Claims for Patent: 10,035,822

Summary for Patent: 10,035,822

Title:	Cell-reactive, long-acting, or targeted compstatin analogs and related compositions and methods
Abstract:	Long-acting compstatin analogs comprising a clearance-reducing moiety attached to two compstatin analog moieties, each compstatin analog moiety comprising a cyclic peptide 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 rigid or flexible spacer comprising an oligo(ethylene glycol) moiety, the clearance reducing moiety comprises a linear polymer, wherein each end of the linear polymer is linked to one of the compstatin analog moieties by way of a carbamate, wherein (i) the spacer comprises --(CH2).sub.m-- and --(O--CH2-CH2--).sub.n joined covalently, wherein m is between 1 and 10 and n is between 1 and 10; and/or (ii) the spacer comprises 8-amino-3,6-dioxaoctanoic acid (AEEAc) or 11-amino-3,6,9-trioxaundecanoic acid.
Inventor(s):	Francois; Cedric (Louisville, KY), Deschatelets; Pascal (Louisville, KY)
Assignee:	Apellis Pharmaceuticals, Inc. (Crestwood, KY)
Application Number:	14/443,143
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 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 rigid or flexible spacer comprising an oligo(ethylene glycol) moiety; the clearance reducing moiety comprises a linear polymer, wherein each end of the linear polymer is linked to one of the compstatin analog moieties by way of a carbamate; wherein (i) the spacer comprises --(CH2).sub.m-- and --(O--CH2--CH2--).sub.n joined covalently, wherein m is between 1 and 10 and n is between 1 and 10; and/or (ii) the spacer comprises 8-amino-3,6-dioxaoctanoic acid (AEEAc) or 11-amino-3,6,9-trioxaundecanoic acid. 2. The long-acting compstatin analog of claim 1, wherein the cyclic peptide comprises an amino acid sequence as set forth in any of SEQ ID NOs: 3-36, 71, 72, 73, or 74. 3. The long-acting compstatin analog of claim 1, wherein the spacer comprises --(CH2).sub.m-- and --(O--CH2--CH2--).sub.n joined covalently, wherein m is between 1 and 10 and n is between 1 and 10. 4. The long-acting compstatin analog of claim 3, wherein m is 1 and n is 2. 5. The long-acting compstatin analog of claim 1, wherein the spacer comprises 8-amino-3,6-dioxaoctanoic acid (AEEAc) or 11-amino-3,6,9-trioxaundecanoic acid. 6. The long-acting compstatin analog of claim 1, wherein the linear polymer is polyethylene glycol (PEG) or polyoxazoline (POZ). 7. The long-acting compstatin analog of claim 6, wherein the linear polymer is PEG. 8. The long-acting compstatin analog of claim 7, wherein the PEG has an average molecular weight of about 40 kD. 9. The long-acting compstatin analog of claim 1, having a terminal half-life of at least about 3 days when administered to a primate. 10. The long-acting compstatin analog of claim 9, having a terminal half-life of at least about 5 days when administered to a primate. 11. The long-acting compstatin analog of claim 1, having an activity on a molar basis of at least 90% of that of a compstatin analog comprising the same compstatin analog sequence as the compstatin analog moiety but not linked to the clearance-reducing moiety. 12. The long-acting compstatin analog of claim 2, wherein the cyclic peptide comprises an amino acid sequence as set forth in SEQ ID NO: 28.