Methods and compositions for the treatment of hepatitis B infection
AssigneeMelbourne Health
InventorsRenae Walsh, Stephen Locarnini, Hans Netter, Ronald Farquhar
Life of this patent
Estimating the term…
Abstract
Disclosed herein are compositions and methods for the treatment of hepatitis B infection, including chronic hepatitis B (CHB).
Claims31
A bio-nanoparticle (BNP) comprising a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said one or more antigenic epitope repeat regions are expressed in the Loop 1 and Loop 2 regions of HBsAg-S domain, and are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX-PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is F or Y;
- or (b) the amino acid sequence PCX:TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and X11 is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A method of treating hepatitis B infection in a subject in need thereof, comprising administering to the subject a bio-nanoparticle (BNP) comprising a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said one or more antigenic epitope repeat regions are expressed in the Loop 1 and Loop 2 regions of HBsAg-S domain, and are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX-PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is For Y;
- or (b) the amino acid sequence PCX:TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and X11 is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A method for inducing an immune response against hepatitis B virus in a subject comprising administering to the subject a bio-nanoparticle (BNP) comprising a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said one or more antigenic epitope repeat regions are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX-PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is For Y;
- or (b) the amino acid sequence PCX8TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and X11 is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A kit for treating hepatitis B infection in a subject in need thereof comprising a bio-nanoparticle (BNP), wherein the BNP comprises a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said antigenic epitope repeat regions are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX-PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is F or Y;
- or (b) the amino acid sequence PCX8TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and Xu is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A recombinant mRNA encoding a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said antigenic epitope repeat regions are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX-PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is F or Y;
- or (b) the amino acid sequence PCX8TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and X11 is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A method of treating hepatitis B infection in a subject in need thereof, comprising administering to the subject a recombinant mRNA encoding a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said antigenic epitope repeat regions are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX7PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is F or Y;
- or (b) the amino acid sequence PCX8TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and X11 is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A method for inducing an immune response against hepatitis B virus in a subject comprising administering to the subject a recombinant mRNA encoding modified hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said antigenic epitope repeat regions are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX7PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is F or Y;
- or (b) the amino acid sequence PCX8TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and X11 is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A kit for treating hepatitis B infection in a subject in need thereof comprising a recombinant mRNA , wherein the recombinant mRNA encodes a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope repeat regions, wherein said antigenic epitope repeat regions are selected from the group consisting of:
- (1) antigenic epitope repeat regions expressed in Loop 1 and defined by (a) the amino acid sequence CX1TCX2X3X4X5QGX6SMX-PC (SEQ ID NO:
- 24), wherein X1 is K or R, X2 is T or M, X3 is T or I, X4 is P T or L, X5 is A or V, X6 is N or T, and X7 is F or Y;
- or (b) the amino acid sequence PCX:TCX9X10X11 (SEQ ID NO:
- 25), wherein X8 is K or R, X9 is T or M, X10 is T, I or S, and X11 is P, T or L;
- (2) antigenic epitope repeat regions expressed in Loop 2 and defined by the amino acid sequence CCCTKPX12DGNCX13 (SEQ ID NO:
- 26), wherein X12 is T or S;
- and X13 is T or S;
- and
- (3) antigenic epitope repeat regions consisting of the amino acid sequence PCKTCTTP (SEQ ID NO:
- 28), PCRTCTTP (SEQ ID NO:
- 33), CTKPTDGNC (SEQ ID NO:
- 34), CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35), CTKPSDGNC (SEQ ID NO:
- 54), PC(K/R)TC(T/M)TP (SEQ ID NO:
- 37), C(K/R)TC(T/M)T(P/T)AQG(N/T)SM(F/Y)PS (SEQ ID NO:
- 38), PCRTCMTTAQGTSMYPSCCCTKPSDGNC (SEQ ID NO:
- 39), or PCKTCTTPAQGNSMFPSCCCTKPTDGNC (SEQ ID NO:
- 40).
A composition comprising one or more peptides selected from the group consisting of TCTTPAQGNSMFPSC (SEQ ID NO:
- 17), TCTIPAQGTSMFPSC (SEQ ID NO:
- 18), TCTTPAQGTSMFPSC (SEQ ID NO:
- 19), CTKPTDGNCT (SEQ ID NO:
- 20), and CTKPSDGNCT (SEQ ID NO:
- 21).
A method of treating hepatitis B infection in a subject in need thereof, comprising administering to the subject one or more peptides selected from the group consisting of TCTTPAQGNSMFPSC (SEQ ID NO:
- 17), TCTIPAQGTSMFPSC (SEQ ID NO:
- 18), TCTTPAQGTSMFPSC (SEQ ID NO:
- 19), CTKPTDGNCT (SEQ ID NO:
- 20), and CTKPSDGNCT (SEQ ID NO:
- 21).
A bio-nanoparticle (BNP) comprising a hepadnaviral envelope HBsAg-S fusion protein comprising an HBsAg-S template comprising the amino acids set forth in SEQ ID NO:
- 50 and an epitope insert consisting of the amino acids set forth SEQ ID NO:
- 44, wherein the epitope insert replaces amino acid residues 125-128 of SEQ ID NO:
- 50.
A bio-nanoparticle (BNP) comprising a hepadnaviral envelope HBsAg-S fusion protein comprising an HBsAg-S template comprising the amino acids set forth in SEQ ID NO:
- 50 and an epitope insert consisting of the amino acids set forth in SEQ ID NO:
- 45, wherein the epitope insert replaces residues 137-151 of SEQ ID NO:
- 50.
A bio-nanoparticle (BNP) comprising a hepadnaviral envelope HBsAg-S fusion protein comprising one or more antigenic epitope regions selected from the group consisting of:
- CTKPTDGNC (SEQ ID NO:
- 34), CTKPSDGNC (SEQ ID NO:
- 54), and CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35).
A composition comprising a first bio-nanoparticle (BNP) and a second bio-nanoparticle (BNP);
- wherein the first BNP comprises a hepadnaviral envelope HBsAg-S fusion protein comprising a first and a second antigenic epitope region comprising CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35);
- and
- wherein the second BNP comprises a hepadnaviral envelope HBsAg-S fusion protein comprising a first, a second, and a third antigenic epitope region, wherein the first antigenic epitope region comprises CTKPSDGNC (SEQ ID NO:
- 54) and the second and third antigenic epitope regions comprise CTKPTDGNC (SEQ ID NO:
- 34).
A composition comprising a bio-nanoparticle (BNP) wherein the BNP comprises a hepadnaviral envelope HBsAg-S fusion protein comprising a first and a second antigenic epitope region comprising CKTCTTPAQGNSMFPS (SEQ ID NO:
- 35).
A composition comprising a bio-nanoparticle (BNP);
- wherein the BNP comprises a hepadnaviral envelope HBsAg-S fusion protein comprising a first, a second, and a third antigenic epitope region, wherein the first antigenic epitope region comprises CTKPSDGNC (SEQ ID NO:
- 54) and the second and third antigenic epitope regions comprise CTKPTDGNC (SEQ ID NO:
- 34).
Dependencies are inferred from the claim text.