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101. 发明授权

US06808902B1 Process for correction of a disulfide misfold in IL-1ra FC fusion molecules 失效
标题翻译：用于校正IL-1Ra Fc融合分子中二硫键错误的方法
公开(公告)号：US06808902B1
公开(公告)日：2004-10-26
申请号：US09709704
申请日：2000-11-09
申请人： Michael J. Treuheit , Sheila R. O'Conner , Andrew A. Kosky
发明人： Michael J. Treuheit , Sheila R. O'Conner , Andrew A. Kosky
IPC分类号： C12P2104
CPC分类号： C07K1/1133 , C07K14/70578 , C07K2319/00 , C07K2319/30 , Y10S530/825 , Y10S530/866 , Y10S530/867
摘要： The present invention concerns a process by which a misfold in an Fc fusion molecule can be prevented or corrected. In one embodiment, the process comprises (a) preparing a pharmacologically active compound comprising an Fc domain; (b) treating the fusion molecule with a copper (II) halide; and (c) isolating the treated fusion molecule. The pharmacologically active compound can be an antibody or a fusion molecule comprising a pharmacologically active domain and an Fc domain. The preferred copper (II) halide is CuCl2. The preferred concentration thereof is at least about 10 mM for fusion molecules prepared in E. coli; at least about 30 mM for fusion molecules prepared in CHO cells. The process can be employed with any number of pharmacologically active domains. Preferred pharmacologically active domains include OPG proteins, leptin proteins, soluble portions of TNF receptors (e.g., wherein the fusion molecule is etanercept), IL-1ra proteins, and TPO-mimetic peptides. The Fc domain preferably has a human sequence, with an Fc sequence derived from IgG1 most preferred. An exemplary Fc sequence is shown in FIG. 5 hereinafter.
摘要翻译：本发明涉及可以防止或校正Fc融合分子中的错误折叠的方法。在一个实施方案中，该方法包括（a）制备包含Fc结构域的药理活性化合物; （b）用卤化铜（II）处理融合分子; 和（c）分离经处理的融合分子。药理活性化合物可以是包含药理活性结构域和Fc结构域的抗体或融合分子。优选的卤化铜（II）是CuCl 2。对于在大肠杆菌中制备的融合分子，其优选的浓度为至少约10mM; 对CHO细胞中制备的融合分子至少约30mM。该方法可以与任何数量的药理活性结构域一起使用。优选的药理活性结构域包括OPG蛋白，瘦素蛋白，TNF受体的可溶性部分（例如，其中融合分子是依那西普），IL-1ra蛋白和TPO-模拟肽。 Fc结构域优选具有人序列，最优选来源于IgG1的Fc序列。示例性Fc序列示于图1。 5。

102. 发明授权

US06806070B1 Use of bacterial extracts of the pseudomonadaceae family as cosmetic agents 有权
标题翻译：使用假单胞菌科的细菌提取物作为化妆品
公开(公告)号：US06806070B1
公开(公告)日：2004-10-19
申请号：US10049552
申请日：2002-04-18
申请人： Richard Martin , Pascal Hilaire , Nathalie Pineau , Lionel Breton
发明人： Richard Martin , Pascal Hilaire , Nathalie Pineau , Lionel Breton
IPC分类号： C12P104
CPC分类号： A61K8/99 , A61Q19/08 , Y10S435/825 , Y10S435/849 , Y10S435/874 , Y10S530/866 , Y10S530/867
摘要： Use of an extract of bacterium from the family Pseudomonadaceae in the production of cosmetic compositions in particular for combating ageing of the skin.
摘要翻译：在化妆品组合物的生产中使用来自假单胞菌科的细菌提取物，特别是用于对抗皮肤老化。

103. 发明授权

US06593081B1 Production of anti-self antibodies from antibody segment repertoires and displayed on phage 失效
公开(公告)号：US06593081B1
公开(公告)日：2003-07-15
申请号：US09532840
申请日：2000-03-21
申请人： Andrew David Griffiths , Hendricus Renerus Jacobus Mattheus Hoogenboom , James David Marks , John McCafferty , Gregory Paul Winter , Geoffrey Walter Grigg
发明人： Andrew David Griffiths , Hendricus Renerus Jacobus Mattheus Hoogenboom , James David Marks , John McCafferty , Gregory Paul Winter , Geoffrey Walter Grigg
IPC分类号： C12O170
CPC分类号： C40B40/02 , B01J2219/00718 , C07K16/005 , C07K16/18 , C07K16/22 , C07K16/241 , C07K16/26 , C07K16/28 , C07K16/2812 , C07K16/2863 , C07K16/2866 , C07K16/3007 , C07K16/3092 , C07K16/34 , C07K16/40 , C07K16/4208 , C07K16/4241 , C07K16/44 , C07K16/462 , C07K16/468 , C07K2317/21 , C07K2317/24 , C07K2317/55 , C07K2317/622 , C07K2317/92 , C07K2319/00 , C07K2319/02 , C07K2319/41 , C07K2319/735 , C12N15/1037 , C12N15/62 , Y10S530/867
摘要： Methods are disclosed for the production of human self-antibodies and antibody fragments, which bind human antigens. Methods comprise providing a library of replicable genetic display packages (rgdps), such as filamentous phage, each rgdp displaying at its surface a member of a specific binding pair which is an antibody or antibody fragment, and each rgdp containing nucleic acid sequence derived from a species of mammal. The nucleic acid sequence in each rgdp encodes a polypeptide chain which is a component part of the sbp member displayed at the surface of that rgdp. Human antibodies or antibody fragments are selected by binding with human antigens. The displayed antibody fragments may be scFv, Fd, Fab or any other fragment which has the capability of binding to and is a human antigen. Nucleic acid libraries used may be derived from V-gene sequences of unimmunised humans. Part or all of the nucleic acid may be derived from oligonucleotide synthesis.

104. 发明授权

US06558672B1 Methods of making recombinant disulfide-stabilized polypeptide fragments having binding specificity 有权
标题翻译：制备具有结合特异性的重组二硫键稳定的多肽片段的方法
公开(公告)号：US06558672B1
公开(公告)日：2003-05-06
申请号：US09657274
申请日：2000-09-07
申请人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
发明人： Ira H. Pastan , Byungkook Lee , Sun-Hee Jung , Ulrich Brinkmann
IPC分类号： A61K3900
CPC分类号： C07K14/7051 , A61K38/00 , A61K47/6829 , A61K47/6835 , C07K16/00 , C07K2319/00 , C07K2319/33 , C07K2319/55 , Y10S530/866 , Y10S530/867
摘要： The present invention relates to disulfide-stabilized recombinant polypeptide molecules which have the binding ability and specificity for another peptide, such as the variable region of an antibody molecule. Methods of producing these molecules and nucleic acid sequences encoding these molecules are also described. In particular, the invention discloses Fv antibody fragments stabilized by a disulfide bond connecting the VH and VL regions of the Fv fragment. The &agr; and &bgr; chains of T cell receptors may be similarly stabilized by means described in the invention.
摘要翻译：本发明涉及对另一种肽（例如抗体分子的可变区）具有结合能力和特异性的二硫键稳定的重组多肽分子。还描述了生产这些分子的方法和编码这些分子的核酸序列。特别地，本发明公开了通过连接Fv片段的VH和VL区的二硫键稳定的Fv抗体片段。 T细胞受体的α链和β链可以通过本发明所述的手段相似地稳定。

105. 发明授权

US06441141B1 Synthetic peptides, antibodies against them and their use 失效
标题翻译：合成肽，抗体及其用途
公开(公告)号：US06441141B1
公开(公告)日：2002-08-27
申请号：US09408172
申请日：1999-09-29
申请人： Michael Kraus , Werner Stüber
发明人： Michael Kraus , Werner Stüber
IPC分类号： C07K1600
CPC分类号： C07K16/36 , A61K38/00 , C07K14/75 , Y10S530/867 , Y10S930/10
摘要： The present invention is directed to the generation of antibodies which preferentially bind to fibrinogen fragments E1, E2 and E3, but exhibit little or no cross-reactivity against fibrin monomer and fibrinogen. Thus, the invention provides synthetic peptides containing defined amino acid sequences corresponding to the carboxy terminal regions of the E fragments which arise as a result of plasmin cleavage of fibrin and fibrinogen. The synthetic peptides may be synthesized chemically, or through genetic manipulations, and may contain additional amino acid sequences which are not contiguous with the defined E fragment sequences.
摘要翻译：本发明涉及产生优先结合纤维蛋白原片段E1，E2和E3的抗体，但对纤维蛋白单体和纤维蛋白原表现出很少的或没有交叉反应性的抗体。因此，本发明提供了含有对应于由纤维蛋白和纤维蛋白原的纤溶酶切割引起的E片段的羧基末端区域的限定氨基酸序列的合成肽。合成肽可以化学合成或通过遗传操作合成，并且可以含有与所定义的E片段序列不连续的另外的氨基酸序列。

106. 发明授权

US06369204B1 Antibodies to &agr;v&bgr;3 integrin 失效
标题翻译：抗体为alphavbeta3整合素
公开(公告)号：US06369204B1
公开(公告)日：2002-04-09
申请号：US09560743
申请日：2000-04-28
申请人： Kyung Jin Kim , Michael A. Horton , Sarah C. Bodary , Anan Chuntharapai
发明人： Kyung Jin Kim , Michael A. Horton , Sarah C. Bodary , Anan Chuntharapai
IPC分类号： C12P2108
CPC分类号： C07K16/2848 , A61K38/00 , Y10S530/867
摘要： The invention relates to monoclonal antibodies to the &agr;v&bgr;3 integrin receptor known to be expressed in large amounts on the surface of osteoclasts and accordingly, associated with bone resorption. The disclosed monoclonal antibodies are believed to recognize unique epitopes on &agr;v&bgr;3 and are useful in the treatment of conditions associated with excessive bone resorption and/or in the inhibition of tumor cell growth.
摘要翻译：本发明涉及已知在破骨细胞表面上大量表达的α受体α整联蛋白受体的单克隆抗体，因此与骨吸收有关。据信所公开的单克隆抗体识别出在α2β3上的独特表位，并且可用于治疗与过量骨吸收和/或抑制肿瘤细胞生长相关的病症。

107. 发明授权

US06274324B1 Specific binding reagent comprising a variable domain protein linked to a support or tracer 失效
标题翻译：特异性结合试剂包含与支持物或示踪剂连接的可变结构域蛋白质
公开(公告)号：US06274324B1
公开(公告)日：2001-08-14
申请号：US08226376
申请日：1994-04-12
申请人： Paul James Davis , Martine Elisa Verhoeyen , Ronald Frank Jacobus De Winter
发明人： Paul James Davis , Martine Elisa Verhoeyen , Ronald Frank Jacobus De Winter
IPC分类号： G01N3353
CPC分类号： C12N9/0065 , C07K16/00 , C07K16/40 , C07K16/44 , C07K2319/00 , C12N9/16 , C12N15/62 , G01N33/532 , G01N33/54353 , G01N33/6857 , Y10S530/81 , Y10S530/866 , Y10S530/867
摘要： Small specific binding molecules, such as single variable domain antibodies (Dabs) and Fv fragments, can be coupled to solid plastics surfaces or to tracers such as enzymes by means of linkers comprising polypeptides containing from 5 to 20 amino acids and which are hydrophobic and/or contain at least one lysine residue. The coupling can be achieved without significant loss of specific binding activity. The combined Dab/linker or Fv/linker can be prepared by expression in genetically-modified organisms.
摘要翻译：小的特异性结合分子，例如单可变结构域抗体（Dabs）和Fv片段可以通过包含5至20个氨基酸的多肽的接头偶联到固体塑料表面或示踪剂如酶，并且它们是疏水和/ 或含有至少一个赖氨酸残基。可以实现偶联，而不会明显损失特异性结合活性。组合的Dab /接头或Fv /接头可以通过在遗传修饰的生物中表达来制备。

108. 发明授权

US6139869A Human monoclonal antibody specifically binding to surface antigen of cancer cell membrane 失效
标题翻译：特异性结合癌细胞膜表面抗原的人单克隆抗体
公开(公告)号：US6139869A
公开(公告)日：2000-10-31
申请号：US450363
申请日：1995-05-25
申请人： Saiko Hosokawa , Toshiaki Tagawa , Yoko Hirakawa , Norihiko Ito , Kazuhiro Nagaike
发明人： Saiko Hosokawa , Toshiaki Tagawa , Yoko Hirakawa , Norihiko Ito , Kazuhiro Nagaike
IPC分类号： A61K9/127 , A61K38/00 , A61K47/48 , C07K16/30 , C12N5/28 , C12P21/08 , A61K9/133 , A61K39/395
CPC分类号： B82Y5/00 , A61K47/48615 , A61K47/48823 , A61K9/1271 , C07K16/3046 , A61K2039/505 , A61K38/00 , C07K2317/21 , C07K2317/50 , Y10S424/812 , Y10S530/808 , Y10S530/809 , Y10S530/865 , Y10S530/866 , Y10S530/867
摘要： A human monoclonal antibody specifically binding to a surface antigen of cancer cell membrane, an isolated DNA encoding the antibody, and a hybridoma producing the antibody. An anti-cancer formulation comprising the monoclonal antibody bonded to the surface of a liposome enclosing an anti-cancer agent or toxin is also provided.
摘要翻译：特异性结合癌细胞膜的表面抗原的人单克隆抗体，编码抗体的分离的DNA和产生抗体的杂交瘤。还提供了包含结合到包围抗癌剂或毒素的脂质体表面的单克隆抗体的抗癌制剂。

109. 发明授权

US5990296A Single chain B3 antibody fusion proteins and their uses 失效
标题翻译：单链B3抗体融合蛋白及其用途
公开(公告)号：US5990296A
公开(公告)日：1999-11-23
申请号：US759804
申请日：1996-12-03
申请人： Ira Pastan , Mark Willingham , David Fitzgerald , Ulrich Brinkmann , Lee Pai
发明人： Ira Pastan , Mark Willingham , David Fitzgerald , Ulrich Brinkmann , Lee Pai
IPC分类号： A61K38/00 , A61K47/48 , A61P35/00 , C07K14/21 , C07K16/18 , C07K16/30 , C07K16/34 , C07K19/00 , G01N33/574 , C07H21/04
CPC分类号： A61K47/48569 , C07K14/21 , C07K16/18 , C07K16/30 , C07K16/34 , C07K19/00 , G01N33/57419 , G01N33/57446 , G01N33/57449 , G01N33/57492 , A61K38/00 , C07K2317/24 , C07K2317/56 , C07K2317/622 , C07K2319/00 , Y10S530/866 , Y10S530/867
摘要： This invention provides for recombinant single chain antibodies capable of specifically binding to a Lewis.sup.Y -related carbohydrate antigen and fusion proteins comprising these antibodies. More particularly, the invention provides for single chain Fv regions of the monoclonal antibody B3. The invention also provides for a method of improving the binding affinity of antibodies lacking a serine at position 95 of the V.sub.H region that involves mutating position 95 to a serine.
摘要翻译：本发明提供能够特异性结合LewisY相关糖类抗原的重组单链抗体和包含这些抗体的融合蛋白。更具体地，本发明提供单克隆抗体B3的单链Fv区。本发明还提供了一种方法，其将VH区域的95位缺失丝氨酸的抗体与包含突变位置95的丝氨酸相结合。

110. 发明授权

US5990287A Human monoclonal antibody specifically binding to surface antigen of cancer cell membrane 失效
公开(公告)号：US5990287A
公开(公告)日：1999-11-23
申请号：US17628
申请日：1998-02-02
申请人： Saiko Hosokawa , Toshiaki Tagawa , Yoko Hirakawa , Norihiko Ito , Kazuhiro Nagaike
发明人： Saiko Hosokawa , Toshiaki Tagawa , Yoko Hirakawa , Norihiko Ito , Kazuhiro Nagaike
IPC分类号： A61K9/127 , A61K38/00 , A61K47/48 , C07K16/30 , C12N5/28 , C12P21/08 , C07K16/18 , C07K16/28
CPC分类号： B82Y5/00 , A61K47/48615 , A61K47/48823 , A61K9/1271 , C07K16/3046 , A61K2039/505 , A61K38/00 , C07K2317/21 , C07K2317/50 , Y10S424/812 , Y10S530/808 , Y10S530/809 , Y10S530/865 , Y10S530/866 , Y10S530/867
摘要： A human monoclonal antibody specifically binding to a surface antigen of cancer cell membrane, an isolated DNA encoding the antibody, and a hybridoma producing the antibody. An anti-cancer formulation comprising the monoclonal antibody bonded to the surface of a liposome enclosing an anti-cancer agent or toxin is also provided.

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