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    • 3. 发明申请
    • MUTANT FORMS OF FAS LIGAND AND USES THEREOF
    • FAS配偶的突变形式及其用途
    • WO1998021232A2
    • 1998-05-22
    • PCT/US1997020864
    • 1997-11-13
    • CHIRON CORPORATION
    • CHIRON CORPORATIONCHU, Keting
    • C07K14/00
    • C07K14/70575A61K38/00C07K2319/00C12N2799/021C12N2799/022C12N2799/027
    • The invention provides for DNA encoding Fas ligand muteins and chimeras and the proteins encoded thereby. The invention further includes the use of DNA and vectors to produce transformed cells expressing the mutant or chimeric Fas ligand. When the Fas ligand of the invention is a non cleavable form, the cells expressing the Fas ligand are useful in vitro for identifying Fas expressing cells and in vitro or in vivo for reducing populations of Fas expressing cells. Thus, in other embodiments, the present invention is also directed to a method for treating a patient, for example a mammal, for autoimmune disease or transplant rejection by administering a Fas ligand therapeutic agent. The therapeutic agent is a polypeptide, a polynucleotide encoding the polypeptide or a small molecule. The polypeptides include full-length Fas ligand polypeptide, or a biologically active variant, derivative, portion, fusion or peptide thereof.
    • 本发明提供编码Fas配体突变蛋白和嵌合体的DNA及其编码的蛋白质。 本发明还包括使用DNA和载体产生表达突变体或嵌合Fas配体的转化细胞。 当本发明的Fas配体是不可切割的形式时,表达Fas配体的细胞在体外可用于鉴定Fas表达细胞,并在体外或体内用于减少Fas表达细胞的群体。 因此,在其它实施方案中,本发明还涉及通过施用Fas配体治疗剂来治疗患者,例如哺乳动物用于自身免疫疾病或移植排斥的方法。 治疗剂是多肽,编码多肽的多核苷酸或小分子。 多肽包括全长Fas配体多肽或其生物活性变体,衍生物,部分,融合物或肽。
    • 6. 发明申请
    • MULTIPLE EPITOPE FUSION PROTEIN
    • 多功能融合蛋白融合蛋白
    • WO1997044469A2
    • 1997-11-27
    • PCT/US1997008950
    • 1997-05-23
    • CHIRON CORPORATION
    • CHIRON CORPORATIONVALENZUELA, Pablo, D., T.CHIEN, David, Ying
    • C12N15/62
    • C07K14/005C07K2319/00C12N2770/24222
    • Multiple copy epitope immunoassays are produced by: (1) identifying nucleotide sequences that encode a plurality of different epitopes; (2) placing the nucleotide sequences into an expression cassette wherein at least two copies of a sequence coding for the same epitope, preferably from different strains of a pathogen, are placed in the cassette; (3) transforming a suitable host with the cassette in order to express the sequences encoding the epitopes; (4) purifying the expressed epitopes; and (5) coating the epitopes on a surface of a substrate. The purified epitopes are encompassed by the general structural formula (A)x-(B)y-(C)z which represents a linear amino acid sequence, B is an amino acid sequence of an epitope or cluster of epitopes and each B contains at least five and not more than 1,000 amino acids, y is an integer of 2 or more, A and C are each independently an amino acid sequence of an epitope or cluster of epitopes not adjacent to B in nature and x and z are each independently an integer of 0 or more wherein at least one of x and z is 1 or more. The epitopes of the invention are more soluble than and are therefore more easily purified than conventional epitopes. Further, the presence of repeating epitope sequences (repeating at least B in the same linear amino acid sequence from different strains of a pathogen) increases the sensitivity and specificity of the assay. Repeated epitope sequences in a single linear antigen also decreases masking problems and makes it possible to include a greater number of epitopes on a unit area of substrate thereby improving sensitivity in the detection of antibodies.
    • 多拷贝表位免疫测定通过以下方式产生:(1)鉴定编码多个不同表位的核苷酸序列; (2)将核苷酸序列置于表达盒中,其中编码相同表位,优选来自病原体的不同菌株的序列的至少两个拷贝被放置在盒中; (3)用盒子转化合适的宿主以表达编码表位的序列; (4)纯化表达的表位; 和(5)在基材的表面上涂覆表位。 纯化的表位被代表线性氨基酸序列的一般结构式(A)x-(B)y-(C)z所涵盖,B是表位或表位簇的氨基酸序列,每个B含有 至少5个且不超过1,000个氨基酸,y是2或更大的整数,A和C各自独立地是本质上不与B相邻的表位的表位或簇的氨基酸序列,x和z各自独立地为 0以上的整数,x和z中的至少一个为1以上。 本发明的表位比常规表位更可溶,因此更容易纯化。 此外,重复表位序列的存在(在来自不同病原体的菌株的同一线性氨基酸序列中至少重复B)增加了测定的灵敏度和特异性。 单一线性抗原中的重复表位序列也减少掩蔽问题,并且可以在底物的单位面积上包含更多数目的表位,从而提高抗体检测的灵敏度。