Kunitz domain peptides
View Patent ↗The invention relates to a Kunitz domain peptide, designated DPI-14 herein, for inhibiting human neutrophil elastase. The invention also relates to a method of using a DPI-14 for treating cystic fibrosis or cystic fibrosis-related disease or disorder.
1. A polypeptide comprising (a) the following sequence: EAVREVCSEQAETGPCIAFFPRWYFDVTEGKCAPFFYGGCGGNRNNFDTE EYCMAVCGSA (SEQ ID NO:39), (b) a sequence that is at least 90% identical to SEQ ID NO:39 and inhibits human neutrophil elastase, (c) a sequence that is encoded by a nucleic acid that hybridizes under highly stringent conditions to a nucleic acid encoding SEQ ID NO:39 and inhibits human neutrophil elastase; or (d) a sequence that is a functional fragment of SEQ ID NO:39, inhibits human neutrophil elastase, and has a length of about 51 to 64 amino acids.
2. A method of inhibiting human neutrophil elastase, comprising contacting the polypeptide of claim 1 to human neutrophil elastase.
3. A method of treating a disorder ameliorated by inhibition of human neutrophil elastase, the method comprising administering the polypeptide of claim 1 to a subject who requires treatment for a disorder ameliorated by inhibition of human neutrophil elastase.
4. The method of claim 3 wherein the disorder is cystic fibrosis or a cystic fibrosis-related disorder.
5. The method of claim 4 wherein the subject has cystic fibrosis.
6. The method of claim 3 wherein the disorder is emphysema.
7. The method of claim 3 wherein the disorder is chronic obstructive pulmonary disease (COPD).
8. The method of claim 3 wherein the disorder is bronchitis.
9. The method of claim 3 wherein the disorder is pulmonary hypertension.
10. The method of claim 3 wherein the disorder is acute respiratory distress syndrome.
11. The method of claim 3 wherein the disorder is interstitial lung disease.
12. The method of claim 3 wherein the disorder is asthma.
13. The method of claim 3 wherein the disorder is broncho-pulmonary dysplasia.
14. The method of claim 3 wherein the disorder is pneumonia.
15. The method of claim 3 wherein the disorder is lung transplant rejection.
16. The method of claim 3 wherein the polypeptide comprises (b) a sequence encoded by a nucleic acid that hybridizes under highly stringent conditions to a nucleic acid encoding SEQ ID NO:39.
17. The method of claim 4 wherein the polypeptide comprises (b) a sequence encoded by a nucleic acid that hybridizes under highly stringent conditions to a nucleic acid encoding SEQ ID NO:39.
18. The method of claim 3 wherein the polypeptide comprises a sequence that is at least 95% identical to SEQ ID NO:39.
19. The method of claim 4 wherein the polypeptide comprises a sequence that is at least 95% identical to SEQ ID NO:39.
20. The method of claim 3 wherein the polypeptide comprises SEQ ID NO:39.
21. The method of claim 4 wherein the polypeptide comprises SEQ ID NO:39.
22. The polypeptide of claim 1 that comprises a sequence that is at least 90% identical to SEQ ID NO:39.
23. The polypeptide of claim 22 that comprises a sequence that is at least 95% identical to SEQ ID NO:39.
24. The polypeptide of claim 23 that comprises a sequence that is at least 98% identical to SEQ ID NO:39.
25. The polypeptide of claim 24 that comprises SEQ ID NO:39.
26. The polypeptide of claim 1 that comprises a sequence encoded by a nucleic acid that hybridizes under highly stringent conditions to a nucleic acid encoding SEQ ID NO:39.
27. A method of treating cystic fibrosis, the method comprising administering a polypeptide that comprises SEQ ID NO:39 and inhibits human neutrophil elastase to a subject who has cystic fibrosis.