WO2012102625A2 - Therapeutic composition - Google Patents
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- WO2012102625A2 WO2012102625A2 PCT/NZ2012/000005 NZ2012000005W WO2012102625A2 WO 2012102625 A2 WO2012102625 A2 WO 2012102625A2 NZ 2012000005 W NZ2012000005 W NZ 2012000005W WO 2012102625 A2 WO2012102625 A2 WO 2012102625A2
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- glyargargalaalaproglyargaibglygly
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Definitions
- the invention relates to a ophthalmic compositions and methods of inhibiting degeneration of cells of the retina.
- the invention relates to a method and
- composition for use in the treatment of diabetics and retina transplantation is provided.
- Neurodegeneration of the retina is a complication of a number of diseases, including diabetes. In diabetic retinopathy the gradual loss of neurons suggests that progress of the disease is ultimately irreversible, since these cells cannot usually be replaced (Barber (2003)).
- Neurodegeneration is one of the many factors limiting the transplantation of retinas from donors to recipients.
- Ischemic induced oxidative stress is known to trigger glial activation and apoptotic cell death in in vitro models of neurodegeneration .
- the invention provides a composition comprising one or more ophthalmologically acceptable
- the peptide consists of the 11 amino acid residue sequence:
- GlyArgArgAlaAlaProGlyArgAibGlyGly and ophthalmologically acceptable derivatives thereof include the sequence wherein the C-terminus of the peptide is amidated to give: GlyArgArgAlaAlaProGlyArgAibGlyGly-NH 2 (SEQ ID NO:2) .
- the invention provides a method of inhibiting degeneration of cells of the retina of a subject comprising the step of:
- the administration step to the subject is by way of an intraocular injection.
- the subject has been diagnosed as having the metabolic disorder diabetes mellitus.
- the subject is selected from the group consisting of: humans and companion animals.
- the invention provides a method of inhibiting degeneration of cells of the retina of a diabetic subject by administering to the subject by way of an intraocular injection a composition comprising ophthalmologically acceptable excipients and an effective amount of at least one of the peptides selected from SEQ ID NO:l and SEQ ID NO: 2.
- a composition comprising ophthalmologically acceptable excipients and an effective amount of at least one of the peptides selected from SEQ ID NO:l and SEQ ID NO: 2.
- the invention provides a method of
- transplanting a retina from a donor subject to a recipient subject comprising the step of intravitreal administration of an effective amount of at least one of the peptides selected from SEQ ID NO:l and SEQ ID NO: 2 to the eye of the donor prior to transplantation of the retina.
- the subject is selected from the group consisting of: humans and companion animals.
- the effective amount is indicated to be in the range of pmol amounts. Because the administration is to the internal volume of the eye the effective amount will be dependent, at least in part, on the internal volume of the eye of the subj ect .
- Effective amount means an amount effective to inhibit degeneration of cells of the retina.
- “Functionally similar amino acid” means an amino acid with similar properties according to the following groupings:
- Intraocular injection means injection into the eyeball and specifically includes injection into the vitreous humour (intravitreal administration) .
- Optologically acceptable derivatives means derivatives of the peptide defined in SEQ ID NO:l obtained by amidation, acylation, alkylation, carboxylation, glycosylation,
- phosphorylation phosphorylation, prenylation, salification, sulfation, or a combination thereof, that are suitable for inclusion in a composition for administration to the eye.
- Optologically acceptable excipients means excipients selected from stabilizing agents, surfactants, buffering agents, chelating agents, viscosity agents, tonicity agents and preservative agents that are suitable for inclusion in a composition for administration to the eye.
- nucleotides and amino acids of biosequences are identified in accordance with Tables 1 to 4 of Annex C, Appendix 2 of the PCT Administrative Instructions (as in force from January 1, 2010) .
- Figure 1 Comparison of ex vivo ischemic induced glial activation in retinal tissue following: no treatment (A) and three daily intravitreal administrations of 2 pmol SEQ ID NO: 2 (B) (ONL - Outer Nuclear Layer; INL - Inner Nuclear Layer; IPL - Inner Plexiform Layer; GCL - Ganglionic Cell Layer; NFL - Nerve Fibre Layer) .
- Figure 2 Comparison of ex vivo ischemic induced apoptotic cell death in retinal tissue following: no treatment (A) and three daily intravitreal administrations of 2 pmol SEQ ID NO: 2 (B) .
- Figure 3. Composite of Figure 1 and Figure 2 comparing ex vivo ischemic induced glial activation and apoptotic cell death in retinal tissue following: no treatment (A) and three daily intravitreal administrations of 2 pmol SEQ ID NO: 2 (B) .
- Harris et al (2009) have described a number of synthetic peptides that are effective to promote neural regeneration, migration, proliferation, differentiation and/or axonal outgrowth .
- a composition comprising 667n SEQ ID NO: 2 in 0.9% NaCl phosphate buffer was prepared as a stock solution.
- An amount of 2 pmol of SEQ ID NO: 2 was injected into the left eye of a Wistar rat daily for three days by administering 3 ⁇ 1 of the stock solution (treatment).
- a volume of 3 ⁇ 1 of 0.9% NaCl phosphate buffer was administered to the right eye (control) .
- Twenty four hours after the third injection the rats are sacrificed by injection of ketamine and the retinal tissue extracted and placed into HEPES-buffered extraction medium under a nitrogen atmosphere (oxygen and glucose-free
- the retinal tissue was fixed, cut into slices by the use of a microtome and incubated with anti-glial fibrillary acid protein (anti-GFAP) antibodies and analysed with the Terminal deoxynucleotidyl transferase dUTP Nick End Labelling (TUNEL) kit.
- anti-GFAP anti-glial fibrillary acid protein
- the treatment sample shows a significantly reduced glial cell-inflammatory response and no apoptotic cell death. It appears that daily administration of 2 pmol SEQID NO: 1 was effective to inhibit degeneration of cells of the retina under ischemic stress.
- retinal neuronal cell types receptor cells (cones and rods) , ganglionic cells, amacrine and horizontal cells
- retinal transplantation the time factor between the potential choice of the right donor tissue and the
- Cisplatin neurotoxicity the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity. J. Clin. Oncol. 10: 795-803.
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Gastroenterology & Hepatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Ophthalmology & Optometry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention provides a composition comprising ophthalmologically acceptable excipients and an effective amount of a peptide comprising the sequence: GlyArgArgAlaAlaProGlyArgAibGlyGly (SEQ ID NO:1)or the sequence GlyArgArgAlaAlaProGlyArgAibGlyGly-NH2 (SEQ ID NO: 2) and methods of use thereof.
Description
THERAPEUTIC COMPOSITION
FIELD OF INVENTION
The invention relates to a ophthalmic compositions and methods of inhibiting degeneration of cells of the retina. In particular, the invention relates to a method and
composition for use in the treatment of diabetics and retina transplantation.
BACKGROUND ART
Neurodegeneration of the retina is a complication of a number of diseases, including diabetes. In diabetic retinopathy the gradual loss of neurons suggests that progress of the disease is ultimately irreversible, since these cells cannot usually be replaced (Barber (2003)).
The vision of people with diabetes will only be protected when a means to prevent the gradual, but constant loss of neurons within the inner retina has been developed.
Neurodegeneration is one of the many factors limiting the transplantation of retinas from donors to recipients.
Ischemic induced oxidative stress is known to trigger glial activation and apoptotic cell death in in vitro models of neurodegeneration .
A need exists for treatments that inhibit neurodegeneration as a complication of diseases such as diabetes and in the transplantation of retinas. It is an object of this invention to provide a method and composition for use in such treatment or at least to provide a useful choice.
STATEMENT OF INVENTION
In a first aspect the invention provides a composition comprising one or more ophthalmologically acceptable
excipients and an effective amount of a peptide comprising the sequence:
GlyArgArgAlaAlaProGlyArgAibGlyGly (SEQ ID NO:l)
In one embodiment the peptide consists of the 11 amino acid residue sequence:
GlyArgArgAlaAlaProGlyArgAibGlyGly and ophthalmologically acceptable derivatives thereof. One such ophthalmically acceptable derivative includes the sequence wherein the C-terminus of the peptide is amidated to give: GlyArgArgAlaAlaProGlyArgAibGlyGly-NH2 (SEQ ID NO:2) .
In a second aspect the invention provides a method of inhibiting degeneration of cells of the retina of a subject comprising the step of:
• Administering to the subject an effective amount of the peptide SEQ ID N0:1 and/or SEQ ID NO: 2. In one embodiment the administration step to the subject is by way of an intraocular injection.
In one embodiment the subject has been diagnosed as having the metabolic disorder diabetes mellitus.
In one embodiment the subject is selected from the group consisting of: humans and companion animals.
In another embodiment of the second aspect the invention provides a method of inhibiting degeneration of cells of the retina of a diabetic subject by administering to the subject
by way of an intraocular injection a composition comprising ophthalmologically acceptable excipients and an effective amount of at least one of the peptides selected from SEQ ID NO:l and SEQ ID NO: 2. In a third aspect the invention provides a method of
transplanting a retina from a donor subject to a recipient subject comprising the step of intravitreal administration of an effective amount of at least one of the peptides selected from SEQ ID NO:l and SEQ ID NO: 2 to the eye of the donor prior to transplantation of the retina.
In one embodiment the subject is selected from the group consisting of: humans and companion animals.
It will be understood from the following description that the effective amount is indicated to be in the range of pmol amounts. Because the administration is to the internal volume of the eye the effective amount will be dependent, at least in part, on the internal volume of the eye of the subj ect .
In the description and claims of this specification the following acronyms, terms and phrases have the meaning provided:
"Effective amount" means an amount effective to inhibit degeneration of cells of the retina.
"Functionally similar amino acid" means an amino acid with similar properties according to the following groupings:
Neutral-weakly hydrophobic (Ala, Gly, Pro, Ser, Thr)
Hydrophilic-Acid Amine (Asn, Asp, Gin, Glu)
Hydrophilic-Basic (Arg, His, Lys)
Hydrophobic (lie, Met, Leu, Val)
Hydrophobic-Aromatic (Phe, Trp, Tyr)
Cross-linking (Cys)
"Intraocular injection" means injection into the eyeball and specifically includes injection into the vitreous humour (intravitreal administration) .
"Ophthalmologically acceptable derivatives" means derivatives of the peptide defined in SEQ ID NO:l obtained by amidation, acylation, alkylation, carboxylation, glycosylation,
phosphorylation, prenylation, salification, sulfation, or a combination thereof, that are suitable for inclusion in a composition for administration to the eye.
"Ophthalmologically acceptable excipients" means excipients selected from stabilizing agents, surfactants, buffering agents, chelating agents, viscosity agents, tonicity agents and preservative agents that are suitable for inclusion in a composition for administration to the eye.
In the description and claims of this specification the nucleotides and amino acids of biosequences (nucleic acids and peptides) are identified in accordance with Tables 1 to 4 of Annex C, Appendix 2 of the PCT Administrative Instructions (as in force from January 1, 2010) .
The terms "first", "second", "third", etc. used with
reference to elements, features or integers of the subject matter defined in the Statement of Invention and Claims, or when used with reference to alternative embodiments of the invention are not intended to imply an order of preference.
The invention will now be described with reference to
embodiments or examples and the figures of the accompanying drawings pages.
BRIEF DESCRIPTION OF DRAWINGS
Figure 1. Comparison of ex vivo ischemic induced glial activation in retinal tissue following: no treatment (A) and three daily intravitreal administrations of 2 pmol SEQ ID NO: 2 (B) (ONL - Outer Nuclear Layer; INL - Inner Nuclear Layer; IPL - Inner Plexiform Layer; GCL - Ganglionic Cell Layer; NFL - Nerve Fibre Layer) .
Figure 2. Comparison of ex vivo ischemic induced apoptotic cell death in retinal tissue following: no treatment (A) and three daily intravitreal administrations of 2 pmol SEQ ID NO: 2 (B) . Figure 3. Composite of Figure 1 and Figure 2 comparing ex vivo ischemic induced glial activation and apoptotic cell death in retinal tissue following: no treatment (A) and three daily intravitreal administrations of 2 pmol SEQ ID NO: 2 (B) .
DETAILED DESCRIPTION Whole vascular permeability is a target that is often
considered for new treatments of diabetic retinopathy.
Barber (2003) has suggested that apoptosis of neurons is also an essential target for pharmacological studies.
Harris et al (2009) have described a number of synthetic peptides that are effective to promote neural regeneration, migration, proliferation, differentiation and/or axonal outgrowth .
It has now been demonstrated that the synthetic peptide designated here as SEQ ID NO: 2 can be administered
prophylactically to inhibit neurodegeneration in the retina.
A composition comprising 667n SEQ ID NO: 2 in 0.9% NaCl phosphate buffer was prepared as a stock solution. An amount of 2 pmol of SEQ ID NO: 2 was injected into the left eye of a Wistar rat daily for three days by administering 3μ1 of the stock solution (treatment). A volume of 3μ1 of 0.9% NaCl phosphate buffer was administered to the right eye (control) .
Twenty four hours after the third injection the rats are sacrificed by injection of ketamine and the retinal tissue extracted and placed into HEPES-buffered extraction medium under a nitrogen atmosphere (oxygen and glucose-free
containing 5% C02 and 95% N2) containing all essential amino acids and lipids for a period of 40 min (ischemia) .
Subsequently, the retinal tissue was fixed, cut into slices by the use of a microtome and incubated with anti-glial fibrillary acid protein (anti-GFAP) antibodies and analysed with the Terminal deoxynucleotidyl transferase dUTP Nick End Labelling (TUNEL) kit.
The distribution of the Mueller glial retinal marker GFAP in the control and treatment samples is presented in the
fluorescent photomicrographs of Figure 3. Far more
pronounced glial inflammatory reaction was observed in the control, i.e. untreated, sample.
Analysis with the TUNEL kit is presented in the fluorescent photomicrographs of Figure 4. A far higher number of apoptotic neurons is observed in the inner retinal layer of the control sample.
The treatment sample shows a significantly reduced glial cell-inflammatory response and no apoptotic cell death. It appears that daily administration of 2 pmol SEQID NO: 1 was effective to inhibit degeneration of cells of the retina under ischemic stress.
The ability to induce prolonged survival of different retinal neuronal cell types (receptor cells (cones and rods) , ganglionic cells, amacrine and horizontal cells) will be advantageous in mitigating degeneration of the retina, such as that induced by disease or trauma, including retinal transplantation .
In retinal transplantation the time factor between the potential choice of the right donor tissue and the
preparedness of the recipient in a clinical setting is a considerable factor for a successful transplantation
strategy. It is anticipated that administration of SEQ IDs NO: 1 and 2 will improve the survival of donor retinal tissue .
Although the invention has been described with reference to an embodiment or example it should be appreciated that variations and modifications may be made to this embodiment or example without departing from the scope of the invention.
Where known equivalents exist to specific features, such equivalents are incorporated as if specifically referred to in this specification. In particular, it is anticipated that functionally similar peptide sequences may be obtained by substitution of one or more amino acids of the biosequence with a functionally similar amino acid. It is suggested that the functionality of similar peptide sequences may be confirmed without undue additional experimentation by use of the method disclosed in this specification.
NZ2012/000005 REFERENCES
Albin et al. (1987) Acute sensory neuropathy-neuronopathy from pyridoxine overdose. Neurology 37: 1729-1732.
Barber (2003) A new view of diabetic retinopathy: a neurodegenerative disease of the eye. Progress in neuro-psychopharmacology and biological psychiatry, 27 (2 ), 283-290.
Bell & Hye (1983) Animal models of diabetes mellitus : physiology and pathology. J. Surg. Res. 35: 433-460.
Callizot et al. (2001) Pyridoxine-induced neuropathy in rats: a sensory neuropathy that responds to 4-methylcatechol . Neurobiol . Dis. 8: 626-635.
Chong & Hester (2007) Diabetic painful neuropathy. Current and future treatment options. Drugs 67: 569-585.
Courteix et al. (1993) Streptozocin-induced diabetic rats: behavioural evidence for a model of chronic pain. Pain. 53: 81-88. Dalton & Dalton (1987) Characteristics of pyridoxine overdose neuropathy syndrome. Acta Neurol. Scand. 76: 8-1 1.
Dyck & Giannini (1996) Pathologic alterations in the diabetic
neuropathies of humans: a review. J. Neuropathol . Exp. Neurol. 55: 1 181 -1 193. Gregg et al. (1992) Cisplatin neurotoxicity: the relationship between dosage, time, and platinum concentration in neurologic tissues, and morphologic evidence of toxicity. J. Clin. Oncol. 10: 795-803.
Harris et al. (2009) Synthetic analogues of neural regeneration peptides . International application no. PCT/US2008/011951 (publ. no. WO
2009/051844).
Helgren et al. (1997) Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large-fiber sensory neuropathy. J. Neurosci. 17: 372-382.
Jakobsen et al. (1976) Neuropathy in experimental diabetes: an animal model. Br. Med. J. 2: 278-279
Krinke et al. (1985) Pyridoxine megavitaminosis : an analysis of the early changes induced with massive doses of vitamin B6 in rat primary sensory neurons. J Neuropathol. Exp. Neurol. 44: 1 17-129.
0005
Mattingly & Fischer (1983) Peripheral neuropathy following prolonged exposure to streptozotocin-induced diabetes in rats: a teased nerve fiber study. Acta Neuropathol. 59: 133-138.
Perry et al. (2004) Pyridoxine-induced toxicity in rats: a stereological quantification of the sensory neuropathy. Exp Neurol. 190: 133-144.
Perry et al. (2007) Evidence of GLP-I -mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy. Exp. Neurology 203: 293-303.
Quasthoff & Hartung (2002) Chemotherapy-induced peripheral neuropathy. J. Neurol. 249: 9-17.
Schaumburg et al. (1983) Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome N. Engl. J. Med. 309: 445-448.
Schmeichel et al. (2003) Oxidative injury and apoptosis of dorsal root ganglion neurons in chronic experimental diabetic neuropathy. Diabetes 52: 165-171.
Szkudelski, T. (2001) The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res. 50: 536-546.
Tomlinson & Gardiner (2008) Glucose neurotoxicity. Nature Neurosci. Rev. 9:36-45. Windebank & Grisold (2008) Chemotherapy-induced neuropathy. J. Peripher. Nerv. Syst. 13: 27-46.
Windebank et al. (1985) Pyridoxine neuropathy in rats: specific
degeneration of sensory axons . Neurology 35: 1617-1622.
Wuarin-Bierman et al. (1987) Hyperalgesia in spontaneous and experimental animal models of diabetic neuropathy. Diabetologia . 30: 653-658.
Xu et al. (1989) Dose-dependent expression of neuropathy after
experimental pyridoxine intoxication. Neurology 39: 1077-1083.
Yagihashi et al. (2007) Pathology and pathogenic mechanisms of diabetic neuropathy: correlation with clinical signs and symptoms . Diab. Res.
Clin. Prac. 77S: S 184-S 189.
Claims
1) A composition comprising ophthalmologically acceptable excipients and an effective amount of a peptide
comprising the sequence:
GlyArgArgAlaAlaProGlyArgAibGlyGly (SEQ ID N0:1).
2) The composition of claim 1 where the peptide comprises the 11 amino acid residue sequence:
GlyArgArgAlaAlaProGlyArgAibGlyGly (SEQ ID N0:1) and ophthalmologically acceptable derivatives thereof.
3) The composition of claim 2 where the C-terminus of the peptide is amidated to give the ophthalmologically acceptable derivative GlyArgArgAlaAlaProGlyArgAibGlyGly- NH2 (SEQ ID NO: 2) .
4) A composition comprising ophthalmologically acceptable excipients and an effective amount of the amidated peptide GlyArgArgAlaAlaProGlyArgAibGlyGly-NH2 (SEQ ID NO: 2) .
5) A method of inhibiting degeneration of cells of the
retina of a subject comprising the step of:
• administering to the subject an effective amount of at least one of the peptides selected from :
GlyArgArgAlaAlaProGlyArgAibGlyGly (SEQ ID NO:l) and
GlyArgArgAlaAlaProGlyArgAibGlyGly-NH2 (SEQ ID
NO: 2) .
6) The method of claim 5 wherein the peptide selected is GlyArgArgAlaAlaProGlyArgAibGlyGly-NH2 (SEQ ID N0:2).
7) The method of claim 5 or claim 6 wherein the
administering to the subject is by way of an intraocular inj ection .
8) The method of any one of claims 5 to 7 where the subject has been diagnosed as having the metabolic disorder diabetes mellitus.
9) The method of claim 8 where the subject is selected from the group consisting of: humans and companion animals.
10) A method of inhibiting degeneration of cells of the
retina of a diabetic subject by administering to the subject by intraocular injection a composition
comprising ophthalmologically acceptable excipients and an effective amount of at least one of the peptides designated SEQ ID NO: 1 or SEQ ID NO: 2.
11) A method of transplanting a retina from a donor subject to a recipient subject comprising the step of
intravitreal administration of an effective amount of at least one of the peptides designated SEQ ID NO: 1 or SEQ ID NO: 2 to the eye of the donor prior to
transplantation of the retina.
12) The method of claim 11 wherein the peptide selected is GlyArgArgAlaAlaProGlyArgAibGlyGly-NH2 (SEQ ID NO:2).
13) The method of claim 11 or claim 12 where the subject is selected from the group consisting of: humans and companion animals.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ590769 | 2011-01-28 | ||
| NZ59076911 | 2011-01-28 |
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| Publication Number | Publication Date |
|---|---|
| WO2012102625A2 true WO2012102625A2 (en) | 2012-08-02 |
| WO2012102625A3 WO2012102625A3 (en) | 2012-11-01 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/NZ2012/000005 WO2012102625A2 (en) | 2011-01-28 | 2012-01-27 | Therapeutic composition |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2877195A4 (en) * | 2012-07-27 | 2015-12-02 | Curonz Holdings Company Ltd | Method of treating optic nerve damage, ophthalmic ischemia or ophthalmic reperfusion injury |
| JP2016514954A (en) * | 2013-03-08 | 2016-05-26 | クロンズ ホールディングズ カンパニー リミテッドＣｕｒｏｎｚ Ｈｏｌｄｉｎｇｓ Ｃｏｍｐａｎｙ Ｌｉｍｉｔｅｄ | Nerve regeneration peptide and use thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5919813A (en) * | 1998-03-13 | 1999-07-06 | Johns Hopkins University, School Of Medicine | Use of a protein tyrosine kinase pathway inhibitor in the treatment of diabetic retinopathy |
| US20050131212A1 (en) * | 2001-08-24 | 2005-06-16 | Neuren Pharmaceuticals Ltd. | Neural regeneration peptides and methods for their use in treatment of brain damage |
| WO2009051844A1 (en) * | 2007-10-17 | 2009-04-23 | Neuren Pharmaceuticals Limited | Synthetic analogues of neural regeneration peptides |
| US20090148886A1 (en) * | 2007-12-07 | 2009-06-11 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Methods of identifying compounds that decrease intraocular pressure |
-
2012
- 2012-01-27 WO PCT/NZ2012/000005 patent/WO2012102625A2/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5919813A (en) * | 1998-03-13 | 1999-07-06 | Johns Hopkins University, School Of Medicine | Use of a protein tyrosine kinase pathway inhibitor in the treatment of diabetic retinopathy |
| US5919813C1 (en) * | 1998-03-13 | 2002-01-29 | Univ Johns Hopkins Med | Use of a protein tyrosine kinase pathway inhibitor in the treatment of diabetic retinopathy |
| US20050131212A1 (en) * | 2001-08-24 | 2005-06-16 | Neuren Pharmaceuticals Ltd. | Neural regeneration peptides and methods for their use in treatment of brain damage |
| WO2009051844A1 (en) * | 2007-10-17 | 2009-04-23 | Neuren Pharmaceuticals Limited | Synthetic analogues of neural regeneration peptides |
| US20090148886A1 (en) * | 2007-12-07 | 2009-06-11 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Methods of identifying compounds that decrease intraocular pressure |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2877195A4 (en) * | 2012-07-27 | 2015-12-02 | Curonz Holdings Company Ltd | Method of treating optic nerve damage, ophthalmic ischemia or ophthalmic reperfusion injury |
| AU2013293645B2 (en) * | 2012-07-27 | 2018-04-12 | Curonz Holdings Company Limited | Method of treating optic nerve damage, ophthalmic ischemia or ophthalmic reperfusion injury |
| JP2016514954A (en) * | 2013-03-08 | 2016-05-26 | クロンズ ホールディングズ カンパニー リミテッドＣｕｒｏｎｚ Ｈｏｌｄｉｎｇｓ Ｃｏｍｐａｎｙ Ｌｉｍｉｔｅｄ | Nerve regeneration peptide and use thereof |
| EP2964332A4 (en) * | 2013-03-08 | 2016-09-14 | Curonz Holdings Company Ltd | Neural regeneration peptides and uses therefor |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2012102625A3 (en) | 2012-11-01 |
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