# US 5,707,795 A · Therapy and diagnosis of conditions related to telomere length and/or telomerase activity

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 5,707,795 A
- Document ID: US5707795A
- Status: Granted
- Kind: A
- Application number: 08/487,290
- Filed: 1995-06-07
- Granted: 1998-01-13
- Earliest claimed: 1992-05-13
- Assignees: Board of Regents, The University of Texas System
- Inventors: Michael D. West; Jerry Shay; Woodring Wright
- Web page: https://patentgrep.com/patent/US5707795A

## CPC

- C12N 15/10: Processes for the isolation, preparation or purification of DNA or RNA (chemical preparation of DNA or RNA C07H21/00; preparation of non-structural polynucleotides from microorganisms or with enzymes C12P19/34)
- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61K 31/70: Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047)
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61K 31/711: Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C12N 5/0018: {Culture media for cell or tissue culture (media for specific animal cell type C12N5/06)}
- C12N 5/163: {one of the fusion partners being a B or a T lymphocyte}
- C12N 9/1241: {Nucleotidyltransferases (2.7.7)}
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 15/1137: {against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138)}
- C12Q 1/48: involving transferase
- C12Q 1/68: involving nucleic acids
- C12Q 1/6827: for detection of mutation or polymorphism
- C12Q 1/686: Polymerase chain reaction [PCR]
- C12Q 1/6876: Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- C12Q 1/703: {Viruses associated with AIDS}
- C12Y 207/07049: RNA-directed DNA polymerase (2.7.7.49), i.e. telomerase or reverse-transcriptase
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C12N 2501/70: Enzymes
- C12N 2510/04: Immortalised cells
- C12Q 2600/112: Disease subtyping, staging or classification
- C12Q 2600/136: Screening for pharmacological compounds
- G01N 2333/91245: Nucleotidyltransferases (2.7.7)
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- Y10S 977/773: Nanoparticle, i.e. structure having three dimensions of 100 nm or less
- Y10S 977/801: Drug
- Y10S 977/918: Immunological
- Y10S 977/927: Diagnostic contrast agent
- Y10T 436/10: Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T 436/105831: Protein or peptide standard or control [e.g., hemoglobin, etc.]
- Y10T 436/11: Automated chemical analysis
- Y10T 436/115831: Condition or time responsive
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C12Y: ENZYMES
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

Method and compositions are provided for the determination of telomere length and telomerase activity, as well as the ability to inhibit telomerase activity in the treatment of proliferative diseases. Particularly, primers are elongated under conditions which minimize interference from other genomic sequences, so as to obtain accurate determinations of telomeric length or telomerase activity. In addition, compositions are provided for intracellular inhibition of telomerase activity.

## Claims

### Claim 1

A method for diagnosis of a stage of disease progression in an individual having a disease associated with an increased rate of proliferation of a cell population, said method comprising steps of:
(a) measuring telomere lengths of telomeres from a cell or tissue sample obtained from said individual to obtain a measured telomere length:
(b) comparing said measured telomere length to a control telomere length obtained by measuring telomere length ill a control sample; and
(c) correlating differences between said measured telomere length and said control telomere length with said stage of disease progression.

### Claim 2 (depends on 1)

The method of claim 1, wherein said disease is HIV-infection or AIDS.

### Claim 3 (depends on 1)

The method of claim 1, wherein said disease is atherosclerosis.

### Claim 4 (depends on 1)

The method of claim 1, wherein said disease is cancer.

### Claim 5 (depends on 4)

The method of claim 4, wherein said cancer is ovarian cancer.

### Claim 6 (depends on 4)

The method of claim 4, wherein said cancer is breast cancer.

### Claim 7 (depends on 1)

The method of claim 1, wherein said disease is Down's Syndrome.

### Claim 8 (depends on 1)

The method of claim 1, wherein said disease is liver disease.

### Claim 9 (depends on 1)

The method of claim 1, wherein said disease is muscular dystrophy.

### Claim 10 (depends on 1)

The method of claim 1, wherein said measuring step comprises steps of:
(a) digesting genomic DNA of said sample to obtain terminal restriction fragments;
(b) separating said terminal restriction fragments by size;
(c) hybridizing an oligonucleotide probe complementary to telomeric DNA under conditions such that said probe hybridizes specifically to telomeric DNA in said terminal restriction fragments;
(d) measuring amount of bound probe; and
(e) correlating amount of bound probe with telomere length.

### Claim 11 (depends on 10)

The method of claim 10, wherein said disease is HIV-infection or AIDS.

### Claim 12 (depends on 10)

The method of claim 10, wherein said disease atherosclerosis.

### Claim 13 (depends on 10)

The method of claim 10, wherein said disease is cancer.

### Claim 14 (depends on 10)

The method of claim 10, wherein said condition is Down's Syndrome.

### Claim 15 (depends on 10)

The method of claim 10, wherein said condition is liver disease.

### Claim 16 (depends on 10)

The method of claim 10, wherein said condition is muscular dystrophy.

### Claim 17 (depends on 1)

The method of claim 1, wherein said measuring step comprises steps of:
(a) adding a primer sufficiently complementary to a 3'-end of a telomere in double-stranded chromosomal DNA of said sample to hybridize specifically thereto in a mixture containing only those deoxynucleotides complementary to nucleotides in telomeric DNA under conditions such that said primer is extended by an agent for polymerization until reaching a non-telomeric deoxynucleotide to form a primer extension product complementary to telomeric DNA; and
(b) measuring primer extension product size to provide a measure of telomere length.

### Claim 18 (depends on 17)

The method of claim 17, wherein said primer is 5'-CCCTAACCCTAACCCTAACCCTAA-3' (Seq. ID No. 6).

### Claim 19 (depends on 17)

The method of claim 17, wherein one of said deoxynucleotides is radiolabeled.

### Claim 20 (depends on 17)

The method of claim 17, wherein said disease is HIV-infection or AIDS.

### Claim 21 (depends on 17)

The method of claim 17, wherein said disease atherosclerosis.

### Claim 22 (depends on 17)

The method of claim 17, wherein said disease is cancer.

### Claim 23 (depends on 17)

The method of claim 17, wherein said condition is Down's Syndrome.

### Claim 24 (depends on 17)

The method of claim 17, wherein said condition is liver disease.

### Claim 25 (depends on 17)

The method of claim 17, wherein said condition is muscular dystrophy.

### Claim 26 (depends on 1)

The method of claim 1, wherein said measuring step comprises the steps of:
(a) denaturing cellular DNA of said sample in situ;
(b) adding an oligonucleotide probe labeled with a detectable label and complementary to telomeric DNA to said denatured DNA under conditions such that said probe anneals to said DNA;
(c) measuring signal intensity of said label from said probe annealed to said denatured DNA; and
(d) correlating said signal intensity with telomere length.

### Claim 27 (depends on 1)

The method of claim 1, wherein said cell or tissue sample obtained from said individual is enriched for a particular cell type.

### Claim 28 (depends on 1)

The method of claim 1, wherein said control sample is obtained from said individual at an earlier stage of disease progression.

### Claim 29 (depends on 1)

The method of claim 1, wherein said stage of disease progression is a stage after the administration of a therapeutic for treating said disease.

### Claim 30 (depends on 2)

The method of claim 2, wherein said disease is HIV-infection and said stage of disease progression is a stage after seroconversion and prior to AIDS.

### Claim 31 (depends on 2)

The method of claim 2, wherein said sample obtained from said individual is a peripheral lymphocyte cell sample.

### Claim 32 (depends on 2)

The method of claim 2, wherein said stage of disease progression is a stage after the administration of a therapeutic for treating said disease.

### Claim 33 (depends on 29)

The method of claim 29, wherein said peripheral lymphocyte cell sample is a CD4.sup.+ cell sample.