JP2009511000A5 - - Google Patents
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- JP2009511000A5 JP2009511000A5 JP2008530608A JP2008530608A JP2009511000A5 JP 2009511000 A5 JP2009511000 A5 JP 2009511000A5 JP 2008530608 A JP2008530608 A JP 2008530608A JP 2008530608 A JP2008530608 A JP 2008530608A JP 2009511000 A5 JP2009511000 A5 JP 2009511000A5
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- 108010077397 Pseudomonas aeruginosa toxA protein Proteins 0.000 claims 36
- 230000035772 mutation Effects 0.000 claims 8
- 102000004965 antibodies Human genes 0.000 claims 7
- 108090001123 antibodies Proteins 0.000 claims 7
- 150000007523 nucleic acids Chemical class 0.000 claims 7
- 230000000875 corresponding Effects 0.000 claims 6
- 108020004707 nucleic acids Proteins 0.000 claims 5
- 125000000511 arginine group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 229920001850 Nucleic acid sequence Polymers 0.000 claims 2
- 101700037498 PE38 Proteins 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 102000037240 fusion proteins Human genes 0.000 claims 2
- 108020001507 fusion proteins Proteins 0.000 claims 2
- 239000004615 ingredient Substances 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000004475 Arginine Substances 0.000 claims 1
- 102000004127 Cytokines Human genes 0.000 claims 1
- 108090000695 Cytokines Proteins 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
- 235000004279 alanine Nutrition 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 claims 1
- 239000003102 growth factor Substances 0.000 claims 1
- 229920001184 polypeptide Polymers 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 230000001131 transforming Effects 0.000 claims 1
Claims (24)
- 親シュードモナス外毒素A (PE)と比較して少なくとも1つの突然変異を含むPE変異体であって、少なくとも1つの該突然変異が、親PE内の配列番号２、３、４、５、および６のうちの1つ以上に対応する少なくとも1つのペプチド配列内にあり;
ただし、変異体が、配列番号２および６内の配列番号１の224位に対応するアルギニン残基の位置にアミノ酸置換を含む場合、親PE内の配列番号２、３、４、５、および６のうちの1つ以上に対応する少なくとも1つのペプチド配列内に少なくとも1つのさらなる突然変異が存在することを条件とする、上記PE変異体。 - 少なくとも1つの突然変異が、配列番号２に対応するペプチド配列内にある、請求項１に記載のPE変異体。
- 親PEが野生型PEである、請求項１または請求項２に記載のPE変異体。
- 親PEがPE38である、請求項１または請求項２に記載のPE変異体。
- 配列番号１の224位に対応するアルギニン残基の位置に突然変異を含む、請求項４に記載のPE変異体。
- 親PEが、配列番号１の224位に対応するアルギニン残基の位置に突然変異を有するPE38である、請求項１または請求項２に記載のPE変異体。
- アルギニンの位置の突然変異がアラニンへの突然変異である、請求項５または請求項６に記載のPE変異体。
- 親PEと比較して低下した免疫原性を有する、請求項１〜７のいずれか一項に記載のPE変異体。
- 抗体分子にコンジュゲートされている、請求項１〜８のいずれか一項に記載のPE変異体。
- 抗体分子が、抗CD22、抗メソテリン(mesothelin)、抗CD25および抗ルイスY抗体分子からなる群から選択される、請求項９に記載のPE変異体。
- 抗体分子が抗CD22抗体分子である、請求項１０に記載のPE変異体。
- 癌ターゲティング分子にコンジュゲートされている、請求項１〜８のいずれか一項に記載のPE変異体。
- 癌ターゲティング分子が、成長因子およびサイトカインからなる群から選択される、請求項１２に記載のPE変異体。
- 抗体分子もしくは癌ターゲティング分子またはそれらのポリペプチド鎖を含む融合タンパク質の部分として、ペプチド結合によって、抗体分子または癌ターゲティング分子にコンジュゲートされている、請求項９〜１３のいずれか一項に記載のPE変異体。
- 請求項１〜８、または請求項１４のいずれか一項に記載のPE変異体をコードする、単離された核酸。
- 請求項１〜８、または請求項１４のいずれか一項に記載のPE変異体をコードする核酸を含む発現ベクター。
- 請求項１６に記載の発現ベクターで形質転換された宿主細胞。
- PE変異体を製造する方法であって、請求項１７に記載の宿主細胞を培養するステップおよびコード核酸から発現された変異体を精製するステップを含む、上記方法。
- 製薬的に許容される成分を含む組成物中に変異体を製剤化するステップをさらに含む、請求項１８に記載の方法。
- 請求項１〜８のいずれか一項に記載のPE変異体を製造する方法であって、親PEをコードする核酸配列を突然変異させてPE変異体をコードする核酸を得るステップ、該PE変異体をコードする突然変異核酸を含む発現ベクターで宿主細胞を形質転換するステップ、および該コード核酸から発現されたPE変異体を精製するステップを含む、上記方法。
- 親PEと比較して免疫原性に関してPE変異体を検査するステップをさらに含む、請求項２０に記載の方法。
- PE変異体が、親PEと比較して低下した免疫原性を有する、請求項２０または請求項２１に記載の方法。
- 製薬的に許容される成分を含む組成物中に変異体を製剤化するステップをさらに含む、請求項２０〜２２のいずれか一項に記載の方法。
- 配列番号２、３、４、５、および６のいずれかのアミノ酸配列からなる、単離されたペプチド。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71686205P | 2005-09-14 | 2005-09-14 | |
| PCT/GB2006/003384 WO2007031741A1 (en) | 2005-09-14 | 2006-09-12 | Pseudomonas exotoxin a cd4+ t-cell epitopes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009511000A JP2009511000A (ja) | 2009-03-19 |
| JP2009511000A5 true JP2009511000A5 (ja) | 2009-11-05 |
Family
ID=37499328
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008530608A Pending JP2009511000A (ja) | 2005-09-14 | 2006-09-12 | シュードモナス外毒素ａｃｄ４＋ｔ細胞エピトープ |
Country Status (6)
| Country | Link |
|---|---|
| US (2) | US20080193976A1 (ja) |
| EP (1) | EP1922330A1 (ja) |
| JP (1) | JP2009511000A (ja) |
| AU (1) | AU2006290475A1 (ja) |
| CA (1) | CA2622525A1 (ja) |
| WO (1) | WO2007031741A1 (ja) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR112013031262A2 (pt) | 2011-06-09 | 2016-11-22 | Us Health | "exotoxinas a de pseudomonas com menos epítopos imunogênicos de célula b e t, e seu uso no tratamento e prevenção de câncer, bem como molécula quimérica, ácido nucleico, vetor de expressão, células, composição farmacêutica e métodos para inibir crescimento de célula-alvo e de produção de endotoxinas a de pseudomonas e de molécula quimérica". |
| US8932586B2 (en) | 2011-09-06 | 2015-01-13 | Intrexon Corporation | Modified forms of Pseudomonas exotoxin A |
| PL2755993T3 (pl) | 2011-09-16 | 2018-04-30 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Egzotoksyna A Pseudomonas z mniej immunogennymi epitopami komórek B |
| AR093378A1 (es) | 2012-11-08 | 2015-06-03 | Hoffmann La Roche | PROTEINAS LIGANTES DE ANTIGENO HER3 DE UNION A LA HORQUILLA b DE HER3 |
| WO2014165282A1 (en) | 2013-03-12 | 2014-10-09 | Institute of Arthritis Research, LLC | Immunologically active polypeptide |
| WO2015051199A2 (en) * | 2013-10-06 | 2015-04-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Modified pseudomonas exotoxin a |
| WO2016146833A1 (en) | 2015-03-19 | 2016-09-22 | F. Hoffmann-La Roche Ag | Biomarkers for nad(+)-diphthamide adp ribosyltransferase resistance |
| EP3184547A1 (en) | 2015-10-29 | 2017-06-28 | F. Hoffmann-La Roche AG | Anti-tpbg antibodies and methods of use |
| WO2017196847A1 (en) | 2016-05-10 | 2017-11-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Variable new antigen receptor (vnar) antibodies and antibody conjugates targeting tumor and viral antigens |
| WO2017214182A1 (en) | 2016-06-07 | 2017-12-14 | The United States Of America. As Represented By The Secretary, Department Of Health & Human Services | Fully human antibody targeting pdi for cancer immunotherapy |
| US11066479B2 (en) | 2016-08-02 | 2021-07-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Monoclonal antibodies targeting glypican-2 (GPC2) and use thereof |
| EP3559038B1 (en) | 2016-12-21 | 2022-12-14 | The United States of America as represented by The Secretary Department of Health and Human Services | Human monoclonal antibodies specific for flt3 and uses thereof |
| EP3625256A1 (en) | 2017-05-19 | 2020-03-25 | The U.S.A. as represented by the Secretary, Department of Health and Human Services | Human monoclonal antibody targeting tnfr2 for cancer immunotherapy |
| WO2019005208A1 (en) | 2017-06-30 | 2019-01-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | ANTIBODIES TO HUMAN MESOTHELIN AND USES IN ANTICANCER THERAPY |
| WO2019067740A1 (en) * | 2017-09-27 | 2019-04-04 | Emory University | FUSION PROTEINS COMPRISING CANCER TOXIN AND MARKER, NANOPARTICLES AND USES THEREOF |
| WO2020014482A1 (en) | 2018-07-12 | 2020-01-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Affinity matured cd22-specific monoclonal antibody and uses thereof |
| EP3833684A1 (en) | 2018-08-08 | 2021-06-16 | The United States of America, as represented by the Secretary, Department of Health and Human Services | High affinity monoclonal antibodies targeting glypican-2 and uses thereof |
| WO2020146182A1 (en) | 2019-01-08 | 2020-07-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cross-species single domain antibodies targeting mesothelin for treating solid tumors |
| EP3883971A1 (en) | 2019-01-22 | 2021-09-29 | The United States of America, as represented by the Secretary, Department of Health and Human Services | High affinity monoclonal antibodies targeting glypican-1 and methods of use |
| JP2022552875A (ja) | 2019-10-22 | 2022-12-20 | ザ ユナイテッド ステイツ オブ アメリカ， アズ リプレゼンテッド バイ ザ セクレタリー， デパートメント オブ ヘルス アンド ヒューマン サービシーズ | 多様な固形腫瘍を処置するためのｂ７ｈ３（ｃｄ２７６）を標的とする高親和性ナノボディ |
| US20230391852A1 (en) | 2020-10-26 | 2023-12-07 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting sars coronavirus spike protein and uses thereof |
| WO2022232612A1 (en) | 2021-04-29 | 2022-11-03 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Lassa virus-specific nanobodies and methods of their use |
| AU2022291120A1 (en) | 2021-06-09 | 2023-11-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Cross species single domain antibodies targeting pd-l1 for treating solid tumors |
| WO2023076881A1 (en) | 2021-10-26 | 2023-05-04 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting the s2 subunit of sars-cov-2 spike protein |
| WO2024050399A1 (en) | 2022-09-01 | 2024-03-07 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Single domain antibodies targeting hpv e6/e7 oncogenic peptide/mhc complexes |
| WO2024104584A1 (en) | 2022-11-17 | 2024-05-23 | University Of Cape Town | Deimmunized pseudomonas exotoxin a |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5458878A (en) * | 1990-01-02 | 1995-10-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | P. exotoxin fusio proteins have COOHG220101al alterations which increase cytotoxicity |
| US6835550B1 (en) * | 1998-04-15 | 2004-12-28 | Genencor International, Inc. | Mutant proteins having lower allergenic response in humans and methods for constructing, identifying and producing such proteins |
| US7355012B2 (en) * | 2001-09-26 | 2008-04-08 | United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Mutated anti-CD22 antibodies with increased affinity to CD22-expressing leukemia cells |
| US7982011B2 (en) * | 2003-11-25 | 2011-07-19 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Mutated anti-cd22 antibodies and immunoconjugates |
-
2006
- 2006-09-12 WO PCT/GB2006/003384 patent/WO2007031741A1/en active Application Filing
- 2006-09-12 JP JP2008530608A patent/JP2009511000A/ja active Pending
- 2006-09-12 CA CA002622525A patent/CA2622525A1/en not_active Abandoned
- 2006-09-12 AU AU2006290475A patent/AU2006290475A1/en not_active Abandoned
- 2006-09-12 US US12/066,709 patent/US20080193976A1/en not_active Abandoned
- 2006-09-12 EP EP06779398A patent/EP1922330A1/en not_active Withdrawn
-
2010
- 2010-08-02 US US12/848,387 patent/US20100291150A1/en not_active Abandoned
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