JP2021526542A - ヒトヒアルロニダーゼph20の変異体及び薬物を含む皮下投与用医薬組成物 - Google Patents
ヒトヒアルロニダーゼph20の変異体及び薬物を含む皮下投与用医薬組成物 Download PDFInfo
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Abstract
Description
図2は、トラスツズマブ及び新規のPH20変異体HP46が含まれた剤形に対してタンパク質凝集温度を測定した結果を示すものである。
図3の(a)は、45℃苛酷安定性試験においてトラスツズマブに対するWCX(weak cation exchange)クロマトグラフィーのクロマトグラム、図3の(b)は、各剤形に対する45℃苛酷安定性試験における酸性変異体(acidic variants)の相対含有量変化(%)、図3の(c)は、各剤形に対する45℃苛酷安定性試験におけるメインピーク(Main peak)の相対含有量変化(%)、図3の(d)は、各剤形に対する45℃苛酷安定性試験における塩基性変異体(basic variants)の相対含有量変化(%)を示すものである。
図4は、剤形5〜7に対する45℃苛酷安定性試験におけるトラスツズマブ単量体(monomer)タンパク質の純度変化を示すものである。
図5の(a)は、剤形5〜7による45℃苛酷安定性試験における酸性変異体(acidic variants)の相対含有量変化(%)、図5の(b)は、剤形5、6、7による45℃苛酷安定性試験におけるメインピーク(Main peak)の相対含有量変化(%)、図5の(c)は、剤形5、6、7による45℃苛酷安定性試験における塩基性変異体(basic variants)の相対含有量変化(%)を示すものである。
図6の(a)は、40℃苛酷安定性試験において0日と1日目にハーセプチン皮下注射剤形(Herceptin SC)、トラスツズマブ+野生型PH20(HW2)、そしてトラスツズマブ+PH20変異体HP46の残存酵素活性測定結果、図6の(b)は、45℃苛酷安定性試験において0日目と1日目にハーセプチン皮下注射剤形、トラスツズマブ+野生型PH20(HW2)、トラスツズマブ+PH20変異体HP46の残存酵素活性測定結果を示すものである。
図7は、14日間の40℃苛酷安定性試験において剤形8〜10に対するサイズ排除クロマトグラフィー分析を行った結果を示すものである。
図8の(a)は、DLS装備を用いて剤形8〜10のタンパク質粒子サイズの変化を測定した結果であり、(b)は、タンパク質凝集温度測定結果を示すものである。
図9の(a)は、40℃苛酷安定性試験において剤形8に対するWCX(weak cation exchange)クロマトグラフィーのクロマトグラム、図9の(b)は、剤形8〜10に対する40℃苛酷安定性試験における酸性変異体(acidic variants)の相対含有量変化(%)、図9の(c)は、剤形8〜10に対する40℃苛酷安定性試験におけるメインピーク(Main peak)の相対含有量変化(%)、図9の(d)は剤形8〜10に対する40℃苛酷安定性試験における塩基性変異体(basic variants)の相対含有量変化(%)を示すものである。
図10は、剤形8〜10に対する40℃苛酷安定性試験における相対的な酵素活性変化(%)を示すものである。
図11は、剤形11〜13に対する40℃苛酷安定性試験におけるトラスツズマブ単量体(monomer)の純度変化を示すものである。
図12の(a)は、40℃苛酷安定性試験において剤形11に対するWCX(weak cation exchange)クロマトグラフィーのクロマトグラム、図12の(b)は、剤形11〜13に対する40℃苛酷安定性試験における酸性変異体(acidic variants)の相対含有量変化(%)、図12の(c)は剤形11〜13に対する40℃苛酷安定性試験におけるメインピーク(Main peak)の相対含有量変化(%)、図12の(d)は、剤形11〜13に対する40℃苛酷安定性試験における塩基性変異体(basic variants)の相対含有量変化(%)を示すものである。
図13は、剤形11〜13に対する40℃苛酷安定性試験における相対的な酵素活性変化(%)を示すものである。
図14は、剤形14〜16に対する40℃苛酷安定性試験におけるリツキシマブ単量体(monomer)タンパク質の純度変化を示すものである。
図15は、剤形14〜16に対する40℃苛酷安定性試験における相対的な酵素活性変化を示すものである。
図16は、剤形17〜18に対する40℃苛酷安定性試験における相対的な酵素活性変化を示すものである。
図17は、剤形19〜22に対する40℃サイズ排除クロマトグラフィー分析を行った結果を示すものである。
図18は、剤形19〜22に対する40℃苛酷安定性試験における相対的な酵素活性変化を示すものである。
図19は、組換えヒトPH20及びHP46のpH変化に従う酵素活性変化を示すものである。
図20は、ハーセプチン皮下注射製品(Herceptin SC)とハーセプチン皮下注射バイオシミラー候補(トラスツズマブ+HP46;Herceptin SC BS)に対する9週齢Sprague−Dawleyラットにおける薬物動態学(pharmacokinetics)試験結果を示すものである。ハーセプチンとハーセプチンバイオシミラー候補はそれぞれ18mg/kgで注射し、皮下注射剤形にはrHuPH20とHP46がそれぞれ100units(pH5.3基準)含まれている。
アルファヘリックス部位及び/又はその連結部位に該当する部位、好ましくはアルファヘリックス8部位(S347〜C381)及び/又はアルファヘリックス7とアルファヘリックス8との連結部位(A333〜R346)、より好ましくはT341〜N363、T341〜I361、L342〜I361、S343〜I361、I344〜I361、M345〜I361又はM345〜N363に該当するアミノ酸部位において1つ以上のアミノ酸残基が置換されたことを特徴とする。
さらにT341〜N363における1つ以上の位置、特にT341、L342、S343、I344、M345、S347、M348、K349、L352、L353、D355、E359、I361及びN363からなる群から選ばれる1つ以上の位置におけるアミノ酸残基の置換を含むことが好ましいが、これに限定されず、
より好ましくは、T341S、L342W、S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、D355K、E359D、I361T及びN363Gからなる群から選ばれる1つ以上のアミノ酸残基の置換をさらに含むことを特徴とするが、これに限定されない。
さらに、T341S、L342W、S343E、I344N及びN363Gからなる群から選ばれる1つ以上のアミノ酸残基の置換を含むことを特徴としてもよいが、これに限定されない。
(a)T341S、L342W、S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;
(b)L342W、S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;
(c)M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;
(d)M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D、I361T、及びN363G;
(e)I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;及び
(f)S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T。
4−1BBに対する抗体は、ウトミルマブ(Utomilumab);
インテグリンに対する抗体は、ナタリズマブ(Natalizumab)、エトロリズマブ(Etrolizumab)、ベドリズマブ(Vedolizumab)、ビマグルマブ(Bimagrumab);
アミロイドベータに対する抗体は、バピネオズマブ(Bapineuzumab)、クレネズマブ(Crenezumab)、ソラネズマブ(Solanezumab)、アデュカヌマブ(Aducanumab)、ガンテネルマブ(Gantenerumab);
アンジオポエチンに対する抗体は、アンジオポエチン1及び2に対するAMG 780、アンジオポエチン2に対するMEDI 3617、ネスバクマブ(Nesvacumab)とアンジオポエチン2とVEGFの二重抗体であるバヌシズマブ(Vanucizumab);
アンジオポエチン類似物質3に対する抗体は、エビナクマブ(Evinacumab);
B細胞活性因子(B−cell activating factor,BAFF)に対する抗体は、タバルマブ(Tabalumab)、ラナルマブ(Lanalumab)、ベリムマブ(Belimumab);
B7−H3に対する抗体は、オムブルタマブ(omburtamab);
補体5(complement 5)に対する抗体は、ラブリズマブ(Ravulizumab)、エクリズマブ(Eculizumab);
CCR4に対する抗体は、モガムリズマブ(Mogamulizumab);
CD3に対する抗体は、オテリキシズマブ(Otelixizumab)、テプリズマブ(Teplizumab)、ムロモナブ(Muromonab)、GP100とCD3に対する二重抗体であるテベンタフスプ(Tebentafusp)、CD19とCD3に対する二重抗体であるブリナツモマブ(Blinatumomab)、及びCD20とCD3に対する二重抗体であるREGN1979;
CD4に対する抗体は、イバリズマブ(Ibalizumab)、ザノリムマブ(Zanolimumab);
CD6に対する抗体は、イトリズマブ(Itolizumab);
CD11aに対する抗体は、エファリズマブ(Efalizumab);
CD19に対する抗体は、イネビリズマブ(Inebilizumab)、タファシタマブ(Tafasitamab)、及びADCであるロカツキシマブテシリン(Loncastuximab tesirine);
CD20に対する抗体は、オクレリズマブ(Ocrelizumab)、ウブリツキシマブ(Ublituximab)、オビヌツズマブ(Obinutuzumab)、オファツムマブ(Ofatumumab)、リツキシマブ(Rituximab)、トシツモマブ(Tositumomab)、及びADCであるイブリツモマブチウキセタン(Ibritumomab tiuxetan);
CD22に対する抗体は、エプラツズマブ(Epratuzumab)、ADCであるイノツズマブオゾガマイシン(Inotuzumab ozogamicin)、及びモキセツモマブパスドトックス(Moxetumomab pasudotox);
CD30に対するADCは、ブレンツキシマブベドチン(Brentuximab vedotin);
CD33に対するADCは、バダスツキシマブタリリン(Vadastuximab talirine)、ゲムツズマブオゾガマイシン(Gemtuzumab ozogamicin);
CD38に対する抗体は、ダラツムマブ(Daratumumab)、イサツキシマブ(Isatuximab);
CD52に対する抗体は、アレムツズマブ(Alemtuxumab);
CD62に対する抗体は、クリザンリズマブ(Crizanlizumab);
CD79bに対するADCは、ポラツズマブベドチン(Polatuzumab vedotin);
CD80に対する抗体は、ガリキシマブ(Galiximab);
CGRPに対する抗体は、エプチネズマブ(Eptinezumab)、フレマネズマブ(Fremanezumab)、ガルカネズマブ(Galcanezumab)、エレヌマブ(Erenumab);
クローディン18(Claudin−18)に対する抗体は、ゾルベツキシマブ(Zolbetuximab);
補体要素D(complement factor D)に対する抗体は、ランパリズマブ(Lampalizumab);
CTLA4に対する抗体は、トレメリムマブ(Tremelimumab)、ザリフレリマブ(Zalifrelimab)、イピリムマブ(Ipilimumab);
DLL3に対するADCは、ロバルピツズマブテシリン(Rovalpituzumab tesirine);
EGF受容体に対する抗体は、セツキシマブ(Cetuximab)、デパツキシズマブ(Depatuxizumab)、ザルツムマブ(Zalutumumab)、ネシツムマブ(Necitumumab)、パニツムマブ(Panitumumab);
血友病因子であるcoagulation factor IX及びFactor Xに対する二重抗体は、エミシズマブ(Emicizumab);
Fc受容体に対する抗体は、ニポカリマブ(Nipocalimab)、ロザノリキシズマブ(Rozanolixizumab);
FGF23に対する抗体は、ブロスマブ(Burosumab);
フォレート(folate)受容体に対する抗体は、ファルレツズマブ(Farletuzumab)、及びADCであるミルベツキシマブソラブタンシン(Mirvetuximab soravtansine);
GD2に対する抗体は、ジヌツキシマブ(Dinutuximab)、ナキシタマブ(Naxitamab);
GM−CSFに対する抗体は、オチリマブ(Otilimab);
HER2に対する抗体は、マルゲツキシマブ(Margetuximab)、ペルツズマブ(Pertuzumab)、トラスツズマブ(Trastuzumab)とADCはトラスツズマブデルクステカン(Trastuzumab deruxtecan)、トラスツズマブエムタンシン(Trastuzumab emtansine)、トラスツズマブデュオカルマジン(Trastuzumab duocarmazine);
HER3に対する抗体は、パトリツマブ(Patritumab);
インターフェロン受容体に対する抗体は、アニフロルマブ(Anifrolumab);
インターフェロンガンマに対する抗体は、エマパルマブ(Emapalumab);
IgEに対する抗体は、リゲリズマブ(Ligelizumab)、オマリズマブ(Omalizumab);
IGF−1受容体に対する抗体は、ダロツズマブ(Dalotuzumab)、フィギツムマブ(Figitumumab)、テプロツムマブ(Teprotumumab);
インターロイキン1に対する抗体は、ゲボキズマブ(Gebokizumab)、カナキヌマブ(Canakinumab);
インターロイキン2受容体に対する抗体は、ダクリズマブ(Daclizumab)、バシリキシマブ(Basiliximab);
インターロイキン4受容体に対する抗体は、デュピルマブ(Dupilumab);
インターロイキン5に対する抗体は、メポリズマブ(Mepolizumab)、レスリズマブ(Reslizumab);
インターロイキン5受容体に対する抗体は、ベンラリズマブ(Benralizumab);
インターロイキン6に対する抗体は、クラザキズマブ(Clazakizumab)、オロキズマブ(Olokizumab)、シルクマブ(Sirukumab)、シルツキシマブ(Siltuximab);
インターロイキン6受容体に対する抗体は、サリルマブ(Sarilumab)、サトラリズマブ(Satralizumab)、トシリズマブ(Tocilizumab)、REGN88;
インターロイキン7に対する抗体は、セクキヌマブ(Secukinumab);
インターロイキン12/23に対する抗体は、ウステキヌマブ(Ustekinumab)、ブリアキヌマブ(Briakinumab);
インターロイキン13に対する抗体は、レブリキズマブ(Lebrikizumab)、トラロキヌマブ(Tralokinumab);
インターロイキン17Aに対する抗体は、イキセキズマブ(Ixekizumab)、ビメキズマブ(Bimekizumab);
インターロイキン17受容体Aに対する抗体は、ブロダルマブ(Brodalumab);
インターロイキン23に対する抗体は、ブラジクマブ(Brazikumab)、グセルクマブ(Guselkumab)、リサンキズマブ(Risankizumab)、ティルドラキズマブ(Tildrakizumab)、ミリキズマブ(Mirikizumab);
インターロイキン31受容体に対する抗体は、ネモリズマブ(Nemolizumab);
インターロイキン36受容体に対する抗体は、スペソリマブ(Spesolimab);
LAG3に対する抗体は、レラトリマブ(Relatlimab);
NASP2に対する抗体は、ナルソプリマブ(Narsoplimab);
NGFに対する抗体は、ファシヌマブ(Fasinumab)、タネズマブ(Tanezumab);
PVSK9に対する抗体は、アリロクマブ(Alirocumab)、エボロクマブ(Evolocumab)、ボコシズマブ(Bococizumab);
PD−1に対する抗体は、ランブロリズマブ(Lambrolizumab)、バルスチリマブ(Balstilimab)、カムレリズマブ(Camrelizumab)、セミプリマブ(Cemiplimab)、ドスタリマブ(Dostarlimab)、プロゴリマブ(Prolgolimab)、シンチリマブ(Sintilimab)、スパルタリズマブ(Spartalizumab)、チスレリズマブ(Tislelizumab)、ペムブロリズマブ(Pembrolizumab)、ニボルマブ(Nivolumab);
PD−L1に対する抗体は、アテゾリズマブ(Atezolizumab)、アベルマブ(Avelumab)、エンバホリマブ(Envafolimab)、デュルバルマブ(Durvalumab)とTGF beteとPD−L1の二重抗体であるビントラフスアルファ(Bintrafusp alpha);
RANK−Lに対する抗体は、デノスマブ(Denosumab);
SLAMF7に対する抗体は、エロツズマブ(Elotuzumab);
組織因子(Tissue factor)に対する抗体は、コンシズマブ(Concizumab)、マルスタシマブ(Marstacimab);
TNF、特にTNFαに対する抗体は、インフリキシマブ(Infliximab)、アダリムマブ(Adalimumab)、ゴリムマブ(Golimumab)と抗体断片であるセルトリズマブペゴル(Certolizumab pegol)、TNFとアルブミンに対する二重抗体であるオゾラリズマブ(Ozoralizumab);
VEGFに対する抗体は、ブロルシズマブ(Brolucizumab)、ラニビズマブ(Ranibizumab)、ベバシズマブ(Bevacizumab)とVEGFとAng2の二重抗体であるファリシマブ(Faricimab);
VEGF受容体に対する抗体は、ラムシルマブ(Ramucirumab);及び
vWFに対する抗体は、カプラシズマブ(Caplacizumab)
実施例1.剤形開発
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Claims (33)
- (a)薬物、及び
(b)PH20変異体を含み、
前記PH20変異体は、配列番号1の配列を有する野生型PH20において、S343E、M345T、K349E、L353A、L354I、N356E及びI361Tからなる群から選ばれる1つ以上のアミノ酸残基の置換を含むことを特徴とする医薬組成物。 - 前記PH20変異体は、L354I及びN356Eからなる群から選ばれる1つ以上のアミノ酸残基の置換を含むことを特徴とする、請求項1に記載の医薬組成物。
- 前記PH20変異体は、配列番号1の野生型PH20のアルファヘリックス部位及びその連結部位に該当する部位からなる群から選ばれる1つ以上の部位で1つ以上のアミノ酸残基の置換をさらに含むことを特徴とする、請求項1に記載の医薬組成物。
- 前記配列番号1の野生型PH20のアルファヘリックス部位はアルファヘリックス8部位(S347〜C381)であり、その連結部位はアルファヘリックス7とアルファヘリックス8との連結部位(A333〜R346)であることを特徴とする、請求項3に記載の医薬組成物。
- 前記配列番号1の野生型PH20のアルファヘリックス部位及びその連結部位に該当する部位は、T341〜N363、T341〜I361、L342〜I361、S343〜I361、I344〜I361、M345〜I361又はM345〜N363であることを特徴とする、請求項4に記載の医薬組成物。
- 前記配列番号1の野生型PH20のアルファヘリックス8部位(S347〜C381)及びアルファヘリックス7とアルファヘリックス8との連結部位(A333〜R346)からなる群から選ばれる1つ以上の部位が、Hyal1の対応する部位のアミノ酸配列の一部のアミノ酸残基に置換されたことを特徴とする、請求項4に記載の医薬組成物。
- 前記PH20変異体は、L354I及び/又はN356Eのアミノ酸残基の置換を含み、
さらに、T341、L342、S343、I344、M345、S347、M348、K349、L352、L353、D355、E359、I361及びN363からなる群から選ばれる1つ以上の位置におけるアミノ酸残基の置換を含むことを特徴とする、請求項1に記載の医薬組成物。 - 前記PH20変異体はL354I及び/又はN356Eのアミノ酸残基置換を含み、
さらに、T341S、L342W、S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、D355K、E359D、I361T及びN363Gからなる群から選ばれる1つ以上のアミノ酸残基の置換を含むことを特徴とする、請求項7に記載の医薬組成物。 - 前記PH20変異体は、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361Tのアミノ酸残基の置換を含むことを特徴とする、請求項7に記載の医薬組成物。
- 前記PH20変異体はさらに、T341S、L342W、S343E、I344N及びN363Gからなる群から選ばれる1つ以上のアミノ酸残基の置換を含むことを特徴とする、請求項9に記載の医薬組成物。
- 前記PH20変異体は、次に構成された群から選ばれるいずれか一つのアミノ酸置換を含むことを特徴とする、請求項10に記載の医薬組成物:
(a)T341S、L342W、S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;
(b)L342W、S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;
(c)M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;
(d)M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D、I361T、及びN363G;
(e)I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T;及び
(f)S343E、I344N、M345T、S347T、M348K、K349E、L352Q、L353A、L354I、D355K、N356E、E359D及びI361T。 - 前記PH20変異体はさらに、C末端及びN末端のいずれか1つ以上の末端で一部のアミノ酸残基が欠失されたことを特徴とする、請求項1〜11のいずれか一項に記載の医薬組成物。
- 前記PH20変異体は、N末端のM1〜P42からなる群から選ばれるアミノ酸残基の前で切断されて一部のアミノ酸残基が欠失されたことを特徴とする、請求項12に記載の医薬組成物。
- 前記PH20変異体は、N末端のL36、N37、F38、R39、A40、P41又はP42残基の前で切断されて一部のアミノ酸残基が欠失されたことを特徴とする、請求項13に記載の医薬組成物。
- 前記PH20変異体は、C末端のV455〜L509からなる群から選ばれるアミノ酸残基の次で切断されて一部のアミノ酸残基が欠失されたことを特徴とする、請求項12に記載の医薬組成物。
- 前記PH20変異体は、C末端のV455〜S490からなる群から選ばれるアミノ酸残基の次で切断されて一部のアミノ酸残基が欠失されたことを特徴とする、請求項15に記載の医薬組成物。
- 前記PH20変異体は、C末端のV455、C458、D461、C464、I465、D466、A467、F468、K470、P471、P472、M473、E474、T475、E476、P478、I480、Y482、A484、P486、T488又はS490残基の次で切断されて一部のアミノ酸残基が欠失されたことを特徴とする、請求項16に記載の医薬組成物。
- 前記PH20変異体は、N末端にさらに、ヒトヒアルロニダーゼ−1(Hyal1)、ヒト成長ホルモン又はヒト血清アルブミン由来のシグナルペプチドを含むことを特徴とする、請求項1〜17のいずれか一項に記載の医薬組成物。
- 前記PH20変異体は、配列番号5〜配列番号50のアミノ酸配列からなる群から選ばれることを特徴とする、請求項1〜11のいずれか一項に記載の医薬組成物。
- 前記PH20変異体は配列番号44の配列を有することを特徴とする、請求項19に記載の医薬組成物。
- 前記薬物は、タンパク質医薬品(protein drugs)、抗体(antibody)、低分子化合物(small molecules)、アプタマー(aptamer)、RNAi、アンチセンス又は細胞治療剤であることを特徴とする、請求項1に記載の医薬組成物。
- 前記薬物は、抗体、可溶性受容体、又は可溶性受容体とのFc融合タンパク質であることを特徴とする、請求項21に記載の医薬組成物。
- 前記抗体は、4−1BB、インテグリン(integrin)、アミロイドベータ(amyloid beta)、アンジオポエチン、アンジオポエチン類似物質3、B細胞活性因子(B−cell activating factor,BAFF)、B7−H3、補体5(complement 5)、CCR4、CD3、CD4、CD6、CD11a、CD19、CD20、CD22、CD30、CD33、CD38、CD52、CD62、CD79b、CD80、CGRP、クローディン18(Claudin−18)、補体要素D(complement factor D)、CTLA4、DLL3、EGF受容体、血友病因子、Fc受容体、FGF23、フォレート(folate)受容体、GD2、GM−CSF、HER2、HER3、インターフェロン受容体、インターフェロンガンマ、IgE、IGF−1受容体、インターロイキン1、インターロイキン2受容体、インターロイキン4受容体、インターロイキン5、インターロイキン5受容体、インターロイキン6、インターロイキン6受容体、インターロイキン7、インターロイキン12/23、インターロイキン13、インターロイキン17A、インターロイキン17受容体A、インターロイキン31受容体、インターロイキン36受容体、LAG3、LFA3、NGF、PVSK9、PD−1、PD−L1、RANK−L、SLAMF7、組織因子(Tissue factor)、TNF、VEGF及びVWFからなる群から選ばれる1つ以上の抗原と結合することを特徴とする、請求項22に記載の医薬組成物。
- 前記抗体は、ウトミルマブ(Utomilumab)、ナタリズマブ(Natalizumab)、エトロリズマブ(Etrolizumab)、ベドリズマブ(Vedolizumab)、ビマグルマブ(Bimagrumab)、バピネオズマブ(Bapineuzumab)、クレネズマブ(Crenezumab)、ソラネズマブ(Solanezumab)、アデュカヌマブ(Aducanumab)、ガンテネルマブ(Gantenerumab)、AMG 780、MEDI 3617、ネスバクマブ(Nesvacumab)、バヌシズマブ(Vanucizumab)、エビナクマブ(Evinacumab)、タバルマブ(Tabalumab)、ラナルマブ(Lanalumab)、ベリムマブ(Belimumab)、オムブルタマブ(omburtamab)、ラブリズマブ(Ravulizumab)、エクリズマブ(Eculizumab)、モガムリズマブ(Mogamulizumab)、オテリキシズマブ(Otelixizumab)、テプリズマブ(Teplizumab)、ムロモナブ(Muromonab)、テベンタフスプ(Tebentafusp)、ブリナツモマブ(Blinatumomab)、REGN1979、イバリズマブ(Ibalizumab)、ザノリムマブ(Zanolimumab)、イトリズマブ(Itolizumab)、エファリズマブ(Efalizumab)、イネビリズマブ(Inebilizumab)、タファシタマブ(Tafasitamab)、ロカツキシマブテシリン(Loncastuximab tesirine)、オクレリズマブ(Ocrelizumab)、ウブリツキシマブ(Ublituximab)、オビヌツズマブ(Obinutuzumab)、オファツムマブ(Ofatumumab)、リツキシマブ(Rituximab)、トシツモマブ(Tositumomab)、イブリツモマブチウキセタン(Ibritumomab tiuxetan)、エプラツズマブ(Epratuzumab)、イノツズマブオゾガマイシン(Inotuzumab ozogamicin)、モキセツモマブパスドトックス(Moxetumomab pasudotox)、ブレンツキシマブベドチン(Brentuximab vedotin)、バダスツキシマブタリリン(Vadastuximab talirine)、ゲムツズマブオゾガマイシン(Gemtuzumab ozogamicin)、ダラツムマブ(Daratumumab)、イサツキシマブ(Isatuximab)、アレムツズマブ(Alemtuxumab)、クリザンリズマブ(Crizanlizumab)、ポラツズマブベドチン(Polatuzumab vedotin)、ガリキシマブ(Galiximab)、エプチネズマブ(Eptinezumab)、フレマネズマブ(Fremanezumab)、ガルカネズマブ(Galcanezumab)、エレヌマブ(Erenumab)、ゾルベツキシマブ(Zolbetuximab)、ランパリズマブ(Lampalizumab)、トレメリムマブ(Tremelimumab)、ザリフレリマブ(Zalifrelimab)、イピリムマブ(Ipilimumab)、ロバルピツズマブテシリン(Rovalpituzumab tesirine)、セツキシマブ(Cetuximab)、デパツキシズマブ(Depatuxizumab)、ザルツムマブ(Zalutumumab)、ネシツムマブ(Necitumumab)、パニツムマブ(Panitumumab)、エミシズマブ(Emicizumab)、ニポカリマブ(Nipocalimab)、ロザノリキシズマブ(Rozanolixizumab)、ブロスマブ(Burosumab)、ファルレツズマブ(Farletuzumab)、ミルベツキシマブソラブタンシン(Mirvetuximab soravtansine)、ジヌツキシマブ(Dinutuximab)、ナキシタマブ(Naxitamab)、オチリマブ(Otilimab)、マルゲツキシマブ(Margetuximab)、ペルツズマブ(Pertuzumab)、トラスツズマブ(Trastuzumab)、トラスツズマブデルクステカン(Trastuzumab deruxtecan)、トラスツズマブエムタンシン(Trastuzumab emtansine)、トラスツズマブデュオカルマジン(Trastuzumab duocarmazine)、パトリツマブ(Patritumab)、アニフロルマブ(Anifrolumab)、エマパルマブ(Emapalumab)、リゲリズマブ(Ligelizumab)、オマリズマブ(Omalizumab)、ダロツズマブ(Dalotuzumab)、フィギツムマブ(Figitumumab)、テプロツムマブ(Teprotumumab)、ゲボキズマブ(Gebokizumab)、カナキヌマブ(Canakinumab)、ダクリズマブ(Daclizumab)、バシリキシマブ(Basiliximab)、デュピルマブ(Dupilumab)、メポリズマブ(Mepolizumab)、レスリズマブ(Reslizumab)、ベンラリズマブ(Benralizumab)、クラザキズマブ(Clazakizumab)、オロキズマブ(Olokizumab)、シルクマブ(Sirukumab)、シルツキシマブ(Siltuximab)、サリルマブ(Sarilumab)、サトラリズマブ(Satralizumab)、トシリズマブ(Tocilizumab)、REGN88、セクキヌマブ(Secukinumab)、ウステキヌマブ(Ustekinumab)、ブリアキヌマブ(Briakinumab)、レブリキズマブ(Lebrikizumab)、トラロキヌマブ(Tralokinumab)、イキセキズマブ(Ixekizumab)、ビメキズマブ(Bimekizumab)、ブロダルマブ(Brodalumab)、ブラジクマブ(Brazikumab)、グセルクマブ(Guselkumab)、リサンキズマブ(Risankizumab)、ティルドラキズマブ(Tildrakizumab)、ミリキズマブ(Mirikizumab)、ネモリズマブ(Nemolizumab)、スペソリマブ(Spesolimab)、レラトリマブ(Relatlimab)、ナルソプリマブ(Narsoplimab)、ファシヌマブ(Fasinumab)、タネズマブ(Tanezumab)、アリロクマブ(Alirocumab)、エボロクマブ(Evolocumab)、ボコシズマブ(Bococizumab)、ランブロリズマブ(Lambrolizumab)、バルスチリマブ(Balstilimab)、カムレリズマブ(Camrelizumab)、セミプリマブ(Cemiplimab)、ドスタリマブ(Dostarlimab)、プロゴリマブ(Prolgolimab)、シンチリマブ(Sintilimab)、スパルタリズマブ(Spartalizumab)、チスレリズマブ(Tislelizumab)、ペムブロリズマブ(Pembrolizumab)、ニボルマブ(Nivolumab)、アテゾリズマブ(Atezolizumab)、アベルマブ(Avelumab)、エンバホリマブ(Envafolimab)、デュルバルマブ(Durvalumab)、ビントラフスアルファ(Bintrafusp alpha)、デノスマブ(Denosumab)、エロツズマブ(Elotuzumab)、コンシズマブ(Concizumab)、マルスタシマブ(Marstacimab)、インフリキシマブ(Infliximab)、アダリムマブ(Adalimumab)、ゴリムマブ(Golimumab)、セルトリズマブペゴル(Certolizumab pegol)、オゾラリズマブ(Ozoralizumab)、ブロルシズマブ(Brolucizumab)、ラニビズマブ(Ranibizumab)、ベバシズマブ(Bevacizumab)、ファリシマブ(Faricimab)、ラムシルマブ(Ramucirumab)及びカプラシズマブ(Caplacizumab)からなる群から選ばれる1種以上であることを特徴とする、請求項22に記載の医薬組成物。
- 前記可溶性受容体又は可溶性受容体とのFc融合タンパク質に含まれる可溶性受容体は、TNF−α可溶性受容体、VEGF可溶性受容体、CTLA−4、インターロイキン1可溶性受容体及びLFA3可溶性受容体からなる群から選ばれることを特徴とする、請求項22に記載の医薬組成物。
- 前記可溶性受容体とのFcの融合タンパク質は、エタネルセプト(Etanercept)、アフリベルセプト(Aflibercept)、アバタセプト(Abatacept)、ベラタセプト(Belatacept)、リロナセプト(Rilonacept)及びアレファセプト(Alefacept)からなる群から選ばれることを特徴とする、請求項25に記載の医薬組成物。
- 緩衝剤、安定化剤及び界面活性剤からなる群から選ばれる1つ以上をさらに含むことを特徴とする、請求項1に記載の医薬組成物。
- 前記緩衝剤は、リンゴ塩酸(malate)、ぎ酸塩(formate)、クエン酸塩(citrate)、アセテート(acetate)、プロピオネート(propionate)、ピリジン(pyridine)、ピペラジン(piperazine)、カコジル酸塩(cacodylate)、コハク酸塩(succinate)、2−(N−モルホリノ)エタンスルホン酸(2−(N−morpholino)ethanesulfonic acid,MES)、ヒスチジン(histidine)、トリス(Tris)、ビス−トリス(bis−Tris)、リン酸塩(phosphate)、エタノールアミン(ethanolamine)、炭酸塩(carbonate)、ピペラジン−N、N’ビス(2−エタンスルホン酸)(piperazine−N,N’−bis(2−ethanesulfonic acid)、PIPES)、イミダゾール(imidazole)、ビス−トリスプロパン(BIS−TRIS propane)、BES(N,N−bis(2−hydroxyethyl)−2−aminoethanesulfonic acid)、MOPS(3−(N−morpholino)propanesulfonic acid)、HEPES(Hydroxyethyl piperazine Ethane Sulfonic acid)、ピロリン酸塩(pyrophosphate)、及びトリエタノールアミン(triethanolamine)からなる群から選ばれる1種以上の緩衝剤であり;
前記安定化剤は、炭水化物、糖類又はこれらの水和物、糖アルコール類又はこれらの水和物及びアミノ酸からなる群から選ばれる1種以上であり;
前記界面活性剤は、ポリオキシエチレン−ソルビタン脂肪酸、ポリエチレン−ポリプロピレングリコール、ポリオキシエチレン−ステアレート、ポリオキシエチレンアルキルエーテル、ポリオキシエチレン−ポリオキシプロピレン共重合体及びナトリウムドデシルサルフェート(SDS)からなる群から選ばれる1つ以上の非イオン性界面活性剤であることを特徴とする、請求項27に記載の医薬組成物。 - 前記炭水化物、糖類又は糖アルコール類は、トレハロース又はその水和物、スクロース、サッカリン、グリセロール、エリスリトール、トレイトール、キシリトール、アラビトール、リビトール、マンニトール、ソルビトール、ガラクチトール、フシトール、イジトール、イノシトール、ボレミトール、イソマルトール、マルチトール、ポリグリシトール、シクロデキストリン(cyclodextrin)、ヒドロキシプロピル−β−シクロデキストリン(Hydroxypropyl Beta−cyclodextrin)及びグルコースからなる群から選ばれる1種以上であり、
前記アミノ酸は、グルタミン、グルタミン酸、グリシン、リシン、リシルリシン、ロイシン、メチオニン、バリン、セリン、セレノメチオニン、シトルリン、アルギニン、アスパラギン、アスパラギン酸、オルニチン、イソロイシン、タウリン、テアニン、トレオニン、トリプトファン、チロシン、フェニルアラニン、プロリン、ピロリシン、ヒスチジン及びアラニンからなる群から選ばれる1種以上であることを特徴とする、請求項28に記載の医薬組成物。 - pH5.5±2.0のヒスチジン緩衝液、トレハロース及びメチオニンを含むことを特徴とする、請求項27に記載の医薬組成物。
- pH5.5±2.0のヒスチジン緩衝液、トレハロース、メチオニン及びポリソルベートを含むことを特徴とする、請求項27に記載の医薬組成物。
- pH5.5±2.0のヒスチジン緩衝液、10〜400mMのα,α−トレハロース、1〜50mMのメチオニン及び0.0000001%〜0.5%(w/v)のポリソルベートを含むことを特徴とする、請求項31に記載の医薬組成物。
- 請求項1〜32のいずれか一項に記載の医薬組成物を含む皮下投与用注射剤形。
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IL303350A (en) | 2020-12-04 | 2023-08-01 | Macrogenics Inc | Preparations containing an antibody against HER2/NEU and their use |
EP4267172A1 (en) | 2020-12-28 | 2023-11-01 | Bristol-Myers Squibb Company | Subcutaneous administration of pd1/pd-l1 antibodies |
PE20240820A1 (es) | 2020-12-28 | 2024-04-18 | Bristol Myers Squibb Co | Composiciones de anticuerpos y metodos de uso de los mismos |
IL310608A (en) | 2021-08-02 | 2024-04-01 | argenx BV | Dosage forms for subcutaneous administration |
KR20240055077A (ko) | 2021-09-14 | 2024-04-26 | 다케다 야쿠힌 고교 가부시키가이샤 | 히알루로니데이스를 이용한 농축된 항체 제형의 촉진된 전달 |
WO2023075506A1 (ko) * | 2021-10-29 | 2023-05-04 | (주)알테오젠 | 인간 히알루로니다제 ph20과 약물을 포함하는 약학 조성물 |
WO2023168305A1 (en) | 2022-03-01 | 2023-09-07 | Exuma Biotech Corp. | Viral particles with membrane-bound hyaluronidase |
WO2023169986A1 (en) * | 2022-03-07 | 2023-09-14 | Mabxience Research, S.L. | Stable formulations for antibodies |
KR20230150203A (ko) * | 2022-04-20 | 2023-10-30 | 주식회사 알토스바이오로직스 | 오크렐리주맙(Ocrelizumab)을 포함하는 약학적 조성물과 그의 용도 |
WO2023235847A1 (en) | 2022-06-02 | 2023-12-07 | Bristol-Myers Squibb Company | Antibody compositions and methods of use thereof |
WO2023249408A1 (ko) * | 2022-06-22 | 2023-12-28 | (주)알테오젠 | N-말단 및/또는 c-말단이 절단된 가용성 ph20 폴리펩티드 및 이의 용도 |
WO2024005502A1 (ko) * | 2022-06-29 | 2024-01-04 | 주식회사 오디스젠 | 중성 ph에서 활성을 나타내는 히알루로니다제 hyal1 변이체 |
KR20240038901A (ko) * | 2022-09-16 | 2024-03-26 | (주)피앤피바이오팜 | 신규한 히알루로니다제 ph-20 변이체 및 그 용도 |
KR102554775B1 (ko) * | 2023-02-07 | 2023-07-12 | 한국코러스 주식회사 | 히알루로니다제의 안정화제 및 이를 포함하는 히알루로니다제 제형 |
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