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    • 3. 发明申请
    • METHOD OF MAKING MONOCLONAL ANTIBODIES USING POLYMORPHIC TRANSGENIC ANIMALS
    • 使用多态性转基因动物制备单克隆抗体的方法
    • WO1998021316A1
    • 1998-05-22
    • PCT/US1997020783
    • 1997-11-14
    • THE NEW YORK BLOOD CENTER, INC.
    • THE NEW YORK BLOOD CENTER, INC.REID, Marion, E.
    • C12N05/28
    • C12N15/8509A01K67/0278A01K2207/15A01K2217/00A01K2227/105A01K2267/01C07K16/34
    • The invention relates to a method for making monoclonal antibodies having pre-defined specificity of an epitope characteristic of or unique to a single form of a polymorphic protein. The method includes constructing a first transgenic animal to express a first form of a polymorphic protein encoded by a first allele of a gene encoding the protein; constructing a second transgenic animal to express a second form of the polymorphic protein encoded by a second allele of the gene encoding the protein; and immunizing the first transgenic animal with cells from the second transgenic animal expressing the second form of the polymorphic protein to induce an immune response in the first transgenic animal yielding an antibody specific for an epitope peculiar to the second form of the polymorphic protein. The invention further includes hybridoma cells secreting a monoclonal antibody specific for the second form of the protein. The invention is particularly advantageous in the context of making monoclonal antibodies and derivative reagents specifically identifying polymorphic blood group proteins, such as the Duffy gp-Fy protein.
    • 本发明涉及制备具有单一形式的多态性蛋白质特征性或独特性的表位的预定特异性的单克隆抗体的方法。 该方法包括构建第一转基因动物以表达由编码该蛋白质的基因的第一等位基因编码的第一形式的多态性蛋白; 构建第二转基因动物以表达由编码蛋白质的基因的第二等位基因编码的第二形式的多态性蛋白质; 以及用表达第二形式的多态性蛋白质的第二转基因动物的细胞免疫第一转基因动物,以在第一转基因动物中诱导免疫应答,产生对第二形式的多态性蛋白质特异性表位的抗体。 本发明还包括分泌针对第二种蛋白质特异性的单克隆抗体的杂交瘤细胞。 本发明在制备单克隆抗体和特异性鉴定多形性血型蛋白如Duffy gp-Fy蛋白的衍生试剂的背景下是特别有利的。
    • 5. 发明申请
    • THE CLONING OF DUFFY BLOOD GROUP ANTIGEN
    • DUFFY血液组抗原克隆
    • WO1998021224A1
    • 1998-05-22
    • PCT/US1997021067
    • 1997-11-14
    • THE NEW YORK BLOOD CENTER, INC.
    • THE NEW YORK BLOOD CENTER, INC.POGO, Oscar, A.CHAUDHURI, Asok
    • C07H21/00
    • A01K67/0275A01K2217/05A01K2227/105A01K2267/0337A01K2267/0381C07K14/715C12N15/8509
    • The major subunit of the Duffy blood group antigenic system, gp-Fy protein, has been isolated, as have two variants, gp-Fy alpha and/or gp-Fy beta , which are produced from the Duffy FY gene by a differential splicing mechanism. gp-Fy protein contains the receptor by which P. vivax enters red cells and causes malaria. gp-Fy protein has therapeutic value in the prevention of malaria and in the regulation of erythrocyte, neural and renal functions and can be combined with physiologically acceptable diluents to yield a therapeutic agent suitable for these purposes. Peptides corresponding to a portion of gp-Fy protein that contains the receptor also have been synthesized. gp-Fy protein and derived peptides have utility in the production of therapeutics, e.g., antibodies, complementary peptides, etc., which are also useful to treat malaria and regulate essential erythrocyte, neural and renal functions. Also provided are nucleic acid primers and probes which specifically bind to or hybridize with portions of the FY gene or DNA or RNA derived therefrom for detecting the presence of gp-Fy alpha and/or gp-Fy beta nucleic acids in tissues samples. Methods for detecting Duffy protein expression, i.e., differential expression of gp-Fy alpha and/or gp-Fy beta proteins are provided.
    • 已经分离了Duffy血型抗原系统gp-Fy蛋白的主要亚单位,其具有通过差异剪接机制从Duffy FY基因产生的两种变体gp-Fyα和/或gp-Fyβ 。 gp-Fy蛋白含有间日疟原虫进入红细胞并引起疟疾的受体。 gp-Fy蛋白在预防疟疾和调节红细胞,神经和肾功能方面具有治疗价值,并且可以与生理上可接受的稀释剂组合以产生适合于这些目的的治疗剂。 对应于含有受体的gp-Fy蛋白的一部分的肽也已经合成。 gp-Fy蛋白质和衍生肽可用于生产治疗剂,例如抗体,互补肽等,其也可用于治疗疟疾和调节重要的红细胞,神经和肾功能。 还提供了与FY基因的部分或其衍生的DNA或RNA特异性结合或杂交的核酸引物和探针,用于检测组织样品中gp-Fyα和/或gp-Fyβ核酸的存在。 提供了检测Duffy蛋白表达的方法,即gp-Fyα和/或gp-Fyβ蛋白的差异表达。
    • 6. 发明申请
    • FIBRIN(OGEN) DEGRADATION AND CLOT LYSIS BY FIBRINOLYTIC MATRIX METALLOPROTEINASE
    • 纤维素(OGEN)降解和纤维素基质金属蛋白酶的衣物
    • WO1996036227A1
    • 1996-11-21
    • PCT/US1996007188
    • 1996-05-17
    • THE NEW YORK BLOOD CENTER, INC.BINI, Alessandra
    • THE NEW YORK BLOOD CENTER, INC.
    • A01N37/18
    • A61K38/4886
    • The invention provides a method of causing the degradation of fibrin(ogen) (i.e., fibrin, fibrinogen, and related substances) by means of a fibrinolytic metalloproteinase, preferably an endogenous metalloproteinase such as MMP-3. The method of the invention can be performed in vitro to provide diagnostic information characterizing fibrin(ogen) and fibrinolytic physiology. The method can also be performed in vivo as a method of thrombolytic therapy in which a fibrinolytic metalloproteinase is administered to a subject to degrade thrombus in situ. The endogenous fibrinolytic metalloproteinase can be administered in conjunction with other active agents, preferably with agents having thrombolytic activity to improve thrombolytic and fibrinolytic therapy. The invention further provides compositions containing a fibrinolytic metalloproteinase for the performance of fibrinolytic or thrombolytic procedures. Also provided are kits which include a fibrinolytic metalloproteinase for performing fibrinolytic or thrombolytic procedures.
    • 本发明提供了通过纤维蛋白溶解性金属蛋白酶(优选内源性金属蛋白酶如MMP-3)引起纤维蛋白(原子)(即纤维蛋白,纤维蛋白原和相关物质)降解的方法。 本发明的方法可以在体外进行以提供表征纤维蛋白(ogen)和纤维蛋白溶解生理学的诊断信息。 该方法也可以作为血栓溶解治疗方法在体内进行,其中向受试者施用纤维蛋白溶解性金属蛋白酶以原位降解血栓。 内源性纤维蛋白溶解性金属蛋白酶可以与其他活性剂联合施用,优选与具有溶栓活性的试剂一起施用以改善溶栓和纤维蛋白溶解治疗。 本发明还提供含有纤维蛋白溶解性金属蛋白酶用于纤维蛋白溶解或血栓溶解过程的组合物。 还提供了包括用于进行纤维蛋白溶解或血栓溶解过程的纤维蛋白溶解性金属蛋白酶的试剂盒。
    • 7. 发明申请
    • MALARIAL BINDING SITE ON DUFFY BLOOD GROUP PROTEIN
    • 疟疾组合蛋白质中的疟疾结合位点
    • WO1998021235A1
    • 1998-05-22
    • PCT/US1997021063
    • 1997-11-14
    • THE NEW YORK BLOOD CENTER, INC.
    • THE NEW YORK BLOOD CENTER, INC.POGO, Oscar, A.CHAUDHURI, Asok
    • C07K14/445
    • C07K14/715A61K38/00A61K39/00Y02A50/412
    • A composition and method for inhibiting binding of malarial Duffy-binding ligand to Duffy blood group antigens on mammalian erythrocytes is disclosed. The composition includes a Duffy-related peptide which interferes with binding between Duffy antigen expressed on erythrocyte cell surfaces and the Duffy-binding ligands of merozoites. Particularly preferred peptides are the peptides having the sequences AELSPSTENSSQLDFEDVWNSSYGVNDSFPDGDYD (SEQ ID NO:1) or AELSPSTQNSSQLNSDLWNFSYDGNDSFPDVDYD (SEQ ID NO:4), as well as peptides which comprise either of those sequences in their primary structure, or other peptides having equivalent function. A method is disclosed which comprises administering a Duffy-based peptide which interferes with malarial binding to Duffy antigen in an amount sufficient to inhibit binding of merozoites to erythrocytes.
    • 公开了一种用于抑制疟疾Duffy结合配体与哺乳动物红细胞上的Duffy血型抗原结合的组合物和方法。 组合物包含Duffy相关肽,其干扰在红细胞表面上表达的Duffy抗原与裂殖子的Duffy结合配体之间的结合。 特别优选的肽是具有序列AELSPSTENSSQLDFEDVWNSSYGVNDSFPDGDYD(SEQ ID NO:1)或AELSPSTQNSSQLNSDLWNFSYDGNDSFPDVDYD(SEQ ID NO:4)的肽以及包含其一级结构的那些序列之一的肽或具有等同功能的其它肽。 公开了一种方法,其包括以足以抑制裂殖子与红细胞结合的量施用干扰疟疾结合Duffy抗原的Duffy基肽。
    • 8. 发明申请
    • DIAGNOSTIC METHOD AND KIT FOR DETERMINING Rh BLOOD GROUP GENOTYPE
    • 诊断方法和用于确定Rh血液组基因组的试剂盒
    • WO1997017468A1
    • 1997-05-15
    • PCT/US1996017465
    • 1996-10-28
    • THE NEW YORK BLOOD CENTER, INC.
    • THE NEW YORK BLOOD CENTER, INC.HUANG, Cheng-Han
    • C12Q01/68
    • C12Q1/6881C12Q1/683C12Q2600/156C12Q2600/172Y10S435/81
    • The invention provides a diagnostic method of determining Rh genotypes by the identification of the molecular basis of Rh polymorphisms. Specifically, the invention provides a method for directly determining Dd and associated CcEe genotypes with great accuracy, overcoming problems associated with traditional serologic typing methods and leading to a direct discrimination of D/D, D/d, and d/d genetic status. The diagnostic method allows genotyping of fetuses to assess the risk of hemolytic diseases caused by Rh alloimmunization and genetic counseling and/or testing of couples to predict the outcome of pregnancies in relation to Rh incompatibilities. The method of the invention preferably employs amplification of Rh nucleic acid sequences, and employs differential cleavage of RhD-, RhCc- and/or RhEe-specific nucleic acid sequences by a restriction enzyme. Furthermore, diagnostic kits for the determination of Rh genotypes are provided.
    • 本发明提供了通过鉴定Rh多态性的分子基础来确定Rh基因型的诊断方法。 具体地说,本发明提供了一种以高精度直接测定Dd和相关CcEe基因型的方法,克服了与传统血清学分型方法相关的问题,导致直接鉴别D / D,D / d和d / d基因状态。 诊断方法允许胎儿进行基因分型,以评估Rh同种异体免疫和遗传咨询和/或夫妇检测引起的溶血性疾病的风险,以预测与Rh不相容性相关的妊娠结局。 本发明的方法优选使用Rh核酸序列的扩增,并采用限制性酶对RhD-,RhCc-和/或RhEe-特异性核酸序列进行差异切割。 此外,提供了用于确定Rh基因型的诊断试剂盒。