Lipases for Pharmaceutical Use
The pharmaceutical use of lipases related to a variant of the Thermomyces lanuginosus ( Humicola lanuginosa ) lipase comprising amino acids 1-269 of SEQ ID NO: 1, optionally in combination with a protease 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. The lipases of the invention have an improved efficacy in vivo, are stable against protease-degradation, and/or are stable in the presence of bile salts.
1 - 18 . (canceled)
19 . An isolated lipase for use as a medicament, wherein the lipase has at least 90% identity to amino acids 1-269 of SEQ ID NO: 1, provided that the lipase is not amino acids 1-269 of SEQ ID NO: 2.
20 . The lipase of claim 19 , wherein
(a) the lipase comprises amino acids 1-269 of SEQ ID NO: 1, or
(b) the lipase is a variant of amino acids 1-269 of SEQ ID NO: 1, wherein the variant differs from amino acids 1-269 of SEQ ID NO: 1 by no more than twenty-five amino acids, and wherein:
(i) the variant comprises at least one conservative substitution and/or insertion of one or more amino acids as compared to amino acids 1-269 of SEQ ID NO: 1; and/or
(ii) the variant comprises at least one small deletion as compared to amino acids 1-269 of SEQ ID NO: 1; and/or
(iii) the variant comprises at least one small N- or C-terminal extension as compared to amino acids 1-269 of SEQ ID NO: 1; and/or
(iv) the variant is an allelic variant of the lipase having amino acids 1-269 of SEQ ID NO: 2; and/or
(v) the variant is a fragment of the lipase having amino adds 1-269 of SEQ ID NO: 1.
21 . The lipase of claim 19 , which comprises amino acids 2-269 of SEQ ID NO: 1.
22 . A pharmaceutical composition comprising a lipase of claim 20 and a pharmaceutically acceptable auxiliary material.
23 . The composition of claim 22 , further comprising a protease.
24 . The composition of claim 23 , wherein the protease has at least 70% identity to a protease selected from the group consisting of
(a) a protease having amino acids 1-274 of SEQ ID NO: 3,
(b) a protease having amino acids 1-188 of SEQ ID NO: 4, and
(c) a protease having amino acids 1-188 of SEQ ID NO: 5.
25 . The composition of claim 22 , 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 1481 of SEQ ID NO: 6,
(b) an amylase having amino acids 1-481 of SEQ ID NO: 7, and
(c) an amylase having amino acids 1-483 of SEQ ID NO: 8.
27 . The composition of claim 22 , further comprising a protease and an amylase.
28 . The composition of claim 27 , wherein
(a) the protease has at least 70% identity to a protease selected from the group consisting of
(i) a protease having amino acids 1-274 of SEQ ID NO: 3,
(ii) a protease having amino acids 1-188 of SEQ ID NO: 4, and
(iii) a protease having amino acids 1-188 of SEQ ID NO: 5; 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: 6,
(ii) an amylase having amino acids 1-481 of SEQ ID NO: 7, and
(iii) an amylase having amino acids 1-483 of SEQ ID NO: 8.
29 . 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 lipase of claim 20 .
30 . The method of claim 29 , further comprising administering a therapeutically effective amount of a protease or an amylase.
31 . The method of claim 29 , further comprising administering a therapeutically effective amount of a protease and an amylase.