DOSING REGIMENS AND RELATED COMPOSITIONS AND METHODS
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.
1 .- 336 . (canceled)
337 . A method of treating a subject in need of treatment of C3 glomerulopathy comprising administering a long-acting compstatin analog (LACA) to the subject subcutaneously according to a dosing schedule in which about 1080 mg of the LACA is administered 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 the 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.
338 . The method of claim 337 , wherein the LACA is administered weekly.
339 . The method of claim 337 , wherein the LACA is administered twice weekly.
340 . The method of claim 337 , wherein the LACA is administered thrice weekly.
341 . The method of claim 337 , wherein the LACA is administered every three days.
342 . The method of claim 337 , wherein the LACA is administered using an on-body delivery device.
343 . The method of claim 337 , wherein the LACA comprises a compound having a structure
344 . A method of treating a subject in need of treatment of membranoproliferative glomerulonephritis, the method comprising administering a long-acting compstatin analog (LACA) to the subject subcutaneously according to a dosing schedule in which about 1080 mg of the LACA is administered 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 the 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.
345 . The method of claim 344 , wherein the LACA is administered weekly.
346 . The method of claim 344 , wherein the LACA is administered twice weekly.
347 . The method of claim 344 , wherein the LACA is administered thrice weekly.
348 . The method of claim 344 , wherein the LACA is administered every three days.
349 . The method of claim 344 , wherein the LACA is administered using an on-body delivery device.
350 . The method of claim 344 , wherein the LACA comprises a compound having a structure
351 . A method of treating a subject who has received an organ transplant comprising administering a long-acting compstatin analog (LACA) to the subject subcutaneously according to a dosing schedule in which about 1080 mg of the LACA is administered 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 the 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.
352 . The method of claim 351 , wherein the LACA is administered weekly.
353 . The method of claim 351 , wherein the LACA is administered twice weekly.
354 . The method of claim 351 , wherein the LACA is administered thrice weekly.
355 . The method of claim 351 , wherein the LACA is administered every three days.
356 . The method of claim 351 , wherein the LACA is administered using an on-body delivery device.
357 . The method of claim 351 , wherein the subject has received a kidney transplant.
358 . The method of claim 351 , wherein the LACA, wherein the LACA comprises the compound having a structure