Platelet derived growth factor (PDGF) nucleic acid ligand complexes

• US 6,582,918 B2
• Filed: 05/08/2001
• Issued: 06/24/2003
• Est. Priority Date: 06/07/1995
• Status: Expired due to Fees

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Janjic, Nebojsa, Gold, Larry
• Primary Examiner(s): ZITOMER, STEPHANIE W
• Application Number:
  US09/851,486
• Publication Number:
  US 20030036642A1
• Time in Patent Office: 777 Days
• Field of Search: 435/6, 435/91.2, 530/350, 530/827, 536/22.1, 536/23.1, 536/24.2, 536/25.4, 514/44, 424/1.21, 424/1.73
• US Class Current: 435/6.16
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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: A61K 47/544 Phospholipids
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/49 Platelet-derived growth factor [PDGF]
• CPC Class Codes: C07K 14/495 Transforming growth factor [TGF]
• CPC Class Codes: C07K 14/50 Fibroblast growth factor [FGF]
• CPC Class Codes: C07K 14/52 Cytokines; Lymphokines; Interferons
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• 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 2310/13 Decoys
• CPC Class Codes: C12N 2310/317 with an inverted bond, e.g. a cap structure
• CPC Class Codes: C12N 2310/3183 Diol linkers, e.g. glycols or propanediols
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/322 2'-R Modification
• CPC Class Codes: C12N 2310/351 Conjugate
• CPC Class Codes: C12N 2310/3515 : Lipophilic moiety, e.g. cholesterol
• CPC Class Codes: C12N 2310/3521 : Methyl
• CPC Class Codes: C12Q 1/6811 : Selection methods for production or design of target specific oligonucleotides or binding molecules
• CPC Class Codes: C40B 30/04 : by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding

Abstract

This invention discloses a method for preparing a complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound by identifying a PDGF Nucleic Acid Ligand by SELEX methodology and associating the PDGF Nucleic Acid Ligand with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further discloses Complexes comprising one or more PDGF Nucleic Acid Ligands in association with a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound. The invention further includes a Lipid construct comprising a PDGF Nucleic Acid Ligand or Complex and methods for making the same.

Claims

1. A method for treating a patient having a PDGF mediated disease or medical condition comprising administering to a patient in need thereof a pharmaceutically effective amount of a Complex comprised of a PDGF Nucleic Acid Ligand and a Non-Immunogenic, High Molecular Weight Compound or a Lipophilic Compound.

2. The method of claim 1 wherein said Complex further comprises a Linker between said Ligand and said Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound.

3. The method of claim 1 wherein said Ligand comprises a Linker.

4. The method of claim 1 wherein said Non-Immunogenic, High Molecular Weight Compound is a Polyalkylene Glycol.

5. The method of claim 4 wherein said Polyalkylene Glycol is polyethylene glycol.

6. The method of claim 5 wherein said polyethylene glycol has a molecular weight of about between 10-80 K.

7. The method of claim 5 wherein said polyethylene glycol has a molecular weight of about 20-45 K.

8. The method of claim 4 wherein said Complex has the structure

9. The method of claim 1 wherein said Lipophilic Compound is a glycerol lipid.

10. The method of claim 9 wherein said Complex is associated with a lipid construct.

11. A method of inhibiting PDGF mediated angiogenesis comprising:

covalently linking a PDGF Nucleic Acid Ligand to a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound to form a Complex; and

administering said Complex to a patient having a disease or condition comprising PDGF mediated angiogenesis.

12. A method of inhibiting the growth of tumors comprising:

covalently linking a PDGF Nucleic Acid Ligand to a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound to form a Complex; and

administering said Complex to a patient having a disease or condition comprising tumors expressing PDGF.

13. The method of claim 12 wherein said tumors or cells or tissues surrounding said tumors are expressing PDGF.

14. The method of claim 12 wherein said tumors or cells or tissues surrounding said tumors are expressing PDGF receptors.

15. A method of inhibiting fibrosis comprising:

covalently linking a PDGF Nucleic Acid Ligand to a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound to form a Complex; and

administering said Complex to a patient having a disease or condition comprising fibrosis.

16. The method of claim 15 wherein said Complex further comprises a Linker between said Ligand and said Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound.

17. The method of claim 15 wherein said Ligand comprises a Linker.

18. The method of claim 15 wherein said fibrosis is kidney fibrosis.

19. The method of claim 15 wherein said fibrosis is lung fibrosis.

20. The method of claim 15 wherein said fibrosis is bone marrow fibrosis.

21. The method of claim 15 wherein said fibrosis is radiation treatment-associated fibrosis.

22. The method of claim 16 wherein said Non-Immunogenic, High Molecular Weight Compound is a polyalkylene glycol.

23. The method of claim 22 wherein said polyalkylene glycol is polyethylene glycol.

24. The method of claim 23 wherein said polyethylene glycol has a molecular weight of about between 10-80k.

25. The method of claim 23 wherein said polyethylene glycol has a molecular weight of about between 20-45k.

26. The method of claim 25 wherein said complex has the structure

27. A method of inhibiting restenosis comprising:

covalently linking a PDGF Nucleic Acid Ligand to a Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound to form a Complex; and

administering said Complex to a patient having a disease or condition comprising restenosis.

28. The method of claim 27 wherein said Complex further comprises a Linker between said Ligand and said Non-Immunogenic, High Molecular Weight Compound or Lipophilic Compound.

29. The method of claim 27 wherein said Ligand comprises a Linker.

30. The method of claim 27 wherein said Non-Immunogenic, High Molecular Weight Compound is a polyalkylene glycol.

31. The method of claim 30 wherein said polyalkylene glycol is polyethylene glycol.

32. The method of claim 31 wherein said polyethylene glycol has a molecular weight of about between 10-80k.

33. The method of claim 31 wherein said polyethylene glycol has a molecular weight of about between 20-45k.

34. The method of claim 33 wherein said complex has the structure

35. The method of claim 27 wherein said restenosis is in-stent restenosis.

36. The method of claim 27 wherein said restenosis is in a coronary artery.

37. The method of claim 27 wherein said restenosis is in a non-coronary vessel.