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 . An albumin fusion protein comprising a member selected from the group consisting of:
 (a) a Therapeutic protein:X and albumin comprising the amino acid sequence of SEQ ID NO: 18;   (b) a Therapeutic protein:X and a fragment or a variant of the amino acid sequence of SEQ ID NO: 18, wherein said fragment or variant has albumin activity;   (c) a Therapeutic protein:X and a fragment or a variant of the amino acid sequence of SEQ ID NO: 18, wherein said fragment or variant has albumin activity, and further wherein said albumin activity is the ability to prolong the shelf life of the Therapeutic protein:X compared to the shelf-life of the Therapeutic protein:X in an unflised state;   (d) a Therapeutic protein:X and a fragment or a variant of the amino acid sequence of SEQ ID NO: 18, wherein said fragment or variant has albumin activity, and further wherein the fragment or variant comprises the amino acid sequence of amino acids 1-387 of SEQ ID NO: 18;   (e) a fragment or variant of a Therapeutic protein:X and albumin comprising the amino acid sequence of SEQ ID NO: 18, wherein said fragment or variant has a biological activity of the Therapeutic protein:X;   (f) a Therapeutic protein:X, or fragment or variant thereof, and albumin, or fragment or variant thereof, of (a) to (e), wherein the Therapeutic protein:X, or fragment or variant thereof, is fused to the N-terminus of albumin, or the N-terminus of the fragment or variant of albumin;   (g) a Therapeutic protein:X, or fragment or variant thereof, and albumin, or fragment or variant thereof, of (a) to (e), wherein the Therapeutic protein:X, or fragment or variant thereof, is fused to the C-terminus of albumin, or the C-terminus of the fragment or variant of albumin;   (h) a Therapeutic protein:X, or fragment or variant thereof, and albumin, or fragment or variant thereof, of (a) to (e), wherein the Therapeutic protein:X, or fragment or variant thereof, is fused to the N-terminus and C-terminus of albumin, or the N-terminus and the C-terminus of the fragment or variant of albumin;   (i) a Therapeutic protein:X, or fragment or variant thereof, and albumin, or fragment or variant thereof, of (a) to (e), which comprises a first Therapeutic protein:X, or fragment or variant thereof, and a second Therapeutic protein:X, or fragment or variant thereof, wherein said first Therapeutic protein:X, or fragment or variant thereof, is different from said second Therapeutic protein:X, or fragment or variant thereof;   (j) a Therapeutic protein:X, or fragment or variant thereof, and albumin, or fragment or variant thereof, of (a) to (i), wherein the Therapeutic protein:X, or fragment or variant thereof, is separated from the albumin or the fragment or variant of albumin by a linker; and   (k) a Therapeutic protein:X, or fragment or variant thereof, and albumin, or fragment or variant thereof, of (a) to (j), wherein the albumin fusion protein has the following formula:
   R1-L-R2; R2-L-R1; or R1-L-R2-L-R1, 
    and further wherein R1 is Therapeutic protein:X, or fragment or variant thereof, L is a peptide linker, and R2 is albumin comprising the amino acid sequence of SEQ ID NO: 18 or a fragment or variant of albumin.   
     
     
         2 . The albumin fusion protein of  claim 1 , wherein the shelf-life of the albumin fusion protein is greater than the shelf-life of the Therapeutic protein:X, or fragment or variant thereof, in an unfused state. 
     
     
         3 . The albumin fusion protein of  claim 1 , wherein the in vitro biological activity of the Therapeutic protein:X, or fragment or variant thereof, fused to albumin, or fragment or variant thereof, is greater than the in vitro biological activity of the Therapeutic protein:X, or fragment or variant thereof, in an unfused state. 
     
     
         4 . The albumin fusion protein of  claim 1 , wherein the in vivo biological activity of the Therapeutic protein:X, or fragment or variant thereof, fused to albumin, or fragment or variant thereof, is greater than the in vivo biological activity of the Therapeutic protein:X, or fragment or variant thereof, in an unfused state. 
     
     
         5 - 13 . (canceled) 
     
     
         14 . The albumin fusion protein of  claim 1 , which is expressed in yeast. 
     
     
         15 - 16 . (canceled) 
     
     
         17 . The albumin fusion protein of  claim 1 , which is expressed by a mammalian cell. 
     
     
         18 - 19 . (canceled) 
     
     
         20 . A composition comprising the albumin fusion protein of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         21 . (canceled) 
     
     
         22 . A method of treating a disease or disorder in a patient, comprising the step of administering the albumin fusion protein of  claim 1 . 
     
     
         23 . The method of  claim 22 , wherein the disease or disorder comprises indication:Y. 
     
     
         24 . A method of treating a patient with a disease or disorder that is modulated by Therapeutic protein:X, or fragment or variant thereof, comprising the step of administering an effective amount of the albumin fusion protein of  claim 1 . 
     
     
         25 . The method of  claim 24 , wherein the disease or disorder is indication:Y. 
     
     
         26 . (canceled) 
     
     
         27 . A nucleic acid molecule comprising a polynucleotide sequence encoding the albumin fusion protein of  claim 1 . 
     
     
         28 . A vector comprising the nucleic acid molecule of  claim 27 . 
     
     
         29 . A host cell comprising the nucleic acid molecule of  claim 28 . 
     
     
         30 - 58 . (canceled) 
     
     
         59 . An albumin fusion protein comprising albumin, or a fragment or variant thereof, and a protein selected from the group consisting of:
 (a) serum cholinesterase;   (b) alpha-I antitrypsin;   (c) aprotinin;   (d) coagulation complex;   (e) von Willebrand factor;   (f) fibrinogen;   (g) factor VII;   (h) factor VIIA activated factor;   (i) factor VIII;   (j) factor IX;   (k) factor X;   (l) factor XIII;   (m) c1 inactivator;   (n) antithrombin III;   (o) thrombin;   (p) prothrombin;   (q) apo-lipoprotein;   (r) c-reactive protein;   (s) protein C; and   (t) immunoglobulin.   
     
     
         60 . (canceled)