Device and method for regeneration and repair of cartilage lesions 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
US6511958 B1 2003-01-28 [US6511958] / 2003-01-28
申请号/申请日
2000US-09505209 / 2000-02-16
发明人
ATKINSON BRENT;BENEDICT JAMES J;
申请人
ZIMMER ORTHOBIOLOGICS;
主分类号
IPC分类号
A61B-017/06A61F-002/00A61F-002/02A61F-002/28A61F-002/30A61L-027/22A61L-027/24A61L-027/26A61L-027/54
摘要
(US6511958) Disclosed is a cartilage repair product that induces both cell ingrowth into a bioresorbable material and cell differentiation into cartilage tissue.  Such a product is useful for regenerating and/or repairing both vascular and avascular cartilage lesions, particularly articular cartilage lesions, and even more particularly mensical tissue lesions, including tears as well as segmental defects.  Also disclosed is a method of regenerating and repairing cartilage lesions using such a product.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
代理机构
;
优先权号
1997EP-0810567 1997-08-14 1998WO-EP05100 1998-08-12 1999US-09250370 1999-02-16 2000US-09505209 2000-02-16
主权利要求
(US6511958) What is claimed is: 1.  A product for repair of cartilage lesions, comprising: a. a cartilage repair matrix suitable for conforming to a defect in cartilage;  and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: transforming growth factor  BETA 1 (TGF BETA 1), bone morphogenetic protein (BMP)-2, BMP-3, and BMP-7; - wherein the quantity of said TGF BETA 1 in said mixture is greater than 1% of total proteins in said mixture; - wherein the quantity of said BMP-2 in said mixture is from about 0.01% to about 10% of total proteins in said mixture; - wherein the quantity of said BMP-3 in said mixture is from about 0.1% to about 15% of total proteins in said mixture;  and, - wherein the quantity of said BMP-7 in said mixture is from about 0.01% to about 10% of total proteins in said mixture. 2. The product of claim 1, wherein the quantity of said TGF BETA 1 in said mixture is at least about 10% of total proteins in said mixture. 3. The product of claim 1, wherein said mixture of proteins further comprises TGF BETA 2, TGF BETA 3, BMP-4, BMP-5, BMP-6, cartilage-derived morphogenetic protein (CDMP), FGF-I, osteocalcin, osteonectin, BSP, lysyloxidase, cathepsin L pre, albumin, transferrin, Apo Al LP and Factor XIIIb. 4. A product for repair of cartilage lesions, comprising: a. a cartilage repair matrix;  and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: - (i) a bone-derived osteogenic or chondrogenic formulation containing at least one bone morphogenetic protein (BMP);  and, - (ii) a TGF BETA  protein that is exogenous to said formulation of (i); wherein the ratio of said exogenous TGF BETA  protein to total BMP in said mixture of proteins is greater than about 10:1;  and, wherein said exogenous TGF BETA  protein is present in an amount sufficient to increase cartilage induction by said composition over a level of cartilage induction by said bone-derived osteogenic or chondrogenic protein formulation in the absence of said exogenous TGF BETA  protein. 5. The product of claim 4, wherein said exogenous TGF BETA  protein is TGF BETA 1. 6. The product of any one of claim 1 or 5, wherein the ratio of TGF BETA 1 to all other proteins in said mixture of proteins is at least about 1:10. 7. The product of any one of claim 1 or 5, wherein the ratio of TGF BETA 1 to all other proteins in said mixture of proteins is at least about 10:1. 8. The product of claim 4, wherein said mixture of proteins comprises TGF BETA  superfamily proteins consisting of: TGF BETA 1, bone morphogenetic protein (BMP)-2, BMP-3, and BMP-7, wherein said TGF BETA  superfamily proteins comprise from about 0.5% to about 99.99% of said mixture of proteins. 9. The product of claim 4, wherein said bone-derived osteogenic or chondrogenic formulation comprises TGF BETA 1, TGF BETA 2, TGF BETA 3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, CDMP, FGF-I, osteocalcin, osteonectin, BSP, lysyloxidase, cathepsin L pre, albumin, transferrin, Apo Al LP and Factor XIIIb. 10. A product for repair of cartilage lesions, comprising: a. a cartilage repair matrix;  and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: - (i) a TGF BETA  protein;  and, - (ii) at least one bone morphogenetic protein (BMP); wherein the ratio of said TGF BETA  protein to total BMP in said mixture of proteins is greater than about 10:1. 11. The product of any one of claim 1, 4 or 10, wherein said mixture of proteins comprises Bone Protein (BP). 12. The product of any one of claim 1, 4 or 10, wherein said cartilage-inducing composition is at a concentration of from about 0.5% to about 33% by weight of said product. 13. The product of any one of claim 1, 4 or 10, wherein said cartilage repair matrix is bioresorbable. 14. The product of claim 1, 4 or 10, wherein said cartilage repair matrix comprises collagen from bovine tendon. 15. The product of claim 10, wherein said mixture of proteins comprises TGF BETA  superfamily proteins consisting of: TGF BETA 1, bone morphogenetic protein (BMP)-2, BMP-3, and BMP-7, wherein said TGF BETA  superfamily proteins comprise from about 0.5% to about 99.99% of said mixture of proteins. 16. The product of any one of claim 8 or 15, wherein said TGF BETA  superfamily proteins comprise from about 0.5% to about 25% of said mixture of proteins. 17. The product of any one of claim 8 or 15, wherein the quantity of said TGF BETA 1 in said mixture is from about 0.01% to about 75% of total proteins in said mixture. 18. The product of any one of claim 1, 8 or 15, wherein the quantity of said TGF BETA 1 in said mixture is from about 33% to about 99.99% of total proteins in said mixture. 19. The product of any one of claim 1, 8 or 15, wherein said mixture of proteins further comprises at least one bone matrix protein selected from the group consisting of osteocalcin, osteonectin, bone sialoprotein (BSP), lysyloxidase, cathepsin L pre, osteopontin, matrix GLA protein (MGP), biglycan, decorin, proteoglycan-chondroitin sulfate III (PG-CS III), bone acidic glycoprotein (BAG-75), thrombospondin (TSP) and fibronectin;  wherein said bone matrix protein comprises from about 20% to about 98% of said mixture of proteins. 20. The product of any one of claim 1, 8 or 15, wherein said mixture of proteins further comprises at least one growth factor protein selected from the group consisting of fibroblast growth factor-I (FGF-I), FGF-II, FGF-9, leukocyte inhibitory factor (LIF), insulin, insulin-like growth factor I (IGF-I), IGF-II, platelet-derived growth factor AA (PDGF-AA), PDGF-BB, PDGF-AB, stromal derived factor-2 (SDF-2), pituitary thyroid hormone (PTH), growth hormone, hepatocyte growth factor (HGF), epithelial growth factor (EGF), transforming growth factor- ALPHA  (TGF ALPHA ) and hedgehog proteins;  wherein said growth factor protein comprises from about 0.01% to about 50% of said mixture of proteins. 21. The product of any one of claim 1, 8 or 15, wherein said composition further comprises one or more serum proteins. 22. The product of any one of claim 4 or 10, wherein the ratio of said TGF BETA  protein to total BMP in said mixture of proteins is greater than about 100:1. 23. A product for repair of cartilage lesions, comprising: a. a cartilage repair matrix suitable for conforming to a defect in cartilage;  and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: transforming growth factor  BETA 1 (TGF BETA 1), bone morphogenetic protein (BMP)-2, BMP-3, and BMP-7; - wherein the quantity of said TGF BETA 1 in said mixture is greater than 1% of total proteins in said mixture; - wherein the quantity of said BMP-2 in said mixture is from about 0.01% to about 10% of total proteins in said mixture; - wherein the quantity of said BMP-3 in said mixture is at least about 0.38% of total proteins in said mixture;  and, - wherein the quantity of said BMP-7 in said mixture is from about 0.01% to about 10% of total proteins in said mixture. 24. The product of claim 10, wherein said BMP protein is selected from the group consisting of BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, BMP-8, BMP-9 and cartilage-derived morphogenetic protein (CDMP). 25. The product of claim 10, wherein said mixture of proteins comprises TGF BETA 1, TGF BETA 2, TGF BETA 3, BMP-2, BMP-3, BMP-4, BMP-5, BMP-6, BMP-7, cartilage-derived morphogenetic protein (CDMP), FGF-I, osteocalcin, osteonectin, BSP, lysyloxidase, cathepsin L pre, albumin, transferrin, Apo Al LP and Factor XIIIb. 26. A method for repair of cartilage lesions, comprising implanting and fixing into a cartilage lesion a product comprising: a. a cartilage repair matrix suitable for conforming to a defect in cartilage;  and b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: transforming growth factor  BETA 1 (TGF BETA 1), bone morphogenetic protein (BMP)-2, BMP-3, and BMP-7; - wherein the quantity of said TGF BETA 1 in said mixture is greater than 1% of total proteins in said mixture; - wherein the quantity of said BMP-2 in said mixture is from about 0.01% to about 10% of total proteins in said mixture; - wherein the quantity of said BMP-3 in said mixture is from about 0.1% to about 15% of total proteins in said mixture;  and, - wherein the quantity of said BMP-7 in said mixture is from about 0.01% to about 10% of total proteins in said mixture; whereby implanting and fixing said product into said cartilage lesion enhances repair of said defect in cartilage as compared to in the absence of said product. 27. A method for repair of cartilage lesions, comprising implanting and fixing into a cartilage lesion a product comprising: a. a cartilage repair matrix;  and, b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: - (i) a bone-derived osteogenic or chondrogenic formulation of proteins containing at least one bone morphogenetic protein (BMP);  and, - (ii) a TGF BETA  protein that is exogenous to said formulation of (i); wherein the ratio of said exogenous TGF BETA  protein to total BMP in said mixture of proteins is greater than about 10:1;  and, wherein said exogenous TGF BETA  protein is present in an amount sufficient to increase cartilage induction by said composition over a level of cartilage induction by said bone-derived osteogenic or chondrogenic protein formulation in the absence of said exogenous TGF BETA  protein; whereby implanting and fixing said product into said cartilage lesion enhances repair of said defect in cartilage as compared to in the absence of said product. 28. The method of claim 27, wherein said TGF BETA  protein is TGF BETA 1. 29. The method of any one of claim 26 or 28, wherein the ratio of TGF BETA 1 to all other proteins in said mixture of proteins is at least about 1:10. 30. The method of any one of claim 26 or 28, wherein the ratio of TGF BETA 1 to all other proteins in said mixture of proteins is at least about 10:1. 31. A method for repair of cartilage lesions, comprising implanting and fixing into a cartilage lesion a product comprising: a. a cartilage repair matrix;  and, b. a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: - (i) a TGF BETA  protein;  and, - (ii) at least one bone morphogenetic protein (BMP); wherein the ratio of said TGF BETA  protein to total BMP in said mixture of proteins is greater than about 10:1; whereby implanting and fixing said product into said cartilage lesion enhances repair of said defect in cartilage as compared to in the absence of said product. 32. The method of claim 31, wherein said TGF BETA  protein is TGF BETA 1. 33. The method of any one of claim 26, 27 or 31, wherein said cartilage lesion is an articular cartilage lesion. 34. The method of any one of claim 26, 27 or 31, wherein said cartilage lesion is a meniscal cartilage lesion. 35. The method of claim 34, wherein said lesion is a vascular meniscus lesion. 36. The method of claim 34, wherein said lesion is an avascular meniscus lesion. 37. The method of any one of claim 27 or 31, wherein the ratio of said TGF BETA  protein to total BMP in said mixture of proteins is greater than about 100:1. 38. The product of claim 10, wherein said TGF BETA  protein is TGF BETA 1. 39. A method for repair of segmental cartilage lesions, comprising implanting and fixing into a segmental cartilage lesion: a. a first product comprising: - (i) a cartilage repair matrix configured as a sheet;  and - (ii) a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: transforming growth factor  BETA 1 (TGF BETA 1), bone morphogenetic protein (BMP)-2, BMP-3, and BMP-7; -  wherein the quantity of said TGF BETA 1 in said mixture is greater than 1% of total proteins in said mixture; -  wherein the quantity of said BMP-2 in said mixture is from about 0.01% to about 10% of total proteins in said mixture; -  wherein the quantity of said BMP-3 in said mixture is from about 0.1% to about 15% of total proteins in said mixture;  and, -  wherein the quantity of said BMP-7 in said mixture is from about 0.01% to about 10% of total proteins in said mixture;  and, b. a second product comprising a cartilage repair matrix configured to replace cartilage removed from a segmental lesion; wherein said second product is implanted into said lesion and wherein said first product is implanted between an edge of said lesion and said second product to provide an interface between said lesion and said second product. 40. The method of claim 39, wherein said second product further comprises a cartilage-inducing composition contained on or within said matrix comprising a mixture of proteins comprising: transforming growth factor  BETA 1 (TGF BETA 1), bone morphogenetic protein (BMP)-2, BMP-3, and BMP-7; wherein the quantity of said TGF BETA 1 in said mixture is greater than 1% of total proteins in said mixture; wherein the quantity of said BMP-2 in said mixture is from about 0.01% to about 10% of total proteins in said mixture; wherein the quantity of said BMP-3 in said mixture is from about 0.1% to about 15% of total proteins in said mixture;  and, wherein the quantity of said BMP-7 in said mixture is from about 0.01% to about 10% of total proteins in said mixture. 41. The method of any one of claim 26, 27 or 31, wherein said lesion is a tear and wherein said matrix is configured as a sheet, wherein said step of implanting comprises inserting said product directly into said tear.
法律状态
(US6511958) LEGAL DETAILS FOR US6511958  Actual or expected expiration date=2010-04-27    Legal state=DEAD    Status=REVOKED     Event publication date=2000-02-16  Event code=US/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=US US09505209  Application date=2000-02-16  Standardized application number=2000US-09505209     Event publication date=2000-02-16  Event code=US/EXMR  Event type=Administrative notifications  USPTO Examiner Name Primary Examiner: FALK, ANNE MARIE    Event publication date=2000-02-16  Event code=US/ART  Event type=Administrative notifications  USPTO Art Group  ART=1632     Event publication date=2000-02-16  Event code=US/ENT  Event type=Administrative notifications  Entity Status Set to Undiscounted Business Entity Status: UNDISCOUNTED    Event publication date=2000-02-16  Event code=US/AIA  Event type=Administrative notifications  First Inventor File Indicated:  AIA=No     Event publication date=2000-02-16  Event code=US/DK  Event type=Examination events  Attorney Docket Number Docket Nbr: 3394.014US1    Event publication date=2000-02-16  Event code=US/CUST  Event type=Examination events  Attorney/Agent Customer Number Customer Nbr: 21186    Event publication date=2000-02-16  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): 0  Overlap Delays: 0  Non Overlap Delays: 0   PTO Office Delays: 0  Applicant Delays: 0  Adjustment total:  Number of days of extension=0    Event publication date=2000-04-27  Event code=US/INCD  Event type=Examination events  Event type=OAO  Notice Mailed--Application Incomplete--Filing Date Assigned    Event publication date=2000-05-30  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment Owner: SULZER BIOLOGICS INC., TEXAS  Effective date of the event=2000-05-11  ASSIGNMENT OF ASSIGNORS INTEREST ASSIGNORS:ATKINSON, BRENT BENEDICT, JAMES J. REEL/FRAME:010858/0460     Event publication date=2000-06-08  Event code=US/IDS  Event type=Examination events  Event type=OAI  Information Disclosure Statement Filed    Event publication date=2000-06-14  Event code=US/DOCK  Event indicator=Pos  Event type=Examination events  Case Docketed to Examiner    Event publication date=2001-01-18  Event code=US/DOCK  Event indicator=Pos  Event type=Examination events  Case Docketed to Examiner    Event publication date=2001-02-21  Event code=US/IDS  Event type=Examination events  Event type=OAI  Information Disclosure Statement Filed    Event publication date=2001-05-07  Event code=US/CTNF  Event type=Examination events  Event type=OA  Event type=OAO  Non-Final Rejection    Event publication date=2001-09-24  Event code=US/CTNFR  Event type=Examination events  Event type=OAI  Response after Non-Final Action    Event publication date=2001-09-24  Event code=US/136G  Event type=OAO  Request for Extension of Time - Granted    Event publication date=2001-10-19  Event code=US/DOCK  Event indicator=Pos  Event type=Examination events  Case Docketed to Examiner    Event publication date=2001-12-17  Event code=US/CTNF  Event type=Examination events  Event type=OA  Event type=OAO  Non-Final Rejection    Event publication date=2002-03-26  Event code=US/CTNFR  Event type=Examination events  Event type=OAI  Response after Non-Final Action    Event publication date=2002-06-17  Event code=US/CTNF  Event type=Examination events  Event type=OA  Event type=OAO  Non-Final Rejection    Event publication date=2002-09-23  Event code=US/DOCK  Event indicator=Pos  Event type=Examination events  Case Docketed to Examiner    Event publication date=2002-09-24  Event code=US/NOAM  Event indicator=Pos  Event type=Examination events  Event type=OAO  Mail Notice of Allowance    Event publication date=2002-11-27  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment Owner: CENTERPULSE BIOLOGICS INC., TEXAS  Effective date of the event=2002-09-12  ASSIGNMENT OF ASSIGNORS INTEREST ASSIGNOR:SULZER BIOLOGICS INC. REEL/FRAME:013546/0239     Event publication date=2002-11-27  Event code=US/APRDY  Event indicator=Pos  Event type=Examination events  Application Is Considered Ready for Issue    Event publication date=2003-01-09  Event code=US/PAT  Event indicator=Pos  Event type=Event indicating In Force  Patented Case    Event publication date=2003-01-09  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=2003-01-28  Event code=US/B1  Event indicator=Pos  Event type=Event indicating In Force  Granted patent as first publication  Publication country=US  Publication number=US6511958  Publication stage Code=B1  Publication date=2003-01-28  Standardized publication number=US6511958     Event publication date=2003-05-27  Event code=US/CC  Event type=Corrections  Event type=Restitution or restoration  Certificate of Correction - Post Issue Communication    Event publication date=2005-02-02  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment Owner: ZIMMER ORTHOBIOLOGICS, INC., TEXAS  Effective date of the event=2004-04-28  CHANGE OF NAME ASSIGNOR:CENTERPULSE BIOLOGICS INC. REEL/FRAME:015819/0707     Event publication date=2005-05-10  Event code=US/RF  Event type=Opposition and reexamination events  Reissue application filed  Effective date of the event=2005-01-28     Event publication date=2006-02-07  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=2006-07-28  Event code=US/FPAY  Event indicator=Pos  Event type=Event indicating In Force  Event type=Payment or non-payment notifications  Fee payment recorded   Annual fees payment date=2006-07-28     Year of payment of annual fees=4     Event publication date=2009-08-26  Event code=US/POAC  Event type=Change of name or address  Change in Power of Attorney (May Include Associate POA)    Event publication date=2010-02-09  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=7     Event publication date=2010-03-23  Event code=US/RF  Event type=Opposition and reexamination events  Reissue application filed  Effective date of the event=2010-01-15     Event publication date=2010-04-27  Event code=US/SURR  Event indicator=Neg  Event type=Event indicating Not In Force  According to 37 C.F.R. 1.178, the patent was automatically surrendered upon the grant of the reissue patent.    Event publication date=2011-06-02  Event code=US/POAC  Event type=Change of name or address  Change in Power of Attorney (May Include Associate POA)    Event publication date=2014-02-11  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=11
专利类型码
B1
国别省市代码
若您需要申请原文,请登录。

最新评论

暂无评论。

登录后可以发表评论

意见反馈
返回顶部