COMPOSITIONS OF PEGYLATED SOLUBLE TUMOR NECROSIS FACTOR RECEPTORS AND METHODS OF PREPARING

• US 20100197751A1
• Filed: 04/29/2009
• Published: 08/05/2010
• Est. Priority Date: 06/20/2002
• Status: Abandoned Application

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Shi, Lei, Chang, Byeong, Kerwin, Bruce
• Application Number:
  US12/432,452
• Publication Number:
  US 20100197751A1
• Time in Patent Office: Days
• US Class Current: 514/400
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• 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 47/183 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 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• 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 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 : for peripheral neuropathies
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• 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 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 : Antianaemics
• 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: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention provides for improved compositions comprising a PEGsTNF-R1 which, in addition to having useful higher concentrations, demonstrate decreased viscosity (<400 cP) and improved stability.

Claims

1. A method for decreasing the viscosity of a pharmaceutical formulation comprising including a tonicity modifier selected from the group consisting of glycine, sorbitol, and sucrose,

wherein the pharmaceutical formulation comprises a surfactant,

wherein the pharmaceutical formulation comprises a TNF inhibitor at a concentration of at least 45 mg/ml,

wherein the pharmaceutical formulation is between pH 4.0 and 5.5, and

wherein the viscosity of the pharmaceutical formulation including the tonicity modifier is less than 400 cP.

2. The method of claim 1, wherein the surfactant is a polysorbate.

3. The method of claim 2, wherein the polysorbate is polysorbate 20.

4. The method of claim 2, wherein the polysorbate is polysorbate 80.

5. The method of claim 2, wherein the tonicity modifier is sucrose.

6. The method of claim 4, wherein the tonicity modifier is sorbitol.

7. The method of claim 6, wherein the pharmaceutical formulation further comprises histidine and the pharmaceutical formulation comprises the TNF inhibitor at a concentration of at least 57 mg/ml.

8. The method of claim 2, wherein the tonicity modifier is glycine.

11. The method of claim 5, wherein the TNF inhibitor comprises polyethylene glycol (PEG) and wherein the pharmaceutical formulation comprises the TNF inhibitor at concentration of at least 57 mg/ml.

12. The method of claim 11, wherein the PEG has a molecular weight between about 5 kilodaltons and about 50 kilodaltons.

17. The method of claim 12, wherein the pharmaceutical composition has been stored in a lyophilized form prior to reconstitution.

9-10. -10. (canceled)

13. A method for decreasing the viscosity of a pharmaceutical formulation comprising including mannitol in the pharmaceutical formulation,

wherein the pharmaceutical formulation comprises polysorbate 80, sodium chloride, sodium phosphate, citric acid, and sodium citrate

wherein the pharmaceutical formulation comprises a TNF inhibitor at a concentration of at least 45 mg/ml,

and

wherein the viscosity of the pharmaceutical formulation including the mannitol is less than 400 cP.

14. A method for decreasing the viscosity of a pharmaceutical formulation comprising including sorbitol in the pharmaceutical formulation,

wherein the pharmaceutical formulation comprises polysorbate 80, histidine, and a TNF inhibitor,

wherein the concentration of the TNF inhibitor is at least 57 mg/ml,

and

wherein the viscosity of the pharmaceutical formulation including sorbitol is less than 400 cP.

15. The method of claim 14, wherein the pH of the pharmaceutical formulation is between pH 4.0 and 5.5.

16. A method for decreasing the viscosity of a pharmaceutical formulation comprising including sucrose in the formulation,

wherein the pharmaceutical formulation comprises sodium chloride, sodium phosphate, and a TNF inhibitor,

wherein the TNF inhibitor is at a concentration of at least 45 mg/ml,

wherein the TNF inhibitor comprises the 40 kD TNF inhibitor, and

wherein the viscosity of the pharmaceutical formulation including the sucrose is less than 400 cP.

18. A pharmaceutical formulation comprising

(a) tonicity modifier selected from the group consisting of sorbitol and sucrose,

(b) a polysorbate, and

(c) a TNF inhibitor at a concentration of at least 57 mg/ml,

wherein the viscosity of the pharmaceutical formulation including the tonicity modifier is less than 400 cP.

19. The pharmaceutical formulation of claim 18, wherein

the tonicity modifier is sucrose,

the TNF inhibitor comprises PEG, which has a molecular weight between about 5 kilodaltons and about 50 kilodaltons, and

the pH of the pharmaceutical formulation is between pH 4.0 and 5.5.

20. The pharmaceutical formulation of claim 18, wherein

the tonicity modifier is sorbitol,

the polysorbate is polysorbate 80, and

the pharmaceutical composition further comprises histidine.

21. The pharmaceutical formulation of claim 20, wherein the pH of the pharmaceutical formulation is between pH 4.0 and 5.5.

22. A pharmaceutical formulation comprising mannitol, sodium chloride, sodium phosphate, sodium citrate, citric acid, polysorbate 80, and a TNF inhibitor,

wherein the TNF inhibitor is at a concentration of at least 45 mg/ml, and

wherein the viscosity of the formulation is less than 400 cP.

23. A pharmaceutical formulation comprising sucrose, sodium chloride, sodium phosphate, and a TNF inhibitor comprising the 40 kD TNF inhibitor,

wherein the TNF inhibitor is at a concentration of at least 45 mg/ml, and

wherein the viscosity of the formulation is less than 400 cP.