TW515715B - Vaccine compositions having immunologically active QS21 - Google Patents

Vaccine compositions having immunologically active QS21 Download PDF

Info

Publication number
TW515715B
TW515715B TW85104841A TW85104841A TW515715B TW 515715 B TW515715 B TW 515715B TW 85104841 A TW85104841 A TW 85104841A TW 85104841 A TW85104841 A TW 85104841A TW 515715 B TW515715 B TW 515715B
Authority
TW
Taiwan
Prior art keywords
patent application
scope
item
composition according
vaccine composition
Prior art date
Application number
TW85104841A
Other languages
English (en)
Inventor
Nathalie Marie-Josephe Garcon
Martin Friede
Original Assignee
Smithkline Beecham Biolog
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26306923&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=TW515715(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GBGB9508326.7A external-priority patent/GB9508326D0/en
Priority claimed from GBGB9513107.4A external-priority patent/GB9513107D0/en
Application filed by Smithkline Beecham Biolog filed Critical Smithkline Beecham Biolog
Application granted granted Critical
Publication of TW515715B publication Critical patent/TW515715B/zh

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/002Protozoa antigens
    • A61K39/015Hemosporidia antigens, e.g. Plasmodium antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • A61K39/245Herpetoviridae, e.g. herpes simplex virus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/12Viral antigens
    • A61K39/29Hepatitis virus
    • A61K39/292Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/39Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00Antiparasitic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/04Immunostimulants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/54Medicinal preparations containing antigens or antibodies characterised by the route of administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505Inorganic adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55555Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55572Lipopolysaccharides; Lipid A; Monophosphoryl lipid A
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55577Saponins; Quil A; QS21; ISCOMS
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011Details
    • C12N2710/16011Herpesviridae
    • C12N2710/16611Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16634Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2730/00Reverse transcribing DNA viruses
    • C12N2730/00011Details
    • C12N2730/10011Hepadnaviridae
    • C12N2730/10111Orthohepadnavirus, e.g. hepatitis B virus
    • C12N2730/10134Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)

Description

經濟部中央標準局員工消費合作社印製 515715 A7 B7 五、發明説明(3 ) A,也稱爲3D-MPL)。由英國專利第2 220 211號(Ribi)得知, 3D-MPL就像三種類型的De_0-醯基化之單磷酸脂A與4、5或 酉&基化鏈的混合物一樣,並由Ribi Immunochem,Montana製 造。較佳的形式揭示於國際專利申請案第92/116556號中。 本發明中適當的組合物,是其中開始製備微脂粒時不含 MPL,然後再加入MPL的那些,而MPL最好是100毫微米的 顆粒。因此在囊膜之中不含有MPL(稱爲MPL在外)。其中含 有在囊膜之内的MPL之組合物(稱爲MPL在内),也形成本發 明的目標。所含有的抗原可在囊膜之内或在囊膜之外。較 好是可溶解的抗原在外側,而忌水性或經過脂化之抗原則 可包含在囊膜之内或其外側。 通常本發明之疫苗不需要任何特定的載劑,並在含水的 或其他藥學可接受之緩衝溶液中調配。在一些案例中,本 發明之疫苗進一步含有明蓉或存在於水包油型乳劑或其他 適當的媒劑中,可能是有利的,該適當媒劑像是例如微脂 粒、中心體或經過包膠的抗原顆粒。 較佳的疫苗調配物將含有能夠謗發對抗人類或動物病原 之免疫反應的抗原或抗原組合物。在本發明之組合物中, 可使用此項技藝中已知的抗原或抗原组合物,包括多醣抗 原、衍生自HIV-1 (諸如gpl20或gpl60等)的抗原或抗原組合物 、任何的免疫缺乏病毒、人類或動物的苑療病毒,諸如 gD或其衍生物,或是速早蛋白,如得自HSV1或HSV2的 ICP27、巨細胞病毒(特別是人類的)(如gB或其衍生物)、帶 狀水痘病毒(如gpl、II或III),或肝炎病毒之形式,如B型肝 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閱讀背面之注意事項再填寫本頁) -------訂-- 515715 A7 B7 五、發明説明(4 ) (請先閲讀背面之注意事項再填寫本頁) 炎病毒,例如B型肝炎表面抗原或其衍生物、A型肝炎病毒 、C型肝炎病毒和E型肝炎病毒,或其他病毒病原之形式, 如呼吸道融合細胞病毒(例如揭示於美國專利5,149,650號中 的HSRV F和G蛋白及其免疫原性之片段,或揭示於美國專 利第5,194,595號中,含有得自1181^蛋白質?和(3,6§?0糖蛋 白的嵌合多肽類)、衍生自腦膜炎品系的抗原,如腦膜炎A 、8和C,肺炎鏈球菌、人類乳頭狀瘤病毒、流行性感冒病 毒、嗜血性流行性感冒B(Hib)、愛氏頓病毒(EBV),或衍生 自細菌性病原者,如沙門桿菌屬、奈瑟球菌屬、螺旋體屬 (Borrelia)(例如OspA或OspB或其衍生物),或是衣形菌屬或博 德氏菌屬,例如P.69、PT和FHA,或衍生自寄生蟲者,如瘧 原蟲或毒漿體(toxoplasma)。 經濟部中央標準局員工消費合作社印製 HSV糖蛋白D(gD)或其衍生物是較佳的疫苗抗原。它位在 病毒膜上,亦在受感染之細胞的細胞質中發現它(Eisenberg R.J.等人;J of Virol 1980拉428-435)。其由393個胺基酸構 成,包括一個信號肽,並具有大約60kD的分子量。大概所 有HSV被膜糖蛋白均具有最佳的特性(Cohen等人J. Virology ㊇157-166)。在活體内,已知其在病毒附著細胞膜時扮演主 要的角色。然而,已經顯示糖蛋白D能夠在活體内謗發中 和抗體,並保護動物免於致命的挑戰。截短形式之gD分子 缺乏C終端的固定區域,並可在哺乳動物細胞中以可溶性 蛋白質之形式產製,再將其輸出到細胞培養基的上清液中 。這類可溶性形式的gD是較佳的。在歐洲專利0,1 3 9,4 1 7 號中描述了截短形式之gD的產製。gD最好是衍生HSV-2 -7- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 經濟部中央標準局員工消費合作社印製 515715 A7 B7 五、發明説明(5 ) 。本發明的一個具體實施例爲具有3 0 8個胺基酸的經過截 短之H S V - 2糖蛋白D,其包括含有從1到3 0 6之天然存在的 胺基酸的糖蛋白,並在經過截短、缺乏其膜固定區域之蛋 白質的C終端處帶有額外的天冬醯胺和穀胺醯胺。這種形 式之蛋白質包含了信號肽,將其切開以容許從宿主細胞中 分泌出成熟的可溶性2 8 3胺基酸蛋白質。 在本發明另外的觀點中,Β型肝炎表面抗原也是較佳的疫 苗抗原。 當此處使用ΠΒ型肝炎表面抗原”或"HBsAg”之措辭時,包 括任何HBsAg抗原或其表現出HBV表面抗原之抗原性的片段 。將瞭解到,除了 226個胺基酸序列的HBsAg抗原(參見 Tiollais等人,Nature,317,489(1985)並在此作爲參考)之外 ,如同此文中描述的HBsAg,若需要可含有全部或部份的 在上述參考文獻中和在歐洲專利-A-0 278 940號中描述的-S 前序列。特定而言,HBsAg可包括含有下列胺基酸序列的 多肽,該胺基酸序列包括在ad血清型之B型肝炎病毒上,與 打開密碼有關之HBsAg的L-蛋白質的殘基12-52,隨後是殘 基133-145,再來是殘基175-400(該多肽也叫作L* ;參見歐洲 專利0 414 374號)。在本發明範圍内的HBsAg也可以包含歐 洲專利0 198 474號中描述的-S1-S2-S多肽(Endotronics)及其密 切類似物,如歐洲專利0 304 578號中描述的那些(Me Cormick和Jones)。此處描述之HBsAg也可以適用於突變體, 例如描述於WO91/14703或歐洲專利申請案第0 51 1 855A1號 中的1逃逸突變體’,特別是其中在位置145處有由甘胺酸對 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X 297公釐) (請先閲讀背面之注意事項再填寫本頁) ---II-----. 515715 經濟部中央標準局員工消費合作社印製 A7 B7 五、發明説明(6 精胺酸進行胺基酸取代的HBsAg。 HBsAg通常是顆粒形式的。顆粒可能僅含有例如蛋白質 ,或可以是综合的顆粒,例如(L*,S),其中L*如同上述之 定義,且S代表HBsAgi S_蛋白質。該顆粒以此形式可有利 地在酵母中表現出來。 令人滿意地證明了 B型肝炎表面抗原S-蛋白質的製備。參 見例如 Harford等人(1983),在 Develop. Biol. Standard 54,第 125 頁中、Gregg等人(1987),在Biotechnology 5,第 479 頁中、 歐洲專利0 226 846號、歐洲專利0 299 108號,並在此作爲參考。 在本發明範圍中的調配物也可以含有抗-腫瘤的抗原,並 在免疫治療上用來治療癌症。 疫苗製品通常描述於Voller等人編輯的New Trends and Developments in Vaccines,University Park Press,Baltimore ’ Maryland,U.S.A. 1987中。包膠到微脂粒中的作用則由例如 Fullerton描述於美國專利第4,235,877號中。蛋白質對巨分子 的共軏作用則由例如Likhite描述於美國專利第4,372,945號中 ,以及由Armor等人描述於美國專利第4,474,了57號中。 在每個疫苗劑量中蛋白質的用量,係按照在典型免疫反 應中能引起免疫保護反應,但沒有重大不利之副作用的用 量來選擇。這類用量將依據所使用的特定免疫原及其如何 表達來加以改變。通常期望每個劑量將含有卜1 000mCg的 蛋白質,較佳的是2-l〇〇mcg,最好是4_40mcg。特殊疫 苗的最佳用量,可藉著涉及在患者身上觀察適當之免疫反 應的標準研究來探知。在最初的疫苗接種之後’可使患者 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閲讀背面之注意事項再填寫本頁)
經濟部中央標準局員工消費合作社印製 515715 A7 __— —____B7 五、發明説明(7 ) 接雙一或數次保持適當間隔的補強免疫作用。 本發明之調配物或許可用於預防和治療兩種目的中。 根據更進一步的觀點,因此本發明提供本發明之疫苗在 治療人類患者方面的用途。本發明提供一種治療方法,其 包括對患者投予有效量的本發明之疫苗。特定而言,本發 明提供一種治療病毒、細菌、寄生蟲感染或癌症的方法, 其包括對患者投予有效量的本發明之疫苗。 以下列實例和數據解釋本發明。 實例 1.1製備微脂粒的方法: 在眞空下(或另外在惰性氣體的蒸氣下),使在有機溶劑 中的脂質(諸如得自卵黃或合成的磷脂醯膽鹼)與膽固醇的混 合物脱水。然後加入含水的溶液(如磷酸緩衝的生理鹽水), 並搖動容器,直到所有的脂質均懸浮爲止。然後使該懸浮 液微流體化,直到微脂粒的大小減少到1 00毫微米爲止,並 通過0.2微米之濾紙進行無菌過濾。擠壓或聲波振盪可取代 此一步驟。 通常膽固醇:磷脂醯膽鹼的比例爲1 : 4(重量/重量),益 加入含水的溶液,而獲得5到50毫克/毫升的終膽固醇濃度 。如果在含有脂質的有機溶液中,加入在有機溶液中的 MPL ’則最後的微脂粒在膜中會含有]VIPL(稱爲MPL在内)。 具有100毫微米之限定大小的微脂粒,被稱爲SUV(小的單層 囊泡)。若重複冷凍並融解該溶液,囊泡合會融合而形成的 大的多層結構(MLV),其具有從500毫微米到15微米之大小 -10-
________________^^J 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) (請先閱讀背面之注意事項再填寫本頁) -----_---訂-----▲ 515715 A7 B7 五、發明説明(8 ) 經濟部中央標準局員工消費合作社印製 。微脂粒本身對於時間而言是穩定的,且沒有融合的能力 〇 1·2調配物程序: 在微脂粒中加入在含水之溶液中的QS21。然後將該混合 物加至抗原溶液中,如果需要其可含有以1〇〇亳微米顆粒之 形式存在的MPL。 1 · 3藉著含有膽固醇的微脂粒,抑制QS21的溶解活性 當將QS21加至紅血球中時,紅血球溶解而釋出紅血素。 每種溶解活性也可以利用在其膜内含有膽固醇的微脂粒和 被捕捉的螢光染料,羧基螢光素來測定之―當微脂粒被溶 解而釋放出可由螢光光譜監視的染料。若螢光微脂粒在其 膜中未含有膽固醇,則沒有觀察到微脂粒的溶解作用。八 如果在將QS21加至紅血球之前,先將㈨幻與含有膽固醇 的微脂粒一起培養,則紅血球的溶解會隨著膽固醇對qs21 之比例而減少。若使用〗:Ϊ之比例,則檢測不到溶解活性 。若微脂粒不含膽固醇,則抑制溶解作用需要超過卜 1000倍過量的磷脂。 同樣適用於使用螢光微脂粒來測定溶解活性。在下圖中 ,以螢光來測定經利用缺乏膽固醇(每赛 _ 回 、巧Γ毛升含1耄克的卵黃 卵磷脂)或含有膽固醇(每毫升含1毫克卵磕 、 ^ I ,脂和500微克膽固 醇)之微脂粒處理過的4微克QS2!之溶解、、舌座 (請先閱讀背面之注意事項再填寫本頁) 訂 -11 - 各紙張尺度適用中國國家標準(CNS ) Α4規格(210X297公釐) 515715 A7 _ B7 五、發明説明(1G) (請先閲讀背面之注意事項再填寫本頁) 著在逆相HPLC上測量符合QS21之峰値的減少來監視之。例 如,下圖顯示在pH値9和溫度37°C,90%的QS21會在16小時 内水解。如果以2 : 1之比例(膽固醇:QS21重量/重量)在 QS21中加入含有膽固醇的微脂粒,則在同樣的條件下未檢 測出QS21的水解。如果該比例爲1 : 1,則有10%的QS21會 降解。 在37°C下在含有膽固醇之SUV的存在下,在 pH値9下培養2〇微克QS21 16小時
經濟部中央標準局員工消費合作社印製 結論是當QS21與含有膽固醇之微脂粒連結時,它會變的 較不易受到鹼-調節之水解作用的影響。當以非經腸方式給 予時,水解產物被描述爲不具佐劑活性,因此含有QS21的 疫苗必須在酸性的p Η値下調製,並存放在4 °C下來保護佐 劑組合物。而微脂粒的使用可以克服此一需求。 1 . 5反應原性之研究: -13- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 515715 A7 B7 五、發明説明(11 ) 在老鼠脛骨肌中注射5微克QS21(或毛地黃皂甞),加上漸 增量的微脂粒(以換算成膽固醇的微克量來表示之)。以相 當於QS21的微克量來表示溶解活性,其意指達到與試樣相 同的溶血所需的QS21量。 在肌肉注射部位的發紅、壞死和毒性,在犧牲老鼠之後 以目視記錄之。 調配物 溶解活性微克 發紅 壞死 毒性 QS21+PBS 5 +++ 士 +++ QS21+1微克膽固醇(SUV) 4 -H-+ + ++++ QS21 +5微克膽固醇(SUV) 0 麵 士 QS21 +25微克膽固醇(SUV) 0 土 + 僅有SUV 0 画 一 一 毛地黃皂甞 5 讀 土 PBS 0 一 麵 幢 數據顯示,當藉著添加含有膽固醇的微脂粒而廢除了溶 解活性時,因QS21而引起之毒性也被廢除了。 經濟部中央標準局員工消費合作社印製 1 . 6在兔子身上以肌肉内注射時的反應原性 U.I./L中的値 -14- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 515715
7 B 五、發明説明(12 ) 經濟部中央標準局員工消費合作社印製 實驗 調配物 第0天 溶血 第1天 溶血 第3天 溶血 兔子編號1 1078 + 8650 1523 兔子編號2 1116 4648 1435 兔子編號3 QS21 50微克 660 4819 684 兔子編號4 592 5662 684 兔子編號5 3400 7528 1736 平均値 1369 6261 1212 標準差 1160 1757 495 實驗 調配物 第0天 溶血 第1天 溶血 第3天 溶血 兔子編號6 596 1670 460 兔子编號7 QS21 50微克 540 602 594 兔子編號8 在SUV中的膽 611 1873 803 兔子編號9 固醇50微克 521 507 616 兔子編號10 (1:1) 1092 + 787 555 平均値 672 1088 606 標準差 238 636 125 (請先閲讀背面之注意事項再填寫本頁) -15-本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 515715 A7 B7五、發明説明(13 ) 實驗 調配物 第0天 溶血 第1天 溶血 第3天 溶血 兔子編號11 332 344 387 兔子編號12 QS21 50微克 831 662 694 兔子編號13 在SUV中的膽 464 356 519 兔子編號14 固醇150微克 528 720 614 兔子編號15 (1:3) 1027 568 849 平均値 637 530 613 標準差 285 173 175 經濟部中央標準局員工消費合作社印製 實驗 調配物 第0天 溶血 第1天 溶血 第3天 溶血 兔子編號16 540 769 745 兔子編號17 QS21 50微克 498 404 471 兔子編號18 在SUV中的膽 442 717 (4535) 兔子編號19 固醇250微克 822 801 925 兔子編號20 (1:5) 3182 土 2410 960 平均値 1097 1020 775 (1527) 標準差 1175 793 224 (1692) -16- (請先閱讀背面之注意事項再填寫本頁)
本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 515715 A7 B7 五、發明説明(14 ) 實驗 調配物 第0天 溶血 第1天 溶血 第3天 溶血 兔子編號21 321 290 378 兔子編號22 660 535 755 兔子編號23 PBS 650 603 473 兔子編號24 1395 (3545) (5749) 兔子編號25 429 土 323 263 平均値 691 438 (1059) 467 (1523) 標準差 419 155 (1396) 210 (2369) (請先閱讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 數據顯示,在調配物中添加含有膽固醇的微脂粒,明顯 地減少了由QS21所引之CPK(磷酸肌酸酶)的高度。因爲 CPK增加是肌肉損傷的程度,這表示降低了肌肉的損傷, 並藉著组織病理學來證實。 1。7微脂粒-QS21複合物對明礬的結合。 將QS21與含有過量膽固醇和具放射線活性之膽固醇的中 性微脂粒一起培養,然後與在PBS中的明礬(A1(0H)3)—起培 養。當單獨的時候,中性的微脂粒或QS21皆不與P B S中的 明礬結合,而只有帶負電荷的微脂粒與之結合。然而當同 時在一起時,QS21和中性微脂粒均與明礬結合。上清液中 不含QS21(藉著地衣酚試驗來分析),也不含具放射線活性 的膽固醇。 這顯示QS21已經與微脂粒結合,並允許微脂粒-QS21的組 合與明礬結合。這可能起因於QS21將負電荷加在微脂粒上 -17- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 515715 A7 B7 五、發明説明(15 ) ,或是暴露出微脂粒上的忌水性區域。結果也暗示QS21未 從膜中引出膽固醇。 (請先閲讀背面之注意事項再填寫本頁) 這表示本發明之組合物可被用在以明礬爲基礎的疫苗中 〇 1.8就抗體和CMI的謗導,比較微脂粒之QS21/MPL和自由的 QS21+MPL藉著壓擠來製備SUV (EYPC :膽固醇:MPL 20 : 5 : 1)。 關於MPL在外,製備不含MPL的微脂粒,再加入100毫微 米之顆粒大小的MPL。 在加入抗原之前先加入QS21。膽固醇:QS21=5 : 1 (重量 /重量)。 藉著在加入抗原之前,先將SUV冷凍-融解三次,來製造 MLV。 爲了要使抗原被捕捉,在冷凍-融解之前先加入抗原,並 在冷凍-融解之後再加入QS21。抗原包膠作用=5%在内, 95%在外。 經濟部中央標準局員工消費合作社印製 -在老鼠的腳蟄中注射兩次(關於gD使用balb/c品系的老鼠, 關於RTSs則使用B10BR品系的老鼠)。gD爲得自單純疱疹病 毒的糖蛋白D。RTSs爲以基因方式修改的B型肝炎表面抗原 (HBsAg),而使其含有來自鐮狀癔原蟲(Plasmodiium falciparum)種蟲的抗原決定位。 -18- 本紙張尺度適用中國國家標準(CNS ) A4規格(210'〆297公釐) 515715
A B 五、發明説明(16) 經濟部中央榡準局員Η消費合作衽印製
Ag(抗原)=1〇微克RTSs 抗HBsAg力價 在補強之後15天 調配物 IgGl IgG2a IgG2b SUV/QS+MPL(在外) +Ag 1175 10114 71753 MLV/QS+MPL(在外) +Ag 2247 11170 41755 MLV/QS+MPL(在内) +Ag 969 7073 18827 MLV/QS+MPL(在内)/Ag(在内)+Ag 1812 2853 9393 QS+MPL +Ag 372 9294 44457 Ag <100 <100 <100 SUV/QS+MPL (在外) <100 <100 <100 MLV/QS/MPL (在内) <100 <100 <100
Ag(抗原)=20微克gD 抗gD CMI 調配物 IgG IFN-,96 小時 (微微克/毫升) IL2 48小時 (微微克/毫升) SUV/QS+MPL(在外) +Ag 2347 1572 960 SUV/QS+MPL(在内) +Ag 2036 1113 15 MLV/QS+MPL(在外) +Ag 1578 863 15 MLV/QS+MPL(在内) +Ag 676 373 15 MLV/QS+MPL(在内)/Ag(在内)+Ag 1064 715 15 QS+MPL +Ag 1177 764 15 Ag <100 567 44 SUV/QS+MPL (在外) <100 181 15 MLV/QS/MPL (在内) <100 814 105 (請先閲讀背面之注意事項再填寫本頁) -19-本紙張尺度適用中國國家標準(CNS ) Α4規格(210X 297公釐) 515715 A7 B7 五、發明説明(17) (請先閱讀背面之注意事項再填寫本頁) 該數據顯示SUV/QS+MPL(在外),謗導出至少像qS21+mPL 一樣好的高抗體力價,以及謗導出細胞調節免疫的標記 IL 2,同時譽抑了 QS21的反應原性。 另外的結果顯示於下’遠結果係得自balb/c老鼠身上,以 HSV gD作爲抗原,比較QS21與在膽固醇(SUV)存在下的 QS21 : 同型第II次之後7天 調酉嫩 ίηΜ 第欠嫌天 (GMT) 第1D欠之後14天 (GMT) IgGl 微嫌斤 % IgG2a 微綠斤 % IgG2b % SUV/QS21+MPL 在外 gp&m 20290 16343 331 26 716 56 222 17 SUV/QS21/MPL 在内 gD(5f敗克) 12566 10731 418 44 412 44 111 12 QS21+MPL gD»克) 10504 10168 200 34 285 48 107 18 SUV/QS21+MPL 在外 無 0 0 0 0 0 0 0 0 QS21 gD(5f版克) 3468 4132 156 66 67 28 14 6 SUV/QS21 gD (滅) 11253 11589 484 57 304 36 65 8 1.9比較gpl20加微脂粒的MPL/QS21與自由的MPL/QS21 微脂粒=SUV在膜中含有MPL 膽固醇:QS21=6 : 1 在一次免疫接種之後兩週測試其反應 經濟部中央標準局員工消費合作社印製 調配物 增殖 IFN-g 毫微克/毫升 IL2 微微克/毫升 IL5 微微克/毫升 SUV/MPL/QS21+Ag 12606 16.6 59 476 MPL+QS21+Ag 16726 15.8 60 404 -20- 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X297公釐) 經濟部中央標準局員工消費合作社印製 515715 A7 B7 五、發明説明(19 ) 這證實僅有QS21可謗導出CTL活性,而在含有膽固醇之微 脂粒的存在下,QS21謗導出至少和僅有QS21—樣好或更好 的CTL活性。 2 .疫苗 2.1 HBsAg L*,S顆粒的調配物 可依照下列方式來調製HBsAgL*,S顆粒: 在室溫下,在攪動之下培養10微克HBsAg L*,S顆粒/劑量1小 時。利用注射用水和PBS溶液來調整體積,達到帶有QS21水 溶液(10微克/劑量)的70微升/劑量之終體積。pH値保持在7土 0.5 〇 可利用1和5 0微克HBsAg L*,S來製備類似的調配物,亦使 用HBsAg S4元原。 可在Woodchuck代用品治療模式中測試這些調配物,利用 Woodchuck HBV抗原作爲模型。
Woodchuck 模式 可在Woodchuck治療模式中測試DQ QS21(也就是QS21/膽固 醇或受到壓抑的QS21),在其中以病毒慢性地感染動物。可 加入特定的Woodchuck肝炎病毒疫苗,與QS21本身,或是帶 有或不帶有MPL的DQ混合,並每個月投予動物一共6個月。 可經由病毒DNA清除作用來評估疫苗的效力。 2.2天竺鼠模式(HSV) 2.2.1預防模式 一組1 2隻雌性的Hartley天竺鼠,在第0天和第28天肌肉内 注射下列的調配物: -22- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) (請先閲讀背面之注意事項再填寫本頁)
515715 A7 B7 五、發明説明(2G ) 第一個實驗: (請先閲讀背面之注意事項再填寫本頁) gD 5微克+QS21 50微克+含有50微克膽固醇的SUV gD 5微克+QS21 100微克+含有100微克膽固醇的SUV gD 5微克+QS21 50微克+含有250微克膽固醇的SUV gD 5微克+QS21 50微克 第二個實驗: §0 5微克+1^1?1^12.5微克+(^2112.5微克+含有62.5微克膽固 醇的SUV,或保留不加以處理。 在第二次免疫接種後第14和28天時將動物放血,並對其 gD-特異性之ELISA抗體力價進行血清測試。 然後利用1〇5 pfu個HSV-2MS品系,以陰道内之方式來挑戰 這些動物。從4到12天,每天對主要痕療病變的評估計分。 計分方式如下·· 陰道病變: -出血=0.5 -發紅一或兩天,但未出血=0.5 -發紅且出血一天=1 -發紅但未出血,持續3天=1 外部的疱疹水泡: 經濟部中央標準局員工消費合作社印製 -<4個小水泡=2 ->=4個小水泡或一個大水泡=4,>=4個大的病變=8,匯合的 大病變=16 •在整個外生殖器區域均有匯合的大病變=32。 結果顯示於下表中: -23- 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X 297公釐) 515715 A7 B7 五、發明説明(21 經濟部中央標準局員工消費合作社印製 Η-^ 1—A H-A ^ Η-A μ to to Ν> 一 bJ VI crq ciq 〇Q oq ^ σ σ σ σ 才、、' W % χ /Ο Ο /Ο /Ο E3 X GO CO OD 〇 ύ§ cn cn Ln cri t ??i > ^ ^ > Ο Ο Λ nr sr g. a a 〇 K ^ S ^ 沒有病變 的動物之 百分比 ° 〇 〇〇 i 陰道病變 發生率的 百分比 ui ^ 〇 SS ^ ^卜部病變 發生率的 百分比 馋2 * ,sgss 對對照組 的降低率 1__ 1.50 2.50 0.75 55.00 病變嚴 ,......_ 中間値 v〇 〇\ » as iirttli VW 口 * 物 丨+m 颯 s XTL < %% (請先閲讀背面之注意事項再填寫本頁) ----:---Ϊ1Τ------- -24- 本紙張尺度適用中國國家標準(CNS ) A4規格(210 X 297公釐) 515715 A7 B7 五、發明説明(22 ) 經濟部中央標準局員工消費合作社印製 * 私韌淞菸4^12^3:孰飧茸今容箨命(^<%麵涔斜孰)«容》參)0 孰濰孳今”龄孰飧(0二醪麻孰飧(0.5涔1了岑者泠鉍夭浚(2-4“8^16) ** 澳淞鈦犛=翁命(鄭斤今»:ix(lf^^%);3ii=0-0.5 1r2 4 4 -S16 —· to to 、 3 is〜 < 調配物 Ϊ 47006 <400 EL] 第Π次之後 第14天 抗體力價;(GMT) 31574 <400 SA 第Π次之核 第28天 ί 八廿 U\ 4^ 〇 VO • %% t ^ h* c1^ 58,33 16.67 刮~择 今梦斜 ~ s m 1 1 33.33 8.33 . 陰道病變 發生率的 百分比 国1 8.33 75.00 外部病變 發生率的 百分比 • 1 37.50 丨 587.50 ‘ PI 指數# 主要疾病 94% 對對照組 的降低率 1.00 11.50 病變嚴i 中間値 〇 ^ 3 贪 * 碲棼2 -25» (請先閱讀背面之注意事項再填寫本頁)
木紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) 515715 A7 B7 五、發明説明(23 ) 表和圖表顯示,在預防模式中,當以gD/MPL/QS21/SUV免 疫接種時,對主要疾病诱導出非常南程度的保護作用。外 部病變的發生率和病變嚴重性上,在以gD/MPL/QS21/SUV免 疫接種的動物組中顯示出高度的減少。 、2.2.2治療模式 在治療模式中,第一次以1〇5 pfu個HSVdMS品系挑戰雌性 的Hartley天竺鼠。然後將有痕療病變的動物隨機分成16隻 一組0 在第2 1天和第4 2天,以下列調配物其中一種來免疫牠們 -gD+MPL 50微克+QS21 50微克+含有250微克膽固醇的SUV, -gD+Al(OH)3+MPL 50微克+QS21 50微克+含有250微克膽固醇 的SUV或保留不加以處理。 從第22到75天,每天監視評估再發性疾病。計分方式按 照預防模式之描述。結果顯示於下表和圖表中: (請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 -26- 本紙張尺度適用中國國家標準(CNs ) A4規格(210 X 297公釐) 515715 A7 B7 五、發明説明(24 ) 治療模式: η 調配物 嚴, 中間値 f性* 對對照組 降低的% 期Η 中間値 對對照組 降低的% 偶發事利 中間値 卜數目*** 對對照組 降低的% 16 gD+MPL+QS21 9.00 43% 7.00 18% 3.00 14% +SUV 15 gD+Al(OH)3 + 8.50 46% 7.00 18% 3.00 14% MPL+QS21+SUV 16 未處理 15.75 8.50 3.50 * 感染後第22到75天的病變計分之總合。 (請先閱讀背面之注意事項再填寫本頁) ** 在感染後第22到75天,動物體驗到再發性疾病的總曰數 ***在感染後第22到75天,再發性偶發事件的數目。一個偶 發事件先發生,之後一天沒有病變,且其特徵爲出現 紅斑至少兩天(分數=0.5),或是出現外邵水泡一天(分數 >=2) 〇 在第21和42天時進行免疫治療的處理。 經濟部中央標準局員工消費合作社印製 結果顯示,在HSV-2感染的治療模式中也謗導出良好程度 的保護。以帶有或不帶有明礬的gD/MPL/QSZl/SUVf^疫,對 中間嚴重性的再發性疾病有明顯的效果。也稍微減少了偶 發事件的數量和期間(參見表中)。 -27- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X297公釐) .公%. r _ 1,一 ,本 +請曰期 85.4.23 案 號 085104841 類 別 (以上各欄由本局填註) 修丨 A4, C4 中文說明書修正頁(91年f月)515715 || ^專利説明書 中 文 、爹明 新型 名稱 英 文 姓 名 國 籍 具有免疫活性QS21之疫苗組合物 VACCINE COMPOSITIONS HAVING IMMUNOLOGICALLY ACTIVE QS21 1·納沙力·馬力-約瑟·克勞德·加肯 2·馬丁·佛萊德 發明 創作 人 住、居所 國 籍 1.法國 2,英國 均比利時利克森沙特市第一學院路89號 裝· 三、申請人 住、居所 (事務所) 比利時商史密斯克萊美占生物公司 比利時 比利時利克森吵特市弟一學院路89號 詹恩·史帝芬 本紙張尺度適财S國家鲜(CNS) Μ規格⑽χ 297公爱) 515715 第085104841號專利申請案 中文說明書修正頁(91年|月) 修ill丨 五、發明説明( ) 1 本發明係關於新穎的疫苗調配物·、其產製方法,及其在 醫學上的用途。特定而言,本發明係關於疫苗,其包括抗 原或抗原性組合物免疫活性之QS21,以犮固醇。 在此項技藝中,已知具有佐劑活性並具有免疫活性的皂 角嘗部份,係衍生自南美樹Quillaja Saponaria Molina的樹皮 。例如,QS21,也叫作 QA21,為一種從 Quillaja Saponaria Molina樹中,經Hplc純化的部份,及其產製方法,均揭示於 美國專利第5,057,540號(叫作QS21)。亦曾由Scott等人,Int. Archs. Allergy Appl. Immun·,1985,77,409揭示了皂樹可作 為佐劑。然而,使用QS21作為佐劑,與某種不利有關。例 如,當把自由分子之形式的QS21注射到哺乳動物體内時, 已經觀察到壞死,也就是說,在注射部位發生局部的組織 死亡。 現在已經意外地發現,藉著使用含有QS21與固醇混合的 調配物,可避免注射部位的壞死。較佳的固醇包括/3 -麥胚 脂醇、豆脂醇、麥角留醇、麥角鈣化留醇和膽固醇。這些 固醇類為此項技藝中已熟知的,例如膽固醇被揭示於Merck Index,第11版,341頁,被發現是一種天然存在於動物脂質 中的固醇。 因此本發明的主要觀點是提供一種疫苗組合物,其包括 抗原、具有.免疫活性的皂角苷部份和固醇。本發明之組合 物較好是包含大體上為純粹形式的皂角甞部份。最好是本 發明之組合物含有大體上為純粹形式之QS21,也就是說, 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐)
515715 第85104841號專利申請案 I ~ 中文說明書修正頁(90年1〇月) Α7
QS,純度至少為90%,較佳的是純度至少為95%,而最佳 的疋純度至少為98% °其他可使用於本發明組合物中, 免後活性的m部份包括QA17/QS17。含有讲21和膽固醇 的本發明組合物,當與缺乏膽固醇之組合物相比較時,顯 π出降低的反應原性,同時乃保留佐劑效力。除此之外, 已知(^21在?11值約為7或更高的驗性條件下會降解。本發明 化合物具有更多的優點,就是在含有膽固醇的調配物中, 促進了 QS21對驗-調節之水解作用的穩定性。 本發明中較佳的組合物是形成微脂粒結構的那些。 QS21 :固醇的比例,通常將按照以重量計丨:1〇〇到1 ··工的 順序。較佳的是出現過量的固醇,QS21 :固醇之比例至少 為1 · 2的重量/重量。代表性對人類投藥用的1和固醇, 在疫苗中將以每個劑量出現大約丨微克到大約100微克之間 ’幸父佳的是大約10微克到大約50微克之間。 微脂粒最好是含有中性的脂質,例如磷脂醯膽鹼,最好 疋在室溫下無結晶的,例如卵黃磷脂醯膽鹼、二油醯磷脂 酿膽驗或二月桂基磷脂醯膽驗。微脂粒也可以含有帶電荷 的脂質,其增加微脂粒-QS2U#構對於由飽和脂質構成之微 脂粒的穩定性。在這些案例中,帶電荷脂質的量,較佳的 是1-20%重量/重量,最好是5··1〇%。而固醇對磷脂的比例為 1-50%(莫耳/莫耳),最好是20-25%。 本發明中較佳的組合物含有MPL(3-脫醯基化的單-磷酸脂 ___ -5- 本纸張尺度適用中國國家標準⑴!^^ A4規格(21〇χ 297公釐)
裝* % 515715 第85104841號專利申請案 中文説明書修正頁(87年9月) A7 B7
五、發明説明(9) 比較以含有或缺乏膽固 醇之微脂粒壓抑的QS21
Γ (窆贫鋈轻)J
微脂粒的微升量
(請先閲讀背面之注意事項再填寫本頁) 經濟部中央標準局員工消費合作社印製 數據顯示,以特定方式與在膜中之膽固醇連結的QS21, 因此而引起(細胞或螢光微脂粒)的溶解。 若先使QS21與膽固醇在微脂粒中連結,則其不再使細胞 或其他微脂粒溶解。所需要的最低比例爲0.5 : 1的膽固醇: QS21(重量/重量)。 膽固醇在含水的溶液中是不可溶的,且不會形成穩定的 懸浮液。當磷脂存在時,膽固醇存在於鱗脂雙層之中,可 形成穩定的囊泡懸浮液,稱作微脂粒。要避免加入鱗1脂的 需求,嘗試可溶性的衍生物。多氧乙烯基膽固醇癸二酸酯 能夠以60毫克/毫升之濃度而溶於水中,然而即使其超過 QS21的2000倍過量(重量/重量),也不能檢測到QS21溶解活 性的減少。 1.4藉著含有膽固醇之微脂粒來增加QS21的穩定性。 QS21在pH値高於7時是非常容易水解的。該水解作用可藉 12- 本紙張尺度適用中國國家標準(CNS ) A4規格(210X 297公釐) 515715 第85104841號專利申請案' A7. 厂杉正 中文説明書修正頁(87年9月)_Β7_1^ 充 五、發明説明(18) 在第二次免疫接種之後: 調配物 增殖 IFN-g IL4 IL5 毫微克/毫升 微微克/毫升 微微克/毫升 SUV/MPL/〇S21+Ae 12606 135 0 250 MPL+QS21+As 16726 60 0 500 (請先閱讀背面之注意事項再填寫本頁) 該數據顯示與含有膽固醇之微脂粒和MPL連結的QS21, 謗導出相當於MPL+QS21的Thl/ThO反應。 以這樣的膽固醇對QS21之比例,QS21對兔子是無毒性的(由 CPK得知)。 在第二個實驗中,在QS21或QS21 +含有膽固醇之SUV的存 在下,利用gpl20以腳塾内注射之方式來免疫balb/c老鼠。·測 量在脾臟細胞中胞毒T-淋巴球的活性。 yp!20 +QS21 經濟部中央標準局員工消費合作社印製 □Kfi—Tf 5 Ό 5 ο 5 2 2 11 ——Ρ815 —〇—Ρ815 + Ε7 gpl20 +QS21 +SUV 0050432020100
——P8) •5 —σ—Ρ81 5 + Β7 〇. C3 ΓΊ 〇 Q CO ^ ” O' 效為物/目標之比例 效應物:蛀標i比例:: -21 - 本紙張尺度適用中國國家標準(CNS)A4規格(210X 297公釐)

Claims (1)

  1. 中文i1^4^41號專利申請案 —專利範圍修正太⑼年^月)申請專利範圍 A8 B8 C8 D8 Π1 % ¥ Η
    種疫苗組合物,包括抗原或抗原性組合物、Q S 2 1和固 醇’特徵在於QS21對固醇之比例為1 ·· 1至1 : 100(w/w) 〇 2 ·根據申請專利範圍第1項之疫苗組合物,其中Q S 2 1對固 醇之比例為1 : 1至1 : 5(w/w)。 3 ·根據申請專利範圍第1項之疫苗組合物,其中Q S 2 1對固 辱之比例為1 : 2 (w / w)。 4 ·根據申請專利範圍第1項之疫苗組合物,其中該固醇為 膽固醇。 5 ·根據申請專利範圍第1項之疫苗組合物,其另含有3去- 〇-酿基化單磷酸酯A (3D-MPL)。 6 ·根據申请專利範圍第1項之疫苗組合物,其另含一載劑 〇 7.根據申請專利範圍第6項之疫苗組合物,其中載劑選自含 油落於水乳劑、明礬、微球體及抗原被包囊顆粒之群組 〇 8 ·根據申請專利範圍第1項之疫苗組合物,其中該Q s 2 i係 呈脂小體結構。 9 ·根據申請專利範圍第8項之疫苗組合物,其中該卩$ 2 1之 純度大於95 %。 ι〇·根據申請專利範圍第9項之疫苗組合物,其中該Qs2ii 純度大於9 8 %。 1 1 .根據申請專利範圍第8項之疫苗組合物, MPL包含於該脂小體中。 ^ 51571f A B c D 、申請專利祀圍 1 2 .根據申請專利範圍第1項之疫苗\组合物,其中該抗原或 抗原性組合物衍生自:任何人類的免疫缺乏病毒、貓的 免疫缺乏病毒、帶狀水痘病毒、單純⑴療病毒1型、單純 ⑴疹病毒2型、人類巨細胞病毒、A、B、C或E型肝炎、 呼吸道融合細胞病毒、人類乳頭狀瘤病毒、流行性感冒 病毒、Hib、腦膜炎病毒、沙門桿菌屬(Salmonella)、奈瑟 球菌屬(Neisseria)、螺旋體屬(Borrelia)、衣形菌屬 (Chlamydia)、博德氏菌屬(Bordetella)、癔原蟲(Plasmodium) 或毒漿體(Toxoplasma)。 1 3 .根據申請專利範圍第1至7項之疫苗組合物,另包括衍生 自腫瘤之抗原。 1 4 .根據申請專利範圍第1至7項之疫苗組合物.,用於醫藥品 〇 1 5 .根據申請專利範圍第1至7項之疫苗組合物,用於病毒、 細菌或寄生蟲感染之預防性治療。 1 6 .根據申請專利範圍第1至7項中任一項之疫苗組合物,用 於癌症之免疫醫療處理。 1 7 . —種使Q S 2 1對於碱引發性水解安定之方法,其包括使 Q S 2 1與含固醇之脂小體混合。 1 8 . —種使Q S 2 1對於碱引發性水解安定之方法,其包括使 Q S 2 1與固醇以1 : 1至1: 1 0 0之重量比混合。 1 9 .根據申請專利範圍第1 7或1 8項之方法,其中該固醇為膽 固醇。 2 0 . —種製備根據申請專利範圍第1項之疫苗組合物之方法, -2- 本紙張尺度適用中國國家標準(CNS) A4規格(210 x 297公釐)
    515715 8 8 8 8 A BCD 六、申請專利範圍 其包括下列步騾: a) 製備含有固醇之脂質懸浮液; b) 使該脂質懸浮液微流體化,直至脂小體之體積降低至 1 0 0 nm ;及 c) 力π 入 QS21 〇 2 1 . —種製造根據申請專利範圍第1項之疫苗組合物的方法 ,其包括將Q S 2 1和膽固醇,與抗原或抗原性組合物混合 -3- 本紙張尺度適用中國國家標準(CNS) A4規格(210 X 297公釐)
TW85104841A 1995-04-25 1996-04-23 Vaccine compositions having immunologically active QS21 TW515715B (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9508326.7A GB9508326D0 (en) 1995-04-25 1995-04-25 Vaccines
GBGB9513107.4A GB9513107D0 (en) 1995-06-28 1995-06-28 Vaccines

Publications (1)

Publication Number Publication Date
TW515715B true TW515715B (en) 2003-01-01

Family

ID=26306923

Family Applications (1)

Application Number Title Priority Date Filing Date
TW85104841A TW515715B (en) 1995-04-25 1996-04-23 Vaccine compositions having immunologically active QS21

Country Status (37)

Country Link
EP (3) EP0884056A1 (zh)
JP (1) JP3901731B2 (zh)
KR (1) KR100463372B1 (zh)
CN (3) CN1111071C (zh)
AP (1) AP771A (zh)
AR (1) AR001686A1 (zh)
AT (2) ATE186842T1 (zh)
AU (2) AU693022B2 (zh)
BG (1) BG63491B1 (zh)
BR (1) BR9608199B1 (zh)
CA (1) CA2217178C (zh)
CY (1) CY2588B2 (zh)
CZ (1) CZ296216B6 (zh)
DE (2) DE69605296T3 (zh)
DK (2) DK0822831T4 (zh)
DZ (1) DZ2026A1 (zh)
EA (1) EA000839B1 (zh)
ES (2) ES2293708T3 (zh)
GR (1) GR3031912T3 (zh)
HK (2) HK1009086A1 (zh)
HU (1) HU227944B1 (zh)
IL (1) IL118004A (zh)
MA (1) MA23850A1 (zh)
MY (1) MY134811A (zh)
NO (1) NO322190B1 (zh)
NZ (1) NZ305365A (zh)
OA (1) OA10629A (zh)
PL (1) PL184061B1 (zh)
PT (1) PT955059E (zh)
RO (1) RO119068B1 (zh)
SA (1) SA96170297B1 (zh)
SI (2) SI0822831T2 (zh)
SK (1) SK282017B6 (zh)
TR (1) TR199701252T1 (zh)
TW (1) TW515715B (zh)
UA (1) UA56132C2 (zh)
WO (1) WO1996033739A1 (zh)

Families Citing this family (494)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6207646B1 (en) 1994-07-15 2001-03-27 University Of Iowa Research Foundation Immunostimulatory nucleic acid molecules
GB9620795D0 (en) * 1996-10-05 1996-11-20 Smithkline Beecham Plc Vaccines
AUPO517897A0 (en) 1997-02-19 1997-04-11 Csl Limited Chelating immunostimulating complexes
US6406705B1 (en) 1997-03-10 2002-06-18 University Of Iowa Research Foundation Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant
AUPO732997A0 (en) * 1997-06-12 1997-07-03 Csl Limited Ganglioside immunostimulating complexes and uses thereof
ES2500490T3 (es) * 1997-08-29 2014-09-30 Antigenics Inc. Composiciones que comprenden el adyuvante QS-21 y polisorbato o ciclodextrina como excipiente
GB9718901D0 (en) * 1997-09-05 1997-11-12 Smithkline Beecham Biolog Vaccine
DE69815692T2 (de) * 1997-09-05 2004-04-29 Glaxosmithkline Biologicals S.A. Öl in wasser emulsionen mit saponinen
GB9724531D0 (en) 1997-11-19 1998-01-21 Smithkline Biolog Novel compounds
US20080050367A1 (en) 1998-04-07 2008-02-28 Guriq Basi Humanized antibodies that recognize beta amyloid peptide
TWI239847B (en) 1997-12-02 2005-09-21 Elan Pharm Inc N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease
US7964192B1 (en) 1997-12-02 2011-06-21 Janssen Alzheimer Immunotherapy Prevention and treatment of amyloidgenic disease
BR9907691B1 (pt) 1998-02-05 2011-05-31 derivado de antìgeno e antìgeno da famìlia mage associado a tumor, seqüência de ácido nucléico, codificando os mesmos, seus usos na preparação de vacina, processo para produção de vacina e vacina.
US20020147143A1 (en) 1998-03-18 2002-10-10 Corixa Corporation Compositions and methods for the therapy and diagnosis of lung cancer
CN1163602C (zh) 1998-04-07 2004-08-25 科里克萨公司 结核杆菌抗原融合蛋白及其应用
GB9808866D0 (en) 1998-04-24 1998-06-24 Smithkline Beecham Biolog Novel compounds
GB9817052D0 (en) * 1998-08-05 1998-09-30 Smithkline Beecham Biolog Vaccine
KR20010085348A (ko) 1998-08-07 2001-09-07 추후보정 면역능을 갖는 헤르페스 심플렉스 바이러스 항원 및 이를이용하는 방법
US6692752B1 (en) 1999-09-08 2004-02-17 Smithkline Beecham Biologicals S.A. Methods of treating human females susceptible to HSV infection
US20030235557A1 (en) 1998-09-30 2003-12-25 Corixa Corporation Compositions and methods for WT1 specific immunotherapy
CA2773698C (en) 1998-10-16 2015-05-19 Glaxosmithkline Biologicals S.A. Adjuvant systems comprising an immunostimulant adsorbed to a metallic salt particle and vaccines thereof
AU1580300A (en) 1998-12-08 2000-06-26 Smithkline Beecham Biologicals (Sa) Novel compounds
KR20100132086A (ko) 1998-12-08 2010-12-16 코릭사 코포레이션 클라미디아 감염을 치료 및 진단하기 위한 조성물 및 이를 포함하는 약제학적 조성물 및 진단 키트
US20020119158A1 (en) 1998-12-17 2002-08-29 Corixa Corporation Compositions and methods for the therapy and diagnosis of ovarian cancer
US6579973B1 (en) 1998-12-28 2003-06-17 Corixa Corporation Compositions for the treatment and diagnosis of breast cancer and methods for their use
WO2000048630A1 (en) * 1999-02-17 2000-08-24 Csl Limited Immunogenic complexes and methods relating thereto
ATE279943T1 (de) * 1999-02-26 2004-11-15 Chiron Srl Verbesserung der bakterizidaktivität von neisseria antigenen mit cg enthaltende oligonukleotiden
EP1163343B1 (en) 1999-03-12 2009-12-09 GlaxoSmithKline Biologicals S.A. Neisseria meningitidis antigenic polypeptides, corresponding polynucleotides and protective antibodies
GB9909077D0 (en) 1999-04-20 1999-06-16 Smithkline Beecham Biolog Novel compositions
HU228499B1 (en) * 1999-03-19 2013-03-28 Smithkline Beecham Biolog Streptococcus vaccine
CZ20013527A3 (cs) 1999-04-02 2002-10-16 Corixa Corporation Sloučeniny a způsoby pro terapii a diagnostiku karcinomu plic
GB9908885D0 (en) * 1999-04-19 1999-06-16 Smithkline Beecham Biolog Vccine
PT1187629E (pt) * 1999-04-19 2005-02-28 Glaxosmithkline Biolog Sa Composicao adjuvante que compreende saponina e um oligonucleotido imunoestimulador
US6558670B1 (en) 1999-04-19 2003-05-06 Smithkline Beechman Biologicals S.A. Vaccine adjuvants
US7166573B1 (en) 1999-05-28 2007-01-23 Ludwig Institute For Cancer Research Breast, gastric and prostate cancer associated antigens and uses therefor
US6432411B1 (en) 1999-07-13 2002-08-13 Hawaii Biotechnology Group Recombinant envelope vaccine against flavivirus infection
GB9918319D0 (en) 1999-08-03 1999-10-06 Smithkline Beecham Biolog Vaccine composition
GB9923176D0 (en) 1999-09-30 1999-12-01 Smithkline Beecham Biolog Novel composition
CA2721011A1 (en) 1999-10-22 2001-05-03 Aventis Pasteur Limited Modified gp100 and uses thereof
AU2243801A (en) * 1999-12-08 2001-06-18 Statens Veterinarmedicinska Anstalt Vaccine adjuvants comprising ginseng plant extract and added aluminium salt
US6905712B2 (en) 1999-12-08 2005-06-14 Statens Veterinarmedicinska Anstalt Vaccine adjuvants comprising ginseng plant extract and added aluminum salt
DK1265915T3 (da) 2000-02-23 2011-02-14 Glaxosmithkline Biolog Sa Nye forbindelser
US20040002068A1 (en) 2000-03-01 2004-01-01 Corixa Corporation Compositions and methods for the detection, diagnosis and therapy of hematological malignancies
ATE398463T1 (de) * 2000-04-13 2008-07-15 Corixa Corp Immunostimulierende zusammnensetzungen die aminoalkyl glucosaminidephosphat und qs-21 enthalten
DE60133190T2 (de) 2000-04-21 2009-04-02 CORIXA CORP., Wilmington Verbindungen und verfahren zur behandlung und diagnose von chlamydia-infektionen
WO2001085932A2 (en) 2000-05-10 2001-11-15 Aventis Pasteur Limited Immunogenic polypeptides encoded by mage minigenes and uses thereof
SI1542732T1 (sl) 2000-06-20 2010-01-29 Corixa Corp Csc The United Sta Fuzijski proteini Mycobacterium tuberculosis
WO2002000174A2 (en) 2000-06-28 2002-01-03 Corixa Corporation Compositions and methods for the therapy and diagnosis of lung cancer
AP1695A (en) 2000-06-29 2006-12-17 Glaxosmithkline Biologicals Sa Multivalent vaccine composition.
GB0108364D0 (en) 2001-04-03 2001-05-23 Glaxosmithkline Biolog Sa Vaccine composition
UA79735C2 (uk) 2000-08-10 2007-07-25 Глаксосмітклайн Байолоджікалз С.А. Очищення антигенів вірусу гепатиту b (hbv) для використання у вакцинах
US6858590B2 (en) 2000-08-17 2005-02-22 Tripep Ab Vaccines containing ribavirin and methods of use thereof
US7022830B2 (en) 2000-08-17 2006-04-04 Tripep Ab Hepatitis C virus codon optimized non-structural NS3/4A fusion gene
GB0022742D0 (en) 2000-09-15 2000-11-01 Smithkline Beecham Biolog Vaccine
NZ525320A (en) * 2000-10-18 2004-10-29 Glaxosmithkline Biolog S Combinations of immunostimulatory oligonucleotides (CpG), saponin and optionally lipopolysaccharides as potent vaccine adjuvants
PT2266603E (pt) * 2000-10-18 2012-11-02 Glaxosmithkline Biolog Sa Vacinas tumorais
EP1201250A1 (en) * 2000-10-25 2002-05-02 SMITHKLINE BEECHAM BIOLOGICALS s.a. Immunogenic compositions comprising liver stage malarial antigens
US7306806B2 (en) 2001-01-26 2007-12-11 United States Of America As Represented By The Secretary Of The Army Recombinant P. falciparum merozoite protein-142 vaccine
CA2462951A1 (en) * 2001-01-26 2003-01-16 Jeffrey A. Lyon Isolation and purification of plasmodium falciparum merozoite protein-142
GB0103171D0 (en) 2001-02-08 2001-03-28 Smithkline Beecham Biolog Vaccine composition
DE60239594D1 (de) * 2001-02-23 2011-05-12 Glaxosmithkline Biolog Sa Influenza vakzinzusammensetzungen zur intradermaler verabreichung
AR032575A1 (es) * 2001-02-23 2003-11-12 Smithkline Beecham Biolog Uso de una preparacion antigenica de gripe para la fabricacion de una vacuna intradermica de la gripe y estuche farmaceutico que comprende dicha vacuna
US20030031684A1 (en) 2001-03-30 2003-02-13 Corixa Corporation Methods for the production of 3-O-deactivated-4'-monophosphoryl lipid a (3D-MLA)
US7713942B2 (en) * 2001-04-04 2010-05-11 Nordic Vaccine Technology A/S Cage-like microparticle complexes comprising sterols and saponins for delivery of polynucleotides
GB0109297D0 (en) 2001-04-12 2001-05-30 Glaxosmithkline Biolog Sa Vaccine
WO2002089747A2 (en) 2001-05-09 2002-11-14 Corixa Corporation Compositions and methods for the therapy and diagnosis of prostate cancer
TWI228420B (en) 2001-05-30 2005-03-01 Smithkline Beecham Pharma Gmbh Novel vaccine composition
US20100221284A1 (en) 2001-05-30 2010-09-02 Saech-Sisches Serumwerk Dresden Novel vaccine composition
WO2003005952A2 (en) 2001-07-10 2003-01-23 Corixa Corporation Compositions and methods for delivery of proteins and adjuvants encapsulated in microspheres
MXPA04000653A (es) 2001-07-27 2004-11-22 Chiron Srl Adhesinas de meningococcus nada, app y orf 40.
GB0118367D0 (en) 2001-07-27 2001-09-19 Glaxosmithkline Biolog Sa Novel use
US20030138434A1 (en) * 2001-08-13 2003-07-24 Campbell Robert L. Agents for enhancing the immune response
US7361352B2 (en) 2001-08-15 2008-04-22 Acambis, Inc. Influenza immunogen and vaccine
GB0123580D0 (en) * 2001-10-01 2001-11-21 Glaxosmithkline Biolog Sa Vaccine
CA2476755C (en) 2001-12-17 2014-08-26 Corixa Corporation Compositions and methods for the therapy and diagnosis of inflammatory bowel disease
US7351413B2 (en) 2002-02-21 2008-04-01 Lorantis, Limited Stabilized HBc chimer particles as immunogens for chronic hepatitis
DE10211088A1 (de) 2002-03-13 2003-09-25 Ugur Sahin Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung
MY139983A (en) 2002-03-12 2009-11-30 Janssen Alzheimer Immunotherap Humanized antibodies that recognize beta amyloid peptide
US6861410B1 (en) 2002-03-21 2005-03-01 Chiron Corporation Immunological adjuvant compositions
EP1497321B1 (en) 2002-04-19 2011-06-29 The Governing Council Of The University Of Toronto Immunological methods and compositions for the treatment of alzheimer's disease
DK1523582T3 (da) 2002-07-18 2009-03-02 Univ Washington Hurtig, effektiv rensning af HSV-specifikke T-lymfocytter samt HSV-antigener identificeret derved
WO2004015099A2 (en) 2002-08-02 2004-02-19 Glaxosmithkline Biologicals Sa Vaccine composition comprising lipooligosaccharide with reduced phase variability
CA2501812C (en) 2002-10-11 2012-07-10 Mariagrazia Pizza Polypeptide-vaccines for broad protection against hypervirulent meningococcal lineages
PL376792A1 (pl) 2002-10-23 2006-01-09 Glaxosmithkline Biologicals S.A. Sposoby szczepienia przeciwko malarii
DE10254601A1 (de) 2002-11-22 2004-06-03 Ganymed Pharmaceuticals Ag Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung
CA2511907A1 (en) 2003-01-06 2004-07-22 Wyeth Compositions and methods for diagnosing and treating colon cancers
ES2303046T3 (es) * 2003-01-29 2008-08-01 Pfizer Products Inc. Vacunas caninas contra bordetella bronchiseptica.
US20050089533A1 (en) * 2003-01-29 2005-04-28 Joseph Frantz Canine vaccines against Bordetella bronchiseptica
ES2411080T3 (es) 2003-01-30 2013-07-04 Novartis Ag Vacunas inyectables contra múltiples serogrupos de meningococos
PL1613346T3 (pl) 2003-04-04 2013-03-29 Zoetis Services Llc Poddane mikrofluidyzacji emulsje typu olej w wodzie i kompozycje szczepionek
WO2005032457A2 (en) 2003-07-21 2005-04-14 Boyce Thompson Institute For Plant Research, Inc. Vectors and methods for immunization against norwalk virus using transgenic plants
PL1648500T3 (pl) 2003-07-31 2014-12-31 Novartis Vaccines & Diagnostics Inc Kompozycje immunogenne dla Streptococcus pyogenes
DE10341812A1 (de) 2003-09-10 2005-04-07 Ganymed Pharmaceuticals Ag Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung
DE10344799A1 (de) 2003-09-26 2005-04-14 Ganymed Pharmaceuticals Ag Identifizierung von Oberflächen-assoziierten Antigenen für die Tumordiagnose und -therapie
WO2005032584A2 (en) 2003-10-02 2005-04-14 Glaxosmithkline Biologicals S.A. Pertussis antigens and use thereof in vaccination
GB0323103D0 (en) 2003-10-02 2003-11-05 Chiron Srl De-acetylated saccharides
RU2378010C2 (ru) 2003-10-02 2010-01-10 Новартис Вэксинес Энд Дайэгностикс С.Р.Л. Жидкие вакцины для множественных серогрупп менингококков
DE10347710B4 (de) 2003-10-14 2006-03-30 Johannes-Gutenberg-Universität Mainz Rekombinante Impfstoffe und deren Verwendung
WO2005063286A1 (en) 2003-12-23 2005-07-14 Arbor Vita Corporation Antibodies for oncogenic strains of hpv and methods of their use
WO2005076972A2 (en) 2004-02-05 2005-08-25 The Ohio State University Research Foundation Chimeric vegf peptides
US7767792B2 (en) 2004-02-20 2010-08-03 Ludwig Institute For Cancer Research Ltd. Antibodies to EGF receptor epitope peptides
DE202005022108U1 (de) 2004-03-09 2013-11-12 Novartis Vaccines And Diagnostics, Inc. Influenza-Virus-Impfstoffe
KR20090051129A (ko) 2004-04-05 2009-05-20 화이자 프로덕츠 인코포레이티드 미세유체화된 수중유 유화액 및 백신 조성물
GB0500787D0 (en) 2005-01-14 2005-02-23 Chiron Srl Integration of meningococcal conjugate vaccination
GB0409745D0 (en) 2004-04-30 2004-06-09 Chiron Srl Compositions including unconjugated carrier proteins
BRPI0510315A (pt) 2004-04-30 2007-10-16 Chiron Srl integração de vacinação com conjugado meningocócico
DE102004023187A1 (de) 2004-05-11 2005-12-01 Ganymed Pharmaceuticals Ag Identifizierung von Oberflächen-assoziierten Antigenen für die Tumordiagnose und -therapie
GB0410866D0 (en) 2004-05-14 2004-06-16 Chiron Srl Haemophilius influenzae
DE102004024617A1 (de) 2004-05-18 2005-12-29 Ganymed Pharmaceuticals Ag Differentiell in Tumoren exprimierte Genprodukte und deren Verwendung
WO2006078294A2 (en) 2004-05-21 2006-07-27 Novartis Vaccines And Diagnostics Inc. Alphavirus vectors for respiratory pathogen vaccines
AU2005285513B2 (en) 2004-05-25 2011-02-24 Oregon Health And Science University SIV and HIV vaccination using RhCMV- and HCMV-based vaccine vectors
DE602005025342D1 (de) 2004-05-28 2011-01-27 Glaxosmithkline Biolog Sa Impfstoffzusammensetzungen mit virosomen und einem saponin-adjuvans
US20090317420A1 (en) 2004-07-29 2009-12-24 Chiron Corporation Immunogenic compositions for gram positive bacteria such as streptococcus agalactiae
GB0417494D0 (en) 2004-08-05 2004-09-08 Glaxosmithkline Biolog Sa Vaccine
GB0420634D0 (en) * 2004-09-16 2004-10-20 Glaxosmithkline Biolog Sa Vaccines
EP2305294B1 (en) 2004-09-22 2015-04-01 GlaxoSmithKline Biologicals SA Immunogenic composition for use in vaccination against staphylococcei
EP2808384B1 (en) 2004-10-08 2017-12-06 The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services Modulation of replicative fitness by using less frequently used synonymous codons
GB0424092D0 (en) 2004-10-29 2004-12-01 Chiron Srl Immunogenic bacterial vesicles with outer membrane proteins
US7902143B2 (en) 2004-12-07 2011-03-08 Toray Industries, Inc. Cancer antigen peptide and the use thereof
CA2590337C (en) 2004-12-15 2017-07-11 Neuralab Limited Humanized amyloid beta antibodies for use in improving cognition
GB0502095D0 (en) 2005-02-01 2005-03-09 Chiron Srl Conjugation of streptococcal capsular saccharides
GB0503337D0 (en) 2005-02-17 2005-03-23 Glaxosmithkline Biolog Sa Compositions
HUE027400T2 (en) 2005-02-18 2016-10-28 Glaxosmithkline Biologicals Sa Proteins and nucleic acids from meningitis / sepsis with Escherichia coli
ES2385045T3 (es) 2005-02-18 2012-07-17 Novartis Vaccines And Diagnostics, Inc. Inmunógenos de Escherichia coli uropatogénica
GB0504436D0 (en) * 2005-03-03 2005-04-06 Glaxosmithkline Biolog Sa Vaccine
HUE027837T2 (en) 2005-03-23 2016-11-28 Glaxosmithkline Biologicals Sa Adjuvant use of influenza virus and oil-in-water emulsion to induce CD4 T-cell and / or enhanced B-cell cellular response
DE102005013846A1 (de) 2005-03-24 2006-10-05 Ganymed Pharmaceuticals Ag Identifizierung von Oberflächen-assoziierten Antigenen für die Tumordiagnose und -therapie
EA201001322A1 (ru) 2005-03-31 2011-02-28 Глаксосмитклайн Байолоджикалс С.А. Вакцины против хламидиоза
US8541007B2 (en) 2005-03-31 2013-09-24 Glaxosmithkline Biologicals S.A. Vaccines against chlamydial infection
ATE543832T1 (de) 2005-04-29 2012-02-15 Glaxosmithkline Biolog Sa Verfahren zur vorbeugung oder behandlung einer m.-tuberculosis-infektion
AU2006261342B2 (en) 2005-06-15 2012-02-02 The Ohio State University Research Foundation Her-2 peptides
GB0513421D0 (en) * 2005-06-30 2005-08-03 Glaxosmithkline Biolog Sa Vaccines
CN101365714A (zh) 2005-07-01 2009-02-11 福赛特儿童口腔医院 结核抗原的检测分析及疫苗
EP1762575A1 (en) 2005-09-12 2007-03-14 Ganymed Pharmaceuticals AG Identification of tumor-associated antigens for diagnosis and therapy
GB0519871D0 (en) 2005-09-30 2005-11-09 Secr Defence Immunogenic agents
WO2007047749A1 (en) 2005-10-18 2007-04-26 Novartis Vaccines And Diagnostics Inc. Mucosal and systemic immunizations with alphavirus replicon particles
AU2006310171B2 (en) 2005-11-01 2011-02-17 Seqirus UK Limited Cell-derived viral vaccines with low levels of residual cell DNA by beta-propiolactone treatment
US11707520B2 (en) 2005-11-03 2023-07-25 Seqirus UK Limited Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture
CA2628152C (en) 2005-11-04 2016-02-02 Novartis Vaccines And Diagnostics S.R.L. Adjuvanted vaccines with non-virion antigens prepared from influenza viruses grown in cell culture
EP2360175B1 (en) 2005-11-22 2014-07-16 Novartis Vaccines and Diagnostics, Inc. Norovirus and Sapovirus virus-like particles (VLPs)
EP1790664A1 (en) 2005-11-24 2007-05-30 Ganymed Pharmaceuticals AG Monoclonal antibodies against claudin-18 for treatment of cancer
GB0524066D0 (en) 2005-11-25 2006-01-04 Chiron Srl 741 ii
DE102005059242A1 (de) 2005-12-12 2007-06-14 Johannes Gutenberg-Universität Mainz, Vertreten Durch Den Präsidenten Molekulare Marker für eine Tumordiagnose und -therapie
TWI457133B (zh) * 2005-12-13 2014-10-21 Glaxosmithkline Biolog Sa 新穎組合物
LT3017827T (lt) 2005-12-22 2019-01-10 Glaxosmithkline Biologicals S.A. Pneumokokinė polisacharidinė konjuguota vakcina
GB0607088D0 (en) 2006-04-07 2006-05-17 Glaxosmithkline Biolog Sa Vaccine
EP1981905B1 (en) 2006-01-16 2016-08-31 THE GOVERNMENT OF THE UNITED STATES OF AMERICA as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES Chlamydia vaccine
ZA200805602B (en) 2006-01-17 2009-12-30 Arne Forsgren A novel surface exposed haemophilus influenzae protein (protein E; pE)
PL1976559T6 (pl) 2006-01-27 2020-08-10 Novartis Influenza Vaccines Marburg Gmbh Szczepionki przeciw grypie zawierające hemaglutyninę i białka macierzy
EP2357184B1 (en) 2006-03-23 2015-02-25 Novartis AG Imidazoquinoxaline compounds as immunomodulators
JP2009534303A (ja) 2006-03-24 2009-09-24 ノバルティス ヴァクシンズ アンド ダイアグノスティクス ゲーエムベーハー アンド カンパニー カーゲー 冷蔵しないインフルエンザワクチンの保存
KR101541383B1 (ko) 2006-03-30 2015-08-03 글락소스미스클라인 바이오로지칼즈 에스.에이. 면역원성 조성물
WO2007126816A2 (en) 2006-03-30 2007-11-08 Embrex, Inc. Methods and compositions for vaccination of poultry
US20100285062A1 (en) 2006-03-31 2010-11-11 Novartis Ag Combined mucosal and parenteral immunization against hiv
US10138279B2 (en) 2006-04-13 2018-11-27 Regents Of The University Of Michigan Compositions and methods for Bacillus anthracis vaccination
US8784810B2 (en) 2006-04-18 2014-07-22 Janssen Alzheimer Immunotherapy Treatment of amyloidogenic diseases
TW200806315A (en) 2006-04-26 2008-02-01 Wyeth Corp Novel formulations which stabilize and inhibit precipitation of immunogenic compositions
CA2653949A1 (en) 2006-06-02 2007-12-13 Glaxosmithkline Biologicals S.A. Method
US20110206692A1 (en) 2006-06-09 2011-08-25 Novartis Ag Conformers of bacterial adhesins
JP5275983B2 (ja) 2006-06-12 2013-08-28 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム ワクチン
CN101479293A (zh) 2006-06-29 2009-07-08 诺华有限公司 脑膜炎奈瑟球菌多肽
SI2422810T1 (sl) 2006-07-17 2015-01-30 Glaxosmithkline Biologicals S.A. Influenčno cepivo
US9364525B2 (en) 2006-07-18 2016-06-14 Glaxosmithkline Biologicals Sa Vaccines for malaria
GB0614460D0 (en) 2006-07-20 2006-08-30 Novartis Ag Vaccines
EP2040744B1 (en) 2006-07-25 2016-03-09 The Secretary of State for Defence Live vaccine strains of francisella
EP2586790A3 (en) 2006-08-16 2013-08-14 Novartis AG Immunogens from uropathogenic Escherichia coli
MX2009002560A (es) 2006-09-07 2009-03-20 Glaxosmithkline Biolog Sa Vacuna.
CA2663196A1 (en) 2006-09-11 2008-03-20 Novartis Ag Making influenza virus vaccines without using eggs
TR201807756T4 (tr) 2006-09-26 2018-06-21 Infectious Disease Res Inst Sentetik adjuvan içeren aşı bileşimi.
US20090181078A1 (en) 2006-09-26 2009-07-16 Infectious Disease Research Institute Vaccine composition containing synthetic adjuvant
SI2086582T1 (sl) 2006-10-12 2013-02-28 Glaxosmithkline Biologicals S.A. Cepivo, ki obsega emulzijo olja v vodi kot adjuvans
PT2086582E (pt) 2006-10-12 2013-01-25 Glaxosmithkline Biolog Sa Vacina compreendendo uma emulsão adjuvante óleo em água
DK2094278T3 (en) * 2006-11-20 2017-07-24 Duecom USE OF LIPID-CONTAINING PARTICLES INCLUDING QUILLAJA SAPONINS FOR CANCER TREATMENT
JP2011506264A (ja) 2006-12-06 2011-03-03 ノバルティス アーゲー インフルエンザウイルスの4つの株に由来する抗原を含むワクチン
GB0700562D0 (en) 2007-01-11 2007-02-21 Novartis Vaccines & Diagnostic Modified Saccharides
MX2009009342A (es) 2007-03-02 2009-09-11 Glaxosmithkline Biolog Sa Metodo novedoso y composiciones.
US8486414B2 (en) 2007-04-04 2013-07-16 Infectious Disease Research Institute Immunogenic compositions comprising Mycobacterium tuberculosis polypeptides and fusions thereof
US8003097B2 (en) 2007-04-18 2011-08-23 Janssen Alzheimer Immunotherapy Treatment of cerebral amyloid angiopathy
TW200908994A (en) 2007-04-20 2009-03-01 Glaxosmithkline Biolog Sa Vaccine
EP2152903A2 (en) 2007-04-26 2010-02-17 Ludwig Institute for Cancer Research, Ltd. Methods for diagnosing and treating astrocytomas
EA201490303A1 (ru) 2007-05-02 2014-05-30 Глаксосмитклайн Байолоджикалс С.А. Вакцина
CA2688284A1 (en) 2007-05-25 2008-12-04 Novartis Ag Streptococcus pneumoniae pilus antigens
GB0711858D0 (en) * 2007-06-19 2007-07-25 Glaxosmithkline Biolog Sa Vaccine
KR20100045445A (ko) 2007-06-26 2010-05-03 글락소스미스클라인 바이오로지칼즈 에스.에이. 스트렙토코쿠스 뉴모니애 캡슐 다당류 컨쥬게이트를 포함하는 백신
SI2185191T1 (sl) 2007-06-27 2012-12-31 Novartis Ag Cepiva proti influenci z majhnimi dodatki
GB0713880D0 (en) 2007-07-17 2007-08-29 Novartis Ag Conjugate purification
PT2182983E (pt) 2007-07-27 2014-09-01 Janssen Alzheimer Immunotherap Tratamento de doenças amiloidogénicas com anticorpos anti-abeta humanizados
GB0714963D0 (en) 2007-08-01 2007-09-12 Novartis Ag Compositions comprising antigens
HUE025149T2 (hu) 2007-08-02 2016-01-28 Biondvax Pharmaceuticals Ltd Multimer multiepitóp influenza vakcinák
CA2695421A1 (en) 2007-08-03 2009-02-12 President And Fellows Of Harvard College Chlamydia antigens
EP2190470B1 (en) 2007-08-13 2017-12-13 GlaxoSmithKline Biologicals SA Vaccines
EP2185195A2 (en) 2007-08-16 2010-05-19 Tripep Ab Immunogen platform
RU2471497C2 (ru) 2007-09-12 2013-01-10 Новартис Аг Мутантные антигены gas57 и антитела против gas57
NZ583796A (en) 2007-09-17 2011-12-22 Oncomethylome Sciences Sa Improved detection of mage-a expression
JO3076B1 (ar) 2007-10-17 2017-03-15 Janssen Alzheimer Immunotherap نظم العلاج المناعي المعتمد على حالة apoe
EP2060583A1 (en) 2007-10-23 2009-05-20 Ganymed Pharmaceuticals AG Identification of tumor-associated markers for diagnosis and therapy
CA2703350C (en) 2007-10-25 2018-02-20 Toray Industries, Inc. Immune response inducer
EP2062594A1 (en) 2007-11-21 2009-05-27 Wyeth Farma, S.A. Bluetongue virus vaccine and immunogenic compositions, methods of use and methods of producing same
GB0810305D0 (en) 2008-06-05 2008-07-09 Novartis Ag Influenza vaccination
AU2008331800A1 (en) 2007-12-03 2009-06-11 President And Fellows Of Harvard College Chlamydia antigens
AU2008352942B2 (en) 2007-12-19 2013-09-12 The Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Soluble forms of Hendra and Nipah virus F glycoprotein and uses thereof
GB0818453D0 (en) 2008-10-08 2008-11-12 Novartis Ag Fermentation processes for cultivating streptococci and purification processes for obtaining cps therefrom
CN104292312A (zh) 2007-12-21 2015-01-21 诺华股份有限公司 链球菌溶血素o的突变形式
EP4206231A1 (en) 2007-12-24 2023-07-05 ID Biomedical Corporation of Quebec Recombinant rsv antigens
EP2245048B1 (en) 2008-02-21 2014-12-31 Novartis AG Meningococcal fhbp polypeptides
EP2268309B1 (en) 2008-03-18 2015-01-21 Novartis AG Improvements in preparation of influenza virus vaccine antigens
JP5749642B2 (ja) 2008-04-16 2015-07-15 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム ワクチン
US9527906B2 (en) 2008-04-18 2016-12-27 The General Hospital Corporation Immunotherapies employing self-assembling vaccines
WO2009131673A1 (en) 2008-04-25 2009-10-29 Ludwig Institute For Cancer Research Ltd. Targeted treatment for subjects with estrogen receptor negative and progesterone receptor negative breast cancers
EP2293813A4 (en) 2008-05-23 2012-07-11 Univ Michigan NANOEMULSION VACCINES
WO2010012045A1 (en) 2008-08-01 2010-02-04 Gamma Vaccines Pty Limited Influenza vaccines
PL2324842T3 (pl) 2008-08-05 2015-08-31 Toray Industries Środek indukujący odporność
GB0815872D0 (en) 2008-09-01 2008-10-08 Pasteur Institut Novel method and compositions
AU2009296458A1 (en) 2008-09-26 2010-04-01 Nanobio Corporation Nanoemulsion therapeutic compositions and methods of using the same
US9067981B1 (en) 2008-10-30 2015-06-30 Janssen Sciences Ireland Uc Hybrid amyloid-beta antibodies
EP2376089B1 (en) 2008-11-17 2018-03-14 The Regents of the University of Michigan Cancer vaccine compositions and methods of using the same
WO2010064243A1 (en) 2008-12-03 2010-06-10 Protea Vaccine Technologies Ltd. GLUTAMYL tRNA SYNTHETASE (GtS) FRAGMENTS
MX2011007456A (es) 2009-01-12 2011-08-03 Novartis Ag Antigenos del dominio de proteina de superficie de union a colageno tipo b (can_b) en vacunas contra bacteria gram positiva.
GB0900455D0 (en) 2009-01-13 2009-02-11 Secr Defence Vaccine
GB0901411D0 (en) 2009-01-29 2009-03-11 Secr Defence Treatment
GB0901423D0 (en) 2009-01-29 2009-03-11 Secr Defence Treatment
US20100234283A1 (en) 2009-02-04 2010-09-16 The Ohio State University Research Foundation Immunogenic epitopes, peptidomimetics, and anti-peptide antibodies, and methods of their use
AU2010212550B2 (en) 2009-02-10 2016-03-10 Seqirus UK Limited Influenza vaccines with reduced amounts of squalene
WO2010094663A1 (en) 2009-02-17 2010-08-26 Glaxosmithkline Biologicals S.A. Inactivated dengue virus vaccine with aluminium-free adjuvant
EP2221375A1 (en) 2009-02-20 2010-08-25 Ganymed Pharmaceuticals AG Methods and compositions for diagnosis and treatment of cancer
EP2221063A1 (en) 2009-02-20 2010-08-25 Ganymed Pharmaceuticals AG Methods and compositions for diagnosis and treatment of cancer
FI2398902T3 (fi) 2009-02-20 2023-11-28 Astellas Pharma Inc Menetelmiä ja koostumuksia syövän diagnoosia ja hoitoa varten
US8568732B2 (en) 2009-03-06 2013-10-29 Novartis Ag Chlamydia antigens
EA021100B1 (ru) 2009-03-17 2015-04-30 МДхХЭЛС СА Усовершенствованное определение экспрессии генов
SG175092A1 (en) 2009-04-14 2011-11-28 Novartis Ag Compositions for immunising against staphylococcus aerus
GB0906234D0 (en) 2009-04-14 2009-05-20 Secr Defence Vaccine
EP2249159A1 (en) 2009-04-29 2010-11-10 Ganymed Pharmaceuticals AG Identification of tumor-associated markers for diagnosis and therapy
WO2010132833A1 (en) 2009-05-14 2010-11-18 The Regents Of The University Of Michigan Streptococcus vaccine compositions and methods of using the same
EP2437753B1 (en) 2009-06-05 2016-08-31 Infectious Disease Research Institute Synthetic glucopyranosyl lipid adjuvants and vaccine compositions containing them
GB0910046D0 (en) * 2009-06-10 2009-07-22 Glaxosmithkline Biolog Sa Novel compositions
GB0910045D0 (en) * 2009-06-10 2009-07-22 Glaxosmithkline Biolog Sa Novel compositions
DK2442826T3 (en) 2009-06-15 2015-09-21 Univ Singapore Influenza vaccine, composition and methods of using
CN102596243B (zh) 2009-06-16 2015-10-21 密执安大学评议会 纳米乳剂疫苗
WO2010149745A1 (en) 2009-06-24 2010-12-29 Glaxosmithkline Biologicals S.A. Recombinant rsv antigens
MX2012000036A (es) 2009-06-24 2012-02-28 Glaxosmithkline Biolog Sa Vacuna.
SG177533A1 (en) 2009-07-07 2012-02-28 Novartis Ag Conserved escherichia coli immunogens
HRP20220756T1 (hr) 2009-07-15 2022-09-02 Glaxosmithkline Biologicals S.A. Proteinski pripravci rsv f i postupci za izradu istih
SG178035A1 (en) 2009-07-16 2012-03-29 Novartis Ag Detoxified escherichia coli immunogens
KR101425404B1 (ko) 2009-07-17 2014-08-01 한림대학교 산학협력단 리포좀에 포집된 올리고뉴클레오타이드 및 에피토프를 포함하는 면역증강용 조성물
GB0913681D0 (en) 2009-08-05 2009-09-16 Glaxosmithkline Biolog Sa Immunogenic composition
GB0913680D0 (en) 2009-08-05 2009-09-16 Glaxosmithkline Biolog Sa Immunogenic composition
EP2281579A1 (en) 2009-08-05 2011-02-09 BioNTech AG Vaccine composition comprising 5'-Cap modified RNA
WO2011025286A2 (ko) 2009-08-26 2011-03-03 주식회사 알엔에이 리포테이코익산 유래 당지질 및 이를 포함하는 조성물
AU2010288240B2 (en) 2009-08-27 2014-03-27 Novartis Ag Hybrid polypeptides including meningococcal fHBP sequences
US20120283115A1 (en) 2009-08-31 2012-11-08 Ludwig Institute For Cancer Research Ltd. Seromic analysis of ovarian cancer
US20110110980A1 (en) 2009-09-02 2011-05-12 Wyeth Llc Heterlogous prime-boost immunization regimen
US20120237536A1 (en) 2009-09-10 2012-09-20 Novartis Combination vaccines against respiratory tract diseases
KR101746880B1 (ko) 2009-09-10 2017-06-14 메리얼 인코포레이티드 사포닌-함유 면역보강제를 포함하는 신규 백신 제형
WO2011034950A1 (en) 2009-09-16 2011-03-24 Vaxart, Inc. Immunization strategy to prevent h1n1 infection
GB0917457D0 (en) 2009-10-06 2009-11-18 Glaxosmithkline Biolog Sa Method
GB0917002D0 (en) 2009-09-28 2009-11-11 Novartis Vaccines Inst For Global Health Srl Improved shigella blebs
GB0917003D0 (en) 2009-09-28 2009-11-11 Novartis Vaccines Inst For Global Health Srl Purification of bacterial vesicles
JP2013506651A (ja) 2009-09-30 2013-02-28 ノバルティス アーゲー Staphylococcus.aureus5型および8型莢膜多糖の結合体
WO2011039631A2 (en) 2009-09-30 2011-04-07 Novartis Ag Expression of meningococcal fhbp polypeptides
WO2011040978A2 (en) 2009-10-02 2011-04-07 Ludwig Institute For Cancer Research Ltd. Immunodominant mhc dr52b restricted ny-eso-1 epitopes, mhc class ii monomers and multimers, and uses thereof
GB0918392D0 (en) 2009-10-20 2009-12-02 Novartis Ag Diagnostic and therapeutic methods
AU2010310985B2 (en) 2009-10-27 2014-11-06 Glaxosmithkline Biologicals S.A. Modified meningococcal fHBP polypeptides
GB0919690D0 (en) 2009-11-10 2009-12-23 Guy S And St Thomas S Nhs Foun compositions for immunising against staphylococcus aureus
EP2322555A1 (en) 2009-11-11 2011-05-18 Ganymed Pharmaceuticals AG Antibodies specific for claudin 6 (CLDN6)
KR102126964B1 (ko) 2009-11-11 2020-06-25 가니메드 파마슈티칼스 게엠베하 클라우딘 6 특이적 항체
WO2011067758A2 (en) 2009-12-02 2011-06-09 Protea Vaccine Technologies Ltd. Immunogenic fragments and multimers from streptococcus pneumoniae proteins
EP2519265B1 (en) 2009-12-30 2018-11-14 GlaxoSmithKline Biologicals SA Polysaccharide immunogens conjugated to e. coli carrier proteins
GB201003333D0 (en) 2010-02-26 2010-04-14 Novartis Ag Immunogenic proteins and compositions
GB201003920D0 (en) 2010-03-09 2010-04-21 Glaxosmithkline Biolog Sa Method of treatment
GB201003924D0 (en) 2010-03-09 2010-04-21 Glaxosmithkline Biolog Sa Immunogenic composition
JP2013521770A (ja) 2010-03-10 2013-06-13 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム ワクチン組成物
EP2366709A1 (en) 2010-03-16 2011-09-21 BioNTech AG Tumor vaccination involving a humoral immune response against self-proteins
CA2786940C (en) 2010-03-16 2019-09-24 Biontech Ag Tumor vaccination involving a humoral immune response, and proteins therefor including all or a portion of a hepatitis b virus core antigen protein and an epitope of claudin 18.2
CN103221065A (zh) 2010-03-26 2013-07-24 葛兰素史密斯克莱生物公司 Hiv疫苗
GB201005625D0 (en) 2010-04-01 2010-05-19 Novartis Ag Immunogenic proteins and compositions
WO2011127316A1 (en) 2010-04-07 2011-10-13 Novartis Ag Method for generating a parvovirus b19 virus-like particle
WO2011130379A1 (en) 2010-04-13 2011-10-20 Novartis Ag Benzonapthyridine compositions and uses thereof
JP2013532008A (ja) 2010-05-28 2013-08-15 テトリス オンライン インコーポレイテッド 対話式ハイブリッド非同期コンピュータ・ゲーム・インフラストラクチャ
PL2575870T3 (pl) 2010-06-04 2017-05-31 Wyeth Llc Preparaty szczepionek
GB201009861D0 (en) 2010-06-11 2010-07-21 Novartis Ag OMV vaccines
US8658603B2 (en) 2010-06-16 2014-02-25 The Regents Of The University Of Michigan Compositions and methods for inducing an immune response
US9192661B2 (en) 2010-07-06 2015-11-24 Novartis Ag Delivery of self-replicating RNA using biodegradable polymer particles
EP2404936A1 (en) 2010-07-06 2012-01-11 Ganymed Pharmaceuticals AG Cancer therapy using CLDN6 target-directed antibodies in vivo
US20130171185A1 (en) 2010-07-06 2013-07-04 Ethan Settembre Norovirus derived immunogenic compositions and methods
GB201015132D0 (en) 2010-09-10 2010-10-27 Univ Bristol Vaccine composition
GB201101665D0 (en) 2011-01-31 2011-03-16 Novartis Ag Immunogenic compositions
AU2011304728A1 (en) 2010-09-20 2013-03-14 Biontech Ag Antigen-specific T cell receptors and T cell epitopes
BR112013004582A2 (pt) 2010-09-27 2016-09-06 Crucell Holland Bv método para induzir uma resposta imune em um sujeito contra um antígeno de um parasita que causa a malária
AU2011315447A1 (en) 2010-10-15 2013-05-09 Glaxosmithkline Biologicals S.A. Cytomegalovirus gB antigen
GB201017519D0 (en) 2010-10-15 2010-12-01 Novartis Vaccines Inst For Global Health S R L Vaccines
WO2012057904A1 (en) 2010-10-27 2012-05-03 Infectious Disease Research Institute Mycobacterium tuberculosis antigens and combinations thereof having high seroreactivity
GB201101331D0 (en) 2011-01-26 2011-03-09 Glaxosmithkline Biolog Sa Compositions and uses
EA201390676A1 (ru) 2010-11-08 2013-11-29 Инфекшес Дизиз Рисерч Инститьют Вакцины, содержащие полипептиды неспецифической нуклеозидгидролазы и стерол 24-c-метилтрансферазы (smt), для лечения и диагностики лейшманиоза
WO2012072769A1 (en) 2010-12-01 2012-06-07 Novartis Ag Pneumococcal rrgb epitopes and clade combinations
EP3593813A1 (en) 2010-12-14 2020-01-15 GlaxoSmithKline Biologicals S.A. Mycobacterium antigenic composition
GB201022007D0 (en) 2010-12-24 2011-02-02 Imp Innovations Ltd DNA-sensor
CA2860331A1 (en) 2010-12-24 2012-06-28 Novartis Ag Compounds
TR201908715T4 (tr) 2011-01-26 2019-07-22 Glaxosmithkline Biologicals Sa Rsv immünizasyon rejimi.
AU2012211043B2 (en) 2011-01-27 2017-04-06 Gamma Vaccines Pty Limited Combination vaccines
WO2012114323A1 (en) 2011-02-22 2012-08-30 Biondvax Pharmaceuticals Ltd. Multimeric multiepitope polypeptides in improved seasonal and pandemic influenza vaccines
US9321813B2 (en) 2011-03-29 2016-04-26 Uab Research Foundation Methods and compositions for cytomegalovirus IL-10 protein
GB201106357D0 (en) 2011-04-14 2011-06-01 Pessi Antonello Composition and uses thereof
AU2012243039B2 (en) 2011-04-08 2017-07-13 Immune Design Corp. Immunogenic compositions and methods of using the compositions for inducing humoral and cellular immune responses
TW201302779A (zh) 2011-04-13 2013-01-16 Glaxosmithkline Biolog Sa 融合蛋白質及組合疫苗
PL2707385T3 (pl) 2011-05-13 2018-03-30 Glaxosmithkline Biologicals Sa Prefuzyjne antygeny RSV F
DK3026064T3 (en) 2011-05-13 2019-01-14 Ganymed Pharmaceuticals Gmbh ANTIBODIES FOR TREATMENT OF CANCER EXPRESSING CLAUDIN 6
BR112013029514A2 (pt) 2011-05-17 2019-09-24 Glaxosmithkline Biologicals Sa composição imunogênica, vacina, e, método de tratar ou impedir uma doença
WO2012157736A1 (ja) 2011-05-19 2012-11-22 東レ株式会社 免疫誘導剤
CA2836568C (en) 2011-05-19 2020-07-21 Toray Industries, Inc. Immunity induction agent
DK2714071T3 (da) 2011-05-24 2019-09-16 Biontech Rna Pharmaceuticals Gmbh Individualiserede vacciner mod cancer
PL2714071T3 (pl) 2011-05-24 2019-12-31 Biontech Rna Pharmaceuticals Gmbh Zindywidualizowane szczepionki przeciwrakowe
WO2012159643A1 (en) 2011-05-24 2012-11-29 Biontech Ag Individualized vaccines for cancer
CA2838188C (en) 2011-06-04 2017-04-18 Rochester General Hospital Research Institute Compositions and methods related to p6 of haemophilus influenzae
AU2012273153A1 (en) 2011-06-21 2013-05-02 Oncofactor Corporation Compositions and methods for the therapy and diagnosis of cancer
US11896636B2 (en) 2011-07-06 2024-02-13 Glaxosmithkline Biologicals Sa Immunogenic combination compositions and uses thereof
EP2729168A2 (en) 2011-07-06 2014-05-14 Novartis AG Immunogenic compositions and uses thereof
WO2013009564A1 (en) 2011-07-08 2013-01-17 Novartis Ag Tyrosine ligation process
WO2013016460A1 (en) 2011-07-25 2013-01-31 Novartis Ag Compositions and methods for assessing functional immunogenicity of parvovirus vaccines
GB201113570D0 (en) 2011-08-05 2011-09-21 Glaxosmithkline Biolog Sa Vaccine
GB201114919D0 (en) 2011-08-30 2011-10-12 Glaxosmithkline Biolog Sa Method
CN103917245B (zh) 2011-09-14 2017-06-06 葛兰素史密丝克莱恩生物有限公司 用于制备糖‑蛋白质糖缀合物的方法
SG11201400193SA (en) 2011-09-16 2014-05-29 Ucb Pharma Sa Neutralising antibodies to the major exotoxins tcda and tcdb of clostridium difficile
CA2854934A1 (en) 2011-11-07 2013-05-16 Novartis Ag Carrier molecule comprising a spr0096 and a spr2021 antigen
WO2013074501A1 (en) 2011-11-14 2013-05-23 Crucell Holland B.V. Heterologous prime-boost immunization using measles virus-based vaccines
KR102024066B1 (ko) 2011-11-23 2019-09-24 비오벤 쓰리 리미티드 재조합 단백질 및 그들의 치료적 용도
CA3131037A1 (en) 2011-11-30 2013-06-06 Emory University Antiviral jak inhibitors useful in treating or preventing retroviral and other viral infections
PT2785683T (pt) 2011-11-30 2020-04-16 Ludwig Inst For Cancer Res Ltd Moduladores de célula inkt e métodos para o seu uso
GB201120860D0 (en) 2011-12-05 2012-01-18 Cambridge Entpr Ltd Cancer immunotherapy
WO2013108272A2 (en) 2012-01-20 2013-07-25 International Centre For Genetic Engineering And Biotechnology Blood stage malaria vaccine
CN104363892A (zh) 2012-02-07 2015-02-18 传染性疾病研究院 包含tlr4激动剂的改进佐剂制剂及其使用方法
US20130236484A1 (en) 2012-03-08 2013-09-12 Detectogen Inc. Leishmaniasis antigen detection assays and vaccines
EP3492095A1 (en) 2012-04-01 2019-06-05 Technion Research & Development Foundation Limited Extracellular matrix metalloproteinase inducer (emmprin) peptides and binding antibodies
WO2013167153A1 (en) 2012-05-09 2013-11-14 Ganymed Pharmaceuticals Ag Antibodies useful in cancer diagnosis
RS57420B1 (sr) 2012-05-16 2018-09-28 Immune Design Corp Vakcine za hsv-2
SG11201407440WA (en) 2012-05-22 2014-12-30 Novartis Ag Meningococcus serogroup x conjugate
EP2666785A1 (en) 2012-05-23 2013-11-27 Affiris AG Complement component C5a-based vaccine
JP2015522580A (ja) 2012-07-06 2015-08-06 ノバルティス アーゲー 免疫学的組成物およびその使用
GB201213364D0 (en) 2012-07-27 2012-09-12 Glaxosmithkline Biolog Sa Purification process
WO2014042780A1 (en) 2012-08-03 2014-03-20 Infectious Disease Research Institute Compositions and methods for treating an active mycobacterium tuberculosis infection
AU2013301312A1 (en) 2012-08-06 2015-03-19 Glaxosmithkline Biologicals S.A. Method for eliciting in infants an immune response against RSV and B. pertussis
US20140037680A1 (en) 2012-08-06 2014-02-06 Glaxosmithkline Biologicals, S.A. Novel method
EP2703483A1 (en) 2012-08-29 2014-03-05 Affiris AG PCSK9 peptide vaccine
WO2014043189A1 (en) 2012-09-14 2014-03-20 The Regents Of The University Of Colorado, A Body Corporate Conditionally replication deficient herpes viruses and use thereof in vaccines
AU2013320313B2 (en) 2012-09-18 2018-07-12 Glaxosmithkline Biologicals Sa Outer membrane vesicles
EA201590427A1 (ru) 2012-10-02 2015-09-30 Глаксосмитклайн Байолоджикалс С.А. Нелинейные сахаридные конъюгаты
SG11201500979RA (en) 2012-10-03 2015-07-30 Glaxosmithkline Biolog Sa Immunogenic composition
BR112015009229B1 (pt) 2012-10-24 2021-07-20 Platelet Targeted Therapeutics, Llc Composição tendo como alvo a expressão de genes para plaquetas, uso de uma célula tronco compreendendo a referida composição para tratar hemofilia e método in vitro ou ex vivo para gerar uma célula tronco modificada
WO2014074785A1 (en) 2012-11-08 2014-05-15 Ludwig Institute For Cancer Research Ltd. Methods of predicting outcome and treating breast cancer
AU2013351542B2 (en) 2012-11-28 2018-08-09 BioNTech SE Individualized vaccines for cancer
US9987344B2 (en) 2012-11-30 2018-06-05 Glaxosmithkline Biologicals Sa Pseudomonas antigens and antigen combinations
EP3513806B1 (en) 2012-12-05 2023-01-25 GlaxoSmithKline Biologicals SA Immunogenic composition
UY34506A (es) 2012-12-10 2014-06-30 Fernando Amaury Ferreira Chiesa Adyuvante de vacunación, preparación y vacunas que lo contienen
WO2014160463A1 (en) 2013-03-13 2014-10-02 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Prefusion rsv f proteins and their use
AR095425A1 (es) 2013-03-15 2015-10-14 Glaxosmithkline Biologicals Sa Vacuna, uso y procedimiento para prevenir una infección por picornavirus
CN111978409B (zh) 2013-03-15 2024-01-26 因斯瑞拜奥有限公司 自组装合成蛋白
ES2728865T3 (es) 2013-03-28 2019-10-29 Infectious Disease Res Inst Vacunas que comprenden polipéptidos de Leishmania para el tratamiento y el diagnóstico de la leishmaniasis
CA2909221A1 (en) 2013-04-18 2014-10-23 Immune Design Corp. Gla monotherapy for use in cancer treatment
WO2014180490A1 (en) 2013-05-10 2014-11-13 Biontech Ag Predicting immunogenicity of t cell epitopes
US9463198B2 (en) 2013-06-04 2016-10-11 Infectious Disease Research Institute Compositions and methods for reducing or preventing metastasis
GB201310008D0 (en) 2013-06-05 2013-07-17 Glaxosmithkline Biolog Sa Immunogenic composition for use in therapy
KR20160027019A (ko) 2013-06-26 2016-03-09 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 뎅기 바이러스 백신에 대한 방법 및 조성물
EP3027203B1 (en) 2013-07-30 2020-07-29 BioNTech SE Tumor antigens for determining cancer therapy
WO2015014376A1 (en) 2013-07-31 2015-02-05 Biontech Ag Diagnosis and therapy of cancer involving cancer stem cells
KR20160040290A (ko) 2013-08-05 2016-04-12 글락소스미스클라인 바이오로지칼즈 에스.에이. 조합 면역원성 조성물
JP6306700B2 (ja) 2013-11-01 2018-04-04 ユニバーシティ オブ オスロUniversity of Oslo アルブミン改変体及びその使用
EP2870974A1 (en) 2013-11-08 2015-05-13 Novartis AG Salmonella conjugate vaccines
CA2929126C (en) 2013-11-13 2020-01-07 University Of Oslo Outer membrane vesicles and uses thereof
US11452767B2 (en) 2013-11-15 2022-09-27 Oslo Universitetssykehus Hf CTL peptide epitopes and antigen-specific t cells, methods for their discovery, and uses thereof
WO2015077442A2 (en) 2013-11-20 2015-05-28 La Jolla Institute For Allergy And Immunology Grass pollen immunogens and methods and uses for immune response modulation
WO2015077434A2 (en) 2013-11-20 2015-05-28 La Jolla Institute For Allergy And Immunology Pan pollen immunogens and methods and uses for immune response modulation
WO2015092710A1 (en) 2013-12-19 2015-06-25 Glaxosmithkline Biologicals, S.A. Contralateral co-administration of vaccines
US11801223B2 (en) 2013-12-31 2023-10-31 Access To Advanced Health Institute Single vial vaccine formulations
CN106255508B (zh) 2014-02-20 2020-07-07 瓦克萨特公司 用于小肠递送的制剂
TW201620927A (zh) 2014-02-24 2016-06-16 葛蘭素史密斯克藍生物品公司 Uspa2蛋白質構築體及其用途
WO2015131053A1 (en) 2014-02-28 2015-09-03 Alk-Abelló A/S Polypeptides derived from phl p and methods and uses thereof for immune response modulation
JP6608422B2 (ja) * 2014-03-25 2019-11-20 ザ ガバメント オブ ザ ユナイテッド ステイツ,アズ リプリゼンティッド バイ ザ セクレタリー オブ ジ アーミー モノホスホリルリピッドa(mpla)含有リポソーム組成物およびサポニンを含む非毒性アジュバント製剤
EA037818B1 (ru) 2014-03-26 2021-05-25 Глаксосмитклайн Байолоджикалс С.А. Мутантные стафилококковые антигены
GB201405921D0 (en) * 2014-04-02 2014-05-14 Glaxosmithkline Biolog Sa Novel methods for inducing an immune response
US11571472B2 (en) 2014-06-13 2023-02-07 Glaxosmithkline Biologicals Sa Immunogenic combinations
DK3160500T3 (da) 2014-06-25 2019-11-11 Glaxosmithkline Biologicals Sa Clostridium difficile immunogen sammensætning
TW201623329A (zh) 2014-06-30 2016-07-01 亞佛瑞司股份有限公司 針對骨調素截斷變異體的疫苗及單株抗體暨其用途
EP3169699A4 (en) 2014-07-18 2018-06-20 The University of Washington Cancer vaccine compositions and methods of use thereof
WO2016012385A1 (en) 2014-07-21 2016-01-28 Sanofi Pasteur Vaccine composition comprising ipv and cyclodextrins
WO2016057921A1 (en) 2014-10-10 2016-04-14 Baker Jr James R Nanoemulsion compositions for preventing, suppressing or eliminating allergic and inflammatory disease
WO2016062323A1 (en) 2014-10-20 2016-04-28 Biontech Ag Methods and compositions for diagnosis and treatment of cancer
MY179251A (en) 2014-11-02 2020-11-02 Univ North Carolina Chapel Hill Methods and compositions for recombinant dengue viruses for vaccine and diagnostic development
BE1023004A1 (fr) 2014-12-10 2016-10-31 Glaxosmithkline Biologicals Sa Procede de traitement
WO2016128060A1 (en) 2015-02-12 2016-08-18 Biontech Ag Predicting t cell epitopes useful for vaccination
US10596247B2 (en) 2015-02-20 2020-03-24 Board Of Regents, The University Of Texas System Methods and compositions for attenuated chlamydia as vaccine and vector
CA2977493C (en) 2015-03-03 2023-05-16 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Display platform from bacterial spore coat proteins
WO2016141320A2 (en) 2015-03-05 2016-09-09 Northwestern University Non-neuroinvasive viruses and uses thereof
JP2018511655A (ja) 2015-03-20 2018-04-26 ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン ボルデテラ属に対するワクチン接種における使用のための免疫原性組成物
CN116603058A (zh) 2015-03-26 2023-08-18 Gpn疫苗有限公司 链球菌疫苗
RU2017140856A (ru) 2015-05-26 2019-06-26 Огайо Стейт Инновейшн Фаундейшн Стратегия вакцинации против вируса свиного гриппа вакциной на основе наночастиц
WO2016200951A1 (en) 2015-06-12 2016-12-15 Vaxart, Inc. Formulations for small intestinal delivery of rsv and norovirus antigens
EP3138579A1 (en) 2015-09-05 2017-03-08 Biomay Ag Fusion protein for use in the treatment of a hepatitis b virus infection
EP3365006A1 (en) * 2015-10-19 2018-08-29 Cadila Healthcare Limited New adjuvant and vaccine composition containing the same
GB201518668D0 (en) 2015-10-21 2015-12-02 Glaxosmithkline Biolog Sa Immunogenic Comosition
GB201518684D0 (en) 2015-10-21 2015-12-02 Glaxosmithkline Biolog Sa Vaccine
JP6900385B2 (ja) 2015-11-06 2021-07-07 アジュバンス・テクノロジーズ・インコーポレーテッド トリテルペンサポニン類似物
GB201522132D0 (en) * 2015-12-15 2016-01-27 Glaxosmithkline Biolog Sa Vaccine
WO2017109698A1 (en) 2015-12-22 2017-06-29 Glaxosmithkline Biologicals Sa Immunogenic formulation
GB201603625D0 (en) 2016-03-02 2016-04-13 Glaxosmithkline Biolog Sa Novel influenza antigens
CA3017356A1 (en) 2016-03-10 2017-09-14 Aperisys, Inc. Antigen-binding fusion proteins with modified hsp70 domains
CR20180445A (es) 2016-03-14 2019-02-08 Univ Oslo Inmunoglobulinas diseñadas por ingeniería genética con unión alterada al fcrn
WO2017158421A1 (en) 2016-03-14 2017-09-21 University Of Oslo Anti-viral engineered immunoglobulins
WO2017167768A1 (en) 2016-03-28 2017-10-05 Glaxosmithkline Biologicals S.A. Novel vaccine composition
JP7035534B2 (ja) 2016-03-28 2022-03-15 東レ株式会社 免疫誘導剤
US11173207B2 (en) 2016-05-19 2021-11-16 The Regents Of The University Of Michigan Adjuvant compositions
JP2019521095A (ja) 2016-05-21 2019-07-25 インフェクシャス ディズィーズ リサーチ インスティチュート 二次性結核および非結核性マイコバクテリウム感染症を治療するための組成物および方法
EP3471761A2 (en) 2016-06-21 2019-04-24 University Of Oslo Hla binding vaccine moieties and uses thereof
PT3488443T (pt) 2016-07-20 2021-09-24 BioNTech SE Seleção de neoepítopos como alvos específicos da doença para terapia com eficácia melhorada
CA3034124A1 (en) 2016-08-23 2018-03-01 Glaxosmithkline Biologicals Sa Fusion peptides with antigens linked to short fragments of invariant chain (cd74)
GB201614799D0 (en) 2016-09-01 2016-10-19 Glaxosmithkline Biologicals Sa Compositions
CA3036218A1 (en) 2016-09-16 2018-03-22 Infectious Disease Research Institute Vaccines comprising mycobacterium leprae polypeptides for the prevention, treatment, and diagnosis of leprosy
EP3295956A1 (en) 2016-09-20 2018-03-21 Biomay Ag Polypeptide construct comprising fragments of allergens
US11466292B2 (en) 2016-09-29 2022-10-11 Glaxosmithkline Biologicals Sa Compositions and methods of treatment
GB201616904D0 (en) 2016-10-05 2016-11-16 Glaxosmithkline Biologicals Sa Vaccine
WO2018077385A1 (en) 2016-10-25 2018-05-03 Biontech Rna Pharmaceuticals Gmbh Dose determination for immunotherapeutic agents
WO2018096396A1 (en) 2016-11-22 2018-05-31 University Of Oslo Albumin variants and uses thereof
GB201620968D0 (en) 2016-12-09 2017-01-25 Glaxosmithkline Biologicals Sa Adenovirus polynucleotides and polypeptides
MX2019006349A (es) 2016-12-16 2019-08-22 Inst Res Biomedicine Proteinas recombinantes rsv f de prefusion nuevas y usos de las mismas.
GB201621686D0 (en) 2016-12-20 2017-02-01 Glaxosmithkline Biologicals Sa Novel methods for inducing an immune response
WO2018178265A1 (en) 2017-03-31 2018-10-04 Glaxosmithkline Intellectual Property Development Limited Immunogenic composition, use and method of treatment
BR112019020209A2 (pt) 2017-03-31 2020-06-02 Glaxosmithkline Intellectual Property Development Limited Composição imunogênica, uso de uma composição imunogênica, método de tratamento ou prevenção de uma recorrência de uma exacerbação aguda de doença pulmonar obstrutiva crônica, e, terapia de combinação.
CN110945022B (zh) 2017-04-19 2024-04-05 生物医学研究所 作为疫苗及新疟疾疫苗和抗体结合靶标的疟原虫子孢子npdp肽
CA3061205A1 (en) * 2017-04-25 2018-11-01 Adjuvance Technologies, Inc. Triterpene saponin analogues
EP3615061A1 (en) 2017-04-28 2020-03-04 GlaxoSmithKline Biologicals S.A. Vaccination
GB201707700D0 (en) 2017-05-12 2017-06-28 Glaxosmithkline Biologicals Sa Dried composition
JP7291633B2 (ja) * 2017-05-30 2023-06-15 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム アジュバントを製造する方法
CN107375921B (zh) * 2017-06-12 2019-10-29 商丘美兰生物工程有限公司 一种甘草皂苷脂质体免疫佐剂及其制备方法
US20200254083A1 (en) 2017-06-16 2020-08-13 Glaxosmithkline Biologicals Sa Method of treatment
BR112020001045A2 (pt) 2017-07-18 2020-09-08 In3Bio Ltd. proteínas sintéticas e usos terapêuticos das mesmas
BR112020001768A2 (pt) 2017-08-14 2020-09-29 Glaxosmithkline Biologicals S.A. método de reforçar uma resposta imune pré-existente contra haemophilus influenzae e moraxella catarrhalis não tipáveis em um indivíduo, e, protocolo de vacinação.
US11123415B2 (en) 2017-08-16 2021-09-21 Ohio State Innovation Foundation Nanoparticle compositions for Salmonella vaccines
WO2019048936A1 (en) 2017-09-07 2019-03-14 University Of Oslo VACCINE MOLECULES
WO2019048928A1 (en) 2017-09-07 2019-03-14 University Of Oslo VACCINE MOLECULES
CN111315406A (zh) 2017-09-08 2020-06-19 传染病研究所 包括皂苷的脂质体调配物及其使用方法
WO2019079594A1 (en) 2017-10-18 2019-04-25 The University Of North Carolina At Chapel Hill METHODS AND COMPOSITIONS FOR VACCINES AGAINST NOVOVIRUS AND DIAGNOSIS OF NOVOVIRUS
GB201721068D0 (en) 2017-12-15 2018-01-31 Glaxosmithkline Biologicals Sa Hepatitis B immunisation regimen and compositions
GB201721069D0 (en) 2017-12-15 2018-01-31 Glaxosmithkline Biologicals Sa Hepatitis B Immunisation regimen and compositions
KR102286397B1 (ko) 2018-02-02 2021-08-05 주식회사 에스엘백시젠 신규 백신 면역보조제
KR20200143391A (ko) 2018-03-15 2020-12-23 비온테크 알엔에이 파마슈티컬스 게엠베하 5'-캡-트리뉴클레오티드- 또는 고차의 올리고뉴클레오티드 화합물 및 이들의 rna 안정화, 단백질 발현 및 치료에서의 사용
EP3569612A1 (en) 2018-05-18 2019-11-20 Biomay Ag Treatment and prevention of house dust mite allergies
CN112638936A (zh) 2018-06-12 2021-04-09 葛兰素史密丝克莱恩生物有限公司 腺病毒多核苷酸和多肽
EP3581201A1 (en) 2018-06-15 2019-12-18 GlaxoSmithKline Biologicals S.A. Escherichia coli o157:h7 proteins and uses thereof
MX2021001479A (es) 2018-08-07 2021-04-28 Glaxosmithkline Biologicals Sa Novedosos procesos y vacunas.
CN112912097A (zh) 2018-08-23 2021-06-04 葛兰素史密丝克莱恩生物有限公司 免疫原性蛋白和组合物
JP7320601B2 (ja) 2018-09-11 2023-08-03 上▲海▼市公共▲衛▼生▲臨▼床中心 広域スペクトルな抗インフルエンザワクチン免疫原及びその使用
EP3849521A1 (en) 2018-09-14 2021-07-21 Massachusetts Institute Of Technology Nanoparticle vaccine adjuvant and methods of use thereof
WO2020115171A1 (en) 2018-12-06 2020-06-11 Glaxosmithkline Biologicals Sa Immunogenic compositions
EP3897846A1 (en) 2018-12-21 2021-10-27 GlaxoSmithKline Biologicals SA Methods of inducing an immune response
WO2020154595A1 (en) 2019-01-24 2020-07-30 Massachusetts Institute Of Technology Nucleic acid nanostructure platform for antigen presentation and vaccine formulations formed therefrom
GB201901608D0 (en) 2019-02-06 2019-03-27 Vib Vzw Vaccine adjuvant conjugates
CN113573730A (zh) 2019-03-05 2021-10-29 葛兰素史密斯克莱生物公司 乙型肝炎免疫方案和组合物
CN114340665A (zh) 2019-05-25 2022-04-12 传染病研究所 用于对佐剂疫苗乳剂进行喷雾干燥的组合物和方法
BR112021026132A2 (pt) 2019-06-25 2022-02-08 In3Bio Ltd Proteínas sintéticas quiméricas estabilizadas e usos terapêuticos das mesmas
AU2020318680A1 (en) 2019-07-21 2022-02-17 Glaxosmithkline Biologicals Sa Therapeutic viral vaccine
EP4004018A1 (en) 2019-07-24 2022-06-01 GlaxoSmithKline Biologicals SA Modified human cytomegalovirus proteins
WO2021023691A1 (en) 2019-08-05 2021-02-11 Glaxosmithkline Biologicals Sa Immunogenic composition
EP3777884A1 (en) 2019-08-15 2021-02-17 GlaxoSmithKline Biologicals S.A. Immunogenic composition
EP3799884A1 (en) 2019-10-01 2021-04-07 GlaxoSmithKline Biologicals S.A. Immunogenic compositions
AU2020358862A1 (en) 2019-10-02 2022-04-14 Janssen Vaccines & Prevention B.V. Staphylococcus peptides and methods of use
EP4058581A1 (en) 2019-11-15 2022-09-21 Infectious Disease Research Institute Rig-i agonist and adjuvant formulation for tumor treatment
US20230045642A1 (en) 2019-12-19 2023-02-09 Glaxosmithkline Biologicals Sa S. aureus antigens and compositions thereof
EP4090363B1 (en) 2020-01-16 2024-09-04 Janssen Pharmaceuticals, Inc. Fimh mutant, compositions therewith and use thereof
EP4114848A4 (en) 2020-02-26 2024-04-03 Versitech Limited PD-1-BASED VACCINES AGAINST CORONAVIRUS INFECTION
WO2021245611A1 (en) 2020-06-05 2021-12-09 Glaxosmithkline Biologicals Sa Modified betacoronavirus spike proteins
US20230293659A1 (en) 2020-08-03 2023-09-21 Glaxosmithkline Biologicals Sa Truncated fusobacterium nucleatum fusobacterium adhesin a (fada) protein and immunogenic compositions thereof
US11225508B1 (en) 2020-09-23 2022-01-18 The University Of North Carolina At Chapel Hill Mouse-adapted SARS-CoV-2 viruses and methods of use thereof
CN113999315A (zh) 2020-10-23 2022-02-01 江苏省疾病预防控制中心(江苏省公共卫生研究院) 融合蛋白及其应用
CA3199937A1 (en) 2020-10-28 2022-05-05 Sanofi Pasteur Liposomes containing tlr4 agonist, preparation and uses thereof
EP4255919A2 (en) 2020-12-02 2023-10-11 GlaxoSmithKline Biologicals S.A. Donor strand complemented fimh
EP4277921A1 (en) 2021-01-12 2023-11-22 Janssen Pharmaceuticals, Inc. Fimh mutants, compositions therewith and use thereof
EP4032547A1 (en) 2021-01-20 2022-07-27 GlaxoSmithKline Biologicals S.A. Hsv1 fce derived fragements for the treatment of hsv
JP2024510717A (ja) 2021-02-22 2024-03-11 グラクソスミスクライン バイオロジカルズ ソシエテ アノニム 免疫原性組成物、使用及び方法
US20220288181A1 (en) 2021-03-12 2022-09-15 Northwestern University Antiviral vaccines using spherical nucleic acids
CN117320745A (zh) 2021-03-30 2023-12-29 维拉瓦克斯股份公司 Sars-cov-2亚单位疫苗
US20240156935A1 (en) 2021-03-31 2024-05-16 Vib Vzw Vaccine Compositions for Trypanosomatids
WO2022208430A1 (en) 2021-04-01 2022-10-06 Janssen Pharmaceuticals, Inc. Production of e. coli o18 bioconjugates
CA3222568A1 (en) 2021-06-28 2023-01-05 Glaxosmithkline Biologicals Sa Novel influenza antigens
EP4405374A1 (en) 2021-09-23 2024-07-31 Viravaxx AG Hbv vaccine inducing pres-specific neutralizing antibodies
WO2023079529A1 (en) 2021-11-05 2023-05-11 King Abdullah University Of Science And Technology Re-focusing protein booster immunization compositions and methods of use thereof
WO2023079528A1 (en) 2021-11-05 2023-05-11 King Abdullah University Of Science And Technology Compositions suitable for use in a method for eliciting cross-protective immunity against coronaviruses
CN118510790A (zh) 2021-12-13 2024-08-16 美国政府(由卫生和人类服务部的部长所代表) 噬菌体λ-疫苗系统
WO2023114570A1 (en) 2021-12-19 2023-06-22 Massachusetts Institute Of Technology Compositions and methods for long-lasting germinal center responses to a priming immunization
WO2023144665A1 (en) 2022-01-28 2023-08-03 Glaxosmithkline Biologicals Sa Modified human cytomegalovirus proteins
CN118695869A (zh) 2022-02-14 2024-09-24 佐治亚大学研究基金会股份有限公司 泛-肺病毒疫苗组合物及其使用方法
WO2024116096A1 (en) 2022-12-01 2024-06-06 Pfizer Inc. Pneumococcal conjugate vaccine formulations
WO2024130009A1 (en) 2022-12-14 2024-06-20 Yale University Compositions and methods of use thereof for the treatment of virally driven cancers
WO2024133160A1 (en) 2022-12-19 2024-06-27 Glaxosmithkline Biologicals Sa Hepatitis b compositions
GB202219228D0 (en) 2022-12-20 2023-02-01 Glaxosmithkline Biologicals Sa Novel influenza antigens
WO2024160901A1 (en) 2023-02-02 2024-08-08 Glaxosmithkline Biologicals Sa Immunogenic composition
GB202303250D0 (en) 2023-03-06 2023-04-19 King S College London Method and compounds

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ230747A (en) * 1988-09-30 1992-05-26 Bror Morein Immunomodulating matrix comprising a complex of at least one lipid and at least one saponin; certain glycosylated triterpenoid saponins derived from quillaja saponaria molina
DK0454735T3 (da) * 1989-01-23 1996-10-07 Auspharm Int Ltd Vaccine sammensætning
GB8919819D0 (en) * 1989-09-01 1989-10-18 Coopers Animal Health Complexes having adjuvant activity
NL9002314A (nl) * 1990-10-23 1992-05-18 Nederlanden Staat Immunogene complexen, in het bijzonder iscoms.
ES2143716T3 (es) * 1992-06-25 2000-05-16 Smithkline Beecham Biolog Composicion de vacuna que contiene adyuvantes.
CA2156525A1 (en) * 1993-02-19 1994-09-01 Susan Dillon Influenza vaccine compositions containing 3-o-deacylated monophosphoryl lipid a
SG48309A1 (en) * 1993-03-23 1998-04-17 Smithkline Beecham Biolog Vaccine compositions containing 3-0 deacylated monophosphoryl lipid a
ATE196737T1 (de) * 1993-05-25 2000-10-15 American Cyanamid Co Adjuvantien für impfstoffe gegen das respiratorische synzitialvirus
AUPM873294A0 (en) * 1994-10-12 1994-11-03 Csl Limited Saponin preparations and use thereof in iscoms
GB9718901D0 (en) 1997-09-05 1997-11-12 Smithkline Beecham Biolog Vaccine

Also Published As

Publication number Publication date
EP0822831B2 (en) 2006-08-23
ES2140076T5 (es) 2007-04-16
SK144297A3 (en) 1998-05-06
WO1996033739A1 (en) 1996-10-31
DE69637254T2 (de) 2008-06-19
NZ305365A (en) 1999-05-28
EP0955059A3 (en) 2000-07-12
EP0884056A1 (en) 1998-12-16
DE69605296T3 (de) 2007-02-15
IL118004A0 (en) 1996-08-04
EP0955059B1 (en) 2007-09-19
SK282017B6 (sk) 2001-10-08
EP0822831A1 (en) 1998-02-11
EP0955059A2 (en) 1999-11-10
MA23850A1 (fr) 1996-12-31
DE69637254D1 (de) 2007-10-31
TR199701252T1 (xx) 1998-03-21
ES2140076T3 (es) 2000-02-16
BG63491B1 (bg) 2002-03-29
HU227944B1 (en) 2012-06-28
DK0955059T3 (da) 2007-12-17
CN1480214A (zh) 2004-03-10
SI0955059T1 (sl) 2008-02-29
ES2293708T3 (es) 2008-03-16
KR19990008003A (ko) 1999-01-25
AU693022B2 (en) 1998-06-18
BG101995A (en) 1998-11-30
HK1025244A1 (en) 2000-11-10
RO119068B1 (ro) 2004-03-30
JPH11504020A (ja) 1999-04-06
UA56132C2 (uk) 2003-05-15
BR9608199B1 (pt) 2009-05-05
DK0822831T3 (da) 2000-05-01
CA2217178A1 (en) 1996-10-31
NO974859D0 (no) 1997-10-21
AU5334596A (en) 1996-11-18
DE69605296T2 (de) 2000-05-18
KR100463372B1 (ko) 2005-02-28
SA96170297B1 (ar) 2005-11-15
CZ337997A3 (cs) 1998-03-18
BR9608199A (pt) 1999-05-18
ATE373487T1 (de) 2007-10-15
HK1009086A1 (en) 1999-05-28
DZ2026A1 (fr) 2002-07-21
CN1248737C (zh) 2006-04-05
EA199700272A1 (ru) 1998-04-30
EP0822831B1 (en) 1999-11-24
PL184061B1 (pl) 2002-08-30
GR3031912T3 (en) 2000-02-29
AP771A (en) 1999-10-07
CA2217178C (en) 2009-09-29
CZ296216B6 (cs) 2006-02-15
CN1289065C (zh) 2006-12-13
CN1515245A (zh) 2004-07-28
HUP9801560A3 (en) 1999-07-28
EA000839B1 (ru) 2000-04-24
JP3901731B2 (ja) 2007-04-04
PL322968A1 (en) 1998-03-02
DK0822831T4 (da) 2006-12-27
CN1182370A (zh) 1998-05-20
MX9708226A (es) 1998-06-30
MY134811A (en) 2007-12-31
NO322190B1 (no) 2006-08-28
AU699213B2 (en) 1998-11-26
NO974859L (no) 1997-10-21
AR001686A1 (es) 1997-11-26
OA10629A (en) 2002-09-16
CY2588B2 (en) 2009-11-04
AP9701123A0 (en) 1997-10-31
PT955059E (pt) 2007-11-27
SI0822831T1 (en) 2000-02-29
HUP9801560A1 (hu) 1998-10-28
SI0822831T2 (sl) 2006-12-31
CN1111071C (zh) 2003-06-11
IL118004A (en) 1999-11-30
AU6987398A (en) 1998-07-23
ATE186842T1 (de) 1999-12-15
DE69605296D1 (de) 1999-12-30

Similar Documents

Publication Publication Date Title
TW515715B (en) Vaccine compositions having immunologically active QS21
US6846489B1 (en) Vaccines containing a saponin and a sterol
AU714930B2 (en) Vaccines
JP3755890B2 (ja) アジュバント含有ワクチン組成物
ES2285036T3 (es) Coadyuvantes basados en una emulsion y mpl para vacunas.
US20110243971A1 (en) Vaccines
AU687494C (en) Vaccines
MXPA97008226A (es) Vacunas que contienen una saponina y un esterol

Legal Events

Date Code Title Description
GD4A Issue of patent certificate for granted invention patent
MK4A Expiration of patent term of an invention patent