RU2016123597A - Анти-her2 конъюгат антитела с лекарственным средством - Google Patents
Анти-her2 конъюгат антитела с лекарственным средством Download PDFInfo
- Publication number
- RU2016123597A RU2016123597A RU2016123597A RU2016123597A RU2016123597A RU 2016123597 A RU2016123597 A RU 2016123597A RU 2016123597 A RU2016123597 A RU 2016123597A RU 2016123597 A RU2016123597 A RU 2016123597A RU 2016123597 A RU2016123597 A RU 2016123597A
- Authority
- RU
- Russia
- Prior art keywords
- cancer
- antibody
- conjugate
- drug
- succinimid
- Prior art date
Links
- 229940079593 drug Drugs 0.000 claims 32
- 239000003814 drug Substances 0.000 claims 32
- 239000000562 conjugate Substances 0.000 claims 23
- 206010009944 Colon cancer Diseases 0.000 claims 8
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 5
- 206010028980 Neoplasm Diseases 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims 5
- 230000000259 anti-tumor effect Effects 0.000 claims 4
- 239000002246 antineoplastic agent Substances 0.000 claims 4
- 229940041181 antineoplastic drug Drugs 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 235000001014 amino acid Nutrition 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 claims 3
- 208000029742 colonic neoplasm Diseases 0.000 claims 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 3
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims 2
- CKLJMWTZIZZHCS-UWTATZPHSA-N D-aspartic acid Chemical compound OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims 2
- 206010014733 Endometrial cancer Diseases 0.000 claims 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 2
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 claims 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 2
- 206010025323 Lymphomas Diseases 0.000 claims 2
- 208000032271 Malignant tumor of penis Diseases 0.000 claims 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 2
- 206010033128 Ovarian cancer Diseases 0.000 claims 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 2
- 208000002471 Penile Neoplasms Diseases 0.000 claims 2
- 206010034299 Penile cancer Diseases 0.000 claims 2
- 206010035226 Plasma cell myeloma Diseases 0.000 claims 2
- 208000007452 Plasmacytoma Diseases 0.000 claims 2
- 206010060862 Prostate cancer Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 206010038389 Renal cancer Diseases 0.000 claims 2
- 208000004337 Salivary Gland Neoplasms Diseases 0.000 claims 2
- 206010061934 Salivary gland cancer Diseases 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 2
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 2
- 206010047741 Vulval cancer Diseases 0.000 claims 2
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- 239000011230 binding agent Substances 0.000 claims 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 2
- 201000010881 cervical cancer Diseases 0.000 claims 2
- 201000004101 esophageal cancer Diseases 0.000 claims 2
- 206010017758 gastric cancer Diseases 0.000 claims 2
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 claims 2
- 201000010982 kidney cancer Diseases 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 125000005647 linker group Chemical group 0.000 claims 2
- 201000007270 liver cancer Diseases 0.000 claims 2
- 208000014018 liver neoplasm Diseases 0.000 claims 2
- 201000005202 lung cancer Diseases 0.000 claims 2
- 208000020816 lung neoplasm Diseases 0.000 claims 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims 2
- 201000002528 pancreatic cancer Diseases 0.000 claims 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims 2
- 201000002628 peritoneum cancer Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 201000011549 stomach cancer Diseases 0.000 claims 2
- 201000002510 thyroid cancer Diseases 0.000 claims 2
- 206010044412 transitional cell carcinoma Diseases 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- 206010046766 uterine cancer Diseases 0.000 claims 2
- 201000005102 vulva cancer Diseases 0.000 claims 2
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 claims 1
- 208000003837 Second Primary Neoplasms Diseases 0.000 claims 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000000611 antibody drug conjugate Substances 0.000 claims 1
- 229940049595 antibody-drug conjugate Drugs 0.000 claims 1
- 235000003704 aspartic acid Nutrition 0.000 claims 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims 1
- 235000013477 citrulline Nutrition 0.000 claims 1
- 229960002173 citrulline Drugs 0.000 claims 1
- 235000013922 glutamic acid Nutrition 0.000 claims 1
- 239000004220 glutamic acid Substances 0.000 claims 1
- 210000003494 hepatocyte Anatomy 0.000 claims 1
- 229940127121 immunoconjugate Drugs 0.000 claims 1
- 210000005229 liver cell Anatomy 0.000 claims 1
- 235000018977 lysine Nutrition 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims 1
- 235000004400 serine Nutrition 0.000 claims 1
- 206010041823 squamous cell carcinoma Diseases 0.000 claims 1
- 208000017572 squamous cell neoplasm Diseases 0.000 claims 1
- 235000014393 valine Nutrition 0.000 claims 1
- 239000004474 valine Substances 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
- A61K47/68037—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a camptothecin [CPT] or derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6855—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from breast cancer cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6857—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from lung cancer cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6859—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from liver or pancreas cancer cell
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6851—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell
- A61K47/6869—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a determinant of a tumour cell the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3015—Breast
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3023—Lung
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/303—Liver or Pancreas
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3046—Stomach, Intestines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
- C07K16/3069—Reproductive system, e.g. ovaria, uterus, testes, prostate
-
- 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
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Reproductive Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Mycology (AREA)
- Microbiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Claims (122)
1. Конъюгат антитела с лекарственным средством, где противоопухолевое соединение, представленное следующей формулой:
[Формула 1]
конъюгировано с анти-HER2 антителом через связующую группу, имеющую структуру, представленную следующей формулой:
-L1-L2-LP-NH-(CH2)n1-La-(CH2)n2-C(=O)-
через тиоэфирную связь, которая формируется на дисульфидной связующей группе, присутствующей в шарнирной части анти-HER2 антитела,
где
анти-HER2 антитело соединено с концом L1,
противоопухолевое соединение соединено с карбонильной группой -(CH2)n2-C(=O)- части с атомом азота аминогруппы в положении 1 в качестве связующего положения,
где
n1 является целым числом от 0 до 6,
n2 является целым числом от 0 до 5,
L1 является -(Сукцинимид-3-ил-N)-(CH2)n3-C(=O)-,
где n3 является целым числом от 2 до 8,
L2 является -NH-(CH2CH2-O)n4-CH2CH2-C(=O)- или одинарной связью,
где n4 является целым числом от 1 до 6,
LP является пептидным остаток, состоящим из от 2 до 7 аминокислот,
La является -O- или одинарной связью, и
-(Сукцинимид-3-ил-N)- имеет структуру, представленную следующей формулой:
[Формула 2]
которая соединена с анти-HER2 антителом в положении 3, и соединена с метиленовой группой в связующей структуре, содержащей эту структуру, на атоме азота в положении 1.
2. Конъюгат антитела с лекарственным средством по п.1, где пептидным остатком LP является пептидный остаток, содержащий аминокислоту, выбранную из фенилаланина, глицина, валина, лизина, цитруллина, серина, глутаминовой кислоты и аспарагиновой кислоты.
3. Конъюгат антитела с лекарственным средством по п.1 или 2, где LP является пептидным остатком, выбранным из следующей группы:
-GGF-
-DGGF-
-(D-)D-GGF-
-EGGF-
-GGFG-
-SGGF-
-KGGF-
-DGGFG-
-GGFGG-
-DDGGFG-
-КДGGFG-
-GGFGGGF-
где "(D-)D" является D-аспарагиновой кислотой.
4. Конъюгат антитела с лекарственным средством по п.1 или 2, где LP является пептидным остатком, содержащим 4 аминокислоты.
5. Конъюгат антитела с лекарственным средством по любому из пп.1-4, где LP является тетрапептидным остатком -GGFG-.
6. Конъюгат антитела с лекарственным средством по любому из пп.1-5, где n3 является целым числом от 2 до 5 и L2 является одинарной связью.
7. Конъюгат антитела с лекарственным средством по любому из пп.1-5, где n3 является целым числом от 2 до 5, L2 является -NH-(CH2CH2-O)n4-CH2CH2-C(=O)- и n4 равно 2 или 4.
8. Конъюгат антитела с лекарственным средством по любому из пп.1-7, где -NH-(CH2)n1-La-(CH2)n2-C(=O)- является подструктурой, имеющей длину цепи от 4 до 7 атомов.
9. Конъюгат антитела с лекарственным средством по любому из пп.1-7, где -NH-(CH2)n1-La-(CH2)n2-C(=O)- является подструктурой, имеющей длину цепи 5 или 6 атомов.
10. Конъюгат антитела с лекарственным средством по любому из пп.1-9, где -NH-(CH2)n1-La-(CH2)n2-C(=O)- является любым из следующей группы:
-NH-CH2CH2-C(=O)-
-NH-CH2CH2CH2-C(=O)-
-NH-CH2CH2CH2CH2-C(=O)-
-NH-CH2CH2CH2CH2CH2-C(=O)-
-NH-CH2-O-CH2-C(=O)-
-NH-CH2CH2-O-CH2-C(=O)-
-NH-CH2CH2-O-C(=O)-
11. Конъюгат антитела с лекарственным средством по п.10, где -NH-(CH2)n1-La-(CH2)n2-C(=O)- является любым из следующей группы:
-NH-CH2CH2CH2-C(=O)-
-NH-CH2-O-CH2-C(=O)-
-NH-CH2CH2-O-CH2-C(=O)-
12. Конъюгат антитела с лекарственным средством по любому из пп.1-9, где структурой лекарственное средство-связующая группа, содержащей лекарственное средство, связанное с -L1-L2-LP-NH-(CH2)n1-La-(CH2)n2-C(=O)-, является одна из структур лекарственное средство-связующая группа, выбранных из следующей группы:
-(Сукцинимид-3-ил-N)-CH2CH2-C(=O)-GGFG-NH-CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2-C(=O)-GGFG-NH-CH2CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2CH2CH2CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2-O-CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2CH2-O-CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2CH2-O-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2-C(=O)-NH-CH2CH2-O-CH2CH2-O-CH2CH2-C(=O)-GGFG-NH-CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2-C(=O)-NH-CH2CH2-O-CH2CH2-O-CH2CH2-C(=O)-GGFG-NH-CH2CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2-C(=O)-NH-CH2CH2-O-CH2CH2-O-CH2CH2-O-CH2CH2-O-CH2CH2-C(=O)-GGFG-NH-CH2CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2-C(=O)-NH-CH2CH2-O-CH2CH2-O-CH2CH2-O-CH2CH2-O-CH2CH2-C(=O)-GGFG-NH-CH2CH2CH2-C(=O)-(NH-DX)
где -(Сукцинимид-3-ил-N)- имеет структуру, представленную следующей формулой:
[Формула 3]
которая соединена с анти-HER2 антителом в положении 3 и соединена с метиленовой группой в связующей структуре, содержащей эту структуру на атоме азота в положении 1,
-(NH-DX) является группой, представленной следующей формулой:
[Формула 4]
где атом азота аминогруппы в положении 1 является связующим положением, и
-GGFG- является тетрапептидным остатком -Gly-Gly-Phe-Gly-.
13. Конъюгат антитела с лекарственным средством по п.12, где структурой лекарственное средство-связующая группа является одна из структур лекарственное средство-связующая группа, выбранных из следующей группы:
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2-O-CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2CH2CH2CH2-C(=O)-GGFG-NH-CH2CH2-O-CH2-C(=O)-(NH-DX)
-(Сукцинимид-3-ил-N)-CH2CH2-C(=O)-NH-CH2CH2-O-CH2CH2-O-CH2CH2-C(=O)-GGFG-NH-CH2CH2CH2-C(=O)-(NH-DX)
14. Конъюгат антитела с лекарственным средством, где противоопухолевое соединение представлено следующей формулой:
[Формула 5]
и конъюгировано с анти-HER2 антителом через связующую группу, имеющую структуру, представленную следующей формулой:
-L1-L2-LP-NH-(CH2)n1-La-(CH2)n2-C(=O)-
через тиоэфирную связь, которая образуется на дисульфидной связи, присутствующей в шарнирной части анти-HER2 антитела,
где
анти-HER2 антитело соединено с концом L1,
противоопухолевое соединение соединено с карбонильной группой -(CH2)n2-C(=O)- группы,
где
n1 является целым числом от 0 до 6,
n2 является целым числом от 0 до 5,
L1 является -(Сукцинимид-3-ил-N)-(CH2)n3-C(=O)-,
где n3 является целым числом от 2 до 8,
L2 является -NH-(CH2CH2-O)n4-CH2CH2-C(=O)- или одинарной связью,
где n4 является целым числом от 1 до 6,
LP является тетрапептидным остатком -GGFG-,
La является -O- или одинарной связью, и
-(Сукцинимид-3-ил-N)- имеет структуру, представленную следующей формулой:
[Формула 6]
которая соединена с анти-HER2 антителом в положении 3 и соединена с метиленовой группой в связующей структуре, содержащей эту структуру, на атоме азота в положении 1.
15. Конъюгат антитела с лекарственным средством по п.14, где
n1 равно 3, n2 равно 0, n3 равно 2, L2 является -NH-(CH2CH2-O)n4-CH2CH2-C(=O)-, n4 равно 2 и La является одинарной связью,
n1 равно 1, n2 равно 1, n3 равно 5, L2 является одинарной связью и La является -O-, или
n1 равно 2, n2 равно 1, n3 равно 5, L2 является одинарной связью и La является -O-.
16. Конъюгат антитела с лекарственным средством по п.14 или 15, где n3 равно 2 или 5 и L2 является одинарной связью.
17. Конъюгат антитела с лекарственным средством по п.14 или 15, где n3 равно 2 или 5, L2 является -NH-(CH2CH2-O)n4-CH2CH2-C(=O)- и n4 равно 2 или 4.
18. Конъюгат антитела с лекарственным средством по любому из пп.14-17, где -NH-(CH2)n1-La-(CH2)n2-C(=O)- является любой из следующих групп:
-NH-CH2CH2CH2-C(=O)-
-NH-CH2-O-CH2-C(=O)-
-NH-CH2CH2-O-CH2-C(=O)-
19. Конъюгат антитела с лекарственным средством по любому из пп.1-18, где среднее количество единиц выбранной одной структуры лекарственное средство-связующая группа, конъюгированной с молекулой антитела составляет от 1 до 10.
20. Конъюгат антитела с лекарственным средством по любому из пп.1-18, где среднее количество единиц выбранной одной структуры лекарственное средство-связующая группа, конъюгированной с молекулой антитела составляет от 2 до 8.
21. Конъюгат антитела с лекарственным средством по любому из пп.1-18, где среднее количество единиц выбранной одной структуры лекарственное средство-связующая группа, конъюгированной с молекулой антитела составляет от 3 до 8.
22. Лекарственное средство, содержащее конъюгат антитела с лекарственным средством по любому из пп.1-21, его соль или его гидрат.
23. Противоопухолевое лекарственное средство и/или противораковое лекарственное средство, содержащее конъюгат антитела с лекарственным средством по любому из пп.1-21, его соль или его гидрат.
24. Противоопухолевое лекарственное средство и/или противораковое лекарственное средство по п.23, предназначенное для использования при раке легкого, уротелиальном раке, раке ободочной и прямой кишки, раке предстательной железы, раке яичников, раке поджелудочной железы, раке молочной железы, раке мочевого пузыря, раке желудка, гастроинтестинальной стромальной опухоли, раке шейки матки, раке пищевода, плоскоклеточном раке, перитонеальном раке, раке печени, печеночно-клеточном раке, раке толстой кишки, раке прямой кишки, раке ободочной и прямой кишки, раке эндометрия, раке матки, раке слюнной железы, раке почки, раке вульвы, раке щитовидной железы, раке полового члена, лейкемии, злокачественной лимфоме, плазмоцитоме, миеломе или саркоме.
25. Фармацевтическая композиция, содержащая конъюгат антитела с лекарственным средством по любому из пп.1-21, его соль или его гидрат, в качестве активного компонента, и фармацевтические приемлемый наполнитель.
26. Фармацевтическая композиция по п.25, предназначенная для использования при раке легкого, уротелиальном раке, раке ободочной и прямой кишки, раке предстательной железы, раке яичников, раке поджелудочной железы, раке молочной железы, раке мочевого пузыря, раке желудка, гастроинтестинальной стромальной опухоли, раке шейки матки, раке пищевода, плоскоклеточном раке, перитонеальном раке, раке печени, печеночно-клеточном раке, раке толстой кишки, раке прямой кишки, раке ободочной и прямой кишки, раке эндометрия, раке матки, раке слюнной железы, раке почки, раке вульвы, раке щитовидной железы, раке полового члена, лейкемии, злокачественной лимфоме, плазмоцитоме, миеломе или саркоме.
27. Способ лечения опухоли и/или рака, включающий введение конъюгата антитела с лекарственным средством по любому из пп.1-21, его соли или его гидрата.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2014017777 | 2014-01-31 | ||
| JP2014-017777 | 2014-01-31 | ||
| JP2014-168944 | 2014-08-22 | ||
| JP2014168944 | 2014-08-22 | ||
| JP2014-227886 | 2014-11-10 | ||
| JP2014227886 | 2014-11-10 | ||
| PCT/JP2015/000355 WO2015115091A1 (ja) | 2014-01-31 | 2015-01-28 | 抗ｈｅｒ２抗体－薬物コンジュゲート |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019107788A Division RU2794183C2 (ru) | 2014-01-31 | 2015-01-28 | Анти-her2 конъюгат антитела с лекарственным средством |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| RU2016123597A true RU2016123597A (ru) | 2018-03-02 |
| RU2016123597A3 RU2016123597A3 (ru) | 2018-10-12 |
| RU2683780C2 RU2683780C2 (ru) | 2019-04-02 |
| RU2683780C3 RU2683780C3 (ru) | 2023-10-13 |
Family
ID=
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2016143351A (ru) | Конъюгат анти-her3 антитело-лекарственное средство | |
| JP2017095457A5 (ru) | ||
| ES2966473T3 (es) | Derivados de camptotecina | |
| ES2826398T3 (es) | Enlazadores-fármacos pegilados para una mejor farmacocinética de los conjugados ligando-fármaco | |
| US9884123B2 (en) | Ligand-targeted molecules and methods thereof | |
| RU2015113767A (ru) | Конъюгат антитело-лекарственное средство | |
| US20200392108A1 (en) | Antibody-drug conjugates and related compounds, compositions and methods | |
| JP2015508074A5 (ru) | ||
| FI3283521T3 (fi) | Lääkekonjugaatteja käsittäen vasta-aineita claudiinia 18.2 vastaan | |
| ES2975330T3 (es) | Compuestos que comprenden un enlazador para aumentar la estabilidad del trans-cicloocteno | |
| BR112020020466A2 (pt) | Conjugados de peptídeo de camptotecina | |
| CY1122662T1 (el) | Προϊοντα συζευξης αντισωματος φαρμακου | |
| JP2021503450A5 (ru) | ||
| ES2909486T3 (es) | Sistemas de administración para liberación controlada de fármaco | |
| WO2014145090A1 (en) | Biologically active molecules, conjugates thereof, and therapeutic uses | |
| ES2981364T3 (es) | Compuestos para liberación clic rápida y eficiente | |
| US20200297693A1 (en) | Glucose conjugates of triptolide, analogs and uses thereof | |
| TR201900176T4 (tr) | Anti-TROP2 antikor-ilaç konjugatı. | |
| JP2014511348A5 (ru) | ||
| JP2014523412A5 (ru) | ||
| WO2004073656A3 (en) | Anti-cd70 antibody-drug conjugates and their use for the treatment of cancer and immune disorders | |
| RU2018104266A (ru) | Полилигандные лекарственные конъюгаты и их применения | |
| RS20080002A (en) | N-phenyl-2-pyrimidine-amine derivatives and process for the preparation thereof | |
| JP2018058822A5 (ru) | ||
| JPWO2020027100A5 (ru) |