Stable aqueous formulations of adalimumab

• US 10,195,275 B2
• Filed: 01/09/2018
• Issued: 02/05/2019
• Est. Priority Date: 09/07/2012
• Status: Active Grant

• Current Assignee: Coherus BioSciences Inc.
• Original Assignee: Coherus BioSciences Inc.
• Inventors: Manning, Mark, Payne, Robert W.
• Primary Examiner(s): Kim, Yunsoo
• Application Number:
  US15/866,154
• Publication Number:
  US 20180140701A1
• Time in Patent Office: 392 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/542 oral/gastrointestinal
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 39/39533 against materials from animals
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 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 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/241 : Tumor Necrosis Factors
• 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 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The invention provides aqueous pharmaceutical adalimumab compositions suitable for long-term storage of adalimumab, methods of manufacture of these compositions, methods of administration, and kits containing same.

Claims

1. A stable aqueous pharmaceutical composition comprising:

(i) adalimumab;

(ii) buffer;

(iii) surfactant;

(iv) stabilizer; and

(v) sugar;

wherein the composition is free of mannitol and has a pH of about 5 to about 6.

2. The composition of claim 1, wherein the buffer is selected from the group consisting of citrate, phosphate, succinate, histidine, tartrate maleate, and combinations thereof except the combination of citrate and phosphate.

3. The composition of claim 1, wherein the buffer does not comprise citrate and the composition results in less pain upon administration to a subject in comparison to an adalimumab composition having a buffer comprising citrate.

4. The composition of claim 1, wherein the surfactant is selected from the group consisting of polysorbate 80, polysorbate 40, and polysorbate 20.

5. The composition of claim 1, wherein the stabilizer is selected from the group consisting of an amino acid, a salt, ethylenediaminetetraacetic acid (EDTA), and a metal ion.

6. The composition of claim 1, wherein the stabilizer is selected from the group consisting of glycine, alanine, glutamate, arginine, methionine, EDTA, sodium chloride, sodium sulfate, metal ions, and combinations thereof.

7. The composition of claim 6, wherein the stabilizer is combination of EDTA and one or more of glycine, alanine, glutamate, arginine, and methionine.

8. The composition of claim 1, wherein the sugar comprises sucrose, glucose, lactose, maltose, and dextrose.

9. The composition of claim 1, wherein the composition has a pH of about 5.5.

10. The composition of claim 1, wherein the concentration of adalimumab is about 50 mg/ml.

11. The composition of claim 1, wherein the composition has osmolality of about 180 to 420 mOsM;

the composition is suitable for administration to a subject as a single dosage;

the composition has a concentration of adalimumab in the range of 30 to about 50 mg/ml, and the dosage contains about 10 to 80 mg of adalimumab.

12. The composition of claim 11, wherein the concentration of adalimumab is about 50 mg/ml and the dosage is about 40 mg.

13. A stable aqueous pharmaceutical composition comprising:

(i) adalimumab;

(ii) buffer;

(iii) surfactant;

(iv) amino acid;

(v) ethylenediaminetetraacetic acid (EDTA); and

(vi) sugar;

wherein the composition is free of citrate/phosphate buffer combinations, is free of mannitol, and has a pH of about 5 to about 6.

14. The composition of claim 13, wherein the buffer is histidine.

15. The composition of claim 13, wherein the surfactant is polysorbate 80.

16. The composition of claim 13, wherein the amino acid is methionine.

17. The composition of claim 13, wherein the sugar is sucrose.

18. The composition of claim 17, wherein the composition has a pH of about 5.5.

19. The composition of claim 13, wherein the concentration of adalimumab is about 50 mg/ml.

20. The composition of claim 13, wherein the composition has osmolality of about 180 to 420 mOsM;

the composition is suitable for administration to a subject as a single dosage;

the composition has a concentration of adalimumab in the range of 30 to about 50 mg/ml, and the dosage contains about 10 to 80 mg of adalimumab.

21. The composition of claim 20, wherein the concentration of adalimumab is about 50 mg/ml and the dosage is about 40 mg.

22. A stable aqueous pharmaceutical composition comprising:

(i) adalimumab;

(ii) histidine buffer;

(iii) polysorbate 80;

(iv) methionine;

(v) ethylenediaminetetraacetic acid (EDTA); and

(vi) sucrose;

wherein the composition is free of citrate/phosphate buffer combinations, is free of mannitol, and has a pH of about 5.5.

23. The composition of claim 22, wherein the concentration of adalimumab is about 50 mg/ml.

24. The composition of claim 22, wherein the composition has osmolality of about 180 to 420 mOsM;

the composition is suitable for administration to a subject as a single dosage;

the composition has a concentration of adalimumab in the range of 30 to about 50 mg/ml, and the dosage contains about 10 to 80 mg of adalimumab.

25. The composition of claim 24, wherein the concentration of adalimumab is about 50 mg/ml and the dosage is about 40 mg.