Epoch Biosciences, Inc.

Epoch Pharmaceuticals, Inc.

Elitech Holding B.v.

Berlex Laboratories, Inc.

Joel Hedgpeth

Eugeny Alexander Lukhtanov

Igor V Kutyavin

Rich B Meyer, Jr

Irina Aleksandrovna Afonina

Evgeniy S Belousov

Mikhail A Podyminogin

Helmut Wachtel

Rich B Meyer

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.

Hybridization and mismatch discrimination using oligonucleotides conjugated to minor groove binders

Derivatized oligonucleotides (ODNs) are coupled to a solid support in improved yield resulting in a high density of coupled oligonucleotide per surface unit of the support, through a Schiff base type bond formed between an NH group attached either to the solid support or to the ODN and an aromatic aldehyde attached to the other of the solid support and the ODN. The preferred solid support-ODN conjugate is formed between semicarbazide groups attached to a glass surface and an aromatic aldehyde attached at either 3&prime;, or 5&prime; end of an ODN or to an intermediate nucleotide of the ODN.

Attachment of oligonucleotides to solid supports through schiff base type linkages for capture and detection of nucleic acids

Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo&lsqb;3,2-e&rsqb;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.

Attachment of oligonucleotides to solid supports through Schiff base type linkages for capture and detection of nucleic acids

Conjugates between a minor groove binding molecule, such as the trimer of 1,2-dihydro-(3H)-pyrrolo&lsqb;3,2-e&rsqb;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.

The present invention is a method of preventing or ameliorating the episodic recurrence of MS, comprising administering an effective amount of selective phosphodiesterase inhibitors of Type IV, e.g., Rolipram, e.g., wherein the severity of the episodic recurrences is ameliorated or the time period between episodes is lengthened.

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San Francisco, CA, United States of America

Joel Hedgpeth