JP2017529067A - Cd3結合ドメイン - Google Patents
Cd3結合ドメイン Download PDFInfo
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- JP2017529067A JP2017529067A JP2017506890A JP2017506890A JP2017529067A JP 2017529067 A JP2017529067 A JP 2017529067A JP 2017506890 A JP2017506890 A JP 2017506890A JP 2017506890 A JP2017506890 A JP 2017506890A JP 2017529067 A JP2017529067 A JP 2017529067A
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Abstract
Description
(a)配列識別番号6、7、8又は9に示される可変重鎖ドメイン(VH)から選択される可変重鎖ドメイン(VH)と、配列識別番号1、2、3又は4に示される可変軽鎖ドメイン(VL)から選択される可変軽鎖ドメイン(VL)、もしくは、
(b)位置111のアミノ酸残基がY又はHで、配列識別番号8に示される可変重鎖ドメイン(VH)との比較で少なくとも95%の配列同一性を有する可変重鎖ドメイン(VH)と、位置49のアミノ酸残基がG又はAで、配列識別番号3に示される可変軽鎖ドメイン(VL)との比較で少なくとも95%の配列同一性を有する可変軽鎖ドメイン(VL)、もしくは、
(c)位置111のアミノ酸残基がY又はHで、配列識別番号8に示される可変重鎖ドメイン(VH)との比較で1〜5の保存アミノ酸置換を有する可変重鎖ドメイン(VH)と、位置49のアミノ酸残基がG又はAで、配列識別番号3に示される可変軽鎖ドメイン(VL)との比較で1〜5の保存アミノ酸置換を有する可変軽鎖ドメイン(VL)。
(i)VL(CD3)- L1 - VH(第2抗原結合部位)- L2 - VL(第2抗原結合部位)- L3 - VH(CD3)、又は、
(ii)VH(CD3)- L1 - VL(第2抗原結合部位)- L2 - VH(第2抗原結合部位)- L3 -VL(CD3)、又は、
(iii)VL(第2抗原結合部位)- L1 - VH(CD3)-L2 - VL(CD3)- L3 - VH(第2抗原結合部位)、又は、
(iv )VH(第2抗原結合部位)- L1 - VL(CD3)- L2 - VH(CD3)- L3 - VL(第2抗原結合部位)。
Claims (16)
- 少なくとも一つのCD3結合部位を含む抗原結合タンパク質であって、ここで前記CD3結合部位は以下を有する、
(a)配列識別番号8に示す可変重鎖ドメイン(VH)と配列識別番号3に示す可変軽鎖ドメイン(VL)、もしくは、
(b)配列識別番号9に示す可変重鎖ドメイン(VH)と配列識別番号4に示す可変軽鎖ドメイン(VL)、もしくは、
(c)配列識別番号8に示す前記VHに対して少なくとも95%の配列同一性を有する可変重鎖ドメイン(VH)、ここで、位置111のアミノ酸残基はY又はHである、そして、配列識別番号3に示す前記VLに対して少なくとも95%の配列同一性を有する可変軽鎖ドメイン(VL)、ここで、位置49のアミノ酸残基はG又はAである、もしくは、
(c)配列識別番号8に示す前記VHに対して1〜5の保存アミノ酸置換を含む可変重鎖ドメイン(VH)、ここで、位置111のアミノ酸残基はY又はHである、そして、配列識別番号3に示す前記VLに対して1〜5の保存アミノ酸置換を含む可変軽鎖ドメイン(VL)、ここで、位置49のアミノ酸残基はG又はAである、そして
(a)、(b)又は(c)の前記抗原結合タンパク質は、ヒトCD33とヒトCD3とに特異的に結合する二重特異性結合タンパク質ではなく、前記CD3結合部位は、配列識別番号1〜3から成るグループから選択される抗-CD3可変軽鎖ドメインと配列識別番号6〜8から成るグループから選択される抗-CD3可変重鎖ドメインとを含む、抗原結合タンパク質。 - 前記抗原結合タンパク質は、CD33とCD3とに結合する二重特異性タンデムダイアボディ(tandem diabody)ではない請求項1に記載の抗原結合タンパク質。
- 前記抗原結合タンパク質は、少なくとも一つの別の機能ドメインを有する請求項1又は2に記載の抗原結合タンパク質。
- 前記少なくとも一つの別の機能ドメインは、別の抗原結合部位である請求項3に記載の抗原結合タンパク質。
- 前記別の抗原結合部位は、腫瘍細胞に対して特異的である請求項4に記載の抗原結合タンパク質。
- 前記別の抗原結合部位は、CD33に対して特異的ではない請求項5に記載の抗原結合タンパク質。
- 前記抗原結合タンパク質は、多価である請求項1〜6の何れか一項に記載の抗原結合タンパク質。
- 前記抗原結合タンパク質は、多重特異性である請求項7に記載の抗原結合タンパク質。
- 前記抗原結合タンパク質は、多量体である請求項8に記載の抗原結合タンパク質。
- 前記抗原結合タンパク質は、二量体であり、第1ポリペプチドと第2ポリペプチドとを有し、これらポリペプチドのそれぞれは、互いに連結された少なくとも四つの可変鎖ドメインを有し、前記抗原結合タンパク質は、請求項1に記載の少なくとも一つのCD3結合部位と、第2の抗原に対して特異的な少なくとも一つの別の抗原結合部位とを有する請求項9に記載の抗原結合タンパク質。
- 各ポリペプチドは、以下の順序でペプチドリンカーL1、L2及びL3によって互いに融合された少なくとも四つの可変ドメインを有する請求項10に記載の抗原結合タンパク質。
(i)VL(CD3)- L1 - VH(第2抗原)- L2 - VL(第2抗原)- L3 - VH(CD3)、
(ii)VH(CD3)- L1 - VL(第2抗原)- L2 - VH(第2抗原)- L3 - VL(CD3)、
(iii)VL(第2抗原)- L1 - VH(CD3)- L2 - VL(CD3)-L3 - VH(第2抗原)、もしくは、
(iv)VH(第2抗原)- L1 - VL(CD3)- L2 - VH(CD3)- L3 - VL(第2抗原) - 前記ペプチドリンカーL1、L2及びL3は、約12以下のアミノ酸残基から成る請求項10に記載の抗原結合タンパク質。
- 請求項1〜12の何れか一項に記載の抗原結合タンパク質をコードするポリヌクレオチド。
- (i)請求項1〜12の何れか一項に記載の抗原結合タンパク質、請求項13に記載のポリヌクレオチド、或いは、請求項13に記載のポリヌクレオチドを含むベクター、及び、
(ii)薬学的に許容可能なキャリア、を有する医薬組成物。 - (i)宿主細胞に、請求項13に記載のポリヌクレオチドを導入する工程、
(ii)前記宿主細胞を、前記抗原結合タンパク質が発現される条件下で培養する工程、及び、
(iii)前記発現された抗原結合タンパク質を精製する工程、を有する請求項1〜12の何れか一項に記載の抗原結合タンパク質の製造方法。 - 請求項1〜12の何れか一項に記載の抗原結合タンパク質の医薬としての使用。
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JP2021501571A (ja) * | 2017-10-20 | 2021-01-21 | グリーン・クロス・コーポレイションGreen Cross Corp. | 抗cd3抗体およびそれを含む癌処置用医薬組成物 |
WO2021162098A1 (ja) * | 2020-02-14 | 2021-08-19 | 協和キリン株式会社 | Cd3に結合するバイスペシフィック抗体 |
JP2022525393A (ja) * | 2019-03-29 | 2022-05-13 | グリーン・クロス・コーポレイション | 抗メソテリン抗体、抗cd3抗体又は抗egfr抗体を含む融合タンパク質、それを含む二重特異性又は三重特異性抗体、及びその使用 |
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JP6669722B2 (ja) | 2020-03-18 |
CA2957462C (en) | 2023-10-17 |
CN107001468A (zh) | 2017-08-01 |
BR112017002422B1 (pt) | 2024-02-20 |
RU2742691C2 (ru) | 2021-02-09 |
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CN107001468B (zh) | 2021-04-09 |
EP3177646B1 (en) | 2020-10-07 |
LT3177646T (lt) | 2021-01-11 |
BR112017002422A2 (pt) | 2017-11-28 |
US20160039934A1 (en) | 2016-02-11 |
WO2016020444A1 (en) | 2016-02-11 |
RU2017105120A3 (ja) | 2019-02-20 |
AU2015299039A1 (en) | 2017-03-02 |
HUE051919T2 (hu) | 2021-04-28 |
RU2017105120A (ru) | 2018-09-10 |
DK3177646T3 (da) | 2020-12-07 |
EP2982693A1 (en) | 2016-02-10 |
AU2015299039B2 (en) | 2021-01-21 |
CA2957462A1 (en) | 2016-02-11 |
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SI3177646T1 (sl) | 2021-04-30 |
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