CA2407046A1 - Immunoregulator - Google Patents

Immunoregulator Download PDF

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Publication number
CA2407046A1
CA2407046A1 CA002407046A CA2407046A CA2407046A1 CA 2407046 A1 CA2407046 A1 CA 2407046A1 CA 002407046 A CA002407046 A CA 002407046A CA 2407046 A CA2407046 A CA 2407046A CA 2407046 A1 CA2407046 A1 CA 2407046A1
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CA
Canada
Prior art keywords
immunoregulator
immune
disorder
peptide
mediated disorder
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Granted
Application number
CA002407046A
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French (fr)
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CA2407046C (en
Inventor
Nisar Ahmed Khan
Robbert Benner
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Biotempt BV
Original Assignee
Erasmus Universiteit Rotterdam
Nisar Ahmed Khan
Robbert Benner
Biotempt B.V.
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Publication of CA2407046A1 publication Critical patent/CA2407046A1/en
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    • 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
    • C07K14/575—Hormones
    • C07K14/59—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
    • 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
    • A61K38/22—Hormones
    • A61K38/24—Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/06—Antiabortive agents; Labour repressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • 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
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

The invention relates to the field of immunology, more specifically to the field of immune-mediated disorders such as allergies, auto-immune disease, transplantation-related disease or inflammatory disease. The invention provides among others an immunoregulator (NMPF), use of an NMPF in preparing a pharmaceutical composition for treating an immune-mediated disorder, a pharmaceutical composition and a method for treating an immune-mediated disorder.

Claims (44)

Claims
1. An immunoregulator obtainable or derivable from beta-HCG capable of regulating Th1 and/or Th2 cell activity.
2. An immunoregulator according to claim 1 capable of modulating dendritic cell differentiation.
3. An immunoregulator according to claim 1 capable of protecting a mouse against a lipopolysaccharide induced septic shock.
4. An immunoregulator according to claim 1 to 3 obtainable from nicked beta-hCG or beta-core hCG.
5. An immunoregulator according to anyone of claims 1 to 4 which comprises a peptide having an amino acid sequence MTRVLQGVLPALPQVVC or functional fragment or functional analogue thereof.
6. An immunoregulator according to claim 5 wherein said functional fragment comprises an amino acid sequence LQGVLPALPQVVC or functional analogue thereof.
7. An immunoregulator according to 6 wherein said functional fragment comprises an amino acid sequence VLPALPQVVC or LQGVLPALPQ or functional analogue thereof.
8. An immunoregulator according to claim 7 wherein said functional fragment comprises an amino acid sequence VLPALPQ or GVLPALPQ or GVLPALP or VLPALP or QVVC or PALP
or LQGV or MTRV or VVC or MTR or LQG or functional analogue thereof.
9. An immunoregluator according to any of the preceding claims wherein one or more amino acids have been replaced by an alanine residue.
10. An immunoregulator according to claims 8 or 9 capable of protecting a mouse against a lipopoly-saccharide induced septic shock or diabetes or Experimental Auto-immune Encephalitis/multiple sclerosis.
21. Use of an immunoregulator according to anyone of claims 1-10 for the production of a pharmaceutical composition for the treatment of an immune-mediated-disorder.
12. Use according to claim 11 wherein said immune-mediated disorder comprises chronic inflammation, such as diabetes, multiple sclerosis or acute or chronic a transplant rejection.
13. Use according to claim 11 wherein said immune-mediated disorder comprises acute inflammation, such as septic or anaphylactic shock or hyper-acute transplant rejection.
14. Use according to claim 11 wherein said immune-mediated disorder comprises auto-immune disease, such as systemic lupus erythematosus or rheumatoid arthritis.
15. Use according to claim 11 wherein said immune-mediated disorder comprises allergy, such as asthma or parasitic disease.
16. Use according to claim 11 wherein said immune-mediated disorder comprises an overly strong immune response directed against an infectious agent, such as a virus or bacterium.
17. Use according to claim 11 wherein said immune-mediated disorder comprises pre-eclampsia or another pregnancy related immune-mediated disorder.
18. Use according to claim 12 to 17 wherein said treatment comprises regulating relative ratios and/or cytokine activity of lymphocyte, dendritic or antigen presenting cell subset-populations in a treated individual.
19. Use according to claim 18 wherein said subset populations comprise Th1 or Th2, or DC1 or DC2 cells.
20. Use according to anyone of claims 12 to 19 wherein said immunoregulator comprises a hCG preparation or a fraction derived thereof.
21. A pharmaceutical composition for treating an immune-mediated disorder comprising an immunoregulator according to anyone of claims 1 to 10.
22. A pharmaceutical composition for treating an immune-mediated disorder comprising an active component obtainable from a urinary metabolite of HCG capable of protecting a mouse against a lipopolysaccharide induced septic shock or diabetes or Experimental Auto-immune Encephalitis/multiple sclerosis.
23. A method for treating an immune-mediated-disorder comprising subjecting an animal to treatment with at least one immunoregulator according to any one of claims 1 to 10.
24. A method according to claim 23 wherein said disorder comprises diabetes.
25. A method according to claim 23 wherein said disorder comprises sepsis.
26. A method according to any one of claims 24 or 25 further comprising regulating relative ratios and/or cytokine activity of lymphocyte, dendritic or antigen presenting cell subset-populations in said animal.
27. A method according to claim 26 wherein said subset-populations comprise Th1 or Th2, or DC1 or DC2 cells.
28. A method according to any one of the claims 23-27, wherein the immunoregulator is used in combination with a targeting agent, such as a monoclonal antibody, for controlled and/or localized delivery.
29. Use of an immunoregulator according to any of the claims 1-10 for the manufacture of a medicament for modulating a cardiovascular or circulatory disorder, in particular a pregnancy related cardiovascular or circulatory disorder.
30. A pharmaceutical composition for modulating a cardiovascular or circulatory disorder, in particular a pregnancy related cardiovascular or circulatory disorder, comprising an immunoregulator according to any of the claims 1-10.
31. A method for modulating a cardiovascular or circulatory disorder, in particular a pregnancy related cardiovascular or circulatory disorder, comprising subjecting an animal to treatment with at least one immunoregulator according to any of the claims 1-10.
32. A method for diagnosing a pregnancy related immune-mediated disorder, such as pre-eclampsia, or other immune-mediated disorder comprising determining in a sample, preferably a urine or blood sample, the relative ratio of a relative long-chain peptide versus a relative short-chain peptide, said peptides derivable from breakdown of beta-HCG.
33. A method according to claim 32 comprising determining the relative ratio of a relative long-chain peptide versus a relative short-chain peptide derived from breakdown a peptide having an amino acid sequence MTRVLQGVLPALPQVVC.
34. A method according to claim 33 wherein said relative long-chain peptide comprises an amino acid sequence LQGVLPALPQ or GVLPALPQ or VLPALPQ or GVLPALP or VLPALP.
35. A method according to claim 32 or 33 wherein said relative short-chain peptide comprises MTRV or MTR or PALP or QWC or VVC, or LQGV or LQG.
36. A method for diagnosing a pregnancy related immune-mediated disorder, such as pre-eclampsia, or other immune-mediated disorder comprising determining in a sample, preferably a urine or blood sample, the relative ratio of a septic shock enhancing peptide versus a septic shock decreasing peptide, said peptides being derivable from breakdown of beta-HCG.
37. A method for diagnosing a pregnancy related immune-mediated disorder, such as pre-eclampsia, or other immune-mediated disorder comprising determining in a sample, preferably a urine or blood sample, the relative ratio of a diabetes enhancing peptide versus a diabetes decreasing peptide, said peptides being derivable from breakdown of beta-HCG.
38. A method for diagnosing a cardiovascular disorder comprising determining in a sample, preferably a urine or blood sample, the relative ratio of a heart failure enhancing peptide versus a heart failure decreasing peptide, said peptides being derivable from breakdown of beta-HCG.
39. A method for selecting an immunoregulator comprising determining therapeutic effect of an immunoregulator by subjecting an animal prone to show signs of diabetes to a peptide composition or fraction thereof, and determining the development of diabetes in said animal.
40. A method for selecting an immunoregulator comprising determining therapeutic effect of an immunoregulator by subjecting an animal prone to show signs of septic shock to a peptide composition or fraction thereof and determining the development of septic shock in said animal.
41. A method according to claim 39 or 40 wherein said therapeutic effect is further measured by determining relative ratios and/or cytokine activity of lymphocyte, dendritic or antigen presenting cell subset-populations in said animal.
42. A method according to claim 41 wherein said therapeutic effect is further measured by determining enzyme levels in said animal.
43. An immunoregulator selected by a method according to anyone of claims 39 to 42.
44. A pharmaceutical composition comprising an immunoregulator according to claim 43.
CA2407046A 2000-03-29 2001-03-29 Immunoregulator Expired - Lifetime CA2407046C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP00201139.3 2000-03-29
EP00201139A EP1138692A1 (en) 2000-03-29 2000-03-29 Fragments of human chorionic gonadotropin (hcg) as immunoregulator
PCT/NL2001/000259 WO2001072831A2 (en) 2000-03-29 2001-03-29 Immunoregulator

Publications (2)

Publication Number Publication Date
CA2407046A1 true CA2407046A1 (en) 2001-10-04
CA2407046C CA2407046C (en) 2011-02-15

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CA2407046A Expired - Lifetime CA2407046C (en) 2000-03-29 2001-03-29 Immunoregulator

Country Status (18)

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US (2) US7365155B2 (en)
EP (3) EP1138692A1 (en)
JP (1) JP5172064B2 (en)
KR (1) KR100800876B1 (en)
AT (2) ATE411340T1 (en)
AU (1) AU781632B2 (en)
CA (1) CA2407046C (en)
CY (2) CY1108706T1 (en)
DE (2) DE60136577D1 (en)
DK (2) DK1272515T3 (en)
ES (2) ES2315278T3 (en)
HK (1) HK1052360B (en)
IL (2) IL151945A0 (en)
NZ (1) NZ521703A (en)
PT (2) PT1887016E (en)
SG (1) SG127739A1 (en)
SI (2) SI1272515T1 (en)
WO (1) WO2001072831A2 (en)

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