KR960705051A - 클로닝된 글루탐산 탈카르복실라아제(cloned glutamic acid decarboxy-lase) - Google Patents
클로닝된 글루탐산 탈카르복실라아제(cloned glutamic acid decarboxy-lase) Download PDFInfo
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- 108091022930 Glutamate decarboxylase Proteins 0.000 title description 9
- 102000008214 Glutamate decarboxylase Human genes 0.000 title 2
- 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 5
- 239000000523 sample Substances 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 238000000034 method Methods 0.000 claims 29
- 150000001413 amino acids Chemical group 0.000 claims 10
- 239000012634 fragment Substances 0.000 claims 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 5
- 208000035475 disorder Diseases 0.000 claims 5
- 239000002157 polynucleotide Substances 0.000 claims 5
- 102000040430 polynucleotide Human genes 0.000 claims 5
- 108091033319 polynucleotide Proteins 0.000 claims 5
- 150000001875 compounds Chemical class 0.000 claims 4
- 210000001744 T-lymphocyte Anatomy 0.000 claims 2
- 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
- 210000000936 intestine Anatomy 0.000 claims 2
- 201000006938 muscular dystrophy Diseases 0.000 claims 2
- 239000002773 nucleotide Substances 0.000 claims 2
- 125000003729 nucleotide group Chemical group 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
- 108090000790 Enzymes Proteins 0.000 claims 1
- 102000004190 Enzymes Human genes 0.000 claims 1
- 108090001090 Lectins Proteins 0.000 claims 1
- 102000004856 Lectins Human genes 0.000 claims 1
- 230000005867 T cell response Effects 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
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 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
- 229910052751 metal Inorganic materials 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- 150000002739 metals Chemical class 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 239000013610 patient sample Substances 0.000 claims 1
- 239000007790 solid phase Substances 0.000 claims 1
- 230000000638 stimulation Effects 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
- 108700012359 toxins Proteins 0.000 claims 1
- 238000002405 diagnostic procedure Methods 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 125000003275 alpha amino acid group Chemical group 0.000 description 2
- 101100223310 Homo sapiens GAD1 gene Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 238000002105 Southern blotting Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
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- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/51—Lyases (4)
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
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Abstract
본 발명은, GAD-관련 자기면역 질환을 개선하는데 유용한 분리된 폴리펩티드 및 상기 펩티드를 사용하는 진단학적 및 치료학적 방법에 관한 것이다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 GAD65및 GAD67에 특이적인 cDNA 프로브를 얻기 위한 클로닝 전략을 도시한 도면이다,
제2도는 쥐의 GAD65에 대한 DNA 서열 및 유사한 아미노산 서열을 도시한 도면이다,
제4도는 쥐의 GAD65및 사람 GAD65아미노산 서열을 비교하여 도시한 도면이다,
제6도는 GAD65및 GAD67에 특이적인 CDNA 프로브와 혼성화된 서던 블로팅을 도시한 도면이다,
제11도는 GAD65로 면역화시킨 후에 IDDM의 개시가 지연되는 것을 도시한 도면이다.
Claims (38)
- 하기로 이루어진 그룹으로부터 선택되는 아미노산 서열을 포함하는 폴리펩티드 : KPCSCSKVDVNYAFLHATDL; NMYAMMTARFKMFPEVKEKG; TAGTTVYGAFDPLLAVADICKK; EYLYNIIKNREGYEMVFDGK; IPPSLRYLEDNEERMSRLSK; SRLSKVAPVIKARMMEYGTT; EYGTTMVSYQPLGDKVNFFR; ATHQDIDFLIEEIERLGQDL; LAFLQDVMNILLQYVVKSFDRS; EEILMHCQTTLKYAIKTGHP; DERGKMIPSKLERRILEAKQ; KHYDLSYDTGDKALQCGRHV; AALGIGTDSVILIKCDERGK; GLLMSRKHKWKLSGVERANS; GLLMSRKHKWKLSGVERANS; LEAKQKGFVPFLVSATAGTT; 및 VNFFRMVISNPAATHQDIDF.
- 제1항의 폴리펩티드를 암호화하는 분리된 폴리누클레오티드 서열.
- 제2항에 있어서, 폴리누클레오티드가 DNA인 것을 특징으로 하는 폴리누클레오티드 서열.
- 표본과 함께 GAD 단편을 접촉시키는 단계, 및 자기항체가 단편에 결합하는지의 여부를 결정하는 단계를 포함하는, 환자 표본내의 GAD에 대한 항체를 검출하는 방법.
- 제4항에 있어서, 단편은 약 16개 이상의 아미노산 길이의 폴리펩티드로, GAD65의 아미노산 약 224번 내지 약 585번의 아미노산 서열로부터 선택되는 것을 특징으로 하는 방법.
- 제4항에 있어서, 단편이 제1항에 따른 폴리펩티드인 것을 특징으로 하는 방법.
- 제4항에 있어서, 표본이 혈액인 것을 특징으로 하는 방법.
- 제4항에 있어서, 펩티드가 검출가능하게 라벨링된 것을 특징으로 하는 방법.
- 제8항에 있어서, 검출가능한 라벨이 방사성 동위원소, 형광 화합물, 콜로이드성 금속, 화학발광 화합물, 생물발광 화합물, 인광성 화합물, 및 효소로 이루어진 그룹으로부터 선택되는 것을 특징으로 하는 방법.
- 제4항에 있어서, 펩티드가 고체상에 결합되어 있는 것을 특징으로 하는 방법.
- 제1항에 따른 펩티드에 대한 단클론성 항체.
- 제9항에 따른 단클론성 항체를 생성할 수 있는 하이브리도마 세포주.
- 제2항에 따른 폴리누클레오티드를 포함하는 벡터.
- 제2항에 따른 폴리누클레오티드를 형질변환된 숙주 세포.
- 환자에게 치료학적으로 유효량의 전체 GAD65또는 치료학적으로 효과적인 그것의 단편을 투여하는 단계를 포함하는, GAD-연관성 자기면역 장애를 가지거나, 가질 위험이 있는 환자의 GAD-연관성 자기면역 장애를 개선시키는 방법.
- 제15항에 있어서, 치료학적으로 효과적인 단편이 16개 이상의 아미노산 길이의 폴리펩티드이고, GAD65의 아미노산 약 224번 내지 약 585번인 아미노산 서열로부터 선택되는 것을 특징으로 하는 방법.
- 제15항에 있어서, 치료학적으로 효과적인 단편이 하기로 이루어진 그룹으로부터 선택되는 것을 특징으로 하는 방법 : KPCSCSKVDVNYAFLHATDL; NMYAMMTARFKMFPEVKEKG; TAGTTVYGAFDPLLAVADICKK; EYLYNIIKNREGYEMVFDGK; IPPSLRYLEDNEERMSRLSK; SRLSKVAPVIKARMMEYGTT; EYGTTMVSYQPLGDKVNFFR; 및 ATHQDIDFLIEEIERLGQDL.
- 제15항에 있어서, 치료학적으로 효과적인 단편이 하기로 이루어진 그룹으로부터 선택되는 것을 특징으로 하는 방법 : KPCSCSKVDVNYAFLHATDL; NMYAMMTARFKMFPEVKEKG; TAGTTVYGAFDPLLAVADICKK; EYLYNIIKNREGYEMVFDGK; IPPSLRYLEDNEERMSRLSK; SRLSKVAPVIKARMMEYGTT; EYGTTMVSYQPLGDKVNFFR; 및 ATHQDIDFLIEEIERLGQDL.
- 제16항에 있어서, 장애가 IDDM인 것을 특징으로 하는 방법.
- 제16항에 있어서, 장애가 근 강직병인 것을 특징으로 하는 방법.
- 제16항에 있어서, 투여 후 장내에서 흡수되는 것을 특징으로 하는 방법.
- 제21항에 있어서, 경구내 투여가 장내에서 흡수되는 것을 특징으로 하는 방법.
- 제15항 또는 제16항에 있어서, 투여가 비경구적인 것을 특징으로 하는 방법.
- 제23항에 있어서, 비경구적 투여가 피하, 근육내, 복강내, 강내, 트랜스더멀, 비강내, 또는 정맥내 주사인 것을 특징으로 하는 방법.
- 제15항에 있어서, 약 0.01㎎/㎏/투여 내지 약 2000㎎/㎏/투여의 투여량으로 투여되는 것을 특징으로 하는 방법.
- 제15항에 있어서, 폴리펩티드가 치료학적으로 라벨링된 것을 특징으로 하는 방법.
- 제26항에 있어서, 치료학적 라벨이 방사성 동위원소, 약물, 렉틴, 및 독소로 이루어진 그룹으로부터 선택되는 것을 특징으로 하는 방법.
- 환자의 T-세포에 1개 이상의 제1항에 따른 폴리펩티드를 접촉시키는 단계, 및 펩티드에 대한 T-세포의 반응을 검출하는 단계를 포함하며, 환자내의 GAD-연관성 자기면역 장애의 상태를 검지하는 방법.
- 제26항에 있어서, T-세포의 반응이 자극인 것을 특징으로 하는 방법.
- 제27항에 있어서, 자극이 방사성 동위원소로 라벨링된 누클레오티드의 세포 흡수에 의해 측정되는 것을 특징으로 하는 방법.
- 제30항에 있어서, 누클레오티드가3H 티미딘인 것을 특징으로 하는 방법.
- 제1항에 따른 폴리펩티드를 포함하는 컨테이너를 포함하는 1개 이상의 컨테이너를 밀접히 제한하여 수용하도록 구획된 담체 수단을 포함하는 킷으로, 그러한 항체를 포함하는 것으로 추정되는 표본내의 제1항의 폴리펩티드에 대한 항체를 검출하는데 유용한 킷.
- 제1항에 따른 폴리펩티드를 포함하는 컨테이너를 포함하는 1개 이상의 컨테이너를 밀접히 제한하여 수용하도록 구획된 담체 수단을 포함하는 킷으로, 환자 표본내에서 GAD-연관성 장애의 상태를 결정하는데 유용한 킷.
- 진단학적으로 효과적인 GAD65단편을 진단학적으로 유효량으로 환자에게 투여하는 단계를 포함하여, 장애를 가지거나, 가질 위험이 있는 환자내에서 GAD-연관성 자기면역 장애를 검지하는 방법.
- 제34항에 있어서, 진단학적으로 효과적인 단편이 16개 이상의 아미노산 길이인 폴리펩티드이고, GAD65의 아미노산 약 34번 내지 573번인 아미노산 서열로부터 선택되는 것을 특징으로 하는 방법.
- 제35항에 있어서, 진단학적으로 효과적인 단편이 하기로 이루어진 그룹으로부터 선택되는 것을 특징으로 하는 방법 : KPCSCSKVDVNYAFLHATDL; LAFLQDVMNILLQYVVKSFDRS; EEILMHCQTTLKYAIKTGHP; DERGKMIPSKLERRILEAKQ; KHYDLSYDTGDKALQCGRHV; AALGIGTDSVILIKCDERGK; GLLMSRKHKWKLSGVERANS; LEAKQKGFVPFLVSATAGTT; 및 VNFFRMVISNPAATHQDIDF.
- 제35항에 있어서, 장애가 IDDM인 것을 특징으로 하는 방법.
- 제35항에 있어서, 장애가 근 강직병인인 것을 특징으로 하는 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/123,859 | 1993-09-17 | ||
| US08/123,859 US5674978A (en) | 1990-09-21 | 1993-09-17 | Peptides derived from glutamic acid decarboxylase |
| US08/123859 | 1993-09-17 |
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| Publication Number | Publication Date |
|---|---|
| KR960705051A true KR960705051A (ko) | 1996-10-09 |
| KR100367943B1 KR100367943B1 (ko) | 2003-06-18 |
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|---|---|---|---|
| KR1019960701348A KR100367943B1 (ko) | 1993-09-17 | 1994-08-24 | 클로닝된 글루탐산 디카르복실라아제 |
Country Status (11)
| Country | Link |
|---|---|
| US (5) | US5674978A (ko) |
| EP (1) | EP0719340B1 (ko) |
| JP (1) | JP3133339B2 (ko) |
| KR (1) | KR100367943B1 (ko) |
| AT (1) | ATE221125T1 (ko) |
| AU (1) | AU697058B2 (ko) |
| CA (1) | CA2170523C (ko) |
| DE (1) | DE69431060T2 (ko) |
| DK (1) | DK0719340T3 (ko) |
| ES (1) | ES2179077T3 (ko) |
| WO (1) | WO1995007992A2 (ko) |
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| JPH06508030A (ja) * | 1991-05-15 | 1994-09-14 | ザイモジェネティクス，インコーポレイティド | ヒトすい島グルタミン酸デカルボキシラーゼ自己抗原のクローニング及び発現 |
| JP4242446B2 (ja) * | 1992-12-03 | 2009-03-25 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 糖尿病及びスティフマン症候群の診断及び治療用改良試薬及び方法 |
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1993
- 1993-09-17 US US08/123,859 patent/US5674978A/en not_active Expired - Lifetime
-
1994
- 1994-08-24 AU AU79201/94A patent/AU697058B2/en not_active Expired
- 1994-08-24 DE DE69431060T patent/DE69431060T2/de not_active Expired - Lifetime
- 1994-08-24 CA CA2170523A patent/CA2170523C/en not_active Expired - Lifetime
- 1994-08-24 KR KR1019960701348A patent/KR100367943B1/ko not_active IP Right Cessation
- 1994-08-24 JP JP07509191A patent/JP3133339B2/ja not_active Expired - Lifetime
- 1994-08-24 DK DK94927940T patent/DK0719340T3/da active
- 1994-08-24 AT AT94927940T patent/ATE221125T1/de active
- 1994-08-24 ES ES94927940T patent/ES2179077T3/es not_active Expired - Lifetime
- 1994-08-24 WO PCT/US1994/009478 patent/WO1995007992A2/en active IP Right Grant
- 1994-08-24 EP EP94927940A patent/EP0719340B1/en not_active Expired - Lifetime
-
1995
- 1995-06-07 US US08/476,501 patent/US6455267B1/en not_active Expired - Lifetime
- 1995-06-07 US US08/485,725 patent/US8926966B1/en active Active
- 1995-06-07 US US08/483,952 patent/US6011139A/en not_active Expired - Lifetime
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Also Published As
| Publication number | Publication date |
|---|---|
| US8926966B1 (en) | 2015-01-06 |
| US5674978A (en) | 1997-10-07 |
| CA2170523A1 (en) | 1995-03-23 |
| EP0719340B1 (en) | 2002-07-24 |
| US6455267B1 (en) | 2002-09-24 |
| JP3133339B2 (ja) | 2001-02-05 |
| AU697058B2 (en) | 1998-09-24 |
| ES2179077T3 (es) | 2003-01-16 |
| WO1995007992A3 (en) | 1995-06-22 |
| KR100367943B1 (ko) | 2003-06-18 |
| JPH09503387A (ja) | 1997-04-08 |
| US6011139A (en) | 2000-01-04 |
| ATE221125T1 (de) | 2002-08-15 |
| US5846740A (en) | 1998-12-08 |
| CA2170523C (en) | 2010-03-30 |
| EP0719340A1 (en) | 1996-07-03 |
| WO1995007992A2 (en) | 1995-03-23 |
| DE69431060T2 (de) | 2002-11-14 |
| AU7920194A (en) | 1995-04-03 |
| DK0719340T3 (da) | 2002-11-18 |
| DE69431060D1 (de) | 2002-08-29 |
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