Humanized neutralizing antibodies against hemolytic uremic syndrome
Novel human monoclonal antibodies derived from a transgenic mouse are disclosed as well as a process for the preparation of the novel monoclonals and a therapeutic method of treating an individual for hemolytic uremic syndrome or of protecting an individual against hemolytic uremic syndrome by administration of the monoclonals to the individual in need of treatment or protection.
1. A dosage formulation comprising
an effective amount of human or humanized monoclonal antibodies for intravenous administration to humans to produce a serum level of anti-Shiga toxin II antibodies of at least 0.5 micrograms/ml to prevent or treat systemic hemolytic uremic syndrome in a human,
the antibodies consisting of antibodies having percent neutralization of Shiga-like toxin II in a HeLa cell cytotoxity assay of greater than 70% and neutralizing Shiga-like toxin II in vivo,
wherein the antibodies are specifically reactive with the alpha subunit of Shiga-like toxin II produced by Escherichia coli which causes hemolytic uremic syndrome in humans.
2. The dosage formulation of claim 1 , wherein the antibodies are human monoclonal antibodies.
3. The dosage formulation of claim 1 , wherein the antibodies are produced by recombinant DNA methodology.
4. The dosage formulation of claim 1 , wherein the antibodies are chimeric monoclonal antibodies.
5. The dosage formulation of claim 1 wherein the antibodies are effective to prevent neurological signs of hemolytic uremic syndrome or lesions,
wherein the neurological signs or lesions are selected from the group consisting of cerebral hemorrhaging and convulsions.
6. The dosage formulation of claim 1 , wherein the antibodies are effective to prolong survival.
7. The dosage formulation of claim 1 equivalent to 4 ml serum from an animal immunized with Shiga-like toxin II/kg body weight.
8. The dosage formulation of claim 1 equivalent to a dosage of 3 mg human monoclonal antibody to Shiga-like toxin II administered to a newborn pig.
9. The dosage formulation of claim 1 having a percent neutralization of Shiga-like toxin II in a HeLa cell cytotoxity assay of between greater than 90%.
10. The dosage formulation of claim 1 wherein the antibodies are a human monoclonal antibody specifically reactive with the alpha subunit of the Shiga-like toxin II deposited on Dec. 12, 2001 with the American Type Culture Collection, ATCC Accession No. 5C12.