Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) structure and uses thereof in drug identification and screening 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
US2003190600 A1 2003-10-09 [US20030190600] / 2003-10-09
申请号/申请日
2002US-10118471 / 2002-04-05
发明人
HOLMES KATHRYN V;ZELUS BRUCE D;TAN KEMIN;WANG JIA-HUAI;MEIJERS ROB;
申请人
DANA FARBER CANCER INSTITUTE;UNIVERSITY OF COLORADO;
主分类号
IPC分类号
A61K-038/17C07K-014/705G01N-033/574
摘要
(US20030190600) Disclosed are novel crystal structures of a carcinoembryonic cell adhesion antigen functional domain that is characterized as having a unique N-terminal domain structure, called a CC' loop.  This tertiary structure is used in a number of screening methods for identifying candidate molecules that have a binding affinity for the tertiary structure of the CC' loop.  Pharmaceutical preparations that include one or more of such identified candidate may then be provided and used in treatments for bacterial infections, dysentery, angiogenesis, immune cell mediated disease, and related conditions thereto.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2002US-10118471 2002-04-05
主权利要求
(US20030190600) What is claimed is: 1.  A method for screening a candidate substance for binding to and/or inhibiting binding to CEACAM1 or a structurally related CEA family member of a ligand or inhibiting a biological activity such as cell adhesion, tumor metastasis, angiogenesis, virus binding and infection, or (bacterial inhibiting, or cell adhesion inhibiting) activity comprising:preparing a soluble CEACAM1 protein comprising a functional binding domain, D1, having a protruding, convoluted CC' loop amino acid sequence for humans of K G E R V D G N R Q);  a C-TERMINAL domain, D4, having an elongated CD loop, and a flexible linker connecting D1 to D4, to provide a target protein;  preparing a control sample comprising the target protein and a monoclonal antibody having specific binding affinity for the CC' loop, and preparing a test sample comprising the target protein and a candidate substance;  incubating the control sample and the test sample for a period of time and under appropriate conditions to permit binding to the target protein in the control sample;  and comparing the amount of antibody-bound target protein in the control sample to the amount of candidate agent bound target protein in the test sample, wherein a candidate agent having at least 40% the amount of bound candidate agent to target protein compared to the amount of bound target protein in the control sample is selected as having sufficient binding/inhibiting activity. 2. The method of claim 1 wherein D1 further comprises a first and a second anti-parallel beta-sheet connected to one another by a salt bridge. 3. The method of claim 1 wherein the ligand is a homophilic binding domain of CEACAM1, MHV viral spike glycoprotein, Neisseria, or Hemophilus bacteria. 4. The method of claim 1 wherein the target protein comprises a cell surface receptor. 5. The method of claim 4 wherein the target protein comprises a cell surface protein on an epithelial cell, a leukocyte, an endothelial cell, or a placental cell. 6. The method of claim 1 wherein the selected candidate substance inhibits virus binding. 7. The method of claim 3 wherein the selected candidate substance inhibits binding of a pathogenic strain of bacteria of Neisseria or Hemophilus. 8. The method of claim 7 wherein the pathogenic strain is a Hemophilus strain. 9. The method of claim 7 wherein the pathogenic strain of bacteria is a Hemophilus strain. 10. The method of claim 1 wherein the selected candidate substance is capable of blocking cell-mediated immune responses. 11. The method of claim 1 wherein the selected candidate substance provides a bacterial inhibiting activity. 12. The method of claim 10 wherein the selected candidate substance provides a treatment for bacterial infection. 13. The method of claim 10 wherein the selected candidate substance provides a treatment for diarrhea. 14. The method of claim 10 wherein the selected candidate substance provides a treatment for hepatitis. 15. A soluble protein in the CEA family comprising:a hydrophobic core molecule;  a functional CC' binding domain having a convoluted and protruding structure;  and a carboxy terminal D4 containing an elongated CD loop. 16. The soluble CEA family protein of claiml4 further defined as having an A-A' kink comprising a cis-proline amino acid residue. 17. The soluble CEA family protein of claim 14 further comprising a detectable molecular tag molecule. 18. The soluble CEA family protein of claim 14 further defined as comprising an amino acid sequence of SEQ ID NO: 1. 19. The soluble CEA family protein of claim 14 further defined as comprising an amino acid sequence of SEQ ID NO: 2. 20. The soluble CEA family protein of claim 14 further defined as comprising an amino acid sequence of SEQ ID NO: 3. 21. The soluble CEA family protein of claim 15 further defined as a cellular receptor for a coronavirus. 22. A pharmaceutical formulation comprising the molecule of claim 15 in a pharmaceutically acceptable excipient. 23. The pharmaceutical formulation of claim 22 further defined as an antiviral agent. 24. An antiviral agent comprising a molecule capable of binding with high affinity and under stringent conditions to a target antigen molecule having:a virus binding domain, D1, having a first and a second anti-parallel beta-sheet connected to one another by a salt bridge, a protruding, convoluted CC' loop, and an A-A' kink, a C-terminal domain, D4, having an elongated CD loop, and a flexible linker connecting D1 to D4. 25. The antiviral agent of claim 24 wherein the anti-viral agent is further defined as binding to the target antigen molecule with an affinity of about 10(4) to about 10(10).
法律状态
(US20030190600) LEGAL DETAILS FOR US2003190600  Actual or expected expiration date=2004-04-02    Legal state=DEAD    Status=LAPSED     Event publication date=2002-04-05  Event code=US/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=US US11847102  Application date=2002-04-05  Standardized application number=2002US-10118471     Event publication date=2002-04-05  Event code=US/EXMR  Event type=Administrative notifications  USPTO Examiner Name Primary Examiner: LUCAS, ZACHARIAH    Event publication date=2002-04-05  Event code=US/ART  Event type=Administrative notifications  USPTO Art Group  ART=1648     Event publication date=2002-04-05  Event code=US/DK  Event type=Examination events  Attorney Docket Number Docket Nbr: 400425    Event publication date=2002-04-05  Event code=US/SMALL  Event type=Administrative notifications  Appl Has Filed a Verified Statement of Micro to Small Entity Status Business Entity Status: SMALL    Event publication date=2002-04-05  Event code=US/AIA  Event type=Administrative notifications  First Inventor File Indicated:  AIA=No     Event publication date=2002-05-22  Event code=US/INCD  Event type=Examination events  Event type=OAO  Notice Mailed--Application Incomplete--Filing Date Assigned    Event publication date=2002-08-22  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment Owner: DANA-FABER CANCER INSTITUTE, COLORADO  Effective date of the event=2002-04-17  ASSIGNMENT OF ASSIGNORS INTEREST ASSIGNORS:WANG, JAI-HUAI TAN, KEMIN MEIJERS, ROB REEL/FRAME:013225/0384     Event publication date=2002-08-22  Event code=US/APE  Event type=Corrections  Preliminary amendments    Event publication date=2002-08-26  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment Owner: REGENTS OF THE UNIVERSITY OF COLORADO, THE, COLORA ASSIGNMENT OF ASSIGNORS INTEREST ASSIGNORS:HOLMES, KATHRYN V. ZELUS, BRUCE D. REEL/FRAME:013225/0392 SIGNING DATES FROM 20020703 TO 20020820     Event publication date=2002-10-21  Event code=US/DOCK  Event indicator=Pos  Event type=Examination events  Case Docketed to Examiner    Event publication date=2003-01-29  Event code=US/POAC  Event type=Change of name or address  Change in Power of Attorney (May Include Associate POA)    Event publication date=2003-09-08  Event code=US/RESTREQ  Event type=Examination events  Event type=Corrections  Event type=OAO  Restriction/Election Requirement    Event publication date=2003-10-09  Event code=US/A1  Event type=Examination events  Application published  Publication country=US  Publication number=US2003190600  Publication stage Code=A1  Publication date=2003-10-09  Standardized publication number=US20030190600     Event publication date=2004-04-02  Event code=US/ABNOA  Event indicator=Neg  Event type=Event indicating Not In Force  Event type=OAO  Abandoned -- Failure to Respond to an Office Action
专利类型码
A1
国别省市代码
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