Growth hormone polypeptides fused to extended recombinant polypeptides and methods of making and using same
View Patent ↗The present invention relates to compositions comprising growth hormone linked to extended recombinant polypeptide (XTEN), isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of making and using such compositions in administration to animals.
1. An isolated fusion protein, comprising an amino acid sequence which is at least 95% identical to SEQ ID NO: 289 or 741, wherein the fusion protein comprises a growth hormone (GH) sequence that is at least 95% identical compared to an amino acid sequence selected from SEQ ID NO: 669 and SEQ ID NO: 2.
2. The isolated fusion protein of claim 1 , comprising a growth hormone sequence which is a bovine growth hormone sequence.
3. The isolated fusion protein of claim 2 , wherein the bovine growth hormone sequence is at least 95% identical to the amino acid sequence of SEQ ID NO: 669.
4. The isolated fusion protein of claim 3 , wherein the bovine growth hormone sequence has the amino acid sequence of SEQ ID NO: 669.
5. The isolated fusion protein of claim 1 , comprising a first extended recombinant polypeptide (XTEN) which is at least 95% identical to the amino acid sequence of SEQ ID NO:75.
6. The isolated fusion protein of claim 1 , wherein the growth hormone sequence is linked to an extended recombinant polypeptide (XTEN) via a spacer sequence, wherein the spacer sequence comprises between 1 to about 50 amino acid residues, and wherein the spacer sequence optionally comprises a cleavage sequence, and wherein the XTEN is at least 95% identical to an amino acid sequence chosen from SEQ ID NOS: 61 and 75.
7. The isolated fusion protein of claim 1 , wherein the fusion protein binds to the same target receptor of a corresponding native growth hormone that lacks the extended recombinant polypeptide (XTEN), and wherein said fusion protein retains at least about 0.1%-30% of the binding affinity of the corresponding growth hormone not linked to the XTEN.
8. A pharmaceutical composition comprising the isolated fusion protein of claim 1 , and a pharmaceutically acceptable carrier.
9. An isolated nucleic acid comprising a nucleotide sequence encoding the fusion protein of claim 1 or the complement thereof.
10. The isolated nucleic acid of claim 9 , wherein the polynucleotide molecule encoding the fusion protein comprises a nucleic acid sequence exhibiting at least 90% sequence identity compared to a nucleic acid sequence selected from SEQ ID NOs: 107-123.
11. An expression vector comprising the nucleic acid of claim 9 .
12. An isolated host cell comprising the nucleic acid of claim 9 , wherein the host cell is a eukaryotic host cell.
13. An isolated host cell comprising the nucleic acid of claim 9 , wherein the host cell is a prokaryotic host cell.
14. The isolated host cell of claim 13 , wherein the host cell is E. coli.
15. The isolated fusion protein of claim 1 , wherein the growth hormone is a porcine growth hormone.
16. The isolated fusion protein of claim 15 , wherein the porcine growth hormone sequence is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.
17. The isolated fusion protein of claim 16 , wherein the porcine growth hormone sequence has the amino acid sequence of SEQ ID NO: 2.
18. A method of enhancing a growth-hormone related parameter in an animal, comprising administering to the animal a physiologically effective amount of an isolated fusion protein, comprising an amino acid sequence which is at least 95% identical to SEQ ID NO: 741, wherein the fusion protein comprises a growth hormone (GH) sequence that is at least 95% identical compared to an amino acid sequence selected from SEQ ID NO: 669 and SEQ ID NO: 2.
19. The method of claim 18 , wherein the growth-hormone related parameter is selected from IGF-1 levels, IGFBP3 levels, growth velocity, total body fat, muscle mass, bone growth, lactation, duration of lactation, hoof growth, lipolysis, efficiency of converting feed to meat or milk, and multiplication rate of chondrocytes.
20. The method of claim 18 , wherein the isolated fusion protein comprises at least one extended recombinant polypeptide (XTEN) sequence which is at least 95% identical to an amino acid sequence selected from SEQ ID NOS: 61 and 75.
21. The method of claim 18 , wherein the growth hormone sequence is a bovine growth hormone sequence.
22. The method of claim 21 , wherein the bovine growth hormone sequence is at least 95% identical to the amino acid sequence of SEQ ID NO: 669.
23. The method of claim 22 , wherein the bovine growth hormone sequence has the amino acid sequence of SEQ ID NO: 669.
24. The method of claim 18 , wherein the growth hormone sequence is a porcine growth hormone sequence.
25. The method of claim 24 , wherein the porcine growth hormone sequence is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.
26. The isolated fusion protein of claim 25 , wherein the porcine growth hormone sequence has the amino acid sequence of SEQ ID NO: 2.