JP6613294B2 - 糖尿病を処置するための組成物および方法 - Google Patents
糖尿病を処置するための組成物および方法 Download PDFInfo
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- JP6613294B2 JP6613294B2 JP2017500321A JP2017500321A JP6613294B2 JP 6613294 B2 JP6613294 B2 JP 6613294B2 JP 2017500321 A JP2017500321 A JP 2017500321A JP 2017500321 A JP2017500321 A JP 2017500321A JP 6613294 B2 JP6613294 B2 JP 6613294B2
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/90—Isomerases (5.)
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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Description
本発明の実施形態において、例えば以下の項目が提供される。
(項目1)
FKBP11ペプチドのレベルを対象において増加させるための組成物であって、該組成物は、FKBP11ペプチドまたはFKBP11ペプチドをコードする核酸を含み、前記FKBP11ペプチドは、FKBP11ポリペプチド、その変異体もしくは断片、またはFKBP11ポリペプチド、その変異体もしくは断片を含有する融合タンパク質からなる群から選択される、組成物。
(項目2)
乾燥粉末、錠剤、ウエハー、フィルム、ロゼンジおよびカプセルからなる群から選択される形態である、項目1に記載の組成物。
(項目3)
非経口投与に適した形態である、項目1に記載の組成物。
(項目4)
前記FKBP11ポリペプチドが配列番号1を含む、項目1に記載の組成物。
(項目5)
ベクター中に、FKBP11ポリペプチド、その変異体または断片をコードする核酸を含む、項目1に記載の組成物。
(項目6)
前記ベクターが、バクテリオファージ、バキュロウイルス、タバコモザイクウイルス、ヘルペスウイルス、サイトメガロウイルス、レトロウイルス、ワクシニアウイルス、アデノウイルスおよびアデノ随伴ウイルスからなる群から選択される、項目5に記載の組成物。
(項目7)
前記FKBP11ペプチドが前記対象において血糖レベルを低減する、項目1に記載の組成物。
(項目8)
FKBP11ペプチドまたはペプチドをコードする核酸を含む組成物を投与する工程を含む、対象においてFKBP11ペプチドのレベルを増加させる方法であって、前記FKBP11ペプチドは、FKBP11ポリペプチド、その変異体もしくは断片、またはFKBP11ポリペプチド、その変異体もしくは断片を含有する融合タンパク質からなる群から選択される、方法。
(項目9)
前記対象が、I型糖尿病の対象、II型糖尿病の対象、肥満の対象、妊娠期糖尿病患者およびインスリン耐性を示している対象からなる群から選択される、項目8に記載の方法。
(項目10)
前記FKBP11ペプチドが前記対象において血糖レベルを低減する、項目8に記載の方法。
(項目11)
前記組成物が、乾燥粉末、錠剤、ウエハー、フィルム、ロゼンジおよびカプセルからなる群から選択される形態である、項目8に記載の方法。
(項目12)
前記組成物が非経口投与される、項目8に記載の方法。
(項目13)
FKBP11ペプチドをコードする前記核酸が発現されるように1つまたは複数の細胞をex vivoで形質転換する工程、および形質転換された前記細胞を前記対象に移入させる工程をさらに含む、項目8に記載の方法。
(項目14)
前記細胞が、膵臓の細胞、島細胞および膵臓の前駆体細胞からなる群から選択される、項目13に記載の方法。
(項目15)
第1の保存容器および第2の保存容器を含むキットであって、前記第1の保存容器は、FKBP11ペプチドまたはFKBP11ペプチドをコードする核酸を含有し、前記第2の保存容器は賦形剤を含み、ここで、前記FKBP11ペプチドは、FKBP11ポリペプチド、その変異体もしくは断片、またはFKBP11ポリペプチド、その変異体もしくは断片を含有する融合タンパク質からなる群から選択される、キット。
(項目16)
前記第1の容器がキャップであり、前記第2の容器は、前記キャップが閉められているバイアルであり、ここで、2つの容器が障壁によって分離されている、項目15に記載のキット。
I.定義
II.組成物
A.FKBP11ペプチド−FKBP11ポリペプチド、その断片/変異体、およびFKBP11を含有する融合タンパク質
1.FKB11ポリペプチド
ヒトFKBP11配列が公知である(AF238079_1)。
2.FKBP11ポリペプチドの変異体/断片
3.FKBP11ペプチドを含有する融合タンパク質
i.タンパク質導入ドメイン(PTD)
RRQRRTSKLM KR(配列番号5);
GWTLNSAGYL LGKINLKALA ALAKKIL(配列番号6);
WEAKLAKALA KALAKHLAKA LAKALKCEA(配列番号7);および
ii.標的化シグナルまたはドメイン
B.FKBP11ペプチドをコードする核酸
C.FKBP11活性を改変する化合物
D.剤形
III.キット
IV.組成物を使用する方法
スクリーニングアッセイ
肥満(ob/ob)および痩身マウスでのFKBP11の発現レベル
材料および方法
結果
(実施例2)
グルコース耐性、肝臓の糖新生活動およびインスリン感受性への回復されたFKBP11発現の効果
材料および方法
結果
(実施例3)
1型糖尿病のin vivoモデルでのFKBP11過剰発現の効果
材料および方法
結果
(実施例4)
痩身マウスおよび肥満のマウス/FKBP11を過剰発現するマウスでのFKBP11の分泌
材料および方法
結果
(実施例5)
組換え完全長FKBP11の単一の静脈内注射は、空腹時血糖を低減する
材料および方法
考察
Claims (12)
- FKBP11ペプチドのレベルを対象において増加させることによって血糖レベルを下げ、グルコース耐性を改善し、肝臓の糖新生活動を減少させ、および/またはインスリン感受性を改善させるための製剤であって、前記製剤は、FKBP11ペプチドまたはFKBP11ペプチドをコードする核酸を含み、前記FKBP11ペプチドは、配列番号1を含むFKBP11ポリペプチド、その変異体もしくは断片、または配列番号1を含むFKBP11ポリペプチド、その変異体もしくは断片を含有する融合タンパク質からなる群から選択され、ここで、前記その変異体もしくは断片は配列番号1と少なくとも90%の配列同一性を含む、製剤。
- 乾燥粉末、錠剤、ウエハー、フィルム、ロゼンジおよびカプセルからなる群から選択される形態である、請求項1に記載の製剤。
- 非経口投与に適した形態である、請求項1に記載の製剤。
- ベクター中に、FKBP11ポリペプチド、その変異体または断片をコードする核酸を含む、請求項1に記載の製剤。
- 前記ベクターが、バクテリオファージ、バキュロウイルス、タバコモザイクウイルス、ヘルペスウイルス、サイトメガロウイルス、レトロウイルス、ワクシニアウイルス、アデノウイルスおよびアデノ随伴ウイルスからなる群から選択される、請求項4に記載の製剤。
- 前記FKBP11ペプチドが前記対象において血糖レベルを低減する、請求項1に記載の製剤。
- 前記対象が、I型糖尿病の対象、II型糖尿病の対象、肥満の対象、妊娠期糖尿病患者およびインスリン耐性を示している対象からなる群から選択される、請求項1に記載の製剤。
- 非経口投与されることを特徴とする、請求項1に記載の製剤。
- FKBP11ペプチドをコードする核酸が発現されるように形質転換された1つまたは複数の細胞を含む、組成物であって、前記組成物は、対象においてFKBP11ペプチドのレベルを増加させることによって血糖レベルを下げ、グルコース耐性を改善し、肝臓の糖新生活動を減少させ、および/またはインスリン感受性を改善させるための組成物であり、前記FKBP11ペプチドは配列番号1を含むFKBP11ペプチドである、組成物。
- 前記細胞が、膵臓の細胞、島細胞および膵臓の前駆体細胞からなる群から選択される、請求項9に記載の組成物。
- 対象においてFKBP11ペプチドのレベルを増加させることによって血糖レベルを下げ、グルコース耐性を改善し、肝臓の糖新生活動を減少させ、および/またはインスリン感受性を改善させるための、第1の保存容器および第2の保存容器を含むキットであって、前記第1の保存容器は、FKBP11ペプチドまたはFKBP11ペプチドをコードする核酸を含有し、前記第2の保存容器は賦形剤を含み、ここで、前記FKBP11ペプチドは、配列番号1を含むFKBP11ポリペプチド、その変異体もしくは断片、または配列番号1を含むFKBP11ポリペプチド、その変異体もしくは断片を含有する融合タンパク質からなる群から選択され、ここで、前記その変異体もしくは断片は配列番号1と少なくとも90%の配列同一性を含む、キット。
- 前記第1の容器がキャップであり、前記第2の容器は、前記キャップが閉められているバイアルであり、ここで、2つの容器が障壁によって分離されている、請求項11に記載のキット。
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US11376308B2 (en) | 2016-10-19 | 2022-07-05 | Royal College Of Surgeons In Ireland | Use of FKBP-L polypeptides and nucleic acids for the treatment of obesity |
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EP3166622A1 (en) | 2017-05-17 |
CA2954539A1 (en) | 2016-01-14 |
CA2954539C (en) | 2021-04-20 |
AU2015287833B2 (en) | 2018-09-13 |
AU2015287833A1 (en) | 2017-01-19 |
EP3166622B1 (en) | 2019-10-23 |
AU2018278890A1 (en) | 2019-01-03 |
WO2016007644A1 (en) | 2016-01-14 |
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