Identification of immunogenic mutant peptides using genomic, transcriptomic and proteomic information

Patent metadata

Field	Value
Publication number	US-12372533-B2
Application number	US-202016733988-A
Country	US
Kind code	B2
Filing date	Jan 3, 2020
Priority date	Sep 10, 2014
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

The present disclosure provides methods of identifying a disease-specific immunogenic peptide through a series of selection steps. Immunogenic epitopes identified by methods of the present disclosure are applicable for use in peptide-based immunotherapy, preferably cancer therapy. Furthermore, the methods of the present disclosure may be performed in a high-throughput manner and serve as a means of personalized vaccine development and therapy. Also provided are compositions of immunogenic peptides as well as methods of treatment comprising said compositions.

First claim

What is claim is:

1. An individualized vaccine comprising
a plurality of patient-specific, disease-specific immunogenic mutant peptides or
at least one nucleic acid encoding the plurality of patient-specific, disease-specific immunogenic mutant peptides,
wherein each patient-specific, disease-specific peptide is identified from a disease tissue sample in a patient by a method comprising:
(a) obtaining a first set of variant-coding sequences based on genomic sequences of the disease tissue sample, each variant-coding sequence of the first set having a sequence variation compared to a reference sample;
(b) selecting a second set of variant-coding sequences from the first set based on transcriptomic sequences of the disease tissue in the patient and predicted ability of peptides encoded by the variant-coding sequences to bind to an MHC molecule; and
(c) selecting immunogenic variant-coding sequences from the second set of variant- coding sequences,
wherein selecting immunogenic variant-coding sequences comprises predicting immunogenicity of the peptides comprising a variant amino acid encoded by the variant-coding sequences, and
wherein predicting immunogenicity is based on solvent exposure of the variant amino acid when bound to the MHC molecule,

thereby identifying a patient-specific, disease-specific immunogenic mutant peptide.

2. The vaccine of claim 1 , wherein the disease is cancer.

3. The vaccine of claim 2 , wherein the cancer is pancreatic cancer or bladder cancer.

4. The vaccine of claim 1 , further comprising an adjuvant.

5. The vaccine of claim 1 , wherein the vaccine comprises a plurality of patient-specific, disease-specific immunogenic mutant peptides.

6. The vaccine of claim 1 , wherein the vaccine comprises at least one nucleic acid encoding the the plurality of patient-specific, disease-specific immunogenic mutant peptides.

7. The vaccine of claim 6 , wherein the nucleic acid is RNA.

8. The vaccine of claim 7 , wherein the nucleic acid is mRNA comprising a modified 5′ cap.

9. The vaccine of claim 6 , wherein the nucleic acid is contained in a liposome delivery system.

Assignees

• Genentech Inc

Inventors

• Delamarre Lelia
• Lupardus Patrick
• Mellman Ira
• Yadav Mahesh
• Jhunjhunwala Suchit
• Lill Jennie

Classifications

• G01N33/6878

  in epitope analysis · CPC title

• A61K2039/55516

  Proteins; Peptides · CPC title

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61K2039/55561

  CpG containing adjuvants; Oligonucleotide containing adjuvants · CPC title

• G01N33/56977

  HLA or MHC typing · CPC title