Platelet Derived Growth Factor (PDGF) Nucleic Acid Ligand Complexes

• US 20100029922A1
• Filed: 07/30/2009
• Published: 02/04/2010
• Est. Priority Date: 12/16/1997
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Sciences Inc.
• Inventors: Janjic, Nebojsa, Gold, Larry
• Granted Patent: US 7,939,654 B2
• Time in Patent Office: Days
• US Class Current: 536/23.500
• 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 complex comprising a platelet derived growth factor (PDGF) nucleic acid ligand of SEQ ID NO:

146 and a non-immunogenic, high molecular weight compound, wherein the PEG spacer of SEQ ID NO;

146 is

2. The complex of claim 1, wherein the non-immunogenic, high molecular weight compound is a polyalkylene glycol.

3. The complex of claim 2, having one or more polyalkylene glycols.

4. The complex of claim 3, wherein each of the one or more polyalkylene glycols is polyethylene glycol.

5. The complex of claim 4, wherein the polyethylene glycol has a molecular weight of about 10-80K.

6. The complex of claim 5, wherein the polyethylene glycol has a molecular weight of about 20-45K.

7. The complex of claim 3, wherein the one or more polyalkylene glycols are two 20K polyethylene glycols.

8. The complex of claim 1, wherein the non-immunogenic, high molecular weight compound is attached to the PDGF nucleic acid ligand via a linker.

9. The complex of claim 7, wherein the two 20K polyethylene glycols are attached to the PDGF nucleic acid ligand via a linker.

10. The complex of claim 9, wherein the linker is formed by conjugation of the following compound

11. A complex having the structure A-B-Y, wherein A is one or more polyalkylene glycols, B is a spacer, and Y is a PDGF nucleic acid ligand of SEQ ID NO:

146, wherein the PEG spacer of SEQ ID NO;

146 is

12. The complex of claim 11, wherein each of the one or more polyalkylene glycols is polyethylene glycol.

13. The complex of claim 12, wherein the polyethylene glycol has a molecular weight of about 10-80 K.

14. The complex of claim 12, wherein the polyethylene glycol has a molecular weight of about 20-45K.

15. The complex of claim 11, wherein the one or more polyalkylene glycols are two 20K polyethylene glycols.

16. The complex of claim 11, wherein each of the one or more polyalkylene glycols (A) is attached to the spacer (B) via a linker.

17. A complex comprising a non-immunogenic, high molecular weight compound and a platelet derived growth factor (PDGF) nucleic acid ligand, wherein the nucleic acid ligand has the structure:

18. The complex of claim 17, wherein the non-immunogenic, high molecular weight compound is a polyalkylene glycol.

19. The complex of claim 18, having one or more polyalkylene glycols.

20. The complex of claim 19, wherein each of the one or more polyalkylene glycols is polyethylene glycol.

21. The complex of claim 20, wherein the polyethylene glycol has a molecular weight of about 10-80K.

22. The complex of claim 20, wherein the polyethylene glycol has a molecular weight of about 20-45K.

23. The complex of claim 19, wherein the one or more polyalkylene glycols are two 20K polyethylene glycols.

24. The complex of claim 17, wherein the non-immunogenic, high molecular weight compound is attached to the PDGF nucleic acid ligand via a linker.

25. The complex of claim 23, wherein the two 20K polyethylene glycols are attached to the PDGF nucleic acid ligand via a linker.

26. The complex of claim 25, wherein the linker is formed by conjugation of the following compound