EP1353622A2 - Procede pour ameliorer l'exposition systemique de proteines therapeutiques administrees par voie sous-cutanee - Google Patents

Procede pour ameliorer l'exposition systemique de proteines therapeutiques administrees par voie sous-cutanee

Info

Publication number
EP1353622A2
EP1353622A2 EP01273890A EP01273890A EP1353622A2 EP 1353622 A2 EP1353622 A2 EP 1353622A2 EP 01273890 A EP01273890 A EP 01273890A EP 01273890 A EP01273890 A EP 01273890A EP 1353622 A2 EP1353622 A2 EP 1353622A2
Authority
EP
European Patent Office
Prior art keywords
therapeutic protein
systemic exposure
administration
systemic
day
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Withdrawn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
EP01273890A
Other languages
German (de)
English (en)
Other versions
EP1353622A4 (fr
Inventor
Charles B. Davis
Amarnath Sharma
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.)
SmithKline Beecham Corp
Original Assignee
SmithKline Beecham Corp
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 SmithKline Beecham Corp filed Critical SmithKline Beecham Corp
Publication of EP1353622A2 publication Critical patent/EP1353622A2/fr
Publication of EP1353622A4 publication Critical patent/EP1353622A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K38/20—Interleukins [IL]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • a therapeutic delivered iv takes longer to administer when compared to sc administration, and as a result is a more costly therapy.
  • sc administration is not without drawbacks. For example, there are physical limitations on the maximum dose which can be delivered at the injection site.
  • the systemic exposure of, e.g., an anti-RSN monoclonal antibody administered sc is comparable to that administered iv and the bioavailability is not affected by the amount of the therapeutic protein administered (see, e.g., Davis et al., Drug Met. Disp., 23:1028-1036 (1995)).
  • the extent of absorption i.e., systemic exposure
  • the amount of the therapeutic protein that enters the blood stream see e.g., Davis and Bugelski, Drug Delivery, 5: 95-100 (1998).
  • systemic diseases such as cancer
  • the present invention relates generally to the field of therapeutic proteins, and dosing regimens that enhance systemic exposure and thus pharmacologic effectiveness of therapy.
  • the present invention provides an improved method for treating diseases by increasing the systemic response to a therapeutic protein which binds to specific receptors and/or endogenous proteins present in the lymphatic system. More specifically, the present invention provides an improved method for treating diseases by increasing the systemic exposure to interleukin-18 (IL-18) which binds to specific receptors and/or endogenous proteins present in the lymphatic system.
  • IL-18 interleukin-18
  • Fig 1 - Figure 1 is a graph showing mean plasma IL-18 concentration versus time profiles following an intravenous dose (0.1, 1 or 10 mg/kg) to Cynomolgus monkeys.
  • Fig 2(a) - Figure 2a is a graph showing mean plasma IL-18 concentrations versus time profiles following single and repeat intravenous administration (10 mg kg/day for 5 days).
  • Fig 2(b) - Figure 2b is a graph showing mean plasma IL-18 concentrations versus time profiles following single and repeat intravenous administration (30 mg/kg/day for 5 days).
  • Fig 2(c) - Figure 2c is a graph showing mean plasma D -18 concentrations versus time profiles following single and repeat intravenous administration (75 mg/kg/day for 5 days).
  • Fig 3(a) - Figure 3a is a graph showing mean plasma IL-18 concentration versus time profiles following single and repeat subcutaneous administration (10 mg/kg/day for 4 days).
  • Fig 3(b) - Figure 3b is a graph showing mean plasma IL-18 concentration versus time profiles following single and repeat intravenous administration (10 mg/kg/day for 5 days).
  • Fig 4 - Figure 4 is a graph showing mean (SD) bioavailability of IL-18 following single and repeat subcutaneous administration.
  • IL-18 therapeutic proteins
  • systemic exposure to a therapeutic protein, such as IL-18 is increased more than expected based on the single subcutaneous dose pharmacokinetic profile and more than expected based on the single and multiple intravenous dose pharmacokinetic profile and allows for the improved treatment of systemic diseases, such as cancer, bacterial infections, viral infections, fungal infections and parasitic infections.
  • a saturating subcutaneous dose (or doses) of a therapeutic protein such as IL-18
  • subsequent administrations also given subcutaneously, result in at least 50% greater systemic exposure than an equivalent subcutaneous dose administered without the benefit of the saturating dose or doses.
  • the systemic exposure of such therapeutic protein is increased by at least 2-fold, more preferably it is increased by at least 4-fold.
  • the relative systemic exposure of a single sc dose compared to a single iv dose, i.e., the apparent absolute bioavailability is approximately 15% in Cynomolgus monkeys (compare Tables 1 and 2, day 1 AUC 0 . 2 , 10 mg/kg).
  • Figure 1 shows mean plasma IL-18 concentration versus time profiles following a single intravenous dose (0.1, 1 or 10 mg/kg) to monkeys.
  • Plasma concentrations declined in a bi-phasic manner after intravenous administration with a steep initial phase characterized by a half-life of ⁇ 5 min.
  • the terminal disposition phase had a long half-life of -24 h but the concentrations during this phase were low.
  • Due to a relatively rapid clearance from blood following iv administration iv administered IL-18 does not accumulate with multiple dosing, and when IL-18 is administered daily, the systemic exposure over 24 h (AUC 0-2 ) is approximately the same from day to day (Table 1, day 1 vs day 5 AUC 0-2 ).
  • Figures 2a- 2c show mean plasma IL-18 concentraton versus time profiles following single and repeat intravenous administration (10-75 mg/kg).
  • the daily systemic exposure increased in a dose proportional manner between doses of 10 and 75 mg/kg following single and repeat iv dosing, indicating linear pharmacokinetics of IL-l ⁇ " (see also Table 1).
  • FIGS. 3a and 3b show the mean plasma EL- 18 concentration versus time profiles following single and repeat subcutaneous or intravenous administration (10 mg kg dose). After subcutaneous administration, the maximum plasma concentrations were observed at ⁇ 0.5 hours indicating that IL-18 is rapidly absorbed from the sc injection site.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention se rapporte à un procédé servant à améliorer l'exposition systémique de protéines thérapeutiques administrées par voie sous-cutanée.
EP01273890A 2000-11-03 2001-11-01 Procede pour ameliorer l'exposition systemique de proteines therapeutiques administrees par voie sous-cutanee Withdrawn EP1353622A4 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US24561800P 2000-11-03 2000-11-03
US245618P 2000-11-03
PCT/US2001/051617 WO2002083063A2 (fr) 2000-11-03 2001-11-01 Procede pour ameliorer l'exposition systemique de proteines therapeutiques administrees par voie sous-cutanee

Publications (2)

Publication Number Publication Date
EP1353622A2 true EP1353622A2 (fr) 2003-10-22
EP1353622A4 EP1353622A4 (fr) 2005-06-22

Family

ID=22927410

Family Applications (1)

Application Number Title Priority Date Filing Date
EP01273890A Withdrawn EP1353622A4 (fr) 2000-11-03 2001-11-01 Procede pour ameliorer l'exposition systemique de proteines therapeutiques administrees par voie sous-cutanee

Country Status (4)

Country Link
EP (1) EP1353622A4 (fr)
JP (1) JP2004532843A (fr)
AU (1) AU2001297793A1 (fr)
WO (1) WO2002083063A2 (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010503680A (ja) * 2006-09-14 2010-02-04 ザ・トラステイーズ・オブ・ザ・ユニバーシテイ・オブ・ペンシルベニア ヒトｉｌ−１８による調節ｔ細胞のモジュレーション

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1013763A1 (fr) * 1997-08-07 2000-06-28 Toray Industries, Inc. INTERLEUKINE 18 CANINE, INTERLEUKINE-1 $g(b)-CONVERTASE CANINE, SEQUENCES D'ADN CODANT CETTE ENZYME, PROCEDE DE PRODUCTION DE L'INTERLEUKINE 18, ET REMEDES CONTRE LES MALADIES IMMUNOLOGIQUES CHEZ LE CHIEN

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4847325A (en) * 1988-01-20 1989-07-11 Cetus Corporation Conjugation of polymer to colony stimulating factor-1
US5993527A (en) * 1994-11-17 1999-11-30 Canon Kabushiki Kaisha Ink-jet color recording process and ink set therefor

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1013763A1 (fr) * 1997-08-07 2000-06-28 Toray Industries, Inc. INTERLEUKINE 18 CANINE, INTERLEUKINE-1 $g(b)-CONVERTASE CANINE, SEQUENCES D'ADN CODANT CETTE ENZYME, PROCEDE DE PRODUCTION DE L'INTERLEUKINE 18, ET REMEDES CONTRE LES MALADIES IMMUNOLOGIQUES CHEZ LE CHIEN

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
HERZYK, D. J. ÄREPRINT AUTHORÜ ET AL: "Activity of human interleukin - 18 in cynomolgus monkey." FASEB JOURNAL, (APRIL 20, 2000) VOL. 14, NO. 6, PP. A1181. PRINT. MEETING INFO.: JOINT ANNUAL MEETING OF THE AMERICAN ASSOCIATION OF IMMUNOLOGISTS AND THE CLINICAL IMMUNOLOGY SOCIETY. SEATTLE, WASHINGTON, USA. MAY 12-16, 2000. CODEN: FAJOEC. ISSN: 08, April 2000 (2000-04), XP008046234 *
See also references of WO02083063A2 *

Also Published As

Publication number Publication date
WO2002083063A3 (fr) 2003-08-28
JP2004532843A (ja) 2004-10-28
EP1353622A4 (fr) 2005-06-22
AU2001297793A1 (en) 2002-10-28
WO2002083063A2 (fr) 2002-10-24

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