# US 2025/0084485 A1 · Gep5 model for multiple myeloma

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- Number: US 2025/0084485 A1
- Document ID: US20250084485A1
- Status: Published application
- Kind: A1
- Application number: 18/800,794
- Filed: 2024-08-12
- Published: 2025-03-13
- Earliest claimed: 2013-05-20
- Assignees: BioVentures, LLC
- Applicants: BioVentures, LLC
- Inventors: Bart BARLOGIE; Pingping QU; Christoph HEUCK; Joshua EPSTEIN
- Web page: https://patentgrep.com/patent/US20250084485A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 35/00: Antineoplastic agents
- G16B 25/00: ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
- G16B 25/10: Gene or protein expression profiling; Expression-ratio estimation or normalisation
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- C12Q 2600/16: Primer sets for multiplex assays
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## Abstract

The invention provides, inter alia, methods of prognosing a subject with, or suspected of having, multiple myeloma. In certain embodiments, the methods entail testing the gene expression levels of enolase 1 (ENO1), fatty acid binding protein 5 (FABP5), thyroid hormone receptor interactor 13 (TRIP13), transgelin 2 (TAGLN2), and replication factor C (activator 1) 4 (RFC4) in a biological sample isolated from the subject. The invention also provides methods of treatment for multiple myeloma, as well as kits, oligonucleotides, and systems for performing the methods provided by the invention.

## Claims

### Claim at position 1

-37. (canceled)

### Claim 38

A method of prognosing a subject suspected of having multiple myeloma or has multiple myeloma, comprising:
(a) obtaining a biological sample from a subject;
(b) extracting nucleic acids from the sample to generate an isolated nucleic acid sample; and
(c) measuring gene expression levels of enolase 1 (ENO1), fatty acid binding protein 5 (FABP5), thyroid hormone receptor interactor 13 (TRIP13), transgelin 2 (TAGLN2), and replication factor C (activator 1) 4 (RFC4) by contacting the isolated nucleic acid sample with detectably labeled nucleic acid probes that hybridize to each gene and detecting the complex formed between each gene and probe, wherein an elevated mean, log-normalized gene expression level of at least two of ENO1, FABP5, TRIP13, TAGLN2, and RFC4 as compared to a suitable control for each gene is associated with a poor multiple myeloma prognosis for the subject.

### Claim 39 (depends on 38)

The method of claim 38, wherein at least one of the nucleic acid probes is selected from among SEQ ID NOs:1, 4, 7, 10, and 13.

### Claim 40 (depends on 38)

The method of claim 38, wherein the measuring gene expression levels further comprises contacting the isolated nucleic acid sample with a primer set comprising a primer selected from SEQ ID NOs:2, 3, 5, 6, 8, 9, 11, 12, 14, or 15.

### Claim 41 (depends on 38)

The method of claim 38, wherein the biological sample processed to generate a sample comprising CD138+myeloma cells.

### Claim 42 (depends on 38)

The method of claim 38, wherein the biological sample comprises about 50,000 or fewer myeloma cells.

### Claim 43 (depends on 38)

The method of claim 38, wherein the detectable label is a fluorescent label.

### Claim 44 (depends on 38)

The method of claim 38, wherein the measuring gene expression levels is by quantitative polymerase chain reaction (qPCR), quantitative real-time polymerase chain reaction (qRTPCR), digital droplet PCR, (ddPCR), sequencing, northern blotting, or Southern blotting.

### Claim 45 (depends on 44)

The method of claim 44, wherein the measuring gene expression levels is by qRTPCR.

### Claim 46 (depends on 38)

The method of claim 38, wherein subject is under-going myeloma therapy.

### Claim 47 (depends on 38)

The method of claim 38, wherein the subject is undergoing TT6 and the prognosing is overall survival (OS).

### Claim 48

A method of detecting a gene expression profile, comprising:
(a) contacting a biological sample obtained from a subject with detectably labeled nucleic acid probes that hybridize to each of enolase 1 (ENO1), fatty acid binding protein 5 (FABP5), thyroid hormone receptor interactor 13 (TRIP13), transgelin 2 (TAGLN2), and replication factor C (activator 1) 4 (RFC4); and
(b) measuring gene expression levels of ENO1, FABP5, TRIP13, TAGLN2, and RFC4; and
(c) detecting a gene expression profile by determining a mean, log-normalized gene expression level of at least two of ENO1, FABP5, TRIP13, TAGLN2, and RFC4.

### Claim 49 (depends on 48)

The method of claim 48, wherein at least one of the nucleic acid probes is selected from among SEQ ID NOS:1, 4, 7, 10, and 13.

### Claim 50 (depends on 48)

The method of claim 48, wherein (a) further comprises contacting the biological sample with a primer set comprising a primer selected from SEQ ID NOs:2, 3, 5, 6, 8, 9, 11, 12, 14, or 15.

### Claim 51 (depends on 48)

The method of claim 48, wherein the subject is suspected of having multiple myeloma or has multiple myeloma.

### Claim 52 (depends on 51)

The method of claim 51, wherein the biological sample comprises about 50,000 or fewer myeloma cells.

### Claim 53 (depends on 48)

The method of claim 48, wherein the gene expression levels are measured by quantitative polymerase chain reaction (qPCR), quantitative real-time polymerase chain reaction (qRTPCR), digital droplet PCR, (ddPCR), sequencing, northern blotting, or Southern blotting.

### Claim 54 (depends on 48)

The method of claim 48, wherein an elevated mean, log-normalized gene expression level of at least two of ENO1, FABP5, TRIP13, TAGLN2, and RFC4 as compared to a suitable control for each gene is associated with a poor multiple myeloma prognosis for the subject.

### Claim 55 (depends on 54)

The method of claim 54, wherein the subject is undergoing TT6 and the prognosing is overall survival (OS).
