Stabilised protein compositions based on semifluorinated alkanes

Patent metadata

Field	Value
Publication number	US-9757460-B2
Application number	US-201314373877-A
Country	US
Kind code	B2
Filing date	Jan 22, 2013
Priority date	Jan 23, 2012
Publication date	Sep 12, 2017
Grant date	Sep 12, 2017

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.

First claim

The invention claimed is:

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.

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.

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.

13. The method of claim 7 , 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.

Assignees

• Novaliq Gmbh

Inventors

• Günther Bernhard
• Theisinger Bastian
• Theisinger Sonja
• Scherer Dieter
• Wilson Clive
• Pettigrew Anthony
• Hüttig Annette

Classifications

• A61K38/4826

  Trypsin (3.4.21.4) Chymotrypsin (3.4.21.1) · CPC title

• C12Y304/21001

  Chymotrypsin (3.4.21.1) · CPC title

• A61K9/0019

  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 title

• A61K47/24

  containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids · CPC title

• A61K38/23

  Calcitonins · CPC title