Albumin fusion proteins

Abstract

Provided herein are albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins and vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins and using these nucleic acids, vectors, and/or host cells also are provided. Further described are pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

What is claimed: 
     
         1 . An albumin fusion protein comprising an insulin polypeptide fused to albumin, wherein the fusion protein has insulin activity, and wherein: (a) the insulin polypeptide is selected from a wild-type insulin, an insulin fragment, and an insulin variant, and (b) the albumin is selected from a wild-type albumin, an albumin fragment, and an albumin variant, wherein the albumin increases the serum plasma half-life of the insulin polypeptide. 
     
     
         2 . The albumin fusion protein of  claim 1 , wherein the insulin polypeptide comprises the amino acid sequence selected from SEQ ID NO: 569, SEQ ID NO: 572, SEQ ID NO: 576, SEQ ID NO: 577, SEQ ID NO: 1708, SEQ ID NO: 1709, SEQ ID NO: 1710, SEQ ID NO: 1711, SEQ ID NO: 1717, SEQ ID NO: 1718, SEQ ID NO: 1720, SEQ ID NO: 1721, SEQ ID NO: 1729, SEQ ID NO: 1730, SEQ ID NO: 1734, SEQ ID NO: 1745, SEQ ID NO: 1746, SEQ ID NO: 1747, SEQ ID NO: 1748, SEQ ID NO: 1754, SEQ ID NO: 1755, SEQ ID NO: 1763, SEQ ID NO: 1764, SEQ ID NO: 1765, SEQ ID NO: 1773, SEQ ID NO: 1774, SEQ ID NO: 1805, SEQ ID NO: 1806, SEQ ID NO: 1831, and SEQ ID NO: 1832. 
     
     
         3 . The albumin fusion protein of  claim 1 , wherein the albumin is selected from: a) human albumin; b)  Bos taurus  albumin; c)  Sus scrofa  albumin; d)  Equus caballus  albumin; e)  Ovis aries  albumin; f)  Salmo salar  albumin; g)  Gallus gallus  albumin; h)  Felis catus  albumin; i)  Canis Familiaris  albumin; j) an albumin fragment; k) an albumin variant; l) SEQ ID NO:1038; m) a fragment of albumin consisting of amino acids 1-194 of SEQ ID NO:1038; n) a fragment of albumin consisting of amino acids 195-387 of SEQ ID NO:1038; o) a fragment of albumin consisting of amino acids 388-585 of SEQ ID NO:1038; p) a fragment of albumin consisting of amino acids 1-387 of SEQ ID NO: 1038; q) a fragment of albumin consisting of amino acids 195-585 of SEQ ID NO:1038; r) a fragment of albumin consisting of amino acids 1-105 of SEQ ID NO:1038; s) a fragment of albumin consisting of amino acids 120-194 of SEQ ID NO:1038; t) a fragment of albumin consisting of amino acids 195-291 of SEQ ID NO:1038; u) a fragment of albumin consisting of amino acids 316-387 of SEQ ID NO:1038; v) a fragment of albumin consisting of amino acids 388-491 of SEQ ID NO:1038; w) a fragment of albumin consisting of amino acids 512-585 of SEQ ID NO:1038; x) a fragment of albumin that is 10, 15, 20, 25, 30, 50, 100, or 150 amino acids in length; y) a fragment of albumin consisting of one or more domains of albumin; and z) a variant of SEQ ID NO: 1038 selected from i) L407A; ii) L408V; iii) V409A; iv) R410A; v) K413Q; and vi) K414Q. 
     
     
         4 . The albumin fusion protein of  claim 1 , wherein the albumin fusion protein further comprises a leader sequence. 
     
     
         5 . The albumin fusion protein of  claim 4 , wherein the leader sequence is selected from: a) HSA; b) kex2; c) invertase; d) killer toxin; e) acid phosphatase; f) MFα-1; g) MPIF; h) TA57 propeptide; i) insulinase; and j) a fusion of at least one of the leader sequences selected from HSA, kex2, invertase, killer toxin, acid phosphatase, MFα-1, MPIF, TA57 propeptide and insulinase. 
     
     
         6 . The albumin fusion protein of  claim 1 , further comprising one or more additional therapeutic polypeptides. 
     
     
         7 . The albumin fusion protein of  claim 1  comprising the amino acid sequence selected from SEQ ID NO: 353, SEQ ID NO: 356, SEQ ID NO: 360, SEQ ID NO: 361, SEQ ID NO: 1540, SEQ ID NO: 1541, SEQ ID NO: 1542, SEQ ID NO: 1543, SEQ ID NO: 1549, SEQ ID NO: 1550, SEQ ID NO: 1552, SEQ ID NO: 1553, SEQ ID NO: 1561, SEQ ID NO: 1562, SEQ ID NO: 1566, SEQ ID NO: 1577, SEQ ID NO: 1578, SEQ ID NO: 1579, SEQ ID NO: 1580, SEQ ID NO: 1586, SEQ ID NO: 1587, SEQ ID NO: 1595, SEQ ID NO: 1596, SEQ ID NO: 1597, SEQ ID NO: 1605, SEQ ID NO: 1606, SEQ ID NO: 1637, SEQ ID NO: 1638, SEQ ID NO: 1663, and SEQ ID NO: 1664. 
     
     
         8 . A nucleotide sequence encoding the albumin fusion protein of  claim 1 . 
     
     
         9 . The nucleotide sequence of  claim 8 , wherein the insulin nucleotide sequence is selected from SEQ ID NO: 137, SEQ ID NO: 140, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 1372, SEQ ID NO: 1373, SEQ ID NO: 1374, SEQ ID NO: 1375, SEQ ID NO: 1381, SEQ ID NO: 1382, SEQ ID NO: 1384, SEQ ID NO: 1385, SEQ ID NO: 1393, SEQ ID NO: 1394, SEQ ID NO: 1398, SEQ ID NO: 1409, SEQ ID NO: 1410, SEQ ID NO: 1411, SEQ ID NO: 1412, SEQ ID NO: 1418, and SEQ ID NO: 1419, SEQ ID NO: 1427, SEQ ID NO: 1428, SEQ ID NO: 1429, SEQ ID NO: 1437, SEQ ID NO: 1438, SEQ ID NO: 1469, SEQ ID NO: 1470, SEQ ID NO: 1495, and SEQ ID NO: 1496. 
     
     
         10 . A construct expressing the albumin fusion protein of  claim 1 . 
     
     
         11 . The construct of  claim 10 , selected from ID 2250, 2255, 2276, 2278, 2656, 2668, 2669, 2671, 2821, 2822, 2832, 2877, 2878, 2882, 2885, 2891, 2897, 2930, 2931, 2942, 2986, 3025, 3133, 3134, 3197, 3198, 2726, 2727, 2784, and 2789. 
     
     
         12 . The construct of  claim 10 , selected from construct ID 2250, 2255 and 2276. 
     
     
         13 . The construct of  claim 12 , wherein said construct comprises the nucleotide sequence of ATCC Deposit No. PTA-3916, PTA-3917 or PTA-3918, and wherein said nucleotide sequence encodes insulin polypeptide sequence fused to albumin. 
     
     
         14 . A host cell expressing the albumin fusion protein of  claim 1 . 
     
     
         15 . The host cell of  claim 14 , wherein the host cell is a mammalian cell, a yeast cell or a prokaryotic cell. 
     
     
         16 . A method for expressing an albumin fusion protein comprising culturing the host cell of  claim 14  under conditions suitable for the expression of the albumin fusion protein and recovering the albumin fusion protein. 
     
     
         17 . An albumin fusion protein expressed by the host cell of  claim 14 , wherein the albumin fusion protein is glycosylated, non-glycosylated or a glycosylation isomer. 
     
     
         18 . A composition comprising the albumin fusion protein of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         19 . A kit comprising the composition of  claim 18  and instructions for the use thereof. 
     
     
         20 . A method of treating, preventing, diagnosing or ameliorating a disease, disorder or condition in a subject in need thereof comprising administering an effective amount of an albumin fusion protein comprising an insulin polypeptide fused to albumin, wherein the fusion protein has insulin activity, and wherein: (a) the insulin polypeptide is selected from a wild-type insulin, an insulin fragment, and an insulin variant, and (b) the albumin is selected from a wild-type albumin, an albumin fragment, and an albumin variant, wherein the albumin increases the serum plasma half-life of the insulin polypeptide. 
     
     
         21 . The method of  claim 20 , wherein the disease, disorder or condition 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, insulin-dependent diabetes mellitus, metabolic disorders, immune disorders, obesity, vascular disorders, suppression of body weight, suppression of appetite, Syndrome X, obesity associated with diabetes, heart disease associated with diabetes, hyperglycemia associated with diabetes, infections associated with diabetes, retinopathy associated with diabetes, and ulcers associated with diabetes.