公开(公告)号：EP0833941B1

公开(公告)日：2008-10-22

申请号：EP96910696.2

申请日：1996-04-04

申请人： CYTOGEN CORPORATION ,  UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL

发明人： SPARKS, Andrew, B. ,  HOFFMAN, Noah ,  KAY, Brian, K. ,  FOWLKES, Dana, M. ,  MCCONNELL, Stephen, J.

IPC分类号： C12Q1/68 ,  C12N5/10 ,  C12N15/12 ,  C07K14/00 ,  C07K16/18 ,  G01N33/53 ,  G01N33/50

CPC分类号： C40B30/04 ,  A61K38/00 ,  C12N15/1037 ,  C40B40/02 ,  G01N33/6842 ,  G01N33/6845 ,  G01N2500/02 ,  G01N2500/04

摘要： Novel polypeptides having functional domains of interest are described, along with DNA sequences that encode the same. A method of identifying these polypeptides by means of a sequence-independent (that is, independent of the primary sequence of the polypeptide sought), recognition unit-based functional screen is also disclosed. Various applications of the method and of the polypeptides identified are described, including their use in assay kits for drug discovery, modification, and refinement.

公开(公告)号：EP0897392B1

公开(公告)日：2004-11-17

申请号：EP97905952.4

申请日：1997-02-14

申请人： CYTOGEN CORPORATION ,  The University of North Carolina at Chapel Hill

发明人： SPARKS, Andrew, B. ,  KAY, Brian, K. ,  THORN, Judith, M. ,  QUILLIAM, Lawrence, A. ,  DER, Channing, J. ,  FOWLKES, Dana, M. ,  RIDER, James, E.

IPC分类号： C07K5/04 ,  C07K7/04 ,  C07K7/06 ,  C07K7/08 ,  C07K14/00 ,  C07K14/435 ,  C07K14/705 ,  G01N33/53 ,  G01N33/567 ,  G01N33/50

CPC分类号： C07K7/06 ,  A61K38/00 ,  A61K47/62 ,  C07K7/08 ,  C07K14/001 ,  C07K14/435 ,  C07K2319/00 ,  C40B30/04 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5041 ,  G01N33/573 ,  G01N33/68 ,  G01N33/6845

摘要： Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins comprising SH3 and glutathione S-transferase (GST). Preferred peptides are disclosed which comprise a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.

公开(公告)号：EP0777748A1

公开(公告)日：1997-06-11

申请号：EP95929609.0

申请日：1995-08-17

申请人： CYTOGEN CORPORATION

发明人： RODWELL, John, D. ,  FOWLKES, Dana, M.

IPC分类号： C12N15 ,  A61K38 ,  A61K48 ,  A61P43 ,  C07K14 ,  C12P21 ,  C12Q1 ,  C40B40 ,  C12R1

CPC分类号： C40B40/02 ,  A61K48/00 ,  C07K14/4702 ,  C07K2319/02 ,  C07K2319/61 ,  C07K2319/73 ,  C07K2319/735 ,  C12N15/1037 ,  C12N15/62

摘要： The present invention relates generally to synthetic gene sequences ('syngenes') that are identified by screening random peptide librairies for peptides that bind a ligand of choice. The synthetic gene sequences, together with, optionally, other DNA sequences that target the synthetic gene sequences or their encoded proteins to particular locations in vivo or intracellularly, or that contain processing signals, or that code for other peptides or amino acid sequences, are cloned into suitable expression vectors. The syngenes are used, for example, in gene therapy to supply, via expression of their encoded proteins, a therapeutic product. In another aspect, the invention relates to protein or peptide products of syngenes and their therapeutic and diagnsotic uses.

公开(公告)号：EP0724576A1

公开(公告)日：1996-08-07

申请号：EP94929152.0

申请日：1994-09-15

申请人： CYTOGEN CORPORATION

发明人： BELINKA, Benjamin, A., Jr. ,  COUGHLIN, Daniel, J.

IPC分类号： C07D255 ,  C07F9

CPC分类号： C07F9/6524 ,  C07F9/025 ,  C07F9/3817

摘要： A process for the purification of aminophosphonic acids under non-alkaline conditions is described. In particular, aminophosphonic acids are slurred in neutral or acidic water, heated to reflux, cooled and then filtered. Product purities approaching 100 % are thus obtained.

公开(公告)号：EP0382796A4

公开(公告)日：1991-08-28

申请号：EP89902339

申请日：1989-02-02

申请人： CYTOGEN CORPORATION

发明人： ULTEE, MICHAEL, E. ,  ALVAREZ, VERNON, L.

IPC分类号： G01N33/563 ,  A61K39/395 ,  A61K47/48 ,  A61K49/00 ,  A61K51/10 ,  A61P35/00 ,  G01N33/532 ,  G01N33/577 ,  G01N33/68 ,  G01N33/53

CPC分类号： A61K51/1093 ,  A61K47/68 ,  A61K47/6835 ,  A61K2123/00 ,  G01N33/532 ,  G01N33/6857 ,  Y10S530/866

公开(公告)号：EP0382796A1

公开(公告)日：1990-08-22

申请号：EP89902339.0

申请日：1989-02-02

申请人： CYTOGEN CORPORATION

发明人： ULTEE, Michael, E. ,  ALVAREZ, Vernon, L.

IPC分类号： G01N33 ,  A61K39 ,  A61K47 ,  A61K49 ,  A61K51 ,  A61P35

CPC分类号： A61K51/1093 ,  A61K47/68 ,  A61K47/6835 ,  A61K2123/00 ,  G01N33/532 ,  G01N33/6857 ,  Y10S530/866

摘要： Le nouveau procédé décrit sert à préparer des compositions de fragments d'anticorps solubles ayant des caractéristiques de ciblage supérieures lorsqu'elles sont administrées in vivo. Ces compositions de fragments d'anticorps se caractérisent sensiblement par la même immunospécificité que les anticorps non conjugués et par une solubilité aqueuse telle qu'elles sont appropriées pour une administration in vivo. Des procédés thérapeutiques et diagnostiques utilisant ces compositions de fragments d'anticorps sont également décrits.

公开(公告)号：EP1281718A2

公开(公告)日：2003-02-05

申请号：EP02021532.3

申请日：1996-11-11

申请人： ELAN CORPORATION, Plc ,  CYTOGEN CORPORATION

发明人： O'Mahony, Daniel Joseph ,  Alvarez, Vernon Leon

IPC分类号： C07K14/47

CPC分类号： C12N15/1037 ,  C07K14/47 ,  C07K14/705 ,  C40B40/02 ,  G01N33/5088 ,  G01N33/56983

摘要： A peptide which permits or facilitates the transport of an active agent through a human or animal tissue. A predetermined amount of phage from a random phage library or a preselected phage library is administered in vivo or in s6itu to a site in an animal, such as into the gastro-intestinal tract. At a predetermined time, the phage which is transported across a tissue barrier is harvested at a harvesting site which is separated from the site of administration by the tissue barrier to select transported phage. This transported phage is amplified in a host. This cycle of events is repeated (using the transported phage produced in the most recent cycle) a predetermined number of times to obtain a selected phage library containing phage which can be transported from the site of administration to the harvesting site. The identity of at least one peptide coded by phage in the selected phage library is determined to identify a peptide which permits or facilitates the transport of an active agent through a human or animal tissue.

摘要翻译： 允许或促进活性剂通过人或动物组织的运输的肽。 来自随机噬菌体文库或预选噬菌体文库的预定量的噬菌体在体内或在动物（例如进入胃肠道）的位点施用。 在预定时间内，跨越组织屏障传送的噬菌体在收集部位收获，该收获部位通过组织屏障与施用部位分离，以选择输送的噬菌体。 这种转运的噬菌体在宿主中被扩增。 重复这个事件循环（使用最近循环中产生的转运噬菌体）预定次数，以获得包含可以从施用部位运送到收获部位的噬菌体的选定噬菌体文库。 测定所选择的噬菌体文库中由噬菌体编码的至少一种肽的身份，以鉴定允许或促进活性剂通过人或动物组织的转运的肽。

公开(公告)号：EP0981649A1

公开(公告)日：2000-03-01

申请号：EP98923466.1

申请日：1998-05-15

申请人： ELAN CORPORATION PLC ,  CYTOGEN CORPORATION

发明人： O'MAHONY, Daniel, Joseph ,  ALVAREZ, Vernon, Leon ,  SEVESO, Michela,Apartment 89

IPC分类号： C12Q1/68 ,  C07K5/00

CPC分类号： C40B40/02 ,  A61K9/167 ,  A61K47/42 ,  A61K47/62 ,  A61K47/6937 ,  B82Y5/00 ,  C12N15/1037 ,  G01N33/68 ,  Y10S977/805

摘要： Targeting agents that are capable of permitting or facilitating transport of an active agent through a human or animal gastro-intestinal tissue. These targeting agents are peptides or their derivatives (e.g., fragments) and peptidomimetics thereof, and the nucleotide sequences coding for the peptides and derivatives. The targeting agents have use in facilitating transport of active agents from the lumenal side of the GIT into the systemic blood system, and/or in targeting active agents to the GIT. Therapeutic methods of administration, pharmaceutical compositions and formulations based on the targeting agent peptides are also provided. Preferably, the active agent is a drug or drug-containing nano- or microparticle.

公开(公告)号：EP0721353A1

公开(公告)日：1996-07-17

申请号：EP94930452.0

申请日：1994-09-28

申请人： CYTOGEN CORPORATION

发明人： BELINKA, Benjamin A., Jr. ,  COUGHLIN, Daniel J. ,  ALVAREZ, Vernon Leon ,  WOOD, Richard

IPC分类号： A61K49 ,  A61K51

CPC分类号： A61K49/122 ,  A61K49/085 ,  A61K49/14 ,  A61K51/088 ,  A61K2121/00 ,  A61K2123/00

摘要： This invention relates to the preparation and use of novel open-chain or cyclic polypeptide constructs in which two or more polypeptide chains, in an open-chain construct, or one or more chains, in a cyclic construct, are chemically derivatized such that the resulting construct exhibits both metal-binding capability and tissue-, organ- or cell-targeting selectivity. In particular, the polypeptide constructs of the present invention comprise compounds of formula (I), in which, 'B' is a hydrocarbon backbone, 'P' is polypeptide capable of targeting particular cells, tissues or organs of the body, 'A' may be the group -NR' -NR' - or the group -NR' -NR' -L- in which L may be an aliphatic or aromatic linker group, R, R', and R' may be the same or different and may be hydrogen or an aliphatic group, m is an integer ≥ 2, provided that the groups R, R', R', L and 'P' of a given chain may be the same or different from the groups R, R', R', L and 'P' of another chain, n is an integer ≥ 0; or a pharmaceutically acceptable salt thereof. The constructs of the present invention are capable of binding a variety of metallic species.

公开(公告)号：EP0251455B1

公开(公告)日：1994-05-11

申请号：EP87304093.5

申请日：1987-05-07

申请人： CYTOGEN CORPORATION

发明人： Coughlin, Daniel J. ,  Lopes, Anthony Dwight ,  Radcliffe, Robert D. ,  Rodwell, John D.

IPC分类号： A61K39/395 ,  G01N33/531 ,  G01N33/532 ,  C07D475/08

CPC分类号： A61K47/6803 ,  A61K47/6889