US2003171538A1PendingUtilityA1
Peptides for inducing cytotoxic T lymphocyte responses to hepatitis B virus
Est. expiryAug 26, 2011(expired)· nominal 20-yr term from priority
Inventors:Francis V. Chisari
A61P 31/12C07K 14/005C12N 2730/10134C12N 2730/10122A61K 2039/572A61K 39/12A61K 40/46A61K 40/11A61K 39/00A61K 2039/57A61K 39/29
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Claims
Abstract
Peptides are used to define epitopes that stimulate HLA-restricted cytotoxic T lymphocyte activity against hepatitis B virus antigens. The peptides are derived from regions of HBV polymerase, and are particularly useful in treating or preventing HBV infection, including methods for stimulating the immune response of chronically infected individuals to respond to HBV antigens.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A CTL inducing peptide comprising from eight to thirteen amino acids, wherein at least a majority of the amino acids are homologous to a corresponding portion of HBpol having the sequence:
HBpol4-13
[Seq ID No. 12]
Ser-Tyr-Gln-His-Phe-Arg-Lys-Leu-Leu-Leu;
HBpol108-116
[Seq ID No. 13]
Arg-Leu-Lys-Leu-Ile-Met-Pro-Ala-Arg;
HBpol139-147
[Seq ID No. 14]
Val-Val-Asn-His-Tyr-Phe-Gln-Thr-Arg
HBpol151-160
[Seq ID No. 15]
His-Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr
HBpol152-161
[Seq ID No. 16]
Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr-Lys
HBpol 455-463
[Seq ID No. 2]
Gly-Leu-Ser-Arg-Tyr-Val-Ala-Arg-Leu;
HBpol505-514
[Seq ID No. 17]
Leu-Tyr-Ser-His-Pro-Ile-Ile-Leu-Gly-Phe;
HBpol551-559
[Seq ID No. 18]
Tyr-Met-Asp-Asp-Val-Val-Leu-Gly-Ala;
HBpol575-583
[Seq ID No. 19]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu;
HBpol655-663
[Seq ID No. 20]
Ala-Leu-Met-Pro-Leu-Tyr-Ala-Cys-Ile;
HBpol748-757
[Seq ID No. 21]
Gly-Thr-Asp-Asn-Ser-Val-Val-Leu-Ser-Arg;
HBpol758-766
[Seq ID No. 22]
Lys-Tyr-Thr-Ser-Phe-Pro-Trp-Leu-Leu);
HBpol773-782
[Seq ID No. 3]
Ile-Leu-Arg-Gly-Thr-Ser-Phe-Val-Tyr-Val or
HBpol816-824
[Seq ID No. 5]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu
2 . The CTL inducing peptide of claim 1 , which comprises from nine to eleven amino acids.
3 . The CTL inducing peptide of claim 1 , which comprises:
HBpol4-13
[Seq ID No. 12]
Ser-Tyr-Gln-His-Phe-Arg-Lys-Leu-Leu-Leu
HBpol108-116
[Seq ID No. 13]
Arg-Leu-Lys-Leu-Ile-Met-Pro-Ala-Arg;
HBpol139-147
[Seq ID No. 14]
Val-Val-Asn-His-Tyr-Phe-Gln-Thr-Arg
HBpol151-160
[Seq ID No. 15]
His-Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr
HBpol152-161
[Seq ID No. 16]
Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr-Lys
HBpol455-463
[Seq ID No. 2]
Gly-Leu-Ser-Arg-Tyr-Val-Ala-Arg-Leu;
HBpol505-514
[Seq ID No. 17]
Leu-Tyr-Ser-His-Pro-Ile-Ile-Leu-Gly-Phe;
HBpol551-559
[Seq ID No. 18]
Tyr-Met-Asp-Asp-Val-Val-Leu-Gly-Ala;
HBpol575-583
[Seq ID No. 19]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu;
HBpol655-663
[Seq ID No. 20]
Ala-Leu-Met-Pro-Leu-Tyr-Ala-Cys-Ile;
HBpol748-757
[Seq ID No. 21]
Gly-Thr-Asp-Asn-Ser-Val-Val-Leu-Ser-Arg;
HBpol758-766
[Seq ID No. 22]
Lys-Tyr-Thr-Ser-Phe-Pro-Trp-Leu-Leu);
HBpol773-782
[Seq ID No. 3]
Ile-Leu-Arg-Gly-Thr-Ser-Phe-Val-Tyr-Val or
HBpol816-824
[Seq ID No. 5]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu
4 . The peptide of claim 1 , suspended in pharmaceutically acceptable carrier which comprises a liposome.
5 . The CTL inducing peptide of claim 1 , wherein the peptide also contains a T helper epitope.
6 . The peptide of claim 1 , conjugated to a immunogenic lipid carrier.
7 . A method for stimulating a cytotoxic T lymphocyte response to hepatitis B virus which comprises exposing cytotoxic T lymphocytes of a host to a peptide which contains a CTL epitope and which comprises from eight to thirteen amino acids, wherein at least a majority of the amino acids are homologous to a corresponding portion of HBpol having the sequence:
HBpol14-13
[Seq ID No. 12]
Ser-Tyr-Gln-His-Phe-Arg-Lys-Leu-Leu-Leu;
HBpol108-116
[Seq ID No. 13]
Arg-Leu-Lys-Leu-Ile-Met-Pro-Ala-Arg;
HBpol139-147
[Seq ID No. 14]
Val-Val-Asn-His-Tyr-Phe-Gln-Thr-Arg
HBpol151-160
[Seq ID No. 15]
His-Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr
HBpol152-161
[Seq ID No. 16]
Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr-Lys
HBpol 455-463
[Seq ID No. 23]
Gly-Leu-Ser-Arg-Tyr-Val-Ala-Arg-Leu;
HBpol505-514
[Seq ID No. 17]
Leu-Tyr-Ser-His-Pro-Ile-Ile-Leu-Gly-Phe;
HBpol551-559
[Seq ID No. 18]
Tyr-Met-Asp-Asp-Val-Val-Leu-Gly-Ala;
HBpol575-583
[Seq ID No. 19]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu;
HBpol655-663
[Seq ID No. 20]
Ala-Leu-Met-Pro-Leu-Tyr-Ala-Cys-Ile
HBpol748-757
[Seq ID No. 21]
Gly-Thr-Asp-Asn-Ser-Val-Val-Leu-Ser-Arg
HBpol758-766
[Seq ID No. 22]
Lys-Tyr-Thr-Ser-Phe-Pro-Trp-Leu-Leu)
HBpol773-782
[Seq ID No. 3]
Ile-Leu-Arg-Gly-Thr-Ser-Phe-Val-Tyr-Val or
HBpol816-824
[Seq ID No. 5]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu
8 . The method of claim 7 , wherein the CTL inducing peptide is:
HBpol4-13
[Seq ID No. 12]
Ser-Tyr-Gln-His-Phe-Arg-Lys-Leu-Leu-Leu;
HBpol108-116
[Seq ID No. 13]
Arg-Leu-Lys-Leu-Ile-Met-Pro-Ala-Arg;
HBpol139-147
[Seq ID No. 14]
Val-Val-Asn-His-Tyr-Phe-Gln-Thr-Arg
HBpol151-160
[Seq ID No. 15]
His-Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr
HBpol152-161
[Seq ID No. 16]
Thr-Leu-Trp-Lys-Ala-Gly-Ile-Leu-Tyr-Lys
HBpol 455-463
[Seq ID No. 2]
Gly-Leu-Ser-Arg-Tyr-Val-Ala-Arg-Leu;
HBpol505-514
[Seq ID No. 17]
Leu-Tyr-Ser-His-Pro-Ile-Ile-Leu-Gly-Phe;
HBpol551-559
[Seq ID No. 18]
Tyr-Met-Asp-Asp-Val-Val-Leu-Gly-Ala;
HBpol575-583
[Seq ID No. 19]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu;
HBpol655-663
[Seq ID No. 20]
Ala-Leu-Met-Pro-Leu-Tyr-Ala-Cys-Ile;
HBpol748-757
[Seq ID No. 21]
Gly-Thr-Asp-Asn-Ser-Val-Val-Leu-Ser-Arg;
HBpol758-766
[Seq ID No. 22]
Lys-Tyr-Thr-Ser-Phe-Pro-Trp-Leu-Leu);
HBpol773-782
[Seq ID No. 3]
Ile-Leu-Arg-Gly-Thr-Ser-Phe-Val-Tyr-Val or
HBpol816-824
[Seq ID No. 5]
Phe-Leu-Leu-Ser-Leu-Gly-Ile-His-Leu.
9 . The method of claim 8 , wherein the host cells exposed to the CTL-inducing peptides are HLA-A2.
10 . The method of claim 8 , wherein the cytotoxic T cells are removed from the host prior to being exposed to the CTL-inducing peptide.
11 . The method according to claim 10 , further comprising the step of returning the stimulated CTLs to the host.
12 . The method of claim 8 , wherein the host has chronic hepatitis B infection or is a hepatitis B carrier.
13 . The method of claim 8 , wherein the host has acute hepatitis B infection.
14 . The method of claim 8 , wherein the CTL inducing peptide is administered prophylactically to the host's cells.
15 . The method of claim 8 , wherein the CTL inducing peptide is administered to the host with a second peptide which elicits a T helper response to HBV.
16 . The method of claim 15 , wherein the CTL inducing peptide and the T helper inducing peptide are linked.Join the waitlist — get patent alerts
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