JP2016510596A5 - - Google Patents
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- JP2016510596A5 JP2016510596A5 JP2015561737A JP2015561737A JP2016510596A5 JP 2016510596 A5 JP2016510596 A5 JP 2016510596A5 JP 2015561737 A JP2015561737 A JP 2015561737A JP 2015561737 A JP2015561737 A JP 2015561737A JP 2016510596 A5 JP2016510596 A5 JP 2016510596A5
- Authority
- JP
- Japan
- Prior art keywords
- fusion protein
- seq
- acid sequence
- amino acid
- protein according
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 102000037240 fusion proteins Human genes 0.000 claims 21
- 108020001507 fusion proteins Proteins 0.000 claims 21
- 150000001413 amino acids Chemical class 0.000 claims 14
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims 5
- 102100000643 SMAD7 Human genes 0.000 claims 5
- 108010021883 Smad7 Protein Proteins 0.000 claims 5
- 230000000694 effects Effects 0.000 claims 5
- 230000004663 cell proliferation Effects 0.000 claims 3
- 230000002401 inhibitory effect Effects 0.000 claims 3
- 230000002265 prevention Effects 0.000 claims 3
- 230000001737 promoting Effects 0.000 claims 3
- 102000004169 proteins and genes Human genes 0.000 claims 3
- 108090000623 proteins and genes Proteins 0.000 claims 3
- 230000026683 transduction Effects 0.000 claims 3
- 238000010361 transduction Methods 0.000 claims 3
- 230000003110 anti-inflammatory Effects 0.000 claims 2
- 210000004027 cells Anatomy 0.000 claims 2
- 230000004083 survival Effects 0.000 claims 2
- 206010059512 Apoptosis Diseases 0.000 claims 1
- 206010003816 Autoimmune disease Diseases 0.000 claims 1
- 231100000277 DNA damage Toxicity 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 206010061218 Inflammation Diseases 0.000 claims 1
- 206010028116 Mucosal inflammation Diseases 0.000 claims 1
- 102100017669 SMAD2 Human genes 0.000 claims 1
- 241000580858 Simian-Human immunodeficiency virus Species 0.000 claims 1
- 108010007585 Smad2 Protein Proteins 0.000 claims 1
- 230000002159 abnormal effect Effects 0.000 claims 1
- 230000033115 angiogenesis Effects 0.000 claims 1
- 230000003172 anti-dna Effects 0.000 claims 1
- 230000006907 apoptotic process Effects 0.000 claims 1
- 230000012292 cell migration Effects 0.000 claims 1
- 238000002512 chemotherapy Methods 0.000 claims 1
- 229920003013 deoxyribonucleic acid Polymers 0.000 claims 1
- 201000004624 dermatitis Diseases 0.000 claims 1
- 231100000406 dermatitis Toxicity 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000010393 epithelial cell migration Effects 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 230000003176 fibrotic Effects 0.000 claims 1
- 230000004054 inflammatory process Effects 0.000 claims 1
- 201000010927 mucositis Diseases 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 238000006366 phosphorylation reaction Methods 0.000 claims 1
- 230000000865 phosphorylative Effects 0.000 claims 1
- 201000004681 psoriasis Diseases 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 230000004044 response Effects 0.000 claims 1
- 230000037390 scarring Effects 0.000 claims 1
- 102000015609 tat Gene Products Human genes 0.000 claims 1
- 108010038756 tat Gene Products Proteins 0.000 claims 1
- 230000000451 tissue damage Effects 0.000 claims 1
- 231100000827 tissue damage Toxicity 0.000 claims 1
- 200000000019 wound Diseases 0.000 claims 1
- 230000029663 wound healing Effects 0.000 claims 1
Claims (17)
- タンパク質導入ドメインおよびSmad7ドメインを含む、医薬として使用するための融合タンパク質であって、前記Smad7ドメインが
(i)SEQ ID NO:12に記載のアミノ酸配列のアミノ酸2〜258、または位置216のMetがLeuに改変されているその変異体;
(ii)SEQ ID NO:12に記載のアミノ酸配列のアミノ酸203〜258、または位置216のMetがLeuに改変されているその変異体;
(iii)SEQ ID NO:12に記載のアミノ酸配列のアミノ酸259〜426;
(iv)SEQ ID NO:12に記載のアミノ酸配列のアミノ酸203〜217、または位置216のMetがLeuに改変されているその変異体;および
(v)位置216のMetがLeuに改変されているSEQ ID NO:12に記載のアミノ酸配列;
からなる群より選択され、
前記Smad7ドメインが1または複数のSmad7の生物学的活性を有する、
融合タンパク質。 - 位置216のMetがLeuに改変されている、請求項1に記載の融合タンパク質。
- タンパク質導入ドメインがHIV由来のTatタンパク質の変異体である、請求項1に記載の融合タンパク質。
- タンパク質導入ドメインがSEQ ID NO:2、SEQ ID NO:4、およびSEQ ID NO:6からなる群より選択される、請求項3に記載の融合タンパク質。
- 1または複数のエピトープタグまたは精製タグをさらに含む、請求項1〜4のいずれかに記載の融合タンパク質。
- 融合タンパク質のアミノ酸配列がSEQ ID NO:27に示される、請求項1に記載の融合タンパク質。
- 1または複数の生物学的活性が細胞遊走の媒介、細胞増殖の増加、放射線誘発DNA損傷の減少、および線維化反応の阻害からなる群より選択される、請求項6に記載の融合タンパク質。
- 融合タンパク質のアミノ酸配列がSEQ ID NO:25に示される、請求項1に記載の融合タンパク質。
- 1または複数の生物学的活性がSmad2のリン酸化の減少または除去、NF−κBp50サブユニットの核転座の減少または除去、細胞増殖の増加、上皮細胞遊走の増加、アポトーシスの減少、放射線誘発DNA損傷の減少、炎症の減少、および脈管形成の減少からなる群より選択される、請求項8に記載の融合タンパク質。
- 融合タンパク質のアミノ酸配列がSEQ ID NO:98に示される、請求項1に記載の融合タンパク質。
- 1または複数の生物学的活性が細胞生存の促進、抗炎症、およびpSmad2の阻害からなる群より選択される、請求項10に記載の融合タンパク質。
- Smad7ドメインのアミノ酸配列がSEQ ID NO:12におけるアミノ酸203〜258として示される、請求項1記載の融合タンパク質。
- 1または複数の生物学的活性が細胞増殖の促進、細胞生存の促進、抗炎症、抗DNA損傷、およびpSmad2の阻害からなる群より選択される、請求項12に記載の融合タンパク質。
- 放射線療法または化学療法により誘発される口腔粘膜炎または組織損傷の治療または予防において使用するための、請求項1〜13のいずれかに記載の融合タンパク質。
- 自己免疫疾患、乾癬、または皮膚炎の治療または予防において使用するための、請求項1〜13のいずれかに記載の融合タンパク質。
- 創傷、異常な創傷治癒、瘢痕、または線維症の治療または予防において使用するための、請求項1〜13のいずれかに記載の融合タンパク質。
- 請求項1〜16のいずれかに記載の融合タンパク質をコードする核酸分子。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361775252P | 2013-03-08 | 2013-03-08 | |
US61/775,252 | 2013-03-08 | ||
PCT/US2014/022052 WO2014138670A1 (en) | 2013-03-08 | 2014-03-07 | Ptd-smad7 therapeutics |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2016510596A JP2016510596A (ja) | 2016-04-11 |
JP2016510596A5 true JP2016510596A5 (ja) | 2017-03-30 |
JP6576251B2 JP6576251B2 (ja) | 2019-09-18 |
Family
ID=51492023
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015561737A Active JP6576251B2 (ja) | 2013-03-08 | 2014-03-07 | PTD−Smad7薬物療法 |
Country Status (9)
Country | Link |
---|---|
US (5) | US10456448B2 (ja) |
EP (1) | EP2964774B1 (ja) |
JP (1) | JP6576251B2 (ja) |
CN (1) | CN105358704B (ja) |
CA (1) | CA2904329C (ja) |
HK (1) | HK1219986A1 (ja) |
IL (1) | IL241190B (ja) |
SG (1) | SG11201507045TA (ja) |
WO (1) | WO2014138670A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105457016B (zh) | 2010-09-22 | 2022-06-24 | 科罗拉多大学董事会 | Smad7的治疗应用 |
US10456448B2 (en) | 2013-03-08 | 2019-10-29 | The Regents Of The University Of Colorado, A Body Corporate | PTD-SMAD7 therapeutics |
KR101853923B1 (ko) * | 2016-01-25 | 2018-05-02 | 연세대학교 산학협력단 | Smad 단백질을 포함하는 자가 면역 질환 치료용 조성물, Smad 단백질을 포함하는 융합 단백질, 이를 제조하기 위한 벡터, 및 이의 제조 방법 |
CN112004546A (zh) * | 2017-12-30 | 2020-11-27 | 科罗拉多大学董事会 | Ptd-smad7融合蛋白治疗剂 |
WO2023044277A1 (en) * | 2021-09-15 | 2023-03-23 | The Regents Of The University Of Colorado, A Body Corporate | Smad7 polypeptide formulations |
WO2023150743A2 (en) * | 2022-02-07 | 2023-08-10 | Aavogen Inc. | Codon-optimized smad7 gene therapy to treat and prevent muscle wasting and to enhance muscle mass |
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-
2014
- 2014-03-07 US US14/773,167 patent/US10456448B2/en active Active
- 2014-03-07 JP JP2015561737A patent/JP6576251B2/ja active Active
- 2014-03-07 CA CA2904329A patent/CA2904329C/en active Active
- 2014-03-07 US US14/201,488 patent/US9422352B2/en active Active
- 2014-03-07 EP EP14761076.0A patent/EP2964774B1/en active Active
- 2014-03-07 CN CN201480025596.9A patent/CN105358704B/zh active Active
- 2014-03-07 WO PCT/US2014/022052 patent/WO2014138670A1/en active Application Filing
- 2014-03-07 SG SG11201507045TA patent/SG11201507045TA/en unknown
-
2015
- 2015-09-06 IL IL241190A patent/IL241190B/en active IP Right Grant
-
2016
- 2016-06-23 HK HK16107300.2A patent/HK1219986A1/zh unknown
- 2016-07-12 US US15/208,424 patent/US20170000851A1/en not_active Abandoned
-
2019
- 2019-09-26 US US16/584,608 patent/US20200023037A1/en not_active Abandoned
-
2022
- 2022-04-22 US US17/727,579 patent/US20220370560A1/en not_active Abandoned
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