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

1 . 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 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: 1038, 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, and (iii) said fusion protein has GLP-1 activity.  
     
     
         2 . The method of  claim 1 , wherein said tandemly oriented GLP-1 polypeptides are selected from wild type GLP-1 sequences.  
     
     
         3 . The method of  claim 1 , wherein said tandemly oriented GLP-1 polypeptides are selected from GLP-1 fragment sequences.  
     
     
         4 . The method of  claim 1 , wherein said tandemly oriented GLP-1 polypeptides are selected from GLP-1 variant sequences.  
     
     
         5 . The method of  claim 1 , wherein said GLP-1 fragments 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)).    
     
     
         6 . The method of  claim 5 , wherein said GLP-1 fragments or GLP-1 variants are selected from two tandemly oriented GLP-1 (7-36(A8G)).  
     
     
         7 . The method of  claim 6 , wherein said two tandemly oriented GLP-1(7-36(A8G)) are fused at the N-terminus or C-terminus of albumin, or albumin fragment or albumin variant.  
     
     
         8 . The method of  claim 1 , wherein said tandemly oriented GLP-1 polypeptides are fused at the N-terminus or C-terminus of albumin, or albumin fragment or albumin variant.  
     
     
         9 . 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;    l. 3069;    m. 3071;    n. 3072;    o. 3085;    p. 3086;    q. 3087;    r. 3309; and    s. 2904.    
     
     
         10 . The method of  claim 1 , wherein the albumin fusion protein is in a composition comprising a pharmaceutically acceptable carrier.  
     
     
         11 . 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 comprising two or more tandemly oriented GLP-1 polypeptides fused to albumin comprising the amino acid sequence of SEQ ID NO:1038, or albumin fragment or albumin variant thereof, wherein said GLP-1 polypeptides comprise at least one of an amino acid sequence selected from the group consisting of: 
 (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.    
     
     
         12 . The method of  claim 11 , wherein said GLP-1 polypeptides comprise at least 1 amino acid sequence of (a).  
     
     
         13 . The method of  claim 11 , wherein said GLP-1 polypeptides comprise at least two amino acid sequences of (a).  
     
     
         14 . The method of  claim 11 , wherein said GLP-1 polypeptides comprise at least 1 amino acid sequence of (b).  
     
     
         15 . The method of  claim 11 , wherein said GLP-1 polypeptides comprise at least two amino acid sequences of (b).  
     
     
         16 . The method of  claim 11 , wherein said GLP-1 polypeptides comprise at least I amino acid sequence of (c).  
     
     
         17 . The method of  claim 11 , wherein said GLP-1 polypeptides comprise at least two amino acid sequences of (c).  
     
     
         18 . The method of  claim 11 , wherein said GLP-1 polypeptides are fused at the N-terminus or C-terminus of albumin.  
     
     
         19 . The method of  claim 11 , wherein the albumin fusion protein is in a composition comprising a pharmaceutically acceptable carrier.  
     
     
         20 . A method 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 comprising two or more tandemly oriented GLP-1 polypeptides fused to albumin, wherein said albumin fusion protein comprises an amino acid sequence selected from the group consisting of: 
 (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 SEQIDNO: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 20 , wherein the albumin fusion protein is in a composition comprising a pharmaceutically acceptable carrier.  
     
     
         22 . 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 bloceing the secretion of glucagon in a patient, comprising administering to said patient an albumin fusion protein comprising two or more tandemly oriented GLP-1 polypeptides fused to albumin, wherein said fusion protein is produced from a host cell comprising the amino acid sequence of the 3070 construct contained in ATCC Deposit No. PA-4671.  
     
     
         23 . The method of  claim 22 , wherein the albumin fusion protein is in a composition comprising a pharmaceutically acceptable carrier.