Ravindra N Singh

US Patent:

7838657, Nov 23, 2010

Filed:

Dec 5, 2005

Appl. No.:

11/295725

Inventors:

Ravindra N. Singh - Shrewsbury MA, US
Natalia N. Singh - Shrewsbury MA, US
Nirmal K. Singh - Temple TX, US
Elliot J. Androphy - Natick MA, US

Assignee:

University of Massachusetts - Boston MA

International Classification:

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

US Classification:

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

Abstract:

The present invention is directed to methods and compositions capable of blocking the inhibitory effect of a newly-identified intronic inhibitory sequence element, named ISS-N1 (for “intronic splicing silencer”), located in the SMN2 gene. The compositions and methods of the instant invention include oligonucleotide reagents (e. g. , oligoribonucleotides) that effectively target the SMN2 ISS-N1 site in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The ISS-N1 blocking agents of the invention cause elevated expression of SMN protein, thus compensating for the loss of SMN protein expression commonly observed in subjects with spinal muscular atrophy (SMA).

US Patent:

8110560, Feb 7, 2012

Filed:

Aug 21, 2009

Appl. No.:

12/545536

Inventors:

Ravindra N. Singh - Shrewsbury MA, US
Natalia N. Singh - Shrewsbury MA, US
Nirmal K. Singh - Temple TX, US
Elliot J. Androphy - Natick MA, US

Assignee:

University of Massachusetts - Boston MA

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 is directed to methods and compositions capable of blocking the inhibitory effect of a newly-identified intronic inhibitory sequence element, named ISS-N1 (for “intronic splicing silencer”), located in the SMN2 gene. The compositions and methods of the instant invention include oligonucleotide reagents (e. g. , oligoribonucleotides) that effectively target the SMN2 ISS-N1 site in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The ISS-N1 blocking agents of the invention cause elevated expression of SMN protein, thus compensating for the loss of SMN protein expression commonly observed in subjects with spinal muscular atrophy (SMA).

US Patent:

8586559, Nov 19, 2013

Filed:

Dec 19, 2011

Appl. No.:

13/329926

Inventors:

Ravindra N. Singh - Shrewsbury MA, US
Natalia N. Singh - Shrewsbury MA, US
Nirmal K. Singh - Temple TX, US
Elliot J. Androphy - Natick MA, US

Assignee:

University of Massachusetts - Boston MA

International Classification:

A61K 48/00
C07H 21/04

US Classification:

514 44, 536 234, 536 2431, 536 3433

Abstract:

The present invention is directed to methods and compositions capable of blocking the inhibitory effect of a newly-identified intronic inhibitory sequence element, named ISS-N1 (for “intronic splicing silencer”), located in the SMN2 gene. The compositions and methods of the instant invention include oligonucleotide reagents (e. g. , oligoribonucleotides) that effectively target the SMN2 ISS-N1 site in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The ISS-N1 blocking agents of the invention cause elevated expression of SMN protein, thus compensating for the loss of SMN protein expression commonly observed in subjects with spinal muscular atrophy (SMA).

US Patent:

20110269820, Nov 3, 2011

Filed:

Apr 26, 2011

Appl. No.:

13/093958

Inventors:

RAVINDRA SINGH - AMES IA, US
NATALIA SINGH - AMES IA, US

Assignee:

IOWA STATE UNIVERSITY RESEARCH FOUNDATION, INC. - AMES IA

International Classification:

A61K 31/7088
C07H 21/00
C12N 5/0793
A61P 25/00
C12N 5/0735
C12N 5/0797
A61P 21/00
C12N 5/071
C12N 5/077

US Classification:

514 44 A, 435375, 536 245

Abstract:

The present invention is directed to methods and compositions for blocking the effect of the intronic inhibitory splicing region of intron 7 of the SMN2 gene. The compositions and methods of the instant invention include short oligonucleotide reagents (e.g., oligoribonucleotides) that effectively target sites in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The short target regions are 8-mers and 5-mers and also include the identification of a single nucleotide base that is essential for initiating a long distance stearic inhibitory interactions as well as novel targets distant from intron 7 which block the intronic inhibitory splicing of the same. These short target regions and concomitant inhibitory blocking oligonucleotides are less expensive and easier to manufacture and are small enough to cross the blood brain barrier.

Author:

Ravindra Singh

ISBN #:

0792340450

Author:

Ravindra Pratap Singh

ISBN #:

8170220254

Author:

Ravindra Pratap Singh

ISBN #:

8185484244

Author:

Ravindra N. Singh

ISBN #:

8171100902

Author:

Ravindra Prasad Singh

ISBN #:

8171691862