Method for the diagnosis and prognosis of malignant diseases

• US 20050053607A1
• Filed: 10/09/2003
• Published: 03/10/2005
• Est. Priority Date: 04/08/2002
• Status: Active Grant

• Current Assignee: University of Louisville
• Original Assignee: University of Louisville
• Inventors: Bates, Paula J., Xu, Xiaohua, Trent, John O., Miller, Donald M.
• Granted Patent: US 7,357,928 B2
• Time in Patent Office: Days
• US Class Current: 424/155.100
• CPC Class Codes: 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
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: 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
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: G01N 33/5005 involving human or animal cells immunoassay G01N33/56966; immunoassays of protozoa G01N33/56905; protozoa in screening assays C12Q1/025
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

Abstract

Methods for the treatment of tumors and cancer by exploiting the surface expression of the usually nuclear-localized protein, nucleolin.

Claims

1. A method of treating cancer in a subject comprising administering to said subject a therapeutically effective amount of an anti-nucleolin agent and a pharmaceutically acceptable carrier.

2. The method of claim 1, further comprising administering to said subject a chemotoxic or chemotherapeutic agent.

3. The method of claim 1, further comprising treating said subject with radiation therapy.

4. The method of claim 2, wherein said chemotoxic or chemotherapeutic agent is selected from the group consisting of cyclophosphamide, etoposide, doxorubicin, methotrexate, vincristine, procabazine, prednizone, dexamethasone, tamoxifen citrate, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, camptothecin, zoledronic acid, Ibandronate and mytomycin.

5. A method of treating cancer in a subject, comprising administering to said subject a therapeutically effective amount of an anti-nucleolin antibody and a pharmaceutically acceptable carrier, wherein said nucleolin antibody is substantially non-immunogenic to human.

6. The method of claim 5, further comprising administering to said subject a chemotoxic or chemotherapeutic agent.

7. The method of claim 5, further comprising treating said subject with radiation therapy.

8. The method of claim 6 wherein said chemotoxic or chemotherapeutic agent is selected from the group consisting of cyclophosphamide, etoposide, doxorubicin, methotrexate, vincristine, procabazine, prednizone, dexamethasone, tamoxifen citrate, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, camptothecin, zoledronic acid, Ibandronate and mytomycin.

9. A method of treating cancer in a subject comprising administering to said subject a therapeutically effective amount of an anti-nucleolin antibody, a chemotoxic or chemotherapeutic agent and a pharmaceutically acceptable carrier.

10. The method of claim 9, wherein said chemotoxic or chemotherapeutic agent is selected from the group consisting of cyclophosphamide, etoposide, doxorubicin, methotrexate, vincristine, procabazine, prednizone, dexamethasone, tamoxifen citrate, carboplatin, cisplatin, oxaliplatin, 5-fluorouracil, camptothecin, zoledronic acid, Ibandronate and mytomycin.

11. A method of treating cancer in a subject comprising administering to said subject a therapeutically effective amount of an anti-nucleolin antibody and a pharmaceutically acceptable carrier, and further treating said subject with radiation therapy.

12. A method of treating cancer, comprising administering a therapeutically effective amount of a duplex interfering RNA to nucleolin and a pharmaceutically acceptable carrier.

13. A method of treating a cancer patient, comprising administering to said patient a nucleolin anti-sense molecule which inhibits production of a nucleolin polypeptide.

14. A method of treating a cancer patient, comprising administering to said patient a nucleolin-interfering RNA molecule which inhibits expression of a nucleolin gene.

15. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and an anti-sense oligonucleotide directed against nucleolin.

16. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and an inhibitory RNA against nucleolin

17. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a nucleolin antibody.