Clarence T Bennett

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:

6753423, Jun 22, 2004

Filed:

Apr 10, 2000

Appl. No.:

09/546596

Inventors:

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

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 2104

US Classification:

536 245, 536 231, 536 243, 435 6, 514 44

Abstract:

The invention is directed to oligonucleotides and oligonucleosides functionalized to include lipophilic moieties and having improved biostability and altered biodistribution in mammals. In one embodiment, such lipophilic oligonucleotide conjugates are used in a method of targeting antisense oligonucleotides to hepatic tissues and thereby preferentially modulating gene expression in the liver and associated tissues of a mammal.

US Patent:

6831166, Dec 14, 2004

Filed:

Feb 11, 2002

Appl. No.:

10/073718

Inventors:

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

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 1900

US Classification:

536 231, 514 1, 514 44, 435 6, 536 243, 536 253, 536 266

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:

6919439, Jul 19, 2005

Filed:

May 23, 2002

Appl. No.:

10/154993

Inventors:

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

Assignee:

ISIS Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H021/00
C07H021/02
A01N043/04

US Classification:

536 231, 536 221, 536 253, 536 2532, 536 266, 514 44

Abstract:

Linked nucleosides having at least one functionalized nucleosid 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, 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 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining linked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ 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:

7122649, Oct 17, 2006

Filed:

Jan 9, 2004

Appl. No.:

10/755109

Inventors:

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

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 21/04
C07H 21/00
C12Q 1/68
A01N 61/00
A01N 43/04

US Classification:

536 231, 536 253, 536 266, 435 6, 514 1, 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 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ 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:

7125975, Oct 24, 2006

Filed:

Jan 9, 2004

Appl. No.:

10/755166

Inventors:

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

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 21/04
C07H 19/04
A01N 61/00
A01N 43/04
C12Q 1/68

US Classification:

536 231, 536 253, 536 266, 514 1, 514 44, 435 6

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 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ 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:

7235650, Jun 26, 2007

Filed:

Oct 31, 2002

Appl. No.:

10/284742

Inventors:

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

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

C07H 21/00
C07H 21/02
C07H 21/04
C12Q 1/68

US Classification:

536 231, 536 253, 536 266, 435 6

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 2′-position of the functionalized nucleoside via a linking group. If at least a portion of the remaining liked nucleosides are 2′-deoxy-2′-fluoro, 2′-O-methoxy, 2′-O-ethoxy, 2′-O-propoxy, 2′-O-aminoalkoxy or 2′-O-allyloxy nucleosides, the substituent can be attached via a linking group at any of the 3′ or the 5′ 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:

8153602, Apr 10, 2012

Filed:

May 20, 1999

Appl. No.:

09/315292

Inventors:

Clarence Frank Bennett - Carlsbad CA, US
David J. Ecker - Encinitas CA, US
Phillip Dan Cook - Fallbrook CA, US

Assignee:

Isis Pharmaceuticals, Inc. - Carlsbad CA

International Classification:

A61K 48/00
C07H 21/04
C07H 21/02

US Classification:

514 44, 536 231, 536 2431, 536 2433, 536 245

Abstract:

The present invention relates to compositions and methods for the pulmonary delivery of nucleic acids, particularly oligonucleotides. In one preferred embodiment, the compositions and methods of the invention are utilized to effect the pulmonary delivery of an antisense oligonucleotide to an animal in order to modulate the expression of a gene in the animal for investigative, therapeutic or prophylactic purposes.