STABILIZED ANTIBODY COMPOSITIONS

• US 20160159902A1
• Filed: 07/23/2014
• Published: 06/09/2016
• Est. Priority Date: 07/23/2013
• Status: Active Grant

• Current Assignee: Novaliq GmbH
• Original Assignee: Novaliq GmbH
• Inventors: G?nther, Bernhard, Scherer, Dieter, Pettigrew, Anthony, Graf, Gesche
• Granted Patent: US 10,273,298 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/626 Diabody or triabody
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

The invention provides novel compositions of antibodies based on liquid vehicles selected from semifluorinated alkanes. The use of these vehicles provides for improved stability and shelf-life of antibodies and their derivatives. The compositions are useful for topical administration or for parenteral injection.

Claims

1. Composition comprising an antigen-binding polypeptide or protein 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 antigen-binding polypeptide or protein is incorporated in the composition such as to form a dispersion or suspension.

2. The composition of claim 1, wherein the antigen-binding polypeptide or protein is selected from a monoclonal antibody, polyclonal antibody, an antibody fragment, a fusion protein comprising an antibody fragment, an antibody-drug conjugate, or any combination thereof.

3. The composition of claim 2, wherein the antibody fragment is a fragment antigen-binding (Fab), a single-chain variable fragment (scFv), a single-domain antibody, a minibody, or a diabody.

4. The composition of claim 2, wherein the monoclonal antibody is a chimeric, humanized, or human antibody.

5. The composition of claim 1, wherein the antigen-binding polypeptide or protein has a molecular mass of at least 90 kDa.

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. The composition of claim 1, wherein the composition retains at least 85% of its initial antigen-binding activity during storage of 6 months at a temperature of between RT to 40°

C.

9. The composition of claim 1, wherein the antigen-binding polypeptide or protein is at a concentration of at least 0.5 mg/mL.

10. A method for treating or preventing a disease or condition in a patient in need thereof, comprising the step of administering to the patient an effective amount of a composition according to claim 1.

11. The method of claim 10, wherein the composition is administered by subcutaneous, dermal, intramuscular, or locoregional injection.

14. The method of claim 10, wherein the disease or condition is cancer or an autoimmune disease.

15. The composition of claim 1, wherein the antigen-binding polypeptide or protein is an angiogenesis inhibitor, an anti-proliferative agent or a TNF inhibitor.

16. The composition of claim 2, wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10.

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

12. A method of stabilizing an antigen-binding polypeptide or protein, comprising the step of mixing the antigen-binding polypeptide or protein with a liquid vehicle comprising 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 suspension or a dispersion.

13. The method of claim 12, wherein the antigen-binding polypeptide or protein retains at least 85% of initial antigen-binding activity during storage of 6 months at a temperature between RT to 40°

C.

18. The method of claim 12, wherein the antigen-binding polypeptide or protein is a monoclonal antibody, a polyclonal antibody, an antibody fragment, a fusion protein comprising an antibody fragment, an antibody-drug conjugate, or any combination thereof.

19. The method of claim 18, wherein the semifluorinated alkane is selected from F4H5, F4H6, F4H8, F6H4, F6H6, F6H8, and F6H10.

20. The method of claim 19, wherein the antigen-binding polypeptide or protein is at a concentration of at least 0.5 mg/mL.