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Due to the growingnumbers of our antisense drugdevelopment partners and the clinical successes of our antisense drugs,
includingKYNAMRO, in2009we increasedourmanufacturing capacitybyupgrading andoptimizing the efficiencyof our
manufacturing facility. Our drug substancemanufacturing facility is located in an approximately28,704 square foot building in
Carlsbad, California.We lease this buildingunder a lease that has an initial term endingonDecember 31, 2031with anoption to
extend the lease for up to four additional five-year periods. In addition,we have an approximately25,792 square foot building that
houses support functions for ourmanufacturing activities. We lease this facility under a lease that has an initial term ending in
June 2021with anoption to extend the lease for up to two additional five-year periods. Ourmanufacturing facility is subject to
periodic inspectionby theFDA to ensure that it is operating in compliancewith currentGoodManufacturingPractices, or cGMP,
requirements.
As part of our collaborationswemay agree tomanufacture clinical trialmaterials and/or commercial supply for our partners.
For example, in the past we havemanufactured clinical supplymaterials forATL, Atlantic Pharmaceuticals, Bristol-Myers Squibb, Eli
Lilly andCompany, Genzyme, iCo, OncoGenex, Ortho-McNeil-JanssenPharmaceuticals, Inc., Biogen Idec andAstraZeneca.
We believewe have sufficientmanufacturing capacity tomeet our current and future obligations under existing agreements
withour partners for commercial, research and clinical needs, aswell as tomeet our current internal research and clinical needs,
including for the Phase 3 clinical trials for ISIS-TTR
Rx
, ISIS-SMN
Rx
, and ISIS-APOCIII
Rx
.We believe that we have, orwill be able to
develop or acquire, sufficient supply capacity tomeet our anticipatedneeds, including the initial launch supplies for ISIS-TTR
Rx
, ISIS-
SMN
Rx
, and ISIS-APOCIII
Rx
.We alsobelieve thatwith reasonably anticipatedbenefits from increases in scale and improvements in
chemistry, we canmanufacture antisense drugs at commercially competitive prices.
In January2013, theFDA approved themarketing application forKYNAMRO for patientswithHoFH. We provided the
drug substance necessary for the initial launchofKYNAMRO andGenzyme is responsible for the long-term supply ofKYNAMRO
drug substance. Genzymemanufactures the finisheddrugproduct forKYNAMRO and is offeringKYNAMRO in theUnitedStates in
pre-filled syringes. Genzyme is producing the pre-filled syringes usingone of its ownmanufacturing facilities.
Patents andProprietaryRights
Our success depends, in part, on our ability toobtain patent protection for our products in theUnitedStates andother
countries. As of February10, 2014, we ownedor exclusively licensed approximately1,200 issuedpatentsworldwide. This number is
lower than years past due to a careful restructuringof our patent portfolio to focus our resources onpatents andnewpatent
applications that drive value for our company.
We ownor control patents that provide exclusivity for products in our pipeline andpatents that provide exclusivity for our
core technology in the fieldof antisensemore generally. Our core technologypatents include claims to chemically-modified
nucleosides andoligonucleotides aswell as antisense drugdesigns utilizing these chemically-modifiednucleosides. These core claims
are each independent of specific therapeutic target, nucleic acid sequence, or clinical indication. We alsoown a large number of
patents claiming specific antisense compounds havingnucleic acid sequences complementary to therapeutic target nucleic acids,
independent of the particular chemicalmodifications incorporated into the antisense compound. Most importantly, we seek andobtain
issued patent claims to specificallyprotect eachof our drugs. For example, we file and seek to obtain claims covering eachdrug’s
nucleic acid sequence andprecise drugdesign. In sum, wemaintain our competitive advantage in the field of antisense technologyby
protectingour core platform technology, which applies tomost of our drugs, andby creatingmultiple layers of patent protection for
eachof our specific drugs indevelopment.
Type of PatentClaim
Breadth
BroadlyApplicable
Specific
Description
ChemicallyModifiedNucleosides and
Target and sequence independent
Oligonucleotides
AntisenseDrugDesignMotifs
Target and sequence independent
TherapeuticMethods
Sequence independent
AntisenseSequence
Chemistry independent
DrugComposition
Specific claim to drug candidates
