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1. 发明授权

US09238080B2 Bi-specific fusion proteins 有权
标题翻译：双特异融合蛋白
公开(公告)号：US09238080B2
公开(公告)日：2016-01-19
申请号：US13068808
申请日：2011-05-20
申请人： Ulrik Nielsen , Thomas Wickham , Birgit Schoeberl , Brian Harms , Bryan Linggi , Matthew Onsum , Byron DeLaBarre , Shaun M. Lippow
发明人： Ulrik Nielsen , Thomas Wickham , Birgit Schoeberl , Brian Harms , Bryan Linggi , Matthew Onsum , Byron DeLaBarre , Shaun M. Lippow
IPC分类号： C07K14/475 , C12N15/62 , A61K47/48 , B82Y5/00 , A61K45/06 , C07K16/46 , A61K38/00
CPC分类号： C07K16/44 , A61K38/00 , A61K45/06 , A61K47/66 , A61K47/6811 , A61K47/6891 , B82Y5/00 , C07K14/47 , C07K14/475 , C07K14/485 , C07K14/65 , C07K16/46 , C07K2317/31 , C07K2317/76 , C07K2319/00 , C07K2319/80 , C12N15/62
摘要： Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair or regenerate damaged or diseased tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to a target molecule; and (b) an activator domain that detectably modulates tissue regeneration.
摘要翻译：提供了具有治疗用途的双特异性融合蛋白，以及包含这种融合蛋白的药物组合物，以及使用这种融合蛋白修复或再生受损或患病组织的方法。双特异性融合蛋白通常包含：（a）靶向靶分子结合的靶向多肽结构域; 和（b）可检测地调节组织再生的活化剂结构域。

2. 发明授权

US08623592B2 Methods and systems for predicting response of cells to a therapeutic agent 有权
标题翻译：用于预测细胞对治疗剂的反应的方法和系统
公开(公告)号：US08623592B2
公开(公告)日：2014-01-07
申请号：US13058687
申请日：2009-08-17
申请人： Birgit Schoeberl , Brian Harms , Francis David Gibbons , Jonathan Basil Fitzgerald , Matthew David Onsum , Ulrik Nielsen , William Kubasek
发明人： Birgit Schoeberl , Brian Harms , Francis David Gibbons , Jonathan Basil Fitzgerald , Matthew David Onsum , Ulrik Nielsen , William Kubasek
IPC分类号： C12Q1/00 , C12Q1/68 , G01N33/574
CPC分类号： G01N33/6893 , A61K2039/505 , C07K16/2863 , C07K16/32 , C07K2317/31 , C12Q1/6809
摘要： The invention provides methods for treating patients which methods comprise methods for predicting responses of cells, such as tumor cells, to treatment with therapeutic agents. These methods involve measuring, in a sample of the cells, levels of one or more components of a cellular network and then computing a Network Activation State (NAS) or a Network Inhibition State (NIS) for the cells using a computational model of the cellular network. The response of the cells to treatment is then predicted124 based on the NAS or NIS value that has been computed. The invention also comprises predictive methods for cellular responsiveness in which computation of a NAS or NIS value for the cells (e.g., tumor cells) is combined with use of a statistical classification algorithm. Biomarkers for predicting responsiveness to treatment with a therapeutic agent that targets a component within the ErbB signaling pathway are also provided.
摘要翻译：本发明提供了治疗患者的方法，所述方法包括用于预测细胞如肿瘤细胞的应答的方法用于治疗剂的治疗。这些方法包括在细胞样本中测量细胞网络的一个或多个组分的水平，然后使用细胞的计算模型计算细胞的网络激活状态（NAS）或网络抑制状态（NIS）网络。然后基于已经计算的NAS或NIS值来预测细胞对治疗的反应124。本发明还包括用于细胞反应性的预测方法，其中使用统计分类算法将细胞（例如，肿瘤细胞）的NAS或NIS值的计算结合在一起。还提供了用于预测用靶向ErbB信号通路中的组分的治疗剂对治疗的反应性的生物标志物。

3. 发明授权

US06493376B1 Multi-layered PN code spreading in a multi-user communications system 有权
标题翻译：在多用户通信系统中扩展的多层PN码
公开(公告)号：US06493376B1
公开(公告)日：2002-12-10
申请号：US09169358
申请日：1998-10-09
申请人： Brian Harms , Brian Butler , Gordon Skinner
发明人： Brian Harms , Brian Butler , Gordon Skinner
IPC分类号： H04B1500
CPC分类号： H04B1/7077 , H04B1/707 , H04B1/7075 , H04B1/70755 , H04B7/216 , H04J13/0022
摘要： A technique for spreading information signals in a spread spectrum communication system to provide increased signal acquisition speed. A first PN spreading code or code set is used to spread information signals along with a second PN spreading code sequence or function. The second PN code is synchronized with the first PN spreading code, but has a larger code period so that each code chip of the second PN code extends over the entire period of the first PN code. The longer period spreading code forms an outer code which helps provide unambiguous beam identification and easily acquired frame timing in the presence of dynamically changing signal path delay, improving signal acquisition.
摘要翻译：一种用于在扩展频谱通信系统中扩展信息信号以提供增加的信号采集速度的技术。第一PN扩展码或码组用于扩展信息信号以及第二PN扩展码序列或函数。第二PN码与第一PN扩展码同步，但是具有较大的码周期，使得第二PN码的每个码片在第一PN码的整个周期内延伸。较长周期扩展码形成外码，有助于在存在动态变化的信号路径延迟的情况下提供明确的波束识别和容易获取的帧定时，从而改善信号采集。

4. 发明授权

US06249539B1 System and method for narrowing the range of frequency uncertainty of a doppler shifted signal 失效
标题翻译：用于缩小多普勒偏移信号的频率不确定度范围的系统和方法
公开(公告)号：US06249539B1
公开(公告)日：2001-06-19
申请号：US09097842
申请日：1998-06-15
申请人： Brian Harms , Sherman A. Gregory , Brian K. Butler , Avneesh Agrawal
发明人： Brian Harms , Sherman A. Gregory , Brian K. Butler , Avneesh Agrawal
IPC分类号： H04B1500
CPC分类号： H04B7/216 , G01S19/29 , H04B1/707 , H04L2027/0034
摘要： A system and method for narrowing the range of frequency uncertainty of a Doppler shifted pilot signal in a satellite or other communications system with relative signal source and receiver motion. The satellite communications system includes a user terminal (for example, a mobile wireless telephone), a gateway (terrestrial base station), and at least one satellite with unknown position and unknown relative velocity. The method includes the steps of shifting the pilot signal over a plurality of frequency hypotheses, coherently accumulating samples of the pilot signal over a plurality of chips, measuring the energy of the accumulated pilot signal samples, accumulating the energy measurements over a plurality of chips to produce an energy accumulation value, and determining which of the plurality of frequency hypotheses results in the highest energy accumulation value.
摘要翻译：一种用于在具有相对信号源和接收机运动的卫星或其他通信系统中缩小多普勒频移导频信号的频率不确定度的范围的系统和方法。卫星通信系统包括用户终端（例如，移动无线电话），网关（地面基站）和至少一个具有未知位置和未知相对速度的卫星。该方法包括以下步骤：通过多个频率假设移位导频信号，通过多个码片相干累加导频信号的采样，测量累积的导频信号样本的能量，将多个码片上的能量测量累积到产生能量累积值，并且确定多个频率假设中的哪一个导致最高的能量积累值。

5. 发明申请

US20110286976A1 BI-SPECIFIC FUSION PROTEINS 有权
标题翻译：双特异融合蛋白
公开(公告)号：US20110286976A1
公开(公告)日：2011-11-24
申请号：US13112907
申请日：2011-05-20
申请人： ULRIK NIELSEN , THOMAS WICKHAM , BIRGIT SCHOEBERL , BRIAN HARMS , BRYAN LINGGI , MATTHEW ONSUM , BYRON DELABARRE
发明人： ULRIK NIELSEN , THOMAS WICKHAM , BIRGIT SCHOEBERL , BRIAN HARMS , BRYAN LINGGI , MATTHEW ONSUM , BYRON DELABARRE
IPC分类号： A61K38/16 , C07H21/04 , A61K35/12 , C07K19/00 , A61P9/00
CPC分类号： C07K16/44 , A61K38/00 , A61K45/06 , A61K47/66 , A61K47/6811 , A61K47/6891 , B82Y5/00 , C07K14/47 , C07K14/475 , C07K14/485 , C07K14/65 , C07K16/46 , C07K2317/31 , C07K2317/76 , C07K2319/00 , C07K2319/80 , C12N15/62
摘要： Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair damaged tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to an ischemia-associated molecule; and (b) an activator domain that that detectably modulates the activity of a cellular network.
摘要翻译：提供了具有治疗用途的双特异性融合蛋白，以及包含这种融合蛋白的药物组合物，以及使用这种融合蛋白修复受损组织的方法。双特异性融合蛋白通常包含：（a）与缺血相关分子结合的靶向多肽结构域; 和（b）可检测地调节细胞网络的活性的激活子结构域。

6. 发明申请

US20110027291A1 METHODS, SYSTEMS AND PRODUCTS FOR PREDICTING RESPONSE OF TUMOR CELLS TO A THERAPEUTIC AGENT AND TREATING A PATIENT ACCORDING TO THE PREDICTED RESPONSE 审中-公开
标题翻译：肿瘤细胞对治疗药物的预测反应的方法，系统和产品，并根据预测的反应治疗患者
公开(公告)号：US20110027291A1
公开(公告)日：2011-02-03
申请号：US12707521
申请日：2010-02-17
申请人： Birgit SCHOEBERL , Brian HARMS , Francis David GIBBONS , Jonathan Basil FITZGERALD , Matthew David ONSUM , Ulrik NIELSEN , William KUBASEK
发明人： Birgit SCHOEBERL , Brian HARMS , Francis David GIBBONS , Jonathan Basil FITZGERALD , Matthew David ONSUM , Ulrik NIELSEN , William KUBASEK
IPC分类号： A61K39/395 , G01N33/566 , A61P35/00 , G06F7/60 , G06F19/00
CPC分类号： G01N33/6893 , A61K2039/505 , C07K16/2863 , C07K16/32 , C07K2317/31 , C12Q1/6809
摘要： The invention provides methods for treating patients which methods comprise methods for predicting responses of cells, such as tumor cells, to treatment with therapeutic agents. These methods involve measuring, in a sample of the cells, levels of one or more components of a cellular network and then computing a Network Activation State (NAS) or a Network Inhibition State (NIS) for the cells using a computational model of the cellular network. The response of the cells to treatment is then predicted based on the NAS or NIS value that has been computed. The invention also comprises predictive methods for cellular responsiveness in which computation of a NAS or NIS value for the cells (e.g., tumor cells) is combined with use of a statistical classification algorithm. Biomarkers for predicting responsiveness to treatment with a therapeutic agent that targets a component within the ErbB signaling pathway are also provided.
摘要翻译：本发明提供了治疗患者的方法，所述方法包括用于预测细胞如肿瘤细胞的应答的方法用于治疗剂的治疗。这些方法包括在细胞样本中测量细胞网络的一个或多个组分的水平，然后使用细胞的计算模型计算细胞的网络激活状态（NAS）或网络抑制状态（NIS）网络。然后基于已经计算的NAS或NIS值来预测细胞对治疗的反应。本发明还包括用于细胞反应性的预测方法，其中使用统计分类算法将细胞（例如，肿瘤细胞）的NAS或NIS值的计算结合在一起。还提供了用于预测用靶向ErbB信号通路中的组分的治疗剂对治疗的反应性的生物标志物。

7. 发明授权

US5577025A Signal acquisition in a multi-user communication system using multiple walsh channels 失效
标题翻译：使用多个沃尔什通道的多用户通信系统中的信号采集
公开(公告)号：US5577025A
公开(公告)日：1996-11-19
申请号：US497240
申请日：1995-06-30
申请人： Gordon Skinner, deceased , Brian Harms
发明人： Gordon Skinner, deceased , Brian Harms
IPC分类号： H04L27/32 , B60R11/00 , B60R11/02 , B60R11/04 , H04B1/7075 , H04B1/7077 , H04J13/02 , H04J3/06
CPC分类号： H04B1/70775 , B60R11/04 , B60R11/02 , B60R2011/0035 , B60R2011/0059 , B60R2011/0075 , H04B1/70752 , H04B1/70755
摘要： A technique for using energy received by subscriber units over multiple orthogonal channels within a spread spectrum communication system to acquire signal timing by controlling signal amplitude integration intervals used in detecting such timing. Received signals are despread and respective amplitudes integrated over periods that are divisible by factors of 2 into the length of Walsh functions used to generate orthogonal signal channels. Non-coherent combinations of the results of this integration are subsequently formed over periods that commence and terminate on Walsh function boundaries, and used to determine when a correct time offset has been selected for despreading signals. Additional advantages are realized by assigning signals that consistently provide a higher energy content such as paging, synchronization, and most frequently assigned traffic channels to specific orthogonal channels within the communication system. In exemplary embodiments, Walsh functions of length 128 are used as channelizing codes and a pilot signal is assigned to channel 0. This results in traffic channels or paging and synchronization functions being assigned to channel 64 when the integration periods are 64 chips long, and to channels 32, 64, and 96 when the periods are 32 chips long. In this manner, additional energy is available during the integration process for use in determining when correct signal acquisition timing offsets have been selected, without the use of additional hardware.
摘要翻译：一种用于在扩频通信系统内的多个正交信道上使用由用户单元接收的能量的技术，用于通过控制在检测这种定时中使用的信号幅度积分间隔来获取信号定时。接收信号被去扩展，并且各个幅度在可被因子2整除为用于产生正交信号信道的沃尔什函数的长度的周期上被积分。随后在沃尔什函数边界开始和终止的周期形成该积分结果的非相干组合，并用于确定何时为解扩信号选择正确的时间偏移。额外的优点是通过分配一致地向通信系统内的特定正交信道提供诸如寻呼，同步和最频繁分配的业务信道的更高能量内容的信号来实现。在示例性实施例中，使用长度为128的沃尔什函数作为信道化码，并且将导频信号分配给信道0.这导致当积分周期为64码长时分配给信道64的业务信道或寻呼和同步功能，通道32,64和96当这些周期是32码长时。以这种方式，在集成过程期间可以使用额外的能量，以用于确定何时选择正确的信号采集定时偏移，而不需要使用额外的硬件。

8. 发明申请

US20110159513A1 METHODS AND SYSTEMS FOR PREDICTING RESPONSE OF CELLS TO A THERAPEUTIC AGENT 有权
标题翻译：用于预测细胞对治疗剂的反应的方法和系统
公开(公告)号：US20110159513A1
公开(公告)日：2011-06-30
申请号：US13058687
申请日：2009-08-17
申请人： Birgit Schoeberl , Brian Harms , Francis David Gibbons , Jonathan Basil Fitzgerald , Matthew David Onsum , Ulrik Nielsen , William Kubasek
发明人： Birgit Schoeberl , Brian Harms , Francis David Gibbons , Jonathan Basil Fitzgerald , Matthew David Onsum , Ulrik Nielsen , William Kubasek
IPC分类号： C12Q1/68 , G01N33/574
CPC分类号： G01N33/6893 , A61K2039/505 , C07K16/2863 , C07K16/32 , C07K2317/31 , C12Q1/6809
摘要： The invention provides methods for treating patients which methods comprise methods for predicting responses of cells, such as tumor cells, to treatment with therapeutic agents. These methods involve measuring, in a sample of the cells, levels of one or more components of a cellular network and then computing a Network Activation State (NAS) or a Network Inhibition State (NIS) for the cells using a computational model of the cellular network. The response of the cells to treatment is then predicted based on the NAS or NIS value that has been computed. The invention also comprises predictive methods for cellular responsiveness in which computation of a NAS or NIS value for the cells (e.g., tumor cells) is combined with use of a statistical classification algorithm. Biomarkers for predicting responsiveness to treatment with a therapeutic agent that targets a component within the ErbB signaling pathway are also provided.
摘要翻译：本发明提供了治疗患者的方法，所述方法包括用于预测细胞如肿瘤细胞的应答的方法用于治疗剂的治疗。这些方法包括在细胞样本中测量细胞网络的一个或多个组分的水平，然后使用细胞的计算模型计算细胞的网络激活状态（NAS）或网络抑制状态（NIS）网络。然后基于已经计算的NAS或NIS值来预测细胞对治疗的反应。本发明还包括用于细胞反应性的预测方法，其中使用统计分类算法将细胞（例如，肿瘤细胞）的NAS或NIS值的计算结合在一起。还提供了用于预测用靶向ErbB信号通路中的组分的治疗剂对治疗的反应性的生物标志物。

9. 发明申请

US20110125468A1 USING RESPONSE SURFACES FOR SCREENING INHIBITOR COMBINATIONS AND DIGITAL PROCESSING METHODS 审中-公开
标题翻译：使用反应表面筛选抑制剂组合和数字处理方法
公开(公告)号：US20110125468A1
公开(公告)日：2011-05-26
申请号：US12912567
申请日：2010-10-26
申请人： Jonathan Basil Fitzgerald , Brian Harms
发明人： Jonathan Basil Fitzgerald , Brian Harms
IPC分类号： G06F17/10 , G06G7/60
CPC分类号： G16B5/00
摘要： A method for selecting a combination of therapeutic agents can include: providing a response surface having data that relates network activation states of a downstream component of a biological network with activation states of at least two upstream components of the network; identifying a desired network activation state of the downstream component from the response surface; identifying the corresponding activation states of the upstream components and identifying at least two therapeutic agents that modulate the upstream components and that are capable of obtaining the desired network activation state. The response surface can be visual or virtual. Optionally, the desired network activation state is an optimal network activation state.
摘要翻译：用于选择治疗剂的组合的方法可以包括：提供具有数据的响应表面，所述数据将生物网络的下游部件的网络激活状态与网络的至少两个上游部件的激活状态相关联; 从所述响应表面识别所述下游组件的期望的网络激活状态; 识别上游组分的相应活化状态并鉴定调节上游组分并且能够获得所需网络活化状态的至少两种治疗剂。响应面可以是视觉还是虚拟。可选地，期望的网络激活状态是最佳网络激活状态。

10. 发明授权

US08691771B2 Bi-specific fusion proteins for tissue repair 有权
标题翻译：用于组织修复的双特异性融合蛋白
公开(公告)号：US08691771B2
公开(公告)日：2014-04-08
申请号：US13112907
申请日：2011-05-20
申请人： Ulrik Nielsen , Thomas Wickham , Birgit Schoeberl , Brian Harms , Bryan Linggi , Matthew Onsum , Byron DeLaBarre
发明人： Ulrik Nielsen , Thomas Wickham , Birgit Schoeberl , Brian Harms , Bryan Linggi , Matthew Onsum , Byron DeLaBarre
IPC分类号： A61K38/16
CPC分类号： C07K16/44 , A61K38/00 , A61K45/06 , A61K47/66 , A61K47/6811 , A61K47/6891 , B82Y5/00 , C07K14/47 , C07K14/475 , C07K14/485 , C07K14/65 , C07K16/46 , C07K2317/31 , C07K2317/76 , C07K2319/00 , C07K2319/80 , C12N15/62
摘要： Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair damaged tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to an ischemia-associated molecule; and (b) an activator domain that that detectably modulates the activity of a cellular network.
摘要翻译：提供了具有治疗用途的双特异性融合蛋白，以及包含这种融合蛋白的药物组合物，以及使用这种融合蛋白修复受损组织的方法。双特异性融合蛋白通常包含：（a）与缺血相关分子结合的靶向多肽结构域; 和（b）可检测地调节细胞网络的活性的激活子结构域。

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