| US 7,361,352 B2 | ||
| Influenza immunogen and vaccine | ||
| Ashley J. Birkett, Escondido, Calif. (US); and Walter Fiers, Destelbergen (Belgium) | ||
| Assigned to Acambis, Inc., Cambridge, Mass. (US); and Vlaams Interuniversitair Institutuut voor Biotechnologie, Zwinjaarde (Belgium) | ||
| Filed on Feb. 26, 2004, as Appl. No. 10/787,734. | ||
| Application 10/787734 is a continuation in part of application No. 10/732862, filed on Dec. 10, 2003. | ||
| Application 10/732862 is a continuation in part of application No. PCT/US03/05196, filed on Feb. 21, 2003. | ||
| Application PCT/US03/05196 is a continuation in part of application No. 10/274616, filed on Oct. 21, 2002, abandoned. | ||
| Application 10/274616 is a continuation in part of application No. 10/082014, filed on Feb. 21, 2002, abandoned. | ||
| Prior Publication US 2006/0115489 A1, Jun. 01, 2006 | ||
| Int. Cl. A61K 39/29 (2006.01); A61K 39/00 (2006.01) | ||
| U.S. Cl. 424—189.1 [424/184.1; 424/185.1; 424/186.1; 424/192.1] | 45 Claims |
| 1. A recombinant hepatitis B virus core (HBc) protein chimer molecule with a length of about 150 to about 375 amino acid residues
that contains four peptide-linked amino acid residue sequence domains from the N-terminus that are denominated Domains I,
II, III and IV, wherein
(a) Domain I comprises (i) about 75 to about 160 amino acid residues whose sequence includes at least the sequence of the
residues of position 4 through about position 75 of HBc, (ii) one to three Cysteine residues present at a position in the
chimer molecule of about one to about −55 relative to the N-terminus of HBc of SEQ ID NO:1 [N-terminal Cysteine residue(s)],
said one or more N-terminal Cysteine residues being present within a sequence other than that of the pre-core sequence of
HBc, and (iii) includes two to four sequences of about 6 to about 24 residues of the influenza A M2 polypeptide of SEQ ID
NO:9 that is peptide-bonded to or within about 15 residues of the N-terminus of the HBc sequence;
(b) Domain II comprises about zero to about 60 amino acid residues peptide-bonded to about residue 75 of which (i) zero to
all of the sequence of HBc is present from position 76 through 85 and (ii) an optional sequence of 6 to about 48 residues
that constitute one or more repeats of 6 to about 24 residues of an influenza A M2 polypeptide of SEQ ID NO:9;
(c) Domain III is an HBc sequence from about position 86 through about position 135 peptide-bonded to about residue 85; and
d) Domain IV comprises (i) the residues of about positions 136 through 140 plus up to sixteen residues of an HBc amino acid
residue sequence from position 141 through 156 peptide-bonded to the residue of about position 135 of Domain III, (ii) zero
to three Cysteine residues, and (iii) up to about 100 amino acid residues in a sequence heterologous to HBc from position
156 to the HBc C-terminus;
said chimer molecule (i) containing no more than 10 percent conservatively substituted amino acid residues in the HBc sequence,
(ii) self-assembling into particles that are substantially free of binding to nucleic acids on expression in a host cell,
and said particles being more stable on formation than are particles formed from an otherwise identical HBc chimer that lacks
said N-terminal Cysteine residue(s) or in which an N-terminal Cysteine residue present in the chimer molecule is replaced
by another residue.
|