CA2170523A1 - Cloned glutamic acid decarboxylase - Google Patents

Cloned glutamic acid decarboxylase

Info

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
Application number
CA002170523A
Other languages
French (fr)
Other versions
CA2170523C (en
Inventor
Allan J. Tobin
Mark G. Erlander
Daniel L. Kaufman
Michael J. Clare-Salzler
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.)
University of California
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 CA2170523A1 publication Critical patent/CA2170523A1/en
Application granted granted Critical
Publication of CA2170523C publication Critical patent/CA2170523C/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43Enzymes; Proenzymes; Derivatives thereof
    • A61K38/51Lyases (4)
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/88Lyases (4.)
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12YENZYMES
    • C12Y401/00Carbon-carbon lyases (4.1)
    • C12Y401/01Carboxy-lyases (4.1.1)
    • C12Y401/01015Glutamate decarboxylase (4.1.1.15)
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/564Immunoassay; 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
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/573Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/04Endocrine or metabolic disorders
    • G01N2800/042Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/24Immunology or allergic disorders
    • YGENERAL 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
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10STECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S435/00Chemistry: molecular biology and microbiology
    • Y10S435/975Kit

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 .
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.
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.
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.
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.
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.
37. The method of claim 35, wherein the disorder is IDDM.
38. The method of claim 35, wherein the disorder is stiff man disease.
CA2170523A 1993-09-17 1994-08-24 Cloned glutamic acid decarboxylase Expired - Lifetime CA2170523C (en)

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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US6011139A (en) 2000-01-04
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US6455267B1 (en) 2002-09-24
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EP0719340A1 (en) 1996-07-03
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WO1995007992A3 (en) 1995-06-22

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