Synthetic ribonucleic acids with RNAse activity

• US 6,528,640 B1
• Filed: 12/29/1999
• Issued: 03/04/2003
• Est. Priority Date: 11/05/1997
• Status: Expired due to Fees

• Current Assignee: Ribozyme Pharmaceuticals, Inc. (Alnylam Pharmaceuticals Incorporated)
• Original Assignee: Ribozyme Pharmaceuticals, Inc. (Alnylam Pharmaceuticals Incorporated)
• Inventors: Beigelman, Leonid, Zinnen, Shawn, Sweedler, David, Matulic-Adamic, Jasenka, Karpeisky, Alexander, Burgin, Alex, Beaudry, Amber
• Primary Examiner(s): Geist, Gary
• Assistant Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US09/474,432
• Time in Patent Office: 1,161 Days
• Field of Search: 536/23.1, 536/25.1, 536/29.3, 536/24.31, 536/24.32
• US Class Current: 536/25.1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/111 spanning the whole gene, or a large part of it
• CPC Class Codes: C12N 2310/12 catalytic nucleic acids, e.g. ribozymes
• CPC Class Codes: C12N 2310/121 Hammerhead
• CPC Class Codes: C12N 2310/122 Hairpin
• CPC Class Codes: C12N 2310/18 acting by a non-sequence specific mechanism
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/317 with an inverted bond, e.g. a cap structure
• CPC Class Codes: C12N 2310/318 where the PO2 is completely replaced, e.g. MMI or formacetal
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/33 of the base
• CPC Class Codes: C12N 2310/332 : Abasic residue
• CPC Class Codes: C12N 2310/345 : having at least two different backbone modifications
• CPC Class Codes: C12N 2310/346 : having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3521 : Methyl
• CPC Class Codes: C12N 2310/3523 : Allyl
• CPC Class Codes: C12P 19/30 : Nucleotides
• CPC Class Codes: C12P 19/305 : Pyrimidine nucleotides
• CPC Class Codes: C12Y 204/02001 : Purine-nucleoside phosphorylase (2.4.2.1)
• CPC Class Codes: C12Y 207/01037 : Protein kinase (2.7.1.37) C12Y207/11001, C12Y207/11008 - C12Y207/11013, C12Y207/11021, C12Y207/11022, C12Y207/11024, C12Y207/11025, C12Y207/1103, C12Y207/12001 take precedence
• CPC Class Codes: C12Y 207/07049 : RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
• CPC Class Codes: C12Y 301/03048 : Protein-tyrosine-phosphatase (3.1.3.48)

Abstract

Novel nucleotide triphosphates, methods of synthesis and process of incorporating these nucleotide triphosphates into oligonucleotides, and isolation of novel nucleic acid catalysts (e.g., ribozymes) are disclosed. Also, described are the use of novel enzymatic nucleic acid molecules to inhibit HER2/neu/ErbB2 gene expression and their applications in human therapy.

Claims

1. An enzymatic nucleic acid molecule having formula II:

wherein each X, Y, and Z represents independently a nucleotide which may be the same or different;

q is an integer ranging from 3 to 100;

m is an integer ranging from 1 to 10;

n is an integer ranging from 1 to 10;

o is an integer ranging from 3 to 100;

Z′

is a nucleotide complementary to Z;

Y′

is a nucleotide complementary to Y;

each X(q) and X(o) are oligonucleotides which are of sufficient length to stably interact independently with a target nucleic acid sequence;

W is a linker ranging from 2 to 70 nucleotides;

A, U, G, and C represent nucleotides;

C is 2′

-deoxy-2′

-amino cytidine; and

_ represents a chemical linkage.

2. An enzymatic nucleic acid molecule having formula III namely:

wherein each X, Y, and Z represents independently a nucleotide which may be the same or different;

q is an integer ranging from 3 to 100;

m is an integer ranging from 1 to 10;

n is an integer ranging from 1-10;

o is an integer ranging from 3-100;

Z′

is a nucleotide complementary to Z;

Y′

is a nucleotide complementary to Y;

each X(q) and X(o) are oligonucleotides which are of sufficient length to stably interact independently with a target nucleic acid sequence;

W is a linker ranging from 2 to 70 nucleotides;

A, U, G, and C represent nucleotides;

C 2′

-deoxy-2′

-aminocytidine; and

_ represents a chemical linkage.

3. The enzymatic nucleic acid molecule of claim 2, wherein said nucleic acid molecule has an endonuclease activity to cleave RNA of a mammalian HER2 gene.