Factor H variants for treatment of disease
AssigneeThe Trustees of the University of Pennsylvania
InventorsWenchao Song, Damodar Gullipalli, Takashi Miwa
Life of this patent
Estimating the term…
Abstract
Disclosed herein are factor H variants, vectors comprising said factor H variants, and pharmaceutical compositions comprising the same for treatment of disorders.
Claims24
A recombinant vector having packaged therein an expression cassette comprising an engineered human complement factor H (hfH) gene operably linked to expression control sequences which direct expression thereof, wherein the hfH gene encodes a soluble hfH protein variant that retains complement regulatory function, wherein the hfH protein variant comprises:
- amino acids 1 to 62 of SEQ ID NO:
- 3 (SCR1)—L1—amino acids 1 to 57 of SEQ ID NO:
- 5 (SCR2)—L2—amino acids 1 to 60 of SEQ ID NO:
- 7 (SCR3)—L3—amino acids 1 to 53 of SEQ ID NO:
- 9 (SCR4)—L4—amino acids 1 to 61 of SEQ ID NO:
- 13 (SCR6)—L4′—amino acids 1 to 54 of SEQ ID NO:
- 14 (SCR7)—L5—amino acids 1 to 58 of SEQ ID NO:
- 16 (SCR8)—L5″—amino acids 1 to 56 of SEQ ID NO:
- 33 (SCR17)—L5″′—amino acids 1 to 55 of SEQ ID NO:
- 35 (SCR18)—L5″″—amino acids 1 to 55 of SEQ ID NO:
- 37 (SCR19)—L6—amino acids 1 to 65 of SEQ ID NO:
- 38 (SCR20), wherein “L” refers to a linker, and each of L1, L2, L3, L4, L4′, L5, L5″, L5″′, L5″″, and L6 is independently selected from an amino acid sequence of 1 to 18 amino acids, and wherein SCR5, SCR9, SCR10, SCR11, SCR12, SCR13, SCR14, SCR15, and SCR16 are absent.
A recombinant AAV vector comprising an AAV capsid having packaged therein an expression cassette comprising an engineered human complement regulator factor H (hfH) gene operably linked to expression control sequences which direct expression thereof, wherein the hfH gene encodes a soluble hfH protein variant that retains complement regulatory function, wherein the hfH protein variant comprises:
- amino acids 1 to 62 of SEQ ID NO:
- 3 (SCR1)—L1—amino acids 1 to 57 of SEQ ID NO:
- 5 (SCR2)—L2—amino acids 1 to 60 of SEQ ID NO:
- 7 (SCR3)—L3—amino acids 1 to 53 of SEQ ID NO:
- 9 (SCR4)—L4—amino acids 1 to 61 of SEQ ID NO:
- 13 (SCR6)—L4′—amino acids 1 to 54 of SEQ ID NO:
- 14 (SCR7)—L5—amino acids 1 to 58 of SEQ ID NO:
- 16 (SCR8)—L5″—amino acids 1 to 56 of SEQ ID NO:
- 33 (SCR17)—L5″′—amino acids 1 to 55 of SEQ ID NO:
- 35 (SCR18)—L5″″—amino acids 1 to 55 of SEQ ID NO:
- 37 (SCR19)—L6—amino acids 1 to 65 of SEQ ID NO:
- 38 (SCR20), wherein “L” refers to a linker, and each of L1, L2, L3, L4, L4′, L5, L5″, L5″′, L5″″, and L6 is independently selected from an amino acid sequence of 1 to 18 amino acids, and wherein SCR5, SCR9, SCR10, SCR11, SCR12, SCR13, SCR14, SCR15, and SCR16 are absent.
A plasmid comprising a nucleotide sequence that encodes an engineered human complement regulator factor H (hfH) gene operably linked to expression control sequences which direct expression thereof, wherein the hfH gene encodes a soluble hfH protein variant that retains complement regulatory function, wherein the hfH protein variant comprises:
- amino acids 1 to 62 of SEQ ID NO:
- 3 (SCR1)—L1—amino acids 1 to 57 of SEQ ID NO:
- 5 (SCR2)—L2—amino acids 1 to 60 of SEQ ID NO:
- 7 (SCR3)—L3—amino acids 1 to 53 of SEQ ID NO:
- 9 (SCR4)—L4—amino acids 1 to 61 of SEQ ID NO:
- 13 (SCR6)—L4′—amino acids 1 to 54 of SEQ ID NO:
- 14 (SCR7)—L5—amino acids 1 to 58 of SEQ ID NO:
- 16 (SCR8)—L5″—amino acids 1 to 56 of SEQ ID NO:
- 33 (SCR17)—L5″′—amino acids 1 to 55 of SEQ ID NO:
- 35 (SCR18)—L5″″—amino acids 1 to 55 of SEQ ID NO:
- 37 (SCR19)—L6—amino acids 1 to 65 of SEQ ID NO:
- 38 (SCR20), wherein “L” refers to a linker, and each of L1, L2, L3, L4, L4′, L5, L5″, L5″′, L5″″, and L6 is independently selected from an amino acid sequence of 1 to 18 amino acids, and wherein SCR5, SCR9, SCR10, SCR11, SCR12, SCR13, SCR14, SCR15, and SCR16 are absent.
Dependencies are inferred from the claim text.