Albumin fusion proteins

• US 20080213886A1
• Filed: 05/08/2006
• Published: 09/04/2008
• Est. Priority Date: 12/21/2001
• Status: Active Grant

• Current Assignee: Human Genome Sciences Incorporated (GSK plc)
• Original Assignee: Human Genome Sciences Incorporated (GSK plc)
• Inventors: Rosen, Craig A., Haseltine, William A., Ruben, Steven M.
• Granted Patent: US 7,847,079 B2
• Time in Patent Office: Days
• US Class Current: 435/358
• 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
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/04 Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof enzyme inhibitors A61K38/005; gastrins A61K38/2207, somatostatins A61K38/31, melanotropins A61K38/34 ; protease inhibitors A61K38/55
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 39/21 Retroviridae, e.g. equine infectious anemia virus
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• 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 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 : Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 : for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/10 : for impotence
• 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 19/02 : for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 : for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/06 : Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/08 : for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 : Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/04 : for myasthenia gravis
• CPC Class Codes: A61P 25/00 : Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/10 : for petit-mal
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 27/06 : Antiglaucoma agents or miotics
• CPC Class Codes: A61P 27/16 : Otologicals
• 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 3/00 : 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 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/08 : for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/12 : for electrolyte homeostasis
• CPC Class Codes: A61P 3/14 : for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 31/14 : for RNA viruses
• CPC Class Codes: A61P 31/16 : for influenza or rhinoviruses
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 31/22 : for herpes viruses
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 33/02 : Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/04 : Immunostimulants
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• 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
• CPC Class Codes: A61P 5/40 : Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
• CPC Class Codes: A61P 5/50 : for increasing or potentiating the activity of insulin
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 7/12 : Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/02 : Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• 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: 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
• CPC Class Codes: C07K 14/565 : IFN-beta
• CPC Class Codes: C07K 14/575 : Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin C07K14/665, e.g. corticotropin C07K14/695
• 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
• CPC Class Codes: C07K 14/82 : Translation products from oncogenes
• CPC Class Codes: C07K 16/00 : Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• 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
• CPC Class Codes: C12N 2740/16134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2740/16171 : Demonstrated in vivo effect
• CPC Class Codes: C12N 7/00 : Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00
• 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. A nucleic acid molecule comprising a first polynucleotide encoding two or more tandem GLP-1 polypeptides, wherein said GLP-1 polypeptides are selected from wild-type GLP-1, GLP-1 fragments, and GLP-1 variants, and a second polynucleotide encoding human albumin or a human albumin fragment or variant thereof.

2. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are wild-type GLP-1.

3. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are GLP-1 fragments.

4. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are GLP-1 variants.

5. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are at least one wild-type GLP-1 and at least one GLP-1 fragment.

6. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are at least one wild-type GLP-1 and at least one GLP-1 variant.

7. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are at least one GLP-1 fragment and at least one GLP-1 variant.

8. The nucleic acid molecule of claim 1, wherein said encoded GLP-1 fragments or GLP-1 variants are selected from the group:

a. GLP-1(9-36);

b. GLP-1(7-36);

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

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

9. The nucleic acid molecule of claim 8, wherein said encoded GLP-1 variants are two tandem GLP-1(7-36(A8G)).

10. The nucleic acid molecule of claim 9, wherein said two tandem GLP-1(7-36(A8G)) variants are positioned at the N-terminus of albumin.

11. The nucleic acid molecule of claim 9, wherein said two tandem GLP-1(7-36(A8G)) variants are positioned at the C-terminus of albumin.

12. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are positioned at the N-terminus of albumin.

13. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are positioned at the C-terminus of albumin.

14. An albumin fusion construct comprising the nucleic acid molecule of claim 1, which upon expression in a host produces an albumin fusion protein comprising two or more tandem GLP-1 polypeptides fused to human albumin or a human albumin fragment or variant thereof, wherein said albumin fusion construct is selected from the group:

a. 2900;

b. 2964;

c. 2803;

d. 2804;

e. 2945;

f. 2982;

g. 3070;

h. 3027;

i. 3028;

j. 3045;

k. 3046;

l. 3069;

m. 3071;

n. 3072;

o. 3085;

p. 3086;

q. 3087;

r. 3309; and

S. 2904.

15. The nucleic acid molecule of claim 1, which encodes an N-terminal methionine.

16. The nucleic acid molecule of claim 1, which encodes a signal sequence.

17. The nucleic acid molecule of claim 1, which comprises a heterologous polynucleotide.

18. The nucleic acid molecule of claim 17, wherein said heterologous polynucleotide is at least one selected from a vector sequence, a promoter sequence, a selectable marker, and a region for termination of transcription.

19. The nucleic acid molecule of claim 1, which is part of an expression cassette.

20. A vector comprising the nucleic acid molecule of claim 1.

21. An isolated host cell comprising the nucleic acid molecule of claim 1.

22. An isolated host cell comprising the vector of claim 20.

23. The isolated host cell of claim 21 or 22, which is prokaryotic or eukaryotic.

24. The isolated host cell of claim 23, which is a yeast cell.

25. The isolated host cell of claim 24, wherein said yeast cell is S. cerevisiae.

26. The isolated host cell of claim 23, which is a mammalian cell.

27. The isolated host cell of claim 26, wherein said mammalian cell is a CHO cell.

28. The nucleic acid molecule of claim 1, wherein said encoded GLP-1 polypeptides comprise at least one amino acid sequence selected from the group:

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

1808;

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

1249; and

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

1250.

29. The nucleic acid molecule of claim 1, comprising an amino acid sequence selected from the group:

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

1231;

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

1232;

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

1233;

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

1234;

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

1235;

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

1236;

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

1237;

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

1280;

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

1607;

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

1608;

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

1609;

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

1610;

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

1621;

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

1622;

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

1623;

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

1624;

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

1625;

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

1626; and

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

2170.

30. A nucleic acid molecule comprising the cDNA contained in ATCC Deposit No. PTA-4671.