EOY - End of year. It's not over.

Copyright © Françoise Herrmann

Van Cleef & Arpels
High Jewelry - Flowers Collection

Reference

Van Cleef & Arpels (Company website) https://www.vancleefarpels.com/us/en

Terminology - US COVID-19 vaccine rollout plan (Plan de déploiement des vaccins COVID-19 aux USA)

 Copyright Françoise Herrmann

The US rollout for COVID 19 vaccines and vaccinations is managed by Operation Warp Speed (OWS), funded through the CARES Act, on March 27, 2020. Operation Warp Speed (OWS) is an interagency partnership between the Department of Health and Human Services (HHS) and the Department of Defense (DOD) with the mission to coordinate federal efforts to accelerate the development, acquisition, and distribution of COVID-19 “medical countermeasures”. Additional federal agencies collaborating with the HHS include the Centers for Disease Control (CDCs), the National Institutes of Health (NIH), and the Biomedical Advanced Research and Development Authority (BARDA).

OWS has supported the development and acquisition of six different COVID-19 vaccine candidates, two of which the Federal Drug Agency (FDA) authorized for emergency use in December 2020. A total of approximately one billion doses have been ordered, for the approximately 330 million people living in the US. Doses exceed the number of people, considering that 2 doses are required for all vaccines, except the Johnson & Johnson single-dose vaccine (OWS Contracts, Dec. 22, 2020).

OWS vaccine and vaccination information is summarized below.

THE VACCINES

WHO GETS IT FIRST?

FDA-AUTHORIZED FOR ER USE (EUA) PFIZER (US) & BIONTECH (DE)  Type: mRNA  Effectiveness: 95%  Supply: 40 M doses by end of 2020  200M doses ordered  Storage: ultracold -70◦C  Trial Phase: Phase II/III  FDA EUA: issued Dec. 11, 2020  MODERNA Inc. (US)  Type : mRNA  Effectiveness : 94.5%  Supply: 20M doses by end of 2020  200M doses ordered  Storage: Cold storage, 6 months @ -20 ◦C  Refrigerator 30 days @ -2◦C to -8◦C  Trial Phase : Phase III  FDA EUA : issued Dec. 18, 2020  YET TO FILE FOR APPROVAL ASTRAZANECA (UK) – OXFORD UNIV. (UK)  Type: Recombinant viral-vector  Supply: 300 million doses ordered  Storage: Refrigerator (-2◦C to -8◦C)  Trial Phase: Phase II/III  JOHNSON & JOHNSON (US)  Type: Single-dose, Recombinant viral vector  Supply: 100 million doses ordered  Storage: Refrigerator (3 months -2◦C to -8◦C)  Trial Phase: Phase III  Expected FDA file date: February 2021  NOVARAX Inc.  Type: Adjuvanted recombinant nanoparticle protein  Supply: 100 million doses ordered  Storage: Refrigerator (-2◦C to -8◦C)  Trial Phase: Phase III  SANOFI/GLAXOSMITHKLINE  Type: Adjuvanted recombinant nanoparticle protein  Supply: 100 million doses ordered  Storage: Refrigerator (-2◦C to -8◦C)  Trial Phase: Phase I/II

PHASE 1A: STARTING IN DECEMBER 2020 Healthcare workers Nursing home & long-term care facility residents PHASE 1B: POSSIBLY STARTING IN JANUARY 2021  Non-healthcare essential workers Over 70s Over 65s Over 60s Over 50s People with chronic health conditions LATER PHASES: BY SPRING 2021 Young adults Young children

Note: Temperatures are listed in degrees Celsius. 

References

Astrazaneca – Staff (Nov. 13, 2020) AZD1222 vaccine met primary efficacy endpoint in preventing.    https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html

Biomedical Advanced Research and Development Authority (BARDA)   https://www.phe.gov/about/barda/Pages/default.aspx

Danner, C.  & M. Stieb (Dec. 18, 2020) What We Know About the U.S. COVID-19 Vaccine Distribution Plan.   https://nymag.com/intelligencer/2020/12/what-we-know-about-u-s-covid-19-vaccine-distribution-plan.html

CARES Act https://www.congress.gov/bill/116th-congress/senate-bill/3548/text?q=product+actualizaci%C3%B3n

Centers for Disease Control (CDCs) www.cdc.gov

CDC- Information about the Pfizer-BioNTech COVID-19 Vaccine. Dec. 22, 2020.  https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Pfizer-BioNTech.html

CDC - Information about the Moderna COVID-19 Vaccine. Dec. 23,2020.   https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/Moderna.htm l

CDC – Different COVID-19  vaccines. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines.html

Department of Defense (DOD) https://dod.defense.gov/

Federal Drug Administration (FDA) COVID-19 vaccines  https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines

Health & Human Services https://www.hhs.gov/ 

Health & Human Services (HSS) - Explaining Operation Warp Speed (OWS).   https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html

Johnson & Johnson https://www.jnj.com/coronavirus

Moderna Inc. https://www.modernatx.com/

National Institutes of Health (NIH) www.nih.gov

Novarax Vaccine technology (Novarax website)  https://www.novavax.com/our-unique-technology#:~:text=Our%20recombinant%20nanoparticle%20vaccine%20technology,a%20variety%20of%20viral%20pathogens.

Operation Warp Speed Contracts for COVID-19 Vaccines and Ancillary Vaccination Materials. Congressional Research Service Reports. Dec, 22, 2020.   https://crsreports.congress.gov/product/pdf/IN/IN11560

Pfizer Staff (Dec. 11, 2020) Pfizer and Biontech celebrate historic first authorization in the U.S. of vaccine to prevent COVID-19.   https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-celebrate-historic-first-authorization

Sanofi/GSL (Dec. 11, 2020) Sanofi and GSK announce a delay in their adjuvanted recombinant protein-based COVID-19 vaccine program to improve immune response in the elderly.   https://www.sanofi.com/-/media/Project/One-Sanofi-Web/Websites/Global/Sanofi-COM/Home/media-room/press-releases/2020/2020-12-11-07-00-00-2143517-en.pdf

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

Terminology - WOTTIES (3) - Time Magazine

 Copyright © Françoise Herrmann

In 2020, the big dictionaries of the English language are not the only ones publishing their usual, end-of-the-year, selection of the Word of the Year (WOTY), together with lists of the runners-up (WOTTIES). Time Magazine also kept an ear out, this year, listening for new, repurposed or high-frequency words of the English language. Words of the year that capture a pandemic year of previously uncharted territory, adjustment, coping, resilience, and social activism. Social activism, under the banner of Black Lives Matter. A movement against racism in the US, plagued with shocking incidents of unchecked police violence that stunned the whole nation. The following is the Time Magazine list of 2020 WOTTIES—unabridged.  

“Antiracist, adjective: Relating to people or actions working against systemic racism and the historical oppression of marginalized groups.

BIPOC, initialism: A term for Black, Indigenous and other people of color intended to highlight, in particular, the identities and experiences of Black and Native American communities in the U.S.

Blursday, noun: The fuzzy merging of time since the pandemic shut down so much of the world down, often making it difficult to determine what day of the week it is.

Bubble, noun: Also known as a pod; a small group of individuals who follow the same rules and standards for behavior—and can thus spend time together—during the pandemic, popularized by the isolation zone the NBA created at Disney World to protect basketball players.

Covidiot, noun: A pejorative term for someone who ignores health and safety guidelines intended to prevent the spread of COVID-19.

Defund, verb: To withdraw financial support, as in calls to defund the police, a movement promoting a public-safety model that shifts resources from law enforcement to community-led social programs and initiatives.

Doomscroll, verb: To addictively thumb through the deluge of bad news shared on social media in 2020, often undertaken at bedtime.

Entanglement, noun: A reference to an extramarital affair, popularized when Jada Pinkett Smith discussed an instance of marital infidelity on an episode of her Red Table Talk show with her husband Will Smith.

Karen, noun: A colloquial term for a white woman weaponizing her privilege, often at the expense or well-being of a BIPOC individual. When used as a meme, it’s often paired with images of a short, angled and heavily highlighted hairstyle that’s been dubbed the “Can I speak to the manager” haircut.

On mute, idiom: Used when a fellow video-call participant is speaking without their microphone on, as in “you’re on mute,” a refrain popularized this year on Zoom calls across the world.

Quarantini, noun: The day or nighttime cocktail many have used to unwind, amid remote work and COVID-19 lockdowns.

Simp, noun, verb (simping): A colloquial term popularized on TikTok, for a man who is overly accommodating or devoted to someone (usually a woman); or a very devoted fan.

Social distancing, noun: A set of measures implemented to prevent the spread of a contagious disease, the usage of which increased by 400% this year, as authorities encouraged people to keep a safe space from people who are not in their household or “bubble” during the COVID-19 pandemic.

Superspreader, noun, adjective: A person or event responsible for transmitting an infectious disease to a large number of people.

Zoombombing, noun, verb: the unplanned and unwanted intrusion of someone, usually an Internet troll, into a video conference that they were not invited to.”

"Karen is asking for the Manager."

References

Black Lives Matter  https://blacklivesmatter.com/

Lang, C. (Dec. 14, 2020) Social Distancing, Doomscroll and Defund: Words that defined 2020.  https://time.com/5919615/words-that-defined-2020/?utm_medium=email&utm_source=sfmc&utm_campaign=newsletter+brief-pm+default+ac&utm_content=+++20201216+++body&et_rid=110884839

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

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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/

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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/