Isolation of antisense oligonucleotides

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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C536S024500

Reexamination Certificate

active

10535728

ABSTRACT:
The present invention relates to a method of isolating fully thioated single stranded antisense oligonucleotides from a biological solution, which method comprises the steps of contacting the biological solution with an immobilised metal ion adsorption chromatography (IMAC) resin to adsorb the antisense oligonucleotides to the resin and subsequently contacting the resin with an eluent under conditions that provide desorption of the antisense oligonucleotides from the resin, wherein the fully thioated antisense oligonucleotides are separated from incorrectly thioated antisense oligonucleotides in the solution. The invention also relates to the use of an immobilised metal ion adsorption chromatography (IMAC) resin for isolation of fully thioated single stranded antisense oligonucleotides from a biological solution.

REFERENCES:
patent: WO 98/00435 (1998-01-01), None
patent: WO 99/09045 (1999-02-01), None
patent: WO 02/46398 (2002-06-01), None
Hubert et al. Journal of Chromatography 1980, vol. 198, pp. 247-255.
Dobrowolska et al. Journal of Chromatography 1991, vol. 541, pp. 333-339.
Deshmukh, R., et al., “Process Development for Purification of Therapeutic Antisense Oligonucleotides by Anion-Exchange Chromatography”,Organic Process Research&Development, vol. 4, No. 3, 2000, p. 205-213.
Deshmukh, R., et al., “Large-scale purification of antisense oligonucleotides by high-performance membrane adsorber chromatography”,Journal of Chromatography A, vol. 890, 2000, p. 179-192.

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