Albumin fusion proteins

• US 20070244047A1
• Filed: 03/07/2007
• Published: 10/18/2007
• Est. Priority Date: 12/21/2001
• Status: Abandoned Application

• Current Assignee: Delta Biotechnology Limited, Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Original Assignee: Delta Biotechnology Limited, Human Genome Sciences Incorporated (GlaxoSmithKline PLC)
• Inventors: Rosen, Craig, Haseltine, William, Ruben, Steven
• Application Number:
  US11/714,841
• Publication Number:
  US 20070244047A1
• Time in Patent Office: Days
• US Class Current: 514/4.900
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/4965 Non-condensed pyrazines
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• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
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• CPC Class Codes: A61P 5/06 : of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
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• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
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• CPC Class Codes: A61P 9/06 : Antiarrhythmics
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• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 14/005 : from viruses
• CPC Class Codes: C07K 14/435 : from animals; from humans
• 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 14/4723 : Cationic antimicrobial peptides, e.g. defensins
• CPC Class Codes: C07K 14/475 : Growth factors; Growth regulators
• CPC Class Codes: C07K 14/50 : Fibroblast growth factor [FGF]
• CPC Class Codes: C07K 14/505 : Erythropoietin [EPO]
• CPC Class Codes: C07K 14/51 : Bone morphogenetic factor; Osteogenins; Osteogenic factor; Bone-inducing factor
• CPC Class Codes: C07K 14/521 : Chemokines
• CPC Class Codes: C07K 14/525 : Tumour necrosis factor [TNF]
• CPC Class Codes: C07K 14/535 : Granulocyte CSF; Granulocyte-macrophage CSF
• CPC Class Codes: C07K 14/54 : Interleukins [IL]
• CPC Class Codes: C07K 14/5406 : IL-4
• CPC Class Codes: C07K 14/55 : IL-2
• CPC Class Codes: C07K 14/555 : Interferons [IFN]
• CPC Class Codes: C07K 14/56 : IFN-alpha
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• CPC Class Codes: C07K 14/57563 : Vasoactive intestinal peptide [VIP]; Related peptides
• CPC Class Codes: C07K 14/5759 : Products of obesity genes, e.g. leptin, obese (OB), tub, fat
• CPC Class Codes: C07K 14/585 : Calcitonins
• CPC Class Codes: C07K 14/59 : Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g.hCG [human chorionic gonadotropin]; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: C07K 14/60 : Growth hormone-releasing factor [GH-RF], i.e. somatoliberin
• CPC Class Codes: C07K 14/605 : Glucagons
• CPC Class Codes: C07K 14/61 : Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: C07K 14/62 : Insulins
• CPC Class Codes: C07K 14/635 : Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: C07K 14/65 : Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2
• CPC Class Codes: C07K 14/655 : Somatostatins
• CPC Class Codes: C07K 14/665 : derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
• CPC Class Codes: C07K 14/705 : Receptors; Cell surface antigens; Cell surface determinants tumour specific antigens C07K14/4748
• CPC Class Codes: C07K 14/7151 : for tumor necrosis factor [TNF], for lymphotoxin [LT]
• CPC Class Codes: C07K 14/765 : Serum albumin, e.g. HSA
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• CPC Class Codes: C07K 16/241 : Tumor Necrosis Factors
• CPC Class Codes: C07K 16/26 : against hormones ; against hormone releasing or inhibiting factors
• CPC Class Codes: C07K 2317/10 : characterized by their source of isolation or production
• CPC Class Codes: C07K 2317/622 : Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2319/00 : Fusion polypeptide
• CPC Class Codes: C07K 2319/20 : containing a tag with affinity for a non-protein ligand
• CPC Class Codes: C07K 2319/30 : Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
• CPC Class Codes: C07K 2319/31 : fusions, other than Fc, for prolonged plasma life, e.g. albumin
• CPC Class Codes: C07K 7/06 : having 5 to 11 amino acids
• CPC Class Codes: C12N 15/62 : DNA sequences coding for fusion proteins
• CPC Class Codes: C12N 2501/335 : Glucagon; Glucagon-like peptide [GLP]; Exendin
• CPC Class Codes: C12N 2740/16111 : concerning HIV env
• CPC Class Codes: C12N 2740/16122 : New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
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• CPC Class Codes: C12N 9/0006 : acting on CH-OH groups as donors (1.1)
• CPC Class Codes: C12N 9/0008 : acting on the aldehyde or oxo group of donors (1.2)
• CPC Class Codes: C12Y 101/01105 : Retinol dehydrogenase (1.1.1.105)
• CPC Class Codes: C12Y 102/01 : with NAD+ or NADP+ as acceptor (1.2.1)
• CPC Class Codes: C12Y 207/01095 : Kanamycin kinase (2.7.1.95), i.e. neomycin-kanamycin phosphotransferase

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, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Claims

1. An albumin fusion protein comprising an exendin-4 polypeptide fused to an albumin polypeptide, wherein said exendin-4 polypeptide is selected from:

(a) a full-length exendin-4;

(b) a mature exendin-4;

(c) a fragment of exendin-4, wherein said fragment has exendin-4 activity;

(d) a polypeptide consisting of an amino acid sequence at least 90% identical to exendin-4, wherein said polypeptide has exendin-4 activity;

(e) a polypeptide consisting of an amino acid sequence at least 95% identical to exendin-4, wherein said polypeptide has exendin-4 activity;

(f) a polypeptide consisting of an amino acid sequence at least 99% identical to exendin-4, wherein said polypeptide has exendin-4 activity;

(g) a polypeptide comprising amino acids 1 to 87 of SEQ ID NO;

635;

(h) a polypeptide comprising amino acids 48 to 86 of SEQ ID NO;

635; and

wherein said albumin polypeptide is selected from;

(i) a full-length albumin;

(ii) a mature albumin;

(iii) a fragment of albumin, wherein said fragment of albumin has the ability to prolong the serum half-life of the exendin-4 polypeptide;

(iv) a polypeptide consisting of an amino acid sequence at least 95% identical to albumin, wherein said polypeptide has the ability to prolong the serum half-life of the exendin-4 polypeptide;

(v) amino acids 1 to 585 of SEQ ID NO;

1038; and

(vi) amino acids 1 to 387 of SEQ ID NO;

1038.

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

(a) 2469; and

(b) 2470.

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

(a) amino acids 25 to 648 of SEQ ID NO;

419; and

(b) amino acids 25 to 648 of SEQ ID NO;

420.

4. The albumin fusion protein of claim 1, wherein said exendin-4 polypeptide is fused to the N-terminus, the C-terminus, or both the N-terminus and C-terminus of said albumin polypeptide.

5. The albumin fusion protein of claim 1, which is expressed in a host cell.

6. The albumin fusion protein of claim 5, wherein said host cell is a yeast, mammalian, or bacterial cell.

16. A method of treating a disease or disorder in a patient comprising the step of administering an effective amount of the albumin fusion protein of claim 1.

17. The method of claim 16, wherein the disease or disorder is selected from:

hyperglycemia, diabetes, diabetes insipidus, diabetes mellitus, type 1 diabetes, type 2 diabetes, insulin resistance, insulin deficiency, hyperlipidemia, hyperketonemia, non-insulin dependent diabetes mellitus (NIDDM), insulin-dependent diabetes mellitus (IDDM), obesity, heart disease, infections, retinopathy, ulcers, metabolic disorders, immune disorders, vascular disorders, suppression of body weight, suppression of appetite, and syndrome X.

18. The method of claim 17, wherein the disease or disorder is diabetes.

19. The method of claim 17, wherein the disease or disorder is obesity or of losing weight in a patient.

20. A method of stimulating insulin synthesis and release, enhancing adipose, muscle or liver tissue sensitivity towards insulin uptake, stimulating glucose uptake, slowing digestive process, or blocking the secretion of glucagon in a patient, comprising administering to said patient an albumin fusion protein of claim 1.

7. A nucleic acid molecule comprising a first polynucleotide and a second polynucleotide, wherein said first polynucleotide encodes an exendin-4 polypeptide selected from:

(a) a full-length exendin-4;

(b) a mature exendin-4;

(c) a fragment of exendin-4, wherein said fragment has exendin-4 activity;

(d) a polypeptide consisting of an amino acid sequence at least 90% identical to exendin-4, wherein said polypeptide has exendin-4 activity;

(e) a polypeptide consisting of an amino acid sequence at least 95% identical to exendin-4, wherein said polypeptide has exendin-4 activity;

(f) a polypeptide consisting of an amino acid sequence at least 99% identical to exendin-4, wherein said polypeptide has exendin-4 activity;

(g) a polypeptide comprising amino acids 1 to 87 of SEQ ID NO;

635;

(h) a polypeptide comprising amino acids 48 to 86 of SEQ ID NO;

635; and

wherein said second polynucleotide encodes an albumin polypeptide selected from;

(i) a full-length albumin;

(ii) a mature albumin;

(iii) a fragment of albumin, wherein said fragment of albumin has the ability to prolong the serum half-life of the exendin-4 polypeptide;

(iv) a polypeptide consisting of an amino acid sequence at least 95% identical to albumin, wherein said polypeptide has the ability to prolong the serum half-life of the exendin-4 polypeptide;

(v) amino acids 1 to 585 of SEQ ID NO;

1038; and

(vi) amino acids 1 to 387 of SEQ ID NO;

1038.

8. An albumin fusion construct comprising the nucleic acid molecule of claim 7, which upon expression in a host cell produces an albumin fusion protein comprising exendin-4 fused to human albumin or a human albumin fragment or variant, wherein said albumin fusion construct is selected from:

(a) 2469; and

(b) 2470.

9. A vector comprising the nucleic acid molecule of claim 7.

10. An isolated host cell comprising the nucleic acid molecule of claim 7.

11. An isolated host cell comprising the vector of claim 9.

12. An isolated host cell comprising the albumin fusion construct of claim 8.

13. A method for producing a fusion protein, comprising:

(a) culturing the host cell of claim 10 under conditions suitable to produce the fusion protein encoded by said polynucleotide; and

(b) recovering said fusion protein.

14. A method for producing a fusion protein, comprising:

(a) culturing the host cell of claim 11 under conditions suitable to produce the fusion protein encoded by said vector; and

(b) recovering said fusion protein.

15. A method for producing a fusion protein, comprising:

(a) culturing the host cell of claim 12 under conditions suitable to produce the fusion protein encoded by said albumin fusion construct; and

(b) recovering said fusion protein.