- Patent Application Relates to Production of Adeno-Associated Virus (AAV) via Use of LinearDNA™ Amplicons; AAV Viral Vectors Used in Gene and Redirected Cell Therapies; Current Production of AAV Relies Heavily on Use of Plasmid-derived DNA -
Applied DNA Sciences, Inc. (NASDAQ: APDN) ("Applied DNA" or the "Company"), a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing that enables in vitro diagnostics, pre-clinical nucleic acid-based therapeutic drug candidates, supply chain security, anti-counterfeiting and anti-theft technology, today announced that it has filed a nonprovisional patent application with the United States Patent and Trademark Office (USPTO) entitled "Methods and Systems of PCR-Based Recombinant Adeno-Associated Virus (AAV) Manufacture" (the "Patent"). The Patent claims priority to a previously filed provisional patent application filed with the USPTO in August of 2019.
AAV is utilized to deliver a therapeutic gene of interest to a patient or a patient’s cells to cause the expression of the necessary protein to address a targeted disease. Reflective of its potential as one of the most promising delivery vehicles for genetic medicines, there are approximately 80 active or enrolling clinical trials that utilize AAV1. With its new patent application, Applied DNA seeks to leverage its LinearDNA™ platform to give gene and redirected cell therapy developers the ability to greatly improve the manufacture and quality of their AAV-vectored medicines that have the potential to address many diseases, including COVID-19.
"AAV is generally accepted as the preferred vector for gene therapy, and so, has an enormous breadth as a therapeutic gene delivery system. AAV vectors are manufactured utilizing multiple plasmid DNAs as starting materials, and as the number of gene therapy programs increase, and with improving levels of clinical success and progression of therapies into late-phase clinical studies, the field is being challenged by the need for larger manufacturing scales," said Dr. James A. Hayward, president and CEO of Applied DNA Sciences. "At Applied DNA, we believe we have solved the linear DNA production challenge and can make the DNA sequences at scale for gene therapies. Utilizing our LinearDNA™ platform to manufacture amplicons, we can deliver gene therapy constructs that potentially lower the risks that come with the use of plasmid-based AAV manufacture. As one of the only companies in the marketplace commercializing a scaled linear DNA manufacturing platform, we believe we are uniquely positioned to deliver linear DNA as an alternative to plasmids, and with this patent filing, we expand our addressable market to including AAVs."
AAV is manufactured by the triple transfection of three plasmid DNA constructs into packaging cell lines to produce recombinant adeno-associated virus. This triple transfection requires large amounts of DNAs that are currently manufactured via plasmids – circular DNA constructs which are propagated in bacteria. The three DNA constructs necessary for successful AAV production are: (i) AAV Rep and Cap; (ii) AAV Helper; and (iii) the therapeutic cargo (transgene) flanked on either side by inverted terminal repeat sequences (ITR). The manufacture of plasmid DNA for the production of AAV, however, presents a number of significant challenges, including scalability, fidelity, mis-incorporation of plasmid-derived DNA sequences, high costs, and long lead times for cGMP production.
Concluded Dr. Hayward, "The ITRs serve as the viral origins of replication and for packaging signals to assemble AAV in the host cell. But the triple transfection of the required plasmids, and in the strict stoichiometries required for AAV assembly, we believe adds enormously to the cost of traditional AAV manufacturing, limiting the availability of many gene therapies. Our success in simplifying the production of the critical plasmid genes for AAV production we believe enable AAV production with minimal or absent plasmids, potentially greatly enhancing production and lowering costs. The use of LinearDNA potentially lowers the risks that come with plasmids, including off-target DNA, contamination by the genes for antimicrobial resistance or other bacterial DNA, endotoxin contamination and the use of antibiotics."
The Patent claims methods for the use of specialized LinearDNATM amplicons, instead of plasmids, to manufacture AAV. The patent also claims methods and systems for the PCR-based manufacturing of AAV transgene constructs flanked on either side by the necessary ITR sequences via the Company’s LinearDNA platform. Due to their complex secondary structures, the ITR sequences necessary for AAV production have historically been very challenging to amplify via PCR. Leveraging the Company’s PCR expertise, the methods and systems claimed in the Patent utilize specialized PCR techniques and primer designs to mitigate the challenges caused by the ITR secondary structures, allowing for the high yield and high-fidelity manufacture of transgene –ITR amplicons.
About Applied DNA Sciences
Applied DNA is a provider of molecular technologies that enable supply chain security, anti-counterfeiting and anti-theft technology, product genotyping and pre-clinical nucleic acid-based therapeutic drug candidates.
The Company’s common stock is listed on NASDAQ under ticker symbol ‘APDN’, and its publicly-traded warrants are listed on OTC under ticker symbol ‘APPDW’.
Applied DNA is a member of the Russell Microcap® Index.
The statements made by Applied DNA in this press release may be "forward-looking" in nature within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. Forward-looking statements describe Applied DNA’s future plans, projections, strategies and expectations, and are based on assumptions and involve a number of risks and uncertainties, many of which are beyond the control of Applied DNA. Actual results could differ materially from those projected due to the possibility of a failure to make timely payment on its outstanding secured convertible notes and resulting enforcement by noteholders of remedies on collateral which includes substantially all of Applied DNA’s assets, its history of net losses, limited financial resources, limited market acceptance, the uncertainties inherent in research and development, future clinical data and analysis, including whether any of Applied DNA’s or its partners diagnostic candidates will advance further in the preclinical research or clinical trial process, including receiving clearance from the U.S. Food and Drug Administration or equivalent foreign regulatory agencies to conduct clinical trials and whether and when, if at all, they will receive final approval from the U.S. FDA or equivalent foreign regulatory agencies, the unknown outcome of any applications or requests to U.S. FDA, equivalent foreign regulatory agencies and/or the New York State Department of Health, the fact that there has never been a commercial drug or viral vector product utilizing PCR-produced DNA technology approved for therapeutic use, disruptions in the supply of raw materials and supplies, the unknown outcome of the patent application, and various other factors detailed from time to time in Applied DNA’s SEC reports and filings, including our Annual Report on Form 10-K filed on December 12, 2019 and our subsequent quarterly reports on Form 10-Q filed on February 6, 2020, May 14, 2020 and August 6, 2020, and other reports we file with the SEC, which are available at www.sec.gov. Applied DNA undertakes no obligation to update publicly any forward-looking statements to reflect new information, events or circumstances after the date hereof or to reflect the occurrence of unanticipated events, unless otherwise required by law.
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