公开(公告)号：JP2009106290A

公开(公告)日：2009-05-21

申请号：JP2008290560

申请日：2008-11-13

Applicant: Abbott Lab ,  Childrens Medical Center Corp ,  アボット・ラボラトリーズAbbott Laboratories ,  ザ・チルドレンズ・メデイカル・センター・コーポレイシヨン

Inventor： DAVIDSON DONALD J ,  WANG JIEYI ,  GUBBINS EARL J ,  CAO YIHAI ,  FOLKMAN JUDAH M ,  O'REILLY MICHAEL S

IPC: C12N15/09 ,  A61K38/00 ,  A61K48/00 ,  A61P19/02 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07K14/745 ,  C12N5/10 ,  C12N9/68 ,  C12P21/02 ,  C12P21/06

CPC classification number: C12N9/6435 ,  A61K38/00 ,  A61K48/00 ,  C12Y304/21007

Abstract: PROBLEM TO BE SOLVED: To provide a compound useful for the treatment of angiogenic diseases of mammals, especially safe in therapeutic use, and usable as an antiangiogenic agent exhibiting selective toxicity to pathological symptoms e.g. by the selective inhibition of the proliferation of endothelial cells without or scarcely developing toxicity to normal (non-cancer) cells. SOLUTION: Mammalian kringle 5 fragments and kringle 5 fusion proteins are disclosed as compounds for treating angiogenic diseases. Methods and compounds for inhibiting angiogenic diseases are also disclosed. The kringle fragment is expressed by structure formula A-B-C-X-Y (in the formula, A is absent or a nitrogen-protective group; Y is absent or a carboxylic acid protective group; B is a natural amino acid residue; C is expressed by formula R 1 -R 2 -R 3 -R 4 (the groups are lysyl, leucyl or arginyl, tyrosyl, etc., and aspartyl, respectively); and X is absent or a natural amino acid residue or the like). COPYRIGHT: (C)2009,JPO&INPIT

Abstract translation: 待解决的问题：提供可用于治疗哺乳动物的血管生成疾病的化合物，特别是在治疗用途中安全，并且可用作对病理学症状具有选择性毒性的抗血管生成剂。 通过选择性抑制内皮细胞的增殖而没有或几乎不发展对正常（非癌症）细胞的毒性。 解决方案：公开了哺乳动物kringle 5片段和kringle 5融合蛋白作为治疗血管生成疾病的化合物。 还公开了用于抑制血管生成疾病的方法和化合物。 三环片段由结构式ABCXY表示（在该式中，A不存在或氮保护基; Y不存在或羧酸保护基; B为天然氨基酸残基; C由式R 1 -R 2 -R 3 -R 4 （这些基团是赖氨酰，亮氨酰或精氨酰，酪氨酰等 ，和天冬氨酰基）; X不存在或天然氨基酸残基等）。 版权所有（C）2009，JPO＆INPIT

公开(公告)号：JP2008231107A

公开(公告)日：2008-10-02

申请号：JP2008095692

申请日：2008-04-02

Applicant: Abbott Lab ,  アボット・ラボラトリーズAbbott Laboratories

Inventor： HENKIN JACK ,  DAVIDSON DONALD J

IPC: A61K38/48 ,  A61K38/00 ,  A61K47/48 ,  A61P1/04 ,  A61P7/04 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P9/14 ,  A61P15/18 ,  A61P17/00 ,  A61P17/02 ,  A61P17/06 ,  A61P19/02 ,  A61P27/02 ,  A61P27/06 ,  A61P29/00 ,  A61P35/00 ,  A61P35/02 ,  A61P35/04 ,  A61P37/06 ,  C12N5/06 ,  C12N9/68 ,  C12N9/74

CPC classification number: C12N9/6435 ,  A61K38/00 ,  C07K2319/00 ,  C12Y304/21007

Abstract: PROBLEM TO BE SOLVED: To provide a composition for inhibition of angiogenic diseases such as cancer, arthritis, macular degeneration, diabetic retinopathy, primary and metastatic solid tumors, cancerous tumor, sarcoma, lymphoma, psoriasis and vascular neoplasm. SOLUTION: The composition contains a kringle peptide fragment complex composed of mPEG-SLLPD-K5 or mPEG-SEED-K5, however, mPEG-SLLPD-K5 represents a peptide containing a specific 450-543 amino acid sequence combined with methoxypolyethylene glycol and serine to the N-terminal of the amino acid sequence and mPEG-SEED-K5 represents a peptide containing a specific 458-543 amino acid sequence combined with methoxypolyethylene glycol to the N-terminal of the amino acid sequence. COPYRIGHT: (C)2009,JPO&INPIT

Abstract translation: 待解决的问题：提供抑制血管生成疾病如癌症，关节炎，黄斑变性，糖尿病性视网膜病变，原发性和转移性实体瘤，癌性肿瘤，肉瘤，淋巴瘤，牛皮癣和血管肿瘤的组合物。 解决方案：组合物含有由mPEG-SLLPD-K5或mPEG-SEED-K5组成的三环肽片段复合物，然而，mPEG-SLLPD-K5代表含有特定的450-543氨基酸序列与甲氧基聚乙二醇组合的肽 并且丝氨酸至氨基酸序列的N-末端，并且mPEG-SEED-K5表示含有氨基酸序列的N-末端与甲氧基聚乙二醇组合的特定的458-543个氨基酸序列的肽。 版权所有（C）2009，JPO＆INPIT

公开(公告)号：WO9741824A2

公开(公告)日：1997-11-13

申请号：PCT/US9707700

申请日：1997-05-05

Applicant: ABBOTT LAB

Inventor： DAVIDSON DONALD J ,  WANG JIEYI ,  GUBBINS EARL J

IPC: C12N15/09 ,  A61K20060101 ,  A61K35/14 ,  A61K38/00 ,  A61K38/04 ,  A61K38/48 ,  A61K39/00 ,  A61K45/00 ,  A61K48/00 ,  A61K101/00 ,  A61P1/04 ,  A61P15/18 ,  A61P17/06 ,  A61P19/02 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07K1/00 ,  C07K14/00 ,  C07K14/47 ,  C07K14/515 ,  C07K19/00 ,  C12N20060101 ,  C12N9/68 ,  C12N15/02 ,  C12N15/57 ,  C12P21/06 ,  A61K

CPC classification number: C12N9/6435 ,  A61K38/00 ,  A61K48/00 ,  C12Y304/21007

Abstract: Mammalian kringle (5) fragments and kringle (5) fusion proteins are disclosed as compounds for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.

Abstract translation: 公开了哺乳动物kringle（5）片段和kringle（5）融合蛋白作为治疗血管生成疾病的化合物。 还公开了用于抑制血管生成疾病的方法和组合物。

公开(公告)号：WO2006039173A3

公开(公告)日：2006-07-20

申请号：PCT/US2005033914

申请日：2005-09-22

Applicant: ABBOTT LAB ,  DAVIDSON DONALD J

Inventor： DAVIDSON DONALD J

IPC: C12Q1/68 ,  C07K16/28 ,  G01N33/543

CPC classification number: C12Q1/6897 ,  C07K16/28 ,  C07K2317/34 ,  C07K2317/73 ,  C07K2317/74 ,  C07K2317/76 ,  G01N33/54306 ,  G01N2333/71

Abstract: The subject invention relates to uses of a receptor referred to as GRP78 and to other endothelial cell receptors which bind to the kringle 5 region of mammalian plasminogen. More specifically, identification of the functional properties of this receptor and other such receptors allows for the development and screening of agents which, for example, mimic K5 (i.e, mimetics) and therefore inhibit angiogenesis.

Abstract translation: 本发明涉及称为GRP78的受体的用途和与哺乳动物纤溶酶原的三环5区结合的其它内皮细胞受体。 更具体地，鉴定该受体和其它此类受体的功能特性允许开发和筛选例如模拟K5（即模拟物）并因此抑制血管发生的药剂。

公开(公告)号：WO03054550A8

公开(公告)日：2004-08-05

申请号：PCT/US0240966

申请日：2002-12-19

Applicant: ABBOTT LAB

Inventor： DAVIDSON DONALD J

IPC: G01N33/53 ,  A61K38/00 ,  C07K16/18 ,  C07K16/28 ,  C12N15/09 ,  C12Q1/02 ,  C12R1/91 ,  G01N33/15 ,  G01N33/50 ,  G01N33/543 ,  G01N33/566 ,  G01N33/577 ,  A61K38/48

CPC classification number: C07K16/28 ,  A61K38/00 ,  G01N33/54306 ,  G01N33/566 ,  G01N2500/10

Abstract: The subject invention relates to uses of a receptor referred to as GRP78 and to other endothelial cell receptors which bind to the kringle 5 region of mammalian plasminogen. More specifically, identification of the functional properties of this receptor and other such receptors allows for the development and screening of agents which, for example, mimic K5 (i.e, mimetics) and therefore inhibit angiogenesis.

Abstract translation: 本发明涉及称为GRP78的受体和结合哺乳动物纤溶酶原的三环5区域的其他内皮细胞受体的用途。 更具体地说，鉴定这种受体和其它这类受体的功能特性允许开发和筛选例如模拟K5（即模拟物）并因此抑制血管生成的试剂。

公开(公告)号：WO2008076868A3

公开(公告)日：2008-10-09

申请号：PCT/US2007087542

申请日：2007-12-14

Applicant: ABBOTT LAB ,  DAVIDSON DONALD J ,  HASKELL CATHERINE J

Inventor： DAVIDSON DONALD J ,  HASKELL CATHERINE J

IPC: G01N33/68

CPC classification number: G01N33/566 ,  C07K16/2803 ,  C07K2317/73 ,  G01N33/574 ,  G01N2333/91215 ,  G01N2800/52

Abstract: The present invention relates to the discovery of the role of tyrosine kinase orphan receptor-1 (ROR-1) and its interactions with glucose-regulated protein 78 (GRP78) and Wnt in processes such as angiogenesis and apoptosis. The invention provides diagnostic methods based on ROR-1 and GRP78, as well as methods of modulating ROR-1, antibodies specific for ROR-1, GRP78, and Wnt, and related screening methods.

Abstract translation: 本发明涉及酪氨酸激酶孤儿受体-1（ROR-1）及其与葡萄糖调节蛋白78（GRP78）和Wnt在诸如血管生成和凋亡过程中的相互作用的发现。 本发明提供了基于ROR-1和GRP78的诊断方法，以及调节ROR-1，ROR-1，GRP78和Wnt特异性抗体的方法以及相关的筛选方法。

公开(公告)号：WO0226782A3

公开(公告)日：2003-01-16

申请号：PCT/US0142423

申请日：2001-09-27

Applicant: ABBOTT LAB

Inventor： HENKIN JACK ,  DAVIDSON DONALD J

IPC: A61K38/00 ,  A61K47/48 ,  A61P9/00 ,  A61P17/06 ,  A61P19/02 ,  A61P27/02 ,  A61P35/00 ,  C12N9/68 ,  C12N9/74 ,  A61K38/48

CPC classification number: C12N9/6435 ,  A61K38/00 ,  C07K2319/00 ,  C12Y304/21007

Abstract: Conjugated kringle protein fragments are disclosed as compounds for treating angiogenic diseases. Methods and compositions for inhibiting angiogenic diseases are also disclosed.

Abstract translation: 公开了缀合的三环蛋白片段作为治疗血管生成疾病的化合物。 还公开了用于抑制血管生成疾病的方法和组合物。

公开(公告)号：AT410507T

公开(公告)日：2008-10-15

申请号：AT01979922

申请日：2001-09-27

Applicant: ABBOTT LAB

Inventor： HENKIN JACK ,  DAVIDSON DONALD J

IPC: C12N9/68 ,  A61K38/00 ,  A61K38/48 ,  A61K47/48 ,  A61P9/00 ,  A61P17/06 ,  A61P19/02 ,  A61P27/02 ,  A61P35/00 ,  C12N9/74

公开(公告)号：AU2002358265B2

公开(公告)日：2008-07-03

申请号：AU2002358265

申请日：2002-12-19

Applicant: ABBOTT LAB

Inventor： DAVIDSON DONALD J

IPC: G01N33/53 ,  A61K38/00 ,  C07K16/18 ,  C07K16/28 ,  C12N15/09 ,  C12Q1/02 ,  C12R1/91 ,  G01N33/15 ,  G01N33/50 ,  G01N33/543 ,  G01N33/566 ,  G01N33/577

公开(公告)号：DK0910571T3

公开(公告)日：2005-10-31

申请号：DK97925478

申请日：1997-05-05

Applicant: ABBOTT LAB

Inventor： DAVIDSON DONALD J ,  WANG JIEYI ,  GUBBINS EARL J

IPC: C12N15/09 ,  A61K20060101 ,  A61K35/14 ,  A61K38/00 ,  A61K38/04 ,  A61K38/48 ,  A61K39/00 ,  A61K45/00 ,  A61K48/00 ,  A61K101/00 ,  A61P1/04 ,  A61P15/18 ,  A61P17/06 ,  A61P19/02 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P43/00 ,  C07K1/00 ,  C07K14/00 ,  C07K14/47 ,  C07K14/515 ,  C07K19/00 ,  C12N20060101 ,  C12N9/68 ,  C12N15/02 ,  C12N15/57 ,  C12P21/06

Abstract: Compounds of formulae (I) and (II), and their salts, esters and prodrugs, are new: A-B-C-X-Y (I); A-B1-C1-X1-Y (II); A = absent or a nitrogen-protecting group; Y = absent or a carboxy-protecting group; B = absent or 1-197 naturally occurring amino acids (aa) corresponding to residues 334-530 of the 791 aa human plasminogen (hPA) sequence given in the specification; C = Lys-R2-R3-Asp; R2 = Leu or Arg; R3 = Tyr, 3-iodotyrosinyl (ITyr) or Phe; X = absent or is 1-12 naturally occurring aa corresponding to residues 535-546 of hP and its homologues or analogues; B1 = absent or is 1-176 aa corresponding to residues 334-513 of hP; C1 = the 514-523 aa sequence of hP; X1 = absent or is 1-10 aa corresponding to residues 524-533 of hP.