RU2018112861A - Стабильные антитела, связывающиеся с несколькими антигенами - Google Patents
Стабильные антитела, связывающиеся с несколькими антигенами Download PDFInfo
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- RU2018112861A RU2018112861A RU2018112861A RU2018112861A RU2018112861A RU 2018112861 A RU2018112861 A RU 2018112861A RU 2018112861 A RU2018112861 A RU 2018112861A RU 2018112861 A RU2018112861 A RU 2018112861A RU 2018112861 A RU2018112861 A RU 2018112861A
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- Prior art keywords
- antibody
- binds
- several antigens
- antigens according
- aho
- Prior art date
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- 239000000427 antigen Substances 0.000 title claims 25
- 102000036639 antigens Human genes 0.000 title claims 25
- 108091007433 antigens Proteins 0.000 title claims 25
- 108090000765 processed proteins & peptides Proteins 0.000 claims 9
- 239000004473 Threonine Chemical group 0.000 claims 8
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Chemical group CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims 8
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 7
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical group OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims 4
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 claims 4
- 239000004475 Arginine Substances 0.000 claims 3
- 101710098119 Chaperonin GroEL 2 Proteins 0.000 claims 3
- 101000588258 Taenia solium Paramyosin Proteins 0.000 claims 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 2
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims 2
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims 2
- 235000001014 amino acid Nutrition 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 2
- 238000006467 substitution reaction Methods 0.000 claims 2
- 239000004474 valine Substances 0.000 claims 2
- 101100484454 Arabidopsis thaliana VHA-A gene Proteins 0.000 claims 1
- 239000004471 Glycine Substances 0.000 claims 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims 1
- 239000004472 Lysine Substances 0.000 claims 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 1
- 235000004279 alanine Nutrition 0.000 claims 1
- 238000003745 diagnosis Methods 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
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- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- 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
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Claims (28)
1. Антитело, связывающееся с несколькими антигенами, содержащее:
два вариабельных домена тяжелой цепи, один из которых характеризуется специфичностью к антигену А (VH-A), а другой - специфичностью к антигену B (VH-B), и
два вариабельных домена легкой цепи, один из которых характеризуется специфичностью к антигену A (VL-A) а другой - специфичностью к антигену B (VL-B),
где по меньшей мере один из двух вариабельных доменов тяжелой цепи содержит по меньшей мере один из следующих остатков: серин в положении AHo 12, серин или треонин в положении AHo 103, и серин или треонин в положении AHo 144; и/или
где по меньшей мере один из двух вариабельных доменов легкой цепи содержит аргинин в положении AHo 50.
2. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что VH-A соединен с VL-B посредством пептидного линкера 1 с образованием конструкции VH-A/VL-B, и VH-B соединен с VL-A посредством пептидного линкера 2 с образованием конструкции VH-B/VL-A.
3. Антитело, связывающееся с несколькими антигенами, по п. 2, отличающееся тем, что указанная конструкция VH-A/VL-B находится в ориентации VH-A-(линкер 1)-VL-B.
4. Антитело, связывающееся с несколькими антигенами, по п. 2, отличающееся тем, указанная конструкция VH-B/VL-A находится в ориентации VH-B-(линкер 2)-VL-A.
5. Антитело, связывающееся с несколькими антигенами, по п. 2, отличающееся тем, что пептидный линкер 1 и пептидный линкер 2 каждый содержат 1-10 аминокислот.
6. Антитело, связывающееся с несколькими антигенами, по п. 5, отличающееся тем, что пептидный линкер 1 содержит последовательность GGGGS (SEQ ID №: 1), а пептидный линкер 2 содержит последовательность GGGGS (SEQ ID №: 1).
7. Антитело, связывающееся с несколькими антигенами, по п. 2, отличающееся тем, что конструкция VH-A/VL-B дополнительно связана с конструкцией VH-B/VL-A пептидным линкером 3.
8. Антитело, связывающееся с несколькими антигенами, по п. 7, отличающееся тем, что пептидный линкер 3 содержит 10-30 аминокислот.
9. Антитело, связывающееся с несколькими антигенами, по п. 8, отличающееся тем, что пептидный линкер 3 содержит последовательность (GGGGS)4 (SEQ ID №: 4).
10. Антитело, связывающееся с несколькими антигенами, по п. 1, в форме VH-A-SEQ ID №: 1-VL-B-SEQ ID №: 4-VH-B-SEQ ID №: 1-VL-A.
11. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что указанный VH-A соединен с VL-A, и вместе они образуют одноцепочечное антитело со специфичностью к антигену A (scFv A), а VH-B соединен с VL-B, и вместе они образуют одноцепочечное антитело со специфичностью к антигену B (scFv B).
12. Антитело, связывающееся с несколькими антигенами, по п. 11, отличающееся тем, что указанный scFv-A соединен с scFv-B в следующей форме: VH-A/VL-A - линкер 3 - VH-B/VL-B.
13. Антитело, связывающееся с несколькими антигенами, по п. 12, отличающееся тем, что указанный линкер 3 содержит последовательность SEQ ID №: 4.
14. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что по меньшей мере один из двух вариабельных доменов легкой цепи является или получен из вариабельного домена легкой цепи человека из семейства Vkappa1.
15. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что по меньшей мере один из двух вариабельных доменов тяжелой цепи является или получен из вариабельного домена тяжелой цепи человека из семейства VH3.
16. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что домены VH и VL содержат CDR из антитела зайцеобразных.
17. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что VH-A и/или VH-B содержат серин в положении AHo 12, треонин в положении AHo 103, и треонин в положении AHo 144.
18. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что аргинин в положении AHo 50 of VL-A и/или VL-B вводят посредством замены.
19. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что по меньшей мере один из перечисленных остатков - серин в положении AHo 12, серин или треонин в положении AHo 103, и серин или треонин в положении AHo 144 в VH-A и/или VH-B вводят посредством замены.
20. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что указанное антитело является бивалентным.
21. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что указанное антитело является биспецифическим.
22. Антитело, связывающееся с несколькими антигенами, по п. 1, отличающееся тем, что по меньшей мере один из указанных вариабельных доменов тяжелой цепи содержит по меньшей мере три из следующих остатков: треонин (T) в положении AHo 24, валин (V) в положении AHo 25, аланин (A) or глицин (G) в положении AHo 56, лизин (K) в положении AHo 82, треонин (T) в положении AHo 84, валин (V) в положении AHo 89 и аргинин (R) в положении AHo 108.
23. Фармацевтическая композиция, содержащая антитело, связывающееся с несколькими антигенами, по п. 1.
24. Применение антитела, связывающегося с несколькими антигенами, по п. 1 для диагностики и/или лечения заболевания.
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- 2012-10-19 AR ARP120103914A patent/AR088403A1/es unknown
- 2012-10-19 CA CA2850572A patent/CA2850572A1/en not_active Abandoned
- 2012-10-19 WO PCT/EP2012/004404 patent/WO2013056851A2/en not_active Ceased
-
2017
- 2017-04-21 JP JP2017084447A patent/JP2017125066A/ja active Pending
-
2019
- 2019-02-27 US US16/286,816 patent/US20200048336A1/en not_active Abandoned
- 2019-03-29 JP JP2019067016A patent/JP2019104759A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN103890005A (zh) | 2014-06-25 |
| TWI577696B (zh) | 2017-04-11 |
| KR20140082700A (ko) | 2014-07-02 |
| AR088403A1 (es) | 2014-05-28 |
| MX2014004521A (es) | 2014-05-28 |
| EP3431495A1 (en) | 2019-01-23 |
| UY34404A (es) | 2013-05-31 |
| US20200048336A1 (en) | 2020-02-13 |
| EP2768855B1 (en) | 2018-06-13 |
| JP2019104759A (ja) | 2019-06-27 |
| ES2687245T3 (es) | 2018-10-24 |
| AU2012325232B2 (en) | 2017-08-31 |
| JP2014533239A (ja) | 2014-12-11 |
| AU2012325232A1 (en) | 2014-06-05 |
| CA2850572A1 (en) | 2013-04-25 |
| CN109608543A (zh) | 2019-04-12 |
| TW201323445A (zh) | 2013-06-16 |
| JP2017125066A (ja) | 2017-07-20 |
| BR112014009030A2 (pt) | 2017-09-12 |
| AU2012325232A8 (en) | 2014-06-26 |
| WO2013056851A3 (en) | 2013-06-13 |
| RU2014120154A (ru) | 2015-11-27 |
| RU2018112861A3 (ru) | 2021-08-12 |
| RU2652886C2 (ru) | 2018-05-03 |
| US20130101586A1 (en) | 2013-04-25 |
| WO2013056851A2 (en) | 2013-04-25 |
| EP2768855A2 (en) | 2014-08-27 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20220126 |