# US 2010/0167266 A1 · Compositions and Methods for Determining Whether a Subject Would Benefit from Co-Receptor Inhibitor Therapy

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- Number: US 2010/0167266 A1
- Document ID: US20100167266A1
- Status: Published application
- Kind: A1
- Application number: 12/527,863
- Filed: 2008-02-26
- Published: 2010-07-01
- Earliest claimed: 2007-02-26
- Assignees: Laboratory Corporation of America Holdings
- Inventors: Wei Huang; Signe Franson; Christos J. Petropoulos; Jonathan Toma; Jeannette Whitcomb
- Web page: https://patentgrep.com/patent/US20100167266A1

## CPC

- C12Q 1/703: {Viruses associated with AIDS}
- G01N 33/56988: {HIV or HTLV}
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/156: Polymorphic or mutational markers
- C12Q 2600/158: Expression markers
- G01N 2333/16: HIV-1, HIV-2
- G01N 2333/162: env, e.g. gp160, gp110/120, gp41, V3, peptid T, DC4-Binding site
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- 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 provides methods and compositions for determining whether a subject would benefit from co-receptor inhibitor therapy. In certain aspects, the methods can be used to determine whether a subject infected with a dual-mixed tropic population of HIV would benefit from CCCR5-inhibitor therapy or CXCR4-inhibitor therapy, the methods comprising determining whether the HIV population is a homogeneous or heterogeneous population of HIV, wherein the nature of the homogenous or heterogenous population of HIV indicates whether the patient would benefit from co-receptor inhibitor therapy.

## Claims

### Claim 1

A method for determining whether a subject infected with a dual-mixed tropic population of human immunodeficiency viruses (HIV) would benefit from CXCR4-inhibitor or CCR5-inhibitor therapy, comprising:
a. determining whether the population is a homogeneous or heterogeneous population; wherein if the population is a homogeneous population, step b but not step c of the method is performed, and wherein if the population is a heterogeneous population, step c but not step b of the method is performed;
b. determining whether the homogeneous population is Dual_R tropic or CXCR4-tropic or neither, wherein if the homogeneous population is Dual_R tropic, the subject would benefit from CCR5-inhibitor therapy, wherein if the homogeneous population is Dual_X tropic, the subject would benefit from CXCR4-inhibitor therapy, and wherein if the homogeneous population is neither Dual_R tropic nor CXCR4-tropic, the subject would not benefit from either CCR5-inhibitor or CXCR4-inhibitor therapy; and
c. determining the relative proportions of CCR5-tropic, CXCR4-tropic, Dual_R tropic, Dual_X tropic, or dual tropic HIV of the heterogeneous population, wherein
i. if the heterogeneous population contains CCR5-tropic and/or Dual_R tropic and CXCR4-tropic and/or Dual_X tropic HIV and comprises substantially more CCR5-tropic and/or Dual_R tropic HIV than CXCR4-tropic and/or Dual_X tropic HIV, the subject would benefit from CCR5-inhibitor therapy;
ii. if the heterogeneous population contains CCR5-tropic and/or Dual_R tropic and CXCR4-tropic and/or Dual_X tropic HIV and comprises comparable amounts of CCR5-tropic and/or Dual_R tropic and CXCR4-tropic and/or Dual_X tropic HIV, the subject would not benefit from either CCR5-inhibitor or CXCR4-inhibitor therapy;
iii. if the heterogeneous population contains CCR5-tropic and/or Dual_R tropic and CXCR4-tropic and/or Dual_X tropic HIV and comprises substantially more CXCR4-tropic and/or Dual_X tropic HIV than CCR5-tropic and/or Dual_R tropic HIV, the subject would benefit from CXCR4-inhibitor therapy;
iv. if the heterogeneous population contains CCR5-tropic and/or Dual_R tropic and dual-tropic HIV and comprises substantially more CCR5-tropic and/or Dual_R tropic HIV than dual-tropic HIV, the subject would benefit from CCR5-inhibitor therapy;
v. if the heterogeneous population contains CCR5-tropic and/or Dual_R tropic and dual-tropic HIV and comprises relatively comparable amounts of CCR5-tropic and/or Dual_R tropic HIV and dual-tropic HIV or comprises substantially more dual-tropic HIV than CCR5-tropic and/or Dual_R tropic HIV, the subject would not benefit from CCR5-inhibitor therapy;
vi. if the heterogeneous population contains CXCR4-tropic and/or Dual_X tropic and dual-tropic HIV and comprises substantially more CXCR4-tropic and/or Dual_X tropic HIV than dual-tropic HIV, the subject would benefit from CXCR4-inhibitor therapy;
vii. if the heterogeneous population contains CXCR4-tropic and/or Dual_X tropic and dual-tropic HIV and comprises relatively comparable amounts of CXCR4-tropic and/or Dual_X tropic HIV and dual-tropic HIV or comprises substantially more dual-tropic HIV than CXCR4-tropic and/or Dual_X tropic HIV, the subject would not benefit from either CXCR4-inhibitor or CCR5-inhibitor therapy;
viii. if the heterogeneous population contains CCR5-tropic and/or
Dual_R tropic, CXCR4-tropic and/or Dual_X tropic, and dual-tropic HIV and comprises substantially more CCR5-tropic and/or Dual_R tropic HIV than CXCR4-tropic and/or Dual_X tropic and dual-tropic HIV, the subject would benefit from CCR5-inhibitor therapy;
ix. if the heterogeneous population contains CCR5-tropic and/or Dual_R tropic, CXCR4-tropic and/or Dual_X tropic, and dual-tropic HIV and comprises relatively comparable amounts of CCR5-tropic and/or Dual_R tropic HIV and CXCR4-tropic and/or Dual_X tropic and dual-tropic HIV, the subject would not benefit from either CCR5-inhibitor or CXCR4-inhibitor therapy; and
x. if the heterogeneous population contains CCR5-tropic and/or Dual_R tropic, CXCR4-tropic and/or Dual_X tropic, and dual-tropic HIV and comprises substantially more CXCR4-tropic and/or Dual_X tropic HIV than CCR5-tropic and/or Dual_R tropic and dual-tropic HIV, the subject would benefit from CXCR4-inhibitor therapy.

### Claim 2 (depends on 1)

The method of claim 1, wherein the population is a homogeneous population.

### Claim 3 (depends on 2)

The method of claim 2, wherein the homogeneous population is Dual_R tropic.

### Claim 4 (depends on 2)

The method of claim 2, wherein the homogeneous population is Dual_X tropic.

### Claim 5 (depends on 2)

The method of claim 2, wherein the homogeneous population is neither Dual_R tropic nor CXCR4-tropic.

### Claim 6 (depends on 1)

The method of claim 1, wherein the population is a heterogeneous population.

### Claim 7 (depends on 6)

The method of claim 6, wherein the heterogeneous population contains CCR5-tropic and/or Dual_R tropic and CXCR4-tropic and/or Dual_X tropic HIV.

### Claim 8 (depends on 7)

The method of claim 7, wherein the population comprises substantially more CCR5-tropic and/or Dual_R tropic HIV than CXCR4-tropic and/or Dual_X tropic HIV.

### Claim 9 (depends on 7)

The method of claim 7, wherein the population comprises comparable amounts of CCR5-tropic and/or Dual_R tropic and CXCR4-tropic and/or Dual_X tropic HIV.

### Claim 10 (depends on 7)

The method of claim 7, wherein the population comprises substantially more CXCR4-tropic and/or Dual_X tropic HIV than CCR5-tropic and/or Dual_R tropic HIV.

### Claim 11 (depends on 6)

The method of claim 6, wherein the heterogeneous population contains CCR5-tropic and/or Dual_R tropic and dual-tropic HIV.

### Claim 12 (depends on 11)

The method of claim 11, wherein the population comprises substantially more CCR5-tropic and/or Dual_R tropic HIV than dual-tropic HIV.

### Claim 13 (depends on 11)

The method of claim 11, wherein the population comprises relatively comparable amounts of CCR5-tropic and/or Dual_R tropic HIV and dual-tropic HIV.

### Claim 14 (depends on 11)

The method of claim 11, wherein the population comprises substantially more dual-tropic HIV than CCR5-tropic and/or Dual_R tropic HIV.

### Claim 15 (depends on 6)

The method of claim 6, wherein the heterogeneous population contains CXCR4-tropic and/or Dual_X tropic and dual-tropic HIV.

### Claim 16 (depends on 15)

The method of claim 15, wherein the population comprises substantially more CXCR4-tropic and/or Dual_X tropic HIV than dual-tropic HIV.

### Claim 17 (depends on 15)

The method of claim 15, wherein the population comprises relatively comparable amounts of CXCR4-tropic and/or Dual_X tropic HIV and dual-tropic HIV.

### Claim 18 (depends on 15)

The method of claim 15, wherein the population comprises substantially more dual-tropic HIV than CXCR4-tropic and/or Dual_X tropic HIV.

### Claim 19 (depends on 6)

The method of claim 6, wherein the heterogeneous population contains CCR5-tropic and/or Dual_R tropic, CXCR4-tropic and/or Dual_X tropic, and dual-tropic HIV.

### Claim 20 (depends on 19)

The method of claim 19, wherein the population comprises substantially more CCR5-tropic and/or Dual_R tropic HIV than CXCR4-tropic and/or Dual_X tropic and dual-tropic HIV.

### Claim 21 (depends on 19)

The method of claim 19, wherein the population comprises relatively comparable amounts of CCR5-tropic and/or Dual_R tropic HIV and CXCR4-tropic and/or Dual_X tropic and dual-tropic HIV.

### Claim 22 (depends on 19)

The method of claim 19, wherein the population comprises substantially more CXCR4-tropic and/or Dual_X tropic HIV than CCR5-tropic and/or Dual_R tropic and dual-tropic HIV.

### Claim 23 (depends on 1)

The method of claim 1, wherein the step of determining whether the HIV population is a homogeneous or heterogeneous population is performed by determining a tropism phenotype for a statistically significant number of individual viruses infecting the subject.

### Claim 24 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 100 HIV.

### Claim 25 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 112 HIV.

### Claim 26 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 125 HIV.

### Claim 27 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 137 HIV.

### Claim 28 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 150 HIV.

### Claim 29 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 162 HIV.

### Claim 30 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 175 HIV.

### Claim 31 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 187 HIV.

### Claim 32 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 192 HIV.

### Claim 33 (depends on 23)

The method of claim 23, wherein a tropism phenotype is determined for at least about 200 HIV.

### Claim 34

A method for determining whether a subject infected with a dual-mixed tropic population of HIV would benefit from CXCR4-inhibitor therapy, comprising determining whether the HIV population is a homogeneous or heterogeneous population of HIV, wherein
a. if the subject is infected with a homogeneous population of HIV and the homogeneous population is Dual_X tropic, the subject would benefit from CXCR4-inhibitor therapy; or
b. if the subject is infected with a heterogeneous population of HIV and the heterogeneous population of HIV comprises substantially more CXCR4-tropic or Dual_X tropic HIV than total CCR5-tropic, Dual_R tropic, and dual-tropic HIV, the subject would benefit from CXCR4-inhibitor therapy,
thereby determining whether the subject would benefit from CXCR4-inhibitor therapy.

### Claim 35 (depends on 34)

The method of claim 34, wherein the HIV population is homogeneous.

### Claim 36 (depends on 34)

The method of claim 34, wherein the HIV population is heterogeneous.

### Claim 37 (depends on 34)

The method of claim 34, wherein the step of determining whether the HIV population is a homogeneous or heterogeneous population is performed by determining a tropism phenotype for a statistically significant number of individual viruses infecting the subject.

### Claim 38

A method for determining whether a subject infected with a dual-mixed tropic population of HIV would benefit from CCR5-inhibitor therapy, comprising determining whether the HIV population is a homogeneous or heterogeneous population of HIV, wherein
a. if the subject is infected with a homogeneous population of HIV and the homogeneous population is Dual_R tropic, the subject would benefit from CCR5-inhibitor therapy; or
b. if the subject is infected with a heterogeneous population of HIV and the heterogeneous population of HIV comprises substantially more CCR5-tropic or Dual_R tropic HIV than total CXCR4-tropic, Dual_X tropic, and dual-tropic HIV, the subject would benefit from CCR5-inhibitor therapy,
thereby determining whether the subject would benefit from CCR5-inhibitor therapy.

### Claim 39 (depends on 34)

The method of claim 34, wherein the HIV population is homogeneous.

### Claim 40 (depends on 34)

The method of claim 34, wherein the HIV population is heterogeneous.

### Claim 41 (depends on 34)

The method of claim 34, wherein the step of determining whether the HIV population is a homogeneous or heterogeneous population is performed by determining a tropism phenotype for a statistically significant number of individual viruses infecting the subject.