Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing

• US 20030236196A1
• Filed: 06/12/2003
• Published: 12/25/2003
• Est. Priority Date: 06/20/2002
• Status: Active Grant

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Shi, Lei, Chang, Byeong, Kerwin, Bruce
• Granted Patent: US 7,700,722 B2
• Time in Patent Office: Days
• US Class Current: 514/21.2
• 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 stable pharmaceutical formulation comprising at least 45 mg/ml PEGsTNF-R1, at least one tonicity modifier that is not NaCl, a surfactant and a buffer, wherein said pharmaceutical formulation is between pH 4.0 and 5.5 and wherein the viscosity is less than 400 cP.

2. The pharmaceutical formulation of claim 1 wherein the tonicity modifier is sorbitol and/or glycine.

3. The pharmaceutical formulation of claim 2 wherein the sorbitol is from zero to 5.48% (w/v).

4. The pharmaceutical formulation of claim 3 wherein the sorbitol is from 2.56% to 5.48% (w/v).

5. The pharmaceutical formulation of claim 3 wherein the sorbitol is 5.48% (w/v).

6. The pharmaceutical formulation of claim 2 wherein the glycine is from zero to 2.19% (w/v).

7. The pharmaceutical formulation of claim 6 wherein the glycine is from 1% to 2.19% (w/v).

8. The pharmaceutical formulation of claim 6 wherein the glycine is 2.19% (w/v).

9. The pharmaceutical formulation of claim 2 wherein the Glycine is 1.10% (w/v) and the Sorbitol is 2.74% (w/v).

10. The pharmaceutical formulation of claim 1 wherein the buffer is acetate.

11. The pharmaceutical formulation of claim 10 wherein the pH is 5.0.

12. The pharmaceutical formulation of claim 1 wherein the viscosity is less than 200 cP.

13. The pharmaceutical formulation of claim 1 wherein the PEGsTNF-R1 is 55 mg/ml.

14. A pre-filled syringe containing the pharmaceutical formulation of any of one of claims 1-13.

15. An article of manufacture comprising a container holding a stable pharmaceutical formulation comprising at least 45 mg/ml PEGsTNF-R1, at least one tonicity modifier that is not NaCl, and a buffer, wherein said pharmaceutical formulation is between pH 4.0 and 5.5 and wherein the viscosity is less than 400 cP.

16. A method of making a stable pharmaceutical formulation comprising:

a) admixing at least 45 mg/ml PEGsTNF-R1, at least one tonicity modifier that is not NaCl, and a buffer, and

b) adjusting the pH to between pH 4.0 and 5.5, wherein said pharmaceutical formulation has a viscosity less than 400 cP.