JP5864472B2 - 患者に合わせてカスタマイズした治療レジメン - Google Patents
患者に合わせてカスタマイズした治療レジメン Download PDFInfo
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Description
米国特許法§119(e)の下、本願は、2006年5月2日に出願された米国仮特許出願第60/746,250号の出願日の優先権を主張し、この仮出願の開示は、本明細書中に参考として援用される。
(発明の分野)
本発明は、全般的には医療に関し、特に治療レジメンに関する。さらに具体的には、本発明は、処置プロトコルの進行に伴い調整することができる、個々の患者に合わせてカスタマイズした治療レジメンに従い、患者を処置する方法およびシステムに関する。
処方薬は、たとえば、指示に従って適切に服用すると、多くの患者にとって有効な治療薬である。しかしながら、大きな患者集団から得た臨床データを用いて策定される事前設定の服薬スケジュールに従って、処方薬を服用するのが一般的である。そのため、患者がある処方薬で効果が得られると医療従事者が判断する場合、その医療従事者は通常、1日1回の服用、12時間おきに1日2回の服用など、標準的な投与プロトコルを患者に与える。
本発明は、個々の患者に合わせてカスタマイズする治療レジメンの開発を初めて可能にする。このレジメンでは、薬学的介入などの治療的介入の用量が、個々の患者に合わせて具体的に工夫され、患者が服用している他の薬剤の影響、患者の日常生活の予定および同種のものなど、様々な患者別の基準に基づき用量を決定することができる。本発明はまた、たとえば、前の処置に対する患者の反応の程度、前の服薬スケジュールに対する患者の遵守の程度など、個々の患者に特有の相違を勘案して、経時的に個々の治療レジメンを修正できるようにする。
他に記載がない限り、本明細書で使用するすべての技術用語および科学用語は、本発明が属する技術分野の当業者が一般に理解しているのと同じ意味を有する。しかしながら、具体的に参照しやすいように、以下に一部の要素を定義する。
本発明は、例えば、以下を提供する。
(項目1)
ある症候について患者を処置する方法であって:
(a)上記患者への医療用組成物の投与に関する検証的データを取得すること:
(i)上記患者は、上記症候を処置するための治療レジメンを受けており;
(ii)上記検証的データが、第1の装置により作成され、第2の装置に送信され、上記第1の装置および上記第2の装置はともに上記患者の身体に装着されている;
(b)上記検証的データを評価し、上記治療レジメンの変更がいつ望ましいのかを判定すること;および
(c)変更が望ましいと判定した場合、上記治療レジメンを調節すること
を含む、方法。
(項目2)
上記検証的データは、上記第2の装置によって記録される、項目1に記載の方法。
(項目3)
上記第1の装置および上記第2の装置は、上記身体に電気的に接続されている、項目1に記載の方法。
(項目4)
上記検証的データは、上記第1装置と上記第2の装置の間に電流を設けることで、上記第1の装置から上記第2の装置に送信される、項目1に記載の方法。
(項目5)
上記電流は、上記第1装置、上記第2の装置および上記身体の間に限定される、項目4に記載の方法。
(項目6)
上記電流は、上記第1装置と上記第2の装置との間に限定され、かつ、上記第1装置および上記第2の装置はそれぞれ、上記患者の外部の導体または接地用導体に容量結合されている、項目4に記載の方法。
(項目7)
上記検証的データは、自動的に取得される、項目1に記載の方法。
(項目8)
上記第1装置と上記第2の装置とは、異なるタイプの装置である、項目1に記載の方法。
(項目9)
上記第1の装置は、活性剤を含む、項目8に記載の方法。
(項目10)
上記第2の装置は、活性剤を含まない、項目9に記載の方法。
(項目11)
上記方法は、検証的データの第2のセットを第3の装置から上記第2の装置に送信することをさらに含む、項目10に記載の方法。
(項目12)
上記第3の装置は、活性剤を含む、項目11に記載の方法
(項目13)
上記医療用組成物は、薬物、ビタミン、生理食塩水、注入剤、透析液および制酸薬からなる群から選択される、項目1に記載の方法。
(項目14)
上記第1の装置は、医薬組成物に取り付けられているアイデンティファイアを含み、上記アイデンティファイアは、上記患者の標的生理学的部位との接触時に上記検証的データを作成する、項目1に記載の方法。
(項目15)
上記評価は、上記データを決定支援ツールに入力することと、上記治療レジメンの(is)変更が望ましいかどうかに関する上記検証的データに基づいた推奨を上記決定支援ツールから取得することとを含む、項目1に記載の方法。
(項目16)
上記評価は、上記患者から取得した生理学的データを検討することをさらに含む、項目15に記載の方法。
(項目17)
上記評価は、上記患者から取得した生活習慣情報を検討することをさらに含む、項目15に記載の方法。
(項目18)
上記方法は、上記患者から得た上記検証的データを第2の場所に送付することをさらに含む、項目1に記載の方法。
(項目19)
上記第2の場所は、離れた場所である、項目18に記載の方法。
(項目20)
上記方法は、推奨を検討して上記治療レジメンの変更を行うべきかどうかを判定する医療従事者に上記推奨を提供することをさらに含む、項目15に記載の方法。
(項目21)
上記医療従事者は、上記推奨を踏まえて上記治療レジメンを調節し、調節した治療レジメンを上記患者に通信する、項目20に記載の方法。
(項目22)
上記調節した治療レジメンは、医薬品投与レジメンの変更を含む、項目21に記載の方法。
(項目23)
上記医薬品投与レジメンの上記変更は、医薬品の量の変更を含む、項目22に記載の方法。
(項目24)
上記医薬品投与レジメンの上記変更は、上記患者に投与される医薬品の少なくとも1つのタイプの変更を含む、項目22に記載の方法。
(項目25)
上記方法は、1種または複数種の活性剤を含む物理的な医薬品製剤を調製することと、上記物理的な医薬品製剤を上記患者に送付することとをさらに含む、項目20に記載の方法。
(項目26)
上記物理的な医薬品製剤は、2種以上の異なる組成物を含む、項目25に記載の方法。
(項目27)
上記物理的な医薬品製剤は、2種以上の活性剤を含む組成物を含む、項目25に記載の方法。
(項目28)
上記組成物は、上記治療レジメンの上記調節を踏まえて作製される、項目27に記載の方法。
(項目29)
上記物理的な医薬品製剤の上記組成物は、用法用量コンプライアンスのアイデンティファイアを含む、項目25に記載の方法。
(項目30)
ある症候について患者を処置するシステムであって:
(a)患者への医療用組成物の投与に関する検証的データを受け取る入力マネージャ;
(b)受け取った検証的データに基づき治療レジメンを検討し、治療レジメンの変更が望ましいかどうかを判定し、上記判定に基づく推奨を提供するように構成された治療レジメン評価装置を含む処理モジュール;および
(c)上記推奨をユーザに提供する出力マネージャを含む、システム。
(項目31)
ある症候について患者を処置する方法であって:
上記患者から受け取った検証的データを項目30に記載のシステムに入力すること;および
上記システムから推奨を取得し、上記推奨に従って上記患者を処置すること
を含む、方法。
(項目32)
コンピュータプログラムが格納されたコンピュータ読み取り可能な記憶媒体を含む、コンピュータプログラム製品であって、上記コンピュータプログラムは、コンピュータ上にロードされると、上記コンピュータを以下:
(a)患者への医療用組成物の投与に関する検証的データを受け取る;
(b)上記検証的データに照らして上記患者の治療レジメンを検討し、治療レジメンの変更が望ましいかどうかを判定し、上記判定に基づく推奨を提供する;そして
(c)上記推奨をユーザに提供する
ように動作させる、コンピュータプログラム製品。
本発明は、たとえば、個々の患者に合わせて治療レジメンをカスタマイズすることを可能にする、臨床医にとって治療施設における重要な新しいツールを提供する。本発明は、実際の用法用量情報、すなわち、医療用組成物の患者への投与に関する検証的データに基づく治療レジメンの開発および修正を可能にする。そうした情報には、生活習慣情報などの投与量に関する追加情報を補足してもよい。このように、臨床医は、個々の患者に合わせてカスタマイズした最適な治療レジメンを処方することができる。たとえば、実際のコンプライアンスデータなど多くの因子に基づき、強心薬を最も適切な投与量に調節し、特に心筋の疲弊および反跳現象などの副作用を最低限にとどめ、1人1人の患者の投与量およびタイミングの両方を最適化することができる。
一面において、本発明は、ある症候について患者を処置する方法であって、その症候が、何らかの医療用組成物を患者に投与する薬学的介入、栄養学的/ビタミン介入、液体による介入(透析など)など、ある種の医療介入で効果が得られる症候である、方法を提供する。「医療用組成物」という語については広義に用いており、何らかの形での患者の健康の改善を最終目標として患者に投与してもよい種々様々なタイプの組成物を指す。医療用組成物の例として、医薬品または薬物(たとえば、処方箋または店頭で入手できるもの)、ビタミン剤および栄養補助剤、たとえば、生理食塩水、透析液などの注入剤のような治療液、制酸薬などがあるが、これに限定されるものではない。次に、説明の都合上、主に医薬品組成物の観点から、本発明をさらに記載する。しかしながら、本発明をそれに限定するものではない。
さらに、当該発明は、たとえば、上記のようなデータ評価ステップなど、この方法の態様の1つ(on)または複数の実施に用いることができるシステムを提供する。ある実施形態では、システムは、たとえば、データベースにアクセスし、適切なアルゴリズムを実行するプロセッサの形態の決定ツールを含む。決定ツールは、入力データを検討し、変更が望ましいか否かの推奨を提供する治療レジメン評価装置として機能するデータ評価モジュールの形態をとっても構わない。
And System For Monitoring And Treating Hemodynamic Parameters」という発明の名称で米国特許出願公開第2004/0193021号として公開された米国特許出願第10/734490号;「Methods And Apparatus For Tissue Activation And Monitoring」という発明の名称で米国特許出願公開第2006/0058588号として公開された米国特許出願第11/219,305号;「Implantable Addressable Segmented Electrodes」を発明の名称とする国際出願PCT/US2005/046815号;「Implantable Accelerometer−Based Cardiac Wall Position Detector」を発明の名称とする米国特許出願第11/324,196号;「Method and Apparatus for Enhancing Cardiac Pacing」を発明の名称とする米国特許出願第10/764,429号、「Methods and Systems for Measuring Cardiac Parameters」を発明の名称とする米国特許出願第10/764,127号、「Method and System for Remote Hemodynamic Monitoring」を発明の名称とする米国特許出願第10/764,125号;「Implantable Hermetically Sealed Structures」を発明の名称とする国際出願PCT/US2005/046815号;「Fiberoptic Tissue Motion Sensor」を発明の名称とする米国特許出願第11/368,259号;「Implantable Pressure Sensors」を発明の名称とする国際出願PCT/US2004/041430号;「Implantable Doppler Tomography
System」を発明の名称とし、米国特許仮出願第60/617,618号に対する優先権を主張する米国特許出願第11/249,152号;「Cardiac Motion Characterization by Strain Gauge」を発明の名称とする国際出願PCT/US05/39535号があるが、これに限定されるものではない。これらの出願については、参照によってその全体を本明細書に援用する。
図4に、特定の病状の患者の管理に用いることができる上記の方法およびシステムの具体的で代表的な実施形態を示す。患者410は、たとえば、心不全、高血圧など、種々の循環器の病状に悩んでいるかもしれない循環器患者である。患者410には、心血管医療装置420が埋め込まれている。420は、電気治療要素、センサ要素(以下に記載のセンサに限定されるものではない)および監視要素の1つまたは複数を含んでもよい。ある実施形態では、監視要素は、実際の用法用量情報を、アイデンティファイアを組み込んだ医薬組成物から取得し、格納し、送付するように構成されている。そうした組成物は、たとえば、2006年4月28日に出願され、2006年11月2日に国際公開第2006/116718号として公開された「Pharma Informatics System」を発明の名称とする国際出願PCT/US2006/016370号;さらには米国特許仮出願第60/866,581号;同第60/829,832号;同第60/887,780号;同第60/889,868号;同第60/889,870号;同第60/889,871号;同第60/894,171号および同第60/894,167号に記載されているようなスマート薬剤の追加の実施形態に記載されている。これらの出願の開示については、参照によって本明細書に援用する。さらに、患者410は、処方された医薬品投与レジメンに従って複数の異なる医薬品430を服用している。医薬品430は、アイデンティファイアを組み込んだ医薬品であり、たとえば、標的生理学的部位に接触すると信号を発する識別IC(integrated circuit)チップを含む。そうした医薬品は、2006年4月28日に出願され、2006年11月2日に国際公開第2006/116718号として公開された「Pharma Informatics System」を発明の名称とする国際出願PCT/US2006/016370号;さらには米国特許仮出願第60/866,581号;同第60/829,832号;同第60/887,780号;同第60/889,868号;同第60/889,870号;同第60/889,871号;同第60/894,171号および同第60/894,167号に記載されているようなスマート薬剤の追加の実施形態に記載されている。これらの出願の開示については、参照によって本明細書に援用する。また、図4に示すモデム440は、取得した投与情報を、たとえば、診療所のような患者410から離れた場所にリレーする役割を果たす。モデル440は、たとえば、ベッドサイドなど自宅内の場所にあって、たとえば、無線接続によりインターネットに接続されていてもよい。そのため、たとえば、患者がベッドで就寝していると予想される午前3時など、患者がモデムの近くにいると予想される事前に設定した日常の時間に、モデムによりデータをインターネットおよびその指定アドレスに自動的にアップロードすることができる。言うまでもなく、モデム440の代わりにネットワーク中継局など任意の簡便な通信要素を用いても構わない。注目すべき実施形態では、たとえば、ファルマインフォマティクス対応投与製剤のアイデンティファイアが発する信号により用法用量を検出するように構成された埋め込み型または局所的信号受信機要素(健康管理コンパニオン装置など)を介して430、420および440の各要素が通信を行う。かかる信号受信器要素は、「Signal Receivers for Pharma−Informatics Systems」を発明の名称とする係属中の米国特許仮出願第60/887,780号に記載されており、その開示については、参照によって本明細書に援用する。
さらに、本発明は、たとえば、コンピュータプログラム製品の形で、この方法の実施に使用するプログラミングも提供する。本発明によるプログラミングを、コンピュータ読み取り可能な媒体、たとえば、コンピュータによる読み取りおよび直接アクセスが可能な任意の媒体に記録してもよい。そうした媒体として、フロッピー(登録商標)ディスク、ハードディスク記憶媒体および磁気テープなどの磁気記憶媒体;CD−ROMなどの光学記憶媒体;RAM、ROM、フラッシュドライブ、マイクロドライブなどの電気記憶媒体;および磁気/光学記憶媒体などのこれらのカテゴリの複合型があるが、これに限定されるものではない。当業者であれば、任意のコンピュータ読み取り可能な媒体を用いて、上記の方法を実施するための本プログラミング/アルゴリズムの記録を含む製造物を製造する方法を容易に理解するであろう。
本発明は、治療施設における重要な新規のツールを臨床医に提供する。すなわち、個々の患者に合わせて治療レジメンをカスタマイズすることが可能になる。本発明により、実際の用法用量情報に基づいた治療レジメンの開発および修正が可能になる。そうした用量用法情報には、追加の生理学的パラメータ、生活習慣情報などの投与量に関する追加情報を補足することができる。こうして、臨床医は、個々の患者に合わせてカスタマイズした最適な治療レジメンを処方することができる。本発明の実施による多くの利点として、たとえば、ばらつきのあるコンプライアンス環境において標準化された治療レジメンの使用に起因し得るような医療ミスの減少;ミスの減少に伴う負担の軽減;その他のうち1つまたは複数が挙げられるが、これに限定されるものではない。
また、当該方法を実施するためのキットを提供する。キットは、たとえば、スマートパッケージ薬剤、スマート医薬組成物、受信機およびモデム、コンピュータプログラミングなど、上記のようなシステムの1つまたは複数の構成要素を含んでもよい。
Claims (31)
- ある症候の処置のための治療レジメンを受けている患者に対して、前記治療レジメンに対する変更がいつ必要であるかを判定するためのシステムであって、前記システムは:
(a)前記患者への医療用組成物の投与に関する検証的データを生成する第1の装置であって、前記検証的データは、前記患者による医療用組成物の実際の摂取を表し、前記第1の装置は、前記患者によって摂取され、前記第1の装置は、前記患者の身体内で起こる電源の完了により標的身体場所との接触時に活性化され、前記第1の装置は、前記患者の身体に電気的に接続されており、前記検証的データは、前記電源が完了した後に前記身体を導電媒体として用いて前記第1の装置により送信される、第1の装置;
(b)前記検証的データを記録するための第2の装置であって、前記第2の装置は、前記患者の身体に装着されており、前記第2の装置は、前記患者の前記身体の外部に電気的に接続されている、第2の装置;
(c)前記検証的データを取得するための手段であって、前記手段は、前記第1の装置と前記第2の装置との間の電流を含み、前記患者の前記身体は、前記電流が流れる導電媒体としての役目を果たす、手段;
(d)前記患者からの前記検証的データに加えて、生理学的データを取得するための手段;
(e)前記検証的データおよび前記生理学的データを評価し、前記治療レジメンの変更がいつ必要とされるかを判定するための手段であって、前記評価し、判定するための手段は、前記患者から取得された生理学的データを検討するための手段をさらに含み、前記評価し、判定するための手段は、前記データを決定支援ツールに入力するための手段を含む、手段;および
(f)前記検証的データおよび前記生理学的データの評価に基づいて、推奨を提供するための手段であって、推奨を提供するための手段は、前記治療レジメンの変更が必要であるかどうかに関する評価に基づいて、前記決定支援ツールから推奨を取得するための手段を含む、手段、
を含む、システム。 - 前記電流は、前記第1の装置、前記第2の装置および前記身体の間に限定される、請求項1に記載のシステム。
- 前記電流は、前記第1の装置と前記第2の装置との間に限定され、かつ、前記第1の装置および前記第2の装置はそれぞれ、前記患者の外部の導体または接地用導体に容量結合されている、請求項1に記載のシステム。
- 前記検証的データは、自動的に取得される、請求項1に記載のシステム。
- 前記第1の装置と前記第2の装置とは、異なるタイプの装置である、請求項1に記載のシステム。
- 前記第1の装置は、活性剤を含む、請求項5に記載のシステム。
- 前記第2の装置は、活性剤を含まない、請求項6に記載のシステム。
- 前記システムは、検証的データの第2のセットを第3の装置から前記第2の装置に送信するための手段をさらに含む、請求項7に記載のシステム。
- 前記第3の装置は、活性剤を含む、請求項8に記載のシステム。
- 前記医療用組成物は、薬物、ビタミン、生理食塩水、注入剤、透析液および制酸薬からなる群から選択される、請求項1に記載のシステム。
- 前記第1の装置は、医薬組成物に取り付けられているアイデンティファイアを含み、前記アイデンティファイアは、前記患者の標的生理学的部位との接触時に前記検証的データを作成する、請求項1に記載のシステム。
- 前記評価し、判定するための手段は、前記データを決定支援ツールに入力するための手段を含み、推奨を提供するための手段は、前記治療レジメンの変更が必要であるかどうかに関する前記検証的データに基づいた推奨を前記決定支援ツールから取得するための手段を含む、請求項1に記載のシステム。
- 前記評価し、判定するための手段は、前記患者から取得した生活習慣情報を検討するための手段をさらに含む、請求項12に記載のシステム。
- 前記システムは、前記患者から得た前記検証的データを第2の場所に送付するための手段をさらに含む、請求項1に記載のシステム。
- 前記第2の場所は、離れた場所である、請求項14に記載のシステム。
- 前記推奨を提供するための手段は、前記推奨を検討して前記治療レジメンの変更を行うべきかどうかを判定する医療従事者に前記推奨を提供するための手段を含む、請求項12に記載のシステム。
- 調節した治療レジメンは、医薬品投与レジメンの変更を含む、請求項16に記載のシステム。
- 前記医薬品投与レジメンの前記変更は、医薬品の量の変更を含む、請求項17に記載のシステム。
- 前記医薬品投与レジメンの前記変更は、前記患者に投与される医薬品の少なくとも1つのタイプの変更を含む、請求項17に記載のシステム。
- 前記システムは、1種または複数種の活性剤を含む物理的な医薬品製剤を調製するための手段と、前記物理的な医薬品製剤を前記患者に送付するための手段とをさらに含む、請求項16に記載のシステム。
- 前記物理的な医薬品製剤は、2種以上の異なる組成物を含む、請求項20に記載のシステム。
- 前記物理的な医薬品製剤は、2種以上の活性剤を含む組成物を含む、請求項20に記載のシステム。
- 前記組成物は、前記治療レジメンの調節を踏まえて作製される、請求項22に記載のシステム。
- 前記物理的な医薬品製剤の前記組成物は、用法用量コンプライアンスのアイデンティファイアを含む、請求項20に記載のシステム。
- 前記評価し、判定するための手段は、最適化された治療レジメンを処方するために、生理学的反応に対し、薬剤送達、バッチ、投与を相関させるための手段をさらに含む、請求項1に記載のシステム。
- 前記生理学的データを取得するための手段は、前記患者の身体に装着された1つ以上のセンシング装置を含み、前記1つ以上のセンシング装置は、前記生理学的データを前記第2の装置に送信する、請求項1に記載のシステム。
- 前記1つ以上のセンシング装置は、前記身体に電気的に接続されており、前記1つ以上のセンシング装置と前記第2の装置との間に電流を設けることで、前記生理学的データを前記第2の装置に送信する、請求項26に記載のシステム。
- 前記第2の装置は、埋め込み型装置を含み、前記埋め込み型装置は、生理学的データを感知するためのセンサ要素と、前記第1の装置から受信された検証的データを取得し、格納し、送付するように構成されている監視要素とを含む、請求項1に記載のシステム。
- ある症候の処置のための治療レジメンを受けている患者に対して、前記治療レジメンに対する変更がいつ必要であるかを判定するためのシステムであって、前記システムは:
(a)患者への医療用組成物の投与に関する検証的データおよび生理学的データを受け取り、記録するための入力マネージャであって、前記検証的データは、前記患者による医療用組成物の実際の摂取を表し、前記検証的データは、前記患者によって摂取された第1の装置によって生成され、そして、前記第1の装置は、前記患者の身体内で起こる電源の完了により標的身体場所との接触時に活性化され、前記検証的データは、前記電源が完了した後に前記身体を導電媒体として用いて前記第1の装置により送信される、入力マネージャ;
(b)受け取った検証的データおよび生理学的データに基づき治療レジメンを検討するように構成された治療レジメン評価装置を含む処理モジュールであって、前記処理モジュールは、治療レジメンの変更が望ましいかどうかを判定し、前記判定に基づく推奨を提供する決定支援ツールをさらに含む、処理モジュール;および
(c)前記推奨を前記患者に提供する出力マネージャ
を含む、システム。 - ある症候について患者を処置するためのシステムであって、前記システムは:
前記患者から受け取った検証的データおよび生理学的データを請求項29に記載のシステムに入力するための手段
を含む、システム。 - コンピュータプログラムが格納された非一時性コンピュータ読み取り可能媒体であって、前記コンピュータプログラムは、コンピュータ上にロードされると、前記コンピュータを以下:
(a)患者への医療用組成物の投与に関する検証的データおよび生理学的データを受け取り、記録することであって、前記検証的データは、前記患者に対する医療用組成物の実際の摂取を表し、前記検証的データは、前記患者によって摂取される装置によって生成され、前記装置は、前記患者の身体内で起こる電源の完了により標的身体場所との接触時に活性化され、前記検証的データは、前記電源が完了した後に前記身体を導電媒体として用いて前記装置により送信される、こと;
(b)前記検証的データおよび前記生理学的データに照らして前記患者の治療レジメンを検討し、治療レジメンの変更が望ましいかどうかを判定し、前記判定に基づく推奨を提供することであって、前記検討は、決定支援ツールによって行われる、こと;および
(c)前記推奨を前記患者に提供すること
を行うように動作させる、非一時性コンピュータ読み取り可能媒体。
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- 2007-05-02 US US12/299,303 patent/US8956287B2/en active Active
- 2007-05-02 CN CNA2007800244235A patent/CN101496042A/zh active Pending
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Also Published As
Publication number | Publication date |
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CN105468895A (zh) | 2016-04-06 |
US20180089393A1 (en) | 2018-03-29 |
JP2013157026A (ja) | 2013-08-15 |
US8956287B2 (en) | 2015-02-17 |
CA2650920C (en) | 2016-10-18 |
WO2007130491A3 (en) | 2008-01-03 |
US20090076338A1 (en) | 2009-03-19 |
EP3367386A1 (en) | 2018-08-29 |
EP2013829A4 (en) | 2010-07-07 |
EP2013829A2 (en) | 2009-01-14 |
IL195052A (en) | 2016-08-31 |
JP2009544338A (ja) | 2009-12-17 |
US11928614B2 (en) | 2024-03-12 |
JP2015213775A (ja) | 2015-12-03 |
US20150193593A1 (en) | 2015-07-09 |
KR20090033837A (ko) | 2009-04-06 |
IL195052A0 (en) | 2009-08-03 |
KR20140018439A (ko) | 2014-02-12 |
CA2650920A1 (en) | 2007-11-15 |
CN101496042A (zh) | 2009-07-29 |
KR101568660B1 (ko) | 2015-11-12 |
WO2007130491A2 (en) | 2007-11-15 |
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