Oxidized a beta peptide

外国特許コード	F190009713
整理番号	E112P03US2
掲載日	2019年1月24日
出願国	アメリカ合衆国
出願番号	201816018447
公報番号	20180312558
出願日	平成30年6月26日(2018.6.26)
公報発行日	平成30年11月1日(2018.11.1)
国際出願番号	JP2014065749
国際公開番号	WO2014200091
国際出願日	平成26年6月13日(2014.6.13)
国際公開日	平成26年12月18日(2014.12.18)
優先権データ	特願2013-125797 (2013.6.14) JP 特願2013-239622 (2013.11.20) JP 2014JP65749 (2014.6.13) WO 201514898409 (2015.12.14) US
発明の名称 （英語）	Oxidized a beta peptide
発明の概要（英語）	The invention provides an Aβ peptide aggregation inhibitor, an Aβ peptide toxicity reducing agent, and a preventive and/or therapeutic agent for Alzheimer's disease.The oxidized Aβ peptide in which one or more amino acid residues of Aβ peptide have been oxidized (excluding an oxidized Aβ peptide in which only Met has been oxidized).
従来技術、競合技術の概要（英語）	BACKGROUND ART Alzheimer's disease is a neurodegenerative disease having pathological characteristics of degeneration and loss of nerve cells, senile plaque formation, and neurofibrillary tangle.Alzheimer's disease induces a cognitive impairment that a memory, recognition, thinking, judgment, and the like are lost progressively, and finally leads to death. The main substance of the senile plaque deposited in the brain is amyloid β peptide (Aβ peptide) composed of 39 to 43 amino acids.Aβ peptide shows cytotoxicity, and this is considered to induce Alzheimer's disease (Non-Patent Document 1).Aβ peptide secreted from cells is a polypeptide mainly composed of 40 or 42 amino acids.It is known that, among other Aβ peptides, an Aβ peptide composed of 42 amino acids is aggregated strongly, is deposited in the brain early, and has strong cytotoxicity (Non-Patent Document 2).Accordingly, a medical agent for inhibiting production of Aβ peptide and a medical agent for inhibiting aggregation of Aβ peptide are expected to be useful as a preventive and/or therapeutic agent for Alzheimer's disease. Concerning a medical agent that inhibits production of Aβ peptide, studies have been focused on a substance capable of inhibiting β-secretase and γ-secretase, which are enzymes involved in production of Aβ peptide.In addition, an Aβ peptide degrading enzyme promoter, an anti-Aβ peptide antibody, a medical agent that inhibits aggregation of Aβ peptide, or the like have also been studied. On the other hand, there have been reported that a Met-oxidized Aβ peptide (i.e., an oxidized product of Aβ peptide in which the sulfur atom of the Met residue has been oxidized) is present in a low amount in the living body, and the Met-oxidized product has lower aggregation than Aβ peptide (Non-Patent Documents 3 to 5).
特許請求の範囲（英語）	[claim1] 1. A method of producing an oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized), the method comprising oxidizing an Aβ peptide. [claim2] 2. The method according to claim 1, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized. [claim3] 3. The method according to claim 1, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct. [claim4] 4. The method according to claim 1, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35. [claim5] 5. A method of inhibiting aggregation of an Aβ peptide, the method comprising administering the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized). [claim6] 6. The method according to claim 5, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized. [claim7] 7. The method according to claim 5, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct. [claim8] 8. The method according to claim 5, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35. [claim9] 9. A method of reducing toxicity of an Aβ peptide, the method comprising administering the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized). [claim10] 10. The method according to claim 9, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized. [claim11] 11. The method according to claim 9, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct. [claim12] 12. The method according to claim 9, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35. [claim13] 13. A method of preventing and/or treating Alzheimer's disease, the method comprising administering the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized). [claim14] 14. The method according to claim 13, wherein the oxidized Aβ peptide is an oxidized Aβ peptide wherein one or more amino acid residues selected from the group consisting of at least Tyr and His have been oxidized. [claim15] 15. The method according to claim 13, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct. [claim16] 16. The method according to claim 13, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35. [claim17] 17. A method of inhibiting aggregation of an Aβ peptide, the method comprising oxidizing an Aβ peptide to the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized). [claim18] 18. The method according to claim 17, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct. [claim19] 19. The method according to claim 17, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35. [claim20] 20. A method of reducing toxicity of an Aβ peptide, the method comprising oxidizing an Aβ peptide to the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized). [claim21] 21. The method according to claim 20, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct. [claim22] 22. The method according to claim 20, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35. [claim23] 23. A method of preventing and/or treating Alzheimer's disease, the method comprising oxidizing an Aβ peptide to the oxidized Aβ peptide wherein one or more amino acid residues of an Aβ peptide have been oxidized (excluding an oxidized Aβ peptide wherein only Met has been oxidized). [claim24] 24. The method according to claim 23, wherein the oxidized Aβ peptide comprises histidine 13 oxidized as a 14 Da adduct and histidine 14 oxidized as a 14 Da adduct. [claim25] 25. The method according to claim 23, wherein the oxidized Aβ peptide further comprises at least one of oxidized Histidine 6, oxidized Tyrosine 10, and oxidized Methionine 35.
発明者/出願人（英語）	Kanai Motomu Soma Yohei Taniguchi Atsuhiko Sasaki Daisuke JAPAN SCIENCE AND TECHNOLOGY AGENCY
国際特許分類(IPC)	A61K  38/00      ペプチドを含有する医療製剤 C07K   1/113     一次構造を変更しないもの C07K  14/47      哺乳動物から
参考情報 （研究プロジェクト等）	ERATO KANAI Life Science Catalysis AREA