Igor V Kutyavin

US Patent:

6426408, Jul 30, 2002

Filed:

Feb 18, 2000

Appl. No.:

09/507345

Inventors:

Igor V. Kutyavin - Bothell WA
Eugeny A. Lukhtanov - Bothell WA
Howard B. Gamper - Woodinville WA

Assignee:

Epoch Biosciences, Inc. - Bothell WA

International Classification:

C07H 1900

US Classification:

536 221, 536 231, 536 253, 536 2532, 514 44, 514419, 514422, 514383, 514397, 514363, 514341, 5483111, 5483124, 5483641, 546270, 546271

Abstract:

Minor groove binding molecules are covalently bound to oligonucleotides which in their base sequence are complementary to a target sequence of single stranded or double stranded DNA, RNA or hybrids thereof. The covalently bound oligonucleotide minor groove binder conjugates strogly bind to the target sequence of the complementary strand.

US Patent:

6485906, Nov 26, 2002

Filed:

Nov 1, 1999

Appl. No.:

09/431385

Inventors:

Irina A. Afonina - Mill Creek WA
Igor V. Kutyavin - Bothell WA

Assignee:

Epoch Pharmaceuticals, Inc. - Bothell WA

International Classification:

C12Q 168

US Classification:

435 6, 422 50, 422 681, 536 231, 536 243, 536 2431, 536 2432

Abstract:

Oligonucleotides in which one or more purine residues are substituted by pyrazolo[3,4-d]pyrimidines exhibit improved hybridization properties. Oligonucleotides containing pyrazolo[3,4-d]pyrimidine base analogues have higher melting temperatures than unsubstituted oligonucleotides of identical sequence. Thus, in assays involving hybridization of an oligonucleotide probe to a target polynucleotide sequence, higher signals are obtained. In addition, mismatch discrimination is enhanced when pyrazolo[3,4-d]pyrimidine-containing oligonucleotides are used as hybridization probes, making them useful as probes and primers for hybridization, amplification and sequencing procedures, particularly those in which single- or multiple-nucleotide mismatch discrimination is required.

US Patent:

6486308, Nov 26, 2002

Filed:

Dec 18, 2000

Appl. No.:

09/739928

Inventors:

Igor V. Kutyavin - Bothell WA
Eugeny A. Lukhtanov - Bothell WA
Howard B. Gamper - Woodinville WA

Assignee:

Epoch Biosciences, Inc. - Bothell WA

International Classification:

C07H 2100

US Classification:

536 231, 536 253, 536 2532, 514 44, 5462701, 5462711, 5483111, 5483124

Abstract:

Minor groove binding molecules are covalently bound to oligonucleotides which in their base sequence are complementary to a target sequence of single stranded or double stranded DNA, RNA or hybrids thereof. The covalently bound oligonucleotide minor groove binder conjugates strogly bind to the target sequence of the complementary strand.

US Patent:

6492346, Dec 10, 2002

Filed:

Aug 16, 2000

Appl. No.:

09/640953

Inventors:

Joel Hedgpeth - San Francisco CA
Irina A. Afonina - Mill Creek WA
Igor V. Kutyavin - Bothell WA
Eugeny A. Lukhtanov - Bothell WA
Evgeniy S. Belousov - Mill Creek WA

Assignee:

Epoch Pharmaceuticals, Inc. - Bothell WA

International Classification:

A01N 4304

US Classification:

514 44, 514 19, 435 6, 536 253, 536 2532, 5483111, 5483124, 5483641, 546270, 546271

Abstract:

Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI ), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPI group resides in the minor groove of the duplex. These conjugates can be used as probes and primers. Due to their unusually high binding affinity, conjugates as short as 8-mers can be used as amplification primers with high specificity and efficiency. MGB conjugation also increases the discriminatory power of short oligonucleotides, providing enhanced detection of nucleotide sequence mismatches by short oligonucleotides. The MGB-conjugated probes and primers described herein facilitate various analytic and diagnostic procedures, such as amplification reactions, PCR, detection of single-nucleotide polymorphisms, gene hunting, differential display, fluorescence energy transfer, hydrolyzable probe assays and others; by allowing the use of shorter oligonucleotides, which have higher specificity and better discriminatory power.

US Patent:

6660845, Dec 9, 2003

Filed:

Nov 23, 1999

Appl. No.:

09/447936

Inventors:

Alexander A. Gall - Bothell WA
Igor V. Kutyavin - Bothell WA
Nicolaas M. J. Vermeulen - Woodinville WA
Robert O. Dempcy - Kirkland WA

Assignee:

Epoch Biosciences, Inc. - Bothell WA

International Classification:

C07H 2100

US Classification:

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

Abstract:

The invention provides compositions and methods for improved hybridization analysis utilizing DNA, RNA, PNA and chimeric oligomers in which one or more purine bases are substituted by a pyrazolo[5,4-d]pyrimidine or by a 7-deazapurine purine analogue. Reduced self-aggregation and reduced fluorescence quenching are obtained when the oligomers are used in various methods involving hybridization. Methods of synthesis, as well as novel synthetic precursors, are also provided.

US Patent:

6683173, Jan 27, 2004

Filed:

Dec 21, 2001

Appl. No.:

10/032307

Inventors:

Robert O. Dempcy - Kirkland WA
Alexander A. Gall - Woodinville WA
Sergey G. Lokhov - Kirkland WA
Irina A. Afonina - Mill Creek WA
Michael J. Singer - Seattle WA
Igor V. Kutyavin - Woodinville WA
Nicolaas M. J. Vermeulen - Woodinville WA

Assignee:

Epoch Biosciences, Inc. - Bothell WA

International Classification:

C07H 2104

US Classification:

536 253, 435 6

Abstract:

Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.

US Patent:

6884584, Apr 26, 2005

Filed:

Apr 22, 2002

Appl. No.:

10/127936

Inventors:

Joel Hedgpeth - San Francisco CA, US
Irina A. Afonina - Mill Creek WA, US
Igor V. Kutyavin - Bothell WA, US
Eugeny A. Lukhtanov - Bothell WA, US
Evgeniy S. Belousov - Mill Creek WA, US

Assignee:

Epoch Biosciences, Inc. - Bothell WA

International Classification:

C12Q001/68
C12P019/34
C07H019/04

US Classification:

435 6, 435 911, 435 912, 536 256

Abstract:

Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPIgroup resides in the minor groove of the duplex. These conjugates can be used as probes and primers. Due to their unusually high binding affinity, conjugates as short as 8-mers can be used as amplification primers with high specificity and efficiency. MGB conjugation also increases the discriminatory power of short oligonucleotides, providing enhanced detection of nucleotide sequence mismatches by short oligonucleotides. The MGB-conjugated probes and primers described herein facilitate various analytic and diagnostic procedures, such as amplification reactions, PCR, detection of single-nucleotide polymorphisms, gene hunting, differential display, fluorescence energy transfer, hydrolyzable probe assays and others; by allowing the use of shorter oligonucleotides, which have higher specificity and better discriminatory power.

US Patent:

6949367, Sep 27, 2005

Filed:

Nov 28, 2000

Appl. No.:

09/724959

Inventors:

Robert O. Dempcy - Kirkland WA, US
Irina A. Afonina - Mill Creek WA, US
Michael J. Singer - Seattle WA, US
Igor V. Kutyavin - Woodinville WA, US

Assignee:

Epoch Pharmaceuticals, Inc. - Bethell WA

International Classification:

C12P019/34
C12Q001/68
C07H021/02

US Classification:

435 911, 435 6, 435 912, 536 231, 536 243, 536 2431, 536 2433

Abstract:

Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.