High affinity nucleic acid ligands of complement system proteins

• US 6,566,343 B2
• Filed: 01/03/2002
• Issued: 05/20/2003
• Est. Priority Date: 02/01/1996
• Status: Expired due to Term

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Biesecker, Gregory, Gold, Larry
• Primary Examiner(s): ZITOMER, STEPHANIE W
• Application Number:
  US10/037,282
• Publication Number:
  US 20030078221A1
• Time in Patent Office: 502 Days
• Field of Search: 514/44, 536/23.1, 435/6, 435/91.2, 435/325, 435/366, 435/243, 435/235.1, 436/501
• US Class Current: 514/44.00R
• 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: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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: C07K 14/472 Complement proteins, e.g. anaphylatoxin, C3a, C5a
• CPC Class Codes: C12N 15/1048 SELEX
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/151 more than 3 strands, e.g. tetrads, H-DNA
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C40B 40/00 Libraries per se, e.g. arrays, mixtures

Abstract

Methods are described for the identification and preparation of high-affinity Nucleic Acid Ligands to Complement System Proteins. Methods are described for the identification and preparation of high affinity Nucleic Acid Ligands to Complement System Proteins C1q, C3 and C5. Included in the invention are specific RNA ligands to C1q, C3 and C5 identified by the SELEX method.

Claims

1. A method for treating a Complement System-mediated disease comprising administering to a patient in need thereof a pharmaceutically effective amount of a Nucleic Acid Ligand of a Complement System Protein, wherein said Nucleic Acid Ligand is selected from the group consisting of SEQ ID NOS:

5-155.

2. A method of treating an infection caused by bacterial or viral cells comprising:

a) conjugating a Nucleic Acid Ligand that has been generated to a bacterial cell surface target of said bacteria or viral particle target of said virus with a C1q Nucleic Acid Ligand; and

b) administering the conjugate to a patient in need thereof in an amount effective to activate the Complement System and lyse the bacterial or viral cells.

3. A method of killing tumor cells in a patient comprising:

a) conjugating a Nucleic Acid Ligand that has been generated to a tumor cell surface target with a C1q Nucleic Acid Ligand; and

b) administering the conjugate to the patient in need thereof in an amount effective to activate the Complement System and kill the tumor or tumor cell.