JP2016507525A5 - - Google Patents
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- JP2016507525A5 JP2016507525A5 JP2015556172A JP2015556172A JP2016507525A5 JP 2016507525 A5 JP2016507525 A5 JP 2016507525A5 JP 2015556172 A JP2015556172 A JP 2015556172A JP 2015556172 A JP2015556172 A JP 2015556172A JP 2016507525 A5 JP2016507525 A5 JP 2016507525A5
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- 102000004965 antibodies Human genes 0.000 claims 26
- 108090001123 antibodies Proteins 0.000 claims 26
- 125000003275 alpha amino acid group Chemical group 0.000 claims 15
- 210000004027 cells Anatomy 0.000 claims 9
- 230000003013 cytotoxicity Effects 0.000 claims 5
- 231100000135 cytotoxicity Toxicity 0.000 claims 5
- 108020004707 nucleic acids Proteins 0.000 claims 5
- 150000007523 nucleic acids Chemical class 0.000 claims 5
- 102100015545 FCGR2A Human genes 0.000 claims 4
- 102100015543 FCGR2B Human genes 0.000 claims 4
- 108010021468 Fc gamma receptor IIA Proteins 0.000 claims 4
- 108010021472 Fc gamma receptor IIB Proteins 0.000 claims 4
- 108091006028 chimera Proteins 0.000 claims 4
- 108020001507 fusion proteins Proteins 0.000 claims 4
- 102000037240 fusion proteins Human genes 0.000 claims 4
- 230000000875 corresponding Effects 0.000 claims 3
- 102100015541 FCGR3A Human genes 0.000 claims 1
- 101710044656 FCGR3A Proteins 0.000 claims 1
- 102100015542 FCGR3B Human genes 0.000 claims 1
- 101710044657 FCGR3B Proteins 0.000 claims 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims 1
- 210000004962 mammalian cells Anatomy 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
Claims (20)
- Ｎ末端からＣ末端で、ＣＨ１ドメイン、キメラヒンジ、ＣＨ２ドメイン、およびＣＨ３ドメインを含む重鎖定常（ＣＨ）領域を含む、抗体であって、
（ａ）前記ＣＨ１ドメインが、少なくとも２１２位〜２１５位（ＥＵ付番）のアミノ酸配列ＤＫＫＶまたはＤＫＲＶを有する、ヒトＩｇＧ１ ＣＨ１ドメインまたはヒトＩｇＧ４ ＣＨ１ドメインを含み、
（ｂ）前記キメラヒンジが、２１６位〜２２７位（ＥＵ付番）のヒトＩｇＧ１またはヒトＩｇＧ４上部ヒンジアミノ酸配列、および２２８位〜２３６位（ＥＵ付番）のヒトＩｇＧ２下部ヒンジアミノ酸配列ＰＣＰＡＰＰＶＡ（配列番号３）を含み、
（ｃ）前記ＣＨ２ドメインが、２３７位〜３４０位（ＥＵ付番）のヒトＩｇＧ４ ＣＨ２ドメインアミノ酸配列を含み、
（ｄ）前記ＣＨ３ドメインが、３４１位〜４４７位（ＥＵ付番）のヒトＩｇＧ１またはヒトＩｇＧ４ ＣＨ３ドメイン配列を含み、そして
ここで前記抗体が、野生型ＩｇＧ１または野生型ＩｇＧ４重鎖定常領域を含む対応する抗体の結合親和性と比較してより低い親和性で、ＦｃγＲに結合することができる、
抗体。 - 前記ＣＨ領域が、配列番号１、配列番号２、配列番号３０、配列番号３１、配列番号３７、または配列番号３８のうち任意の１つを含むアミノ酸配列を有する、請求項１に記載の抗体。
- 前記ＣＨ１ドメインがアミノ酸配列ＤＫＫＶ（配列番号４）を含み、前記キメラヒンジがアミノ酸配列ＥＰＫＳＣＤＫＴＨＴＣＰＰＣＰＡＰＰＶＡ（配列番号８）を含む、請求項１または請求項２に記載の抗体。
- 前記ＣＨ１ドメインがアミノ酸配列ＤＫＲＶ（配列番号５）を含み、前記キメラヒンジがアミノ酸配列ＥＳＫＹＧＰＰＣＰＰＣＰＡＰＰＶＡ（配列番号９）を含む、請求項１または請求項２に記載の抗体。
- 前記ＣＨ２ドメインが配列番号１０のアミノ酸配列を含む、請求項１〜４のいずれか一項に記載の抗体。
- 前記ＣＨ３ドメインが、配列番号１１、配列番号１２、配列番号４１、および配列番号４２からなる群から選択されるアミノ酸配列を含む、請求項１〜５のいずれか一項に記載の抗体。
- 前記抗体が、少なくとも１０ｎＭの抗体濃度で、２０％未満のＣＤＣ細胞傷害性および／またはＡＤＣＣ細胞傷害性、または１０％未満、あるいは５％、４％、３％、２％、または更に０％のもしくは検出不能なＣＤＣおよび／またはＡＤＣＣ細胞傷害性を呈する、請求項１〜６のいずれか一項に記載の抗体。
- 前記ＣＤＣおよび／またはＡＤＣＣ細胞傷害性が、野生型ＩｇＧ１または野生型ＩｇＧ４ ＣＨ領域を含む対応する抗体の前記ＣＤＣおよび／またはＡＤＣＣ細胞傷害性よりも、少なくとも約５倍少ない、または少なくとも約１０倍少ない、請求項７に記載の抗体。
- 単一特異性抗体である、請求項１〜８のいずれか一項に記載の抗体。
- 二重特異性抗体である、請求項１〜８のいずれか一項に記載の抗体。
- 抗体が、ＦｃγＲＩ、ＦｃγＲＩＩＩＡ、またはＦｃγＲＩＩＩＢと結合しない、請求項１〜１０のいずれか一項に記載の抗体。
- 抗体が、ＦｃγＲＩＩＡおよび場合によりＦｃγＲＩＩＢと結合できる、請求項１〜１１のいずれか一項に記載の抗体。
- 抗体が、ＦｃγＲＩＩＢへのその結合親和性と比較してより高い親和性で、ＦｃγＲＩＩＡに結合できる、請求項１〜１２のいずれか一項に記載の抗体。
- 請求項１〜１３のいずれか一項に記載の抗体をコードする、核酸分子。
- 請求項１４に記載の核酸分子を含む、ベクター。
- 前記核酸分子が、宿主細胞中の発現に好適な発現制御配列に作動的に連結される、請求項１５に記載のベクター。
- 請求項１４に記載の核酸分子、または請求項１５もしくは１６に記載のベクターを含む細胞であって、場合によりここで前記核酸分子が、前記細胞のゲノム中に統合される、細胞。
- 前記細胞が哺乳動物細胞であり、場合によりここで前記細胞がＣＨＯ細胞であり、場合によりここで前記細胞がＣＨＯ−Ｋ１細胞である、細胞。
- Ｎ末端からＣ末端で、ＣＨ１ドメイン、キメラヒンジ、ＣＨ２ドメイン、およびＣＨ３ドメインを含む重鎖定常（ＣＨ）領域を含む、受容体−Ｆｃ融合タンパク質であって、
（ａ）前記ＣＨ１ドメインが、少なくとも２１２位〜２１５位（ＥＵ付番）のアミノ酸配列ＤＫＫＶまたはＤＫＲＶを有する、ヒトＩｇＧ１ ＣＨ１ドメインまたはヒトＩｇＧ４ ＣＨ１ドメインを含み、
（ｂ）前記キメラヒンジが、２１６位〜２２７位（ＥＵ付番）のヒトＩｇＧ１またはヒトＩｇＧ４上部ヒンジアミノ酸配列、および２２８位〜２３６位（ＥＵ付番）のヒトＩｇ
Ｇ２下部ヒンジアミノ酸配列ＰＣＰＡＰＰＶＡ（配列番号３）を含み、
（ｃ）前記ＣＨ２ドメインが、２３７位〜３４０位（ＥＵ付番）のヒトＩｇＧ４ ＣＨ２ドメインアミノ酸配列を含み、
（ｄ）前記ＣＨ３ドメインが、３４１位〜４４７位（ＥＵ付番）のヒトＩｇＧ１またはヒトＩｇＧ４ ＣＨ３ドメイン配列を含み、そして
ここで前記受容体−Ｆｃ融合タンパク質が、野生型ＩｇＧ１または野生型ＩｇＧ４重鎖定常領域を含む対応する抗体の結合親和性と比較してより低い親和性で、ＦｃγＲに結合することができる、
受容体−Ｆｃ融合タンパク質。 - ＦｃγＲＩＩＡ、および場合によりＦｃγＲＩＩＢに結合し、ここで受容体−Ｆｃタンパク質はＦｃγＲＩＩＢへのその結合親和性と比較してより高い親和性で、ＦｃγＲＩＩＡに結合できる、請求項１９に記載の受容体−Ｆｃ融合タンパク質。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361759578P | 2013-02-01 | 2013-02-01 | |
| US61/759,578 | 2013-02-01 | ||
| PCT/US2014/014175 WO2014121087A1 (en) | 2013-02-01 | 2014-01-31 | Antibodies comprising chimeric constant domains |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018193951A Division JP6687702B2 (ja) | 2013-02-01 | 2018-10-15 | キメラ定常領域を含む抗体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016507525A JP2016507525A (ja) | 2016-03-10 |
| JP2016507525A5 true JP2016507525A5 (ja) | 2017-03-02 |
| JP6422445B2 JP6422445B2 (ja) | 2018-11-14 |
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015556172A Active JP6422445B2 (ja) | 2013-02-01 | 2014-01-31 | キメラ定常領域を含む抗体 |
| JP2018193951A Active JP6687702B2 (ja) | 2013-02-01 | 2018-10-15 | キメラ定常領域を含む抗体 |
| JP2020065490A Active JP6895558B2 (ja) | 2013-02-01 | 2020-04-01 | キメラ定常領域を含む抗体 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018193951A Active JP6687702B2 (ja) | 2013-02-01 | 2018-10-15 | キメラ定常領域を含む抗体 |
| JP2020065490A Active JP6895558B2 (ja) | 2013-02-01 | 2020-04-01 | キメラ定常領域を含む抗体 |
Country Status (23)
| Country | Link |
|---|---|
| US (4) | US9359437B2 (ja) |
| EP (3) | EP2951207B1 (ja) |
| JP (3) | JP6422445B2 (ja) |
| KR (1) | KR102229732B1 (ja) |
| CN (1) | CN104955844B (ja) |
| AR (1) | AR095115A1 (ja) |
| AU (2) | AU2014212148B2 (ja) |
| CA (1) | CA2899457C (ja) |
| DK (2) | DK3406634T3 (ja) |
| EA (1) | EA032960B1 (ja) |
| ES (1) | ES2687866T3 (ja) |
| FI (1) | FI3406634T3 (ja) |
| HK (1) | HK1217955A1 (ja) |
| HU (1) | HUE040415T2 (ja) |
| IL (1) | IL239688B (ja) |
| MX (2) | MX360746B (ja) |
| MY (2) | MY189467A (ja) |
| NZ (1) | NZ710598A (ja) |
| PL (1) | PL2951207T3 (ja) |
| SG (2) | SG11201505072RA (ja) |
| TW (2) | TWI682941B (ja) |
| WO (1) | WO2014121087A1 (ja) |
| ZA (1) | ZA201504697B (ja) |
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