Long-acting veterinary polypeptides and methods of producing and administering same
A polypeptide and polynucleotides comprising at least two carboxy-terminal peptides (CTP) of chorionic gonadotrophin attached to a non-human peptide-of-interest are disclosed. Pharmaceutical compositions comprising the non-human polypeptides and polynucleotides of the invention and methods of using both human and non-human polypeptides and polynucleotides are also disclosed.
1 . A polypeptide comprising a non-human peptide of interest and at least two chorionic gonadotrophin carboxy terminal peptides, wherein a first chorionic gonadotrophin carboxy terminal peptide of said at least two chorionic gonadotrophin carboxy terminal peptides is attached to an amino terminus of said non-human peptide of interest, and a second chorionic gonadotrophin carboxy terminal peptide of said at least two chorionic gonadotrophin carboxy terminal peptides is attached to a carboxy terminus of said non-human peptide of interest.
2 . The polypeptide of claim 1 , wherein the sequence of at least 1 of said at least two chorionic gonadotrophin carboxy terminal peptides comprises an amino acid sequence selected from sequences set forth in SEQ ID NO: 17 and SEQ ID NO: 18.
3 . The polypeptide of claim 1 , wherein at least 1 of said at least two chorionic gonadotrophin carboxy terminal peptides is truncated.
4 . The polypeptide of claim 1 , wherein said non-human peptide of interest is a GH peptide.
5 . The polypeptide of claim 1 , wherein said non-human peptide of interest is an EPO peptide.
6 . The polypeptide of claim 1 , wherein said non-human peptide of interest is selected from an interferon peptide and a GLP-1 peptide.
7 . The polypeptide of claim 1 , wherein said non-human peptide of interest is glycosylated.
8 . The polypeptide of claim 1 , wherein said non-human peptide of interest is non-glycosylated.
9 . The polypeptide of claim 1 , wherein at least 1 of said at least two chorionic gonadotrophin carboxy terminal peptides is glycosylated.
10 . The polypeptide of claim 1 , wherein at least 1 of said at least two chorionic gonadotrophin carboxy terminal peptides is attached to said non-human peptide of interest via a linker.
11 . The polypeptide of claim 10 , wherein said linker is a peptide bond.
12 . The polypeptide of claim 1 , further comprising a signal peptide.
13 . The polypeptide of claim 12 , wherein said signal peptide is as set forth in SEQ ID NO: 19.
14 . The polypeptide of claim 1 , wherein said polypeptide further comprises a third chorionic gonadotrophin carboxy terminal peptide attached in tandem to said second chorionic gonadotrophin carboxy terminal peptide.
15 . A polynucleotide comprising a coding portion encoding a polypeptide, said polypeptide comprising a non-human peptide of interest and at least two chorionic gonadotrophin carboxy terminal peptides, wherein a first chorionic gonadotrophin carboxy terminal peptide of said at least two chorionic gonadotrophin carboxy terminal peptides is attached to an amino terminus of said non-human peptide of interest, and a second chorionic gonadotrophin carboxy terminal peptide of said at least two chorionic gonadotrophin carboxy terminal peptides is attached to the carboxy terminus of said non-human peptide of interest.
16 . The polynucleotide of claim 15 , wherein said polypeptide further comprises a third chorionic gonadotrophin carboxy terminal peptide attached in tandem to said second chorionic gonadotrophin carboxy terminal peptide.
17 . The polynucleotide of claim 15 , wherein said non-human peptide of interest is a GH peptide.
18 . The polynucleotide of claim 15 , wherein said non-human peptide of interest is an EPO peptide.
19 . The polynucleotide of claim 15 , wherein said non-human peptide of interest is selected from an interferon peptide and a GLP-1 peptide.
20 . The polynucleotide of claim 15 , wherein said non-human polypeptide further comprises a signal peptide.
21 . The polynucleotide of claim 20 , wherein the sequence of said signal peptide is as set forth in SEQ ID NO: 19.
22 . A cell comprising the expression vector of claim 22 .
23 . A veterinary pharmaceutical composition comprising the expression vector of claim 22 .
24 . A method of treating or reducing the incidence associated with a growth, weight-related, or metabolic condition in a non-human subject, said method comprising administering to said subject a therapeutically effective amount of a polypeptide, said polypeptide comprising:
(a) a peptide of interest and (b) at least two chorionic gonadotrophin carboxy terminal peptides, wherein:
a first chorionic gonadotrophin carboxy terminal peptide of said at least two chorionic gonadotrophin carboxy terminal peptides is attached to an amino terminus of said peptide of interest, and a second chorionic gonadotrophin carboxy terminal peptide of said at least two chorionic gonadotrophin carboxy terminal peptides is attached to the carboxy terminus of said peptide of interest,
thereby treating said non-human subject having a growth, weight-related, or metabolic condition.
25 . A method of administering a peptide of interest to a non-human subject in need thereof, comprising the step of attaching a first chorionic gonadotrophin carboxy terminal peptide to an amino terminus of said peptide of interest and a second chorionic gonadotrophin carboxy terminal peptide to the carboxy terminus of said peptide of interest, thereby generating an improved polypeptide for administration to said subject, thereby administering a peptide of interest to a subject in need thereof.
26 . The method of claim 25 , further comprising the step of attaching a third chorionic gonadotrophin carboxy terminal peptide in tandem to said second chorionic gonadotrophin carboxy terminal peptide.
27 . The method of claim 25 , wherein the sequence of at least one of said chorionic gonadotrophin carboxy terminal peptides comprises an amino acid sequence selected from the sequences as set forth in SEQ ID NO: 17-18.
28 . The method of claim 25 , wherein said peptide of interest is a GH peptide.
29 . The method of claim 25 , wherein said peptide of interest is an EPO peptide.
30 . The method of claim 25 , wherein said peptide of interest is selected from an interferon peptide and a GLP-1 peptide.
31 . The method of claim 25 , wherein said peptide of interest is glycosylated.
32 . The method of claim 25 , wherein said improved polypeptide further comprises a signal peptide.
33 . The method of claim 32 , wherein the sequence of said signal peptide is as set forth in SEQ ID NO: 19.