公开(公告)号：US20050175591A1

公开(公告)日：2005-08-11

申请号：US11046219

申请日：2005-01-28

申请人： J. Stout ,  Trevor McFarland ,  Peter Francis ,  Binoy Appukuttan

发明人： J. Stout ,  Trevor McFarland ,  Peter Francis ,  Binoy Appukuttan

IPC分类号： A61K48/00 ,  C07H21/04 ,  C07K14/71 ,  C12N15/85 ,  C12N15/86

CPC分类号： C07K14/71 ,  C12N15/85 ,  C12N2740/15043 ,  C12N2750/14143 ,  C12N2830/50 ,  C12N2840/203

摘要： The human soluble neuropilin-1 (sNRP) polyadenylation signal (sNRP-poly(A)), situated downstream of the GT splice donor site of intron 12 of the full-length neuropilin-1 gene, also functions as the termination codon for sNRP. This 17 nucleotide sequence efficiently facilitates addition of poly(A) tails to RNAs expressed in cells. The present invention shows that this optimally succinct sequence has similar activity to the SV40 polyadenylation signal that is currently used in expression vectors. By using this shorter dual termination/polyadenylation signal and avoiding the need for large and cumbersome polyadenylation signals, expression vectors may be engineered to carry considerably larger genes.

摘要翻译： 位于全长神经蛋白-1基因的内含子12的GT剪接供体位点下游的人可溶性神经丝氨酸-1（sNRP）聚腺苷酸化信号（sNRP-聚（A））也用作sNRP的终止密码子。 该17个核苷酸序列有效地促进了在细胞中表达的RNA的poly（A）尾。 本发明表明，该最佳简洁的序列具有与当前在表达载体中使用的SV40多聚腺苷酸化信号相似的活性。 通过使用这种更短的双重终止/多聚腺苷酸化信号并避免对大的和麻烦的多聚腺苷酸化信号的需要，表达载体可以被工程化以携带相当大的基因。

公开(公告)号：US07557197B2

公开(公告)日：2009-07-07

申请号：US11046219

申请日：2005-01-28

申请人： J. Timothy Stout ,  Trevor McFarland ,  Peter J. Francis ,  Binoy Appukuttan

发明人： J. Timothy Stout ,  Trevor McFarland ,  Peter J. Francis ,  Binoy Appukuttan

IPC分类号： C07H21/02 ,  C12N15/00 ,  A01N43/04

CPC分类号： C07K14/71 ,  C12N15/85 ,  C12N2740/15043 ,  C12N2750/14143 ,  C12N2830/50 ,  C12N2840/203

摘要： The human soluble neuropilin-1 (sNRP) polyadenylation signal (sNRP-poly(A)), situated downstream of the GT splice donor site of intron 12 of the full-length neuropilin-1 gene, also functions as the termination codon for sNRP. This 17 nucleotide sequence efficiently facilitates addition of poly(A) tails to RNAs expressed in cells. The present invention shows that this optimally succinct sequence has similar activity to the SV40 polyadenylation signal that is currently used in expression vectors. By using this shorter dual termination/polyadenylation signal and avoiding the need for large and cumbersome polyadenylation signals, expression vectors may be engineered to carry considerably larger genes.

摘要翻译： 位于全长神经蛋白-1基因的内含子12的GT剪接供体位点下游的人可溶性神经丝氨酸-1（sNRP）聚腺苷酸化信号（sNRP-聚（A））也用作sNRP的终止密码子。 该17个核苷酸序列有效地促进了在细胞中表达的RNA的poly（A）尾。 本发明表明，该最佳简洁的序列具有与当前在表达载体中使用的SV40多聚腺苷酸化信号相似的活性。 通过使用这种更短的双重终止/多聚腺苷酸化信号并避免对大的和麻烦的多聚腺苷酸化信号的需要，表达载体可以被工程化以携带相当大的基因。

公开(公告)号：US08785385B2

公开(公告)日：2014-07-22

申请号：US13089687

申请日：2011-04-19

申请人： J. Timothy Stout ,  Binoy Appukuttan ,  Trevor McFarland ,  Anna Dye

发明人： J. Timothy Stout ,  Binoy Appukuttan ,  Trevor McFarland ,  Anna Dye

IPC分类号： C07K14/435 ,  A61K38/00 ,  A61K38/16 ,  A61K38/17

CPC分类号： C07K14/4705 ,  A61K38/00 ,  A61K38/1709 ,  A61K45/06 ,  A61K48/00 ,  A61K48/0058 ,  C07K14/4703 ,  C07K2319/02 ,  C07K2319/033 ,  C12N7/00 ,  C12N2740/16043

摘要： Disclosed are variant RTEF-1 polypeptides having an RTEF-1 amino acid sequence with one or more internal deletions, wherein the polypeptides reduce VEGF promoter activity. Some of the RTEF-1 polypeptides include an amino acid sequence that is at least 80% identical to the contiguous amino acids of 1) amino acids 24 to 47 of SEQ ID NO:15 and 2) each of SEQ ID NOs:16 and 17, but does not comprise the contiguous amino acids of SEQ ID NOs:8, 9, 11, or 12. Also disclosed are nucleic acids encoding the variant RTEF-1 polypeptides of the present invention. Pharmaceutical compositions that include the polypeptides and nucleic acids of the present invention are also disclosed. Methods of inducing cell contact inhibition, regulating organ size, and reducing intracellular YAP activity are also set forth, as well as methods of treating hyperproliferative diseases such as cancer using the pharmaceutical compositions of the present invention.

摘要翻译： 公开了具有一个或多个内部缺失的RTEF-1氨基酸序列的变体RTEF-1多肽，其中多肽降低VEGF启动子活性。 一些RTEF-1多肽包括与SEQ ID NO：15的1）氨基酸24至47和2）SEQ ID NO：16和17各自的连续氨基酸至少80％相同的氨基酸序列 但不包含SEQ ID NO：8,9,11或12的连续氨基酸。还公开了编码本发明变体RTEF-1多肽的核酸。 还公开了包括本发明的多肽和核酸的药物组合物。 还提出诱导细胞接触抑制，调节器官大小和减少细胞内YAP活性的方法，以及使用本发明的药物组合物治疗过度增殖性疾病如癌症的方法。

公开(公告)号：US10336797B2

公开(公告)日：2019-07-02

申请号：US13511267

申请日：2010-11-22

申请人： J. Timothy Stout ,  Binoy Appukuttan ,  Trevor McFarland

发明人： J. Timothy Stout ,  Binoy Appukuttan ,  Trevor McFarland

IPC分类号： A61K8/64 ,  A61K38/00 ,  A61Q17/04 ,  A61Q19/00 ,  A61Q19/04 ,  C07K14/47

摘要： Disclosed are recombinant polypeptides that include (a) a filaggrin amino acid sequence and (b) a cell importation signal sequence that includes a motif of two to fifteen amino acids, wherein the motif includes at least one arginine residue and at least one methionine residue. Also disclosed are nucleic acids encoding the recombinant polypeptides of the present invention, and compositions that include the recombinant polypeptides and nucleic acids of the present invention. Methods of treating or preventing a skin disease or skin disorder using the compositions of the present invention are also included, as well as kits that include a sealed containing that includes a recombinant polypeptide of the present invention.

公开(公告)号：US20120063994A1

公开(公告)日：2012-03-15

申请号：US13089687

申请日：2011-04-19

申请人： J. Timothy Stout ,  Binoy Appukuttan ,  Trevor McFarland ,  Anna Dye

发明人： J. Timothy Stout ,  Binoy Appukuttan ,  Trevor McFarland ,  Anna Dye

IPC分类号： A61K51/00 ,  C07K19/00 ,  C12N15/12 ,  C12N15/85 ,  C12N15/86 ,  C12N15/869 ,  C12N15/867 ,  C12N15/861 ,  C12N15/863 ,  A61K9/127 ,  A61K38/17 ,  A61K31/7088 ,  C12N5/071 ,  A61K39/395 ,  A61K38/18 ,  A61P35/00 ,  A61P37/04 ,  A61P19/02 ,  A61P35/02 ,  A61P35/04 ,  A61N5/00 ,  C07K14/47

CPC分类号： C07K14/4705 ,  A61K38/00 ,  A61K38/1709 ,  A61K45/06 ,  A61K48/00 ,  A61K48/0058 ,  C07K14/4703 ,  C07K2319/02 ,  C07K2319/033 ,  C12N7/00 ,  C12N2740/16043

摘要： Disclosed are variant RTEF-1 polypeptides having an RTEF-1 amino acid sequence with one or more internal deletions, wherein the polypeptides reduce VEGF promoter activity. Some of the RTEF-1 polypeptides include an amino acid sequence that is at least 80% identical to the contiguous amino acids of 1) amino acids 24 to 47 of SEQ ID NO:15 and 2) each of SEQ ID NOs:16 and 17, but does not comprise the contiguous amino acids of SEQ ID NOs:8, 9, 11, or 12. Also disclosed are nucleic acids encoding the variant RTEF-1 polypeptides of the present invention. Pharmaceutical compositions that include the polypeptides and nucleic acids of the present invention are also disclosed. Methods of inducing cell contact inhibition, regulating organ size, and reducing intracellular YAP activity are also set forth, as well as methods of treating hyperproliferative diseases such as cancer using the pharmaceutical compositions of the present invention.

摘要翻译： 公开了具有一个或多个内部缺失的RTEF-1氨基酸序列的变体RTEF-1多肽，其中多肽降低VEGF启动子活性。 一些RTEF-1多肽包括与SEQ ID NO：15的1）氨基酸24至47和2）SEQ ID NO：16和17各自的连续氨基酸至少80％相同的氨基酸序列 但不包含SEQ ID NO：8,9,11或12的连续氨基酸。还公开了编码本发明变体RTEF-1多肽的核酸。 还公开了包括本发明的多肽和核酸的药物组合物。 还提出诱导细胞接触抑制，调节器官大小和减少细胞内YAP活性的方法，以及使用本发明的药物组合物治疗过度增殖性疾病如癌症的方法。