Cellectis Announces the Issuance of U.S. Patent 9,458,439 Following U.S. Patent 8,921,332 Issued in December 2014

NEW YORK–(BUSINESS WIRE)– Regulatory News:

Cellectis
(Paris:ALCLS) (NASDAQ:CLLS) (Alternext: ALCLS; Nasdaq: CLLS), a
biopharmaceutical company focused on developing immunotherapies based on
gene edited CAR T-cells (UCART), today announced the issuance of U.S.
patent 9,458,439 – which claims gene inactivation by use of chimeric
restriction endonucleases. This patent granted by the USPTO to the
Institut Pasteur and Boston Children’s Hospital naming Dr. André
Choulika and Pr. Richard C. Mulligan as co-inventors, is exclusively
licensed to Cellectis.

This issued U.S. patent 9,458,439 claims the method of introducing
chromosomal modifications at a locus by induction of double-stranded DNA
cleavage using a chimeric restriction endonuclease and non-homologous
end joining recombination (NHEJ). This pivotal invention is at the basis
of current nuclease-based precise gene inactivation techniques using
chimeric restriction endonuclease such as Cas9/CRISPR (and related
families), Zinc finger Nucleases, TAL-Effector Nucleases, Mega-TALEs,
some Meganucleases i.e. endonucleases generated by the
juxtaposition of specific DNA binding sequences and DNA cleavage domains
with a recognition site of at least 12 base pairs. This technology is
universal as it can be applied to any types of cells, including human,
animal, plant cells or microorganisms.

This new patent follows U.S. patent 8,921,332 issued on December 30^th,
2014, which claims the use of chimeric restriction endonucleases for
directing chromosomal gene editing in cells by homologous recombination.

This new patent complements Cellectis’ strong portfolio of gene editing
technologies that are implemented in its CAR T-cell product candidates,
as well as within its Minnesota-based agricultural biotechnology
subsidiary, Calyxt, which develops food products with healthier
characteristics.

The inventors of this patent are Dr. André Choulika, Chairman & CEO of
Cellectis and one of the pioneers in the development of nuclease-based
genome editing technologies, and Professor Richard C. Mulligan,
Mallinckrodt Professor of Genetics, Emeritus, at Harvard Medical School
and a Founding Partner of Sarissa Capital Management. Professor Mulligan
is a world-renowned scientist and former member of Cellectis’ Board of
Directors whose laboratory has made seminal contributions to the
development of fundamental gene transfer and gene therapy technologies.

Claim 1 of the U.S. patent 9,458,439:

“A method for attenuating or inactivating an endogenous gene of interest
in a cell in vitro comprising:
inducing in the cell double stranded
cleavage of chromosomal DNA at a genomic site of interest in the
specific sequence to be modified, wherein the inducing comprises
contacting the genomic site of interest with a chimeric restriction
endonuclease, said chimeric restriction endonuclease comprising a DNA
binding sequence and a DNA cleavage domain, and said restriction
endonuclease recognizing a DNA sequence of at least 12 bp, wherein said
restriction endonuclease is introduced as a protein or is encoded by a
nucleic acid vector that is expressed, thereby inducing a cellular
repair mechanism which leads to highly efficient recombinational events
at said genomic site of interest, wherein said recombinational events
introduce a mutation into said genomic site of interest, thereby
modifying the specific sequence in the chromosomal DNA of the cell and
thereby attenuating or inactivating an endogenous gene of interest in
said cell.”

Claim 1 of the U.S. patent 8,921,332:

“A method of modifying a specific sequence in chromosomal DNA of a cell in
vitro comprising:
inducing in the cell double stranded cleavage
of chromosomal DNA at a genomic site of interest in the specific
sequence to be modified, wherein the inducing comprises contacting the
genomic site of interest with a chimeric restriction endonuclease, said
chimeric restriction endonuclease comprising a DNA binding sequence and
a DNA cleavage domain, and said restriction endonuclease recognizing a
DNA sequence of at least 12 bp, wherein said restriction endonuclease is
introduced as a protein or is encoded by a nucleic acid vector that is
expressed; and contacting said cell with a targeting DNA or a nucleic
acid vector encoding said targeting DNA in an amount sufficient to
produce recombination between said targeting DNA and said chromosomal
DNA at the site of interest, wherein said targeting DNA comprises (1)
DNA homologous to the region surrounding the genomic site of interest
and (2) DNA which modifies the specific sequence upon recombination
between said targeting DNA and said chromosomal DNA, thereby modifying
the specific sequence in the chromosomal DNA of the cell.”

About Cellectis

Cellectis is a biopharmaceutical company focused on developing
immunotherapies based on gene edited CAR T-cells (UCART). The company’s
mission is to develop a new generation of cancer therapies based on
engineered T-cells. Cellectis capitalizes on its 16 years of expertise
in genome engineering – based on its flagship TALEN® products and
meganucleases and pioneering electroporation PulseAgile technology – to
create a new generation of immunotherapies. CAR technologies are
designed to target surface antigens expressed on cells. Using its
life-science-focused, pioneering genome-engineering technologies,
Cellectis’ goal is to create innovative products in multiple fields and
with various target markets. Cellectis is listed on the Nasdaq market
(ticker: CLLS) and on the NYSE Alternext market (ticker: ALCLS). To find
out more about us, visit our website: www.cellectis.com

Talking about gene editing? We do it. TALEN® is a registered trademark
owned by the Cellectis Group.

Disclaimer

This press release and the information contained herein do not
constitute an offer to sell or subscribe, or a solicitation of an offer
to buy or subscribe, for shares in Cellectis in any country. This press
release contains forward-looking statements that relate to the Company’s
objectives based on the current expectations and assumptions of the
Company’s management only and involve risk and uncertainties that could
cause the Company to fail to achieve the objectives expressed by the
forward-looking statements above.

View source version on businesswire.com: http://www.businesswire.com/news/home/20161004006542/en/