Title of Invention

AN IMMUNOREGULATOR PEPTIDE

Abstract This invention relates to an immunoregulator peptide obtainable or derivable from beta-HCG and is capable of regulating Thl and/or Thl cell activity, said peptide having the amino acid sequence VLP ALP or having 3-5 amino acids comprising the amino acid sequence QVVC or CLQG or P ALP or LQGV or MTRV or VVC or MTR or LQG.
Full Text WE CLAIM :
1. A sterilization method comprising :
a step of ionizing water vapor molecules present in a first atmosphere into negative and positive ions to generate O2'(H2O)n (where n is a natural number) as negative ions and H+(H2O)ni (where m is a natural number) as positive ions,
a step of carrying the ions from the first atmosphere to a second atmosphere located away from the first atmosphere,
a step of attaching the ions to germs floating in the second atmosphere, and
a step of killing the germs floating in the second atmosphere through an oxidization reaction by hydrogen peroxide H2O2 or radical hydroxyl OH generated as an active species through a chemical reaction between the negative and positive ions.
2. The sterilization method as claimed in claim 1 wherein concentrations of the negative and positive ions are both 10,000 ions/cc or higher at a distance of 10 cm from a point at which the ions are generated.
3. An ion generating device for generating O2'(H2O)n (where n is a natural number) as negative ions and H+(H2O)m (where mis a natural number) as positive ions in such a way that concentrations of the negative and positive ions are both 10,000 ions/cc or higher at a distance of 10 cm from a point at which the ions are generated, the ion generating device comprising a dielectric, a first electrode, and a second electrode, the first and second electrodes being arranged so as to face each other with the dielectric disposed in between, and the ion generating device generating the ions by applying an altemating-current voltage of 2.0 kV rms or lower between the first and second electrodes.

4. An ion generating apparatus comprising an ion generating device as claimed in claim 3 comprising:
a high alternating-current voltage source for feeding the ion generating device with the alternating-current voltage with which the ion generating device generates the negative and positive ions; and
a blower for producing a forced flow of the negative and positive ions generated by the ion generating device.
Dated this 21 day Of October 2002



Claims
1 „ An immunoregulator obtainable or derivable from beta-HCG capable of regulating Thl 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 MTRVLQGVLPALPQWC or functional fragment or functional analogue thereof.
6. An immunoregulator according to claim 5 wherein said functional fragment comprises an amino acid sequence LQGVLPALPQWC or functional analogue thereof.
7. An immunoregulator according to 6 wherein said functional fragment comprises an amino acid sequence VLPALPQWC 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 QWC or PALP or LQGV or MTRV or WC 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.
11. 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 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 ah 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 Thl 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 Thl 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 circul'atory 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 MTRVLQGVLPALPQWC.
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 WC, 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.

45. An immunoregulator substantially as herein described with reference to the accompanying drawings.
46. A pharmaceutical composition substantially as herein described with reference to the accompanying drawings.


Documents:

in-pct-2002-1756-che-abstract.pdf

in-pct-2002-1756-che-assignment.pdf

in-pct-2002-1756-che-claims duplicate.pdf

in-pct-2002-1756-che-claims original.pdf

in-pct-2002-1756-che-correspondance others.pdf

in-pct-2002-1756-che-correspondance po.pdf

in-pct-2002-1756-che-description complete duplicate.pdf

in-pct-2002-1756-che-description complete original.pdf

in-pct-2002-1756-che-drawings.pdf

in-pct-2002-1756-che-form 1.pdf

in-pct-2002-1756-che-form 18.pdf

in-pct-2002-1756-che-form 26.pdf

in-pct-2002-1756-che-form 3.pdf

in-pct-2002-1756-che-form 5.pdf

in-pct-2002-1756-che-pct.pdf


Patent Number 206931
Indian Patent Application Number IN/PCT/2002/1756/CHE
PG Journal Number 26/2007
Publication Date 29-Jun-2007
Grant Date 16-May-2007
Date of Filing 24-Oct-2002
Name of Patentee BIOTEMPT B V
Applicant Address HOGE LINTHORST 1, 7958 NZ KOEKANGE
Inventors:
# Inventor's Name Inventor's Address
1 KHAN, Nisar, Ahmed Groene Hilledijk 256-a2 NL-3074 AD Rotterdam
2 BENNER, Robbert Middeldijk 25 NL-2992 SH Barendrecht
PCT International Classification Number C07K14/59
PCT International Application Number PCT/NL2001/000259
PCT International Filing date 2001-03-29
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 00201139.3 2000-03-29 EUROPEAN UNION