# US 2017/0285030 A1 · Methods of diagnosing proliferative disorders

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- Number: US 2017/0285030 A1
- Document ID: US20170285030A1
- Status: Published application
- Kind: A1
- Application number: 15/491,305
- Filed: 2017-04-19
- Published: 2017-10-05
- 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/US20170285030A1

## 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 assaying 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 proliferative disorder in a subject, the method comprising performing spectroscopic analysis upon a blood sample or component thereof of the subject to produce a spectroscopic signature characteristic of the blood sample (or component thereof); wherein the spectroscopic analysis is Attenuated Total Reflection FTIR (ATR-FTIR) in which ATR crystals support the blood sample during IR analysis.

### Claim 33 (depends on 32)

The method of claim 32, wherein the proliferative disorder being diagnosed and/or prognosed is brain cancer and/or associated tumors.

### Claim 34 (depends on 33)

The method of claim 33, wherein the brain tumor is glioma.

### Claim 35 (depends on 34)

The method of claim 34, wherein the blood sample film is of a substantially uniform thickness within a tolerance of +/−40 μm or less and/or wherein the blood sample film has a maximum film thickness (i.e. the point of maximum thickness) across the surface of the ATR crystal (or at least the part of it exposed to IR analysis) of between 1 and 200 μm.

### Claim 36 (depends on 32)

The method of claim 32, wherein a film of the blood sample is applied to the surface of the ATR crystal prior to FTIR analysis.

### Claim 37 (depends on 36)

The method of claim 36, wherein the blood sample film is of a substantially uniform thickness within a tolerance of +/−40 μm or less and/or wherein the blood sample film has a maximum film thickness (i.e. the point of maximum thickness) across the surface of the ATR crystal (or at least the part of it exposed to IR analysis) of between 1 and 200 μm.

### Claim 38 (depends on 36)

The method of claim 36, further comprising depositing 0.1-10 μl of said blood sample upon the surface of an ATR crystal and allowing the blood sample to dry to yield a blood sample film of an appropriate thickness.

### Claim 39 (depends on 38)

The method of claim 38, wherein the blood sample film is of a substantially uniform thickness within a tolerance of +/−40 μm or less and/or wherein the blood sample film has a maximum film thickness (i.e. the point of maximum thickness) across the surface of the ATR crystal (or at least the part of it exposed to IR analysis) of between 1 and 200 μm.

### Claim 40 (depends on 36)

The method of claim 36, wherein drying is effected at standard ambient temperature and pressure (SATP) for between 4 and 16 minutes, or other equivalent conditions yielding the same level of drying.

### Claim 41 (depends on 32)

The method of claim 32, wherein the spectroscopic signature characteristic of the blood sample is the spectrum between 900 and 1800 cm−1.

### Claim 42 (depends on 32)

The method of claim 32, wherein the spectroscopically obtained signature is compared to a plurality of pre-correlated signatures stored in a database in order to derive a correlation with a favorable or unfavorable diagnosis and/or prognosis or wherein the spectroscopically obtained signature is 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 43 (depends on 32)

The method claim 32, wherein the blood sample is blood serum or blood plasma.

### Claim 44 (depends on 32)

The method of claim 32, wherein the method additionally comprises assaying a blood sample, or a component thereof, of the subject in respect of one or more cytokines and/or angiogenesis factors.

### Claim 45 (depends on 32)

A method of diagnosing whether a tumor is malignant or benign, comprising the steps of the method of diagnosing and/or prognosing a brain cancer or proliferative disorder according to claim 32.

### Claim 46

A diagnostic kit for diagnosing and/or prognosing a proliferative disorder in a subject, comprising a device configured to receive a blood sample or component thereof from the subject and to perform spectroscopic analysis upon the blood sample or component thereof of the subject to produce a spectroscopic signature characteristic of the blood sample or component thereof; and a device to correlate or facilitate correlation of the spectroscopic signature of the blood sample or component thereof with a favorable or unfavorable diagnosis and/or prognosis; wherein the spectroscopic analysis is Attenuated Total Reflection FTIR (ATR-FTIR) in which ATR crystals support the blood sample during IR analysis.

### Claim 47 (depends on 46)

The diagnostic kit according to claim 46, wherein the device to correlate or facilitate correlation of the spectroscopic signature of the blood sample or component thereof wherein the same as the device configured to receive a blood sample.

### Claim 48 (depends on 46)

The diagnostic kit of claim 46, wherein the device for assaying or analyzing the blood sample is the same as the device for correlating or facilitating correlation of the results.

### Claim 49 (depends on 46)

The diagnostic kit of claim 46, 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 50 (depends on 46)

The diagnostic kit of claim 46, wherein the device which is configured to receive a blood sample is configured to automatically prepare a blood sample or component thereof of a required thickness and dryness.