Miles Inc.

Miles Laboratories, Inc.

Milton M Mozen

Gautam Mitra

Robert E Louie

The effects of Cohn-Oncley cold alcohol fractionation on infectivity of two prototype retroviruses, mouse xenotropic type C and the LAV strain of AIDS retrovirus result in a significant reduction in retrovirus titer. At least a 100,000-fold reduction of LAV was obtained when fractionating plasma to fraction II. Adjustment to pH 4.0 at filtrate III was as effective for viral inactivation as was precipitation of fraction II from filtrate III with 25% ethanol. Liquid immunoglobulin preparations spiked with LAV and incubated at 27.degree. C. for 3 days resulted in an additional 1,000-10,000-fold reduction of LAV titer. Our results support the clinical and epidemiological evidence that therapeutic immunoglobulin preparations prepared by Cohn-Oncley cold ethanol processing (at least about 18% v/v alcohol, pH.ltoreq.5.4) and then stored at a pH equal to or less than about 5.4 and a temperature of at least 27.degree. C. for at least 3 days, do not transmit retroviruses such as the LAV strain of the AIDS virus. Similar fractionation followed by storage at a higher pH (6.8) followed by a storage at a higher temperature (45.degree. C.) for at least 8 hours also appears effective in avoiding transmission of the retroviruses.

Preparation of human immunoglobulin free of hepatitis C

Antibodies, including monoclonal antibodies (Mabs), can be made substantially free of infectious viruses by storing them in a liquid state at conditions of pH, temperature and time sufficient to inactive substantially all infectious viruses. Preferred inactivation methods involve use of a pH equal to or less than about 4.0 at a temperature of at least about 5.degree. C. for at least about 16 hours.

Preparation of virus-free antibodies

Immune serum globulins (ISG) can be made substantially free of infectious retroviruses by storing the ISG in a liquid state at conditions of pH, temperature and time sufficient to inactivate substantially all infectious retroviruses. Preferred inactivation methods involve use of either of two specified storage conditions: (1) at a pH equal to or less than about 4.25 at a temperature of about 27.degree. C. for at least 3 days, or (2) at a pH equal to or less than about 6.8 at a temperature of about 45.degree. C. for at least about 8 hours.

Preparation of retrovirus-free immunoglobulins

Immune serum globulins (ISG) can be made substantially free of infectious retroviruses by preparing the ISG from human plasma using a cold ethanol plasma fractionation process at a pH equal to or less than 5.4 and then storing the ISG at either of two specified storage conditions: (1) at a pH equal to or less than about 4.25 at a temperature of about 27.degree. C. for at least 3 days, or (2) at a pH equal to or less than about 6.8 at a temperature of about 45.degree. C. for at least about 8 hours. pg,10

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Berkeley, CA, United States of America

Milton M Mozen