Toxin conjugates
AssigneeCetus Corporation
InventorsLawrence I. Greenfield, Donald A. Kaplan, Danute E. Nitecki
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Abstract
A novel class of polypeptides of the general formula (F-(Pro).sub.n).sub.m F, wherein F represents a flexible amino acid sequence wherein each amino acid is individually selected from the group consisting of serine, glycine, and threonine, and n is an integer from 4-8 inclusive and m is an integer from 1-4 inclusive, is disclosed. Thses polypeptides are useful in the construction of conjugates between antibodies and peptide toxins. The preparation of such conjugate toxins by linking antibodies to toxin/spacer composites prepared by recombinant techniques is also disclosed.
Claims3
A recombinant polypeptide, useful in making toxin conjugates, comprising:
- a diptheria toxin, or an enzymatic fragment of diptheria toxin;
- and a spacer covalently linked to said diptheria toxin comprising an amino acid sequence which has the formula:
- Gly-Thr-Gly-Ser-Gly-(Pro).sub.6 -Ser-Gly-Ser-Gly-Thr-Cys.
A method of killing undesirable cells in mammals comprising administering to a mammal in need of such treatment an effective amount of a conjugated toxin comprising;
- an antibody or fragment thereof which binds to a target cell which comprises the corresponding antigenic determinant;
- and a recombinant protein comprising:
- a spacer covalently bound to said antibody or fragment thereof comprising an amino acid sequence which has the formula:
- Gly-Thr-Gly-Ser-Gly-(Pro).sub.6 -Ser-Gly-Ser-Gly-Thr-Cys;
- and a cytotoxic protein fragment covalently bound to said spacer selected from the group consisting of diptheria toxin and enzymatically active fragments of diptheria toxin.
Dependencies are inferred from the claim text.