JP2022060368A - 免疫刺激オリゴヌクレオチドを含む組合せ - Google Patents
免疫刺激オリゴヌクレオチドを含む組合せ Download PDFInfo
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Abstract
Description
a. GTTCCTGGAG ACGTTCTTAG GAACGTTCTC CTTGACGTTG GAGAGAAC(配列番号1)、または
b. ACCTTCCTTG TACTAACGTT GCCTCAAGGA AGGTTGATCT TCATAACGTT GCCTAGATCA(配列番号2)、または
c. AACGTTCTTCGGGG CGTT(配列番号3)、または
d. AGGTGGTAAC CCCTAGGGGT TACCACCTTC ATCGTCGTTT TGTCGTTTTG TCGTTCTT(配列番号4)
を少なくとも1つ含んでよい。
特定の実施形態では、例えば以下の項目が提供される:
(項目1)
a.T細胞調節因子としての機能に影響を与えるため、PD1、PD-L1、OX40、TIM-3、LAG3、CD137(4-1BB)を含む群から選択される少なくとも1つの分子に結合する化学物質または分子を含む第1の群、および
b.少なくとも1つの配列モチーフN 1 N 2 CGN 3 N 4 (ここで、NはA、C、T、またはGを含むヌクレオチドであり、ならびにCはデオキシシチジン、Gはデオキシグアノシン、Aはデオキシアデノシン、およびTはデオキシチミジンである)を含む非コード配列のデオキシリボ核酸を含む第2の群
の構成成分を含む組合せ。
(項目2)
N 1 N 2 がGT、GG、GA、AT、およびAAの群からの要素であり、N 3 N 4 がCT、TG、およびTTの群からの要素である、項目1に記載の組合せ。
(項目3)
前記非コード配列のデオキシリボ核酸は、両側が直鎖状で開鎖している、二本鎖部分の片側が直鎖状で開鎖しており該二本鎖の他方側が一本鎖ヘアピンである、またはダンベル型で部分的に一本鎖の共有結合で閉鎖したデオキシリボ核酸の鎖のいずれかである、項目1または2に記載の組合せ。
(項目4)
T細胞調節因子に免疫系のチェックポイント阻害剤および免疫系の共刺激分子が含まれる、項目1から3のいずれか一項に記載の組合せ。
(項目5)
前記配列モチーフN 1 N 2 CGN 3 N 4 を少なくとも3つ含む、項目1から4のいずれか一項に記載の組合せ。
(項目6)
直鎖状で開鎖した非コード配列のデオキシリボ核酸が、少なくとも1個のL-立体配座のヌクレオチドを有する、項目1から5のいずれか一項に記載の組合せ。
(項目7)
前記直鎖状で開鎖した非コード配列のデオキシリボ核酸のDNA一本鎖の5’-および/または3’-末端に位置した5個の末端ヌクレオチドの1個が、L-立体配座である、項目6に記載の組合せ。
(項目8)
a. GTTCCTGGAG ACGTTCTTAG GAACGTTCTC CTTGACGTTG GAGAGAAC(配列番号1)、または
b. ACCTTCCTTG TACTAACGTT GCCTCAAGGA AGGTTGATCT TCATAACGTT GCCTAGATCA(配列番号2)、または
c. AACGTTCTTCGGGG CGTT(配列番号3)、または
d. AGGTGGTAAC CCCTAGGGGT TACCACCTTC ATCGTCGTTT TGTCGTTTTG TCGTTCTT(配列番号4)
の配列を少なくとも1つ含む、項目1から7のいずれか一項に記載の組合せ。
(項目9)
前記非コード配列のデオキシリボ核酸の長さが40~200ヌクレオチドである、項目1から8のいずれか一項に記載の組合せ。
(項目10)
項目8c)の前記配列が、配列CCTAGGGGTT ACCACCTTCA TTGGAAAACG TTCTTCGGGG CGTTCTTAGG TGGTAACC CCTAGGGGTT ACCACCTTCA TTGGAAAACG TTCTTCGGGG CGTTCTTAGG TGGTAACC(配列番号5)の一部である、項目8または9に記載の組合せ。
(項目11)
前記非コード配列のデオキシリボ核酸の長さが48~116ヌクレオチドである、項目1から10のいずれか一項に記載の組合せ。
(項目12)
前記配列モチーフN 1 N 2 CGN 3 N 4 が、一本鎖領域の一部である、項目1から11のいずれか一項に記載の組合せ。
(項目13)
T細胞調節因子に結合する分子が抗体である、項目1から12のいずれか一項に記載の組合せ。
(項目14)
前記の両群からの構成成分を、最大15mg/kg体重で適用するため、固体、液体、または気体の形態で提供する、項目1から13のいずれか一項に記載の組合せ。
(項目15)
項目1から13のいずれか一項に記載の組合せの構成成分を、同時に、交互に、または連続して提供するステップを含む方法。
(項目16)
前記T細胞調節因子に影響を与えるための前記化学物質または前記分子より先に、前記非コード配列のデオキシリボ核酸を提供する、項目14に記載の方法。
(項目17)
医薬として使用するための、項目1から13のいずれか一項に記載の組合せの使用。
(項目18)
がん、自己免疫疾患、および炎症の治療のための、項目1から13のいずれか一項に記載の組合せの使用。
(項目19)
前記組合せの化合物を、同時に、交互に、または連続して投与する、項目16または17に記載の使用。
(項目20)
前記組合せを含む医薬組成物の製造のための、項目1から13のいずれか一項に記載の組合せの使用。
(項目21)
医薬品が前記組合せの前記化合物を、同時に、交互に、または連続して放出する、項目19に記載の使用。
(項目22)
治療的または予防的ワクチン接種のアジュバントとしての、項目1から13のいずれか一項に記載の組合せの使用。
配列番号5と抗PD-1の組合せは、マウスA20腫瘍モデルにおいて、抗PD-1または配列番号5のいずれかによる単独療法と比較して、驚くほど極めて増強した抗腫瘍効果を示した。
この群の例として、配列番号10(GGGGTCATTAAACGTTCTTCGGGG CGTTCTTTTT、L-デオキシリボースを含む塩基に下線)を、抗PD-1との組合せを検討するために使用した。
Claims (21)
- 配列番号7、配列番号8、配列番号9または配列番号11の直鎖状で開鎖した非コード配列のデオキシリボ核酸。
- 配列番号7を有する、請求項1に記載の直鎖状で開鎖した非コード配列。
- 配列番号8を有する、請求項1に記載の直鎖状で開鎖した非コード配列。
- 配列番号9を有する、請求項1に記載の直鎖状で開鎖した非コード配列。
- 配列番号11を有する、請求項1に記載の直鎖状で開鎖した非コード配列。
- a.T細胞調節因子としての機能に影響を与えるため、PD1またはPD-L1に結合する分子を含む第1の群、および
b.配列番号7、配列番号8、配列番号9または配列番号11を含む非コード配列のデオキシリボ核酸を含む第2の群
の構成成分を含む、免疫調節のための組合せ物。 - 前記第1の群が、PD1に結合する分子を含む、請求項6に記載の組合せ物。
- 前記第1の群が、PD-L1に結合する分子を含む、請求項6に記載の組合せ物。
- 前記デオキシリボ核酸の非コード配列が配列番号7を含む、請求項6に記載の組合せ物。
- 前記デオキシリボ核酸の非コード配列が配列番号8を含む、請求項6に記載の組合せ物。
- 前記デオキシリボ核酸の非コード配列が配列番号9を含む、請求項6に記載の組合せ物。
- 前記デオキシリボ核酸の非コード配列が配列番号11を含む、請求項6に記載の組合せ物。
- 前記デオキシリボ核酸の非コード配列の長さが40~200ヌクレオチドである、請求項6から12のいずれか一項に記載の組合せ物。
- 前記デオキシリボ核酸の非コード配列の長さが48~116ヌクレオチドである、請求項6から13のいずれか一項に記載の組合せ物。
- T細胞調節因子に結合する分子が抗体である、請求項6から14のいずれか一項に記載の組合せ物。
- 前記の両群からの構成成分が、最大15mg/kg体重で適用するため、固体、液体、または気体の形態で提供される、請求項6から15のいずれか一項に記載の組合せ物。
- 前記組合せ物の構成成分が、同時に、交互に、または連続して提供される、請求項6から16のいずれか一項に記載の組合せ物。
- 前記T細胞調節因子に影響を与えるための前記化学物質または前記分子より先に、前記非コード配列のデオキシリボ核酸が提供される、請求項17に記載の組合せ物。
- 前記組合せ物を含む医薬組成物の製造のための、請求項6から18のいずれか一項に記載の組合せ物の使用。
- 医薬品が前記組合せ物の前記化合物を、同時に、交互に、または連続して放出する、請求項19に記載の使用。
- 治療的または予防的ワクチン接種のアジュバントとして使用するための、請求項6から18のいずれか一項に記載の組合せ物。
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