WO2000021554A1 - Prevention et traitement de la cachexie - Google Patents

Prevention et traitement de la cachexie Download PDF

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Publication number
WO2000021554A1
WO2000021554A1 PCT/JP1999/005570 JP9905570W WO0021554A1 WO 2000021554 A1 WO2000021554 A1 WO 2000021554A1 JP 9905570 W JP9905570 W JP 9905570W WO 0021554 A1 WO0021554 A1 WO 0021554A1
Authority
WO
WIPO (PCT)
Prior art keywords
cachexia
amino acid
ocif
active ingredient
seq
Prior art date
Application number
PCT/JP1999/005570
Other languages
English (en)
Japanese (ja)
Inventor
Kiyoshi Oizumi
Shinichi Kurakata
Original Assignee
Sankyo Company, Limited
Snow Brand Milk Products Co., Ltd.
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 Sankyo Company, Limited, Snow Brand Milk Products Co., Ltd. filed Critical Sankyo Company, Limited
Priority to AU60060/99A priority Critical patent/AU6006099A/en
Publication of WO2000021554A1 publication Critical patent/WO2000021554A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the present invention relates to an agent for preventing or treating cachexia comprising an osteoclast formation inhibitory factor (Ost. Eoclastogenesis Inhibitory Factor; hereinafter, referred to as FOCI Fj) as an active ingredient.
  • an osteoclast formation inhibitory factor Ost. Eoclastogenesis Inhibitory Factor; hereinafter, referred to as FOCI Fj
  • Fluid mainly causes progressive weight loss, anemia, edema, anorexia, etc., which develop in chronic diseases such as malignant tumors, tuberculosis, diabetes, blood diseases, endocrine diseases, infectious diseases and acquired immunodeficiency syndrome. It is a systemic disease that causes symptoms (see J. Parenteral and Enteral Nutrition. Vol. 12, 286-298, (1988): American Journal of Medicine, vol. 85, 289-291. (1988) ).
  • OC.1 F is composed of the amino acid sequences described in Amino Acid Numbers 1 to 380 of SEQ ID NO: 1 and has been found as a protein having an activity of inhibiting osteoclast differentiation or maturation. And bone loss such as osteoporosis, osteoarthritis, multiple myeloma, etc. It is known to be useful as a preventive or therapeutic agent for bone metabolism and dysfunction (WO% / 262 ⁇ 7), however, the protein has a preventive and therapeutic effect on cachexia That isn't true. ' ⁇ ;
  • OCIF or a mutant thereof exerts an excellent preventive or therapeutic effect on cachexia, and completed the present invention.
  • a cachexia comprising, as an active ingredient, an osteoclast formation inhibitory factor (OCIF) comprising an amino acid sequence represented by any one of amino acid numbers 1 to 380 of SEQ ID NO: 1 or a mutant thereof.
  • OCIF osteoclast formation inhibitory factor
  • a preventive or therapeutic agent for cachexia comprising, as an active ingredient, an osteoclast formation inhibitory factor (OCIF) comprising an amino acid sequence represented by amino acid numbers 1 to 380 of SEQ ID NO: 1 in the sequence listing,
  • OCIF osteoclast formation inhibitory factor
  • mutant refers to a protein in which one or more amino acids in the amino acid sequence of OCIF have been substituted, deleted, added or inserted, and the OCIF activity (inhibition of osteoclast formation) is determined. Activity).
  • the OC1 F protein can be produced by the method described in W096 / 26217 ...
  • eukaryotic genes are considered to exhibit polymorphism as is known for interferon genes (eg, Nishi, T. et al. (1985) Biochem. HI, 153- 159), this polymorphism may result in the replacement of one or more amino acids, or the nucleotide sequence may be replaced but the amino acids remain the same.
  • OCIF protein consisting of the amino acid sequences of amino acids 1 to 380 of SEQ ID NO: 1, one or more amino acid residues are substituted or deleted. Lost, added or inserted proteins often also have OCIF activity. In the present invention, these proteins are referred to as OCIF mutants. That is, as long as these naturally occurring or artificially synthesized proteins have OCIF activity, all of those proteins can be used in the present invention.
  • DNA encoding such a protein can be obtained, for example, by the phosphite 'triester method (Nature, ⁇ , 105-111, (1984)! [!
  • the codon for amino acid can be selected arbitrarily, for example, considering the codon usage of ⁇ : 3 ⁇ 4 ⁇ : to be used. (Refer to Nucleic Acid Res. I>, 143-174. (1981).) Further, partial modification of these nucleotide sequence codons can be carried out according to a conventional method. Site-directed mutagenesis / Proc. Natl. Acad. Sci. USA 81, 5662-5666, (] 984) using the primer consisting of the synthetic nucleotide to be used.
  • any -- ⁇ 'or multiple amino acid residues may be deleted.
  • the DNA is trimmed from the end using exonuclease Bal3l (see “Seismological Chemistry Laboratory Lecture 1, Genetic Research Method II”, pages 335-354), cassette mutation (Refer to “Shinogen Chemistry Laboratory Course 2: Nucleic Acid I] I Recombinant DNA Technology”, pp. 242-251.)
  • the codon for the amino acid is known per se, and Selection is optional, and can be determined according to a conventional method, taking into account, for example, the codon usage of the ffj host.
  • the OC [F activity can be measured by the method described in W096 / 26217.
  • the term "cachexia” refers to a progressive weight loss, anemia, which develops in chronic diseases such as malignant tumors, tuberculosis, diabetes, blood diseases, endocrine diseases, infectious diseases and acquired immunodeficiency syndrome. It refers to a systemic disease with edema and anorexia as the main symptoms.
  • OCIF protein represented by amino acid No. 1-No. 3H0 of SEQ ID NO: 1
  • OCIF was 0.0% Tween80 in PBS.
  • Body change ( ⁇ ) body weight on day 12 after cancer transplantation (g) Body weight on day 7 after cancer transplantation
  • Body ® "yl birefringence index (%) Double ( ⁇ Alpha - delta beta) / ( ⁇ c - ⁇ ⁇ ) X 1 0 0
  • Example 1 According to the method described in the above, mouse colon cancer Colon26 cells of about 2 mm square were transplanted under the skin of 10 Balb / c mice (female, 7 weeks old) per group.
  • Life extension activity was evaluated by the survival rate (%) according to the following formula. Life extension (%) ' ⁇ (A /-1) X 1 0 0
  • the cachexia preventive or therapeutic agent containing OC1F of the present invention or a variant thereof as an active ingredient is a water-soluble sterile solution or suspension of adipule dissolved in another pharmacologically acceptable solution. It is also used as a sterile powder formulation (filled in an ampoule with J, preferably a solution of OCIF or a variant thereof, which is preferably dried and dried), and simultaneously diluted with a pharmacologically acceptable solution.
  • the prophylactic or therapeutic agent for serum of the present invention contains OCIF or a mutant thereof as an active ingredient, and can be administered in various forms.
  • the administration form include oral administration by tablets, capsules, granules, powders, and syrups, and parenteral administration by injection, infusion, suppository and the like.
  • the dosage varies depending on symptoms, age, body weight, etc., but in general, for oral administration, it is about 0.1 mg to 1000 mg per day for an adult, and these may be divided into one or several doses. Can be administered. In addition, for parenteral administration, 0.1 mg or 1000 mg can be administered by subcutaneous injection, intramuscular injection or intravenous injection once.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Genetics & Genomics (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention concerne des substances utilisées pour la prévention ou le traitement de la cachexie qui renferment comme principe actif un facteur inhibiteur de l'ostéoclastogenèse ou une variante de ce facteur.
PCT/JP1999/005570 1998-10-09 1999-10-08 Prevention et traitement de la cachexie WO2000021554A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU60060/99A AU6006099A (en) 1998-10-09 1999-10-08 Preventives or remedies for cachexia

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP10/287738 1998-10-09
JP28773898 1998-10-09

Publications (1)

Publication Number Publication Date
WO2000021554A1 true WO2000021554A1 (fr) 2000-04-20

Family

ID=17721126

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1999/005570 WO2000021554A1 (fr) 1998-10-09 1999-10-08 Prevention et traitement de la cachexie

Country Status (2)

Country Link
AU (1) AU6006099A (fr)
WO (1) WO2000021554A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002097033A2 (fr) 2001-05-25 2002-12-05 Human Genome Sciences, Inc. Anticorps se liant de maniere immunospecifique a des recepteurs de trail
US7749960B2 (en) 2001-04-03 2010-07-06 Nestec S.A. Osteoprotegerin in milk
US8703725B2 (en) 2002-09-20 2014-04-22 Nestec S.A. Nutritional compositions

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0816380A1 (fr) * 1995-02-20 1998-01-07 Snow Brand Milk Products Co., Ltd. Proteine nouvelle et ses procedes de production
WO1998012344A1 (fr) * 1996-09-18 1998-03-26 Human Genome Sciences, Inc. Genes de type recepteurs du facteur de necrose tumorale humain

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0816380A1 (fr) * 1995-02-20 1998-01-07 Snow Brand Milk Products Co., Ltd. Proteine nouvelle et ses procedes de production
WO1998012344A1 (fr) * 1996-09-18 1998-03-26 Human Genome Sciences, Inc. Genes de type recepteurs du facteur de necrose tumorale humain

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
YASUDA H. ET AL.: "Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis", ENDOCRINOLOGY, vol. 139, no. 3, March 1998 (1998-03-01), pages 1329 - 1337 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7749960B2 (en) 2001-04-03 2010-07-06 Nestec S.A. Osteoprotegerin in milk
WO2002097033A2 (fr) 2001-05-25 2002-12-05 Human Genome Sciences, Inc. Anticorps se liant de maniere immunospecifique a des recepteurs de trail
US8703725B2 (en) 2002-09-20 2014-04-22 Nestec S.A. Nutritional compositions

Also Published As

Publication number Publication date
AU6006099A (en) 2000-05-01

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