WO2004082705A1 - Treatment of dupuytren’s contracture - Google Patents
Treatment of dupuytren’s contracture Download PDFInfo
- Publication number
- WO2004082705A1 WO2004082705A1 PCT/GB2004/001192 GB2004001192W WO2004082705A1 WO 2004082705 A1 WO2004082705 A1 WO 2004082705A1 GB 2004001192 W GB2004001192 W GB 2004001192W WO 2004082705 A1 WO2004082705 A1 WO 2004082705A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- disease
- dupuytren
- contracture
- treatment
- vegf
- Prior art date
Links
- 208000001708 Dupuytren contracture Diseases 0.000 title claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 18
- 230000035755 proliferation Effects 0.000 claims abstract description 9
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 claims abstract description 5
- 208000019553 vascular disease Diseases 0.000 claims abstract description 5
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 4
- 210000000555 contractile cell Anatomy 0.000 claims abstract description 4
- 230000037314 wound repair Effects 0.000 claims abstract description 3
- 239000003814 drug Substances 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 5
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 claims description 4
- 230000008827 biological function Effects 0.000 claims description 3
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 claims description 2
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 claims description 2
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 claims description 2
- 239000012634 fragment Substances 0.000 claims 2
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 claims 1
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 claims 1
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 abstract 2
- 201000010099 disease Diseases 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 12
- 210000000651 myofibroblast Anatomy 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 8
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 210000002889 endothelial cell Anatomy 0.000 description 3
- 210000002950 fibroblast Anatomy 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 208000031481 Pathologic Constriction Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000001120 cytoprotective effect Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 208000037804 stenosis Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000001960 triggered effect Effects 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 1
- 108010085238 Actins Proteins 0.000 description 1
- 102000002585 Contractile Proteins Human genes 0.000 description 1
- 108010068426 Contractile Proteins Proteins 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 101000817629 Homo sapiens Dymeclin Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 102000009520 Vascular Endothelial Growth Factor C Human genes 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000002399 angioplasty Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000009989 contractile response Effects 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 210000001145 finger joint Anatomy 0.000 description 1
- 238000002683 hand surgery Methods 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000037456 inflammatory mechanism Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Classifications
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1858—Platelet-derived growth factor [PDGF]
- A61K38/1866—Vascular endothelial growth factor [VEGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
Definitions
- This invention relates to the treatment of fibrotic diseases.
- Dupuytren's Contracture is a progressive proliferative fibroplasia of the subcutaneous palmar tissue, which results in contraction of the finger joints which, ultimately, can become disabling (Calandruccio, J.H. (1998) Campbell's Operative Orthopaedic, 9th edn., ed S. Terry Canale Mosby (St. Louis, USA)). Patients suffer progressive development of thickened bands and nodules around the tendons of the palm and fingers - and sometimes the wrist - that leads to reduction in movement of the fingers and ultimately inability to extend them.
- Dupuytren's Disease is the term often given to non-disabling palmar fibroses: as progression can be slow, Dupuytren's Disease is substantially more common than Dupuytren's Contracture, but the aetiology of the two is believed to be the same.
- myofibroblasts a phenotype common in wound healing
- myofibroblasts a phenotype common in wound healing
- Molecular and pharmacological markers in these 'myofibroblasts' are intermediate between those of normal fibroblasts and those of smooth muscle cells: for example, myofibroblasts contain 'smooth muscle' subtype of ⁇ -actin (SMA-actin), but not other muscle-specific contractile proteins (Arora, P.D., McCulloch, C.A.G. (1994). J.
- myofibroblasts from Dupuytren's disease have a smooth-muscle-like contractile response to prostaglandins (Hurst, L.C., Badalêt, M.A., Makowski, J. (1986). J. Hand Surgery.11 A: 18-22), although they do not respond (as SMCs do) to 5- hydroxytryptamine.
- myofibroblasts are characteristic of many diseases where a wound- response is generated inappropriately, particularly in other fibroses.
- An abnormal, proliferation of smooth muscle cells is also characteristic of some vascular diseases such as post-graft stenosis and re-stenosis following coronary artery angioplasty (Martin, J. (2000). Clinical and Experimental Allergy. 30: 33- 36). Summary of the Invention
- agents which reduce/reverse the pathological wound-repair-related proliferation of contractile cells in vascular disease can also be used to prevent or reverse the differentiation and subsequent proliferation of myofibroblasts in Dupuytren's Contracture.
- agents which have a cytoprotective effect on the vascular endothelium can be used to reduce or prevent the development of Dupuytren's Contracture.
- the present application discloses a method for retarding the development of Dupuytren's Disease and Dupuytren's Contracture by the treatment of actually or potentially affected areas with a therapeutic agent which is a cytoprotective agent for endothelial cells.
- a therapeutic agent which is a cytoprotective agent for endothelial cells.
- Such an agent is a member of the Vascular Endothelial Growth Factor family of gene products.
- the present invention is based on the realisation that Dupuytren's Disease is caused primarily by the proliferation and contraction of myofibroblasts, that myofibroblasts are one cell type in a continuum of cell types that have fibroblasts at one extreme and smooth muscle cells at the other, and that therefore agents which are observed to regulate the proliferation of smooth muscle cells may act to prevent the abnormal proliferation of other cell types in this continuum, including myofibroblasts.
- Dupytren's Disease and “Dupuytren's Contracture” are used interchangeably herein.
- Contractile cells are those cells that fall within the continuum of fibroblasts at one end and smooth muscle cells at the other end.
- the agents intended for use in the present invention will reduce/reverse the proliferation of such cells in vascular disease.
- Therapeutic agents useful for this invention include VEGF-A, VEGF-B, VEGF-C etc..
- Specific examples of these proteins include P15692 (amino acids 27 through 232), CAA 09179, AAD55345, P49765 (amino acids 22-207), S69207 (amino acids 103-419), P97946 (amino acids 94-210), AAL27435 AAD03735, P52584 (amino acids 21-132) and CAA44447, and sequence variants and splice variants of these.
- Other proteins with similar biological function but different sequence will also be useful for this invention.
- a DNA sequence which causes the cell to produce such a protein is also a therapeutic agent useful for this invention: such agents may code for the protein themselves, or induce the cells into which they are put to synthesise the protein from their own gene or genes.
- a peptide which is designed to have the same biological effect as the proteins is also a useful therapeutic for this invention.
- a non-peptide small molecule is also a useful therapeutic for this invention. The method for designing or identifying a peptide or a small molecule which has the same effect as a protein, through structure- based chemical design or through a variety of combinatorial chemistry and screening processes, is well known to the skilled man.
- the therapeutic agent will typically be targeted to the site of the Dupuytren's Disease. This may be done by local physical delivery (for example by injection or implantation), or by physically or chemically associating it with an agent which preferentially localises to the site of disease, for example an antibody or a liposome.
- the amount of therapeutic agent so delivered can readily be determined by the skilled man, having regard to conventional factors such as the condition of the patient, the severity of the problem to be treated, the potency of the agent and the desired effect. By way of example only, a suitable amount for administration is 0.1 picograms to 1 milligram per disease site.
- the therapeutic agent is preferably delivered to the site of the
- Dupuytren's Disease Most preferably, it is delivered to the site of disease immediately after corrective surgery, when the disease burden is minimal and the site is open for physical access.
- the agent may also be delivered through the blood vessels, by systemic injection, local injection, or by means of a stent, catheter or other device.
- the therapeutic agent may be delivered as a solution which can be injected, sprayed or otherwise mechanically delivered, impregnated into a gel, tissue or other material which is implanted in the site as a sheet, as particles or in other physical form, or pre-loaded into cells which are then implanted by any method into the site of disease.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Agents which reverse the wound-repair related proliferation of contractile cells in vascular disease may be used in the treatment of Dupuytren's Contracture or Disease. Suitable agents include those of the vascular endothelial growth factor family (VEGF).
Description
TREATMENT OF DUPUYTREN'S CONTRACTURE
Field of the Invention
This invention relates to the treatment of fibrotic diseases. Background to the Invention Dupuytren's Contracture is a progressive proliferative fibroplasia of the subcutaneous palmar tissue, which results in contraction of the finger joints which, ultimately, can become disabling (Calandruccio, J.H. (1998) Campbell's Operative Orthopaedic, 9th edn., ed S. Terry Canale Mosby (St. Louis, USA)). Patients suffer progressive development of thickened bands and nodules around the tendons of the palm and fingers - and sometimes the wrist - that leads to reduction in movement of the fingers and ultimately inability to extend them. Dupuytren's Disease is the term often given to non-disabling palmar fibroses: as progression can be slow, Dupuytren's Disease is substantially more common than Dupuytren's Contracture, but the aetiology of the two is believed to be the same.
The only demonstrated effective therapy is surgery to remove the bands and nodules, although radiotherapy is becoming accepted as effective in blocking disease progression (Seegenschmeidt, M.H., Olschewski, T., Guntrum, F. (2001) Int. J. Radiation Oncology, Biology, Phys. 49: 785-798). Both are effective in the short-term, but recurrence of the disease is almost inevitable. The mechanism by which the fibrosis is triggered or developed is unknown, although damage to and occlusion of the palmar microvasculature is likely to be a triggering event (Kischer, C.W., Speer, D.P. (1984). J. Hand. Surgery 9A: 58- 62), and an inflammatory mechanism may be involved (Baird, K.S., Alwan, W.H., Crossan, J.F., Wojciak, B (1993) Lancet 341 : 1622-1623).
The contraction in Dupuytrens is probably caused by contractile fibroblast-like cells called myofibroblasts, a phenotype common in wound healing (Gabbiani, G., Ryan, G.B., Majne, G. (1971). Experientia 27: 549-550). Molecular and pharmacological markers in these 'myofibroblasts' are intermediate between those of normal fibroblasts and those of smooth muscle cells: for example, myofibroblasts contain 'smooth muscle' subtype of α-actin (SMA-actin), but not other muscle-specific contractile proteins (Arora, P.D.,
McCulloch, C.A.G. (1994). J. Cellular Physiology 159: 161-175), myofibroblasts from Dupuytren's disease have a smooth-muscle-like contractile response to prostaglandins (Hurst, L.C., Badalamente, M.A., Makowski, J. (1986). J. Hand Surgery.11 A: 18-22), although they do not respond (as SMCs do) to 5- hydroxytryptamine.
Such myofibroblasts are characteristic of many diseases where a wound- response is generated inappropriately, particularly in other fibroses. An abnormal, proliferation of smooth muscle cells is also characteristic of some vascular diseases such as post-graft stenosis and re-stenosis following coronary artery angioplasty (Martin, J. (2000). Clinical and Experimental Allergy. 30: 33- 36). Summary of the Invention
This invention results from the realisation that agents which reduce/reverse the pathological wound-repair-related proliferation of contractile cells in vascular disease can also be used to prevent or reverse the differentiation and subsequent proliferation of myofibroblasts in Dupuytren's Contracture. Specifically, agents which have a cytoprotective effect on the vascular endothelium can be used to reduce or prevent the development of Dupuytren's Contracture. The present application discloses a method for retarding the development of Dupuytren's Disease and Dupuytren's Contracture by the treatment of actually or potentially affected areas with a therapeutic agent which is a cytoprotective agent for endothelial cells. Such an agent is a member of the Vascular Endothelial Growth Factor family of gene products. Without being bound by theory, it is expected that treatment of Dupyutren's contracture with such agents will reduce the development of the disease through renormalising the phenotype of the myofibroblasts that cause the disease. The treatment described in this invention is therefore expected to be most effective if used very early in the disease, or immediately after the bulk of the myofibroblasts have been removed by surgery, radiation therapy or other ablative treatment.
Description of the Invention
While not wishing to be bound by theory, the present invention is based on the realisation that Dupuytren's Disease is caused primarily by the proliferation and contraction of myofibroblasts, that myofibroblasts are one cell type in a continuum of cell types that have fibroblasts at one extreme and smooth muscle cells at the other, and that therefore agents which are observed to regulate the proliferation of smooth muscle cells may act to prevent the abnormal proliferation of other cell types in this continuum, including myofibroblasts.
One group of such agents are the vascular endothelial gene family protein products, which act on endothelial cells which in turn act on smooth muscle cells in the walls of blood vessels. This invention is based on the understanding that, because Dupyutren's Disease is triggered in part by damage to the palmar microvasculature, agents which have this effect on endothelial cells will have a preventative effect on the development of Dupuytren's Disease. The term "Dupuytren's Disease" and "Dupuytren's Contracture" are used interchangeably herein.
"Contractile cells" are those cells that fall within the continuum of fibroblasts at one end and smooth muscle cells at the other end. The agents intended for use in the present invention will reduce/reverse the proliferation of such cells in vascular disease.
Therapeutic agents useful for this invention include VEGF-A, VEGF-B, VEGF-C etc.. Specific examples of these proteins (described by their NCBI database accession numbers) include P15692 (amino acids 27 through 232), CAA 09179, AAD55345, P49765 (amino acids 22-207), S69207 (amino acids 103-419), P97946 (amino acids 94-210), AAL27435 AAD03735, P52584 (amino acids 21-132) and CAA44447, and sequence variants and splice variants of these. Other proteins with similar biological function but different sequence will also be useful for this invention. A DNA sequence which causes the cell to produce such a protein is also a therapeutic agent useful for this invention: such agents may code for the protein themselves, or induce the cells into which they are put to synthesise the protein from their own gene or genes. A peptide which is designed to have the same biological effect as the proteins is also a useful
therapeutic for this invention. A non-peptide small molecule is also a useful therapeutic for this invention. The method for designing or identifying a peptide or a small molecule which has the same effect as a protein, through structure- based chemical design or through a variety of combinatorial chemistry and screening processes, is well known to the skilled man.
The therapeutic agent will typically be targeted to the site of the Dupuytren's Disease. This may be done by local physical delivery (for example by injection or implantation), or by physically or chemically associating it with an agent which preferentially localises to the site of disease, for example an antibody or a liposome. The amount of therapeutic agent so delivered can readily be determined by the skilled man, having regard to conventional factors such as the condition of the patient, the severity of the problem to be treated, the potency of the agent and the desired effect. By way of example only, a suitable amount for administration is 0.1 picograms to 1 milligram per disease site. The therapeutic agent is preferably delivered to the site of the
Dupuytren's Disease. Most preferably, it is delivered to the site of disease immediately after corrective surgery, when the disease burden is minimal and the site is open for physical access. The agent may also be delivered through the blood vessels, by systemic injection, local injection, or by means of a stent, catheter or other device.
The therapeutic agent may be delivered as a solution which can be injected, sprayed or otherwise mechanically delivered, impregnated into a gel, tissue or other material which is implanted in the site as a sheet, as particles or in other physical form, or pre-loaded into cells which are then implanted by any method into the site of disease.
Claims
1. Use of an agent that reduces the wound-repair-related proliferation of contractile cells in vascular disease, in the manufacture of a medicament for the treatment of Dupuytren's disease or contracture.
2. Use according to claim 1 , wherein the agent is or encodes a member of the Vascular Endothelial Growth Factor family, or a fragment thereof which retains biological function.
3. Use according to claim 1 or claim 2, wherein the agent is or encodes VEGF-A, VEGF-B, VEGF-C or VEGF-D or a fragment thereof which retains biological function.
4. A method for the treatment if Dupuytren's disease or contracture, comprising administering to a patient a medicament as defined in any of claims 1 to 3.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0306165.2 | 2003-03-18 | ||
| GBGB0306165.2A GB0306165D0 (en) | 2003-03-18 | 2003-03-18 | Medical treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2004082705A1 true WO2004082705A1 (en) | 2004-09-30 |
Family
ID=9954984
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2004/001192 WO2004082705A1 (en) | 2003-03-18 | 2004-03-18 | Treatment of dupuytren’s contracture |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB0306165D0 (en) |
| WO (1) | WO2004082705A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012056044A1 (en) | 2010-10-30 | 2012-05-03 | Imperial Innovations Ltd | Treatment for dupuytren's disease |
| WO2013064585A1 (en) | 2011-11-04 | 2013-05-10 | Isis Innovation Ltd | Treatment of musculoskeletal fibroproliferative disorders |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6086872A (en) * | 1997-03-27 | 2000-07-11 | Advance Biofactures Of Curacao, Nv | Amelioration of dupuytren's disease |
| US6335320B1 (en) * | 1998-12-24 | 2002-01-01 | Ucb S.A. | Method of treating fibrotic conditions |
-
2003
- 2003-03-18 GB GBGB0306165.2A patent/GB0306165D0/en not_active Ceased
-
2004
- 2004-03-18 WO PCT/GB2004/001192 patent/WO2004082705A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6086872A (en) * | 1997-03-27 | 2000-07-11 | Advance Biofactures Of Curacao, Nv | Amelioration of dupuytren's disease |
| US6335320B1 (en) * | 1998-12-24 | 2002-01-01 | Ucb S.A. | Method of treating fibrotic conditions |
Non-Patent Citations (2)
| Title |
|---|
| DATABASE MEDLINE [online] US NATIONAL LIBRARY OF MEDICINE (NLM), BETHESDA, MD, US; June 2003 (2003-06-01), BAINS WILLIAM: "Vasoprotective VEGF as a candidate for prevention of recurrence of fibrotic diseases such as Dupuytren's contracture.", XP002285366, Database accession no. NLM12699705 * |
| MEDICAL HYPOTHESES. JUN 2003, vol. 60, no. 6, June 2003 (2003-06-01), pages 793 - 796, ISSN: 0306-9877 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012056044A1 (en) | 2010-10-30 | 2012-05-03 | Imperial Innovations Ltd | Treatment for dupuytren's disease |
| US9138458B2 (en) | 2010-10-30 | 2015-09-22 | Isis Innovation Limited | Treatment for dupuytren's disease |
| US10273296B2 (en) | 2010-10-30 | 2019-04-30 | Oxford University Innovation Limited | Treatment for dupuytren's disease |
| AU2017204267B2 (en) * | 2010-10-30 | 2019-05-23 | Oxford University Innovation Limited | Treatment for dupuytren's disease |
| US10669334B2 (en) | 2010-10-30 | 2020-06-02 | Oxford University Innovation Limited | Treatment for Dupuytren's disease |
| WO2013064585A1 (en) | 2011-11-04 | 2013-05-10 | Isis Innovation Ltd | Treatment of musculoskeletal fibroproliferative disorders |
Also Published As
| Publication number | Publication date |
|---|---|
| GB0306165D0 (en) | 2003-04-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Stefanini et al. | State of the art: coronary artery stents-past, present and future | |
| Junge et al. | Mesh biocompatibility: effects of cellular inflammation and tissue remodelling | |
| JP6857214B2 (en) | Sustained release composition for injection and its use for treating joint inflammation and associated pain | |
| Sauerland et al. | Risks and benefits of preoperative high dose methylprednisolone in surgical patients: a systematic review | |
| Hagberg | Exogenous hyaluronate as an adjunct in the prevention of adhesions after flexor tendon surgery: a controlled clinical trial | |
| Di Lorenzo et al. | Benefits of drug-eluting stents as compared to bare metal stent in ST-segment elevation myocardial infarction: four year results of the PaclitAxel or Sirolimus-Eluting stent vs bare metal stent in primary angiOplasty (PASEO) randomized trial | |
| JP2018198954A (en) | Improved medical device | |
| US20070134290A1 (en) | Drug eluting implantable medical device | |
| JP2003501151A (en) | Device and compound for treating arterial restenosis | |
| JP5329435B2 (en) | Coronary stent with asymmetric drug release controlled coating | |
| EP1723976A3 (en) | Intraluminal medical devices in combination with therapeutic agents | |
| KR101959571B1 (en) | Platelet-derived growth factor compositions and methods for the treatment of tendinopathies | |
| Jeon et al. | Silicone implants capable of the local, controlled delivery of triamcinolone for the prevention of fibrosis with minimized drug side effects | |
| EP1824532A2 (en) | Medical devices and compositions for treating restenosis | |
| Ahuja et al. | Biocompatibility analysis of PLA based candidate materials for cardiovascular stents in a rat subcutaneous implant model | |
| CZ225098A3 (en) | Healing process control | |
| Zhang et al. | Clinical and multimodality imaging results at 6 months of a bioresorbable sirolimus-eluting scaffold for patients with single de novo coronary artery lesions: the NeoVas first-in-man trial | |
| WO2004082705A1 (en) | Treatment of dupuytren’s contracture | |
| US7425217B2 (en) | System and method for inhibiting cellular proliferation with tachykinins | |
| Lee et al. | Development of a New Hybrid Biodegradable Drug‐Eluting Stent for the Treatment of Peripheral Artery Disease | |
| US8357653B2 (en) | System and method for inhibiting cellular proliferation with tachykinins | |
| Apisarnthanarax et al. | Intravascular brachytherapy: a review of the current vascular biology | |
| Shi et al. | Safety and efficacy of a novel 3D-printed bioresorbable sirolimus-eluting scaffold in a porcine model | |
| Callaghan et al. | Cell dynamics and metabolism of the foreign body response: characterizing host-biomaterial interactions for next-generation medical implant biocompatibility | |
| JP2004506690A (en) | A novel specific mechanism for suppressing platelet adhesion to collagen |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): BW GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 122 | Ep: pct application non-entry in european phase |