WO2001087331A1 - Produits pharmaceutiques destines a la suppression de troubles auto-immuns au moyen de fragments liant les idiotypes des anticorps anti-idiotypiques - Google Patents

Produits pharmaceutiques destines a la suppression de troubles auto-immuns au moyen de fragments liant les idiotypes des anticorps anti-idiotypiques Download PDF

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Publication number
WO2001087331A1
WO2001087331A1 PCT/RU2001/000033 RU0100033W WO0187331A1 WO 2001087331 A1 WO2001087331 A1 WO 2001087331A1 RU 0100033 W RU0100033 W RU 0100033W WO 0187331 A1 WO0187331 A1 WO 0187331A1
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WIPO (PCT)
Prior art keywords
antibodies
insulin
anτiτel
κορρeκtsii
φρagmenτy
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PCT/RU2001/000033
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English (en)
Russian (ru)
Inventor
Sergey Georgievich Morozov
Aleksandr Borisovich Poletaev
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Priority claimed from RU2000112366/14A external-priority patent/RU2000112366A/ru
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Priority to AU32504/01A priority Critical patent/AU3250401A/en
Publication of WO2001087331A1 publication Critical patent/WO2001087331A1/fr
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Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/42—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins
    • C07K16/4208—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig
    • C07K16/4241—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against immunoglobulins against an idiotypic determinant on Ig against anti-human or anti-animal Ig
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies

Definitions

  • a new variant of introducing antigen into the body of the patient is to achieve specific therapeutic care, i.e.
  • the pressure of the autoimmune process is the use of the corresponding antigens in the form of applications on the mucous membrane of the nose or sprayed aerosols of the antigen. It is important that, with such alternative (not original) methods of introducing antigens into the body, to achieve the desired effect is minimized (minimally)
  • IP-fragments have a low species-specificity, which is used to administer the patient for medical purposes, for example, horse-shaped murine or murine murine anus.
  • ISDM-1 insulin-dependent diabetes mellitus type 1
  • ISD-2 non-insulin-dependent diabetes mellitus type 2
  • P ⁇ i death b ⁇ lee 70% be ⁇ a- ⁇ le ⁇ in ⁇ ganizme nachina- e ⁇ ⁇ schuscha ⁇ sya vy ⁇ azhennaya ne ⁇ va ⁇ a s ⁇ bs ⁇ venn ⁇ g ⁇ insulin s ⁇ all vy ⁇ e- ⁇ ayuschimi ⁇ sleds ⁇ viyami (gi ⁇ e ⁇ gli ⁇ emiya, glyu ⁇ zu ⁇ iya, ⁇ e ⁇ atsid ⁇ z, gene ⁇ ali- z ⁇ vannye na ⁇ usheniya uglev ⁇ dn ⁇ g ⁇ , li ⁇ idn ⁇ g ⁇ , and ene ⁇ ge ⁇ iches ⁇ g ⁇ bel ⁇ v ⁇ g ⁇ ⁇ bmen ⁇ v) and nablyudae ⁇ sya ⁇ liniches ⁇ aya mani ⁇ es ⁇ atsiya IZSD- 1.
  • ISD-2 insulin-producing cells in the initial stages of illness do not suffer from illness.
  • ⁇ a ⁇ iv, and ⁇ du ⁇ tsiya se ⁇ etsiya insulin ⁇ bychn ⁇ ⁇ vyshayu ⁇ sya, ⁇ dna ⁇ nesm ⁇ ya on e ⁇ , and ⁇ a ⁇ ⁇ i IDDM-1, y b ⁇ lny ⁇ ⁇ mechae ⁇ sya ⁇ ez ⁇ vy ⁇ azhennaya gi ⁇ e ⁇ gli ⁇ emiya, glyu ⁇ zu ⁇ iya, ⁇ e ⁇ atsid ⁇ z, gene ⁇ a- liz ⁇ vannye na ⁇ usheniya uglev ⁇ dn ⁇ g ⁇ , li ⁇ idn ⁇ g ⁇ , and ene ⁇ ge ⁇ iches ⁇ g ⁇ bel ⁇ v ⁇ g ⁇ ⁇ bmen ⁇ v.
  • ISDM-1 The difference between ISDM-1 and the phenomenon of ISDM-2 is not associated with a lack of insulin, but with the development of insulin insensitivity to the patient (a patient) ⁇ A small proportion of cases (less than 10%) in the basis of such insulin resistance are due to the born, genetically caused, functional failure of the insulin rate.
  • Diabetic disease DF
  • DF Diabetic disease
  • ⁇ a ⁇ dinalnym s ⁇ s ⁇ b ⁇ m ⁇ esheniya ⁇ blemy treatment mn ⁇ gi ⁇ (v ⁇ zm ⁇ zhn ⁇ b ⁇ lshins ⁇ va) b ⁇ lny ⁇ , s ⁇ adayuschi ⁇ insulin and by direct insulinnezavisi- sa ⁇ a ⁇ nym diabe ⁇ m (IDDM I ⁇ SD-1 and-2), ⁇ busl ⁇ vlennym au ⁇ immunn ⁇ y ag ⁇ essiey, ⁇ asseyannym s ⁇ le ⁇ z ⁇ m, bes ⁇ l ⁇ diem, ⁇ busl ⁇ vlennym vys ⁇ im u ⁇ v- an ⁇ is ⁇ e ⁇ malny ⁇ an ⁇ i ⁇ el therein, and a ⁇ a ⁇ zhe ⁇ a ⁇ same mn ⁇ gi ⁇ d ⁇ ugi ⁇ zab ⁇ levany, m ⁇ zhe ⁇ by ⁇ s ⁇ s ⁇ b s ⁇ y ⁇ g ⁇ and
  • P ⁇ i insulinzavisim ⁇ m sa ⁇ a ⁇ n ⁇ m diabe ⁇ e is ⁇ lzuyu ⁇ na ⁇ iv- ny insulin or eg ⁇ immun ⁇ imiches ⁇ ie anal ⁇ gi, na ⁇ ime ⁇ , immun ⁇ a ⁇ inn ⁇ ⁇ chischennye ⁇ a- ⁇ a or 2 - ⁇ agmen ⁇ y an ⁇ idi ⁇ i ⁇ iches ⁇ i ⁇ an ⁇ i ⁇ el (or themselves an ⁇ i ⁇ ela) ⁇ i insulinnezavisim ⁇ m sa ⁇ a ⁇ n ⁇ m diabe ⁇ e - insulin ⁇ vye ⁇ etse ⁇ - ⁇ y or immun ⁇ imiches ⁇ ie anal ⁇ gi and ⁇ ,
  • immunocompletely cleansed carbohydrates or 2- antigens and anti-insulin antibodies (or antibodies themselves) in the amount of 0.01 - 0.5 mg are not feasible.
  • Antidiostatic IP-fragments which are structural analogues of insulin n ⁇ m diabe ⁇ m) bel ⁇ a ⁇ B ⁇ ( ⁇ i ⁇ e ⁇ tsii s ⁇ s ⁇ yaniya b ⁇ lny ⁇ ⁇ asseyannym s ⁇ le ⁇ z ⁇ m) memb ⁇ ann ⁇ g ⁇ bel ⁇ a-an ⁇ igena s ⁇ e ⁇ ma ⁇ z ⁇ id ⁇ v ( ⁇ i ⁇ e ⁇ tsii s ⁇ s ⁇ yaniya b ⁇ lny ⁇ , s ⁇ adayuschi ⁇ bes ⁇ l ⁇ diem, ⁇ busl ⁇ vlennym an ⁇ is ⁇ e ⁇ malnym au ⁇ immunnym ⁇ tsess ⁇ m) s ⁇ u ⁇ u ⁇ nye an ⁇ iidi ⁇ i ⁇ iches ⁇ ie anal ⁇ gi iny ⁇ an ⁇ igen ⁇ v target, ⁇ azhaemy ⁇ ⁇ i iny ⁇ au ⁇ immunny ⁇ zab ⁇
  • the technique for applying to mucous membranes of the nose is as follows: - 0.1 ml of water or salt and salt (with or without 50% glycerol) excrets a mild daily discharge of 0 mg. the application is issued on a private tampon (for example, with important tambourines on wooden fingers of the “Jones and Jones” company) one day a day; A fully-knit tampon is placed in the room for 5 minutes one time per day.
  • the products can be used in the form of rectal or vaginal discharges for daily use for 2-4 months.
  • ISDM-1 insulin-dependent diabetes mellitus type 1
  • the following drugs are used (for example or as a combination):
  • the human insulin is optimized, for example, by glutaraldehyde (disruption or suppression). • Other immunological analogs of insulin.
  • the products can be used in the form of regular or vaginal discharges in the same dose for daily use for 2 to 4 months.
  • ⁇ chas ⁇ n ⁇ s ⁇ i and ⁇ a- ⁇ a 2 - ⁇ agmen ⁇ y an ⁇ iidi ⁇ i ⁇ iches ⁇ i ⁇ an ⁇ i ⁇ el, yav--governing s ⁇ u ⁇ u ⁇ nymi anal ⁇ gami insulin ⁇ luchayu ⁇ on ⁇ l ⁇ n ⁇ a ⁇ with imm ⁇ - biliz ⁇ vannym on ine ⁇ n ⁇ m n ⁇ si ⁇ ele ⁇ e ⁇ a ⁇ a ⁇ m insulin ⁇ m chel ⁇ ve ⁇ a, na ⁇ i- me ⁇ on ⁇ l ⁇ n ⁇ a ⁇ insulin se ⁇ a ⁇ zy, ⁇ v ⁇ dya ⁇ selection an ⁇ iinsulin ⁇ vy ⁇ an ⁇ i ⁇ el ( ⁇ -1-Ins), using in the quality of the initial raw materials the raw raw materials of patients, the sick ISDM-1.
  • the cleaned preparations of Kap or Kap 2 -fragments of the K-1-Ins molecule are used to immunize general publics.
  • ⁇ as ⁇ lagayuschimisya is ⁇ edel ⁇ v an ⁇ igensvyazyvayuschi ⁇ say ⁇ v ⁇ -1-Ins, ⁇ - v ⁇ dya ⁇ d ⁇ chis ⁇ u ⁇ I ⁇ -2-Ins, ⁇ us ⁇ aya i ⁇ che ⁇ ez imm ⁇ biliz ⁇ vannye on ine ⁇ n ⁇ m n ⁇ si ⁇ ele ⁇ e ⁇ a ⁇ a ⁇ y "neimmunny ⁇ " immun ⁇ gl ⁇ bulin ⁇ v.
  • D ⁇ ya s ⁇ etsi ⁇ iches ⁇ g ⁇ ⁇ davleniya ⁇ a ⁇ l ⁇ giches ⁇ i ⁇ au ⁇ immunny ⁇ ⁇ - tsess ⁇ v with na ⁇ avlenn ⁇ s ⁇ yu ⁇ ⁇ ani ⁇ dzhelud ⁇ chn ⁇ y gland is ⁇ lzuyu ⁇ ⁇ a ⁇ zhe ⁇ as ⁇ v ⁇ y ⁇ mme ⁇ ches ⁇ i ⁇ ⁇ e ⁇ a ⁇ a ⁇ v insulin lib ⁇ ⁇ e ⁇ a ⁇ a ⁇ y ⁇ lime ⁇ iz ⁇ - vann ⁇ g ⁇ (na ⁇ ime ⁇ , glu ⁇ a ⁇ vym aldegid ⁇ m) insulin.
  • na ⁇ ime ⁇ on ⁇ l ⁇ n ⁇ a ⁇ insulin se ⁇ a ⁇ zy ⁇ v ⁇ dya ⁇ vyde- Leniye an ⁇ iinsulin ⁇ vy ⁇ an ⁇ i ⁇ el ( ⁇ -1-Ins) is ⁇ lzuya in ⁇ aches ⁇ ve is ⁇ dn ⁇ g ⁇ sy ⁇ ya ⁇ uli ⁇ vannuyu syv ⁇ u ⁇ vi ⁇ atsien ⁇ v, b ⁇ lny ⁇ -1 IDDM, lib ⁇ sy- v ⁇ i zhiv ⁇ ny ⁇ (na ⁇ ime ⁇ , ⁇ li ⁇ v, immunizi ⁇ vanny ⁇ insulin ⁇ m).
  • Received preparations are used for specific suppression of palyologicheskih autoimmune processes.
  • Desensitizing therapy was performed in the form of applications for a mucous nose of a drug for naive insulin. After 2 weeks, complaints of irritation of the mucous membranes (dryness, itching, nausea) appeared. The drug was replaced by the structural insulin analogs - antibiotic antigens (daily 0.1 mg for 15 weeks). Complaints were pending.
  • Desensitizing therapy was performed in the form of applications for a mucous nose of preparations of 2 types of antibodies - an analogous period of very little more than 0.1 weekly (daily).
  • the duration of the disease is 6 years.
  • the patient After the completion of the immunoassection, the level of antibodies to the ani- mous membrane antigens of the sperm, the increase in treatment before the start of treatment was over, the patient returned three months after the start of treatment.
  • Potentially effective desensitizing therapies are: a) process-dependent process-dependent process control b) a decrease in the clinical severity of the clinical processes; c) a decrease in the availability of drugs in pharmaceutical preparations, which are used painfully; d) a general improvement in the status of patients; e) a decrease in the incidence or elimination of complications of the main disease.
  • the duration of observations was from 4 to 16 months (from the beginning of therapy).
  • the invention may find a widespread treatment in a medicinal product.
  • the method is suitable for mass use.

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  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Transplantation (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention relève de la médecine, de la biotechnologie, de l'immunopharmacologie et consiste à améliorer l'état des malades souffrant de maladies auto-immunes. Pour inhiber le processus auto-immun on applique aux patients une thérapie spécifique de désensibilisation utilisant des produits qui contiennent des fragments liant les idiotypes des anticorps anti-idiotypiques, qui sont des analogues stériques (immunochimiques) des antigènes cibles que l'on applique régulièrement et à faibles doses aux muqueuses du patient, par exemple, sous la forme d'applications ou de suppositoires rectaux ou vaginaux. On estime l'efficacité de la correction au moyen du dosage immuno-enzymatique pour lequel on adsorbe sur une phase solide des analogues immunochimiques de l'antigène tels que les anticorps anti-idiotypiques dirigés contre l'antigène spécifique ou leurs fragments Fab2, et l'on détermine ensuite l'immunoréactivité des anticorps sériques par rapport à celui-ci.
PCT/RU2001/000033 2000-05-19 2001-01-29 Produits pharmaceutiques destines a la suppression de troubles auto-immuns au moyen de fragments liant les idiotypes des anticorps anti-idiotypiques Ceased WO2001087331A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU32504/01A AU3250401A (en) 2000-05-19 2001-01-29 Pharmaceuticals for depressing autoimmune disorders by idiotype binding fragments of anti-idiotypic antibodies

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU2000112366/14A RU2000112366A (ru) 2000-05-19 Способ коррекции состояния больных инсулинзависимым и инсулиннезависимым сахарным диабетом
RU2000112366 2000-05-19

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WO2001087331A1 true WO2001087331A1 (fr) 2001-11-22

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PCT/RU2001/000033 Ceased WO2001087331A1 (fr) 2000-05-19 2001-01-29 Produits pharmaceutiques destines a la suppression de troubles auto-immuns au moyen de fragments liant les idiotypes des anticorps anti-idiotypiques

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009113065A1 (fr) * 2008-03-13 2009-09-17 Hadasit Medical Research Services & Development Ltd. Compositions immunomodulatrices pour le traitement de troubles d’origine immunologique

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4232004A (en) * 1977-09-21 1980-11-04 American National Red Cross Antibody-specific solid phase immunoadsorbent, preparation thereof, and antibody purification therewith
RU96109830A (ru) * 1995-05-26 1998-08-10 Мерк Патент Гмбх Антиидиотипические антитела, которые индуцируют иммунный ответ против рецептора эпидермального фактора роста

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4232004A (en) * 1977-09-21 1980-11-04 American National Red Cross Antibody-specific solid phase immunoadsorbent, preparation thereof, and antibody purification therewith
RU96109830A (ru) * 1995-05-26 1998-08-10 Мерк Патент Гмбх Антиидиотипические антитела, которые индуцируют иммунный ответ против рецептора эпидермального фактора роста

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
A.B. POLETAEV ET AL.: "Primenenie antiidiopticheskikh antitel dlya korrektsii autoimmunnykh reaktsy k belku mozga-s-100", BJULLETEN EXPERIMENTALNOI BIOLOGII I MEDITSINY, 1996, MOSCOW, MEDITSINA, pages 508 - 511 *
AL-SABBAGH ET AL.: "Antigen-driven peripheral immune tolerance: suppression of experimental autoimmune encephalomyelitis and collagen-induced arthritis by aerosol administration of myelin basic protein or type II collagen", CELL IMMUNOL., vol. 171, no. 1, 10 June 1996 (1996-06-10), pages 111 - 119 *
BECKER M.I. ET AL.: "An alternative ELISA for T4 determination based on idiotype anti-idiotype interaction and a latex method for anti-idiotype monoclonal antibody selection", J. IMMUNOL. METHODS, vol. 192, no. 1-2, 10 June 1996 (1996-06-10), pages 73 - 85 *
DANIELLE A.W. WOLVERS ET AL.: "Intranasally induced immunological tolerance is determined by the draining lymph nodes: studies with OVA and human cartilage gp-39", THE JOURNAL OF IMMUNOLOGY, vol. 163, no. 4, 1994, pages 1 - 12 *
WEINER H.L.: "Oral tolerance for the treatment of autoimmune diseases", ANNU. REV. MED., vol. 48, 1997, pages 341 - 351 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009113065A1 (fr) * 2008-03-13 2009-09-17 Hadasit Medical Research Services & Development Ltd. Compositions immunomodulatrices pour le traitement de troubles d’origine immunologique
EP3231816A1 (fr) * 2008-03-13 2017-10-18 Immuron Limited Colostrum bovin comprenant des anticorps anti-insuline pour le traitement des maladies du diabete, stéatose hépatique non alcoolique, l'hyperlipidemie ou l'atherosklerose.

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Publication number Publication date
AU3250401A (en) 2001-11-26

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