RU2014142680A - Способ улучшения функциональных свойств антитела или его антигенсвязывающего фрагмента - Google Patents
Способ улучшения функциональных свойств антитела или его антигенсвязывающего фрагмента Download PDFInfo
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- 239000012634 fragment Substances 0.000 title claims abstract 9
- 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 abstract 19
- 235000001014 amino acid Nutrition 0.000 claims abstract 12
- 150000001413 amino acids Chemical group 0.000 claims abstract 12
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims abstract 9
- 238000002703 mutagenesis Methods 0.000 claims abstract 8
- 231100000350 mutagenesis Toxicity 0.000 claims abstract 8
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims abstract 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims abstract 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims abstract 6
- 229960000310 isoleucine Drugs 0.000 claims abstract 6
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims abstract 6
- 239000004474 valine Substances 0.000 claims abstract 6
- 238000006467 substitution reaction Methods 0.000 claims abstract 5
- 239000000427 antigen Substances 0.000 claims abstract 4
- 102000036639 antigens Human genes 0.000 claims abstract 4
- 108091007433 antigens Proteins 0.000 claims abstract 4
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- 239000004473 Threonine Substances 0.000 claims abstract 3
- 229940024606 amino acid Drugs 0.000 claims abstract 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims abstract 2
- 101001057612 Homo sapiens Dual specificity protein phosphatase 5 Proteins 0.000 claims abstract 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims abstract 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims abstract 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims abstract 2
- 235000004279 alanine Nutrition 0.000 claims abstract 2
- 235000013922 glutamic acid Nutrition 0.000 claims abstract 2
- 239000004220 glutamic acid Substances 0.000 claims abstract 2
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims abstract 2
- 102000043381 human DUSP5 Human genes 0.000 claims abstract 2
- 239000003471 mutagenic agent Substances 0.000 claims abstract 2
- 231100000707 mutagenic chemical Toxicity 0.000 claims abstract 2
- 230000003505 mutagenic effect Effects 0.000 claims abstract 2
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims abstract 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 1
- 102000018358 immunoglobulin Human genes 0.000 claims 1
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- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/241—Tumor Necrosis Factors
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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
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
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- 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
- C07K2317/567—Framework region [FR]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
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Abstract
1. Способ улучшения функциональных свойств антитела или его антигенсвязывающего фрагмента, в котором антитело или антигенсвязывающий фрагмент включают (i) вариабельную область тяжелой цепи или ее фрагмент, при этом вариабельная область тяжелой области содержит каркасные остатки V, и (ii) вариабельную область легкой цепи или ее фрагмент, при этом вариабельная область легкой цепи содержит каркасные остатки V, указанный способ включает:проведение мутагена по одному положению аминокислоты в каркасных участках Vпри этом(i) если тяжелая цепь является тяжелой цепью человеческого VH3 семейства и мутагенез включает замену аланина (А), валина (V), или фенилаланина (F) в 89 положении аминокислоты, по системе нумерации АНо (в положении 78 по системе нумерации Kabat)); и/или(ii) легкая цепь является легкой цепью человеческого Vk1, мутагенез включает заменуa) глутаминовой кислоты (E) или изолейцина (I) в положении аминокислоты 1 по системе нумерации АНо или системе нумерации Kabat;b) валина (V) или изолейцина (I) в положении аминокислоты 3 по системе нумерации АНо или система нумерации или системе нумерации Kabat;c) валина (V), лейцина (L) или изолейцина (I) в положении аминокислоты 4 по системе нумерации АНо или системе нумерации Kabat и/илиd) глутамина (Q) в положении аминокислоты 24 при использовании системы нумерации АНо или системы нумерации Kabat.2. Способ по п. 1, в котором мутазенез дополнительно включает одну или более или более замены в тяжелой цепи, выбранные из группы, состоящей из(i) серина (S) в положении 12 согласно АНо или Kabat;(ii) серина (S) в положении 103 согласно АНо (в положении 85 согласно Kabat); и(iii) серина (S) или треонина (Т) в положении 144 согласно АНо (в положении 103 согласно Kabat).3. Способ по п. 1, в котором мутагенез дополнительно включает следующие замены
Claims (4)
1. Способ улучшения функциональных свойств антитела или его антигенсвязывающего фрагмента, в котором антитело или антигенсвязывающий фрагмент включают (i) вариабельную область тяжелой цепи или ее фрагмент, при этом вариабельная область тяжелой области содержит каркасные остатки VH, и (ii) вариабельную область легкой цепи или ее фрагмент, при этом вариабельная область легкой цепи содержит каркасные остатки VL, указанный способ включает:
проведение мутагена по одному положению аминокислоты в каркасных участках VL при этом
(i) если тяжелая цепь является тяжелой цепью человеческого VH3 семейства и мутагенез включает замену аланина (А), валина (V), или фенилаланина (F) в 89 положении аминокислоты, по системе нумерации АНо (в положении 78 по системе нумерации Kabat)); и/или
(ii) легкая цепь является легкой цепью человеческого Vk1, мутагенез включает замену
a) глутаминовой кислоты (E) или изолейцина (I) в положении аминокислоты 1 по системе нумерации АНо или системе нумерации Kabat;
b) валина (V) или изолейцина (I) в положении аминокислоты 3 по системе нумерации АНо или система нумерации или системе нумерации Kabat;
c) валина (V), лейцина (L) или изолейцина (I) в положении аминокислоты 4 по системе нумерации АНо или системе нумерации Kabat и/или
d) глутамина (Q) в положении аминокислоты 24 при использовании системы нумерации АНо или системы нумерации Kabat.
2. Способ по п. 1, в котором мутазенез дополнительно включает одну или более или более замены в тяжелой цепи, выбранные из группы, состоящей из
(i) серина (S) в положении 12 согласно АНо или Kabat;
(ii) серина (S) в положении 103 согласно АНо (в положении 85 согласно Kabat); и
(iii) серина (S) или треонина (Т) в положении 144 согласно АНо (в положении 103 согласно Kabat).
3. Способ по п. 1, в котором мутагенез дополнительно включает следующие замены в тяжелой цепи:
(i) серина (S) в положении 12 согласно АНо или Kabat;
(ii) серина (S) в положении 103 согласно АНо (в положении 85 согласно Kabat); и
(iii) серина (S) или треонина (Т) в положении 144 согласно АНо (в положении 103 согласно Kabat).
4. Способ по любому из п.п. 1-3, в котором антитело представляет собой scFv антитело, полноразмерный иммуноглобулин, Fab фрагмент, Dab или нанотело.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93711207P | 2007-06-25 | 2007-06-25 | |
| US60/937,112 | 2007-06-25 | ||
| US6905608P | 2008-03-12 | 2008-03-12 | |
| US61/069,056 | 2008-03-12 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2010102065/10A Division RU2540150C2 (ru) | 2007-06-25 | 2008-06-25 | Способы модификации антител и модифицированные антитела с улучшенными функциональными свойствами |
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| Publication Number | Publication Date |
|---|---|
| RU2014142680A true RU2014142680A (ru) | 2016-05-20 |
| RU2014142680A3 RU2014142680A3 (ru) | 2018-05-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2010102065/10A RU2540150C2 (ru) | 2007-06-25 | 2008-06-25 | Способы модификации антител и модифицированные антитела с улучшенными функциональными свойствами |
| RU2014142680A RU2014142680A (ru) | 2007-06-25 | 2014-10-22 | Способ улучшения функциональных свойств антитела или его антигенсвязывающего фрагмента |
| RU2019118109A RU2019118109A (ru) | 2007-06-25 | 2019-06-11 | Способы модификации антител и модифицированные антитела с улучшенными функциональными свойствами |
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| RU2010102065/10A RU2540150C2 (ru) | 2007-06-25 | 2008-06-25 | Способы модификации антител и модифицированные антитела с улучшенными функциональными свойствами |
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| RU2019118109A RU2019118109A (ru) | 2007-06-25 | 2019-06-11 | Способы модификации антител и модифицированные антитела с улучшенными функциональными свойствами |
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| Country | Link |
|---|---|
| US (2) | US20090074780A1 (ru) |
| EP (1) | EP2158315B1 (ru) |
| JP (5) | JP5611820B2 (ru) |
| KR (1) | KR101573086B1 (ru) |
| CN (6) | CN105017427A (ru) |
| AU (1) | AU2008267734B9 (ru) |
| BR (1) | BRPI0813645A2 (ru) |
| CA (1) | CA2689941C (ru) |
| DK (1) | DK2158315T3 (ru) |
| ES (1) | ES2566737T3 (ru) |
| HR (1) | HRP20160730T1 (ru) |
| HU (1) | HUE027507T2 (ru) |
| IL (1) | IL202360A (ru) |
| MX (1) | MX2009013328A (ru) |
| NZ (2) | NZ581468A (ru) |
| PL (1) | PL2158315T3 (ru) |
| RU (3) | RU2540150C2 (ru) |
| SI (1) | SI2158315T1 (ru) |
| WO (1) | WO2009000099A2 (ru) |
| ZA (1) | ZA200908384B (ru) |
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| IN2009DN05758A (ru) | 2007-03-12 | 2015-07-24 | Esbatech Ag | |
| PL2158315T3 (pl) | 2007-06-25 | 2016-10-31 | Sposoby modyfikowania przeciwciał i zmodyfikowane przeciwciała o ulepszonych właściwościach funkcjonalnych | |
| KR101530723B1 (ko) | 2007-06-25 | 2015-06-22 | 에스바테크 - 어 노바티스 컴파니 엘엘씨 | 단일 쇄 항체의 서열에 기초한 공학처리 및 최적화 |
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| CA2727992C (en) | 2008-06-25 | 2017-10-17 | Esbatech, An Alcon Biomedical Research Unit Llc | Stable and soluble antibodies inhibiting tnf.alpha. |
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| EP2725034B1 (en) | 2010-09-22 | 2019-04-03 | Amgen Inc. | Carrier immunoglobulins with no specificity for human tissues and uses thereof |
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| AU2011312106B8 (en) | 2010-10-08 | 2017-09-14 | City Of Hope | A monoclonal antibody framework binding interface for meditopes, meditope delivery systems and methods for their use |
| AU2013203189B2 (en) * | 2010-10-22 | 2014-12-11 | Novartis Ag | Stable and soluble antibodies |
| UY33679A (es) * | 2010-10-22 | 2012-03-30 | Esbatech | Anticuerpos estables y solubles |
| AU2016277637B2 (en) * | 2010-10-22 | 2018-11-08 | Novartis Ag | Stable and soluble antibodies |
| BR112013013354A2 (pt) | 2010-11-30 | 2020-10-06 | Chugai Seiyaku Kabushiki Kaisha | molécula de ligação ao antígeno capaz de se ligar a uma pluralidade de moléculas de antígeno repetidamente |
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| JP2024054410A5 (ru) |
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| Date | Code | Title | Description |
|---|---|---|---|
| FA92 | Acknowledgement of application withdrawn (lack of supplementary materials submitted) |
Effective date: 20190715 |