Xoma Corporation

Julie A Lane

Marc D Better

Susan L Bernhard

Steve F Carroll

Shau-Ping Lei

The present invention provides purified and isolated polynucleotides encoding Type I ribosome-inactivating proteins (RIPs) such as gelonin and analogs of the RIPs having a cysteine available for disulfide bonding to targeting molecules. Vectors comprising the polynucleotides and host cells transformed with the vectors are also provided. The RIPs and RIP analogs are particularly suited for use as components of cytotoxic therapeutic agents of the invention which include gene fusion products and immunoconjugates. Cytotoxic therapeutic agents or immunotoxins according to the present invention may be used to selectively eliminate any cell type to which the RIP component is targeted by the specific binding capacity of the second component of the agent, and are suited for treatment of diseases where the elimination of a particular cell type is a goal, such as autoimmune disease, cancer and graft-versus-host disease.

Materials comprising and methods of preparation and use for

The present invention provides purified and isolated polynucleotides encoding Type I ribosome-inactivating proteins and analogs thereof having a cysteine available for disulfide bonding to targeting molecules. Vectors comprising the polynucleotides and host cells transformed with the vectors are also provided. Preferred analogs according to the present invention are analogs of Type I ribosome-inactivating proteins (1) having a cysteine available for intermolecular disulfide bonding located at an amino acid position corresponding to a position not naturally available for intermolecular disulfide bonding in the Type I ribosome-inactivating protein and corresponding to a position on the surface of ricin A-chain in its natural conformation and (2) retaining ribosome-inactivating activity of the Type I ribosome-inactivating protein. The RIP analogs are particularly suited for use as components of cytotoxic therapeutic agents and, more specifically, as components of immunotoxins. Cytotoxic agents according to the present invention may be used to selectively eliminate any cell type to which the RIP component is targeted by the specific binding capacity of the second component, and are suited for treatment of diseases where the elimination of a particular cell type is a goal, such as autoimmune disease, cancer and graft-versus-host disease.

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Castro Valley, CA, United States of America

Julie A Lane