Antisense Drug DesignMotifs
MOEGapmers
Other Isis patents claim oligonucleotides comprising specific antisense drug design motifs, or patterns of
nucleoside modifications at specified positions in the oligonucleotide. Patent claims covering our antisense drug
design motifs are independent of nucleic acid sequence, so they cover oligonucleotides having the recited motif,
regardless of cellular target or clinical indication. The claimed motifs generally confer properties that optimize
oligonucleotides for a particular antisense mechanism of action, such as ribonuclease H, or RNase H, RNAi, or
splicing. We have designed oligonucleotides incorporating motifs, which we refer to as chimeric compounds or
gapmers to exploit the RNase Hmechanism to achieve target RNA reduction. Almost all of our drugs, including
KYNAMRO, contain this gapmer antisense drug design motif. In fact, we own a U.S. patent that covers each of
our second generation gapmer antisense drugs until March of 2023. We also have issued patents covering other
gapmer drug designs, and methods of lowering a target RNA in an animal with these gapmer compositions. The
following patent is one example of our patents in this category.
Jurisdiction
Patent/
Application
No.
Title
Expiration
Description of Claims
United States
7,015,315
GAPPEDOLIGONUCLEOTIDES
2023
Covers 2’-O-alkyl-O-alkyl gapmer
oligonucleotides.
Bicyclic Nucleoside Gapmer Oligonucleotides
In addition, we have pursued patent claims to antisense drug design motifs incorporating bicyclic nucleoside
analogs, which include locked nucleic acids, or LNAs. In Europe, we have granted claims drawn to short gapmer
oligonucleotides with bicyclic nucleosides, which include locked nucleic acids, in the wings for the treatment of
cardiovascular or metabolic disorders. We have also successfully obtained issued patent claims covering gapmer
antisense drug design motifs that incorporate our cEt modified nucleosides. Santaris has opposed this granted
patent and we intend to vigorously defend our patent in these proceedings. The following patents are some
examples of our issued patents and allowed patent applications in this category:
Jurisdiction
Patent/
Application
No.
Title
Expiration
Description of Claims
Europe
EP2021472
COMPOUNDSANDMETHODS
FORMODULATINGGENE
EXPRESSION
2027
Short gapmer oligonucleotides, 10 to 14
nucleotides in length, with bicyclic
nucleosides, which includes cEt locked
nucleic acids, in the wings for the
treatment of cardiovascular or metabolic
disorders
United States
7,750,131
6-MODIFIEDBICYCLIC
NUCLEICACIDANALOGS
2027
Covers cEt containing gapmer compounds
Europe
EP2092065
ANTISENSE COMPOUNDS
2027
Gapmer compounds having wings
comprised of 2’-MOE and bicyclic
nucleosides
TherapeuticMethods of Treatment and Antisense Drug Sequences
In addition to our broad core patents, we also own hundreds of patents, worldwide, with claims to antisense
sequences and compounds directed to particular therapeutically important targets or methods of achieving clinical
endpoints using these antisense compounds. Target patents may also include claims reciting the specific nucleic
acid sequences utilized by our products, independent of chemical modifications and motifs. In addition, our
product specific patents typically include claims combining specific nucleic acid sequences with nucleoside
modifications and motifs. In this way, we seek patent claims narrowly tailored to protect our products
specifically, in addition to the broader core antisense patents described above.
ApoB 100 and KYNAMRO
In 2008, we obtained patent claims in the United States drawn to the use of both single-stranded and
double-stranded antisense drugs complementary to any site of the mRNAof human apoB, regardless of chemistry
or antisense mechanism of action. The patent provides broad protection of the Isis-Genzyme apoB franchise,
including KYNAMRO and potential future follow-on compounds. Similar claims granted inAustralia and Japan
in 2009 and 2010, respectively. We and Genzyme obtained issued claims to the specific antisense sequence and
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