IP Library Granted Patent US 12,354,709
Granted Patent B2
US 12,354,709 · App. 16/562,186 · Granted Jul 8, 2025

Systems, methods, and compositions for viral-associated tumors

Inventors: John Zachary Sanborn (Santa Cruz, CA); Charles Joseph Vaske (Santa Cruz, CA); Stephen Charles Benz (Santa Cruz, CA); Shahrooz Rabizadeh (Los Angeles, CA); Nicole Hensley (Culver City, CA); Patrick Soon-Shiong (Los Angeles, CA)
Assignee: Five3 Genomics, LLC
G16B30/10G16B30/00
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Quick Facts
Patent No.
US 12,354,709
App. No.
16/562,186
Granted
Jul 8, 2025
Kind
B2
Abstract

Contemplated systems and methods employ chimeric reference sequences that include a plurality of viral genome sequences to identify/quantify integration and co-amplification events. Most typically, the viral genome sequences are organized in the chimeric reference sequences as single chromosomes and the chimeric reference sequences are in BAM format.

Claims (20)

1. A computer-implemented method of identifying a treatment for a virus associated tumor of a patient, comprising:

obtaining, by a computer and from a sequence database, a whole genome nucleic acid sequence from a reference non-diseased tissue of the patient, a whole genome sequence from a diseased tissue of the same patient, and a nucleic acid sequence of a virus;

merging the whole genome nucleic acid sequence from the reference non-diseased tissue and the nucleic acid sequence of the virus to obtain a chimeric reference nucleic acid sequence;

aligning the chimeric reference nucleic acid sequence and the nucleic acid sequence from the diseased tissue, using incremental synchronized alignment, by the computer, to identify an integration of the viral nucleic acid sequence in the chimeric reference nucleic acid sequence with the nucleic acid sequence from the virus-associated tumor;

identifying a co-amplification of an oncogene sequence of the diseased tissue of the patient and the viral nucleic acid sequence, wherein the oncogene sequence comprises the nucleic acid sequence from the virus-associated tumor of the patient, and wherein the oncogene is ERBB2 (Erythroblastic Leukemia Viral Oncogene Homolog 2);

treating, upon identifying integration and co-amplification, the virus associated tumor in the patient by using a drug targeting the oncogene;

wherein the virus is an HPV virus (Human Papillomavirus).

2. The method of claim 1 , wherein the nucleic acid sequence from the virus-associated tumor comprises at least nucleic acid sequences of one chromosome of the virus-associated tumor.

3. The method of claim 1 , wherein the whole genome nucleic acid sequence from a reference non-diseased tissue of the patient comprises nucleic acid sequences of one chromosome of the mammalian tissue.

4. The method of claim 1 , wherein the whole genome nucleic acid sequence from a reference non-diseased tissue of the patient comprises at least 50% of an exome of the mammalian tissue.

5. The method of claim 1 , wherein the whole genome nucleic acid sequence from a reference non-diseased tissue of the patien comprises at least 50% of an entire genome of the mammalian tissue.

6. The method of claim 1 , wherein the nucleic acid sequence from the virus-associated tumor and the chimeric reference nucleic acid sequence are in BAM, SAM, FASTA, or FASTA index format.

7. A method of determining viral replication in a patient having a virus associated tumor, comprising;

obtaining a whole genome nucleic acid sequence from a reference non-diseased tissue of the patient, a whole genome sequence from a diseased tissue of the same patient, and a nucleic acid sequence of a virus;

merging the whole genome nucleic acid sequence from the reference non-diseased tissue and the nucleic acid sequence of the virus to obtain a chimeric reference nucleic acid sequence;

aligning the chimeric reference nucleic acid sequence and the nucleic acid sequence from the diseased tissue, using incremental synchronized alignment, to identify an oncogene in the nucleic acid sequence from the virus-associated tumor comprising a portion of the patient's genome nucleic acid and a portion of the viral genome nucleic acid sequence;

quantifying a co-amplification of the portion of the patient's genome nucleic acid and the portion of the viral genome nucleic acid sequence; and

treating, upon identifying co-amplification, the virus associated tumor in the patient by administering a drug targeting the oncogene, wherein the oncogene is ERBB2 (Erythroblastic Leukemia Viral Oncogene Homolog 2);

wherein the virus is an HPV virus (Human Papillomavirus).

8. The method of claim 7 , wherein a copy number of the genome sequence from the diseased tissue and a copy number of the viral genome nucleic acid sequence are substantially same.

Continuity (4)
Division 16032421 · Jul 11, 2018
Division 14499023 · Sep 26, 2014
Provisional Application 61883153 · Sep 26, 2013
Related Publication 20190392921A1 · Dec 26, 2019
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