Albumin fusion proteins
First Claim
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.
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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.
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Citations
30 Claims
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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.
- View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29)
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2. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are wild-type GLP-1.
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3. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are GLP-1 fragments.
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4. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are GLP-1 variants.
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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.
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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.
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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.
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8. The nucleic acid molecule of claim 1, wherein said encoded GLP-1 fragments or GLP-1 variants are selected from the group:
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a. GLP-1(9-36); b. GLP-1(7-36); c. GLP-1(7-36(A8G)); and d. GLP-1(7-36(A8S)).
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9. The nucleic acid molecule of claim 8, wherein said encoded GLP-1 variants are two tandem GLP-1(7-36(A8G)).
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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.
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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.
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12. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are positioned at the N-terminus of albumin.
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13. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are positioned at the C-terminus of albumin.
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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:
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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.
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15. The nucleic acid molecule of claim 1, which encodes an N-terminal methionine.
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16. The nucleic acid molecule of claim 1, which encodes a signal sequence.
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17. The nucleic acid molecule of claim 1, which comprises a heterologous polynucleotide.
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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.
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19. The nucleic acid molecule of claim 1, which is part of an expression cassette.
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20. A vector comprising the nucleic acid molecule of claim 1.
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21. An isolated host cell comprising the nucleic acid molecule of claim 1.
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22. An isolated host cell comprising the vector of claim 20.
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23. The isolated host cell of claim 21 or 22, which is prokaryotic or eukaryotic.
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24. The isolated host cell of claim 23, which is a yeast cell.
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25. The isolated host cell of claim 24, wherein said yeast cell is S. cerevisiae.
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26. The isolated host cell of claim 23, which is a mammalian cell.
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27. The isolated host cell of claim 26, wherein said mammalian cell is a CHO cell.
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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:
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(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.
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29. The nucleic acid molecule of claim 1, comprising an amino acid sequence selected from the group:
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(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.
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2. The nucleic acid molecule of claim 1, wherein said encoded tandem GLP-1 polypeptides are wild-type GLP-1.
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30. A nucleic acid molecule comprising the cDNA contained in ATCC Deposit No. PTA-4671.
Specification
- Resources
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Current AssigneeHuman Genome Sciences Incorporated (GSK plc)
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Original AssigneeHuman Genome Sciences Incorporated (GSK plc)
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InventorsRosen, Craig A., Haseltine, William A., Ruben, Steven M.
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Primary Examiner(s)Desai; Anand U
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Application NumberUS11/429,374Publication NumberTime in Patent Office1,674 DaysField of SearchNoneUS Class Current536/23.4CPC Class CodesA61K 31/155 Amidines (), e.g. guanidine...A61K 31/426 1,3-ThiazolesA61K 31/4439 containing a five-membered ...A61K 31/4965 Non-condensed pyrazinesA61K 38/00 Medicinal preparations cont...A61K 38/04 Peptides having up to 20 am...A61K 38/17 from animals; from humans e...A61K 38/28 InsulinsA61K 39/21 Retroviridae, e.g. equine i...A61P 1/02 Stomatological preparations...A61P 1/04 for ulcers, gastritis or re...A61P 1/16 for liver or gallbladder di...A61P 1/18 for pancreatic disorders, e...A61P 11/00 Drugs for disorders of the ...A61P 11/02 Nasal agents, e.g. deconges...A61P 11/06 AntiasthmaticsA61P 13/02 of urine or of the urinary ...A61P 13/08 of the prostateA61P 13/10 of the bladderA61P 13/12 of the kidneysA61P 15/00 : Drugs for genital or sexual...A61P 15/08 : for gonadal disorders or fo...A61P 15/10 : for impotenceA61P 17/00 : Drugs for dermatological di...A61P 17/02 : for treating wounds, ulcers...A61P 19/02 : for joint disorders, e.g. a...A61P 19/04 : for non-specific disorders ...A61P 19/06 : Antigout agents, e.g. antih...A61P 19/08 : for bone diseases, e.g. rac...A61P 21/00 : Drugs for disorders of the ...A61P 21/04 : for myasthenia gravisA61P 25/00 : Drugs for disorders of the ...A61P 25/10 : for petit-malA61P 25/16 : Anti-Parkinson drugsA61P 25/28 : for treating neurodegenerat...A61P 27/02 : Ophthalmic agentsA61P 27/06 : Antiglaucoma agents or mioticsA61P 27/16 : OtologicalsA61P 29/00 : Non-central analgesic, anti...A61P 3/00 : Drugs for disorders of the ...A61P 3/04 : Anorexiants; Antiobesity ag...A61P 3/06 : AntihyperlipidemicsA61P 3/08 : for glucose homeostasis pan...A61P 3/10 : for hyperglycaemia, e.g. an...A61P 3/12 : for electrolyte homeostasisA61P 3/14 : for calcium homeostasis vit...A61P 31/00 : Antiinfectives, i.e. antibi...A61P 31/04 : Antibacterial agentsA61P 31/10 : AntimycoticsA61P 31/12 : AntiviralsA61P 31/14 : for RNA virusesA61P 31/16 : for influenza or rhinovirusesA61P 31/18 : for HIVA61P 31/20 : for DNA virusesA61P 31/22 : for herpes virusesA61P 33/00 : Antiparasitic agentsA61P 33/02 : Antiprotozoals, e.g. for le...A61P 33/06 : AntimalarialsA61P 35/00 : Antineoplastic agentsA61P 35/02 : specific for leukemiaA61P 35/04 : specific for metastasisA61P 37/02 : ImmunomodulatorsA61P 37/04 : ImmunostimulantsA61P 37/06 : Immunosuppressants, e.g. dr...A61P 37/08 : Antiallergic agents antiast...A61P 43/00 : Drugs for specific purposes...A61P 5/00 : Drugs for disorders of the ...A61P 5/06 : of the anterior pituitary h...A61P 5/14 : of the thyroid hormones, e....A61P 5/40 : Mineralocorticosteroids, e....A61P 5/50 : for increasing or potentiat...A61P 7/00 : Drugs for disorders of the ...A61P 7/04 : Antihaemorrhagics; Procoagu...A61P 7/06 : AntianaemicsA61P 7/12 : Antidiuretics, e.g. drugs f...A61P 9/00 : Drugs for disorders of the ...A61P 9/02 : Non-specific cardiovascular...A61P 9/04 : Inotropic agents, i.e. stim...A61P 9/06 : AntiarrhythmicsA61P 9/08 : Vasodilators for multiple i...A61P 9/10 : for treating ischaemic or a...A61P 9/12 : AntihypertensivesA61P 9/14 : Vasoprotectives; Antihaemor...C07K 14/005 : from virusesC07K 14/435 : from animals; from humansC07K 14/4713 : Autoimmune diseases, e.g. I...C07K 14/4723 : Cationic antimicrobial pept...C07K 14/475 : Growth factors; Growth regu...C07K 14/50 : Fibroblast growth factor [FGF]C07K 14/505 : Erythropoietin [EPO]C07K 14/51 : Bone morphogenetic factor; ...C07K 14/521 : ChemokinesC07K 14/525 : Tumour necrosis factor [TNF]C07K 14/535 : Granulocyte CSF; Granulocyt...C07K 14/54 : Interleukins [IL]C07K 14/5406 : IL-4C07K 14/55 : IL-2C07K 14/555 : Interferons [IFN]C07K 14/56 : IFN-alphaC07K 14/565 : IFN-betaC07K 14/575 : Hormones derived from pro-o...C07K 14/57563 : Vasoactive intestinal pepti...C07K 14/5759 : Products of obesity genes, ...C07K 14/585 : CalcitoninsC07K 14/59 : Follicle-stimulating hormon...C07K 14/60 : Growth hormone-releasing fa...C07K 14/605 : GlucagonsC07K 14/61 : Growth hormone [GH], i.e. s...C07K 14/62 : InsulinsC07K 14/635 : Parathyroid hormone, i.e. p...C07K 14/65 : Insulin-like growth factors...C07K 14/655 : SomatostatinsC07K 14/665 : derived from pro-opiomelano...C07K 14/705 : Receptors; Cell surface ant...C07K 14/7151 : for tumor necrosis factor [...C07K 14/765 : Serum albumin, e.g. HSAC07K 14/82 : Translation products from o...C07K 16/00 : Immunoglobulins [IGs], e.g....C07K 16/241 : Tumor Necrosis FactorsC07K 16/26 : against hormones ; against ...C07K 2317/10 : characterized by their sour...C07K 2317/622 : Single chain antibody (scFv)C07K 2317/76 : Antagonist effect on antige...C07K 2319/00 : Fusion polypeptideC07K 2319/20 : containing a tag with affin...C07K 2319/30 : Non-immunoglobulin-derived ...C07K 2319/31 : fusions, other than Fc, for...C07K 7/06 : having 5 to 11 amino acidsC12N 15/62 : DNA sequences coding for fu...C12N 2501/335 : Glucagon; Glucagon-like pep...C12N 2740/16111 : concerning HIV envC12N 2740/16122 : New viral proteins or indiv...C12N 2740/16134 : Use of virus or viral compo...C12N 2740/16171 : Demonstrated in vivo effectC12N 7/00 : Viruses; Bacteriophages; Co...C12N 9/0006 : acting on CH-OH groups as d...C12N 9/0008 : acting on the aldehyde or o...C12Y 101/01105 : Retinol dehydrogenase (1.1....C12Y 102/01 : with NAD+ or NADP+ as accep...C12Y 207/01095 : Kanamycin kinase (2.7.1.95)...