Bruce A Ross

US Patent:

6642367, Nov 4, 2003

Filed:

Dec 22, 2000

Appl. No.:

09/747009

Inventors:

Phillip Dan Cook - Escondido CA
Yogesh S. Sanghvi - Encinitas CA
Kelly G. Sprankle - Vista CA
Bruce S. Ross - Carlsbad CA
Rich H. Griffey - Vista CA
Robert H. Springer - Carlsbad CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 1900

US Classification:

536 221, 536 231, 536 253

Abstract:

Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2â and 5â positions. Monomeric sub-units having these modifications may be further modified at the 2â position. Improved processes for the synthesis of 2â-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2â-anhydropyrimidine nucleoside or a 2S,2â-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.

US Patent:

7002006, Feb 21, 2006

Filed:

Feb 12, 2003

Appl. No.:

10/365183

Inventors:

Quanlai Song - Encinitas CA, US
Bruce S. Ross - Carlsbad CA, US

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 19/00

US Classification:

536 281, 536 221, 536 2711

Abstract:

A process of manufacturing protected nucleosides comprises reacting a nucleoside with a protecting reagent in the presence of a regioselective activator to produce a regioselectively protected nucleoside. In some embodiments of the inventive method, an optionally substituted trityl or optionally substituted pixyl group is selectively added to the 5′-O-position of a nucleoside in the presence of lutidine as activator or activator/solvent. The inventive method results in improved selectivity of the 5′-O-position over the 3′-O-position, thereby improving overall product yield and purity, and permitting simplified purification protocols, in some cases obviating the need for chromatography to produce a purified protected nucleoside suitable for automated synthesis of oligonucleotides, such as primers, probes and antisense molecules.

US Patent:

7030230, Apr 18, 2006

Filed:

Oct 25, 2002

Appl. No.:

10/280383

Inventors:

Bruce Ross - Carlsbad CA, US
Quanlai Song - Encinitas CA, US

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 21/04
C07H 19/04

US Classification:

536 161, 536 27, 544243, 544244

Abstract:

A process of purifying phosphoramidite precursors useful in inter alia synthesis of oligonucleotides comprises dissolving a crude phosphoramidite in a polar phase, adding a basic compound to the polar phase, adding a portion of water to the polar phase, contacting the polar phase with a first apolar phase to extract impurity into the apolar phase, separating the first apolar phase from the polar phase, adding a second aliquot of water to the polar phase, and contacting the polar phase with a second apolar phase, whereby the phosphoramidite partitions into the second apolar phase.

US Patent:

7057062, Jun 6, 2006

Filed:

Apr 11, 2002

Appl. No.:

10/120680

Inventors:

Quanlai Song - Encinitas CA, US
Bruce Ross - Carlsbad CA, US

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07F 9/02

US Classification:

558386

Abstract:

A scalable process for purification of phosphorodiamidite includes steps of solubilizing a crude phosphorodiamidite in an apolar organic solvent, contacting the non-polar organic solvent with a polar phase comprising a polar organic solvent to remove impurities from the solubilized phosphorodiamidite, and removing the non-polar organic solvent from the phosphorodiamidite.

US Patent:

8530640, Sep 10, 2013

Filed:

Feb 6, 2009

Appl. No.:

12/866708

Inventors:

Punit P. Seth - Carlsbad CA, US
Michael T. Migawa - Carlsbad CA, US
Eric E. Swayze - Encinitas CA, US
Quanlai Song - Carlsbad CA, US
Mingming Han - Nazareth PA, US
Bruce S. Ross - Princeton NJ, US

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 19/24
C07H 19/04

US Classification:

536 267, 536 187

Abstract:

The present disclosure provides bicyclic cyclohexitol nucleoside analogs of formula I and oligomeric compounds comprising these nucleoside analogs. These bicyclic nucleoside analogs are expected to be useful for enhancing properties of oligomeric compounds including for example nuclease resistance.

US Patent:

20050059815, Mar 17, 2005

Filed:

Oct 31, 2003

Appl. No.:

10/699240

Inventors:

Phillip Cook - Escondido CA, US
Yogesh Sanghvi - Encinitas CA, US
Kelly Sprankle - Vista CA, US
Bruce Ross - Carlsbad CA, US
Rich Griffey - Vista CA, US

International Classification:

C07H021/02
C07H021/04

US Classification:

536023100

Abstract:

Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at eh 2′ and 5′ positions. Monomeric sub-units having these modifications may be further modified at the 2′ position. Improved processes for the synthesis of 2′-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2′-anhydropyrimidine nucleoside or a 2S,2′-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.

US Patent:

20070232798, Oct 4, 2007

Filed:

Mar 12, 2007

Appl. No.:

11/685035

Inventors:

Phillip Cook - Escondido CA, US
Yogesh Sanghvi - Encinitas CA, US
Kelly Sprankle - Vista CA, US
Bruce Ross - Carlsbad CA, US
Rich Griffey - Vista CA, US
Robert Springer - Carlsbad CA, US

International Classification:

C07H 19/06
C07D 401/04

US Classification:

536028400, 544333000

Abstract:

Oligonucleotide analogs are disclosed having pyrimidine monomeric sub-units therein that are modified at the 2′ and 5′ positions. Monomeric sub-units having these modifications may be further modified at the 2′ position. Improved processes for the synthesis of 2′-O-substituted pyrimidine nucleosides are also provided. The processes feature alkylation of a 2,2′-anhydropyrimidine nucleoside or a 2S,2′-anhydropyrimidine nucleoside with a weak nucleophile in the presence of a Lewis acid.

US Patent:

20070276139, Nov 29, 2007

Filed:

Feb 10, 2005

Appl. No.:

10/597808

Inventors:

Quanlai Song - Carlsbad CA, US
Sak Khammungkhune - San Diego CA, US
Bruce Ross - Carlsbad CA, US
Richard Griffey - Vista CA, US

International Classification:

C07D 311/82
C07D 335/12
C07H 19/06
C07H 21/00

US Classification:

544243000, 544317000, 549223000, 549027000

Abstract:

The present invention describes an improved hydroxyl protecting group of formula (1), wherein Rand Rare specified substituents and Q is O, S, NRor N(C═O)R.