Claims for Patent: 10,875,893

Summary for Patent: 10,875,893

Title:	Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods
Abstract:	In some aspects, the present invention provides compositions and methods of treatment comprising long-acting compstatin analogs. In some aspects, long-acting compstatin analogs comprise a clearance-reducing moiety attached to two compstatin analog moieties, wherein each compstatin analog moiety comprises a cyclic peptide comprising the 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) moiety, 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 linker moiety that is or comprises a carbamate, and wherein the polymer is a PEG having an average molecular weight of about 40 kDa.
Inventor(s):	Francois; Cedric (Prospect, KY), Deschatelets; Pascal (Prospect, KY)
Assignee:	Apellis Pharmaceuticals, Inc. (Waltham, MA)
Application Number:	16/020,987
Patent Claims:	1. A long-acting compstatin analog comprising a clearance-reducing moiety attached to two compstatin analog moieties, wherein: each compstatin analog moiety comprises a cyclic peptide having an amino acid sequence as set form 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 an 8-amino-3,6-dioxaoctanoic acid (AEEAc) spacer; and the clearance reducing moiety comprises a PEG polymer having an average molecular weight of about 40 kDa, wherein each end of the polymer is linked to one of the compstatin analog moieties by way of a linker moiety that is or comprises a carbamate. 2. The long-acting compstatin analog of claim 1, having a structure ##STR00045## 3. A method of treating a complement-mediated disorder in a subject, the method comprising administering to the subject a composition comprising a long-acting compstatin analog, wherein the long-acting compstatin analog comprises a clearance-reducing moiety attached to two compstatin analog moieties, wherein: each compstatin analog moiety comprises a cyclic peptide having an amino acid sequence as set form 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 an 8-amino-3,6-dioxaoctanoic acid (AEEAc) spacer; and the clearance reducing moiety comprises a PEG polymer having an average molecular weight of about 40 kDa, wherein each end of the polymer is linked to one of the compstatin analog moieties by way of a linker moiety that is or comprises a carbamate. 4. The method of claim 3, wherein the administering step comprises administration of the long-acting compstatin analog through a parenteral route of administration. 5. The method of claim 4, wherein the route of administration is subcutaneous, intravenous, intravitreal, or intramuscular. 6. The method of claim 3, wherein the complement-mediated disorder is age-related macular degeneration. 7. The method of claim 3, wherein the long-acting compstatin analog has a structure ##STR00046## 8. The long-acting compstatin analog of claim 1, having a structure as is produced when first and second compstatin analogs of SEQ ID NO:28, incorporating an AEEAc-Lys moiety C-terminal to the Thr residue of SEQ ID NO:28, are each conjugated with an NETS-ester-activated PEG with molecular weight of 40 kD. 9. The long-acting compstatin analog of claim 8, wherein the NETS-ester-activated PEG is a carbonate-ester-activated PEG.