Oh, patents! New vaccine for honeybees!

Copyright © Françoise Herrmann

On January 7th, the United States Department of Agriculture (USDA), Center for Veterinary Biologics conditionally approved the first vaccine for honeybees. A vaccine designed to protect bees against a deadly bacterial disease called American FoulBrood (AFB). A disease caused by a gram-positive, spore-forming bacterium, Paenibacillus larvae, that is highly contagious to bees, and known to wipe out entire colonies.

To date the only cure for AFB was burning the infected hives, and all of the associated equipment, since the disease is not treatable. According to Dalan Animal Health, the company that masterminded the honeybee vaccine, an estimated 40% of the 2.8 million commercially operated beehives in the US died, during the year April 2018 to April 2019. Honeybee death with an impact not only on beekeeper jobs, but on farmers, who depend on bees for the pollination of their crops. In the US, bees are estimated to pollinate approximately one-third of all crops. Thus, bee health is crucial to biodiversity, ecosystems, food security, and trade of agricultural products.

A vaccine for bees? Having survived the COVID-19 pandemic largely due to two vaccines, and two boosters, each of which may have given you a really sore arm, and left you in a zombie state for at least 24 hours, you are probably wondering how on earth bees might get vaccinated.

The new honeybee vaccine is an oral formulation. It is incorporated into Royal jelly, the food secreted by nurse bees to feed queen bees and larvae. Upon ingestion, the vaccine is transported to the queen bee’s ovaries, from where all the larvae receive immunity before they hatch. The prophylactic vaccine was developed by Dalan Animal Health, a company in Athens, Georgia, dedicated to the health of honeybees.

This invention is patented. The below-cited two World Intellectual Property Organization (WIPO) patents recite the first honeybee vaccine, effective against both American FoulBrood (AFB), and European FoulBrood (EFB), caused by the bacterium Melissococcus plutonius. In fact, the scope of the invention even extends to other insects and invertebrates, such as shrimp, grasshoppers, mealworms and other pollinators, where the maternal invertebrate would be vaccinated with a targeted inactive bacterium to confer immunity to her offspring.

• WO2022192752A1 - Vaccine method and composition for bacterial diseases in invertebrates.
• WO2022051406A1 - Use of vitellogenin for defining and testing novel immunogens in insects.

Below, the sounds of a very busy queen bee, with a healthy court of worker bees. 

References

American Foulbrood Bee Aware.
https://beeaware.org.au/archive-pest/american-foulbrood/#ad-image-0

European Foulbrood Bee Aware.
https://beeaware.org.au/archive-pest/european-foulbrood/#ad-image-0

Dalan Animal Health – Dedicated to honeybee health.
https://www.dalan.com/

Hughes, R.A. (Jan. 5, 2023). Breakthrough: World's first vaccine for bees could save hives from devastating disease.
https://www.euronews.com/green/2023/01/05/endangered-colonies-worlds-first-vaccine-for-bees-could-save-hives-from-devastating-diseas

Tumin, R. (Jan. 7, 2023). U.S.D.A. Approves First Vaccine for Honeybees. NYTimes.
https://www.nytimes.com/2023/01/07/science/honeybee-vaccine.html

Rascoe, A. (Jan. 8, 2023). A new vaccine will protect honeybees from a bacterial disease affecting their larvae.
https://www.npr.org/2023/01/08/1147737268/a-new-vaccine-will-protect-honeybees-from-a-bacterial-disease-affecting-their-la

USDA - Center for Veterinary Biologics.
https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/veterinary-biologics

Terminology - WOTTIES 2021 - "vax" OED Word of the Year

Copyright © Françoise Herrmann

The Oxford English Dictionary (OED) selected the term "vax", short for vaccine, as the 2021 Word Of The Year (WOTY). The term vax not only increased frequency of usage by 72% compared to 2019, vaxxes no doubt saved humanity from extinction during the COVID 19 pandemic. Indeed, as of Nov. 1, 2021, according to the  WHO Dashboards, the SARS-COV2 pandemic killed almost 5 million people worldwide, including 750,000 in the US alone (NYTimes COVID 19 Maps).

With synonyms  jab, shot or Fauci-Ouchi, the term vax (noun and verb) inflects with a double “ x “ as in “ vaxxed” or “anti-vaxxer”. Neologisms associated with the term include such items as:

• vaxxie (n): selfie taken while getting a COVID -19 vaccination (Urban Dictionary).
• vaxinista (n): person who gets the vaccine, and flaunts it with high-end shopping, trips and parties (Urban Dictionary).
• vax(x)(i)cation (n): after getting vaccinated, vacation taken without wearing a mask in 2021 (Urban Dictionary). 
• vax-a-thon (n): administration of a record number of jabs at a dedicated event. 
• vaxxident (n) (unrelated to chewing-gum): post-vaccine automobile accident on roadways, caused by mini-strokes and blood clots in the brain (Urban Dictionary).

On the occasion of the OED WOTY 2021 announcement, Oxford Languages also released a Report into the language of vaccines. Oxford Languages claims that "no word better captures the atmosphere of the past year than vax."

 Long live the vax! 

References

BBC News (Nov. 1, 2021).  Vax declared Oxford English Dictionary's word of the year. 
https://www.bbc.com/news/entertainment-arts-59089596

COVID in the US: Latest Maps and Case counts. NYTimes.   https://www.nytimes.com/interactive/2021/us/covid-cases.html

Oxford Languages – Word of the Year 2021: Vax.  https://languages.oup.com/word-of-the-year/2021/

Oxford Languages - A Report into the language of vaccines. https://languages.oup.com/word-of-the-year/2021/ (download link)

Petter, O. (Nov. 1, 2021). ‘Vax’ named Oxford English Dictionary’s word of the year. The Independent. https://www.independent.co.uk/life-style/oxford-english-dictionary-word-vax-b1948929.html

Schuessier, J. (Nov. 1, 2021). Oxford’s 2021 Word of the Year Is a Shot in the Arm. NYTimes.    https://www.nytimes.com/2021/10/31/arts/vax-oxford-word-year.htm

Urban Dictionary  https://www.urbandictionary.com/

WHO Coronavirus (COVID-19)  Dashboards -  https://covid19.who.int/

Oh, patents! Cellectra® Inovio’s DNA plasmid delivery technology (2)

Copyright © Françoise Herrmann 

Cellectra®, Inovio’s smart device for delivering DNA plasmids, is designed to solve one of the most pervasive technical challenges of gene therapy: the unaltered delivery of engineered nucleic acid molecules (DNA or mRNA) to human cells. Safe delivery that enables the engineered molecules to carry out their instructions in vivo, such as the production of target antigens. Indeed, “naked” engineered nucleic acid molecules are fragile with very low cell uptake, when they are administered via intramuscular injection alone. Thus, different approaches to resolving the issue of delivering DNA or mRNA gene therapy, inside cells, have been proposed. Approaches each aimed at increasing cell uptake, and thus obtaining more optimal expression of the gene therapy within cells.

 One approach to engineered nucleic acid delivery is viral vector-based (Naso et al.,2017). An approach where nucleic acid instructions are transported to cells via the DNA of another virus, engineered as a harmless vector. For example, adenoviruses (common cold viruses) might be engineered as harmless vectors for nucleic acid instructions, systematically delivering the new payload upon entry through cell membranes.  Specifically, adenovirus viral vector technology was the approach used for the development of the Johnson & Johnson COVID-19 vaccine. A SARS CoV-2 vaccine candidate, still under investigation in the Ensemble Phase III clinical trials (Staff J&J, Dec. 17, 2020).

Another approach, to gene therapy delivery is lipid nanoparticle (LNP) technology (Reichmuth et al., 2016). LNP technology encapsulates nucleic acid molecules to protect them during administration into the human body, through to cell membranes, thus allowing engineered genes to deliver their instructions directly inside cells. Specifically, LNP technology was invoked as part of the galenic formulation of the engineered mRNA strands of both the Pfizer-BioNTech, and Moderna,  COVID 19 vaccines. A nucleic acid delivery technology that is not without potential side-effects, since polyethylene glycol (PEG), one of the components of the LNP technology was, quite recently, hypothesized as potentially responsible for the very rare severe allergic reactions to the Pfizer-BionTech vaccine (de Vrieze, Dec. 21, 2020).

Inovio’s solution to the problematic situation of gene therapy delivery is a mechanical one that bypasses previous approaches. The company has invented an electroporation (EP) smart device, designated Cellectra®.  Cellectra® reversibly opens cell pores via application of brief (and tolerable) electrical pulses. The pulses open aqueous pathways in the otherwise less permeable cell membrane, through which large molecules such as DNA can pass to carry out their instructions from within cells. Thus, the Cellectra® device increases cell uptake of the engineered genes, which in turn results in better immune responses, and more efficient gene therapy doses. The Cellectra® device is further designed nearly painless (per score of visual analog scale) for pediatric use. Cellectra® is also designed user-friendly and cost-efficient for mass manufacture. Specifically, for example, Cellectra® was effectively used for delivery of the Inovio (INO-4800) SARS CoV-2 vaccine candidate, in Phase I clinical trials  (Tebas,et al., 2020). Similarly, prior to the COVID-19 pandemic, the Cellectra® EP device was also found effective in Phase I clinical trials for delivery of the MERS-CoV DNA vaccine candidate, co-developed by GeneOne Life Science and  Inovio (Carlson, 2020). 

The Cellectra® invention is recited in the US utility patent US10668279, titled Minimally invasive dermal electroporation device. The invention recites a hand-held, electroporation (EP) smart device, for delivering gene therapy, intradermally or intramuscularly, directly to cells. The abstract of this invention is included below, together with the patent Figure 1A of an embodiment of the device, and an image of a corresponding embodiment of the marketed Cellectra® product.

The disclosure is directed to a device for electroporating and delivering one or more antigens and a method of electroporating and delivering one or more antigens to cells of epidermal tissues using the device. The device comprises a housing, a plurality of electrode arrays projecting from the housing, each electrode array including at least one electrode, a pulse generator electrically coupled to the electrodes, a programmable microcontroller electrically coupled to the pulse generator, and an electrical power source coupled to the pulse generator and the microcontroller. The electrode arrays define spatially separate sites.     [Abstract US 10668279 ]

 

The patent Figure 1A depicts the Minimally Invasive Device (MID) 100, comprising a housing 102 and a tip portion 104. A plurality of electrode arrays 106, 108 for electroporating, are coupled to the tip 104. The tip 104 of the MID 100, and the electrode arrays 106, 108, together or separately, are detachable, sterilizable and thus re-usable.  Alternatively, the tip 104, and/or arrays 106, 108, might be designed for single use. The electrodes are arranged in 4x4 arrays. Each electrode array 106, 108, is configured to vary the electroporating pulse, thus enabling heterogeneous delivery of gene therapy (e.g.; when an adjuvant plasmid is used, in combination with an antigen plasmid). The number, dimension and pattern of each electrode array 106, 108, may vary, depending on the embodiment of the MID. Pulse generators (undepicted), electrically coupled to a programmable microcontroller (undepicted), are connected to each of the electrode arrays 106, 108. In response to input, the microcontroller adjusts the electroporation parameters (e.g.; pulse voltage, current, duration and quantity of applied pulses) of each electrode array 106, 108, depending on usage, or requirements of the gene therapy.

The Inovio Youtube video below illustrates the delivery of DNA plasmids, using the Cellectra® EP device.

References

Carlson, R. MD (July 2020)  INO-4700 MERS-CoV Vaccine.
https://www.precisionvaccinations.com/vaccines/ino-4700-mers-cov-vaccine

GeneOne Life Science, Inc. (Company website) http://www.genels.com/en/

Inovio Pharmaceuticasl Inc. (Company website) www.inovio.com

Naso, M.F., Tomkowicz, B.,  Perry, III, W. L.,  and W.R. Strohl 2 (July 1,2017) Adeno-Associated Virus (AAV) as a vector for gene therapy.  BioDrugs. 2017; 31(4): 317–334. Published online 2017 Jul 1. DOI: 10.1007/s40259-017-0234-5   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5548848/  https://link.springer.com/article/10.1007/s40259-017-0234-5

Reichmuth, A.M.,  Oberli, M.A.,   Jaklenec, A., Langer, R. and D.l Blankschtein (2016) mRNA vaccine delivery using lipid nanoparticles. Ther Deliv. 2016 May; 7(5): 319–334. DOI: 10.4155/tde-2016-0006    https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&log%24=relatedarticles&logdbfrom=pmc&from_uid=27075952

Staff (Dec. 17, 2020) Johnson & Johnson announces its first phase 3 COVID-19 vaccine trial ENSEMBLE is fully enrolled. JNJ Company website.  https://www.jnj.com/our-company/johnson-johnson-announces-its-first-phase-3-covid-19-vaccine-trial-ensemble-is-fully-enrolled

Tebas, P., et al. (2020) Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial. EClinical Medicine – The Lancet, December 23, 2020. DOI: https://doi.org/10.1016/j.eclinm.2020.100689   https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30433-8/fulltext

de Vrieze, J. (Dec. 21, 2020) Suspicions grow that nanoparticles in Pfizer’s COVID-19 vaccine trigger rare allergic reactions. Sciencemag.org https://www.cnet.com/how-to/recycling-electronics-what-to-do-with-your-old-laptops-phones-cameras-and-batteries/?ftag=CAD-03-10aaj8j

Oh, patents! Inovio’s SARS CoV-2 DNA vaccine candidate (INO-4800) (1)

Copyright © Françoise Herrmann 

A deoxyribonucleic acid (DNA) vaccine delivers an engineered plasmid directly to a cell. A plasmid is a small double-stranded DNA molecule, which is engineered to code for a specific target antigen and able to replicate independently of chromosomal DNA. In the case of COVID-19, the Inovio plasmid was engineered to code for the spike antigen of the SARS Coronavirus-2. Thus, once transfected, by the introduction of an engineered DNA molecule, the cell is instructed to produce a specific (harmless) antigen in vivo. Production in vivo of a (harmless) antigen, against which the body, in turn, mounts an immune reaction.  An immune reaction, consisting in the production of T-cells and antibodies, henceforth also able to recognize the SARS CoV-2 spikes attached to the virus, and in significant enough quantities to block replication of the (harmful) virus, when a person is infected.

On December 24, 2020, Inovio published the results of Clinical Testing Phase I (on healthy human volunteers) of the Inovio SARS CoV-2 DNA vaccine candidate: INO-4800. Succinctly, the vaccine candidate was found 100% effective in triggering a strong immune response, in all 38 vaccinated subjects. The INO-4800 vaccine candidate also presented an excellent tolerability and safety profile (Tebas, et al., 2020). Funded by the Coalition for Epidemic Preparedness Innovations (CEPI), the Inovio (INO-4800) DNA vaccine candidate trials move on to Phase II of the Federal Drug Administration (FDA) approval process, for bringing drugs to market.

Compared to the Pfizer and Moderna mRNA COVID-19 vaccines, currently deployed in the US, Great Britain and Canada, the Inovio SARS CoV-2 DNA vaccine candidate is touted as having the advantage of requiring no refrigeration, at all.

The development of the Inovio SARS CoV-2 vaccine candidate, as well as future(1) Inovio COVID-19 treatments, rely on the prior development of the company's patented DNA vaccines, against the Middle East Respiratory Syndrome (MERS) coronavirus, the human papillomavirus (HPV) and influenza viruses, as well as on the development of  cancer tumor-fighting drugs, and the treatment of HPV-related diseases, using the company's proprietary DNA monoclonal antibody (dMAb™) biotechnology.

 The following sample patents, assigned to Inovio, cover various aspects of the subsumed biotechnologies.

• US10016497 - MERS-CoV vaccine.
• US10087240 - DNA antibody constructs and method of using same.
• US10166288 - Vaccines having an antigen and interleukin-21 as an adjuvant.
• US10226526 - Vaccines for human papillomavirus and methods for using the same.
• US10232030 - Vaccines for human papillomavirus and methods for using the same.
• US10398769 - Influenza nucleic acid molecules and vaccines made therefrom.
• US10548971 - MERS-CoV vaccine.

The Youtube video below introduces Inovio's COVID 19 vaccine candidate. 

Note (1) Future Inovio drug development, for COVID 19, is under contract with the US Department of Defense (DoD), Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), and the Defense Advanced Research Projects Agency (DARPA).

References

CEPI - Coalition for Epidemic Preparedness Innovations https://cepi.net/ 

FDA - The Drug Development Process - https://www.fda.gov/patients/learn-about-drug-and-device-approvals/drug-development-process

Inovio Pharmaceuticals (Company website) www.inovio.com

Inovio DNA medicines technology https://www.inovio.com/dna-medicines-technology/

Pablo Tebas 1, ShuPing Yang 1, Jean D. Boyer 1, Emma L. Reuschel, Ami Patel, Aaron Christensen-Quick et al. (2020)  Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2: A preliminary report of an open-label, Phase 1 clinical trial. EClinical Medicine – The Lancet, December 23w 2020.  DOI: https://doi.org/10.1016/j.eclinm.2020.100689  https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30433-8/fulltext

FDA Advisory Committee-recommended! The Moderna COVID-19 vaccine.

 Copyright © Françoise Herrmann

Moderna filed for an Emergency Use Authorization from the FDA on November 30th, 2020, just a few days after Pfizer-BionTech. On December 17, 2020 the request was reviewed by a panel of twenty experts (Hearing Announcement). At the conclusion of the hearing, the Committee of experts voted 20 to 0 to recommend the Moderna vaccine for FDA Emergency Use Authorization.   

Moderna, a biotechnology company headquartered in Boston MA, is specialized in the design of mRNA as a vaccine and drug. Since their foundation, in 2010, they have designed mRNA vaccines and treatments for a host of diseases and conditions, such as methylmalonic acidemia, Zika and cytomegalovirus (CMV) (Moderna Clinical Trials). Within the context of the COVID-19 pandemic Moderna has officially stated that they will not enforce any of their intellectual property rights against others, who are also part of the scientific emergency response, designing vaccines and treatments for COVID 19, and that they will license the technology post-pandemic (Moderna Statement on IP). 

The Moderna COVID-19 vaccine is designated mRNA- 1273. It is currently undergoing phase 3 clinical testing. Like the Pfizer-BioNTech COVID-19 vaccine, it is an mRNA vaccine, which means that Moderna scientists have also engineered mRNA to code for the SARS CoV2 surface spike protein. The engineered mRNA strands are then delivered via Lipid NanoParticle (LNP) technology, in an intramuscular injection, to human cells, where they instruct cells to produce (harmless) spike glycoproteins, that will trigger an immune response. An immune response that will then be able to recognize viral spikes attached to the (dangerous) CoV-2, in view of binding and preventing the coronavirus replication, and thus preventing infection with COVID-19 (see diagram below).

 One of the most significant differences between the Moderna and Pfizer BioNTech vaccines is the issue of cold storage. The Moderna vaccine does not have to be stored at extremely cold temperatures. Thus, the Moderna vaccine is a good candidate for Third World countries, providing that costs, or availability, become commensurate with Third World public health budgets. 

The mRNA-1273 vaccine is made available as a frozen suspension, in multi-dose vials, each containing ten 0.5 mL doses. Two 0.5 mL injections are required, 28 days apart (FDA Briefing Document). The first is intended to prime the production of antibodies. The second is to boost, or significantly increase, the effectiveness of the vaccine's protection. 

The following US design patents, listed on the Moderna website, cover the various inventions specifically related to research and development of the Moderna mRNA COVID -19 vaccine.

• US 10703789 - Modified polynucleotides for the production of secreted proteins
• US 10702600 - Betacoronavirus mRNA vaccine
• US 10577403 - Modified polynucleotides for the production of secreted proteins
• US 10442756 - Compounds and compositions for intracellular delivery of therapeutic agents
• US 10266485 - Compounds and compositions for intracellular delivery of therapeutic agents
• US 10064959 - Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
• US 9868692 - Compounds and compositions for intracellular delivery of therapeutic agents

According to Moderna CEO Stéphane Blancel, in a 2013 TEDx lecture, Moderna is a company that knew they had a game-changing idea, when they started researching the possibility of mRNA as a drug, whether for vaccination, or the design of drugs for cancer or rare metabolic and genetic diseases (Blancel, TEDx 2013). What they probably did not anticipate, seven years ago, was just how soon their drug contributions would be saving the world from potential extinction and economic collapse, within the context of the COVID 19 pandemic. 

Most importantly, Moderna is also leveling the playing field a bit, setting its agenda on rare diseases, and making vaccination possible, within the context of the COVID 19 pandemic, in the Third World. Thus, Moderna is slated to prevent much human suffering in traditionally forsaken places, and to design treatments for previously incurable patients.

Cheers Moderna! 

References

Blancel, S.  (Dec. 27, 2013) What if mRNA could be a drug? TEDX lecture - Youtube video  https://youtu.be/T4-DMKNT7xI   

FDA ADvisory Committee  hearing on Dec. 17. 9 to 6 pm -  For Moderna Vaccine – Public hearing  https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-december-17-2020-meeting-announcement

FDA Briefing Document - Moderna COVID-19 Vaccine  https://www.fda.gov/media/144434/download

Moderna (Company website)   https://www.modernatx.com

Moderna’s mRNA technology    https://www.modernatx.com/modernas-mrna-technology

Moderna’s IP (for mRNA & delivery technologies).   https://www.modernatx.com/mrna-technology/modernas-intellectual-property

Moderna Statement of IP matters during COVID-19 pandemic.   https://investors.modernatx.com/news-releases/news-release-details/statement-moderna-intellectual-property-matters-during-covid-19

Moderna Clinical Trials  https://www.modernatx.com/pipeline/modernas-mrna-clinical-trials-cmv-mma-zika-several-types-cancer-and-other-diseases

Oh patents! In silico 3D-modeling for drug design

Copyright © Françoise Herrmann

Pharmaceutical R&D includes in vitro (test-tube), in vivo (live, animal or human) testing, and fairly recently in silico (computer) 3D-modeling of molecular interactions, for the design of vaccines and drugs.

Within the context of the COVID-19 pandemic, all of the groundwork for the accelerated vaccine development, currently underway, was launched early. Indeed, it was as early as January 12, 2020, that Chinese Health authorities made public the complete sequencing of the new coronavirus (2019 n-CoV), or Wuhan virus, as it was then called, prior to being officially designated the SARS CoV-2 by the World Health Organization (CCDCP, 2020; CAS, 2020, Institut Pasteur in Shanghai, 2020). Sequenced at lightning speed, using Next Generation Sequencing (NGS) (Shang, Oct. 2020), the Chinese preemptive release of the SARS CoV-2 virus genomes, crucial to modern drug and vaccine development, included further research. Research, such as the description of the virus (a single-strand RNA virus, belonging to the Betacoraonavirus group), identification of the S-protein as critical for binding to the host cell receptor, therefore designated as the prime target of vaccine and drug treatments, and comparative data on both the suspected origin of the virus in bats, and transmission to humans, via the infected animals of the Huanan Seafood Wholesale Market, in Wuhan (Staff, CCDCP, Jan 2020; Shi, Oct. 2020).

In turn, the Chinese public release of genomic information prompted immediate and unprecedented scientific collaboration across frontiers. The collaboration to develop vaccine and drug candidates was both immediate and unprecedented, in the face of a documented emergency. Documented, because the genomic data, released from China, included supporting data on how robust the role of the viral S-protein in securing entry into human cells. An entry point where the virus could replicate, attacking the lungs and other organs of infected persons, prior to triggering massive inflammatory responses that were fatal, when they could not be prevented.  

Drug or vaccine development at the genomic level relies significantly on in silico 3D modeling, in view of supporting such queries as molecular dynamics simulating receptor molecule and substance; secondary, tertiary and quaternary protein structure prediction, binding site prediction, homology modeling for analyzing previously unknown protein function, protein threading (fold recognition) in protein modeling. In sum, programs supporting simulations for comparing nucleic acids, and the search for existing drugs and their targets, that might potentially be repurposed.  

One such patented in silico 3D-modeling system, used for enzyme modeling is called  Catalophore,™. This system was actually used in January 2020 by Innnophore, an Austrian company, specialized in enzyme discovery, to search for already designed protease inhibitors that could also bind to the SARS CoV-2, and be repurposed as an effective antiviral treatment for COVID-19 (Gruber, C & G. Steinkellner, Jan 23, 2020; Wang, 2020).  

The technology used for this purpose, embodied in the Catalophore™ enzyme modeling system, is patented in the US utility patent application US2015302142A1, titled Determining novel enzymatic functionalities using three-dimensional point clouds representing physicochemical properties of protein cavities.

Below, the January 2020 Catalophore™ modeling of the SARS CoV-2 protease point clouds, showing favored cavities where ligands could bind for inhibiting CoV-2 protease activity, thus deactivating virus replication. [Innophore, Jan 23, 2020]. In turn, the Innophore emergency response team searched their point cloud databases for proteins with similar physicochemical configurations and known protease inhibitors to see if any of them could also bind to the SARS CoV-2 protease. Lopinavir, a previously approved HIV protease inhibitor, was then identified as the best match for inhibiting the SARS CoV-2 protease (Gruber & Steinkellner, Jan 23, 2020).  

With FDA authorization granted last week for emergency use of the Pfizer-BioNTech BNT162b2 vaccine, and the upcoming review, on Dec. 17th, 2020, of the Moderna mRNA-1273 vaccine, the concerted emergency response of scientists worldwide for the development of treatments and vaccines, able to halt the spread of  COVID -19, offers the glimpse of a real triumph. In other words, hope exists for effective prevention of the spread of COVID-19, at the conclusion of very grim news for the year 2020, and unspeakable statistics of the human toll. 

References

Chinese Academy of Sciences (CAS). https://english.cas.cn/

Chinese Center for Disease Control and Prevention (CCDCP).   http://www.chinacdc.cn/en/

Chinese Center for Disease Control and Prevention (CCDCP) - COVID-19.   http://www.chinacdc.cn/en/COVID19/

CCDCP - Staff (Jan, 23, 2020) Study reveals how novel coronavirus infects humans.   http://www.china.org.cn/china/2020-01/23/content_75643109.htm

Chinese Center for Disease Control (Wuhan satellite).   https://www.natureindex.com/institution-outputs/china/wuhan-center-for-disease-prevention-and-control/52ae6a29140ba06f3d000003 

Gruber, C and G. Steinkellner (Jan. 23, 2020) Coronavirus COVID-19, formerly called Wuhan coronavirus and 2019-nCoV: What we can find out on a structural bioinformatics level.  (Austria)   https://innophore.com/2019-ncov/

Innophore (company website) https://innophore.com/

Institut Pasteur of Shanghai - Chinese Academy of Sciences.   http://english.shanghaipasteur.cas.cn/

Karlin-Smith, S. (Jan. 29, 2020) U.S. officials praise Chinese transparency on virus — up to a point.   https://www.politico.com/news/2020/01/29/officials-praise-china-transparency-virus-108926

SARS CoV-2 – Wikipedia   https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2

Shang, Y. (October 2020) Next-generation sequencing in  SARS CoV- 2 identification. http://www.chinacdc.cn/en/COVID19/202011/P020201119531938682677.pdf

Shi, W. (October 2020) Genetic sequencing reveals natural origin, early spread and infectomes of SARSCoV-2 in China.      http://www.chinacdc.cn/en/COVID19/202011/P020201119531353047965.pdf

Wang, J. (2020) Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study  - J. Chem. Inf. Model. 2020, 60, 6, 3277–3286  https://pubs.acs.org/doi/10.1021/acs.jcim.0c00179#

WHO COVID -19 Timeline  (Archived). https://www.who.int/news/item/27-04-2020-who-timeline---covid-19

WHO (Jan 12, 2020) Novel Coronavirus – China. https://www.who.int/csr/don/12-january-2020-novel-coronavirus-china/en

Wuhan Institute of Virology http://english.whiov.cas.cn/                  

FDA Advisory Committee-recommended! The Pfizer-BioNTech COVID-19 vaccine

 Copyright © Françoise Herrmann

On December 10, 2020, the US Federal Drug Administration (FDA) Vaccine Advisory Committee recommended an Emergency Use Authorization (EUA) for the COVID-19 BNT162b2 vaccine, developed and manufactured by Pfizer-BioNTech, in Germany. Thus, the BNT162b2 vaccine has cleared a major hurdle to become the first, long-awaited, FDA-authorized vaccine in the US, designed for the prevention of COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).  A virus that has infected, to date, close to 70 million people worldwide (1.5 million in the US), claiming more than 1.5 million lives worldwide (close to 300 thousand in the US) (WHO Dashboard; JohnHopkins CoV Resource Center). A virus, now raging a second time, that is also paralyzing world economies.

The FDA Vaccine Advisory Committee recommendation comes exactly one week after the United Kingdom authorized the same vaccine for a mass vaccination campaign, on December 3^rd; and one day after authorization in Canada, on December 9^th. The votes, recommending emergency vaccine use in the US, cast by 17 of the 23 expert scientists on the FDA Vaccine Advisory Committee, kickstarts the FDA authorization process. A process that escalates the Advisory Committee recommendation to the FDA Commissioner, Stephen Hall, who has to sign off on the authorization for emergency use, before US Marshal-escorted shipments of the vaccine, from Germany to every US State, can begin, and Operation Warp Speed kicks off. Vaccinations would then be administered approximately 96 hours, following FDA authorization (Smith & Rahhal, Dec 10, 2020).

The Pfizer-BioNtech COVID-19 vaccine is a nucleoside-modified messenger ribonucleic acid (modRNA) type vaccine (FDA - Pfizer-BioNTech). This means that to produce the vaccine an mRNA strand was modified to code for the coronavirus spike glyco-protein (S). The spike viral glycoprotein S is the red tentacle-like glycoprotein, represented on the surface the SARS coronavirus-2, that gives the virus its unique profile (see image). Once engineered, and covered with protective lipid nanoparticle (NP) carriers, the modRNA strands are then injected into the human body, where the message to produce (harmless) glyco-protein spikes is delivered within human cells. The production of spike glyco-proteins is then believed to trigger an immune response, where the human body creates antibodies against the (harmless) intruding glyco-protein spikes. Antibodies, which will then circulate, ready to mount an attack, in case a person is actually infected with the SARS coronavirus 2, since the antibodies will be able to recognize the glyco-protein spikes, attached to the surface of the (dangerous ) virus, for the purposes of binding to the virus and preventing its replication (extrapolated from Weintraub & Padilla, June 21 2020).

The Pfizer-BioNTech vaccine is supplied in a multi-dose (5-dose) vial stored at extremely low temperature, between -80°C to -60°C (- 112°F to -76°F)].  Once thawed and diluted into five, 0.3 mL, doses, the vaccine has to be injected within 6 hours. Thus, the vaccine’s temperature storage requirements make it difficult to transport and deliver, not to mention almost impossible to use in Third World countries where facilities for such extremely cold storage might not be readily available. The vaccine is otherwise administered as a series of two, 30 µg (0.3 mL) doses, via intramuscular injection, 21 days apart (FDA - Pfizer-BioNTech). Another FDA Advisory Committee recommended that vaccinations in the US begin with health care workers, the elderly in nursing homes, and the staff taking care of them.  

Different sorts of bio-engineering technologies are invoked in the Pfizer-BioNTech vaccine. The Lipid nanoparticle (NP) carrier technology for the modRNA strands is, for example, recited in the following US utility patent applications and patents, granted to BioNtech.

• US2020/0155671 – Particles comprising a shell with RNA.
• US2018/0263907 - Lipid Particle Formulations for Delivery of RNA and Water-Soluble Therapeutically Effective Compounds to a Target Cell.
• US2017/0273907 – Stable formulations of lipids and liposomes.
• US10576146 – Particles comprising a shell with RNA.
• US10485884 – RNA formulation for immunotherapy.
• US9950065 – Particle comprising a shell with RNA.

References

FDA Briefing Document  - Pfizer-BioNTech COVID-19 Vaccine (Dec. 10, 2020).   https://www.fda.gov/media/144245/download

John Hopkins CoV Resource Center.     https://coronavirus.jhu.edu/map.html

Smith, J, and N. RAhhal (Dec 10, 2020) FDA panel votes to give emergency approval to Pfizer's coronavirus vaccine - but the shot won't ship to Americans until the agency signs off and a final verdict could take DAYS. DailyMail.com.      https://www.dailymail.co.uk/news/article-9039119/  

Weintraub, K.  and R. Padilla (June 21, 2020) Vaccines are not all created equal: A variety of ways to stop the virus that causes COVID-19.      https://www.usatoday.com/in-depth/news/health/2020/06/21/different-technologies-developing-vaccine-against-covid-19/5318458002/

WHO  Coronavirus Disease (COVID 19) Dashboard.   https://covid19.who.int/?gclid=CjwKCAiAq8f-BRBtEiwAGr3DgTBY2t_njp3yW4kHF--UtD3vhq5bCvzrTIAjtppWIC9P-J5FRvmtQhoCI-EQAvD_BwE

European Inventor Awards – The 2015 winners!

Copyright © Françoise Herrmann

So... who are the lucky winners who received one of the 3D stereolithographic and cast in bronze sail trophies, fabricated in France, on the occasion of the 10th 2015 EPO Inventor Awards competition?

The 2015 EPO Inventor award trophies were granted to the following winners:

In the Lifetime Achievement category – Andreas Manz (Switzerland) inventor of the microchip laboratory for point-of-service diagnostics and analysis (e.g.; portable diabetes monitor).

In the Industry category - Franz Amtmann (Austria) and Philippe Maugars (France) inventors of Near Field Communication (NFC), which secures data transfer between mobile devices.

In the Small and Medium-sized enterprises (SMEs) category, Laura Van 'T Veer, inventor of a gene-based breast cancer test called MammaPrint® that informs the best treatment options.

In the research category, Ludwik Leibler (France) – Inventor of Vitrimers (a new category of supramolecular polymers, with the capicity for infinite repair when heated, which means less waste (imagine scratches on the hood of a car which could be “cured”).

In the non-European Patent Organization country category: Sumio Iijima, Akira Koshio and Masako Yudasaka (Japan) – Inventors of the carbon nanotube (the strongest, lightest and most conductive material known)

And in the popular vote category, with 33% of the 47,000 votes cast, the prize was awarded to Ian Frazer (Australia) and Jian Zhout (China)– Inventors of the HPV (Human Papilloma Virus) vaccine.

Congratulations to everyone!

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Now…nominations are being accepted for the 2016 EPO Inventor awards…. Here is the Entry form! And here is the link to the nomination FAQs.

You can participate too, and nominate your favorite (qualifying) inventor!


References

Andreas Manz

http://www.frias.uni-freiburg.de/de/das-institut/archiv-frias/school-of-softmatter/fellows/manz

The Vitrimer : A french Team (CNRS-ESPCI ParisTech) discovers a revolutionary material

www.univ-psl.fr/default/EN/all/psl_en/the_vitrimer.htm 
Laura Van 'T Veer
http://profiles.ucsf.edu/laura.vantveer
Near Field Communication
http://www.nearfieldcommunication.org/
What are carbon nanotubes?
http://www.nanocomptech.com/what-are-carbon-nanotubes 
Human Papillomavirus (HPV)
http://www.cdc.gov/hpv/

2016 Entry Form
https://forms.epo.org/learning-events/european-inventor/nominate/entry-form.html
2016 Nomination FAQs
http://www.epo.org/learning-events/european-inventor/nominate/faq.html