JP2019520184A - ステント付き心臓弁または生体補綴物の狭窄、閉塞、または石灰化を阻害するための方法 - Google Patents
ステント付き心臓弁または生体補綴物の狭窄、閉塞、または石灰化を阻害するための方法 Download PDFInfo
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- JP2019520184A JP2019520184A JP2019519962A JP2019519962A JP2019520184A JP 2019520184 A JP2019520184 A JP 2019520184A JP 2019519962 A JP2019519962 A JP 2019519962A JP 2019519962 A JP2019519962 A JP 2019519962A JP 2019520184 A JP2019520184 A JP 2019520184A
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Abstract
Description
本願は、2016年6月27日に出願した係属中の米国出願第15/193,208号の一部継続出願であり、米国出願第15/193,208号は、2014年4月28日に出願した米国出願第14/263,438号の分割出願であり、米国出願第14/263,438号は、2012年10月22日に出願し、放棄した米国出願第13/656,925号の一部継続出願である。そして本願は、2015年4月15日に出願した係属中の米国出願第14/687,479号の一部継続出願であり、米国出願第14/687,479号は、2014年4月28日に出願した係属中の米国出願第14/263,438号の一部継続出願であり、米国出願第14/263,438号は、2012年10月22日に出願し、放棄した米国出願第13/656,925号の一部継続出願である。そして本願は、2016年4月22日に出願した係属中の米国出願第15/031,532号の一部継続出願であり、米国出願第15/031,532号は、2014年10月22日に出願した国際特許出願第PCT/US2014/061745号に対する優先権を主張する371(c)国内段階出願である。これらの全体は、本明細書に参考として援用される。
本発明は、心臓弁および心臓弁補綴物の狭窄、閉塞、または石灰化を阻害するための方法に関する。
心臓は、律動的に収縮することによって生物の身体全体に血液を循環させる中空の筋性の器官である。哺乳動物において、心臓は、右心房および右心室が、左心房および左心室から完全に隔てられているように配置されている4つの部屋を有する。通常は、血液は、体静脈から右心房へと流れ、次いで、右心室へ、右心室から血液が肺へと肺動脈を介して駆出される。肺から戻ると、血液は左心房に入り、次いで左心室へと流れ、左心室から血液は体動脈へと駆出される。
本発明に従う心臓弁および方法は、従来の生体心臓弁、手術用心臓弁および機械式心臓弁に伴う欠点に対処する。
本発明は、弁の固定およびその後の弁移植の必要な患者における弁移植の後に、ソーイングリング12ありまたはなしのステント付きの生体心臓弁11または手術用置換弁10における弁尖および弁組織の狭窄、閉塞、および/または石灰化を阻害するための方法を提供する。本発明はまた、機械式心臓弁のソーイングリング18の周りのGortexライニング16を有する機械式心臓弁14の狭窄、閉塞、および/または石灰化を阻害するための方法を提供する。
http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedoc-uments/ucm071863.htmおよび米国特許第7,998,404号(発明の名称「Reduced temperature sterilization of stents」)を参照のこと)。
生体心臓弁を、eNOSアクチベーター、アトルバスタチン、抗増殖剤、パクリタキセル;細胞外生成のインヒビター、抗ファルネシルトランスフェラーゼインヒビター;および骨芽細胞生成のインヒビターであるビスホスホネート薬物を含む被覆組成物で被覆する。その生体心臓弁を、75歳の女性患者に移植する。その患者はまた、毎日経口でアトルバスタチン 80mgおよび皮下注射によって75mgの量の1ヶ月に1回のPCSK9インヒビターを含む脂質降下治療を受けて、彼女のLDLコレステロールレベルを350mg/mlから80mg/mlへと降下させる。彼女の心エコー図を検討すると、その移植した生体弁の弁尖およびステントは、平均勾配10mmHgおよび大動脈弁面積2.0cm2で、25年間の期間にわたって正常な血行力学を有する。その生体弁尖およびステントは、コンピューター断層撮影法および心エコー法によって診断される場合、石灰化のいかなる証拠をも示さない。
本願は、2017年5月22日に出願した国際特許出願第PCT/US2017/033792号の国内段階特許出願である。
特定の実施形態において、例えば、以下が提供される:
(項目1)
壁を有する脈管における移植後の心臓弁の狭窄、閉塞および/または石灰化を阻害するための方法であって、該方法は、
1またはこれより多くの弁尖を有する組織を含む生体心臓弁を提供することであって、該生体心臓弁は、罹患した生得の弁の置換のために弾性ステント上に取り付けられていること;
該生体心臓弁を組織固定液で処理すること;
該ステント、1もしくはこれより多くの弁尖、または両方を、1種またはこれより多くの治療剤を含む被覆組成物で被覆すること;
該生体弁を罹患した生得の弁の部位において該脈管に移植すること;
該被覆組成物を該弾性ステント、1種もしくはこれより多くの弁尖、または両方から溶出すること;
(i)循環する幹細胞における、(ii)該生体心臓弁組織を覆う内皮細胞ライニングにおける、または(iii)両方における、一酸化窒素生成を活性化することによって、該生体心臓弁、弾性ステントまたは両方の外部または近辺を循環する幹細胞の、該生体心臓弁への付着を防止することによって、該生体心臓弁の狭窄、閉塞および/または石灰化を阻害すること、
を包含する方法。
(項目2)
前記幹細胞は、cKit陽性幹細胞 SCA1細胞、COP細胞、間葉系幹細胞および前述のものの組み合わせから選択される、項目1に記載の方法。
(項目3)
前記生体心臓弁組織を、アトルバスタチン、ロスバスタチン、プラバスタチン、メバスタチン、フルバスタチン、シンバスタチン、ロバスタチン、L−アルギニン、シトルリン、NADPH、アセチルコリン、ヒスタミン、アルギニンバソプレッシン、ノルエピネフリン、エピネフリン、ブラジキニン、アデノシン二リン酸・三リン酸、5−ヒドロキシトリプタミン、トロンビン、インスリン、グルココルチコイド、サリチレート、L−NMMA、L−NAME、ニトログリセリン、二硝酸イソソルビド、5−一硝酸イソソルビド、亜硝酸アミル、ニコランジル、テトラヒドロビオプテリン、ゼチーアおよび前述のものの組み合わせから選択されるeNOSアクチベーターで処理することをさらに包含する、項目1に記載の方法。
(項目4)
前記被覆組成物は、前記幹細胞から発生する骨芽細胞における骨形成を阻害するための、(i)抗増殖剤;(ii)細胞外生成のインヒビター;(iii)骨芽細胞生成のインヒビター;および(iv)前述のものの組み合わせのうちの1またはこれより多くを含む、項目1に記載の方法。
(項目5)
前記抗増殖剤は、パクリタキセル、シロリムス、ビオリムス、エベロリムスおよび前述のものの組み合わせから選択される、項目4に記載の方法。
(項目6)
前記細胞外生成のインヒビターは、抗ファルネシルトランスフェラーゼインヒビター、抗パルミトイル化インヒビターまたは両方から選択される、項目4に記載の方法。
(項目7)
前記抗ファルネシルトランスフェラーゼインヒビター、抗パルミトイル化インヒビターは、ロナファルニブ、Zarnestra R115777、FTI SCH66336、STI571、FLT−3インヒビター、プロテアソームインヒビター、MAPKインヒビター、BMS−214662、タンパク質パルミトイル化、ファルネシル−ペプチドパルミトイル化のタイプI非脂質インヒビターまたはミリストイル−ペプチドパルミトイル化のタイプ2インヒビター、パルミトイル化アシルトランスフェラーゼインヒビター、2−ブロモパルミトイル(2BP)を含む脂質ベースのパルミトイル化インヒビター、ツニカマイシン、セルレニンおよび前述のものの組み合わせから選択される、項目6に記載の方法。
(項目8)
前記骨芽細胞生成のインヒビターは、アレンドロネート、リセドロネート、ゾレドロン酸、エチドロネート、イバンドロネート、パミドロネート、チルドロネート、デノスマブ抗体、カルシトニン−カルシメア、ミアカルシン、フォルテオテリパラチド、ラロキシフェン(エビスタ)および前述のものの組み合わせを含むビスホスホネート薬物のような抗骨粗鬆症剤から選択される、項目4に記載の方法。
(項目9)
前記eNOSアクチベーターの経口投与量を投与することをさらに包含する、項目3に記載の方法。
(項目10)
前記経口投与量は、1日あたり10mg〜80mgのアトルバスタチン;1日あたり10mg〜40mgのシンバスタチン;1日あたり5mg〜40mgのロスバスタチン;1日あたり10mg〜40mgのプラバスタチン;1日あたり1mg〜4mgのピタバスタチン;1日あたり10mgのゼチーアおよび前述のものの組み合わせを含む、項目9に記載の方法。
(項目11)
前記抗ファルネシルトランスフェラーゼインヒビター、前記抗パルミトイル化インヒビターまたは両方の経口投与量を投与することをさらに包含する、項目7に記載の方法。
(項目12)
前記投与量は、有効量のゼチーア10mgと組み合わせて115mg/m 2 〜150mg/m 2 の範囲で、115mg/m 2 用量の投与量でのロナファルニブを含む、項目11に記載の方法。
(項目13)
筋肉内注射または皮下注射によって有効量のPCSK9インヒビターを投与することをさらに包含する、項目1に記載の方法。
(項目14)
前記PCSK9インヒビターの最初の用量は、0.25mg/kg〜1.5mg/kgである、項目13に記載の方法。
(項目15)
前記PCSK9インヒビターの前記最初の用量は、0.5mg/kg〜1mg/kgである、項目14に記載の方法。
(項目16)
前記PCSK9インヒビターの前記有効量は、2〜4週間ごとにアリロクマブ75〜150mg、2週間ごとにもしくは1ヶ月に1回のエボロクマブ140mg、および前述のものの組み合わせである、項目13に記載の方法。
(項目17)
壁を有する脈管における移植後の機械式心臓弁の狭窄、閉塞および/または石灰化を阻害するための方法であって、該方法は、
Gortex材料によって覆われたソーイングリングを有する機械式心臓弁を提供すること;
該機械式心臓弁、該Gortex材料、または両方を、1種またはこれより多くの治療剤を含む被覆組成物で被覆すること;
該機械式心臓弁を罹患した生得の弁の部位の部位において該脈管に移植すること;
該被覆組成物を、該機械式心臓弁、該Gortex材料または両方から溶出すること;
(i)循環する幹細胞において、(ii)該機械式心臓弁および/もしくはGortex材料を覆う内皮細胞ライニングにおいて、または(iii)両方において、一酸化窒素生成を活性化することによって、該機械式心臓弁の外部または近辺を循環する幹細胞の、該機械式心臓弁またはGortex材料への付着を防止することによって、該機械式心臓弁の狭窄、閉塞および/または石灰化を阻害すること、
を包含する方法。
(項目18)
壁を有する脈管における移植後の心臓弁の狭窄、閉塞および/または石灰化を阻害するための方法であって、該方法は、
ソーイングリングを有しステントのない手術用心臓弁を提供することであって、該手術用心臓弁は、1もしくはこれより多くの弁尖を有する組織を含み、該手術用心臓弁は、罹患した生得の弁の置換用である、こと;
該手術用心臓弁を組織固定液で処理すること;
該手術用心臓弁、1もしくはこれより多くの弁尖および/またはソーイングリングを、1種またはこれより多くの治療剤を含む被覆組成物で被覆すること;
該手術用心臓弁を、罹患した生得の弁の部位において該脈管に移植すること;
該被覆組成物を該ソーイングリング、1もしくはこれより多くの弁尖、または両方から溶出すること;
(i)循環する幹細胞において、(ii)該手術用心臓弁を覆う内皮細胞ライニングにおいて、または(iii)両方において、一酸化窒素生成を活性化することによって、該手術用心臓弁の外部または近辺を循環する幹細胞の、該手術用心臓弁への付着を防止することによって、該手術用心臓弁の狭窄、閉塞および/または石灰化を阻害すること、
を包含する方法。
Claims (18)
- 壁を有する脈管における移植後の心臓弁の狭窄、閉塞および/または石灰化を阻害するための方法であって、該方法は、
1またはこれより多くの弁尖を有する組織を含む生体心臓弁を提供することであって、該生体心臓弁は、罹患した生得の弁の置換のために弾性ステント上に取り付けられていること;
該生体心臓弁を組織固定液で処理すること;
該ステント、1もしくはこれより多くの弁尖、または両方を、1種またはこれより多くの治療剤を含む被覆組成物で被覆すること;
該生体弁を罹患した生得の弁の部位において該脈管に移植すること;
該被覆組成物を該弾性ステント、1種もしくはこれより多くの弁尖、または両方から溶出すること;
(i)循環する幹細胞における、(ii)該生体心臓弁組織を覆う内皮細胞ライニングにおける、または(iii)両方における、一酸化窒素生成を活性化することによって、該生体心臓弁、弾性ステントまたは両方の外部または近辺を循環する幹細胞の、該生体心臓弁への付着を防止することによって、該生体心臓弁の狭窄、閉塞および/または石灰化を阻害すること、
を包含する方法。 - 前記幹細胞は、cKit陽性幹細胞 SCA1細胞、COP細胞、間葉系幹細胞および前述のものの組み合わせから選択される、請求項1に記載の方法。
- 前記生体心臓弁組織を、アトルバスタチン、ロスバスタチン、プラバスタチン、メバスタチン、フルバスタチン、シンバスタチン、ロバスタチン、L−アルギニン、シトルリン、NADPH、アセチルコリン、ヒスタミン、アルギニンバソプレッシン、ノルエピネフリン、エピネフリン、ブラジキニン、アデノシン二リン酸・三リン酸、5−ヒドロキシトリプタミン、トロンビン、インスリン、グルココルチコイド、サリチレート、L−NMMA、L−NAME、ニトログリセリン、二硝酸イソソルビド、5−一硝酸イソソルビド、亜硝酸アミル、ニコランジル、テトラヒドロビオプテリン、ゼチーアおよび前述のものの組み合わせから選択されるeNOSアクチベーターで処理することをさらに包含する、請求項1に記載の方法。
- 前記被覆組成物は、前記幹細胞から発生する骨芽細胞における骨形成を阻害するための、(i)抗増殖剤;(ii)細胞外生成のインヒビター;(iii)骨芽細胞生成のインヒビター;および(iv)前述のものの組み合わせのうちの1またはこれより多くを含む、請求項1に記載の方法。
- 前記抗増殖剤は、パクリタキセル、シロリムス、ビオリムス、エベロリムスおよび前述のものの組み合わせから選択される、請求項4に記載の方法。
- 前記細胞外生成のインヒビターは、抗ファルネシルトランスフェラーゼインヒビター、抗パルミトイル化インヒビターまたは両方から選択される、請求項4に記載の方法。
- 前記抗ファルネシルトランスフェラーゼインヒビター、抗パルミトイル化インヒビターは、ロナファルニブ、Zarnestra R115777、FTI SCH66336、STI571、FLT−3インヒビター、プロテアソームインヒビター、MAPKインヒビター、BMS−214662、タンパク質パルミトイル化、ファルネシル−ペプチドパルミトイル化のタイプI非脂質インヒビターまたはミリストイル−ペプチドパルミトイル化のタイプ2インヒビター、パルミトイル化アシルトランスフェラーゼインヒビター、2−ブロモパルミトイル(2BP)を含む脂質ベースのパルミトイル化インヒビター、ツニカマイシン、セルレニンおよび前述のものの組み合わせから選択される、請求項6に記載の方法。
- 前記骨芽細胞生成のインヒビターは、アレンドロネート、リセドロネート、ゾレドロン酸、エチドロネート、イバンドロネート、パミドロネート、チルドロネート、デノスマブ抗体、カルシトニン−カルシメア、ミアカルシン、フォルテオテリパラチド、ラロキシフェン(エビスタ)および前述のものの組み合わせを含むビスホスホネート薬物のような抗骨粗鬆症剤から選択される、請求項4に記載の方法。
- 前記eNOSアクチベーターの経口投与量を投与することをさらに包含する、請求項3に記載の方法。
- 前記経口投与量は、1日あたり10mg〜80mgのアトルバスタチン;1日あたり10mg〜40mgのシンバスタチン;1日あたり5mg〜40mgのロスバスタチン;1日あたり10mg〜40mgのプラバスタチン;1日あたり1mg〜4mgのピタバスタチン;1日あたり10mgのゼチーアおよび前述のものの組み合わせを含む、請求項9に記載の方法。
- 前記抗ファルネシルトランスフェラーゼインヒビター、前記抗パルミトイル化インヒビターまたは両方の経口投与量を投与することをさらに包含する、請求項7に記載の方法。
- 前記投与量は、有効量のゼチーア10mgと組み合わせて115mg/m2〜150mg/m2の範囲で、115mg/m2用量の投与量でのロナファルニブを含む、請求項11に記載の方法。
- 筋肉内注射または皮下注射によって有効量のPCSK9インヒビターを投与することをさらに包含する、請求項1に記載の方法。
- 前記PCSK9インヒビターの最初の用量は、0.25mg/kg〜1.5mg/kgである、請求項13に記載の方法。
- 前記PCSK9インヒビターの前記最初の用量は、0.5mg/kg〜1mg/kgである、請求項14に記載の方法。
- 前記PCSK9インヒビターの前記有効量は、2〜4週間ごとにアリロクマブ75〜150mg、2週間ごとにもしくは1ヶ月に1回のエボロクマブ140mg、および前述のものの組み合わせである、請求項13に記載の方法。
- 壁を有する脈管における移植後の機械式心臓弁の狭窄、閉塞および/または石灰化を阻害するための方法であって、該方法は、
Gortex材料によって覆われたソーイングリングを有する機械式心臓弁を提供すること;
該機械式心臓弁、該Gortex材料、または両方を、1種またはこれより多くの治療剤を含む被覆組成物で被覆すること;
該機械式心臓弁を罹患した生得の弁の部位の部位において該脈管に移植すること;
該被覆組成物を、該機械式心臓弁、該Gortex材料または両方から溶出すること;
(i)循環する幹細胞において、(ii)該機械式心臓弁および/もしくはGortex材料を覆う内皮細胞ライニングにおいて、または(iii)両方において、一酸化窒素生成を活性化することによって、該機械式心臓弁の外部または近辺を循環する幹細胞の、該機械式心臓弁またはGortex材料への付着を防止することによって、該機械式心臓弁の狭窄、閉塞および/または石灰化を阻害すること、
を包含する方法。 - 壁を有する脈管における移植後の心臓弁の狭窄、閉塞および/または石灰化を阻害するための方法であって、該方法は、
ソーイングリングを有しステントのない手術用心臓弁を提供することであって、該手術用心臓弁は、1もしくはこれより多くの弁尖を有する組織を含み、該手術用心臓弁は、罹患した生得の弁の置換用である、こと;
該手術用心臓弁を組織固定液で処理すること;
該手術用心臓弁、1もしくはこれより多くの弁尖および/またはソーイングリングを、1種またはこれより多くの治療剤を含む被覆組成物で被覆すること;
該手術用心臓弁を、罹患した生得の弁の部位において該脈管に移植すること;
該被覆組成物を該ソーイングリング、1もしくはこれより多くの弁尖、または両方から溶出すること;
(i)循環する幹細胞において、(ii)該手術用心臓弁を覆う内皮細胞ライニングにおいて、または(iii)両方において、一酸化窒素生成を活性化することによって、該手術用心臓弁の外部または近辺を循環する幹細胞の、該手術用心臓弁への付着を防止することによって、該手術用心臓弁の狭窄、閉塞および/または石灰化を阻害すること、
を包含する方法。
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US10701428B2 (en) | 2017-02-24 | 2020-06-30 | At&T Mobility Ii Llc | System and method for switching video presentations between devices |
US10798180B1 (en) * | 2017-04-11 | 2020-10-06 | Wells Fargo Bank, N.A. | Systems and methods for optimizing information collaboration |
US10848578B1 (en) | 2017-04-11 | 2020-11-24 | Wells Fargo Bank, N.A. | Systems and methods for content delivery |
US10382836B2 (en) * | 2017-06-30 | 2019-08-13 | Wipro Limited | System and method for dynamically generating and rendering highlights of a video content |
US10135632B1 (en) | 2017-12-12 | 2018-11-20 | Rovi Guides, Inc. | Systems and methods for determining whether a user is authorized to perform an action in response to a detected sound |
US10425247B2 (en) | 2017-12-12 | 2019-09-24 | Rovi Guides, Inc. | Systems and methods for modifying playback of a media asset in response to a verbal command unrelated to playback of the media asset |
US11082383B2 (en) | 2018-03-13 | 2021-08-03 | ROVl GUIDES, INC. | Systems and methods for displaying a notification at an area on a display screen that is within a line of sight of a subset of audience members to whom the notification pertains |
US10412450B1 (en) | 2018-03-27 | 2019-09-10 | Rovi Guides, Inc. | Systems and methods for managing local and cloud storage for media assets |
PL238190B1 (pl) | 2018-07-24 | 2021-07-19 | American Heart Of Poland Spolka Akcyjna | Biologiczna niskoprofilowa, rozprężana na balonie zastawka serca, zwłaszcza aortalna, implantowana przezskórnie i sposób jej wytwarzania |
US10491940B1 (en) | 2018-08-23 | 2019-11-26 | Rovi Guides, Inc. | Systems and methods for displaying multiple media assets for a plurality of users |
US10986404B2 (en) | 2018-10-24 | 2021-04-20 | Rovi Guides, Inc. | Systems and methods for overriding user input of commands in a multi-user environment |
WO2022066460A1 (en) * | 2020-09-25 | 2022-03-31 | Arris Enterprises Llc | System and method for the access and routing of content on the basis of facial recognition |
US11405687B1 (en) * | 2021-04-22 | 2022-08-02 | Shopify Inc. | Systems and methods for controlling transmission of live media streams |
US11558664B1 (en) * | 2021-08-24 | 2023-01-17 | Motorola Mobility Llc | Electronic device that pauses media playback based on interruption context |
US11837062B2 (en) | 2021-08-24 | 2023-12-05 | Motorola Mobility Llc | Electronic device that pauses media playback based on external interruption context |
WO2023167687A1 (en) * | 2022-03-04 | 2023-09-07 | Mabiala Kibabou Bleck Gaetan | Systems and methods for user recognition |
Family Cites Families (58)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6239794B1 (en) | 1994-08-31 | 2001-05-29 | E Guide, Inc. | Method and system for simultaneously displaying a television program and information about the program |
JPH11196345A (ja) * | 1997-10-07 | 1999-07-21 | Masanobu Kujirada | 表示システム |
US6564378B1 (en) | 1997-12-08 | 2003-05-13 | United Video Properties, Inc. | Program guide system with browsing display |
CN1867068A (zh) | 1998-07-14 | 2006-11-22 | 联合视频制品公司 | 交互式电视节目导视***及其方法 |
AR020608A1 (es) | 1998-07-17 | 2002-05-22 | United Video Properties Inc | Un metodo y una disposicion para suministrar a un usuario acceso remoto a una guia de programacion interactiva por un enlace de acceso remoto |
CN101383945B (zh) | 1998-07-17 | 2012-11-21 | 联合视频制品公司 | 将用户配置信息应用到电视设备装置的***和方法 |
US7165098B1 (en) | 1998-11-10 | 2007-01-16 | United Video Properties, Inc. | On-line schedule system with personalization features |
EP2293564A1 (en) * | 2000-10-11 | 2011-03-09 | United Video Properties, Inc. | Systems and methods for supplementing on-demand media |
BR0114605A (pt) | 2000-10-11 | 2003-07-01 | United Video Properties Inc | Sistema e métodos para colocar dados em cache de memória em sistemas de mìdia sob demanda |
IL148080A0 (en) * | 2001-02-13 | 2002-09-12 | Hosen Eliav | System for distributing video and content on demand |
KR101775064B1 (ko) | 2001-02-21 | 2017-09-06 | 로비 가이드스, 인크. | 개인용 비디오 녹화 특징을 갖는 대화식 프로그램 가이드를 위한 시스템 및 방법 |
US7536704B2 (en) * | 2001-10-05 | 2009-05-19 | Opentv, Inc. | Method and apparatus automatic pause and resume of playback for a popup on interactive TV |
US8086093B2 (en) * | 2002-12-05 | 2011-12-27 | At&T Ip I, Lp | DSL video service with memory manager |
US20050160465A1 (en) | 2004-01-21 | 2005-07-21 | United Video Properties, Inc. | Interactive television system with automatic switching from broadcast media to streaming media |
WO2006061770A1 (en) * | 2004-12-07 | 2006-06-15 | Koninklijke Philips Electronics N.V. | Intelligent pause button |
WO2006113655A1 (en) * | 2005-04-18 | 2006-10-26 | Home Box Office, Inc. | Pausing and resuming content streaming on wireless devices |
US20070033607A1 (en) * | 2005-08-08 | 2007-02-08 | Bryan David A | Presence and proximity responsive program display |
TWI273566B (en) * | 2005-12-29 | 2007-02-11 | Inventec Corp | Media recording device and method thereof |
US20100153885A1 (en) | 2005-12-29 | 2010-06-17 | Rovi Technologies Corporation | Systems and methods for interacting with advanced displays provided by an interactive media guidance application |
JP2009522860A (ja) | 2005-12-29 | 2009-06-11 | ユナイテッド ビデオ プロパティーズ, インコーポレイテッド | プログラムセグメント関心に基づくメディアプログラム選択アクセス用システムおよび方法 |
US20070154168A1 (en) * | 2005-12-29 | 2007-07-05 | United Video Properties, Inc. | Systems and methods for accessing media program options based on program segment interest |
US8161412B2 (en) * | 2006-01-13 | 2012-04-17 | At&T Intellectual Property I, L.P. | Systems, methods, and computer program products for providing interactive content |
US7620390B2 (en) * | 2006-05-22 | 2009-11-17 | Nortel Networks Limited | Establishing a call session during an advertisement time period |
JP4887905B2 (ja) * | 2006-05-25 | 2012-02-29 | 富士ゼロックス株式会社 | 支持台、スキャナ装置、および画像記録装置 |
JP2007318431A (ja) | 2006-05-25 | 2007-12-06 | Fujifilm Corp | 表示制御システムおよび表示制御方法 |
US8798433B2 (en) * | 2007-05-04 | 2014-08-05 | United Video Properties, Inc. | Systems and methods for recording overlapping media content during scheduling conflicts |
EP2042969A1 (en) | 2007-09-28 | 2009-04-01 | Alcatel Lucent | Method for determining user reaction with specific content of a displayed page. |
US20090113481A1 (en) * | 2007-10-24 | 2009-04-30 | At&T Intellectual Property I, L.P. | Systems, methods and computer program products for providing presence based services |
US9286616B2 (en) * | 2008-03-10 | 2016-03-15 | Hulu, LLC | Method and apparatus for providing directed advertising based on user preferences |
CN101635706A (zh) * | 2008-07-23 | 2010-01-27 | 曼谢克·安东尼·黄 | 动态媒体信息传递的方法、装置以及*** |
US8806551B2 (en) * | 2008-12-03 | 2014-08-12 | Alcatel Lucent | Prioritized retransmission of internet protocol television (IPTV) packets |
US8667549B2 (en) * | 2009-04-28 | 2014-03-04 | Microsoft Corporation | Personal video recorder E-mail alerts and status |
US9652783B2 (en) | 2009-06-30 | 2017-05-16 | Verizon Patent And Licensing Inc. | Methods and systems for controlling presentation of media content based on user interaction |
CA2771274A1 (en) * | 2009-09-23 | 2011-03-31 | United Video Properties, Inc. | Systems and methods for automatically detecting users within detection regions of media devices |
JP5316452B2 (ja) | 2010-03-23 | 2013-10-16 | 株式会社デンソー | 排気熱回収装置 |
US8837900B2 (en) * | 2010-05-11 | 2014-09-16 | Cisco Technology, Inc. | Unintended video recording detection in a video recording device |
US8577092B2 (en) * | 2010-11-11 | 2013-11-05 | Lg Electronics Inc. | Multimedia device, multiple image sensors having different types and method for controlling the same |
US8666818B2 (en) * | 2011-08-15 | 2014-03-04 | Logobar Innovations, Llc | Progress bar is advertisement |
US9520957B2 (en) * | 2011-08-19 | 2016-12-13 | Lenovo (Singapore) Pte. Ltd. | Group recognition and profiling |
US8621019B2 (en) * | 2011-09-21 | 2013-12-31 | Color Labs, Inc. | Live content sharing within a social networking environment |
EP2780021A4 (en) * | 2011-11-16 | 2015-08-05 | Univ Duke | BISPHOSPHONATE COMPOSITIONS AND METHODS FOR TREATING AND / OR REDUCING HEART FAILURE |
US9456244B2 (en) * | 2012-06-25 | 2016-09-27 | Intel Corporation | Facilitation of concurrent consumption of media content by multiple users using superimposed animation |
US20140007154A1 (en) | 2012-06-29 | 2014-01-02 | United Video Properties, Inc. | Systems and methods for providing individualized control of media assets |
WO2015061431A1 (en) * | 2013-10-22 | 2015-04-30 | ConcieValve LLC | Methods for inhibiting stenosis, obstruction, or calcification of a stented heart valve or bioprosthesis |
US20150306281A1 (en) * | 2014-04-28 | 2015-10-29 | Nalini Marie Rajamannan | Devices and methods for inhibiting stenosis, obstruction, or calcification of a native heart valve, stented heart valve or bioprosthesis |
US8955002B2 (en) * | 2013-01-16 | 2015-02-10 | Comcast Cable Communications, Llc | Tracking and responding to distracting events |
US9344291B2 (en) * | 2013-04-24 | 2016-05-17 | Mitel Networks Corporation | Conferencing system with catch-up features and method of using same |
US20140331242A1 (en) * | 2013-05-01 | 2014-11-06 | Microsoft Corporation | Management of user media impressions |
US9313545B2 (en) * | 2013-08-27 | 2016-04-12 | At&T Mobility Ii Llc | Method and apparatus for managing viewing of media content |
EP3049952A4 (en) * | 2013-09-26 | 2017-03-15 | Mark W. Publicover | Providing targeted content based on a user's moral values |
CA2939507A1 (en) * | 2014-02-14 | 2015-08-20 | Regeneron Pharmaceuticals, Inc. | Methods for treating patients with hypercholesterolemia that is not adequately controlled by moderate-dose statin therapy |
US9852774B2 (en) * | 2014-04-30 | 2017-12-26 | Rovi Guides, Inc. | Methods and systems for performing playback operations based on the length of time a user is outside a viewing area |
US20150350729A1 (en) * | 2014-05-28 | 2015-12-03 | United Video Properties, Inc. | Systems and methods for providing recommendations based on pause point in the media asset |
CN105392035A (zh) * | 2014-09-03 | 2016-03-09 | 深圳市同方多媒体科技有限公司 | 一种智能电视机播放节目切换***及方法 |
US9661091B2 (en) * | 2014-09-12 | 2017-05-23 | Microsoft Technology Licensing, Llc | Presence-based content control |
US9729915B2 (en) | 2014-10-31 | 2017-08-08 | Paypal, Inc. | Detecting user devices to determine state of watched show |
KR20180063051A (ko) * | 2015-09-01 | 2018-06-11 | 톰슨 라이센싱 | 어텐션 검출에 기초한 미디어 콘텐츠 제어를 위한 방법들, 시스템들 및 장치 |
US10939164B2 (en) | 2016-05-10 | 2021-03-02 | Rovi Guides, Inc. | Method and system for transferring an interactive feature to another device |
-
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