JP6466332B2 - ウイルス含有製剤およびその使用 - Google Patents
ウイルス含有製剤およびその使用 Download PDFInfo
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- JP6466332B2 JP6466332B2 JP2015535011A JP2015535011A JP6466332B2 JP 6466332 B2 JP6466332 B2 JP 6466332B2 JP 2015535011 A JP2015535011 A JP 2015535011A JP 2015535011 A JP2015535011 A JP 2015535011A JP 6466332 B2 JP6466332 B2 JP 6466332B2
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- formulation
- virus
- phosphate
- poxvirus
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Description
WO95/10601は、糖類、高分子量構造添加剤、アミノ酸、緩衝剤および水を含む組み換えウイルス水溶液を開示する。
WO03/053463は、スクロース、デキストラン、グルタミン酸およびリン酸塩フリーの緩衝剤を含むワクシニアウイルス製剤を開示する。
WO2005/066333は、尿素、糖、塩、緩衝剤、分散剤ならびに必須および非必須アミノ酸の混合物を含むウイルス組成物を記載している。
WO2007/056847は、スクロース、ソルビトール、ポリビニルピロリドン、尿素、TRIS緩衝剤、グルタミン酸ナトリウムおよびアルギニン、アラニン、セリンまたはグリシン等の他のアミノ酸を含むウイルス含有製剤を開示する。
WO2008/114021およびWO2011/121306は、ポリエチレンイミン化合物を、任意に一つ以上の糖と組み合わせて含むウイルス組成物を記載している。
第一の態様によれば、本発明は、(i)少なくとも一つのウイルス由来材料、(ii)ポリビニルピロリドンおよびその誘導体の群から選択される少なくとも一つのポリマー、(iii)少なくとも一つの糖、(iv)少なくとも二つの異なるアミノ酸、(v)少なくとも二つの薬学的に許容される塩であって、塩の少なくとも1つがリン酸塩である塩、ならびに任意に(vi)薬学的に許容される緩衝剤を含む製剤に関する。
MUC−1抗原およびIL−2を発現するMVAであるMVA−[MUC1−IL2](WO92/07000およびWO95/09241参照)、TG4010ともいう;ならびに
HPV−16の非腫瘍形成性E6およびE7抗原ならびにIL−2を発現するMVAであるMVA−[HPV−IL2](WO90/10459、WO95/09241、WO98/04705、WO99/03885およびWO07/121894参照)、TG4001ともいう
である。
本発明は、さらに、乾燥形状、好ましくは凍結乾燥形状の上記開示の製剤を含む安定なウイルス由来材料含有ワクチンに関する。
上述のとおり、本発明の製剤、好ましくは水性製剤は、乾燥、好ましくは凍結乾燥に適する。好ましくは、凍結乾燥に付される製剤中に含まれるウイルス由来材料は、上記定義のとおり、精製され、または少なくとも部分的に精製される。
本発明はさらに再構成材料に関する。「再構成材料」(再構成製剤、再構成組成物、再構成生成物、再構成ワクチン、再構成ウイルス由来材料含有ワクチンを含む)は、適切な量の薬学的に許容される溶媒の添加によって再構成された「乾燥材料」(乾燥製剤、乾燥組成物、乾燥生成物、乾燥ワクチン、乾燥ウイルス由来材料含有ワクチンを含む)に相当する。特別な態様によれば、薬学的に許容される溶媒は、注射用水(WFI)、生理学的血清またはNaCl溶液等の生理食塩水からなる群から選択される。
乾燥プロセス、より具体的には凍結乾燥プロセスの主要な欠点の一つは、それらが不安定で、保管中に増加できるウイルスにおいてウイルスの全力価が低下し得ることである。
L−アルギニン塩酸塩粉末(J.T BACKER−SIGMA);
SVF(PAA);
TRIS=トリス(ヒドロキシメチル)アミノメタン粉末(J.T BACKER);
塩酸(HCl)1M(MERCK);
水酸化ナトリウム(NaOH)1N(VWR);
スクロース粉末(MERCK);
塩化ナトリウム(NaCl)粉末(MERCK);
PVP25粉末(MERCK);
L−グルタミン酸一ナトリウム塩(MERCK);
リン酸水素二ナトリウム無水粉末(MERCK);
リン酸二水素カリウム無水粉末(MERCK);
注射用水(COOPER);
バイアル=TopLyo(登録商標)バイアル(SCHOTT);
Stoppers(STELMI);
DAB=3,3’−ジアミノベンジジン(SIGMA);
宿主細胞 BHK−21(ATCC、CCL10);
抗ワクチン抗体(Meridian Life science);
ペルオキシダーゼ結合抗ウサギ抗体(DAKO);
MilliQ水(Millipore);
PBS(DULBECCO SIGMA);
Triton X−100(SIGMA);
DMEM(GIBCO)
Cations 100X(10g/L酢酸マグネシウム4水和物(MERCK)および10g/L塩化カルシウム二水和物(JT BACKER))
凍結乾燥中および長期間保管中の本発明の製剤の安定性を評価するためのウイルス滴定方法を以下詳述する。
以下で参照される液状製剤I〜Vを以下の工程に従って製造した。これらの製剤はMVA−由来生成物を含む。より正確には、製剤I〜IIIはTG4001を含み、製剤IVおよびVはTG4040を含む。
より正確には:
製剤I〜IIIを製造するために、170μlの溶液B1〜B3を、340μLのTG4001を含む工程a)のウイルス溶液A1に添加した;ならびに
製剤IVおよびVを製造するために、170μlの溶液B4およびB5を、340μLのTG4040を含む工程a)のウイルス溶液A’2に添加した。
以下の実施例において、すべての凍結乾燥は凍結乾燥機TELSTAR LYOBETA 25で行った。
a)乾燥生成物I〜IIIの製造
実施例1で得た液状製剤I〜IIIをTopLyo(登録商標)バイアル(SCHOTT)に充填し、凍結乾燥プロセスを以下のとおり行った。
実施例1で得た液状製剤IVおよびVをTopLyo(登録商標)バイアル(SCHOTT)に充填し、凍結乾燥プロセスを以下のとおり行った。手順は製剤I〜IIIで行ったものと同様であるが、このケースにおいてはさらなる真空工程が行われた。
3.a)乾燥生成物I〜Vの再構成
凍結乾燥後すぐに、最終容積680μLにWFIで調製した再構成材料(Reconstit.Compo.)I〜Vを以下の表5に詳述する(すなわち、t0の保管期間なし)。
上記で示したように、各乾燥生成物のウイルス力価の累積低下(すなわち、凍結乾燥プロセスに起因する低下を含む長期保管中の低下)をBHK−21細胞でプラークアッセイ方法を使用して評価した。
宿主細胞BHK−21をDMEM中単層で培養した。コンフルエントになった状態で、細胞を10mlのPBSで洗浄し、次いでトリプシン処理した。トリプシンを除去後、次いで、細胞を37℃で10%SFVを含む10mLのDMEMで再懸濁した。
細胞播種の約1日後、ウイルス懸濁液の一定分量を工程1のBHK−21細胞を含む各ウェルに添加した。必要に応じて、当業者に周知の方法に従って、最初に前記懸濁液をPBS、cations 100Xおよび1%SVFで連続的に希釈した。場合に応じて、工程1のBHK−21細胞に添加されたウイルス懸濁液は、凍結乾燥前のウイルス含有液状組成物であるか、またはウイルス含有再構成組成物であった(すなわち、凍結乾燥後、異なる期間と温度における)。
培地を除去後、細胞をPBS(ウェル当たり約1mL)で洗浄した。次いで、1mLのメタノール/アセトン(50/50)溶液を添加し、得られた混合物を室温で穏やかに撹拌した。
ウイルス力価の決定は、抗ワクチン抗体と、ペルオキシダーゼに結合する抗ウサギ抗体とを使用する周知のペルオキシダーゼ反応に従って行った。より正確には、反応前、抗ワクチン抗体をPBS+2%SVFで100倍希釈した。次いで500μLの前記抗体を各ウェルに添加し、37℃で約30分間培養し、次いで1mLのPBS+1%Triton X−100で3回洗浄した。
5℃での安定性試験の結果を以下の表6に示す。
SDは標準偏差である。
−1日のウイルス力価は、凍結乾燥前の液状組成物I〜Vのウイルス力価に相当する。
0日のウイルス力価は、凍結乾燥直後の乾燥組成物I〜Vのウイルス力価に相当する。凍結乾燥前の液状組成物I〜Vのウイルス力価との比較により凍結乾燥中のウイルス力価の低下が決定される。
28日、60日および90日のウイルス力価は、それぞれ28日、60日および90日保管後の乾燥組成物I〜Vのウイルス力価に相当する。凍結乾燥直後(すなわち、0日)の再構成組成物I〜Vウイルス力価との比較により、5℃保管中のウイルス力価の低下が決定される。
乾燥生成物I〜Vの安定性をさらに評価するために、45℃で安定性試験を行った。上記で説明したように、このような昇温は加速的な方法におけるウイルスの分解を予測させる。
45℃での加速安定性試験の結果を以下の表7に示す。
SD、−1日のウイルス力価および0日のウイルス力価は、上記表6と同様の意味を示す。
4日、7日、28日および60日のウイルス力価は、それぞれ4日、7日、28日および60日保管後の乾燥組成物I〜Vのウイルス力価に相当する。凍結乾燥直後(すなわち、0日)の再構成組成物I〜Vのウイルス力価との比較により45℃保管中のウイルス力価の低下が決定される。
C0は最初の力価(PFU/mL)(凍結乾燥後)であり、
Tは温度(ケルビン温度)であり、
tは時間(日)であり、
Cは時間tに対応する力価(PFU/mL)である]
三つの参考サンプル(RS2〜RS4)をTG4040の精製バッチから、および一つ(RS1)を精製TG4001ウイルスバッチから生成した。参考サンプルは、RSサンプルをリン酸塩を使用せずに製剤化した以外は、実施例1〜3に記載の組成物I〜Vと一緒に処理した。ArgおよびNaClの濃度もサンプルに応じて変更した。
TG4040ウイルス調製物を上記のように製剤化した。さらに具体的には、二つの異なる濃度、高用量(約1.70×108pfu/mL)および低用量(約7.00×107pfu)のそれぞれで試験し、ウイルス調製物を、1mMのNa2HPO4および10mMのTris、10mMのグルタミン酸Na塩、3.75%のスクロース、50mMのNaCl、2.5%のPVP25kDaならびに30mMのArgを含有する製剤に製剤化した。150mMのArgを有する製剤も低用量のTG4040調製物とともに試験した。
Claims (23)
- (i)野生型、弱毒化もしくは組み換えポックスウイルスおよびポックスウイルス粒子からなる群から選択される少なくとも一つのポックスウイルス由来材料、(ii)ポリビニルピロリドンおよびコポビドンならびにそれらの混合物の群から選択される少なくとも一つのポリマー、(iii)少なくとも一つの二糖、(iv)アルギニンおよびグルタミン酸塩、ならびに、(v)少なくとも一つの薬学的に許容されるリン酸塩および少なくとも一つの薬学的に許容される一価の塩を含む、製剤。
- 薬学的に許容される緩衝剤をさらに含む、請求項1に記載の製剤。
- 水性製剤である、請求項1または2に記載の製剤。
- 前記(ii)少なくとも一つのポリマーが、ポリビニルピロリドンである、請求項1〜3のいずれか一項に記載の製剤。
- 前記ポリビニルピロリドンまたはコポビドンの分子量が10kDa〜40kDaである、請求項1〜4のいずれか一項に記載の製剤。
- 前記製剤が、10g/L〜50g/Lのポリビニルピロリドンまたはコポビドンもしくは混合物を含む、請求項1〜5のいずれか一項に記載の製剤。
- 前記二糖が、スクロース、ラクツロース、ラクトース、マルトース、トレハロース、セロビオース、イソマルトースおよびマルツロースからなる群から選択される、請求項1〜6のいずれか一項に記載の製剤。
- 前記製剤が、20g/L〜80g/Lの糖を含む、請求項1〜7のいずれか一項に記載の製剤。
- 前記製剤が、50g/Lのスクロースを含む、請求項8に記載の製剤。
- 前記製剤が、5g/L〜100g/Lのアルギニンを含む、請求項1〜9のいずれか一項に記載の製剤。
- 前記製剤が、1g/L〜10g/Lのグルタミン酸塩を含む、請求項1〜10のいずれか一項に記載の製剤。
- 前記リン酸塩が、ナトリウム塩およびカリウム塩ならびにそれらの組み合わせからなる群から選択される、請求項1〜11のいずれか一項に記載の製剤。
- 前記リン酸塩が、一塩基性リン酸塩、二塩基性リン酸塩および三塩基性リン酸塩からなる群から選択される、請求項12に記載の製剤。
- 前記薬学的に許容される一価の塩が、NaClおよびKClからなる群から選択される、請求項1〜13のいずれか一項に記載の製剤。
- 前記製剤が、1g/L〜5g/Lの前記薬学的に許容される一価の塩を含む、請求項1〜14のいずれか一項に記載の製剤。
- 前記野生型、弱毒化もしくは組み換えポックスウイルスまたはポックスウイルス粒子が、ワクシニアウイルス(VV)および改変ワクシニアウイルスアンカラ(MVA)からなる群から選択される、請求項1〜15のいずれか一項に記載の製剤。
- 前記野生型、弱毒化もしくは組み換えポックスウイルスまたはポックスウイルス粒子が、
HCV NS3、NS4およびNS5B抗原を発現するMVA、MUC−1抗原およびIL−2を発現するMVA、ならびに、HPV−16の非腫瘍形成性E6およびE7抗原およびIL−2を発現するMVAからなる群から選択される組み換えMVA、または、
顆粒球マクロファージコロニー刺激因子である免疫刺激性サイトカインを発現するチミジンキナーゼ(TK)不活性化ワクシニアウイルス、および、チミジンキナーゼ(TK)およびリボヌクレオチドレダクターゼ(I4L)が不活性化された、自殺遺伝子を発現するワクシニアウイルスからなる群から選択される組み換えワクシニアウイルスである、請求項16に記載の製剤。 - 前記製剤中のウイルス力価が、1.106Pfu/mL〜1.1010Pfu/mLである、請求項1〜17のいずれか一項に記載の製剤。
- 前記製剤が、下記a)〜h):
a)(i)ポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、ならびに(v)リン酸二ナトリウム塩およびリン酸一カリウム塩の混合物、
b)(i)ポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、(v)リン酸二ナトリウム塩およびリン酸一カリウム塩の混合物、ならびに(vi)薬学的に許容される緩衝剤、
c)(i)MVAおよびVVからなる群から選択されるポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、(v)リン酸二ナトリウム塩およびリン酸一カリウム塩の混合物ならびにNaCl、ならびに(vi)TRIS、BES、TES、DIPSO、MOBS、TAPSO、HEPPSO、POPSO、MOPS、HEPESおよび重炭酸塩の群から選択される薬学的に許容される緩衝剤を含む製剤、
d)(i)MVAおよびVVからなる群から選択されるポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、(v)リン酸二ナトリウム塩およびリン酸一カリウム塩の混合物ならびにNaCl、ならびに(vi)TRIS緩衝剤、
e)(i)ポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、(v)少なくとも一つのリン酸塩および少なくとも一つの一価の塩、ならびに(vi)薬学的に許容される緩衝剤、
f)(i)ポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、(v)リン酸二ナトリウム塩および少なくとも一つの一価の塩、ならびに(vi)薬学的に許容される緩衝剤、
g)(i)ポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、(v)リン酸二ナトリウム塩およびNaCl、ならびに(vi)薬学的に許容される緩衝剤、および、
h)(i)ポックスウイルス、(ii)ポリビニルピロリドン、(iii)スクロース、(iv)アルギニンおよびグルタミン酸塩、(v)リン酸二ナトリウム塩およびNaCl、ならびに(vi)TRIS緩衝剤
のいずれかを含む、請求項1〜18のいずれか一項に記載の製剤。 - 請求項3〜19のいずれか一項に記載の水性製剤を凍結乾燥する工程を含む、凍結乾燥製剤の製造方法。
- 請求項20に記載の方法により製造される、凍結乾燥製剤。
- 適切な量の薬学的に許容される溶媒を、請求項21に記載の凍結乾燥製剤に添加することにより製造される、再構成製剤。
- 請求項1〜19のいずれか一項に記載の製剤または請求項22に記載の再構成製剤を含む、癌、感染性疾患および/または自己免疫疾患の中から選択される病態の治療および/または予防のためのワクチンを製造するための医薬組成物。
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Families Citing this family (33)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11273127B2 (en) | 2014-05-06 | 2022-03-15 | The Regents Of The University Of Colorado, A Body Corporate | Compositions, methods and uses for thermally stable multi-targeted antigens |
US10555981B2 (en) | 2014-07-16 | 2020-02-11 | Transgene S.A. | Oncolytic virus for expression of immune checkpoint modulators |
EP3226894B1 (en) | 2014-12-01 | 2019-08-07 | Transgene SA | Stable liquid vaccinia virus formulations |
WO2016128542A1 (en) * | 2015-02-13 | 2016-08-18 | Transgene Sa | Immunotherapeutic vaccine and antibody combination therapy |
WO2016131945A1 (en) | 2015-02-20 | 2016-08-25 | Transgene Sa | Combination product with autophagy modulator |
KR20170138996A (ko) | 2015-02-25 | 2017-12-18 | 메모리얼 슬로안-케터링 캔서 센터 | 고형 종양을 위한 단일면역요법으로서 또는 면역 체크포인트 차단제와 조합된 불활성화 비복제성 변형 백시니아 바이러스 안카라의 용도 |
KR20180006916A (ko) | 2015-04-17 | 2018-01-19 | 메모리얼 슬로안-케터링 캔서 센터 | 고형 종양에 대한 면역치료제로서 mva 또는 mva델타e3l의 용도 |
AU2017222687B2 (en) | 2016-02-25 | 2022-02-24 | Memorial Sloan Kettering Cancer Center | Recombinant MVA or MVADELE3L expressing human Flt3L and use thereof as immuno-therapeutic agents against solid tumors |
MX2018010204A (es) | 2016-02-25 | 2019-05-06 | Memorial Sloan Kettering Cancer Center | Virus de la vaccinia atenuada competentes para replicacion con la supresion de timidina quinasa con y sin la expresion del flt3l o gm-csf humanos para inmunoterapia del cancer. |
BR112018068544A2 (pt) * | 2016-03-14 | 2019-04-24 | Baylor College Medicine | tc24-c4, antígeno para vacina contra doença de chagas com estabilidade melhorada e agregação diminuída |
KR20180135912A (ko) * | 2016-03-31 | 2018-12-21 | 다케다 백신즈 인코포레이티드 | 개선된 제형을 이용한 알파바이러스의 안정화 조성물 및 방법 |
US20190134190A1 (en) | 2016-05-04 | 2019-05-09 | Transgene Sa | Combination therapy with cpg tlr9 ligand |
WO2018049261A1 (en) | 2016-09-09 | 2018-03-15 | Icellhealth Consulting Llc | Oncolytic virus expressing immune checkpoint modulators |
WO2018069316A2 (en) | 2016-10-10 | 2018-04-19 | Transgene Sa | Immunotherapeutic product and mdsc modulator combination therapy |
CN111107872A (zh) | 2017-05-12 | 2020-05-05 | 纪念斯隆-凯特林癌症中心 | 有用于癌症免疫疗法的牛痘病毒突变体 |
WO2018210804A1 (en) | 2017-05-15 | 2018-11-22 | Janssen Vaccines & Prevention B.V. | Stable virus-containing composition |
KR102658198B1 (ko) | 2017-05-15 | 2024-04-16 | 얀센 백신스 앤드 프리벤션 비.브이. | 안정한 바이러스 함유 조성물 |
EP3641803A2 (en) | 2017-06-21 | 2020-04-29 | Transgene | Personalized vaccine |
WO2019113202A1 (en) * | 2017-12-05 | 2019-06-13 | Applied Genetic Technologies Corporation | Formulation optimization for viral particles |
WO2019170820A1 (en) | 2018-03-07 | 2019-09-12 | Transgene | Parapoxvirus vectors |
AU2019296451B2 (en) | 2018-06-29 | 2021-04-29 | Wuhan Neurophth Biotechnology Limited Company | Compositions and methods for treating leber's hereditary optic neuropathy |
JP7403852B2 (ja) | 2018-08-20 | 2023-12-25 | ウーハン ニューロフス バイオテクノロジー リミテッド カンパニー | レーベル遺伝性視神経症を治療するための組成物及び方法 |
WO2020049151A1 (en) | 2018-09-06 | 2020-03-12 | Bavarian Nordic A/S | Storage improved poxvirus compositions |
JPWO2020090871A1 (ja) | 2018-10-30 | 2021-10-07 | 国立大学法人 東京大学 | がん治療のための腫瘍溶解性ウイルス |
WO2020136232A1 (en) | 2018-12-28 | 2020-07-02 | Transgene Sa | Immunosuppressive m2 protein |
EP3902562A1 (en) | 2018-12-28 | 2021-11-03 | Transgene SA | M2-defective poxvirus |
CN113025633A (zh) | 2019-12-09 | 2021-06-25 | 武汉纽福斯生物科技有限公司 | 编码人nadh脱氢酶亚单位1蛋白的核酸及其应用 |
EP3842065A1 (en) | 2019-12-23 | 2021-06-30 | Transgene | Process for designing a recombinant poxvirus for a therapeutic vaccine |
CA3170701A1 (en) | 2020-03-12 | 2021-09-16 | Bavarian Norcig A/S | Compositions improving poxvirus stability |
WO2022148736A1 (en) | 2021-01-05 | 2022-07-14 | Transgene | Vectorization of muc1 t cell engager |
WO2024003353A1 (en) | 2022-07-01 | 2024-01-04 | Transgene | Fusion protein comprising a surfactant-protein-d and a member of the tnfsf |
CN115040656B (zh) * | 2022-07-05 | 2024-04-26 | 吉林惠康生物药业有限公司 | 狂犬疫苗冻干保护剂、应用和疫苗及其制备方法 |
TW202413636A (zh) | 2022-08-18 | 2024-04-01 | 法商傳斯堅公司 | 嵌合痘病毒 |
Family Cites Families (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2076787A5 (en) * | 1970-01-28 | 1971-10-15 | Merieux Inst | Lyophilisation stabiliser - for viruses contg potassium phosphate lactose and albumin |
US3915794A (en) * | 1973-02-09 | 1975-10-28 | Rit Rech Ind Therapeut | Stabilizing compositions for cell-free viruses and cell-free virus preparations containing them |
US4338335A (en) * | 1980-02-05 | 1982-07-06 | Merck & Co., Inc. | Vaccine stabilizer containing L-glutamic acid and L-arginine |
FR2505657A1 (fr) * | 1981-05-13 | 1982-11-19 | Pasteur Institut | Perfectionnements apportes aux agents de stabilisation de virus vivants pour la preparation de vaccins, et vaccins stabilises contenant lesdits agents de stabilisation |
AU568666B2 (en) * | 1983-08-25 | 1988-01-07 | Thomas, G. | Production of phosphates from alkali-proecessed phosphate rock |
FR2643817B1 (fr) | 1989-03-06 | 1993-12-17 | Transgene Sa | Composition pharmaceutique, utile a titre preventif ou curatif contre les tumeurs induites par les papillomavirus |
GB8801338D0 (en) | 1988-01-21 | 1988-02-17 | Quadrant Bioresources Ltd | Preservation of viruses |
WO1991002543A1 (en) * | 1989-08-15 | 1991-03-07 | Massachusetts Institute Of Technology | Stabilized vaccine compositions |
FR2668064B1 (fr) | 1990-10-23 | 1994-12-16 | Transgene Sa | Composition pharmaceutique pour le traitement ou la prevention d'une tumeur maligne. |
US5756102A (en) | 1990-11-20 | 1998-05-26 | Virogenetics Corporation | Poxvirus-canine distemper virus (CDV) recombinants and compositions and methods employing the recombinants |
EP0575491B1 (en) | 1991-03-07 | 2003-08-13 | Virogenetics Corporation | Genetically engineered vaccine strain |
FR2710536B1 (fr) | 1993-09-29 | 1995-12-22 | Transgene Sa | Usage anti-cancéreux d'un vecteur viral comportant un gène modulateur de la réponse immunitaire et/ou inflammatoire. |
WO1995010601A1 (en) | 1993-10-12 | 1995-04-20 | Chiron Viagene, Inc. | Methods for preserving recombinant viruses |
DE69535288T2 (de) | 1994-05-13 | 2007-04-05 | Thomas Jefferson University | Verfahren zur induzierung einer immunantwort mittels rekombinanten vaccinia-viren, die das gm-csf-gen exprimieren |
US5869306A (en) | 1995-03-17 | 1999-02-09 | Hisamitsu Pharmaceutical Co., Inc. | Gene transfer preparation |
FR2742756B1 (fr) * | 1995-12-22 | 1998-04-03 | Pasteur Merieux Serums Vacc | Stabilisants pour vaccins vivants, vaccins les contenant et procedes pour leur preparation |
FR2751879B1 (fr) | 1996-07-30 | 1998-10-30 | Transgene Sa | Composition pharmaceutique contre les tumeurs et infections a papillomavirus |
FR2766091A1 (fr) | 1997-07-18 | 1999-01-22 | Transgene Sa | Composition antitumorale a base de polypeptide immunogene de localisation cellulaire modifiee |
US6210683B1 (en) * | 1997-09-05 | 2001-04-03 | Merck & Co., Inc. | Stabilizers containing recombinant human serum albumin for live virus vaccines |
AU2002361962A1 (en) | 2001-12-10 | 2003-07-09 | Bavarian Nordic A/S | Poxvirus-containing compositions and process for their preparation |
FR2855758B1 (fr) | 2003-06-05 | 2005-07-22 | Biomerieux Sa | Composition comprenant la polyproteine ns3/ns4 et le polypeptide ns5b du vhc, vecteurs d'expression incluant les sequences nucleiques correspondantes et leur utilisation en therapeutique |
EP1651272A1 (en) * | 2003-08-05 | 2006-05-03 | Fuji Photo Film B.V. | Use of recombinant or synthetic gelatin as a stabiliser in vaccines |
JP4691509B2 (ja) * | 2003-12-17 | 2011-06-01 | ワイス・エルエルシー | 保存安定性のあるウイルスおよびその免疫原性組成物の製造のための方法 |
WO2005066333A1 (en) * | 2003-12-30 | 2005-07-21 | Aventis Pasteur, Inc. | Stabilizing compositions for recombinant viruses |
CN100475268C (zh) | 2004-01-17 | 2009-04-08 | 上海三维生物技术有限公司 | 重组腺病毒冻干制剂及制备方法 |
TR201820559T4 (tr) * | 2004-11-24 | 2019-01-21 | Meda Pharmaceuticals Inc | Azelastin içeren kompozisyonlar ve bunların kullanım metotları. |
TWI398272B (zh) | 2005-03-08 | 2013-06-11 | Intervet Int Bv | 化學定義的安定劑 |
PL1928492T3 (pl) * | 2005-09-01 | 2011-09-30 | Celgene Corp | Immunologiczne zastosowania związków immunomodulujących do szczepionki i przeciwzakaźnego leczenia choroby |
WO2007030668A2 (en) | 2005-09-07 | 2007-03-15 | Jennerex Biotherapeutics Ulc | Systemic treatment of metastatic and/or systemically-disseminated cancers using gm-csf-expressing poxviruses |
CN101360821A (zh) * | 2005-11-21 | 2009-02-04 | 圣诺菲·帕斯图尔有限公司 | 重组病毒的稳定制剂 |
KR20090005010A (ko) | 2006-04-21 | 2009-01-12 | 트랜스진 에스.에이. | Hpv-18-기재의 유두종바이러스 백신 |
CA2656259C (en) | 2006-06-20 | 2013-03-19 | Transgene S.A. | Process for producing poxviruses and poxvirus compositions |
TW200815033A (en) * | 2006-08-10 | 2008-04-01 | Cipla Ltd | Antiretroviral solid oral composition |
KR20080084528A (ko) | 2007-03-15 | 2008-09-19 | 제네렉스 바이오테라퓨틱스 인크. | 종양살상형 백시니아 바이러스 암 치료 |
GB0705245D0 (en) | 2007-03-19 | 2007-04-25 | Stabilitech Ltd | Stable biological products |
EP2212345B1 (en) | 2007-11-19 | 2016-01-27 | Transgene SA | Poxviral oncolytic vectors |
CN101868546B (zh) | 2007-11-19 | 2013-06-05 | 特朗斯吉有限公司 | 痘病毒溶瘤载体 |
AU2010247374A1 (en) | 2009-05-12 | 2011-12-15 | Transgene Sa | Immortalized avian cell lines and use thereof |
KR20120052352A (ko) | 2009-08-07 | 2012-05-23 | 트랜스진 에스.에이. | Hbv 감염을 치료하는 조성물 |
US20110243988A1 (en) * | 2009-10-01 | 2011-10-06 | Aridis Pharmaceuticals | Methods and Compositions for Stabilization of a Virus Vaccine |
US8557253B2 (en) * | 2009-10-07 | 2013-10-15 | Sanofi Pasteur Sa | Stabilizing excipient for inactivated whole virus vaccine |
HUE026885T2 (en) | 2010-03-31 | 2016-08-29 | Stabilitech Ltd | Stabilize virus fragments |
EP2558120A4 (en) | 2010-04-15 | 2013-08-28 | Shin Nippon Biomedical Lab Ltd | METHOD AND COMPOSITION FOR INTRANASAL ADMINISTRATION |
TWI575070B (zh) | 2011-07-12 | 2017-03-21 | 傳斯堅公司 | Hbv聚合酶突變體 |
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CN104797242B (zh) | 2019-10-01 |
IL238064B (en) | 2019-07-31 |
KR102181658B1 (ko) | 2020-11-23 |
CN104797242A (zh) | 2015-07-22 |
AU2013326548A1 (en) | 2015-05-14 |
US20150250869A1 (en) | 2015-09-10 |
EP2903600B1 (en) | 2022-08-31 |
CA2887156A1 (en) | 2014-04-10 |
EP2903600A1 (en) | 2015-08-12 |
IL238064A0 (en) | 2015-05-31 |
SG11201502621XA (en) | 2015-05-28 |
CA2887156C (en) | 2021-01-19 |
RU2015116539A (ru) | 2016-11-27 |
TWI690322B (zh) | 2020-04-11 |
ES2928670T3 (es) | 2022-11-22 |
AU2013326548B2 (en) | 2018-07-19 |
BR112015007314B1 (pt) | 2023-05-09 |
HK1211206A1 (en) | 2016-05-20 |
NZ707328A (en) | 2018-07-27 |
BR112015007314A2 (ja) | 2017-08-15 |
WO2014053571A1 (en) | 2014-04-10 |
DK2903600T3 (da) | 2022-09-26 |
US10111947B2 (en) | 2018-10-30 |
TW201417820A (zh) | 2014-05-16 |
KR20150087206A (ko) | 2015-07-29 |
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