US2007166296A1PendingUtilityA1

Therapeutic Systems

58
Assignee: ENZACTA R & D LTDPriority: Jun 14, 1997Filed: Nov 9, 2006Published: Jul 19, 2007
Est. expiryJun 14, 2017(expired)· nominal 20-yr term from priority
Inventors:Philip John BurkeRichard Knox
C07K 2319/74A61K 47/6899C12N 9/0036A61K 38/00A61K 31/455A61K 48/005A61P 43/00A61K 47/6815B82Y 5/00A61P 35/00
58
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Claims

Abstract

A compound comprising a target cell-specific portion and human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug, or a polynucleotide encoding said NQO2 or said variant or fragment or fusion or derivative. A recombinant polynucleotide comprising a target cell-specific promoter operably linked to a polynucleotide encoding human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug. The compounds and polynucleotides are useful in a method of treating a patient in conjunction with a suitable prodrug. A method of treating a human patient with a target cell to be destroyed wherein the target cell expresses NQO2 the method comprising administering to the patient a prodrug which is converted to a substantially cytotoxic drug by the action of NQO2 and nicotinamide riboside (reduced) (NRH) or an analogue thereof which can pass reducing equivalents to NQO2.

Claims

exact text as granted — not AI-modified
1 . A compound comprising a target cell-specific portion and human NAD(P)H:quinone reductase 2 (NQO2) or variant or fragment or fusion or derivative thereof, which has substantially the same activity as NQO2 towards a given prodrug, or a polynucleotide encoding said NQO2 or said variant or fragment or fusion or derivative.  
     
     
         2 . A compound according to  claim 1  comprising a target cell-specific portion and human NAD(P)H:quinone reductase 2 (NQO2).  
     
     
         3 . A compound according to  claim 1  wherein the target cell-specific portion is tumour cell-specific.  
     
     
         4 . A compound according to  claim 1  wherein the target cell-specific portion comprises an antibody or fragment or derivative.  
     
     
         5 . A compound according to  claim 1  wherein the human NAD(P)H:quinone reductase 2 (NQO2) or variant or fragment or fusion or derivative thereof is located substantially inside or following expression of the polynucleotide is located substantially inside the target cell.  
     
     
         6 . A compound according to  claim 1  comprising means for delivering said polynucleotide to said target cell.  
     
     
         7 . A recombinant polynucleotide comprising a target cell-specific promoter operably linked to a polynucleotide encoding human NAD(P)H:quinone reductase 2 (NQO2) or a variant or fragment or fusion or derivative thereof which has substantially the same activity as NQO2 towards a given prodrug.  
     
     
         8 . A recombinant polynucleotide according to  claim 7  wherein said promoter is tumour cell-specific.  
     
     
         9 . A recombinant polynucleotide according to  claim 7  comprising a polynucleotide encoding NQO2.  
     
     
         10 . A recombinant polynucleotide according to  claim 7  wherein following expression in the target cell the NQO2 or a variant or fragment or fusion or derivative thereof is located substantially inside the target cell.  
     
     
         11 . A compound according to  claim 1  wherein said polynucleotide is the recombinant polynucleotide of  claim 7 .  
     
     
         12 . A therapeutic system comprising a compound according to  claim 1  or a polynucleotide according to  claim 7  and a prodrug which is converted to a substantially cytotoxic drug by the action of NQO2.  
     
     
         13 . A system according to  claim 12  wherein the prodrug is CB 1954 or an analogue thereof.  
     
     
         14 . A system according to  claim 13  wherein the prodrug is CB 1954.  
     
     
         15 . A system according to  claim 12  further comprising a cosubstrate for NQO2.  
     
     
         16 . A system according to  claim 15  wherein the cosubstrate is nicotinamide riboside (reduced) (NRH) or an analog thereof which can pass reducing equivalents to NQO2.  
     
     
         17 . A method of treating a patient with a target cell to be destroyed the method comprising (a) administering to the patient a compound according to  claim 1  or a recombinant polynucleotide according to  claim 7 , (b) allowing the NQO2 or a variant or fragment or fusion or derivative thereof to localize at, or be expressed in, the target cell; and (c) administering a prodrug which is converted to a substantially cytotoxic drug by the action of NQO2.  
     
     
         18 . A method according to  claim 17  wherein the patient has a tumour to be treated.  
     
     
         19 . A method according to  claim 17  wherein the prodrug is CB 1954 or an analogue thereof.  
     
     
         20 . A method according to  claim 19  wherein the prodrug is CB 1954.  
     
     
         21 . A method according to  claim 17  the method further comprising administering to the patient a cosubstrate for NQO2.  
     
     
         22 . A method according to  claim 21  wherein the cosubstrate is nicotinamide riboside (reduced) (NRH) or an analogue thereof which can pass reducing equivalents to NQO2.  
     
     
         23 . A compound according to  claim 1  or a recombinant polynucleotide according to  claim 7 , for use in medicine.  
     
     
         24 - 27 . (canceled)  
     
     
         28 . A method of treating a human patient with a target cell to be destroyed wherein the target cell expresses NQO2 the method comprising administering to the patient a prodrug which is converted to a substantially cytotoxic drug by the action of NQO2 and nicotinamide riboside (reduced) (NRH) or an analogue thereof which can pass reducing equivalents to NQO2.  
     
     
         29 . A method according to  claim 28  wherein the cytotoxic drug is CB 1954 or an analogue thereof.  
     
     
         30 . A method according to  claim 28  wherein the analogue of NRH is able to permeate the target cell membrane.  
     
     
         31 . A method according to  claim 28  wherein the target cell is a tumour.  
     
     
         32 . A method according to  claim 28  the method further comprising determining, before administering the prodrug or NRH or an analogue thereof, whether the target cell to be treated expresses NQO2.  
     
     
         33 . A therapeutic system comprising a prodrug which is converted to a substantially cytotoxic drug by the action of NQO2 and nicotinamide riboside (reduced) (NRH) or an analogue thereof which can pass reducing equivalents to NQO2.  
     
     
         34 . Nicotinamide riboside (reduced) (NRH) or an analogue thereof which can pass reducing equivalents to NQO2 for use in medicine.  
     
     
         35 - 39 . (canceled)

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