公开(公告)号：US20060003933A1

公开(公告)日：2006-01-05

申请号：US11145587

申请日：2005-06-06

Applicant: Martin Friedlander ,  Hilda Aguilar ,  Michael Dorrell

Inventor： Martin Friedlander ,  Hilda Aguilar ,  Michael Dorrell

IPC: A61K38/47 ,  A61K31/7072 ,  A61K31/538

CPC classification number: A61K31/7072 ,  A61K9/0048 ,  A61K31/538 ,  A61K38/00 ,  A61K45/06 ,  C12N9/93 ,  C12Y601/01002 ,  A61K2300/00

Abstract: The present invention provides compositions and methods of treating neovascular diseases, such as a retinal neovascular diseases and tumors, by administering to a patient suffering from a neovascular disease or tumor a vascular development inhibiting amount of a combination of the angiogenesis suppressing drugs comprising an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one compound selected from the group consisting of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor. Compositions for use in the methods include an admixture of an angiostatic fragment of tryptophanyl-tRNA synthetase (TrpRS) and at least one of a vascular endothelial growth factor (VEGF) signaling inhibitor and an integrin signaling inhibitor, together with a pharmaceutically acceptable excipient.

公开(公告)号：US20070207154A1

公开(公告)日：2007-09-06

申请号：US11578338

申请日：2005-04-15

Applicant: Martin Friedlander ,  Wolfram Ruf ,  Michael Dorrell ,  Mattias Belting

Inventor： Martin Friedlander ,  Wolfram Ruf ,  Michael Dorrell ,  Mattias Belting

IPC: A61K39/395 ,  A61K38/36

CPC classification number: C12N15/86 ,  A61K38/17 ,  A61K38/4846 ,  A61K48/00 ,  A61K2039/505 ,  C07K16/36 ,  C12N2710/10343

Abstract: A method of modulating vascularization in a tissue of a mammal comprises controlling a PAR signaling pathway (e.g., the PAR-1 or PAR-2 signaling pathway) in a mammalian tissue, for example, by controlling phosphorylation of tissue factor cytoplasmic domain (i.e., phosphorylation of Ser258 of the cytoplasmic tail of TF). In a preferred method pathological is treated by administering to a mammal suffering from pathological neovascularization, a therapeutically effective amount of a PAR signaling pathway inhibitor. Preferably the mammal is a human.

Abstract translation: 调节哺乳动物组织中血管形成的方法包括控制哺乳动物组织中PAR信号通路（例如PAR-1或PAR-2信号通路），例如通过控制组织因子细胞质结构域的磷酸化（即， TF的细胞质尾部的Ser255磷酸化）。 在优选的方法中，通过给予患有病理性新生血管形成的哺乳动物治疗有效量的PAR信号通路抑制剂来治疗病理学。 优选地，哺乳动物是人。

公开(公告)号：US20050004013A1

公开(公告)日：2005-01-06

申请号：US10836289

申请日：2004-04-30

Applicant: Martin Friedlander ,  Michael Dorrell

Inventor： Martin Friedlander ,  Michael Dorrell

IPC: A61K38/00 ,  A61K38/06 ,  A61K38/08 ,  A61K38/10 ,  A61K38/12 ,  C07K20060101 ,  C07K14/705

CPC classification number: C07K14/705 ,  A61K38/00

Abstract: An isolated peptide useful as a selective antagonist of mammalian R-cadherin comprises 3 to 30 amino acid residues, three contiguous residues of the peptide having the amino acid sequence Ile-Xaa-Ser; wherein Xaa is an amino acid residue selected from the group consisting of Asp, Asn, Glu, and Gln. Preferably Xaa is Asp or Asn. In one preferred embodiment the peptide is a cyclic peptide having 3 to 10 amino acid residues arranged in a ring. The selective R-cadherin antagonist peptides of the invention are useful for inhibiting the targeting of stem cells, such as endothelial precursor cells, to developing vasculature, for inhibiting R-cadherin mediated cellular adhesion, and for inhibiting retinal angiogenesis.

Abstract translation: 可用作哺乳动物R-钙粘蛋白的选择性拮抗剂的分离的肽包含3-30个氨基酸残基，具有氨基酸序列Ile-Xaa-Ser的肽的三个连续残基; 其中Xaa是选自Asp，Asn，Glu和Gln的氨基酸残基。 Xaa是Asp或Asn。 在一个优选实施方案中，肽是以环形排列的具有3至10个氨基酸残基的环肽。 本发明的选择性R-钙粘蛋白拮抗剂肽可用于抑制干细胞如内皮前体细胞靶向发展血管，抑制R-钙粘蛋白介导的细胞粘附和抑制视网膜血管生成。