# US 7,608,259 B2 · Methods of cancer diagnosis and therapy targeted against a cancer stem line

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

- Number: US 7,608,259 B2
- Document ID: US7608259B2
- Status: Granted
- Kind: B2
- Application number: 11/583,744
- Filed: 2006-10-18
- Published: 2007-02-15
- Granted: 2009-10-27
- Earliest claimed: 1997-09-18
- Inventors: Ivan Bergstein
- Web page: https://patentgrep.com/patent/US7608259B2

## CPC

- C07K 16/30: from tumour cells
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 35/00: Antineoplastic agents
- G01N 33/5017: {for testing neoplastic activity}
- G01N 33/575: for cancer
- A61K 2039/505: {comprising antibodies}
- C07K 2317/77: Internalization into the cell
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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
- 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

Improved methods for treatment of cancer which involve the targeting of slow-growing, relatively mutationally-spared cancer stem line are provided. These methods are an improvement over previous cancer therapeutic methods because they provide for very early cancer treatment and reduce the likelihood of clinical relapse after treatment.

## Claims

### Claim 1

A method of treating cancer comprising administering to a human patient diagnosed with cancer an antibody that binds to AC133 in an amount sufficient to inhibit the proliferation of cancer cells in the patient, wherein the cancer is not acute leukemia.

### Claim 2

A method of treating cancer comprising administering to a human patient diagnosed with cancer an antibody fragment attached to a therapeutic moiety, wherein said antibody fragment binds to AC133, in an amount sufficient to inhibit the proliferation of cancer cells in the patient, wherein the cancer is not acute leukemia.

### Claim 3

A method of treating cancer comprising administering to a human patient diagnosed with cancer an antibody that binds to AC133 in an amount sufficient to inhibit the proliferation of cancer cells in the patient, wherein the cancer is not leukemia.

### Claim 4

A method of treating cancer comprising administering to a human patient diagnosed with cancer an antibody fragment attached to a therapeutic moiety, wherein said antibody fragment binds to AC133, in an amount sufficient to inhibit the proliferation of cancer cells in the patient, wherein the cancer is not leukemia.

### Claim 5

A method of treating cancer comprising administering to a human patient diagnosed with a solid tumor an antibody that binds to AC133 in an amount sufficient to inhibit the proliferation of cancer cells in the patient.

### Claim 6

A method of treating cancer comprising administering to a human patient diagnosed with a solid tumor an antibody fragment attached to a therapeutic moiety, wherein said antibody fragment binds to AC133, in an amount sufficient to inhibit the proliferation of cancer cells in the patient.

### Claim 7 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the cancer cells are reduced in the patient.

### Claim 8 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the cancer cells do not increase in the patient.

### Claim 9 (depends on 7)

The method of claim 7, wherein the method further comprises detecting cancer cells.

### Claim 10 (depends on 9)

The method of claim 9, wherein the method detects a reduction in tumor size.

### Claim 11 (depends on 9)

The method of claim 9, wherein the detection utilizes a specimen from the patient.

### Claim 12 (depends on 11)

The method of claim 11, wherein the specimen is from a blood sample, a bone marrow sample, or a tumor biopsy.

### Claim 13 (depends on 9)

The method of claim 9, wherein the detection utilizes an imaging technique.

### Claim 14 (depends on 13)

The method of claim 13, wherein the technique is accomplished using radionuclide imaging, fluorescent imaging, CT scan, X-ray or MRI scan.

### Claim 15 (depends on 8)

The method of claim 8, wherein the method further comprises detecting cancer cells.

### Claim 16 (depends on 15)

The method of claim 15, wherein the method detects that tumor size does not increase.

### Claim 17 (depends on 15)

The method of claim 15, wherein the detection utilizes a specimen from the patient.

### Claim 18 (depends on 17)

The method of claim 17, wherein the specimen is from a blood sample, a bone marrow sample, or a tumor biopsy.

### Claim 19 (depends on 15)

The method of claim 15, wherein the detection utilizes an imaging technique.

### Claim 20 (depends on 19)

The method of claim 19, wherein the technique is accomplished using radionuclide imaging, fluorescent imaging, CT scan, X-ray or MRI scan.

### Claim 21 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the method further comprises detecting cancer cells.

### Claim 22 (depends on 21)

The method of claim 21, wherein cancer cells do not increase.

### Claim 23 (depends on 21)

The method of claim 21, wherein the method detects a reduction in cancer cells.

### Claim 24 (depends on 21)

The method of claim 21, wherein the detection utilizes a specimen from the patient.

### Claim 25 (depends on 24)

The method of claim 24, wherein the specimen is from a blood sample, a bone marrow sample, or a tumor biopsy.

### Claim 26 (depends on 21)

The method of claim 21, wherein the detection utilizes an imaging technique.

### Claim 27 (depends on 26)

The method of claim 26, wherein the technique is accomplished using radionuclide imaging, fluorescent imaging, CT scan, X-ray or MRI scan.

### Claim 28 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the method further comprises detecting cancer stem cells.

### Claim 29 (depends on 28)

The method of claim 28, wherein the detection utilizes a specimen from the patient.

### Claim 30 (depends on 29)

The method of claim 29, wherein the specimen is from a blood sample, a bone marrow sample, or a tumor biopsy.

### Claim 31 (depends on 28)

The method of claim 28, wherein the detection utilizes an imaging technique.

### Claim 32 (depends on 28)

The method of claim 28, wherein the technique is accomplished using radionuclide imaging, fluorescent imaging, CT scan, X-ray or MRI scan.

### Claim 33 (depends on 1, 3)

The method of claim 1, 3, or 5, wherein the antibody is attached to a therapeutic moiety.

### Claim 34 (depends on 33)

The method of claim 33, wherein the therapeutic moiety is selected from alkylating agents, anti-metabolites, plant alkaloids, chemotherapeutic agents, radionuclides, therapeutic enzymes, cytokines, cytotoxins, or growth modulators.

### Claim 35 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof results in a decrease in viability of cancer stem cells.

### Claim 36 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof results in a decrease in growth of cancer stem cells.

### Claim 37 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof modulates cancer stem cells.

### Claim 38 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof results in the differentiation of cancer stem cells.

### Claim 39 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof results in asymmetric cell division of cancer stem cells.

### Claim 40 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof binds to the target that is expressed on a cancer stem cell.

### Claim 41 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the patient has been diagnosed with a solid tumor and has undergone cancer therapy.

### Claim 42 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the patient has been diagnosed with a hematologic cancer and has undergone cancer therapy.

### Claim 43 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the patient has undergone cancer therapy.

### Claim 44 (depends on 43)

The method of claim 43, wherein the patient is in remission from cancer.

### Claim 45 (depends on 43)

The method of claim 43, wherein the patient has relapsed from cancer.

### Claim 46 (depends on 43)

The method of claim 43, wherein the patient has failed cancer treatment.

### Claim 47 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the cancer is brain cancer, neural cancer, breast cancer, kidney cancer, colon cancer, prostate cancer, rhabdomyosarcoma, retinoblastoma, liver cancer, skin cancer, gastrointestinal cancer, pancreatic cancer, cervical cancer, or lung cancer.

### Claim 48 (depends on 37)

The method of claim 37, wherein the cancer stem cells to be modulated are slow growing.

### Claim 49 (depends on 37)

The method of claim 37, wherein the cancer stem cells to be modulated are mutationally spared relative to tumor bulk.

### Claim 50 (depends on 37)

The method of claim 37, wherein the cancer stem cells to be modulated symmetrically divide.

### Claim 51 (depends on 2, 4)

The method of claim 2, 4, or 6, wherein the therapeutic moiety is selected from alkylating agents, anti-metabolites, plant alkaloids, chemotherapeutic agents, radionuclides, therapeutic enzymes, cytokines, cytotoxins, or growth modulators.

### Claim 52 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof kills cancer stem cells when assayed in vitro.

### Claim 53 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof inhibits the proliferation of cancer stem cells when assayed in vitro.

### Claim 54 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof results in a decrease in viability of cancer stem cells when assayed in vitro.

### Claim 55 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof results in a decrease in growth of cancer stem cells when assayed in vitro.

### Claim 56 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof modulates cancer stem cells when assayed in vitro.

### Claim 57 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof kills cancer stem cells.

### Claim 58 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the antibody or fragment thereof inhibits the proliferation of cancer stem cells.

### Claim 59 (depends on 1, 2, 3, 4, 5)

The method of claim 1, 2, 3, 4, 5, or 6, wherein the method comprises the initial therapy for treating the patient.
