WO1999000071A1 - Method for coating stents with dna and expression of recombinant genes from dna coated stent in vivo - Google Patents
Method for coating stents with dna and expression of recombinant genes from dna coated stent in vivo Download PDFInfo
- Publication number
- WO1999000071A1 WO1999000071A1 PCT/US1998/013301 US9813301W WO9900071A1 WO 1999000071 A1 WO1999000071 A1 WO 1999000071A1 US 9813301 W US9813301 W US 9813301W WO 9900071 A1 WO9900071 A1 WO 9900071A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- therapeutically useful
- agent
- dna
- stent
- useful protein
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 30
- 108090000623 proteins and genes Proteins 0.000 title claims description 47
- 238000001727 in vivo Methods 0.000 title claims description 7
- 239000011248 coating agent Substances 0.000 title description 13
- 238000000576 coating method Methods 0.000 title description 13
- 230000014509 gene expression Effects 0.000 title description 7
- 208000037803 restenosis Diseases 0.000 claims abstract description 19
- 208000019553 vascular disease Diseases 0.000 claims abstract description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 25
- -1 pi 6 Proteins 0.000 claims description 11
- 108010049003 Fibrinogen Proteins 0.000 claims description 10
- 102000008946 Fibrinogen Human genes 0.000 claims description 10
- 229940012952 fibrinogen Drugs 0.000 claims description 10
- 108010080611 Cytosine Deaminase Proteins 0.000 claims description 8
- 102000006601 Thymidine Kinase Human genes 0.000 claims description 8
- 108020004440 Thymidine kinase Proteins 0.000 claims description 8
- 239000003146 anticoagulant agent Substances 0.000 claims description 8
- 239000011159 matrix material Substances 0.000 claims description 8
- 102000000311 Cytosine Deaminase Human genes 0.000 claims description 7
- 229940127090 anticoagulant agent Drugs 0.000 claims description 7
- 229940127218 antiplatelet drug Drugs 0.000 claims description 7
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 6
- 239000002256 antimetabolite Substances 0.000 claims description 6
- 239000003080 antimitotic agent Substances 0.000 claims description 6
- 208000031481 Pathologic Constriction Diseases 0.000 claims description 5
- 210000004351 coronary vessel Anatomy 0.000 claims description 5
- 230000035755 proliferation Effects 0.000 claims description 5
- 208000037804 stenosis Diseases 0.000 claims description 5
- 230000036262 stenosis Effects 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- 201000000582 Retinoblastoma Diseases 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 4
- 229910001220 stainless steel Inorganic materials 0.000 claims description 3
- 239000010935 stainless steel Substances 0.000 claims description 3
- 210000005166 vasculature Anatomy 0.000 claims description 3
- 206010003226 Arteriovenous fistula Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010072557 Peripheral artery restenosis Diseases 0.000 claims description 2
- 206010072563 Peripheral artery stenosis Diseases 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims 3
- 108020004414 DNA Proteins 0.000 description 43
- 239000012634 fragment Substances 0.000 description 20
- 239000000203 mixture Substances 0.000 description 12
- 210000001367 artery Anatomy 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 239000013598 vector Substances 0.000 description 8
- 101150073031 cdk2 gene Proteins 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 210000003090 iliac artery Anatomy 0.000 description 6
- 230000002093 peripheral effect Effects 0.000 description 6
- 210000001105 femoral artery Anatomy 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 108020004705 Codon Proteins 0.000 description 4
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 4
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 229960002897 heparin Drugs 0.000 description 4
- 229920000669 heparin Polymers 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 229960003766 thrombin (human) Drugs 0.000 description 4
- 108090000190 Thrombin Proteins 0.000 description 3
- 238000002399 angioplasty Methods 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
- 229960004072 thrombin Drugs 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- LCSKNASZPVZHEG-UHFFFAOYSA-N 3,6-dimethyl-1,4-dioxane-2,5-dione;1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1.CC1OC(=O)C(C)OC1=O LCSKNASZPVZHEG-UHFFFAOYSA-N 0.000 description 2
- 102100026189 Beta-galactosidase Human genes 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102100033295 Glial cell line-derived neurotrophic factor Human genes 0.000 description 2
- 102000007625 Hirudins Human genes 0.000 description 2
- 108010007267 Hirudins Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000974934 Homo sapiens Cyclic AMP-dependent transcription factor ATF-2 Proteins 0.000 description 2
- 101000997829 Homo sapiens Glial cell line-derived neurotrophic factor Proteins 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 208000018262 Peripheral vascular disease Diseases 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 108010005774 beta-Galactosidase Proteins 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 230000010339 dilation Effects 0.000 description 2
- 238000002224 dissection Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 229940006607 hirudin Drugs 0.000 description 2
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 2
- 206010020718 hyperplasia Diseases 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- PUDHBTGHUJUUFI-SCTWWAJVSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-p Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 PUDHBTGHUJUUFI-SCTWWAJVSA-N 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101150012716 CDK1 gene Proteins 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 101100059559 Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139) nimX gene Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108091061960 Naked DNA Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229930182556 Polyacetal Natural products 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 241000910050 Sacothrips catheter Species 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 108700019146 Transgenes Proteins 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 101100273808 Xenopus laevis cdk1-b gene Proteins 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 230000001399 anti-metabolic effect Effects 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000002506 anticoagulant protein Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 239000000560 biocompatible material Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- HGAZMNJKRQFZKS-UHFFFAOYSA-N chloroethene;ethenyl acetate Chemical compound ClC=C.CC(=O)OC=C HGAZMNJKRQFZKS-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 229940072645 coumadin Drugs 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000013020 embryo development Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 210000003195 fascia Anatomy 0.000 description 1
- 229940081104 fibrinogen / thrombin Drugs 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229940106780 human fibrinogen Drugs 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000013152 interventional procedure Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229960002437 lanreotide Drugs 0.000 description 1
- 108010021336 lanreotide Proteins 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- CJWXCNXHAIFFMH-AVZHFPDBSA-N n-[(2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5r)-2-acetamido-4,5,6-trihydroxy-1-oxohexan-3-yl]oxy-3,5-dihydroxy-6-methyloxan-4-yl]acetamide Chemical compound C[C@H]1O[C@@H](O[C@@H]([C@@H](O)[C@H](O)CO)[C@@H](NC(C)=O)C=O)[C@H](O)[C@@H](NC(C)=O)[C@@H]1O CJWXCNXHAIFFMH-AVZHFPDBSA-N 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 238000007888 peripheral angioplasty Methods 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 210000003200 peritoneal cavity Anatomy 0.000 description 1
- 210000004303 peritoneum Anatomy 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001707 polybutylene terephthalate Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 210000003689 pubic bone Anatomy 0.000 description 1
- 230000001177 retroviral effect Effects 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000003393 splenic effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229910052715 tantalum Inorganic materials 0.000 description 1
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 description 1
- 229940052907 telazol Drugs 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/711—Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/45—Transferases (2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/50—Hydrolases (3) acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
- A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/258—Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
- A61L2300/606—Coatings
Definitions
- Coronary and peripheral angioplasty is routinely performed to treat obstructive atherosclerotic lesions in the coronary and peripheral blood vessels Following balloon dilation of
- Restenosis is the reclosure of a peripheral or coronary artery following trauma to that
- restenosis is characterized by both elastic recoil or chronic constriction of the vessel in addition to abnormal cell proliferation
- the stent is typically inserted by catheter into a vascular lumen and expanded into contact with the diseased portion of the arterial wall, thereby providing mechanical support for the lumen
- restenosis can still occur with such stents in place, likely, because although the stent prevents elastic recoil of the artery, it fails to prevent the cell proliferation which
- tissue-type plasminogen activator The stents were studied ex vivo in tissue culture dishes only The feasibility of implanting the stents into arteries were not explored This procedure of coating
- one object of this invention is to provide an intravascular DNA coated stent
- a second object of this invention is to provide methods for expressing recombinant genes
- a third object of this invention is to provide methods for treating coronary and peripheral
- vascular diseases particularly restenosis and vein by-pass grafts, using the DNA coated stents
- Figure 1 is a restriction map of plasmid pCMV-CAT (VR1332)
- Stents are devices which can be delivered percutaneously to treat coronary artery
- Suitable stents useful in the invention are polymeric or metallic Examples of polymeric stents include stents made with biostable or bioabsorbable polymers such as poly(ethylene terephthalate),
- polyacetal poly(lactic acid), and poly(ethylene oxide)/poly(butylene terephthalate) copolymer
- metallic stents examples include stents made from tantalum or stainless steel Stents are available in myriad designs; all of which can be used in the present invention and are either
- stents Commercial sources include Johnson & Johnson, Boston Scientific, Cordis, Advanced Catheter Systems, and U. S. Catheter, Ine
- Suitable genes which encode for therapeutic proteins useful in the invention include genes
- antiplatelet agents which encode antiplatelet agents, anticoagulant agents, antimitotic agents, antioxidants,
- genes which encode therapeutic proteins include proteins which can inhibit proliferation of cells (particular of vascular smooth
- fusion proteins of the above can be used.
- the preferred genes encode thymidine kinase (HSV-tk) or cytosine deaminase gene
- the DNA can be naked or can be
- vectors include shuttle vectors, expression vectors, retroviral
- vectors Preferably a replication-
- defective adenovirus vector such as pAd-Bglll as described by Davidson et al (1993,
- CMVp27revcitetk results from the ligation of 3 fragments: (1) Hindlll-EcoRI from 1332 DSacll + (2) Sall-Ncol from p27revcite + (3) Ncol-Hindlll from 1012-tk
- CMVp27SNtk CMVp27citetk with the Sacll-Ncol fragment deleted (containing the C-terminus of p27) CMVp27Sp21 Ftk CMVp27tk with the Hindlll-Ncol fragment from 1012-p21 N inserted between the Sacll and Fspl sites
- CMVp27Np21 Ftk CMVp27tk with the Hindlll-Ncol fragment from 1012-p21 N inserted between the Narl and Fspl sites
- CMVp27Np21 Fcitetk CMVp27citetk with the Hindlll-Ncol fragment from 1012-p21 N inserted between the Narl and Fspl sites CMVp27Sp21 Clal-Sacll fragment from CMVp27citetk fused to the Ncol-Clal fragment of VR 1012-p21 N (giving a fusion between p27N and p21 N)
- CMVp27DKNcitetk CMVp27Dkcitetk with a stop codon between Sacll and Xbal in p27 (only the N-terminus of p27 remains)
- the stent can optionally be coated with other therapeutic proteins such as heparin, hirudin,
- angiopeptin angiopeptin, ACE inhibitors, growth factors (such as IL 2 - 10 ), nitric oxide or with DNA encoding
- Suitable polymerizable matrix useful for binding the DNA to the stent include any
- the stent is preferably coated with about 50 ⁇ g to about 5 mg of DNA The thickness of
- the polymerizable matrix containing the DNA is typically about 5-500 ⁇ m
- the matrix preferably
- a liquid monomeric matrix can be mixed with the DNA and polymerization initiated
- the stent can then be added to the polymerizing solution, such that polymer forms over its entire surface
- coated stent is then removed and dried Multiple application steps can be used to provide improved coating uniformity and improved control over the amount of DNA applied to the stent.
- an aqueous mixture of DNA and human thrombin is added to an aqueous suspension of fibrinogen.
- the fibrinogen concentration of the suspension is typically
- the of the DNA in the aqueous mixture is typically about 1-20, preferably about 5-15, more preferably
- the amount of human thrombin in the aqueous mixture about 0.5 to 5, preferably
- the DNA and human thrombin are first added together to form a mixture and that mixture is then added to the fibrinogen suspension Thereafter, a stent is dipped into the polymerizing solution After the mixture solidifies, the stent is removed.
- the stent can be placed onto the balloon at a distal end of a balloon catheter and delivered
- the stent may therefore provide both a supporting structure for the lumen at the site of treatment and also a site for instillation of DNA at the lumen
- the site of instillation can be either an arterial or venous wall
- the stent can be placed in any peripheral or coronary artery or vein
- the stent is preferably placed at the site of injury either immediately or soon after mechanical vessel injury
- Recombinant genes can be expressed in vivo by implanting the DNA coated stents of the
- Gene expression in an artery or vein of a patient Gene expression is continuous and can
- viral promoters optionally be controlled with viral promoters or cell specific promoters such as smc, in particular
- SM 22oc is a putative calcium-binding protein that is expressed in cardiac, smooth and
- Promoters of smcs are of particular interest because they direct transgene expression specifically in vascular and not visceral smooth muscle cells
- Coronary and peripheral diseases including restenosis, atherosclerosis, coronary artery bypass
- graft stenosis can be treated by implanting the DNA coated stent of the
- Suitable patients include
- mammals such as dogs, horses, cattle, humans, etc. Humans are preferred patients.
- the DNA coated stent is implanted into the patient and an
- antiplatelet agent antiplatelet agent, anticoagulant agent, antimicrobial agent, anti-inflammatory agent, antimetabolic
- agent an antimitotic agent or other drug is administered to reduce the incidence of restenosis.
- Suitable anticoagulant agents can include drugs such as heparin, coumadin, protamine, hirudin and
- Suitable antimitotic agents and antimetabolite agents can include drugs
- Ganciclovir or acyclovir is preferably administered.
- Human fibrinogen was dissolved in water at concentrations of 30 mg/ml. 100 ⁇ l of
- fibrinogen was diluted in the preparation.
- Plasmid CAT (pCMV-CAT) was dissolved in water at concentrations of 10 mg/ml.
- DNA was diluted in water in an Eppendorf tube to a final volume of 100 ⁇ g/ml. 1 U of human thrombin was added in the DNA solution and mixed gently
- the coated stent was installed into the left and right pig iliac femoral arteries using routine
- Pigs were anesthetized using Telazol (6 0 mg/kg IM) and xylazine (2 2 mg/kg IM) and
Abstract
Description
Claims
Priority Applications (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002295040A CA2295040C (en) | 1997-06-27 | 1998-06-26 | Method for coating stents with dna and expression of recombinant genes from dna coated stent in vivo |
JP50576199A JP2002507136A (en) | 1997-06-27 | 1998-06-26 | Methods for coating stents with DNA and expression of recombinant genes in vivo from stents coated with DNA |
DE69841041T DE69841041D1 (en) | 1997-06-27 | 1998-06-26 | STENT COATED WITH DNA |
EP98932887A EP1023005B1 (en) | 1997-06-27 | 1998-06-26 | Stent coated with dna |
AT98932887T ATE438361T1 (en) | 1997-06-27 | 1998-06-26 | STENT COATED WITH DNA |
AU82676/98A AU8267698A (en) | 1997-06-27 | 1998-06-26 | Method for coating stents with dna and expression of recombinant genes from dna coated stent in vivo |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/884,352 | 1997-06-27 | ||
US08/884,352 US6818016B1 (en) | 1997-06-27 | 1997-06-27 | Methods for coating stents with DNA and expression of recombinant genes from DNA coated stents in vivo |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999000071A1 true WO1999000071A1 (en) | 1999-01-07 |
Family
ID=25384436
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1998/013301 WO1999000071A1 (en) | 1997-06-27 | 1998-06-26 | Method for coating stents with dna and expression of recombinant genes from dna coated stent in vivo |
Country Status (8)
Country | Link |
---|---|
US (3) | US6818016B1 (en) |
EP (1) | EP1023005B1 (en) |
JP (2) | JP2002507136A (en) |
AT (1) | ATE438361T1 (en) |
AU (1) | AU8267698A (en) |
CA (1) | CA2295040C (en) |
DE (1) | DE69841041D1 (en) |
WO (1) | WO1999000071A1 (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001074413A1 (en) * | 2000-04-04 | 2001-10-11 | Boston Scientific Limited | Medical devices suitable for gene therapy regimens |
US6335029B1 (en) | 1998-08-28 | 2002-01-01 | Scimed Life Systems, Inc. | Polymeric coatings for controlled delivery of active agents |
WO2002058752A2 (en) * | 2000-12-04 | 2002-08-01 | Medtronic, Inc. | Medical device and methods of use |
EP1319416A1 (en) | 2001-12-12 | 2003-06-18 | Hehrlein, Christoph, Dr. | Porous metallic stent with a ceramic coating |
WO2004050140A2 (en) * | 2002-12-03 | 2004-06-17 | Scimed Life Systems, Inc. | Medical devices for delivery of therapeutic agents |
EP1444995A1 (en) * | 2003-02-06 | 2004-08-11 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | FGF-2 derived proteins for the preparation of biomaterials or medical devices such as stents |
DE10311729A1 (en) * | 2003-03-18 | 2004-09-30 | Schultheiss, Heinz-Peter, Prof. Dr. | Endovascular implant with an at least sectionally active coating of ratjadon and / or a ratjadon derivative |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2178541C (en) * | 1995-06-07 | 2009-11-24 | Neal E. Fearnot | Implantable medical device |
US8088060B2 (en) | 2000-03-15 | 2012-01-03 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
US9522217B2 (en) | 2000-03-15 | 2016-12-20 | Orbusneich Medical, Inc. | Medical device with coating for capturing genetically-altered cells and methods for using same |
US8038708B2 (en) * | 2001-02-05 | 2011-10-18 | Cook Medical Technologies Llc | Implantable device with remodelable material and covering material |
US7691140B2 (en) * | 2003-05-12 | 2010-04-06 | Cook Incorporated | Anastomosis device for vascular access |
WO2007016251A2 (en) * | 2005-07-28 | 2007-02-08 | Cook Incorporated | Implantable thromboresistant valve |
US20070196423A1 (en) * | 2005-11-21 | 2007-08-23 | Med Institute, Inc. | Implantable medical device coatings with biodegradable elastomer and releasable therapeutic agent |
CN100358483C (en) * | 2005-12-28 | 2008-01-02 | 中国医学科学院生物医学工程研究所 | Implanting device carried with plasmid DNA nanometer particle and its prepn. method |
US8642063B2 (en) * | 2008-08-22 | 2014-02-04 | Cook Medical Technologies Llc | Implantable medical device coatings with biodegradable elastomer and releasable taxane agent |
JP5749649B2 (en) * | 2008-10-27 | 2015-07-15 | バクスター・インターナショナル・インコーポレイテッドBaxter International Incorp0Rated | Model of thrombotic thrombocytopenic purpura and method of use thereof |
CN105050614B (en) | 2013-03-15 | 2019-04-05 | 加利福尼亚大学董事会 | Stimulate the peptide with reduced toxicity of Cholesterol Efflux |
CN104825249B (en) * | 2015-04-28 | 2017-11-07 | 温州医科大学 | A kind of surface mediated gene therapeutic type intraocular lens and preparation method thereof |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5628785A (en) * | 1992-03-19 | 1997-05-13 | Medtronic, Inc. | Bioelastomeric stent |
US5686409A (en) * | 1994-04-08 | 1997-11-11 | Research Corporation Technologies, Inc. | Antirestenosis protein |
US5698531A (en) * | 1989-03-31 | 1997-12-16 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
Family Cites Families (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5439446A (en) * | 1994-06-30 | 1995-08-08 | Boston Scientific Corporation | Stent and therapeutic delivery system |
US5190540A (en) | 1990-06-08 | 1993-03-02 | Cardiovascular & Interventional Research Consultants, Inc. | Thermal balloon angioplasty |
EP0558697A1 (en) | 1991-06-28 | 1993-09-08 | Massachusetts Institute Of Technology | Localized oligonucleotide therapy |
US5500013A (en) | 1991-10-04 | 1996-03-19 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
WO1993006792A1 (en) | 1991-10-04 | 1993-04-15 | Scimed Life Systems, Inc. | Biodegradable drug delivery vascular stent |
US5464450A (en) | 1991-10-04 | 1995-11-07 | Scimed Lifesystems Inc. | Biodegradable drug delivery vascular stent |
US5336615A (en) * | 1992-01-06 | 1994-08-09 | Yale University | Genetically engineered endothelial cells exhibiting enhanced migration and plasminogen activator activity |
US5571166A (en) * | 1992-03-19 | 1996-11-05 | Medtronic, Inc. | Method of making an intraluminal stent |
US5599352A (en) * | 1992-03-19 | 1997-02-04 | Medtronic, Inc. | Method of making a drug eluting stent |
US5383928A (en) * | 1992-06-10 | 1995-01-24 | Emory University | Stent sheath for local drug delivery |
US5464650A (en) | 1993-04-26 | 1995-11-07 | Medtronic, Inc. | Intravascular stent and method |
US5443827A (en) * | 1993-05-03 | 1995-08-22 | President And Fellows Of Harvard College | Fibrin-targeted inhibitors of thrombin |
WO1994027612A1 (en) | 1993-05-20 | 1994-12-08 | Baylor College Of Medicine | Genetic therapy for cardiovascular disease |
US5994341A (en) * | 1993-07-19 | 1999-11-30 | Angiogenesis Technologies, Inc. | Anti-angiogenic Compositions and methods for the treatment of arthritis |
US6780406B1 (en) | 1994-03-21 | 2004-08-24 | The Regents Of The University Of Michigan | Inhibition of vascular smooth muscle cell proliferation administering a thymidine kinase gene |
US5588962A (en) * | 1994-03-29 | 1996-12-31 | Boston Scientific Corporation | Drug treatment of diseased sites deep within the body |
AU6905696A (en) * | 1995-09-01 | 1997-03-27 | Emory University | Endovascular support device and method of use |
US5863904A (en) | 1995-09-26 | 1999-01-26 | The University Of Michigan | Methods for treating cancers and restenosis with P21 |
US6090618A (en) * | 1996-10-07 | 2000-07-18 | Arch Development Corporation | DNA constructs and viral vectors comprising a smooth muscle promoter |
US5833651A (en) | 1996-11-08 | 1998-11-10 | Medtronic, Inc. | Therapeutic intraluminal stents |
ZA9710342B (en) * | 1996-11-25 | 1998-06-10 | Alza Corp | Directional drug delivery stent and method of use. |
-
1997
- 1997-06-27 US US08/884,352 patent/US6818016B1/en not_active Expired - Fee Related
-
1998
- 1998-06-26 JP JP50576199A patent/JP2002507136A/en active Pending
- 1998-06-26 EP EP98932887A patent/EP1023005B1/en not_active Expired - Lifetime
- 1998-06-26 DE DE69841041T patent/DE69841041D1/en not_active Expired - Fee Related
- 1998-06-26 AT AT98932887T patent/ATE438361T1/en not_active IP Right Cessation
- 1998-06-26 WO PCT/US1998/013301 patent/WO1999000071A1/en active Application Filing
- 1998-06-26 CA CA002295040A patent/CA2295040C/en not_active Expired - Fee Related
- 1998-06-26 AU AU82676/98A patent/AU8267698A/en not_active Abandoned
-
2004
- 2004-09-22 US US10/946,785 patent/US20050038499A1/en not_active Abandoned
-
2007
- 2007-08-16 JP JP2007212501A patent/JP2007301402A/en active Pending
- 2007-10-31 US US11/980,983 patent/US20080112997A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5698531A (en) * | 1989-03-31 | 1997-12-16 | The Regents Of The University Of Michigan | Treatment of diseases by site-specific instillation of cells or site-specific transformation of cells and kits therefor |
US5628785A (en) * | 1992-03-19 | 1997-05-13 | Medtronic, Inc. | Bioelastomeric stent |
US5686409A (en) * | 1994-04-08 | 1997-11-11 | Research Corporation Technologies, Inc. | Antirestenosis protein |
Cited By (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6335029B1 (en) | 1998-08-28 | 2002-01-01 | Scimed Life Systems, Inc. | Polymeric coatings for controlled delivery of active agents |
US6589546B2 (en) | 1998-08-28 | 2003-07-08 | Scimed Life Systems, Inc. | Polymeric coatings for controlled delivery of active agents |
AU2001238518B2 (en) * | 2000-04-04 | 2006-09-07 | Boston Scientific Limited | Medical devices suitable for gene therapy regimens |
WO2001074413A1 (en) * | 2000-04-04 | 2001-10-11 | Boston Scientific Limited | Medical devices suitable for gene therapy regimens |
WO2002058752A2 (en) * | 2000-12-04 | 2002-08-01 | Medtronic, Inc. | Medical device and methods of use |
WO2002058752A3 (en) * | 2000-12-04 | 2002-11-21 | Medtronic Inc | Medical device and methods of use |
EP1319416A1 (en) | 2001-12-12 | 2003-06-18 | Hehrlein, Christoph, Dr. | Porous metallic stent with a ceramic coating |
WO2004050140A2 (en) * | 2002-12-03 | 2004-06-17 | Scimed Life Systems, Inc. | Medical devices for delivery of therapeutic agents |
WO2004050140A3 (en) * | 2002-12-03 | 2004-08-19 | Scimed Life Systems Inc | Medical devices for delivery of therapeutic agents |
US7491234B2 (en) | 2002-12-03 | 2009-02-17 | Boston Scientific Scimed, Inc. | Medical devices for delivery of therapeutic agents |
US8361143B2 (en) | 2002-12-03 | 2013-01-29 | Boston Scientific Scimed, Inc. | Medical devices for delivery of therapeutic agents |
US9248216B2 (en) | 2002-12-03 | 2016-02-02 | Boston Scientific Scimed, Inc. | Medical devices for delivery of therapeutic agents |
WO2004069298A1 (en) * | 2003-02-06 | 2004-08-19 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Fgf-2 derived proteins for the preparation of biomaterials or medical devices such as stents |
EP1444995A1 (en) * | 2003-02-06 | 2004-08-11 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | FGF-2 derived proteins for the preparation of biomaterials or medical devices such as stents |
DE10311729A1 (en) * | 2003-03-18 | 2004-09-30 | Schultheiss, Heinz-Peter, Prof. Dr. | Endovascular implant with an at least sectionally active coating of ratjadon and / or a ratjadon derivative |
Also Published As
Publication number | Publication date |
---|---|
DE69841041D1 (en) | 2009-09-17 |
US20050038499A1 (en) | 2005-02-17 |
US20080112997A1 (en) | 2008-05-15 |
EP1023005A4 (en) | 2006-06-14 |
CA2295040C (en) | 2005-08-23 |
CA2295040A1 (en) | 1999-01-07 |
JP2007301402A (en) | 2007-11-22 |
JP2002507136A (en) | 2002-03-05 |
AU8267698A (en) | 1999-01-19 |
US6818016B1 (en) | 2004-11-16 |
EP1023005A1 (en) | 2000-08-02 |
ATE438361T1 (en) | 2009-08-15 |
EP1023005B1 (en) | 2009-08-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20080112997A1 (en) | Methods for coating stents with DNA and expression of recombinant genes from DNA coated stents in vivo | |
US5833651A (en) | Therapeutic intraluminal stents | |
US5957971A (en) | Intraluminal stent | |
US6380154B1 (en) | Synthetic proteins for in vivo drug delivery and tissue augmentation | |
US6143037A (en) | Compositions and methods for coating medical devices | |
EP0920342B1 (en) | Medical device for delivering a therapeutic substance | |
JP2004537344A (en) | Medical equipment | |
Herrmann et al. | Antithrombogenic coating of stents using a biodegradable drug delivery technology | |
US20030059463A1 (en) | Medical device | |
WO2001067992A1 (en) | Stent having cover with drug delivery capability | |
WO1997047254A9 (en) | Compositions and methods for coating medical devices | |
KR101692392B1 (en) | Compounds and methods for the prevention or treatment of restenosis | |
EP1399094A2 (en) | Medicated stent having multi-layer polymer coating | |
Kocsis et al. | Heparin-coated stents | |
WO2004112863A1 (en) | Biodegradable membrane-covered implant comprising chitosan | |
JP2006503605A (en) | Medical equipment | |
Stampfl et al. | Reduction of late in-stent stenosis in a porcine coronary artery model by cobalt chromium stents with a nanocoat of polyphosphazene (Polyzene-F) | |
EP1073427B1 (en) | Periadventitial delivery device | |
Schoen et al. | Future directions and therapeutic approaches | |
Lee et al. | Control of clot lysis by gene transfer | |
WO2023099957A2 (en) | Biomimetic coating for endovascular stent | |
Gammon et al. | Bioabsorbable endovascular stent prostheses |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM GW HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
CFP | Corrected version of a pamphlet front page | ||
CR1 | Correction of entry in section i |
Free format text: PAT. BUL. 01/99 UNDER (51) REPLACE "A61M 1/30" BY "A61N 1/30" |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
ENP | Entry into the national phase |
Ref document number: 2295040 Country of ref document: CA Ref country code: CA Ref document number: 2295040 Kind code of ref document: A Format of ref document f/p: F |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1998932887 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: 1998932887 Country of ref document: EP |
|
NENP | Non-entry into the national phase |
Ref country code: CA |