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1. 发明授权

US07067132B2 Antagonists of interleukin-15 失效
标题翻译：白细胞介素15的拮抗剂
公开(公告)号：US07067132B2
公开(公告)日：2006-06-27
申请号：US10289114
申请日：2002-11-06
申请人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
发明人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
IPC分类号： A61K39/395 , C07K16/00
CPC分类号： C07K16/244 , A61K38/00 , A61K47/60 , C07K14/5443 , C07K2317/76
摘要： Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15Rα-subunit and that are incapable of transducing a signal through either the β- or γ-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the β- or γ-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.
摘要翻译：公开了哺乳动物白细胞介素-15（“IL-15”）的拮抗剂，并且包括IL-15和修饰的IL-15分子的突变蛋白，其各自能够结合IL-15Rα-亚基并且不能通过 IL-15受体复合物的β亚基或γ亚基。还包括针对IL-15的单克隆抗体，其阻止IL-15通过IL-15受体复合物的β亚基或γ亚基进行信号转导。公开了治疗各种疾病状态的方法，包括治疗同种异体移植排斥和移植物抗宿主病。

2. 发明授权

US06451986B1 Site specific protein modification 失效
标题翻译：位点特异性蛋白质修饰
公开(公告)号：US06451986B1
公开(公告)日：2002-09-17
申请号：US09102530
申请日：1998-06-22
申请人： Dean K. Pettit
发明人： Dean K. Pettit
IPC分类号： C07K100
CPC分类号： C07K1/1077 , A61K47/60 , A61K47/62 , C07K14/7151
摘要： Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of deleting at least one amino acid residue on the protein, replacing the at least one amino acid residue with an amino acid residue that does not react with polyethylene glycol, and contacting the protein with polyethylene glycol under conditions sufficient to conjugate the polyethylene glycol to the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains free to interact with a binding partner ligand or cognate subsequent to the conjugation process.
摘要翻译：公开了将蛋白质与聚乙二醇缀合的方法。所公开的方法提供了其活性几乎没有或没有降低的修饰的蛋白质，包括删除蛋白质上的至少一个氨基酸残基的步骤，用不与聚乙二醇反应的氨基酸残基取代至少一个氨基酸残基并在足以将聚乙二醇与蛋白质缀合的条件下使蛋白与聚乙二醇接触。所需蛋白质活性的这种有利的保留归因于在缀合过程中未改变的一个或多个蛋白质结合位点的可用性，因此在缀合过程之后保持与结合配偶体配体或同源物相互作用。

3. 发明授权

US6165466A Antagonists of interleukin-15 有权
标题翻译：白细胞介素15的拮抗剂
公开(公告)号：US6165466A
公开(公告)日：2000-12-26
申请号：US134134
申请日：1998-08-14
申请人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
发明人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61K47/48 , A61P37/06 , C07K14/54 , C07K16/24 , C07K16/42 , C07K19/00 , C12N1/19 , C12N15/24 , C12P21/02 , C12P21/08 , C12R1/865 , C07K16/00
CPC分类号： C07K16/244 , A61K38/00 , A61K2039/505 , C07K14/5443
摘要： Antagonists of mammalian interleukin-15 ("IL-15") are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R.alpha.-subunit and that are incapable of transducing a signal through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed including treating allograft rejection and graft-versus-host disease.
摘要翻译：公开了哺乳动物白细胞介素-15（“IL-15”）的拮抗剂，并且包括IL-15和修饰的IL-15分子的突变蛋白，其各自能够结合IL-15Rα-亚基并且不能转导信号通过IL-15受体复合物的β或γ亚基。还包括针对IL-15的单克隆抗体，其阻止IL-15通过IL-15受体复合物的β或γ亚基进行信号转导。公开了治疗各种疾病状态的方法，包括治疗同种异体移植排斥和移植物抗宿主病。

4. 发明授权

US5795966A Antagonists of interleukin-15 失效
公开(公告)号：US5795966A
公开(公告)日：1998-08-18
申请号：US392317
申请日：1995-02-22
申请人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
发明人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
IPC分类号： C12N15/09 , A61K38/00 , A61K39/395 , A61K47/48 , A61P37/06 , C07K14/54 , C07K16/24 , C07K16/42 , C07K19/00 , C12N1/19 , C12N15/24 , C12P21/02 , C12P21/08 , C12R1/865 , C07K16/00 , C12N5/12 , C12N5/20
CPC分类号： C07K16/244 , C07K14/5443 , A61K2039/505 , A61K38/00
摘要： Antagonists of mammalian interleukin-15 ("IL-15") are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R.alpha.-subunit and that are incapable of transducing a signal through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the .beta.- or .gamma.-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

5. 发明授权

US07008624B1 Antagonists of interleukin-15 失效
公开(公告)号：US07008624B1
公开(公告)日：2006-03-07
申请号：US09578669
申请日：2000-05-25
申请人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
发明人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
IPC分类号： A61K39/00 , A61K39/38 , A61K39/385 , C12P21/06 , C07K1/00
CPC分类号： C07K16/244 , A61K38/00 , A61K47/60 , C07K14/5443 , C07K2317/76
摘要： Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15Rα-subunit and that are incapable of transducing a signal through either the β- or γ-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the β- or γ-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.

6. 发明授权

US06548644B1 Site protected protein modification 失效
标题翻译：现场保护蛋白质修饰
公开(公告)号：US06548644B1
公开(公告)日：2003-04-15
申请号：US08814305
申请日：1997-03-10
申请人： Dean K. Pettit
发明人： Dean K. Pettit
IPC分类号： C07K1400
CPC分类号： A61K47/642 , A61K47/60 , Y10S530/81
摘要： Processes for conjugating proteins with polyethylene glycol are disclosed. The disclosed processes provide modified proteins having little or no decrease in their activity and include the steps of protecting one or more sites on the protein, contacting the protected protein with polyethylene glycol under conditions suitable for conjugating the polyethylene glycol to the protein, and deprotecting the protein. This advantageous retention of a desired protein activity is attributed to the availability of one or more protein binding sites which is unaltered in the conjugation process and thus remains sterically free to interact with a binding partner ligand or cognate subsequent to the conjugation process.
摘要翻译：公开了将蛋白质与聚乙二醇缀合的方法。所公开的方法提供其活性几乎没有或没有降低的修饰的蛋白质，并且包括保护蛋白质上的一个或多个位点的步骤，在适于将聚乙二醇与蛋白质缀合的条件下使受保护的蛋白质与聚乙二醇接触，并使蛋白。所需蛋白质活性的这种有利的保留归因于在缀合过程中未改变的一个或多个蛋白质结合位点的可用性，因此在缀合过程之后保持空间上与结合配偶体配体或同源物相互作用。

7. 发明授权

US06274175B1 Prolonged release of GM-CSF 失效
标题翻译：长时间释放GM-CSF
公开(公告)号：US06274175B1
公开(公告)日：2001-08-14
申请号：US09442370
申请日：1999-11-17
申请人： Wayne R. Gombotz , Dean K. Pettit , Susan C. Pankey
发明人： Wayne R. Gombotz , Dean K. Pettit , Susan C. Pankey
IPC分类号： A61K916
CPC分类号： A61K9/0019 , A61K9/0024 , A61K9/06 , A61K9/1635 , A61K9/1641 , A61K9/1647 , A61K38/193 , Y10T428/2989
摘要： Formulations for controlled, prolonged release of GM-CSF have been developed. These are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof with excipients and drug loadings that yield zero order or first order release, or multiphasic release over a period of approximately three to twenty one days, preferably one week, when administered by injection. In the preferred embodiment, the microparticles are microspheres having diameters in the range of 10 to 60 microns, formed of a blend of PLGA having different molecular weights, most preferably 6,000, 30,000 and 41,000. Other embodiments have been developed to alter the release kinetics or the manner in which the drug is distributed in vivo. For example, in some cases a polymer is selected which elicits a mild inflammatory reaction, for example, PLGA and polyanhydrides can act as chemoattractant, either due to the polymer itself or minor contaminants in the polymer, or polymers which are bioadhesive are used for transmucosal or oral delivery. In another embodiment, the GM-CSF is administered in a hydrogel which can be injected subcutaneous or at a specific site for controlled release. The microparticles or hydrogel are administered to the patient in an amount effect to stimulate proliferation of hematopoietic cells, especially white cells.
摘要翻译：已经开发了控制，长期释放GM-CSF的制剂。这些基于由生物可降解的合成聚合物如聚（乳酸）（PLA），聚（乙醇酸）（PGA））及其与赋形剂的共聚物和药物负载的组合形成的固体微粒，其产生零级或一级当通过注射给药时，在约3至20天，优选1周的时间内释放或多相释放。在优选的实施方案中，微粒是具有10至60微米范围内的直径的微球，由具有不同分子量，最优选6,000,300和41,000的PLGA的共混物形成。已经开发了其它实施方案来改变药物在体内分布的释放动力学或方式。例如，在一些情况下，选择引起轻度炎症反应的聚合物，例如PLGA和聚酐可以作为化学引诱剂，这是由于聚合物本身或聚合物中的微量污染物，或生物粘附剂的聚合物用于经粘膜或口服。在另一个实施方案中，GM-CSF以可以皮下注射或在特定部位注射用于控制释放的水凝胶施用。将微粒或水凝胶以刺激造血细胞，特别是白细胞增殖的量施用于患者。

8. 发明授权

US06168783A Antagonists of interleukin-15 有权
标题翻译：白细胞介素15的拮抗剂
公开(公告)号：US06168783A
公开(公告)日：2001-01-02
申请号：US09134456
申请日：1998-08-14
申请人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
发明人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
IPC分类号： A61K4500
CPC分类号： C07K16/244 , A61K38/00 , A61K2039/505 , C07K14/5443
摘要： Antagonists of mammalian interleukin-15 (“IL-l5”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15R&agr;-subunit and that are incapable of transducing a signal through either the &bgr;- or &ggr;-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the &bgr;- or &ggr;-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.
摘要翻译：公开了哺乳动物白细胞介素-15（“IL-15”）的拮抗剂，并且包括IL-15和修饰的IL-15分子的突变蛋白，其各自能够结合IL-15Rα-亚基并且不能通过 IL-15受体复合物的β亚基或γ亚基。还包括针对IL-15的单克隆抗体，其阻止IL-15通过IL-15受体复合物的β亚基或γ亚基进行信号转导。公开了治疗各种疾病状态的方法，包括治疗同种异体移植排斥和移植物抗宿主病。

9. 发明授权

US4880426A Haptic to optic attachment for a soft IOL 失效
标题翻译：触觉为软IOL的光学附件
公开(公告)号：US4880426A
公开(公告)日：1989-11-14
申请号：US228709
申请日：1988-08-04
申请人： Albert C. Ting , Timothy R. Willis , F. Richard Christ , Steven R. Bacich , Dean K. Pettit , Stanley L. Van Gent , Jeffrey C. Day
发明人： Albert C. Ting , Timothy R. Willis , F. Richard Christ , Steven R. Bacich , Dean K. Pettit , Stanley L. Van Gent , Jeffrey C. Day
IPC分类号： A61F2/16
CPC分类号： A61F2/1613 , A61F2/1608
摘要： A method of making an intraocular lens including providing a fixation member having a proximal end portion with the proximal end portion including an elongated filament, converting a region of said filament at said proximal end portion from a first configuration into a second configuration which is adapted to provide a mechanical interlock and molding an optic about the proximal end portion of the fixation member to form a mechanical interlock between the second configuration and the optic and to attach the fixation member to the optic.
摘要翻译：一种制造眼内透镜的方法，包括提供具有近端部分的固定构件，其基端部分包括细长细丝，将所述近端部分处的所述细丝的区域从第一构型转换成适于提供机械互锁并围绕固定构件的近端部分模制光学器件，以在第二构造和光学元件之间形成机械互锁并将固定构件附接到光学元件。

10. 发明授权

US07763434B2 Antagonists of interleukin-15 失效
标题翻译：白细胞介素15的拮抗剂
公开(公告)号：US07763434B2
公开(公告)日：2010-07-27
申请号：US11805835
申请日：2007-05-23
申请人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
发明人： Kenneth H. Grabstein , Dean K. Pettit , Raymond J. Paxton
IPC分类号： G01N33/53
CPC分类号： C07K16/244 , A61K38/00 , A61K47/60 , C07K14/5443 , C07K2317/76
摘要： Antagonists of mammalian interleukin-15 (“IL-15”) are disclosed and include muteins of IL-15 and modified IL-15 molecules that are each capable of binding to the IL-15Rα-subunit and that are incapable of transducing a signal through either the β- or γ-subunits of the IL-15 receptor complex. Also included are monoclonal antibodies against IL-15 that prevent IL-15 from effecting signal transduction through either the β- or γ-subunits of the IL-15 receptor complex. Methods of treating various disease states are disclosed, including treating allograft rejection and graft-versus-host disease.
摘要翻译：公开了哺乳动物白细胞介素-15（“IL-15”）的拮抗剂，并且包括IL-15和修饰的IL-15分子的突变蛋白，其各自能够结合IL-15Rα-亚基并且不能通过 IL-15受体复合物的b-或γ亚基。还包括针对IL-15的单克隆抗体，其阻止IL-15通过IL-15受体复合物的β亚基或γ亚基进行信号转导。公开了治疗各种疾病状态的方法，包括治疗同种异体移植排斥和移植物抗宿主病。

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