Patents Assigned to Epoch Pharmaceuticals, Inc.
  • Patent number: 6949367
    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.
    Type: Grant
    Filed: November 28, 2000
    Date of Patent: September 27, 2005
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Robert O. Dempcy, Irina A. Afonina, Michael J. Singer, Igor V. Kutyavin
  • Publication number: 20040191796
    Abstract: Oligonucleotide-fluorophore-quencher conjugates wherein the fluorophore moiety has emission wavelengths in the range of about (300) to about (800) nm, and or where the quencher includes a substituted 4-(phenyldiazenyl)phenylamine structure provide improved signal to noise ratios and other advantageous characteristics in hybridization and related assays. The oligonucleotide-fluorophore-quencher conjugates can be synthesized by utilizing novel phosphoramidite reagents that incorporate the quencher moiety based on the substituted 4-(phenyldiazenyl)phenylamine structure, and or novel phosphoramidite reagents that incorporate a fluorophore moiety based on the substituted coumarin, substituted 7-hydroxy-3H-phenoxazin-3-one, or substituted 5,10-dihydro-10 [phenyl]pyrido[2,3-d;6,5-d′]dipyrimidine-2,4,6,8-(1H, 3H, 7H, 9H, 10H)-tetrone structure.
    Type: Application
    Filed: June 25, 2003
    Publication date: September 30, 2004
    Applicant: EPOCH PHARMACEUTICALS, INC.
    Inventors: Michael W. Reed, Eugeny Alexander Lukhtanov, Alexander A. Gall, Robert O. Dempcy
  • Patent number: 6727356
    Abstract: Oligonucleotide-fluorophore-quencher conjugates wherein the fluorophore moiety has emission wavelengths in the range of about 300 to about 800 nm, and or where the quencher includes a substituted 4-(phenyldiazenyl)phenylamine structure provide improved signal to noise ratios and other advantageous characteristics in hybridization and related assays. The oligonucleotide-fluorophore-quencher conjugates can be synthesized by utilizing novel phosphoramidite reagents that incorporate the quencher moiety based on the substituted 4-(phenyldiazenyl)phenylamine structure, and or novel phosphoramidite reagents that incorporate a fluorophore moiety based on the substituted coumarin, substituted 7-hydroxy-3H-phenoxazin-3-one, or substituted 5,10-dihydro-10-[phenyl]pyrido[2,3-d;6,5-d′]dipyrimidine-2,4,6,8-(1H,3H,7H,9H,10H)-tetrone structure.
    Type: Grant
    Filed: December 8, 1999
    Date of Patent: April 27, 2004
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Michael W. Reed, Eugeny Alexander Lukhtanov, Alexander A. Gall, Robert O. Dempcy
  • Publication number: 20040058322
    Abstract: Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPI3 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.
    Type: Application
    Filed: April 22, 2002
    Publication date: March 25, 2004
    Applicant: Epoch Pharmaceuticals, Inc.
    Inventors: Joel Hedgpeth, Irina A. Afonina, Igor V. Kutyavin, Eugeny A. Lukhtanov, Evgeniy S. Belousov, Rich B. Meyer
  • Patent number: 6492346
    Abstract: Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPI3 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.
    Type: Grant
    Filed: August 16, 2000
    Date of Patent: December 10, 2002
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Joel Hedgpeth, Irina A. Afonina, Igor V. Kutyavin, Eugeny A. Lukhtanov, Evgeniy S. Belousov, Rich B. Meyer, Jr.
  • Patent number: 6485906
    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.
    Type: Grant
    Filed: November 1, 1999
    Date of Patent: November 26, 2002
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Jr., Irina A. Afonina, Igor V. Kutyavin
  • Publication number: 20020155484
    Abstract: Oligonucleotide-fluorophore-quencher conjugates wherein the fluorophore moiety has emission wavelengths in the range of about 300 to about 800 nm, and or where the quencher includes a substituted 4-(phenyldiazenyl)phenylamine structure provide improved signal to noise ratios and other advantageous characteristics in hybridization and related assays. The oligonucleotide-fluorophore-quencher conjugates can be synthesized by utilizing novel phosphoramidite reagents that incorporate the quencher moiety based on the substituted 4-(phenyidiazenyl)phenylamine structure, and or novel phosphoramidite reagents that incorporate a fluorophore moiety based on the substituted coumarin, substituted 7-hydroxy-3H-phenoxazin-3-one, or substituted 5,10-dihydro-10-[phenyl]pyrido[2,3-d;6,5-d′]dipyrimidine-2,4,6,8-(1H,3H,7H,9H,10H)-tetrone structure.
    Type: Application
    Filed: March 7, 2002
    Publication date: October 24, 2002
    Applicant: EPOCH PHARMACEUTICALS, INC.
    Inventors: Michael W. Reed, Eugeny Alexander Lukhtanov, Alexander A. Gall, Robert O. Dempcy
  • Patent number: 6312894
    Abstract: Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo[3,2-e]indole-7-carboxylate (CDPI3), and an oligonucleotide form unusually stable hybrids with complementary target sequences, in which the tethered CDPI3 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.
    Type: Grant
    Filed: April 3, 1998
    Date of Patent: November 6, 2001
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Joel Hedgpeth, Irina A. Afonina, Igor V. Kutyavin, Eugeny A. Lukhtanov, Evgeniy S. Belousov, Rich B. Meyer, Jr.
  • Patent number: 6312925
    Abstract: Methods and compositions for efficient targeting and modification of target sequences in duplex DNA are provided, utilizing oligonucleotides or oligonucleotide compositions containing two domains. The first domain comprises an entity capable of recognizing a double-stranded DNA sequence. This can be a protein, peptide, antibiotic, minor groove binding agent or a nucleotide sequence capable of triplex formation The second domain, which is covalently joined to the first, is capable of recognizing a single-stranded DNA sequence. This second domain will most often be complementary, in the Watson-Crick sense, to a target sequence in the double-stranded nucleic acid. The second domain can optionally carry one or more modifying groups, capable of causing a mutation, a pre-mutagenic lesion, or some other type of heritable change in the target sequence.
    Type: Grant
    Filed: May 7, 1998
    Date of Patent: November 6, 2001
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Jr., Howard B. Gamper, Jr.
  • Patent number: 6312953
    Abstract: Chemically modified oligonucleotides (ODNS) are complementary, either in the sense of the classic “four letter code” recognition motif, or in the sense required for triple strand formation based on the more limited “two letter code recognition motif”, to a target sequence of double stranded DNA of an invading cell, organism or pathogen, such as a virus, fungus, parasite, bacterium, malignant cell, or any duplex DNA which is desired to be broken into segments for the purpose of “mapping”. The ODNs have cross-linking agents covalently attached at least to two different sites of the ODN. Alternatively, the cross-linking agent which is attached to one site on the ODN has two cross-linking functionalities, and therefore in effect comprises two cross-linking agents.
    Type: Grant
    Filed: June 27, 1994
    Date of Patent: November 6, 2001
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Jr., Howard B. Gamper, Igor V. Kutyavin, Alexander A. Gall
  • Patent number: 6143877
    Abstract: A triplex forming oligonucleotide is complementary pursuant to the G/T or A/G recognition motif to a homopurine, or substantially homopurine target sequence in double stranded nucleic acids, and at least one and preferably all of the guanine bases are replaced by their pyrazolo[3,4-d]pyrimidine analog, namely by 6-amino-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one. The oliginucleotides containing the pyrazolo[3,4-d]pyrimidine analog of guanine exhibit a lesser degree of self-association, and lack the nucleophilic nitrogen atom in the 7 position of guanine. The latter feature results in a diminished extent of self-crosslinking in ODNs which also have a covalently attached cross-linking agent.
    Type: Grant
    Filed: April 30, 1997
    Date of Patent: November 7, 2000
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Alexander Gall, Igor V. Kutyavin
  • Patent number: 6136601
    Abstract: A method for introducing a site-specific mutation into a target polynucleotide sequence is presented. The method involves the use of an oligonucleotide capable of binding to the target sequence, either by triplex formation (mediated by Hoogsteen, reverse Hoogsteen or equivalent base pairing) or by Watson/Crick base pairing (in the presence of a recombinase enzyme). The oligonucleotide of the invention is modified by the covalent attachment of one or more electrophilic groups. When a modified oligonucleotide is bound to its target sequence, the electrophilic group is able to interact with a nearby nucleotide in the target sequence, causing a modification to the nucleotide that results in a change in nucleotide sequence. Compositions used in the practice of the method are also disclosed.
    Type: Grant
    Filed: March 26, 1997
    Date of Patent: October 24, 2000
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Jr., Howard B. Gamper, Igor V. Kutyavin, Alexander A. Gall
  • Patent number: 6127121
    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.
    Type: Grant
    Filed: April 3, 1998
    Date of Patent: October 3, 2000
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Jr., Irina A. Afonina, Igor V. Kutyavin
  • Patent number: 6084102
    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 strongly bind to the target sequence of the complementary strand.
    Type: Grant
    Filed: August 27, 1998
    Date of Patent: July 4, 2000
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Igor V. Kutyavin, Eugeny A. Lukhtanov, Howard B. Gamper, Rich B. Meyer, Jr.
  • Patent number: 6072046
    Abstract: Diaziridinyl-aryl and bis-[di(chloroethyl)amino]-aryl oligonucleotide conjugates have a sequence that is complementary in the triplex forming sense to a target sequence in duplex nucleic acid. The diaziridinyl-aryl and bis-[di(chloroethyl)amino]-aryl oligonucleotide conjugates effectively cross-link with both strands of the targeted duplex nucleic acid.
    Type: Grant
    Filed: August 26, 1998
    Date of Patent: June 6, 2000
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Michael W. Reed, Igor V. Kutyavin, Eugeny A. Lukhtanov, J. Ansel Wald, Rich B. Meyer, Jr.
  • Patent number: 5935830
    Abstract: A method for introducing a site-specific mutation into a target polynucleotide sequence is presented. The method involves the use of an oligonucleotide capable of binding to the target sequence, either by triplex formation (mediated by Hoogsteen, reverse Hoogsteen or equivalent base pairing) or by Watson/Crick base pairing (in the presence of a recombinase enzyme). The oligonucleotide of the invention is modified by the covalent attachment of one or more electrophilic groups. When a modified oligonucleotide is bound to its target sequence, the electrophilic group is able to interact with a nearby nucleotide in the target sequence, causing a modification to the nucleotide that results in a change in nucleotide sequence. Compositions used in the practice of the method are also disclosed.
    Type: Grant
    Filed: March 26, 1997
    Date of Patent: August 10, 1999
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Jr., Howard B. Gamper, Igor V. Kutyavin, Alexander A. Gall
  • Patent number: 5912340
    Abstract: In a matched pair of oligonucleotides (ODNS) each member of the pair is complementary or substantially complementary in the Watson Crick sense to a target sequence of duplex nucleic acid where the two strands of the target sequence are themselves complementary to one another. The ODNs include modified bases of such nature that the modified base forms a stable hydrogen bonded base pair with the natural partner base, but does not form a stable hydrogen bonded base pair with its modified partner. This is accomplished when in a hybridized structure the modified base is capable of forming two or more hydrogen bonds with its natural complementary base, but only one hydrogen bond with its modified partner. Due to the lack of stable hydrogen bonding with each other, the matched pair of oligonucleotides have a melting temperature under physiological or substantially physiological conditions of approximately 40.degree. C. or less.
    Type: Grant
    Filed: October 4, 1995
    Date of Patent: June 15, 1999
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Igor V. Kutyavin, Jinsuk Woo, Eugeny A. Lukhtanov, Rich B. Meyer, Jr., Howard B. Gamper
  • Patent number: 5849482
    Abstract: Oligonucleotides (ODNs) include a sequence that is complementary to a target sequence in single stranded RNA, or single or double stranded DNA, and an alkylating function which after hybridization alkylates the target sequence. ODNs adapted for alkylating single stranded RNA, such as messenger RNA, are complementary to the target sequence in the Watson Crick sense. ODNs adapted for alkylating double stranded DNA have at least two alkylating functions and are complementary to the target sequence in the Hoogsteen or reverse Hoogsteen sense. With these ODNs both strands of the target sequence are alkylated. A third class of ODNs have at least approximately 26 nucleotide units in a continous sequence which are complementary to the target sequence of double stranded DNA, and the alkylating function is covalently attached to a nucleotide unit in the continuous sequence. Alkylation or cross-linking with this class of ODNs occurs in the presence of a recombinase enzyme.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: December 15, 1998
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Rich B. Meyer, Jr., Howard B. Gamper, Igor V. Kutyavin, Alexander A. Gall, Charles R. Petrie, John C. Tabone, Gerald D. Hurst
  • Patent number: 5824796
    Abstract: This invention is directed to novel substituted nucleotide bases with a crosslinking arm which accomplish crosslinking between specific sites on adjoining strands of oligonucleotides or oligodeoxynucleotides. The invention is also directed to oligonucleotides comprising at least one of these crosslinking agents and to the use of the resulting novel oligonucleotides for diagnostic and therapeutic purposes. The crosslinking agents of the invention are of the following formula (I'):R.sub.1 --B--(CH.sub.2).sub.q --(Y).sub.r --(CH.sub.2).sub.m --A'(I')wherein,R.sub.1 is hydrogen, or a sugar moiety or analog thereof optionally substituted at its 3' or its 5' position with a phosphorus derivative attached to the sugar moiety by an oxygen and including groups Q.sub.1 Q.sub.2 and Q.sub.3 or with a reactive precursor thereof suitable for nucleotide bond formation;Q.sub.1 is hydroxy, phosphate or diphosphate;Q.sub.2 is .dbd.O or .dbd.S;Q.sub.3 is CH.sub.
    Type: Grant
    Filed: November 4, 1994
    Date of Patent: October 20, 1998
    Assignee: EPOCH Pharmaceuticals, Inc.
    Inventors: Charles R. Petrie, Rich B. Meyer, John C. Tabone, Gerald D. Hurst
  • Patent number: 5801155
    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 strongly bind to the target sequence of the complementary strand.
    Type: Grant
    Filed: April 3, 1995
    Date of Patent: September 1, 1998
    Assignee: Epoch Pharmaceuticals, Inc.
    Inventors: Igor V. Kutyavin, Eugeny A. Lukhtanov, Howard B. Gamper, Rich B. Meyer, Jr.