# US 2013/0157267 A1 · Marker for Cancer Prognosis and Methods Related Thereto

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- Number: US 2013/0157267 A1
- Document ID: US20130157267A1
- Status: Published application
- Kind: A1
- Application number: 13/662,898
- Filed: 2012-10-29
- Published: 2013-06-20
- Earliest claimed: 2007-11-14
- Assignees: National Jewish Health
- Inventors: Aftab Ahmad; Carl W. White
- Web page: https://patentgrep.com/patent/US20130157267A1

## CPC

- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 9/007: {Pulmonary tract; Aromatherapy}
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/56966: {Animal cells}
- G01N 33/57557: {of other specific parts of the body, e.g. brain}
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- G01N 33/6893: {related to diseases not provided for elsewhere}
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/118: Prognosis of disease development
- C12Q 2600/158: Expression markers
- C12Q 2600/178: miRNA, siRNA or ncRNA
- G01N 2800/56: Staging of a disease; Further complications associated with the disease
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- 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
- 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)

## Abstract

The present invention is related to the novel discovery that HIF-2α, but not HIF-1 a, selectively regulates adenosine A2A receptor in endothelial cells, thereby revealing a unique and hitherto unknown pathway by which HIF-2α can regulate angiogenesis independent of HIF-1α. This discovery allows for design of new diagnostic tools and novel therapies targeted against angiogenesis-associated diseases, such as cancer. In another aspect, the present invention shows that A2A receptor expression is a marker of the developing lung, and can be used as a marker of lung diseases, such as pulmonary hypertension.

## Claims

### Claim at position 1

-14. (canceled)

### Claim 15

A method to identify agents that inhibit the development of pulmonary hypertension and related conditions, comprising identifying agents that decrease the expression or activity of adenosine A2A receptor (A2A) in lung cells.

### Claim 16

A method to inhibit the development of pulmonary hypertension and related conditions, comprising inhibiting the expression or activity of adenosine A2A receptor (A2A) in lung cells of a patient with pulmonary hypertension or a related condition.

### Claim at position 4

-20. (canceled)

### Claim 21 (depends on 15)

The method of claim 15, wherein the agent is an A2A receptor antagonist.

### Claim 22 (depends on 16)

The method of claim 16, wherein the expression or activity of the A2A receptor (A2A) is inhibited by an A2A receptor antagonist.

### Claim 23

A method to diagnose a patient with pulmonary hypertension, comprising:
a) detecting the expression of adenosine A2A receptor (A2A) in a lung cell sample from a patient;
b) comparing the level of expression of A2A detected in the patient sample to a level of expression of A2A in a control sample; and
c) diagnosing the patient as having pulmonary hypertension, if the expression level of A2A in the sample from the patient is statistically higher than the expression level of A2A in the control sample.

### Claim 24 (depends on 23)

The method of claim 23, wherein expression of A2A is detected by measuring amounts of transcripts of the gene in the lung cells.

### Claim 25 (depends on 23)

The method of claim 23, wherein expression of A2A is detected by detecting the A2A protein.

### Claim 26 (depends on 23)

The method of claim 23, wherein the control sample is from lung cells from a subject that does not have pulmonary hypertension.

### Claim 27 (depends on 23)

The method of claim 23, wherein control expression levels of A2A have been predetermined.

### Claim 28

A method to select a patient having pulmonary hypertension who is predicted to benefit from therapeutic administration of an A2A receptor (A2A) antagonist, or a drug having substantially similar biological activity as the A2A receptor (A2A) antagonist, comprising:
a) detecting the expression of adenosine A2A receptor (A2A) in a lung cell sample from a patient;
b) comparing the level of expression of A2A detected in the patient sample to a level of expression of A2A in a control sample; and
c) selecting the patient as being predicted to benefit from therapeutic administration of the A2A receptor (A2A) antagonist, if the expression level of A2A in the sample from the patient is statistically higher than the expression level of A2A in the control sample.

### Claim 29 (depends on 28)

The method of claim 28, wherein expression of A2A is detected by measuring amounts of transcripts of the gene in the lung cells.

### Claim 30 (depends on 28)

The method of claim 28, wherein expression of A2A is detected by detecting the A2A protein.

### Claim 31 (depends on 28)

The method of claim 28, wherein the control sample is from lung cells from a subject that does not have pulmonary hypertension.

### Claim 32 (depends on 28)

The method of claim 28, wherein control expression levels of A2A have been predetermined.

### Claim 33

A method to select a patient having pulmonary hypertension who is predicted to benefit from therapeutic administration of an antagonist of the PI3K/Akt signal transduction pathway, comprising:
a) detecting the expression of adenosine A2A receptor (A2A) in a lung cell sample from a patient;
b) comparing the level of expression of A2A detected in the patient sample to a level of expression of A2A in a control sample; and
c) selecting the patient as being predicted to benefit from therapeutic administration of the A2A receptor (A2A) antagonist, if the expression level of A2A in the sample from the patient is statistically higher than the expression level of A2A in the control sample.

### Claim 34 (depends on 33)

The method of claim 33, wherein expression of A2A is detected by measuring amounts of transcripts of the gene in the lung cells.

### Claim 35 (depends on 33)

The method of claim 33, wherein expression of A2A is detected by detecting the A2A protein.

### Claim 36 (depends on 33)

The method of claim 33, wherein the control sample is from lung cells from a subject that does not have pulmonary hypertension.

### Claim 37 (depends on 33)

The method of claim 33, wherein control expression levels of A2A have been predetermined.
