Abstract
Extremophilic microorganisms from a wide variety of extreme natural environments
have been researched, and many biotechnological applications have been carried
out, due to their capacity to produce biomolecules resistant to extreme conditions, such
as fibrinolytic proteases. The search for new fibrinolytic enzymes is important in the development
of new therapies against cardiovascular diseases. This article aimed to evaluate
the patents filed about protease with fibrinolytic activity produced by extremophilic
microorganisms whose use is aimed at the development of new drugs for the treatment of
cardiovascular diseases. The prospecting was carried out using data on deposits and patent
concessions made available on the technological bases: European Patent Office (EPO),
United States Patent and Trademark Office (USPTO), World Intellectual Property
Organization (WIPO), Instituto Nacional de Propriedade Industrial – Brazil (INPI), The
LENS and Patent Inspiration. The International Patent Classification and subclasses and
groups for each document were also evaluated. Although 382 patents were selected using
terms related to extreme environments, such as “thermophile” and “acidophiles”, few
were related to clinical use and were mainly performed using Bacillus subtilis and Streptomyces
megasporus strains. A highlight of nattokinase was produced by Bacillus subtilis
GDN and actinokinase by Streptomyces megasporus SD5. The low number of patents on
enzymes with this profile (extreme environments) revealed a little-explored field, promising
in the development of new microbial thrombolytic drugs, such as fibrinolytic enzymes
with less adverse effects.
Keywords:
Cardiovascular disease, fibrinolytic activity, innovation, pharmaceutical patents, thrombolytic
drugs, technological bases.
Graphical Abstract
[1]
World health statistics 2019: Monitoring health for the SDGs, sustainable development goals. World Health Organization 2019; 31-5.
[3]
Banerjee A, Chen S, Pasea L, et al. Excess deaths in people with cardiovascular diseases during the COVID-19 pandemic. Euro J Prev Cardiol 2021.
[8]
Musso C, Pereira FEL. Circulation changes.Bogliolo, Pathology. 9th ed. Brazil: Guanabara Koogan 2016; pp. 93-160.
[12]
Verma MK, Pulicherla KK. Lumbrokinase – A Potent and Stable Fibrin–Specific Plasminogen Activator. International Journal of Bio-Science and Bio-Technology 2011; 3(2): 57-70.
[48]
Kour D, Rana KL, Kaur T, et al. Extremophiles for hydrolytic enzymes productions: Biodiversity and potential biotechnological applications, bioprocessing for biomolecules production. Bioprocessing for Biomolecules Production. United States of America: John Wiley & Sons 2019; pp. 321-72.
[49]
Otohinoyi DA, Ibraheem O. Prospecting microbial extremophiles as valuable resources of biomolecules for biotechnological applications. Int J Sci Res (Ahmedabad) 2015; 4(1): 1042-59. [IJSR
[57]
Chitte RR, Dey S. Streptomyces megasporus sd5, process for the isolation thereof, novel fibrinolytic enzyme prepared therefrom, process for the production of said enzyme and method of treatment of thrombolytic disorders using said enzyme. US patent US20030170221, 2003.
[58]
Chitte RR, Dey S. Streptomyces megasporus sd5, process for the isolation thereof, novel fibrinolytic enzyme prepared therefrom, process for the production of said enzyme and method of treatment of thrombolytic disorders using said enzyme. US patent US6638503B2, 2003.
[59]
Rhee H, KIM HW. Bacillus subtilis strain for high yield of thrombolytic enzymes. JP2018525988A 2018.
[60]
Rhee H, Kim HW. Bacillus subtilis strain for high yield of thrombolytic enzymes. WO2017222141 2017.
[65]
Urano T, Ihara H, Umemura K, et al. The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type 1. J Biol Chem 2001; 276(6): 25690-4696.
[72]
Cheigh CI, Cho SC, Choe EA, et al. Novel fibrinolytic protease. KR100753002B1, 2007.
[74]
Rahul K, Kirti V, Sharma RC. Thermophilic microbial diversity and physicochemical attributes of thermal springs in the Garhwal Himalaya. Environ Exp Biol 2020; 18(2): 143-52.
[75]
Dey S, Chitte RR. A new thrombolytic enzyme for acute myocardial infarction. Med Chem Res 2001; 10(7): 507-15.