PE20190512A1 - Conjugados de anticuerpo anti-egfr y farmaco - Google Patents
Conjugados de anticuerpo anti-egfr y farmacoInfo
- Publication number
- PE20190512A1 PE20190512A1 PE2018003191A PE2018003191A PE20190512A1 PE 20190512 A1 PE20190512 A1 PE 20190512A1 PE 2018003191 A PE2018003191 A PE 2018003191A PE 2018003191 A PE2018003191 A PE 2018003191A PE 20190512 A1 PE20190512 A1 PE 20190512A1
- Authority
- PE
- Peru
- Prior art keywords
- halo
- hydrogen
- optionally substituted
- antibody
- drug
- Prior art date
Links
- 229940127121 immunoconjugate Drugs 0.000 title 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 4
- 229910052739 hydrogen Inorganic materials 0.000 abstract 4
- 239000001257 hydrogen Substances 0.000 abstract 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 4
- 239000003814 drug Substances 0.000 abstract 3
- 229940079593 drug Drugs 0.000 abstract 3
- 229940122035 Bcl-XL inhibitor Drugs 0.000 abstract 2
- 206010028980 Neoplasm Diseases 0.000 abstract 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 abstract 2
- 125000005647 linker group Chemical group 0.000 abstract 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 abstract 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- 125000000217 alkyl group Chemical group 0.000 abstract 1
- 125000000732 arylene group Chemical group 0.000 abstract 1
- 125000004429 atom Chemical group 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 125000004093 cyano group Chemical group *C#N 0.000 abstract 1
- 125000004474 heteroalkylene group Chemical group 0.000 abstract 1
- 229940116978 human epidermal growth factor Drugs 0.000 abstract 1
- 230000002401 inhibitory effect Effects 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 229920005862 polyol Polymers 0.000 abstract 1
- 150000003077 polyols Chemical class 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
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- 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
- A61K39/39591—Stabilisation, fragmentation
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- 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
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- 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
- A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
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- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- 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
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- 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
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/51—Complete heavy chain or Fd fragment, i.e. VH + CH1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/515—Complete light chain, i.e. VL + CL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- 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)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Gastroenterology & Hepatology (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Se refiere a un conjugado de anticuerpo y farmaco (ADC) anti-receptor del factor de crecimiento epidermico humano (hEGFR), siendo el farmaco un inhibidor de Bcl-xL de formulas estructurales (IIa), (IIb), (IIc) y (IId), donde Ar1 es (a), (b), (c), entre otros, opcionalmente sustituidos por halo, hidroxi, nitro, entre otros; Ar2 es (aa), (bb), (cc), entre otros, opcionalmente sustituidos por halo, hidroxi, nitro, entre otros; Z1 se selecciona entre N, CH, entre otros; Z2a y Z2b son un enlace, O, S, S(O)2, entre otros; R' es (ab) o (ac); X' es -O- u otros; n es 0-3; G es un poliol, una sal, entre otros; SPa es oxigeno, -N(H)-, arileno, entre otros; m2 es 0-12; R1 y R2 son hidrogeno, metilo, halo, entre otros; R4 es hidrogeno, alquilo inferior, entre otros; R11a y R11b son hidrogeno, halo, metilo, metoxi, entre otros; R12 es R', hidrogeno, ciano, entre otros; R13 es heteroalquileno opcionalmente sustituido, heterocicleno opcionalmente sustituido, entre otros; #, si esta unido a R', se une en cualquier atomo sustituible de este, siendo el punto de union a un enlazador L segun la formula estructural (I), donde D es el farmaco inhibidor de Bcl-xL de formula IIa, IIb, IIc o IId; Ab es el anticuerpo anti-hEGFR; LK es la union covalente entre el enlazador (L) y el anticuerpo anti-hEGFR (Ab); y m es un numero entero entre 1 y 20. Tambien se refiere a composiciones y metodos de preparacion. La presente invencion es util para el tratamiento del cancer mediante inhibicion o reduccion de los tumores solidos
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662347416P | 2016-06-08 | 2016-06-08 |
Publications (1)
Publication Number | Publication Date |
---|---|
PE20190512A1 true PE20190512A1 (es) | 2019-04-10 |
Family
ID=59078219
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PE2018003191A PE20190512A1 (es) | 2016-06-08 | 2017-06-07 | Conjugados de anticuerpo anti-egfr y farmaco |
Country Status (21)
Country | Link |
---|---|
US (2) | US20190343961A1 (es) |
EP (2) | EP3468996B1 (es) |
JP (3) | JP2019521106A (es) |
KR (2) | KR20230035690A (es) |
CN (4) | CN109563168A (es) |
AU (1) | AU2017277517A1 (es) |
BR (1) | BR112018075636A2 (es) |
CA (1) | CA3027178A1 (es) |
CL (2) | CL2018003527A1 (es) |
CO (1) | CO2018013497A2 (es) |
CR (1) | CR20180614A (es) |
DO (2) | DOP2018000272A (es) |
EC (1) | ECSP19000157A (es) |
IL (3) | IL308054A (es) |
MX (2) | MX2018015286A (es) |
PE (1) | PE20190512A1 (es) |
PH (1) | PH12018502602A1 (es) |
RU (1) | RU2018147224A (es) |
SG (2) | SG11201810970WA (es) |
TW (2) | TW202320860A (es) |
WO (1) | WO2017214282A1 (es) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109562190A (zh) * | 2016-06-08 | 2019-04-02 | 艾伯维公司 | 抗egfr抗体药物偶联物 |
CN116284404A (zh) | 2016-06-08 | 2023-06-23 | 艾伯维公司 | 抗b7-h3抗体和抗体药物偶联物 |
WO2018218004A1 (en) * | 2017-05-24 | 2018-11-29 | The Board Of Regents Of The University Of Texas System | Linkers for antibody drug conjugates |
US11717575B2 (en) | 2019-05-20 | 2023-08-08 | Mabplex International Co., Ltd. | One-pot process for preparing intermediate of antibody-drug conjugate |
PE20220218A1 (es) | 2019-05-20 | 2022-02-02 | Novartis Ag | Conjugados de anticuerpo-farmaco inhibidores de mcl-1 y sus metodos de uso |
KR20210097627A (ko) | 2020-01-30 | 2021-08-09 | 성균관대학교산학협력단 | 면역관문 억제제 및 엑소좀 분비 억제제를 포함하는 항체-약물 접합체 및 이를 포함하는 약학적 조성물 |
IL298284A (en) | 2020-05-19 | 2023-01-01 | Servier Lab | Para-amino-benzyl linkers, a process for their preparation and their use in conjugates |
IL303048A (en) | 2020-11-24 | 2023-07-01 | Novartis Ag | BCL-XL inhibitor antibody-drug conjugates and methods of using them |
AR124681A1 (es) | 2021-01-20 | 2023-04-26 | Abbvie Inc | Conjugados anticuerpo-fármaco anti-egfr |
WO2022271722A1 (en) * | 2021-06-22 | 2022-12-29 | Regeneron Pharmaceuticals, Inc. | Anti-egfrviii antibody drug conjugates and uses thereof |
CN117580846A (zh) * | 2022-04-29 | 2024-02-20 | 石药集团中奇制药技术(石家庄)有限公司 | 具有肝靶向递送效应的化合物及其寡聚核苷酸缀合物 |
TW202408588A (zh) | 2022-05-20 | 2024-03-01 | 瑞士商諾華公司 | 抗體-藥物結合物抗腫瘤化合物及其使用方法 |
WO2023223097A1 (en) | 2022-05-20 | 2023-11-23 | Novartis Ag | Antibody drug conjugates |
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2017
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- 2017-06-07 US US16/308,463 patent/US20190343961A1/en not_active Abandoned
- 2017-06-07 KR KR1020237007108A patent/KR20230035690A/ko active Application Filing
- 2017-06-07 CN CN201780048216.7A patent/CN109563168A/zh active Pending
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2018
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2019
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2021
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