Methods and compositions for inactivating viruses

A method of inactivating a non-enveloped virus in a biological composition, said method comprising the steps of:

• (a) contacting the composition with an organic solvent under viral inactivating conditions, wherein said organic solvent is selected from the group consisting of (i) trialkylphosphates of the formula PO(OR1)(OR2)(OR3), wherein each of R1, R2, and R3 is, independently, C1-10 alkyl, (ii) ethers of the formula R4—O—R5, wherein each of R4 and R5 is, independently, a C1 to C18 alkyl or alkenyl radical which can contain an oxygen or sulfur atom, and (iii) alcohols of the formula R6—OH, wherein R6 is a C1 to C18 alkyl or alkenyl radical which can contain 1 to 4 oxygen or sulfur atoms, inclusive, in the chain, and which can be substituted by 1 to 4 hydroxy groups, inclusive;
• (b) contacting the composition with an inactivating agent under viral inactivating conditions, wherein said inactivating agent has the formula:
• wherein each of R1, R2, R3, R4, R6, R7, and R8 is, independently, H or a monovalent hydrocarbon moiety containing between 1 and 4 carbon atoms, inclusive, provided that R1, R2, R3, R4, R6, R7, and R8 cannot all be H;
• R5 is a divalent hydrocarbon moiety containing between 2 and 4 carbon atoms, inclusive;
• X is a pharmaceutically acceptable counter-ion;
• and n is an integer between 1 and 10, inclusive;
• and
• (c) contacting the composition with a nonionic detergent under viral inactivating conditions, wherein steps (a), (b), and (c) are performed less than 24 hours apart.

A method of inactivating a non-enveloped virus in a biological composition, said method comprising the steps of

• (a) contacting the composition with an organic solvent under viral inactivating conditions, wherein said organic solvent is selected from the group consisting of (i) trialkylphosphates of the formula PO(OR1)(OR2)(OR3), wherein each of R1, R2, and R3 is, independently, C1-10 alkyl, (ii) ethers of the formula R4—O—R5, wherein each of R4 and R5 is, independently, a C1-C18 alkyl or alkenyl radical which can contain an oxygen or sulfur atom, and (iii) alcohols of the formula R6—OH, wherein R6 is a C1 to C18 alkyl or alkenyl radical which can contain 1 to 4 oxygen or sulfur atoms, inclusive, in the chain and which can be substituted by 1 to 4 hydroxy groups, inclusive;
• (b) contacting the composition with an inactivating agent under viral inactivating conditions, wherein said inactivating agent has the formula
• ω-X1—[R1—N+(R2, R3)—]nR4.(X2−)n
• wherein X1 is Cl or Br;
• R1 is a divalent hydrocarbon moiety containing between 2 and 4 carbon atoms, inclusive;
• each of R2, R3, and R4 is, independently, H or a monovalent hydrocarbon moiety containing between 1 and 4 carbon atoms, inclusive;
• X2 is a pharmaceutically acceptable counter-ion;
• and n is an integer between 2 and 10, inclusive;
• and
• (c) contacting the composition with a nonionic detergent under viral inactivating conditions, wherein steps (a), (b), and (c) are performed less than 24 hours apart.

A method of inactivating a non-enveloped virus in a biological composition, said method comprising the steps of:

• (a) contacting the composition with an organic solvent under viral inactivating conditions, wherein said organic solvent is selected from the group consisting of (i) trialkylphosphates of the formula PO(OR1)(OR2)(OR3), wherein each of R1, R2, and R3 is, independently, C1-10 alkyl, (ii) ethers of the formula R4—O—R5, wherein each of R4 and R5 is, independently, a C1 to C18 alkyl or alkenyl radical which can contain an oxygen or sulfur atom, and (iii) alcohols of the formula R6—OH, wherein R6 is a C1 to C18 alkyl or alkenyl radical which can contain 1 to 4 oxygen or sulfur atoms, inclusive, in the chain, and which can be substituted by 1 to 4 hydroxy groups, inclusive;
• (b) contacting the composition with an inactivating agent under viral inactivating conditions, wherein said inactivating agent has the formula:
• ω—X1—CH2CH2—N+H(R1)—[R2—N+(R3, R4)—]nR5.(X2−)n+1
• wherein X1 is Cl or Br;
• each of R1, R3, R4, and R5, is, independently, H or a monovalent hydrocarbon moiety containing between 1 and 4 carbon atoms, inclusive;
• R2 is a divalent hydrocarbon moiety containing 3 or 4 carbon atoms;
• X2 is a pharmaceutically acceptable counter-ion;
• and n is an integer between 1 and 10, inclusive;
• and
• (c) contacting the composition with a nonionic detergent under viral inactivating conditions, wherein steps (a), (b), and (c) are performed less than 24 hours apart.