- 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.
Visit adnas.com for more information. Follow us on Twitter and
LinkedIn. Join our mailing list.
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.
Forward-Looking Statements
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.
1
https://clinicaltrials.gov/ct2/results?term=adeno-associated+virus&recrs=b&recrs=a&recrs=f&recrs=d&age_v=&gndr=&type=&rslt=&Search=Applyhttps://clinicaltrials.gov/ct2/results?cond=&term=%22AAV+gene+therapy%22&cntry=&state=&city=&dist=
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version on businesswire.com: https://www.businesswire.com/news/home/20200817005155/en/
Investor contact: Sanjay M. Hurry, Applied DNA Sciences,
917.733.5573, sanjay.hurry@adnas.com Program contact: Brian
Viscount, Applied DNA Sciences, 631-240-8877,
brian.viscount@adnas.com Web: www.adnas.com Twitter:
@APDN
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