Claims for Patent: 11,014,965

Summary for Patent: 11,014,965

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:	US16/732,502
Patent Claims:	1. A polypeptide that binds complement component C5, the polypeptide comprising the formula R1-Tyr-Xaa0-Glu-Tyr-R2, wherein: R1 comprises a polypeptide; Xaa0 is selected from the group consisting of Trp, azaTrp, N-methyl Trp, 1-methyl Trp, and 3-aminomethyl Phe; and R2 comprises a polypeptide. 2. The polypeptide of claim 1, wherein the polypeptide comprises a bridging moiety between two amino acids. 3. The polypeptide of claim 2, wherein the R1 polypeptide comprises the formula Xaa1-Val-Glu-Arg-Xaa2-Xaa3, wherein: Xaa1 is Cys or Lys; Xaa2 is Phe or Ala; and Xaa3 is Cys or Asp. 4. The polypeptide of claim 3, wherein the polypeptide comprises a bridging moiety between Xaa1 and Xaa3. 5. The polypeptide of claim 4, wherein the R1 polypeptide comprises the formula Xaa1-Val-Glu-Arg-Xaa2-Xaa3-Xaa4, wherein Xaa4 is selected from the group consisting of Asp, Ala, (S)-2-amino-3-(1H-tetrazol-5-yl)propanoic acid, alpha-methyl Asp, N-methyl Asp, cycloleucine, and 4-amino-tetrahydro-pyran-4-carboxylic acid. 6. The polypeptide of claim 5, wherein the R1 polypeptide comprises the formula Xaa1-Glu-Arg-Xaa2-Xaa3-Xaa4-Xaa5, wherein Xaa5 is selected from the group consisting of tert-butylglycine and Val. 7. The polypeptide of claim 1, wherein the R2 polypeptide comprises the formula Pro-Xaa6-Xaa7, wherein: Xaa6 is selected from the group consisting of cyclohexylglycine, phenylglycine (Phg), D-Phg, N-methyl Phg, Ala, and amino isobutyric acid, or is absent; and Xaa7 is selected from the group consisting of Lys, norvaline, and Pro, or is absent. 8. The polypeptide of claim 7, wherein Xaa7 is Lys. 9. The polypeptide of claim 8, wherein the Xaa7 Lys is conjugated with a lipid. 10. The polypeptide of claim 8, wherein the Xaa7 Lys comprises a modified lysine residue selected from the group consisting of N-ε-palmitoyl lysine, N-ε-lauryl lysine, N-ε-capryl lysine, N-ε-caprylic lysine, N-ε-(PEG2-γ-glutamic acid-N-α-octadecanedioic acid)lysine, N-ε-(PEG24-γ-glutamic acid-N-α-hexadecanoyl)lysine, and N-ε-1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl-L-lysine. 11. The polypeptide of claim 1, wherein the polypeptide comprises an N-terminal acetyl group. 12. The polypeptide of claim 1, wherein the polypeptide comprises a C-terminal —NH2. 13. A C5 inhibitor comprising the polypeptide of claim 1. 14. A method of treating a complement-related disease, disorder, or condition in a subject, the method comprising inhibiting C5 cleavage in the subject by administering to the subject the C5 inhibitor of claim 13. 15. The method of claim 14, wherein the complement-related disease, disorder, or condition comprises hemolysis. 16. The method of claim 15, wherein the complement-related disease, disorder, or condition is selected from the group consisting of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. 17. The method of claim 14, 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, and an ocular disease. 18. The method of claim 14, wherein the complement-related disease, disorder, or condition is selected from the group consisting of myasthenia gravis and amyotrophic lateral sclerosis.