Delivery of molecules and complexes to mammalian cells in vivo

• US 7,589,059 B2
• Filed: 07/28/2003
• Issued: 09/15/2009
• Est. Priority Date: 07/26/2002
• Status: Expired due to Fees

• Current Assignee: Roche Madison Inc. (Arrowhead Pharmaceuticals, Inc.)
• Original Assignee: Roche Madison Inc. (Arrowhead Pharmaceuticals, Inc.)
• Inventors: Monahan, Sean D., Herweijer, Hans, Hagstrom, James E., Wolff, Jon A., Hegge, Julia, Budker, Vladimir G., Subbotin, Vladimir
• Primary Examiner(s): Tsang; Cecilia
• Assistant Examiner(s): Ha; Julie
• Application Number:
  US10/628,792
• Publication Number:
  US 20040023850A1
• Time in Patent Office: 2,241 Days
• Field of Search: None
• US Class Current: 514/1.1
• 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: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
• CPC Class Codes: C12N 2799/022 where the vector is derived from an adenovirus

Abstract

Disclosed is a system for providing in vivo delivery of molecules or complexes to extravascular mammalian cells using an intravascular administration route. The molecules or complexes are inserted in an injection solution into a mammalian vasculature. Insertion of the injection solution at an appropriate rate transiently increases the volume of extravascular fluid in the tissue thereby facilitating delivery of the molecule to the cell.

Claims

1. A process for delivering a protein or peptide to an extravascular cell in a mammalian target tissue in vivo comprising:

inserting an injection solution containing the protein or peptide into the lumen of an efferent or afferent vessel of the target tissue wherein the inserting of the injection solution results in an increase in pressure in a vein of the target tissue of 10 mm Hg or greater thereby resulting in delivery of the protein or peptide to the extravascular cell.

2. The process of claim 1 wherein fluid flow out of the target tissue is occluded.

3. The process of claim 1 wherein the protein or peptide consists of a biologically active protein or peptide.

4. The process of claim 3 wherein the protein or peptide is greater than 5 kDa.

5. The process of claim 4 wherein the protein or peptide is greater than 30 kDa.

6. The process of claim 5 wherein the protein or peptide is greater than 500 kDa.

7. The process of claim 1 wherein the protein or peptide consists of a therapeutic molecule.

8. The process of claim 1 wherein the protein or peptide is in a complex.

9. The process of claim 1 wherein the injection solution contains a compound that increases vessel permeability.

10. The process of claim 9 wherein the compound consists of a vasodilator.

11. The process of claim 1 wherein the cell consists of a liver cell.

12. The process of claim 11 wherein the liver cell consists of a hepatocyte.

13. The process of claim 1 wherein the cell consists of a skeletal muscle cell.

14. The process of claim 1 wherein the cell consists of a heart muscle cell.

15. The process of claim 1 wherein the cell consists of a prostate cell.

16. The process of claim 1 wherein the vessel consists of a blood vessel.

17. The process of claim 16 wherein the blood vessel consists of an artery.

18. The process of claim 16 wherein the blood vessel consists of a vein.

19. The process of claim 1 wherein the vessel consists of a bile duct.

20. The process of claim 1 wherein the injection solution contains less than 20 mM salt.

21. The process of claim 20 wherein the injection solution contains less than 5 mM salt.

22. The process of claim 1 wherein the injection solution contains zwitterions.

23. The process of claim 1 wherein the injection solution is hypotonic.

24. The process of claim 1 wherein the injection solution is hypertonic.

25. A process for delivering a protein or peptide to an extravascular in vivo mammalian cell in a target tissue comprising:

rapidly inserting a sufficient volume of injection solution containing the protein or peptide into the lumen of an efferent or afferent vessel of the target tissue and impeding fluid flow away from the tissue during the injection wherein the inserting of the injection solution results in an increase in pressure in a vein of the target tissue of 10 mm Hg or greater thereby resulting in delivery of the protein or peptide to the extravascular mammalian cell in the tissue.