World's largest antisense oligonucleotide synthesis scale per run produced more than four kilograms of high-quality crude 20mer oligonucleotide in 5.3 hours
Amersham Biosciences says that Isis Pharmaceuticals recently completed the world's largest antisense oligonucleotide synthesis scale per single run.
Isis accomplished this pharmaceutical industry manufacturing first by using OligoProcess from Amersham Biosciences, combined with its proprietary synthesis methods and custom reactor column.
The OligoProcess synthesizer produced more than four kilograms (600-millimole scale) of high-quality crude 20mer oligonucleotide in approximately 5.3 hours.
The synthesis demonstrates the utility of OligoProcess and Isis's synthesis methods as well as the ability to produce a metric tonne of crude oligonucleotide on an annual basis.
Amersham Biosciences designed a custom OligoProcess, according to Isis's functional specifications, which accommodated its proprietary synthesis methods. OligoProcess operates on the Unicorn platform and is an automated system of pumps that delivers the precise levels of solvents at appropriate intervals with high capacity, through a column packed with solid support, called Primer Support 200.
The solid support used by Isis to achieve the single run consisted of beads of polystyrene cross linked with divinylbenzene, with the first nucleoside attached at a density of 200 micromoles per gram.
The high density of nucleoside loading on this solid support resulted in an elevated scale of synthesis per reaction volume.
The advantage of this high synthesis scale is a reduction in the quantity of reagents consumed per run and an increased yield of full-length oligonucleotide.
"Amersham Biosciences continues to demonstrate its leadership in the supply of cGMP compliant, highly customised oligonucleotide synthesizers and reagents, " said Anthony Scozzari, vice president, drug substance manufacturing and process chemistry of Isis.
"Amersham Biosciences's base knowledge of oligonucleotide synthesizer design, developed over the past 15 years, has been critical to our synthesis and process development successes".
The synergy of the OligoProcess, Primer Support 200 and Isis's synthesis methods has the potential to produce up to 10 kilograms of crude oligonucleotide (1.5 Molar scale) every 6.3 hours or 6800kg per year.
Isis is currently planning to initiate an 800-millimole scale run later this year.