Formulated composition

• US 7,186,686 B2
• Filed: 05/06/2003
• Issued: 03/06/2007
• Est. Priority Date: 04/08/1999
• Status: Expired due to Fees

• Current Assignee: Genentech, Inc. (Roche Holding AG)
• Original Assignee: Genentech, Inc. (Roche Holding AG)
• Inventors: Oeswein, James Q., Wang, Sharon X., Yeung, Douglas A., Smikahl, John R.
• Primary Examiner(s): Weber; Jon
• Assistant Examiner(s): Mohamed; Abdel A.
• Application Number:
  US10/431,175
• Publication Number:
  US 20030195142A1
• Time in Patent Office: 1,400 Days
• Field of Search: 514/3, 514/4, 514/866, 530/303, 530/399, 435/808
• US Class Current: 514/6.5
• 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 47/40 Cyclodextrins; 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: Y10S 435/808 Optical sensing apparatus
• CPC Class Codes: Y10S 530/808 Materials and products related to genetic engineering or hybrid or fused cell technology, e.g. hybridoma, monoclonal products

Abstract

A composition is disclosed that comprises a mixture of polypeptides of opposite charge and an excipient selected from the group consisting of arginine, lysine, glutamic acid, sodium dodecyl sulfate, beta-hydroxy cyclodextrin, and beta-cyclodextrin sulfobutyl ether.

Claims

1. A stable liquid composition comprising a mixture of insulin-like growth factor-I (IGF-I) and insulin, and an excipient selected from the group consisting of arginine, lysine, glutamate, sodium dodecyl sulfate, and a combination of beta-hydroxy cyclodextrin and arginine, wherein the excipient is present in a concentration keeping said IGF-I and insulin completely dissolved in the composition.

2. The composition of claim 1 additionally comprising histidine and a phenol, and wherein the excipient is arginine.

3. The composition of claim 1 wherein the excipient is sodium dodecyl sulfate in a concentration of about 1–

10% and the volume;

volume ratio of insulin;

IGF-I is about 1;

1 to 6;

1.

4. The composition of claim 1 wherein the excipient is arginine in a concentration of about 100 to 300 mM and the volume:

volume ratio of insulin;

IGF-I is from about 0.1;

1 to 10;

1.

5. The composition of claim 4 further comprising beta-cyclodextrin sulfobutyl ether in a concentration of about 1–

10%.

6. The composition of claim 1 wherein insulin:

IGF-I is present in a volume;

volume ratio of from about 1;

15 to 15;

1.

7. The composition of claim 6 comprising about 5–

20 mg/ml IGF-I, about 2–

10 mg/ml insulin, about 100–

200 mM arginine, and further comprising about 5–

20 mM histidine at pH about 7–

7.5 and about 1–

5 mg/ml phenol.

8. The composition of claim 6 wherein insulin:

IGF-I is present in a volume;

volumc ratio of froth about 1;

6 to 6;

1.

9. The composition of claim 8 wherein insulin:

IGF-I is present in a volurne;

volume ratio of from about 0.2;

1 to about 1;

1.

10. The composition of claim 8 comprising about 10 mg/ml IGF-I, about 3–

4 mg/ml insulin, about 160 mM arginine, and further comprising about 10 mM histidine at pH 7.2 and about 3 mg/ml phenol.

11. A kit comprising:

(a) a container comprising an effective amount of the composition of claim 1; and

(b) instructions for using the above composition to treat a disorder against which the composition is effective.

12. The kit of claim 11 wherein the disorder is a hyperglycemic disorder.

13. A method for preparing the composition of claim 1 comprising mixing together as components (a) insulin-like growth factor-I (IGF-I) in an excipient selected from the group consisting of arginine, lysine, glutamate, sodium dodecyl sulfate, and a combination of beta-hydroxy cyclodextrin and arginine;

and as component (b) insulin in solution.