# US 8,148,086 B2 · Methods to predict and prevent resistance to taxoid compounds

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- Number: US 8,148,086 B2
- Document ID: US8148086B2
- Status: Granted
- Kind: B2
- Application number: 12/085,125
- Filed: 2006-11-17
- Published: 2009-12-17
- Granted: 2012-04-03
- Earliest claimed: 2005-11-17
- Assignees: Children's Medical Center Corporatioin
- Inventors: Bruce R. Zetter; Sabarni K. Chatterjee
- Web page: https://patentgrep.com/patent/US8148086B2

## CPC

- G01N 33/6893: {related to diseases not provided for elsewhere}
- 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)
- A61K 38/45: Transferases (2)
- A61K 51/00: Preparations containing radioactive substances for use in therapy or testing in vivo
- A61P 35/00: Antineoplastic agents
- C07K 16/18: against material from animals or humans
- 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)}
- G01N 33/575: for cancer
- G01N 33/94: involving narcotics {or drugs or pharmaceuticals, neurotransmitters or associated receptors}
- C07K 2317/55: Fab or Fab'
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2320/32: Special delivery means, e.g. tissue-specific
- C12Y 205/01018: Glutathione transferase (2.5.1.18)
- G01N 2800/44: Multiple drug resistance
- 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)
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

Embodiments of the invention are directed to methods for predicting the resistance of cancer to members of the taxoid family by measuring the levels of prohibitin. Methods for treating cancer and taxoid family member resistant cancers using inhibitors of prohibitin, as well as therapeutic complexes that target prohibitin are also provided.

## Claims

### Claim 1

A method for predicting the resistance of a tumor in a subject to a member of the taxoid family, the method comprising:
(a). measuring a level of cell surface prohibitin in a tumor sample obtained from the subject;
(b). comparing the level measured in step (a) to a standard level of cell surface prohibitin; and
(c) identifying the tumor in the subject as resistant to a member of the taxoid family when the measured level of cell surface prohibitin in the tumor sample is increased relative to the standard level of cell surface prohibitin.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject had been treated with the member of the taxoid family.

### Claim 3 (depends on 1)

The method of claim 1, wherein the member of the taxoid family is paclitaxel or docetaxel.

### Claim 4

A method for predicting the resistance of a tumor in a subject to a member of the taxoid family, the method comprising:
(a). measuring the level of cell surface prohibitin in multiple tumor samples obtained from the subject periodically over a period time; and
(b). measuring a change in the measured level of cell surface prohibitin in the tumor samples,
wherein an elevation of the level of cell surface prohibitin in the tumor samples over the period of time is indicative of resistance of the tumor to a member of the taxoid family.

### Claim 5 (depends on 4)

The method of claim 4, wherein the subject had been treated with the member of the taxoid family.

### Claim 6 (depends on 4)

The method of claim 4, wherein the member of the taxoid family is paclitaxel or docetaxel.

### Claim 7

A method for improving the effectiveness of tumor treatment in a subject comprising:
measuring the level of cell surface prohibitin in a tumor sample obtained from the subject, and identifying the tumor in the subject as resistant to a member of the taxoid family when if the measured level of cell surface prohibitin in the tumor sample is elevated as compared to a standard level of cell surface prohibitin indicates that the subject is in need of alternative treatment so as to improve the effectiveness of tumor treatment.

### Claim 8 (depends on 7)

The method of claim 7, wherein the subject had been treated with the member of the taxoid family.

### Claim 9 (depends on 8)

The method of claim 8, wherein the member of the taxoid family is paclitaxel or docetaxel.