STABILISED PROTEIN COMPOSITIONS BASED ON SEMIFLUORINATED ALKANES

• US 20140369993A1
• Filed: 01/22/2013
• Published: 12/18/2014
• Est. Priority Date: 01/23/2012
• Status: Active Grant

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: Gnther, Bernhard, Theisinger, Bastian, Theisinger, Sonja, Scherer, Dieter, Wilson, Clive, Pettigrew, Anthony, Httig, Annette
• Granted Patent: US 9,757,460 B2
• Time in Patent Office: Days
• US Class Current: 424/94.64
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/385 Serum albumin
• CPC Class Codes: A61K 38/4826 Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1)
• CPC Class Codes: A61K 47/06 Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• 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: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: C12Y 304/21001 Chymotrypsin (3.4.21.1)

Abstract

The invention provides novel compositions of bioactive polypeptides and proteins with improved stability and shelf-life. The compositions are based on liquid vehicles selected from semifluorinated alkanes. These vehicles are remarkably effective in protecting polypeptides and proteins from degradation and/or aggregation. The compositions are useful for topical administration, e.g. into an eye, or by parenteral injection, e.g. via the subcutaneous or intramuscular route.

Claims

1. Composition comprising a bioactive compound and a liquid vehicle, wherein the liquid vehicle comprises a semifluorinated alkane of the formula

RFRH

wherein RF is a linear perfluorinated hydrocarbon segment with 4 to 12 carbon atoms, and wherein RH is a linear alkyl group with 4 to 8 carbon atoms;

and wherein the bioactive compound is a therapeutic or diagnostic agent or vaccine selected from polypeptides and proteins and is incorporated in the composition such as to form a dispersion or suspension.

2. The composition of claim 1, wherein the polypeptide or protein has a molecular mass of at least about 1,500 Da.

3. The composition of claim 1, wherein the bioactive compound is sensitive to degradation and/or aggregation.

4. The composition of claim 1, wherein the bioactive compound is a single-domain protein or a two-domain protein.

5. The composition of claim 1, wherein the bioactive compound is an insulin.

6. The composition of claim 1, wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10.

7. The composition of claim 1, wherein the composition is substantially free of water.

8. A method of treating a disease or condition of a patient in need of such treatment, comprising administering an effective amount of the pharmaceutical composition of claim 1 to the patient.

9. The method of claim 8, wherein the pharmaceutical composition is administered parenterally by subcutaneous, dermal, intramuscular, or locoregional injection.

10. The method of claim 8, wherein the pharmaceutical composition is topically administered to the eye, ear, lung, skin or nose of a patient.

15. The composition of claim 5, wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10.

16. The composition of claim 15, wherein the composition is substantially free of water.

17. The composition of claim 1, wherein the polypeptide or protein has a molecular mass of at least about 2,000 Da.

11. Method of preparing a composition comprising a bioactive therapeutic or diagnostic agent or vaccine selected from a polypeptide or protein, comprising the step of incorporating the bioactive polypeptide or protein within a liquid vehicle which comprises a semifluorinated alkane of the formula

RFRH

wherein RF is a linear perfluorinated hydrocarbon segment with 4 to 12 carbon atoms, and wherein RH is a linear alkyl group with 4 to 8 carbon atoms such as to form a dispersion or suspension.

12. The method of claim 11, wherein the polypeptide or protein has a molecular mass of at least about 1,500 Da.

13. The method of claim 11, wherein the bioactive polypeptide or protein is sensitive to degradation and/or aggregation.

14. The method of any of claim 11, wherein the composition is chemically and/or physically stabilised.

18. The method of claim 11, wherein the polypeptide or protein has a molecular mass of at least about 2,000 Da.