PHARMACEUTICAL COMPOSITIONS CONTAINING sc(Fv)2

• US 20160168259A1
• Filed: 12/14/2015
• Published: 06/16/2016
• Est. Priority Date: 06/10/2005
• Status: Active Grant

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Igawa, Tomoyuki
• Granted Patent: US 9,777,066 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/2869 against hormone receptors for antibodies against neuromediator receptors C07K16/286
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/626 Diabody or triabody
• CPC Class Codes: C07K 2317/75 Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding

Abstract

The present inventor discovered stabilizing agents/stabilizing conditions for suppressing isomerization reactions of sc(Fv)2. It was also discovered that the above-mentioned isomerization reactions can be suppressed through use of freeze-dried formulations. As disclosed herein, by applying the discovered stabilizing agents/stabilizing conditions or the freeze-dried formulation, the isomerization reaction of an sc(Fv)2-type molecule from the bivalent scFv type to the single chain diabody type, and/or the isomerization reaction from a single chain diabody type to a bivalent scFv type can be suppressed in both directions or one direction.

Claims

1-12. -12. (canceled)

13. A pharmaceutical sc(Fv)2 composition comprising a specific conformational isomer of sc(Fv)2, the specific conformational isomer of sc(Fv)2 being either a bivalent scFv-type sc(Fv)2 or a single chain diabody type sc(Fv)2, wherein at least 80% of the sc(Fv)2 in the composition is in the form of the specific conformational isomer.

14. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition comprises at least one substance selected from the group consisting of a salt, an amino sugar, a sugar alcohol, an amino acid, and a pH adjusting agent.

15. The pharmaceutical composition of claim 14, wherein the substance is a salt selected from the group consisting of sodium chloride and magnesium chloride.

16. The pharmaceutical composition of claim 14, wherein the substance is the amino sugar 1-deoxy-1-methylamino-D-glucitol.

17. The pharmaceutical composition of claim 14, wherein the substance is the sugar alcohol mannitol.

18. The pharmaceutical composition of claim 14, wherein the substance is the amino acid lysine.

19. The pharmaceutical composition of claim 14, wherein the substance is a pH adjusting agent selected from the group consisting of a sodium citrate buffer and histidine hydrochloride.

20. The pharmaceutical composition of claim 13, wherein the composition has a pH of 4.5 to 9.0.

21. The pharmaceutical composition of claim 13, wherein the composition has a pH of 6.0 to 9.0.

22. The pharmaceutical composition of claim 13, wherein the composition has a salt concentration of 50 mM to 1000 mM.

23. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition is in the form of a freeze-dried formulation.

24. The pharmaceutical composition of claim 13, wherein the pharmaceutical composition is in the form of a spray-dried formulation.

25. The pharmaceutical composition of claim 13, wherein the specific conformational isomer constitutes 90% or more of the sc(Fv)2 present in the pharmaceutical sc(Fv)2 composition.

26. The pharmaceutical composition of claim 13, wherein the specific conformational isomer constitutes 95% or more of the sc(Fv)2 present in the pharmaceutical sc(Fv)2 composition.

27. The pharmaceutical composition of claim 13, wherein the specific conformational isomer is a bivalent scFv-type sc(Fv)2.

28. The pharmaceutical composition of claim 13, wherein the specific conformational isomer is a single chain diabody type sc(Fv)2.