CA2336218A1 - Neurotrophic factors - Google Patents

Neurotrophic factors Download PDF

Info

Publication number
CA2336218A1
CA2336218A1 CA002336218A CA2336218A CA2336218A1 CA 2336218 A1 CA2336218 A1 CA 2336218A1 CA 002336218 A CA002336218 A CA 002336218A CA 2336218 A CA2336218 A CA 2336218A CA 2336218 A1 CA2336218 A1 CA 2336218A1
Authority
CA
Canada
Prior art keywords
polypeptide
neublastin
seq
nucleic acid
nos
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002336218A
Other languages
French (fr)
Other versions
CA2336218C (en
Inventor
Teit E. Johansen
Nikolaj Blom
Claus Hansen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
NsGene AS
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2336218A1 publication Critical patent/CA2336218A1/en
Application granted granted Critical
Publication of CA2336218C publication Critical patent/CA2336218C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/475—Growth factors; Growth regulators
    • C07K14/4756—Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/06—Anabolic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • 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
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/02—Antidotes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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

Abstract

The invention relates to neublastin neurotrophic factor polypeptides, nuclei c acids encoding neublastin polypeptides, and antibodies that bind specificall y to neublastin polypeptides as well as methods of making and methods of using the same.

Claims (67)

1. An isolated neublastin nucleic acid comprising the sequence of any one of SEQ ID NOS: 1, 3, 8 or 13, and which codes on expression for a neublastin polypeptide which comprises at least 70% homology to SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12.
2. A nucleic acid sequence comprising an open reading frame which codes on expression for a neublastin polypeptide or a bioactive polypeptide derived therefrom having at least 70% homology to SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12.
3. The nucleic acid sequence of claim 2, wherein the bioactive polypeptide is selected from the group consisting of SEQ ID NOS: 5, 6, 7, 10, 11 or 12.
4. A nucleic acid that hybridizes specifically under high stringency solution hybridization conditions to the nucleic acid of claims 1-3.
5. A nucleic acid that comprises a nucleic acid sequence that is complementary to the nucleic acid of claim 4.
6. A method of using a nucleic acid of any one of claims 1-5, comprising the step of causing a polypeptide encoded by said nucleic acid to be expressed in a cell.
7. The method of claim 6, further comprising the step of administering said nucleic acid to an animal, and causing said polypeptide to be expressed in said anima.
8. A vector comprising the nucleic acid of any one of claims 1-5.
9. The vector of claim 8, wherein said vector is an expression vector.
10. A method of using the vector of claim 9, comprising the step of causing a polypeptide encoded by said nucleic acid to be expressed from said nucleic acid.
11. A cell transformed with the nucleic acid of any one of claims 1-5.
12. The cell of claim 11, wherein said cell its selected from the group consisting of mammalian cells, fungal cells, yeast cell, insect cells and bacterial cells.
13. The cell of claim 12, wherein said cell is a Chinese hamster ovary cell.
14. The cell of claim 12, wherein said cell is a cell derived from the mammalian central nervous system.
15. A neublastin neurotrophic factor polypeptide comprising any one of the amino acid sequences set forth in SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12.
16. The polypeptide of claim 15, wherein said polypeptide is glycosylated.
17. The polypeptide of claim 15, wherein said polypeptide is coded for by a nucleic acid of any one of claims 1-5.
18. A method of making the polypeptide of any one of claims 15-16, said method comprising the step of expressing said polypeptide from a neublastin neurotrophic factor nucleic acid.
19. The method of claim 18, comprising the step of culturing a cell comprising said neublastin neurotrophic factor nucleic acid in a culture medium which permits the production of said polypeptide.
20. The method of claim 19, further comprising the step of recovering said polypeptide from said culture medium.
21. A purified polypeptide obtained by the method of claim 20.
22. A composition comprising the polypeptide of any one of claims 15-17 or 21, and a pharmaceutically acceptable carrier.
23. A polypeptide having an amino acid sequence which is at least 90%
homologous to any one of the sequences set forth in SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12.
24. A method of administering the polypeptide of any one of claims 15-17 and 21, comprising the step of delivering said polypeptide to an in vitro cell culture or in vivo to a mammal.
25. The method of claim 24, wherein said administration comprises systemic administration.
26. The method of claim 24, wherein said mammal is afflicted with a condition selected from the group consisting of cerebral iachaemic neuronal damage, traumatic brain injury, peripheral neuropathy, Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and memory impairment.
27. The method of claim 24, wherein said mammal is afflicted with a neuronal disorder of the peripheral nervous system, the medulla, or the spinal cord.
28. A method of treating a neurodegenerative disease or disorder in an animal, comprising administering to said animal one or more of the neublastin nucleic acids set forth in SEQ ID NOS: 1, 3, 8 or 13.
29. A method of treating a neurodegenerative disease or disorder in an animal, comprising administering to said animal a neublastin polypeptide one or more of the neublastin polypeptides set forth in SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12.
30. An antibody that binds to any one of the polypeptides set forth in SEQ ID
NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12.
31. The antibody of claim 30, wherein said antibody is a monoclonal antibody.
32. A method of determining whether a neurodegenerative disease or disorder in an animal is associated with an altered activity in a neublastin neurotrophic factor polypeptide, said method comprising the steps of:
(a) contacting a biological sample from said animal with the antibody of claims 30 or 31, (b) determining whether an immune complex forms between said antibody and said protein, (c) comparing a level of said immune complex that forms in said sample with a level of said immune complex that forms in a corresponding biologicaae sample from a patient lacking said neural condition, and (d) determining from said comparison whether said disease or disorder is associated with said altered level of activity in said neublastin neurotrophic factor polypeptide.
33. A nucleic acid comprising any one of the sequences set forth in SEQ ID
NOS: 17, 18, 19, 20, 23, 24, 25, 26, or 28.
34. A method of producing any one of the polypeptides set forth in set forth in SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12, comprising culturing a cell that contains any one of the nucleic acid sequences set forth in SEQ ID NOS: 1, 3, 8 or 13 under conditions permitting the production of the polypeptide, and recovering the polypeptide from the culture medium.
35. A method for producing a neublastin polypeptide of any one of claims 15, 23 or 26, the method comprising:
(a) introducing a polynucleotide which codes on expression for a neublastin polypeptide into a cell, or introducing a regulatory sequence by homologous recombination into a cell, such that the regulatory sequence regulates expression of an endogenous neublastin gene, to make a neublastin production cell;

(b) culturing the neublastin production cell under culture conditions which result in expression of a neublastin polypeptide.
36. A neublastin polypeptide comprising:
(a) conserved Cys residues characteristic of the GDNF family and the TGF-.beta. superfamily; and (b) at least 70% homology to any one of the sequences set forth in SEQ
ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12, wherein said neublastin polypeptide exhibits neurotrophic activity.
37. The neublastin polypeptide of claim 36, wherein the polypeptide has a C-terminal amino acid sequence as set forth in AA72-AA105 of SEQ ID NO: 2.
38. The neublastin polypeptide of claim 36, wherein the polypeptide has a C-terminal amino acid sequence as set forth in AA41-AA105 of SEQ ID NO: 2.
39. The neublastin polypeptide of any one of claims 36, 37 or 38, wherein said homology to any one of the sequences set forth in SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12 is greater than 85%.
40. The neublastin polypeptide of any one of claims 36, 37 or 38, wherein said homology to any one of the sequences set forth in SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12 is greater than 95%.
41. A neublastin polypeptide of any one of SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12, and variants thereof with conservative amino acid substitutions.
42. The neublastin polypeptide of claim 41 wherein the conservative amino acid substitutions represent less than 10% of the total number of residues in the polypeptide.
43. The neublastin polypeptide of claim 41 wherein the conservative amino acid substitutions represent less than 2% of the polypeptide.
44. The neublastin polypeptide of claim 41 wherein the conservative amino acid substitutions represent a single amino acid substitution in the mature sequence, wherein the both the substituted and replacement amino acid are non-cyclic.
45. An isolated nucleic acid sequence as set forth in any one of SEQ ID
NOS: 17, 18, 19, 20, 23, 24, 25, 26 or 28.
46. An isolated nucleic acid sequence comprising nucleotides 721 - 865 of SEQ ID NO: 1, nucleotides 718 - 861 of SEQ ID NO: 3, or nucleotides 718 - 861 of SEQ ID NO: 8.
47. An isolated nucleic acid sequence consisting of between 10-25 contiguous nucleotides falling within or derived from any one of the sequences of claim 46.
48. An isolated nucleic acid sequence comprising nucleotides 1-10 of SEQ
1D NO: 1, or nucleotides 1 - 57 of SEQ ID NO: 8.
49. An isolated nucleic acid sequence consisting of between 10-25 contiguous nucleotides falling within or derived from any one of the sequences of claim 48.
50. A method for identifying, isolating or amplifying a neublastin nucleic acid sequence comprising using the nucleic acids of any one of claims 45-49 as a primer or a probe.
51. A neublastin nucleic acid comprising any one of SEQ ID NOS: 1, 3, 8 or 13, and which codes on expression for a neublastin polypeptide which comprises at least 70% homology to SEQ ID NOS: 2, 4, 5, 6, 7, 9, 10, 11 or 12, wherein said nucleic acid is isolated by the method of claim 50.
52. An isolated nucleic acid sequence comprising the sequence set forth in SEQ ID NO: 13.
53. A synthetic gene encoding a neublastin polypeptide, the synthetic gene having a sequence set forth in SEQ ID NOS: 29 or 30.
54. A neublastin peptide having any of the following sequences:
GPGSRARAAGARGC (AA 30-43 of SEQ ID NO: 9);

LGHRSDELVRFRFC (AA 57-70 of SEQ ID NO: 9);

CRRARSPHDLSL (AA 74-85 of SEQ ID NO: 9);

LRPPPGSRPVSQPC (AA 94-107 of SEQ ID NO:9};

STWRTVDRLSATAC (AA 123-136 of SEQ ID N0: 9);

CRLRSQLVPVRALGLGHRSDELVRFRFC (AA 43-70 of SEQ ID NO: 9);

CRRARSPHDLSLASLLGAGALRPPPGSRPVSQPC (AA 74-107 of SEQ ID
NO: 9);

CRPTRYEAVSFMDVNSTWRTVDRLSATAC (AA 108-136 of SEQ ID NO: 9);

CRPTRYEAVSFMDVNST (AA 108-124 of SEQ ID NO: 9); or ALRPPPGSRPVSQPC (AA 93-107 of SEQ ID NO: 9).
55. An antibody generated against any of the peptides of claim 54.
56. The neublastin polypeptide of claim 36 wherein said polypeptide com-prises seven cysteine residues conserved as set forth in SEQ ID NO: 2 at positions 8, 35, 39, 72, 73, 101 and 103, or as in SEQ. ID NOS: 4 and 9 at positions 43, 70, 74, 107, 108, 136 and 138.
57. A kit comprising, in one or more containers, a substance selected from the group consisting of a neublastin polypeptide according to any one of claims 15, 23 or 36;
an antibody against a neublastin polypeptide;
one or more nucleic acid probes capable of hybridizing to RNA of neublastin;
or at least one pairs of nucleic acid primers capable of priming amplification of at least a portion of a neublastin gene.
58. A method of diagnosing or screening for the presence of or a predisposition for developing a disease or disorder characterised by an aberrant level of a neublastin polypeptide according to any one of claims 15, 23 or 36 in a subject comprising measuring the level of said neublastin polypeptide, RNA encoding the neublastin polypeptide, or functional activity of the neublastin polypeptide in a sample derived from the subject, in which an increase or decrease in the level of the neublastin polypeptide, neublastin RNA, or functional activity of neublastin polypeptide in the sample, relative to the level of the neublastin polypeptide, neublastin RNA or functional activity of neublastin found in an analogous sample not having the disease or disorder or a predisposition for developing the disease or disorder, indicates the presence of the disease or disorder or a predisposition for developing the disease or disorder.
59. A method for screening a purified neublastin polypeptide according to any one of claims 15, 23 or 36, or derivative or fragment thereof, or a modulator of the activity of the foregoing, for activity in treating or preventing a disease, the method comprising (a} measuring alterations in the phenotype, genotype, behaviour, survival or proliferation of cells from a cell line or test animal, said cells or animal being derived from or display characteristics associated with the disease, and said cells or animals having been contacted with or administered with the neublastin polypeptide, derivative, fragment, or modulator, and (b} comparing said alterations with the phenotype, genotype, behavior, survival or proliferation in cells or animals not so contacted with or administered with the nebulation polypeptide, derivative, fragment, or modulator.
60. A method of treating peripheral neuropathies in a mammal, which method comprises administering a therapeutically effective amount of a neublastin polypeptide according to any one of claims 16, 23 or 36, wherein said peripheral neuropathy is selected from the group consisting of trauma-induced neuropathies, chemotherapy-induced neuropathies, toxin-induced neuropathies, drug-induced neuropathies, vitamin-deficiency-induced neuropathies; idiopathic neuropathies; and diabetic neuropathies.
61. The method of claim 24 wherein the neublastin is delivered directly into the central nervous system.
62. The method of claim 24 wherein the neublastin is delivered systemically by subcutaneous injection, intravenous administration, or intravenous infusion administration.
63. A method of using the sequence of one or more nucleic acids of any one of claims 1-5 or 45-49 in a computer program for identifying, isolating or detecting novel nucleic acid sequences.
64. A fixed substrate or DNA chip comprising one or more nucleic acids of any one of claims 1-5, 33 or 45-49.
65. A method of using the fixed substrate or DNA chip of claim 64 for identifying, isolating or detecting novel nucleic acid sequences.
66. A method of using the sequence of one or more polypeptides of any one of claims 15-17, 21, 23 or 36-44 in a computer program for identifying, isolating or detecting novel nucleic acid sequences.
67. A method for identifying a candidate compound that induces a neuroblastin-mediated biological effect, the method comprising the steps of:

(a) providing a test cell, said cell when contacted with neublastin polypeptide of any one of claims 15, 23 or 36 being induced to express a detectable product;

(b) exposing the cell to the candidate compound; and (c) detecting the detectable product, said expression of the detectable product indicating the ability of the candidate compound to induce said neuroblastin-mediated biological effect.
CA2336218A 1998-07-06 1999-07-05 Neurotrophic factors Expired - Fee Related CA2336218C (en)

Applications Claiming Priority (15)

Application Number Priority Date Filing Date Title
DKPA199800904 1998-07-06
DK199800904 1998-07-06
US9222998P 1998-07-09 1998-07-09
US60/092,229 1998-07-09
DKPA199801048 1998-08-19
DK199801048 1998-08-19
US9777498P 1998-08-25 1998-08-25
US60/097,774 1998-08-25
DKPA199801265 1998-10-06
DK199801265 1998-10-06
US10390898P 1998-10-13 1998-10-13
US60/103,908 1998-10-13
US09/347,613 1999-07-02
US09/347,613 US6593133B1 (en) 1998-07-06 1999-07-02 Neurotrophic factors
PCT/DK1999/000384 WO2000001815A2 (en) 1998-07-06 1999-07-05 Neurotrophic factors

Publications (2)

Publication Number Publication Date
CA2336218A1 true CA2336218A1 (en) 2000-01-13
CA2336218C CA2336218C (en) 2011-09-27

Family

ID=27561795

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2336218A Expired - Fee Related CA2336218C (en) 1998-07-06 1999-07-05 Neurotrophic factors

Country Status (18)

Country Link
US (6) US6593133B1 (en)
EP (2) EP1095140B1 (en)
JP (5) JP2002519061A (en)
KR (1) KR100743376B1 (en)
AT (1) ATE522609T1 (en)
AU (1) AU755114B2 (en)
CA (1) CA2336218C (en)
CY (1) CY1112101T1 (en)
DK (1) DK1095140T3 (en)
EE (1) EE05590B1 (en)
ES (1) ES2373173T3 (en)
HU (1) HU227870B1 (en)
IS (1) IS2835B (en)
NZ (1) NZ508994A (en)
PT (1) PT1095140E (en)
SI (1) SI1095140T1 (en)
TR (1) TR200100056T2 (en)
WO (1) WO2000001815A2 (en)

Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020055467A1 (en) * 1998-07-06 2002-05-09 Johansen Teit E. Novel neurotrophic factors
US6593133B1 (en) * 1998-07-06 2003-07-15 Nsgene A/S Neurotrophic factors
US7067473B1 (en) * 1998-07-14 2006-06-27 Janssen Pharmaceutica N.V. Neurotrophic growth factor
BRPI9912819B8 (en) * 1998-07-14 2021-05-25 Janssen Pharmaceutica Nv expression vector, transgenic microorganism, uses of a nucleic acid molecule and a neurotrophic growth factor, as well as pharmaceutical compositions comprising the same
US6284540B1 (en) 1998-09-29 2001-09-04 Washington University Artemin, a novel neurotrophic factor
JP2002531128A (en) * 1998-12-09 2002-09-24 アムジエン・インコーポレーテツド Neurotrophic factor GRNF4
WO2000054813A2 (en) * 1999-03-15 2000-09-21 Chiron Corporation Use of recombinant gene delivery vectors for treating or preventing diseases of the eye
US6943153B1 (en) 1999-03-15 2005-09-13 The Regents Of The University Of California Use of recombinant gene delivery vectors for treating or preventing diseases of the eye
EP1867719A3 (en) * 1999-06-02 2008-03-19 Genentech, Inc. Methods and compositions for inhibiting neoplastic cell growth
NZ526610A (en) * 2000-12-22 2009-08-28 Genentech Inc New use of artemin, a member of the GDNF ligand family
UA100967C2 (en) * 2001-02-01 2013-02-25 Байоджен Айдек Ма Інк. Normal;heading 1;heading 2;heading 3;POLYMER CONJUGATES OF NEUBLASTIN AND METHODS OF USING SAME
US7442370B2 (en) * 2001-02-01 2008-10-28 Biogen Idec Ma Inc. Polymer conjugates of mutated neublastin
US7276580B2 (en) * 2001-03-12 2007-10-02 Biogen Idec Ma Inc. Neurotrophic factors
US20040077543A1 (en) * 2001-03-28 2004-04-22 Sah Dinah W. Y. Treatment using neublastin polypeptides
WO2002078730A2 (en) * 2001-03-28 2002-10-10 Biogen, Inc. Use of neublastin polypeptides for treating neuropathic pain
AU2003249013A1 (en) * 2002-07-09 2004-01-23 Bristol-Myers Squibb Company Polynucleotides encoding a novel testis-specific tubulin tyrosine-ligase-like protein, bgs42
JP4571776B2 (en) * 2002-11-05 2010-10-27 Ｊｘ日鉱日石エネルギー株式会社 Lubricating oil composition
SI1594436T1 (en) 2003-01-31 2011-01-31 Biogen Idec Inc Mutated neublastin
NZ543365A (en) 2003-04-18 2009-02-28 Biogen Idec Inc Polymer-conjugated glycosylated neublastin
ES2323066T3 (en) 2003-06-10 2009-07-06 Nsgene A/S IMPROVED SECRETION OF NEUBLASTIN.
US7598059B2 (en) 2003-10-02 2009-10-06 Biogen Idec Ma Inc. Neublastin expression constructs
US20060239966A1 (en) * 2003-10-20 2006-10-26 Tornoee Jens In vivo gene therapy of parkinson's disease
KR101241551B1 (en) * 2004-08-19 2013-03-11 바이오겐 아이덱 엠에이 인코포레이티드 Refolding transforming growth factor beta family proteins
KR101215697B1 (en) * 2004-08-19 2012-12-28 바이오겐 아이덱 엠에이 인코포레이티드 Neublastin variants
BRPI0614419A2 (en) * 2005-08-16 2011-03-29 Copenhagen University gdnf-derived peptides
WO2007042040A2 (en) * 2005-10-11 2007-04-19 Ns Gene A/S TREATMENT OF RETINOPATHIES USING GFRα3 AGONISTS
TWI501774B (en) 2006-02-27 2015-10-01 Biogen Idec Inc Treatments for neurological disorders
EP1993590B1 (en) * 2006-03-01 2013-12-25 Biogen Idec MA Inc. Compostions and methods for administering gdnf ligand family proteins
TWI445544B (en) * 2007-05-01 2014-07-21 Biogen Idec Inc Compositions and methods for increasing vascularization
AU2008269689A1 (en) * 2007-06-27 2008-12-31 Auckland Uniservices Limited Polypeptides and polynucleotides for artemin and related ligands, and methods of use thereof
WO2009020964A2 (en) * 2007-08-08 2009-02-12 Biogen Idec Ma Inc. Anti-neublastin antibodies and uses thereof
TWI702955B (en) 2012-05-15 2020-09-01 澳大利亞商艾佛蘭屈澳洲私營有限公司 Treatment of amd using aav sflt-1
US10376562B2 (en) 2013-03-15 2019-08-13 The Jackson Laboratory Methods for promoting wound healing and hair growth comprising GDNF administration
PL3058371T3 (en) 2013-10-14 2021-11-08 Indiana University Research And Technology Corporation Use of acamprosate to modulate erk 1-2 activation in animal models for fxs and asd and individuals diagnosed with fxs and asd
CN112626125A (en) 2014-03-17 2021-04-09 阿德夫拉姆生物技术股份有限公司 Compositions and methods for enhanced gene expression in cone cells
EP3804747A1 (en) * 2015-01-18 2021-04-14 Gloriana Therapeutics, Inc. Therapeutic protein formulations
CA2978068A1 (en) 2015-03-02 2016-09-09 Adverum Biotechnologies, Inc. Compositions and methods for intravitreal delivery of polynucleotides to retinal cones
GB2545763A (en) 2015-12-23 2017-06-28 Adverum Biotechnologies Inc Mutant viral capsid libraries and related systems and methods

Family Cites Families (54)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4352883A (en) 1979-03-28 1982-10-05 Damon Corporation Encapsulation of biological material
US4353888A (en) 1980-12-23 1982-10-12 Sefton Michael V Encapsulation of live animal cells
US4407957A (en) 1981-03-13 1983-10-04 Damon Corporation Reversible microencapsulation of a core material
US5525464A (en) 1987-04-01 1996-06-11 Hyseq, Inc. Method of sequencing by hybridization of oligonucleotide probes
US4883666A (en) 1987-04-29 1989-11-28 Massachusetts Institute Of Technology Controlled drug delivery system for treatment of neural disorders
US5158881A (en) 1987-11-17 1992-10-27 Brown University Research Foundation Method and system for encapsulating cells in a tubular extrudate in separate cell compartments
US5283187A (en) 1987-11-17 1994-02-01 Brown University Research Foundation Cell culture-containing tubular capsule produced by co-extrusion
DE3829766A1 (en) 1988-09-01 1990-03-22 Akzo Gmbh METHOD FOR PRODUCING MEMBRANES
DE3829752A1 (en) 1988-09-01 1990-03-22 Akzo Gmbh INTEGRAL ASYMMETRICAL POLYAETHERSULPHONE MEMBRANE, METHOD FOR THE PRODUCTION AND USE FOR ULTRAFILTRATION AND MICROFILTRATION
US5082670A (en) 1988-12-15 1992-01-21 The Regents Of The University Of California Method of grafting genetically modified cells to treat defects, disease or damage or the central nervous system
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5800992A (en) 1989-06-07 1998-09-01 Fodor; Stephen P.A. Method of detecting nucleic acids
US5084350A (en) 1990-02-16 1992-01-28 The Royal Institution For The Advance Of Learning (Mcgill University) Method for encapsulating biologically active material including cells
US5618531A (en) 1990-10-19 1997-04-08 New York University Method for increasing the viability of cells which are administered to the brain or spinal cord
DK0585368T3 (en) 1991-04-25 1998-03-16 Univ Brown Res Found Implantable biocompatible immuno-insulating vehicle for delivery of selected therapeutic products
ES2123001T5 (en) 1991-06-27 2009-04-16 Bristol-Myers Squibb Company CTL4A RECEIVER, FUSION PROTEINS CONTAINING IT AND ITS USES.
CA2112674C (en) 1991-07-02 2005-10-04 John S. Patton Method and device for delivering aerosolized medicaments
US5750376A (en) 1991-07-08 1998-05-12 Neurospheres Holdings Ltd. In vitro growth and proliferation of genetically modified multipotent neural stem cells and their progeny
ES2225819T3 (en) 1991-09-20 2005-03-16 Amgen Inc. GLIAL ORIGIN NEUROTROPHIC FACTOR.
US5733761A (en) 1991-11-05 1998-03-31 Transkaryotic Therapies, Inc. Protein production and protein delivery
US5284350A (en) * 1992-05-22 1994-02-08 Medical Composite Technology Foldable wheelchair and side frame assembly
US5785049A (en) 1994-09-21 1998-07-28 Inhale Therapeutic Systems Method and apparatus for dispersion of dry powder medicaments
ATE220327T1 (en) 1992-09-29 2002-07-15 Inhale Therapeutic Syst PULMONARY RELEASE OF ACTIVE FRAGMENTS OF THE PARATHORMONE
CA2092271C (en) 1993-03-09 2009-10-13 Eddie Reed Use of g-csf for treating taxol side-effects
EP1179350A3 (en) 1993-08-12 2003-01-02 Cytotherapeutics, Inc. Encapsulated cell system for implantation into the human CNS
DE4339605A1 (en) 1993-11-20 1995-05-24 Beiersdorf Ag Deodorant active ingredient combinations based on alpha, omega-alkanedicarboxylic acids and fatty acid partial glycerides
US5834029A (en) 1994-07-20 1998-11-10 Cytotherapeutics, Inc. Nerve guidance channel containing bioartificial three-dimensional hydrogel extracellular matrix derivatized with cell adhesive peptide fragment
US5795716A (en) 1994-10-21 1998-08-18 Chee; Mark S. Computer-aided visualization and analysis system for sequence evaluation
US5780014A (en) 1995-04-14 1998-07-14 Inhale Therapeutic Systems Method and apparatus for pulmonary administration of dry powder alpha 1-antitrypsin
US5654007A (en) 1995-06-07 1997-08-05 Inhale Therapeutic Systems Methods and system for processing dispersible fine powders
US5739307A (en) 1995-08-28 1998-04-14 Washington University Polynucleotide encoding neurturin neurotrophic factor
US5733729A (en) 1995-09-14 1998-03-31 Affymetrix, Inc. Computer-aided probability base calling for arrays of nucleic acid probes on chips
US5641749A (en) * 1995-11-29 1997-06-24 Amgen Inc. Method for treating retinal ganglion cell injury using glial cell line-derived neurothrophic factor (GDNF) protein product
US6299895B1 (en) * 1997-03-24 2001-10-09 Neurotech S.A. Device and method for treating ophthalmic diseases
US6878544B2 (en) * 1996-04-19 2005-04-12 Neurotech Sa Retinal cell lines with extended life-span and their applications
KR20060024843A (en) 1996-05-08 2006-03-17 바이오겐 아이덱 엠에이 인코포레이티드 Ret ligand (retl) for stimulating neural and renal growth
US5754524A (en) 1996-08-30 1998-05-19 Wark; Barry J. Computerized method and system for analysis of an electrophoresis gel test
KR100195886B1 (en) 1996-11-01 1999-06-15 김상조 Pharmaceutical composition for treating diabetes mellitus
WO1998032869A1 (en) 1997-01-29 1998-07-30 Neurosearch A/S Expression vectors and methods for in vivo expression of therapeutic polypeptides
US20020192209A1 (en) * 1997-09-17 2002-12-19 Genentech, Inc. Methods and compositions for inhibiting neoplastic cell growth
US20020055467A1 (en) * 1998-07-06 2002-05-09 Johansen Teit E. Novel neurotrophic factors
US6593133B1 (en) * 1998-07-06 2003-07-15 Nsgene A/S Neurotrophic factors
BRPI9912819B8 (en) 1998-07-14 2021-05-25 Janssen Pharmaceutica Nv expression vector, transgenic microorganism, uses of a nucleic acid molecule and a neurotrophic growth factor, as well as pharmaceutical compositions comprising the same
AU778998B2 (en) * 1998-09-22 2004-12-23 University Of Maryland At Baltimore Cystine knot growth factor mutants
US6284540B1 (en) * 1998-09-29 2001-09-04 Washington University Artemin, a novel neurotrophic factor
JP2002531128A (en) * 1998-12-09 2002-09-24 アムジエン・インコーポレーテツド Neurotrophic factor GRNF4
ES2321954T3 (en) * 1999-03-08 2009-06-15 Genentech, Inc. COMPOSITIONS AND PROCEDURES FOR TUMORS DIAGNOSIS.
US6361771B1 (en) * 1999-04-06 2002-03-26 Neurotech S.A. ARPE-19 as a platform cell line for encapsulated cell-based delivery
PT1185648E (en) * 1999-06-22 2007-06-29 Genentech Inc Methods and compositions for inhibiting neoplastic cell growth
JP2001329126A (en) 2000-05-22 2001-11-27 Bridgestone Corp Curable composition
EP1325966B1 (en) * 2000-09-12 2009-04-01 JFE Steel Corporation Super-high strength cold-rolled steel sheet and method for production thereof
US7276580B2 (en) * 2001-03-12 2007-10-02 Biogen Idec Ma Inc. Neurotrophic factors
US20040077543A1 (en) * 2001-03-28 2004-04-22 Sah Dinah W. Y. Treatment using neublastin polypeptides
US7598059B2 (en) * 2003-10-02 2009-10-06 Biogen Idec Ma Inc. Neublastin expression constructs

Also Published As

Publication number Publication date
IS5769A (en) 2000-12-14
JP2006122053A (en) 2006-05-18
US6593133B1 (en) 2003-07-15
ES2373173T3 (en) 2012-02-01
AU755114B2 (en) 2002-12-05
ATE522609T1 (en) 2011-09-15
IS2835B (en) 2013-05-15
HUP0103758A3 (en) 2005-11-28
WO2000001815A3 (en) 2000-02-17
SI1095140T1 (en) 2012-01-31
EP2290079A2 (en) 2011-03-02
EP1095140A2 (en) 2001-05-02
EE200100008A (en) 2002-06-17
JP2007252381A (en) 2007-10-04
NZ508994A (en) 2004-01-30
US6734284B1 (en) 2004-05-11
WO2000001815A2 (en) 2000-01-13
US20120252726A1 (en) 2012-10-04
JP2008133282A (en) 2008-06-12
AU4769399A (en) 2000-01-24
TR200100056T2 (en) 2001-11-21
US20080227703A1 (en) 2008-09-18
JP2005341968A (en) 2005-12-15
HU227870B1 (en) 2012-05-29
US20100234293A1 (en) 2010-09-16
EP2290079A3 (en) 2011-09-07
US20040230043A1 (en) 2004-11-18
EE05590B1 (en) 2012-10-15
KR20010053411A (en) 2001-06-25
HUP0103758A2 (en) 2002-01-28
JP2002519061A (en) 2002-07-02
KR100743376B1 (en) 2007-07-30
PT1095140E (en) 2011-12-16
DK1095140T3 (en) 2011-10-31
CY1112101T1 (en) 2015-11-04
EP1095140B1 (en) 2011-08-31
CA2336218C (en) 2011-09-27

Similar Documents

Publication Publication Date Title
CA2336218A1 (en) Neurotrophic factors
Topilko et al. Krox-20 controls myelination in the peripheral nervous system
Takahashi et al. A null mutation in the human CNTF gene is not causally related to neurological diseases
Stuermer et al. Trying to understand axonal regeneration in the CNS of fish
Tuttle et al. Defects in thalamocortical axon pathfinding correlate with altered cell domains in Mash-1-deficient mice
Harrison et al. Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology
AU2010202722B2 (en) Juvenile hemochromatosis gene (HFE2A), expression products and uses thereof
US8394932B2 (en) Survival motor neurons (SMN) gene: a gene for spinal muscular atrophy
JP2005341968A5 (en)
US8101380B2 (en) Schizophrenia-related isoform of KCNH2 and development of antipsychotic drugs
DE04777457T1 (en) RNA PROCESSING PROTEIN COMPLEXES AND USES THEREOF
JP2005512515A5 (en)
EP2009103A1 (en) Neurotrophic peptides
Parquet et al. Identification of three novel spectrin alpha I/74 mutations in hereditary elliptocytosis: further support for a triple-stranded folding unit model of the spectrin heterodimer contact site
US8871443B2 (en) Schizophrenia-related isoform of KCNH2 and development of antipsychotic drugs
CA2634488A1 (en) Catecholamine regulated protein
KR930701624A (en) Ciliated Neuronal Receptor (CNTFR)
CA2408051A1 (en) Nucleotide sequences involved in increasing or decreasing mammalian ovulation rate
EP0711833B1 (en) Survival motor neuron (SMN) gene: a gene for spinal muscular atrophy
Hayakawa et al. A novel neuropeptide (FRamide) family identified by a peptidomic approach in Hydra magnipapillata
EA006367B1 (en) Schizophrenia-related voltage-gated ion channel gene and protein
Borrego et al. Evaluation of germline sequence variants of GFRA1, GFRA2, and GFRA3 genes in a cohort of Spanish patients with sporadic medullary thyroid cancer
US20080102463A1 (en) Gene 4
EP2032601B1 (en) Peptides regulating the surface expression of the t cell receptor
Dattani The candidate gene approach to the diagnosis of monogenic disorders

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20170705