JP2014519524A - 抗psgl−1抗体およびその使用 - Google Patents
抗psgl−1抗体およびその使用 Download PDFInfo
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- JP2014519524A JP2014519524A JP2014515918A JP2014515918A JP2014519524A JP 2014519524 A JP2014519524 A JP 2014519524A JP 2014515918 A JP2014515918 A JP 2014515918A JP 2014515918 A JP2014515918 A JP 2014515918A JP 2014519524 A JP2014519524 A JP 2014519524A
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- psgl
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Abstract
Description
本出願は、2011年6月13日に出願された米国仮特許出願第61/496,249号、名称「抗PSGL−1抗体およびその使用(ANTI-PSGL-1 ANTIBODIES AND USES THEREOF)」の出願日の利益を主張する。参照された仮出願の全体の教示および内容は、参照により本明細書に組み込まれる。
2.分野
3.背景技術
4.概要
5.図面の簡単な説明
6.1 抗体
以下の表4は、抗体15A7HのVLフレームワーク(FR)アミノ酸配列(特に、VL FR1、VL FR2、VL FR3、およびVL FR4配列)を示す。以下の表5は、抗体15A7HのVH FRアミノ酸配列(特に、VH FR1、VH FR2、VH FR3、およびVH FR4配列)を示す。
6.2 ポリヌクレオチド
6.3 宿主細胞および抗体の組み換え発現
6.4 医薬組成物
6.5 治療法
6.6 細胞に基づく方法
6.7 キット
7.例
7.1 例1:抗PSGL−1モノクローナル抗体を生成する
7.2 例2:15A7H抗体の活性化初代ヒトT細胞上の結合
7.2.1 材料および方法
7.2.2 結果:
trans vivo遅延型過敏症マウスモデル
7.3.1 材料および方法
7.3.2 結果
7.4 例4:補体依存性の細胞障害性の評価(CDC)
7.4.1 材料および方法
・試料:100μlの標準ウサギ補体(アッセイ培地中1:6に希釈)+50μlの標的細胞(アッセイ培地中のRamos細胞)+50μlの抗体希釈
・バックグラウンド対照:200μlのアッセイ培地
・最大放出制御:50μlの標的細胞+100μlの標準ウサギ補体+50μlのアッセイ培地
・自然放出制御:50μlの標的細胞+100μlの標準ウサギ補体+50μlのアッセイ培地
7.4.2 結果
15A7Hは、Ramos細胞で実施されたアッセイにおいて、1:12の補体希釈にて5μg/mlの抗体濃度まで、CDC活性を示さなかった。
7.5 臨床研究
15A7Hは、ある複数対象に対しては125μg/kg、500μg/kg、1000μg/kg、および2000μg/kgの単回の増加用量の静脈内投与によって与え、別の複数対象に対しては、500μg/kgおよび1000μg/kgの単回の皮下投与で与えた。投与は適応される。表6に記載の、製剤中に再懸濁させた15A7Hが用いられる。投与後、臨床検査(例えば、血液学、臨床化学および尿検査)を、当該分野で知られている方法を用いて、例えば週単位で実施する。薬物動態学的パラメータも、当該分野で知られている方法を用いて、例えば週単位で決定する。
Claims (16)
- ヒトPSGL−1に免疫特異的に結合するモノクローナル抗体であって、
(i)配列番号3のアミノ酸配列を含む可変軽(「VL」)鎖領域;
(ii)配列番号4のアミノ酸配列を含む可変重(「VH」)鎖領域を含む重鎖;および
(iii)EUインデックスの番号付けによる重鎖のアミノ酸228において、セリンからプロリンへの置換を含む、ヒトIgG4定常領域;
を含む、前記モノクローナル抗体。 - ヒトPSGL−1に免疫特異的に結合するモノクローナル抗体であって、
(i)配列番号1のアミノ酸配列を含む軽鎖;および
(ii)配列番号2のアミノ酸配列を含む重鎖;
を含む、前記モノクローナル抗体。 - ヒトPSGL−1に免疫特異的に結合するモノクローナル抗体であって、
(i)配列番号2からなる重鎖;および
(ii)配列番号1からなる軽鎖;
を含む、前記モノクローナル抗体。 - ヒトPSGL−1に免疫特異的に結合し、かつ
(i)配列番号8、9、および10を含むVH鎖領域;および
(ii)EUインデックスの番号付けによる重鎖のアミノ酸228において、セリンからプロリンへのアミノ酸置換を含む、ヒトIgG4重鎖定常領域;
を含む重鎖を含む、モノクローナル抗体。 - モノクローナル抗体が、配列番号5、6、および7を含むVL鎖領域を含む軽鎖をさらに含む、請求項4に記載のモノクローナル抗体。
- 抗体が精製されている、請求項1〜5のいずれか一項に記載のモノクローナル抗体。
- 請求項1〜6のいずれか一項に記載のモノクローナル抗体および薬学的に許容し得る担体を含む、医薬組成物。
- モノクローナル抗体が精製されている、請求項7に記載の医薬組成物。
- 配列番号2を含む、抗体重鎖。
- 請求項1〜6のいずれか一項に記載のモノクローナル抗体を含む第1容器を含む、キット。
- 請求項1〜6のいずれか一項に記載のモノクローナル抗体を含む、注入装置。
- 注入装置が注射器である、請求項11に記載の注入装置。
- 炎症性障害を処置する方法であって、これを必要とする対象に対して、請求項1〜6のいずれか一項に記載のモノクローナル抗体または請求項8もしくは9に記載の医薬組成物の、治療有効量を投与することを含む、前記方法。
- 炎症性障害を処置する方法であって、これを必要とする対象に対して、請求項7または8に記載の医薬組成物の治療有効量を投与することを含む、前記方法。
- 炎症性障害が自己免疫疾患である、請求項13または14に記載の方法。
- 炎症性障害が、乾癬、尋常性乾癬、慢性尋常性乾癬、滴状乾癬、逆位乾癬、膿疱性乾癬、乾癬性紅皮症、乾癬性関節炎、関節リウマチ、クローン病、強直性脊椎炎、または糖尿病である、請求項13〜15のいずれか一項に記載の方法。
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