JP2020502149A - 組成物およびその使用 - Google Patents
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- JP2020502149A JP2020502149A JP2019532008A JP2019532008A JP2020502149A JP 2020502149 A JP2020502149 A JP 2020502149A JP 2019532008 A JP2019532008 A JP 2019532008A JP 2019532008 A JP2019532008 A JP 2019532008A JP 2020502149 A JP2020502149 A JP 2020502149A
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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Abstract
Description
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
で示される化合物と共に投与することを含む、癌を処置または予防する方法を提供する。
式(I)で示される化合物が
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
であり;
医薬が免疫チェックポイントモジュレーターとの投与のために製剤化される、使用を提供する。
医薬が式(I):
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
で示される化合物との投与のために製剤化される、使用を提供する。
式(I)で示される化合物が
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、使用を提供する。
式(I)で示される化合物が
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、免疫チェックポイントモジュレーターと式(I)で示される化合物を提供する。
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、医薬組成物を提供する。
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、キットを提供する。
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、組合せ医薬を提供する。
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
で示される化合物と共に投与することを含む、方法を提供する。
PG545(または3β,5α-コレスタニル2,3,4,6-テトラ-O-ナトリウムスルホナト-α-D-グルコピラノシル-(1→4)-2,3,6-トリ-O-ナトリウムスルホナト-α-D-グルコピラノシル-(1→4)-2,3,6-トリ-O-ナトリウムスルホナト-α-D-グルコピラノシル-(1→4)-2,3,6-トリ-O-ナトリウムスルホナト-β-D-グルコピラノシド)は、下記の構造を有する。PG545は、ピキサチモド(酸について)との世界保健機関により提案された国際一般名(INN)が割り当てられている。この化合物は、WO2009/049370に開示されている。PG545は、Ferro et al 2012またはWO2009/049370において提供されるように合成され得る。
雌性Balb/cマウス(8週齢;Walter and Eliza Hall Institute of Medical Research (WEHI), Victoria Australia)の乳腺内脂肪体にリン酸緩衝生理食塩水中1×105個の4T1.2細胞を接種した。4T1.2は、マウス乳腺腫瘍モデルである。
上記実施例1において移植されたコホートからの16匹のマウスを、実施例1について4匹のマウスからなる4群への接種の1週間後に、無作為化した(平均腫瘍体積=77 mm3)。PG545を15 mg/kg(0.1 ml/10g体重)にて1および8日目に腹腔内投与し、抗PD-1またはコントロール抗体(100μl)を1、4および8日目に腹腔内投与した。
- 染色1(グランザイムB細胞内染色による固定群)採取のための停止ゲートをすべての群についてCD45.2に設定して、腫瘍サイズに関連するいずれのバイアスも取り除いた。
- 染色2 明確なデータセットを作らず、更なる分析から除去した。
- 染色3および4 採取のための停止ゲートをすべての群についてDAPI陰性細胞(生存可能細胞採取日)に設定して、腫瘍サイズに関連するいずれのバイアスも取り除いた。
PG545および抗PD-1群の%TGI(84%)は、ビヒクル+抗PD1抗体群(44%)と比較してほぼ2倍高く、PG545+コントロール抗体群(68%)より高い。
Boyango I, Barash U, Naroditsky I, Li JP, Hammond E, Ilan N, Vlodavsky I. (2014) Heparanase cooperates with Ras to drive breast and skin tumorigenesis. Cancer Res. 74(16): 4504-14.
Claims (21)
- 処置または予防を必要とする患者に、免疫チェックポイントモジュレーターを式(I):
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
で示される化合物と共に投与することを含む、癌を処置または予防する方法。 - 少なくとも90%のX基が、SO3Mである、請求項1に記載の方法。
- 式(I)で示される化合物が、式(VI):
で示される化合物である、請求項1または2に記載の方法。 - 免疫チェックポイントモジュレーターが、免疫チェックポイント阻害剤である、請求項1〜3のいずれか一項に記載の方法。
- 免疫チェックポイントモジュレーターが、T細胞、抗原提示細胞(APC)/腫瘍細胞、ナチュラルキラー(NK)細胞、ナチュラルキラーT細胞(NKT)、γδT細胞、インバリアントT細胞、またはインバリアントナチュラルキラーT細胞(NKT)の1つ以上を標的とする、請求項1〜4のいずれか一項に記載の方法。
- 免疫チェックポイントモジュレーターが、T細胞免疫チェックポイント阻害剤である、請求項1〜5のいずれか一項に記載の方法。
- 免疫チェックポイントモジュレーターが、PD-1阻害剤である、請求項1〜4のいずれか一項に記載の方法。
- 免疫チェックポイントモジュレーターが、ニボルマブである、請求項1〜3のいずれか一項に記載の方法。
- 癌が、固形腫瘍である、請求項1〜8のいずれか一項に記載の方法。
- 癌の処置または予防のための医薬の製造における式(I)で示される化合物の使用であって、
式(I)で示される化合物が、
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
であり;
医薬が、免疫チェックポイントモジュレーターとの投与のために製剤化される、使用。 - 癌の処置または予防のための医薬の製造における免疫チェックポイントモジュレーターの使用であって、
医薬が、式(I):
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
で示される化合物との投与のために製剤化される、使用。 - 少なくとも90%のX基が、SO3Mである、請求項10または11に記載の使用。
- 式(I)で示される化合物が、式(VI):
で示される化合物である、請求項10〜12のいずれか一項に記載の使用。 - 免疫チェックポイントモジュレーターが、免疫チェックポイント阻害剤である、請求項10〜13のいずれか一項に記載の使用。
- 免疫チェックポイントモジュレーターが、T細胞、抗原提示細胞(APC)/腫瘍細胞、ナチュラルキラー(NK)細胞、ナチュラルキラーT細胞(NKT)、γδT細胞、インバリアントT細胞、またはインバリアントナチュラルキラーT細胞(NKT)の1つ以上を標的とする、請求項10〜14のいずれか一項に記載の使用。
- 免疫チェックポイントモジュレーターが、T細胞免疫チェックポイント阻害剤である、請求項10〜15のいずれか一項に記載の使用。
- 免疫チェックポイントモジュレーターが、PD-1阻害剤である、請求項10〜14のいずれか一項に記載の使用。
- 免疫チェックポイントモジュレーターが、ニボルマブである、請求項10〜13のいずれか一項に記載の使用。
- 癌の処置または予防における使用のための免疫チェックポイントモジュレーターと式(I)で示される化合物であって、
式(I)で示される化合物が、
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、免疫チェックポイントモジュレーターと式(I)で示される化合物。 - 式(I)で示される化合物および免疫チェックポイントモジュレーターを含む医薬組成物または組合せ医薬であって、式(I)で示される化合物は、
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、医薬組成物または組合せ医薬。 - 式(I)で示される化合物および免疫チェックポイントモジュレーターを含むキットであって、式(I)で示される化合物が、
[式中、Xは、SO3MまたはHであり、Mは、任意の医薬的に許容されるカチオンであり;少なくとも70%のX基は、SO3Mである]
である、キット。
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WO2015176033A1 (en) * | 2014-05-15 | 2015-11-19 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
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CN103788141B (zh) | 2004-03-04 | 2016-08-17 | 普罗吉恩制药有限公司 | 硫酸化寡聚糖衍生物 |
USRE46955E1 (en) | 2007-10-16 | 2018-07-17 | Progen Pg500 Series Pty Ltd | Sulfated oligosaccharide derivatives |
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EP3554511A1 (en) | 2019-10-23 |
CN110475560A (zh) | 2019-11-19 |
AU2019204696B2 (en) | 2020-07-23 |
EP3554511A4 (en) | 2019-12-25 |
CN110475560B (zh) | 2023-06-20 |
JP2023027292A (ja) | 2023-03-01 |
KR20190134591A (ko) | 2019-12-04 |
US20190314393A1 (en) | 2019-10-17 |
AU2017376836A1 (en) | 2019-07-18 |
WO2018107244A1 (en) | 2018-06-21 |
AU2019204696A1 (en) | 2019-07-18 |
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