Stabilised protein compositions based on semifluorinated alkanes

• US 9,757,460 B2
• Filed: 01/22/2013
• Issued: 09/12/2017
• Est. Priority Date: 01/23/2012
• Status: Expired

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: Gnther, Bernhard, Theisinger, Bastian, Theisinger, Sonja, Scherer, Dieter, Wilson, Clive, Pettigrew, Anthony, Httig, Annette
• Primary Examiner(s): Blanchard, David J
• Assistant Examiner(s): Coughlin, Daniel F
• Application Number:
  US14/373,877
• Publication Number:
  US 20140369993A1
• Time in Patent Office: 1,694 Days
• Field of Search: None
• 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 having a molecular mass of at least 1,500 Da, dispersed or suspended in the liquid vehicle;

wherein the semifluorinated alkane is selected from the group consisting of F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10.

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

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

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

5. The composition of claim 1, wherein the semifluorinated alkane is selected from F4H5 and F6H8.

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

10. The composition of claim 4, wherein the semifluorinated alkane is selected from F4H5 and F6H8.

11. The composition of claim 10, wherein the composition is substantially free of water.

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

14. The composition of claim 1, wherein the semifluorinated alkane is F6H8.

15. The composition of claim 4, wherein the semifluorinated alkane is F6H8.

16. The composition of claim 1, wherein the bioactive compound is sensitive to degradation and/or aggregation, and wherein the bioactive compound is easily re-dispersed by gentle shaking after flotation or sedimentation.

7. 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;

wherein the bioactive compound is a therapeutic or diagnostic agent or vaccine selected from polypeptides and proteins having a molecular mass of at least 1,500 Da, dispersed or suspended in the liquid vehicle; and

wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10.

8. The method of claim 7, wherein the bioactive polypeptide or protein is sensitive to degradation and/or aggregation.

9. The method of claim 7, wherein the composition is chemically and/or physically stabilised.

13. The method of claim 7, wherein the polypeptide or protein has a molecular mass of at least about 2,000 Da.