Modification method of isoelectric point of antibody by means of amino-acid replacements in cdr

FIELD: biotechnologies.

SUBSTANCE: invention refers to a method for obtaining an antibody, the pharmacokinetic properties of which have been changed at maintaining antigen-binding activity of a variable area, which provides for the following stages: (a) obtaining antibodies in which there has been modified a charge of amino-acid residues chosen from amino-acid residues in positions 31, 61, 62, 64 and 65 of the variable area of a heavy chain and in positions 24, 27, 53, 54 and 55 of the variable area of a light chain in compliance with numbering as per Kabat system, where modification of the charge of amino-acid residues leads to the change of 1.0 or more at a theoretical isoelectric point of the variable area of the antibody, and (b) extracting an antibody with stored antigen-binding activity from antibodies obtained at stage (a).

EFFECT: invention allows effective change in pharmacokinetic properties of an antibody, thus maintaining its antigen-binding activity.

 

The text descriptions are given in facsimile form.

1. A method of producing an antibody, which modified pharmacokinetic properties plasma while retaining the antigen-binding activity of variable region that provides for stages:
(a) obtaining antibody, which modified the charge of amino acid residues selected from amino acid residues at positions 31, 61, 62, 64 and 65 variable regions of the heavy chain and at positions 24, 27, 53, 54 and 55 of the variable region of the light chain in accordance with the numbering system of Kabat, where the modification of the charge of amino acid residues leads to a change of 1.0 or more in theoretical isoelectric point of the variable regions of antibodies, and
(b) the selection of antibodies with retained antigen-binding activity of antibodies obtained in stage (a).

2. The method according to claim 1, where the antibodies which additionally contains FcRn-binding domain.

3. The method according to claim 1, where the antibody is an IgG antibody.

4. The method according to claim 1, where the antibody is a chimeric antibody, humanitariannet antibody or a human antibody.

5. The method according to claim 1, where the antibody is a polyspecific antibody that binds at least two different types of antigens.

6. The method according to claim 1, where the charge of amino acid residue is modified by replacing amino acids.

7. The method according to claim 1, where the modified amino acid selected from amino acid residues of any group (a) or (b) below:
(a) glutamic acid (E) and aspartic acid (D); and
(b) lysine (K), arginine (R) and histidine (H).

8. The method according to claim 1, where the change in pharmacokinetic parameters refers to the increase or decrease of any parameter of clearance (CL) of the plasma area under the concentration curve (AUC), the average retention time in plasma and the time half-life in plasma (t1/2).



 

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7 cl, 4 tbl

FIELD: biotechnologies.

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FIELD: biotechnologies.

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FIELD: biotechnologies.

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FIELD: biotechnologies.

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4 cl, 5 dwg, 7 ex, 3 tbl

FIELD: biotechnologies.

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FIELD: biotechnologies.

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17 cl, 3 dwg, 6 tbl, 7 ex

FIELD: biotechnologies.

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24 cl, 4 tbl, 20 ex

FIELD: biotechnology.

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16 cl, 2 dwg, 4 tbl

FIELD: chemistry.

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51 cl, 24 ex, 8 dwg, 5 tbl

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FIELD: medicine, pharmaceutics.

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29 cl, 42 dwg, 14 tbl, 14 ex

FIELD: medicine, pharmaceutics.

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22 cl, 30 dwg, 9 tbl, 8 ex

FIELD: medicine, pharmaceutics.

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18 cl, 26 dwg, 8 ex

FIELD: chemistry.

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50 cl, 23 tbl, 2 ex

FIELD: medicine, pharmaceutics.

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5 cl, 5 dwg, 6 ex

FIELD: chemistry.

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80 cl, 62 dwg, 47 tbl, 65 ex

FIELD: medicine.

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115 cl, 24 tbl, 2 ex

Anti-axl antibodies // 2506276

FIELD: chemistry.

SUBSTANCE: present invention relates to immunology. Disclosed are monoclonal antibodies which bind to the extracellular domain of receptor tyrosine kinase AXL and which at least partially inhibit AXL activity, as well as antigen-binding fragments. Also provided is an isolated nucleic acid molecule, a host cell and a method of producing a monoclonal antibody and an antigen-binding fragment thereof, as well as use of the monoclonal antibody or antigen-binding fragment thereof to produce a drug, pharmaceutical compositions, a method of diagnosing and a method of preventing or treating a condition associated with expression, overexpression and/or hyperactivity of AXL.

EFFECT: invention can be used in therapy and diagnosis of diseases associated with AXL.

23 cl, 20 dwg, 24 ex, 3 tbl

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