Antibodies specific for CD44v6

#1. Field of the Invention

#The present invention belongs to the field of oncology. The invention relates to antibodies with specified sequence which are specific for an epitope which is coded by the variant exon v6 of the CD44 gene and to derivatives of said antibody. The invention also provides nucleic acid molecules encoding said antibody proteins. The invention furthermore pertains to methods for producing said antibody proteins. The invention also provides pharmaceutical compositions comprising said antibody proteins. The invention furthermore is concerned with the use in the manufacture of a medicament for the treatment of cancer.

#2. Background Art

#FIG. 1: Evaluation of relative binding affinities tested in a competitive cell ELISA.

#IC50: concentrations of cMAb and hMAbs at which binding of mMAb BIWA 1 to attached A431 cells is reduced by 50%. IC50 values relative to BIWA 2 are indicated.

#FIG. 2. Biodistributions of co-injected 125I- and 131I-labeled CD44v6-specific MAbs (10 μCi, 50 μg) in HNX-OE xenograft-bearing mice at 3 or 4 days p.i. Three groups of mice received either (A) 131I- U36 (black bars) and 125I-BIWA 1 (hatched bars) (n=5), (B) 131I-BIWA 4 (black bars) and 125I-BIWA 2 (hatched bars) (n=6) or (C) 131I-BIWA 4 (black bars) and 125I-BIWA 8 (hatched bars) (n=6). At 3 (A) or 4 days (B,C) after injection mice were bled, sacrificed, dissected and the radioactivity levels (% ID/g±s.e.m.) of tumor, blood and several organs were assessed. (Bld: blood, Tum: tumor, Liv: liver, Spl: spleen, Kid: kidney, Hrt: heart, Stm: stomach, Ilm: ileum, Cln: colon, Blr: bladder, Str: sternum, Msc: muscle, Lng: lung, Skn: skin, Tng: tongue).

#Before the embodiments of the present invention it must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural reference unless the context clearly dictates otherwise. Thus, for example, reference to “an antibody” includes a plurality of such antibodies, reference to the “cell” is a reference to one or more cells and equivalents thereof known to those skilled in the art, and so forth. Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods, devices, and materials are now described. All publications mentioned herein are incorporated herein by reference for the purpose of describing and disclosing the cell lines, vectors, and methodologies which are reported in the publications which might be used in connection with the invention. Nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.

#The terms “antibody molecule” or “antibody protein” or “antibody” as used herein shall be considered equivalent.

#“Complementarity determining regions of a monoclonal antibody” are understood to be those amino acid sequences involved in specific antigen binding according to Kabat (Kabat E. A., Wu T. T., Perry H. M., Gottesman K. S. and Foeller C. (1991) Sequences of Proteins of Immunological Interest (5th Ed.). NIH Publication No. 91-3242. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, Md.) in connection with Chothia and Lesk (Chothia and Lesk (1987) J. Mol. Biol. 196:901-917).