Stabilized formulations of adenovirus
AssigneesBerlex Biosciences, Schering Corporation
InventorsElisabeth Lehmberg, Erno Pungor
Life of this patent
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Abstract
A method is disclosed to stabilize compositions comprising airborne viruses, particularly Adenoviruses; and more particularly recombinant Adenoviruses, by adding to the compositions a non-ionic detergent which comprises an alkyl moiety and a polyethylene glycol (PEG). Pharmaceutical and other compositions of Adenoviruses, particularly recombinant Adenoviruses suitable for methods of gene therapy, which comprise such detergents are also disclosed.
Claims51
A method for stabilizing a composition comprising an airborne virus comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein
- X is 4-30, and R is a linear or branched alkyl of 10-70 carbon atoms,
- or Formula II
- 18
- wherein R is —CO2R′ having 10 to 70 carbons, and W+X+Y+Z=20, wherein R′ is as above for R,
- or Formula III
- 19
- wherein R is as above, and X is 5-100, Y is 25-75 and Z is 50-100,
- or Formula IV
- 20
- wherein X is 5-15 ring A is phenylene or cyclohexylene, and R′ is R as above,
- or a combination thereof.
A method for stabilizing a composition comprising an airborne virus comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent which comprises an alkyl moiety and a polyethylene glycol moiety.
A method for stabilizing a composition comprising an Adenovirus comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent which comprises an alkyl moiety and a polyethylene glycol (PEG) moiety.
A method for stabilizing a composition comprising an Adenovirus, comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein X is 4-30, and
- R is a linear or branched alkyl of 10-70 carbon atoms,
- or Formula II
- 24
- wherein R is a —CO2R′ having 10 to 70 carbons, and W+X+Y+Z=20, wherein R′ is as defined above for R,
- or Formula III
- 25
- wherein R is as above, and X is 5-100, Y is 25-75 and Z is 50-100,
- or Formula IV
- 26
- wherein X is 5-15, ring A is phenylene or cyclohexylene, and R′ is R as above,
- or a combination thereof.
A method for stabilizing a composition comprising Adenovirus, comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein X is 4-30, and R is (CH3)(CH2)Y—, wherein Y is 10-15,
- or Formula II
- 27
- wherein R is CaH(2a+1)CO2—, a is 10 to 70,
- or Formula III
- 28
- wherein R is CH3, X is 55, Y is 29 and Z is 55, or R is CH3, X is 98, Y is 67 and Z is 98,
- or Formula IV,
- 29
- wherein R′ is (CH3)3C.CH2C(CH3)2—,A is phenylene, and X is 9-10 or R′ (CH3)3C.C2C(CH3)2—,
- A is cyclohexylene, and X is 9-10,
- or a combination thereof.
A method to stabilize a composition comprising Adenovirus, comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein R is (CH3)(CH2)Y—, and
- wherein X is 23 and Y is 12, or X is 20 and Y is 12,
- or Formula II
- 30
- wherein R is R═C11H23CO2—,
- or a combination thereof.
A method for stabilizing a composition comprising an airborne virus, comprising adding to the composition a stabilizing-effective amount of a non-Ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein X is 4-30, and R is a linear or branched alkyl of 10-70 carbon atoms,
- or Formula II
- 31
- wherein R is a —CO2R′ having 10 to 70 carbons, and W+X+Y+Z=20, wherein R′ is as defined above for R,
- or Formula III
- 32
- wherein R is as above, and X is 5-100, Y is 25-75 and Z is 50-100,
- or Formula IV.
- 33
- wherein X is 5-15, ring A is phenylene or cyclohexylene, and R′ is R as above,
- or a combination thereof, in a concentration ranging from about 0.005% to about 0.1% (vol/vol).
A method for stabilizing a composition comprising an airborne virus, comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent of Formula I.
- R—O(CH2CH2O)X—H I
- wherein X is 4-30, and R is (CH3)(CH2)Y—, wherein Y is 10-15,
- or Formula III
- 34
- wherein R is CaH(2a+1)CO2—, a is 10 to 70,
- or Formula III
- 35
- wherein R is CH3, X is 55 Y is 29 and Z is 55, or R is CH3, X is 98, Y is 67 and Z is 98,
- or Formula IV,
- 36
- wherein R′ is (CH3)3C.CH2C(CH3)2—, A is phenylene, and X is 9-10, or R′ (CH3)3C.CH2C(CH3)2—,
- A is cyclohexylene, and X is 9-10,
- or a combination thereof.
A method to stabilize a composition comprising airborne virus, comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein R is (CH3(CH2)Y—, and wherein X is 23 and Y is 12, or X is 20 and Y is 12,
- or Formula II
- 37
- wherein R is R═C11H23CO2—,
- or a combination thereof.
A method for stabilizing a composition comprising an airborne virus to reduce loss of virus amount or activity comprising adding to the composition a stabilizing-effective amount of a non-ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein
- X is 4-30, and R is a linear or branched alkyl of 10-70 carbon atoms,
- or Formula II
- 38
- wherein R is —CO2R′ having 10 to 70 carbons, and W+X+Y+Z=20, wherein R′ is as above for R,
- or Formula III
- 39
- wherein R is as above, and X is 5-100, Y is 25-75 and Z is 50-100,
- or Formula IV
- 40
- wherein X is 5-15 ring A is phenylene or cyclohexylene, and R′ is R as above, or a combination thereof, wherein the loss of virus amount or activity is less than about 30% over a given period of time at about 2-8° C., room temperature, 37° C., −20° C. or −70° C. compared to the loss when said non-ionic detergent is not present.
A pharmaceutical composition comprising an airborne virus a stabilizing-effective amount of a non-ionic detergent of Formula I,
- R—O(CH2 CH2O)X—H I
- wherein
- X is 4-30 and R is a linear or branched alkyl of 10-70 carbon atoms,
- or Formula II
- 41
- wherein R IS —CO2R′ having 10 to 70 carbons, and W+X+Y+Z=20, wherein R′ is as above for R,
- or Formula III
- 42
- wherein R is as above, and X is 5-100, Y is 25-75 and Z is 50-100,
- or Formula IV
- 43
- wherein X is 5-15 ring A is phenylene or cyclohexylene, and R′ is R as above,
- or a combination thereof and at least one pharmaceutically acceptable carrier, salt or excipient.
A pharmaceutical composition comprising an Adenovirus, Tween 20 at a concentration of about 0.05% (vol/vol), and a pharmaceutically acceptable carrier comprising 2 mM MgCl2 , 2% sucrose (wt/vol) and water.
A pharmaceutical composition, comprising
- a) an Adenovirus,
- b) a stabilizing-effective amount of a non-ionic detergent of Formula I
- R—O(CH2CH2O)X—H I
- wherein
- X is 4-30, and R is a linear or branched alkyl of 10-70 carbon atoms,
- or Formula II
- 44
- wherein R is —CO2R′ having 10 to 70 carbons, and W+X+Y+Z=20, wherein R′ is as
- above for R,
- or Formula III
- 45
- wherein R is as above, and X is 5-100, Y is 25-75 and Z is 50-100,
- or Formula IV
- 46
- wherein X is 5-15 ring A is phenylene or cyclohexylene, and R′ is R as above,
- or a combination thereof, and
- c) at least one pharmaceutically acceptable carrier.
A pharmaceutical composition, comprising
- a) an airborne virus,
- b) a stabilizing-effective amount of a non-ionic detergent of according to Formula I
- R—O(CH2CH2O)X—H I
- wherein
- X is 4-30, and R is a linear or branched alkyl of 10-70 carbon atoms, or Formula II
- 47
- wherein R is —CO2R′ having 10 to 70 carbons, and W+X+Y+Z=20, wherein R′ is as above for R,
- or Formula III
- 48
- wherein R is as above, and X is 5-100, Y is 25-75 and Z is 50-100,
- or Formula IV
- 49
- wherein X is 5-15 ring A is phenylene or cyclohexylene, and R′ is R as above,
- or a combination thereof;
- and
- c) at least one pharmaceutically acceptable carrier.
Dependencies are inferred from the claim text.