Claims for Patent: 10,435,438

Summary for Patent: 10,435,438

Title:	Modulation of complement activity
Abstract:	The present invention provides modulators of complement activity. Also provided are methods of utilizing such modulators as therapeutics.
Inventor(s):	Hoarty Michelle Denise, Dhamnaskar Ketki Ashok, Elbaum Daniel, Josephson Kristopher, Larson Kelley Cronin, Ma Zhong, Nims Nathan Ezekiel, Ricardo Alonso, Seyb Kathleen, Tang Guo-Qing, Treco Douglas A., Wang Zhaolin, Ye Ping, Zheng Hong, Perlmutter Sarah Jacqueline, Hammer Robert Paul
Assignee:	Ra Pharmaceuticals, Inc.
Application Number:	US16237893
Patent Claims:	1. A C5 inhibitor polypeptide of the formula R-Tbg-Tyr-Xaa0-Glu-R , wherein:{'sub': '1', 'Rcomprises a polypeptide;'}Xaa0 is selected from the group consisting of Trp and azaTrp; and{'sub': '2', 'Rcomprises a polypeptide.'}2. The C5 inhibitor polypeptide of claim 1 , wherein the polypeptide of Rcomprises an N-terminal acetyl group.3. The C5 inhibitor polypeptide of claim 2 , wherein the polypeptide of Rcomprises from about 3 amino acids to about 7 amino acids.4. The C5 inhibitor polypeptide of claim 3 , wherein the polypeptide of Rcomprises the formula Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7 claim 3 , wherein:Xaa1 is Cys or absent;Xaa2 is Val, Tbg, or is absent;Xaa3 is Glu, Nvl, or is absent;Xaa4 is selected from the group consisting of Arg, Cys, and Ser, or is absent;Xaa5 is Phe or Tyr;Xaa6 is Cys or Glu; andXaa7 is Asp or Asn.5. The C5 inhibitor polypeptide of claim 1 , wherein the polypeptide of Rcomprises a C-terminal —NH.6. The C5 inhibitor polypeptide of claim 1 , wherein the polypeptide of Rcomprises from about 1 to about 4 amino acids.7. The C5 inhibitor polypeptide of claim 6 , wherein the polypeptide of Rcomprises the formula Xaa8-Xaa9-Xaa10-Xaa11 claim 6 , wherein:Xaa8 is selected from the group consisting of Trp, Tyr, Phe, 2-naphthylalanine, and meta-chloro homophenylalanine;Xaa9 is selected from the group consisting of Pro, N-methyl-Gly, and Ala, or is absent;Xaa10 is selected from the group consisting of cyclohexylglycine and norvaline, or is absent; andXaa11 is selected from the group consisting of norvaline and N-methyl-serine, or is absent.8. The C5 inhibitor polypeptide of comprising a bridging moiety between two amino acids.10. The C5 inhibitor polypeptide of claim 8 , wherein the bridging moiety comprises a feature selected from the group consisting of a disulfide bond claim 8 , an amide bond (lactam) claim 8 , a thioether bond an aromatic ring claim 8 , an unsaturated aliphatic hydrocarbon chain claim 8 , a saturated aliphatic hydrocarbon chain and a triazole ring.11. The C5 inhibitor polypeptide of claim 8 , wherein the bridging moiety is formed by reaction with a poly(bromomethyl)benzene.12. The polypeptide of claim 1 , wherein said polypeptide is conjugated to a hydrophilic polymer.13. The polypeptide of claim 12 , wherein the hydrophilic polymer is selected from the group consisting of polyalkylene oxide homopolymers claim 12 , polypropylene glycols claim 12 , polyoxyethylenated polyols and copolymers thereof.14. The polypeptide of claim 12 , wherein the hydrophilic polymer comprises polyethylene glycol (PEG).15. The polypeptide of comprising at least one lipid moiety.16. The polypeptide of claim 1 , wherein said polypeptide is conjugated to an albumin-binding polypeptide claim 1 , wherein the albumin-binding polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 202-204.17. The polypeptide of claim 1 , wherein said polypeptide is conjugated to a cell penetrating polypeptide claim 1 , wherein the cell penetrating polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 205-210.18. A method of treating a complement-related disease claim 1 , disorder claim 1 , or condition in a subject claim 1 , the method comprising administering the polypeptide of to the subject.19. The method of claim 18 , wherein the complement-related disease claim 18 , disorder claim 18 , or condition comprises hemolysis.20. The method of claim 19 , wherein the hemolysis is caused by thrombin-induced complement activation.21. The method of claim 18 , wherein the complement-related disease claim 18 , disorder claim 18 , or condition is selected from the group consisting of an inflammatory indication claim 18 , a wound claim 18 , an injury claim 18 , an autoimmune disease claim 18 , a vascular indication claim 18 , a neurological indication claim 18 , a kidney-related indication claim 18 , an ocular disease claim 18 , paroxysmal nocturnal hemoglobinuria claim 18 , and atypical hemolytic uremic syndrome.