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Publication numberUS20080160169 A1
Publication typeApplication
Application numberUS 11/963,677
Publication date3 Jul 2008
Filing date21 Dec 2007
Priority date22 Jun 2006
Publication number11963677, 963677, US 2008/0160169 A1, US 2008/160169 A1, US 20080160169 A1, US 20080160169A1, US 2008160169 A1, US 2008160169A1, US-A1-20080160169, US-A1-2008160169, US2008/0160169A1, US2008/160169A1, US20080160169 A1, US20080160169A1, US2008160169 A1, US2008160169A1
InventorsPaul O. Zamora, Brent Lee Atkinson
Original AssigneeZamora Paul O, Brent Lee Atkinson
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Coating device and method for coating medical device with bioactive peptide
US 20080160169 A1
Abstract
A method for coating a medical device with a bioactive peptide comprising: providing a medical device to be coated with a bioactive peptide to a cylinder; attaching a syringe containing a bioactive peptide coating solution; introducing into the cylinder the bioactive peptide coating solution when the first valve of the connector and the second valve of the connector are open; incubating the medical device within the cylinder with the bioactive peptide coating solution; removing the bioactive peptide coating solution from the cylinder after the medical device is coated with the bioactive peptide.
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Claims(10)
1. A method for coating a medical device with a bioactive peptide comprising:
providing a medical device to be coated with a bioactive peptide to a cylinder having a plunger that inserts into a first end of the cylinder and fits snuggly against the sides of the cylinder and at the other end of the cylinder is located a connector having a first valve that is attached to the second end of the cylinder for creating a closed cylinder when the first valve is closed;
attaching a syringe containing a bioactive peptide coating solution to a second valve of the connector;
introducing into the cylinder the bioactive peptide coating solution when the first valve of the connector and the second valve of the connector are open;
incubating the medical device within the cylinder with the bioactive peptide coating solution;
removing the bioactive peptide coating solution from the cylinder after the medical device is coated with the bioactive peptide.
2. The method of claim 1 wherein the step of incubating further comprises placing the cylinder in a substantially horizontal position to increase the solution to granule contact.
3. The method of claim 1 wherein the cylinder is a first syringe.
4. The method of claim 1 wherein the medical device is osteoconductive material.
5. The method of claim 1 wherein the cylinder is in a substantially vertical position during the introducing step.
6. The method of claim 1 wherein the plunger of the cylinder is pushed to discharge the bioactive peptide coating solution from the cylinder.
7. The method of claim 1 wherein the bioactive peptide coating solution comprises a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor.
8. A system for coating a medical device with a bioactive peptide comprising:
a cylinder for housing a medical device to be coated with a bioactive peptide coating solution wherein the cylinder comprises a plunger that inserts into a first end of the cylinder and fits snuggly against the sides of the cylinder and at the other end of the cylinder is located a connector having a first valve that is attached to the second end of the cylinder for creating a closed cylinder when the first valve is closed;
a syringe that is attached to a second valve of the connector wherein the syringe contains a bioactive peptide coating solution that is introduced into the cylinder via the connector; and
a connector having a first valve attached to the cylinder and a second valve attached to the syringe.
9. A kit for use in coating a medical device with a bioactive peptide comprising:
a bioactive peptide;
a first syringe;
a second syringe and
a connector having a first valve and a second valve.
10. The kit of claim 9 wherein the bioactive peptide comprises a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor.
Description
    CROSS-REFERENCE TO RELATED APPLICATIONS
  • [0001]
    This application is a continuation-in-part application of U.S. patent application Ser. No. 11/767,391, entitled “COMPOSITION AND METHOD FOR DELIVERY OF A PARTIAL AGONIST OF BMP-2 FOR ENHANCEMENT OF OSTEOGENESIS”, filed on Jun. 22, 2007 which claims priority to and the benefit of the filing of U.S. Provisional Patent Application Ser. No. 60/805,594, entitled “COMPOSITION AND METHOD FOR DELIVERY OF A PARTIAL AGONIST OF BMP-2 FOR ENHANCEMENT OF OSTEOGENESIS”, filed on Jun. 22, 2006, and the specification and claims thereof are incorporated herein by reference.
  • INTRODUCTION
  • [0002]
    The present invention relates generally to the field of a system and method for coating medical devices with coating materials.
  • BACKGROUND OF THE INVENTION
  • [0003]
    Implantable medical devices are frequently used in a variety of reparative and regenerative medical procedures. Use of bioactive peptides in concert with these devices is one way to improve the performance of the device. However, sample preparation methods, especially with regard to the application of the peptide coating, are difficult to control but require accuracy and precision. There is a need for a coating device to apply a fine, uniform coating of onto the implantable in order to simplify the sample preparation process.
  • SUMMARY OF THE INVENTION
  • [0004]
    According to one embodiment of the present invention a method for coating a medical device with a bioactive peptide comprising providing a medical device to be coated with a bioactive peptide to a cylinder having a plunger that inserts into a first end of the cylinder and fits snuggly against the sides of the cylinder and at the other end of the cylinder is located a connector having a first valve that is attached to the second end of the cylinder for creating a closed cylinder when the first valve is closed; attaching a syringe containing a bioactive peptide coating solution to a second valve of the connector; introducing into the cylinder the bioactive peptide coating solution when the first valve of the connector and the second valve of the connector are open; incubating the medical device within the cylinder with the bioactive peptide coating solution; removing the bioactive peptide coating solution from the cylinder after the medical device is coated with the bioactive peptide. In a preferred embodiment the step of incubating further comprises placing the cylinder in a substantially horizontal position to increase the solution to granule contact. In another preferred embodiment the cylinder is a first syringe. In another preferred embodiment the medical device is osteoconductive material. In yet another preferred embodiment the cylinder is in a substantially vertical position during the introducing step. In another preferred embodiment the plunger of the cylinder is pushed to discharge the bioactive peptide coating solution from the cylinder. In still another preferred embodiment the bioactive peptide coating solution comprises a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor.
  • [0005]
    Another embodiment of the present invention is a system for coating a medical device with a bioactive peptide comprising a cylinder for housing a medical device to be coated with a bioactive peptide coating solution wherein the cylinder comprises a plunger that inserts into a first end of the cylinder and fits snuggly against the sides of the cylinder and at the other end of the cylinder is located a connector having a first valve that is attached to the second end of the cylinder for creating a closed cylinder when the first valve is closed; a syringe that is attached to a second valve of the connector wherein the syringe contains a bioactive peptide coating solution that is introduced into the cylinder via the connector; and a connector having a first valve attached to the cylinder and a second valve attached to the syringe.
  • [0006]
    In yet another embodiment of the present invention comprises a kit for use in coating a medical device with a bioactive peptide comprises a bioactive peptide; a first syringe; a second syringe and a connector having a first valve and a second valve. In a preferred embodiment, the bioactive peptide comprises a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor.
  • [0007]
    One aspect of the present invention provides an improved bioactive peptide coating method for medical devices.
  • [0008]
    Another aspect of the present invention provides for use of bioactive peptides in concert with implantable medical devices to improve the performance of the medical device.
  • [0009]
    Another aspect of the present invention provides improved methods for application of the peptide coating to medical devices.
  • [0010]
    Another aspect of the present invention provides for a method of accurately applying a bioactive peptide coating device to an implantable medical device.
  • [0011]
    Additional objects and advantages of the present invention will be apparent in the following detailed description read in conjunction with the accompanying drawing figures.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0012]
    The file of this patent contains at least one drawing executed in color. Copies of this patent with color drawing(s) will be provided by the Patent and Trademark Office upon request and payment of the necessary fee.
  • [0013]
    FIG. 1 illustrates a coating device according to one embodiment of the present invention.
  • DETAILED DESCRIPTION OF THE INVENTION
  • [0014]
    One embodiment of the present invention is a coating device system. The system comprises a container, typically a cylinder, for example a syringe. The syringe is attached to a connector at one end. The connector may be a valve used to turn on, turn off, or regulate the flow of a fluid in a cylinder. The valve may be a stop cock for example a multi-way stop cock. In a preferred embodiment the multi-way stop cock is a three way stop cock valve. The cylinder may be a syringe capable of receiving a plunger with a head that is sized to fit snugly against the sides of the syringe barrel to push liquid and particles through the syringe barrel toward the tip.
  • [0015]
    The container is capable of housing a medical device referred to herein as materials to be treated. The container may be vented at one end. The container may also be a syringe barrel with an enclosed medical device which is closured with a second syringe barrel. The container in all cases houses the medical device. In a preferred embodiment the container is a syringe that is identical in shape and volume capacity to the second syringe but is not limited thereto as other volume capacities and shapes will function equivalently.
  • [0016]
    According to another embodiment, the container with the materials to be coated therein is placed in a substantially vertical position and is attached at one end to one of the valves of the connector. A syringe containing an appropriate coating solution is attached to a second of the valves of the connector. The solution is introduced into the container housing the materials to be coated. The solution fills the container from the bottom up. The coating is allowed to incubate with the material to be coated for an appropriate length of time. The coating solution is then removed by withdrawing the solution back into the syringe or by pushing the solution out of the container with the container plunger. The coated material is then removed from the container and is ready for use.
  • [0017]
    In a preferred embodiment the container is a syringe with graduated markings allowing additional materials, such as bone chips, to be added and measured.
  • [0018]
    In some cases the container may house a material which requires pre-wetting. A wetting syringe may be used, in that case, to introduce a wetting solution prior to the coating process. Similarly, a rinsing syringe may be used to introduce into the container a separate rinse for the coated device to remove residual unbound materials.
  • [0019]
    Referring now to FIG. 1, a container 5 contains a medical device (not shown) that is the target of a bioactive peptide coating solution. The container 5 has a plunger 3 inserted into a first end. At the second end of the container 5 is attached a connector valve 7 on connector 15. A syringe 17 having a syringe barrel 11 and a plunger 13 contains a bioactive peptide coating solution. The tip of the syringe is attached to a connector valve 9 on connector 15. Plunger 13 forces bioactive peptide coating solution (not shown) into the container 5 containing the medical device to be coated. After incubation of the bioactive peptide solution with the medical device in container 5, plunger 3 is depressed to discharge the bioactive peptide solution from container 5.
  • EXAMPLE 1
  • [0020]
    Hydroxyapatite/tricalcium phosphate granules with nominal diameters of 1-2 mm where placed in a first 20 ml syringe barrel (referred to in example 1 as syringe A) wherein the barrel is attached to a 3-way valve connector at its tip. The plunger of the barrel is replaced with care not to compress the granules. The first 20 ml syringe barrel is placed in an upright position.
  • [0021]
    A second 20 ml syringe (referred to in example 1 as syringe B) with an attached needle is used to draw 6 ml of the peptide coating solution from a vial. The needle is removed from the second syringe containing the coating solution and the second syringe is attached to a first valve of the 3-way valve connector that is already connected to syringe A thereby connecting the syringe A to syringe B via the 3-way valve connector. The valves connected to the syringe A and syringe B are opened and the coating solution is introduced into syringe A. The material housed in syringe A is mixed with solution comprising a bioactive peptide. Both syringes are positioned on their sides to achieve improved solution-to-granule contact during incubation. The material and coating solution are incubated together for the appropriate incubation time with periodic mixing, for example 15 minutes. The syringe A is returned to a substantially vertical position. The plunger of syringe A is slowly depressed so that the plunger pushes the coating solution back into syringe B. Air from within syringe A can be pushed across the granules to improve solution removal. Syringe B is then disconnected from the connector.
  • [0022]
    The syringe plunger from syringe A can be removed and bone chips added to the desired volume (for example 5 cc). Once measured the contents of the syringe barrel can be removed into a surgical tray for final mixing and placement.
  • EXAMPLE 2
  • [0023]
    A small-bore ePTFE vascular graft is placed in a 10 ml syringe barrel wherein the barrel had an attached 3-way valve. A black rubber stopper was placed in the opening of the barrel. Through the stopper a venting needle is positioned with an attached 0.22 micron filter and is referred to in example 2 as syringe A.
  • [0024]
    Syringe A is placed in an upright position. Using a second 20 ml syringe (referred to in example 2 as syringe B) with an attached needle about 6 ml of the ePTFE wetting solution is drawn into syringe B. The needle is then removed from syringe B and syringe B is attached to syringe A with their female adopters in the three way stopcock. The valves attached to the syringes are opened and the wetting solution is introduced into syringe A. The wetting solution is subsequently removed from syringe A and into syringe B by pulling on the plunger of syringe B. Syringe B can be removed from the valve of the three way stop cock.
  • [0025]
    Using a fresh 10 ml syringe prefilled with a peptide coating solution (referred to in example 2 as syringe C), connect syringe C to syringe A with their female adopters in the three way stopcock. Introduce the coating solution in syringe C into the bottom of syringe A. Incubate the coating solution with the ePTFE for about 15 minutes with periodic mixing. Using syringe C, remove the coating solution. Remove the black rubber stopper. The coated vascular graft can be removed into a surgical tray for subsequent placement.
  • EXAMPLE 3
  • [0026]
    An ePTFE tissue patch was placed in a 20 ml syringe barrel wherein the barrel had an attached 3-way valve. A black rubber stopper was placed in the opening of the barrel. Through the stopper was placed a venting needle with an attached 0.22 micron filter. This device will be referred to as syringe A for Example 3.
  • [0027]
    Syringe A in placed in a substantially upright position. Using a separate 20 ml syringe (referred to as syringe B in example 3) with an attached needle 15 ml of the ePTFE wetting solution is withdraw into syringe B. The needle is removed and the syringe is attached to a female adopter in the three way stopcock. The valve is opened and the wetting solution is introduced into syringe A. After sufficient time to allow wetting of the material to be coated with the bioactive peptide coating solution, the wetting solution is removed by pulling on the plunger of syringe B. Syringe B is removed from the connector.
  • [0028]
    A fresh 20 ml syringe prefilled with a peptide coating solution (referred to as syringe C in example 3) is connected to syringe A with their female adopters in the three way stopcock. When the valves of the connector are in the open position, the peptide coating solution is introduced into the barrel of syringe A. The solution and the contents of syringe A are incubated for 15 minutes with periodic mixing. Using syringe C the coating solution is removed. Remove the black rubber stopper. The coated patch can be removed into a surgical tray for subsequent placement.
  • [0029]
    In one embodiment of the present invention the bioactive peptide comprises a compound of formula I
  • [0000]
  • [0000]
    wherein:
  • [0030]
    X is a peptide chain that (i) has a minimum of three amino acid residues, (ii) has a maximum of about fifty amino acid residues, and (iii) binds specifically to a specifically to a cell surface receptor;
  • [0031]
    R1 is independently hydrogen, such that the terminal group is NH2, an acyl group with a linear or branched C1 to C17 alkyl, aryl, heteroaryl, alkene, alkenyl or aralkyl chain including an N-terminus NH2, NH3 +, or NH group or a corresponding acylated derivative, or is amino acid, a dipeptide or a tripeptide with an N-terminus NH2, NH3 +, or NH group;
  • [0032]
    R2 is independently a trifunctional alpha amino acid residue, wherein X is covalently bonded through a side chain of R2;
  • [0033]
    R3 is independently a linker comprising a chain from 0 to about 15 backbone atoms covalently bonded to R2;
  • [0034]
    R4 is OH such that the terminal group is a carboxyl, NH2, an acyl group with a linear or branched C1 to C17 alkyl, aryl, heteroaryl, alkene, alkenyl or aralkyl chain including an N-terminus NH2, NH3 +, or NH group or a corresponding acylated derivative, or NH—R1;
  • [0035]
    Y is a linker comprising a chain from 0 to about 50 backbone atoms covalently bonded to R2 and Z; and
  • [0036]
    Z is a non-signaling peptide chain that includes a heparin binding domain comprising an amino acid sequence that comprises (i) a minimum of one heparin binding motif, (ii) a maximum of about ten heparin binding motifs, and (iii) a maximum of about thirty amino acids.
  • [0037]
    In another embodiment the bioactive peptide comprises a compound of formula II comprising:
  • [0000]
  • [0000]
    wherein:
  • [0038]
    X is a peptide chain that (i) has a minimum of three amino acid residues, (ii) has a maximum of about fifty amino acid residues, and (iii) binds specifically to a specifically to a cell surface receptor;
  • [0039]
    R1 is independently hydrogen, such that the terminal group is NH2, an acyl group with a linear or branched C1 to C17 alkyl, aryl, heteroaryl, alkene, alkenyl or aralkyl chain including an N-terminus NH2, NH3 +, or NH group or a corresponding acylated derivative, or is amino acid, a dipeptide or a tripeptide with an N-terminus NH2, NH3 +, or NH group;
  • [0040]
    R6 is independently a linker comprising a chain from 0 to about 15 backbone atoms covalently bonded to R3 when the linker is greater than 0 atoms;
  • [0041]
    R5 is a trifunctional alpha amino acid residue, wherein X is covalently bonded through a side chain of R3;
  • [0042]
    R4 is OH such that the terminal group is a carboxyl, NH2, an acyl group with a linear or branched C1 to C17 alkyl, aryl, heteroaryl, alkene, alkenyl or aralkyl chain including an N-terminus NH2, NH3 +, or NH group or a corresponding acylated derivative, or NH—R1;
  • [0043]
    Y is a linker comprising a chain from 0 to about 50 backbone atoms covalently bonded to R5 and Z; and
  • [0044]
    Z is a non-signaling peptide chain that includes a heparin binding domain comprising an amino acid sequence that comprises (i) a minimum of one heparin binding motif, (ii) a maximum of about ten heparin binding motifs, and (iii) a maximum of about thirty amino acids.
  • [0045]
    In another embodiment the bioactive peptide comprises a synthetic growth factor analogue comprising a non-growth factor heparin binding region, a linker and a sequence that binds specifically to a cell surface receptor.
  • [0046]
    The present invention has been described in terms of preferred embodiments, however, it will be appreciated that various modifications and improvements may be made to the described embodiments without departing from the scope of the invention. The entire disclosures of all references, applications, patents, and publications cited above and/or in the attachments, and of the corresponding application(s), are hereby incorporated by reference.
Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3272204 *22 Sep 196513 Sep 1966Ethicon IncAbsorbable collagen prosthetic implant with non-absorbable reinforcing strands
US4172128 *12 May 197723 Oct 1979Erhard ThieleProcess of degrading and regenerating bone and tooth material and products
US4193138 *17 Aug 197718 Mar 1980Sumitomo Electric Industries, Ltd.Composite structure vascular prostheses
US4563350 *24 Oct 19847 Jan 1986Collagen CorporationInductive collagen based bone repair preparations
US4747848 *17 Oct 198531 May 1988Vascutek LimitedVascular grafts
US4842575 *5 Aug 198827 Jun 1989Meadox Medicals, Inc.Method for forming impregnated synthetic vascular grafts
US5108436 *23 Nov 198828 Apr 1992Collagen CorporationImplant fixation
US5197977 *30 Apr 199230 Mar 1993Meadox Medicals, Inc.Drug delivery collagen-impregnated synthetic vascular graft
US5509899 *22 Sep 199423 Apr 1996Boston Scientific Corp.Medical device with lubricious coating
US5510418 *3 Nov 199323 Apr 1996Collagen CorporationGlycosaminoglycan-synthetic polymer conjugates
US5608035 *2 Feb 19944 Mar 1997Affymax Technologies N.V.Peptides and compounds that bind to the IL-1 receptor
US5635597 *27 May 19943 Jun 1997Affymax Technologies, N.V.Peptides that bind IL-2 receptors
US5643873 *11 May 19941 Jul 1997Affymax Technologies N.V.Peptides and compounds that bind selectins including endothelial leukocyte adhesion molecule 1
US5648458 *16 Feb 199515 Jul 1997Affymax Technologies N.V.Peptides and compounds that bind to ELAM-1
US5650234 *9 Sep 199422 Jul 1997Surface Engineering Technologies, Division Of Innerdyne, Inc.Electrophilic polyethylene oxides for the modification of polysaccharides, polypeptides (proteins) and surfaces
US5654276 *7 Jun 19955 Aug 1997Affymax Technologies N.V.Peptides and compounds that bind to the IL-5 receptor
US5665114 *12 Aug 19949 Sep 1997Meadox Medicals, Inc.Tubular expanded polytetrafluoroethylene implantable prostheses
US5668110 *7 Jun 199516 Sep 1997Affymax Technologies N.V.Peptides and compounds that bind to the IL-5 receptor
US5728802 *12 May 199517 Mar 1998Affymax Technologies N.V.Peptides and compounds that bind selectins including endothelium leukocyte adhesion molecule 1 (ELAM-1)
US5759515 *30 Jun 19942 Jun 1998Rhomed IncorporatedPolyvalent peptide pharmaceutical applications
US5767234 *1 Feb 199516 Jun 1998Affymax Technologies, N.V.Peptides and compounds that bind to the IL-1 receptor
US5770704 *31 Jan 199723 Jun 1998Genentech, Inc.Receptor activation with inactive hepatocyte growth factor ligands
US5773569 *7 Jun 199530 Jun 1998Affymax Technologies N.V.Compounds and peptides that bind to the erythropoietin receptor
US5786322 *7 Jun 199528 Jul 1998Affymax Technologies N.V.Peptides and compounds that bind selectins including endothelium leukocyte adhesion molecule 1
US5786331 *5 Jun 199528 Jul 1998Affymax Technologies N.V.Peptides and compounds that bind to the IL-1 receptor
US5789182 *14 Dec 19934 Aug 1998The Children's Medical Center CorporationSystem for assaying binding to a heparin-binding growth factor receptor
US5861476 *5 Jun 199519 Jan 1999Affymax Technologies N.V.Peptides and compounds that bind to the IL-1 receptor
US5866113 *7 Mar 19972 Feb 1999Medtronic, Inc.Medical device with biomolecule-coated surface graft matrix
US5869451 *11 Dec 19969 Feb 1999Glaxo Group LimitedPeptides and compounds that bind to a receptor
US5880096 *5 Jun 19959 Mar 1999Affymax Technologies N.V.Peptides and compounds that bind to the IL-1 receptor
US5902799 *5 Aug 199711 May 1999The Trustees Of The University Of PennsylvaniaMethods of modulating tissue growth and regeneration
US5916585 *30 May 199729 Jun 1999Gore Enterprise Holdings, Inc.Materials and method for the immobilization of bioactive species onto biodegradable polymers
US5930995 *6 Aug 19973 Aug 1999Toyota Jidosha Kabushiki KaishaExhaust gas purification device for a compression-ignition combustion engine
US5932462 *17 May 19953 Aug 1999Shearwater Polymers, Inc.Multiarmed, monofunctional, polymer for coupling to molecules and surfaces
US5945457 *1 Oct 199731 Aug 1999A.V. Topchiev Institute Of Petrochemical Synthesis, Russian Academy Of ScienceProcess for preparing biologically compatible polymers and their use in medical devices
US5952474 *1 Jul 199714 Sep 1999The Public Health Research Institute Of The City Of New York, Inc.Fusion glycoproteins
US5955588 *22 Sep 199821 Sep 1999Innerdyne, Inc.Non-thrombogenic coating composition and methods for using same
US6011002 *6 Apr 19954 Jan 2000The United States Of America As Represented By The Department Of Health And Human ServicesCircularly permuted ligands and circularly permuted chimeric molecules
US6030812 *6 Jun 199529 Feb 2000G. D. Searle & CompanyFusion proteins comprising multiply mutated interleukin-3 (IL-3) polypeptides and second growth factors
US6051648 *13 Jan 199918 Apr 2000Cohesion Technologies, Inc.Crosslinked polymer compositions and methods for their use
US6096798 *30 Apr 19971 Aug 2000Luthra; Ajay KumarNon-thrombogenic and anti-thrombogenic polymers
US6099562 *22 Dec 19978 Aug 2000Schneider (Usa) Inc.Drug coating with topcoat
US6120904 *24 May 199919 Sep 2000Schneider (Usa) Inc.Medical device coated with interpenetrating network of hydrogel polymers
US6121236 *24 Mar 199819 Sep 2000The Children's Medical Center CorporationMultivalent ligands which modulate angiogenesis
US6168784 *28 Aug 19982 Jan 2001Gryphon SciencesN-terminal modifications of RANTES and methods of use
US6174530 *31 Aug 199316 Jan 2001Gryphon SciencesHomogeneous polyoxime compositions and their preparation by parallel assembly
US6174721 *14 Oct 199716 Jan 2001Chiron CorporationChimeric proteins
US6214795 *12 Nov 199610 Apr 2001Praecis Pharmaceuticals, Inc.Peptide compounds useful for modulating FGF receptor activity
US6217873 *5 May 199417 Apr 2001Gryphon SciencesPolyoxime compounds and their preparation
US6231600 *26 May 199915 May 2001Scimed Life Systems, Inc.Stents with hybrid coating for medical devices
US6231892 *13 Nov 199715 May 2001The Board Of Regents, The University Of Texas SystemCompositions for coating microcapsules and other surfaces
US6235716 *29 Dec 199922 May 2001Children's Medical Center CorporationMultivalent ligands which modulate angiogenesis
US6248057 *27 Jul 199919 Jun 2001Innerdyne, Inc.Absorbable brachytherapy and chemotherapy delivery devices and methods
US6251864 *1 Mar 200026 Jun 2001Glaxo Group LimitedPeptides and compounds that bind to a receptor
US6258371 *3 Apr 199810 Jul 2001Medtronic IncMethod for making biocompatible medical article
US6270788 *4 Oct 19997 Aug 2001Medtronic IncImplantable medical device
US6284503 *15 Jan 19974 Sep 2001University Of Utah Research FoundationComposition and method for regulating the adhesion of cells and biomolecules to hydrophobic surfaces
US6294359 *16 Jun 199825 Sep 2001Scios Inc.Human basic fibroblast growth factor analog
US6342591 *31 Jul 200029 Jan 2002Biosurface Engineering Technologies, Inc.Amphipathic coating for modulating cellular adhesion composition and methods
US6350731 *2 Nov 199926 Feb 2002Trigen LimitedPlatelet-derived growth factor analogues
US6368347 *23 Apr 19999 Apr 2002Sulzer Vascutek Ltd.Expanded polytetrafluoroethylene vascular graft with coating
US6377349 *30 Mar 199923 Apr 2002Carl Zeiss Jena GmbhArrangement for spectral interferometric optical tomography and surface profile measurement
US6387978 *8 Jan 200114 May 2002Boston Scientific CorporationMedical devices comprising ionically and non-ionically crosslinked polymer hydrogels having improved mechanical properties
US6406687 *4 Nov 199818 Jun 2002Ajay Kumar LuthraNon-thrombogenic and anti-thrombogenic polymers
US6410044 *16 May 200025 Jun 2002Surmodics, Inc.Crosslinkable macromers
US6426332 *22 Jun 200130 Jul 2002Stryker CorporationMatrix-free osteogenic devices, implants and methods of use thereof
US6451543 *26 Aug 199917 Sep 2002Gryphon SciencesLipid matrix-assisted chemical ligation and synthesis of membrane polypeptides
US6514534 *14 Aug 19984 Feb 2003Incept LlcMethods for forming regional tissue adherent barriers and drug delivery systems
US6534591 *17 Aug 200118 Mar 2003Cohesion Technologies, Inc.Cross-linked polymer compositions and methods for their use
US6548634 *28 Sep 199915 Apr 2003Chiron CorporationSynthetic peptides having FGF receptor affinity
US6585765 *29 Jun 20001 Jul 2003Advanced Cardiovascular Systems, Inc.Implantable device having substances impregnated therein and a method of impregnating the same
US6596699 *22 Jan 200222 Jul 2003Biosurface Engineering Technologies, Inc.Nucleic acid coating compositions and methods
US6846853 *16 Jul 200225 Jan 2005Osteotech, Inc.Calcium phosphate bone graft material, process for making same and osteoimplant fabricated from same
US6863899 *7 Jun 20028 Mar 2005Vita Special Purpose CorporationComposite shaped bodies and methods for their production and use
US6921811 *31 Jul 200126 Jul 2005Biosurface Engineering Technologies, Inc.Bioactive coating composition and methods
US6949251 *21 Sep 200127 Sep 2005Stryker CorporationPorous β-tricalcium phosphate granules for regeneration of bone tissue
US6984393 *7 May 200210 Jan 2006Queen's University At KingstonBiodegradable elastomer and method of preparing same
US7025990 *8 Oct 200211 Apr 2006Incept LlcMethods for forming regional tissue adherent barriers and drug delivery systems
US7041641 *20 Mar 19979 May 2006Stryker CorporationOsteogenic devices and methods of use thereof for repair of endochondral bone and osteochondral defects
US7166574 *20 Aug 200223 Jan 2007Biosurface Engineering Technologies, Inc.Synthetic heparin-binding growth factor analogs
US7241736 *12 May 200510 Jul 2007Angiotech International AgCompositions and methods for treating diverticular disease
US7414028 *4 Feb 200519 Aug 2008Biosurface Engineering Technologies, Inc.Growth factor analogs
US7482427 *22 Feb 200527 Jan 2009Biosurface Engineering Technologies, Inc.Positive modulator of bone morphogenic protein-2
US7528105 *10 Feb 20055 May 2009Biosurface Engineering TechnologiesHeterodimeric chain synthetic heparin-binding growth factor analogs
US20010014662 *20 Mar 199716 Aug 2001David C RuegerImproved osteogenic devices and methods of use thereof for repair of endochondral bone and osteochondral defects
US20020115836 *14 Jan 200222 Aug 2002Ray TsangNon-thrombogenic coating composition and methods for using same
US20040038348 *20 Aug 200226 Feb 2004Pena Louis A.Synthetic heparin-binding growth factor analogs
US20040068266 *4 Oct 20028 Apr 2004Yves DelmotteDevices and methods for mixing and extruding medically useful compositions
US20040087505 *19 Aug 20036 May 2004Pena Louis A.Synthetic heparin-binding factor analogs
US20040151764 *10 Oct 20035 Aug 2004Biosurface Engineering Technologies, Inc.Bioactive medical films
US20050196425 *22 Feb 20058 Sep 2005Biosurface Engineering Technologies, Inc.Positive modulator of bone morphogenic protein-2
US20060024347 *27 Jun 20052 Feb 2006Biosurface Engineering Technologies, Inc.Bioactive peptide coatings
US20060199764 *23 Feb 20067 Sep 2006Biosurface Engineering Technologies, Inc.FGF growth factor analogs
US20060205652 *23 Feb 200614 Sep 2006Biosurface Engineering Technologies, Inc.Formulations and methods for delivery of growth factor analogs
US20080063622 *22 Jun 200713 Mar 2008Biosurface Engineering Technologies, Inc.Composition and Method for Delivery of BMP-2 Amplifier/Co-Activator for Enhancement of Osteogenesis
US20080166392 *31 Jan 200810 Jul 2008Zamora Paul OPositive Modulator of Bone Morphogenic Protein-2
US20080227696 *21 Feb 200618 Sep 2008Biosurface Engineering Technologies, Inc.Single branch heparin-binding growth factor analogs
US20090111743 *23 Feb 200630 Apr 2009Biosurface Engineering Technologies, Inc.Cysteine-branched heparin-binding growth factor analogs
US20090143566 *29 Oct 20074 Jun 2009Biosurface Engineering Technologies, Inc.Growth Factor Analogs
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US770056319 Aug 200320 Apr 2010Biosurface Engineering Technologies, Inc.Synthetic heparin-binding factor analogs
US78201721 Jun 200726 Oct 2010Biosurface Engineering Technologies, Inc.Laminin-derived multi-domain peptides
US798186222 Jun 200719 Jul 2011Biosurface Engineering Technologies, Inc.Composition comprising BMP-2 amplifier/co-activator for enhancement of osteogenesis
US810157024 May 201024 Jan 2012Biosurface Engineering Technologies, Inc.Single branch heparin-binding growth factor analogs
US81637176 Oct 200924 Apr 2012Biosurface Engineering Technologies, Inc.Dual chain synthetic heparin-binding growth factor analogs
US822741123 Feb 200624 Jul 2012BioSurface Engineering Technologies, IncleFGF growth factor analogs
US879621219 Jul 20115 Aug 2014Biosurface Engineering Technologies, Inc.Composition and method for delivery of BMP-2 amplifier/co-activator for enhancement of osteogenesis
US967025818 Aug 20166 Jun 2017Ferring B.V.Positive modulator of bone morphogenic protein-2
US20040087505 *19 Aug 20036 May 2004Pena Louis A.Synthetic heparin-binding factor analogs
US20080063622 *22 Jun 200713 Mar 2008Biosurface Engineering Technologies, Inc.Composition and Method for Delivery of BMP-2 Amplifier/Co-Activator for Enhancement of Osteogenesis
US20080166392 *31 Jan 200810 Jul 2008Zamora Paul OPositive Modulator of Bone Morphogenic Protein-2
US20080227696 *21 Feb 200618 Sep 2008Biosurface Engineering Technologies, Inc.Single branch heparin-binding growth factor analogs
US20100298218 *24 May 201025 Nov 2010Biosurface Engineering Technologies, Inc.Single Branch Heparin-Binding Growth Factor Analogs
Classifications
U.S. Classification427/2.26, 118/50
International ClassificationA61L27/28
Cooperative ClassificationA61L27/34, A61L27/16, A61L27/22, A61L27/507
European ClassificationA61L27/16, A61L27/34, A61L27/50E, A61L27/22
Legal Events
DateCodeEventDescription
24 Mar 2008ASAssignment
Owner name: BIOSURFACE ENGINEERING TECHNOLOGIES, INC., MARYLAN
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:ZAMORA, PAUL O.;ATKINSON, BRENT LEE;REEL/FRAME:020694/0363
Effective date: 20080115