Aqueous sustained-release formulations of proteins

• US 6,818,613 B2
• Filed: 11/07/2001
• Issued: 11/16/2004
• Est. Priority Date: 11/07/2001
• Status: Expired due to Term

• Current Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Original Assignee: Ortho-McNeil Pharmaceutical Incorporated (Johnson & Johnson)
• Inventors: Jin, Renzhe, Kelley, Marian, Rudolph, Sunitha, Sharma, Basant, Begum, Selima, Cheung, Wing K.
• Primary Examiner(s): MELLER, MICHAEL V
• Application Number:
  US10/037,369
• Publication Number:
  US 20030148938A1
• Time in Patent Office: 1,105 Days
• Field of Search: 514/8
• US Class Current: 514/7.7
• CPC Class Codes: A61K 38/1816 Erythropoietin [EPO]
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• 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: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid

Abstract

The present invention is directed to sustained-release pharmaceutical formulations of therapeutic proteins containing carboxymethyl ether cellulose polymer and methods of manufacture and use thereof.

Claims

1. A pharmaceutical formulation comprising:

a) a pharmaceutically active amount of erythropoietin;

b) a pharmaceutically acceptable pH buffering agent to provide a pH in a range of about pH 6 to about pH 9;

c) a tonicity agent in a concentration range of about 0 to about 200 millimolar; and

d) sodium carboxymethyl ether cellulose in a concentration range of about 0.5% to about 7% total formula weight, said sodium carboxymethyl ether cellulose having a molecular weight in a range of about 50,000 daltons to about 1,000,000 daltons.

2. The formulation of claim 1 wherein the erythropoietin is selected from the group consisting of recombinant human erythropoietin, epoietin alfa, epoietin omega, darbepoetin alfa, and PEG conjugated erythropoietin.

3. The formulation of claim 1 wherein the pH buffering agent is present in the formulation at a concentration in the range of about 10 mM to about 30 mM and wherein the pH buffering agent is a sodium phosphate monobasic/sodium phosphate dibasic buffer system.

4. The formulation of claim 1 wherein the tonicity agent is selected from the group consisting of NaCl, KCl, and glycine.

5. The formulation of claim 1 wherein the tonicity agent is NaCl at a concentration of about 75 mM to about 125 mM.

6. The formulation of claim 1 wherein the pH of the formulation is in the range of about 6.5 to about 7.4.