US2021196770A1PendingUtilityA1

Platform oncolytic vector for systemic delivery

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Assignee: KaliVir Immunotherapeutics LLCPriority: Oct 31, 2017Filed: Mar 4, 2021Published: Jul 1, 2021
Est. expiryOct 31, 2037(~11.3 yrs left)· nominal 20-yr term from priority
Inventors:Stephen H. ThorneDaniel J. ByrdMingrui Zhang
Y02A50/30C12N 15/86C12N 9/2474A61K 35/768C12Y 302/01035A61P 35/00C12N 7/00C07K 14/7158C12N 2710/24132C12N 2710/24143A61K 38/47
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Claims

Abstract

This disclosure provides a modified oncolytic virus that can contain modifications in the viral genome and exogenous nucleic acids coding for proteins. The modified oncolytic virus can be utilized as a platform vector for systemic delivery.

Claims

exact text as granted — not AI-modified
1 .- 206 . (canceled) 
     
     
         207 . An oncolytic virus comprising a mutation or a deletion or a partial deletion of the viral gene K7R, and further comprising at least one of:
 (a) an exogenous nucleic acid that codes for a cytokine, or a functional domain or a fragment or a variant thereof;   (b) an exogenous nucleic acid that codes for a cytokine receptor, or a functional domain or a fragment or a variant thereof;   (c) an exogenous nucleic acid that codes for a chemokine, or a functional domain, or a fragment or a variant thereof; or   (d) any combination of (a)-(c).   
     
     
         208 . The oncolytic virus of  claim 207 , comprising the exogenous nucleic acid that codes for the chemokine, or a functional domain or a fragment or a variant thereof, wherein the chemokine, or a functional domain or a fragment or a variant thereof comprises at least one of: CCL5, ITAC (CXCL11), a fractalkine, or a functional domain or a fragment or a variant thereof. 
     
     
         209 . The oncolytic virus of  claim 207 , comprising the exogenous nucleic acid that codes for the cytokine, or a functional domain or a fragment or a variant thereof, wherein the cytokine, or a functional domain or a fragment or a variant thereof comprises IL15, IL7, or a functional domain or a fragment or a variant thereof. 
     
     
         210 . The oncolytic virus of  claim 207 , comprising the exogenous nucleic acid that codes for the cytokine receptor, or a functional domain or a fragment or a variant thereof, wherein the cytokine receptor, or a functional domain or a fragment or a variant thereof comprises IL15 receptor alpha, or a functional domain or a fragment or a variant thereof. 
     
     
         211 . The oncolytic virus of  claim 207 , further comprising an exogenous nucleic acid that codes for at least one of: HMGB1, PIAS3, LIGHT, or a functional domain or a fragment or a variant thereof. 
     
     
         212 . The oncolytic virus of  claim 207 , further comprising at least one of: an exogenous nucleic acid that codes for a chemokine receptor, or a functional domain or a fragment or a variant thereof; a mutation or a deletion or a partial deletion of viral gene A52R; and an exogenous nucleic acid that codes for a protein, or a functional domain or a fragment or a variant thereof, that enhances degradation of an extracellular matrix (ECM) of a tumor; or any combination thereof. 
     
     
         213 . The oncolytic virus of  claim 212 , comprising the exogenous nucleic acid that codes for a protein, or a functional domain or a fragment or a variant thereof, that enhances degradation of an extracellular matrix (ECM) of a tumor, wherein the protein, or a functional domain or a fragment or a variant thereof, that enhances degradation of the ECM of a tumor comprises at least one of: a membrane associated protein that is capable of degrading hyaluronan, or a microbial protein that is capable of degrading hyaluronan. 
     
     
         214 . The oncolytic virus of  claim 213 , comprising the membrane associated protein that is capable of degrading hyaluronan, wherein the membrane associated protein that is capable of degrading hyaluronan comprises a membrane associated hyaluronidase. 
     
     
         215 . The oncolytic virus of  claim 214 , wherein the membrane associated hyaluronidase is PH-20. 
     
     
         216 . The oncolytic virus of  claim 213 , comprising the microbial protein that is capable of degrading hyaluronan, wherein the microbial protein comprises a secreted hyaluronidase. 
     
     
         217 . The oncolytic virus of  claim 216 , wherein the secreted hyaluronidase is selected from the group consisting of: HysA, lin, sko, and rv, or any combination thereof. 
     
     
         218 . The oncolytic virus of  claim 217 , wherein the secreted hyaluronidase comprises the HysA. 
     
     
         219 . The oncolytic virus of  claim 213 , comprising the microbial protein that is capable of degrading hyaluronan, wherein the microbial protein comprises hyaluronidase protein HysA from  Loxosceles intermedia.    
     
     
         220 . The oncolytic virus of  claim 207 , further comprising a modification in the genome of the virus, wherein the modification enhances production of an enveloped extracellular form (EEV) of the virus. 
     
     
         221 . The oncolytic virus of  claim 212 , comprising the exogenous nucleic acid that codes for the chemokine receptor, or a functional domain or a fragment or a variant thereof, wherein the chemokine receptor comprises at least one of: a CXC receptor, a CC receptor, a CX3C receptor, and a XC receptor, or a functional domain or a fragment or a variant thereof. 
     
     
         222 . The oncolytic virus of  claim 221 , wherein the chemokine receptor comprises a least one of: CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, CXCR6, CXCR7, CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CX3CR1, XCR1, or a functional domain or a fragment or a variant thereof. 
     
     
         223 . The oncolytic virus of  claim 222 , wherein the chemokine receptor comprises CXCR4 or CCR2, or a functional domain or a fragment or a variant thereof. 
     
     
         224 . The oncolytic virus of  claim 207 , further comprising a modification in the genome of the virus. 
     
     
         225 . The oncolytic virus of  claim 207 , further comprising a mutation or a deletion or a partial deletion of a viral gene selected from the group consisting of: F13L, A36R, A34R, B5R, A33R, B8R, B18R, SPI-1, SPI-2, B15R, VGF, E3L, K3L, A41L, N1L. 
     
     
         226 . The oncolytic virus of  claim 207 , wherein the oncolytic virus comprises a poxvirus, an adeno associated virus, an adenovirus, a reovirus, a lentivirus, a herpes simplex virus, a vesicular stomatitis virus, a mengovirus, or a myxomavir. 
     
     
         227 . The oncolytic virus of  claim 226 , wherein the oncolytic virus comprises the poxvirus, and wherein the poxvirus comprises a vaccinia virus. 
     
     
         228 . The oncolytic virus of  claim 227 , wherein the vaccinia virus comprises a Western Reserve vaccinia virus. 
     
     
         229 . The oncolytic virus of  claim 207 , wherein the viral genome comprises the thymidine kinase gene or the viral genome comprises a mutation or a deletion or a partial deletion of the thymidine kinase gene. 
     
     
         230 . An oncolytic virus comprising an exogenous nucleic acid that codes for IL15 and IL15-Rα, or a functional domain or a fragment or a variant thereof. 
     
     
         231 . An oncolytic virus comprises an exogenous nucleic acid that codes for IL15 and IL15-Rα, or a functional domain or a fragment or a variant thereof, wherein the virus further comprises a mutation or a deletion or a partial deletion of the viral gene K7R. 
     
     
         232 . A method of treating a cancer, the method comprising administering to a subject an oncolytic virus according to  claim 207 .

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