KR950704355A - 혈관 내피 세포 성장 인자에 대한 길항제(Vascular Endothelial Cell Growth Factor Antagonists) - Google Patents
혈관 내피 세포 성장 인자에 대한 길항제(Vascular Endothelial Cell Growth Factor Antagonists)Info
- Publication number
- KR950704355A KR950704355A KR1019950701621A KR19950701621A KR950704355A KR 950704355 A KR950704355 A KR 950704355A KR 1019950701621 A KR1019950701621 A KR 1019950701621A KR 19950701621 A KR19950701621 A KR 19950701621A KR 950704355 A KR950704355 A KR 950704355A
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- KR
- South Korea
- Prior art keywords
- amino acid
- acid sequence
- hvegf
- monoclonal antibody
- antibody amino
- Prior art date
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- 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
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
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- 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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- 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
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
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- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07K2319/00—Fusion polypeptide
Abstract
본 발명은 hVEGF의 유사 분열 촉진, 맥관 형성 또는 다른 생물학적 형성을 억제하는 모노클로날 항체, hVEGF 수용체, 및 hVEGF 변종을 비롯한 혈관 내피 세포 성장 인자(hVEGF) 길항제를 제공한다. 따라서, 이 길항제는 불필요하거나 또는 과도한 내피 세포 중식 또는 혈관 신생에 의해 특징지워지는 질환 및 이상의 치료에 유용하다. 본 발명의 모노클로날 항체 및 수용체는 또한 시험 시료 중의 hVEGF의 존재를 측정하는 진단 및 분석 방법에 유용하다.
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 항-hVEGF 모노클로날 항체가 hVEGF에 결합하는 것에 대한 항-hVEGF 모노클로날 항체 (A4.6. 1 또는 B2.6.2) 또는 무관한 간세포 성장 억제 인자 항체(항-HGF)의 효과를 나타낸다.
제2도는 소의 부신피질 모세 혈관 내피(ACE) 세포의 배양액 중에서의 hVEGF의 생물학적 활성에 대한 항-hVEGF 모노클로날 항체 (A4.6.1 또는 32.6.2) 또는 무관한 항-HGF 항체의 효과를 나타낸다.
제3도는 hVEGF가 소의 ACE 세포들에 결합하는 것에 대한 항-hYEGr모노클로날 항체(A4.6. 1, B2.6.2, 또는 A2.6. 1)의 효과를 나타낸다.
제4도는 마우스의 NEG55종양 성장 속도에 대한 A4.6.1 항-hVEGF 모노클로날 항체로의 처리 효과를 나타낸다.
제5도는 처리한지 5주 후에 마우스의 NEG55 종양 크기에 대한 A4.6.1항-hVEGF 모노클로날 항체로의 처리 효과를 나타낸다.
Claims (30)
- hVEGF 길항제로 이루어지되, 그 길항제가또는또는 KDR 수용체 또는 중성화 항-hVEGF 항체는 아닌 조성물.
- 제1항에 있어서, hVEGF 수용체에 결합할 수 있고 그 수용체에 결합하기 위해 hVEGF와 경쟁하는 항체 아미노산 서열로 이루어진 폴리펩티드를 포함한 조성물.
- 제1항에 있어서, hVEGF에 결합할 수 있고 hVEGF수용체에 대한 hVEGF의 결합을 방해하는 항체 아미노산 서열로 이루어진 폴리펩티드를 포함한 조성물.
- hVEGFr또는 hVEGF-hVEGFr 복합체에 특이적으로 결합할 수 있는 모노클로날 항체 아미노산 서열.
- 제4항에 있어서, hVEGF의 유사 분열 촉진 활성을 억제하거나 또는 소 ACE세포에 대한 hVEGF의 결합을 억제하는 모노클로날 항체 아미노산 서열.
- 제5항에 있어서, hVEGF의 유사 분열 촉진 활성을 약 90% 이상 억제하는 모노클로날 항체 아미노산 서열.
- 제4항에 있어서, hVEGFr에 결합할 수 있는 모노클로날 항체 아미노산 서옅.
- 제7항에 있어서, hVEGFr과의 결합에 대해 모노발런트인 모노클로날 항체 아미노산 서열.
- 제4항에 있어서, 이종 특이성인 모노클로날 항체 아미노산 서열.
- 제9항에 있어서, hVEGF hVEGFr 및 hVEGF-hVEGFr 복합체 이외의 항원에 결합할 수 있는 모노클로날 항체 아미노산 서열.
- 제4항에 있어서, IgA, IgD. IgE, IgGl, IgG2, IgG3, IgG4 또는 IgM중쇄 중 어느 하나의 Fc 도메인으로부터 얻은 아미노산 서열로 이루어진 모노클로날 항체 아미노산 서열.
- 제4항에 있어서, 인간의 Fc 도메인으로 이루어진 모노클로날 항체 아미노산 서열.
- 제14항에 있어서, hVEGF, hVEGFr 및 hVEGF-hVEGFr 복합체에 결합할 수 있는 마우스 Fv 도메인을 더 포함하는 모노클로날 항체 아미노산 서열.
- 제4항에 있어서. 비면역글로불린 중합체를 더 포함하는 모로클로날 항체 아미노산 서열.
- 제4항에 있어서, 세포 독성 잔기 또는 사이토킨의 아미노산 서열을 더 포함하는 모노클로날 항체 아미노산 서열.
- 제15항에 있어서, 세포 독성 잔기 또는 사이토킨의 아미노산 서열이 Fc 서열 대신 대체된 모노클로날 항체 아미노산 서열.
- 제15항에 있어서, 폴리펩티드 독소인 세포 독성 잔기를 갖는 모노클로날 항체 아미노산 서열.
- 제15항에 있어서, Fc효과기 기능을 가질 수 있거나 또는 면역 세포를 충원할 수 있는 세포 독성 잔기를 갖는 모노클로날 항체 아미노산 서열.
- 제18항에 있어서, 세포 독성 잔기가 보체와 결합할 수 있는 폴리펩티드인 모노클로날 항체 아미노산 서열.
- 제18항에 있어서, 세포 독성 잔기가 CD3, CD18, CD11a, CD11b또는 CD11c와 결합할 수 있는 폴리펩티드인 모노클로날 항체 아미노산 서열.
- 제4항에 있어서, hVEGF-hVEGFr 복합체에는 결합할 수 있지만 hVEGF 또는 hVEGFr 만에는 결합할 수 없는 모노클로날 항체 아미노산 서열.
- 제21항에 있어서, 세포 독성 잔기를 더 포함하는 모노클로날 항체 아미노산 서열.
- 제4항에 있어서, hVEGFr에 결합할 수 있고, hVEGFr에 대한 hVEGF의 효과에 길항 작용할 수 있는 모노플로날 항체 아미노산 서열.
- 제4항에 있어서, 생리학상 허용되는 비히클을 더 포함하며 실질적으로 등장성인 용액에 멸균 상태로 존재하며 탄성 중합체 스토퍼로 밀봉된 용기에 저장되는 모노클로날 항체 아미노산 서열.
- 제24항에 있어서, 치료 용도의 취급 설명서를 포함하는 인쇄물이 삽입된 키트 중의 모노클로날 항체 아미노산 서열.
- hVEGFr 및 면역글로불린 사슬을 코딩하는 아미노산 서옅로 이루어진 폴리펩티드.
- 종양의 로기를 감소시키기에 충분한 hVEGF 길항제의 치료 유효량을 포유 동물에게 투여하는 것으로 이루어지는 포유 동물의 종양 치료 방법.
- 제27항에 있어서, hVEGF 길항제가 항-hVEGFr 항체인 방법.
- 제27항에 있어서, hVEGF 길항제가 항-hVEGF-hVEGrr 항체인 방법.
- 제27항에 있어서, hVEGF 길항제가 hVEGFr의 세포의 도메인을 코딩하는 아미노산 서열로 이루어진 방법.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/US1992/009218 WO1994010202A1 (en) | 1992-10-28 | 1992-10-28 | Vascular endothelial cell growth factor antagonists |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
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KR1019997012527A Division KR100315613B1 (ko) | 1999-12-30 | 1992-10-28 | 혈관 내피 세포 성장 인자에 대한 길항제 |
Publications (2)
Publication Number | Publication Date |
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KR950704355A true KR950704355A (ko) | 1995-11-20 |
KR100335584B1 KR100335584B1 (ko) | 2002-11-29 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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KR1019950701621A KR100335584B1 (ko) | 1992-10-28 | 1992-10-28 | 혈관내피세포성장인자에대한길항제 |
Country Status (18)
Country | Link |
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EP (4) | EP0666868B2 (ko) |
JP (1) | JP3398382B2 (ko) |
KR (1) | KR100335584B1 (ko) |
AT (4) | ATE399181T1 (ko) |
AU (1) | AU687727B2 (ko) |
BG (1) | BG99605A (ko) |
BR (1) | BR9207175A (ko) |
CA (1) | CA2145985C (ko) |
CZ (1) | CZ291047B6 (ko) |
DE (3) | DE69232539T3 (ko) |
DK (4) | DK1167384T3 (ko) |
ES (4) | ES2173873T5 (ko) |
FI (1) | FI951987A (ko) |
HU (2) | HU225646B1 (ko) |
NO (1) | NO321825B1 (ko) |
RO (1) | RO119721B1 (ko) |
SK (1) | SK285035B6 (ko) |
WO (1) | WO1994010202A1 (ko) |
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