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HUGE! “DISMISSED WITH PREJUDICE!!!! https://dockets.justia.com/docket/colorado/codce/1:2013cv01777/141766
Can you prove your allegations?
Read: “Dismissed-failure-to-state-a-claim.” Dr. Diwan is the good man. https://www.siliconinvestor.com/readmsgs.aspx?subjectid=55797&msgnum=2587&batchsize=10&batchtype=Next
https://www.google.com/search?q=GENCARELLI+v.+NANOVIRICIDES%2C+INC+&client=safari&channel=iphone_bm&source=hp&ei=lsNoYef_BLOq8gLmyq-QDg&oq=GENCARELLI+v.+NANOVIRICIDES%2C+INC+&gs_lcp=ChFtb2JpbGUtZ3dzLXdpei1ocBADMgUIIRCgATIFCCEQoAE6AggpOg4IABDqAhCPARCMAxDlAlD0Flj0FmDRImgCcAB4AIABvgGIAb4BkgEDMC4xmAEAoAECoAEBsAEU&sclient=mobile-gws-wiz-hp
https://dockets.justia.com/search?parties=Anil+Diwan&cases=mostrecent&sort-by-last-update=false
https://pubmed.ncbi.nlm.nih.gov/23536651/ The viral spike (S) protein is incorporated into the viral envelope and mediates infectious entry of HCoV-229E into host cells, a process that depends on the activation of the S-protein by host cell proteases.However, the proteases responsible for HCoV-229E activation are incompletely defined. Here we show that the type II transmembrane serine proteases TMPRSS2 and HAT cleave the HCoV-229E S-protein (229E-S) and augment 229E-S-driven cell-cell fusion, suggesting that TMPRSS2 and HAT can activate 229E-S. Indeed, engineered expression of TMPRSS2 and HAT rendered 229E-S-driven virus-cell fusion insensitive to an inhibitor of cathepsin L, a protease previously shown to facilitate HCoV-229E infection. Inhibition of endogenous cathepsin L or TMPRSS2 demonstrated that both proteases can activate 229E-S for entry into cells that are naturally susceptible to infection. In addition, evidence was obtained that activation by TMPRSS2 rescues 229E-S-dependent cell entry from inhibition by IFITM proteins. Finally, immunohistochemistry revealed that TMPRSS2 is coexpressed with CD13, the HCoV-229E receptor, in human airway epithelial (HAE) cells, and that CD13(+) TMPRSS2(+) cells are preferentially targeted by HCoV-229E, suggesting that TMPRSS2 can activate HCoV-229E in infected humans. In sum, our results indicate that HCoV-229E can employ redundant proteolytic pathways to ensure its activation in host cells. In addition, our observations and previous work suggest that diverse human respiratory viruses are activated by TMPRSS2, which may constitute a target for antiviral intervention.
{“The various receptors used by different coronaviruses all appear to fall in the broad family of membrane-associated serine proteases. As a family, they share several structural features. Their substrate specificities are dictated by specific amino acid residues and their positions.” https://www.sec.gov/Archives/edgar/data/0001379006/000110465921125343/tm2124471d1_10k.htm
Page 17 of 121} Dr. Diwan defines the protease by the amino acid sequences.
Dr. Diwan clearly knows. And he’s going to invent something else too: “The various receptors used by different coronaviruses all appear to fall in the broad family of membrane-associated serine proteases. As a family, they share several structural features. Their substrate specificities are dictated by specific amino acid residues and their positions.”
This is the tip of the iceberg. All virus variants share common traits. Dr. Diwan is not playing games. He is very educated and innovative.
“Here it is: “Favirpravir is a broad-spectrum nucleoside-like analog drug that is in clinical testing against SARS-CoV-2, originally developed by Fujifilm. We tested these drug candidates for anti-viral effectiveness against two distinctly different, unrelated coronaviruses that cause human disease, namely hCoV-NL63, and hCoV-229E. The assays evaluated the reduction caused by the drug candidate in cell death upon viral infection, formally known as cytopathic effects (CPE) assays.
https://www.sec.gov/Archives/edgar/data/0001379006/000110465921125343/tm2124471d1_10k.htm
Page 17 of 121
We found that the same two nanoviricides drug candidates were highly effective against hCoV-NL63, the coronavirus that uses the same cellular receptor as SARS-CoV-2, as well as another coronavirus, namely hCoV-229E, that causes seasonal common colds in humans. HCoV-229E uses the APN (Aminopeptidase-N) membrane protein on human cells as its receptor to enter cells, different from the ACE2 receptor used by hCoV-NL63 and SARS-CoV-2. ACE2 and APN may be considered to belong to a common superfamily of enzyme membrane proteins in terms of biophysics. The various receptors used by different coronaviruses all appear to fall in the broad family of membrane-associated serine proteases. As a family, they share several structural features. Their substrate specificities are dictated by specific amino acid residues and their positions.”
I also clued the relation in post 145613. There has to be an “evolutionary stem,” in the hereditary lineage of variants. I am more than certain all COVID variants carry a trait that is common to all of them. Dr. Diwan knows this. He’s the nanomachine pioneer. And he has multiple processes built into NV-COV-2-R protocols, along with the rest of his pipeline. He has the viruses by the spheres, so to speak.
NNVC doesn’t need Remdesivir to kill viruses:
See pp. 8 https://www.sec.gov/Archives/edgar/data/0001379006/000110465921125343/tm2124471d1_10k.htm
“It is anticipated that when a virus comes in contact with the nanoviricide, not only would it land on the nanoviricide surface, binding to the copious number of ligands presented there, but it would also get entrapped because the nanomicelle polymer would fuse with the virus lipid envelope, harnessing a well known biophysical phenomenon called “lipid-lipid mixing”. In a sense, a nanoviricide drug acts against viruses like a “venus-fly-trap” flower does against insects. Unlike antibodies that tag the virus and require the human immune system to take over and complete the task of dismantling the virus, a nanoviricide is a nanomachine that is designed to not only bind to the virus but also complete the task of rendering the virus particle ineffective.“
Here it is: “Favirpravir is a broad-spectrum nucleoside-like analog drug that is in clinical testing against SARS-CoV-2, originally developed by Fujifilm. We tested these drug candidates for anti-viral effectiveness against two distinctly different, unrelated coronaviruses that cause human disease, namely hCoV-NL63, and hCoV-229E. The assays evaluated the reduction caused by the drug candidate in cell death upon viral infection, formally known as cytopathic effects (CPE) assays.
https://www.sec.gov/Archives/edgar/data/0001379006/000110465921125343/tm2124471d1_10k.htm
Page 17 of 121
We found that the same two nanoviricides drug candidates were highly effective against hCoV-NL63, the coronavirus that uses the same cellular receptor as SARS-CoV-2, as well as another coronavirus, namely hCoV-229E, that causes seasonal common colds in humans. HCoV-229E uses the APN (Aminopeptidase-N) membrane protein on human cells as its receptor to enter cells, different from the ACE2 receptor used by hCoV-NL63 and SARS-CoV-2. ACE2 and APN may be considered to belong to a common superfamily of enzyme membrane proteins in terms of biophysics. The various receptors used by different coronaviruses all appear to fall in the broad family of membrane-associated serine proteases. As a family, they share several structural features. Their substrate specificities are dictated by specific amino acid residues and their positions.”
Polymeric Micelle drug delivery targets exact infectious, antigenic, infected cell receptors and proteins that release remediating drugs to eliminate disease progression, during or after immune responses. As the pathogens are being engulfed, their replication decreases.
As pathogens are destroyed, the body’s immune system can mount stronger defenses against pathogens’ dismantled components, with greater identification, ease and success. This process simply allows the immune system to recognize exposed proteins and mount successful attacks, without protective viral boundaries. In other words, the Polymeric Micelles are precursors to absolute eradication - - cures - - of pathogenic viral, cancers, bacterial and fungal infections and diseases.
It looks like Dr. Diwan is going to start hiring a lot of disease specialists and assistants, in addition to the collaboration offers that are going to be offered to Nanoviricides. The Polymeric Micelle technology is about to change medical approaches and streamline diagnostic protocols. This is absolutely game changing. And it works. Oh man, did it work!!! This is absolutely amazing. This virtually, and to a certain degree, replaces the immune system.
Dr. Diwan developed a DIRECT multi-disease curing method, OVERRIDING IMMUNE SYSTEM WEAKNESSES and VIRUSES IMMUNE EVADING MECHANISMS. Dr. Diwan JUST TURNED MODERN DAY MEDICINE ON ITS HEAD. THIS IS ABSOLUTE GENIUS. Dr. Diwan has the capacity to design virus targeting “Polymeric Micells” to mount direct attacks against all viruses, without immune weaknesses or virus defenses, and actually fooling viruses by exploiting their infection and replication processes.
HOLY S—-T! THIS IS HUGE! I MEAN, HUUUUUUUUUUUUUUGGGGGGGGGGGEEEEEEEEEEEE!
From the patent office: US 6,521,736B2
https://patentimages.storage.googleapis.com/a6/ab/73/dcce86a00dca35/US6521736.pdf
https://patentimages.storage.googleapis.com/a6/ab/73/dcce86a00dca35/US6521736.pdf
“This invention relates to new drug delivery vehicles, and more particularly to novel micellar amphiphilic polymers that include PEG esters.“
You don’t know what you’re missing.
There’s only one Dr. Diwan that developed NV-CoV-2-R.
Here’s why 229e binds to ACE2: “In contrast, the highly homologous C-terminal parts of the NL63-S1 and 229E-S1 subunits in conjunction with distinct amino acids in the central regions of these proteins confer recognition of ACE2 and CD13, respectively.”
https://pubmed.ncbi.nlm.nih.gov/16912312/
NV-COV-2-R is complete. The ligand works.
“NL63-S does not exhibit significant homology to SARS-S but is highly related to the S-protein of hCoV-229E, which enters target cells by engaging CD13. Employing mutagenic analyses, we found that the N-terminal unique domain in NL63-S, which is absent in 229E-S, does not confer binding to ACE2. In contrast, the highly homologous C-terminal parts of the NL63-S1 and 229E-S1 subunits in conjunction with distinct amino acids in the central regions of these proteins confer recognition of ACE2 and CD13, respectively. Therefore, despite the high homology of these sequences, they likely form sufficiently distinct surfaces, thus determining receptor specificity.”
I do recall writing that NV-CoV-2-R enhances the immune system. But the correct term would be, “assists,” especially vulnerable immune systems. I like your observations. You made me do some extensive research. Thank you.
Here’s your answer to a great question. Read Carefully: “Both viruses utilize the same cell receptor, namely ACE2, to gain entry into the cell.“ https://www.biospace.com/article/strong-effectiveness-of-nanoviricides-drug-candidates-observed-in-an-animal-model-of-infection-by-an-ace2-using-human-coronavirus/
Now look at this:
https://journals.asm.org/doi/10.1128/JVI.02615-14
ACE2 is the primary target, because the ACE2 spike protein is “common” to the COVID-19 Genuses. In other words, the common attribute of the viruses is the weakest link that can be exploited. The ACE2 Spike Protein on the variant genuses makes them all vulnerable to the mimicked ACE2 receptor on the NV-CoV-2-R capsule. The ACE2 Spike is the weakest link. I hope this helps you to understand it better.
Dr. Diwan used a very efficient and practical scientific approach by exploiting the virus’ common characteristics.
NV-CoV-2-R binds to “mimicked” “ACE2” and takes out the “APN” and DPP4 spikes too - - synergistically in a dual pharmacokinetic mechanism.
https://www.esrf.fr/UsersAndScience/Publications/Highlights/2012/sb/sb7
“The strong effectiveness of nanoviricide drug candidates in this model is consistent with the effectiveness observed in cell culture studies against infection of both hCoV-NL63, which was used in this study, and hCoV-229E, another circulating coronavirus that uses a distinctly different receptor, namely APN.” https://www.biospace.com/article/strong-effectiveness-of-nanoviricides-drug-candidates-observed-in-an-animal-model-of-infection-by-an-ace2-using-human-coronavirus/
S protein has a high affinity for DPP4 receptor: https://www.cell.com/iscience/pdf/S2589-0042(20)30345-X.pdf
ONCE THE VIRUS BINDS TO NV-CoV-2-R IT IS DESTROYED. NANOVIRICIDES FIGURED OUT THE GREATEST SYNERGISTIC SOLUTION.
Watch video:
GAME OVER: Diwan is a nano-pioneer, NIH-Funded https://www.internano.org/node/1631
https://www.crunchbase.com/person/anil-r-diwan
https://www.forbesindia.com/article/brand-connect/dr-anil-r-diwan-leads-nanoviricides-in-fight-against-covid19/68581/1
“Dr. Diwan invented novel polymeric micelle-based nanomedicine technologies as early as 1991. As such, he is considered a pioneer in the field of nanomedicines. Dr. Diwan is a prolific inventor and a serial entrepreneur.”
https://www.linkedin.com/in/anildiwan
Dr. Diwan won several NIH SBIR grant awards. https://www.internano.org/node/1631
Dr. Diwan invented novel polymeric micelle-based nanomedicine https://www.internano.org/node/1631
https://sbir.nih.gov/ technologies as early as 1991. Dr. Diwan is a prolific inventor and a serial entrepreneur. Prior to co-founding NanoViricides, Inc., he has founded TheraCour Pharma, Inc., a privately held company focused in nanomedicines and cell-targeted drug delivery, and AllExcel, Inc., a company with diverse portfolios including nanomedicines, small chemicals, device technologies, as well as informatics. He has won several NIH SBIR (small business innovation research) grant awards.
https://www.internano.org/node/1631
https://sbir.nih.gov/
“Many nanomedicines and…are FDA approvedhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474440/and on the market, and many more are in clinical trials. Currently, the most active areas of nanomedical research and product development are in cancer treatments, imaging contrast agents, and biomarker detection.
Although many nanotherapeutics and nanodiagnostics are already in use, there are many barriers that impede bringing nanomedical products to market. However, despite these challenges, both large and small stakeholders are expected to continue to pursue research and investment in nanomedical applications, especially if they have novel properties, fulfill unmet medical needs, and offer a favorable cost–benefit outlook.”
…,yet.
Current FDA & EMA Approved Nanomedicines: 2021/5/12https://www.biochempeg.com/article/188.html
Polymeric Micells for Drug Delivery
https://pubmed.ncbi.nlm.nih.gov/17168771/
“Polymeric micelles are nanoscopic core/shell structures formed by amphiphilic block copolymers. Both the inherent and modifiable properties of polymeric micelles make them particularly well suited for drug delivery purposes. An emphasis of this review has been placed on both the description and characterization techniques of the physical properties of polymeric micelles. Relevant properties discussed include micellar association, morphology, size and stability.
These properties and characterization techniques are included to provide context for the known advantages and applications of polymeric micelles for drug delivery. The advantages and applications discussed include solubilization of poorly soluble molecules, sustained release and size advantages, and protection of encapsulated substances from degradation and metabolism. The three most widely studied block copolymer classes are characterized by their hydrophobic blocks, and are poly(propylene oxide), poly(L-amino acid)s and poly(ester)s. These three classes of block copolymers are reviewed with multiple examples of current research in which formulation techniques with polymeric micelles have been applied to some of the most challenging molecules in the pharmaceutical industry. The polymeric micelles used for drug delivery in these examples have shown the abilities to attenuate toxicities, enhance delivery to desired biological sites and improve the therapeutic efficacy of active pharmaceutical ingredients.“
Game over: “Attacking the reinfection cycle with NV-CoV-1 and simultaneously attacking the replication cycle with an encapsulated drug should produce a cure for the virus infection, scientifically speaking,” said Diwan of the NanoViricides approach in developing NV-CoV-1-R.
https://www.usatoday.com/story/sponsor-story/nanoviricides/2020/12/07/why-nanomachines-could-potentially-end-covid-19-pandemic/3786631001/
….blocks the reinfection cycle, going beyond what antibodies and immunotherapeutics do.”
CDC KNEW SINCE 1960: “Human coronaviruses were first identified in the mid-1960s. The seven coronaviruses that can infect people are….see top of link: https://www.cdc.gov/coronavirus/types.html
https://www.sec.gov/Archives/edgar/data/1379006/000114036107006096/ex10_13.htm
Nanoviricides, Inc. began discussions in September of this year with Dr. Roland Levandowski Chief, Influenza, SARS, and Other Viral Respiratory Diseases Section Division of Microbiology and Infectious Diseases NIAID/NIH/DHH, and program manager Heather Greenstone about participating in NIAID’s Small business testing and evaluation program which provides no-cost testing of novel immunotherapeutic treatment and vaccines against diseases considered priorities for the Institute. Nanoviricides, Inc. and NIAID are now in the process of finalizing paperwork for bioassay (in vitro) testing to be done against HIV (AIDS), Influenzas, H5N1, SARS, and Herpes over the next few months. Assuming adequate effectiveness is shown in the in vitro testing, the goal will be to move on to animal studies on the same diseases. Actual experimentation will be done by NIAID contractor Utah State with all costs (other than production of Nanoviricides, Inc. materials) borne by NIAID. NIAID has indicated that if there are no unforeseen delays, both bioassay and animal studies could begin before the end of calendar year 2007.
Also in 2006, Nanoviricides, Inc. has spent time exploring possible collaboration opportunities with foreign research institutes under the auspices of the Pan American Health Organization and the World Health Organization. The company has met on numerous occasions with Dr. John Ehrenberg of PAHO, well known for his efforts to bring novel pharmaceutical solutions to populations in underdeveloped countries where “orphan” or “neglected” disease take an inordinate toll on indigenous peoples. One of his most important contributions has been arrangement of collaborations with the pharmaceutical industry which have significantly reduced river blindness sickness in Africa. With Dr. Ehrenberg’s encouragement, Nanoviricides, Inc. has met with Dr. Robert Ridley, Executive Director, Tropical Disease Research Institute of the WHO, in Washington, DC and later in Geneva, Switzerland to identify target diseases and research institutes in South and Central America which that may be potential collaborators. This work is expected to produce commercial and humanitarian opportunities relating to diseases common to this region of the world.
I hope this summary adequately explains the state of play between Nanoviricides, Inc. and two key government collaborators. Gencarelli Group stands ready to answer detailed questions on these projects.