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):	Michelle Denise Hoarty, Ketki Ashok Dhamnaskar, Daniel Elbaum, Kristopher Josephson, Kelley Cronin Larson, Zhong Ma, Nathan Ezekiel Nims, Alonso Ricardo, Kathleen Seyb, Guo-Qing Tang, Douglas A. Treco, Zhaolin Wang, Ping Ye, Hong Zheng, Sarah Jacqueline Perlmutter, Robert Paul Hammer
Assignee:	Ucb Holdings Inc
Application Number:	US16/237,893
Patent Claims:	1. A C5 inhibitor polypeptide of the formula R1-Tbg-Tyr-Xaa0-Glu-R2, wherein: R1 comprises a polypeptide; Xaa0 is selected from the group consisting of Trp and azaTrp; and R2 comprises a polypeptide. 2. The C5 inhibitor polypeptide of claim 1, wherein the polypeptide of R1 comprises an N-terminal acetyl group. 3. The C5 inhibitor polypeptide of claim 2, wherein the polypeptide of R1 comprises from about 3 amino acids to about 7 amino acids. 4. The C5 inhibitor polypeptide of claim 3, wherein the polypeptide of R1 comprises the formula Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7, 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; and Xaa7 is Asp or Asn. 5. The C5 inhibitor polypeptide of claim 1, wherein the polypeptide of R2 comprises a C-terminal —NH2. 6. The C5 inhibitor polypeptide of claim 1, wherein the polypeptide of R2 comprises from about 1 to about 4 amino acids. 7. The C5 inhibitor polypeptide of claim 6, wherein the polypeptide of R2 comprises the formula Xaa8-Xaa9-Xaa10-Xaa11, 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; and Xaa11 is selected from the group consisting of norvaline and N-methyl-serine, or is absent. 8. The C5 inhibitor polypeptide of claim 1 comprising a bridging moiety between two amino acids. 9. The C5 inhibitor polypeptide of claim 8, wherein the bridging moiety comprises a structure selected from the group consisting of structures I-XIX; wherein each X is independently N or CH, such that no ring contains more than 2 N; each Z is independently a bond, NR, O, S, CH2, C(O)NR, NRC(O), S(O)vNR, NRS(O)v; each m is independently selected from 0, 1, 2, and 3; each v is independently selected from 1 and 2; each R is independently selected from H and C1-C6; and each bridging moiety is connected to the polypeptide by independently selected C0-C6 spacers. 10. The C5 inhibitor polypeptide of claim 8, wherein the bridging moiety comprises a feature selected from the group consisting of a disulfide bond, an amide bond (lactam), a thioether bond an aromatic ring, an unsaturated aliphatic hydrocarbon chain, 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, polypropylene glycols, polyoxyethylenated polyols and copolymers thereof. 14. The polypeptide of claim 12, wherein the hydrophilic polymer comprises polyethylene glycol (PEG). 15. The polypeptide of claim 1 comprising at least one lipid moiety. 16. The polypeptide of claim 1, wherein said polypeptide is conjugated to an albumin-binding polypeptide, 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, 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, disorder, or condition in a subject, the method comprising administering the polypeptide of claim 1 to the subject. 19. The method of claim 18, wherein the complement-related disease, disorder, 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, disorder, or condition is selected from the group consisting of an inflammatory indication, a wound, an injury, an autoimmune disease, a vascular indication, a neurological indication, a kidney-related indication, an ocular disease, paroxysmal nocturnal hemoglobinuria, and atypical hemolytic uremic syndrome.