificant. Thus, fears that Compass Pathways has been creating a “magic mushroom monopoly” have been drastically overstated.  By way of analogy, Compass Pathways has claimed a few grains of sand in the middle of a vast desert– not the entire desert.

Despite widespread concern that Compass’s patent portfolio would impede psilocybin science, their patent portfolio probably won’t affect psilocybin research or commerce in any meaningful way.  Again referring to the analogy of a few grains of sand in the desert:

  • There are over 180 known species of psilocybin containing “magic” mushrooms
  • Those magic mushrooms contain many active ingredients — psilocybin is just one of them.
  • Psilocybin can exist in many forms, including mushrooms, mushroom preparations, crude mushroom extracts, separated/isolated psilocybin, or synthetic psilocybin.
  • Synthetic psilocybin can exist in many forms, including crystalline material.
  • Pure crystalline psilocybin can exist in a variety of different crystalline forms, aka “polymorphs.”
  • Compass has claimed (but not yet received a patent for) two specific crystalline forms.

The figure below shows how magic mushrooms can be extracted and separated into individual active molecules.  Instead of extracting those molecules (e.g., psilocybin) from a mushroom each of them could be made synthetically in a chemical laboratory.

Naturally occurring psychoactive mushrooms contain many active ingredients. Those ingredients can be extracted with a solvent to eliminate the insoluble structural material of the mushroom. That extract can be further processed to separate out the molecules present in the extract — resulting in a collection of isolated individual molecules that are much easier to study scientifically.
Psilocybin is just one of those molecules. Psilocybin can also be produced synthetically. Synthetic psilocybin can exist as a number of different salts and crystalline forms. Compass Pathways is only claiming one new crystalline form of synthetic psilocybin.

Concerns about Compass Pathways Monopolizing Psilocybin

Over the past year, Compass Pathways has received considerable attention for its commercial interests in psilocybin technology.  Compass Pathways is presently conducting clinical trials for administering pure synthetic psilocybin to patients with Treatment Resistant Depression.  Compass Pathways is poised to become the first legal provider of pure synthetic psilocybin.

Because of a somewhat anti-capitalist reaction towards commercializing psilocybin, Compass has been the subject of considerable criticism.  Much of this criticism has focused on Compass’s filing of several patent applications related to psilocybin. Robert Jesse of John’s Hopkins University fears that corporate influence could create a landscape “clogged by proprietary methods, restrictive licensing, exclusive contracts, patents, and the like.”

In November of 2018, Olivia Goldhill wrote an article in Quartz, stating that “A millionaire couple is threatening to create a magic mushroom monopoly,” referring to Compass’s founders George Goldsmith and Katya Malievskaia.

In her article, Ms. Goldhill explained that Compass was “well ahead of other institutions working in this field—and a recently filed patent application could help the company stay ahead.”

“Compass Pathways has relied on conventional pharmaceutical-industry tactics that could help them dominate the field, including blocking potential rivals’ ability to purchase drugs, filing an application for a manufacturing patent, and requiring contracts that give Compass power over academics’ research and are restrictive even by pharmaceutical-industry standards.

Responding to concerns about the implication of their patent portfolio, Compass Pathways told Quartz “our patents will not restrict research in the field, or preclude others from creating different solutions for the synthesis and formulation of psilocybin.”

In her article, Ms. Goldhill conceded “It’s not clear what exactly would be covered by the patent.”  Now that Compass’s patent application has published, it appears that Compass was telling the truth.  Their patents will not restrict research in the field, or preclude others from creating different solutions for the synthesis and formulation of psilocybin.

Compass’s patent application is extremely narrow. It does not create a threat of any sort of “magic mushroom monopoly.”

Compass Pathways’ Published Patent Applications

Compass Pathways United States Patent Application Number 16/155,386 published on April 25, 2019 as U.S. Patent Application Publication Number 2019/0119310.  International Patent Application Number PCT/IB2018/057811 published on April 18, 2018 as WO2019073379A1.  Both of these applications claim priority dating back to the British Application Number GB1716505.1, filed on October 9, 2017. Both applications claim extremely narrow subject matter.

The claimed subject matter is extremely narrow because all of the claims are limited to one specific crystalline form of psilocybin.  Currently pending claim 1 recites:

1 . Crystalline psilocybin in the form Polymorph A or

Polymorph A ‘ , characterised by one or more of :

a . peaks in an XRPD diffractogram at 11 . 5 , 12 . 0 and

14 . 5°20 + 0 . 1°20 ;

b . peaks in an XRPD diffractogram at 11 . 5 , 12 . 0 and

14 . 5°20 + 0 . 1°20 , further characterised by at least one

further peak at 19 . 7 , 20 . 4 , 22 . 2 , 24 . 3 or 25 . 7°20 + 0 .

1°20 ;

c . an XRPD diffractogram as substantially illustrated in

FIG . 7a or 7b ; or

d . an endothermic event in a DSC thermogram having an

onset temperature of between 205 and 220° C . substantially as illustrated in FIG . 8a or 8b .

Compass’s claims do not read on previously known forms of psilocybin.  Compass’s claims have nothing to do with “magic mushrooms.” Compass’s claims have nothing to do with the other active ingredients found in magic mushrooms.  In short, Compass’s claims are only relevant the particular crystalline form of psilocybin created and used by Compass.

Unless they use Compass’s specific process and crystalline form(s), other entities would be unaffected in their ability to make, use, or sell psilocybin or the other active ingredients in magic mushrooms.

Similarly, other entities would be unaffected in their ability to make, use, or sell other prodrugs of psilocin, such as psilacetin. They would also be unaffected in their ability to make, use, or sell any varieties of magic mushrooms.

The only monopoly sought by Compass Pathways is for the right to make, use, or sell their extremely narrow and specific form(s) of synthetic psilocybin.  Compass claims ownership of new crystalline forms of psilocybin on account of their intellectual contribution to the crystallization of psilocybin.  Compass’s new/inventive crystallization step is described in detail within Example 1 at paragraph 285 of the published application. In short, the crystallization method involves dissolving crude psilocybin in hot water and then gradually cooling the water. The process is similar to making rock candy from sugar.

Compass’s method of making psilocybin is also disclosed in the application.  Their method is best described as an optimized version of a procedure that was published in the Journal of Natural Products 2003, volume 66, pages 885-887.  Compass claims to have optimized this method for making larger batches of psilocybin: “In contrast to the prior art, the present invention sought to produce psilocybin at a commercial large scale.”  Para. 276.

Conclusions

Concerns about Compass Pathways monopolizing magic mushrooms or psilocybin have been drastically overstated. Based on their recently published patent applications, Compass is only claiming a new crystalline form of psilocybin. The patentability of that “new” form has yet to be determined. During examination of the claims, a patent examiner will determine whether crystallizing psilocybin from water to afford Compass’s “new” forms represents a patentable advance beyond the prior art.  Either way, Compass is highly unlikely to impede scientific progress with its patent portfolio.

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Psychedelic Patents

New Psilocybin Patent Application by Paul Stamets

The increasing interest in psychedelic investment opportunities, including some recent developments in China, has led some analysts to begin studying the psychedelic patent landscape. Given the relatively small amount of research in the psychedelic space, very little IP has been generated to date.  Two exceptions to this rule include world-renowned mycologist Paul Stamets and CaaMTech, LLC. The UK based pharmaceutical company, COMPASS Pathways has also filed some psilocybin related patent applications, but they appear to be relatively narrow in terms of both the subject matter and geographical relevance.

Paul Stamets is one of the leading authorities on psychedelic mushrooms. See, e.g., Psilocybin Mushrooms of the World, by Paul Stamets, which is arguably the leading book on magic mushrooms. He is also an inventor of several patents, including some in the psychedelic space. On April 11, 2019, the United States Patent and Trademark Office (the “USPTO”) published a new patent application by  Mr. Stamets.

This article focuses on Mr. Stamets’s new application, US Patent Application serial number 16/211,281 (filed Dec. 6, 2018; herein “the ‘281 Application”). The ‘281 Application is a continuation of Mr. Stamets’s earlier filed U.S. Patent Application serial number 15/494,503, (filed Apr. 23, 2017), which claims priority to U.S. Provisional Patent Application No. 62/365,982, (filed Jul. 23, 2016).  Juxtaposing these two applications raising some interesting questions about the direction of psilocybin research and technology. Or, at least they may signal a change in Paul Stamets’s research focus, which may be significant to the industry in its own right.

Changing Focus of Stamets Patent Applications

Mr. Stamets’s new application (the ‘281 Application) claims a broader subject matter than the earlier filed application.  The (earlier) ‘503 Application was titled “Compositions and methods for enhancing neuroregeneration and cognition by combining mushroom extracts containing active ingredients psilocin or psilocybin with erinacines or hericenones enhanced with niacin.” The new ‘281 Application is simply titled “Psilocybin compositions.”

Arguably, the differences between the application titles illustrate Mr. Stamets’s intentions to broaden the scope of his earlier disclosure– changing the focus from (A) methods comprising at least three ingredients (psilocin or psilocybin + erinacines or hericenones + niacin) to (B) compositions containing three ingredients (a psilocybin derivative + psilocybin mushrooms or extracts + niacin).  The later-described compositions do not require erinacines or hericenones, which were an essential aspect of the original disclosure.

The evolution of the claims in the ‘281 and ‘503 Applications follow a similar trend.

The claims of Mr. Stamets’s earlier filed application (the ‘503 Application) were directed entirely to methods (not compositions), and those methods included more limitations regarding the compositions.  Claim 1 of the ‘503 Application recites:

1. A method for improving neurological health of an animal comprising: administering a therapeutically effective amount of a composition to an animal, wherein the composition comprises one or more of psilocybin, psilocin, baeocystin, norbaeocystin, salts thereof, or combinations thereof, one or more of erinacines, hericenones or combinations thereof, and niacin.

By contrast, the most recent ‘281 Application focuses on compositions.  Claim 1 recites:

1. A composition comprising:
psilocybin, psilocin, baeocystin, norbaeocystin, or salts thereof, psilocybin mushrooms or extracts thereof, or combinations thereof; and
niacin.

Compositions Combining Psilocybin Derivatives + Cannabinoids

Another interesting difference between Mr. Stamets’s earlier disclosure (the ‘503 Application) and the latest published application (the ‘281 Application) is his increased focus on combinations of psilocybin derivatives with cannabinoids.

For example, Claim 6 of the new ‘281 Application recites:

6. A composition comprising:
psilocybin, psilocin, baeocystin, norbaeocystin, or salts thereof, psilocybin mushrooms or extracts thereof, or combinations thereof;
Cannabis extracts comprising cannabidiol, tetrahydrocannabinol, or combinations thereof; and
niacin.

By contrast, the earlier disclosure provided only a limited general disclosure of this idea.  For example, claim 11 of the (earlier) ‘503 Application disclosed the following within claim 11:

11. The method of claim 1, wherein the composition additionally comprises one or more of (Bacopa monnieri), Gotu kola (Centella asiatica), Gingko (Gingko biloba), Ginger (Zingiber officinale), Holy Basil (Ocimum sanctum), Hu Zhang (Polygonum cuspidatum), Oregano (Origanum vulgare, Origanum onites), Rosemary (Rosmarinus officinalis, Rosmarinus eriocalyx, Rosmarinus species), Turmeric (Curcuma longa), Green Tea (Camellia sinensis), lavender (Lavandula spica and Lavandula species), skullcap (Scutellaria lateriflora), oat straw (Avena sativa and Avena byzantine), Diviner’s Sage (Salvia divinorum), ayahuasca (Banisteriopsis caapi and Psychotria species), Tabernanthe iboga, Voacanga africana, Tabernaemontana undulate, peyote (Lophophora williamsii), morning glory (Ipomoea tricolor, Argyreia nervosa), Cannabis sativa, Cannabis indica or Cannabis ruderalis, or combinations thereof.

Accordingly, the newer application narrows the focus considerably from (A) methods including compositions that contain (any one of) an extensive list of plants, to (B) composition having several specific compounds from one specific plant.

Discussion and Remaining Questions

Although neither Mr. Stamets’s ‘281 Application nor his ‘502 Application have issued as patents, the evolution of the claims in these applications suggest that Mr. Stamets has substantially changed the focus of his invention.

  1. Mr. Stamets’s original focus on neuroregenerative methods has evolved into a focus on all-purpose compositions.  Does this signify a departure from neuroregeneration research and development?  If not, why change the focus from particular methods to all-purpose compositions?
  2. Mr. Stamets’s original focus on erinacines or hericenones or both has virtually disappeared in the latest application.  The original disclosure was clear that the disclosed compositions all included niacin combined with erinacines or hericenones.  But the latest published application (the ‘281 Application) appears to eliminate these once critical components from the compositions.  Why the change of heart regarding erinacines or hericenones?  Given that these ingredients were critical ingredients throughout the original disclosure, why aren’t they important now?
  3. One clear consistency between Mr. Stamets’s ‘281 Application and his ‘502 Application is the absolute requirement that all of the disclosed methods or compositions include niacin. Arguably the niacin component of the invention is more important than even the psilocybin derivative: The disclosure provides for some flexibility regarding the chemical compositions of the mushrooms/mushroom extracts; But, all methods and compositions must include niacin.  Arguably, Mr. Stamets’s applications are most appropriately categorized as “Niacin Compositions.”
  4. Why the new and specific focus on psilocybin derivatives and cannabinoids? These are all naturally occurring molecules with therapeutic potential.  But, the earlier application only listed the cannabis plant alongside dozens of other plants and fungi. In the most recent application, cannabis and specific cannabinoids have been elevated to a level of importance that is surprisingly inconsistent with the original filing.
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Psychedelic Patents

Cannabis IP Foreshadows Psychedelic IP

The cannabis industry has recently recognized the importance of intellectual property (IP).  Psilocybin mushrooms and other psychedelics will likely follow a similar path.  Some entities, like CaaMTech, COMPASS Pathways, and Paul Stamets have already filed psilocybin patents. Arguably, the “race to patent” psilocybin technology and/or magic mushroom technology is already underway. See Waking Times (“The Race to Patent Magic Mushrooms Heats Up”). Also, see Paul Stamets and COMPASS Pathways.

Proven Importance of Intellectual Property in the Cannabis Industry

On November 9th, Vanmala Subramaniam published an article in the Financial Post explaining how “Cannabis companies race to clinch an edge in pot industry’s next phase of growth: Intellectual property.”

Both the cannabis industry and the psilocybin industry develop pioneering technology related to new forms of natural products. These advances support broad and extremely valuable IP.

The article highlights the “myriad of possibilities when it comes to the intellectual property of cannabis” and the importance of developing an intellectual property (“IP”) strategy early.

Companies at the forefront of IP in the cannabis industry have enjoyed rapid and incredible success.  For example, ebbu LLC was recently acquired by Canopy Growth Corporation for $400MM+ on account of “Intellectual Property (“IP”) and R&D advancements achieved by ebbu’s team.”

As a result of success stories like ebbu, other “firms are rushing to lock in lucrative patents to come out ahead.”

A while back, we published an article connecting the dots between the rapidly growing cannabis industry and the nascent psilocybin mushroom industry. See Cannabis and Magic Mushrooms – A Near Perfect Analogy.  Both industries leverage naturally occurring organisms for purposes of creating new technology.  And both cannabis and magic mushrooms provide their therapeutic benefits via the so-called Entourage Effect.

Future Importance of IP in the Psychedelic Space

Given the similarities between cannabis and magic mushrooms, it stands to reason that the industries will follow similar trajectories.  Here are some high-level similarities:

  1. Improper classification of a naturally occurring organism as a schedule I drug about 50 years ago
  2. Subsequent scientific evidence of safety and efficacy
  3. Gradual enforcement discretion reflecting scientific evidence
  4. Decriminalization
  5. Medical and/or Recreational Legalization; and
  6. Development and evolution of medical can/or recreational products.

With each step along the path of progress, the importance of IP increases.  Here’s why:

  1. Both cannabis and psilocybin innovation were shut down for about 50 years on account of legal barriers to research and development.
  2. Today’s objective interpretation of scientific evidence is changing our stance regarding cannabis and psilocybin mushrooms.  See John’s Hopkin’s Studies.
  3. Changes in regulations lead to new opportunities for research and development in these areas.
  4. New R&D in these areas gives rise to pioneering technology because the space has been long ignored.
  5. Pioneering technology creates opportunities for generating broad and extremely valuable IP.

Exciting Times ahead

Given the explosion of cannabis technology and IP, the future of the psilocybin industry should be fascinating. And, given the similarities between cannabis and magic mushrooms, it is highly likely the IP will play an important role in that story.