JP2017518976A - 新しいcath2誘導体。 - Google Patents
新しいcath2誘導体。 Download PDFInfo
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- JP2017518976A JP2017518976A JP2016567361A JP2016567361A JP2017518976A JP 2017518976 A JP2017518976 A JP 2017518976A JP 2016567361 A JP2016567361 A JP 2016567361A JP 2016567361 A JP2016567361 A JP 2016567361A JP 2017518976 A JP2017518976 A JP 2017518976A
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Abstract
Description
本明細書において使用される「CMAP27」または「CATH2」は、アミノ酸配列RFGRFLRKIRRFRPKVTITIQGSARFGを有するタンパク質として定義されるだけでなく、C末端でアミド化されたバージョンRFGRFLRKIRRFRPKVTITIQGSARF-NH2(これもCMAP1-26-NH2と命名されている)がこの定義に含まれる。カテリシジンでは、C末端グリシン残基のアミド化が官能基に付加することが知られているので、CMAP1-26-NH2がペプチドの活性型であることが示唆されている(Shinnar, A.E. et al., 2003, Bioorg. Chem. 31:425-436; Tomasinsig, I. And Zanetti, M, 2005, Curr. Prot. Pept. Sci. 6:23-34)。
Claims (10)
- N末端が切断されたCMAP27誘導体。
- インベルソおよびレトロインベルソCMAP27-誘導体。
- CMAP27誘導体を投与することを含む、家禽、好ましくは鶏の卵内ワクチン接種のための方法であって、前記CMAP27誘導体は、C末端切断型CMAP27誘導体、N末端切断型CMAP27誘導体、Dアミノ酸型CMAP27誘導体、環状CMAP27誘導体、インベルソおよびレトロインバーソームCMAP27誘導体の群から選択される、前記方法。
- 動物またはヒトの免疫応答を活性化するための方法であって、前記動物またはヒトにCMAP27誘導体を提供する工程を含み、前記CMAP27誘導体が、C末端短縮型CMAP27誘導体、N末端短縮型CMAP27誘導体、Dアミノ酸型CMAP27誘導体、環状CMAP27誘導体、インベルソおよびインベルソCMAP27誘導体の群から選択される、前記方法。
- 免疫応答の活性化が、増加したDNA摂取、エンドトキシン中和、免疫細胞によるサイトカイン/ケモカイン産生の刺激、直接化学走化性、増強された食作用、および免疫細胞の増殖および分化の刺激による、増大したToll様受容体活性化である、請求項4に記載の方法。
- 請求項1〜2のいずれかに記載のCMAP27誘導体を含む免疫学的組成物。
- 感染症の治療用医薬の調製のためまたはワクチンの調製のための請求項1〜2のいずれかに記載のCMAP27誘導体の使用。
- 抗生物質として用いるための請求項1または請求項2に記載のCMAP27誘導体。
- 動物の体重増加に用いるための請求項1または請求項2に記載のCMAP27誘導体。
- 家禽種の卵をCMAP27誘導体で卵内接種することにより家禽の体重を増加させる方法であって、前記CMAP27誘導体が、C末端短縮型CMAP27誘導体、N末端短縮型CMAP27誘導体、Dアミノ酸型CMAP27誘導体、環状CMAP27誘導体、インベルソおよびインベルソCMAP27誘導体の群から選択される、前記方法。
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US10973908B1 (en) | 2020-05-14 | 2021-04-13 | David Gordon Bermudes | Expression of SARS-CoV-2 spike protein receptor binding domain in attenuated salmonella as a vaccine |
AU2021400851A1 (en) | 2020-12-18 | 2023-07-13 | Universiteit Utrecht Holding B.V. | Cath2 derivatives for stimulating innate immune memory |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004506019A (ja) * | 2000-08-17 | 2004-02-26 | インターツェル・アクチェンゲゼルシャフト | 少なくとも1つの抗原およびカテリシジン由来の抗菌ペプチドまたはその誘導体を含むワクチン |
JP2007513138A (ja) * | 2003-12-03 | 2007-05-24 | ファイザー・プロダクツ・インク | 鳥類におけるカンピロバクターの卵内接種 |
US20080119405A1 (en) * | 2005-12-02 | 2008-05-22 | The Board Of Regents For Oklahoma State University | Fowlicidins and Methods of Their Use |
JP2010516688A (ja) * | 2007-01-16 | 2010-05-20 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 抗菌ペプチド |
Family Cites Families (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4040388A (en) | 1976-02-27 | 1977-08-09 | Agrimatic Corporation | Method and apparatus for automatic egg injection |
US4593646A (en) | 1982-06-01 | 1986-06-10 | Agrimatic Corporation | Egg injection method and apparatus |
US4469047A (en) | 1983-10-25 | 1984-09-04 | Miller Gary E | Apparatus and method for injecting eggs |
US4681063A (en) | 1986-07-02 | 1987-07-21 | Embrex Inc. | High speed automated injection system for avian embryos |
DK0831896T3 (da) * | 1995-06-07 | 2001-09-03 | Pfizer | In ovo-vaccination mod coccidiosis |
NZ500779A (en) | 1997-05-20 | 2001-06-29 | Galenica Pharmaceuticals Inc | Triterpene saponin analogs having adjuvant and immunostimulatory activity |
WO2001093905A1 (en) * | 2000-06-08 | 2001-12-13 | Intercell Biomedizinische Forschungs- Und Entwicklungs Ag | Immunostimulatory oligodeoxynucleotides |
WO2009010968A2 (en) * | 2007-07-15 | 2009-01-22 | Yitzchak Hillman | Disease treatment via antimicrobial peptides or their inhibitors |
HUE042310T2 (hu) * | 2009-02-13 | 2019-06-28 | Univ Utrecht Holding Bv | CMAP27-n alapuló antimikrobiális peptidek |
RU2458526C1 (ru) * | 2011-03-28 | 2012-08-20 | Общество с ограниченной ответственностью "Поливит" (ООО "Поливит") | Пробиотическая кормовая добавка для сельскохозяйственных птиц и пушных зверей |
CA2948455C (en) * | 2014-05-09 | 2023-09-19 | Universiteit Utrecht Holding B.V. | New cath2 derivatives |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004506019A (ja) * | 2000-08-17 | 2004-02-26 | インターツェル・アクチェンゲゼルシャフト | 少なくとも1つの抗原およびカテリシジン由来の抗菌ペプチドまたはその誘導体を含むワクチン |
JP2007513138A (ja) * | 2003-12-03 | 2007-05-24 | ファイザー・プロダクツ・インク | 鳥類におけるカンピロバクターの卵内接種 |
US20080119405A1 (en) * | 2005-12-02 | 2008-05-22 | The Board Of Regents For Oklahoma State University | Fowlicidins and Methods of Their Use |
JP2010516688A (ja) * | 2007-01-16 | 2010-05-20 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 抗菌ペプチド |
Non-Patent Citations (4)
Title |
---|
DIJK A. ET AL., MOLECULAR IMMUNOLOGY, vol. Vol. 46, JPN6019010977, 2009, pages pp. 2465-2473 * |
DIJK A. V. ET AL., VETERINARY MICROBIOLOGY, vol. Vol. 153, JPN6019010979, 2011, pages pp. 27-36 * |
MOLHOEK E. M. ET AL., PEPTIDES, vol. Vol. 32, JPN6019010980, 2011, pages pp. 875-880 * |
XIAO, Y. ET AL., J INNATE IMMUN, vol. Vol. 1, JPN6019010975, 2009, pages pp. 268-280 * |
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CN106488929B (zh) | 2021-08-24 |
MX2016014633A (es) | 2017-04-27 |
RU2016144509A3 (ja) | 2019-02-05 |
US20210246177A1 (en) | 2021-08-12 |
US11603391B2 (en) | 2023-03-14 |
RU2726124C2 (ru) | 2020-07-09 |
US10829524B2 (en) | 2020-11-10 |
JP2020109109A (ja) | 2020-07-16 |
RU2016144509A (ru) | 2018-06-13 |
EP3140315A1 (en) | 2017-03-15 |
CN106488929A (zh) | 2017-03-08 |
US20170145065A1 (en) | 2017-05-25 |
CA2948455A1 (en) | 2015-11-12 |
WO2015170984A1 (en) | 2015-11-12 |
AU2015256729B2 (en) | 2019-09-19 |
AU2015256729A1 (en) | 2016-11-24 |
CA3207425A1 (en) | 2015-11-12 |
US20230382961A1 (en) | 2023-11-30 |
JP6676544B2 (ja) | 2020-04-08 |
CA2948455C (en) | 2023-09-19 |
AU2019283922A1 (en) | 2020-01-30 |
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