Methods of treating chronic disorders with complement inhibitors

Patent metadata

Field	Value
Publication number	US-11712460-B2
Application number	US-202117235281-A
Country	US
Kind code	B2
Filing date	Apr 20, 2021
Priority date	Jun 22, 2011
Publication date	Aug 1, 2023
Grant date	Aug 1, 2023

Abstract

In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic complement-mediated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a Th17-associated disorder. In some aspects, the invention provides methods of treating a subject in need of treatment for a chronic respiratory system disorder. In some aspects, the invention provides methods of administering a complement inhibitor to a subject. In some embodiments, a method of treating a subject comprises administering multiple doses of a complement inhibitor to the subject according to a dosing schedule that leverages the prolonged effect of complement inhibition in chronic respiratory disorders. In some embodiments, a subject has chronic obstructive pulmonary disease. In some embodiments, a subject has asthma.

First claim

We claim:

1. A method of treating a subject in need of treatment for a chronic respiratory disorder or other chronic complement-mediated disorder, the method comprising administering multiple doses of a complement inhibitor to the subject by an intravenous, intramuscular, subcutaneous, or respiratory route according to a dosing schedule in which successive doses are administered on average (i) at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 10% of the maximum plasma concentration that was reached after the previous dose; (ii) at intervals such that the subject's complement activation capacity is at least 50% of baseline for on average at least 3 weeks between doses; or (iii) at intervals at least equal to 10 times the terminal plasma half-life of the complement inhibitor when administered by the same route; and
wherein the complement inhibitor comprises a nucleic acid.

2. The method of claim 1 , wherein successive doses are administered on average at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 10% of the maximum plasma concentration that was reached after the previous dose.

3. The method of claim 1 , wherein successive doses are administered on average at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 5% of the maximum plasma concentration that was reached after the previous dose.

4. The method of claim 1 , wherein successive doses are administered on average at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 1% of the maximum plasma concentration that was reached after the previous dose.

5. The method of claim 1 , wherein the complement inhibitor comprises an RNAi agent.

6. The method of claim 5 , wherein the RNAi agent is a short interfering RNA.

7. The method of claim 5 , wherein the RNAi agent inhibits expression of C3.

8. The method of claim 1 , wherein the complement inhibitor is administered by the intravenous route.

9. The method of claim 1 , wherein the complement inhibitor is administered by the intramuscular route.

10. The method of claim 1 , wherein the complement inhibitor is administered by the respiratory route.

11. The method of claim 1 , wherein the complement inhibitor is administered by the subcutaneous route.

12. A method of treating a subject in need of treatment for a chronic respiratory disorder or other chronic complement-mediated disorder, the method comprising administering multiple doses of a complement inhibitor to the subject by an intravenous, intramuscular, subcutaneous, or respiratory route according to a dosing schedule in which successive doses are administered on average (i) at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 10% of the maximum plasma concentration that was reached after the previous dose; (ii) at intervals such that the subject's complement activation capacity is at least 50% of baseline for on average at least 3 weeks between doses; or (iii) at intervals at least equal to 10 times the terminal plasma half-life of the complement inhibitor when administered by the same route; and
wherein the complement inhibitor comprises a protease that degrades C3.

13. The method of claim 12 , wherein successive doses are administered on average at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 10% of the maximum plasma concentration that was reached after the previous dose.

14. The method of claim 12 , wherein successive doses are administered on average at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 5% of the maximum plasma concentration that was reached after the previous dose.

15. The method of claim 12 , wherein successive doses are administered on average at least 3 weeks after the plasma concentration of the complement inhibitor decreases to no more than 1% of the maximum plasma concentration that was reached after the previous dose.

16. The method of claim 12 , wherein the complement inhibitor is administered by the intravenous route.

17. The method of claim 12 , wherein the complement inhibitor is administered by the intramuscular route.

18. The method of claim 12 , wherein the complement inhibitor is administered by the respiratory route.

19. The method of claim 12 , wherein the complement inhibitor is administered by the subcutaneous route.

Assignees

• Apellis Pharmaceuticals Inc

Inventors

• Francois Cedric
• Deschatelets Pascal

Classifications

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title

• A61B5/14546

  for measuring analytes not otherwise provided for, e.g. ions, cytochromes · CPC title

• A61B5/414

  Evaluating particular organs or parts of the immune or lymphatic systems · CPC title

• A61K31/7088

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K31/7105

  Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links · CPC title