Il-7 versions with low immunising capacity

FIELD: chemistry.

SUBSTANCE: recombinant technique is used to obtain a fused polypeptide with activity of interleukin-7, containing a modified human IL-7 molecule in which the T-cell epitope is modified to reduce T-cell response against IL-7, and the Fc part of an immunoglobulin molecule which is fused through its C-end with the N-end of said modified IL-7 molecule. The obtained polypeptide is used in a pharmaceutical composition to stimulate immune response in a patient.

EFFECT: invention enables to obtain a polypeptide with interleukin-7 activity, having low immunising capacity.

8 cl, 43 dwg, 14 tbl, 12 ex

 

The text descriptions are given in facsimile form.

1. The polypeptide having the activity of interleukin-7, containing the modified molecule of human IL-7, in which T-cell epitope modified to reduce T-cell response against IL-7, where the specified polypeptide also contains a plot of Fc molecules of the immunoglobulin is fused via its C-end N-end of the specified modified molecules IL-7, where this merged molecule Fc-IL-7 is selected from the group consisting of
i. huFcγ2(h)(FN > AQ)-L-IL-7(F39P, F57N, L128S), where Fcγ2(h) represents a portion of a human Fc hinge region of IgG1 and domains CH2 and CH3 IgG2 containing mutations F296A and N297Q, L represents ablinger sequence GGGGSGGGG, a IL-7(F39P, F57N, L128S) denotes IL-7 containing mutations F39P, F57N and L128S, and this molecule has the sequence presented on Fig (SEQ ID NO.34);
ii. huFcγ2(h)(FN > AQ)-L-IL-7(F39P, F57N, L77D, L128S), where Fcγ2(h) represents a portion of a human Fc hinge region of IgG1 and domains CH2 and CH3 TgG2 containing mutations F296A and N297Q, L represents a linker sequence GGGGSGGGG, a IL-7(F39P, F57N, L77D, L128S) denotes IL-7 containing mutations F39P, F57N, L77D and L128S, and this molecule has the sequence presented on Fig (SEQ ID NO.33);
iii. huFcγ2(h)-L-IL-7(F39P, F57N, L77D, L128S), where Fcγ2(h) represents a portion of a human Fc hinge region of IgG1 and domains CH2 and CH3 IgG2, L represents a linker sequence GGGGSGGGG, a IL-7(F39P, F57N, L77D, L128S) denotes IL-7 containing mutations F39P, F57N, L77D and L128S, and this molecule has the sequence presented on Fig (SEQ ID NO.35);
iv. huFcγ2(h)-L-IL-7(F39P, F57N, L128S), where Fcγ2(h) represents a portion of a human Fc hinge region of IgG1 and domains CH2 and CH3 TgG2, L represents a linker sequence GGGGSGGGG, a IL-7(F39P, F57N, L128S) denotes IL-7 containing mutations F39P, F57N and L128S, and this molecule has the sequence presented on Fig (SEQ ID NO.36).

2. The polypeptide according to claim 1, where the specified molecule of the immunoglobulin is a human immunoglobulin.

3. The polypeptide according to the .1 or 2, where specified, the immunoglobulin molecule is an IgG2.

4. The nucleic acid molecule encoding a polypeptide according to claim 1.

5. Expressing the vector for prokaryotic cells containing the nucleic acid molecule according to claim 4, operatively linked with regulatory elements.

6. Prokaryotic cell for production of the polypeptide according to claim 1, containing expressing vector according to claim 5.

7. Pharmaceutical composition for stimulating an immune response in a patient, containing an effective amount of the polypeptide according to claim 1 and a pharmaceutically acceptable carrier.

8. Method of stimulating an immune response in a patient, wherein the patient is administered a pharmaceutical composition according to claim 7 in amounts of between 0.01 and 10 mg/kg/day.



 

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FIELD: medicine.

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3 cl, 1 dwg, 4 ex

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12 cl, 5 dwg, 3 tbl, 2 ex

FIELD: medicine.

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4 cl, 3 dwg, 3 ex

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10 cl, 4 dwg, 5 ex

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28 cl, 12 tbl, 35 dwg, 29 ex

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43 cl, 20 dwg, 10 ex

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15 cl, 37 tbl, 45 ex

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14 cl, 1 dwg, 12 tbl, 19 ex

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2 cl, 4 dwg, 1 tbl, 4 ex

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5 dwg, 6 ex, 11 tbl

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2 dwg, 1 tbl, 3 ex

The invention relates to biotechnology and can be used to obtain Malinov human IL-4 with an activating T-cell activity and reduced activating endothelial cells activity

The invention relates to the field of molecular biology and genetic engineering and can be used in medicine

FIELD: medicine.

SUBSTANCE: method involves cultivation of an obligate methanol-assimilating bacterium Methylophilus methylotrophus or Methylobacillus glycogens in a fluid medium with the bacterium secreting an end protein from a bacterial cell where said bacterium has a DNA structure containing a promoter sequence functioning in the methanol-assimilating bacterium, a nucleotide sequence coding a polypeptide containing a signal sequence which functions in the methanol-assimilating bacterium, and a sequence of the end protein functionally connected with the promoter sequence.

EFFECT: method allows producing the protein effectively by means of extracellular secretion, difficult-to-produce by means of secretory production with application of Escherichia coli bacteria.

5 cl, 7 ex

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