By Donald Zuhn —

Isis Pharmaceuticals, Inc. announced today that the U.S. Patent and Trademark Office has issued notices of allowance for U.S. Application Nos. 10/281,312 and 10/281,297.  According to the company’s press release, the two allowances "significantly expand" the scope of Isis’ Crooke patent estate — a family of patents based on the 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.  Isis noted that the two allowed applications are directed to methods of treating patients by administering an siRNA or a single-stranded RNA-containing compound and to pharmaceutical compositions containing single-stranded RNA-like compounds.

The Crooke patent estate, which includes U.S. Patent Nos. 5,898,031 and 6,107,094, is licensed by Isis Pharmaceuticals to Alnylam Pharmaceuticals, Inc. for the development of double-stranded RNAi therapeutics and to Regulus Therapeutics LLC, a joint venture between Isis and Alnylam, for the development of microRNA-based therapeutics.  Discussing the allowances, Dr. Crooke, Isis’ Chairman and CEO, observed that the company’s patent position with respect to RNA-based therapeutics was "unparalleled" and added that "[t]he Crooke patent series provides broad protection against competitors who are developing RNA-based drugs, including siRNAs."  Alnylam CEO Dr. John Maraganore noted that the allowances were "particularly important because they broaden the scope of our IP covering pharmaceutical compositions and methods of treating patients with RNAi therapeutics."  Regulus CEO Dr. Kleanthis Xanthopoulos similarly noted that "[t]hese new patent allowances significantly strengthen our
efforts to advance microRNA therapeutic products to patients."

With respect to the ‘312 application, representative allowed claim 89 recites:

    89.  A method of treating a patient having a disease characterized by the undesired production of a protein encoded by a target RNA, comprising administering to said patient a pharmaceutically effective amount of an oligomeIic compound, wherein said compound:
    (i)  is specifically hybridizable with said target RNA;
    (ii)  is 15 to 25 nucleoside subunits in length;
    (iii)  comprises a plurality of nucleoside subunits with 2′ -hydroxyl pentofuranosyl sugar moieties; and
    (iv)  compIises at least one modified nucleoside subunit, wherein said modification increases affinity of said compound to said target RNA or increases resistance of said compound to single-stranded nucleases.

With respect to the ‘297 application, representative allowed claims 94 and 111 recite:

    94.  A composition comprising a pharmaceutically acceptable diluent or carrier and a single-stranded oligomeric compound, wherein said compound:
    is 15 to 25 nucleoside subunits in length;
    specifically hybridizes with a preselected target RNA;
    comprises at least four consecutive nucleosides with 2′ -hydroxyl-pentofuranosyl sugar moieties; and
    further comprises at least one sugar modified nucleoside subunit, wherein the modification improves affinity or specificity of said compound to said target RNA or increases resistance of said compound to single-stranded nucleases.

    111.  A composition comprising a pharmaceutically acceptable diluent or carrier and a single-stranded oligomeric compound, wherein said compound:
    is 15 to 25 nucleoside subunits in length;
    is specifically hybridizable with a preselected target RNA;
    comprises at least one sugar modification; and
    comprises a plurality of nucleoside subunits with 2′-hydroxyl pentofuranosyl sugar moieties.