JP2017506230A5 - - Google Patents
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- JP2017506230A5 JP2017506230A5 JP2016550530A JP2016550530A JP2017506230A5 JP 2017506230 A5 JP2017506230 A5 JP 2017506230A5 JP 2016550530 A JP2016550530 A JP 2016550530A JP 2016550530 A JP2016550530 A JP 2016550530A JP 2017506230 A5 JP2017506230 A5 JP 2017506230A5
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- 239000008194 pharmaceutical composition Substances 0.000 claims 24
- 210000002845 Virion Anatomy 0.000 claims 10
- 208000002780 Macular Degeneration Diseases 0.000 claims 6
- 108090000623 proteins and genes Proteins 0.000 claims 6
- 102000004169 proteins and genes Human genes 0.000 claims 6
- 125000003275 alpha amino acid group Chemical group 0.000 claims 5
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 claims 5
- 101710030892 FLT1 Proteins 0.000 claims 4
- 206010064930 Age-related macular degeneration Diseases 0.000 claims 3
- 241000702423 Adeno-associated virus - 2 Species 0.000 claims 2
- 241000432074 Adeno-associated virus Species 0.000 claims 1
- 102000006496 Immunoglobulin Heavy Chains Human genes 0.000 claims 1
- 108010019476 Immunoglobulin Heavy Chains Proteins 0.000 claims 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims 1
- 208000001344 Macular Edema Diseases 0.000 claims 1
- 206010025415 Macular oedema Diseases 0.000 claims 1
- 206010038848 Retinal detachment Diseases 0.000 claims 1
- 210000002301 Subretinal Fluid Anatomy 0.000 claims 1
- 102000009524 Vascular Endothelial Growth Factor A Human genes 0.000 claims 1
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims 1
- 102000016548 Vascular Endothelial Growth Factor Receptor-1 Human genes 0.000 claims 1
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 claims 1
- 125000000539 amino acid group Chemical group 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- 239000000710 homodimer Substances 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 230000004410 intraocular pressure Effects 0.000 claims 1
- 201000010230 macular retinal edema Diseases 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000000051 modifying Effects 0.000 claims 1
- 229920000023 polynucleotide Polymers 0.000 claims 1
- 239000002157 polynucleotide Substances 0.000 claims 1
- 230000002207 retinal Effects 0.000 claims 1
Claims (24)
- ＶＥＧＦ活性を調節することができるＶＥＧＦＲ−１（Ｆｌｔ−１）の少なくとも１つのドメインを含む可溶性タンパク質をコードするポリヌクレオチドを含む組換えアデノ随伴ウイルス（ｒＡＡＶ）ビリオンを含む医薬組成物であって、約１×１０７〜約１×１０１３、または約２×１０１０未満のｒＡＡＶビリオンを対象の眼に送達することによりヒト対象における黄斑変性または黄斑浮腫を処置するために使用するための、前記医薬組成物。
- 眼圧、網膜厚、網膜下液、または網膜内液が減少する、請求項１に記載の医薬組成物。
- 約１×１０７〜約１×１０１２；１×１０８〜約１×１０１２；約１×１０８〜約１×１０１１；約１×１０８〜約１×１０１０；約１×１０８〜約１×１０９；約２×１０７〜約２×１０１２；約２×１０８〜約２×１０１２；約２×１０８〜約２×１０１１；約２×１０８〜約２×１０１０；約２×１０８〜約２×１０９；２×１０９〜約２×１０１０；約１×１０１０〜約１×１０１３；約１×１０１０〜約１×１０１２；約１×１０１０〜約１×１０１１；約２×１０１０〜約１×１０１３；２×１０１０〜約１×１０１２；約２×１０１０〜約２×１０１２；約２×１０１０〜約１×１０１１；または約２×１０１０〜約２×１０１１ｒＡＡＶビリオンが眼に送達される、請求項１または２に記載の医薬組成物。
- 約１×１０７、約２×１０７、約６×１０７、約１×１０８、約２×１０８、約６×１０８、約１×１０９、約２×１０９、約６×１０９、約１×１０１０、約２×１０１０、約６×１０１０、約１×１０１１、約２×１０１１、約６×１０１１、約１×１０１２、約２×１０１２、約６×１０１２、または約１×１０１３ｒＡＡＶビリオンが眼に送達される、請求項１〜３のいずれか１項に記載の医薬組成物。
- 約２×１０８〜２×１０１０ｒＡＡＶビリオン未満が眼に送達される、請求項１または２に記載の医薬組成物。
- 最大約２×１０８ｒＡＡＶビリオンが眼に送達される、請求項１または２に記載の医薬
組成物。 - 最大約２×１０９ｒＡＡＶビリオンが眼に送達される、請求項１または２に記載の医薬組成物。
- 医薬組成物は、眼科学的に許容される媒体をさらに含む、請求項１〜７のいずれか１項に記載の医薬組成物。
- ｒＡＡＶビリオンの単回硝子体内注射が眼に送達される、請求項１〜８のいずれか１項に記載の医薬組成物。
- 可溶性タンパク質は
（ａ）Ｆｌｔ−１の少なくとも１つのドメイン；
（ｂ）免疫グロブリン重鎖に由来する多量体化ドメイン；
および
（ｃ）（ａ）を（ｂ）に連結する長さが５〜２５アミノ酸残基のリンカー
を含み、該可溶性タンパク質が発現される場合、該可溶性タンパク質の多量体が生成する、請求項１〜９のいずれか１項に記載の医薬組成物。 - 少なくとも１つのドメインはＦｌｔ−１のドメイン２を含む、請求項１〜１０のいずれか１項に記載の医薬組成物。
- 多量体はホモ二量体である、請求項１０または１１に記載の医薬組成物。
- 多量体化ドメインは、ＩｇＧのＦｃ領域またはその活性断片を含む、請求項１０〜１２のいずれか１項に記載の医薬組成物。
- 多量体化ドメインは、ＩｇＧのＣＨ３ドメインまたはその活性断片を含む、請求項１０〜１３のいずれか１項に記載の医薬組成物。
- 多量体化ドメインは、ＩｇＧ１、ＩｇＧ２、ＩｇＧ３またはＩｇＧ４に由来する、請求項１０〜１４のいずれか１項に記載の医薬組成物。
- 多量体化ドメインは、ＩｇＧ１重鎖の定常領域に由来する、請求項１５に記載の医薬組成物。
- リンカーは：
ｇｌｙ９（配列番号１）；
ｇｌｕ９（配列番号２）；
ｓｅｒ９（配列番号３）；
ｇｌｙ５ｃｙｓｐｒｏ２ｃｙｓ（配列番号４）；
（ｇｌｙ４ｓｅｒ）３（配列番号５）；
ＳｅｒＣｙｓＶａｌＰｒｏＬｅｕＭｅｔＡｒｇＣｙｓＧｌｙＧｌｙＣｙｓＣｙｓＡｓｎ（配列番号６）；
ＰｒｏＳｅｒＣｙｓＶａｌＰｒｏＬｅｕＭｅｔＡｒｇＣｙｓＧｌｙＧｌｙＣｙｓＣｙｓＡｓｎ（配列番号７）；
ＧｌｙＡｓｐＬｅｕＩｌｅＴｙｒＡｒｇＡｓｎＧｌｎＬｙｓ（配列番号８）および
Ｇｌｙ９ＰｒｏＳｅｒＣｙｓＶａｌＰｒｏＬｅｕＭｅｔＡｒｇＣｙｓＧｌｙＧｌｙＣｙｓＣｙｓＡｓｎ（配列番号９）
からなる群から選択される、請求項１０〜１６のいずれか１項に記載の医薬組成物。 - 可溶性タンパク質は式Ｘ−Ｙ−Ｚを有し、式中、Ｘは、Ｆｌｔ−１のＩｇＧ様ドメイン２を含み、Ｙは、Ｇｌｙ９であり、Ｚは、ＩｇＧ Ｆｃ領域またはＩｇＧ ＣＨ３領域である、請求項１０〜１７のいずれか１項に記載の医薬組成物。
- 多量体化ドメインはヒト化されている、請求項１０〜１８のいずれか１項に記載の医薬組成物。
- 可溶性タンパク質は、（ａ）図２Ａ〜２Ｂに示すアミノ酸配列（配列番号１１）；（ｂ）図６に示すアミノ酸配列（配列番号１５）；（ｃ）図８に示すアミノ酸配列（配列番号１７）；（ｄ）図１２に示すアミノ酸配列（配列番号２１）；および（ｅ）それと少なくとも９０％の配列同一性を有する（ａ）、（ｂ）、（ｃ）または（ｄ）の活性型変異体からなる群から選択されるアミノ酸配列を含む、請求項１〜１９のいずれか１項に記載の医薬組成物。
- 黄斑変性は加齢黄斑変性（ＡＭＤ）である、請求項１〜２０のいずれか１項に記載の医薬組成物。
- 黄斑変性は滲出型ＡＭＤである、請求項２１に記載の医薬組成物。
- ｒＡＡＶビリオンは、ＡＡＶ１、ＡＡＶ２、ＡＡＶ３、ＡＡＶ４、ＡＡＶ５、ＡＡＶ６、ＡＡＶ７、ＡＡＶ８、ＡＡＶ９、ＡＡＶｒｈ８、ＡＡＶｒｈ８Ｒ、ＡＡＶ１０、ＡＡＶｒｈ１０、ＡＡＶ１１またはＡＡＶ１２から選択されるＡＡＶ血清型に由来する、請求項１〜２２のいずれか１項に記載の医薬組成物。
- ｒＡＡＶビリオンはＡＡＶ２に由来する、請求項２３に記載の医薬組成物。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461936797P | 2014-02-06 | 2014-02-06 | |
| US61/936,797 | 2014-02-06 | ||
| PCT/US2015/014872 WO2015120309A1 (en) | 2014-02-06 | 2015-02-06 | Compositions and methods for treating and preventing macular degeneration |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017506230A JP2017506230A (ja) | 2017-03-02 |
| JP2017506230A5 true JP2017506230A5 (ja) | 2018-03-15 |
| JP6719381B2 JP6719381B2 (ja) | 2020-07-08 |
Family
ID=52589781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016550530A Active JP6719381B2 (ja) | 2014-02-06 | 2015-02-06 | 黄斑変性を処置し、予防するための組成物および方法 |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US20170007719A1 (ja) |
| EP (1) | EP3102246B1 (ja) |
| JP (1) | JP6719381B2 (ja) |
| KR (1) | KR102234695B1 (ja) |
| CN (2) | CN111068072A (ja) |
| AU (3) | AU2015213770A1 (ja) |
| BR (1) | BR112016017817A2 (ja) |
| CA (1) | CA2938828A1 (ja) |
| IL (1) | IL247116B (ja) |
| MX (2) | MX2016010215A (ja) |
| RU (1) | RU2703145C2 (ja) |
| SG (1) | SG11201606101WA (ja) |
| TW (1) | TWI687225B (ja) |
| WO (1) | WO2015120309A1 (ja) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170007719A1 (en) * | 2014-02-06 | 2017-01-12 | Genzyme Corporation | Compositions and methods for treating and preventing macular degeneration |
| KR101685532B1 (ko) * | 2016-04-26 | 2016-12-13 | 한국프라임제약주식회사 | 혈관내피성장인자 수용체 융합단백질 |
| CA3054942A1 (en) | 2017-03-17 | 2018-09-20 | Adverum Biotechnologies, Inc. | Compositions and methods for enhanced gene expression |
| KR102205830B1 (ko) * | 2017-10-26 | 2021-01-21 | 주식회사 큐로진생명과학 | 솔루블 VEGFR-1 변이체 cDNA를 함유하는 rAAV를 포함하는 황반변성 치료용 조성물 |
| MX2020008470A (es) * | 2018-02-14 | 2020-09-25 | Generation Bio Co | Vectores de adn no virales y usos de estos para la produccion de anticuerpos y proteinas de fusion. |
Family Cites Families (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5139941A (en) | 1985-10-31 | 1992-08-18 | University Of Florida Research Foundation, Inc. | AAV transduction vectors |
| US5219740A (en) | 1987-02-13 | 1993-06-15 | Fred Hutchinson Cancer Research Center | Retroviral gene transfer into diploid fibroblasts for gene therapy |
| DE10399031I1 (de) | 1987-08-28 | 2004-01-29 | Health Research Inc | Rekombinante Viren. |
| US5693622A (en) | 1989-03-21 | 1997-12-02 | Vical Incorporated | Expression of exogenous polynucleotide sequences cardiac muscle of a mammal |
| US5703055A (en) | 1989-03-21 | 1997-12-30 | Wisconsin Alumni Research Foundation | Generation of antibodies through lipid mediated DNA delivery |
| US6214804B1 (en) | 1989-03-21 | 2001-04-10 | Vical Incorporated | Induction of a protective immune response in a mammal by injecting a DNA sequence |
| US6673776B1 (en) | 1989-03-21 | 2004-01-06 | Vical Incorporated | Expression of exogenous polynucleotide sequences in a vertebrate, mammal, fish, bird or human |
| FR2658432B1 (fr) | 1990-02-22 | 1994-07-01 | Medgenix Group Sa | Microspheres pour la liberation controlee des substances hydrosolubles et procede de preparation. |
| AU8200191A (en) | 1990-07-09 | 1992-02-04 | United States of America, as represented by the Secretary, U.S. Department of Commerce, The | High efficiency packaging of mutant adeno-associated virus using amber suppressions |
| MY109299A (en) | 1990-08-15 | 1996-12-31 | Virogenetics Corp | Recombinant pox virus encoding flaviviral structural proteins |
| US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
| DE69233013T2 (de) | 1991-08-20 | 2004-03-04 | The Government Of The United States Of America As Represented By The Secretary Of National Institute Of Health, Office Of Technology Transfer | Adenovirus vermittelter gentransfer in den gastrointestinaltrakt |
| US5834441A (en) | 1993-09-13 | 1998-11-10 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Adeno-associated viral (AAV) liposomes and methods related thereto |
| AU4594996A (en) | 1994-11-30 | 1996-06-19 | Chiron Viagene, Inc. | Recombinant alphavirus vectors |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| US5763270A (en) | 1995-06-07 | 1998-06-09 | Genemedicine, Inc. | Plasmid for delivery of nucleic acids to cells and methods of use |
| ES2333425T5 (es) | 1995-06-15 | 2012-08-28 | Crucell Holland B.V. | Sistemas de empaquetado para adenovirus recombinante humano destinados a terapia génica |
| US6001650A (en) | 1995-08-03 | 1999-12-14 | Avigen, Inc. | High-efficiency wild-type-free AAV helper functions |
| US5622856A (en) | 1995-08-03 | 1997-04-22 | Avigen | High efficiency helper system for AAV vector production |
| US7034009B2 (en) * | 1995-10-26 | 2006-04-25 | Sirna Therapeutics, Inc. | Enzymatic nucleic acid-mediated treatment of ocular diseases or conditions related to levels of vascular endothelial growth factor receptor (VEGF-R) |
| US6004797A (en) | 1995-11-09 | 1999-12-21 | Avigen, Inc. | Adenovirus helper-free recombinant AAV Virion production |
| US6048551A (en) | 1997-03-27 | 2000-04-11 | Hilfinger; John M. | Microsphere encapsulation of gene transfer vectors |
| US6995006B2 (en) | 1997-09-05 | 2006-02-07 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| US6566118B1 (en) | 1997-09-05 | 2003-05-20 | Targeted Genetics Corporation | Methods for generating high titer helper-free preparations of released recombinant AAV vectors |
| WO2001002440A1 (en) | 1999-07-02 | 2001-01-11 | Genentech, Inc. | Fusion peptides comprising a peptide ligand domain and a multimerization domain |
| EP2369002A1 (en) | 1999-08-09 | 2011-09-28 | Targeted Genetics Corporation | Enhancement of expression of a single-stranded, heterologous nucleotide sequence from recombinant viral vectors by designing the sequence such that it forms intrastrand base pairs |
| WO2001083797A2 (en) | 2000-04-28 | 2001-11-08 | Avigen, Inc. | Polynucleotides for use in recombinant adeno-associated virus virion production |
| CA2410828C (en) | 2000-06-01 | 2012-01-24 | University Of North Carolina At Chapel Hill | Duplexed parvovirus vectors |
| US6593123B1 (en) | 2000-08-07 | 2003-07-15 | Avigen, Inc. | Large-scale recombinant adeno-associated virus (rAAV) production and purification |
| US6723551B2 (en) | 2001-11-09 | 2004-04-20 | The United States Of America As Represented By The Department Of Health And Human Services | Production of adeno-associated virus in insect cells |
| DE602004030327D1 (de) | 2003-05-21 | 2011-01-13 | Genzyme Corp | Verfahren zur herstellung von präparationen rekombinanter aav-virionen, die weitgehend frei von leeren capsiden sind |
| CN100588800C (zh) * | 2003-08-04 | 2010-02-10 | 邱则有 | 一种现浇砼用空腔模壳构件 |
| JP4807802B2 (ja) | 2004-07-30 | 2011-11-02 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Ｖｅｇｆ媒介性活性をブロックすることによるｉ型糖尿病を処置する方法 |
| JP4944032B2 (ja) * | 2004-09-13 | 2012-05-30 | ジェンザイム・コーポレーション | 多量体構築物 |
| EP1827602B1 (en) * | 2004-11-26 | 2011-03-09 | Novagali Pharma S.A. | Modulating retinal pigmented epithelium permeaion by inhibiting vegfr-1 |
| US7765583B2 (en) | 2005-02-28 | 2010-07-27 | France Telecom | System and method for managing virtual user domains |
| US20090105245A1 (en) * | 2006-12-21 | 2009-04-23 | Bingaman David P | Methods for treating macular edema and ocular angiogenesis using an anti-inflammatory agent and a receptor tyrosine kinase inhibitor |
| JP2011512417A (ja) * | 2008-02-20 | 2011-04-21 | ジェンザイム・コーポレーション | 血管形成の阻害 |
| RS62086B1 (sr) | 2009-06-16 | 2021-08-31 | Genzyme Corp | Poboljšani postupci za prečišćavanje vektora rekombinantnog aav |
| TWI702955B (zh) * | 2012-05-15 | 2020-09-01 | 澳大利亞商艾佛蘭屈澳洲私營有限公司 | 使用腺相關病毒（ａａｖ）ｓｆｌｔ-１治療老年性黃斑部退化（ａｍｄ） |
| CN115715797A (zh) * | 2013-04-17 | 2023-02-28 | 建新公司 | 用于治疗和预防黄斑变性的组合物和方法 |
| US20170007719A1 (en) * | 2014-02-06 | 2017-01-12 | Genzyme Corporation | Compositions and methods for treating and preventing macular degeneration |
-
2015
- 2015-02-06 US US15/113,720 patent/US20170007719A1/en not_active Abandoned
- 2015-02-06 WO PCT/US2015/014872 patent/WO2015120309A1/en active Application Filing
- 2015-02-06 TW TW104104067A patent/TWI687225B/zh active
- 2015-02-06 SG SG11201606101WA patent/SG11201606101WA/en unknown
- 2015-02-06 RU RU2016135771A patent/RU2703145C2/ru active
- 2015-02-06 CA CA2938828A patent/CA2938828A1/en active Pending
- 2015-02-06 CN CN201911282594.9A patent/CN111068072A/zh active Pending
- 2015-02-06 CN CN201580017612.4A patent/CN106163573A/zh active Pending
- 2015-02-06 BR BR112016017817A patent/BR112016017817A2/pt not_active Application Discontinuation
- 2015-02-06 AU AU2015213770A patent/AU2015213770A1/en not_active Abandoned
- 2015-02-06 EP EP15706595.4A patent/EP3102246B1/en active Active
- 2015-02-06 JP JP2016550530A patent/JP6719381B2/ja active Active
- 2015-02-06 MX MX2016010215A patent/MX2016010215A/es unknown
- 2015-02-06 KR KR1020167024302A patent/KR102234695B1/ko active IP Right Grant
-
2016
- 2016-08-04 IL IL247116A patent/IL247116B/en active IP Right Grant
- 2016-08-05 MX MX2023011453A patent/MX2023011453A/es unknown
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2019
- 2019-05-15 AU AU2019203413A patent/AU2019203413B2/en active Active
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2021
- 2021-10-15 AU AU2021250986A patent/AU2021250986A1/en active Pending
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