38
ApolipoproteinC-III and ISIS-APOCIII
Rx
We have obtainedpatent claims in theUnitedStates drawn to the use of antisense compounds complementary to a broad
active regionof humanApoC-III including the site targetedby ISIS-APOCIII
Rx
. Similar claims complementary to any site onhuman
ApoC-III have granted inAustralia. We obtained issuedpatent claims to the specific antisense sequence and chemical compositionof
ISIS-APOCIII
Rx
in theUnitedStates, Australia, andEurope. The issuedU.S. claims shouldprotect ISIS-APOCIII
Rx
fromgeneric
competition in theUnitedStates until at least 2023. In addition, wewill seek additional patent term extension to recapture a portionof
the term lost duringFDA regulatory review, extending the termof this patent beyond2023. We are alsopursuing additional patent
applications designed toprotect the ISIS-APOCIII
Rx
composition inCanada and additionalmethods of use in jurisdictionsworldwide.
The table below lists theU.S, European andAustralian issuedpatents:
Jurisdiction
PatentNo.
Title
Expiration
DescriptionofClaims
UnitedStates ....
7,598,227
MODULATIONOF
APOLIPOPROTEINC-III
EXPRESSION
2023
Methods of treatinghyperlipidemia,
lowering cholesterol levels and lowering
triglyceride levelswith an antisense
compound comprising an antisense
oligonucleotide 15-30 linkednucleosides
specifically hybridizablewithin
nucleotides 3253-3558of SEQ ID4
(apoCIII)
UnitedStates ....
7,750,141
MODULATIONOF
APOLIPOPROTEINC-III
EXPRESSION
2023
Antisense sequence and chemistry of
ISIS-
APOCIII
Rx
Europe ..............
EP1622597
MODULATIONOF
APOLIPOPROTEINC-III
EXPRESSION
2023
Antisense sequence and chemist y of
ISIS-
APOCIII
Rx
Australia...........
2004231550
MODULATIONOF
APOLIPOPROTEINC-III
EXPRESSION
2023
Compounds 12-50nucleobases in length
specifically hybridizablewithSEQ ID4
(apoCIII), the antisense sequence and
chemist y of
ISIS-APOCIII
Rx
andmethods
of their use in treating hyperlipidemia,
lowering cholesterol levels and lowering
triglyceride levels
SurvivalMotorNeuronand ISIS-SMN
Rx
ISIS-SMN
Rx
is protected by a suite of patents in theUnitedStates and inEurope fromgeneric competition in theUnited
States until at least 2028 and inEurope until 2026. These issuedpatents include: (i) theBennett patent related tomethods of altering
mRNAprocessing (i.e., splicing)with a fully-modified 2’MOEoligonucleotide, (ii) a patent licensed from theUniversity of
Massachusetts drawn to antisense compounds having the sequence of ISIS-SMN
Rx
, independent of chemicalmodification anduses of
such compounds for treatingSMA, and (iii) a joint patentwithColdSpringHarbor Laboratory claiming fully-modified2’MOE
compositions targetingSMN2, including the precise composition ofmatter of ISIS-SMN
Rx
. Those patents shouldprotect ISIS-
SMN
Rx
fromgeneric and antisense innovator competition in theUnitedStates until at least 2028without patent term extension. The
table below lists theU.S. andEuropean issuedpatents protecting ISIS-SMN
Rx
:
Jurisdiction
PatentNo.
Title
Expiration
DescriptionofClaims
UnitedStates .....
6,210,892
ALTERATIONOFCELLULAR
BEHAVIORBYMODULATION
OFMRNAPROCESSING
2018
Broad claims of alteringmRNAprocessing
with a fully-modified2’MOEoligonucleotide.
UnitedStates .....
8,361,977
COMPOSITIONSAND
METHODSFORMODULATION
OFSMN2SPLICING
2028
Sequence and chemistry (full 2’-MOE) of
ISIS-SMN
Rx
Europe ...............
1910395
COMPOSITIONSAND
METHODSFORMODULATION
OFSMN2SPLICING
2026
Sequence and chemistry (full 2’-MOE) of
ISIS-SMN
Rx
UnitedStates .....
7,838,657
SPINALMUSCULARATROPHY
(SMA) TREATMENTVIA
TARGETINGOFSMN2SPLICE
SITE INHIBITORYSEQUENCES
2027
Oligonucleotides having sequence of ISIS-
SMN
Rx
(chemistry independent)
UnitedStates .....
8,110,560
SPINALMUSCULARATROPHY
(SMA) TREATMENTVIA
TARGETINGOFSMN2SPLICE
SITE INHIBITORYSEQUENCES
2025
Methods of using antisense oligonucleotides
having sequence of SMN
Rx
to alter splicingof
SMN2 and/or to treat SMA
r
r
