Diphtheria toxin receptor-binding region
AssigneesThe Regents of the University of California, President and Fellows of Harvard College
InventorsR. John Collier, David Eisenberg, Haian Fu, Seunghyon Choe
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Abstract
The invention features a polypeptide consisting of amino acids 379-535 of diphtheria toxin, and portions thereof. This region, shown by X-ray crystallographic analysis to comprise the receptor binding domain of diphtheria toxin, is used as an immunogen and clinical therapeutic against diphtheria.
Claims15
A DNA encoding a polypeptide consisting of:
- a) amino acids 379-535;
- b) amino acids 380-535;
- c) amino acids 381-535;
- d) amino acids 382-535;
- e) amino acids 383-535;
- f) amino acids 384-535;
- g) amino acids 385-535;
- h) amino acids 386-535;
- i) amino acids 496-512;
- j) amino acids 379-512;
- k) amino acids 380-512;
- l) amino acids 381-512;
- m) amino acids 382-512;
- n) amino acids 383-512;
- o) amino acids 384-512;
- p) amino acids 385-512;
- q) amino acids 386-512;
- r) amino acids 496-535;
- or
- s) amino acids 496-524 (all of FIG. 5 (SEQ ID NO:
- 1)), wherein said DNA does not encode an amino acid sequence corresponding to amino acids 291 to 378 of FIG. 5 (SEQ ID NO:1) immediately adjacent to the amino terminal end of said polypeptide and said polypeptide is capable of binding a diphtheria toxin sensitive cell.
An essentially pure preparation of nucleic acid, said nucleic acid comprising a sequence encoding a polypeptide consisting of:
- a) amino acids 379-535;
- b) amino acids 380-535;
- c) amino acids 381-535;
- d) amino acids 382-535;
- e) amino acids 383-535;
- f) amino acids 384-535;
- g) amino acids 385-535;
- h) amino acids 386-535;
- i) amino acids 496-512;
- j) amino acids 379-512;
- k) amino acids 380-512;
- l) amino acids 381-512;
- m) amino acids 382-512;
- n) amino acids 383-512;
- o) amino acids 384-512;
- p) amino acids 385-512;
- q) amino acids 386-512;
- r) amino acids 496-535;
- or
- s) amino acids 496-524 (all of FIG. 5 (SEQ ID NO:
- 1)), wherein said nucleic acid does not encode an amino acid sequence corresponding to amino acids 291 to 378 of FIG. 5 (SEQ ID NO:1) immediately adjacent to the amino terminal end of said polypeptide and said polypeptide is capable of binding a diphtheria toxin sensitive cell.
A method of making a polypeptide consisting of
- a) amino acids 379-535;
- b) amino acids 380-535;
- c) amino acids 381-535;
- d) amino acids 382-535;
- e) amino acids 383-535;
- f) amino acids 384-535;
- g) amino acids 385-535;
- h) amino acids 386-535;
- i) amino acids 496-512;
- j) amino acids 379-512;
- k) amino acids 380-512;
- l) amino acids 381-512;
- m) amino acids 382-512;
- n) amino acids 383-512;
- o) amino acids 384-512;
- p) amino acids 385-512;
- q) amino acids 386-512:
- r) amino acids 496-535;
- or
- s) amino acids 496-524 (all of FIG. 5 (SEQ ID NO:
- 1)), comprising synthesizing said polypeptide biologically by expression from genetically-engineered DNA encoding said polypeptide.
A DNA encoding a fusion polypeptide consisting of (1) a first sequence corresponding to
- a) amino acids 379-535;
- b) amino acids 380-535;
- c) amino acids 381-535;
- d) amino acids 382-535;
- e) amino acids 383-535;
- f) amino acids 384-535;
- g) amino acids 385-535;
- h) amino acids 386-535;
- i) amino acids 496-512;
- j) amino acids 379-512;
- k) amino acids 380-512;
- l) amino acids 381-512;
- m) amino acids 382-512;
- n) amino acids 383-512;
- o) amino acids 384-512;
- p) amino acids 385-512;
- q) amino acids 386-512;
- r) amino acids 496-535;
- or
- s) amino acids 496-524 (all of FIG. 5 (SEQ ID NO:
- 1)), linked by a peptide bond to (2) a second sequence, provided that said fusion polypeptide does not comprise amino acids 291 to 378 of FIG. 5 (SEQ ID NO:1) immediately adjacent to the amino terminal end of said first sequence.
Dependencies are inferred from the claim text.