Stabilized aptamers to platelet derived growth factor and their use as oncology therapeutics

• US 8,039,443 B2
• Filed: 11/02/2004
• Issued: 10/18/2011
• Est. Priority Date: 11/21/2002
• Status: Expired due to Fees

• Current Assignee: Archemix LLC
• Original Assignee: Archemix Corp. (Baxter International Inc.)
• Inventors: Grate, Dilara, McCauley, Thomas Greene, Wilson, Charles, Diener, John L.
• Primary Examiner(s): SCHNIZER, RICHARD A
• Application Number:
  US10/980,211
• Publication Number:
  US 20050159351A1
• Time in Patent Office: 2,541 Days
• Field of Search: None
• US Class Current: 514/44.00R
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/427 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/522 having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
• CPC Class Codes: A61K 31/525 Isoalloxazines, e.g. riboflavins, vitamin B2
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/549 Sugars, nucleosides, nucleotides or nucleic acids
• CPC Class Codes: C07K 14/715 for cytokines; for lymphokines; for interferons
• 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 2310/16 Aptamers

Abstract

Materials and methods are provided for producing and using aptamers useful as oncology therapeutics capable of binding to PDGF, PDGF isoforms, PDGF receptor, VEGF, and VEGF receptor or any combination thereof with great affinity and specificity. The compositions of the present invention are particularly useful in solid tumor therapy and can be used alone or in combination with known cytotoxic agents for the treatment of solid tumors. Also disclosed are aptamers having one or more CpG motifs embedded therein or appended thereto.

Claims

1. A monotherapy regimen for reducing angiogenesis and neovascularization in a tumor comprising the step of administering a therapeutically effective amount of an aptamer having the following structure:

2. The monotherapy regimen of claim 1, wherein said tumor is a PDGF mediated tumor.

3. The monotherapy regimen of claim 2, wherein said PDGF mediated tumor is selected from the group consisting of glioblastoma, chronic myelomonocytic leukemia, dermafibrosarcoma protuberans, gastrointestinal stromal tumor and soft tissue sarcoma.