Methods for the selective modification of viral nucleic acids

• US 6,136,586 A
• Filed: 05/13/1997
• Issued: 10/24/2000
• Est. Priority Date: 08/29/1995
• Status: Expired due to Fees

• Current Assignee: V.I. Technologies, Inc. (Panacos Pharmaceuticals, Inc.)
• Original Assignee: V.I. Technologies, Inc. (Panacos Pharmaceuticals, Inc.)
• Inventors: Budowsky, Edward I.
• Primary Examiner(s): Wortman, Donna C.
• Assistant Examiner(s): BRUMBACK, BRENDA G
• Application Number:
  US08/855,378
• Time in Patent Office: 1,260 Days
• Field of Search: 435/238, 435/236, 435/2
• US Class Current: 435/238
• CPC Class Codes: A61L 2/0088 Liquid substances
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: C07C 211/15 the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
• CPC Class Codes: C07D 203/08 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
• CPC Class Codes: C07D 203/12 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C12N 2760/16063 by chemical treatment
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

This invention provides means and methods of inactivating viruses and other organisms in cell-containing or biopolymer-containing compositions without significant alteration of proteins or other biopolymers by contacting such compositions with selective ethyleneimine oligomer inactivating agents, such as the trimer or tetramer.

Claims

1. A method of inactivating an infectious animal virus in a biological composition containing non-viral protein, said method comprising contacting the composition with a selective ethyleneimine oligomer inactivating agent under viral inactivating conditions, wherein the biological composition is selected from the group consisting of human milk, human saliva, human semen, human serum, a human product of a mammalian cell culture, a human product of a non-mammalian cell culture, a human non-blood product produced by recombinant DNA technology, and a human placental extract.

6. The method of claim 1, 2, 3, 4, or 5, wherein the virus is selected from the group consisting of poxviruses, herpes viruses, adenoviruses, papovirus, parvoviruses, reovirases, orbiviruses, rotaviruses, alphaviruses, rubivinuses, flaviviruses coronavirses parimyoxviruses, morbillivirusesmse, pneumaviruses vesiculoviruses, lyssaviruses, picomaviuses, orthomyoxviruses, bunyaviruses, phlebovirases, nairoviruses, hepadnaviruses, arenaviruses, retroviruses, and filoviruses.

7. The method of claim 1, 2, 3, 4, or 5, wherein the step of contacting comprises incubating the biological composition with 0.0001 M to 0.015 M ethyleneimine oligomer;

at pH 6.5 to pH 8.5;

it a solution having an ionic strength of 0.1 M to 0.2 M at 15°

C. to 3°

C. for 1 hour to 500 hours.

8. The method of claim 7, wherein the step of contacting involves incubating the composition with 0.007 M ethyleneimine oligomer;

at pH 7.0 to pH 8.0;

in a solution having an ionic strength of 0.15 M.

9. The method of claim 1, 2, 3, 4, or 5, wherein the virus is an enveloped virus.

10. The method of claim 1, 2, 3, 4, or 5, wherein the virus is a non-enveloped virus.

11. The method of claim 1, 2, 3, or 5, wherein the virus is a non-enveloped virus and the ethyleneimine oligomer is ethyleneimine dimer or trimer.

12. The method of claim 11, wherein said ethyleneimine oligomer is ethyleneimine dimer.

2. A method of inactivate infectious animal viruses in a biological composition containing non-viral protein, said method comprising contacting the composition with a selective ethyleneirnine oligomer inactivating agent under viral inactivating conditions, wherein the biological composition is selected from the group consisting of red blood cell. concentrates, platelet concentrates, and leukocyte concentrates.

13. The method of claim 2, wherein the biological composition is a red blood cell concentrate.

3. A method of inactivating infectious viruses in a biological composition comprising contacting the composition with a selective ethyleneimine oligomer inactivating agent under viral inactivating conditions, wherein the biological composition comprises one or more human purified protein selected from the group consisting of fibrinogen, factor VII, factor VIII, factor IX, factor X, immunoglobin, prealbumin, retinol-binding protein, albumi, alpha-globulins, gammaglobulins, complement components, fibronectin, antitbrombin III, hemoglobin, interferon, growth factors, plasminogen activator, growth hormone, insulin and elropoiefim.

4. A method of inactivating an infectious virus in a biological composition, wherein said virus is contained in a cell, said method comprising contacting the cell with a selective ethyleneimine oligomer inactivating agent.

5. A method of inactivating infectious animal viruses in a biological composition containing non-viral protein, said method comprising contacting the composition with a selective ethyleneimine oligomer inactivating agent under viral inactivating conditions, wherein said biological composition is selected from the group consisting of whole human blood, purified or partially purified blood proteins, purified or partially purified blood plasma, platelet-rich plasma, a plasma concentrate, a precipitate from any fractionation of said plasma, a supernatant from any fractionation of said plasma, and a blood cryoprecipitate.

14. The method of claim 5, wherein said biological composition is whole human blood.

15. The method of claim 14, wherein said ethyleneimine oligomer is ethyleneimine dimer.

16. The method of claim 5, wherein said biological composition is human blood plasma.

17. The method of claim 16, wherein said ethyleneimine oligomer is ethyleneimine dimer.