公开(公告)号：EP1401473A2

公开(公告)日：2004-03-31

申请号：EP02742477.9

申请日：2002-02-14

申请人： Cellgate Inc. ,  THE BOARD OF TRUSTEES OFTHE LELAND STANFORD JUNIOR UNIVERSITY

发明人： WENDER, Paul, A. ,  ROTHBARD, Jonathan, B. ,  WRIGHT, Lee ,  KREIDER, Erik, L. ,  VANDEUSEN, Christopher, L.

IPC分类号： A61K38/00

CPC分类号： A61K47/64

摘要： The present invention provides compositions and methods for enhancing transport of biologically active compounds across biological membranes and across and into animal epithelial or endothelial tissues. The composition includes a biologically active agent and a transport moiety. The transport moiety includes a structure selected from the group consisting of (ZYZ)nZ, (ZY)nZ, (ZYY)nZ and (ZYYY)nZ. Subunit 'Z' is L-arginine or D-arginine, and subunit 'Y' is an amino acid that does not comprise an amidino or guanidino moiety. Subscript 'n' is an integer ranging from 2 to 10. The method for enhancing transport involves the administration of the aforementioned composition.

公开(公告)号：EP1189623A2

公开(公告)日：2002-03-27

申请号：EP00947622.7

申请日：2000-06-05

申请人： THE BOARD OF TRUSTEES OFTHE LELAND STANFORD JUNIOR UNIVERSITY ,  Cellgate Inc.

发明人： COOKE, John, P. ,  FATHMAN, Garrison, C. ,  ROTHBARD, Jonathan, B. ,  UEMURA, Shiro ,  ROBBINS, Robert, C. ,  KNOWN, Murray, H

IPC分类号： A61K38/03 ,  A61K38/08 ,  A61K38/10 ,  A61L27/34 ,  A61L33/00 ,  A61L33/12

CPC分类号： A61L33/12 ,  A61K38/03 ,  A61K38/08 ,  A61K38/10 ,  A61K38/16 ,  A61L27/227 ,  A61L27/34 ,  A61L33/128 ,  C08L77/04

摘要： Cardiovascular cell proliferation in a blood vessel subjected to trauma, such as angioplasty, vascular graft, anastomosis, or organ transplant, can be inhibited by contacting the vessel with a polymer consisting of from 6 to about 30 amino acid subunits, where at least 50 % of the subunits are arginine, and the polymer contains at least six contiguous arginine subunits. Exemplary polymers for this purpose include arginine homopolymers 7 to 15 subunits in length.

公开(公告)号：EP1461084A2

公开(公告)日：2004-09-29

申请号：EP02794232.5

申请日：2002-12-11

申请人： THE BOARD OF TRUSTEES OFTHE LELAND STANFORD JUNIOR UNIVERSITY ,  Cellgate Inc.

发明人： ROTHBARD, Jonathan, B. ,  WENDER, Paul, A. ,  PATTABIRAMAN, Kanaka ,  PELKEY, Erin, T. ,  JESSOP, Theodore, C.

IPC分类号： A61K47/48

CPC分类号： A61K47/54

摘要： Transport reagents and conjugates of therapeutic agents linked to transport reagents are described. In particular, the transport reagents have a plurality of guanidinium moieties that are either contiguous or spaced along a backbone, but are sufficiently removed from the backbone via tethers, to allow their interaction with a cell or tissue surface, leading to uptake of the therapeutic agent.

公开(公告)号：EP0975370A2

公开(公告)日：2000-02-02

申请号：EP98923711.0

申请日：1998-05-21

申请人： THE BOARD OF TRUSTEES OFTHE LELAND STANFORD JUNIOR UNIVERSITY

发明人： ROTHBARD, Jonathan, B. ,  WENDER, Paul, A.

IPC分类号： A61K47/48

CPC分类号： C07D305/14 ,  A61K31/785 ,  A61K47/62 ,  A61K47/645 ,  A61K48/00 ,  C07B2200/11 ,  C40B40/00

摘要： Methods and compositions for transporting drugs and macromolecules across biological membranes are disclosed. In one embodiment, the invention includes a method for enhancing transport of a selected compound across a biological membrane, wherein a biological membrane is contacted with a conjugate containing a biologically active agent that is covalently attached to a transport polymer. In one embodiment, the polymer consists of from 6 to 25 subunits, at 50 % of which contain a guanidino or amidino sidechain moiety. The polymer is effective to impart to the attached agent a rate of trans-membrane transport across a biological membrane that is greater than the rate of trans-membrane transport of the agent in non-conjugated form. The transport-enhancing polymers are exemplified, in a preferred embodiment, by peptides in which arginine residues constitute the subunits. Such a polyarginine peptide may be composed of either all D-, all L- or mixed D- and L-arginines, any may include additional amino acids. More preferably, at least one, and preferably all of the subunits are D-arginine residues, to enhance biological stability of the polymer during transit of the conjugate of its biological target.

公开(公告)号：EP1263469A1

公开(公告)日：2002-12-11

申请号：EP01909135.4

申请日：2001-02-09

申请人： Cellgate Inc.

发明人： ROTHBARD, Jonathan, B. ,  WENDER, Paul, A.

IPC分类号： A61K47/42 ,  A61K47/48

CPC分类号： A61K47/34 ,  A61K47/54 ,  A61K47/645

摘要： This invention provides compositions and methods for enhancing delivery of drugs and other agents across a biological barrier, including epithelial tissues such as the skin, gastrointestinal tract, pulmonary epithelium, and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 50 residues in length.

公开(公告)号：EP1367995A1

公开(公告)日：2003-12-10

申请号：EP02731103.4

申请日：2002-02-25

申请人： Cellgate Inc.

发明人： ROTHBARD, Jonathan, B. ,  WENDER, Paul, A. ,  MCGRANE, P., Leo ,  SISTA, Lalitha, V., S. ,  KIRSCHBERG, Thorsten, A.

IPC分类号： A61K9/02 ,  A61K31/155 ,  A61K38/03 ,  A61K38/16 ,  C07C257/00 ,  C07C279/00 ,  C07K4/00 ,  C07K14/00

CPC分类号： A61K47/48346 ,  A61K31/155 ,  A61K31/337 ,  A61K31/436 ,  A61K31/496 ,  A61K31/573 ,  A61K38/00 ,  A61K38/13 ,  A61K47/54 ,  A61K47/55 ,  A61K47/555 ,  A61K47/557 ,  A61K47/62 ,  A61K47/64 ,  A61K47/645 ,  A61K47/665 ,  A61K49/0043 ,  A61K49/0056 ,  A61K49/085 ,  A61K49/146 ,  B82Y5/00 ,  C07K7/06 ,  C07K7/64

摘要： This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length (see Figure 44).

公开(公告)号：EP1401473B1

公开(公告)日：2009-07-29

申请号：EP02742477.9

申请日：2002-02-14

申请人： Cellgate Inc. ,  THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

发明人： WENDER, Paul, A. ,  ROTHBARD, Jonathan, B. ,  WRIGHT, Lee ,  KREIDER, Erik, L. ,  VANDEUSEN, Christopher, L.

IPC分类号： A61K38/00 ,  C07K4/00 ,  C07K14/00 ,  A61K38/03 ,  A61K38/16 ,  A61P43/00

CPC分类号： A61K47/64

摘要： The present invention provides compositions and methods for enhancing transport of biologically active compounds across biological membranes and across and into animal epithelial or endothelial tissues. The composition includes a biologically active agent and a transport moiety. The transport moiety includes a structure selected from the group consisting of (ZYZ)nZ, (ZY)nZ, (ZYY)nZ and (ZYYY)nZ. Subunit 'Z' is L-arginine or D-arginine, and subunit 'Y' is an amino acid that does not comprise an amidino or guanidino moiety. Subscript 'n' is an integer ranging from 2 to 10. The method for enhancing transport involves the administration of the aforementioned composition.

公开(公告)号：EP1372626A1

公开(公告)日：2004-01-02

申请号：EP02713692.8

申请日：2002-02-25

申请人： Cellgate Inc.

发明人： ROTHBARD, Jonathan, B. ,  WENDER, Paul, A. ,  MCGRANE, P., Leo ,  SISTA, Lalitha, V.S. ,  KIRSCHBERG, Thorsten, A.

IPC分类号： A61K31/155 ,  A61K31/522 ,  A61K38/03 ,  A61K38/04 ,  A61K38/13 ,  A61K38/16

CPC分类号： A61K47/48346 ,  A61K31/155 ,  A61K31/337 ,  A61K31/436 ,  A61K31/496 ,  A61K31/573 ,  A61K38/00 ,  A61K38/13 ,  A61K47/54 ,  A61K47/55 ,  A61K47/555 ,  A61K47/557 ,  A61K47/62 ,  A61K47/64 ,  A61K47/645 ,  A61K47/665 ,  A61K49/0043 ,  A61K49/0056 ,  A61K49/085 ,  A61K49/146 ,  B82Y5/00 ,  C07K7/06 ,  C07K7/64

摘要： This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including into and across ocular tissues and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transporter that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent (Fig. 4) across one or more layers of the tissue, compared to the non-conjugated compound. The delivery-enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.

公开(公告)号：EP1210121A2

公开(公告)日：2002-06-05

申请号：EP00957830.3

申请日：2000-08-24

申请人： Cellgate Inc.

发明人： ROTHBARD, Jonathan, B. ,  WENDER, Paul, A. ,  McGRANE, P., Leo ,  SISTA, Lalitha, V., S. ,  KIRSCHBERG, Thorsten, A.

IPC分类号： A61K47/48

CPC分类号： C07K7/06 ,  A61K47/54 ,  A61K47/55 ,  A61K47/557 ,  A61K47/62 ,  A61K47/645 ,  A61K47/665 ,  A61K49/0043 ,  A61K49/0056 ,  A61K49/085 ,  A61K49/146 ,  B82Y5/00 ,  C07K7/64

摘要： This invention provides compositions and methods for enhancing delivery of drugs and other agents across epithelial tissues, including the skin, gastrointestinal tract, pulmonary epithelium, and the like. The compositions and methods are also useful for delivery across endothelial tissues, including the blood brain barrier. The compositions and methods employ a delivery enhancing transport that has sufficient guanidino or amidino sidechain moieties to enhance delivery of a compound conjugated to the reagent across one or more layers of the tissue, compared to the non-conjugated compound. The delivery enhancing polymers include, for example, poly-arginine molecules that are preferably between about 6 and 25 residues in length.