JP2020517638A - 肺の炎症を治療するための組成物および方法 - Google Patents
肺の炎症を治療するための組成物および方法 Download PDFInfo
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Abstract
Description
本出願は、2017年4月20日に出願された米国特許出願第62/487,812号の35 U.S.C.§119(e)の下で優先権の利益を主張し、その開示が参照によりその全体が組み込まれる。
本出願に関連する配列表は、紙コピーの代わりにテキスト形式で提供され、これによって参照により本明細書に組み込まれる。配列表を含むテキストファイルの名称はATYR_131_01WO_ST25.txtである。テキストファイルは約276KBであり、2018年4月18日に作成され、EFS−Webを介して電子提出されている。
背景
(a)ヒスチジル−tRNAシンテターゼ(HRS)ポリペプチド、またはHRSポリペプチドをコードする発現可能なポリヌクレオチドと、
(b)免疫調節剤と、を含む、治療用組成物に関する。
(a)ヒスチジル−tRNAシンテターゼ(HRS)ポリペプチド、またはHRSポリペプチドをコードする発現可能なポリヌクレオチドと、
(b)免疫調節剤と、を投与することを含む、方法もまた含まれる。
(b)免疫調節剤と、を投与することを含む、患者ケアキットもまた、含まれる。
別途の定義がない限り、本明細書で使用される全ての技術用語および科学用語は、本開示が属する技術分野の当業者によって一般的に理解されている意味と同じ意味を有する。任意の方法、材料、組成物、試薬、細胞、本明細書に説明されるものと類似または同等の類似または類似のものを、本開示の主題の実践または試験で使用することができるが、好ましい方法および材料が本明細書に説明される。本明細書で引用される特許文献および特許出願文献を含むが、これらに限定されない、全ての出版物および参考文献は、各個々の刊行物または参考文献が、完全に記載されたものとして本明細書中に参照により組み込まれるように具体的にかつ個々に示されるように、参照によりそれらの全体が本明細書中に組み込まれる。本出願が優先権を主張する任意の特許出願もまた、刊行物および参考文献のために上述の様式で参照によりそれらの全体が本明細書中に組み込まれる。
ある特定の実施形態は、コンジュゲート(例えば、Fcコンジュゲート)、バリアント、およびその断片、ならびにHRSポリペプチドをコードする発現可能なポリヌクレオチドを含む、ヒスチジル−tRNAシンテターゼポリペプチド(「HRS」または「HisRS」ポリペプチド)を含む。ヒスチジル−tRNAシンテターゼは、3つの高度に保存された配列モチーフを有する、クラスII tRNAシンテターゼファミリーに属する。クラスIおよびII tRNAシンテターゼは、2ステップ反応においてその同族tRNAへのアミノ酸の特異的結合を担うと広く認識されている:アミノ酸(AA)は、ATPによって最初に活性化されてAA−AMPを形成し、次いで、tRNAの受容体末端に転移される。完全長ヒスチジル−tRNAシンテターゼは、典型的に、サイトゾルホモダイマーまたは選択的スプライシングされたミトコンドリア形態のいずれかとして存在する。
酸性:この残基は、生理学的pHにおけるHイオンの喪失に起因して負の電荷を有し、この残基は、ペプチドが生理学的pHにおいて水性媒体中に存在する場合に、この残基が含まれるペプチドのコンフォメーションにおける表面位置を求めるように、水性溶液によって引きつけられる。酸性側鎖を有するアミノ酸は、グルタミン酸およびアスパラギン酸を含む。
表H3中に示される。
以下の表H6は、ある特定のFcRの特徴付けを要約する。
ある特定の実施形態は、1つ以上の免疫調節剤を使用する。例示的な免疫調節剤は、小分子、ポリペプチド、例えば、抗体およびその抗原結合断片、リガンド、少量のペプチド、アンチセンス剤、RNAi剤、ならびにこれらの混合物を含む。
ある特定の実施形態は、免疫療法剤のみまたは免疫療法剤と組み合わせて肺の炎症を治療するために本明細書に記載される、HRSポリペプチド/発現可能なポリヌクレオチドおよび組成物の使用を含む。間質性肺疾患(ILD)および関連障害の治療も含まれる。いくつかの実施形態では、HRSポリペプチド/発現可能なポリヌクレオチドおよび組成物、方法、および/または併用療法は、肺の炎症の治療を必要とする対象における肺の炎症を減少させる、1つ以上のILDを治療する、および/または疾患の臨床症状もしくはパラメータを改善するために使用される。
ある特定の実施形態は、本明細書に記載される、HRSポリペプチド/発現可能なポリヌクレオチドおよび免疫調節剤の治療用送達に適している、薬学的組成物、治療用組成物、および製剤を含む。いくつかの実施形態は、したがって、1つ以上の薬学的に許容される担体および/または希釈剤と一緒に製剤化される、治療上有効な量の、本明細書に記載される、HRSポリペプチド/発現可能なポリヌクレオチドおよび免疫調節剤のうちの1つ以上を含む、薬学的に許容される組成物を含む。
ブレオマイシン誘導性間質性肺疾患の治療用のHRSポリペプチドの評価
研究は、例示的なHRSポリペプチド(HisRS1N8)がブレオマイシン誘導性肺線維症のマウスモデルにおける呼吸障害および/または肺線維症を減少するかどうかを判定するために行われた。炎症性および線維性プロセスにおけるHRSポリペプチドの効果は、気管支肺胞洗浄(BAL)の細胞内含有量、組織学的線維症スコア、および肺コラーゲン含有量を測定することによって判定した。
ブレオマイシン誘導性間質性肺疾患の処置のためのHRSポリペプチド−Fc融合タンパク質の評価
研究は、例示的なHRS−Fc融合タンパク質(HRSFC1)がブレオマイシン誘導性肺線維症のラットモデルにおける呼吸障害および/または肺線維症を減少するかどうかを判定するために行われた。炎症性および線維性プロセスにおけるHRS−Fc融合タンパク質の効果は、組織学的線維症スコアおよび炎症スコア、ならびに肺コラーゲン含有量を測定することによって判定した。
ブレオマイシン誘導性間質性肺疾患の処置のためのニンテダニブまたはピルフェニドンと組み合わされたHRSポリペプチド−Fc融合タンパク質の評価
研究は、IPFの治療用に市販されているニンテダニブまたはピルフェニドンと組み合わされた、例示的なHRS−Fc融合タンパク質(HRSFC1)がブレオマイシン誘導性肺線維症のラットモデルにおける呼吸障害および/または肺線維症を減少するかどうかを判定するために行われた。炎症性および線維性プロセスにおけるHRS−Fc融合タンパク質の効果は、呼吸測定基準、組織学的線維症スコアおよび炎症スコア、ならびに肺コラーゲン含有量を測定することによって判定した。HRSFC1の循環濃度もまた、判定された。
Claims (87)
- (a)ヒスチジル−tRNAシンテターゼ(HRS)ポリペプチド、または前記HRSポリペプチドをコードする発現可能なポリヌクレオチドと、
(b)免疫調節剤と、を含む、治療用組成物。 - 前記HRSポリペプチドが、表H1、表H2、および表H4から選択される配列に対して少なくとも80%、85%、90%、95%、96%、97%、98%、99%、または100%同一であるアミノ酸配列を含むか、それからなるか、または本質的にそれからなる、請求項1に記載の治療用組成物。
- 前記HRSポリペプチドが、500〜506アミノ酸長であり、配列番号8(HRS(1〜506))または9(HRS(2〜506))に対して少なくとも90%同一であり、配列番号1の残基507〜509を欠いている、請求項2に記載の治療用組成物。
- 前記HRSポリペプチドが、配列番号8(HRS(1〜506))を含むか、それからなるか、または本質的にそれからなる、請求項3に記載の治療用組成物。
- 前記HRSポリペプチドが、配列番号9(HRS(2〜506)またはHisRS1N8)を含むか、それからなるか、または本質的にそれからなる、請求項3に記載の治療用組成物。
- 前記HRSポリペプチドが、異種ポリペプチドと融合している、請求項1〜5のいずれか1項に記載の治療用組成物。
- 前記異種ポリペプチドが、Fc領域を含み、HRS−Fc融合ポリペプチドを形成し、任意に、前記HRS−Fc融合ポリペプチドが、表H8から選択される配列に対して少なくとも80%、85%、90%、95%、96%、97%、98%、99%、または100%同一であるアミノ酸配列を含むか、それからなるか、または本質的にそれからなる、請求項6に記載の治療用組成物。
- 前記HRSポリペプチドが、配列番号157(Fc−HRS(2〜60)またはHRSFC1)を含むか、それからなるか、または本質的にそれからなる、請求項7に記載の治療用組成物。
- 前記HRSポリペプチドが、タンパク質ベースで少なくとも約80%、85%、90%、または95%純粋であり、約5%未満凝集している、請求項1〜8のいずれか1項に記載の治療用組成物。
- (a)が、前記HRSポリペプチドをコードする発現可能なポリヌクレオチド、任意に、修飾mRNAポリヌクレオチドであり、前記修飾mRNAポリヌクレオチドは、任意に、1つ以上の非天然ベースおよび/または非天然ヌクレオチド間結合を含む、請求項1〜9のいずれか1項に記載の治療用組成物。
- 前記HRSポリペプチドが、非正準活性、任意に、抗炎症活性を有する、請求項1〜10のいずれか1項に記載の治療用組成物。
- 前記免疫調節剤が、ピルフェニドン、ニンテダニブ、スフィンゴシン−1−ホスフェート(S1P)および/またはS1P受容体(S1PR)モジュレーター、ステロイド、任意にグルココルチコイド、カルシニューリン阻害剤、ラパマイシンの機構的標的(mTOR)阻害剤、インドールアミン−ピロール2,3−ジオキシゲナーゼ(IDO)阻害剤、イノシン−5’−モノホスフェートデヒドロゲナーゼ(IMPDH)阻害剤、サイトカインおよび/またはサイトカイン受容体阻害剤、B細胞受容体阻害剤、キナーゼ阻害剤、ならびに細胞増殖抑制剤、任意にメトトレキサートのうちの1つ以上から選択される、請求項1〜11のいずれか1項に記載の治療用組成物。
- 前記S1Pおよび/またはS1PRモジュレーターが、アミセリモド(S1PRアンタゴニスト)、フィンゴリモド(S1PR1機能的アンタゴニスト)、ソネプシズマブ(S1P特異的モノクローナル抗体)、KRP203(S1PR1アゴニスト)、SEW2871(S1PR1アゴニスト)、シポニモド(S1PR1およびS1PR5モジュレーター)、RPC1063(S1PR1モジュレーター)、ONO−4641(S1PR1およびS1PR5アゴニスト)、JTE−013(S1PR2アンタゴニスト)、GSK2018682(S1PR1アゴニスト)、ポネシモド(S1PR1アゴニスト)、スラミン(選択的S1PR3およびS1PR5アンタゴニスト)、VPC23019(アリール−アミド類似体;競合的S1PR1およびS1PR3アンタゴニスト)、およびW146(選択的S1PR1アンタゴニスト)、S1PRを標的とするアンチセンスまたはRNAi剤、ならびにS1Pおよび/またはS1PRに特異的に結合する抗体または抗原結合断片もしくは小分子から選択される、請求項12に記載の治療用組成物。
- 前記ステロイドが、ベタメタゾン、ブデソニド、コルチゾール(ヒドロコルチゾン)、コルチゾン、デフラザコート、デオキシコルチコステロン、デキサメタゾン、フルドロコルチゾン、ヒドロコルチゾン、メチルプレドニゾロン、プレドニゾン、プレドニゾロン、およびトリアムシノロンから選択される、請求項12に記載の治療用組成物。
- 前記カルシニューリン阻害剤が、シクロスポリン、ピメクロリムス、タクロリムス、カルシニューリンまたはそのサブユニットを標的とするアンチセンスまたはRNAi剤、ならびにカルシニューリンまたはそのサブユニットに特異的に結合する抗体または抗原結合断片もしくは小分子から選択される、請求項12に記載の治療用組成物。
- 前記mTOR阻害剤が、ATP競合的mTORキナーゼ阻害剤、mTORC1/mTORC2二重阻害剤、および/またはmTOR/PI3K二重阻害剤であるか、あるいは、前記mTOR阻害剤が、エベロリムス、ラパマイシン、デフォロリムス、テムシロリムス、ダクトリシブ、BGT226、SF1126、PKI−587、NVPBE235、サパニセルチブ、AZD8055、AZD2014、mTORを標的とするアンチセンスまたはRNAi剤、ならびにmTORに特異的に結合する抗体または抗原結合断片もしくは小分子のうちの1つ以上から選択される、請求項12に記載の治療用組成物。
- 前記IDO阻害剤が、インドキシモド(NLG−8189)、1−メチル−トリプトファン(1MT)、β−カルボリン(ノルハルマン;9H−ピリド[3,4−b]インドール)、ロスマリン酸、およびエパカドスタット、IDOを標的とするアンチセンスまたはRNAi剤、ならびにIDOに特異的に結合する抗体または抗原結合断片もしくは小分子から選択される、請求項12に記載の治療用組成物。
- 前記IMPDH阻害剤が、ミコフェノール酸(ミコフェノール酸モフェチル)、リバビリン、および6TGMP(6−チオグアニンモノホスフェート)、IMPDHを標的とするアンチセンスまたはRNAi剤、ならびにIMPDHに特異的に結合する抗体または抗原結合断片もしくは小分子のうちの1つ以上から選択される、請求項12に記載の治療用組成物。
- 前記サイトカイン阻害剤が、IL−1αおよびIL−1βを含むインターロイキン−1(IL−1)、インターロイキン−5(IL−5)、インターロイキン−6(IL−6)、インターロイキン−8(IL−8)、インターロイキン−11(IL−11)、インターロイキン−12(IL−12)、インターロイキン−17(IL−17)、インターロイキン−18(IL−18)、インターロイキン−20(IL−20)、インターロイキン−33(IL−33)、腫瘍壊死因子(TNF)、インターフェロンガンマ(IFN−ガンマ)、形質転換成長因子−β(TGF−β)、および顆粒球−マクロファージコロニー刺激因子(GM−CSF)、および/またはIL−1R、IL−6R、IL−8R、IL−11R、IL−12R、IL−17R、IL−18R、IL−20Rのうちの1つ以上から選択されるサイトカイン受容体、ST2(インターロイキン1受容体様1、IL1RL1)、TNFR1などのTNFR、インターフェロン−ガンマ受容体(IFNGR)、ならびにTGFβR1(ALK5)またはTGFβR2などのTGF−β受容体のうちの1つ以上から選択されるサイトカインの阻害剤であり、さらに、前記サイトカインおよび/またはサイトカイン受容体阻害剤が、前記サイトカインおよび/またはサイトカイン受容体を標的とするアンチセンスまたはRNAi剤、ならびに前記サイトカインまたはサイトカイン受容体に特異的に結合する抗体または抗原結合断片もしくは小分子から選択される、請求項12に記載の治療用組成物。
- 前記サイトカインおよび/またはサイトカイン受容体阻害剤が、アダリムマブ、アナキンラ、バシリキシマブ、カナキヌマブ、セルトリズマブ、ダクリズマブ、エタネルセプト、ゴリムマブ、インフリキシマブ、イキセキズマブ、メポリズマブ、レスリズマブ、リロナセプト、セクキヌマブ、セリルマブ(serilumab)、シルクマブ、トシリズマブ、およびウステキヌマブのうちの1つ以上から選択される、請求項12または19に記載の治療用組成物。
- 前記キナーゼ阻害剤が、ヤーヌスキナーゼ(JAK1、JAK2、JAK3、TYK2を含むJAK)、上皮成長因子受容体(EGFR)、受容体チロシン−タンパク質キナーゼerbB−2(Her2/neuまたはERBB2)、Bcr−Abl、c−SRC、マイトジェン活性化タンパク質キナーゼ(MAP)キナーゼ、未分化リンパ腫キナーゼ(ALK)、脾臓チロシンキナーゼ(SYK)、ブルトンチロシンキナーゼ(BTK)、血管内皮成長因子(VEGF)、血管内皮成長因子受容体(VEGFR1、VEGFR2、VEGFR3を含むVEGFR)、線維芽細胞成長因子受容体(FGFR)、B−Raf、RETがん原遺伝子、血小板由来成長因子受容体(PDGF−R)、トロポミオシン受容体キナーゼ(TrkA、TrkB、TrkCを含むTrk)、およびc−Metのうちの1つ以上から選択されるキナーゼの阻害剤であり、さらに、前記キナーゼ阻害剤が、前記キナーゼを標的とするアンチセンスまたはRNAi剤、ならびに前記キナーゼに特異的に結合する抗体または抗原結合断片もしくは小分子から選択される、請求項12に記載の治療用組成物。
- 前記キナーゼ阻害剤が、ニンテダニブ、バリシチニブ、フェドラチニブ、フィルゴチニブ、ガンドチニブ、レスタウルチニブ、モメロチニブ、パクリチニブ、ペフィシチニブ、ルキソリチニブ、トファシチニブ、パダシチニブ、アファチニブ、アキシチニブ、ボスチニブ、セツキシマブ、コビメチニブ、クリゾチニブ、カボザンチニブ、ダサチニブ、エヌトレクチニブ(entrectinib)、エルロチニブ、フォスタマチニブ、ゲフィチニブ、イブルチニブ、イマチニブ、ラパチニブ、レンバチニブ、ムブリチニブ、ネラチニブ、ニロチニブ、パゾパニブ、ペガプタニブ、ソラフェニブ、スニチニブ、SU6656、トセラニブ、バンデタニブ、バタラニブ、およびベムラフェニブのうちの1つ以上から選択される、請求項12または21に記載の治療用組成物。
- 前記B細胞受容体阻害剤が、CD20を標的とするアンチセンスまたはRNAi剤、ならびにCD20に特異的に結合する抗体または抗原結合断片もしくは小分子から選択されるか、または前記B細胞受容体阻害剤が、任意に、イブリツモマブ・チウキセタン、オビヌツズマブ、オカラツズマブ、オクレリズマブ、リツキシマブ、トシツモマブ、およびベルツズマブのうちの1つ以上から選択される、請求項12に記載の治療用組成物。
- 前記アンチセンス剤が、約10〜40塩基長であり、任意に、モルホリノオリゴヌクレオチド(PMO)、ペプチド核酸(PNA)、2’O−メチルホスホロチオエートオリゴヌクレオチド、トリシクロ−ホスホロチオエートオリゴヌクレオチド、およびロックド核酸(LNA)から選択される、請求項13〜23のいずれか1項に記載の治療用組成物。
- 前記アンチセンス剤が、標的タンパク質をコードするプレmRNAまたはmRNA標的配列内の標的領域に特異的にハイブリダイズし、前記標的領域が、前記mRNAのAUG開始コドン、前記AUG開始コドンの上流の領域、前記AUGコドンの下流の領域、予め処理したmRNAの3’または5’スプライス部位、分岐点、3’未翻訳領域(UTR)、およびポリアデニル化シグナル配列のうちの1つ以上から選択される、請求項24に記載の治療用組成物。
- 前記RNAi剤が、前記標的タンパク質をコードするmRNA標的配列と実質的に同一であるセンス鎖、および任意に、前記標的タンパク質をコードする前記mRNA標的配列と相補的であるか、または実質的に相補的であるアンチセンス鎖を含み、任意に、前記RNAi剤が、二本鎖短干渉RNA(siRNA)オリゴヌクレオチドであるか、または任意に、前記RNAi剤、任意に、siRNAオリゴヌクレオチドが、ウイルスベクターによってコードされる、請求項13〜23のいずれか1項に記載の治療用組成物。
- 前記抗体またはその抗原結合断片が、モノクローナル抗体、任意に、ヒト化抗体、または任意に、Fv断片もしくは一本鎖Fv(sFv)ポリペプチドである、請求項13〜23のいずれか1項に記載の治療用組成物。
- 前記組成物が、タンパク質ベースまたは重量−重量ベースで少なくとも約80%、85%、90%、95%、98%、または99%の純度を有し、実質的には、凝集体を含まない、請求項1〜27のいずれか1項に記載の治療用組成物。
- 実質的には、内毒素を含まない、請求項1〜28のいずれか1項に記載の治療用組成物。
- 脂質ナノ粒子を含む、請求項1〜29のいずれか1項に記載の治療用組成物。
- 前記組成物が、シリンジ、任意に、注射可能なシリンジ中にあるか、または前記組成物が、カプセル、任意に、経口カプセルである、請求項1〜30のいずれか1項に記載の治療用組成物。
- 肺の炎症の治療を必要とする対象においてそれを行う方法であって、前記対象に、
(a)ヒスチジル−tRNAシンテターゼ(HRS)ポリペプチド、または前記HRSポリペプチドをコードする発現可能なポリヌクレオチドと、
(b)免疫調節剤と、を投与することを含む、方法。 - (a)および(b)が、別々に投与され、任意に、請求項1〜31のいずれか1項に従って定義される、請求項32に記載の方法。
- (a)および(b)が、一緒に、任意に、請求項1〜31のいずれか1項に記載の治療用組成物として投与される、請求項32に記載の方法。
- 前記HRSポリペプチドが、Fc領域を含み、HRS−Fc融合ポリペプチドを形成し、任意に、前記HRS−Fc融合ポリペプチドが、表H8から選択される配列に対して少なくとも80%、85%、90%、95%、96%、97%、98%、99%、または100%同一であるアミノ酸配列を含むか、それからなるか、または本質的にそれからなる、請求項32〜34のいずれか1項に記載の方法。
- 前記HRSポリペプチドが、配列番号157(Fc−HRS(2〜60)またはHRSFC1)を含むか、それからなるか、または本質的にそれからなる、請求項35に記載の方法。
- 前記免疫調節剤が、前記HRSポリペプチドのみと比較して、前記HRSポリペプチドの1つ以上の薬物動態学的特徴を変化させる、請求項32〜36のいずれか1項に記載の方法。
- 前記HRSポリペプチドの前記1つ以上の変化する薬物動態学的特徴が、血清濃度の増加、血清半減期の増加、バイオアベイラビリティの増加、曝露(AUC)の増加、および/またはクリアランスの減少である、請求項37に記載の方法。
- 前記免疫調節剤が、ピルフェニドンまたはニンテダニブである、請求項32〜38のいずれか1項に記載の方法。
- 前記HRSポリペプチドが、配列番号157(Fc−HRS(2〜60)またはHRSFC1を含むか、それからなるか、または本質的にそれからなり、前記免疫調節剤が、ピルフェニドンである、請求項39に記載の方法。
- 前記ピルフェニドンが、前記HRSポリペプチドのみと比較して、前記対象における前記HRSポリペプチドの前記血清濃度を少なくとも約10、20、30、40、50、60、70、80、90、100、150、または200%以上増加させる、請求項39または40に記載の方法。
- 前記ピルフェニドンが、約50〜約1000mgの範囲である個々の投与量単位で、あるいは約50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、もしくは1000mg、約50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、もしくは1000mg以下、または少なくとも約50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、もしくは1000mgの個々の投与量単位で、任意に、経口投与用の1つ、2つ、または3つのカプセルで投与される、請求項39または40に記載の方法。
- 前記ピルフェニドンが、約100〜約4000mg/日の範囲である1日投与量単位で、あるいは約100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000、1200、1300、1400、1500、1600、1700、1800、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、もしくは4000mg/日、約100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000、1200、1300、1400、1500、1600、1700、1800、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、もしくは4000mg/日以下、または少なくとも約100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000、1200、1300、1400、1500、1600、1700、1800、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、もしくは4000mg/日の1日投与量単位で、任意に、経口投与用の約1つ、2つ、3つ、4つ、5つ、6つ、7つ、8つ、9つのカプセルで投与される、請求項39〜42のいずれか1項に記載の方法。
- 前記ピルフェニドンが、約800mg(例えば801mg)の個々の投与量単位で、任意に、個々の投与量につき3つのカプセルとして服用される、経口投与用の3つの約267mgのカプセルとして投与される、請求項39〜43のいずれか1項に記載の方法。
- 前記ピルフェニドンが、約2400mg/日(例えば2403mg/日)の1日投与量単位で、任意に、個々の投与量につき3つのカプセルとして服用される、1日3回の経口投与用の9つの約267mgのカプセルとして投与される、請求項39〜44のいずれか1項に記載の方法。
- 前記ニンテダニブが、約10〜約500mgの範囲である個々の投与量単位で、あるいは約10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、もしくは500mg、約10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、もしくは500mg以下、または少なくとも約10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、もしくは500mgの個々の投与量単位で、任意に、約1つ、2つ、または3つのカプセルで投与される、請求項39に記載の方法。
- 前記ニンテダニブが、約20〜約1000mg/日の範囲である1日投与量単位で、あるいは約20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000mg/日、約20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000mg/日以下、または少なくとも約20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000mg/日の1日投与量単位で、任意に、約1つ、2つ、3つ、4つ、5つ、または6つのカプセルで投与される、請求項39または46に記載の方法。
- 前記ニンテダニブが、約100〜150mgの範囲である、または約200〜300mg/日の範囲である1日投与量単位で、任意に、1日1回または2回の投与量で投与される、請求項39または46〜47のいずれか1項に記載の方法。
- 前記ニンテダニブが、約100〜150mg、または約200〜300mg/日の1日投与量単位で、任意に、1日1回または2回の投与量で投与される、請求項39または46〜48のいずれか1項に記載の方法。
- 前記対象が、間質性肺疾患(ILD)に罹患しているか、または罹患するリスクがある、請求項32〜49のいずれか1項に記載の方法。
- 前記ILDが、特発性であるか、または結合組織疾患、自己免疫疾患、吸入物質もしくは薬物への曝露、感染症、または悪性腫瘍に関連している、請求項32〜50のいずれか1項に記載の方法。
- 前記ILDが、特発性間質性肺炎、特発性肺線維症、サルコイドーシス、ハンマンリッチ症候群、抗合成酵素症候群、特発性好酸球性肺炎、肺胞出血症候群、肺胞タンパク症、石綿肺症、珪肺症、ベリリウム症、リウマチ性関節炎、紅斑性狼瘡、肺障害を伴う慢性移植片対宿主病、硬化症(全身性)または強皮症、多発性筋炎、皮膚筋炎、慢性肺疾患、喘息、気管支炎(呼吸気管支炎)、肺炎、過敏性肺炎、慢性過敏性肺炎、呼吸窮迫症候群、スティル病、急性肺損傷、顕微鏡的多発血管炎、肺水腫、肺ランゲルハンス細胞組織球症、急性吸入曝露、薬物誘導性肺疾患、剥離性間質性肺炎、および/または嚢胞性線維症のうちの1つ以上から選択されるか、またはそれらと関連している、請求項51に記載の方法。
- 前記ILDが、サーファクタントタンパク質B欠乏症(SFTPBにおける変異)、サーファクタントタンパク質C欠乏症(SFTPCにおける変異)、ABCA3欠乏症(ABCA3における変異)、脳肺甲状腺症候群(TTF1における変異)、または先天性肺胞タンパク症(CSFR2A、CSFR2Bにおける変異)、肺胞毛細血管異形成(FoxF1における変異)、テロメラーゼ逆転写酵素(TERT)における変異、テロメラーゼRNA成分(TERC)における変異、テロメア伸長ヘリカーゼ1の調節因子(RTEL1)における変異、および/またはポリ(A)特異的リボヌクレアーゼ(PARN)における変異のうちの1つ以上と関連している、請求項51または52に記載の方法。
- 前記薬物が、抗生物質、化学療法剤、抗不整脈剤、およびスタチン薬のうちの1つ以上から選択される、請求項51に記載の方法。
- 前記感染が、非定型肺炎、ニューモシスチス肺炎(PCP)、結核、クラミジアトラコマチス、および呼吸器合胞体ウイルス(RSV)、特発性器質化肺炎のうちの1つ以上から選択される、請求項51に記載の方法。
- 前記悪性腫瘍が、がん性リンパ管症またはリンパ腫である、請求項51に記載の方法。
- 前記肺の炎症の治療を必要とする対象が、アトピー性喘息、非アトピー性喘息、アレルギー性喘息、アトピー性気管支IgE仲介性喘息、気管支喘息、本態性喘息、真正喘息、病態生理学的かく乱により引き起こされる内因性喘息、環境因子により引き起こされる外因性喘息、知られていないかまたは明らかでない原因の本態性喘息、非アトピー性喘息、気管支炎様喘息、気腫性喘息、運動誘発性喘息、アレルゲン誘発性喘息、冷気誘発性喘息、職業喘息、細菌、真菌、原虫、またはウイルス感染症により引き起こされる感染型喘息、非アレルギー性喘息、初発性喘息、喘鳴乳児症候群および細気管支炎、慢性または急性気管支収縮、慢性気管支炎、末梢気道閉塞、ならびに肺気腫のうちの1つ以上から選択される状態を有する、請求項32〜56のいずれか1項に記載の方法。
- 前記肺の炎症の治療を必要とする対象が、閉塞性または炎症性の気道疾患を有する、請求項32〜57のいずれか1項に記載の方法。
- 前記閉塞性または炎症性の気道疾患が、慢性好酸球性肺炎、慢性閉塞性肺疾患(COPD)、慢性気管支炎、肺気腫または呼吸困難を含むCOPD、不可逆性進行性気道閉塞を特徴とするCOPD、および急性呼吸窮迫症候群(ARDS)のうちの1つ以上から選択される、請求項58に記載の方法。
- 前記肺の炎症の治療を必要とする対象が、他の薬物療法の結果として生じる気道過敏性の悪化、肺高血圧症を伴う気道疾患、気管支炎または急性気管支炎、急性喉頭気管気管支炎、アラキン酸気管支炎、カタル性気管支炎、クループ性気管支炎、乾性気管支炎、感染性喘息性気管支炎、増殖性気管支炎(productive bronchitis)、ブドウ球菌性もしくは連鎖球菌性の気管支炎、小胞性気管支炎、急性肺損傷、気管支拡張症、または円柱状気管支拡張症、嚢状気管支拡張症、紡錘状気管支拡張症、毛細管性気管支拡張症、嚢胞状気管支拡張症、乾性気管支拡張症、または濾胞性気管支拡張症に関連する状態を有する、請求項32〜59のいずれか1項に記載の方法。
- 前記肺の炎症の治療を必要とする対象が、1、2、3、4、5、6、7、または8のアッシュクロフトスコアを有する、請求項32〜60のいずれか1項に記載の方法。
- 前記肺の炎症の治療を必要とする対象の平均余命を、任意に、約または少なくとも約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60年、またはそれ以上増加させる、請求項32〜61のいずれか1項に記載の方法。
- 前記肺の炎症の治療を必要とする対象における肺の炎症の臨床症状またはパラメータのうちの1つ以上を改善する、請求項32〜62のいずれか1項に記載の方法。
- 前記1つ以上の臨床症状またはパラメータが、肺線維症、肺における炎症細胞浸潤、呼吸機能、および体重のうちの1つ以上から選択される、請求項63に記載の方法。
- 任意に、約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、または24カ月間以上の期間にわたって測定されたときに、約または少なくとも約10、20、30、40、50、60、70、80、90、100、200、300、400、500、600、700、800、900、1000%、またはそれ以上、前記肺の炎症の治療を必要とする対象において肺線維症を改善する、請求項64に記載の方法。
- 任意に、初期スコアと比較して、アッシュクロフトスコアが1、2、3、4、5、6、7、または8グレード低下する、アッシュクロフトスコアの低下によって測定されるように、前記肺の炎症の治療を必要とする対象における肺線維症を改善する、請求項65に記載の方法。
- 任意に、約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、または24カ月間以上の期間にわたって測定されたときに、約または少なくとも約10、20、30、40、50、60、70、80、90、100、200、300、400、500、600、700、800、900、1000%、またはそれ以上、前記肺における炎症細胞浸潤を減少させる、請求項64に記載の方法。
- 任意に、約1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、または24カ月間以上の期間にわたって測定されたときに、約または少なくとも約10、20、30、40、50、60、70、80、90、100、200、300、400、500、600、700、800、900、1000%、またはそれ以上、呼吸機能を改善する、請求項64に記載の方法。
- 前記改善した呼吸機能が、呼気時間の増加、吸気時間の増加、最大呼気流量の減少、最大吸気流量の減少、毎分呼吸量(RMV)の減少、および呼吸数の減少のうちの1つ以上から選択される、請求項68に記載の方法。
- (a)ヒスチジル−tRNAシンテターゼ(HRS)ポリペプチド、または前記HRSポリペプチドをコードする発現可能なポリヌクレオチドと、
(b)免疫調節剤と、を含む、患者ケアキット。 - (a)および(b)が、別々の組成物中にあり、任意に、請求項1〜31のいずれか1項に従って定義される、請求項70に記載の患者ケアキット。
- (a)および(b)が、任意に、請求項1〜31のいずれか1項に記載の治療用組成物と同じ組成物中に存在する、請求項70に記載の患者ケアキット。
- 前記免疫調節剤が、ピルフェニドンまたはニンテダニブである、請求項70〜72のいずれか1項に記載の患者ケアキット。
- 前記ピルフェニドンが、約50〜約1000mgの範囲である個々の投与量単位で、あるいは約50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、もしくは1000mg、約50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、もしくは1000mg以下、または少なくとも約50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、もしくは1000mgの個々の投与量単位で、任意に、経口投与用の1つ、2つ、または3つのカプセルで、である、請求項73に記載の患者ケアキット。
- 前記ピルフェニドンが、約100〜約4000mg/日の範囲である1日投与量単位で、あるいは約100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000、1200、1300、1400、1500、1600、1700、1800、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、もしくは4000mg/日、約100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000、1200、1300、1400、1500、1600、1700、1800、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、または4000mg/日以下、または少なくとも約100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、10、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000、1200、1300、1400、1500、1600、1700、1800、2000、2100、2200、2300、2400、2500、2600、2700、2800、2900、3000、3100、3200、3300、3400、3500、3600、3700、3800、3900、もしくは4000mg/日で、任意に、経口投与用の約1つ、2つ、3つ、4つ、5つ、6つ、7つ、8つ、9つのカプセルにおいて、である、請求項73または74に記載の患者ケアキット。
- 前記ピルフェニドンが、約800mg(例えば801mg)の個々の投与量単位で、任意に、個々の投与量につき3つのカプセルとして服用される、経口投与用の3つの約267mgのカプセルとして、である、請求項73〜75のいずれか1項に記載の患者ケアキット。
- 前記ピルフェニドンが、約2400mg/日(例えば2403mg/日)の1日投与量単位で、任意に、個々の投与量につき3つのカプセルとして服用される、1日3回の経口投与用の9つの約267mgのカプセルとして、である、請求項76に記載の患者ケアキット。
- 前記ニンテダニブが、約10〜約500mgの範囲である個々の投与量単位で、あるいは約10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、もしくは500mg、約10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、もしくは500mg以下、または少なくとも約10、20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、もしくは500mgの個々の投与量単位で、任意に、約1つ、2つ、または3つのカプセルで、である、請求項70に記載の患者ケアキット。
- 前記ニンテダニブが、約20〜約1000mg/日の範囲である1日投与量単位で、あるいは約20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000mg/日、約20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000mg/日以下、または少なくとも約20、30、40、50、60、70、80、90、100、110、120、130、140、150、160、170、180、190、200、210、220、230、240、250、260、270、280、290、300、310、320、330、340、350、360、370、380、390、400、410、420、430、440、450、460、470、480、490、500、510、520、530、540、550、560、570、580、590、600、610、620、630、640、650、660、670、680、690、700、710、720、730、740、750、760、770、780、790、800、810、820、830、840、850、860、870、880、890、900、910、920、930、940、950、960、970、980、990、1000mg/日の1日投与量単位で、任意に、約1つ、2つ、3つ、4つ、5つ、または6つのカプセルで、である、請求項70または78に記載の患者ケアキット。
- 前記ニンテダニブが、約100〜150mgの範囲である、または約200〜300mg/日の範囲である1日投与量単位で、任意に、1日1回または2回の投与量である、請求項70または78〜79のいずれか1項に記載の患者ケアキット。
- 前記ニンテダニブが、約100または150mgの1日投与量単位、または約200〜300mg/日で、任意に、1日1回または2回の投与量である、請求項80に記載の患者ケアキット。
- 対象におけるHRS−Fc融合ポリペプチドの1つ以上の薬物動態学的特徴を変化させる方法であって、前記対象に、前記HRS−Fc融合ポリペプチド、またはピルフェニドンと組み合わせて、前記HRS−Fc融合ポリペプチドをコードする発現可能なポリヌクレオチドを投与することを含む、方法。
- 前記HRS−Fc融合ポリペプチドが、表H8から選択される配列に対して少なくとも80%、85%、90%、95%、96%、97%、98%、99%、または100%同一であるアミノ酸配列を含むか、それからなるか、または本質的にそれからなる、請求項82に記載の方法。
- 前記HRSポリペプチドが、配列番号157(Fc−HRS(2〜60)またはHRSFC1)を含むか、それからなるか、または本質的にそれからなる、請求項83に記載の方法。
- 肺の炎症の治療を必要とする対象においてそれを行う方法であって、前記対象に、HRS−Fc融合ポリペプチド、または前記HRS−Fc融合ポリペプチドをコードする発現可能なポリヌクレオチドを投与することを含む、方法。
- 前記HRS−Fc融合ポリペプチドが、表H8から選択される配列に対して少なくとも80%、85%、90%、95%、96%、97%、98%、99%、または100%同一であるアミノ酸配列を含むか、それからなるか、または本質的にそれからなる、請求項85に記載の方法。
- 前記HRSポリペプチドが、配列番号157(Fc−HRS(2〜60)またはHRSFC1)を含むか、それからなるか、または本質的にそれからなる、請求項86に記載の方法。
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Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015513534A (ja) * | 2012-02-16 | 2015-05-14 | エータイアー ファーマ, インコーポレイテッド | 自己免疫および炎症疾患を処置するためのヒスチジルtRNA合成酵素 |
JP2016519569A (ja) * | 2013-03-15 | 2016-07-07 | エータイアー ファーマ, インコーポレイテッド | ヒスチジル−tRNAシンテターゼFcコンジュゲート |
Family Cites Families (409)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH445129A (fr) | 1964-04-29 | 1967-10-15 | Nestle Sa | Procédé pour la préparation de composés d'inclusion à poids moléculaire élevé |
US3459731A (en) | 1966-12-16 | 1969-08-05 | Corn Products Co | Cyclodextrin polyethers and their production |
US3426011A (en) | 1967-02-13 | 1969-02-04 | Corn Products Co | Cyclodextrins with anionic properties |
US3453257A (en) | 1967-02-13 | 1969-07-01 | Corn Products Co | Cyclodextrin with cationic properties |
US3453259A (en) | 1967-03-22 | 1969-07-01 | Corn Products Co | Cyclodextrin polyol ethers and their oxidation products |
US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
JPS5590540A (en) | 1978-12-28 | 1980-07-09 | Daihachi Kagaku Kogyosho:Kk | Cross-linkable vinyl chloride paste resin composition |
US4469863A (en) | 1980-11-12 | 1984-09-04 | Ts O Paul O P | Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof |
US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
US4476301A (en) | 1982-04-29 | 1984-10-09 | Centre National De La Recherche Scientifique | Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon |
US5155214A (en) | 1984-03-05 | 1992-10-13 | The Salk Institute For Biological Studies | Basic fibroblast growth factor |
US5550111A (en) | 1984-07-11 | 1996-08-27 | Temple University-Of The Commonwealth System Of Higher Education | Dual action 2',5'-oligoadenylate antiviral derivatives and uses thereof |
DE3650699T2 (de) | 1985-03-15 | 1999-04-15 | Antivirals Inc | Immunotestmittel für Polynukleotid und Verfahren |
US5405938A (en) | 1989-12-20 | 1995-04-11 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5521063A (en) | 1985-03-15 | 1996-05-28 | Antivirals Inc. | Polynucleotide reagent containing chiral subunits and methods of use |
US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
US5185444A (en) | 1985-03-15 | 1993-02-09 | Anti-Gene Deveopment Group | Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages |
US5166315A (en) | 1989-12-20 | 1992-11-24 | Anti-Gene Development Group | Sequence-specific binding polymers for duplex nucleic acids |
US5235033A (en) | 1985-03-15 | 1993-08-10 | Anti-Gene Development Group | Alpha-morpholino ribonucleoside derivatives and polymers thereof |
US5217866A (en) | 1985-03-15 | 1993-06-08 | Anti-Gene Development Group | Polynucleotide assay reagent and method |
US5506337A (en) | 1985-03-15 | 1996-04-09 | Antivirals Inc. | Morpholino-subunit combinatorial library and method |
US4751180A (en) | 1985-03-28 | 1988-06-14 | Chiron Corporation | Expression using fused genes providing for protein product |
US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
US4737323A (en) | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
DE3788914T2 (de) | 1986-09-08 | 1994-08-25 | Ajinomoto Kk | Verbindungen zur Spaltung von RNS an eine spezifische Position, Oligomere, verwendet bei der Herstellung dieser Verbindungen und Ausgangsprodukte für die Synthese dieser Oligomere. |
US4873192A (en) | 1987-02-17 | 1989-10-10 | The United States Of America As Represented By The Department Of Health And Human Services | Process for site specific mutagenesis without phenotypic selection |
JP3101690B2 (ja) | 1987-03-18 | 2000-10-23 | エス・ビィ・2・インコーポレイテッド | 変性抗体の、または変性抗体に関する改良 |
US5276019A (en) | 1987-03-25 | 1994-01-04 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5264423A (en) | 1987-03-25 | 1993-11-23 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibitors for replication of retroviruses and for the expression of oncogene products |
US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
IL87737A (en) | 1987-09-11 | 1993-08-18 | Genentech Inc | Method for culturing polypeptide factor dependent vertebrate recombinant cells |
US5188897A (en) | 1987-10-22 | 1993-02-23 | Temple University Of The Commonwealth System Of Higher Education | Encapsulated 2',5'-phosphorothioate oligoadenylates |
US4924624A (en) | 1987-10-22 | 1990-05-15 | Temple University-Of The Commonwealth System Of Higher Education | 2,',5'-phosphorothioate oligoadenylates and plant antiviral uses thereof |
US4865841A (en) | 1987-10-23 | 1989-09-12 | Imre Corporation | Methods and compositions for transient elimination of humoral immune antibodies |
DE3855864T2 (de) | 1987-11-30 | 1997-09-25 | Univ Iowa Res Found | Durch modifikationen an der 3'-terminalen phosphodiesterbindung stabilisierte dna moleküle, ihre verwendung als nukleinsäuresonden sowie als therapeutische mittel zur hemmung der expression spezifischer zielgene |
US5403711A (en) | 1987-11-30 | 1995-04-04 | University Of Iowa Research Foundation | Nucleic acid hybridization and amplification method for detection of specific sequences in which a complementary labeled nucleic acid probe is cleaved |
US5543508A (en) | 1987-12-15 | 1996-08-06 | Gene Shears Pty. Limited | Ribozymes |
US6018026A (en) | 1988-01-22 | 2000-01-25 | Zymogenetics, Inc. | Biologically active dimerized and multimerized polypeptide fusions |
EP0406309A4 (en) | 1988-03-25 | 1992-08-19 | The University Of Virginia Alumni Patents Foundation | Oligonucleotide n-alkylphosphoramidates |
US5278302A (en) | 1988-05-26 | 1994-01-11 | University Patents, Inc. | Polynucleotide phosphorodithioates |
US5216141A (en) | 1988-06-06 | 1993-06-01 | Benner Steven A | Oligonucleotide analogs containing sulfur linkages |
US5468481A (en) | 1988-06-23 | 1995-11-21 | Amergen, Inc. | MHC class II-peptide conjugates useful in ameliorating autoimmunity |
US5130297A (en) | 1988-06-23 | 1992-07-14 | Anergen, Inc. | Conjugates useful in ameliorating autoimmunity MHC-II-peptide |
US6106840A (en) | 1988-06-23 | 2000-08-22 | Anergen, Inc. | MHC conjugates useful in ameliorating autoimmunity |
US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
US6406697B1 (en) | 1989-02-23 | 2002-06-18 | Genentech, Inc. | Hybrid immunoglobulins |
US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
US5256775A (en) | 1989-06-05 | 1993-10-26 | Gilead Sciences, Inc. | Exonuclease-resistant oligonucleotides |
US5399676A (en) | 1989-10-23 | 1995-03-21 | Gilead Sciences | Oligonucleotides with inverted polarity |
US5264562A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences, Inc. | Oligonucleotide analogs with novel linkages |
US5264564A (en) | 1989-10-24 | 1993-11-23 | Gilead Sciences | Oligonucleotide analogs with novel linkages |
AU639047B2 (en) | 1989-11-22 | 1993-07-15 | Genentech Inc. | Latency associated peptide and uses therefor |
US5716632A (en) * | 1989-11-22 | 1998-02-10 | Margolin; Solomon B. | Compositions and methods for reparation and prevention of fibrotic lesions |
US5177198A (en) | 1989-11-30 | 1993-01-05 | University Of N.C. At Chapel Hill | Process for preparing oligoribonucleoside and oligodeoxyribonucleoside boranophosphates |
US5623065A (en) | 1990-08-13 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Gapped 2' modified oligonucleotides |
US5955589A (en) | 1991-12-24 | 1999-09-21 | Isis Pharmaceuticals Inc. | Gapped 2' modified oligonucleotides |
US5587361A (en) | 1991-10-15 | 1996-12-24 | Isis Pharmaceuticals, Inc. | Oligonucleotides having phosphorothioate linkages of high chiral purity |
US5556645A (en) | 1990-01-12 | 1996-09-17 | Bockman; Richard | Methods of enhancing wound healing and tissue repair |
KR0166088B1 (ko) | 1990-01-23 | 1999-01-15 | . | 수용해도가 증가된 시클로덱스트린 유도체 및 이의 용도 |
US5149797A (en) | 1990-02-15 | 1992-09-22 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of rna and production of encoded polypeptides |
US5220007A (en) | 1990-02-15 | 1993-06-15 | The Worcester Foundation For Experimental Biology | Method of site-specific alteration of RNA and production of encoded polypeptides |
US5321131A (en) | 1990-03-08 | 1994-06-14 | Hybridon, Inc. | Site-specific functionalization of oligodeoxynucleotides for non-radioactive labelling |
US5470967A (en) | 1990-04-10 | 1995-11-28 | The Dupont Merck Pharmaceutical Company | Oligonucleotide analogs with sulfamate linkages |
US5610289A (en) | 1990-07-27 | 1997-03-11 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogues |
US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
US5618704A (en) | 1990-07-27 | 1997-04-08 | Isis Pharmacueticals, Inc. | Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling |
US5623070A (en) | 1990-07-27 | 1997-04-22 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
US5541307A (en) | 1990-07-27 | 1996-07-30 | Isis Pharmaceuticals, Inc. | Backbone modified oligonucleotide analogs and solid phase synthesis thereof |
US5608046A (en) | 1990-07-27 | 1997-03-04 | Isis Pharmaceuticals, Inc. | Conjugated 4'-desmethyl nucleoside analog compounds |
US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
WO1992002534A2 (en) | 1990-08-03 | 1992-02-20 | Sterling Drug, Inc. | Compounds and methods for inhibiting gene expression |
US5177196A (en) | 1990-08-16 | 1993-01-05 | Microprobe Corporation | Oligo (α-arabinofuranosyl nucleotides) and α-arabinofuranosyl precursors thereof |
US5214134A (en) | 1990-09-12 | 1993-05-25 | Sterling Winthrop Inc. | Process of linking nucleosides with a siloxane bridge |
US5561225A (en) | 1990-09-19 | 1996-10-01 | Southern Research Institute | Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages |
WO1992005186A1 (en) | 1990-09-20 | 1992-04-02 | Gilead Sciences | Modified internucleoside linkages |
SE9100142L (sv) | 1991-01-17 | 1992-07-18 | Bengt Sandberg | En metod och ett system foer foerbaettrad in vivo reducering av diagnostiska och/eller terapeutiska substanser medelst extrakorporeal borttagning, och anvaendandet av naemnda substanser foer detta aendamaal |
US5981606A (en) | 1991-03-01 | 1999-11-09 | Warner-Lambert Company | Therapeutic TGF-beta-wound healing compositions and methods for preparing and using same |
US5149691A (en) | 1991-03-12 | 1992-09-22 | Creative Biomolecules, Inc. | Issue repair and regeneration through the use of platelet derived growth factor (pdgf) in combination with dexamethasone |
US5539082A (en) | 1993-04-26 | 1996-07-23 | Nielsen; Peter E. | Peptide nucleic acids |
US5719262A (en) | 1993-11-22 | 1998-02-17 | Buchardt, Deceased; Ole | Peptide nucleic acids having amino acid side chains |
US5714331A (en) | 1991-05-24 | 1998-02-03 | Buchardt, Deceased; Ole | Peptide nucleic acids having enhanced binding affinity, sequence specificity and solubility |
WO1993002340A1 (en) | 1991-07-25 | 1993-02-04 | The Whitaker Corporation | Liquid level sensor |
US5571799A (en) | 1991-08-12 | 1996-11-05 | Basco, Ltd. | (2'-5') oligoadenylate analogues useful as inhibitors of host-v5.-graft response |
DE9115660U1 (de) | 1991-12-18 | 1992-07-30 | Aventis Research & Technologies GmbH & Co KG, 65929 Frankfurt | L-Phenylalanyl-tRNA-Synthetase mit erweiterter Substratselektivität aus Mikroorganismen |
US5700922A (en) | 1991-12-24 | 1997-12-23 | Isis Pharmaceuticals, Inc. | PNA-DNA-PNA chimeric macromolecules |
US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
US5434257A (en) | 1992-06-01 | 1995-07-18 | Gilead Sciences, Inc. | Binding compentent oligomers containing unsaturated 3',5' and 2',5' linkages |
US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
US5652355A (en) | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
US5977079A (en) | 1992-08-21 | 1999-11-02 | Alberta Research Council Edmonton | Compositions for attenuating antibody- mediated xenograft rejection in human recipients |
US6765087B1 (en) | 1992-08-21 | 2004-07-20 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
JP3720353B2 (ja) | 1992-12-04 | 2005-11-24 | メディカル リサーチ カウンシル | 多価および多重特異性の結合タンパク質、それらの製造および使用 |
US5478745A (en) | 1992-12-04 | 1995-12-26 | University Of Pittsburgh | Recombinant viral vector system |
US5476925A (en) | 1993-02-01 | 1995-12-19 | Northwestern University | Oligodeoxyribonucleotides including 3'-aminonucleoside-phosphoramidate linkages and terminal 3'-amino groups |
GB9304618D0 (en) | 1993-03-06 | 1993-04-21 | Ciba Geigy Ag | Chemical compounds |
EP0691977B1 (en) | 1993-03-31 | 1997-11-26 | Sanofi | Oligonucleotides with amide linkages replacing phosphodiester linkages |
US5484703A (en) | 1993-04-22 | 1996-01-16 | United States Of America | Assay using recombinant histidyl-tRNA synthetase |
US6838254B1 (en) | 1993-04-29 | 2005-01-04 | Conopco, Inc. | Production of antibodies or (functionalized) fragments thereof derived from heavy chain immunoglobulins of camelidae |
US5464758A (en) | 1993-06-14 | 1995-11-07 | Gossen; Manfred | Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters |
US5814618A (en) | 1993-06-14 | 1998-09-29 | Basf Aktiengesellschaft | Methods for regulating gene expression |
US5665066A (en) | 1993-09-03 | 1997-09-09 | Ultradent Products, Inc. | Methods and apparatus for mixing and dispensing multi-part compositions |
US5641867A (en) | 1993-09-29 | 1997-06-24 | The Trustees Of Columbia University In The City Of New York | Antibody which specifically binds to endothelial-monocyte activating polypeptide II |
US5420109A (en) | 1993-11-12 | 1995-05-30 | Houghten Pharmaceuticals, Inc. | Cytokine restraining agents |
DE69425903T2 (de) | 1993-12-09 | 2001-02-15 | Thomas Jefferson University Ph | Verbindungen und verfahren zur ortsspezifischen mutation in eukaryotischen zellen |
US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
WO1995031727A1 (en) | 1994-05-13 | 1995-11-23 | Therasorb Medizinische Systeme Gmbh | Sterile and pyrogen-free columns coupled to protein for binding and removal of substances from blood |
US5759833A (en) | 1994-05-27 | 1998-06-02 | Cubist Pharmaceuticals, Inc. | Human isoleucyl-tRNA synthetase proteins, nucleic acids and tester strains comprising same |
US5798240A (en) | 1994-09-13 | 1998-08-25 | Cubist Pharmaceuticals, Inc. | Recombinant mycobacterial methionyl-tRNA synthetase genes and methods of use therefore |
US5756327A (en) | 1994-09-13 | 1998-05-26 | Cubist Pharmaceuticals, Inc. | Recombinant mycobacterial isoleucyl-tRNA synthetase genes, tester strains and assays |
IL115849A0 (en) | 1994-11-03 | 1996-01-31 | Merz & Co Gmbh & Co | Tangential filtration preparation of liposomal drugs and liposome product thereof |
US5545729A (en) | 1994-12-22 | 1996-08-13 | Hybridon, Inc. | Stabilized ribozyme analogs |
US5635363A (en) | 1995-02-28 | 1997-06-03 | The Board Of Trustees Of The Leland Stanford Junior University | Compositions and methods for the detection, quantitation and purification of antigen-specific T cells |
US5801013A (en) | 1995-05-26 | 1998-09-01 | Cubist Pharmaceuticals, Inc. | Helicobacter aminoacyl-tRNA synthetase proteins, nucleic acids and strains comprising same |
CA2212992A1 (en) | 1995-06-05 | 1996-12-12 | Human Genome Sciences, Inc. | Fibroblast growth factor-14 |
US6013483A (en) | 1995-06-07 | 2000-01-11 | Human Genome Sciences, Inc. | DNA encoding endothelial monocyte activating polypeptide III |
US5652356A (en) | 1995-08-17 | 1997-07-29 | Hybridon, Inc. | Inverted chimeric and hybrid oligonucleotides |
EP1876241A3 (en) | 1996-01-11 | 2008-07-30 | Corixa Corporation | Compositions and methods for the treatment and diagnosis of breast cancer |
GB9601067D0 (en) | 1996-01-19 | 1996-03-20 | Smithkline Beecham Plc | Novel compounds |
EP1288299A3 (en) | 1996-01-19 | 2003-12-17 | Smithkline Beecham Plc | TRNA synthetase |
EP0785262A1 (en) | 1996-01-19 | 1997-07-23 | Smithkline Beecham Plc | Phenylalanyl-tRNA synthetase from Staphylococcus aureus |
US5795757A (en) | 1997-01-17 | 1998-08-18 | Smithkline Beecham, P.L.C. | DNA encoding threonyl tRNA synthetase from staphylococcus aureus |
US5795758A (en) | 1997-04-18 | 1998-08-18 | Smithkline Beecham Corporation | DNA encoding histidyl tRNA synthetase variant from Streptococcus pneumoniae |
GB9607991D0 (en) | 1996-04-18 | 1996-06-19 | Smithkline Beecham Plc | Novel compounds |
GB9607993D0 (en) | 1996-04-18 | 1996-06-19 | Smithkline Beecham Plc | Novel compounds |
US6852512B2 (en) | 1996-10-04 | 2005-02-08 | Hanil Synthetic Fiber Co., Ltd. | Expression vectors for production of foreign proteins as soluble forms |
KR100203919B1 (ko) | 1996-10-04 | 1999-06-15 | 신동권 | 수용성 단백질을 생산하는 새로운 발현 플라스미드 |
US5885815A (en) | 1996-11-01 | 1999-03-23 | Cubist Pharmaceuticals, Inc. | Candida isoleucyl-tRNA synthetase proteins, nucleic acids and strains comprising same |
US5776749A (en) | 1997-01-17 | 1998-07-07 | Smithkline Beecham P.L.C. | DNA encoding cysteinyl tRNA synthetase from Staphylococcus aureus |
CN1268178A (zh) | 1997-05-06 | 2000-09-27 | 人体基因组科学有限公司 | 粪肠球菌多核苷酸和多肽 |
US5858720A (en) | 1997-07-23 | 1999-01-12 | Smithkline Beecham Corporation | Hiss |
US5939298A (en) | 1997-07-23 | 1999-08-17 | Smithkline Beecham Corporation | DNA encoding phenylalanyl tRNA synthetase alpha sub-unit from chlamydi a trachomatis |
US5882892A (en) | 1997-07-23 | 1999-03-16 | Smithkline Beecham Corporation | Asps |
US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
US7572582B2 (en) | 1997-09-12 | 2009-08-11 | Exiqon A/S | Oligonucleotide analogues |
US6391311B1 (en) | 1998-03-17 | 2002-05-21 | Genentech, Inc. | Polypeptides having homology to vascular endothelial cell growth factor and bone morphogenetic protein 1 |
CA2313607A1 (en) | 1997-12-09 | 1999-06-17 | Children's Medical Center Corporation | Antagonists of neuropilin receptor function and use thereof |
CA2313348A1 (en) | 1997-12-09 | 1999-06-17 | Children's Medical Center Corporation | Soluble inhibitors of vascular endothelial growth factor and use thereof |
WO1999042091A2 (en) | 1998-02-19 | 1999-08-26 | Massachusetts Institute Of Technology | Use of polycations as endosomolytic agents |
FR2775435B1 (fr) | 1998-02-27 | 2000-05-26 | Bioalliance Pharma | Nanoparticules comprenant au moins un polymere et au moins un compose apte a complexer un ou plusieurs principes actifs |
CN1292033A (zh) | 1998-03-04 | 2001-04-18 | 昂尼克斯药物公司 | 用于遗传物质高通量表达的杆状病毒表达系统和方法 |
US6428960B1 (en) | 1998-03-04 | 2002-08-06 | Onyx Pharmaceuticals, Inc. | Selection method for producing recombinant baculovirus |
TR200100254T2 (tr) | 1998-07-13 | 2001-06-21 | Expression Genetics, Inc. | Eriyebilir ve bakterilerle ayrışabilir bir gen iletim taşıyıcısı olarak poly-l-lysine benzeri bir poliyester. |
US6255090B1 (en) | 1998-07-15 | 2001-07-03 | E. I. Du Pont De Nemours & Company | Plant aminoacyl-tRNA synthetase |
US6271441B1 (en) | 1998-07-21 | 2001-08-07 | E. I. Du Pont De Nemours & Company | Plant aminoacyl-tRNA synthetase |
US6800286B1 (en) | 1998-08-19 | 2004-10-05 | The Regents Of The University Of Colorado | Chimeric fibroblast growth factor proteins, nucleic acid molecules, and uses thereof |
US6696619B1 (en) | 1998-11-05 | 2004-02-24 | Omolayo O. Famodu | Plant aminoacyl-tRNA synthetases |
CA2340468A1 (en) | 1998-11-13 | 2000-05-25 | Children's Hospital Of Los Angeles | Methods of facilitating vascular growth |
PL220113B1 (pl) | 1999-01-15 | 2015-08-31 | Genentech Inc | Wariant macierzystego polipeptydu zawierającego region Fc, polipeptyd zawierający wariant regionu Fc o zmienionym powinowactwie wiązania receptora Fc gamma (FcγR), polipeptyd zawierający wariant regionu Fc o zmienionym powinowactwie wiązania noworodkowego receptora Fc (FcRn), kompozycja, wyizolowany kwas nukleinowy, wektor, komórka gospodarza, sposób otrzymywania wariantu polipeptydu, zastosowanie wariantu polipeptydu i sposób otrzymywania wariantu regionu Fc |
AU3395900A (en) | 1999-03-12 | 2000-10-04 | Human Genome Sciences, Inc. | Human lung cancer associated gene sequences and polypeptides |
US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
NZ514348A (en) | 1999-05-04 | 2004-05-28 | Exiqon As | L-ribo-LNA analogues |
AU5047800A (en) | 1999-05-28 | 2000-12-18 | Ludwig Institute For Cancer Research | Breast, gastric and prostate cancer associated antigens and uses therefor |
JP2003533967A (ja) | 1999-07-22 | 2003-11-18 | インサイト・ゲノミックス・インコーポレイテッド | ヒトシンセターゼ |
WO2001019999A1 (fr) | 1999-09-14 | 2001-03-22 | Shanghai Biorigin Gene Development Co. Ltd. | Gene codant une nouvelle threonyl-arnt synthase, ses utilisations et procedes de preparation |
AU4134901A (en) | 1999-10-27 | 2001-05-30 | Cel-Sci Corporation | Methods of preparation and composition of peptide constructs useful for treatment of autoimmune and transplant related host versus graft conditions |
US6548060B1 (en) | 1999-11-18 | 2003-04-15 | Sunghoon Kim | Anti-apoptotic use of human glutaminyl-tRNA synthetase with two consecutive pro-apoptotic mediators |
US7070807B2 (en) | 1999-12-29 | 2006-07-04 | Mixson A James | Branched histidine copolymers and methods for using same |
WO2001047496A1 (en) | 1999-12-29 | 2001-07-05 | Mixson A James | Histidine copolymer and methods for using same |
US20030158400A1 (en) | 2000-02-03 | 2003-08-21 | Tang Y. Tom | Novel nucleic acids and polypeptides |
US20030165921A1 (en) | 2000-02-03 | 2003-09-04 | Tang Y. Tom | Novel nucleic acids and polypeptides |
US20020128187A1 (en) | 2000-02-03 | 2002-09-12 | Tang Y. Tom | Novel nucleic acids and polypeptides |
WO2001057190A2 (en) | 2000-02-03 | 2001-08-09 | Hyseq, Inc. | Novel nucleic acids and polypeptides |
US20070042392A1 (en) | 2000-02-03 | 2007-02-22 | Nuvelo, Inc. | Novel nucleic acids and polypeptides |
CN1311300A (zh) | 2000-03-02 | 2001-09-05 | 上海博德基因开发有限公司 | 一种新的多肽-人苏氨酰-tRNA合成酶14和编码这种多肽的多核苷酸 |
DE10011482B4 (de) | 2000-03-09 | 2004-06-09 | Fresenius Hemocare Gmbh | Verfahren zum Herstellen eines Adsorbens zum Absenken der Konzentration von Fibrinogen und/oder Fibrin, Adsorbens und Verwendung des Adsorbens zur Herstellung eines Adsorbers |
CN1314486A (zh) | 2000-03-17 | 2001-09-26 | 上海博德基因开发有限公司 | 一种新的多肽——人组氨酰-tRNA合成酶85和编码这种多肽的多核苷酸 |
US6436703B1 (en) | 2000-03-31 | 2002-08-20 | Hyseq, Inc. | Nucleic acids and polypeptides |
US7067126B2 (en) | 2000-03-31 | 2006-06-27 | The Scripps Research Institute | Human aminoacyl-tRNA synthetase polypeptides useful for the regulation of angiogenesis |
US7144984B2 (en) | 2000-03-31 | 2006-12-05 | The Scripps Research Institute | Human aminoacyl-tRNA synthetase polypeptides useful for the regulation of angiogenesis |
US7273844B2 (en) | 2000-03-31 | 2007-09-25 | The Scripps Research Institute | Tryptophanyl-tRNA synthetase-derived polypeptides useful for the regulation of angiogenesis |
CN1322818A (zh) | 2000-05-09 | 2001-11-21 | 上海博德基因开发有限公司 | 一种新的多肽——人II类氨酰基-tRNA合成酶10和编码这种多肽的多核苷酸 |
US20040181830A1 (en) | 2001-05-07 | 2004-09-16 | Kovalic David K. | Nucleic acid molecules and other molecules associated with plants and uses thereof for plant improvement |
WO2001088188A2 (en) | 2000-05-18 | 2001-11-22 | Nihon University, School Juridical Person | Method for examining ischemic conditions |
WO2001090330A2 (en) | 2000-05-25 | 2001-11-29 | Incyte Genomics, Inc. | AMINOACYL tRNA SYNTHETASES |
AU5114000A (en) | 2000-06-14 | 2001-12-24 | Imagene Co., Ltd. | P43 anti-tumor therapeutic agent and three dimensional structure of its cytokinedomain |
CN1331293A (zh) | 2000-06-28 | 2002-01-16 | 上海博德基因开发有限公司 | 一种新的多肽——组氨酸tRNA合成酶11.99和编码这种多肽的多核苷酸 |
CN1341727A (zh) | 2000-09-07 | 2002-03-27 | 上海博德基因开发有限公司 | 一种新的多肽——甲硫氨酰tRNA合成酶35.09和编码这种多肽的多核苷酸 |
CN1341725A (zh) | 2000-09-07 | 2002-03-27 | 上海博德基因开发有限公司 | 一种新的多肽——人苏氨酰-tRNA合成酶48.73和编码这种多肽的多核苷酸 |
US20070037165A1 (en) | 2000-09-08 | 2007-02-15 | Applera Corporation | Polymorphisms in known genes associated with human disease, methods of detection and uses thereof |
US6812339B1 (en) | 2000-09-08 | 2004-11-02 | Applera Corporation | Polymorphisms in known genes associated with human disease, methods of detection and uses thereof |
FR2814642B1 (fr) | 2000-10-03 | 2005-07-01 | Ass Pour Le Dev De La Rech En | Souris transgenique pour la recombinaison ciblee mediee par la cre-er modifiee |
US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
CN1352242A (zh) | 2000-11-02 | 2002-06-05 | 上海博德基因开发有限公司 | 一种新的多肽——人谷氨酰tRNA合成酶12.65和编码这种多肽的多核苷酸 |
CN1352252A (zh) | 2000-11-06 | 2002-06-05 | 上海博德基因开发有限公司 | 一种新的多肽——人II类氨酰基-tRNA合成酶11.77和编码这种多肽的多核苷酸 |
US20040082068A1 (en) | 2000-11-28 | 2004-04-29 | Lawrence Kleiman | Incorporation and priming function of trnalys in hiv and related viruses |
ES2727425T3 (es) | 2000-12-12 | 2019-10-16 | Medimmune Llc | Moléculas con semividas prolongadas, composiciones y usos de las mismas |
JP2004537270A (ja) | 2000-12-15 | 2004-12-16 | インサイト・ゲノミックス・インコーポレイテッド | アミノアシルtRNA合成酵素 |
AU2002255478A1 (en) | 2001-01-10 | 2002-09-12 | Pe Corporation (Ny) | Kits, such as nucleic acid arrays, comprising a majority of human exons or transcripts, for detecting expression and other uses thereof |
AU2002245257A1 (en) | 2001-01-12 | 2002-07-24 | Exelixis, Inc. | Srebp pathway modulation through targeting hisrs |
US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
US6743619B1 (en) | 2001-01-30 | 2004-06-01 | Nuvelo | Nucleic acids and polypeptides |
PL208008B1 (pl) | 2001-02-23 | 2011-03-31 | Scripps Research Inst | Izolowany polipeptyd i jego zastosowanie, izolowany polinukleotyd, rekombinowany wektor, rekombinowana komórka gospodarza, kompozycja angiostatyczna i zestaw do hamowania neowaskularyzacji ocznej |
US6903189B2 (en) | 2001-03-21 | 2005-06-07 | The Scripps Research Institute | Human aminoacyl-tRNA synthetase polypeptides useful for the regulation of angiogenesis |
DK1456360T3 (en) | 2001-04-19 | 2015-08-31 | Scripps Research Inst | Methods and Composition for Preparation of Orthogonal TRNA-Aminoacyl-TRNA Synthetase Pairs |
US20030215827A1 (en) | 2001-05-22 | 2003-11-20 | Henry Yue | Aminoacyl trna synthetases |
KR100405919B1 (ko) | 2001-06-05 | 2003-11-14 | 주식회사 이매진 | p43의 N-말단 펩타이드를 유효성분으로 하는 면역증강용 약학조성물 |
US20040018505A1 (en) | 2001-06-29 | 2004-01-29 | Lee Ernestine A. | Aminoacyl trna synthetases |
AU2002332430A1 (en) | 2001-07-26 | 2003-02-17 | Novartis Ag | Methods of treating neuropilin-mediated diseases |
US20030134301A1 (en) | 2001-07-27 | 2003-07-17 | Brooksbank Robert Alan | Identification and use of molecules implicated in pain |
US6900292B2 (en) | 2001-08-17 | 2005-05-31 | Lee-Hwei K. Sun | Fc fusion proteins of human erythropoietin with increased biological activities |
AU2002334307A1 (en) | 2001-09-04 | 2003-03-18 | Exiqon A/S | Novel lna compositions and uses thereof |
US20040142325A1 (en) | 2001-09-14 | 2004-07-22 | Liat Mintz | Methods and systems for annotating biomolecular sequences |
US7785827B2 (en) | 2001-09-20 | 2010-08-31 | University Of Houston System | Method and composition for leucyl-tRNA synthetases and derivatives thereof that activate and aminoacylate non-leucine amino acid to tRNA adaptor molecules |
WO2003035835A2 (en) | 2001-10-25 | 2003-05-01 | Genentech, Inc. | Glycoprotein compositions |
US20040048290A1 (en) | 2001-12-13 | 2004-03-11 | Lee Ernestine A | Aminoacyl trna synthetases |
CN1620309A (zh) | 2001-12-18 | 2005-05-25 | 蒙多生物技术实验室 | 用于结合分子诊断法改进间质性肺疾病的治疗的干扰素γ或甲苯吡啶酮的新型药物组合物 |
US20040101879A1 (en) | 2002-01-11 | 2004-05-27 | Cynthia Seidel-Dugan | Srebp pathway modulation through targeting hisrs |
KR100464261B1 (ko) | 2002-01-24 | 2005-01-03 | 주식회사 파나진 | Pna 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
US7662925B2 (en) | 2002-03-01 | 2010-02-16 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
US7244592B2 (en) | 2002-03-07 | 2007-07-17 | Dyax Corp. | Ligand screening and discovery |
EP1490113A4 (en) | 2002-03-20 | 2007-05-02 | Univ Florida | ADENO-ASSOCIATED RECOMBINANT VIRAL VECTOR (RAAV) COMPOSITIONS AND CORRESPONDING METHODS FOR THE TREATMENT OF CHOROIDAL NEOVASCULARIZATION |
EP1498491A4 (en) | 2002-04-09 | 2006-12-13 | Kyowa Hakko Kogyo Kk | METHOD FOR INCREASING THE ACTIVITY OF AN ANTIBODY COMPOSITION FOR BINDING TO THE FC GAMMA RECEPTOR IIIA |
KR20030084444A (ko) | 2002-04-26 | 2003-11-01 | 주식회사 파나진 | Pna 올리고머를 합성하기 위한 신규한 단량체 및 그의제조방법 |
US7569575B2 (en) | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
AU2003232086A1 (en) | 2002-05-10 | 2003-11-11 | Incyte Corporation | Nucleic acid-associated proteins |
AU2003234600A1 (en) | 2002-05-13 | 2003-11-11 | Rigel Pharmaceuticals, Inc. | tRNA SYNTHASE: MODULATORS OF ANGIOGENESIS |
KR100515016B1 (ko) | 2002-07-22 | 2005-09-15 | 재단법인서울대학교산학협력재단 | p43을 유효성분으로 하는 창상 치료용 약학적 조성물 |
AU2002331356A1 (en) | 2002-07-29 | 2004-03-11 | Nanodel Technologies Gmbh | Nanoparticles for dna administration to a target organ |
CA2495251C (en) | 2002-08-14 | 2018-03-06 | Macrogenics, Inc. | Fc.gamma.riib-specific antibodies and methods of use thereof |
US20090017023A1 (en) | 2002-08-14 | 2009-01-15 | Macrogenics, Inc. | FcGammaRIIB Specific Antibodies and Methods of Use Thereof |
JPWO2004022736A1 (ja) | 2002-08-30 | 2005-12-22 | 独立行政法人科学技術振興機構 | 遺伝子のターゲティング破壊法および超耐熱菌ゲノム、ならびにこれらを利用したゲノムチップ |
US7842476B2 (en) | 2002-09-06 | 2010-11-30 | Isogenica Limited | In vitro peptide expression library |
AU2003289716A1 (en) | 2002-09-12 | 2004-04-30 | Incyte Corporation | Molecules for diagnostics and therapeutics |
CA2500687A1 (en) | 2002-10-02 | 2004-04-15 | Genentech, Inc. | Compositions and methods for the diagnosis and treatment of tumor |
US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
WO2004060262A2 (en) | 2003-01-07 | 2004-07-22 | Lorantis Limited | Modulators of notch signalling for use in immunotherpapy |
WO2004063355A2 (en) | 2003-01-10 | 2004-07-29 | Protein Design Labs, Inc. | Novel methods of diagnosis of metastatic cancer, compositions and methods of screening for modulators of matastatic cancer |
CN1519315A (zh) | 2003-01-21 | 2004-08-11 | 上海博德基因开发有限公司 | 一种多肽——人组氨酰-trna合成酶13.09和编码这种多肽的多核苷酸 |
WO2004064863A1 (en) | 2003-01-23 | 2004-08-05 | Lorantis Limited | Treatment of autoimmune diseases using an activator for the notch signaling pathway |
KR100575251B1 (ko) | 2003-03-03 | 2006-05-02 | 재단법인서울대학교산학협력재단 | p38/JTV-1을 유효성분으로 하는 암 치료용 약학적조성물 및 암 치료용 약학적 조성물의 스크리닝 방법 |
WO2004087875A2 (en) | 2003-03-25 | 2004-10-14 | Incyte Corporation | Nucleic acid-associated proteins |
US20040224981A1 (en) | 2003-05-01 | 2004-11-11 | Nebojsa Janjic | Antibacterial methods and compositions |
US7727969B2 (en) | 2003-06-06 | 2010-06-01 | Massachusetts Institute Of Technology | Controlled release nanoparticle having bound oligonucleotide for targeted delivery |
SI1641483T1 (sl) | 2003-06-12 | 2008-08-31 | Lilly Co Eli | Fuzijski proteini |
US7786290B2 (en) | 2003-06-13 | 2010-08-31 | Alnylam Pharmaceuticals, Inc. | Double-stranded ribonucleic acid with increased effectiveness in an organism |
EP1704242A4 (en) | 2003-07-07 | 2008-06-18 | Scripps Research Inst | COMPOSITIONS WITH PAIRS OF ORTHOGONAL LEUCYL-TRNA AND AMINOACYL-TRNA-SYNTHETASE AND USES THEREOF |
PT1914314E (pt) | 2003-07-07 | 2010-09-08 | Scripps Research Inst | Composições de pares ortogonais de lisil-arnt e aminoacil-arnt-sintetase e suas utilizações |
US7211668B2 (en) | 2003-07-28 | 2007-05-01 | Panagene, Inc. | PNA monomer and precursor |
WO2005019258A2 (en) | 2003-08-11 | 2005-03-03 | Genentech, Inc. | Compositions and methods for the treatment of immune related diseases |
WO2005037867A1 (en) | 2003-10-15 | 2005-04-28 | Pdl Biopharma, Inc. | ALTERATION OF Fc-FUSION PROTEIN SERUM HALF-LIVES BY MUTAGENESIS OF POSITIONS 250, 314 AND/OR 428 OF THE HEAVY CHAIN CONSTANT REGION OF IG |
ES2341009T3 (es) | 2003-11-05 | 2010-06-14 | Roche Glycart Ag | Anticuerpos cd20 con afinidad de union a receptores fc y funcion efectora. |
WO2005063815A2 (en) | 2003-11-12 | 2005-07-14 | Biogen Idec Ma Inc. | Fcϝ receptor-binding polypeptide variants and methods related thereto |
DK2256134T3 (en) | 2003-11-13 | 2014-02-24 | Hanmi Science Co Ltd | IgG Fc fragment to a drug carrier and process for preparation thereof |
US20070054278A1 (en) | 2003-11-18 | 2007-03-08 | Applera Corporation | Polymorphisms in nucleic acid molecules encoding human enzyme proteins, methods of detection and uses thereof |
WO2006001832A2 (en) | 2003-12-18 | 2006-01-05 | The Scripps Research Institute | Selective incorporation of 5-hyroxytryptophan into proteins in mammalian cells |
EP1713914A2 (en) | 2004-01-28 | 2006-10-25 | Celldex Therapeutics Limited | MEDICAL TREATMENT USING AN RNAi AGENT TARGETING A HUMAN NOTCH SIGNALLING PATHWAY MEMBER |
JP2009521905A (ja) | 2004-03-05 | 2009-06-11 | アプレラ コーポレイション | 冠動脈心疾患に関連する遺伝的多型、その検出方法および使用 |
WO2005113812A2 (en) | 2004-04-23 | 2005-12-01 | Invitrogen Corporation | Collections of matched biological reagents and methods for identifying matched reagents |
CA2562685C (en) | 2004-04-27 | 2013-09-17 | Alnylam Pharmaceuticals, Inc. | Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety |
KR100599454B1 (ko) | 2004-04-27 | 2006-07-12 | 재단법인서울대학교산학협력재단 | 종양 억제자로 작용하는 aim3의 신규 용도 |
WO2005116236A2 (en) | 2004-05-14 | 2005-12-08 | The Regents Of The University Of California | Methods for treating cancer using anti-wnt2 monoclonal antibodies and sirna |
US7528106B2 (en) | 2004-06-04 | 2009-05-05 | The Scripps Research Institute | Compositions and methods for treatment of neovascular diseases |
JP2008504840A (ja) | 2004-06-30 | 2008-02-21 | アルニラム ファーマスーティカルズ インコーポレイテッド | 非リン酸骨格結合を含むオリゴヌクレオチド |
WO2006093526A2 (en) | 2004-07-21 | 2006-09-08 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a modified or non-natural nucleobase |
US20060079673A1 (en) | 2004-08-02 | 2006-04-13 | Paul Glidden | Polynucleotides encoding tRNA synthetase fragments and uses thereof |
US8282921B2 (en) | 2004-08-02 | 2012-10-09 | Paul Glidden | tRNA synthetase fragments |
US20060078553A1 (en) | 2004-10-07 | 2006-04-13 | Paul Glidden | Diverse multi-unit complexes including a tRNA synthetase fragment |
US20060024288A1 (en) | 2004-08-02 | 2006-02-02 | Pfizer Inc. | tRNA synthetase fragments |
US7632932B2 (en) | 2004-08-04 | 2009-12-15 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase |
WO2006020114A2 (en) | 2004-08-04 | 2006-02-23 | Applied Molecular Evolution, Inc. | Variant fc regions |
BRPI0516284A (pt) | 2004-09-23 | 2008-09-02 | Genentech Inc | anticorpo construìdo com cisteìna, método de selecionar anticorpos, compostos conjugados de droga-anticorpo, composição farmacêutica, método para matar ou inibir a proliferação de células de tumor, métodos de inibir a proliferação celular e o crescimento de células de tumor, artigo manufaturado e método para produzir um composto |
JP2008518610A (ja) | 2004-11-03 | 2008-06-05 | アルマック ダイアグノスティックス リミテッド | トランスクリプトームマイクロアレイ技法およびそれを使用する方法 |
EP1657232A1 (en) | 2004-11-05 | 2006-05-17 | Cellzome Ag | Use of S-enantiomers of alpha-sustituted aryl acetic acids for the prevention of Alzheimer's disease |
US7462697B2 (en) | 2004-11-08 | 2008-12-09 | Epitomics, Inc. | Methods for antibody engineering |
US8367805B2 (en) | 2004-11-12 | 2013-02-05 | Xencor, Inc. | Fc variants with altered binding to FcRn |
JP4652414B2 (ja) | 2004-11-12 | 2011-03-16 | ゼンコー・インコーポレイテッド | FcRnとの変化した結合を有するFc変異体 |
US7459529B2 (en) | 2004-11-24 | 2008-12-02 | Seoul National University Industry Foundation | AIMP2-DX2 and its uses |
US8003780B2 (en) | 2004-11-24 | 2011-08-23 | Neomics Co., Ltd. | AIMP2-DX2 gene and SiRNA targeting AIMP2-DX2 |
US7838657B2 (en) | 2004-12-03 | 2010-11-23 | University Of Massachusetts | Spinal muscular atrophy (SMA) treatment via targeting of SMN2 splice site inhibitory sequences |
CA2594557C (en) | 2004-12-22 | 2016-04-26 | Ambrx, Inc. | Modified human growth hormone |
WO2006068802A2 (en) | 2004-12-22 | 2006-06-29 | Ambrx, Inc. | COMPOSITIONS OF AMINOACYL-tRNA SYNTHETASE AND USES THEREOF |
JP2008528010A (ja) | 2005-01-31 | 2008-07-31 | アブリンクス ナームローゼ フェンノートシャップ | 重鎖抗体の可変ドメイン配列を作出する方法 |
MX2007009368A (es) | 2005-02-01 | 2008-01-14 | Imagene Co Ltd | Metodo para estimular la sintesis de colagena y/o expresion de factor de crecimiento de queratinocitos. |
US7404969B2 (en) | 2005-02-14 | 2008-07-29 | Sirna Therapeutics, Inc. | Lipid nanoparticle based compositions and methods for the delivery of biologically active molecules |
US20060275794A1 (en) | 2005-03-07 | 2006-12-07 | Invitrogen Corporation | Collections of matched biological reagents and methods for identifying matched reagents |
CA2638892A1 (en) | 2005-03-18 | 2006-09-28 | Oregon Health & Science University | Recombinant mhc molecules useful for manipulation of antigen-specific t cells |
KR100689274B1 (ko) | 2005-03-30 | 2007-03-08 | 김현기 | 인간 원암 유전자, 이에 의해 코드되는 단백질 |
EP1888649A2 (en) | 2005-05-09 | 2008-02-20 | GlycArt Biotechnology AG | Antigen binding molecules having modified fc regions and altered binding to fc receptors |
US7842467B1 (en) | 2005-05-12 | 2010-11-30 | Celera Corporation | Breast disease targets and uses thereof |
US20070072175A1 (en) | 2005-05-13 | 2007-03-29 | Biogen Idec Ma Inc. | Nucleotide array containing polynucleotide probes complementary to, or fragments of, cynomolgus monkey genes and the use thereof |
ES2545223T3 (es) | 2005-06-23 | 2015-09-09 | Isis Pharmaceuticals, Inc. | Composiciones y procedimientos para modular el corte y empalme de SMN2 |
AU2006270057A1 (en) | 2005-07-18 | 2007-01-25 | Trustees Of Boston University | Method to inhibit proliferation and growth of metastases |
US7375188B2 (en) | 2005-07-29 | 2008-05-20 | Mallinckrodt Baker, Inc. | Vegetarian protein a preparation and methods thereof |
US8008453B2 (en) | 2005-08-12 | 2011-08-30 | Amgen Inc. | Modified Fc molecules |
WO2007020075A1 (en) | 2005-08-16 | 2007-02-22 | Klinikum Der Universität Regensburg | Use of neuropilin-2 antagonists |
CN102703446B (zh) | 2005-08-18 | 2014-05-28 | Ambrx公司 | tRNA组合物和其用途 |
DE102005043321A1 (de) | 2005-09-12 | 2007-03-22 | Fresenius Medical Care Deutschland Gmbh | Hohlfasermembrantrennvorrichtung |
NZ591443A (en) * | 2005-09-22 | 2013-04-26 | Intermune Inc | Granule formation of pirfenidone and pharmaceutically acceptable excipients |
US7514229B2 (en) | 2005-09-29 | 2009-04-07 | The Board Of Trustees Of The Leland Stanford Junior University | Methods for diagnosing and evaluating treatment of blood disorders |
EP1931709B1 (en) | 2005-10-03 | 2016-12-07 | Xencor, Inc. | Fc variants with optimized fc receptor binding properties |
SI1945665T1 (sl) | 2005-10-21 | 2012-03-30 | Genzyme Corp | Terapevtska sredstva na osnovi protiteles s povečano ADCC aktivnostjo |
US20080206246A1 (en) | 2006-04-05 | 2008-08-28 | Ravetch Jeffrey V | Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods |
SG10201600950TA (en) | 2005-11-28 | 2016-03-30 | Genmab As | Recombinant monovalent antibodies and methods for production thereof |
CN101336299B (zh) | 2005-12-02 | 2012-12-05 | 斯克里普斯研究学院 | 血管生成性酪氨酰tRNA合成酶组合物和方法 |
US8014957B2 (en) | 2005-12-15 | 2011-09-06 | Fred Hutchinson Cancer Research Center | Genes associated with progression and response in chronic myeloid leukemia and uses thereof |
US20090305973A1 (en) | 2006-01-23 | 2009-12-10 | Sung-Hoon Kim | Novel peptide and use thereof |
CA2641880C (en) | 2006-02-10 | 2014-09-09 | Summit Corporation Plc | Treatment of duchenne muscular dystrophy |
EP1999259B1 (en) | 2006-03-03 | 2014-06-25 | California Institute of Technology | Site-specific incorporation of amino acids into molecules |
JP5242382B2 (ja) | 2006-04-14 | 2013-07-24 | 株式会社医学生物学研究所 | エフェクター機能を有するポリペプチド変異体 |
CA2653752A1 (en) | 2006-05-26 | 2007-12-06 | Vickery Laurence Arcus | Ob fold domains |
WO2008007818A1 (en) | 2006-07-13 | 2008-01-17 | Seoul National University Industry Foundation | Novel use of aimp1 for controlling glucose level |
US20100120627A1 (en) | 2006-08-02 | 2010-05-13 | Abdelmajid Belouchi | Genemap of the human genes associated with psoriasis |
EP2057465A4 (en) | 2006-08-09 | 2010-04-21 | Homestead Clinical Corp | SPECIFIC ORGAN PROTEINS AND METHODS OF USE |
CA2662752C (en) | 2006-09-08 | 2016-04-12 | Ambrx, Inc. | Site specific incorporation of non-natural amino acids by vertebrate cells |
CN106008699A (zh) | 2006-09-08 | 2016-10-12 | Ambrx公司 | 经修饰的人类血浆多肽或Fc骨架和其用途 |
CA2665826A1 (en) | 2006-10-16 | 2008-04-24 | Medimmune, Llc | Molecules with reduced half-lives, compositions and uses thereof |
EP2395022A1 (en) | 2006-11-17 | 2011-12-14 | Novartis AG | Lingo binding molecules and pharmaceutical use thereof |
CA2676640A1 (en) | 2007-02-01 | 2008-08-07 | Imagene Co., Ltd. | Novel polypeptide having anti-tumor activity |
US20100184959A1 (en) | 2007-03-19 | 2010-07-22 | Medimmune Limited | Polypeptide Variants |
CN101688230A (zh) | 2007-04-27 | 2010-03-31 | 伊玛吉恩有限公司 | 免疫调节剂的筛选方法 |
CA2690281A1 (en) | 2007-05-11 | 2008-11-20 | The Johns Hopkins University | Biomarkers for melanoma |
ES2469743T3 (es) | 2007-05-17 | 2014-06-18 | Genentech, Inc. | Inhibición de la metástasis tumoral por anticuerpos anti neuropilina 2 |
EP2158215B1 (en) | 2007-05-17 | 2015-04-22 | Genentech, Inc. | Crystal structures of neuropilin fragments and neuropilin-antibody complexes |
EP2162472B1 (en) | 2007-05-30 | 2013-02-27 | Postech Academy-Industry- Foundation | Immunoglobulin fusion proteins |
US20100016215A1 (en) | 2007-06-29 | 2010-01-21 | Avi Biopharma, Inc. | Compound and method for treating myotonic dystrophy |
EP2167135A2 (en) | 2007-07-12 | 2010-03-31 | Prosensa Technologies B.V. | Molecules for targeting compounds to various selected organs, tissues or tumor cells |
JP2009017840A (ja) | 2007-07-13 | 2009-01-29 | Japan Agengy For Marine-Earth Science & Technology | 外来遺伝子を細胞に安定に保持する方法 |
PL2197900T3 (pl) | 2007-08-24 | 2012-12-31 | Univ Wuerzburg J Maximilians | Zmutowane podwójnie cyklizowane peptydy receptorowe hamujące przeciwciała przeciwko beta 1-adrenoreceptorowi |
CA2698812A1 (en) | 2007-09-14 | 2009-03-19 | Nitto Denko Corporation | Drug carriers |
WO2009097017A2 (en) | 2007-09-18 | 2009-08-06 | The Jackson Laboratory | Antibodies and fc fusion protein modifications with enhanced persistence or pharmacokinetic stability in vivo and methods of use thereof |
RU2010121967A (ru) | 2007-10-31 | 2011-12-10 | Медиммун, Ллк (Us) | Белковые каркасные структуры |
US20090148887A1 (en) | 2007-11-02 | 2009-06-11 | The Scripps Research Institute | Genetically encoded boronate amino acid |
KR101067816B1 (ko) | 2007-11-09 | 2011-09-27 | (주)네오믹스 | Aimp2-dx2의 억제제를 유효성분으로 포함하는 염증성질환 예방 및 치료용 조성물 |
JP5512533B2 (ja) | 2007-11-15 | 2014-06-04 | サレプタ セラピューティクス, インコーポレイテッド | モルホリノオリゴマーの合成方法 |
JP5749494B2 (ja) | 2008-01-02 | 2015-07-15 | テクミラ ファーマシューティカルズ コーポレイション | 核酸の送達のための改善された組成物および方法 |
JP5585904B2 (ja) | 2008-02-08 | 2014-09-10 | 独立行政法人理化学研究所 | アミノアシルtRNA合成酵素活性を有するポリペプチド及びその利用 |
WO2009114623A2 (en) | 2008-03-11 | 2009-09-17 | University Of North Carolina At Chapel Hill | Angiostatic compositions comprising truncated tyrosyl-trna synthetase polypeptides and methods of using same |
US20110269814A1 (en) | 2008-03-26 | 2011-11-03 | Alnylam Pharamaceuticals, Inc. | 2'-f modified rna interference agents |
CA2725637A1 (en) * | 2008-05-27 | 2009-12-03 | Pluristem Ltd. | Methods of treating inflammatory colon diseases |
ES2622444T3 (es) | 2008-06-11 | 2017-07-06 | Atyr Pharma, Inc. | Actividad trombopoyética de polipéptidos tirosil-ARNt sintetasa |
CN102159708B (zh) | 2008-06-26 | 2016-08-31 | Atyr医药公司 | 包含具有非常规生物活性的甘氨酰-tRNA合成酶的组合物和方法 |
AU2008360729A1 (en) | 2008-08-18 | 2010-02-25 | Seoul National University Industry Foundation | Method for controlling cancer metastasis or cancer cell migration by modulating the cellular level of lysyl tRNA synthetase |
FR2935385B1 (fr) | 2008-08-27 | 2013-04-19 | Diaclone | Induction de l'expression de p53 par neutralisation de la neuropiline-2 pour le traitement des cancers |
KR101067817B1 (ko) | 2008-10-10 | 2011-09-27 | 서울대학교산학협력단 | Aimp1 폴리펩티드에 대한 항체를 포함하는 관절염 진단용 조성물 |
WO2010041913A2 (ko) | 2008-10-10 | 2010-04-15 | 서울대학교산학협력단 | Grs 단백질 또는 이의 단편의 신규한 용도 |
KR101067815B1 (ko) | 2009-02-05 | 2011-09-27 | 서울대학교산학협력단 | 제1형 당뇨병의 신규한 진단 마커 |
WO2010096170A2 (en) | 2009-02-19 | 2010-08-26 | President And Fellows Of Harvard College | Inhibition of trna synthetases and therapeutic applications thereof |
WO2010099477A2 (en) | 2009-02-27 | 2010-09-02 | Atyr Pharma, Inc. | Polypeptide structural motifs associated with cell signaling activity |
EP2408905B1 (en) | 2009-03-16 | 2017-05-10 | Pangu Biopharma Limited | Compositions and methods comprising histidyl-trna synthetase splice variants having non-canonical biological activities |
ES2560674T3 (es) | 2009-03-31 | 2016-02-22 | Atyr Pharma, Inc. | Composiciones y procedimientos que comprenden aspartil-ARNt sintetasas con actividades biológicas no canónicas |
CA2758189C (en) | 2009-04-10 | 2020-12-29 | Association Institut De Myologie | Tricyclo-dna antisense oligonucleotides, compositions, and methods for the treatment of disease |
WO2010120820A1 (en) | 2009-04-13 | 2010-10-21 | Isis Pharmaceuticals, Inc. | Compositions and methods for modulation of smn2 splicing |
LT3449926T (lt) | 2009-06-17 | 2020-01-27 | Biogen Ma Inc. | Kompozicijos ir smn2 splaisingo subjekte moduliavimo būdai |
US20110064670A1 (en) | 2009-09-11 | 2011-03-17 | Genentech, Inc. | Method to identify a patient with an increased likelihood of responding to an anti-cancer agent |
ES2948612T3 (es) | 2009-09-21 | 2023-09-14 | Takeda Pharmaceuticals Co | Formulaciones de ADAMTS13 líquidas y liofilizadas estabilizadas |
WO2011044158A1 (en) | 2009-10-09 | 2011-04-14 | New York Blood Center, Inc. | Immunopotentiator-linked oligomeric influenza immunogenic compositions |
WO2011055888A1 (en) | 2009-11-06 | 2011-05-12 | Chung-Ang University Industry-Academy Cooperation Foundtion | Nanoparticle-based gene delivery systems |
US8828395B2 (en) | 2009-12-11 | 2014-09-09 | Atyr Pharma, Inc. | Antibodies that bind tyrosyl-tRNA synthetases |
US20110150885A1 (en) | 2009-12-11 | 2011-06-23 | Atyr Pharma, Inc. | Aminoacyl trna synthetases for modulating hematopoiesis |
ES2535951T3 (es) | 2009-12-11 | 2015-05-19 | Atyr Pharma, Inc. | Histidil ARNt sintetasas para reducir la inflamación |
WO2011097031A2 (en) | 2010-02-04 | 2011-08-11 | The Scripps Research Institute | Monomeric forms of human aminoacyl-trna synthetases having non-canonical biological activities |
WO2011112915A2 (en) | 2010-03-11 | 2011-09-15 | Health Research, Inc. | Methods and compositions containing fc fusiong proteins for enhancing immune responses |
EP2563380B1 (en) | 2010-04-26 | 2018-05-30 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of cysteinyl-trna synthetase |
WO2011139801A2 (en) | 2010-04-27 | 2011-11-10 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of threonyl trna synthetases |
AU2011248614B2 (en) | 2010-04-27 | 2017-02-16 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of isoleucyl tRNA synthetases |
US8802642B2 (en) | 2010-04-28 | 2014-08-12 | Iowa State University Research Foundation, Inc. | Spinal muscular atrophy treatment via targeting SMN2 catalytic core |
EP2563911B1 (en) | 2010-04-28 | 2021-07-21 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of alanyl trna synthetases |
CA2797393C (en) | 2010-04-29 | 2020-03-10 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of valyl trna synthetases |
US9068177B2 (en) | 2010-04-29 | 2015-06-30 | Atyr Pharma, Inc | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutaminyl-tRNA synthetases |
AU2011248490B2 (en) | 2010-04-29 | 2016-11-10 | Pangu Biopharma Limited | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Asparaginyl tRNA synthetases |
CN103140233B (zh) | 2010-05-03 | 2017-04-05 | Atyr 医药公司 | 与甲硫氨酰‑tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的发现 |
EP2566515B1 (en) | 2010-05-03 | 2017-08-02 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of arginyl-trna synthetases |
CA2797799C (en) | 2010-05-03 | 2020-12-08 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of seryl-trna synthetases |
US9034321B2 (en) | 2010-05-03 | 2015-05-19 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-alpha-tRNA synthetases |
US9062301B2 (en) | 2010-05-04 | 2015-06-23 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glutamyl-prolyl-tRNA synthetases |
CA2798139C (en) | 2010-05-04 | 2019-09-24 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of p38 multi-trna synthetase complex |
EP2568996B1 (en) | 2010-05-14 | 2017-10-04 | aTyr Pharma, Inc. | Therapeutic, diagnostic, and antibody compositions related to protein fragments of phenylalanyl-beta-trna synthetases |
CA2799480C (en) | 2010-05-17 | 2020-12-15 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of leucyl-trna synthetases |
CN103118694B (zh) | 2010-06-01 | 2016-08-03 | Atyr医药公司 | 与赖氨酰-tRNA合成酶的蛋白片段相关的治疗、诊断和抗体组合物的发现 |
KR101209266B1 (ko) | 2010-06-30 | 2012-12-06 | 한국과학기술연구원 | 생분해성 및 온도 감응성 폴리포스파젠계 자성 고분자, 그의 제조 방법 및 용도 |
EP2593125B1 (en) | 2010-07-12 | 2017-11-01 | aTyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-trna synthetases |
US8999321B2 (en) | 2010-07-12 | 2015-04-07 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of glycyl-tRNA synthetases |
KR20180059575A (ko) | 2010-07-12 | 2018-06-04 | 에이티와이알 파마, 인코포레이티드 | 아스파르틸trna 합성효소의 단백질 단편에 관련된 치료적, 진단적, 및 항체 조성물의 혁신적 발견 |
ES2653718T3 (es) | 2010-07-12 | 2018-02-08 | Atyr Pharma, Inc. | Descubrimiento innovador de composiciones terapéuticas, de diagnóstico y de anticuerpos relacionadas con fragmentos de proteínas de histidil-ARNt sintetasas |
EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
EP2608801B1 (en) | 2010-08-25 | 2019-08-21 | aTyr Pharma, Inc. | INNOVATIVE DISCOVERY OF THERAPEUTIC, DIAGNOSTIC, AND ANTIBODY COMPOSITIONS RELATED TO PROTEIN FRAGMENTS OF TYROSYL-tRNA SYNTHETASES |
JP5831455B2 (ja) | 2010-09-30 | 2015-12-09 | 日本新薬株式会社 | モルホリノ核酸誘導体 |
CA2812795C (en) | 2010-10-06 | 2021-08-31 | Atyr Pharma, Inc. | Innovative discovery of therapeutic, diagnostic, and antibody compositions related protein fragments of tryptophanyl trna synthetases |
KR101308591B1 (ko) | 2010-12-30 | 2013-09-13 | 주식회사 삼양바이오팜 | 양이온성 지질을 포함하는 음이온성 약물 전달체 및 그 제조방법 |
EP3679933A1 (en) | 2011-04-29 | 2020-07-15 | Selecta Biosciences, Inc. | Tolerogenic synthetic nanocarriers to reduce immune responses to therapeutic proteins |
US8691750B2 (en) | 2011-05-17 | 2014-04-08 | Axolabs Gmbh | Lipids and compositions for intracellular delivery of biologically active compounds |
WO2012158945A2 (en) | 2011-05-19 | 2012-11-22 | The Scripps Research Institute | Compositions and methods for treating charcot-marie-tooth diseases and related neuronal diseases |
US9714419B2 (en) | 2011-08-09 | 2017-07-25 | Atyr Pharma, Inc. | PEGylated tyrosyl-tRNA synthetase polypeptides |
US20130058894A1 (en) | 2011-09-06 | 2013-03-07 | Selecta Biosciences, Inc. | Therapeutic protein-specific induced tolerogenic dendritic cells and methods of use |
PT2581448E (pt) | 2011-10-13 | 2015-05-21 | Institut National De La Santé Et De La Rech Médicale (Inserm) | Dna triciclo-fosforotioato |
KR101383324B1 (ko) | 2011-11-10 | 2014-04-28 | 주식회사 종근당 | 신규한 유전자 전달용 조성물 |
CN111808135A (zh) | 2011-11-18 | 2020-10-23 | 萨勒普塔医疗公司 | 功能改性的寡核苷酸及其亚单元 |
WO2013086228A1 (en) | 2011-12-06 | 2013-06-13 | Atyr Pharma, Inc. | Pegylated aspartyl-trna synthetase polypeptides |
WO2013086216A1 (en) | 2011-12-06 | 2013-06-13 | Atyr Pharma, Inc. | Improved aspartyl-trna synthetases |
RS63244B1 (sr) | 2011-12-16 | 2022-06-30 | Modernatx Inc | Kompozicije modifikovane mrna |
WO2013115926A2 (en) | 2011-12-29 | 2013-08-08 | Atyr Pharma, Inc. | Aspartyl-trna synthetase-fc conjugates |
EP2806900B1 (en) | 2012-01-27 | 2021-12-15 | BioMarin Technologies B.V. | Rna modulating oligonucleotides with improved characteristics for the treatment of duchenne and becker muscular dystrophy |
US9878056B2 (en) | 2012-04-02 | 2018-01-30 | Modernatx, Inc. | Modified polynucleotides for the production of cosmetic proteins and peptides |
US20140066321A1 (en) | 2012-07-23 | 2014-03-06 | Pangu Biopharma Limited | Structures of human histidyl-trna synthetase and methods of use |
CA2884870C (en) | 2012-08-13 | 2022-03-29 | Massachusetts Institute Of Technology | Amine-containing lipidoids and uses thereof |
LT2922554T (lt) | 2012-11-26 | 2022-06-27 | Modernatx, Inc. | Terminaliai modifikuota rnr |
KR20150077770A (ko) | 2013-12-30 | 2015-07-08 | 재단법인 의약바이오컨버젼스연구단 | 항 hrs 모노클로날 항체 및 이의 용도 |
US9209965B2 (en) | 2014-01-14 | 2015-12-08 | Microsemi Semiconductor Ulc | Network interface with clock recovery module on line card |
EP3148564B1 (en) | 2014-06-02 | 2020-01-08 | Children's Medical Center Corporation | Methods and compositions for immunomodulation |
US20160175458A1 (en) * | 2014-12-19 | 2016-06-23 | Alkermes, Inc. | Single chain fc fusion proteins |
US11421016B2 (en) | 2015-04-23 | 2022-08-23 | Nantomics Llc | Cancer neoepitopes |
TW201825118A (zh) | 2016-11-30 | 2018-07-16 | 美商艾堤爾製藥公司 | 抗-hrs抗體及用於治療癌症之組合療法 |
CN110536694A (zh) | 2017-04-20 | 2019-12-03 | Atyr 医药公司 | 用于治疗肺部炎症的组合物和方法 |
AU2019247511A1 (en) | 2018-04-06 | 2020-10-22 | Atyr Pharma, Inc. | Compositions and methods comprising anti-NRP2 antibodies |
JP7490925B2 (ja) | 2018-07-26 | 2024-05-28 | エータイアー ファーマ, インコーポレイテッド | Nrp2関連疾患を治療するための組成物および方法 |
-
2018
- 2018-04-19 CN CN201880026073.4A patent/CN110536694A/zh active Pending
- 2018-04-19 WO PCT/US2018/028417 patent/WO2018195338A1/en unknown
- 2018-04-19 AU AU2018256435A patent/AU2018256435A1/en active Pending
- 2018-04-19 EP EP18787408.6A patent/EP3612215A4/en active Pending
- 2018-04-19 US US16/499,979 patent/US11767520B2/en active Active
- 2018-04-19 CA CA3060514A patent/CA3060514A1/en active Pending
- 2018-04-19 JP JP2019556875A patent/JP2020517638A/ja active Pending
-
2023
- 2023-01-30 JP JP2023011912A patent/JP2023052761A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2015513534A (ja) * | 2012-02-16 | 2015-05-14 | エータイアー ファーマ, インコーポレイテッド | 自己免疫および炎症疾患を処置するためのヒスチジルtRNA合成酵素 |
JP2016519569A (ja) * | 2013-03-15 | 2016-07-07 | エータイアー ファーマ, インコーポレイテッド | ヒスチジル−tRNAシンテターゼFcコンジュゲート |
Non-Patent Citations (1)
Title |
---|
日内会誌, vol. 105, JPN6022012759, 2016, pages 970 - 976, ISSN: 0004739701 * |
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