| US 7,615,225 B2 | ||
| Methods for treating a subject having cancer by the administration of a conjugate between a variant staphylococcal entertoxin E superantigen and an antibody that binds to the 5T4 antigen | ||
| Goran Forsberg, Malmo (Sweden); Eva Erlandsson, Dalby (Sweden); Per Antonsson, Lund (Sweden); and Bjorn Walse, Lund (Sweden) | ||
| Assigned to Active Biotech AB, Lund (Sweden) | ||
| Filed on Sep. 25, 2006, as Appl. No. 11/526,437. | ||
| Application 11/526437 is a division of application No. 09/900766, filed on Jul. 06, 2001, granted, now 7,125,554. | ||
| Claims priority of application No. 0102327 (SE), filed on Jun. 28, 2001. | ||
| Prior Publication US 2007/0082001 A1, Apr. 12, 2007 | ||
| Int. Cl. A61K 39/395 (2006.01) | ||
| U.S. Cl. 424—183.1 [424/134.1; 424/138.1; 424/180.1] | 51 Claims |
| 1. A method of treating a subject having one or more cells expressing the 5T4 cancer antigen, comprising the steps of:
(I) administering to a subject a conjugate comprising a bacterial superantigen and an antibody, wherein
the superantigen is a variant of Staphylococcal enterotoxin E, reference SEQ ID NO: 7, and differs from Staphylococcal enterotoxin
E in comprising amino acid substitutions as follows, wherein the positions of the amino acid substitutions are relative to
the amino acid positions in reference SEQ ID NO: 7:
(i) amino acid position 20 is glycine or a conserved variant thereof, amino acid position 21 is threonine or a conserved variant
thereof, amino acid position 24 is glycine or a conserved variant thereof, amino acid position 27 is lysine or a conserved
variant thereof, and amino acid position 227 is serine or alanine, or a conserved variant thereof; and
(ii) wherein at least one amino acid in a region C is substituted with a different amino acid, such that the superantigen
variant has reduced seroreactivity compared to the seroreactivity of Staphylococcal enterotoxin having the amino acid sequence
of SEQ ID NO: 7, and the position of the amino acid substitution in region C is selected from the group consisting of amino
acid positions 74, 75, 78, 79, 81, 83 and 84; and wherein the antibody binds 5T4 cancer antigen; and
(II) the antibody binding to a 5T4 cancer antigen present on at least one cell in the subject, thereby leading to lysis of
said one or more cells expressing the 5T4 cancer antigen.
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