JP2016515137A - アポリポタンパク質模倣体及びその使用 - Google Patents
アポリポタンパク質模倣体及びその使用 Download PDFInfo
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/775—Apolipopeptides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
本出願は、双方ともその全体が参照によって本明細書に組み入れられる2013年3月14日に出願されたUS61/782,956及び2013年6月14日に出願されたUS61/834,992の利益を主張する。
本発明は、国立衛生研究所によって授与されたR01HL090803のもとで政府の支援を受けた。政府は本発明に特定の権利を有する。
2014年3月14日に創られ、206,473バイトのサイズを有する「21085_0184P1_Sequence_Listing.txt」と名付けられたテキストファイルとしての2014年3月14日に提出された配列表は、37C.F.R.§1.52(e)(5)に従って参照によって本明細書に組み入れられる。
A.定義
B.投与計画
1.治療サイクル
2.休止期
3.用量
4.ApoE模倣体
i.アポリポタンパク質E
ii.単一ドメインペプチド
a.受容体結合ドメインペプチド
b.脂質関連ペプチド
(A)クラスAの両親媒性の螺旋ペプチド
表2.クラスAのペプチド
*リンカーには下線を引く
NMAはN−メチルアントラニリル
(B)非極性面にて芳香族または脂肪族の残基を有するapoA−IのクラスAの両親媒性の螺旋ペプチド模倣体
表3.修飾されたクラスAのペプチド
(C)他のクラスA及び一部のクラスYの両親媒性の螺旋ペプチド
表4.アミノ酸組成:3つのアラニン(A)、2つのアスパラギン酸(D)、2つのグルタミン酸(E)、4つのフェニルアラニン(F)、4つのリジン(K)、1つのバリン(V)、1つのトリプトファン(W)及び1つのチロシン(Y)を持つ説明に役立つ18アミノ酸の長さのクラスAの両親媒性の螺旋ペプチド
4Nph Ac-DWNphKANphYDKVAEKNphKEANph-NH2 (配列番号460)
[D-E交換] 4Nph Ac-EWNphKANphYEKVADKNphKDANph-NH2 (配列番号461)
[D>E]4Nph Ac-EWNphKANphYEKVAEKNphKEANph-NH2 (配列番号462)
[E>D]4Nph Ac-DWNphKANphYDKVADKNphKDANph-NH2 (配列番号463)
[D-1>E]4Nph Ac-EWNphKANphYDKVAEKNphKEANph-NH2 (配列番号464)
[D-8>E]4Nph Ac-DWNphKANphYEKVAEKNphKEANph-NH2 (配列番号465)
[E-12>D]4Nph Ac-DWNphKANphYDKVADKNphKEANph-NH2 (配列番号466)
[E-16>D]4Nph Ac-DWNphKANphYDKVAEKNphKDANph-NH2 (配列番号467)
[F-3, 6,>Nph]4F Ac-DWNphKANphYDKVAEKFKEAF-NH2 (配列番号468)
[F-14, 18>Nph]4F Ac-DWFKAFYDKVAEKNphKEANph-NH2 (配列番号469)
[[F-3>Nph]4F Ac-DWNphKAFYDKVAEKFKEAF-NH2 (配列番号470)
[F-6>Nph]4F Ac-DWFKANphYDKVAEKFKEAF-NH2 (配列番号471)
[F-14>Nph]4F Ac-DWFKAFYDKVAEKNphKEAF-NH2 (配列番号472)
[F-18>Nph]4F Ac-DWFKAFYDKVAEKFKEANph-NH2 (配列番号473)
Rev-4Nph Ac-NphAEKNphKEAVKDYNphAKNphWD-NH2 (配列番号474)
[F-3, 6>Nph]Rev Ac-NphAEKNphKEAVKDYFAKFWD-NH2 (配列番号475)
4F [F-13, 16]Rev-4F Ac-FAEKFKEAVKDYNphAKNphWD-NH2 (配列番号476)
[F-3>Nph]Rev-4F Ac-NphAEKFKEAVKDYFAKFWD-NH2 (配列番号477)
[F-6>Nph]Rev-4F Ac-FAEKNphKEAVKDYFAKFWD-NH2 (配列番号478)
[F-13>Nph]Rev-4F Ac-FAEKFKEAVKDYNphAKFWD-NH2 (配列番号479)
[F-16>Nph]Rev-4F Ac-FAEKEKEAVKDYFAKNphWD-NH2 (配列番号480)
Rev-[D>E]-4F Ac-FAEKFKEAVKEYFAKFWE-NH2 (配列番号481)
Rev-[E>D]4F Ac-FADKFKDAVKDYFAKFWD-NH2 (配列番号482)
Rev-R4-4F Ac-FAERFREAVKDYFAKFWD-NH2 (配列番号483)
Rev-R6-4F Ac-FAEKFREAVKDYFAKFWD-NH2 (配列番号484)
Rev-R10-4F Ac-FAEKFKEAVRDYFAKFWD-NH2 (配列番号485)
Rev-R14-4F Ac-FAEKFKEAVKDYFARFWD-NH2 (配列番号486)
Rev-[D>E]-4F Ac-FAEKFKEAVKEYFAKFWE-NH2 (配列番号481)
Rev-[E>D]4F Ac-FADKFKDAVKDYFAKFWD-NH2 (配列番号482)
Rev-R4-4F Ac-FAERFREAVKDYFAKFWD-NH2 (配列番号483)
Rev-R6-4F Ac-FAEKFREAVKDYFAKFWD-NH2 (配列番号484)
Rev-R10-4F Ac-FAEKFKEAVRDYFAKFWD-NH2 (配列番号485)
Rev-R14-4F Ac-FAEKFKEAVKDYFARFWD-NH2 (配列番号486)
Rev-[D>E]-4F Ac-FAEKFKEAVKEYFAKFWE-NH2 (配列番号481)
Rev-[E>D]4F Ac-FADKFKDAVKDYFAKFWD-NH2 (配列番号482)
Rev-R4-4F Ac-FAERFREAVKDYFAKFWD-NH2 (配列番号483)
Rev-R6-4F Ac-FAEKFREAVKDYFAKFWD-NH2 (配列番号484)
Rev-R10-4F Ac-FAEKFKEAVRDYFAKFWD-NH2 (配列番号485)
Rev-R14-4F Ac-FAEKFKEAVKDYFARFWD-NH2 (配列番号486)
Rev-R4-4F Ac-FAERFREAVKDYFAKFWD-NH2 (配列番号483)
Rev-R6-4F Ac-FAEKFREAVKDYEAKFWD-NH2 (配列番号487)
Rev-R10-4F Ac-FAEKFKEAVRDYFAKFWD-NH2 (配列番号485)
Rev-R14-4F Ac-FAEKFKEAVKDYFARFWD-NH2 (配列番号486)
Rev-[D>E]-4F Ac-FAEKFKEAVKEYFAKFWE-NH2 (配列番号481)
Rev-[E>D]4F Ac-FADKFKDAVKDYFAKFWD-NH2 (配列番号482)
Rev-R4-4F Ac-FAERFREAVKDYFAKFWD-NH2 (配列番号483)
Rev-R6-4F Ac-FAEKFREAVKDYFAKFWD-NH2 (配列番号484)
Rev-R10-4F Ac-FAEKFKEAVRDYFAKFWD-NH2 (配列番号485)
Rev-R14-4F Ac-FAEKFKEAVKDYFARFWD-NH2 (配列番号486)
Rev3F-2 Ac-LFEKFAEAFKDYVAKWKD-NH2 (配列番号488)
RevR4-3F-2 Ac-LFERFAEAFKDYVAKWKD-NH2 (配列番号489)
RevR10-3F2 Ac-LFEKFAEAFRDYVAKWKD-NH2 (配列番号490)
RevR15-3F-2 Ac-LFEKFAEAFKDYVARWKD-NH2 (配列番号491)
RevR17-3F-2 Ac-LFEKFAEAFKDYVAKWRD-NH2 (配列番号492)
Rev[D>E]3F2 Ac-LFEKFAEAFKEYVAKWKE-NH2 (配列番号493)
Rev[E>D]3F-2 Ac-LFDKFADAFKDYVAKWKD-NH2 (配列番号494)
Rev-[E3>D]-3F-2 Ac-LFDKFAEAFKDYVAKWKD-NH2 (配列番号495)
Rev-[E7>D]-3F-2 Ac-LFEKFADAFKDYVAKWKD-NH2 (配列番号496)
Rev[D11>E]3F-2 Ac-LFEKFAEAFKEYVAKWKD-NH2 (配列番号497)
Rev-[D18>E]3F-2 Ac-LFEKFAEAFKDYVAKWKE-NH2 (配列番号498)
Rev3F-1 Ac-FAEKAWEFVKDYFAKLKD-NH2 (配列番号499)
RevR4-3F-1 Ac-FAERAWEFVKDYFAKLKD-NH2 (配列番号500)
RevR10-3F-1 Ac-FAEKAWEFVKDYFAKLKD-NH2 (配列番号501)
RevR15-3F-1 Ac-FAEKAWEFVKDYFAKLKD-NH2 (配列番号502)
RevR17-3F-1 Ac-FAEKAWEFVKDYFAKLRD-NH2 (配列番号503)
Rev[D>E]3F-1 Ac-FAEKAWEFVKEYFAKLKE-NH2 (配列番号504)
Rev[E>D}3F-1 Ac-FADKAWDFVKDYFAKLKD-NH2 (配列番号505)
Rev[E3>D]-3F-1 Ac-FADKAWEFVKDYFAKLKD-NH2 (配列番号506)
Rev[E7>D]3F-1 Ac-FAEKAWDFVKDYFAKLKD-NH2 (配列番号507)
Rev-[D11>E]3F-1 Ac-FAEKAWEFVKEYFAKLKD-NH2 (配列番号508)
Rev-[D18>E]3F-1 Ac-FAEKAWEFVKDYFAKLKE-NH2 (配列番号509)
Rev-5F Ac-FFEKFKEFVKDYFAKLWD-NH2 (配列番号510)
Rev-[D>E]5F Ac-FFEKFKEFVKEYFAKLWE-NH2 (配列番号511)
Rev-[E>D]5F Ac-FFDKFKDFVKDYFAKLWD-NH2 (配列番号512)
Rev-R4-5F Ac-FFERFKEFVKDYFAKLWD-NH2 (配列番号513)
Rev-R6-5F Ac-FFEKFREFVKDYFAKLWD-NH2 (配列番号514)
Rev-R10-5F Ac-FFEKFKEFVRDYFAKLWD-NH2 (配列番号515)
Rev-R15-5F Ac-FFEKFKEFVKDYFARLWD-NH2 (配列番号516)
Rev-[E3>D]-5F Ac-FFDKFKEFVKDYFAKLWD-NH2 (配列番号517)
Rev-[E7>D]5F Ac-FFEKFKDFVKDYFAKLWD-NH2 (配列番号518)
Rev-[D11>E]-5F Ac-FFEKFKEFVKEYFAKLWD-NH2 (配列番号519)
Rev-[D18>E]-5F Ac-FFEKFKEFVKDYFAKLWE-NH2 (配列番号520)
Rev-5F-2 Ac-FLEKFKEFVKDYFAKFWD-NH2 (配列番号521)
Rev-[D>E]-5F-2 Ac-FLEKFKEFVKEYFAKFWE-NH2 (配列番号522)
Rev-[E>D]-5F-2 Ac-FLDKFKEFVKDYFAKFWD-NH2 (配列番号523)
Rev-[E3>D]-5F-2 Ac-FLDKFKEFVKDYFAKFWD-NH2 (配列番号524)
Rev-[E7>D]-5F-2 Ac-FLEKFKDFVKDYFAKFWD-NH2 (配列番号525)
Rev-[D11>E]-5F-2 Ac-FLEKFKEFVKEYFAKFWD-NH2 (配列番号526)
Rev-[D18>E]-5F-2 Ac-FLEKFKEFVKDYFAKFWE-NH2 (配列番号527)
Rev-R4-5F-2 Ac-FLERFKEFVKDYFAKFWD-NH2 (配列番号528)
Rev-R6-5F-2 Ac-FLEKFREFVKDYFAKFWD-NH2 (配列番号529)
RevR10-5F-2 Ac-FLEKFKEFVRDYFAKFWD-NH2 (配列番号530)
Rev-R16-5F-2 Ac-FLEKFKEFVKDYFARFWD-NH2 (配列番号531)
Rev-6F Ac-FFEKFKEFFKDYFAKLWD-NH2 (配列番号532)
Rev-[D>E]-6F Ac-FFEKFKEFFKEYFAKLWE-NH2 (配列番号533)
Rev-[E>D]-6F Ac-FFDKFKDFFKDYFAKLWD-NH2 (配列番号534)
Rev-R4-6F Ac-FFERFKEFFKDYFAKLWD-NH2 (配列番号535)
Rev-R6-6F Ac-FFEKFREFFKDYFAKLWD-NH2 (配列番号536)
Rev-R10-6F Ac-FFEKFKEFFRDYFAKLWD-NH2 (配列番号537)
Rev-R14-6F Ac-FFERFKEFFKDYFARLWD-NH2 (配列番号538)
Rev-[E3>D]-6F Ac-FFDKFKEFFKDYFAKLWD-NH2 (配列番号539)
Rev-[E7>D]-6F Ac-FFEKEKDFFKDYFAKLWD-NH2 (配列番号540)
Rev-[D11>E]-6F Ac-FFEKFKEFFKEYFAKLWD-NH2 (配列番号541)
Rev-[D18>E]-6F Ac-FFEKFKEFFKDYFAKLWE-NH2 (配列番号542)
Rev-4F Ac-FAEKFKEAVKDYFAKFWD-NH2 (配列番号543)
Rev-[D>E]-4F Ac-FAEKFKEAVKEYFAKFWE-NH2 (配列番号481)
Rev-[E>D]4F Ac-FADKFKDAVKDYFAKFWD-NH2 (配列番号482)
Rev-R4-4F Ac-FAERFREAVKDYFAKFWD-NH2 (配列番号483)
Rev-R6-4F Ac-FAEKFREAVKDYFAKFWD-NH2 (配列番号484)
Rev-R10-4F Ac-FAEKFKEAVRDYFAKFWD-NH2 (配列番号485)
Rev-R14-4F Ac-FAEKFKEAVKDYFARFWD-NH2 (配列番号486)
4F-2 Ac-DKWKAVYDKFAEAFKEFF-NH2 (配列番号544)
[D>E]-4F-2 Ac-EKWKAVYEKFAEAFKEFF-NH2 (配列番号545)
[E>D]-4F-2 Ac-DKWKAVYDKFADAFKDFF-NH2 (配列番号546)
R2-4F-2 Ac-DRWKAVYDKFAEAFKEFF-NH2 (配列番号547)
R4-4F-2 Ac-DKWRAVYDKFAEAFKEFF-NH2 (配列番号548)
R9-4F-2 Ac-DKWKAVYDRFAEAFKEFF-NH2 (配列番号549)
R14-4F-2 Ac-DKWKAVYDKFAEAFREFF-NH2 (配列番号550)
Rev4F-2 Ac-FFEKFAEAFKDYVAKWKD-NH2 (配列番号551)
Rev-[D>E]-4F-2 Ac-FFEKFAEAFKEYVAKWKE-NH2 (配列番号552)
Rev-[E>D]-3F-2 Ac-FFDKFADAFKDYVAKWKD-NH2 (配列番号553)
Rev-R4-4F-2 Ac-FFERFAEAFKDYVAKWKD-NH2 (配列番号554)
Rev-R10-4F-2 Ac-EFERFAEAFRDYVAKWKD-NH2 (配列番号555)
Rev-R15-4F-2 Ac-FFEKFAEAFKDYVARWKD-NH2 (配列番号556)
Rev-R17-4F-2 Ac-FFERFAEAFKDYVAKWRD-NH2 (配列番号557)
Rev-[E3>D]-4F-2 Ac-FFDKFAEAFKDYVAKWKD-NH2 (配列番号558)
Rev-[E7>D]-4F-2 Ac-FFEKFADAFKDYVAKWKD-NH2 (配列番号559)
Rev-[D11>E]-4F-2 Ac-FFERFAEAFKEYVAKWKD-NH2 (配列番号560)
Rev-[D18>E]-4F-2 Ac-FFERFAEAFKDYVAKWKE-NH2 (配列番号561)
Rev-7F Ac-FFEKFKEFFKDYFAKFWD-NH2 (配列番号562)
Rev-[E>D]-7F Ac-FFDKFKDFFKDYFAKFWD-NH2 (配列番号563)
Rev-[D>E]-7F Ac-FFEKFKEFFKEYFAKFWE-NH2 (配列番号564)
Rev-R4-7F Ac-FFERFKEFFKDYFAKFWD-NH2 (配列番号565)
Rev-R6-7F Ac-FFEKFREFFKDYFAKFWD-NH2 (配列番号566)
Rev-R10-7F Ac-FFEKFKEFFRDYFAKFWD-NH2 (配列番号567)
Rev-R14-7F Ac-FFEKFKEFFKDYFARFWD-NH2 (配列番号568)
Rev-[E3>D]-7F Ac-FFDKFKEFFKDYFAKFWD-NH2 (配列番号569)
Rev-[E7>D]7F Ac-FFEKFKDFFKDYFAKFWD-NH2 (配列番号570)
Rev-[D11>E]-7F Ac-FFEKFKEFFKEYFAKFWD-NH2 (配列番号571)
Rev-[D18>E]-7F Ac-FFEKFKEFFKDYFAKFWE-NH2 (配列番号572)
表6.修飾されたアミノ酸を含む説明に役立つ4F類似体
iii.二重ドメインペプチド
a.ドメイン交換ペプチド
b.逆方向性のペプチド
c.スクランブルされたペプチド
d.連結
iv.変異体
v.核酸
vi.ブロッキング基/保護基及びD残基
C.治療方法
表13
表14
1.治療サイクル
2.休止期
3.アテローム性動脈硬化
4.送達
5.併用療法
A.実施例1:試験1−ApoE模倣体の延長された効果(hE18AのmR18L、単一ドメインのカチオン性ペプチドとの比較)
B.実施例2:試験2−ApoE−/−マウスにおける後期介入試験
ApoE模倣体による処理は処理期間の間、脂質のレベルを低下させたが、持続効果を有するとは思われなかった(図13及び14)。しかしながら、循環器の分析は、大動脈におけるプラークの比率がApoE模倣体による処理を中止した4週間後でさえ有意に低下することを示した(図16及び17)。さらに、心臓の拡張終期と収縮終期の断面領域の双方がApoE模倣体による処理を中止した4週間後減少していた(図18A及び18B)。駆出分画は同じままだった。心室壁厚の心拍に上昇がなかったということは、心臓が大きな心臓予備力で作動して同じ量の血液を送達していたことを示している。
要約
Claims (17)
- 少なくとも1回の治療サイクルとそれに続く休止期を含む投与計画であって、前記治療サイクルが有効量のApoE模倣体を投与して前記ApoE模倣体の中止後に持続する治療効果を可能にすることを含み、休止期には前記ApoE模倣体は投与されない、前記投与計画。
- 治療サイクルが、週に1回3ヵ月間有効量のApoE模倣体を投与することを含む請求項1に記載の投与計画。
- 治療サイクルが、2週間ごとに1回12週間まで有効量のApoE模倣体を投与することを含む請求項1に記載の投与計画。
- 投与計画がさらに、休止期の後に第2の治療サイクルを含む請求項1に記載の投与計画。
- アテローム性動脈硬化症の治療方法であって、少なくとも1回の治療サイクルの間有効量のApoE模倣体を対象に投与することを含み、前記治療サイクルが有効量のApoE模倣体を投与して前記ApoE模倣体の中止後に持続する治療効果を可能にすることを含み、前記治療サイクルには休止期が続き、前記休止期にはApoE模倣体は投与されない、前記治療方法。
- 休止期が少なくとも4週間である請求項5に記載の方法。
- 休止期の後に第2の治療サイクルをさらに含む請求項5に記載の方法。
- 4週間の休止期の後に第2の治療サイクルが投与される請求項7に記載の方法。
- 当初の治療サイクルの開始から1年で第2の治療サイクルが投与される請求項7に記載の方法。
- 休止期の間にApoE模倣体以外のアテローム性動脈硬化治療剤が投与される請求項5に記載の方法。
- ApoE模倣体以外のアテローム性動脈硬化治療剤が従来の脂質低下療法である請求項10に記載の方法。
- 従来の脂質低下療法がスタチンである請求項11に記載の方法。
- ApoE模倣体がLRKLRKRLLRDWLKAFYDKVAEKLKEAFである請求項5に記載の方法。
- 治療サイクルが、週に1回3ヵ月間、有効量のApoE模倣体を投与することを含む請求項5に記載の方法。
- 少なくとも1回の治療サイクルとそれに続く休止期を含む投与計画であって、前記治療サイクルが有効量のApoE模倣体を投与して前記ApoE模倣体の中止後、持続する治療効果を可能にすることを含み、前記ApoE模倣体がアミノ酸配列LRKLRKRLLRDWLKAFYDKVAEKLKEAF(配列番号1)から成り、休止期の間に前記ApoE模倣体は投与されない、前記投与計画。
- アミノ酸配列LRKLRKRLLRDWLKAFYDKVAEKLKEAF(配列番号1)が、アミノ末端を保護するアセチル基及びカルボキシル末端を保護するアミド基で末端保護される請求項15に記載の投与計画。
- アテローム性動脈硬化症の治療方法であって、少なくとも1回の治療サイクルの間有効量のApoE模倣体を対象に投与することを含み、前記治療サイクルが有効量のApoE模倣体を投与して前記ApoE模倣体の中止後に持続する治療効果を可能にすることを含み、前記ApoE模倣体がアミノ酸配列LRKLRKRLLRDWLKAFYDKVAEKLKEAF(配列番号1)から成り、前記治療サイクルには休止期が続き、前記休止期にはApoE模倣体は投与されない、前記治療方法。
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WO2017120568A1 (en) * | 2016-01-08 | 2017-07-13 | Lipimetix Development, Inc. | Apoe mimetic peptide compositions |
MA44234B1 (fr) * | 2016-02-17 | 2023-10-31 | Regeneron Pharma | Procédés de traitement ou de prévention de l'athérosclérose par administration d'un inhibiteur d'angptl3 |
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US20100286025A1 (en) * | 2007-08-28 | 2010-11-11 | Anantharamaiah Gattadahalli M | Synthetic apolipoprotein e mimicking polypeptides and methods of use |
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NO812612L (no) | 1980-08-06 | 1982-02-08 | Ferring Pharma Ltd | Enzym-inhibitorer. |
GB9022788D0 (en) | 1990-10-19 | 1990-12-05 | Cortecs Ltd | Pharmaceutical formulations |
US5331573A (en) | 1990-12-14 | 1994-07-19 | Balaji Vitukudi N | Method of design of compounds that mimic conformational features of selected peptides |
US5631280A (en) | 1995-03-29 | 1997-05-20 | Merck & Co., Inc. | Inhibitors of farnesyl-protein transferase |
US6506880B2 (en) | 1998-03-17 | 2003-01-14 | The Uab Research Foundation | Synthetic peptides that enhance atherogenic lipoprotein uptake and lower plasma cholesterol |
US6664230B1 (en) | 2000-08-24 | 2003-12-16 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
US7199102B2 (en) | 2000-08-24 | 2007-04-03 | The Regents Of The University Of California | Orally administered peptides synergize statin activity |
EP2521564B1 (en) * | 2010-01-06 | 2016-11-16 | Cognosci, Inc. | Apoe peptide dimers and uses thereof |
CN107074923B (zh) * | 2014-07-31 | 2021-08-03 | Uab研究基金会 | Apoe模拟肽及对清除血浆胆固醇的较高效力 |
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US20100286025A1 (en) * | 2007-08-28 | 2010-11-11 | Anantharamaiah Gattadahalli M | Synthetic apolipoprotein e mimicking polypeptides and methods of use |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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US10653747B2 (en) | 2014-07-31 | 2020-05-19 | Uab Research Foundation | ApoE mimetic peptides and higher potency to clear plasma cholesterol |
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WO2014152776A1 (en) | 2014-09-25 |
EP2996706A4 (en) | 2017-01-18 |
JP6570511B2 (ja) | 2019-09-04 |
EP2996706A1 (en) | 2016-03-23 |
AU2014239186A1 (en) | 2015-10-08 |
CA2903869A1 (en) | 2014-09-25 |
DK2996706T3 (da) | 2019-10-21 |
NZ713291A (en) | 2017-04-28 |
ES2753381T3 (es) | 2020-04-08 |
AU2017203911B2 (en) | 2019-03-07 |
JP6772317B2 (ja) | 2020-10-21 |
AU2014239186B2 (en) | 2017-04-20 |
EP2996706B1 (en) | 2019-07-31 |
IL240787B (en) | 2019-07-31 |
AU2017203911A1 (en) | 2017-06-29 |
MX2015012818A (es) | 2016-05-12 |
IL240787A0 (en) | 2015-10-29 |
BR112015022624A2 (pt) | 2017-10-31 |
JP2019089834A (ja) | 2019-06-13 |
US20160002315A1 (en) | 2016-01-07 |
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