Phillip Dan Cook

US Patent:

6335434, Jan 1, 2002

Filed:

Mar 24, 1999

Appl. No.:

09/275505

Inventors:

Andrei P. Guzaev - Carlsbad CA
Phillip Dan Cook - Fallbrook CA
Muthiah Manoharan - Carlsbad CA
Balkrishen Bhat - Carlsbad CA

Assignee:

ISIS Pharmaceuticals, Inc., - Carlsbad CA

International Classification:

C12Q 168

US Classification:

536 231, 435 6, 536 221, 536 243, 536 253

Abstract:

Oligonucleotide-folate conjugates are described wherein folates are conjugated to one or more sites on an oligonucleotide including the 2â-, 3â-, 5â-, nucleobase and internucleotide linkage sites. The folate can be attached via the - or -carboxylate, optionally through a linking group. Methods for the regiospecific synthesis of the conjugates are diclosed. Also disclosed are nucleosidic and non-nucleosidic linkers conjugated to folic acid and related folates.

US Patent:

6339066, Jan 15, 2002

Filed:

Mar 31, 1997

Appl. No.:

08/829637

Inventors:

C. Frank Bennett - Carlsbad CA
Nicholas M. Dean - Encinitas CA
Phillip Dan Cook - Escondido CA
Glenn Hoke - Mt. Airy MD

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2104

US Classification:

514 44, 435 6, 435 911, 435366, 435375, 536 231, 536 2431, 536 245

Abstract:

Compositions and methods are provided for the treatment and diagnosis of diseases associated with the expression of one or more of the , , , , , or isoforms (isozymes) of protein kinase C (PKC). Oligonucleotides are provided which are targeted to nucleic acids encoding PKC- , PKC- , PKC-, PKC- , PKC- , PKC- or PKC-. Provided herein are oligonucleotides specifically hybridizable with a translation initiation site, 5â-untranslated region, 3â-untranslated region or other targeted region of a , , , , , or isoform of PKC, wherein at least about 75% of the nucleoside units of a given oligonucleotide are joined together by a stereospecific (i. e. , Sp or Rp) phosphorothioate 3â to 5â linkages. In preferred embodiments, the oligonucleotides of the disclosure additionally contain one or more chemical modifications. Also disclosed are methods of using the oligonucleotides of the invention for modulating the expression of at least one of the , , , , , or isoforms of PKC and for treating animals suffering from disease amenable to therapeutic intervention by modulating the expression of one or more of the , , , , , or isoforms of PKC.

US Patent:

6358931, Mar 19, 2002

Filed:

Aug 30, 1994

Appl. No.:

08/295744

Inventors:

Phillip Dan Cook - Carlsbad CA
Thomas Bruice - Carlsbad CA
Charles John Guinosso - Vista CA
Andrew Mamoru Kawasaki - Oceanside CA
Richard Griffey - San Marcos CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2107

US Classification:

514 44, 536221, 536 231, 536 245

Abstract:

Compositions and methods for modulating the activity of RNA are disclosed, In accordance with preferred embodiments, antisense compositions are prepared targeting reactive portions. The reactive portions preferably comprise one or two imidazole functionalities conjugated to the targeting oligonucleotide via linkers with or without intervening intercalating moieties. Therapeutics, diagnostics and research methods also are disclosed, as are synthetic nucleosides and nucleoside fragments that can be elaborated into oligonucleotides.

US Patent:

6359124, Mar 19, 2002

Filed:

Feb 12, 1999

Appl. No.:

09/248386

Inventors:

David J. Ecker - Leucadia CA
Phillip Dan Cook - Escondido CA
Brett P. Monia - La Costa CA
Susan M. Freier - San Diego CA
Yogesh S. Sanghvi - Encinitas CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2102

US Classification:

536 231, 435 6, 536 245, 536 2721, 536 284, 536 285, 514 44

Abstract:

Compositions and methods are provided for the modulation of expression of the human ras gene in both the normal and activated forms. Oligonucleotides are provided that have methylene(methylimino) linkages alternating with phosphorothioate or phosphodiester linkages. Further oligonucleotides are provide that have a first region having a methylene(methylimino) linkage alternating with a phosphorothioate or phosphodiester linkage and a second region having phosphorothioate linkages. Such oligonucleotides can be used for diagnostics as well as for research purposes including methods for diagnosis, detection and treatment of conditions arising from the activation of the H-ras gene.

US Patent:

6369040, Apr 9, 2002

Filed:

Aug 27, 1999

Appl. No.:

09/384826

Inventors:

Oscar L. Acevedo - San Diego CA
Martin G. Dunkel - Göttingen, DE
Phillip Dan Cook - Carlsbad CA

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

A61K 3170

US Classification:

514 49, 514 50, 514 51

Abstract:

Novel 2- and 4-substituted pyrimidine nucleosides and oligonucleosides are provided, as are methods and intermediates useful in preparing same.

US Patent:

6395492, May 28, 2002

Filed:

Aug 7, 2000

Appl. No.:

09/633659

Inventors:

Muthiah Manoharan - Carlsbad CA
Phillip Dan Cook - Carlsbad CA
Clarence Frank Bennett - Carlsbad CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C12Q 168

US Classification:

435 6, 536 221, 536 231, 514 44

Abstract:

Linked nucleosides having at least one functionalized nucleoside that bears a substituent such as a steroid molecule, a reporter molecule, a non-aromatic lipophilic molecule, a reporter enzyme, a peptide, a protein, a water soluble vitamin, a lipid soluble vitamin, an RNA cleaving complex, a metal chelator, a porphyrin, an alkylator, a pyrene, a hybrid photonuclease/intercalator, or an aryl azide photo-crosslinking agent exhibit increased cellular uptake and other properties. The substituent can be attached at the 2â-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2â-deoxy-2â-fluoro, 2â-O-methoxy, 2â-O-ethoxy, 2â-O-propoxy, 2â-O-aminoalkoxy or 2â-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3â or the 5â positions of the nucleoside or on the heterocyclic base of the nucleoside or on the inter-nucleotide linkage linking the nucleoside to an adjacent nucleoside.

US Patent:

6399754, Jun 4, 2002

Filed:

Aug 17, 1998

Appl. No.:

09/135202

Inventors:

Phillip Dan Cook - San Marcos CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2104

US Classification:

536 231, 536 245, 435 6, 435375

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 2â-deoxyfuranosyl moieties of the nucleoside unit is modified. Treatment of diseases caused by various viruses and other causative agents is provided.

US Patent:

6414135, Jul 2, 2002

Filed:

Jul 7, 1999

Appl. No.:

09/349035

Inventors:

Phillip Dan Cook - Fallbrook CA
Haoyun An - Carlsbad CA
Tingmin Wang - San Marcos CA
Muthiah Manoharan - Carlsbad CA

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2100

US Classification:

536 253

Abstract:

The present invention is directed to nucleoside monomers wherein the 3â-O atom is replaced with a methylene group. The present invention also provides oligomers comprising a plurality of such monomers which are linked by methylenephosphonate linkages. Further, methods of preparing monomers and oligomers according to the present invention are provided.