Appeal No. 1996-2539
Application 08/150,776
appears sufficient for protection against infection by any one of the virus
subtypes.
* * *
[T]he S(139-147) segment of S-protein is part of an immunologically
important region recognized by both B and T cells.
h
Since the S(139-147) segment of the S-protein sequence is important for
eliciting HBsAg-specific B and T -cell responses, amino acid replacements
h
within this sequence may profoundly affect the recognition of the S-protein by
both B- and T -cells and the specificity of immune responses to the S-
h
protein. Among well-defined serological subtypes of HBsAg there is a
single amino acid substitution (serine threonine) at residue 143. All other
amino acid residues within this sequence are completely conserved among
the distinct HBV subtypes.
Evidence for the existence of genetic variants of HBV with envelope protein
epitopes distinct from those present on already defined HBV subtypes has
been reported recently.
Amino acid replacements within the S-protein sequence may lead to a loss
of subtype specific determinants d/y or w/r. [T]hese newly discerned HBV
subtypes, which are nonreactive with subtype specific reagents developed
earlier, still contain the group specific “a” determinants considered essential
for eliciting protective immunity. However, HBV variants may have altered or
insufficiently cross-reactive a determinants recognizable by antibodies and T
cells elicited as a result of immunization with defined subtypes of HBV. Such
variants may possibly cause infections not preventable by current hepatitis B
vaccines. For this reason, it is important to define amino acid replacements
within dominant group-specific B and T cell epitopes which would lead to the
generation of escape mutants.
The claims are drawn to vaccines comprising HBsAg “having the sequence
(CTKPSDGNC) within residues S(139-147)” and at least one HBsAg variant having at
least one “non-permitted” amino acid substitution in the S(139-147) region, wherein the
vaccines are “essentially free of permitted variants.” According to the specification, non-
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