US2022169701A1PendingUtilityA1

Enveloped Virus Resistant to Complement Inactivation for the Treatment of Cancer

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Assignee: WELLSTAT IMMUNOTHERAPEUTICS LLCPriority: May 10, 2017Filed: Feb 18, 2022Published: Jun 2, 2022
Est. expiryMay 10, 2037(~10.8 yrs left)· nominal 20-yr term from priority
Inventors:Tianci LuoRene A. MolinaGabriel Castille
C07K 2319/036C07K 19/00C12N 15/625A61K 38/1774C12N 7/00A61K 38/177C07K 14/70517C07K 2319/03C12N 5/16A61P 35/00C07K 14/70596C12N 2760/18132C12N 2760/18152A61K 35/76A61K 38/00A61K 35/768C12N 2760/18121
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Claims

Abstract

A recombinant fusion protein is disclosed. The fusion protein comprises: (a) a CD55 peptide sequence, (b) a linker sequence C-terminal to the CD55 sequence, (c) a transmembrane domain C-terminal to the linker sequence, and (d) an intracellular domain C-terminal to the transmembrane domain. The fusion protein does not contain a GPI anchor. The fusion protein can be expressed with an N-terminal secretory signal peptide, which is cleaved to yield the mature protein on the surface of a cell line or an enveloped virus. An oncolytic virus expressing the fusion protein is resistant to complement inactivation and can be used to treat cancer.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A fusion protein comprising: (a) a CD55 peptide sequence, (b) a linker sequence C-terminal to the CD55 sequence, (c) a transmembrane domain C-terminal to the linker sequence, and (d) an intracellular domain C-terminal to the transmembrane domain; wherein the fusion protein does not contain a GPI anchor. 
     
     
         2 . The protein of  claim 1 , wherein the CD55 peptide sequence is a human CD55 peptide sequence. 
     
     
         3 . The protein of  claim 1 , wherein sequence (a) comprises four short consensus repeats (SCR) of CD55. 
     
     
         4 . The protein of  claim 1 , wherein the linker is a (G4S1)3 linker. 
     
     
         5 . The protein of  claim 1 , wherein transmembrane domain is a CD8 transmembrane domain. 
     
     
         6 . The protein of  claim 1 , wherein the intracellular domain is a truncated CD8 intracellular domain. 
     
     
         7 . The protein of  claim 1 , wherein peptide sequence (a) is covalently bonded to peptide sequence (b) by a single peptide bond. 
     
     
         8 . The protein of  claim 1 , wherein peptide sequence (a) is covalently bonded to peptide sequence (b) by a spacer. 
     
     
         9 . The protein of  claim 1 , wherein peptide sequence (b) is covalently bonded to peptide sequence (c) by a single peptide bond. 
     
     
         10 . The protein of  claim 1 , wherein peptide sequence (b) is covalently bonded to peptide sequence (c) by a spacer. 
     
     
         11 . The protein of  claim 1 , wherein peptide sequence (c) is covalently bonded to peptide sequence (d) by a single peptide bond. 
     
     
         12 . The protein of  claim 1 , wherein peptide sequence (c) is covalently bonded to peptide sequence (d) by a spacer. 
     
     
         13 . The protein of  claim 1 , wherein the fusion protein further comprises a secretory signal peptide N-terminal to sequence (a). 
     
     
         14 . The protein of  claim 13 , wherein the secretory signal peptide is a secretory signal peptide of CD55. 
     
     
         15 . The protein of  claim 13 , wherein the N-terminal secretory signal peptide is covalently bonded to sequence (a) by a single peptide. 
     
     
         16 . The protein of  claim 13 , wherein the N-terminal secretory signal peptide is covalently bonded to sequence (a) by a spacer. 
     
     
         17 . The protein of  claim 1 , having the sequence SEQ ID NO:2. 
     
     
         18 . The protein of  claim 1 , having the sequence SEQ ID NO:3. 
     
     
         19 . A nucleic acid encoding the protein of any one of  claims 1  through  18 . 
     
     
         20 . The nucleic acid of  claim 19 , wherein the nucleic acid is DNA. 
     
     
         21 . The nucleic acid of  claim 20 , further comprising one or more introns. 
     
     
         22 . The nucleic acid of  claim 19 , encoding a protein having the sequence SEQ ID NO:2. 
     
     
         23 . The nucleic acid of  claim 22 , having the sequence SEQ ID NO:1. 
     
     
         24 . An expression vector comprising the nucleic acid of any one of  claims 19  through  23 , operatively linked to a control sequence. 
     
     
         25 . A cell line stably expressing the protein of any one of  claims 1  through  18  on the cell surface. 
     
     
         26 . The cell line of  claim 25 , wherein the cell line is a mammalian cell line. 
     
     
         27 . The cell line of  claim 25 , wherein the cell line is a DF-1 chicken embryonic fibroblast cell line. 
     
     
         28 . An enveloped virus incorporating the protein of any one of  claims 1  through  18  on the virus membrane. 
     
     
         29 . The virus of  claim 28 , wherein the virus is an oncolytic virus. 
     
     
         30 . The virus of  claim 29 , wherein the oncolytic virus is a Newcastle Disease Virus. 
     
     
         31 . A pharmaceutical composition comprising the virus of  claim 29  or  30  and a pharmaceutically acceptable carrier. 
     
     
         32 . A method for treating a neoplastic condition in a mammalian subject, comprising administering to the subject an amount of the virus of  claim 28  effective to treat the condition. 
     
     
         33 . The method of  32 , wherein the virus is administered intratumorally. 
     
     
         34 . The method of  claim 32 , wherein the virus is administered intravenously.

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