JP2010529835A5 - - Google Patents
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- JP2010529835A5 JP2010529835A5 JP2010509405A JP2010509405A JP2010529835A5 JP 2010529835 A5 JP2010529835 A5 JP 2010529835A5 JP 2010509405 A JP2010509405 A JP 2010509405A JP 2010509405 A JP2010509405 A JP 2010509405A JP 2010529835 A5 JP2010529835 A5 JP 2010529835A5
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- JP
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- Prior art keywords
- avpal
- avpal variant
- variant
- subject
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- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 claims 9
- 229920001223 polyethylene glycol Polymers 0.000 claims 8
- 125000003616 serine group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 8
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims 7
- 102100005994 PAH Human genes 0.000 claims 7
- 229960005190 Phenylalanine Drugs 0.000 claims 7
- 108010069013 Phenylalanine Hydroxylase Proteins 0.000 claims 7
- 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 7
- 239000002202 Polyethylene glycol Substances 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 6
- 210000002381 Plasma Anatomy 0.000 claims 5
- 230000035772 mutation Effects 0.000 claims 5
- 230000000694 effects Effects 0.000 claims 3
- 201000011252 phenylketonuria Diseases 0.000 claims 3
- 201000010099 disease Diseases 0.000 claims 2
- 229920003169 water-soluble polymer Polymers 0.000 claims 2
- 102200081291 BBS10 L308F Human genes 0.000 claims 1
- 102200094634 CLCN1 A313T Human genes 0.000 claims 1
- 102200022112 HGD E178G Human genes 0.000 claims 1
- 102200000387 IHH V190A Human genes 0.000 claims 1
- 102200027873 PAH A104D Human genes 0.000 claims 1
- 102200031487 PAH A300S Human genes 0.000 claims 1
- 102200031116 PAH A395P Human genes 0.000 claims 1
- 102200031113 PAH E390G Human genes 0.000 claims 1
- 102200027738 PAH F39L Human genes 0.000 claims 1
- 102200027763 PAH I65T Human genes 0.000 claims 1
- 102200027736 PAH L48S Human genes 0.000 claims 1
- 102200031429 PAH P211T Human genes 0.000 claims 1
- 102200031143 PAH P407S Human genes 0.000 claims 1
- 102200031444 PAH R241C Human genes 0.000 claims 1
- 102200031316 PAH R261Q Human genes 0.000 claims 1
- 102200027764 PAH R68S Human genes 0.000 claims 1
- 102200031124 PAH V388M Human genes 0.000 claims 1
- 102200031139 PAH Y414C Human genes 0.000 claims 1
- 102200021562 PHGDH A373T Human genes 0.000 claims 1
- 102200012481 PROS1 D129G Human genes 0.000 claims 1
- 108091022057 Phenylalanine Ammonia-Lyase Proteins 0.000 claims 1
- 102200104484 TP53 K320N Human genes 0.000 claims 1
- 230000003197 catalytic Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 230000037213 diet Effects 0.000 claims 1
- 235000005911 diet Nutrition 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
Claims (38)
- アナベナ バリアビリスフェニルアラニンアンモニアリアーゼ(AvPAL)変異体であって、１以上のシステイン残基が、セリン残基によって置換されており、かつ野生型AvPAL（配列番号４）と比較して、高いフェニルアラニン変換活性、及び／又は、低減された免疫原性を有する、前記AvPAL変異体。
- セリン残基によって置換されている１以上のシステイン残基が、位置64、318、503及び565のシステイン残基からなる群から選択される、請求項１記載のAvPAL変異体。
- AvPALの位置503のシステイン残基が、セリン残基によって置換されている、請求項２記載のAvPAL変異体（配列番号９）。
- AvPALの位置565のシステイン残基が、セリン残基によって置換されている、請求項２記載のAvPAL変異体（配列番号１０）。
- 位置503及び565のシステイン残基が、セリン残基によって置換されている、請求項２記載のAvPAL変異体（配列番号１１）。
- 更に水溶性ポリマーを含む、請求項１〜５のいずれか１項記載のAvPAL変異体。
- ペグ化されている、請求項１〜５のいずれか１項記載のAvPAL変異体。
- 前記ペグ化が、AvPAL変異体とNHS活性化ポリエチレングリコールとを、AvPAL変異体のリジン残基当たり3のポリエチレングリコールの比で反応させることにより達成される、請求項７記載のAvPAL変異体。
- AvPALの位置503のシステイン残基がセリン残基によって置換されている、AvPAL変異体（配列番号９）。
- AvPALの位置565のシステイン残基がセリン残基によって置換されている、AvPAL変異体（配列番号１０）。
- 位置503及び565のシステイン残基がセリン残基によって置換されている、AvPAL変異体（配列番号１１）。
- 更に水溶性ポリマーを含む、請求項１１記載のAvPAL変異体。
- ペグ化されている、請求項１１記載のAvPAL変異体。
- 前記ペグ化が、AvPAL変異体とNHS活性化ポリエチレングリコールとを、AvPAL変異体のリジン残基当たり少なくとも１．６のポリエチレングリコールの比で反応させることにより達成される、請求項１３記載のAvPAL変異体。
- 前記ペグ化が、AvPAL変異体とNHS活性化ポリエチレングリコールとを、AvPAL変異体のリジン残基当たり少なくとも２．４のポリエチレングリコールの比で反応させることにより達成される、請求項１３記載のAvPAL変異体。
- 前記ペグ化が、AvPAL変異体とNHS活性化ポリエチレングリコールとを、AvPAL変異体のリジン残基当たり3のポリエチレングリコールの比で反応させることにより達成される、請求項１３記載のAvPAL変異体。
- 前記AvPAL変異体の位置2、10、32、145、195、301、413、493及び522のリジン残基の少なくとも28％がペグ化されている、請求項１３記載のAvPAL変異体。
- 前記AvPALの位置2、10、195、413、493及び522のリジン残基の少なくとも51％がペグ化されている、請求項１３記載のAvPAL変異体。
- 前記AvPALの位置2、10、195、493及び522のリジン残基の少なくとも75％がペグ化されている、請求項１３記載のAvPAL変異体。
- 請求項１〜１９のいずれか１項記載のAvPAL変異体を含む、医薬組成物。
- 被験者のフェニルアラニンヒドロキシラーゼ(PAH)の欠乏によってすべて又は一部が生じる疾病を治療するための薬剤の調製における、請求項１〜１９のいずれか１項記載のAvPAL変異体の使用。
- 前記疾病が、上昇したフェニルアラニン量によって特徴付けられる、請求項２１記載の使用。
- 前記被験者が、正常PAH活性の10％以下を有する、請求項２１又は２２記載の使用。
- 被験者の上昇した血漿フェニルアラニン量を治療するための薬剤の調製における、請求項１〜１９のいずれか１項記載のAvPAL変異体の使用。
- 被験者の上昇した血漿フェニルアラニン量を低減させるための薬剤の調製における、請求項１〜１９のいずれか１項記載のAvPAL変異体の使用。
- 前記被験者の血漿フェニルアラニン濃度が、前記AvPAL変異体の投与前において、200μMよりも高い、請求項２２〜２５のいずれか１項記載の使用。
- 前記薬剤が、前記被験者の血漿フェニルアラニン濃度を10％以上低減させるように調製されている、請求項２２〜２６のいずれか１項記載の使用。
- 被験者のフェニルケトン尿症(PKU)を治療するための薬剤の調製における、請求項１〜１９のいずれか１項記載のAvPAL変異体の使用。
- 前記PKUが古典的重症型PKUである、請求項２８記載の使用。
- 前記被験者がPAH活性の欠乏を有する、請求項２１〜２９のいずれか１項記載の使用。
- 前記被験者が突然変異体PAHを有する、請求項２１〜３０のいずれか１項記載の使用。
- 前記突然変異体PAHが、PAHの触媒ドメインでの突然変異を含む、請求項３１記載の使用。
- 前記突然変異が、F39L、L48S、I65T、R68S、A104D、S11OC、D129G、E178G、V190A、P211T、R241C、R261Q、A300S、L308F、A313T、K320N、A373T、V388M E390G、A395P、P407S、及びY414Cからなる群より選択される１以上の突然変異を含む、請求項３２記載の使用。
- 前記被験者が妊婦である、請求項２１〜３３のいずれか１項記載の使用。
- 前記薬剤が、タンパク質制限食と併用して被験者に投与されるように調製されている、請求項２１〜３４のいずれか１項記載の使用。
- 前記被験者が０〜３歳の幼児である、請求項２１〜３３又は３５のいずれか１項記載の使用。
- 前記幼児の血漿フェニルアラニン濃度が、360μM〜4800μMである、請求項３６記載の使用。
- 前記被験者がヒトである、請求項２１〜３７のいずれか１項記載の使用。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/807,227 US7534595B2 (en) | 2006-06-12 | 2007-05-25 | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US11/807,227 | 2007-05-25 | ||
| PCT/US2008/006661 WO2008153776A1 (en) | 2007-05-25 | 2008-05-23 | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using said compositions |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010529835A JP2010529835A (ja) | 2010-09-02 |
| JP2010529835A5 true JP2010529835A5 (ja) | 2011-07-07 |
| JP5670183B2 JP5670183B2 (ja) | 2015-02-18 |
Family
ID=39868905
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010509405A Active JP5670183B2 (ja) | 2007-05-25 | 2008-05-23 | 原核生物フェニルアラニンアンモニアリアーゼの組成物、及び、その組成物の使用方法 |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US7534595B2 (ja) |
| EP (2) | EP2152868B1 (ja) |
| JP (1) | JP5670183B2 (ja) |
| KR (2) | KR20150038753A (ja) |
| CN (1) | CN101842482B (ja) |
| AR (2) | AR066716A1 (ja) |
| AU (1) | AU2008263190B2 (ja) |
| BR (1) | BRPI0811267B8 (ja) |
| CA (1) | CA2687450C (ja) |
| CL (1) | CL2008001497A1 (ja) |
| CY (2) | CY1116894T1 (ja) |
| DK (1) | DK2152868T3 (ja) |
| EA (1) | EA018443B1 (ja) |
| ES (1) | ES2551315T3 (ja) |
| HK (1) | HK1135141A1 (ja) |
| HR (1) | HRP20151268T1 (ja) |
| HU (2) | HUE025784T2 (ja) |
| IL (1) | IL202132A (ja) |
| LT (1) | LTC2152868I2 (ja) |
| LU (1) | LUC00133I2 (ja) |
| MX (1) | MX2009012453A (ja) |
| MY (1) | MY151413A (ja) |
| NL (1) | NL301011I2 (ja) |
| NO (1) | NO2019037I1 (ja) |
| PE (1) | PE20090315A1 (ja) |
| PL (1) | PL2152868T3 (ja) |
| PT (1) | PT2152868E (ja) |
| SI (1) | SI2152868T1 (ja) |
| TW (1) | TWI418633B (ja) |
| WO (1) | WO2008153776A1 (ja) |
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| EP2343317A1 (en) * | 2000-11-10 | 2011-07-13 | F. Hoffmann-La Roche Ltd. | Apolipoprotein analogues |
| EP1476563B1 (en) | 2002-02-26 | 2008-09-17 | E.I. Du Pont De Nemours And Company | Method for the recombination of genetic elements |
| AU2003246690B2 (en) * | 2002-07-17 | 2010-03-11 | Cytos Biotechnology Ag | Molecular antigen arrays using a virus like particle derived from the AP205 coat protein |
| AU2003290780B2 (en) | 2002-11-14 | 2009-05-07 | The Scripps Research Institute | Crystalline form of fatty acid amine hydrolase (FAAH) |
| CA2530972A1 (en) * | 2003-06-11 | 2004-12-23 | Wyeth | Platelet glycoprotein ib alpha variant fusion polypeptides and methods of use thereof |
| FR2868318B1 (fr) * | 2004-04-01 | 2012-11-16 | Commissariat Energie Atomique | Antigene tat stabilise et ses applications pour la vaccination anti-vih |
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| US20090038023A1 (en) * | 2005-03-10 | 2009-02-05 | Verenium Corporation | Lyase Enzymes, Nucleic Acids Encoding Them and Methods For Making and Using Them |
| US7534595B2 (en) | 2006-06-12 | 2009-05-19 | Biomarin Pharmaceutical Inc. | Compositions of prokaryotic phenylalanine ammonia-lyase and methods of using compositions thereof |
| US20090011400A1 (en) | 2006-12-01 | 2009-01-08 | The Salk Institute for Biological Studies and The Regents of the University of California | Substrate switched ammonia lyases and mutases |
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