Philip A Cook

US Patent:

20030096979, May 22, 2003

Filed:

Oct 4, 2001

Appl. No.:

09/970971

Inventors:

Muthiah Manoharan - Carlsbad CA, US
Venkatraman Mohan - Plainsboro NJ, US
Philip Cook - Fallbrook CA, US
Andrew Kawasaki - San Diego CA, US

International Classification:

C07H021/02
C07H021/04
C07F009/6515

US Classification:

536/023100, 544/244000

Abstract:

Modified oligonucleotides containing both A-form conformation geometry and B-from conformation geometry nucleotides are disclosed. The B-form geometry allows the oligonucleotide to serve as substrates for RNase H when bound to a target nucleic acid strand. The A-form geometry imparts properties to the oligonucleotide that modulate binding affinity and nuclease resistance. By utilizing C2′ endo sugars or O4′ endo sugars, the B-form characteristics are imparted to a portion of the oligonucleotide. The A-form characteristics are imparted via use of either 2′-O-modified nucleotides that have 3′ endo geometries or use of end caps having particular nuclease stability or by use of both of these in conjunction with each other.

US Patent:

55764274, Nov 19, 1996

Filed:

May 26, 1995

Appl. No.:

8/452196

Inventors:

Philip D. Cook - Carlsbad CA
Daniel J. Delecki - Radnor PA
Charles Guinosso - Vista CA

Assignee:

Sterling Winthrop, Inc. - New York NY

International Classification:

C07H 2104
C07H 2102
C07D47334
C07D47318

US Classification:

536 231

Abstract:

Compounds of formula I; ##STR1## wherein R. sup. 1 is hydrogen, or a blocking group that is compatible with oligonucleotide synthesis; R. sup. 2 is hydrogen, nitro, lower alkyl amino, diloweralkyl amino or methyl; R. sup. 3 is hydrogen or --P(R. sup. 4)OR. sup. 5 ; R. sup. 4 is chlorine, 4-nitroimidazole, imidazole, tetrazole, triazole or di(lower-alkyl)amino-; R. sup. 5 is methyl, 2-cyanoethyl or 2,2,2-trichloroethyl; n is from 0 to 2 X is oxygen, sulfur, or --NR. sup. 6 ; R. sup. 6 is hydrogen or lower alkyl; Q is chosen from the group consisting of ##STR2## R. sup. 7 is lower-alkyl or loweralkyloxy methylene; and R. sup. 8 is hydrogen, benzoyl, anisoyl, or lower-alkyl carbonyl and its pharmaceutically acceptable addition salts are nucleotide analogs. Modified oligonucleotides containing the nucleoside analogs of formula I are stable to nuclease degradation and are useful in inhibiting gene expression, in sequencing, and in mutagenesis.

US Patent:

53788257, Jan 3, 1995

Filed:

May 21, 1991

Appl. No.:

7/703619

Inventors:

Philip D. Cook - Carlsbad CA
Yogesh S. Sanghvi - Carlsbad CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 100

US Classification:

536 2534

Abstract:

Therapeutic oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in wild type oligomers with four atom linking groups forms unique di- and poly- nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

US Patent:

56146175, Mar 25, 1997

Filed:

Feb 18, 1993

Appl. No.:

7/971978

Inventors:

Philip D. Cook - Carlsbad CA
Yogesh S. Sanghvi - San Marcos CA

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2102
C07H 2104
C07H 1910
A61K 3170

US Classification:

536 231

Abstract:

Oligonucleotide analogs are provided having improved nuclease resistance. Modifications of selected nucleotides through substitutions on the pyrimidine ring are disclosed. Certain preferred embodiments comprise the inclusion of said modified nucleotides at a plurality of sites, especially at the 3' end of a selected oligonucleotide analog.

US Patent:

52236188, Jun 29, 1993

Filed:

Aug 13, 1990

Appl. No.:

7/566836

Inventors:

Philip D. Cook - Carlsbad CA
Yogesh S. Sanghvi - San Marcos CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07D47300

US Classification:

544276

Abstract:

Novel oligonucleotide analogs are provided having improved cellular uptake, improved resistance to nucleases, and good hybridization to target RNA. Such analogs are provided having substantially non-chiral, non-ionic linking functionalities between the sugars and sugar analogs thereof. In accordance with preferred embodiments, the 4' position of a sugar or sugar analog at one nucleoside is linked to the 3' position of a second sugar or sugar analog of a second nucleoside by a linking function that comprises a two- or three- carbon backbone chain. In accordance with preferred embodiments, the linking functions comprise the formula)--R. sub. 1 --O where R. sub. 1 comprises a two or three carbon backbone. Such linking functions also, preferably comprise ether functionalities to effect such linkage. Processes for the automated synthesis of oligonucleotide analogs are also provided.

US Patent:

51380455, Aug 11, 1992

Filed:

Jul 27, 1990

Appl. No.:

7/558663

Inventors:

Philip D. Cook - Carlsbad CA
Charles J. Guinosso - Carlsbad CA

Assignee:

ISIS Pharmaceuticals - Carlsbad CA

International Classification:

C07H 1700

US Classification:

536 27

Abstract:

Oligonucleotide analogs are provided having improved cellular uptake and improved nuclease resistance. Modification of oligonucleotides through the attachment of nitrogenous moieties, especially polyamines, hydrazines and the like to nucleosidic portions of the analogs is disclosed. Oligonucleotides targeted at the tat region of HIV comprise certain preferred embodiments.

US Patent:

52181057, Jun 8, 1993

Filed:

Mar 3, 1992

Appl. No.:

7/844845

Inventors:

Philip D. Cook - Carlsbad CA
Charles J. Guinosso - Carlsbad CA

Assignee:

ISIS Pharmaceuticals - Carlsbad CA

International Classification:

C07H 1512

US Classification:

536 2531

Abstract:

Oligonucleotide analogs are provided having improved cellular uptake and improved nuclease resistance. Modification of oligonucleotides through the attachment of nitrogenous moieties, especially polyamines, hydrazines and the like to nucleosidic portions of the analogs is disclosed. Oligonucleotides targeted at the tat region of HIV comprise certain preferred embodiments.

US Patent:

63070405, Oct 23, 2001

Filed:

Sep 23, 1997

Appl. No.:

8/936166

Inventors:

Philip Dan Cook - Vista CA
Andrew M. Kawasaki - Oceanside CA

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2104

US Classification:

536 245

Abstract:

Compositions and methods are provided for the treatment and diagnosis of diseases amenable to modulation of the production of selected proteins. In accordance with preferred embodiments, oligonucleotides and oligonucleotide analogs are provided which are specifically hybridizable with a selected sequence of RNA or DNA wherein at least one of the 2'-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of HIV, herpes virus, papillomavirus and other infections is provided.