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1. 发明授权

US06794142B2 Amplification using modified primers 有权
标题翻译：使用改良引物进行扩增
公开(公告)号：US06794142B2
公开(公告)日：2004-09-21
申请号：US10083233
申请日：2001-10-24
申请人： Walter J. Laird , John T. Niemiec
发明人： Walter J. Laird , John T. Niemiec
IPC分类号： C12P168
CPC分类号： C12Q1/6848 , C12Q1/6853 , C12Q2525/117
摘要： The present invention provides modified primers for use in the amplification of a nucleic acid sequence. Amplifications carried out using the modified primers result in less template-independent non-specific product (primer dimer) compared to amplifications carried out using unmodified primers.
摘要翻译：本发明提供了用于扩增核酸序列的修饰引物。使用修饰的引物进行的扩增与使用未修饰的引物进行的扩增相比，导致较少的模板非依赖性非特异性产物（引物二聚体）。

2. 发明授权

US06322779B1 Recombinant human CSF-1 dimer and compositions thereof 失效
标题翻译：重组人CSF-1二聚体及其组合物
公开(公告)号：US06322779B1
公开(公告)日：2001-11-27
申请号：US08478712
申请日：1995-06-07
申请人： Robert Halenbeck , Kirston Koths , Cynthia Cowgill , Walter J. Laird
发明人： Robert Halenbeck , Kirston Koths , Cynthia Cowgill , Walter J. Laird
IPC分类号： A61K4500
CPC分类号： C07K14/53 , A61K38/00 , C07K1/1133 , Y10S930/14 , Y10S930/145
摘要： The present invention is directed to an isolated and purified, recombinant, unglycosylated and dimeric CSF-1, the dimeric CSF-1 being biologically active and essentially endotoxin and pyrogen-free, the dimeric CSF-1 consisting essentially of two monomeric human CSF-1 subunits. The present invention is further directed to pharmaceutical compositions comprising the same.
摘要翻译：本发明涉及分离和纯化的重组，未糖基化和二聚体CSF-1，二聚体CSF-1是生物活性的并且基本上是内毒素和无热原的，基本上由两个单体人CSF-1组成的二聚体CSF-1 亚单位。本发明进一步涉及包含其的药物组合物。

3. 发明授权

US4950740A Recombinant diphtheria vaccines 失效
标题翻译：重组白喉疫苗
公开(公告)号：US4950740A
公开(公告)日：1990-08-21
申请号：US164522
申请日：1988-03-07
申请人： Lawrence Greenfield , Anne W. Emerick , Walter J. Laird
发明人： Lawrence Greenfield , Anne W. Emerick , Walter J. Laird
IPC分类号： A61K39/00 , C07K14/34
CPC分类号： C07K14/34 , A61K39/00 , Y10S530/825
摘要： Recombinant diphtheria toxin A fragment muteins which are enzymatically inactive but immunologically crossreactive with diphtheria toxin are disclosed. Intermediates and methods for preparing such proteins using recombinant techniques are also described.
摘要翻译：重组白喉毒素公开了酶促无活性但与白喉毒素交互反应的片段突变蛋白。还描述了使用重组技术制备这种蛋白质的中间体和方法。

4. 发明授权

US4958009A Anti-human ovarian cancer immunotoxins and methods of use thereof 失效
标题翻译：抗人卵巢癌免疫毒素及其使用方法
公开(公告)号：US4958009A
公开(公告)日：1990-09-18
申请号：US69867
申请日：1987-07-06
申请人： Michael J. Bjorn , David J. FitzGerald , Arthur E. Frankel , Walter J. Laird , Ira H. Pastan , David B. Ring , Mark C. Willingham , Jeffrey L. Windelhake
发明人： Michael J. Bjorn , David J. FitzGerald , Arthur E. Frankel , Walter J. Laird , Ira H. Pastan , David B. Ring , Mark C. Willingham , Jeffrey L. Windelhake
IPC分类号： C12N15/02 , A61K38/00 , A61K39/395 , A61K47/00 , A61K47/48 , A61P35/00 , C07K14/00 , C07K14/195 , C07K14/37 , C07K14/41 , C07K14/415 , C07K16/00 , C07K16/30 , C07K19/00 , C12N5/00 , C12N5/10 , C12P21/00 , C12P21/08 , C12R1/91 , G01N33/574 , G01N33/577
CPC分类号： C07K16/30 , A61K47/48638 , A61K38/00 , Y10S424/804 , Y10S424/807 , Y10S514/885 , Y10S530/808 , Y10S530/864
摘要： Immunotoxins comprising a cytotoxic moiety and monoclonal antibodies which bind to human ovarian cancer tissue having at least one of the following capabilities are claimed: cytotoxic ID.sub.50 of 10 nM or less against human ovarian cancer cells, retardation of human ovarian cancer tumor growth in mammals or extension of survival of a mammal carrying a human ovarian cancer tumor. Antigens to which the monoclonal antibody of the immunotoxin bind are identified and characterize the immunotoxins. Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals or extending the survival of mammals carrying human ovarian cancer tumors are claimed.
摘要翻译：包含细胞毒素部分的免疫毒素和结合至少具有以下能力之一的人卵巢癌组织的单克隆抗体是要求保护的：针对人卵巢癌细胞的10nM或更小的细胞毒性ID50，哺乳动物或延伸中人卵巢癌肿瘤生长的延迟携带人卵巢癌肿瘤的哺乳动物的存活。识别免疫毒素结合的单克隆抗体的抗原并表征免疫毒素。要求杀死人类卵巢癌细胞的方法，延缓哺乳动物中人卵巢癌肿瘤的生长或延长携带人卵巢癌肿瘤的哺乳动物的存活。

5. 发明授权

US4771128A Method of purifying toxin conjugates using hydrophobic interaction chromatography 失效
标题翻译：使用疏水作用色谱法纯化毒素结合物的方法
公开(公告)号：US4771128A
公开(公告)日：1988-09-13
申请号：US917469
申请日：1986-10-10
申请人： Robert Ferris , Walter J. Laird
发明人： Robert Ferris , Walter J. Laird
IPC分类号： C12P21/00 , A61K47/48 , C07K1/16 , C07K1/20 , C07K14/00 , C07K14/485 , C07K14/52 , C07K14/525 , C07K14/54 , C07K14/545 , C07K14/55 , C07K14/575 , C07K16/00 , C12N9/64 , C12P21/08 , C07K3/18
CPC分类号： A61K47/48476
摘要： A method of isolating and purifying toxin conjugates using hydrophobic interaction chromatography. Crude conjugate mixtures are sized to remove unconjugated toxin, and loaded onto a column filled with a suitable hydrophobic gel. Elution is effected with salt solutions of decreasing ionic strength, which salt solutions optionally include increasing amounts of an organic solvent. Toxin conjugate substantially free of unconjugated Ig and unconjugated toxin is provided.

6. 发明授权

US5651963A Heterodimers forms of CSF-1 and pharmaceutical compositions thereof 失效
标题翻译： CSF-1的异二聚体形式及其药物组合物
公开(公告)号：US5651963A
公开(公告)日：1997-07-29
申请号：US334456
申请日：1994-11-04
申请人： Robert Halenbeck , Kirston Koths , Cynthia Cowgill , Walter J. Laird
发明人： Robert Halenbeck , Kirston Koths , Cynthia Cowgill , Walter J. Laird
IPC分类号： A61K38/00 , A61K38/19 , C07K1/113 , C07K1/16 , C07K14/53 , C12N15/27 , C12P21/02
CPC分类号： C07K14/53 , C07K1/1133 , A61K38/00 , Y10S930/14 , Y10S930/145
摘要： The present invention relates to the production of CSF-1 heterodimers and pharmaceutical formulations of the heterodimers. The heterodimers can be formed using CSF-1 monomers that have variations in sequence, N or C-terminal processing. For example, CSF/C.gradient.150 can be dimerized with LCSF/C.gradient. 190 to form a heterodimer. Dimerization may occur by separately preparing homodimers and mixing them together under the appropriate conditions. Thereafter, homodimers may be separated from the heterodimers by various chromatographic techniques. Once the heterodimers are isolated, pharmaceutical preparations can be prepared.
摘要翻译：本发明涉及产生异源二聚体的CSF-1异二聚体和药物制剂。异二聚体可以使用具有序列变化，N或C末端加工的CSF-1单体形成。例如，CSF / C NABLA 150可以用LCSF / C NABLA 190二聚化以形成异二聚体。二聚可以通过单独制备同型二聚体并在合适的条件下将它们混合在一起而发生。此后，可以通过各种色谱技术将同二聚体与异二聚体分离。一旦异源二聚体被分离，就可以制备药物制剂。

7. 发明授权

US5153265A Conjugation of polymer to colony stimulating factor-1 失效
标题翻译：聚合物与集落刺激因子-1的结合
公开(公告)号：US5153265A
公开(公告)日：1992-10-06
申请号：US576415
申请日：1990-08-30
申请人： Paula J. Shadle , Kirston E. Koths , Margaret Moreland , Nandini Katre , Walter J. Laird , Lois Aldwin , Danute E. Nitecki , John D. Young
发明人： Paula J. Shadle , Kirston E. Koths , Margaret Moreland , Nandini Katre , Walter J. Laird , Lois Aldwin , Danute E. Nitecki , John D. Young
IPC分类号： A61K38/00 , A61K47/48 , C07K14/53
CPC分类号： A61K47/48215 , A61K47/48176 , C07K14/53 , A61K38/00
摘要： A biologically active CSF-1 protein is selectively conjugated via certain amino acid residues or carbohydrate moieties to a water-soluble polymer selected from polyethylene glycol or polypropylene glycol homopolymers, polyoxyethylated polyols, or polyvinyl alcohol. The resulting conjugated CSF-1 is biologically active and has increased circulating half-life in mammals, compared to that of the unconjugated protein. The conjugated CSF-1 may be used to stimulate the immune response or to provide more cells to be stimulated.
摘要翻译： PCT No.PCT / US89 / 00270 Sec。 371日期1990年8月30日 102（e）1990年8月30日PCT PCT 1989年1月23日提交PCT生物活性CSF-1蛋白通过某些氨基酸残基或碳水化合物部分选择性地与选自聚乙二醇或聚丙二醇均聚物的水溶性聚合物，聚氧乙烯化多元醇或聚乙烯醇。与未缀合的蛋白质相比，得到的共轭CSF-1具有生物活性并且在哺乳动物中具有增加的循环半衰期。缀合的CSF-1可用于刺激免疫应答或提供更多待刺激的细胞。

8. 发明授权

US4956453A Anti-human ovarian cancer immunotoxins and methods of use thereof 失效
标题翻译：抗人卵巢癌免疫毒素及其使用方法
公开(公告)号：US4956453A
公开(公告)日：1990-09-11
申请号：US69720
申请日：1987-07-06
申请人： Michael J. Bjorn , Arthur E. Frankel , Walter J. Laird , David B. Ring , Jeffrey L. Winkelhake
发明人： Michael J. Bjorn , Arthur E. Frankel , Walter J. Laird , David B. Ring , Jeffrey L. Winkelhake
IPC分类号： A61K38/00 , A61K47/48 , C07K16/30
CPC分类号： C07K16/30 , A61K47/48638 , A61K38/00 , Y10S424/804 , Y10S424/807 , Y10S514/885 , Y10S530/808 , Y10S530/861 , Y10S530/864 , Y10S530/866
摘要： Immunotoxins comprising a cytotoxic moiety and an antigen binding portion selected from the group consisting of Fab, Fab' and F(ab').sub.2 fragments of a monoclonal antibody, which binds to human ovarian cancer tissue, having one of the following capabilities are claimed: cytotoxic ID.sub.50 of about 10 nM or less against human ovarian cancer cells, retardation of human ovarian cancer tumor growth in mammals, or extension of survival of a mammal carrying a human ovarian cancer tumor. Antigens or epitopes to which the monoclonal antibodies bind are identified and characterize the immunotoxins. In a preferred embodiment an immunotoxin comprising at least an antigen binding portion of a monoclonal antibody, which binds to human transferrin receptor, but does not block binding of transferrin to the receptor, is described and claimed. Immunotoxin comprising the F(ab').sub.2 region of the antitransferrin monoclonal antibody are also claimed.Methods of killing human ovarian cancer cells, retarding the growth of human ovarian cancer tumors in mammals and extending the survial of mammals carrying human ovarian cancer tumors are claimed.
摘要翻译：要求具有下列能力之一的包含细胞毒素部分和选自Fab，Fab'和F（ab'）2结合部分的单克隆抗体结合人卵巢癌组织的抗原结合部分的免疫毒素：对人卵巢癌细胞约10nM或更少的细胞毒性ID50，哺乳动物中人卵巢癌肿瘤生长的延迟或携带人卵巢癌肿瘤的哺乳动物的存活的延长。识别单克隆抗体结合的抗原或表位，并表征免疫毒素。在优选的实施方案中，描述并要求保护包含至少结合人转铁蛋白受体但不阻断转铁蛋白与受体结合的单克隆抗体的抗原结合部分的免疫毒素。还要求保护包含抗转铁蛋白单克隆抗体的F（ab'）2区的免疫毒素。要求杀死人类卵巢癌细胞的方法，延缓哺乳动物中人卵巢癌肿瘤的生长并延长携带人卵巢癌肿瘤的哺乳动物的存活。

9. 发明授权

US4948729A Production of soluble recombinant proteins 失效
标题翻译：生产可溶性重组蛋白
公开(公告)号：US4948729A
公开(公告)日：1990-08-14
申请号：US171132
申请日：1988-03-17
申请人： Michael Piatak, Jr. , Walter J. Laird , Julie A. Lane
发明人： Michael Piatak, Jr. , Walter J. Laird , Julie A. Lane
IPC分类号： C07K14/415 , C12N9/16 , C12N15/67
CPC分类号： C12N15/67 , C07K14/415 , C12N9/16 , C07K2319/00 , C07K2319/02 , C07K2319/034 , C07K2319/55
摘要： A system for expression of coding sequences for desired heterologous proteins in procaryotic hosts whereby the protein is produced intracellularly in soluble, biologically active form, is disclosed. The expression is obtained by ligation of the coding sequence downstream of, and proximally to, but out of reading frame with, the terminated leader encoding sequence for a secreted bacterial protein, such as alkaline phosphatase. The resultant proteins are influenced by the leader sequence codons to effect the desired three-dimensional conformation, but not to effect secretion.
摘要翻译：公开了一种用于在原核宿主中表达所需异源蛋白的编码序列的系统，其中蛋白质以可溶性，生物活性形式在细胞内产生。通过用分泌的细菌蛋白（例如碱性磷酸酶）的终止的前导序列编码序列连接编码序列的下游和近端，但与阅读框之间的编码序列获得该表达。所得蛋白质受前导序列密码子的影响，以产生所需的三维构象，但不影响分泌。

10. 发明授权

US4929700A Production of purified, biologically active, bacterially produced recombinant human CSF-1 失效
标题翻译：生产纯化的，生物活性的，细菌生产的重组人CSF-1
公开(公告)号：US4929700A
公开(公告)日：1990-05-29
申请号：US173428
申请日：1988-04-08
申请人： Robert Halenbeck , Kriston Koths , Cynthia Cowgill , Walter J. Laird
发明人： Robert Halenbeck , Kriston Koths , Cynthia Cowgill , Walter J. Laird
IPC分类号： A61K38/00 , C07K1/113 , C07K14/53
CPC分类号： C07K1/1133 , C07K14/53 , A61K38/00 , Y10S530/82 , Y10S530/825
摘要： A process for recovering dimeric, biologically active CSF-1 from bacterially expressed recombinant CSF1 genes is described. The process comprises recovery of the solubilized monomeric form, followed by dimerization under refolding conditions and further purification of the dimer. Heterodimers may also be produced by this process.
摘要翻译：描述了从细菌表达的重组CSF1基因中回收二聚体，生物活性CSF-1的方法。该方法包括回收溶解的单体形式，然后在重折叠条件下进行二聚化并进一步纯化二聚体。异源二聚体也可以通过该方法生产。

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