NeXstar Acquires PerSeptive's DNA Production Technology
Shortly after its acquisition by Perkin-Elmer Corp. (Norwalk, Conn.) in late January, PerSeptive Biosystems sold its DNA manufacturing technology to NeXstar Pharmaceuticals, Inc. (Boulder, Colo.). The deal involved the Koester and Caruthers patents, which cover protecting groups for phosphate and coupling chemistry. Virtually every manufacturer of chemically synthesized oligonucleotides uses these techniques, by which synthetic, or "unnatural" DNA/RNA bases are coupled to each other as well as to the five natural bases to create "unnatural" DNA and RNA.
Companies manufacturing DNA using the Koester/Caruthers methods will now have to pay NeXstar a licensing fee. The patents, which are ten years old, have about seven more years before they expire.
NeXstar will apply the patents immediately, at its cGMP pilot plant, on its own oligonucleotide products. These include DCI (a coupling activator that increases the speed of DNA coupling reactions) and PASS, NeXstar's proprietary, large-scale technology for manufacturing oligonucleotide drugs. In addition, NeXstar expects the patents to help it deliver novel chemical building blocks for DNA/RNA, new process reagents, and new technologies for linking gene-based therapeutics to other compounds to enhance their activity.
"All second-generation antisense therapeutics use unnatural monomers," said Bruce Eaton, NeXstar vice president of chemistry, "and these patents represent are the most efficient, well-characterized processes for creating new antisense gene-based drugs." Antisense uses DNA strands that bind to and inactivate genes responsible for diseases. Antisense strands made only from natural monomers usually do not have optimal binding or bioavailability, hence the push towards DNA containing modified nucleotides.
The Koester technique (invented by Hubert Koester, University of Hamburg) uses inorganic polymeric supports such as silica gel and controlled pore glass, capping using acetic anhydride to avoid failure sequences, introduction of B-cyanoethyl-N.N-diisopropylphosphoamidites and fast deprotecting N-acyl protecting groups. The Caruthers method (invented by Marvin Caruthers, Northwestern University), which uses phosphoramidite coupling agents on silica supports, allows the synthesis of large batches (up to several kg) of both natural and unnatural DNA/RNA.
For more information contact: Bruce Eaton, vice president of chemistry, NeXstar Pharmaceuticals, Inc., 2860 Wilderness Place, Boulder, CO 80301.
Tel: 303-444-5893.
by Angelo DePalma