Drug – bio-affecting and body treating compositions – Radionuclide or intended radionuclide containing; adjuvant... – Attached to antibody or antibody fragment or immunoglobulin;...
Patent
1993-12-10
1998-06-09
Eisenschenk, Frank C.
Drug, bio-affecting and body treating compositions
Radionuclide or intended radionuclide containing; adjuvant...
Attached to antibody or antibody fragment or immunoglobulin;...
424 3, 424 94, 5303873, 5303883, 5303885, 536 253, 536 7, 435 5, 4353201, 4352523, 43525233, C12N 1563, C07K 1610, C07H 2104, G01N 3353
Patent
active
057629056
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to the field of immunology and specifically to human monoclonal antibodies which bind and neutralize respiratory syncytial virus (RSV).
2. Description of Related Art
RSV is the major viral pathogen of the pediatric respiratory tract and has been identified as a leading cause of pneumonia and bronchiolitis. In the United States alone, there is a relatively large population of infants and children, about 100,000 to 200,000, at high risk of developing severe or fatal RSV illness. The high risk population includes infants and children with bronchopulmonary dysplasia, congenital heart disease, cystic fibrosis, cancer or various forms of immunodeficiency, as well as adults immunosuppressed prior to bone marrow transplantation, for example (McIntosh and Chanock (1990) Virology, 2nd edn. (Fields and Knipe, eds) Raven Press, Ltd., New York, pp. 1045-1072).
Several lines of evidence indicate that antibodies mediate resistance to RSV infection and illness. First, there is a correlation between levels of maternal IgG antibodies to RSV and the resistance of infants to infection during the first months of life when the risk of severe disease is greatest (Ogilvie, et al., J. Med. Virol., 7:263, 1981). Second, pooled human IgG containing a high level of RSV neutralizing antibodies or appropriate murine monoclonal antibodies that neutralize RSV efficiently can protect small animals from pulmonary infection when administered prophylactically and can reduce the titer of virus in the lungs of small animals and experimental primates at the height of RSV infection when administered therapeutically (Walsh, et al, Infection and Immunity, 43:756, 1984; Prince, et al., J. Virol., 55:517, 1985; Prince, et al., Virus Research, 3:193, 1985; Prince, et al., J. Virol., 63:1851, 1987; Hemming, et al., J. Inf. Dis., 152:1083, 1985). Third, a clinical study of pooled human IgG containing a high titer of RSV neutralizing antibodies has provided preliminary indications that these antibodies can exert a therapeutic effect on serious RSV disease in infants and young children (Hemming, et al., Antimicrob. Agnts. Chemotherap., 31:1882, 1987). Given this evidence, there is considerable interest in developing neutralizing antibodies to RSV for immunoprophylaxis and therapy for protecting infants at high risk of serious disease and for therapy in cases of serious RSV lower respiratory tract infection.
At present, there is no RSV vaccine available. The strategy currently being evaluated for prophylactic efficacy entails periodic intravenous inoculation of human IgG prepared from pooled plasma. Because of the large quantity of globulin required (1 to 2 gm per kg) and the need to administer this material intravenously in the clinic or hospital over a 2 to 4 hour interval every month during the fall, winter and early spring, this strategy is not very practical.
The main neutralization antigens on the surface of the RSV virion are the major glycoproteins F (viral fusion) and G (attachment). Monospecific antiserum prepared against immunoaffinity purified F or G glycoprotein neutralizes RSV with high efficiency (Walsh, et al., J. Gen. Microbiol., 67:505, 1986). The antiserum to F, but not G, also inhibits fusion of RSV-infected cells to neighboring uninfected cells.
There is a need to develop human RSV antibody preparations with greater specific activity than the pooled human plasma preparations. A potentially effective solution to this problem would be the utilization of human monoclonal antibodies to RSV. RSV-specific monoclonal antibody, in contrast to polyclonal antisera, contains, by its very nature, a higher concentration of specific antibody. Therefore, the use of monoclonal antibody would decrease the amount of globulin required for prophylaxis or therapy by several orders of magnitude. As a consequence, an effective dose of monoclonal antibody could be administered intramuscularly (IM), rather than intravenously (IV) over a long period of time. Prophylaxis of
REFERENCES:
patent: 4946778 (1990-08-01), Ladner et al.
patent: 5223409 (1993-06-01), Ladner et al.
patent: 5332567 (1994-07-01), Goldenberg
patent: 5403484 (1995-04-01), Ladner et al.
Paul, Fundamental Immunology, 1993, pp. 241-242.
Wang et al., Mol. Immunol., 28(12):1387, 1991.
Stanworth et al., In Handbook of Experimental Immunology, pp. 12.1-12.25, 1986.
Kimman et al., Arch. Virol., 112:1, 1990.
Tempest et al., Biotechnology, 9:266, 1991.
Barbas, III Carlos F.
Burton Dennis R.
Chanock Robert M.
Crowe, Jr. James E.
Murphy Brian R.
Eisenschenk Frank C.
The Scripps Research Institute
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