CA2170523A1 - Cloned glutamic acid decarboxylase - Google Patents
Cloned glutamic acid decarboxylaseInfo
- Publication number
- CA2170523A1 CA2170523A1 CA002170523A CA2170523A CA2170523A1 CA 2170523 A1 CA2170523 A1 CA 2170523A1 CA 002170523 A CA002170523 A CA 002170523A CA 2170523 A CA2170523 A CA 2170523A CA 2170523 A1 CA2170523 A1 CA 2170523A1
- Authority
- CA
- Canada
- Prior art keywords
- polypeptide
- amino acid
- disorder
- patient
- fragment
- 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
Links
- 102000008214 Glutamate decarboxylase Human genes 0.000 title 1
- 108091022930 Glutamate decarboxylase Proteins 0.000 title 1
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 17
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 13
- 229920001184 polypeptide Polymers 0.000 claims abstract 12
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract 4
- 238000000034 method Methods 0.000 claims 29
- 150000001413 amino acids Chemical group 0.000 claims 12
- 239000012634 fragment Substances 0.000 claims 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 9
- 208000035475 disorder Diseases 0.000 claims 7
- 102000040430 polynucleotide Human genes 0.000 claims 4
- 108091033319 polynucleotide Proteins 0.000 claims 4
- 239000002157 polynucleotide Substances 0.000 claims 4
- 210000001744 T-lymphocyte Anatomy 0.000 claims 3
- 150000001875 compounds Chemical class 0.000 claims 3
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 claims 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 239000002777 nucleoside Substances 0.000 claims 2
- 150000003833 nucleoside derivatives Chemical class 0.000 claims 2
- 230000000638 stimulation Effects 0.000 claims 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000004856 Lectins Human genes 0.000 claims 1
- 108090001090 Lectins Proteins 0.000 claims 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 230000004700 cellular uptake Effects 0.000 claims 1
- 238000001514 detection method Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000007850 fluorescent dye Substances 0.000 claims 1
- 210000004408 hybridoma Anatomy 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000007912 intraperitoneal administration Methods 0.000 claims 1
- 238000010253 intravenous injection Methods 0.000 claims 1
- 239000002523 lectin Substances 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 239000007790 solid phase Substances 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 229940104230 thymidine Drugs 0.000 claims 1
- 239000003053 toxin Substances 0.000 claims 1
- 231100000765 toxin Toxicity 0.000 claims 1
- 238000002405 diagnostic procedure Methods 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 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
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/51—Lyases (4)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- 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
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/88—Lyases (4.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y401/00—Carbon-carbon lyases (4.1)
- C12Y401/01—Carboxy-lyases (4.1.1)
- C12Y401/01015—Glutamate decarboxylase (4.1.1.15)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- 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
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/04—Endocrine or metabolic disorders
- G01N2800/042—Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/24—Immunology or allergic disorders
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/975—Kit
Abstract
Isolated polypeptides useful in ameliorating GAD-associated autoimmune disease as well as diagnostic and therapeutic methods of using the peptides are disclosed.
Claims (38)
1. A polypeptide consisting essentially of an amino acid sequence selected from the group consisting of:
KPCSCSKVDVNUAFLHATDL;
NMYAMMIARFKMFPEVKEKG;
TAGTTVYGAFDPLLAVADICKK;
EYLYNIIKNREGYEMVFDGK;
IPPSLRYLEDNEERMSRLSK;
SRLSKVAPVIKARMMEYGTT;
EYGTTMVSYQPLGDKVNFFR;
ATHQDIDFLIEEIERLGQDL;
LAFLQDVMNILLQYVVKSFDRS;
EEILMHCQTTLKYAIKTGHP;
DERGKMIPSKLERRILEAKQ;
KHYDLSYDTGDKALQCGRHV;
AALGIGTDSVILIKCDERGK;
GLLMSRKHKWKLSGVERANS;
LEAKQKGFVPFLVSATAGTT; and VNFFRMVISNPAATHQDIDF .
KPCSCSKVDVNUAFLHATDL;
NMYAMMIARFKMFPEVKEKG;
TAGTTVYGAFDPLLAVADICKK;
EYLYNIIKNREGYEMVFDGK;
IPPSLRYLEDNEERMSRLSK;
SRLSKVAPVIKARMMEYGTT;
EYGTTMVSYQPLGDKVNFFR;
ATHQDIDFLIEEIERLGQDL;
LAFLQDVMNILLQYVVKSFDRS;
EEILMHCQTTLKYAIKTGHP;
DERGKMIPSKLERRILEAKQ;
KHYDLSYDTGDKALQCGRHV;
AALGIGTDSVILIKCDERGK;
GLLMSRKHKWKLSGVERANS;
LEAKQKGFVPFLVSATAGTT; and VNFFRMVISNPAATHQDIDF .
2. An isolated polynucleotide sequence encoding a polypeptide of claim 1.
3. The polynucleotide of claim 2 which is DNA.
4. A method for detecting autoantibody to GAD in a patient specimen which comprises contacting the specimen with a GAD fragment and determ;ning whether autoantibody binds to the fragment.
5. The method of claim 4, wherein the fragment is a polypeptide of at least about 16 amino acids in length and is selected from the amino acid sequence from about amino acid 224 to about amino acid 585 of GAD65.
6. The method of claim 4, wherein the fragment is a polypeptide of claim 1.
7. The method of claim 4, wherein the specimen is blood.
8. The method of claim 4, wherein the peptide is detectably labeled.
9. The method of claim 8, wherein the detectable label is selected from the group consisting of a radioisotope, a fluorescent compound, a colloidal metal, a chemiluminescent compound, a bioluminescent compound, a phosphorescent compound, and an enzyme.
10. The method of claim 4, wherein the peptide is bound to a solid phase.
11. A monoclonal antibody to the peptide of claim 1.
12. A hybridoma cell line capable of producing the monoclonal antibody of claim 9.
13. A vector containing the polynucleotide of claim 2.
14. A host cell transformed with the polynucleotide of claim 2.
15. A method for ameliorating a GAD associated autoimmune disorder in a patient having or at risk of having the disorder, which comprises administering to the patient a therapeutically effective amount of whole GAD65 or a therapeutically effective fragment thereof.
16. The method of claim 15, wherein the therapeutically effective fragment is a polypeptide of at least about 16 amino acids in length and is selected from the amino acid sequence from about amino acid 224 to about amino acid 585 of GAD65.
17. The method of claim 15, wherein the therapeutically effective fragment is selected from the group consisting of:
KPCSCSKVDVNYAFLHATDL;
NMYAMMIARFKMFPEVKEKG;
TAGTTVYGAFDPLLAVADICKK;
EYLYNIIKNREGYEMVFDGK;
IPPSLRYLEDNEERMSRLSK;
SRLSKVAPVIKARMMEYGTT;
EYGTTMVSYQPLGDKVNFFR; and ATHQDIDFLIEEIERLGQDL.
KPCSCSKVDVNYAFLHATDL;
NMYAMMIARFKMFPEVKEKG;
TAGTTVYGAFDPLLAVADICKK;
EYLYNIIKNREGYEMVFDGK;
IPPSLRYLEDNEERMSRLSK;
SRLSKVAPVIKARMMEYGTT;
EYGTTMVSYQPLGDKVNFFR; and ATHQDIDFLIEEIERLGQDL.
18. The method of claim 15, wherein the therapeutically effective fragment is selected from the group consisting of:
KPCSCSKVDVNYAFLHATDL;
LAFLQDVMNILLQYVVKSFDRS;
EEILMHCQTTLKYAIKTGHP;
DERGKMIPSKLERRILEAKQ;
KHYDLSYDTGDKALQCGRHV;
AALGIGTDSVILIKCDERGK;
GLLMSRKHKWKLSGVERANS;
LEAKQKGFVPFLVSATAGTT; and VNFFRMVISNPAATHQDIDF.
KPCSCSKVDVNYAFLHATDL;
LAFLQDVMNILLQYVVKSFDRS;
EEILMHCQTTLKYAIKTGHP;
DERGKMIPSKLERRILEAKQ;
KHYDLSYDTGDKALQCGRHV;
AALGIGTDSVILIKCDERGK;
GLLMSRKHKWKLSGVERANS;
LEAKQKGFVPFLVSATAGTT; and VNFFRMVISNPAATHQDIDF.
19. The method of claim 16, wherein the disorder is IDDM.
20. The method of claim 16, wherein the disorder is stiff man disease.
21. The method of claim 16, wherein the administration is enteral.
22. The method of claim 21, wherein the enteral administration is oral.
23. The method of claim 15 or 16, wherein the administration is parenteral.
24. The method of claim 23, wherein the parenteral administration is by subcutaneous, intramuscular, intraperitoneal, intracavity, transdermal, intranasal, or intravenous injection.
25. The method of claim 15, wherein said administration is at a dosage of about 0.01 mg/kg/dose to about 2000 mg/kg/dose.
26. The method of claim 15, wherein the polypeptide is therapeutically labeled.
27. The method of claim 26, wherein the therapeutic label is selected from the group consisting of a radioisotope, a drug, a lectin, and a toxin.
28. A method for detecting the status of a GAD
associated autoimmune disorder in a patient which comprises contacting a T-cell of the patient with at least one polypeptide of claim 1 and detecting the response of the T-cell to the peptide.
associated autoimmune disorder in a patient which comprises contacting a T-cell of the patient with at least one polypeptide of claim 1 and detecting the response of the T-cell to the peptide.
29. The method of claim 26, wherein the response of the T-cell is stimulation.
30. The method of claim 27, wherein the stimulation is measured by cellular uptake of radiolabelled nucleoside.
31. The method of claim 30, wherein the nucleoside is 3H thymidine.
32. A kit useful for the detection of antibody to the polypeptide of claim 1 in a specimen suspected of containing such antibody, the kit comprising carrier means compartmentalized to receive in close confinement therein one or more containers comprising a container containing the polypeptide of claim 1.
33. A kit useful for determining the status of a GAD
associated disorder in a specimen of a patient, the kit comprising carrier means compartmentalized to receive in close confinement therein one or more containers comprising a container containing a polypeptide of claim 1.
associated disorder in a specimen of a patient, the kit comprising carrier means compartmentalized to receive in close confinement therein one or more containers comprising a container containing a polypeptide of claim 1.
34. A method for detecting a GAD associated autoimmune disorder in a patient having or at risk of having the disorder, which comprises administering to the patient a diagnostically effective amount of a diagnostically effective fragment of GAD65.
35. The method of claim 34, wherein the diagnostically effective fragment is a polypeptide of at least about 16 amino acids in length and is selected from the amino acid sequence from about amino acid 34 to 573 of GAD65.
36. The method of claim 35, wherein the diagnostically effective fragment is selected from the group consisting of:
KPCSCSKVDVNYAFLHATDL;
LAFLQDVMNILLQYVVKSFDRS;
EEILMHCQTTLKYAIKTGHP;
DERGKMIPSKLERRILEAKQ;
KHYDLSYDTGDKALQCGRHV;
AALGIGTDSVILIKCDERGK;
GLLMSRKHKWKLSGVERANS;
LEAKQKGFVPFLVSATAGTT; and VNFFRMVISNPAATHQDIDF.
KPCSCSKVDVNYAFLHATDL;
LAFLQDVMNILLQYVVKSFDRS;
EEILMHCQTTLKYAIKTGHP;
DERGKMIPSKLERRILEAKQ;
KHYDLSYDTGDKALQCGRHV;
AALGIGTDSVILIKCDERGK;
GLLMSRKHKWKLSGVERANS;
LEAKQKGFVPFLVSATAGTT; and VNFFRMVISNPAATHQDIDF.
37. The method of claim 35, wherein the disorder is IDDM.
38. The method of claim 35, wherein the disorder is stiff man disease.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/123,859 US5674978A (en) | 1990-09-21 | 1993-09-17 | Peptides derived from glutamic acid decarboxylase |
| US08/123,859 | 1993-09-17 | ||
| PCT/US1994/009478 WO1995007992A2 (en) | 1993-09-17 | 1994-08-24 | Cloned glutamic acid decarboxylase |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2170523A1 true CA2170523A1 (en) | 1995-03-23 |
| CA2170523C CA2170523C (en) | 2010-03-30 |
Family
ID=22411325
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2170523A Expired - Lifetime CA2170523C (en) | 1993-09-17 | 1994-08-24 | Cloned glutamic acid decarboxylase |
Country Status (11)
| Country | Link |
|---|---|
| US (5) | US5674978A (en) |
| EP (1) | EP0719340B1 (en) |
| JP (1) | JP3133339B2 (en) |
| KR (1) | KR100367943B1 (en) |
| AT (1) | ATE221125T1 (en) |
| AU (1) | AU697058B2 (en) |
| CA (1) | CA2170523C (en) |
| DE (1) | DE69431060T2 (en) |
| DK (1) | DK0719340T3 (en) |
| ES (1) | ES2179077T3 (en) |
| WO (1) | WO1995007992A2 (en) |
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| US5674978A (en) * | 1990-09-21 | 1997-10-07 | The Regents Of The University Of California | Peptides derived from glutamic acid decarboxylase |
| AU671589B2 (en) * | 1991-05-15 | 1996-09-05 | Board Of Regents Of The University Of Washington, The | Cloning and expression of human islet glutamic acid decarboxylase autoantigen |
| DE69334246D1 (en) * | 1992-12-03 | 2008-12-24 | Univ California | IMPROVED REAGENTS AND METHODS FOR THE DIAGNOSIS AND TREATMENT OF DIABETES AND STIFF MAN SYNDROME |
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| DE69637130T2 (en) * | 1995-02-20 | 2008-02-21 | The Walter And Eliza Hall Institute Of Medical Research, Parkville | IMMUNOREACTIVE AND IMMUNOTHERAPEUTIC MOLECULES THAT INTERACT IN INDIVIDUALS WITH INSULIN-DEPENDENT DIABETES MELLITUS |
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| WO1995007992A3 (en) | 1995-06-22 |
| US5846740A (en) | 1998-12-08 |
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