Albumin fusion proteins

• US 7,977,306 B2
• Filed: 07/02/2007
• Issued: 07/12/2011
• Est. Priority Date: 12/21/2001
• Status: Expired due to Term

• Current Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Rosen, Craig A., Haseltine, William A., Ruben, Steven M.
• Primary Examiner(s): CARLSON, KAREN C
• Application Number:
  US11/772,591
• Publication Number:
  US 20080293629A1
• Time in Patent Office: 1,471 Days
• Field of Search: 514/2
• US Class Current: 514/2
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07K 14/4713 Autoimmune diseases, e.g. Insulin-dependent diabetes mellitus, multiple sclerosis, rheumathoid arthritis, systemic lupus erythematosus; Autoantigens
• CPC Class Codes: C07K 14/76 Albumins
• CPC Class Codes: C07K 14/765 Serum albumin, e.g. HSA
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins

Abstract

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating or preventing diseases, disorders or conditions related to diabetes mellitus using albumin fusion proteins of the invention.

Claims

1. A method of treating diabetes in a patient, comprising administering an albumin fusion protein comprising two or more tandemly oriented GLP-1 polypeptides, wherein (i) said GLP-1 polypeptides are selected from wild-type GLP-1, GLP -1 fragments, and GLP-1 variants, fused to albumin comprising the amino acid sequence of SEQ ID NO:

327, an albumin fragment, or albumin variant thereof, (ii) said albumin fragment or albumin variant increases the serum plasma half-life of the GLP-1 polypeptides, (iii) said fusion protein has GLP-1 activity, and (iv) wherein said patient is also suffering from a condition selected from the group consisting of;

(a) neural disorder;

(b) neuropathy;

(c) retinopathy;

(d) cardiovascular disorder;

(e) renal disorder; and

(f) obesity.

2. The method of claim 1 wherein the diabetes is Type I diabetes.

3. The method of claim 1 wherein the diabetes is Type II diabetes.

4. The method of claim 1 wherein the cardiovascular disorder is heart disease.

5. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are selected from wild type GLP-1 sequences.

6. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are selected from GLP-1 fragment sequences.

7. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are selected from GLP-1 variant sequences.

8. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are selected from at least one wild type GLP-1 sequence fused to at least one GLP-1 fragment sequence.

9. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are selected from at least one wild type GLP-1 sequence fused to at least one GLP-1 variant sequence.

10. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are selected from at least one GLP-1 fragment sequence fused to at least one GLP-1 variant sequence.

11. The method of claim 1, wherein said GLP-1fragments or GLP-1 variants are selected from:

a. GLP-1 (9-36);

b. GLP-1 (7-36);

c. GLP-1 (7-36(A8G)); and

d. GLP-1 (7-36(A8S)).

12. The method of claim 11, wherein said GLP-1fragments or GLP-1 variants are selected from two tandemly oriented GLP-1 (7-36(A8G)).

13. The method of claim 12, wherein said two tandemly oriented GLP-1(7-36(A8G)) are fused at the N-terminus to albumin.

14. The method of claim 12, wherein said two tandemly oriented GLP-1(7-36(A8G)) are fused at the C-terminus to albumin.

15. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are fused at the N-terminus to albumin.

16. The method of claim 1, wherein said tandemly oriented GLP-1 polypeptides are fused at the C-terminus to albumin.

17. The method of claim 1, wherein said albumin fusion protein is produced from a host cell comprising a construct which expresses said albumin fusion protein, and wherein said construct is selected from:

a. 2900;

b. 2964;

c. 2803;

d. 2804;

e. 2945;

f. 2982;

g. 3070;

h. 3027;

i. 3028;

j. 3045;

k. 3046;

I. 3069;

m. 3071;

n. 3072;

o. 3085;

p. 3086;

q. 3087;

r. 3309; and

s. 2904.

18. The method of claim 1, wherein the albumin fusion protein is in a composition comprising a pharmaceutically acceptable carrier.

19. The method of claim 1, wherein said GLP-1 polypeptides comprise at least one amino acid sequence selected from:

(a) amino acids 1 to 30 of SEQ ID NO;

698;

(b) amino acids 100 to 127 of SEQ ID NO;

429; and

(c) amino acids 98 to 127 of SEQ ID NO;

430;

and wherein said fusion protein has GLP-1 activity.

20. The method of claim 1, wherein said albumin fusion protein comprises an amino acid sequence selected from:

(a) amino acids 25 to 669 of SEQ ID NO;

419;

(b) amino acids 25 to 669 of SEQ ID NO;

420;

(c) amino acids 25 to 669 of SEQ ID NO;

421;

(d) amino acids 25 to 667 of SEQ ID NO;

422;

(e) amino acids 25 to 669 of SEQ ID NO;

423;

(f) amino acids 25 to 669 of SEQ ID NO;

424;

(g) amino acids 25 to 667 of SEQ ID NO;

425;

(h) amino acids 30 to 674 of SEQ ID NO;

447;

(i) amino acids 20 to 664 of SEQ ID NO;

598;

(j) amino acids 20 to 664 of SEQ ID NO;

599;

(k) amino acids 19 to 663 of SEQ ID NO;

600;

(l) amino acids 19 to 663 of SEQ ID NO;

601;

(m) amino acids 24 to 668 of SEQ ID NO;

609;

(n) amino acids 86 to 730 of SEQ ID NO;

610;

(o) amino acids 18 to 662 of SEQ ID NO;

611;

(p) amino acids 86 to 730 of SEQ ID NO;

612;

(q) amino acids 24 to 668 of SEQ ID NO;

613;

(r) amino acids 18 to 662 of SEQ ID NO;

614; and

(s) amino acids 30 to 673 of SEQ ID NO;

834;

and wherein said fusion protein has GLP-1 activity.

21. The method of claim 1, wherein said albumin fusion protein is produced from a host cell comprising the amino acid sequence of the 3070 construct contained in ATCC Deposit No. PTA-4671.