Proteases for Pharmaceutical Use
The pharmaceutical use of proteases related to amino acids 1-274 of SEQ ID NO: 2, the serine protease derived from Bacillus licheniformis , which is also designated subtilisin Carlsberg, optionally in combination with a lipase and/or an amylase. Examples of medical indications are: Treatment of digestive disorders, pancreatic exocrine insufficiency (PEI), pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II.
1 - 19 . (canceled)
20 . An isolated protease having at least 50% identity to amino acids 1-274 of SEQ ID NO: 2, for use as a medicament.
21 . The protease of claim 20 , wherein
(a) the protease comprises an amino acid sequence selected from the group consisting of amino acids 1-274 of SEQ ID NO: 2, amino acids 1-274 of SEQ ID NO: 5, amino acids 1-275 of SEQ ID NO: 6, amino acids 1-275 of SEQ ID NO: 7, amino acids 1-275 of SEQ ID NO: 8, amino acids 1-275 of SEQ ID NO: 9, amino acids 1-275 of SEQ ID NO: 10, amino acids 1-269 of SEQ ID NO: 11, amino acids 1-269 of SEQ ID NO: 12, and amino acids 1-268 of SEQ ID NO: 13; and/or
(b) the protease is a variant of an amino acid sequence selected from the group consisting of amino acids 1-274 of SEQ ID NO: 2, amino acids 1-274 of SEQ ID NO: 5, amino acids 1-275 of SEQ ID NO: 6, amino acids 1-275 of SEQ ID NO: 7, amino acids 1-275 of SEQ ID NO: 8, amino acids 1-275 of SEQ ID NO: 9, amino acids 1-275 of SEQ ID NO: 10, amino acids 1-269 of SEQ ID NO: 11, amino acids 1-269 of SEQ ID NO: 12, and amino acids 1-268 of SEQ ID NO: 13, wherein the variant differs from the respective amino acid sequence by no more than twenty-five amino acids, and wherein:
(i) the variant comprises at least one substitution, deletion and/or insertion of one or more amino acids as compared to the respective amino acid sequence; and/or
(ii) the variant comprises at least one small deletion as compared to the respective amino acid sequence; and/or
(iii) the variant comprises at least one small N- or C-terminal extension as compared to the respective amino acid sequence; and/or
(c) the protease is an allelic variant of a protease having amino acids selected from the group consisting of amino acids 1-274 of SEQ ID NO: 2, amino acids 1-274 of SEQ ID NO: 5, amino acids 1-275 of SEQ ID NO: 6, amino acids 1-275 of SEQ ID NO: 7, amino acids 1-275 of SEQ ID NO: 8, amino acids 1-275 of SEQ ID NO: 9, amino acids 1-275 of SEQ ID NO: 10, amino acids 1-269 of SEQ ID NO: 11, amino acids 1-269 of SEQ ID NO: 12, and amino acids 1-268 of SEQ ID NO: 13; and/or
(d) the protease is a fragment of a protease having amino acids selected from the group consisting of amino acids 1-274 of SEQ ID NO: 2, amino acids 1-274 of SEQ ID NO: 5, amino acids 1-275 of SEQ ID NO: 6, amino acids 1-275 of SEQ ID NO: 7, amino acids 1-275 of SEQ ID NO: 8, amino acids 1-275 of SEQ ID NO: 9, amino acids 1-275 of SEQ ID NO: 10, amino acids 1-269 of SEQ ID NO: 11, amino acids 1-269 of SEQ ID NO: 12, and amino acids 1-268 of SEQ ID NO: 13.
22 . The protease of claim 21 , wherein the protease has an amino acid sequence selected from the group consisting of amino acids 1-274 of SEQ ID NO: 2, amino acids 1-274 of SEQ ID NO: 5, amino acids 1-275 of SEQ ID NO: 6, amino acids 1-275 of SEQ ID NO: 7, amino acids 1-275 of SEQ ID NO: 8, amino acids 1-275 of SEQ ID NO: 9, amino acids 1-275 of SEQ ID NO: 10, amino acids 1-269 of SEQ ID NO: 11, amino acids 1-269 of SEQ ID NO: 12, and amino acids 1-268 of SEQ ID NO: 13.
23 . The protease of claim 22 , wherein the protease has amino acids 1-274 of SEQ ID NO: 2.
24 . A pharmaceutical composition comprising a protease of claim 20 and at least one pharmaceutically acceptable auxiliary material.
25 . The composition of claim 24 , further comprising an amylase.
26 . The composition of claim 25 , wherein the amylase has at least 70% identity to an amylase selected from the group consisting of:
(a) an amylase having amino acids 1-481 of SEQ ID NO: 16,
(b) an amylase having amino acids 1-481 of SEQ ID NO: 17, and
(c) an amylase having amino acids 1-483 of SEQ ID NO: 18.
27 . The composition of claim 24 , further comprising a lipase.
28 . The composition of claim 27 , wherein the lipase has at least 70% identity to a lipase having amino acids 1-269 of SEQ ID NO: 15
29 . The composition of claim 24 , further comprising a lipase and an amylase.
30 . The composition of claim 29 , wherein
(a) the lipase has at least 70% identity to a lipase having amino acids 1-269 of SEQ ID NO: 15; and
(b) the amylase has at least 70% identity to an amylase selected from the group consisting of:
(i) an amylase having amino acids 1-481 of SEQ ID NO: 16,
(ii) an amylase having amino acids 1-481 of SEQ ID NO: 17, and
(iii) an amylase having amino acids 1-483 of SEQ ID NO: 18.
31 . The composition of claim 29 , wherein
(a) the protease has amino acids 1-274 of SEQ ID NO: 2;
(b) the lipase comprises amino acids 2-269 of SEQ ID NO: 15; and
(c) the amylase is an amylase selected from the group consisting of:
(i) an amylase comprising amino acids 1-481 of SEQ ID NO: 16,
(ii) an amylase having amino acids 1-481 of SEQ ID NO: 17, and
(iii) an amylase having amino acids 1-483 of SEQ ID NO: 18.
32 . A method for the treatment of digestive disorders, pancreatic exocrine insufficiency, pancreatitis, cystic fibrosis, diabetes type I, and/or diabetes type II, comprising administering a therapeutically effective amount of a protease of claim 20 .
33 . The method of claim 32 , further comprising administering a therapeutically effective amount of an amylase.
34 . The method of claim 32 , further comprising administering a therapeutically effective amount of a lipase.
35 . The method of claim 32 , further comprising administering a therapeutically effective amount of a lipase and an amylase.