Chimeric alkaline phosphatase-like proteins
The invention relates to improved alkaline phosphatases, pharmaceutical compositions comprising improved alkaline phosphatases and the use of improved alkaline phosphatases for preventing, treating or curing diseases.
1. A protein having phosphatase activity, wherein said protein comprises an amino acid sequence of at least 200 consecutive amino acids having at least 90% sequence identity with SEQ ID NO: 5, an amino acid sequence of at least 50 consecutive amino acids having at least 90% sequence identity with SEQ ID NO: 6, and an amino acid sequence of at least 40 consecutive amino acids having at least 90% sequence identity with SEQ ID NO: 7, wherein the full length protein comprises an amino acid sequence having at least 95% sequence identity with the full length amino acid sequence of SEQ ID NO: 1, with the proviso that the amino acid at position 279 is leucine (L), the amino acid at position 328 is valine (V) and the amino acid at position 478 is leucine (L).
2. The protein of claim 1 which comprises an amino acid sequence having at least 98% sequence identity to the amino acid sequence of SEQ ID NO: 1, with the proviso that the amino acid at position 279 is leucine (L), the amino acid at position 328 is valine (V) and the amino acid at position 478 is leucine (L).
3. The protein of claim 1 , wherein said protein comprises an amino acid sequence of 300-365 consecutive amino acids having at least 95% sequence identity with SEQ ID NO: 5, an amino acid sequence of 60-65 consecutive amino acids having at least 95% sequence identity with SEQ ID NO: 6, and an amino acid sequence of 50-54 consecutive amino acids having at least 95% sequence identity with SEQ ID NO: 7, wherein the full length protein comprises an amino acid sequence having at least 95% sequence identity with the full length amino acid sequence of SEQ ID NO: 1, with the proviso that the amino acid at position 279 is leucine (L), the amino acid at position 328 is valine (V) and the amino acid at position 478 is leucine (L).
4. The protein of claim 1 , wherein said protein comprises an amino acid sequence of 350-365 consecutive amino acids having at least 98% sequence identity with SEQ ID NO: 5, an amino acid sequence of 62-65 consecutive amino acids having at least 98% sequence identity with SEQ ID NO: 6, and an amino acid sequence of 52-54 consecutive amino acids having at least 98% sequence identity with SEQ ID NO: 7, wherein the full length protein comprises an amino acid sequence having at least 98% sequence identity with the full length amino acid sequence of SEQ ID NO: 1, with the proviso that the amino acid at position 279 is leucine (L), the amino acid at position 328 is valine (V) and the amino acid at position 478 is leucine (L).
5. A polynucleotide comprising a nucleic acid sequence encoding the protein according to claim 1 .
6. A vector comprising the polynucleotide according to claim 5 .
7. The vector of claim 6 which is a cloning or expression vector.
8. A host cell comprising a vector according to claim 6 .
9. The host cell according to claim 8 , wherein said host cell is a CHO cell.
10. A method for producing the protein of claim 1 , comprising culturing the host cell of claim 8 and allowing the host cell to produce said protein.
11. A composition comprising the protein according to claim 1 and a pharmaceutically acceptable carrier, a diluent, or an excipient.