Albumin fusion proteins
First Claim
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1. An albumin fusion protein comprising a member selected from the group consisting of:
- (a) a brain derived neurotrophic factor protein and albumin, wherein albumin comprises the amino acid sequence of SEQ ID NO;
18;
(b) a brain derived neurotrophic factor protein and a fragment of the amino acid sequence of SEQ ID NO;
18, wherein said fragment has the ability to prolong the shelf-life of the brain derived neurotrophic factor protein compared to the shelf-life of the brain derived neurotrophic factor protein in an unfused state;
(c) a brain derived neurotrophic factor protein and a fragment of the amino acid sequence of SEQ ID NO;
18, wherein said fragment has the ability to prolong the shelf-life of the brain derived growth factor protein compared to the shelf-life of the brain derived neurotrophic factor protein in an unfused state, and further wherein the said fragment comprises amino acid residues 1-387 of SEQ ID NO;
18;
(d) a fragment of a brain derived neurotrophic factor protein and albumin comprising the amino acid sequence of SEQ ID NO;
18, wherein said fragment has a biological activity of the brain derived neurotrophic factor protein;
(e) a brain derived neurotrophic factor protein, or fragment thereof and albumin, or fragment thereof, of (a) to (d), wherein the brain derived neurotrophic factor protein or fragment thereof, is fused to the N-terminus of albumin or the N-terminus of the fragment of albumin;
(f) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the brain derived neurotrophic factor protein or fragment thereof, is fused to the C-terminus of albumin, or the C-terminus of the fragment of albumin;
(g) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the brain derived neurotrophic factor protein or fragment thereof, is fused to the N-terminus and C-terminus of albumin, or the N-terminus and the C-terminus of the fragment of albumin;
(h) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), which comprises a first brain derived neurotrophic factor protein or fragment thereof and a second brain derived neurotrophic factor protein or fragment thereof, wherein said first brain derived neurotrophic factor protein or fragment thereof is different from said second brain derived neurotrophic factor protein or fragment thereof;
(i) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (h), wherein the brain derived neurotrophic factor protein or fragment thereof, is separated from the albumin or the fragment of albumin by a linker; and
(j) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (i), wherein the brain derived neurotrophic factor protein or fragment thereof, 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 brain derived neurotrophic factor protein or fragment thereof, L is linker, and R2 is albumin comprising the amino acid sequence of SEQ ID NO;
18 or a fragment of albumin.
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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, disordrs or conditions using albumin fusion proteins of the invention.
259 Citations
25 Claims
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1. An albumin fusion protein comprising a member selected from the group consisting of:
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(a) a brain derived neurotrophic factor protein and albumin, wherein albumin comprises the amino acid sequence of SEQ ID NO;
18;
(b) a brain derived neurotrophic factor protein and a fragment of the amino acid sequence of SEQ ID NO;
18, wherein said fragment has the ability to prolong the shelf-life of the brain derived neurotrophic factor protein compared to the shelf-life of the brain derived neurotrophic factor protein in an unfused state;
(c) a brain derived neurotrophic factor protein and a fragment of the amino acid sequence of SEQ ID NO;
18, wherein said fragment has the ability to prolong the shelf-life of the brain derived growth factor protein compared to the shelf-life of the brain derived neurotrophic factor protein in an unfused state, and further wherein the said fragment comprises amino acid residues 1-387 of SEQ ID NO;
18;
(d) a fragment of a brain derived neurotrophic factor protein and albumin comprising the amino acid sequence of SEQ ID NO;
18, wherein said fragment has a biological activity of the brain derived neurotrophic factor protein;
(e) a brain derived neurotrophic factor protein, or fragment thereof and albumin, or fragment thereof, of (a) to (d), wherein the brain derived neurotrophic factor protein or fragment thereof, is fused to the N-terminus of albumin or the N-terminus of the fragment of albumin;
(f) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the brain derived neurotrophic factor protein or fragment thereof, is fused to the C-terminus of albumin, or the C-terminus of the fragment of albumin;
(g) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the brain derived neurotrophic factor protein or fragment thereof, is fused to the N-terminus and C-terminus of albumin, or the N-terminus and the C-terminus of the fragment of albumin;
(h) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), which comprises a first brain derived neurotrophic factor protein or fragment thereof and a second brain derived neurotrophic factor protein or fragment thereof, wherein said first brain derived neurotrophic factor protein or fragment thereof is different from said second brain derived neurotrophic factor protein or fragment thereof;
(i) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (h), wherein the brain derived neurotrophic factor protein or fragment thereof, is separated from the albumin or the fragment of albumin by a linker; and
(j) a brain derived neurotrophic factor protein or fragment thereof, and albumin or fragment thereof, of (a) to (i), wherein the brain derived neurotrophic factor protein or fragment thereof, 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 brain derived neurotrophic factor protein or fragment thereof, L is linker, and R2 is albumin comprising the amino acid sequence of SEQ ID NO;
18 or a fragment of albumin. - View Dependent Claims (2, 3, 4, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 24, 25)
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5. An albumin fusion protein comprising a brain derived neurotrophic factor protein or fragment thereof, inserted into an albumin, or fragment thereof, comprising the amino acid sequence of SEQ ID NO:
- 18 or fragment thereof.
- View Dependent Claims (7, 9, 11)
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6. An albumin fusion protein comprising a brain derived neurotrophic factor protein or fragment thereof, inserted into an albumin, or fragment thereof, comprising an amino acid sequence selected from the group consisting of:
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(a) amino acids residues 54 to 61 of SEQ ID NO;
18;
(b) amino acids residues 76 to 89 of SEQ ID NO;
18;
(c) amino acids residues 92 to 100 of SEQ ID NO;
18;
(d) amino acids residues 170 to 176 of SEQ ID NO;
18;
(e) amino acids residues 247 to 252 of SEQ ID NO;
18;
(f) amino acids residues 266 to 277 of SEQ ID NO;
18;
(g) amino acids residues 280 to 288 of SEQ ID NO;
18;
(h) amino acids residues 362 to 368 of SEQ ID NO;
18;
(i) amino acids residues 439 to 447 of SEQ ID NO;
18;
(j) amino acids residues 462 to 475 of SEQ ID NO;
18;
(k) amino acids residues 478 to 486 of SEQ ID NO;
18; and
(l) amino acids residues 560 to 566 of SEQ ID NO;
18. - View Dependent Claims (8, 10, 12)
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22. A method of extending the shelf-life of a brain derived neurotrophic factor protein or fragment thereof, comprising the step of fusing the brain derived neurotrophic factor protein or fragment thereof, to albumin, or fragment thereof, sufficient to extend the shelf-life of the brain derived neurotrophic factor protein, or fragment thereof, compared to the shelf-life of the brain derived neurotrophic factor protein, or fragment thereof in an unfused state.
Specification