发明名称 |
Anticoagulant fusion protein anchored to cell membrane |
摘要 |
The invention relates to the inhibition of blood coagulation, especially during organ rejection, and in particular the inhibition of delayed vascular rejection. The invention provides anticoagulant proteins which are anchored to cell membranes. The anticoagulant function is preferably provided by heparin, antithrombin, hirudin, TFPI, tick anticoagulant peptide, or a snake venom factor. These anticoagulant proteins are preferably prevented from being constitutively expressed at the cell surface. In particular, expression at the cell surface is regulated according to cell activation, for instance by targeting the protein to a suitable secretory granule. Expression of these proteins renders cells, tissues and organs less vulnerable to rejection after transplantation (e.g. after xenotransplantation). |
申请公布号 |
US9376684(B2) |
申请公布日期 |
2016.06.28 |
申请号 |
US201113050120 |
申请日期 |
2011.03.17 |
申请人 |
Imperial Innovations Limited |
发明人 |
Riesbeck Kristian;Dorling Anthony;George Andrew John Timothy;Lechler Robert Ian |
分类号 |
A61K48/00;A61K39/00;C07H21/04;C07K14/00;C12N15/63;C12N15/62;C07K14/73;C07K14/74;C07K14/705;C07K14/81;C07K14/815;C12N9/64;C12N15/85;A61K38/00 |
主分类号 |
A61K48/00 |
代理机构 |
King & Spalding LLP |
代理人 |
King & Spalding LLP |
主权项 |
1. A method of xenotransplantation to provide membrane-bound anticoagulant protein comprising transplanting a genetically modified porcine cell into a recipient wherein the porcine cell comprises a polynucleotide that is expressed on the surface of the cell, wherein the polynucleotide encodes a non-naturally occurring protein comprising a region with anticoagulant activity and a region which can anchor the protein to a cell membrane, wherein the anchor region and anticoagulant region of the protein are from different protein sequences and wherein the anticoagulant region comprises the sequence of an anticoagulant protein selected from the group consisting of hirudin, tissue factor pathway inhibitor, tick anticoagulant peptide, heparin, antithrombin, and protein C activator or fragment thereof. |
地址 |
London GB |