Vibrating fluidized bed oligonucleotide synthesizer

The fluidized bed reactor system addresses inefficiencies in SPOS by ensuring complete liquid-solid contact and integrated multi-pass washing, enabling large-scale, efficient, and environmentally friendly oligonucleotide production.

JP2026001020AActive Publication Date: 2026-01-06ELI LILLY & CO
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Patent Information

Application Number
JP2025154295
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2020-12-18
Filing Date
2025-09-17
Publication Date
2026-01-06
Estimated Expiration
2041-12-14

AI Technical Summary

Technical Problem

Conventional solid-phase oligonucleotide synthesis (SPOS) is inefficient, costly, generates significant waste, and is limited by scalability and uneven reaction efficiency due to uneven liquid-solid contact in packed-bed reactors.

Method used

A fluidized bed reactor system is used for oligonucleotide synthesis, where reagents flow up and down through the resin bed, ensuring complete liquid-solid contact and reducing channeling, with integrated multi-pass washing to enhance efficiency and reduce solvent use.

Benefits of technology

The system increases reaction efficiency, reduces waste, and allows for large-scale production of oligonucleotides with improved purity and reduced solvent consumption.

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Abstract

To provide an efficient solid phase oligonucleotide synthesis (SPOS) method.SOLUTION: A method of adding an oligonucleotide to a solid support in a bed reactor, the method comprising: removing a protecting group from a 5' - position of an oligonucleotide bound to the solid support; and adding an activated amidite solution to the bed reactor, wherein: Wherein the activated amidite solution comprises an amidite and flows up and down or is fluidized by nitrogen bubbling or other agitation in the bed reactor and reacts at the 5 ' position of the oligonucleotide, wherein the phosphite linkage found in the amidite comprises a P atom in oxidation state III, and then converting the P atom from oxidation state III to oxidation state V.SELECTED DRAWING: None
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