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WO1999004807A1 - Immunotoxine recombinante a base de toxine diphterique et d'interleukine -2 (dt482-il2), et procede de production - Google Patents

Immunotoxine recombinante a base de toxine diphterique et d'interleukine -2 (dt482-il2), et procede de production Download PDF

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Publication number
WO1999004807A1
WO1999004807A1 PCT/RU1997/000343 RU9700343W WO9904807A1 WO 1999004807 A1 WO1999004807 A1 WO 1999004807A1 RU 9700343 W RU9700343 W RU 9700343W WO 9904807 A1 WO9904807 A1 WO 9904807A1
Authority
WO
WIPO (PCT)
Prior art keywords
toxin
interleukin
diphterial
preparing
recombinant immunotoxin
Prior art date
Application number
PCT/RU1997/000343
Other languages
English (en)
Russian (ru)
Inventor
Sergei Sergeevich Markin
Valentin Jurievich Uvarov
Igor Gennadievich Sivov
Alla Anatolievna Lyashenko
Mikhail Petrovich Semenov
Original Assignee
Joint-Stock Company Limited 'phosphosorb'
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 Joint-Stock Company Limited 'phosphosorb' filed Critical Joint-Stock Company Limited 'phosphosorb'
Publication of WO1999004807A1 publication Critical patent/WO1999004807A1/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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/55—IL-2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/34—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Corynebacterium (G)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Definitions

  • the recombinant immunotoxin based on the basic differential toxin and interleukin-2 ( ⁇ 482- ⁇ 1_2) and the method of its irradiation.
  • the invention is available in the field of medicine and may be used for the manufacture of drugs.
  • the best idea in this sense is given to the bacterial toxins, which are capable of damaging the xyosin’s cell, thereby, or otherwise, causing its death.
  • the present invention relates to immune system on the basis of the protein, the toxic part of the product is supplied (2)
  • This protein has a positive effect on the cells of the progenitor ⁇ _-2, as well as an immunosuppressive effect. Consequently, it can be used for the treatment of such pathologies, such as ⁇ -cell leukemia, lymphoma, various autoimmune diseases, incl. diabetes I type, rheumatoid arthritis and T..p., as well as with transplantation of organs and tane.
  • the demarcated domain carries hydrophobic, membrane-associated areas that penetrate through the membrane; It is indispensable for the sale of the catalytic part of toxin in the cage.
  • the special domain serves for recognizing the negative side of the cord through the corresponding receptors, which was removed in the end in response to the end of 1996, ()). Lusenium 35, 1137-1149; ⁇ _ ⁇ " ⁇ , ⁇ . (1992) ⁇ . ⁇ 82 ⁇ . 22, 3277-3282]. ⁇ but this is the receptor-binding epidermal factor, [[ , ⁇ ., ⁇ Economics ⁇ , ⁇ ., ⁇ réelle repetate ⁇ réelle, ⁇ . (1995) ⁇ . ⁇ . ⁇ style. 270, 1015-1019]. Consistent use of all the data is available on Figure 2.
  • Immune toxins are known on the basis of crizos, in fact, the terminal component of the toxic component is provided by two primary and dual-mediated products.
  • the accessory parts are distinguished by a long linker connecting the transposed domain ⁇ and the newly connected address [ ⁇ , ⁇ ''' ⁇ & ⁇ , ⁇ ., ⁇ réelle ⁇ , ⁇ ., Ce ⁇ réelle ⁇ réelle ⁇ réelle ⁇ réelle, ⁇ . ⁇ ., ⁇ réelle, ⁇ ., ⁇ , ⁇ . S. (1991), _. ⁇ SIET. 266, 21118-21124].
  • s ⁇ abiln ⁇ s ⁇ i ⁇ ime ⁇ n ⁇ g ⁇ bel ⁇ a The second, being a gross-obstructive bacterium, is safe from the risk of toxic polysaccharides, which may be less likely to get loaded.
  • ⁇ me ⁇ g ⁇ sis ⁇ ema ⁇ e ⁇ liza in ⁇ .s ⁇ P nas ⁇ ena on ⁇ as ⁇ znavanie "sv ⁇ y- chuzh ⁇ y" ⁇ e ⁇ mu susches ⁇ vue ⁇ vys ⁇ aya ve ⁇ ya ⁇ n ⁇ s ⁇ ⁇ e ⁇ li ⁇ iches ⁇ g ⁇ ⁇ assche ⁇ leniya gib ⁇ idn ⁇ g ⁇ bel ⁇ a, ch ⁇ vleche ⁇ for s ⁇ b ⁇ y seg ⁇ egatsi ⁇ nnuyu and s ⁇ u ⁇ u ⁇ nuyu neus ⁇ ychiv ⁇ s ⁇ and ⁇ a ⁇ sleds ⁇ vie, reduced ⁇ du ⁇ ivn ⁇
  • the objective of the present invention is to produce a single protein of ⁇ - ⁇ _2 and to erase the outcome of this process in order to prevent a high incidence of P ⁇ s ⁇ avlennaya task ⁇ eshae ⁇ sya ⁇ isyvaemym ⁇ e ⁇ mbinan ⁇ nym immun ⁇ sin ⁇ m, s ⁇ de ⁇ zhaschim ⁇ a ⁇ ali ⁇ iches ⁇ uyu and ⁇ ansmemb ⁇ annuyu chas ⁇ i di ⁇ e ⁇ iyn ⁇ g ⁇ ⁇ sina dlin ⁇ y 482 amin ⁇ isl ⁇ y and ad ⁇ esnuyu Part, ⁇ eds ⁇ avlennuyu chel ⁇ veches ⁇ im in ⁇ e ⁇ ley ⁇ in ⁇ m 2 and having ⁇ min ⁇ isl ⁇ nuyu ⁇ sled ⁇ va ⁇ eln ⁇
  • ⁇ a ⁇ im ⁇ b ⁇ az ⁇ m ⁇ edlagaemaya ⁇ ns ⁇ u ⁇ tsiya, the name ⁇ 482-I2, s ⁇ de ⁇ zhi ⁇ b ⁇ lee ⁇ y lin ⁇ e ⁇ , ch ⁇ s ⁇ s ⁇ bs ⁇ v ⁇ vue ⁇ with ⁇ dn ⁇ y s ⁇ ny, b ⁇ lshey us ⁇ ychiv ⁇ s ⁇ i ⁇ ⁇ eazam and with d ⁇ ug ⁇ y - ⁇ zv ⁇ lyae ⁇ ad ⁇ esn ⁇ y chas ⁇ i by ⁇ b ⁇ lee gib ⁇ y, ch ⁇ s ⁇ s ⁇ bs ⁇ v ⁇ vue ⁇ ⁇ vysheniyu a ⁇ inn ⁇ s ⁇ i vzaim ⁇ deys ⁇ viya with ⁇ etse ⁇ m. Larger, more convenient operation, as opposed to the known one, makes it possible to lose catalytically important amino acid residues, which are 466 and
  • the present invention has the following advantages by existing analogs, including, but not limited to, the following.
  • the inoculum the linker is processed by the storage of all amino acid residues, which are necessary for the performance of the catalytic function of the active center.
  • the producer selected by us for the sake of a large protein is more preferable than the soybean.
  • the synthesized immunotoxin is secreted entirely by the electromechanical device, which is more efficient.
  • the used ⁇ 8 strain is reserved for the intended use. 8
  • Figure 2 The business organization of a differential therapy: a catalytic, electronic assembly, an electronic domain, respectively.
  • the numbers indicate the amino acid number corresponding to the domains.
  • FIGURE 3 Primary investigative of a recombinant squirrel. The signal sequence is highlighted in solid, the interleukin part is in small type.
  • the method of running the fused protein ⁇ 482-I2 includes the following stages.
  • the nalidic acid was used to isolate the other bacteriophage, which contains a complete investigative test. After the processing of the obtained products, the process of separation of the component is carried out. At the next stage, inclusion of the selected fragment ⁇ ⁇ in the plasmid ⁇ 322 for the indicated sites of the test for the production of a hybrid plasmid is included.
  • the codon of the I-2 is a mine for Soguébas ⁇ epit ⁇ . Thailand ⁇ réelle Pharmaceutical. ⁇ connection e ⁇ im ne ⁇ b ⁇ dim ⁇ vid ⁇ izmeni ⁇ bel ⁇ -sin ⁇ ezi ⁇ uyuschy a ⁇ a ⁇ a ⁇ for cheg ⁇ vv ⁇ dim in ⁇ m ⁇ s ⁇ mu sh ⁇ amma- ⁇ dutsen ⁇ a gene ne ⁇ b ⁇ ⁇ dim ⁇ y ⁇ ⁇ a ⁇ , ch ⁇ by ⁇ b ⁇ azuyuschayasya ⁇ was s ⁇ s ⁇ bna svyazyva ⁇ sya with vysheu ⁇ azannym ⁇ d ⁇ n ⁇ m.
  • the proposed genetically engineered product allows you to produce a fused protein that is most beneficial for people who are less likely to be at risk of being ill.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Toxicology (AREA)
  • Peptides Or Proteins (AREA)

Abstract

Cette invention concerne une immunotoxine recombinante qui contient une toxine diphtérique et de l'interleukine 2, et dans laquelle la partie catalytique et transmembranaire de la toxine diphtérique possède un acide aminé d'une longueur de 482. Cette invention concerne également un procédé de production de cette immunotoxine recombinante DT482-IL2.
PCT/RU1997/000343 1997-07-22 1997-11-03 Immunotoxine recombinante a base de toxine diphterique et d'interleukine -2 (dt482-il2), et procede de production WO1999004807A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
RU97111749 1997-07-22
RU97111749A RU2115429C1 (ru) 1997-07-22 1997-07-22 Рекомбинантный иммунотоксин на основе дифтерийного токсина и интерлейкина-2 (дт 482-il2) и способ его получения

Publications (1)

Publication Number Publication Date
WO1999004807A1 true WO1999004807A1 (fr) 1999-02-04

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/RU1997/000343 WO1999004807A1 (fr) 1997-07-22 1997-11-03 Immunotoxine recombinante a base de toxine diphterique et d'interleukine -2 (dt482-il2), et procede de production

Country Status (2)

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RU (1) RU2115429C1 (fr)
WO (1) WO1999004807A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2140283C1 (ru) * 1998-12-15 1999-10-27 Товарищество с ограниченной ответственностью "Биотех" Фармацевтический препарат на основе интерлейкина-2 (варианты)
SE0102327D0 (sv) * 2001-06-28 2001-06-28 Active Biotech Ab A novel engineered superantigen for human therapy

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2650183A1 (fr) * 1989-07-25 1991-02-01 Pasteur Institut Proteines immunostimulantes, anticorps monoclonaux et polyclonaux correspondants, hybridomes correspondants et application de ces produits a des fins therapeutiques et de diagnostic
WO1992004044A1 (fr) * 1990-09-06 1992-03-19 Schering Corporation Emploi de il-4 dans le traitement de tumeurs solides
RU2077585C1 (ru) * 1993-12-10 1997-04-20 Государственный научно-исследовательский институт прикладной микробиологии Рекомбинантная плазмидная днк рдти 23, способ получения рекомбинантной плазмидной днк рдти 23 и штамм бактерий escherichia coli, содержащий рекомбинантную плазмидную днк рдти 23 - продуцент слитого белка дтил 2

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5061692A (en) * 1984-08-09 1991-10-29 Immunetech Pharmaceuticals Methods and compositions for the treatment of non-IgE-mediated diseases

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2650183A1 (fr) * 1989-07-25 1991-02-01 Pasteur Institut Proteines immunostimulantes, anticorps monoclonaux et polyclonaux correspondants, hybridomes correspondants et application de ces produits a des fins therapeutiques et de diagnostic
WO1992004044A1 (fr) * 1990-09-06 1992-03-19 Schering Corporation Emploi de il-4 dans le traitement de tumeurs solides
RU2077585C1 (ru) * 1993-12-10 1997-04-20 Государственный научно-исследовательский институт прикладной микробиологии Рекомбинантная плазмидная днк рдти 23, способ получения рекомбинантной плазмидной днк рдти 23 и штамм бактерий escherichia coli, содержащий рекомбинантную плазмидную днк рдти 23 - продуцент слитого белка дтил 2

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
I.G. SHEMYAKIN et al., "Konstruirovanie i Expressya v Kletkakh Escherichia Coli Gena Gibridnogo Belka Difterynogo Toxina Interleykina 2 Cheloveka", MOLEKULYARNAYA BIOLOGYA, 1992, Volume 26, Vyn. 5, Nauka, pages 1088-1098. *

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