Strategically modified hepatitis B core proteins and their derivatives
AssigneeImmune Complex Corporation
InventorAshley J. Birkett
Life of this patent
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Abstract
A strategically modified hepatitis B core protein is described, where an insert is provided, preferably in an immunodominant region of the nucleocapsid protein, containing a chemically reactive amino acid residue. The modified hepatitis B core protein or its aggregated nucleocapsid protein particles can be pendently linked to a hapten to form a modified nucleocapsid conjugate. Such a conjugate is useful in the preparation of vaccines or antibodies. The modified hepatitis B core protein can also be modified to include a T cell epitope.
Claims22
A strategically modified hepatitis B core protein conjugate comprising a strategically modified hepadnavirus nucleocapsid protein pendently linked to a hapten, wherein the strategically modified hepatitis B core protein comprises an amino acid sequence corresponding to the hepatitis B core protein amino acid sequence of SEQ ID NO:2 including the amino acid residues numbered about 10 to about 140 and additionally having an insert in the region corresponding to amino acid residues numbered about 50 to about 100, said insert (i) being 1 to about 40 amino acid residues in length, and (ii) containing a chemically-reactive amino acid residue, said hapten being pendently linked to said chemically-reactive amino acid residue.
A strategically modified hepatitis B core protein particle comprising a strategically modified hepatitis B core protein subunit having an insert containing a chemically-reactive amino acid side chain, said insert not itself an antigenic determinant.
A strategically modified hepatitis B core protein particle conjugate comprising a plurality of strategically modified hepatitis B core protein subunits pendently linked to a hapten.
An immunogenic fusion protein conjugate comprising a polypeptide hapten pendently linked to a strategically modified hepatitis B core protein that comprises three peptide-linked domains, I, II and III from the N-terminus, wherein
- (a) Domain I corresponds to residues about 10 through 50 of the amino acid sequence of hepatitis B core protein of SEQ ID NO:2;
- (b) Domain II is bonded to the carboxy terminal residue of Domain I and corresponds to residues 50 to 100 of said amino acid sequence of hepatitis B core protein that further contains a heterologous insert 1 to about 40 amino acid residues in length that includes a chemically-reactive amino acid residue;
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- (c) Domain III is bonded to the carboxy terminal residue of Domain II and corresponds to residues 100 to about 140 of the amino acid sequence of hepatitis B core protein.
A strategically-modified hepatitis B core protein comprising an amino acid sequence corresponding to about amino acid residue 10 to about amino acid residue 140 of the hepatitis B amino acid sequence of SEQ ID NO:2 and having an amino acid sequence insert in the region corresponding to about residue 50 to about residue 100 of the hepatitis B, wherein the insert includes a chemically-reactive amino acid residue and the insert itself is not an antigenic determinant.
An inoculum comprising an immunogenic amount of a strategically modified hepatitis B core protein conjugate dissolved or dispersed in a pharmaceutically acceptable diluent, said strategically modified hepatitis B core protein conjugate comprising a hapten pendently linked to a strategically modified hepatitis B core protein, wherein the strategically modified hepatitis B core protein comprises an amino acid sequence corresponding to the hepatitis B core protein amino acid sequence of SEQ ID NO:2 including the amino acid residues numbered about 10 to about 140 and additionally having an insert in the region corresponding to amino acid residues numbered about 50 to about 100, said insert (i) being 1 to about 40 amino acid residues in length, and (ii) containing a chemically-reactive amino acid residue, said hapten being pendently linked to said chemically-reactive amino acid residue.
A process for inducing antibodies in an animal host comprising the steps of inoculating said animal host with an inoculum that comprises an immunogenic amount of a strategically modified hepatitis B core protein conjugate dissolved or dispersed in a pharmaceutically acceptable diluent, said strategically modified hepatitis B core protein conjugate comprising a hapten pendently linked to a strategically modified hepatitis B core protein, wherein the strategically modified hepatitis B core protein comprises an amino acid sequence corresponding to the hepatitis B core protein amino acid sequence of SEQ ID NO:2 including the amino acid residues numbered about 10 to about 140 and additionally having an insert in the region corresponding to amino acid residues numbered about 50 to about 100, said insert (i) being 1 to about 40 amino acid residues in length, and (ii) containing a chemically-reactive amino acid residue, said hapten being pendently linked to said strategically modified hepatitis B core protein through said chemically-reactive amino acid residue, and maintaining said animal for a time sufficient for antibodies to be induced.
Dependencies are inferred from the claim text.