Anti-mn antibodies and methods of their application

FIELD: medicine.

SUBSTANCE: invention represents antibodies having an anti-MN-protein specific antigen linkage site, combinations and methods of application of such antibodies.

EFFECT: invention can be effectively used in treating and diagnosing MN-related disorders.

13 cl, 49 dwg, 4 tbl, 21 ex

 

The text descriptions are given in facsimile form.

1. The antibody or fragment of the antibody with the antigenic site binding, specific directed against MN-protein antigenic site link includes a set of CDR sequences of the heavy chain selected from the group comprised the soup from:
(a) [EE] SEQ ID NOS: 57, 63, 70;
(b) [3ef2] SEQ ID NOS: 58, 64, 71;
(c) [e] SEQ ID NOS: 59, 65 and 72;
(d) [3a4] SEQ ID NOS: 60, 66, and 73;
(e) [3ab4] SEQ ID NOS: 61, 67, and 74;
(f) [3ah10] SEQ ID NOS: 61, 68 and 75;
(g) [3bb2] SEQ ID NOS: 62, 69 and 76;
(h) [1aa1] SEQ ID NOS: 77, 78 and 79;
(i) [5a6] SEQ ID NOS: 80, 82 and 84; and
G) [5aa3] SEQ ID NOS: 81, 83 and 85,
and a set of CDR sequences of the light chain selected from the group consisting of:
(a) [EE] SEQ ID NOS: 89, 93 and 97;
(b) [3ef2] SEQ ID NOS: 107, 109 and 111;
(c) [e] SEQ ID NOS: 107, 109 and 111;
(d) [3a4] SEQ ID NOS: 108, 110 and 112;
(e) [3ab4] SEQ ID NOS: 87, 91 and 95;
(f) [3ah10] SEQ ID NOS: 88, 92 and 96;
(g) [3bb2] SEQ ID NOS: 98,100 and 102;
(h) [1aa1] SEQ ID NOS: 86, 90 and 94;
(i) [5a6] SEQ ID NOS: 99, 101 and 103; and
(j) [5aa3] SEQ ID NOS: 104, 105 and 106.

2. The antibody or antibody fragment according to claim 1, where the antibody or fragment of the antibody binds to MN protein with a dissociation constant of from approximately 0.15 nm to about 50 nm.

3. The antibody or antibody fragment according to claim 1, where the antibody is an IgG, preferably IgG1, IgG2a, IgG2b, IgG3; IgM; IgD; IgE; IgA; Fab fragment; an F(ab')fragment; scFv-fragment; an Fv fragment; ditelo; linear antibodies; single-chain antibody; biospecific antibody; a chimeric antibody or multispecific antibody.

4. The antibody or antibody fragment according to claim 1, where the antibody or fragment antibodies are humanitarianism.

5. The antibody or antibody fragment according to claim 1, where the CDR1, CDR2 and CDR3 are nechelovecheskimi.

6. The antibody or antibody fragment according to claim 1, where the antibody or antibody fragment conjugated with cytotoxic is the principal agent.

7. The antibody or antibody fragment according to claim 6, where the cytotoxic agent is selected from the group consisting of: monomethylaniline-E or its functional equivalent, aplidine, azaribine, anastrozole, azacytidine, bleomycin, bortezomib, bryostatin-1, busulfan, calicheamicin, camptothecin, 10-hydroxycamptothecin, carmustine, celebrex, hlorambuzila, cisplatin, irinotecan (CST-1 1), SN-38, carboplatin, cladribine, cyclophosphamide, tsitarabina, dacarbazine, docetaxel, dactinomycin, daunomycin glucuronide, daunorubicin, dexamethasone, diethylstilbestrol, doxorubicin, doxorubicin glucuronide, glucuronide of epirubicin, ethinyl estradiol, estramustine, etoposide, etoposide glucuronide, etoposide phosphate, floxuridine (FUdR), 3',5'-O-dioleoyl-FUdR. (FUdR-dO), fludarabine, flutamide, fluorouracil, fluoxymesterone, gemcitabine, kaproata hydroxyprogesterone, hydroxyacetone, idarubitsina, ifosfamide, L-asparaginase, leucovorin, lomustina, mechlorethamine, acetate microprojection, acetate megestrol, melphalan, mercaptopurine, 6-mercaptopurine, methotrexate, mitoxantrone, mithramycin, mitomycin, mitotane, phenylbutyrate, prednisone, procarbazine, paclitaxel, pentostatin, PSI-341, semustine-streptozocin, tamoxifen, taxan, Taxol, testosterone propionate, thalidomide, Tg, thiotepa, teniposide, t is polecana, Aracinovo mustard, Velcade, vinblastine, vinorelbine, vincristine, ricin, abrin, ribonuclease, onconase, rapLRI, Gnkazy I, staphylococcal enterotoxin, virus protein, Phytolacca American, gelonin, diphtheria toxin, Pseudomonas exotoxin, Pseudomonas endotoxin, and combinations thereof.

8. The antibody or antibody fragment according to any one of claims 1 to 6, where the antigenic site link includes a pair of variable regions of the heavy chain and the variable region of the light chain selected from the group consisting of:
(a) variable regions of the heavy chain SEQ ID NO: 133 and the variable region of the light chain SEQ ID NO: 134;
(b) variable regions of the heavy chain SEQ ID NO: 135 and the variable region of the light chain SEQ ID NO: 136;
(c) variable regions of the heavy chain SEQ ID NO: 137 and the variable region of the light chain SEQ ID NO: 138;
(d) variable region heavy chain SEQ ID NO: 139 and the variable region of the light chain SEQ ID NO: 140;
(e) variable regions of the heavy chain SEQ ID NO: 141 and the variable region of the light chain SEQ ID NO: 142;
(f) variable regions of the heavy chain SEQ ID NO: 143 and the variable region of the light chain SEQ ID NO: 144;
(g) variable regions of the heavy chain SEQ ID NO: 145 and the variable region of the light chain SEQ ID NO: 146;
(h) variable regions of the heavy chain SEQ ID NO: 147 and the variable region of the light chain SEQ ID NO: 148;
(i) variable region heavy chain SEQ ID NO: 149 and the variable region in the light chain of SEQ ID NO: 150; and
(j) variable regions of the heavy chain SEQ ID NO: 151 and variable region of the light chain SEQ ID NO: 152.

9. Combination for the treatment of a subject having a MN-related cancer, where the cancer is, by choice, is a tumor or a tumor of the breast, respiratory tract, lung, brain, reproductive organ, digestive tract, colon, urinary tract, kidney, esophagus, cervix, eye, liver, skin, head, neck, thyroid and parathyroid glands, and the combination includes the antibody or the antibody fragment according to any one of claims 1 to 6 and anticancer agent.

10. Pharmaceutical composition for the treatment of MN-related cancer, where the cancer is, by choice, is a tumor or a tumor of the breast, respiratory tract, lung, brain, reproductive organ, digestive tract, colon, urinary tract, kidney, esophagus, cervix, eye, liver, skin, head, neck, thyroid and parathyroid glands, comprising the antibody or the antibody fragment according to any one of claims 1 to 6 and a pharmaceutically acceptable carrier.

11. The use of the antibody or antibody fragment according to any one of claims 1 to 6 in the preparation of medicaments for the treatment of MN-linked disorders where the violation by choice, is a tumor or a tumor of the breast, respiratory Proc. of the KTA, lung, brain, reproductive organ, digestive tract, colon, urinary tract, kidney, esophagus, cervix, eye, liver, skin, head, neck, thyroid and parathyroid glands.

12. The use of the antibody or antibody fragment according to any one of claims 1 to 6 in the preparation of medicaments for the diagnosis of MN-linked disorders where the violation by choice, is a tumor or a tumor of the breast, respiratory tract, lung, brain, reproductive organ, digestive tract, colon, urinary tract, kidney, esophagus, cervix, eye, liver, skin, head, neck, thyroid and parathyroid glands.

13. Anti-MN IgG-antibody encoded by the nucleotide sequence of SEQ ID NO: 153.



 

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