Michael A Parniak

US Patent:

6811970, Nov 2, 2004

Filed:

Jul 25, 2002

Appl. No.:

10/205641

Inventors:

Nicolas Sluis-Cremer - Pittsburgh PA
Michael Parniak - Pittsburgh PA
Alex Pelletier - Fabreville, CA

Assignee:

Boehringer Ingelheim (Canada) Ltd. - Laval

International Classification:

C12Q 170

US Classification:

435 5, 435 6, 435 71, 435 79, 536 2372

Abstract:

A method for measuring heterodimerization of HIV RT, which comprises the steps of: a) providing a first solution comprising p66 subunit homodimers in the presence of a dissociation agent; b) contacting the first solution with p51 RT subunits and incubating in the presence of a reassociation buffer to allow association of a complex of p66/p51 RT subunits, wherein one of the subunits comprises an affinity tag and the other of the subunits comprises a detectable label; c) contacting the incubate of step b) with an affinity medium under conditions that enable the p66/p51 complex to bind to the affinity medium; and d) determining the amount of complex formed by measuring the level of detectable label bound to the affinity medium (or by measuring the reconstituted RT polymerase activity). Steps a) to d) can be carried out in the presence or absence of a test compound followed by e) comparing the test compound sample to a control sample lacking the compound, whereby modulated p66/p51 complex formation in the test compound sample is indicative of the ability of the compound to modulate, inhibit or enhance heterodimerization. The method can be used to screen for inhibitors of HIV RT dimerization.

US Patent:

7186520, Mar 6, 2007

Filed:

Sep 11, 2002

Appl. No.:

10/238952

Inventors:

Michael A. Parniak - Pittsburgh PA, US
Kyung-Lyum Min - Montreal, CA

Assignee:

McGill University - Montreal

International Classification:

C12Q 1/37

US Classification:

435 23, 435 6, 435199, 536 243

Abstract:

The invention relates to a substrate and method for the assay of ribonuclease H activity. The substrate comprises a DNA/RNA heteroduplex molecule having fluorophore and quencher molecules in close proximity, which emit a background level of fluorescence in the absence of ribonuclease H activity due to quenching of the fluorophore as a result of fluorescence resonance energy transfer. Ribonuclease H cleavage of the heteroduplex results in an increase in fluorescence emission due to the destabilization and separation of the DNA and RNA molecules and their associated fluorophore and quencher molecules. The assay method of the present invention is suitable for use in screening (e. g. high throughput screening) for modulators, e. g. inhibitors, of the ribonuclease H activity associated with, for example, reverse transcriptase and ribonuclease H enzymes.

US Patent:

7439035, Oct 21, 2008

Filed:

Jan 24, 2007

Appl. No.:

11/656977

Inventors:

Michael A. Parniak - Pittsburgh PA, US
Kyung-Lyum Min - Montreal, CA

Assignee:

McGill University - Montreal, Quebec

International Classification:

C12Q 1/37

US Classification:

435 23, 435 6, 435199, 436 243

Abstract:

The invention relates to a substrate and method for the assay of ribonuclease H activity. The substrate comprises a DNA/RNA heteroduplex molecule having fluorophore and quencher molecules in close proximity, which emit a background level of fluorescence in the absence of ribonuclease H activity due to quenching of the fluorophore as a result of fluorescence resonance energy transfer. Ribonuclease H cleavage of the heteroduplex results in an increase in fluorescence emission due to the destabilization and separation of the DNA and RNA molecules and their associated fluorophore and quencher molecules. The assay method of the present invention is suitable for use in screening (e. g. high throughput screening) for modulators, e. g. inhibitors, of the ribonuclease H activity associated with, for example, reverse transcriptase and ribonuclease H enzymes.

US Patent:

8178348, May 15, 2012

Filed:

Sep 4, 2001

Appl. No.:

10/363768

Inventors:

Masad Jose Damha - St. Hubert, CA
Michael A. Parniak - Pittsburgh PA, US
Chun-Nam Lok - Shek Tong Shui, HK
Ekaterina Vlazovkina - Montreal, CA

Assignee:

McGill University - Montreal, Quebec

International Classification:

C12N 5/00
C12N 5/02
C12N 15/11
C07H 21/04

US Classification:

435375, 514 44 A, 536 232, 536 245

Abstract:

The present invention relates to novel oligonucleotide chimera used as therapeutic agents to selectively prevent gene transcription and expression in a sequence-specific manner. In particular, this invention is directed to the selective inhibition of protein biosynthesis via antisense strategy using oligonucleotides constructed from arabinonucleotide or modified arabinonucleotide residues, flanking a series of deoxyribose nucleotide residues of variable length. Particularly this invention relates to the use of antisense oligonucleotides constructed from arabinonucleotide or modified arabinonucleotide residues, flanking a series of deoxyribose nucleotide residues of variable length, to hybridize to complementary RNA such as cellular messenger RNA, viral RNA, etc. More particularly this invention relates to the use of antisense oligonucleotides constructed from arabinonucleotide or modified arabinonucleotide residues, flanking a series of deoxyribose nucleotide residues of variable length, to hybridize to and induce cleavage of (via RNaseH activation) the complementary RNA.

US Patent:

8278103, Oct 2, 2012

Filed:

Jan 31, 2003

Appl. No.:

10/503120

Inventors:

Masad J. Damha - St. Hubert, CA
Michael A. Parniak - Pittsburgh PA, US

Assignee:

McGill University - Montreal, Quebec

International Classification:

C12N 5/00
C12N 5/02
C12N 15/11
C07H 21/04

US Classification:

435375, 514 44 A, 536 232, 536 245

Abstract:

The invention relates to oligonucleosides having alternating segments of sugar-modified nucleosides and 2′-deoxynucleosides, and uses thereof. The invention further relates to oligonucleotides having alternating segments of sugar-modified nucleotides and 2′-deoxynucleotides, and uses thereof. Such uses include the preparation of antisense oligonucleotides and their use for the prevention or depletion of function of a target nucleic acid of interest, such as an RNA, in a system. Accordingly, an oligonucleotide of the invention is useful for therapeutic, analytical and diagnostic methods and uses, as well as a component of compositions and commercial packages corresponding to such methods and uses.

US Patent:

20040058948, Mar 25, 2004

Filed:

Mar 3, 2003

Appl. No.:

10/378467

Inventors:

Dennis Curran - Pittsburgh PA, US
Michael Parniak - Pittsburgh PA, US
Ana Gabarda - New York NY, US

International Classification:

A61K031/4745

US Classification:

514/285000

Abstract:

A method of inhibiting retroviral reverse transcriptase or hepadnaviral reverse transcriptase includes the step of administering a pharmaceutically effective amount of a mappicine analog or a pharmaceutically acceptable salt thereof. A method of treating a patient infected with a retrovirus or hepadnavirus includes the step of administering a pharmaceutically effective amount of a mappicine analog or a pharmaceutically acceptable salt thereof

US Patent:

20040077674, Apr 22, 2004

Filed:

Mar 3, 2003

Appl. No.:

10/378221

Inventors:

Dennis Curran - Pittsburgh PA, US
Michael Parniak - Pittsburgh PA, US
Ana Gabarda - New York NY, US
Wei Zhang - Mars PA, US
Zhiyong Luo - San Diego CA, US
Christine Chen - Pittsburgh PA, US

International Classification:

C07D471/14
A61K031/4745
A61K031/655

US Classification:

514/285000, 546/070000, 514/151000

Abstract:

A compound having the following structure: wherein Z is —CHORRor —C(O)R; Ris H, an alkyl group, an aryl group, —OC(O)OR, wherein Ris an alkyl group, —C(O)Rwherein Ris an alkyl group, an aryl group, an alkoxy group, an amino group, an alkylamino group, a dialkylamino group, an aryl amino group, a diarylamino group, an arylalkyl amino group, a protecting group or a fluorous tag; Ris an alkyl group, an aryl group or an arylalkyl group; Ris H, an alkyl group, hydroxyalkyl group or an aryl group; R—Rare independently the same or different and are hydrogen, an alkyl group, an alkenyl group, an alkynyl group, an aryl group, an alkoxy group, an aryloxy group, an acyloxy group, a haloalkyl group, a perfluoroalkyl group, fluorine, chlorine, bromine, a haloalkyloxy group, a carbamoyloxy group, a hydroxy group, a nitro group, a cyano group, a cyanoalkyl group, an azido group, an azidoalkyl group, a formyl group, a hydrazino group, a hydrazinoalkyl group, a hydroxyalkyl group, an alkoxyalkyl group, —NRR, wherein Rand Rare independently hydrogen, an alkyl group, an aryl group, an arylalkyl group, or —C(O)R, an aminoalkyl group, an alkylaminoalkyl group, a dialkylaminoalkyl group, an aryl aminoalkyl group, a diarylaminoalkyl group, an arylalkyl aminoalkyl group, —OC(O)OR, wherein Ris an alkyl group, —C(O)R, —SR, S(O)Ror S(O)Rwherein Ris hydrogen, —C(O)R, an alkyl group, or an aryl group, (CH)SiRRRwherein n is an integer within the range of 0 through 10 and R, Rand Rare independently a Calkyl group, a Calkenyl group, a Calkynyl group, an aryl group, a haloalkyl group, a cyanoalkyl group, an azidoalkyl group, a hydrazinoalkyl group, a hydroxyalkyl group, an alkoxyalkyl group, an aminoalkyl group, an alkylaminoalkyl group, a dialkylaminoalkyl group, an aryl aminoalkyl group, a diarylaminoalkyl group, an arylalkyl aminoalkyl group. Alternatively Rand R, Rand R; Rand R; or Rand Rcan form together a chain of 3 or four groups selected from CH, CH, O, S, N, NH, N-alkyl or N-aryl. Provided that, at least one of R—Ris not H, a lower alkyl group, fluorine, a cyano group, a hydroxyl group, hydroxyalkyl group, an alkoxy group, an aminoalkyl group, an alkylaminoalkyl group, a dialkylaminoalkyl group, an amino group, an alkylamino group, a dialkylamino group, a carbamoyloxy group, a formyl group or —C(O)Rwherein Ris an alkyl group.