Lipid-altering compositions for the treatment of infertility 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
US2003232879 A1 2003-12-18 [US20030232879]US7208467 B2 2007-04-24 [US7208467] / 2003-12-182007-04-24
申请号/申请日
2002US-10164863 / 2002-06-07
发明人
KRIEGER MONTY;MIETTINEN HELENA E;
申请人
MIT - MASSACHUSETTS INSTITUTE OF TECHNOLOGY;
主分类号
IPC分类号
A01N-031/00A01N-037/18A01N-043/08A01N-043/16A61K-031/00A61K-031/095A61K-031/355A61K-031/365A61K-031/375A61K-038/00
摘要
(US7208467) SR-BI is present at relatively high levels on the membranes of hepatocytes and steroidogenic tissues, including the adrenal gland, testes, and ovaries, where it mediates the uptake and transport of cholesteryl ester from high density lipoproteins.  It has been demonstrated that transgenic animals which do not produce SR-BI are healthy, with the exception that the females are infertile.  SR-BI KO females have abnormal HDLs, ovulate dysfunctional oocytes and are infertile.  Surgical, genetic and pharmacologic methods were used to show that the fertility of SR-BI KO females (or their transplanted oocytes) can be restored in the absence of ovarian and/or extraovarian SR-BI expression by manipulations that modify the structure, composition and/or abundance of their abnormal plasma lipoproteins.  These manipulations included inactivation of the apolipoprotein A-I gene and administration of the cholesterol-lowering drug PROBUCOL(TM).  In the absence of treatment, female animals which do not express SR-BI have dramatically reduced levels of offspring, even though they are otherwise healthy and the males normal.  Studies demonstrate that they do not produce viable eggs and have a defect involving implantation of normal eggs.
机翻摘要
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地址
代理人
代理机构
;
优先权号
2002US-10164863 2002-06-07
主权利要求
(US7208467) We claim: 1.  A method for treating reproductive disorders involving abnormal levels of lipids in a female mammal mediated by SR-BI activity comprising administering an effective amount of a compound altering directly or indirectly the transfer of cholesterol or cholesteryl ester from high density lipoprotein or other lipoproteins via SR-BI to liver or steroidogenic tissues to normalize the abnormal levels of lipids and thereby treat one or more symptoms of the reproductive disorder resulting from the abnormal levels of lipids. 2. The method of claim 1 wherein the compound is a hypocholesterolemic agent. 3. The method of claim 1 wherein the compounds is an antioxident. 4. The method of claim 1 comprising administering a hypocholesterolemic agent as the compound in combination with an antioxident to treat the symptoms of the reproductive disorder. 5. The method of claim 1 wherein the compound is 4,4'-(isopropylidenedithio) bis(2,6-di-tert-butylphenol)) or monoesters thereof. 6. The method of claim 1 wherein the compound is 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butyl-benzofuran. 7. The method of claim 1 wherein the compound is vitamin E or C. 8. The method of claim 1 wherein the compound alters SR-BI expression. 9. The method of claim 1 wherein the compound alters binding of SR-BI to high density lipoprotein including cholesteryl ester or other lipoproteins. 10. The method of claim 1 wherein the compound increases SR-BI expression. 11. The method of claim 1 wherein the compound decreases SR-BI binding to lipoprotein or transfer of lipid selected from the group consisting of cholesterol, its derivatives, lipid soluble vitamins, and other lipid soluble molecules. 12. The method of claim 1 wherein the compound increases SR-BI binding to lipoprotein or transfer of lipid selected from the group consisting of cholesterol, its derivatives, lipid soluble vitamins, and other lipid soluble molecules. 13. The method of claim 1 wherein the compound is administered in an amount effective to restore normal reproductive function. 14. The method of claim 1 wherein the mammal has a disorder characterized by an overproduction of steroids. 15. The method of claim 1 wherein the mammal has a disorder characterized by an underproduction of steroids.
法律状态
(US7208467) LEGAL DETAILS FOR US2003232879  Actual or expected expiration date=2011-05-23    Legal state=DEAD    Status=LAPSED     Event publication date=2002-06-07  Event code=US/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=US US10164863  Application date=2002-06-07  Standardized application number=2002US-10164863     Event publication date=2002-06-07  Event code=US/EXMR  Event type=Administrative notifications  USPTO Examiner Name Primary Examiner: LANDSMAN, ROBERT S    Event publication date=2002-06-07  Event code=US/ART  Event type=Administrative notifications  USPTO Art Group  ART=1647     Event publication date=2002-06-07  Event code=US/ENT  Event type=Administrative notifications  Entity Status Set to Undiscounted Business Entity Status: UNDISCOUNTED    Event publication date=2002-06-07  Event code=US/AIA  Event type=Administrative notifications  First Inventor File Indicated:  AIA=No     Event publication date=2002-06-07  Event code=US/DK  Event type=Examination events  Attorney Docket Number Docket Nbr: MIT 9094    Event publication date=2002-06-07  Event code=US/CUST  Event type=Examination events  Attorney/Agent Customer Number Customer Nbr: 23579    Event publication date=2002-07-30  Event code=US/INCD  Event type=Examination events  Event type=OAO  Notice Mailed--Application Incomplete--Filing Date Assigned    Event publication date=2002-09-16  Event code=US/IDS  Event type=Examination events  Event type=OAI  Information Disclosure Statement Filed    Event publication date=2002-10-01  Event code=US/APE  Event type=Corrections  Preliminary amendments    Event publication date=2002-10-29  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment Owner: MASSACHUSETTS INSTITUTE OF TECHNOLOGY, MASSACHUSET ASSIGNMENT OF ASSIGNORS INTEREST ASSIGNORS:KRIEGER, MONTY MIETTINEN, HELENA E. REEL/FRAME:013426/0235 SIGNING DATES FROM 20020829 TO 20020902     Event publication date=2003-06-05  Event code=US/DOCK  Event indicator=Pos  Event type=Examination events  Case Docketed to Examiner    Event publication date=2003-09-11  Event code=US/RESTREQ  Event type=Examination events  Event type=Corrections  Event type=OAO  Restriction/Election Requirement    Event publication date=2003-10-14  Event code=US/ELC  Event type=Examination events  Event type=OAI  Response to Election / Restriction Filed    Event publication date=2003-12-18  Event code=US/A1  Event type=Examination events  Application published  Publication country=US  Publication number=US2003232879  Publication stage Code=A1  Publication date=2003-12-18  Standardized publication number=US20030232879     Event publication date=2004-03-31  Event code=US/DOCK  Event indicator=Pos  Event type=Examination events  Case Docketed to Examiner    Event publication date=2004-04-09  Event code=US/CTNF  Event type=Examination events  Event type=OA  Event type=OAO  Non-Final Rejection    Event publication date=2004-07-12  Event code=US/CTNFR  Event type=Examination events  Event type=OAI  Response after Non-Final Action    Event publication date=2004-08-30  Event code=US/IDS  Event type=Examination events  Event type=OAI  Information Disclosure Statement Filed    Event publication date=2004-09-07  Event code=US/CTNF  Event type=Examination events  Event type=OA  Event type=OAO  Non-Final Rejection    Event publication date=2004-12-08  Event code=US/CTNFR  Event type=Examination events  Event type=OAI  Response after Non-Final Action    Event publication date=2005-02-17  Event code=US/CTFR  Event type=Examination events  Event type=OA  Event type=OAO  Final Rejection    Event publication date=2005-05-17  Event code=US/NOAPLF  Event type=APL  Notice of Appeal Filed    Event publication date=2005-08-17  Event code=US/APB  Event type=APL  Event type=OAI  Appeal Brief Filed    Event publication date=2005-08-17  Event code=US/136G  Event type=OAO  Request for Extension of Time - Granted    Event publication date=2005-09-02  Event code=US/APEA  Event type=APL  Event type=OAO  Examiner's Answer to Appeal Brief    Event publication date=2005-12-28  Event code=US/M327  Event type=Examination events  Event type=OAO  Miscellaneous Communication to Applicant - No Action Count    Event publication date=2006-07-31  Event code=US/BPAIR  Event type=APL  BPAI Decision - Examiner Reversed    Event publication date=2006-11-07  Event code=US/NOAM  Event indicator=Pos  Event type=Examination events  Event type=OAO  Mail Notice of Allowance    Event publication date=2007-02-08  Event code=US/APRDY  Event indicator=Pos  Event type=Examination events  Application Is Considered Ready for Issue    Event publication date=2007-04-04  Event code=US/ISSM  Event indicator=Pos  Event type=Examination events  Event type=OAO  Event type=Restitution or restoration  Issue Notification Mailed    Event publication date=2007-04-24  Event code=US/B2  Event indicator=Pos  Event type=Event indicating In Force  Granted patent as second publication  Publication country=US  Publication number=US7208467  Publication stage Code=B2  Publication date=2007-04-24  Standardized publication number=US7208467     Event publication date=2007-04-24  Event code=US/354  Event indicator=Pos  Event type=Extension of term of duration of protection  Patent term extended under  35 U.S.C 154(b) until/for Delays (A,B,C): 244  Overlap Delays: 0  Non Overlap Delays: 686   PTO Office Delays: 0  Applicant Delays: 126  Adjustment total:  Number of days of extension=560    Event publication date=2007-08-21  Event code=US/CC  Event type=Corrections  Event type=Restitution or restoration  Certificate of Correction - Post Issue Communication    Event publication date=2008-09-08  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment Owner: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF  Effective date of the event=2002-09-30  CONFIRMATORY LICENSE ASSIGNOR:MASSACHUSETTS INSTITUTE OF TECHNOLOGY REEL/FRAME:021492/0896     Event publication date=2010-05-04  Event code=US/NMFP  Event type=Payment or non-payment notifications  Publication of First Notice of Maintenance Fees Payable. PAYMENT NOTICE YEAR:  Year of payment of annual fees=3     Event publication date=2010-11-29  Event code=US/REMI  Event type=Administrative notifications  Maintenance fee reminder mailed    Event publication date=2011-04-24  Event code=US/FP  Event indicator=Neg  Event type=Event indicating Not In Force  Event type=Payment or non-payment notifications  Expired due to failure to pay maintenance fee  Effective date of the event=2011-04-24     Event publication date=2011-04-24  Event code=US/LAPS  Event indicator=Neg  Event type=Event indicating Not In Force  Event type=Payment or non-payment notifications  Lapse for failure to pay maintenance fees    Event publication date=2011-05-23  Event code=US/FP  Event indicator=Neg  Event type=Event indicating Not In Force  Event type=Payment or non-payment notifications  Expired due to failure to pay maintenance fee    Event publication date=2011-05-23  Event code=US/EXP  Event indicator=Neg  Event type=Event indicating Not In Force  Patent expired    Event publication date=2014-05-06  Event code=US/NMFP  Event type=Payment or non-payment notifications  Publication of First Notice of Maintenance Fees Payable. 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专利类型码
A1B2
国别省市代码
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