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EP0154902A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Pre-S gene coded peptide hepatitis B immunogens, vaccines, diagnostics, and synthetic lipid vesicle carriers

Assignee: California Institute of Technology
•
Filing: 1985-02-28
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Granted: —
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Expires: 2005-02-28
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Abstract

Abstract A hepatitis B vaccine containing a peptide with an amino acid chain of at least six consecutive amino acids within the pre-S gene coded region of the envelope of hepatitis B virus. The vaccine being free of an amino acid sequence corresponding to the naturally occuring evelope proteins of hepatitis B virus and a physiologically acceptable diluent. The peptide being free or linked to a carrier. The carrier being a conventional carrier or a novel carrier including a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereon. Such novel carrier being useful not only to link the novel peptide containing an amino acid chain with amino acids within the pre-S gene coded region of the surface antigen of hepatitis B virus, but can also be used to bind synthetic peptide analogues of other viral proteins, as well as bacterial, allergen and parasitic proteins of man and animals. The peptides of the invention can be utilized in diagnostics for the detection of antigens and antibodies.

Inventors

  • 👤 Alexander Robert Neurath
  • 👤 Stephen B. H. Kent

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-24 23:06
CPC Classifications
C; C12; C12N; C12N15/00; C07; C07K; C07K14/00; C07K14/005; A; A61; A61K; A61K39/00; A61K39/12; A61K39/29; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/58; A61K47/62; A61K47/64; A61K47/645; A61K47/69; A61K47/6905; A61K47/6911; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; C07K16/00; C07K16/08; C07K16/081; C07K16/082; C07K7/00; C07K7/04; G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/53; G01N33/576; G01N33/5761; G01N33/5764; C12N2730/00; C12N2730/00011; C12N2730/10011; C12N2730/10111; C12N2730/10122; Y; Y02; Y02A; Y02A50/00; Y02A50/30; Y10; Y10S; Y10S930/00; Y10S930/01; Y10S930/22; Y10S930/221; Y10S930/222; Y10S930/223; Y10S930/26; Y10S930/27

Claims Analysis

Total Claims: 230
Claim 1
Independent Claim 56 words
1 . A hepatitis B peptide immunogen comprising a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of H B V, said peptide immunogen free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus.
Claim 2
Dependent Claim 56 words
1 . A hepatitis B peptide immunogen comprising a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of H B V, said peptide immunogen free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus.
Claim 3
Dependent Claim 24 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain of amino acids is between sequence position pre-S 120 and pre-S 174.
Claim 4
Dependent Claim 23 words
A hepatitis B peptide immunogen according to claim 2, wherein said chain of amino acids includes N-terminal methionine at sequence position pre-S 120.
Claim 5
Dependent Claim 24 words
A heptatis B peptide immunogen according to claim 1, wherein said chain of amino acids is between sequence position pre-S 1 and pre-S 120.
Claim 6
Dependent Claim 21 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide contains a chain of at least 10 amino acids.
Claim 7
Dependent Claim 21 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide contains a chain of at least 15 amino acids.
Claim 8
Dependent Claim 21 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide contains a chain of at least 20 amino acids.
Claim 9
Dependent Claim 21 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide contains a chain of at least 26 amino acids.
Claim 10
Dependent Claim 25 words
9 . A hepatitis B peptide immunogen according to claim 8, wherein said chain is between and including sequence positions pre-S 120 and pre-S 174.
Claim 11
Dependent Claim 20 words
A hepatitis B peptide immunogen according to claim 9, wherein said chain includes N-terminal methionine at sequence position pre-S 120.
Claim 12
Dependent Claim 23 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is between and including sequence position pre-S 15 and pre-S 120.
Claim 13
Dependent Claim 23 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is between and including sequence position pre-S 15 and pre-S 55.
Claim 14
Dependent Claim 23 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is between and including sequence position pre-S 90 and pre-S 120.
Claim 15
Dependent Claim 23 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is between and including sequence position pre-S 10 and pre-S 40.
Claim 16
Dependent Claim 24 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain corresponds to amino acids in the ayw subtype of the pre-S region.
Claim 17
Dependent Claim 24 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain corresponds to amino acids in the adyw subtype of the pre-S region.
Claim 18
Dependent Claim 24 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain corresponds to amino acids in the adw2 subtype of the pre-S region.
Claim 19
Dependent Claim 24 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain corresponds to amino acid in the adw subtype of the pre-S region.
Claim 20
Dependent Claim 24 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain corresponds to amino acids in the adr subtype of the pre-S region.
Claim 21
Dependent Claim 19 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide immunogen is free of any serum proteins.
Claim 22
Dependent Claim 14 words
A heptatis B peptide immunogen according to claim 1, wherein said chain is MQWNSTAFHQTLQDPRVRGLYLPAGG.
Claim 23
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is MGTNLSVPNPLGFFPDHQLDP.
Claim 24
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is PAFGANSNNPDWFNPVKDDWP.
Claim 25
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is PQAMQWNSTAFHQTLQDP.
Claim 26
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is PASTNRQSGRQPTPISPPLRDSHP.
Claim 27
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is PAPNIASHISSISARTGDP.
Claim 28
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is MGGWSSKPRKGMGTNLSVPNP.
Claim 29
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is PAFGANSNNPDWDFNPVKDDWP.
Claim 30
Dependent Claim 16 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is QVGVGAFGPRL TP PHGG.
Claim 31
Dependent Claim 16 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is MGGWSSKPRK G .
Claim 32
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is MGGWSSKPRQG.
Claim 33
Dependent Claim 37 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide immunogen is free of an amino acid sequence corresponding to the entire S gene coded region of the env gene product of hepatitis B virus.
Claim 34
Dependent Claim 19 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide has no more than 100 amino acids.
Claim 35
Dependent Claim 19 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide has no more than 40 amino acids.
Claim 36
Dependent Claim 19 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide has no more than 30 amino acids.
Claim 37
Dependent Claim 25 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide is capable of forming neutralizing antibodies to hepatitis B virus in a humans.
Claim 38
Dependent Claim 17 words
A hepatitis B peptide immunogen according to claim 1, wherein said peptide is linked to a carrier.
Claim 39
Dependent Claim 18 words
A hepatitis B peptide immunogen according to claim 37, wherein said peptide is covalently linked to a carrier.
Claim 40
Dependent Claim 20 words
A hepatitis B peptide immunogen according to claim 38, wherein said peptide is covalently linked to a lipid vesicle carrier.
Claim 41
Dependent Claim 20 words
4 0 . A hepatitis B peptide immunogen according to claim 39, wherein said lipid vesicle is stabilized by cross-linking.
Claim 42
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is pre-S(120-145)..
Claim 43
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is pre-S(12-32).
Claim 44
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is pre-S(117-134).
Claim 45
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is pre-S(94-117).
Claim 46
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is pre-S(153-171).
Claim 47
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is pre-S(1-21).
Claim 48
Dependent Claim 14 words
A hepatitis B peptide immunogen according to claim 1, wherein said chain is pre-S(57-73).
Claim 49
Dependent Claim 34 words
A carrier for a peptide comprising a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereof to bind the peptide to the outer surface of the carrier.
Claim 50
Dependent Claim 34 words
A carrier for a peptide comprising a lipid vesicle stabilized by cross-linking and having covalently bonded active sites on the outer surface thereof to bind the peptide to the outer surface of the carrier.
Claim 51
Dependent Claim 23 words
A carrier according to claim 48, wherein said active sites are selected from the group consisting of -COOH, -CHO, -NH 2 and -SH.
Claim 52
Dependent Claim 45 words
A carrier according to claim 49, wherein said lipid vesicle contains an amino moiety selected from the grorp consisting of aminoalkane, diaminoalkane, aminoalkene and diaminoalkene having 10 to 18 carbon atoms and said lipid vesicle is stabilized by contacting said lipid vesicle with a polyaldehyde.
Claim 53
Dependent Claim 13 words
A carrier according to claim 50, wherein said polyaldehyde is a bifunctional aldehyde.
Claim 54
Dependent Claim 11 words
A carrier according to claim 51, wherein said bisaldehyde is glutaraldehyde.
Claim 55
Dependent Claim 12 words
A carrier according to claim 50, wherein said amino moiety is stearylamine.
Claim 56
Dependent Claim 12 words
A carrier according to claim 52, wherein said amino moiety is stearylamine.
Claim 57
Dependent Claim 28 words
A carrier according to claim 48, wherein said lipid vesicle contains fatty acids having 12 to 18 carbon atoms and said lipid vesicle is stabilized with a carbodiimide.
Claim 58
Dependent Claim 20 words
A carrier according to claim 55, wherein said fatty acid is stearic acid and said carbodiimide is N-ethyl-N I (dimethyl-aminopropyl)-carbodiimide.
Claim 59
Dependent Claim 14 words
A carrier according to claim 48, wherein said lipid vesicle contains fatty acid aldehyde.
Claim 60
Dependent Claim 48 words
A peptide linked to a carrier comprising a peptide having -SH groups and a carrier comprising a liquid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene, diaminoalkene having 10 to 18 carbon atoms activated by a polyaldehyde and further activated by cysteine.
Claim 61
Dependent Claim 48 words
A peptide linked to a carrier comprising a peptide having -SH groups and a carrier comprising a liquid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene, diaminoalkene having 10 to 18 carbon atoms activated by a polyaldehyde and further activated by cysteine.
Claim 62
Dependent Claim 19 words
A peptide linked to a carrier according to claim 58, wherein said - SH groups are supplied by cysteine.
Claim 63
Dependent Claim 23 words
A peptide linked to a carrier comprising a peptide having -SH groups and a carrier comprising a lipid vesicle containing fatty acid mercaptan.
Claim 64
Dependent Claim 23 words
A peptide linked to a carrier comprising a peptide having -SH groups and a carrier comprising a lipid vesicle containing fatty acid mercaptan.
Claim 65
Dependent Claim 17 words
A peptide linked to a carrier according to claim 60, wherein said fatty acid mercaptan is octadecanethiol.
Claim 66
Dependent Claim 22 words
A peptide linked to a carrier according to claim 60, wherein said fatty acid mercaptan contains lipid vesicle activated with a dimaleimide.
Claim 67
Dependent Claim 16 words
A peptide linked to a carrier according to claim 52, wherein said dimaleimide is N-N'-phenylanedi- maleimide.
Claim 68
Dependent Claim 40 words
A peptide linked to a carrier comprising a peptide activated by a carbodiimide and a carrier comprising a lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene, diaminoalkene having 10 to 18 carbon atoms.
Claim 69
Dependent Claim 40 words
A peptide linked to a carrier comprising a peptide activated by a carbodiimide and a carrier comprising a lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene, diaminoalkene having 10 to 18 carbon atoms.
Claim 70
Dependent Claim 16 words
A peptide linked to a carrier according to claim 64, wherein said amino moiety is stearylamine.
Claim 71
Dependent Claim 15 words
A peptide linked to a carrier according to claim 64, wherein said carbodiimide is N-ethyl-N'(dimethylaminopropyl)-carbodiimide.
Claim 72
Dependent Claim 33 words
A peptide linked to a carrier comprising a peptide activated by a carbodiimide and a carrier comprising a lipid vesicle stabilized by a polyaldehyde and further derivatized by reaction with a water-soluble diaminoalkane.
Claim 73
Dependent Claim 33 words
A peptide linked to a carrier comprising a peptide activated by a carbodiimide and a carrier comprising a lipid vesicle stabilized by a polyaldehyde and further derivatized by reaction with a water-soluble diaminoalkane.
Claim 74
Dependent Claim 24 words
A peptide linked to a carrier according to claim 67, wherein said carbodiimide is N-ethyl-N'(dimethylaminopropyl)-carbodiimide, said polyaldehyde is glutaraldehyde and said diaminoalane is ethylenediamine.
Claim 75
Independent Claim 35 words
A method of forming a carrier comprising contacting a lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene and diaminoalkene having 10 to 18 carbon atoms with a polyaldehye.
Claim 76
Independent Claim 35 words
A method of forming a carrier comprising contacting a lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene and diaminoalkene having 10 to 18 carbon atoms with a polyaldehye.
Claim 77
Dependent Claim 12 words
A method according to claim 69, wherein said amino moiety is stearylamine.
Claim 78
Dependent Claim 11 words
A method according to claim 69, wherein said polyaldehyde is glutaraldehye.
Claim 79
Independent Claim 23 words
A method of forming a carrier comprising contacting a lipid vesicle containing fatty acid having 12 to 18 carbon atoms with a carbodiimide.
Claim 80
Independent Claim 23 words
A method of forming a carrier comprising contacting a lipid vesicle containing fatty acid having 12 to 18 carbon atoms with a carbodiimide.
Claim 81
Dependent Claim 22 words
A method of forming a carrier according to claim 72, wherein said fatty acid is stearic acid and said carbodiimide is N-ethyl-N'(dimethylaminopropyl)-carbodiimide.
Claim 82
Independent Claim 16 words
A method of forming a carrier comprising contacting a lipid vesicle with a fatty acid aldehyde.
Claim 83
Independent Claim 16 words
A method of forming a carrier comprising contacting a lipid vesicle with a fatty acid aldehyde.
Claim 84
Independent Claim 54 words
A method of linking a peptide to a carrier comprising contacting a peptide having -SH groups with a carrier comprising a lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene and diaminoalkene having 10 to 18 carbon atoms and contacting said lipid vesicle with a polyaldehyde and cysteine.
Claim 85
Independent Claim 54 words
A method of linking a peptide to a carrier comprising contacting a peptide having -SH groups with a carrier comprising a lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene and diaminoalkene having 10 to 18 carbon atoms and contacting said lipid vesicle with a polyaldehyde and cysteine.
Claim 86
Independent Claim 27 words
A method of linking a pcptide to a carrier comprising contacting a peptide having -SH groups with a carrier comprising a lipid vesicle having fatty acid mercaptan.
Claim 87
Independent Claim 27 words
A method of linking a pcptide to a carrier comprising contacting a peptide having -SH groups with a carrier comprising a lipid vesicle having fatty acid mercaptan.
Claim 88
Dependent Claim 20 words
A method of linking a peptide to a carrier according to claim 76, wherein said fatty acid mercaptan is octadecanediol.
Claim 89
Dependent Claim 28 words
78 . A method of linking a peptide to a carrier according to claim 77, wherein said fatty acid mercaptan containing lipid vesicle is contacted with a dimaleiimide.
Claim 90
Dependent Claim 11 words
A method according to claim 78, wherein said dimaleiimide is N-N'-phenylanedimaleimide.
Claim 91
Independent Claim 49 words
A method of linking a peptide to a carrier comprising contacting a peptide, said peptide contacted with a carbodiimide, with a carrier, said carrier comprising an lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene and diaminoalkene having 10 to 18 carbon atoms.
Claim 92
Independent Claim 49 words
A method of linking a peptide to a carrier comprising contacting a peptide, said peptide contacted with a carbodiimide, with a carrier, said carrier comprising an lipid vesicle containing an amino moiety selected from the group consisting of aminoalkane, diaminoalkane, aminoalkene and diaminoalkene having 10 to 18 carbon atoms.
Claim 93
Dependent Claim 17 words
A method according to claim 80, wherein said amino moiety is stearylamine and said carbodiimide is N-ethyl-N'(dimethylaminopropyl)-carbodiimide.
Claim 94
Independent Claim 35 words
A method of linking a peptide to a carrier comprising contacting a peptide activated by a carbodiimide and a carrier comprising a lipid vesicle stabilizied by a polyaldehyde and further reacted with a water-soluble diaminoalkane.
Claim 95
Independent Claim 35 words
A method of linking a peptide to a carrier comprising contacting a peptide activated by a carbodiimide and a carrier comprising a lipid vesicle stabilizied by a polyaldehyde and further reacted with a water-soluble diaminoalkane.
Claim 96
Dependent Claim 23 words
A method of linking a peptide to a carrier according to claim 82, wherein said polyaldehyde is glutaraldehyde and said diaminoalkane is ethylenediamine.
Claim 97
Dependent Claim 45 words
A peptide comprising an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region or the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus.
Claim 98
Dependent Claim 45 words
A peptide comprising an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region or the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus.
Claim 99
Dependent Claim 21 words
A peptide according to claim 84, wherein said chain of amino acids is between sequence position pre-S 120 and pre-S 174.
Claim 100
Dependent Claim 20 words
A peptide according to claim 85, wherein said chain of amino acids includes N-terminal methionine at sequence position pre-S 120.
Claim 101
Dependent Claim 21 words
A peptide according to claim 84, wherein said chain of amino acids is between sequence position pre-S 1 and pre-S 120.
Claim 102
Dependent Claim 18 words
A peptide according to claim 84, wherein said peptide contains a chain of at least 10 amino acids.
Claim 103
Dependent Claim 18 words
A peptide according to claim 84, wherein said peptide contains a chain of at least 15 amino acids.
Claim 104
Dependent Claim 18 words
A peptide according to claim 84, wherein said peptide contains a chain of at least 20 amino acids.
Claim 105
Dependent Claim 18 words
A peptide according to claim 84, wherein said peptide contains a chain of at least 26 amino acids.
Claim 106
Dependent Claim 20 words
A peptide according to claim 91, wherein said chain is between and including sequence positions pre-S 120 and pre-S 174.
Claim 107
Dependent Claim 17 words
A peptide according to claim 92, wherein said chain includes N-terminal methionine at sequence position pre-S 120.
Claim 108
Dependent Claim 20 words
A peptide according to claim 84, wherein said chain is between and including sequence position pre-S 15 and pre-S i20.
Claim 109
Dependent Claim 22 words
95 . A peptide according to claim 84, wherein said chain is between and including sequence position pre-S 15 and pre-S 55.
Claim 110
Dependent Claim 22 words
96 . A peptide according to claim 84, wherein said chain is between and including sequence position pre-S 90 and pre-S 120.
Claim 111
Dependent Claim 20 words
A peptide according to claim 84, wherein said chain is between and including sequence position pre-S 10 and pre-S 40.
Claim 112
Dependent Claim 21 words
A peptide according to claim 84, wherein said chain corresponds to amino acids in the ayw subtype of the pre-S region.
Claim 113
Dependent Claim 21 words
A peptide according to claim 84, wherein said chain corresponds to amino acids in the adyw subtype of the pre-S region.
Claim 114
Dependent Claim 21 words
A peptide according to claim 84, wherein said chain corresponds to amino acids in the adw2 subtype of the pre-S region.
Claim 115
Dependent Claim 21 words
A peptide according to claim 84, wherein said claim corresponds to amino acids in the adw subtype of the pre-S region.
Claim 116
Dependent Claim 21 words
A peptide according to claim 84, wherein said chain corresponds to amino acids in the adr subtype of the pre-S region.
Claim 117
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is MQWNSTAFHQTLQDPRVRGLYLPAGG.
Claim 118
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is MGTNLSVPNPLGFFPDHQLDP.
Claim 119
Dependent Claim 13 words
10 5. A peptide according to claim 84, wherein said peptide is PAFGANSNPDWFNPVKDDWP.
Claim 120
Dependent Claim 13 words
106 . A peptide according to claim 84, wherein said peptide is PQAMQWNSTAFHQTLQDP.
Claim 121
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is PASTNRQSGRQPTPISPPLRDSHP.
Claim 122
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is PAPNIASHISSISARTGDP.
Claim 123
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is MGGWSSKPRKGMGTNLSVPNP.
Claim 124
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is PAFGANSNNPDWDFNPVKDDWP.
Claim 125
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is QVGVGAFGPRLTPPHGG.
Claim 126
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is MGGWSSKPRKG.
Claim 127
Dependent Claim 11 words
A peptide according to claim 84, wherein said peptide is MGGWSSKPRKG.
Claim 128
Dependent Claim 32 words
A peptide according to claim 84, wherein said peptide is free of an amino acid sequence corresponding to the entire S gene coded region of the surface antigen of hepatitis B virus.
Claim 129
Dependent Claim 16 words
A peptide according to claim 84, wherein said peptide has no more than 100 amino acids.
Claim 130
Dependent Claim 16 words
A peptide according to claim 84, wherein said peptide has no more than 40 amino acids.
Claim 131
Dependent Claim 16 words
A peptide according to claim 84, wherein said peptide has no more than 30 amino acids.
Claim 132
Dependent Claim 11 words
A peptide according to claim 84, wherein said chain is pre-S(120-145).
Claim 133
Dependent Claim 11 words
A peptide according to claim 84, wherein said chain is pre-S(12-32).
Claim 134
Dependent Claim 13 words
1 20. A peptide according to claim 84, wherein said chain is pre-S(117-134).
Claim 135
Dependent Claim 13 words
121 . A peptide according to claim 84, wherein said chain is pre-S(94-117).
Claim 136
Dependent Claim 11 words
A peptide according to claim 84, wherein said chain is pre-S(153-171).
Claim 137
Dependent Claim 11 words
A peptide according to claim 84, wherein said chain is pre-S(1-21).
Claim 138
Dependent Claim 11 words
A peptide according to claim 84, wherein said chain is pre-S(57-73).
Claim 139
Dependent Claim 163 words
A process for the detection of antigens coded for the pre-S gene in sera of HBV infected animals comprising: (a) coating a solid substrate with antibodies to a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV; (b) washing the coated substrate; (c) contacting the washed coated substrate with a protein-containing solution; (d) washing the substrate from step c; (e) incubating the substrate from step d with a sample suspected to contain HB V or HBsAg; (f) washing the substrate from step e; (g) adding radiolabeled antibody, said antibody being an antibody to the peptide or HBsAg, to the substrate from step f; (h) incubating the substrate from step g; (i) washing the substrate from step h; and (j) subjecting the substrate of step i to counting in a gamma counter.
Claim 140
Dependent Claim 163 words
A process for the detection of antigens coded for the pre-S gene in sera of HBV infected animals comprising: (a) coating a solid substrate with antibodies to a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV; (b) washing the coated substrate; (c) contacting the washed coated substrate with a protein-containing solution; (d) washing the substrate from step c; (e) incubating the substrate from step d with a sample suspected to contain HB V or HBsAg; (f) washing the substrate from step e; (g) adding radiolabeled antibody, said antibody being an antibody to the peptide or HBsAg, to the substrate from step f; (h) incubating the substrate from step g; (i) washing the substrate from step h; and (j) subjecting the substrate of step i to counting in a gamma counter.
Claim 141
Dependent Claim 29 words
A process for the detection of antigen coded for by the pre-S gene in sera of HBV infected animals according to claim 125, wherein said substrate is polystyrene beads.
Claim 142
Dependent Claim 33 words
A process for the detection of antigen coded for by the pre-S gene in sera of HBV infected animals according to claim 125, wherein said protein-containing solution contains bovine serum albumin or gelatin.
Claim 143
Dependent Claim 176 words
A process for the detection of antigens coded for the pre-S gene in sera of HBV infected animals comprising: (a) coating a solid substrate with antibodies to a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV; (b) washing the coated substrate; (c) contacting the washed coated substrate with a protein-containing solution; (d) washing the substrate from step c; (e) incubating the substrate from step d with a sample suspected to contain HBV or HBsAg; (f) washing the substrate from step e; (g) adding enzyme labeled antibody, said antibody being an antibody to the peptide or HBsAg, to the substrate from step f; (h) incubating the substrate from step g; (i) washing the substrate from step h; (j) subjecting the substrate of step i to ELISA and comparing the results of said ELISA to EL ISA results from normal sera utilized as a control.
Claim 144
Dependent Claim 176 words
A process for the detection of antigens coded for the pre-S gene in sera of HBV infected animals comprising: (a) coating a solid substrate with antibodies to a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV; (b) washing the coated substrate; (c) contacting the washed coated substrate with a protein-containing solution; (d) washing the substrate from step c; (e) incubating the substrate from step d with a sample suspected to contain HBV or HBsAg; (f) washing the substrate from step e; (g) adding enzyme labeled antibody, said antibody being an antibody to the peptide or HBsAg, to the substrate from step f; (h) incubating the substrate from step g; (i) washing the substrate from step h; (j) subjecting the substrate of step i to ELISA and comparing the results of said ELISA to EL ISA results from normal sera utilized as a control.
Claim 145
Dependent Claim 29 words
A process for the detection of antigens coded for by the pre-S gene in sera of HBV infected animals according to claim 128, wherein said substrate is polystyrene beads.
Claim 146
Dependent Claim 189 words
A process for the detection of antibodies to the pre-S region of hepatitis B virus comprising: (a) adsorbing on a solid substrate, containing binding sites thereon, a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, (b) contacting the substrate from step a with a material to saturate the binding sites thereon, (c) washing the substrate from step b, (d) contacting the substrate from step c with a specimen comprising human sera to form a first resultant mass, (e) incubating the resultant mass of step d, (f) washing the resultant mass of step e, (g) adding radiolabeled antibodies to human IGG or IGM to the resultant mass of step f to form a second resultant mass, (h) subjecting the second resultant mass of step g to counting in a gamma counter, (i) subjecting normal sera utilized as a control to steps a to h and (j) comparing the counts of steps h and i.
Claim 147
Dependent Claim 189 words
A process for the detection of antibodies to the pre-S region of hepatitis B virus comprising: (a) adsorbing on a solid substrate, containing binding sites thereon, a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, (b) contacting the substrate from step a with a material to saturate the binding sites thereon, (c) washing the substrate from step b, (d) contacting the substrate from step c with a specimen comprising human sera to form a first resultant mass, (e) incubating the resultant mass of step d, (f) washing the resultant mass of step e, (g) adding radiolabeled antibodies to human IGG or IGM to the resultant mass of step f to form a second resultant mass, (h) subjecting the second resultant mass of step g to counting in a gamma counter, (i) subjecting normal sera utilized as a control to steps a to h and (j) comparing the counts of steps h and i.
Claim 148
Dependent Claim 12 words
A process according to claim 130, wherein said substrate is polystyrene beads.
Claim 149
Dependent Claim 192 words
A process for the detection of antibodies to the pre-S region of hepatitis B virus comprising: (a) adsorbing on a solid substrate, containing binding sites thereon, a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of H BV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, (b) contacting the substrate from step a with a material to saturate the binding sites thereon, (c) washing the substrate from step b, (d) contacting the substrate from s' ? c with a specimen comprising human sera to form a first , resultant mass, ( e ) incubating the resultant mass of step d, ( f ) washing the resultant mass of step e, (g) adding enzyme labeled antibodies to human IgG or IgM to the resultant mass of step f to form a second resultant mass, (h) subjecting the second resultant mass of step g to ELISA, (i) subjecting a normal sera utilized as a control to ELISA, and (j) comparing the ELISA results from steps h and i.
Claim 150
Dependent Claim 192 words
A process for the detection of antibodies to the pre-S region of hepatitis B virus comprising: (a) adsorbing on a solid substrate, containing binding sites thereon, a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of H BV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, (b) contacting the substrate from step a with a material to saturate the binding sites thereon, (c) washing the substrate from step b, (d) contacting the substrate from s' ? c with a specimen comprising human sera to form a first , resultant mass, ( e ) incubating the resultant mass of step d, ( f ) washing the resultant mass of step e, (g) adding enzyme labeled antibodies to human IgG or IgM to the resultant mass of step f to form a second resultant mass, (h) subjecting the second resultant mass of step g to ELISA, (i) subjecting a normal sera utilized as a control to ELISA, and (j) comparing the ELISA results from steps h and i.
Claim 151
Dependent Claim 12 words
A process according to claim 132, wherein said substrate is polystyrene beads.
Claim 152
Dependent Claim 109 words
A diagnostic test kit for detecting antigens coded for the pre-S gene of HBV in a test sample, comprising a. a solid substrate containing protein binding sites thereon, said substrate coated with antibodies to a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HB V, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV, b. a protein-containing solution to saturate protein binding sites on the solid substrate, and c. a given amount of radiolabeled or enzyme labelled antibody, said antibody to either the peptide or HBsAg.
Claim 153
Dependent Claim 109 words
A diagnostic test kit for detecting antigens coded for the pre-S gene of HBV in a test sample, comprising a. a solid substrate containing protein binding sites thereon, said substrate coated with antibodies to a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HB V, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV, b. a protein-containing solution to saturate protein binding sites on the solid substrate, and c. a given amount of radiolabeled or enzyme labelled antibody, said antibody to either the peptide or HBsAg.
Claim 154
Dependent Claim 109 words
A diagnostic test kit for detecting antibodies to the pre-S region of hepatitis B virus in a test sample, comprising a. a solid substrate containing protein binding sites thereon, said substrate having adsorbed thereon a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV, the solid substrate exposed to a protein-containing solution to saturate protein binding sites on the solid substrate, and b. a given amount of radiolabeled or enzyme labelled antibodies to human IgG or IgM.
Claim 155
Dependent Claim 109 words
A diagnostic test kit for detecting antibodies to the pre-S region of hepatitis B virus in a test sample, comprising a. a solid substrate containing protein binding sites thereon, said substrate having adsorbed thereon a peptide having an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring proteins of HBV, the solid substrate exposed to a protein-containing solution to saturate protein binding sites on the solid substrate, and b. a given amount of radiolabeled or enzyme labelled antibodies to human IgG or IgM.
Claim 156
Dependent Claim 162 words
A process for detecting antibodies to the pre-S region of hepatitis B virus in a sample which comprises: a) contacting the sample with a solid substrate coated with a non-labelled peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the enveloping of HBV, the peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, incubating and washing said contacted sample; b) contacting the incubated washed product obtained from step a above with a labelled peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope protein of hepatitis B virus, incubating and washing the resultant mass; and c) determing the extent of labelled peptide present in the resultant mass obtained by step b above.
Claim 157
Dependent Claim 162 words
A process for detecting antibodies to the pre-S region of hepatitis B virus in a sample which comprises: a) contacting the sample with a solid substrate coated with a non-labelled peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the enveloping of HBV, the peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, incubating and washing said contacted sample; b) contacting the incubated washed product obtained from step a above with a labelled peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide free of an amino acid sequence corresponding to the naturally occurring envelope protein of hepatitis B virus, incubating and washing the resultant mass; and c) determing the extent of labelled peptide present in the resultant mass obtained by step b above.
Claim 158
Dependent Claim 21 words
137 . A process according to claim 136, wherein a solid substrate is rendered substantially free of available protein binding sites.
Claim 159
Dependent Claim 18 words
A process according to claim 137, wherein the solid substrate is contacted with a protein binding site occupier.
Claim 160
Dependent Claim 11 words
A process according to claim 139, wherein the occupier is albumin.
Claim 161
Dependent Claim 169 words
A process for detecting antibodies to the pre-S region of hepatitis B virus in a sample comprising: a) contacting the sample with a solid substrate coated with a non-labelled peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, the peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, incubating and washing said contacted sample; b) contacting the incubated washed product obtained from step a above with labelled antibody to human or animal immunoglobulin product by contact with an immunogen comprising a peptide corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide immunogen free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, incubacing and washing the contacted sample, and c ) determining the exten:- of labelled antibody present in the resultant mass of step b.
Claim 162
Dependent Claim 169 words
A process for detecting antibodies to the pre-S region of hepatitis B virus in a sample comprising: a) contacting the sample with a solid substrate coated with a non-labelled peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, the peptide free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, incubating and washing said contacted sample; b) contacting the incubated washed product obtained from step a above with labelled antibody to human or animal immunoglobulin product by contact with an immunogen comprising a peptide corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide immunogen free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, incubacing and washing the contacted sample, and c ) determining the exten:- of labelled antibody present in the resultant mass of step b.
Claim 163
Dependent Claim 224 words
A process for detecting HBV or HBsAg in a sample comprising: a) contacting a first portion of a composition containing an antibody produced by introducing into an animal or human an immunogen comprising a peptide corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide immunogen free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus with a mixture of said sample and said immunogen which has been labelled, incubating and washing said first protein; b) contacting a second portion of said composition containing antibody with the same amount of said labelled immunogen in an antigen free control, incubating and washing said second portion; c) adding the same amount of Staphylococci bearing protein A to each of the compositions of steps a and b above, incubating both of said compositions, centrifuging each of said compositions and separating liquid from the solids therein; d) determining the extent of labelled immunogen in each of the resultant compositions from step c above, and e) comparing the relative amount of labelled immunogen in e--h such that if the activity of the resultant composition containing the first portion is less than the ` activity for the resultant composition of the second portion, then the sample contains HBV or H B sAg.
Claim 164
Dependent Claim 224 words
A process for detecting HBV or HBsAg in a sample comprising: a) contacting a first portion of a composition containing an antibody produced by introducing into an animal or human an immunogen comprising a peptide corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide immunogen free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus with a mixture of said sample and said immunogen which has been labelled, incubating and washing said first protein; b) contacting a second portion of said composition containing antibody with the same amount of said labelled immunogen in an antigen free control, incubating and washing said second portion; c) adding the same amount of Staphylococci bearing protein A to each of the compositions of steps a and b above, incubating both of said compositions, centrifuging each of said compositions and separating liquid from the solids therein; d) determining the extent of labelled immunogen in each of the resultant compositions from step c above, and e) comparing the relative amount of labelled immunogen in e--h such that if the activity of the resultant composition containing the first portion is less than the ` activity for the resultant composition of the second portion, then the sample contains HBV or H B sAg.
Claim 165
Dependent Claim 86 words
1 42. A diagnostic test kit for detecting hepatitis B virus in sera comprising a) a given amount of antibody to a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide being free of an amino acid chain corresponding to the naturally occurring envelope proteins of hepatitis B virus, the antibody being bound to a solid suppoit, b) labelled antibody to the peptide or to hepatitis B virus.
Claim 166
Dependent Claim 86 words
1 42. A diagnostic test kit for detecting hepatitis B virus in sera comprising a) a given amount of antibody to a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of HBV, said peptide being free of an amino acid chain corresponding to the naturally occurring envelope proteins of hepatitis B virus, the antibody being bound to a solid suppoit, b) labelled antibody to the peptide or to hepatitis B virus.
Claim 167
Dependent Claim 41 words
A diagnostic test kit for detecting hepatitis B virus in sera according to claim 142, which further comprises a set of instructions for effecting an immunoassay wherein the effect of formation of an immune complex is revealed by said labelled antibody.
Claim 168
Dependent Claim 26 words
A diagnostic test kit for detecting hepatitis B virus in sera according to claim 143, wherein said antibody is insolubilized on a water insoluble solid support.
Claim 169
Dependent Claim 74 words
A diagnostic kit for detecting the presence of antibodies to hepatitis B virus comprising a) a given amount of a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of. the. envelope of HBV , said peptide being free of an amino acid chain corresponding to the naturally occurring envelope proteins of hepatitis B virus, b) labelled antibodies to human IgG or IgM.
Claim 170
Dependent Claim 74 words
A diagnostic kit for detecting the presence of antibodies to hepatitis B virus comprising a) a given amount of a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of. the. envelope of HBV , said peptide being free of an amino acid chain corresponding to the naturally occurring envelope proteins of hepatitis B virus, b) labelled antibodies to human IgG or IgM.
Claim 171
Dependent Claim 46 words
146 . A diagnostic kit for detecting the presence of antibodies to hepatitis B virus according to claim 145 , which further comprises a set of instructions for effecting an immunoassay, wherein the extent of formation of an immune complex is revealed by said labelled antibodies.
Claim 172
Dependent Claim 26 words
A diagnostic test kit for detecting hepatitis B virus in sera according to claim 145, wherein said peptide is insolubilized upon a water insoluble solid support.
Claim 173
Dependent Claim 60 words
A process for predicting the outcome of hepatitis B infection which comprises carrying out an immunoassay on serum of a human to detect the presence of an antibody to an antigen coded for by the pre-S gene coded region of the envelope of hepatitis B virus employing the peptide immunogen of claim 1 at regular intervals and evaluating the data.
Claim 174
Dependent Claim 82 words
A process for determining if a human who has been vaccinated with a vaccine against hepatitis B has become immune to hepatitis B virus which comprises effecting a plurality of immunoassays of serum from such human to determine if there are antibodies in said serum to an antigen coded by the pre-S gene coded region of the envelope of hepatitis B virus employing the peptide immunogen of claim 1, said immunoassays being performed on serum taken from said human at different times.
Claim 175
Dependent Claim 67 words
A method for detecting the presence of hepatitis B virus infection comprising effecting quantative immunoassays on a serum sample taken from a human to determine the amount of antibodies present therein which are antibodies to an antigen coded by the pre-S gene coded region of the envelope of the hepatitis B virus employing the peptide immunogen of claim 1 and comparing the value with a known standard.
Claim 176
Dependent Claim 17 words
A process for raising antibodies which comprises introducing into an animal the peptide immunogen of claim 1.
Claim 177
Dependent Claim 93 words
In a process for synthesizing His and Trp containing peptides which includes the steps of a. linking a first amino acid containing an alpha-amino protecting group to a resin; b. removal of said alpha-amino protecting group; c. coupling a second amino acid containing an alpha-amino protecting group to said first amino acid; d. repeating steps b and c - by coupling further alpha-protected amino acids to produce a desired peptide wherein at least one of said amino acids is His and wherein at least one of said amino acids is Trp and the
Claim 178
Dependent Claim 93 words
In a process for synthesizing His and Trp containing peptides which includes the steps of a. linking a first amino acid containing an alpha-amino protecting group to a resin; b. removal of said alpha-amino protecting group; c. coupling a second amino acid containing an alpha-amino protecting group to said first amino acid; d. repeating steps b and c - by coupling further alpha-protected amino acids to produce a desired peptide wherein at least one of said amino acids is His and wherein at least one of said amino acids is Trp and the
Claim 179
Dependent Claim 58 words
e. cleaving the peptide from the resin and removing remaining protective groups to said first amino acids, wherein the improvement comprises substituting an His(ImDNP) for said His, substituting a Trp(InFormyl) for said Trp, removing said DNP prior to cleavage and said removing of protective group, and removing said Formyl during said cleavage and said removing of protective group.
Claim 180
Dependent Claim 58 words
e. cleaving the peptide from the resin and removing remaining protective groups to said first amino acids, wherein the improvement comprises substituting an His(ImDNP) for said His, substituting a Trp(InFormyl) for said Trp, removing said DNP prior to cleavage and said removing of protective group, and removing said Formyl during said cleavage and said removing of protective group.
Claim 181
Dependent Claim 57 words
A hepatitis B vaccine comprising a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of H BV , said vaccine free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, and a physiologically acceptable diluent.
Claim 182
Dependent Claim 57 words
A hepatitis B vaccine comprising a peptide containing an amino acid chain corresponding to at least six consecutive amino acids within the pre-S gene coded region of the envelope of H BV , said vaccine free of an amino acid sequence corresponding to the naturally occurring envelope proteins of hepatitis B virus, and a physiologically acceptable diluent.
Claim 183
Dependent Claim 23 words
A hepatitis B vaccine according to claim 153, wherein said chain of amino acids is between sequence position pre-S 120 and pre-S 174.
Claim 184
Dependent Claim 22 words
A hepatitis B vaccine according to claim 154, wherein said chain of amino acids includes N-terminal methionine at sequence position pre-S 120.
Claim 185
Dependent Claim 23 words
A hepatitis B vaccine according to claim 153, wherein said chain of amino acids is between sequence position pre-S 1 and pre-S 120.
Claim 186
Dependent Claim 20 words
A hepatitis B vaccine according to claim 153, wherein said peptide contains a chain of at least 10 amino acids.
Claim 187
Dependent Claim 20 words
A hepatitis B vaccine according to claim 153, wherein said peptide contains a chain of at least 15 amino acids.
Claim 188
Dependent Claim 20 words
A hepatitis B vaccine according to claim 153, wherein said peptide contains a chain of at least 20 amino acids.
Claim 189
Dependent Claim 20 words
A hepatitis B vaccine according to claim 153, wherein said peptide contains a chain of at least 26 amino acias.
Claim 190
Dependent Claim 26 words
1 . 6 1. A hepatitis B vaccine according to claim 160, wherein said chain is between and including sequence positions pre-S 120 and pre-S 174.
Claim 191
Dependent Claim 21 words
16 2. A hepatitis B vaccine according to claim 161, wherein said chain includes N-terminal methionine at sequence position pre-S 120.
Claim 192
Dependent Claim 22 words
A hepatitis B vaccine according to claim 153, wherein said chain is between and including sequence position pre-S 15 and pre-S 120.
Claim 193
Dependent Claim 22 words
A hepatitis B vaccine according to claim 153, wherein said chain is between and including sequence position pre-S 15 and pre-S 55.
Claim 194
Dependent Claim 22 words
A hepatitis B vaccine according to claim 153, wherein said chain is between and including sequence position pre-S 90 and pre-S 120.
Claim 195
Dependent Claim 22 words
A hepatitis B vaccine according to claim 153, wherein said chain is between and including sequence position pre-S 10 and pre-S 40.
Claim 196
Dependent Claim 23 words
A hepatitis B vaccine according to claim 153, wherein said chain corresponds to amino acids in the ayw subtype of the pre-S region.
Claim 197
Dependent Claim 23 words
A hepatitis B vaccine according to claim 153, wherein said chain corresponds to amino acids in the adyw subtype of the pre-S region.
Claim 198
Dependent Claim 23 words
A hepatitis B vaccine according to claim 153, wherein said chain corresponds to amino acids in the adw2 subtype cf the pre-S region.
Claim 199
Dependent Claim 23 words
A hepatitis B vaccine according to claim 153, wherein said chain corresponds to amino acid in the adw subtype of the pre-S region.
Claim 200
Dependent Claim 24 words
A hepatitis B vaccine according to claim 153 , wherein said chain corresponds to amino acids in the adr subtype of the pre-S region.
Claim 201
Dependent Claim 17 words
A hepatitis B vaccine according to claim 153, wherein said vaccine is free of any serum proteins.
Claim 202
Dependent Claim 13 words
A heptatis B vaccine according to claim 153, wherein said chain is MQWNSTAFHQTLQDPRVRGLYLPAGG.
Claim 203
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is MGTNLSVPNPLGFFPDHQLDP.
Claim 204
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is PAFGANSNNPDNFNPVKDDWP.
Claim 205
Dependent Claim 14 words
-176. A hepatitis B vaccine according to claim 153, wherein said chain is PQAMQWNSTAFHQTLQDP.
Claim 206
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is PASTNRQSGRQPTPISPPLRDSHP.
Claim 207
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is PAPNIASHISSISARTGDP.
Claim 208
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is MGGWSSKPRKGMGTNLSVPNP.
Claim 209
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is PAFGANSNNPDWDFNPVKDDWP.
Claim 210
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is QVGVGAFGPRLTPPHGG.
Claim 211
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is MGGWSSKPRKG.
Claim 212
Dependent Claim 17 words
183 . A hepatitis B vaccine according to claim 1 53 , wherein said chain is MGGWSSKPRQG.
Claim 213
Dependent Claim 37 words
184 . A hepatitis B vaccine according to claim 153, wherein said vaccine is free of an amino acid sequence corresponding to the entire S gene coded region of the env gene product of hepatitis B virus.
Claim 214
Dependent Claim 18 words
A hepatitis B vaccine according to claim 153, wherein said peptide has no more than 100 amino acids.
Claim 215
Dependent Claim 18 words
A hepatitis B vaccine according to claim 153, wherein said peptide has no more than 40 amino acids.
Claim 216
Dependent Claim 18 words
A hepatitis B vaccine according to claim 153, wherein said peptide has no more than 30 amino acids.
Claim 217
Dependent Claim 24 words
A hepatitis B vaccine according to claim 153, wherein said peptide is capable of forming neutralizing antibodies to hepatitis B virus in a humans.
Claim 218
Dependent Claim 16 words
A hepatitis B vaccine according to claim 153, wherein said peptide is linked to a carrier.
Claim 219
Dependent Claim 17 words
A hepatitis B vaccine according to claim 189, wherein said peptide is covalently linked to a carrier.
Claim 220
Dependent Claim 19 words
A hepatitis B vaccine according to claim 190, wherein said peptide is covalently linked to a lipid vesicle carrier.
Claim 221
Dependent Claim 16 words
A hepatitis B vaccine according to claim 191, wherein said lipid vesicle is stabilized by cross-linking.
Claim 222
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is pre-S(120-145).
Claim 223
Dependent Claim 13 words
A hepatitis B vaccine according to claim 153, wherein said chain is pre-S(12-32).
Claim 224
Dependent Claim 15 words
195 . A hepatitis B vaccine according to claim 153, wherein said chain is pre-S(117-134).
Claim 225
Dependent Claim 15 words
19 6. A hepatitis B vaccine according to claim 153, wherein said chain is pre-S(94-117).
Claim 226
Dependent Claim 15 words
197 . A hepatitis B vaccine according to claim 153, wherein said chain is pre-S(153-171).
Claim 227
Dependent Claim 16 words
198 . A hepatitis B vaccine according to claim 153, wherein said chain is pre-S (1-21).
Claim 228
Dependent Claim 15 words
199 . A hepatitis B vaccine according to claim 153, wherein said chain is pre-S(57-73).
Claim 229
Dependent Claim 29 words
2 00. A method of protecting a human against becoming infected with hepatitis B comprising administering to said human an effective dosage of a vaccine according to claim 153.
Claim 230
Dependent Claim 61 words
A method for detecting the presence of hepatitis B virus infection comprising effecting quantative immunoassays on a serum sample taken from a human to determine the amount of antigens coded by the pre-S gene coded region of the envelope of the hepatitis B virus employing antibodies to the peptide immunogen of claim 1 and comparing the value with a known standard.

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