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 method for improving, reducing or removing symptoms in a subject suffering from a disease accompanied by a local or systemic zinc deficiency comprising administering to the subject: 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 90% 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); and wherein said disease is selected from sepsis-associated acute kidney injury, ischemic reperfusion kidney damage or a hypophosphatasia.
2. The method according to claim 1 , wherein said hypophosphatasia is selected from the group consisting of perinatal hypophosphatasia, infantile hypophosphatasia, childhood hypophosphatasia, and adult hypophosphatasia.
3. The method according to claim 1 , wherein the protein having phosphatase activity comprises an amino acid sequence having at least 95% 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).
4. The method according to claim 1 , wherein the protein having phosphatase activity 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).
5. The method according to claim 1 , wherein the protein having phosphatase activity 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).
6. The method according to claim 1 , wherein the protein having phosphatase activity 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).
7. The method according to claim 1 , wherein the protein having phosphatase activity comprises the amino acid sequence as set forth in SEQ ID NO: 1.
8. The method according to claim 1 , wherein the protein having phosphatase activity consists of the amino acid sequence as set forth in SEQ ID NO: 1.