USPTO issues Notice of Allowance for U.S. patent application in the 'Crooke' patent family

Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) and Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) announced today that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. patent application (No. 10/078,949) in the “Crooke” patent family, which broadly covers chemically modified RNA-containing therapeutics. Specifically, the allowed Crooke application includes 75 claims covering methods of using chemically modified double-stranded RNA-containing compounds to activate an RNA nuclease (RNase). The activation of the endogenous cellular RNase “argonaute 2” by double-stranded small interfering RNAs (siRNAs) is a central step in RNAi, resulting in the sequence-specific cleavage of target mRNA.

The Crooke patent family stems from innovative research of Dr. Stanley Crooke and others at Isis to identify and design RNA molecules that harness cellular RNase enzymes as antisense drugs, including RNAi and microRNA therapeutics. The Crooke patents are part of Isis’ overall patent estate, which includes more than 1,600 issued patents worldwide that broadly cover the design and use of RNA-targeting drugs. Under an agreement formed in 2004, the Crooke patent estate and additional Isis-owned patents are licensed exclusively to Alnylam for double-stranded RNAi therapeutics.

“We are very pleased that the U.S. Patent Office has acknowledged these new claims, which will expand the coverage of the Crooke patent series. This series continues to provide broad protection against competitors who are developing RNA-based drugs, including siRNAs,” said Stanley Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis. “With nearly 1,650 patents issued worldwide, we believe that we have an unparalleled intellectual property estate in the field of RNA therapeutics. Because we continue to innovate and advance our technology, we plan to continue to extend our basic patent protections on our drugs and our technologies.”

“Alnylam has maintained an ongoing strategy to consolidate all the intellectual property required to develop and commercialize RNAi therapeutics,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “Our patent licenses from Isis, including the Crooke patent estate, form a key component of Alnylam’s intellectual property position in the field. The allowance of these new claims in the Crooke patent estate clearly validates this strategy and strengthens our efforts and those of our partners to bring RNAi therapeutics to patients.”

Issued patents in the Crooke estate already include U.S. Patent No. 5,898,031 covering chemically modified RNA-containing therapeutic compounds, and U.S. Patent No. 6,107,094 covering methods of using these compounds to interfere with target RNA function, including not only interrupting protein production with single-stranded and double-stranded (siRNA) antisense compounds but also targeting other RNAs, such as microRNAs. U.S. Patent No. 7,432,250 covering methods of treating patients by administering siRNA or single-stranded chemically modified RNA-like compounds; and claims in U.S. Patent No. 7,432,249 cover pharmaceutical compositions containing single-stranded chemically modified RNA-like compounds. U.S. Patent No. 7,629,321 claims methods of cleaving target mRNA using a single-stranded oligonucleotide having a plurality RNA nucleosides and at least one chemical modification.

The newly allowed U.S. patent application (No. 10/078,949) covers methods of activating a double-stranded RNase using a double-stranded chemically modified RNA-containing compound with the following properties:

• two oligonucleotide strands hybridized to each other;
• each oligonucleotide strand comprised of 15 to 25 nucleosides; and
• at least one strand comprising a plurality of ribose sugar moieties and at least one chemical modification.

Following a Notice of Allowance, the process resulting in final issuance of a patent involves several administrative steps that are typically completed within a year.