# US 2016/0252510 A1 · Methods of diagnosing proliferative disorders

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- Number: US 2016/0252510 A1
- Document ID: US20160252510A1
- Status: Published application
- Kind: A1
- Application number: 15/059,797
- Filed: 2016-03-03
- Published: 2016-09-01
- Earliest claimed: 2012-11-15
- Assignees: University of Central Lancashire
- Applicants: University of Central Lancashire
- Inventors: Matthew James BAKER; Peter ABEL; Robert William LEA
- Web page: https://patentgrep.com/patent/US20160252510A1

## CPC

- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- G01N 21/552: Attenuated total reflection
- G01N 33/49: Blood {(chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80)}
- G01N 33/575: for cancer
- G01J 3/433: Modulation spectrometry; Derivative spectrometry
- G01N 21/35: using infrared light (G01N21/39 takes precedence)
- G01N 21/63: optically excited
- G01N 2021/3196: {Correlating located peaks in spectrum with reference data, e.g. fingerprint data}
- G01N 2021/3595: {using FTIR}
- G01N 2030/743: {FTIR}
- G01N 2201/129: Using chemometrical methods
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N 2800/7028: Cancer
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- G01J: MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY (light sources F21, H01J, H01K, H05B; investigating properties of materials by optical means G01N)

## Abstract

The present invention relates to methods of diagnosing and/or prognosing proliferative disorders, especially brain cancers (e.g. gliomas). In particular, the present invention provides a means to conveniently detect malignant tumours merely by as saying or analysing blood (particularly blood serum). Cytokines and/or angiogenesis factors in blood serum have been found to be surprisingly powerful at indicating the presence of brain cancers in a subject. Moreover, spectroscopic analysis, especially ATR-FTIR analysis, of a blood sample has been demonstrated to be surprisingly effective at producing a signature that can be correlated with the presence, extent, severity, or aggressiveness of malignant tumours in a subject.

## Claims

### Claim at position 1

-31. (canceled)

### Claim 32

A method of diagnosing and/or prognosing a glioma in a subject, the method comprising assaying a blood sample or a component thereof of the subject in respect of two or more predesignated cytokines and/or angiogenesis factors selected from prolactin, follistatin, PDGF-BB, PECAM-1, IL-8, IL-10, HGF, angiopoietin, leptin, PDGF-AA, sHER2 neu, sIL-6R alpha, sVEGFR1, G-CSF, and FGF; and correlating elevated or reduced levels of each of the two or more cytokines and/or angiogenesis factors, whether relative to a predetermined threshold or relative to each other, with a favorable or unfavorable diagnosis and/or prognosis.

### Claim 33 (depends on 32)

The method of claim 32, wherein the cytokine and/or angeiogenesis factor analytes are selected from IL-8, PDGF-BB, HGF, follistatin, angiopoietin, leptin, PECAM-1, PDGF-AA, sHER2 neu, sIL-6R alpha, prolactin, sVEGFR1, G-CSF, and FGF.

### Claim 34 (depends on 32)

The method of claim 32, wherein the two or more predesignated cytokines and/or angiogenesis factors are selected from the group consisting of prolactin, follistatin, PDGF-BB, PECAM-1, HGF, angiopoietin, leptin, PDGF-AA, sHER2 neu, sIL-6R alpha, sVEGFR1, G-CSF, and FGF.

### Claim 35 (depends on 32)

The method of claim 32, wherein assaying the blood sample or the component thereof of the subject is performed in respect of three or more predesignated cytokines and/or angiogenesis factors selected from prolactin, follistatin, PDGF-BB, PECAM-1, IL-8, IL-10, HGF, angiopoietin, leptin, PDGF-AA, sHER2 neu, sIL-6R alpha, sVEGFR1, G-CSF, and FGF.

### Claim 36 (depends on 32)

The method of claim 32, wherein the correlating step involves an initial comparison of the analytical results with a reference standard or with previous analytic results that have been pre-correlated with a favorable or unfavorable diagnosis and/or prognosis.

### Claim 37 (depends on 32)

The method of claim 32, wherein the blood sample is assayed with an immunoassay.

### Claim 38 (depends on 32)

The method of claim 32, wherein the blood sample is assayed using a magnetic bead-based multiplex assay designed to measure multiple cytokines and/or angiogenesis factors.

### Claim 39 (depends on 38)

The method of claim 38, wherein the assay suitably employs a plurality of fluorescently dyed beads to simultaneously detect multiple cytokines and/or angiogenesis factors in a single assay.

### Claim 40 (depends on 32)

The method of claim 32, wherein the method further comprises performing spectroscopic analysis upon a blood sample or a component thereof of the subject to produce a spectroscopic signature characteristic of the blood sample or the component thereof; wherein the spectroscopic analysis is Attenuated Total Reflection FTIR (ATR-FTIR), and wherein ATR crystals support the blood sample during IR analysis;
wherein the spectroscopically obtained signature is optionally further correlated with a favorable or unfavorable diagnosis and/or prognosis based on a predictive model developed by training a database of pre-correlated analyses.

### Claim 41 (depends on 32)

The method of claim 32, wherein the glioma is low grade glioma.

### Claim 42 (depends on 32)

The method of claim 32, wherein the glioma is high grade glioma.

### Claim 43 (depends on 32)

The method of claim 32, further comprising diagnosing whether a tumour is malignant or benign.

### Claim 44

A diagnostic kit for diagnosing and/or prognosing a brain cancer in a subject, comprising a device configured to receive a blood sample or a component thereof from the subject and to assay the blood sample or the component thereof in respect of one or more cytokines and/or angiogenesis factors; and a device to correlate or facilitate correlation of the amounts of the one or more cytokines and/or angiogenesis factors within the blood sample or the component thereof with a favorable or unfavorable diagnosis and/or prognosis.

### Claim 45 (depends on 44)

The diagnostic kit of claim 44, wherein the diagnostic kit further comprises a device configured to perform spectroscopic analysis upon the blood sample or a component thereof of the subject to produce a spectroscopic signature characteristic of the blood sample or the component thereof; and a device to correlate or facilitate correlation of the spectroscopic signature of the blood sample or the component thereof with a favorable or unfavorable diagnosis and/or prognosis; wherein the spectroscopic analysis is Attenuated Total Reflection FTIR (ATR-FTIR), and wherein ATR crystals support the blood sample during IR analysis.

### Claim 46 (depends on 44)

The diagnostic kit of claim 44, wherein the device for assaying or analysing the blood sample is the same as the device for correlating or facilitating correlation of the results.

### Claim 47 (depends on 44)

The diagnostic kit of claim 44, wherein the correlating device comprises or is in communication with a computer, which computer is installed with diagnostic computer software configured to operate the computer to perform a predictive diagnosis and/or prognosis in relation to a proliferative disorder based on a spectroscopic signature of a blood sample of a subject.

### Claim 48

A method of diagnosing and/or prognosing a glioma in a subject, the method comprising performing spectroscopic analysis upon a blood sample or a component thereof of the subject to produce a spectroscopic signature characteristic of the blood sample or the component thereof; wherein the spectroscopic analysis is Attenuated Total Reflection FTIR (ATR-FTIR), and wherein ATR crystals support the blood sample during IR analysis;
wherein the spectroscopically obtained signature is optionally correlated with a favorable or unfavorable diagnosis and/or prognosis based on a predictive model developed by training a database of pre-correlated analyses.