JP2017534282A5 - - Google Patents
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- JP2017534282A5 JP2017534282A5 JP2017523394A JP2017523394A JP2017534282A5 JP 2017534282 A5 JP2017534282 A5 JP 2017534282A5 JP 2017523394 A JP2017523394 A JP 2017523394A JP 2017523394 A JP2017523394 A JP 2017523394A JP 2017534282 A5 JP2017534282 A5 JP 2017534282A5
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- 229920001184 polypeptide Polymers 0.000 claims 29
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- 230000027455 binding Effects 0.000 claims 6
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- BGFTWECWAICPDG-UHFFFAOYSA-N 2-[bis(4-chlorophenyl)methyl]-4-N-[3-[bis(4-chlorophenyl)methyl]-4-(dimethylamino)phenyl]-1-N,1-N-dimethylbenzene-1,4-diamine Chemical compound C1=C(C(C=2C=CC(Cl)=CC=2)C=2C=CC(Cl)=CC=2)C(N(C)C)=CC=C1NC(C=1)=CC=C(N(C)C)C=1C(C=1C=CC(Cl)=CC=1)C1=CC=C(Cl)C=C1 BGFTWECWAICPDG-UHFFFAOYSA-N 0.000 claims 1
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- 101700036918 XMT1 Proteins 0.000 claims 1
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- 108010081355 beta 2-Microglobulin Proteins 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
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Claims (24)
- 第1及び第2のドメインを含む融合ポリペプチドであって、第1のドメインが、細胞表面関連抗原に結合する抗体又はその抗原結合部分を含み、第2のドメインが、配列番号1に関して、106位の残基が、欠失している、又は、A、C、D、E、F、G、H、I、K、L、M、N、P、Q、R、S、V、W及びYからなる群から選択される、アミノ酸配列を含む脱グリコシル化(aglycosylated)インターフェロンα2b(IFNα2b)を含み、脱グリコシル化IFNα2bが、脱グリコシル化IFNα2bの活性を減弱させる1つ又は複数のアミノ酸の置換又は欠失を更に含む融合ポリペプチド。
- 106位の残基が、欠失している、又は、A、E、S及びVからなる群から選択される、請求項1に記載の融合ポリペプチド。
- 106位の残基がAである、請求項1又は2に記載の融合ポリペプチド。
- 脱グリコシル化IFNα2bのアミノ酸配列が、L15A、R22A、R23A、S25A、L26A、F27A、L30A、L30V、K31A、D32A、R33A、R33K、R33Q、H34A、Q40A、D114R、L117A、R120A、R120E、R125A、R125E、K131A、E132A、K133A、K134A、M148A、R149A、S152A、L153A、N156A、(L30A、H57Y、E58N及びQ61S)、(R33A、H57Y、E58N、Q61S)、(M148A、H57Y、E58N及びQ61S)、(L153A、H57Y、E58N及びQ61S)、(R144A、H57Y、E58N及びQ61S)、(N65A、L80A、Y85A及びY89A)、(N65A、L80A、Y85A、Y89A及びD114A)、(N65A、L80A、Y85A、Y89A及びL117A)、(N65A、L80A、Y85A、Y89A及びR120A)、(Y85A、Y89A及びD114A)、(Y85A、Y89A及びR120A)、(D114A及びR120A)、(L117A及びR120A)、(L117A、R120A及びK121A)、(R120A及びK121A)、(R120E及びK121E)、144位のRの、A、D、E、G、H、I、K、L、N、Q、S、T、V又はYによる置換、145位のAの、D、E、G、H、I、K、L、M、N、Q、S、T、V又はYによる置換、並びに残基L161〜E165の欠失からなる群から選択される減弱化変異により改変されている、請求項1から3のいずれか一項に記載の融合ポリペプチド。
- 脱グリコシル化IFNα2bのアミノ酸配列が、T106の欠失を含み、L15A、R22A、R23A、S25A、L26A、F27A、L30A、L30V、K31A、D32A、R33A、R33K、R33Q、H34A、Q40A、D113R、L116A、R119A、R119E、R124A、R124E、K130A、E131A、K132A、K133A、M147A、R148A、S149A、L152A、N155A、(L30A、H57Y、E58N及びQ61S)、(R33A、H57Y、E58N、Q61S)、(M147A、H57Y、E58N及びQ61S)、(L152A、H57Y、E58N及びQ61S)、(R143A、H57Y、E58N及びQ61S)、(N65A、L80A、Y85A及びY89A)、(N65A、L80A、Y85A、Y89A及びD113A)、(N65A、L80A、Y85A、Y89A及びL116A)、(N65A、L80A、Y85A、Y89A及びR1190A)、(Y85A、Y89A及びD113A)、(Y85A、Y89A及びR120A)、(D113A及びR119A)、(L116A及びR119A)、(L116A、R119A及びK120A)、(R119A及びK120A)、(R119E及びK120E)、143位のRの、A、D、E、G、H、I、K、L、N、Q、S、T、V又はYによる置換、144位のAの、D、E、G、H、I、K、L、M、N、Q、S、T、V又はYによる置換、並びに残基L160〜E164の欠失からなる群から選択される減弱化変異により更に改変されている、請求項1から3のいずれか一項に記載の融合ポリペプチド。
- 脱グリコシル化IFNα2bのアミノ酸配列が、配列番号3〜30及び配列番号32〜47からなる群から選択される、請求項1から5のいずれか一項に記載の融合ポリペプチド。
- 細胞表面関連抗原が、CD38、CD138、RANK-リガンド、HM1.24、CD56、CS1、CD20、CD74、IL-6R、Blys(BAFF)、BCMA、HLA-SR、HLA-DR、キニノーゲン、ベータ2ミクログロブリン、Ep-CAM、FGFR3、ICAM-1、マトリプターゼ、CD52、EGFR、GM2、アルファ4-インテグリン、IFG-1R、KIR、CD3、CD4、CD8、CD24、CD44、CD69、CD70、CD71、CD79、CD83、CD86、CD96、HLA、PD-1、ICOS、CD33、CD115、CD11c、CD19、CD52、CD14、FSP1、FAP、PDGFRアルファ、PDGFRベータ、ASGR1、ASGR2、FSP1、RTI140/Ti-アルファ、HTI56、VEGF受容体、RCHE遺伝子の生成物CD241、CD117(c-kit)、CD71(トランスフェリン受容体)、CD36(トロンボスポンジン受容体)、CD34、CD45RO、CD45RA、CD115、CD168、CD235、CD236、CD237、CD238、CD239及びCD240からなる群から選択される、請求項1から6のいずれか一項に記載の融合ポリペプチド。
- ポリペプチドリガンドが、CD38に結合する抗体である、請求項1から7のいずれか一項に記載の融合ポリペプチド。
- 抗体のVH アミノ酸配列が、配列番号48〜56及び58からなる群から選択される、請求項8に記載の融合ポリペプチド。
- 抗体のVL アミノ酸配列が、配列番号81、82及び84からなる群から選択される、請求項8又は9に記載の融合ポリペプチド。
- 第1のドメインが、第2のドメインに、ペプチド結合を介して連結している、請求項1から10のいずれか一項に記載の融合ポリペプチド。
- 第1のドメインが、第2のドメインに、ペプチド結合を介して直接連結している、請求項1から10のいずれか一項に記載の融合ポリペプチド。
- 第1のドメインのC末端が、第2のドメインのN末端に連結している、請求項1から10のいずれか一項に記載の融合ポリペプチド。
- 配列番号31、61〜77、83及び87からなる群から選択されるアミノ酸配列、並びに配列番号81、82及び84からなる群から選択される配列を含む融合ポリペプチド。
- アミノ酸配列である配列番号87及び配列番号81を含む融合ポリペプチド。
- i)配列番号1に関して、減弱化変異A145D;又は
ii)106位が欠失している配列番号1に関して、減弱化変異A144D
を含む、請求項2に記載の融合ポリペプチド。 - 脱グリコシル化IFNα2bのアミノ酸配列が、配列番号25である、請求項1に記載の融合ポリペプチド。
- 請求項1から17のいずれか一項に記載の融合ポリペプチド、及び薬学的に許容される担体又は希釈剤を含む組成物。
- 請求項1から17のいずれか一項に記載の融合ポリペプチドを含む、腫瘍の治療剤であって、融合ポリペプチドの第1のドメインが、腫瘍細胞に結合する、治療剤。
- 多発性骨髄腫又は非ホジキンリンパ腫である癌を治療するために使用する、請求項19に記載の治療剤。
- 請求項1から17のいずれか一項に記載の融合ポリペプチドをコードする単離ポリヌクレオチド。
- 請求項21に記載のポリヌクレオチドの1つ又は複数を含むベクター。
- 請求項22に記載のベクターを含む形質転換細胞。
- 哺乳動物細胞中でポリペプチドリガンド-減弱化IFNα2bの融合ポリペプチドを生成する方法であって、ポリペプチドリガンド-減弱化IFNα2bの融合ポリペプチドが、不均一性の低下及び/又はFcRn結合性の増強及び/又は標的選択性の増強を示し; 前記方法が、ポリペプチドリガンド-減弱化IFNα2bの融合ポリペプチドをコードするポリヌクレオチドを1つ又は複数含む組換え哺乳動物細胞を培養する工程を含み、IFNα2b配列のT106が、別のアミノ酸で置換されている又は欠失しており、発現すると、融合タンパク質のIFNα2b成分が脱グリコシル化(aglycosylated)する、方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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JP2020046259A JP6957666B2 (ja) | 2014-10-29 | 2020-03-17 | インターフェロンα2Bバリアント |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2014904326A AU2014904326A0 (en) | 2014-10-29 | Interferon alpha 2b variants | |
AU2014904326 | 2014-10-29 | ||
PCT/AU2015/050654 WO2016065409A1 (en) | 2014-10-29 | 2015-10-23 | INTERFERON α2B VARIANTS |
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JP2020046259A Division JP6957666B2 (ja) | 2014-10-29 | 2020-03-17 | インターフェロンα2Bバリアント |
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JP2017534282A JP2017534282A (ja) | 2017-11-24 |
JP2017534282A5 true JP2017534282A5 (ja) | 2018-11-15 |
JP6730271B2 JP6730271B2 (ja) | 2020-07-29 |
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JP2020046259A Active JP6957666B2 (ja) | 2014-10-29 | 2020-03-17 | インターフェロンα2Bバリアント |
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Country Status (19)
Country | Link |
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US (3) | US10544199B2 (ja) |
EP (1) | EP3212216A4 (ja) |
JP (2) | JP6730271B2 (ja) |
KR (1) | KR102639037B1 (ja) |
CN (1) | CN107106656A (ja) |
AU (1) | AU2015337858B2 (ja) |
BR (1) | BR112017008880A2 (ja) |
CA (1) | CA2965414C (ja) |
CL (1) | CL2017001070A1 (ja) |
CO (1) | CO2017004318A2 (ja) |
EA (1) | EA037749B1 (ja) |
IL (1) | IL251822B2 (ja) |
MX (1) | MX2017005481A (ja) |
PE (1) | PE20170908A1 (ja) |
PH (1) | PH12017500785A1 (ja) |
SG (1) | SG11201703251TA (ja) |
UA (1) | UA125637C2 (ja) |
WO (1) | WO2016065409A1 (ja) |
ZA (1) | ZA201702891B (ja) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
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CN109022465B (zh) | 2011-10-28 | 2022-04-29 | 特瓦制药澳大利亚私人有限公司 | 多肽构建体及其用途 |
ES2774976T3 (es) | 2013-04-29 | 2020-07-23 | Teva Pharmaceuticals Australia Pty Ltd | Anticuerpos anti-CD38 y fusiones con interferón alfa-2b atenuado |
US11117975B2 (en) | 2013-04-29 | 2021-09-14 | Teva Pharmaceuticals Australia Pty Ltd | Anti-CD38 antibodies and fusions to attenuated interferon alpha-2B |
CA2917937C (en) * | 2013-07-18 | 2022-11-01 | Vib Vzw | Fusokines involving cytokines with strongly reduced receptor binding affinities |
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