Alnylam believes that no other company owns a portfolio of such broad and exclusive rights to fundamental RNAi patents and patent applications required for the development and commercialization of RNAi therapeutics. This leading IP estate has been validated in licenses to over 20 companies to date. Alnylam's intellectual property portfolio includes the following.
- Major Alliances
- IP Consolidation
- InterfeRX Partnerships
- Research Reagent/ Service Licenses
- Exclusive rights to certain key issued or granted patents and pending patent applications covering critical aspects of the structure and function of siRNAs and their use as therapeutics.
- U.S. Patent Nos. 7,056,704 and 7,078,196, from the "Tuschl II series" licensed exclusively to Alnylam for RNAi therapeutics, includes 96 claims that broadly cover methods for preparing small interfering RNAs (siRNAs), important for the therapeutic activity, including:
- a double stranded region formed from two RNA strands of a length of 19-25 nucleotides; and, one or more 3’-overhangs at the ends of the double-stranded molecule
- methods of making siRNAs for any target, with or without chemical modifications that are used to introduce certain drug-like properties into siRNAs such as stability and delivery
- EU Patent No. 1407044 also from the Tuschl II patent series and broadly covers compositions, methods, and uses of small interfering RNAs (siRNAs), the molecules that mediate RNAi. The claims cover the compositions, methods, and uses of double-stranded RNAs having key structural elements that are widely recognized as important for the therapeutic activity of siRNAs, including:
- a double stranded region formed from two RNA strands with a length of 19-23 nucleotides;
- one or more 3'-overhangs at the ends of the double-stranded molecule;
- compositions with chemical modifications on the 3'-end of the siRNA to protect against degradation and/or the use of one or more nucleotide modification, such as 2'-O-Me or 2'-F, without any limitation to the number of such modifications; and,
- the use and pharmaceutical compositions of such an siRNA molecule to modulate the function of mammalian or pathogen-derived genes both in vitro and in vivo.
- Patents stemming from the Tuschl II patent series have also been issued in other countries throughout the world, including New Zealand, South Africa, Australia and Singapore.
- U.S. Patent Nos. 5,898,031 and 6,107,094, owned by Isis Pharmaceuticals and licensed to Alnylam, covers degradation of target mRNA mediated by chemically modified RNAi-like oligonucleotides.
- Additional issued patents in Germany, Australia, and South Africa for the Kreutzer-Limmer I patent estate.
- U.S. Patent Nos. 7,056,704 and 7,078,196, from the "Tuschl II series" licensed exclusively to Alnylam for RNAi therapeutics, includes 96 claims that broadly cover methods for preparing small interfering RNAs (siRNAs), important for the therapeutic activity, including:
- Granted patents (EU 1144623 and EU 1214945) in the European Union (EU) and pending patent applications from the "Kreutzer-Limmer I" patent series on compositions, methods, and uses of siRNAs with a length required for developing RNAi therapeutics.
- Broad rights to >150 issued patents and pending patent applications covering synthetic chemistry used in the discovery, development, and commercialization of RNAi therapeutics.
- A granted patent in the EU (EP 1352061) and many additional pending patent applications on the use of specific siRNAs to silence specific targets and to treat particular diseases.
In addition to forming strategic alliances with pharmaceutical companies, Alnylam is capitalizing on the strength of its IP estate by offering target-specific therapeutic licenses in areas outside Alnylam's strategic focus through its InterfeRx™ program, subject to its existing third party obligations, and by offering licenses to life science reagent and service providers.
Fundamental Patents
The fundamental IP that Alnylam believes will be most important in providing competitive advantage and product exclusivity with respect to RNAi therapeutics are the patents referred to as "Tuschl II," "Kreutzer-Limmer" and "Crooke." patents and patent applications. Only Alnylam has access to these patents for RNAi therapeutics.
Tuschl II
The Tuschl II patent series covers a key structural feature of siRNAs, namely the presence of overhangs at the 3'-end of each of the two strands, and was the first and only patent application of the Tuschl series of patents to include data on mammalian cell gene silencing and data regarding the use of chemical modifications with siRNAs. The patent series is exclusively licensed to Alnylam for RNAi therapeutics on a world-wide basis through an agreement with the Max Planck Society. Based on the seminal research by Dr. Tuschl, a founder of Alnylam, U.S. Patent No. 7,056,704 broadly covers methods of making siRNAs for any target, with or without chemical modifications.
In the U.S., the issued Tuschl II patent include claims that broadly cover the preparation of any double-stranded RNA having key structural elements that are important for the therapeutic activity of siRNAs, including:
- The presence of 3'-overhangs at one or both ends of the double-stranded molecule; and
- A length of 19-25 nucleotides that falls within the size range optimal for RNAi therapeutics
Kreutzer-Limmer I
The originally filed patent application of Drs. Kreutzer Limmer has thus far been the basis for the issuance of two European patents, an Australian patent and a South African Patent. The Kreutzer-Limmer patent is pending in other major markets world-wide.The first issued Kreutzer-Limmer I European patent (EP 1144623) was granted in 2002. In June 2006, following opposition proceedings, the European Patent Office (EPO) upheld key features of this patent including the length of 15-21 nucleotides and other required structural features.
A divisional application based on the Kreutzer-Limmer European patent was granted in 2005 (EP 1214945), with even broader claims to methods and medicaments containing dsRNA agents wherein the dsRNA has a total length of 15 to 49 nucleotide pairs. Furthermore, a German utility model was registered in 2003 (DE 20023125) which includes claims to oligoribonucleotides of such composition and which was equally derived from the international parent application of EP 1144623 and EP 1214945.
In addition to the European patent, the Kreutzer-Limmer patent application has resulted in the issuance of patents in South Africa in 2003, Australia in 2004, Canada in 2007, Germany in 2007, and is pending in other countries, including the United States.
Through our acquisition of Ribopharma AG (now Alnylam Europe) in 2003, Alnylam owns the issued European, South African, and Australian patents outright, as well as the pending applications in the rest of the world.
Crooke
Two issued patents, US Patent No.'s 5,898,031 and 6,107,094, owned by Isis Pharmaceuticals and licensed to Alnylam, covers degradation of target mRNA mediated by chemically modified RNAi-like oligonucleotides. This patent has a priority date of June 6, 1997.
In addition, Alnylam has exclusive or non-exclusive access to other fundamental RNAi patents and patent applications, including those known as "Fire and Mello" (licensed from Carnegie Institute), "Glover" (licensed from Cancer Research Technology), "Tuschl I" (licencsed from MIT, Whitehead Institute and Max Planck Society), "Kay"(licensed from Stanford University) and "Hannon" (licensed from Cold Spring Harbor Laboratories).
Alnylam also has licensed over 150 issued patents covering chemical modifications of RNAi therapeutics licensed from Isis Pharmaceuticals, Inc. These patents cover a very broad range of chemical modifications to oligonucleotides including phosphorothioates, 2'-O-methyl, 2'-fluoro and conjugation modifications.
Alnylam also has licensed or filed patent applications covering >200 disease targets. This includes the "Kreutzer-Limmer II" patent that has been granted in the EU and covers siRNAs directed toward over 125 disease targets.