IMPROVEMENTS IN PRODUCTION OF CANNABIS FOR MEDICAL AND INDUSTRIAL USES AND THEIR PROTECTION

The use of Cannabis has been stigmatized due to its psychoactive effects; however, it has several uses in industry and medicine.

Cannabis contains more than 500 components. Two of these have been the subject of scientific investigation due to their pharmacological properties: Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). Other plant-derived cannabinoids include cannabinol (CBN).

Cannabis as a drug and industrial hemp both derive from the species Cannabis sativa and contain the psychoactive component tetrahydrocannabinol (THC), yet they are distinct strains with unique phytochemical compositions and uses. Hemphas lower concentrations of THC (0.3% or less) and higher concentrations of cannabidiol (CBD), which means minimal to no psychoactive effects. The legality of industrial hemp varies widely between countries. Some governments regulate the concentration of THC and allow only hemp that is bred with an especially low THC content.

The discussion on the use and legality of each of these plants, even if they are from the same family, must be carried out for each of them. Separating it into the legal, productive, and social fields would also make it possible to differentiate the recreational, medical, and wellness uses of marijuana from the industrial, medicinal, and useful properties of hemp. This would, in turn, motivate research, health, industrial, and economical advancement, improving the quality of life for hundreds of patients.

USES OF CANNABIS

Recent reports indicate that Cannabis production is increasing and that cannabinoid formulations have been changing over the last two decades, especially with regard to their THC and CBD concentrations.

Therapeutic applications of Cannabis and cannabinoids

THC is the psychoactive principle of Cannabis, inducing the Cannabis inebriation sought by many users. Its addictive potential and negative consequences are now well known. The effects of CBD are distinct and, in many cases, the opposite of THC’s effects. CBD seems not to induce euphoria and seems to have antipsychotic, anxiolytic, antiepileptic, and anti-inflammatory properties.

According to an evaluation (in 1999) by the Institute of Medicine in the United States, on Cannabis as a medication, the future of medical Cannabis lies in isolating its cannabinoid components and their synthetic derivatives. The variable composition within the raw Cannabis plant and especially the differing THC/CBD ratios make therapeutic applications of these products quite complex.

The following medical applications have been described for Cannabis:

THCAnalgesic Anti-bacterial Anti-cancer Anti-inflammatory Anti-spasmodic Appetite Stimulant Bronchodilator NeuroprotectiveTHCVAnti-convulsive Appetite Suppressant Bone Stimulant
CBDAnalgesic Anti-anxiety Anti-bacterial Anti-cancer Anti-convulsive Anti-depressant Anti-emetic Anti-inflammatory Anti-insomnia Anti-ischemic Anti-psychotic Anti-spasmodic Bone Stimulant Immunosuppressive Neuroprotective
CBDVAnti-convulsive Bone Stimulant CBCAnalgesic Anti-bacterial Anti-cancer Anti-depressant Anti-fungal Anti-inflammatory Anti-insomnia Bone StimulantCBGAnalgesic Anti-bacterial Anti-cancer Anti-depressant Anti-fungal Bone Stimulant

Industrial uses

Hamp has been refined into a variety of commercial items, including the following listed below:

TEXTILES Clothing Diapers Handbags Denim Shoes Fine Fabrics
INDUSTRIAL TEXTILES Rope Canvas Tarps Carpeting Netting Caulking Molded Parts
PAPER Printing Newsprint Cardboard Packaging
BUILDING MATERIALS Oil Points Varnishes Printing Inks Fuel Solvents Coatings Fiberboard Insulation Acrylics Fiberglass Substitute
FOODS Hemp Seed Hearts Hemp Seed Oil Hemp Protein Powder EFA Food Supplements
BODY CARE Soaps Shampoos Lotions Balms Cosmetics

PRODUCTION OF CANNABIS

Millennia of selective breeding have resulted in varieties that display a wide range of traits; e.g. suited for particular environments/latitudes, producing different ratios and compositions of terpenoids and cannabinoids (CBD, THC, CBG, CBC, CBN…etc.), fiber quality, oil/seed yield, etc. Hemp grown for fiber, for example, is planted closely, resulting in tall, slender plants with long fibers.

The high THC concentrations obtained from the various Cannabis varieties result from technical advances in production, such as genetic manipulations, cross-breeding, and improvements in indoor hydroponic cultivation. As advanced techniques and more potent seeds have become more widely available, a steady increase of THC concentrations in Cannabis has been made possible.

Genetic modification and engineering could enable industrial-scale production of cannabinoids that have pharmaceutical potential, and provide more efficient alternatives.

The PCT application No. PCT/US2019/017433 describes a method of increasing the cannabinoid levels in a genetically modified Cannabis sativa plant which includes genetically modifying the plant to induce the overexpression of the gene that controls the expression of tetrahydrocannabinolic acid (THCA) synthase and/or cannabidiolic acid (CBDA) synthase.

The PCT application No. PCT/IL2019/050653 discloses methodsof in vitro clonal propagation, regeneration and transformation inCannabis.

Some researchers and biotechnology companies are aspiring to replace Cannabis plants with microorganisms that have been genetically enhanced to produces THC, the non-psychoactive compound cannabidiol (CBD) and many other cannabinoids of pharmaceutical interest. Others are aiming to modify chemical synthesis in the Cannabis plant by genetically altering its cells to make the desired molecules from shoot to tip, thereby boosting yield.

US patent application No. 16/594,733 discloses a method of generating and selecting mutant new varieties of Cannabis plants through chemical mutagenesis of Cannabis cell suspensions.

Benefits of microbial synthesis include the ability to mass-produce rare cannabinoids that are usually present in plants only in trace amounts or even molecules not found in nature. Transgenic plants can also be engineered for superior resistance to pests and environmental stresses.

Ploidy manipulation is a valuable tool in plant breeding. Important consequences of genome doubling can include larger organs and improved production of secondary metabolites, often linked to increased tolerance to biotic and abiotic stress. Polyploid forms also provide a wider germplasm base for breeding. Polyploids have yet to be implemented in most breeding programs for Cannabis.

US patent application No. 16/357,999 describes a method for inducing polyploidy in a Cannabis plant, the method comprising treating the Cannabis plant or a part thereof with an amount of a dinitroaniline compound effective to induce polyploidy.

The PCT application No. PCT/US2017/027643disclosesa plant of the genus Cannabis that does not require flowering in order to produce trichomes comprising secondary compounds. The disclosed plants have a high mass% of secondary compounds and a high degree of trichome coverage on the surface of the plant.

US patent applications Nos. 16/560,260 and 16/510,032 describe the identification and use of particular CBDa synthase alleles, more particularly the use of these alleles to produce Cannabis plants having very high rations of CBGa to CBDa and/or THCa.

IP RIGHTS OF CANNABIS

In recent years, the protection of products, methods, productions, etc. of Cannabis has increased, being China the main country in terms of filed patent applications related to Cannabis. Also, the main field of protection is that related with medical applications.

Statistics obtained with data published by WIPO show who is using PCT system and how it is being used.

Applications filed by Country

CountryNumber of applications
China1,842
United States of America691
PCT424
Canada233
European Patent Office151
Australia119
United Kingdom55
Republic of Korea50
Mexico37
Israel27

Examples of filed PCT applications referred to improvement of Cannabis production are cited hereinbelow.

No.No. PCT PublicationTitle
1WO2020102905A1Dual droplet aeroponic systems and methods for growing plants
2WO2020102905A1
Cannabis variety which produces greater than 50% female plants
3WO/2020/035869Modulation of cannabinoid profile in Cannabis
4WO/2019/186568Physical means and methods for affecting Cannabis plants
5WO/2017/051398Methods for the production of different Cannabis product compositions
6WO/2017/181018Enhanced Cannabis plants and methods of making and using the same
7WO/2019/164689Genetically modifiedCannabissativa plants and modified cannabinoid compounds for treatment of substance addiction and other disorders
8WO/2020/084455Post-harvest optimization
9WO/2019/234750Methods of regenerating and transforming Cannabis
10WO/2019/113497High cannabigerol Cannabis plants, methods of producing and methods of using them
11WO/2020/093103Cannabis plants with a cannabinoid profile enriched for Δ-9-tetrahydrocannabinol and cannabigerol
12WO/2019/069309A novel Cannabis production process and products thereof

InMexico there have been few patents granted, but there are several patent applications pending to be examined. These cases involve all the fields related with Cannabis. It also should be noted that during 2019 the number of applications increased.

No.No. MX applicationTitle
1MX/a/2019/015673Veterinary granules composition containing hemp extract
2MX/a/2019/015315Sleep disorder compositions and treatments thereof
3MX/a/2019/014715Use of cannabidiol in the treatment of tuberous sclerosis complex
4MX/a/2019/012109Cannabinoid extraction process using brine
5MX/a/2019/009708Method and cell line for production of phytocannabinoids and phytocannabinoid analogues in yeast
6MX/a/2019/011583Process for purification and separation of cannabinoids from dried hemp and Cannabis leaves
7MX/a/2019/012779Cannabis fiber, absorbent cellulosic structures containing Cannabis fiber and methods of making the same
8MX/a/2019/009463Methods and apparatus for low-pressure radiant energy processing of Cannabis
9MX/a/2017/005833 Pat. MX 369078 B
Cannabis fiber, absorbent cellulosic structures containing Cannabis fiber and methods of making the same
10MX/a/2019/003063Trichome specific promoters for the manipulation of cannabinoids and other compounds in glandular trichomes
11MX/a/2019/001968Plants and methods for increasing and decreasing synthesis of cannabinoids
12MX/a/2019/001121New Cannabis tablet formulations and compositions and methods of making the same
13MX/a/2014/003310 Pat. MX 367758 B
A pharmaceutical composition comprising the phytocannabinoids cannabidivarin (CBDV) and cannabidiol (CBD)
14MX/a/2019/003269Leak resistant vaporizer device
15MX/a/2019/001286Cannabiscomposition
16MX/a/2019/001285Cannabiscomposition
17MX/a/2017/015304Cannabis plants having modified expression of THCA synthase
18MX/a/2014/000535 Pat. MX 346923 BGenes and proteins for alkanoyl-CoA synthesis
19MX/a/2015/013202Breeding, production, processing and use of specialty Cannabis

The following Variety Plants of Cannabis has been filed at UPOV

Applications filed by Country

CountryNo. Appln.
NL351
IT313
HU309
PL303
FR302
CZ298
GB292
SI291
RO289
DE288

Applications filed according to UPOV Code

UPOV CodeBotanical NamesNo. Applications
CANNBCannabis L. 7
CANNB_SATCannabis sativa L. 807
CANNB_SAT_INDCannabis sativa L. subsp. indica (Lam.) E. Small & Cronquist Cannabis indica Lam.1
CANNB_SAT_SATCannabis sativa L. ssp. sativa 53
CANNB_SINCannabis sativa ssp. sativa x Cannabis sativa subsp. indica 1

CONCLUSIONS

Known uses of Cannabis and new medical and industrial uses thereof have raised an interest to improve Cannabis production to increase industrial-scale productionof cannabinoids. The use of different methods has allowed for these improvements. The methods include, for example, genetic modifications, cultivation methods that increase the content of the substance in interest (CBD), and obtaining plant varieties. It follows that new technologies developed in order to achieve such objectives need to be protected through patents, plant varieties, or any other industrial property rights.

Furthermore, due to the nature and psychoactive effects of Cannabis, there is the need of domestic regulations for the production, use, and marketing of Cannabis for medical and industrial uses.

In recent years, the number of patent applications related to Cannabis around the world has grown significantly and will continue increasing as legal frameworks progress in each country. The research and development of new applications of Cannabis will promote such increase. It is also expected also for other ways of protection to increase, e.g. Plant Variety, or Seed Certification.

In Mexico, the legalization for the use ofCannabis sativafor medicinal and research purposes has been approved. The laws regarding this subject-matter will apply to the following activities:

I. The sowing, harvesting, production, transportation, distribution, marketing, carrying, and consumption of Cannabis and its derivatives for personal, therapeutic and scientific purposes.

II. Public Health control of Cannabis.

In consequence, Universities, Research Centers, and Pharmaceutical Companies will now be able to do research on Cannabis sativa.

Janett Lumbreras

REFERENCES

1.Pertwee R. ed.Handbook of Cannabis.Oxford University Press; 2014. Available at: http://www.oxfordscholarship.eom/view/10.1093/acprof:oso/9780199662685.001.0001/acprof-9780199662685. Published online January 2015. Accessed May 21, 2017

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5741114/#__sec1title

3. HEMP Gazette. The Big List of Cannabis Cannabinoids

4. https://www.forbes.com.mx/140-dias-para-cambiar-a-mexico/

5. https://www.forbes.com.mx/marihuana-vs-hemp-lo-que-tienes-que-conocer/

6. Elie Dolgin.A boosted crop. 29 August 2019. Vol. 572. NATURE S7 – https://www.nature.com/articles/d41586-019-02525-4

7. Jessica L. Parsons, Sara L. Martin, Tracey James, Gregory Golenia, Ekaterina A. Boudko, and Shelley R. Hepworth. Polyploidization for the Genetic Improvement of Cannabis sativa. Front Plant Sci. 2019; 10: 476.

8.S.H. Fox, in Encyclopedia of Movement Disorders, 2010

9.https://patentscope.wipo.int/search/es/search.jsf

10. https://www3.wipo.int/pluto/user/en/

11. https://siga.impi.gob.mx/newSIGA/content/common/principal.jsf