More Provectus Intellectual Property
Company announces U.S. patent allowances & awards in virology, pediatric solid tumor cancers, and vaccines
Introduction
On Tuesday, March 12th, Provectus announced that:
The United States Patent and Trademark Office (USPTO) allowed patent application 17/212,723, Novel Uses of Halogenated Xanthenes in Oncology and Virology, which covers the use of Provectus’s pharmaceutical-grade rose bengal sodium (RBS) drug substance (a.k.a. active pharmaceutical ingredient [API]) for the treatment of infectious diseases, such as coronaviruses,
The USPTO allowed patent application 17/344,418, In Vitro and Xenograft Anti-Tumor Activity of a Halogenated-Xanthene Against Refractory Pediatric Solid Tumors, which covers the use of RBS in combination with one or more immune checkpoint inhibitors, and is a continuation of U.S. patent 11,058,664 (2021), which was Provectus’s first patent in pediatric oncology, and
The Company’s previously allowed patent application 17/488,430, Halogenated Xanthenes as Vaccine Adjuvants (December 2023), which covers RBS’s use as an adjuvant in vaccines to potentially make them work better, will be awarded by the USPTO on March 26, 2024 as U.S. patent 11,938,182.
Innovate Calgary, the innovation company of the University of Calgary in Alberta, Canada, is a co-assignee and Aru Narendran, MD, PhD, Professor of Pediatrics, Oncology, Biochemistry and Molecular Biology and Physiology and Pharmacology at the University’s Cumming School of Medicine is a co-inventor on all patent awards.
More tangible Provectus IP; so what?
“Tangible IP”
Provectus continues to seek ways to protect the potential uses of the Company’s pharmaceutical-grade RBS in different disease areas. One way is through tangible intellectual property (IP), such as patents, trademarks (see Veripure below), etc.
Tuesday’s press release, for example, described allowed patent applications and awarded patents covering the fields of virology, pediatric oncology, and vaccines. The Company also continues to seek ways to lengthen RBS’s patent cliffs through the generation of this tangible IP.
More is better than less. Longer is better than shorter.
“Intangible IP”
There are other ways to potentially protect Provectus, RBS, etc., such as continuing to establish RBS’s potential superiority of purity and purification, itself and especially compared (via chemical analysis) to other grades and versions of rose bengal.
To this end, Provectus noted in its Form 10-Q for the period ending September 30, 2022 that:
“In the first quarter of 2022, the Company began work with a U.S. contract development and manufacturing organization to rigorously and methodically assess three lots of commercial-grade rose bengal, one each from three different specialty chemical suppliers, and compare and contrast these non-pharmaceutical grade materials with the Company’s pharmaceutical-grade RBS. This chemical analytical work was substantially completed by the end of the third quarter of 2022. The Company believes that the preliminary results of these analyses indicate that all three lots of commercial-grade rose bengal had rose bengal purity that was drastically different from what was represented on their respective certificates of analysis (“CofAs”), and that one of the three lots contained gross contaminants that were not represented on its CofA.”
Inaccurate CofAs. Does this mean that Sigma-Aldrich’s (MilliporeSigma’s) rose bengal with 95% dye content may not actually be 95%?
Provectus went on to further note in its 3Q22 10-Q:
“The Company believes that the Company’s proprietary, patented, pharmaceutical-grade RBS possesses several competitive advantages over non-pharmaceutical-grades of rose bengal that researchers, clinicians, and academic, business, and/or governmental competitors have used, are using, and/or may attempt to use for potential biomedical applications. The Company believes that non-pharmaceutical-grades of rose bengal may suffer from the uncontrolled presence of substance-related impurities and/or gross contaminants, substantial lot-to-lot manufacturing variability, inaccurately reported and/or misrepresented purity and contents, and the lack of reproducible, consistent, and fullsome CMC specifications and documentation.”
The crux of the challenges that currently commercial grades or versions of rose bengal face, among other things, is required and demonstrated consistent production of reproducible drug substance/API. The lots of rose bengal material Provectus tested do not presently appear to have sufficient chemistry, manufacturing, and controls (CMC) information.
There is also the intangible way of IP protection through price; that is, being able and willing to wield RBS’s cost of goods sold (COGS), and the COGS of formulations of potential drug product candidates made from RBS, to potentially fend or scare off actual and/or prospective competitors.
And then there’s Provectus’s RBS mixologists…
Veripure
The Veripure trademark application process has to play itself out. The Company applied for a trademark in October 2022. See Substack post Provectus’s Rose Bengal Sodium: A “Proprietary” Molecule and Proprietary Drug Substance.
Animal Health-Canine Cancers Update
Initial in vitro work (Aim #1), including an IC501 analysis of canine cancer and normal cell lines (i.e., a cytotoxicity study of disease-specific cell lines), is complete. According to Provectus’s research collaborators at the University of Tennessee College of Veterinary Medicine (UTCVM), the data are purportedly encouraging. Additional in vitro mechanism work (i.e., apoptosis and cell cycle studies) should potentially be completed in April.2
The in vivo rabbit safety study (Aim #2; UTCVM) could potentially commence this month. If successful, an in vivo dog safety study (also Aim #2; UTCVM) could follow.
Provectus needs a portfolio of (i) foundational preclinical and clinical datasets, (ii) precedent regulatory interaction, application, and acquiescence/acceptance, (iii) initial drug product, and (iv) various supporting materials to potentially out-license an investigational canine cancer drug and/or advance one further towards commercialization:
In vitro cytoxicity and mechanism data (complete; UTCVM),
In vivo safety data (shortly underway; UTCVM),
A Phase 1 clinical trial in dogs for the chosen cancer indication to potentially establish safety, tolerability, and preliminary efficacy of an intratumoral formulation of RBS (pending; UTCVM),
A pre-Investigational New Animal Drug (INAD) meeting with the FDA (to be done; a potential regulatory strategy/affairs firm identified; costed),
Based on the outcome of this meeting, an INAD application submission (to be done; costed), and
An initial modest clinical supply of the drug product candidate (to be done; a potential contract development and manufacturing organization [CDMO] identified; costed).
Ophthalmology Update
Provectus believes it has potentially finalized the exclusive worldwide license agreement with the University of Miami for the intellectual property of Bascom Palmer Eye Institute for its rose bengal photodynamic antimicrobial therapy for the treatment of bacterial, fungal, and viral infections of the eye. The recent time taken related to questions Provectus had of UM regarding indemnification and limitation of liability. All business terms, such as a proposed corporate structure and contemplated funding approach(es), were previously agreed to in February. Barring any hiccups, the license transaction should still potentially be completed in March.
Forward-Looking Statements
The information provided in this Provectus Substack Post may include forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, relating to the business of Provectus and its affiliates, which are based on currently available information and current assumptions, expectations, and projections about future events and are subject to a variety of risks and uncertainties and other factors that could cause actual events or results to differ materially from those projected in the forward-looking statements. Such statements are made in reliance on the safe harbor provisions of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements are often, but not always, identified by the use of words such as “aim,” “likely,” “outlook,” “seek,” “anticipate,” “budget,” “plan,” “continue,” “estimate,” “expect,” “forecast,” “may,” “will,” “would,” “project,” “projection,” “predict,” “potential,” “targeting,” “intend,” “can,” “could,” “might,” “should,” “believe,” and similar words suggesting future outcomes or statements regarding an outlook.
The safety and efficacy of Provectus’s drug agents and/or their uses under investigation have not been established. There is no guarantee that the agents will receive health authority approval or become commercially available in any country for the uses being investigated or that such agents as products will achieve any revenue levels.
Due to the risks, uncertainties, and assumptions inherent in forward-looking statements, readers should not place undue reliance on these forward-looking statements. The forward-looking statements contained in this Provectus Substack Post are made as of the date hereof or as of the date specifically specified herein, and the Company undertakes no obligation to update or revise any forward-looking statements, whether because of new information, future events, or otherwise, except in accordance with applicable securities laws. The forward-looking statements are expressly qualified by this cautionary statement.
Risks, uncertainties, and assumptions include those discussed in the Company’s filings with the U.S. Securities and Exchange Commission, including those described in Item 1A of Provectus’ Annual Report on Form 10-K for the period ended December 31, 2022 and the Company’s Quarterly Report on Form 10-Q for the period ended September 30, 2023.
According to Aykul et al. 2016, “[h]alf-maximal inhibitory concentration (IC50) is the most widely used and informative measure of a drug's efficacy. It indicates how much drug is needed to inhibit a biological process by half, thus providing a measure of potency of an antagonist drug in pharmacological research.”
According to the National Human Genome Research Institute, “[a]poptosis is the process of programmed cell death…Apoptosis also plays a role in preventing cancer.” According to Pucci et al. 2020, the interplay of cell cycle regulators and apoptotic factors…becomes a matter of life and death and the survival of the organism lies in the balance.”