EP1229920A1 - Therapie mit 2-5a und interferon - Google Patents

Therapie mit 2-5a und interferon

Info

Publication number
EP1229920A1
EP1229920A1 EP00977293A EP00977293A EP1229920A1 EP 1229920 A1 EP1229920 A1 EP 1229920A1 EP 00977293 A EP00977293 A EP 00977293A EP 00977293 A EP00977293 A EP 00977293A EP 1229920 A1 EP1229920 A1 EP 1229920A1
Authority
EP
European Patent Office
Prior art keywords
ifn
analog
biostable
subject
cells
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00977293A
Other languages
English (en)
French (fr)
Inventor
Robert H. Silverman
Lorraine Rusch
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cleveland Clinic Foundation
Original Assignee
Cleveland Clinic Foundation
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Cleveland Clinic Foundation filed Critical Cleveland Clinic Foundation
Publication of EP1229920A1 publication Critical patent/EP1229920A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7125—Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/543—Lipids, e.g. triglycerides; Polyamines, e.g. spermine or spermidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • Figure 4 shows the kinetics of apoptosis induced in HEY1B cells by the combination of IFN and 2-5A as determined by Annexin V binding assays.
  • HEY IB cells were plated (2xl0 5 cells/plate) in six-well tissue culture plates and incubated in the absence or presence of EFN (2,000 U/ml) overnight prior to transfection with either A2'p5'A or 2-5A (6 ⁇ M) in serum-free Opti-MEM for 3.5h and then placed in growth media. Cells were harvested at various times for Annexin V binding assays by FACS analysis.
  • the present invention provides methods for treating malignancies and viral diseases in a subject, particularly a human subject.
  • the methods comprise administering a small molecule known as 2-5 A to the subject.
  • interferon is also administered to the subject.
  • Such methods are particularly useful for treating ovarian carcinoma, malignant gliomas, and breast cancer.
  • interferon refers to the type I interferons which include IFN- ⁇ , with all of its subtypes, IFN- ⁇ , IFN- ⁇ and IFN- ⁇ , as well as the Type II interferon, IFN- ⁇ .
  • interferon also refers to IFN con, which is a consensus type I interferon produced by Amgen, and chemically-modified interferons such as pegylated interferon.
  • the interferon is a type I interferon, IFN con, or a chemically-modified version thereof.
  • 2-5 A is a series of short, heat-stable oligoadenylates with unusual 2', 5' phosphodiester linkages in contrast to the typical 3'-5' linkage that is found RNA and DNA chains (Kerr I. M., Brown R.E. (1978), pppA2'p5'A2'p5'A: an inhibitor of protein synthesis synthesized with an enzymes fraction from IFN-treated cells, Proc. Natl. Acad. Sci. USA, 75:256-260).
  • Human HEY IB cells were cultured in RPMI 1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 100 units/ml penicillin, 100 ⁇ g/ml streptomycin/penicillin.
  • the CellTiter 96® AQueous Non-Radioactive Cell Proliferation Assay is a colorimetric method for determining the number of viable cells in proliferation or chemosensitivity assays. It is composed of solutions of a novel tetrazolium compound (3-(4,5dimethylthiazol-2-yl)-5- ⁇ -carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium, inner salt; MTS) and an electron coupling reagent (phenazine methosulfate; PMS).
  • a novel tetrazolium compound 3-(4,5dimethylthiazol-2-yl)-5- ⁇ -carboxymethoxyphenyl)-2-(4- sulfophenyl)-2H-tetrazolium, inner salt; MTS
  • an electron coupling reagent phenazine methosulfate
  • the fusion proteins are eluted with 20 mM of glutathione in 50 mM Tris-HCl, pH 8.0 containing 1 ⁇ g per ml leupeptin, with shaking at room temperature for 20 min.
  • Expression and purity of the protein preparations are determined by SDS/PAGE and coomassie blue staining and by western blots with monoclonal antibody to RNase L.
  • dC SpA2'p5'A2'p5'A2'p3'dC
  • Fig. 7 The compound dC is stablized at both termini against enzymes that can degrade. Specifically, the 5'-terminus is protected against phosphatase activity by a thiophosphate group. The 2',3 '-terminus is protected against 3' to 5' phosphodiesterase activity linking an inverted deoxycytosine in 2' to 3' linkage to the final (third)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
EP00977293A 1999-09-29 2000-09-29 Therapie mit 2-5a und interferon Withdrawn EP1229920A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US15654299P 1999-09-29 1999-09-29
US156542P 1999-09-29
PCT/US2000/041038 WO2001022970A1 (en) 1999-09-29 2000-09-29 Therapy with 2-5a and interferon

Publications (1)

Publication Number Publication Date
EP1229920A1 true EP1229920A1 (de) 2002-08-14

Family

ID=22559994

Family Applications (1)

Application Number Title Priority Date Filing Date
EP00977293A Withdrawn EP1229920A1 (de) 1999-09-29 2000-09-29 Therapie mit 2-5a und interferon

Country Status (5)

Country Link
EP (1) EP1229920A1 (de)
JP (1) JP2003510281A (de)
AU (1) AU1494801A (de)
CA (1) CA2388025A1 (de)
WO (1) WO2001022970A1 (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020123480A1 (en) * 2000-10-24 2002-09-05 Edson Clark M. Methods and compositions utilizing 2'-5' oligoadenylates in the treatment of disorders of cell proliferation
CA2484251C (en) 2002-04-30 2015-06-23 University Of South Florida Materials and methods for inhibition of respiratory syncytial virus infection
US20050084967A1 (en) 2002-06-28 2005-04-21 Xcyte Therapies, Inc. Compositions and methods for eliminating undesired subpopulations of T cells in patients with immunological defects related to autoimmunity and organ or hematopoietic stem cell transplantation
US7595303B1 (en) 2002-09-05 2009-09-29 University Of South Florida Genetic adjuvants for immunotherapy
JP5132025B2 (ja) * 2002-11-19 2013-01-30 第一三共株式会社 新規２’，５’−オリゴアデニル酸類縁体
TWI347948B (en) 2002-11-19 2011-09-01 Sankyo Co Novel 2',5'-oligoadenylic acid compositions
WO2005105136A1 (en) * 2004-04-27 2005-11-10 University Of South Florida Nanogene therapy for cell proliferation disorders

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5550111A (en) * 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
JPH09509647A (ja) * 1993-09-24 1997-09-30 イー． ブドウスキ，エドワルド ２′，５′−オリゴアデニレート−２′，３′−シクロホスフェート
US5908621A (en) * 1995-11-02 1999-06-01 Schering Corporation Polyethylene glycol modified interferon therapy

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0122970A1 *

Also Published As

Publication number Publication date
AU1494801A (en) 2001-04-30
JP2003510281A (ja) 2003-03-18
WO2001022970A9 (en) 2002-08-01
WO2001022970A1 (en) 2001-04-05
CA2388025A1 (en) 2001-04-05

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