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 tissue inhibitor metalloproteinase-1 (TIMP-1) protein and albumin, wherein albumin comprises the amino acid sequence of SEQ ID NO;
18;
(b) a (TIMP-1) 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 (TIMP-1) protein compared to the shelf-life of the (TIMP-1) protein in an unfused state;
(c) a (TIMP-1) protein and a fragment of the amino and sequence of SEQ ID NO;
18, wherein said fragment has the ability to prolong the shelf-life of the (TIMP-1) protein compared to the shelf-life of the (TIMP-1) 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 (TIMP-1) protein and albumin comprising the amino acid sequence of SEQ ID NO;
18, wherein said fragment has a biological activity of the (TIMP-1) protein;
(e) a (TIMP-1) protein, or fragment thereof and albumin, or fragment thereof, of (a) to (d), wherein the (TIMP-1) protein or fragment thereof is fused to the N-terminus of albumin or the N-terminus of the fragment of albumin;
(f) a (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the (TIMP-1) protein or fragment thereof, is fused to the C-terminus of albumin, or the C-terminus of the fragment of albumin;
(g) a (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the (TIMP-1) 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 (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), which comprises a first (TIMP-1) protein or fragment thereof and a second (TIMP-1) protein or fragment thereof, wherein said first (TIMP-1) protein or fragment thereof is different from said second (TIMP-1) protein or fragment thereof;
(i) a (TIMP-1) proten or fragment thereof, and albumin or fragment thereof, of (a) to (h), wherein the (TIMP-1) protein or fragment thereof, is separated from the albumin or the fragment of albumin by a linker; and
(j) a (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (i), wherein the (TIMP-1) 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 (TIMP-1) 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.
134 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 tissue inhibitor metalloproteinase-1 (TIMP-1) protein and albumin, wherein albumin comprises the amino acid sequence of SEQ ID NO;
18;
(b) a (TIMP-1) 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 (TIMP-1) protein compared to the shelf-life of the (TIMP-1) protein in an unfused state;
(c) a (TIMP-1) protein and a fragment of the amino and sequence of SEQ ID NO;
18, wherein said fragment has the ability to prolong the shelf-life of the (TIMP-1) protein compared to the shelf-life of the (TIMP-1) 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 (TIMP-1) protein and albumin comprising the amino acid sequence of SEQ ID NO;
18, wherein said fragment has a biological activity of the (TIMP-1) protein;
(e) a (TIMP-1) protein, or fragment thereof and albumin, or fragment thereof, of (a) to (d), wherein the (TIMP-1) protein or fragment thereof is fused to the N-terminus of albumin or the N-terminus of the fragment of albumin;
(f) a (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the (TIMP-1) protein or fragment thereof, is fused to the C-terminus of albumin, or the C-terminus of the fragment of albumin;
(g) a (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), wherein the (TIMP-1) 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 (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (d), which comprises a first (TIMP-1) protein or fragment thereof and a second (TIMP-1) protein or fragment thereof, wherein said first (TIMP-1) protein or fragment thereof is different from said second (TIMP-1) protein or fragment thereof;
(i) a (TIMP-1) proten or fragment thereof, and albumin or fragment thereof, of (a) to (h), wherein the (TIMP-1) protein or fragment thereof, is separated from the albumin or the fragment of albumin by a linker; and
(j) a (TIMP-1) protein or fragment thereof, and albumin or fragment thereof, of (a) to (i), wherein the (TIMP-1) 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 (TIMP-1) 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 tissue inhibitor metalloproteinase-1 (TIMP-1) 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 tissue inhibitor metalloproteinase-1 (TIMP-1) 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 tissue inhibitor metalloproteinase-1 (TIMP-1) protein or fragment thereof, comprising the step of fusing the (TIMP-1) protein or fragment thereof, to albumin, or fragment thereof, sufficient to extend the shelf-life of the (TIMP-1) protein, or fragment thereof, compared to the shelf-life of the (TIMP-1) protein, or thereof in an unfused state.
Specification