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    Human plasma hyaluronidase
    4.
    发明授权
    Human plasma hyaluronidase 有权
    人血浆透明质酸酶

    公开(公告)号：US07105330B2

    公开(公告)日：2006-09-12

    申请号：US10622283

    申请日：2003-07-18

    申请人： Robert Stern ,  Gregory I. Frost ,  Anthony Csoka ,  Tim M. Wong

    发明人： Robert Stern ,  Gregory I. Frost ,  Anthony Csoka ,  Tim M. Wong

    IPC分类号： G01N33/53 ,  G01N33/537 ,  G01N33/543 ,  C12N5/06 ,  C07K16/40

    CPC分类号： C12Y302/01035 ,  A61K38/00 ,  C07K16/40 ,  C12N9/16 ,  C12N9/2474 ,  C12Y302/01036 ,  G01N33/573

    摘要： The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.

    摘要翻译： 本发明基于发现用于纯化在人血浆（hpHA）中发现的酸活性透明质酸酶的方法，包括生物化学和免疫亲和纯化方法。 本发明的免疫亲和纯化方法基于发现用于鉴定特异性结合天然hpHA（抗天然hpHAse抗体）的抗体的方法，以及通过该筛选方法鉴定的抗天然hpHAse抗体。 本发明还特征在于使用生物素化透明质酸（bHA）敏感检测HAse活性的测定。 hpHAse的纯化和表征导致发明人进一步发现，hpHAse由LuCa-1基因编码，该基因存在于3p21.3的人染色体中，该肿瘤与肿瘤抑制有关。 本发明另外具有通过施用hpHA和/或用hpHA编码DNA转化细胞来治疗荷瘤患者的方法。

    Human urinary hyaluronidase
    5.
    发明授权
    Human urinary hyaluronidase 失效
    人尿透明质酸酶

    公开(公告)号：US6123938A

    公开(公告)日：2000-09-26

    申请号：US987743

    申请日：1997-12-09

    申请人： Robert Stern ,  Anthony Csoka ,  Gregory I. Frost ,  Tim M. Wong

    发明人： Robert Stern ,  Anthony Csoka ,  Gregory I. Frost ,  Tim M. Wong

    IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/46 ,  A61P9/10 ,  A61P27/06 ,  A61P35/00 ,  C07K14/00 ,  C07K16/40 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/16 ,  C12N9/24 ,  C12N9/42 ,  C12Q1/68 ,  C12R1/93 ,  G01N33/573 ,  C07K1/00

    CPC分类号： C07K16/40 ,  C12N9/16 ,  C12N9/2474 ,  C12Y302/01035 ,  C12Y302/01036 ,  G01N33/573 ,  A61K38/00 ,  Y10S530/828 ,  Y10S530/834

    摘要： The present invention is based on the purification and sequencing of isozymes of plasma hyaluronidase (pHAse) found in urine. Specifically, urine contains two hyaluronidases (HAses): 1) a 57 kDa HAse that is apparently the same as the 57 kDa HAse found in plasma; and 2) a 45 kDa HAse, which is found in urine but not plasma. The smaller urine isozyme is composed of two disulfide-linked polypeptides produced by endoproteolytic cleavage of the 57 kDa isoform. The present invention thus features a urinary hyaluronidase (uHAse) polypeptide and nucleotide sequences encoding a Chain A polypeptide and a Chain B polypeptide, the two polypeptides of which uHAse is composed. In a particular aspect, the uHAse is a human uHAse (huHAse), preferably a huHAse composed of the Chain A and B polypeptides having SEQ ID NOS: 2 and 4, respectively. In related aspects the invention features polynucleotide sequence encoding Chain A and Chain B polypeptides, preferably having the sequences of SEQ ID NOS: 1 and 3, respectively. In addition, the invention features polynucleotide sequences that hybridize under stringent conditions to SEQ ID NOS: 1 and 3. In related aspects the invention features expression vectors and host cells comprising polynucleotides that encode uHAse polypeptide Chains A and B. The present invention also features antibodies that bind specifically to uHAse, and methods for producing uHAse.

    摘要翻译： 本发明基于在尿中发现的血浆透明质酸酶（pHAse）的同功酶的纯化和测序。 具体来说，尿液含有两种透明质酸酶（HAses）：1）57kDa的HAse与血浆中57kDa的HAse显然相同; 和2）45kDa的HAse，其存在于尿中而不是血浆中。 较小的尿同功酶由通过57kDa同种型的内切蛋白切割产生的两个二硫键连接的多肽组成。 因此，本发明的特征在于尿液透明质酸酶（uHA））多肽和编码链A多肽和链B多肽的核苷酸序列，其中uHAse组成的两个多肽。 在一个特定方面，uHA是人uHAse（huHAse），优选分别由具有SEQ ID NO：2和4的链A和B多肽组成的huHAse。 在相关方面，本发明具有分别编码链A和链B多肽的多核苷酸序列，优选分别具有SEQ ID NO：1和3的序列。 此外，本发明还提供了在严格条件下与SEQ ID NO：1和3杂交的多核苷酸序列。在相关方面，本发明涉及包含编码uHAse多肽链A和B的多核苷酸的表达载体和宿主细胞。本发明还具有抗体 它们专门用于uHAse，以及生产uHA的方法。

    Human plasma hyaluronidase
    6.
    发明授权
    Human plasma hyaluronidase 有权
    人血浆透明质酸酶

    公开(公告)号：US07781397B2

    公开(公告)日：2010-08-24

    申请号：US11538246

    申请日：2006-10-03

    申请人： Robert Stern ,  Gregory I. Frost ,  Anthony Csoka ,  Tim M. Wong

    发明人： Robert Stern ,  Gregory I. Frost ,  Anthony Csoka ,  Tim M. Wong

    IPC分类号： A01N37/18

    CPC分类号： C12Y302/01035 ,  A61K38/00 ,  C07K16/40 ,  C12N9/16 ,  C12N9/2474 ,  C12Y302/01036 ,  G01N33/573

    摘要： The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.

    摘要翻译： 本发明基于发现用于纯化在人血浆（hpHA）中发现的酸活性透明质酸酶的方法，包括生物化学和免疫亲和纯化方法。 本发明的免疫亲和纯化方法基于发现用于鉴定特异性结合天然hpHA（抗天然hpHAse抗体）的抗体的方法，以及通过该筛选方法鉴定的抗天然hpHAse抗体。 本发明还特征在于使用生物素化透明质酸（bHA）敏感检测HAse活性的测定。 hpHAse的纯化和表征导致发明人进一步发现，hpHAse由LuCa-1基因编码，该基因存在于3p21.3的人染色体中，该肿瘤与肿瘤抑制有关。 本发明另外具有通过施用hpHA和/或用hpHA编码DNA转化细胞来治疗荷瘤患者的方法。

    Hybridoma cell lines producing monoclonal antibodies that bind to human plasma hyaluronidase
    7.
    发明授权
    Hybridoma cell lines producing monoclonal antibodies that bind to human plasma hyaluronidase 失效
    产生结合人血浆透明质酸酶的单克隆抗体的杂交瘤细胞系

    公开(公告)号：US6103525A

    公开(公告)日：2000-08-15

    申请号：US733360

    申请日：1996-10-17

    申请人： Robert Stern ,  Gregory I. Frost ,  Anthony Csoka ,  Tim M. Wong

    发明人： Robert Stern ,  Gregory I. Frost ,  Anthony Csoka ,  Tim M. Wong

    IPC分类号： A61K38/00 ,  C07K16/40 ,  C12N9/16 ,  C12N9/24 ,  G01N33/573 ,  C12N5/12 ,  C07K16/00

    CPC分类号： C12Y302/01035 ,  C07K16/40 ,  C12N9/16 ,  C12N9/2474 ,  C12Y302/01036 ,  G01N33/573 ,  A61K38/00

    摘要： The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression.

    摘要翻译： 本发明基于发现用于纯化在人血浆（hpHA）中发现的酸活性透明质酸酶的方法，包括生物化学和免疫亲和纯化方法。 本发明的免疫亲和纯化方法基于发现用于鉴定特异性结合天然hpHA（抗天然hpHAse抗体）的抗体的方法，以及通过该筛选方法鉴定的抗天然hpHAse抗体。 本发明还特征在于使用生物素化透明质酸（bHA）敏感检测HAse活性的测定。 hpHAse的纯化和表征导致发明人进一步发现，hpHAse由LuCa-1基因编码，该基因存在于3p21.3的人染色体中，该肿瘤与肿瘤抑制有关。

    Method of treating tumor-bearing patients with human plasma hyaluronidase
    8.
    发明授权
    Method of treating tumor-bearing patients with human plasma hyaluronidase 失效
    用人血浆透明质酸酶处理肿瘤患者的方法

    公开(公告)号：US06193963B1

    公开(公告)日：2001-02-27

    申请号：US08916935

    申请日：1997-08-21

    申请人： Robert Stern ,  Gregory I. Frost ,  Anthony Csóka ,  Tim M. Wong

    发明人： Robert Stern ,  Gregory I. Frost ,  Anthony Csóka ,  Tim M. Wong

    IPC分类号： A61K3800

    CPC分类号： C12Y302/01035 ,  A61K38/00 ,  C07K16/40 ,  C12N9/16 ,  C12N9/2474 ,  C12Y302/01036 ,  G01N33/573

    摘要： The invention is based on the discovery of methods for purification of an acid active hyaluronidase found in human plasma (hpHAse), including both biochemical and immunoaffinity purification methods. The method of immunoaffinity purification of the invention is based on the discovery of a method for identifying antibodies that specifically bind native hpHAse (anti-native hpHAse antibodies), and anti-native hpHAse antibodies identified by this screening method. The invention also features an assay for sensitive detection of HAse activity using biotinylated hyaluronic acid (bHA). Purification and characterization of hpHAse lead to the inventors' additional discovery that hpHAse is encoded by the LuCa-1 gene, which gene is present in the human chromosome at 3p21.3, a region associated with tumor suppression. The invention additionally features methods of treating tumor-bearing patients by administration of hpHAse and/or transformation of cells with hpHAse-encoding DNA.

    摘要翻译： 本发明基于发现用于纯化在人血浆（hpHA）中发现的酸活性透明质酸酶的方法，包括生物化学和免疫亲和纯化方法。 本发明的免疫亲和纯化方法基于发现用于鉴定特异性结合天然hpHA（抗天然hpHAse抗体）的抗体的方法，以及通过该筛选方法鉴定的抗天然hpHAse抗体。 本发明还特征在于使用生物素化透明质酸（bHA）敏感检测HAse活性的测定。 hpHAse的纯化和表征导致发明人进一步发现，hpHAse由LuCa-1基因编码，该基因存在于3p21.3的人染色体中，该肿瘤与肿瘤抑制有关。 本发明另外具有通过施用hpHA和/或用hpHA编码DNA转化细胞来治疗荷瘤患者的方法。