Dosing regimens and related compositions and methods

Patent metadata

Field	Value
Publication number	US-11844841-B2
Application number	US-202117244839-A
Country	US
Kind code	B2
Filing date	Apr 29, 2021
Priority date	Apr 7, 2017
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

Abstract

In some aspects, the present invention provides cell-reactive compstatin analogs and compositions comprising cell-reactive compstatin analogs. In some aspects, the invention further provides methods of using cell-reactive compstatin analogs, e.g., treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides long-acting compstatin analogs and compositions comprising long-acting compstatin analogs. In some aspects, the invention further provides methods of using long-acting compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ. In some aspects, the invention provides targeted compstatin analogs and compositions comprising targeted compstatin analogs. In some aspects, the invention further provides methods of using targeted compstatin analogs, e.g., to treat a complement-mediated disorder, e.g., to inhibit complement-mediated damage to a cell, tissue, or organ.

First claim

We claim:

1. A method of treating a subject in need of treatment of a complement-mediated disorder comprising administering a long-acting compstatin analog (LACA) to the subject subcutaneously according to a dosing schedule in which about 20 mL of the LACA is administered at a concentration of between about 50 mg/mL to about 75 mg/mL thrice weekly, every three days, twice weekly, or weekly,
wherein the LACA comprises a clearance-reducing moiety attached to two compstatin analog moieties, wherein each compstatin analog moiety comprises a cyclic peptide comprising an amino acid sequence as set forth in SEQ ID NO: 28 extended by a lysine residue or a sequence comprising a lysine residue at the N-terminus, C-terminus, or both, wherein the lysine residue is separated from the cyclic portion of the peptide by a spacer comprising 8-amino-3,6-dioxaoctanoic acid (AEEAc);
wherein the clearance reducing moiety comprises a polymer,
wherein each end of the polymer is linked to one of the compstatin analog moieties by way of a carbamate, and
wherein the polymer is PEG having an average molecular weight of about 40 kD.

2. The method of claim 1 , wherein the LACA is administered weekly.

3. The method of claim 1 , wherein the LACA is administered twice weekly.

4. The method of claim 1 , wherein the LACA is administered thrice weekly.

5. The method of claim 1 , wherein the LACA is administered every three days.

6. The method of claim 1 , wherein the complement-mediated disorder is hemolytic anemia, Paroxysmal Nocturnal Hemoglobinuria (PNH), myasthenia gravis, glomerulonephritis, Neuromyelitis optica (NMO), polyneuropathy, nephropathy, or vasculitis.

7. The method of claim 1 , wherein the complement-mediated disorder is PNH.

8. A unit dose of a LACA, wherein the unit dose is for subcutaneous administration and wherein the amount of the unit dose is about 20 mL at a concentration of between about 50 mg/mL to about 75 mg/mL,
wherein the LACA comprises a clearance-reducing moiety attached to two compstatin analog moieties, wherein each compstatin analog moiety comprises a cyclic peptide comprising an amino acid sequence as set forth in SEQ ID NO: 28 extended by a lysine residue or a sequence comprising a lysine residue at the N-terminus, C-terminus, or both, wherein the lysine residue is separated from the cyclic portion of the peptide by a spacer comprising 8-amino-3,6-dioxaoctanoic acid (AEEAc);
wherein the clearance reducing moiety comprises a polymer,
wherein each end of the polymer is linked to one of the compstatin analog moieties by way of a carbamate, and
wherein the polymer is PEG having an average molecular weight of about 40 kD.

9. The unit dose of claim 8 , wherein the unit dose is for subcutaneous administration every three days.

10. The unit dose of claim 8 , wherein the unit dose is for weekly subcutaneous administration.

11. The unit dose of claim 8 , wherein the unit dose is for twice weekly subcutaneous administration.

12. The unit dose of claim 8 , wherein the unit dose is for thrice weekly subcutaneous administration.

13. The unit dose of claim 8 , further comprising a pharmaceutically acceptable carrier.

14. A syringe or container comprising the unit dose of claim 8 .

15. A method of treating a subject in need of treatment for a complement-mediated disorder, the method comprising administering the unit dose of claim 8 to the subject subcutaneously.

16. The method of claim 15 , wherein the unit dose is administered using a syringe pump.

17. The method of claim 15 , wherein the unit dose is administered using an on-body delivery device.

18. The method of claim 15 , wherein the unit dose is administered thrice weekly.

19. The method of claim 15 , wherein the unit dose is administered twice weekly.

20. The method of claim 15 , wherein the unit dose is administered weekly.

21. The method of claim 15 , wherein the unit dose is administered every three days.

22. The method of claim 15 , wherein the complement-mediated disorder is hemolytic anemia, Paroxysmal Nocturnal Hemoglobinuria (PNH), myasthenia gravis, glomerulonephritis, Neuromyelitis optica (NMO), polyneuropathy, nephropathy, or vasculitis.

23. The method of claim 15 , wherein the complement-mediated disorder is PNH.

24. The method according to claim 1 , wherein the LACA comprises the compound having a structure

25. The unit dose according to claim 8 , wherein the LACA comprises the compound having a structure

26. The method according to claim 15 , wherein the LACA comprises the compound having a structure

Assignees

• Apellis Pharmaceuticals Inc

Inventors

• Grossi Federico
• Deschatelets Pascal
• Francois Cedric
• Johnson Patrick
• Vega Carolina

Classifications

• A61P7/06

  Antianaemics · CPC title

• A61M5/152

  pressurised by contraction of elastic reservoirs {(containers for dispensing contents by contraction of an elastic bag provided therein, in general B65D83/7711)} · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61M5/14248

  of the skin patch type · CPC title