公开(公告)号：US20050042680A1

公开(公告)日：2005-02-24

申请号：US10831063

申请日：2004-04-23

申请人： David Filpula ,  Karen Yang ,  Amartya Basu ,  Maoliang Wang

发明人： David Filpula ,  Karen Yang ,  Amartya Basu ,  Maoliang Wang

IPC分类号： G01N33/53 ,  A61K39/38 ,  A61K47/48 ,  A61P35/00 ,  C07H21/04 ,  C07K14/00 ,  C07K14/715 ,  C07K16/00 ,  C07K16/30 ,  C07K16/44 ,  C07K19/00 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N15/09 ,  C12P21/02 ,  C12P21/08 ,  C12R1/84 ,  G01N33/68

CPC分类号： G01N33/6857 ,  A61K47/60 ,  A61K2039/505 ,  C07K16/30 ,  C07K19/00 ,  C07K2317/41 ,  C07K2317/622 ,  C07K2319/00

摘要： The present invention relates to monovalent and multivalent single-chain antigen-binding polypeptides with site-specific modifications. The provided polypeptides are capable of being covalently linked or conjugated to polyalkylene oxides at the modified sites. The resulting conjugates retain antigen binding properties and exhibit prolonged circulating time and reduced antigenicity relative to unconjugated single chain antigen binding polypeptides. Methods and compositions for making and using the single chain antigen-binding polypeptides with site-specific modifications are also provided.

摘要翻译： 本发明涉及具有位点特异性修饰的单价和多价单链抗原结合多肽。 所提供的多肽能够在修饰部位共价连接或与聚环氧烷共轭。 所得到的缀合物保留抗原结合性质并且相对于未缀合的单链抗原结合多肽显示延长的循环时间和降低的抗原性。 还提供了用于制备和使用具有位点特异性修饰的单链抗原结合多肽的方法和组合物。

公开(公告)号：US06764853B2

公开(公告)日：2004-07-20

申请号：US09983580

申请日：2001-10-25

申请人： David R. Filpula ,  Maoliang Wang ,  Marc D. Whitlow

发明人： David R. Filpula ,  Maoliang Wang ,  Marc D. Whitlow

IPC分类号： C12N1509

CPC分类号： C07K16/3046 ,  C07K2317/31 ,  C07K2317/622 ,  C07K2319/00 ,  C12N15/87

摘要： The present invention is directed to a method of in vivo and ex vivo gene delivery, for a variety of cells. More specifically, it relates to a novel carrier system and method for targeted delivery of nucleic acids to mammalian cells. More specifically, the present invention relates to carrier system comprising single-chain polypeptide binding molecules having an a region rich in basic amino acid and having the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. The basic amino acid rich region can comprise oligo-lysine, oligo-arginine or combinations thereof. Such preparations of modified single chain polypeptide binding molecules also have ability to bind nucleic acids at the region rich in basic amino acid residues. These properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications including gene therapy. The invention also relates to multivalent antigen-binding molecules having regions rich in basic amino acids. Compositions of, genetic constructions for, methods of use, and methods for producing basic amino acid tailed antigen-binding proteins are disclosed.

摘要翻译： 本发明涉及各种细胞的体内和离体基因递送方法。 更具体地说，本发明涉及用于将核酸靶向递送至哺乳动物细胞的新的载体系统和方法。 更具体地，本发明涉及包含单链多肽结合分子的载体体系，其具有富含碱性氨基酸的区域，并且具有抗体可变区的三维折叠以及因此的结合能力和特异性。 碱性氨基酸富集区可以包含寡赖氨酸，寡精氨酸或其组合。 修饰的单链多肽结合分子的这种制剂还具有在富含碱性氨基酸残基的区域上结合核酸的能力。 修饰的单链多肽结合分子的这些性质使得它们在包括基因治疗在内的各种治疗应用中非常有用。 本发明还涉及具有富含碱性氨基酸的区域的多价抗原结合分子。 公开了用于制备碱性氨基酸尾抗原结合蛋白的遗传构建，使用方法和方法的组合物。

公开(公告)号：US06692942B2

公开(公告)日：2004-02-17

申请号：US09985442

申请日：2001-11-02

申请人： David R. Filpula ,  Maoliang Wang ,  Marc D. Whitlow

发明人： David R. Filpula ,  Maoliang Wang ,  Marc D. Whitlow

IPC分类号： C12N1500

CPC分类号： C07K16/3046 ,  C07K2317/31 ,  C07K2317/622 ,  C07K2319/00 ,  C12N15/87

摘要： The present invention is directed to a method of in vivo and ex vivo gene delivery, for a variety of cells. More specifically, it relates to a novel carrier system and method for targeted delivery of nucleic acids to mammalian cells. More specifically, the present invention relates to carrier system comprising single-chain polypeptide binding molecules having an a region rich in basic amino acid and having the three dimensional folding and, thus, the binding ability and specificity, of the variable region of an antibody. The basic amino acid rich region can comprise oligo-lysine, oligo-arginine or combinations thereof. Such preparations of modified single chain polypeptide binding molecules also have ability to bind nucleic acids at the region rich in basic amino acid residues. These properties of the modified single chain polypeptide binding molecules make them very useful in a variety of therapeutic applications including gene therapy. The invention also relates to multivalent antigen-binding molecules having regions rich in basic amino acids. Compositions of, genetic constructions for, methods of use, and methods for producing basic amino acid tailed antigen-binding proteins are disclosed.

摘要翻译： 本发明涉及各种细胞的体内和离体基因递送方法。 更具体地说，本发明涉及用于将核酸靶向递送至哺乳动物细胞的新的载体系统和方法。 更具体地，本发明涉及包含单链多肽结合分子的载体体系，其具有富含碱性氨基酸的区域，并且具有抗体可变区的三维折叠以及因此的结合能力和特异性。 碱性氨基酸富集区可以包含寡赖氨酸，寡精氨酸或其组合。 修饰的单链多肽结合分子的这种制剂还具有在富含碱性氨基酸残基的区域上结合核酸的能力。 修饰的单链多肽结合分子的这些性质使得它们在包括基因治疗在内的各种治疗应用中非常有用。 本发明还涉及具有富含碱性氨基酸的区域的多价抗原结合分子。 公开了用于制备碱性氨基酸尾抗原结合蛋白的遗传构建，使用方法和方法的组合物。

公开(公告)号：US5804183A

公开(公告)日：1998-09-08

申请号：US792283

申请日：1997-01-31

申请人： David Ray Filpula ,  Maoliang Wang

发明人： David Ray Filpula ,  Maoliang Wang

IPC分类号： C12N15/09 ,  A61K38/00 ,  A61K38/46 ,  A61K38/50 ,  A61K47/48 ,  A61P35/00 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/78 ,  C12N11/08 ,  C12N11/10 ,  C12R1/35 ,  A61K38/43

CPC分类号： A61K38/50 ,  C12N11/08 ,  C12N11/10 ,  C12N9/78

摘要： A purified arginine deiminase (ADI) obtained from Mycoplasma arthritidis having the amino acid sequence of SEQ ID NO:2 as well as an isolated nucleic acid molecule containing a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO:1 are disclosed. Other aspects of the invention include an expression vector, a cloned gene for expressing the Mycoplasma arthritidis derived ADI, (recombinant) host cells useful in expressing the ADI of the present invention and substantially non-antigenic polymer conjugates containing the ADI of the present invention as well as methods of treating arginine deiminase susceptible conditions in mammals. The arginine deiminase-polymer conjugates have high levels of retained enzyme activity and relatively long circulating lives.