Daniel E Mccallus

US Patent:

8614198, Dec 24, 2013

Filed:

Jun 23, 2008

Appl. No.:

12/666057

Inventors:

Daniel E. McCallus - Oaks PA, US
Catherine Pachuk - Northborough MA, US

Assignee:

Alnylam Pharmaceuticals, Inc. - Cambridge MA

International Classification:

A61K 48/00
C12N 15/11
C07H 21/02
C07H 21/04

US Classification:

514 44A, 536 245

Abstract:

The present invention provides agents, compositions, constructs and methods for silencing HCV polynucleotides, as well as methods and compositions for treating or preventing HCV infection in a mammalian cell. In one aspect, the present invention provides an agent or composition comprising at least one double-stranded RNA effector molecule or complex. The double-stranded RNA effector molecule or complex comprises: (1) a sequence of at least 19 nucleotides having at least 90% identity with a nucleotide sequence within HCV Conserved Region 1 (SEQ ID NO: 2), HCV Conserved Region 2 (SEQ ID NO: 3), HCV Conserved Region 5 (SEQ ID NO: 4), (ATR)-1 (SEQ ID NO: 86), ATR-2 (SEQ ID NO: 87), ATR-3 (SEQ ID NO: 88), ATR-4 (SEQ ID NO: 89); and (2) its complementary sequence. In another aspect, the present invention provides a construct suitable for replication in a host cell, and/or suitable for expression of an RNA molecule or complex of the invention in vitro or in vivo. In a third aspect, the present invention provides a method for silencing HCV RNA in a mammalian cell, which comprises administering to the mammalian cell an agent, composition, or construct of the invention in a manner and amount effective to silence HCV RNA in the cell.

US Patent:

20060035344, Feb 16, 2006

Filed:

Oct 20, 2003

Appl. No.:

10/531349

Inventors:

Catherine Pachuk - Lansdale PA, US
C. Satishchandran - Lansdale PA, US
Daniel McCallus - Oaks PA, US

International Classification:

C12Q 1/68
C12P 19/34

US Classification:

435091100, 435006000

Abstract:

The present invention relates to novel double-stranded RNA (dsRNA) structures and dsRNA expression constructs, methods for generating them, and methods of utilizing them for silencing genes. Desirably, these methods specifically inhibit the expression of one or more target genes in a cell of animal (e.g., a mammal such as a human) without inducing toxicity. These methods can be used to prevent or treat a disease or infection by silencing a gene associated with the disease or infection. The invention also provides method for identifying nucleic acid sequences that modulate a detectable phenotype, such as the function of a cell, the expression of a gene, or the biological activity of a target polypeptide.

US Patent:

20090176727, Jul 9, 2009

Filed:

Oct 8, 2008

Appl. No.:

12/247770

Inventors:

Catherine J. PACHUK - Lansdale PA, US
C. Satishchandran - Lansdale PA, US
Daniel Edward McCallus - Oaks PA, US

International Classification:

A61K 31/7105
C12N 15/74
C12N 5/00
A61P 35/00

US Classification:

514 44, 536 231, 4353201, 435375

Abstract:

The present invention relates to novel double-stranded RNA (dsRNA) structures and dsRNA expression constructs, methods for generating them, and methods of utilizing them for silencing genes. Desirably, these methods specifically inhibit the expression of one or more target genes in a cell or animal (e.g., a mammal such as a human) without inducing toxicity. These methods can be used to prevent or treat a disease or infection by silencing a gene associated with the disease or infection. The invention also provides methods for identifying nucleic acid sequences that modulate a detectable phenotype, such as the function of a cell, the expression of a gene, or the biological activity of a target polypeptide.

US Patent:

20090298909, Dec 3, 2009

Filed:

Aug 23, 2005

Appl. No.:

11/660937

Inventors:

Catherine J. Pachuk - Blue Bill PA, US
Daniel E. McCallus - Oaks PA, US
Chandrasekhar Satishchandran - Lansdale PA, US

International Classification:

A61K 31/7105
C12N 15/00
C12N 5/06
C12Q 1/68
C07H 21/02

US Classification:

514 44 A, 4353201, 435375, 435 6, 536 241

Abstract:

Expression constructs comprising at least two different RNA polymerase III promoters, wherein each promoter is operably linked to a nucleic acid sequence encoding an RNA effector molecule, are disclosed herein. Further provided are expression constructs comprising multiple polymerase III promoters operably linked to sequences encoding short hairpin RNA molecules, which may comprise single and/or multiple fingers. The provided constructs are useful for in vivo delivery of RNA molecules effective in gene silencing, including of viral genes including HBV and HCV.

US Patent:

20110245329, Oct 6, 2011

Filed:

May 9, 2011

Appl. No.:

13/103402

Inventors:

Catherine J. Pachuk - Cambridge MA, US
Chandrasekhar Satishchandran - Cambridge MA, US
Daniel Edward McCallus - Oaks PA, US

Assignee:

ALNYLAM PHARMACEUTICALS, INC. - Cambridge MA

International Classification:

A61K 31/713
C07H 21/02
C12N 15/63
C12N 5/071
A61P 37/00

US Classification:

514 44 R, 536 231, 4353201, 435375

Abstract:

The present invention relates to novel double-stranded RNA (dsRNA) structures and dsRNA expression constructs, methods for generating them, and methods of utilizing them for silencing genes. Desirably, these methods specifically inhibit the expression of one or more target genes in a cell or animal (e.g., a mammal such as a human) without inducing toxicity. These methods can be used to prevent or treat a disease or infection by silencing a gene associated with the disease or infection. The invention also provides methods for identifying nucleic acid sequences that modulate a detectable phenotype, such as the function of a cell, the expression of a gene, or the biological activity of a target polypeptide.

US Patent:

20120028348, Feb 2, 2012

Filed:

Jun 15, 2011

Appl. No.:

13/160774

Inventors:

Catherine J. Pachuk - Blue Hill PA, US
Daniel Edward McCallus - Oaks PA, US
Chandrasekhar Satishchandran - Lansdale PA, US

Assignee:

ALNYLAM PHARMACEUTICALS, INC. - Cambridge MA

International Classification:

C12N 15/63
C12N 15/113

US Classification:

4353201, 536 241

Abstract:

Expression constructs comprising at least two different RNA polymerase III promoters, wherein each promoter is operably linked to a nucleic acid sequence encoding an RNA effector molecule, are disclosed herein. Further provided are expression constructs comprising multiple polymerase III promoters operably linked to sequences encoding short hairpin RNA molecules, which may comprise single and/or multiple fingers. The provided constructs are useful for in vivo delivery of RNA molecules effective in gene silencing, including of viral genes including HBV and HCV.