HRP20240005T1 - Multispecifični mutirani fab fragmenti protutijela - Google Patents
Multispecifični mutirani fab fragmenti protutijela Download PDFInfo
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- HRP20240005T1 HRP20240005T1 HRP20240005TT HRP20240005T HRP20240005T1 HR P20240005 T1 HRP20240005 T1 HR P20240005T1 HR P20240005T T HRP20240005T T HR P20240005TT HR P20240005 T HRP20240005 T HR P20240005T HR P20240005 T1 HRP20240005 T1 HR P20240005T1
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- antigen
- multispecific
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Links
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 title claims 12
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 title claims 12
- 239000000427 antigen Substances 0.000 claims 15
- 102000036639 antigens Human genes 0.000 claims 15
- 108091007433 antigens Proteins 0.000 claims 15
- 239000012634 fragment Substances 0.000 claims 11
- 108060003951 Immunoglobulin Proteins 0.000 claims 9
- 102000018358 immunoglobulin Human genes 0.000 claims 9
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 6
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 5
- 229920001184 polypeptide Polymers 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 3
- 102000040430 polynucleotide Human genes 0.000 claims 3
- 108091033319 polynucleotide Proteins 0.000 claims 3
- 239000002157 polynucleotide Substances 0.000 claims 3
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims 3
- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 2
- 210000004899 c-terminal region Anatomy 0.000 claims 2
- 125000000404 glutamine group Chemical group N[C@@H](CCC(N)=O)C(=O)* 0.000 claims 2
- 229940072221 immunoglobulins Drugs 0.000 claims 2
- 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- 229940024606 amino acid Drugs 0.000 claims 1
- 150000001413 amino acids Chemical class 0.000 claims 1
- 125000000613 asparagine group Chemical group N[C@@H](CC(N)=O)C(=O)* 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- 238000011084 recovery Methods 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
-
- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2833—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
-
- 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
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/52—Constant or Fc region; Isotype
- C07K2317/522—CH1 domain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
Claims (11)
1. Multispecifični fragment koji veže antigen koji sadrži dvije ili više regija koje vežu antigen, od kojih svaka prepoznaje drukčiji epitop, koji sadrži barem mutirani Fab fragment koji se sastoji od:
– VH i VL domene protutijela koje prepoznaju epitop od interesa;
– CH1 domene koja je izvedena iz CH1 domene humanog IgG1 imunoglobulina supstitucijom ostatka leucina na položaju 143 navedene CH1 domene s ostatkom glutamina i supstitucijom ostatka serina na položaju 188 navedene CH1 domene s ostatkom valina; i
– CL domene tipa kapa koja je izvedena iz CL domene humanog imunoglobulina supstitucijom ostatka valina na položaju 133 navedene CL domene s ostatkom treonina i supstitucijom ostatka serina na položaju 176 navedene CL domene s ostatkom valina,
pri čemu se brojevi položaja slijeda odnose na shemu za numeriranje Kabat.
2. Multispecifični fragment koji veže antigen u skladu sa zahtjevom 1, koji se sastoji od barem dva sljedeća različita Fab fragmenta:
a) mutiranog Fab fragmenta koji se sastoji od:
* VH i VL domene protutijela koje prepoznaju epitop od interesa;
* CH1 domene koja je izvedena iz CH1 domene humanog IgG1 imunoglobulina supstitucijom ostatka leucina na položaju 143 navedene CH1 domene s ostatkom glutamina i supstitucijom ostatka serina na položaju 188 navedene CH1 domene s ostatkom valina; i
* CL domene tipa kapa koja je izvedena iz CL domene humanog imunoglobulina supstitucijom ostatka valina na položaju 133 navedene CL domene s ostatkom treonina i supstitucijom ostatka serina na položaju 176 navedene CL domene s ostatkom valina;
i
b) barem još jednog Fab fragmenta koji je odabran iz skupine koja se sastoji od:
b1) Fab fragmenta divljeg tipa koji se sastoji od CH1 i CL domena divljeg tipa humanog imunoglobulina te VH i VL domena protutijela koje prepoznaju epitop od interesa;
b2) mutiranog Fab fragmenta (a) koji se sastoji od:
* VH i VL domene protutijela koje prepoznaju epitop od interesa;
* CH1 domene koja je izvedena iz CH1 domene humanog IgG1 imunoglobulina supstitucijom ostatka treonina na položaju 192 navedene CH1 domene s ostatkom glutaminske kiseline; i
* CL domene tipa kapa koja je izvedena iz CL domene humanog imunoglobulina supstitucijom ostatka asparagina na položaju 137 navedene CL domene s ostatkom lizina i supstitucijom ostatka serina na položaju 114 navedene CL domene s ostatkom alanina;
pri čemu se brojevi položaja slijeda odnose na shemu za numeriranje Kabat, i
pri čemu svaki Fab fragment prepoznaje drukčiji epitop od interesa, a navedeni Fab fragmenti tandemski su raspoređeni bilo kojim redoslijedom, pri čemu je C-terminalni kraj CH1 domene prvog Fab fragmenta povezan s N-terminalnim krajem VH domene sljedećeg Fab fragmenta kroz polipeptidni povezivač.
3. Multispecifični fragment koji veže antigen u skladu sa zahtjevom 2, pri čemu polipeptidni povezivač ima duljinu od barem 20 aminokiselina.
4. Multispecifični fragment koji veže antigen u skladu s bilo kojim od zahtjeva 2 ili 3, pri čemu polipeptidni povezivač sadrži cijeli ili dio slijeda zglobne regije jednoga ili više imunoglobulina odabranih između IgA, IgG i IgD.
5. Multispecifični fragment koji veže antigen u skladu s bilo kojim od zahtjeva 2 do 4, pri čemu polipeptidni povezivač ima sljedeći slijed:
EPKSCDKTHTCPPCPAPELLGGPSTPPTPSPSGG
6. Multispecifično protutijelo koje ima dva identična kraka za vezanje antigena, od kojih se svaki sastoji od multispecifičnog fragmenta za vezanje antigena u skladu s bilo kojim od zahtjeva 1 do 5.
7. Multispecifično protutijelo u skladu sa zahtjevom 6 koje se sastoji od:
– dvaju identičnih krakova za vezanje antigena od kojih se svaki sastoji od multispecifičnog fragmenta za vezanje antigena u skladu s bilo kojim od zahtjeva 1 do 5;
– dimeriziranih CH2 i CH3 domena imunoglobulina;
– zglobnih regija IgA, IgG ili IgD, koje povezuju C-terminalne krajeve CH1 domena krakova koji vežu antigen s N-terminalnim krajevima CH2 domena.
8. Stanica domaćina transformirana s polinukleotidom koji kodira teški lanac multispecifičnog fragmenta koji veže antigen u skladu s bilo kojim od zahtjeva 1 do 5 ili multispecifičnog protutijela u skladu s bilo kojim od zahtjeva 6 ili 7 i barem dva polinukleotida koji kodiraju dva različita laka lanca: uparivanje prvog lakog lanca specifično s prvom VH/CH1 regijom navedenog teškog lanca; uparivanje drugog lakog lanca specifično s drugom VH/CH1 regijom navedenog teškog lanca, a barem jedan od navedenih lakih lanaca je laki lanac mutiranog Fab fragmenta kako je definirano u zahtjevu 1.
9. Stanica domaćin u skladu sa zahtjevom 8, koja je dodatno transformirana trećim polinukleotidom koji kodira treći laki lanac koji se razlikuje od prvog i drugog lakog lanca te koji se specifično spaja s trećom VH/CH1 regijom navedenog teškog lanca.
10. Postupak za pripremu multispecifičnog fragmenta koji veže antigen u skladu s bilo kojim od zahtjeva 1 do 4 ili multispecifičnog protutijela u skladu s bilo kojim od zahtjeva 5 ili 6, pri čemu navedena metoda uključuje uzgoj stanice domaćina u skladu sa zahtjevom 8 ili 9 i obnavljanje navedenog fragmenta koji veže antigen ili protutijela iz navedene kulture.
11. Multispecifični fragment koji veže antigen u skladu s bilo kojim od zahtjeva 1 do 5 ili multispecifično protutijelo u skladu s bilo kojim od zahtjeva 6 ili 7, za upotrebu kao lijek.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11305872A EP2543680A1 (en) | 2011-07-07 | 2011-07-07 | Multispecific mutated antibody Fab fragments |
| EP20168633.4A EP3872095B1 (en) | 2011-07-07 | 2012-07-06 | Multispecific mutated antibody fab fragments |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20240005T1 true HRP20240005T1 (hr) | 2024-03-29 |
Family
ID=44904654
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20240005TT HRP20240005T1 (hr) | 2011-07-07 | 2012-07-06 | Multispecifični mutirani fab fragmenti protutijela |
| HRP20201191TT HRP20201191T1 (hr) | 2011-07-07 | 2020-07-28 | Mutirani multispecifični fab fragmenti antitijela |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20201191TT HRP20201191T1 (hr) | 2011-07-07 | 2020-07-28 | Mutirani multispecifični fab fragmenti antitijela |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US9631031B2 (hr) |
| EP (4) | EP2543680A1 (hr) |
| JP (1) | JP6305332B2 (hr) |
| KR (1) | KR102095886B1 (hr) |
| CN (1) | CN103797033B (hr) |
| CA (2) | CA3099509C (hr) |
| CY (1) | CY1123484T1 (hr) |
| DK (2) | DK2729499T3 (hr) |
| ES (1) | ES2816701T3 (hr) |
| FI (1) | FI3872095T3 (hr) |
| HR (2) | HRP20240005T1 (hr) |
| HU (1) | HUE051620T2 (hr) |
| LT (2) | LT3872095T (hr) |
| MX (1) | MX351418B (hr) |
| PL (1) | PL2729499T3 (hr) |
| PT (2) | PT2729499T (hr) |
| SI (1) | SI2729499T1 (hr) |
| WO (1) | WO2013005194A2 (hr) |
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| EP2543680A1 (en) * | 2011-07-07 | 2013-01-09 | Centre National de la Recherche Scientifique | Multispecific mutated antibody Fab fragments |
| US20130058947A1 (en) | 2011-09-02 | 2013-03-07 | Stem Centrx, Inc | Novel Modulators and Methods of Use |
| MX362705B (es) | 2012-05-10 | 2019-02-01 | Bioatla Llc | Anticuerpos monoclonales multiespecíficos. |
| US9914785B2 (en) | 2012-11-28 | 2018-03-13 | Zymeworks Inc. | Engineered immunoglobulin heavy chain-light chain pairs and uses thereof |
| EP2925785A4 (en) * | 2012-11-28 | 2016-11-16 | Zymeworks Inc | MANIPULATED IMMUNOGLOBULIN HEAVY CHAIN LIGHT CHAIN COUPLES AND USES THEREOF |
| US10047163B2 (en) | 2013-02-08 | 2018-08-14 | Abbvie Stemcentrx Llc | Multispecific constructs |
| US20160145355A1 (en) * | 2013-06-24 | 2016-05-26 | Biomed Valley Discoveries, Inc. | Bispecific antibodies |
| DK3107938T3 (da) | 2014-05-28 | 2022-07-11 | Zymeworks Inc | Modificerede, antigenbindende polypeptidkonstrukter og anvendelser heraf |
| GB201411420D0 (en) * | 2014-06-26 | 2014-08-13 | Ucb Biopharma Sprl | Antibody constructs |
| CN104371974B (zh) * | 2014-10-24 | 2017-03-22 | 杭州阿诺生物医药科技股份有限公司 | 一种自体外周血淋巴细胞cik的培养方法 |
| EP3212231B1 (en) * | 2014-10-27 | 2021-04-28 | Agency For Science, Technology And Research | Anti-tim-3 antibodies |
| AU2016252773B2 (en) * | 2015-04-24 | 2022-06-02 | Genentech, Inc. | Multispecific antigen-binding proteins |
| MY192202A (en) * | 2015-10-02 | 2022-08-06 | Hoffmann La Roche | Bispecific antibodies specific for pd1 and tim3 |
| US11161915B2 (en) | 2015-10-08 | 2021-11-02 | Zymeworks Inc. | Antigen-binding polypeptide constructs comprising kappa and lambda light chains and uses thereof |
| AU2016381605A1 (en) | 2015-12-28 | 2018-07-12 | Massachusetts Institute Of Technology | Bispecific antibodies having constant region mutations and uses therefor |
| DK3433273T3 (da) | 2016-03-25 | 2022-02-14 | Biomunex Pharmaceuticals | Binding af molekyler til cd38 og pd-l1 |
| CN109563166B (zh) * | 2016-04-28 | 2022-12-20 | 拜奥穆尼克斯制药 | 靶向egfr和her2的双特异性抗体 |
| KR20170123849A (ko) * | 2016-04-29 | 2017-11-09 | 주식회사유한양행 | Ccl3 변이체를 포함하는 융합 단백질 및 이의 용도 |
| EP3489262A4 (en) * | 2016-07-19 | 2020-07-08 | Ibentrus, Inc. | SPECIFIC PROTEINS AND METHOD FOR THE PRODUCTION THEREOF |
| JP7269167B2 (ja) * | 2016-10-14 | 2023-05-08 | デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド | モジュラー四価二重特異性抗体プラットフォーム |
| CN108264557B (zh) * | 2016-12-30 | 2021-08-24 | 惠和生物技术(上海)有限公司 | 一种结合cd3和t细胞负共刺激分子的双功能分子及其应用 |
| CN108264562B (zh) * | 2016-12-30 | 2021-08-10 | 惠和生物技术(上海)有限公司 | 一种结合cd3和t细胞正共刺激分子的双功能分子及其应用 |
| CN110520444A (zh) | 2017-01-09 | 2019-11-29 | 拜奥穆尼克斯制药 | 用于制备多特异性抗体的多肽接头 |
| BR112019019998A2 (pt) * | 2017-03-27 | 2020-04-28 | Biomunex Pharmaceuticals | anticorpos multiespecíficos estáveis |
| MX2019011770A (es) | 2017-04-03 | 2020-01-09 | Hoffmann La Roche | Inmunoconjugados de un anticuerpo anti-pd-1 con un mutante il-2 o con il-15. |
| CN116375876A (zh) | 2017-04-05 | 2023-07-04 | 豪夫迈·罗氏有限公司 | 特异性结合pd1和lag3的双特异性抗体 |
| FR3072686B1 (fr) | 2017-10-25 | 2021-10-22 | Centre Nat Rech Scient | Systeme d'expression baculovirus |
| CA3084398A1 (en) * | 2018-01-15 | 2019-07-18 | I-Mab Biopharma Us Limited | Modified c.kappa. and ch1 domains |
| EP3674316A1 (en) | 2018-12-24 | 2020-07-01 | Sanofi | Multispecific binding proteins with mutant fab domains |
| AU2019412561A1 (en) * | 2018-12-24 | 2021-08-12 | Sanofi | Multispecific binding proteins with mutant Fab domains |
| WO2021058729A1 (en) | 2019-09-27 | 2021-04-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti-müllerian inhibiting substance type i receptor antibodies and uses thereof |
| EP4322938A1 (en) | 2021-04-14 | 2024-02-21 | Institut National de la Santé et de la Recherche Médicale (INSERM) | New method to improve nk cells cytotoxicity |
| WO2022219076A1 (en) | 2021-04-14 | 2022-10-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New method to improve the anti-tumoral activity of macrophages |
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-
2011
- 2011-07-07 EP EP11305872A patent/EP2543680A1/en not_active Ceased
-
2012
- 2012-07-06 EP EP23173235.5A patent/EP4252772A3/en active Pending
- 2012-07-06 CN CN201280033847.9A patent/CN103797033B/zh active Active
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