JPWO2020102558A5 - - Google Patents

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JPWO2020102558A5
JPWO2020102558A5 JP2021526345A JP2021526345A JPWO2020102558A5 JP WO2020102558 A5 JPWO2020102558 A5 JP WO2020102558A5 JP 2021526345 A JP2021526345 A JP 2021526345A JP 2021526345 A JP2021526345 A JP 2021526345A JP WO2020102558 A5 JPWO2020102558 A5 JP WO2020102558A5
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cancer
compound
cell
foxp3
wing segment
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Priority claimed from PCT/US2019/061508 external-priority patent/WO2020102558A1/en
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８～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも８個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 8-80 linked nucleosides in length and that includes at least 8 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOS:9-3246. ９～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも９個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 9-80 linked nucleosides in length and that includes at least 9 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs:9-3246. １０～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも１０個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 10-80 bound nucleosides in length and that includes at least 10 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs:9-3246. １１～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも１１個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 11-80 linked nucleosides in length and that includes at least 11 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOs:9-3246. １２～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６の核酸塩基配列のいずれかの少なくとも１２個の連続核酸塩基を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence that is 12-80 linked nucleosides in length and that includes at least 12 contiguous nucleobases of any of the nucleobase sequences of SEQ ID NOS:9-3246. １６～８０個の結合ヌクレオシド長であり、且つ配列番号９～３２４６のいずれか１つの核酸塩基配列を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide that is 16-80 linked nucleosides in length and has a nucleobase sequence comprising the nucleobase sequence of any one of SEQ ID NOS:9-3246. 配列番号９～３２４６のいずれか１つからなる核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence consisting of any one of SEQ ID NOS:9-3246. ８～８０個の結合ヌクレオシド長であり、且つ配列番号１のヌクレオチド２２６９～２２８４内に、又は配列番号２のヌクレオチド１２３３～１２４８、２１５６～２１７１、２７３５～２７５０、４６６１～４６７６、７３０７～７３２２、７３３１～７３４６、７９８０～７９９５、１１５８１～１１５９６、若しくは１２３９６～１２４１１内に相補的な修飾オリゴヌクレオチドを含む化合物。 8-80 linked nucleosides long and within nucleotides 2269-2284 of SEQ ID NO:1 or nucleotides 1233-1248, 2156-2171, 2735-2750, 4661-4676, 7307-7322, 7331 of SEQ ID NO:2 A compound comprising complementary modified oligonucleotides within -7346, 7980-7995, 11581-11596, or 12396-12411. 配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つを含む核酸塩基配列を有する、８～８０個の結合ヌクレオシド長である修飾オリゴヌクレオチドを含む化合物。 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575, comprising a modified oligonucleotide that is 8-80 linked nucleosides long and has a nucleobase sequence comprising any one of SEQ ID NOs: Compound. 配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つからなる核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物。 A compound comprising a modified oligonucleotide having a nucleobase sequence consisting of any one of SEQ ID NOs: 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575. 前記修飾オリゴヌクレオチドは、少なくとも１つの修飾ヌクレオシド間結合、少なくとも１つの修飾糖、又は少なくとも１つの修飾核酸塩基を含む、請求項１～１０のいずれか一項に記載の化合物。 11. The compound of any one of claims 1-10, wherein the modified oligonucleotide comprises at least one modified internucleoside linkage, at least one modified sugar, or at least one modified nucleobase. 前記修飾ヌクレオシド間結合は、ホスホロチオアートヌクレオシド間結合である、請求項１１に記載の化合物。 12. The compound of Claim 11, wherein said modified internucleoside linkage is a phosphorothioate internucleoside linkage. 前記修飾糖は、二環式糖である、請求項１１又は１２に記載の化合物。 13. A compound according to claim 11 or 12, wherein said modified sugar is a bicyclic sugar. 前記二環式糖は：４’－（ＣＨ２）－Ｏ－２’（ＬＮＡ）；４’－（ＣＨ２）２－Ｏ－２’（ＥＮＡ）；及び４’－ＣＨ（ＣＨ３）－Ｏ－２’（ｃＥｔ）からなる群から選択される、請求項１３に記載の化合物。 The bicyclic sugars are: 4'-(CH 2 )-O-2'(LNA);4'-(CH 2 ) 2 -O-2'(ENA); and 4'-CH(CH 3 )- 14. The compound of claim 13, selected from the group consisting of O-2'(cEt). 前記修飾糖は、２’－Ｏ－メトキシエチルである、請求項１１又は１２に記載の化合物。 13. The compound of claim 11 or 12, wherein said modified sugar is 2'-O-methoxyethyl. 前記修飾核酸塩基は、５－メチルシトシンである、請求項１１～１５のいずれか一項に記載の化合物。 The compound of any one of claims 11-15, wherein said modified nucleobase is 5-methylcytosine. 前記修飾オリゴヌクレオチドは：
結合デオキシヌクレオシドからなるギャップセグメントと；
結合ヌクレオシドからなる５’ウイングセグメントと；
結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、修飾糖を含む、請求項１～１６のいずれか一項に記載の化合物。 Said modified oligonucleotide:
a gap segment consisting of linked deoxynucleosides;
a 5' wing segment consisting of linked nucleosides;
a 3' wing segment consisting of linked nucleosides;
17. The compound of any one of claims 1-16, wherein the gap segment is located between the 5' wing segment and the 3' wing segment, and each nucleoside of each wing segment comprises a modified sugar. . １６～８０個の結合ヌクレオシド長であり、且つ配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つを含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物であって、前記修飾オリゴヌクレオチドは：
結合デオキシヌクレオシドからなるギャップセグメントと；
結合ヌクレオシドからなる５’ウイングセグメントと；
結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、修飾糖を含む、化合物。 modified oligonucleotides that are 16-80 linked nucleosides long and have a nucleobase sequence that comprises any one of SEQ ID NOs: 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575 A compound comprising the modified oligonucleotide:
a gap segment consisting of linked deoxynucleosides;
a 5' wing segment consisting of linked nucleosides;
a 3' wing segment consisting of linked nucleosides;
The compound, wherein the gap segment is located between the 5' wing segment and the 3' wing segment, and each nucleoside of each wing segment comprises a modified sugar. １６～８０個の結合核酸塩基長であり、且つ配列番号４４９、５０１、５４４、７９４、１２９３、１３０７、１５１１、１７５５、２４９２、又は２５７５のいずれか１つに列挙される配列を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物であって、前記修飾オリゴヌクレオチドは：
１０個の結合デオキシヌクレオシドからなるギャップセグメントと；
３個の結合ヌクレオシドからなる５’ウイングセグメントと；
３個の結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、ｃＥｔヌクレオシドを含み、各ヌクレオシド間結合は、ホスホロチオアート結合であり、各シトシンは、５－メチルシトシンである、化合物。 A nucleobase sequence that is 16-80 bound nucleobases in length and comprises a sequence recited in any one of SEQ ID NOS: 449, 501, 544, 794, 1293, 1307, 1511, 1755, 2492, or 2575 A compound comprising a modified oligonucleotide having:
a gap segment consisting of 10 linked deoxynucleosides;
a 5' wing segment consisting of three linked nucleosides;
a 3' wing segment consisting of three linked nucleosides;
said gap segment is located between said 5′ wing segment and said 3′ wing segment, each nucleoside of each wing segment comprising a cEt nucleoside, each internucleoside linkage being a phosphorothioate linkage; A compound wherein each cytosine is 5-methylcytosine. １６～８０個の結合核酸塩基長であり、且つ配列番号４４９に列挙される配列を含む核酸塩基配列を有する修飾オリゴヌクレオチドを含む化合物であって、前記修飾オリゴヌクレオチドは：
１０個の結合デオキシヌクレオシドからなるギャップセグメントと；
３個の結合ヌクレオシドからなる５’ウイングセグメントと；
３個の結合ヌクレオシドからなる３’ウイングセグメントと
を含み、
前記ギャップセグメントは、前記５’ウイングセグメントと前記３’ウイングセグメントとの間に位置し、各ウイングセグメントの各ヌクレオシドは、ｃＥｔヌクレオシドを含み、各ヌクレオシド間結合は、ホスホロチオアート結合であり、各シトシンは、５－メチルシトシンである、化合物。 A compound comprising a modified oligonucleotide that is between 16 and 80 bound nucleobases in length and has a nucleobase sequence comprising the sequence recited in SEQ ID NO: 449, wherein said modified oligonucleotide:
a gap segment consisting of 10 linked deoxynucleosides;
a 5' wing segment consisting of three linked nucleosides;
a 3' wing segment consisting of three linked nucleosides;
said gap segment is located between said 5′ wing segment and said 3′ wing segment, each nucleoside of each wing segment comprising a cEt nucleoside, each internucleoside linkage being a phosphorothioate linkage; A compound wherein each cytosine is 5-methylcytosine. 前記オリゴヌクレオチドは、配列番号１～５のいずれかに少なくとも８０％、８５％、９０％、９５％、又は１００％相補的である、請求項１～２０のいずれか一項に記載の化合物。 21. The compound of any one of claims 1-20, wherein said oligonucleotide is at least 80%, 85%, 90%, 95%, or 100% complementary to any of SEQ ID NOs: 1-5. 一本鎖である、請求項１～２１のいずれか一項に記載の化合物。 The compound of any one of claims 1-21, which is single-stranded. 二本鎖である、請求項１～２１のいずれか一項に記載の化合物。 The compound of any one of claims 1-21, which is double-stranded. リボヌクレオチドを含む、請求項１～２３のいずれか一項に記載の化合物。 24. The compound of any one of claims 1-23, comprising a ribonucleotide. デオキシリボヌクレオチドを含む、請求項１～２３のいずれか一項に記載の化合物。 24. The compound of any one of claims 1-23, comprising deoxyribonucleotides. 前記修飾オリゴヌクレオチドは、１６～３０個の結合ヌクレオシドからなる、請求項１～２５のいずれか一項に記載の化合物。 The compound of any one of claims 1-25, wherein said modified oligonucleotide consists of 16-30 linked nucleosides. 前記修飾オリゴヌクレオチドからなる、請求項１～２６のいずれか一項に記載の化合物。 27. The compound of any one of claims 1-26, which consists of said modified oligonucleotide. 請求項１～２７のいずれか一項に記載の化合物の薬学的に許容され得る塩からなる化合物。 A compound consisting of a pharmaceutically acceptable salt of a compound according to any one of claims 1-27. 前記薬学的に許容され得る塩は、ナトリウム塩である、請求項２８に記載の化合物。 29. The compound of Claim 28, wherein said pharmaceutically acceptable salt is the sodium salt. 前記薬学的に許容され得る塩は、カリウム塩である、請求項２８に記載の化合物。 29. The compound of Claim 28, wherein said pharmaceutically acceptable salt is the potassium salt. 式：
Figure 2020102558000001
 又はその塩を有する化合物。 formula:
Figure 2020102558000001
 or a compound having a salt thereof. 式：
Figure 2020102558000002
 を有する化合物。 formula:
Figure 2020102558000002
 A compound having 請求項１～３２のいずれか一項に記載の化合物、及び薬学的に許容され得る担体を含む組成物。 33. A composition comprising a compound according to any one of claims 1-32 and a pharmaceutically acceptable carrier. 治療に用いられる、請求項１～３３のいずれか一項に記載の化合物又は修飾オリゴヌクレオチドを含む組成物。 34. A composition comprising the compound or modified oligonucleotide of any one of claims 1-33 for use in therapy. 個体において癌を治療し、又は寛解させるための医薬組成物であって、ＦＯＸＰ３を標的とする化合物を含む、医薬組成物。 A pharmaceutical composition for treating or ameliorating cancer in an individual, the pharmaceutical composition comprising a compound that targets FOXP3. 前記化合物は、ＦＯＸＰ３を標的とするアンチセンス化合物である、請求項３５に記載の医薬組成物。 36. The pharmaceutical composition of claim 35, wherein said compound is an antisense compound targeting FOXP3. 前記癌は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）である、請求項３５又は３６に記載の医薬組成物。 Said cancer is a cancer with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or a draining lymph node tumor, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) ), head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small intestine cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophagus cancer, pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid) , and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer , myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). Pharmaceutical composition as described. 前記医薬組成物を投与することで、免疫抑制、Ｔｒｅｇ免疫抑制活性、癌細胞増殖、腫瘍増殖、又は転移が阻害され、又は引き下げられ、或いは抗癌若しくは抗腫瘍免疫；抗癌若しくは抗腫瘍免疫応答；免疫細胞の活性化若しくは浸潤；炎症細胞の活性化若しくは浸潤；エフェクタ免疫細胞の活性化若しくは浸潤；Ｔ細胞の活性化若しくは浸潤；ＣＤ８ Ｔ細胞の活性化若しくは浸潤；ＮＫ細胞の活性化若しくは浸潤；マクロファージ及び樹状細胞の活性化若しくは浸潤；炎症；又は炎症性サイトカイン若しくはケモカインの発現が誘導され、又は活性化される、請求項３５～３７のいずれか一項に記載の医薬組成物。 Administration of said pharmaceutical composition inhibits or reduces immunosuppression, Treg immunosuppressive activity, cancer cell proliferation, tumor growth, or metastasis, or anti-cancer or anti-tumor immunity; activation or infiltration of immune cells; activation or infiltration of inflammatory cells; activation or infiltration of effector immune cells; activation or infiltration of T cells; activation or infiltration of CD8 T cells; activation or infiltration of macrophages and dendritic cells; inflammation; or expression of inflammatory cytokines or chemokines is induced or activated. 細胞におけるＦＯＸＰ３の発現を阻害する方法であって、前記細胞を、ＦＯＸＰ３を標的とする化合物と接触させることによって、前記細胞におけるＦＯＸＰ３の発現を阻害することを含む方法。 A method of inhibiting expression of FOXP3 in a cell, comprising inhibiting expression of FOXP3 in said cell by contacting said cell with a compound that targets FOXP3. 前記細胞は癌細胞である、請求項３９に記載の方法。 40. The method of claim 39, wherein said cells are cancer cells. 癌は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）である、請求項４０に記載の方法。 Cancers are cancers with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or draining lymph node tumors, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) , head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small bowel cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophageal cancer , pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid, and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer, 41. The method of claim 40, which is myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). . 癌を患っている個体において、免疫抑制、Ｔｒｅｇ免疫抑制活性、癌細胞増殖、腫瘍増殖、又は転移を引き下げる、又は阻害するための医薬組成物であって、ＦＯＸＰ３を標的とする化合物を含む医薬組成物。 A pharmaceutical composition for reducing or inhibiting immunosuppression, Treg immunosuppressive activity, cancer cell proliferation, tumor growth, or metastasis in an individual suffering from cancer, said pharmaceutical composition comprising a compound targeting FOXP3 thing. 癌を患っている個体において、抗癌若しくは抗腫瘍免疫；抗癌若しくは抗腫瘍免疫応答；免疫細胞の活性化若しくは浸潤；炎症細胞の活性化若しくは浸潤；エフェクタ免疫細胞の活性化若しくは浸潤；Ｔ細胞の活性化若しくは浸潤；ＣＤ８ Ｔ細胞の活性化若しくは浸潤；ＮＫ細胞の活性化若しくは浸潤；マクロファージ及び樹状細胞の活性化若しくは浸潤；炎症；又は炎症性サイトカイン若しくはケモカインの発現を誘導又は活性化するための医薬組成物であって、ＦＯＸＰ３を標的とする化合物を含む医薬組成物。 anti-cancer or anti-tumor immunity; anti-cancer or anti-tumor immune response; immune cell activation or infiltration; inflammatory cell activation or infiltration; effector immune cell activation or infiltration; activation or infiltration of CD8 T cells; activation or infiltration of NK cells; activation or infiltration of macrophages and dendritic cells; inflammation; or expression of inflammatory cytokines or chemokines. comprising a compound that targets FOXP3. 前記個体は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）を患っている、請求項４３に記載の医薬組成物。 The individual has a cancer with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or a draining lymph node tumor, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) ), head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small intestine cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophagus cancer, pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid) , and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer , myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). Pharmaceutical composition as described. 前記化合物は、ＦＯＸＰ３を標的とするアンチセンス化合物である、請求項３５～４４のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 35-44, wherein said compound is an antisense compound targeting FOXP3. 前記化合物は、請求項１～３４のいずれか一項に記載の化合物である、請求項３５～４５のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 35-45, wherein said compound is a compound according to any one of claims 1-34. 前記医薬組成物は、非経口的に投与される、請求項３５～４６のいずれか一項に記載の医薬組成物。 The pharmaceutical composition according to any one of claims 35-46, wherein said pharmaceutical composition is administered parenterally. 癌を治療する、又は寛解させる医薬の製造における、ＦＯＸＰ３を標的とする化合物の使用。 Use of a compound targeting FOXP3 in the manufacture of a medicament for treating or ameliorating cancer. 前記癌は、微環境若しくは間質においてＦＯＸＰ３ポジティブ（ＦＯＸＰ３＋）Ｔｒｅｇを有する癌、又は流入領域リンパ節腫瘍、肺癌、非小細胞肺癌（ＮＳＣＬＣ）、小細胞肺癌（ＳＣＬＣ）、扁平上皮細胞癌（ＳＣＣ）、頭頚部癌、頭頚部扁平上皮細胞癌（ＨＮＳＣＣ）、消化管癌、大腸管癌、小腸管癌、胃癌、結腸癌、結腸直腸癌、膀胱癌、肝癌、肝細胞癌（ＨＣＣ）、食道癌、膵癌、胆道癌、胃癌、尿路上皮癌、乳癌、トリプルネガティブ乳癌（ＴＮＢＣ）、卵巣癌、子宮体癌、子宮頸部癌、前立腺癌、中皮腫、肉腫（例えば、類上皮、ラブドイド、及び滑膜）、脊索腫、腎癌、腎細胞癌（ＲＣＣ）、脳癌、神経芽細胞腫、神経膠芽腫、皮膚癌、メラノーマ、基底細胞癌、メルケル細胞癌、血液癌、造血癌、骨髄腫、多発性骨髄腫（ＭＭ）、Ｂ細胞悪性腫瘍、リンパ腫、Ｂ細胞リンパ腫、ホジキンリンパ腫、Ｔ細胞リンパ腫、白血病、若しくは急性リンパ球性白血病（ＡＬＬ）である、請求項４８に記載の使用。 Said cancer is a cancer with FOXP3-positive (FOXP3+) Tregs in the microenvironment or stroma, or a draining lymph node tumor, lung cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), squamous cell carcinoma (SCC) ), head and neck cancer, head and neck squamous cell carcinoma (HNSCC), gastrointestinal cancer, colon cancer, small intestine cancer, gastric cancer, colon cancer, colorectal cancer, bladder cancer, liver cancer, hepatocellular carcinoma (HCC), esophagus cancer, pancreatic cancer, biliary tract cancer, gastric cancer, urothelial cancer, breast cancer, triple negative breast cancer (TNBC), ovarian cancer, endometrial cancer, cervical cancer, prostate cancer, mesothelioma, sarcoma (e.g. epithelioid, rhabdoid) , and synovium), chordoma, renal cancer, renal cell carcinoma (RCC), brain cancer, neuroblastoma, glioblastoma, skin cancer, melanoma, basal cell carcinoma, Merkel cell carcinoma, blood cancer, hematopoietic cancer , myeloma, multiple myeloma (MM), B-cell malignancy, lymphoma, B-cell lymphoma, Hodgkin's lymphoma, T-cell lymphoma, leukemia, or acute lymphocytic leukemia (ALL). use. 前記化合物は、ＦＯＸＰ３を標的とするアンチセンス化合物である、請求項４８又は４９に記載の使用。 50. Use according to claim 48 or 49, wherein said compound is an antisense compound targeting FOXP3. 前記化合物は、請求項１～３２のいずれか一項に記載の化合物である、請求項４８～５０のいずれか一項に記載の使用。 Use according to any one of claims 48-50, wherein said compound is a compound according to any one of claims 1-32.
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Family Cites Families (236)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3687808A (en) 1969-08-14 1972-08-29 Univ Leland Stanford Junior Synthetic polynucleotides
US5132418A (en) 1980-02-29 1992-07-21 University Patents, Inc. Process for preparing polynucleotides
US4458066A (en) 1980-02-29 1984-07-03 University Patents, Inc. Process for preparing polynucleotides
US4500707A (en) 1980-02-29 1985-02-19 University Patents, Inc. Nucleosides useful in the preparation of polynucleotides
US4469863A (en) 1980-11-12 1984-09-04 Ts O Paul O P Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof
US4415732A (en) 1981-03-27 1983-11-15 University Patents, Inc. Phosphoramidite compounds and processes
US4668777A (en) 1981-03-27 1987-05-26 University Patents, Inc. Phosphoramidite nucleoside compounds
US4973679A (en) 1981-03-27 1990-11-27 University Patents, Inc. Process for oligonucleo tide synthesis using phosphormidite intermediates
US5023243A (en) 1981-10-23 1991-06-11 Molecular Biosystems, Inc. Oligonucleotide therapeutic agent and method of making same
US4476301A (en) 1982-04-29 1984-10-09 Centre National De La Recherche Scientifique Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon
DE3329892A1 (en) 1983-08-18 1985-03-07 Köster, Hubert, Prof. Dr., 2000 Hamburg METHOD FOR PRODUCING OLIGONUCLEOTIDES
US5118800A (en) 1983-12-20 1992-06-02 California Institute Of Technology Oligonucleotides possessing a primary amino group in the terminal nucleotide
USRE34036E (en) 1984-06-06 1992-08-18 National Research Development Corporation Data transmission using a transparent tone-in band system
US5550111A (en) 1984-07-11 1996-08-27 Temple University-Of The Commonwealth System Of Higher Education Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof
FR2567892B1 (en) 1984-07-19 1989-02-17 Centre Nat Rech Scient NOVEL OLIGONUCLEOTIDES, THEIR PREPARATION PROCESS AND THEIR APPLICATIONS AS MEDIATORS IN DEVELOPING THE EFFECTS OF INTERFERONS
US5367066A (en) 1984-10-16 1994-11-22 Chiron Corporation Oligonucleotides with selectably cleavable and/or abasic sites
FR2575751B1 (en) 1985-01-08 1987-04-03 Pasteur Institut NOVEL ADENOSINE DERIVATIVE NUCLEOSIDES, THEIR PREPARATION AND THEIR BIOLOGICAL APPLICATIONS
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
US5506337A (en) 1985-03-15 1996-04-09 Antivirals Inc. Morpholino-subunit combinatorial library and method
US5185444A (en) 1985-03-15 1993-02-09 Anti-Gene Deveopment Group Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages
US5235033A (en) 1985-03-15 1993-08-10 Anti-Gene Development Group Alpha-morpholino ribonucleoside derivatives and polymers thereof
US5405938A (en) 1989-12-20 1995-04-11 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
US5166315A (en) 1989-12-20 1992-11-24 Anti-Gene Development Group Sequence-specific binding polymers for duplex nucleic acids
DE3788914T2 (en) 1986-09-08 1994-08-25 Ajinomoto Kk Compounds for cleaving RNA at a specific position, oligomers used in the preparation of these compounds and starting materials for the synthesis of these oligomers.
US5276019A (en) 1987-03-25 1994-01-04 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
US5264423A (en) 1987-03-25 1993-11-23 The United States Of America As Represented By The Department Of Health And Human Services Inhibitors for replication of retroviruses and for the expression of oncogene products
CA1340032C (en) 1987-06-24 1998-09-08 Jim Haralambidis Lucleoside derivatives
US5188897A (en) 1987-10-22 1993-02-23 Temple University Of The Commonwealth System Of Higher Education Encapsulated 2',5'-phosphorothioate oligoadenylates
US4924624A (en) 1987-10-22 1990-05-15 Temple University-Of The Commonwealth System Of Higher Education 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof
ATE151467T1 (en) 1987-11-30 1997-04-15 Univ Iowa Res Found DNA MOLECULES STABILIZED BY MODIFICATIONS TO THE 3'-TERMINAL PHOSPHODIESTER BOND, THEIR USE AS NUCLEIC ACID PROBE AND AS THERAPEUTIC AGENTS FOR INHIBITING THE EXPRESSION OF SPECIFIC TARGET GENES
US5403711A (en) 1987-11-30 1995-04-04 University Of Iowa Research Foundation Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved
JPH03503894A (en) 1988-03-25 1991-08-29 ユニバーシィティ　オブ　バージニア　アランミ　パテンツ　ファウンデイション Oligonucleotide N-alkylphosphoramidate
US5278302A (en) 1988-05-26 1994-01-11 University Patents, Inc. Polynucleotide phosphorodithioates
US5216141A (en) 1988-06-06 1993-06-01 Benner Steven A Oligonucleotide analogs containing sulfur linkages
US5175273A (en) 1988-07-01 1992-12-29 Genentech, Inc. Nucleic acid intercalating agents
US5194599A (en) 1988-09-23 1993-03-16 Gilead Sciences, Inc. Hydrogen phosphonodithioate compositions
US5256775A (en) 1989-06-05 1993-10-26 Gilead Sciences, Inc. Exonuclease-resistant oligonucleotides
US5134066A (en) 1989-08-29 1992-07-28 Monsanto Company Improved probes using nucleosides containing 3-dezauracil analogs
US5591722A (en) 1989-09-15 1997-01-07 Southern Research Institute 2'-deoxy-4'-thioribonucleosides and their antiviral activity
US5721218A (en) 1989-10-23 1998-02-24 Gilead Sciences, Inc. Oligonucleotides with inverted polarity
US5399676A (en) 1989-10-23 1995-03-21 Gilead Sciences Oligonucleotides with inverted polarity
EP0942000B1 (en) 1989-10-24 2004-06-23 Isis Pharmaceuticals, Inc. 2'-Modified oligonucleotides
US5264562A (en) 1989-10-24 1993-11-23 Gilead Sciences, Inc. Oligonucleotide analogs with novel linkages
US5264564A (en) 1989-10-24 1993-11-23 Gilead Sciences Oligonucleotide analogs with novel linkages
US5177198A (en) 1989-11-30 1993-01-05 University Of N.C. At Chapel Hill Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates
US5130302A (en) 1989-12-20 1992-07-14 Boron Bilogicals, Inc. Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same
US5623065A (en) 1990-08-13 1997-04-22 Isis Pharmaceuticals, Inc. Gapped 2' modified oligonucleotides
US5587470A (en) 1990-01-11 1996-12-24 Isis Pharmaceuticals, Inc. 3-deazapurines
US5459255A (en) 1990-01-11 1995-10-17 Isis Pharmaceuticals, Inc. N-2 substituted purines
US5670633A (en) 1990-01-11 1997-09-23 Isis Pharmaceuticals, Inc. Sugar modified oligonucleotides that detect and modulate gene expression
US5859221A (en) 1990-01-11 1999-01-12 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5681941A (en) 1990-01-11 1997-10-28 Isis Pharmaceuticals, Inc. Substituted purines and oligonucleotide cross-linking
US7101993B1 (en) 1990-01-11 2006-09-05 Isis Pharmaceuticals, Inc. Oligonucleotides containing 2′-O-modified purines
US5457191A (en) 1990-01-11 1995-10-10 Isis Pharmaceuticals, Inc. 3-deazapurines
US5587361A (en) 1991-10-15 1996-12-24 Isis Pharmaceuticals, Inc. Oligonucleotides having phosphorothioate linkages of high chiral purity
US5646265A (en) 1990-01-11 1997-07-08 Isis Pharmceuticals, Inc. Process for the preparation of 2'-O-alkyl purine phosphoramidites
US6005087A (en) 1995-06-06 1999-12-21 Isis Pharmaceuticals, Inc. 2'-modified oligonucleotides
US5149797A (en) 1990-02-15 1992-09-22 The Worcester Foundation For Experimental Biology Method of site-specific alteration of rna and production of encoded polypeptides
US5220007A (en) 1990-02-15 1993-06-15 The Worcester Foundation For Experimental Biology Method of site-specific alteration of RNA and production of encoded polypeptides
US5321131A (en) 1990-03-08 1994-06-14 Hybridon, Inc. Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling
US5470967A (en) 1990-04-10 1995-11-28 The Dupont Merck Pharmaceutical Company Oligonucleotide analogs with sulfamate linkages
GB9009980D0 (en) 1990-05-03 1990-06-27 Amersham Int Plc Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides
EP0745689A3 (en) 1990-05-11 1996-12-11 Microprobe Corporation A dipstick for a nucleic acid hybridization assay
US5610289A (en) 1990-07-27 1997-03-11 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogues
US5608046A (en) 1990-07-27 1997-03-04 Isis Pharmaceuticals, Inc. Conjugated 4'-desmethyl nucleoside analog compounds
US5541307A (en) 1990-07-27 1996-07-30 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs and solid phase synthesis thereof
US5623070A (en) 1990-07-27 1997-04-22 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
US5677437A (en) 1990-07-27 1997-10-14 Isis Pharmaceuticals, Inc. Heteroatomic oligonucleoside linkages
US5386023A (en) 1990-07-27 1995-01-31 Isis Pharmaceuticals Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
EP0544824B1 (en) 1990-07-27 1997-06-11 Isis Pharmaceuticals, Inc. Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression
US5618704A (en) 1990-07-27 1997-04-08 Isis Pharmacueticals, Inc. Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5223618A (en) 1990-08-13 1993-06-29 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analog compounds
US5378825A (en) 1990-07-27 1995-01-03 Isis Pharmaceuticals, Inc. Backbone modified oligonucleotide analogs
CA2088673A1 (en) 1990-08-03 1992-02-04 Alexander L. Weis Compounds and methods for inhibiting gene expression
US5177196A (en) 1990-08-16 1993-01-05 Microprobe Corporation Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof
US5214134A (en) 1990-09-12 1993-05-25 Sterling Winthrop Inc. Process of linking nucleosides with a siloxane bridge
US5561225A (en) 1990-09-19 1996-10-01 Southern Research Institute Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages
AU662298B2 (en) 1990-09-20 1995-08-31 Gilead Sciences, Inc. Modified internucleoside linkages
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
US6582908B2 (en) 1990-12-06 2003-06-24 Affymetrix, Inc. Oligonucleotides
US5948903A (en) 1991-01-11 1999-09-07 Isis Pharmaceuticals, Inc. Synthesis of 3-deazapurines
US5672697A (en) 1991-02-08 1997-09-30 Gilead Sciences, Inc. Nucleoside 5'-methylene phosphonates
US7015315B1 (en) 1991-12-24 2006-03-21 Isis Pharmaceuticals, Inc. Gapped oligonucleotides
US5571799A (en) 1991-08-12 1996-11-05 Basco, Ltd. (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response
DE59208572D1 (en) 1991-10-17 1997-07-10 Ciba Geigy Ag Bicyclic nucleosides, oligonucleotides, processes for their preparation and intermediates
US5594121A (en) 1991-11-07 1997-01-14 Gilead Sciences, Inc. Enhanced triple-helix and double-helix formation with oligomers containing modified purines
TW393513B (en) 1991-11-26 2000-06-11 Isis Pharmaceuticals Inc Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines
DE69232816T2 (en) 1991-11-26 2003-06-18 Isis Pharmaceuticals Inc INCREASED FORMATION OF TRIPLE AND DOUBLE HELICOS FROM OLIGOMERS WITH MODIFIED PYRIMIDINES
US5484908A (en) 1991-11-26 1996-01-16 Gilead Sciences, Inc. Oligonucleotides containing 5-propynyl pyrimidines
US5792608A (en) 1991-12-12 1998-08-11 Gilead Sciences, Inc. Nuclease stable and binding competent oligomers and methods for their use
US5359044A (en) 1991-12-13 1994-10-25 Isis Pharmaceuticals Cyclobutyl oligonucleotide surrogates
US5700922A (en) 1991-12-24 1997-12-23 Isis Pharmaceuticals, Inc. PNA-DNA-PNA chimeric macromolecules
FR2687679B1 (en) 1992-02-05 1994-10-28 Centre Nat Rech Scient OLIGOTHIONUCLEOTIDES.
US5633360A (en) 1992-04-14 1997-05-27 Gilead Sciences, Inc. Oligonucleotide analogs capable of passive cell membrane permeation
US5434257A (en) 1992-06-01 1995-07-18 Gilead Sciences, Inc. Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages
EP0577558A2 (en) 1992-07-01 1994-01-05 Ciba-Geigy Ag Carbocyclic nucleosides having bicyclic rings, oligonucleotides therefrom, process for their preparation, their use and intermediates
US5652355A (en) 1992-07-23 1997-07-29 Worcester Foundation For Experimental Biology Hybrid oligonucleotide phosphorothioates
US5476925A (en) 1993-02-01 1995-12-19 Northwestern University Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups
GB9304620D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Compounds
GB9304618D0 (en) 1993-03-06 1993-04-21 Ciba Geigy Ag Chemical compounds
ATE155467T1 (en) 1993-03-30 1997-08-15 Sanofi Sa ACYCLIC NUCLEOSIDE ANALOGUES AND OLIGONUCLEOTIDE SEQUENCES CONTAINING THEM
AU6412794A (en) 1993-03-31 1994-10-24 Sterling Winthrop Inc. Oligonucleotides with amide linkages replacing phosphodiester linkages
US5457035A (en) 1993-07-23 1995-10-10 Immunex Corporation Cytokine which is a ligand for OX40
US5502177A (en) 1993-09-17 1996-03-26 Gilead Sciences, Inc. Pyrimidine derivatives for labeled binding partners
US5801154A (en) 1993-10-18 1998-09-01 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of multidrug resistance-associated protein
US5821332A (en) 1993-11-03 1998-10-13 The Board Of Trustees Of The Leland Stanford Junior University Receptor on the surface of activated CD4+ T-cells: ACT-4
US5457187A (en) 1993-12-08 1995-10-10 Board Of Regents University Of Nebraska Oligonucleotides containing 5-fluorouracil
ATE196311T1 (en) 1993-12-09 2000-09-15 Univ Jefferson COMPOUNDS AND METHODS FOR SITE-SPECIFIC MUTATION IN EUKARYOTIC CELLS
US5446137B1 (en) 1993-12-09 1998-10-06 Behringwerke Ag Oligonucleotides containing 4'-substituted nucleotides
US5519134A (en) 1994-01-11 1996-05-21 Isis Pharmaceuticals, Inc. Pyrrolidine-containing monomers and oligomers
US6242566B1 (en) 1994-02-10 2001-06-05 Board Of Trustees Of The Leland Stanford Junior University Ligand (ACT-4-L) to a receptor on the surface of activated CD4+ T-cells
US5596091A (en) 1994-03-18 1997-01-21 The Regents Of The University Of California Antisense oligonucleotides comprising 5-aminoalkyl pyrimidine nucleotides
US5627053A (en) 1994-03-29 1997-05-06 Ribozyme Pharmaceuticals, Inc. 2'deoxy-2'-alkylnucleotide containing nucleic acid
US5625050A (en) 1994-03-31 1997-04-29 Amgen Inc. Modified oligonucleotides and intermediates useful in nucleic acid therapeutics
US5646269A (en) 1994-04-28 1997-07-08 Gilead Sciences, Inc. Method for oligonucleotide analog synthesis
US5525711A (en) 1994-05-18 1996-06-11 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Pteridine nucleotide analogs as fluorescent DNA probes
US5597909A (en) 1994-08-25 1997-01-28 Chiron Corporation Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use
US5652356A (en) 1995-08-17 1997-07-29 Hybridon, Inc. Inverted chimeric and hybrid oligonucleotides
TW520293B (en) 1995-11-22 2003-02-11 Univ Johns Hopkins Med Delivery system to enhance cellular uptake of biomolecules
JP3756313B2 (en) 1997-03-07 2006-03-15 武 今西 Novel bicyclonucleosides and oligonucleotide analogues
USRE44779E1 (en) 1997-03-07 2014-02-25 Santaris Pharma A/S Bicyclonucleoside and oligonucleotide analogues
US6770748B2 (en) 1997-03-07 2004-08-03 Takeshi Imanishi Bicyclonucleoside and oligonucleotide analogue
US7572582B2 (en) 1997-09-12 2009-08-11 Exiqon A/S Oligonucleotide analogues
US6794499B2 (en) 1997-09-12 2004-09-21 Exiqon A/S Oligonucleotide analogues
US6312700B1 (en) 1998-02-24 2001-11-06 Andrew D. Weinberg Method for enhancing an antigen specific immune response with OX-40L
US20030228597A1 (en) 1998-04-13 2003-12-11 Cowsert Lex M. Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
US6300319B1 (en) 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6043352A (en) 1998-08-07 2000-03-28 Isis Pharmaceuticals, Inc. 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides
US6682736B1 (en) 1998-12-23 2004-01-27 Abgenix, Inc. Human monoclonal antibodies to CTLA-4
US7109003B2 (en) 1998-12-23 2006-09-19 Abgenix, Inc. Methods for expressing and recovering human monoclonal antibodies to CTLA-4
EP1152009B2 (en) 1999-02-12 2017-09-06 Daiichi Sankyo Company, Limited Novel nucleosides and oligonucleotide analogues
US7084125B2 (en) 1999-03-18 2006-08-01 Exiqon A/S Xylo-LNA analogues
NZ514348A (en) 1999-05-04 2004-05-28 Exiqon As L-ribo-LNA analogues
US6525191B1 (en) 1999-05-11 2003-02-25 Kanda S. Ramasamy Conformationally constrained L-nucleosides
JP4151751B2 (en) 1999-07-22 2008-09-17 第一三共株式会社 New bicyclonucleoside analogues
US6936704B1 (en) 1999-08-23 2005-08-30 Dana-Farber Cancer Institute, Inc. Nucleic acids encoding costimulatory molecule B7-4
US7491805B2 (en) 2001-05-18 2009-02-17 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
WO2001077384A2 (en) 2000-04-07 2001-10-18 Epigenomics Ag Detection of single nucleotide polymorphisms (snp's) and cytosine-methylations
AU2001285467A1 (en) 2000-08-21 2002-03-04 Celltech R And D, Inc. Methods for detecting mutations in the human scurfy/foxp3 gene
US7053199B2 (en) 2000-08-29 2006-05-30 Takeshi Imanishi Nucleoside analogs and oligonucleotide derivatives containing these analogs
US6426220B1 (en) 2000-10-30 2002-07-30 Isis Pharmaceuticals, Inc. Antisense modulation of calreticulin expression
JP2004536027A (en) 2000-12-01 2004-12-02 ジョーンズ・ホプキンス・ユニーバーシティー Glycosylated / galactosylated peptide conjugates, bifunctional linkers, and nucleotide monomers / polymers, and related compositions and methods of use
US7507542B2 (en) 2001-05-08 2009-03-24 Ucb Sa Method for regulating immune function using the FOXP3 protein
US20030175906A1 (en) 2001-07-03 2003-09-18 Muthiah Manoharan Nuclease resistant chimeric oligonucleotides
US20030158403A1 (en) 2001-07-03 2003-08-21 Isis Pharmaceuticals, Inc. Nuclease resistant chimeric oligonucleotides
WO2003020739A2 (en) 2001-09-04 2003-03-13 Exiqon A/S Novel lna compositions and uses thereof
JP2005524384A (en) 2001-09-24 2005-08-18 ボストン　プローブス，インコーポレイテッド Methods, kits and compositions for the suppression of detectable probe binding to randomly distributed repetitive sequences in genomic nucleic acids
AU2003281200A1 (en) 2002-07-03 2004-01-23 Tasuku Honjo Immunopotentiating compositions
US20070009955A1 (en) * 2002-07-08 2007-01-11 Lydie Bougueleret Secreted polypeptide species associated with cardiovascular disorders
CA2504694C (en) 2002-11-05 2013-10-01 Isis Pharmaceuticals, Inc. Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
AU2003295387A1 (en) 2002-11-05 2004-06-03 Isis Parmaceuticals, Inc. Modified oligonucleotides for use in rna interference
EP1560931B1 (en) 2002-11-14 2011-07-27 Dharmacon, Inc. Functional and hyperfunctional sirna
US7250496B2 (en) 2002-11-14 2007-07-31 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory genes and uses thereof
US20080268457A1 (en) * 2002-11-14 2008-10-30 Dharmacon, Inc. siRNA targeting forkhead box P3 (FOXP3)
AU2003288675B2 (en) 2002-12-23 2010-07-22 Medimmune Limited Antibodies against PD-1 and uses therefor
US7723509B2 (en) 2003-04-17 2010-05-25 Alnylam Pharmaceuticals IRNA agents with biocleavable tethers
WO2005010215A2 (en) * 2003-07-17 2005-02-03 Tolerrx, Inc. Methods for identifying tolerance modulatory compounds and uses therefor
US7888497B2 (en) 2003-08-13 2011-02-15 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof
JP4731324B2 (en) 2003-08-28 2011-07-20 武 今西 N-O bond cross-linked novel artificial nucleic acid
US7158164B2 (en) 2003-08-29 2007-01-02 Fuji Photo Film Co., Ltd. Thermal development method and apparatus
WO2005027962A1 (en) 2003-09-18 2005-03-31 Isis Pharmaceuticals, Inc. 4’-thionucleosides and oligomeric compounds
US20050118625A1 (en) 2003-10-02 2005-06-02 Mounts William M. Nucleic acid arrays for detecting gene expression associated with human osteoarthritis and human proteases
US7374927B2 (en) 2004-05-03 2008-05-20 Affymetrix, Inc. Methods of analysis of degraded nucleic acid samples
AU2005248147A1 (en) 2004-05-11 2005-12-08 Alphagen Co., Ltd. Polynucleotides for causing RNA interference and method for inhibiting gene expression using the same
US7687616B1 (en) 2004-05-14 2010-03-30 Rosetta Genomics Ltd Small molecules modulating activity of micro RNA oligonucleotides and micro RNA targets and uses thereof
US20060148740A1 (en) 2005-01-05 2006-07-06 Prosensa B.V. Mannose-6-phosphate receptor mediated gene transfer into muscle cells
LT2650020T (en) 2005-05-06 2016-12-12 Providence Health & Services - Oregon Trimeric OX40-immunoglobulin fusion protein and methods of use
CN109485727A (en) 2005-05-09 2019-03-19 小野药品工业株式会社 The human monoclonal antibodies of programmed death-1 (PD-1) and the method for carrying out treating cancer using anti-PD-1 antibody
EP3470072A1 (en) 2005-06-23 2019-04-17 Biogen MA Inc. Compositions and methods for modulation of smn2 splicing
MX2007015942A (en) 2005-07-01 2008-03-07 Medarex Inc Human monoclonal antibodies to programmed death ligand 1 (pd-l1).
CN1904900A (en) 2005-07-28 2007-01-31 中国科学院生物物理研究所 Human autogenous siRNA sequence, its application and screening method
WO2007056539A2 (en) 2005-11-08 2007-05-18 Medarex, Inc. Prophylaxis and treatment of enterocolitis associated with anti-ctla-4 antibody therapy
CN104072611A (en) * 2005-12-21 2014-10-01 维文蒂阿生物公司 Novel cancer-associated antigen
US7569686B1 (en) 2006-01-27 2009-08-04 Isis Pharmaceuticals, Inc. Compounds and methods for synthesis of bicyclic nucleic acid analogs
KR20130042043A (en) 2006-01-27 2013-04-25 아이시스 파마수티컬즈 인코포레이티드 6-modified bicyclic nucleic acid analogs
US8178503B2 (en) 2006-03-03 2012-05-15 International Business Machines Corporation Ribonucleic acid interference molecules and binding sites derived by analyzing intergenic and intronic regions of genomes
WO2007134181A2 (en) 2006-05-11 2007-11-22 Isis Pharmaceuticals, Inc. 5'-modified bicyclic nucleic acid analogs
US7666854B2 (en) 2006-05-11 2010-02-23 Isis Pharmaceuticals, Inc. Bis-modified bicyclic nucleic acid analogs
US8598333B2 (en) 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
GB0614536D0 (en) 2006-07-21 2006-08-30 Metcalfe Susan M Methods of controlling cellular response to LIF
EP2410053B2 (en) 2006-10-18 2020-07-15 Ionis Pharmaceuticals, Inc. Antisense compounds
EP2064350B1 (en) 2006-11-27 2013-01-02 Ludwig Institute for Cancer Research Ltd. Expression of foxp3 by cancer cells
US20100190837A1 (en) 2007-02-15 2010-07-29 Isis Pharmaceuticals, Inc. 5'-Substituted-2-F' Modified Nucleosides and Oligomeric Compounds Prepared Therefrom
US20100105134A1 (en) 2007-03-02 2010-04-29 Mdrna, Inc. Nucleic acid compounds for inhibiting gene expression and uses thereof
WO2008141282A2 (en) 2007-05-11 2008-11-20 The Regents Of The University Of Michigan Materials and methods for foxp3 tumor suppression
US8278425B2 (en) 2007-05-30 2012-10-02 Isis Pharmaceuticals, Inc. N-substituted-aminomethylene bridged bicyclic nucleic acid analogs
ES2386492T3 (en) 2007-06-08 2012-08-21 Isis Pharmaceuticals, Inc. Carbocyclic bicyclic nucleic acid analogs
DK2170959T3 (en) 2007-06-18 2014-01-13 Merck Sharp & Dohme ANTIBODIES AGAINST HUMAN PROGRAMMED DEATH RECEPTOR PD-1
AU2008272918B2 (en) 2007-07-05 2012-09-13 Isis Pharmaceuticals, Inc. 6-disubstituted bicyclic nucleic acid analogs
WO2009023855A2 (en) 2007-08-15 2009-02-19 Isis Pharmaceuticals, Inc. Tetrahydropyran nucleic acid analogs
WO2009067647A1 (en) 2007-11-21 2009-05-28 Isis Pharmaceuticals, Inc. Carbocyclic alpha-l-bicyclic nucleic acid analogs
EP2231195B1 (en) 2007-12-04 2017-03-29 Arbutus Biopharma Corporation Targeting lipids
US20100285039A1 (en) 2008-01-03 2010-11-11 The Johns Hopkins University B7-H1 (CD274) Antagonists Induce Apoptosis of Tumor Cells
US8530640B2 (en) 2008-02-07 2013-09-10 Isis Pharmaceuticals, Inc. Bicyclic cyclohexitol nucleic acid analogs
EP3604533A1 (en) 2008-04-11 2020-02-05 Arbutus Biopharma Corporation Site-specific delivery of nucleic acids by combining targeting ligands with endosomolytic components
CA2746527A1 (en) 2008-09-22 2010-03-25 Rxi Pharmaceuticals Corporation Rna interference in skin indications
DK2356129T3 (en) 2008-09-24 2013-05-13 Isis Pharmaceuticals Inc Substituted alpha-L bicyclic nucleosides
CN102264762B (en) 2008-09-26 2018-03-27 达纳-法伯癌症研究公司 The anti-PD 1 of people, PD L1 and PD L2 antibody and its application
TWI686405B (en) 2008-12-09 2020-03-01 建南德克公司 Anti-pd-l1 antibodies and their use to enhance t-cell function
EP3192811A1 (en) 2009-02-09 2017-07-19 Université d'Aix-Marseille Pd-1 antibodies and pd-l1 antibodies and uses thereof
RU2016137258A (en) * 2009-04-01 2018-12-13 Юниверсити Оф Майами VACCINE COMPOSITIONS AND WAYS OF THEIR APPLICATION
EP2462153B1 (en) 2009-08-06 2015-07-29 Isis Pharmaceuticals, Inc. Bicyclic cyclohexose nucleic acid analogs
RS60033B1 (en) 2009-11-24 2020-04-30 Medimmune Ltd Targeted binding agents against b7-h1
US9102938B2 (en) 2010-04-01 2015-08-11 Alnylam Pharmaceuticals, Inc. 2′ and 5′ modified monomers and oligonucleotides
US10913767B2 (en) 2010-04-22 2021-02-09 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising acyclic and abasic nucleosides and analogs
WO2012037254A1 (en) 2010-09-15 2012-03-22 Alnylam Pharmaceuticals, Inc. MODIFIED iRNA AGENTS
WO2012109395A1 (en) 2011-02-08 2012-08-16 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
RU2625034C2 (en) 2011-04-20 2017-07-11 МЕДИММЬЮН, ЭлЭлСи Antibodies and other molecules binding b7-h1 and pd-1
EP2751270B1 (en) 2011-08-29 2018-08-22 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
US9828432B2 (en) 2012-02-06 2017-11-28 Providence Health & Services—Oregon Cancer treatment and monitoring methods using OX40 agonists
US20150157710A1 (en) 2012-03-02 2015-06-11 Providence Health & Services-Oregon D/B/A Providence Portland Medical Center Dual ox40 agonist/il-2 cancer therapy methods
WO2013159108A2 (en) 2012-04-20 2013-10-24 Isis Pharmaceuticals, Inc. Oligomeric compounds comprising bicyclic nucleotides and uses thereof
JP2016522674A (en) 2012-05-16 2016-08-04 ラナ セラピューティクス インコーポレイテッド Compositions and methods for regulating gene expression
SG11201407486PA (en) 2012-05-16 2014-12-30 Rana Therapeutics Inc Compositions and methods for modulating utrn expression
AU2013266232B2 (en) 2012-05-23 2017-08-03 The Ohio State University Lipid nanoparticle compositions for antisense oligonucleotides delivery
EP2906699A4 (en) 2012-10-11 2016-06-08 Ionis Pharmaceuticals Inc Oligomeric compounds comprising bicyclic nucleosides and uses thereof
US9175291B2 (en) * 2012-10-11 2015-11-03 Isis Pharmaceuticals Inc. Modulation of androgen receptor expression
CN104837996A (en) 2012-11-15 2015-08-12 罗氏创新中心哥本哈根有限公司 Anti APOB antisense conjugate compounds
JP6387084B2 (en) 2013-05-01 2018-09-05 アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． Compositions and methods for modulating apolipoprotein C-III expression
AU2014274730A1 (en) 2013-06-07 2016-01-21 Rana Therapeutics, Inc. Compositions and methods for modulating FOXP3 expression
ES2787600T3 (en) * 2013-07-02 2020-10-16 Ionis Pharmaceuticals Inc Growth hormone receptor modulators
MX2016004570A (en) * 2013-10-11 2016-09-08 Genentech Inc Use of cbp/ep300 bromodomain inhibitors for cancer immunotherapy.
WO2015162422A1 (en) 2014-04-22 2015-10-29 Mina Therapeutics Limited Sarna compositions and methods of use
WO2015181331A1 (en) 2014-05-29 2015-12-03 Medimmune Limited Antagonists of pdl-1 and pd-1 for the treatment of hpv-negative cancers
TW201619200A (en) 2014-10-10 2016-06-01 麥迪紐有限責任公司 Humanized anti-OX40 antibodies and uses thereof
EP3294342A4 (en) * 2015-05-08 2018-11-07 President and Fellows of Harvard College Universal donor stem cells and related methods
AU2016302747A1 (en) * 2015-08-03 2018-02-22 Constellation Pharmaceuticals, Inc. EZH2 inhibitors and modulation of regulatory T-cell function
BR112018004620A2 (en) * 2015-09-24 2018-09-25 Ionis Pharmaceuticals, Inc. kras expression modulators
WO2017181026A1 (en) 2016-04-15 2017-10-19 Translate Bio Ma, Inc. Selective modulation of foxp3 expression
WO2018031871A1 (en) 2016-08-12 2018-02-15 Translate Bio Ma, Inc. Ex vivo modulation of foxp3 expression
US20200030361A1 (en) 2016-09-23 2020-01-30 City Of Hope Oligonucleotides containing 2'-deoxy-2'fluoro-beta-d-arabinose nucleic acid (2'-fana) for treatment and diagnosis of retroviral diseases
FR3058061A1 (en) * 2016-10-27 2018-05-04 Selexel NEW USE OF DOUBLE STRAND OLIGONUCLEOTIDES
WO2019122277A1 (en) * 2017-12-22 2019-06-27 Roche Innovation Center Copenhagen A/S Novel thiophosphoramidites
CA3112809A1 (en) * 2018-09-26 2020-04-02 AUM LifeTech, Inc. 2' fana modified foxp3 antisense oligonucleotides and methods of use thereof

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