KR950005327A - 임파구 항원 CD2 및 종양 항원을 인식하는 이특이적 트리거(Trigger) 분자 - Google Patents

임파구 항원 CD2 및 종양 항원을 인식하는 이특이적 트리거(Trigger) 분자 Download PDF

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KR950005327A
KR950005327A KR1019940018956A KR19940018956A KR950005327A KR 950005327 A KR950005327 A KR 950005327A KR 1019940018956 A KR1019940018956 A KR 1019940018956A KR 19940018956 A KR19940018956 A KR 19940018956A KR 950005327 A KR950005327 A KR 950005327A
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aicd2
bab
mab
bispecific antibody
antibody
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KR1019940018956A
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KR100347465B1 (ko
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스트리트마테르 볼프강
죄글레 카르로타-실비아
모우어 스테판
슈라벤 부르크하르트
빌트 마르틴
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위르겐 호이만, 라인하르트 슈틀러
메르크 파텐트 게젤샤프트 미트 베쉬랭크터 하프퉁
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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
    • 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
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2806—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C07K2317/74—Inducing cell proliferation

Abstract

본 발명읜 임파구 CD2 항원 및 기타 가변 종양 항원을 인식하는 매우 효과적인 신규의 이특이적 항체 단편에 관한 것이다. 더욱이 본 발명은 AICD2. M1 및 AICD2. M2로 명명된 2개의 신규 모노클론 항체에 관한 것이다. 이들중 최소한 하나가 이특이적 항체 단편인 이들항체의 결합은 종양 치료 및 진단 분야에 성공적으로 사용될 수 있다.

Description

임파구 항원 CD2 및 종양 항원을 인식하는 이특이적 트리거(Trigger) 분자
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (14)

  1. BAb<X, AICD2.M1>Y 또는 BAb<X, AICD2.M2>Y로 표시되는, 종양 세포의 에피토프에 대한 제1결합 부위 및 CD2 항원의 에피토프에 대한 제2결합 부위를 포함하는, 종양 세포의 용해에 유용한 이특이적 항체 분자 : 상기 표식에서, BAb는 이특이적 항체를 의미하고, X는 종양 항원을 인식하는 항체 결정기이고, AICD2.M1 및 AICD2.M2는 CD2 항원을 인식하는 항체이고, Y는 전체 항체의 일부이다.
  2. 제1항에 있어서, X가 모노클론 항체 MAb 425, MAb 361 또는 MAb 15로부터 유도되는 항체 결정기인 이특이적 항체 분자.
  3. 제1항 또는 제2항에 있어서, Y가 F(ab′)2 분자인 이특이적 항체 분자.
  4. 제1항 또는 제3항중 어느 한 항에 있어서, BAb<425, AICD2.M1>F(ab′)2, BAb<425, AICD2.M2>F(ab′)2, BAb<361, AICD2.M1>F(ab′)2, BAb<361, AICD2.M2>F(ab′)2, BAb<15, AICD2.M1>F(ab′)2, 및 BAb<15, AICD2.M2>F(ab′)2로 구성되는 군으로부터 선택되는 이특이적 항체 분자.
  5. 하나 또는 그 이상의 이황화 결합에 의해 연결된, 각각 2개의 동일한 L(경쇄-H(중쇄) 반(half) 분자를 포함하는 2개의 다른 모노클론 항체를 2개의 F(ab′)2 분자로 효소적 방법에 의해 전환시키고, 환원 조건하에서 각 F(ab′) 분자를 Fab′티올로 절단시키고, 이러한 각 항체의 Fab′분자중의 하나를 티올 활성화제로 유도체화하고, 종양 특이성을 가지는 활성화된 Fab′분자를 임파구 특이성을 가지는 비-활성화된 Fab′분자와 결합시키거나 또는 그 역으로 결합시켜 원하는 이특이적 항체 F(ab′)2 단편을 얻음으로써, 종양 세포의 에피토프에 대한 제1결합 부위 및 CD2항원의 에피토프에 대한 제2결합 부위를 포함하며, 모노클론 항체 AICD2.M1 및 AICD2.M2를 임파구 항원을 인식하는 항체로서 사용함을 특징으로 하는, 종양 세포의 용해에 유용한 이특이적 항체 F(ab′)단편의 제조방법.
  6. 제5항에 있어서, MAb 425, MAb 361 또는 MAb 15를 종양 세포를 인식하는 항체로 사용함을 특징으로 하는 방법.
  7. 세포주 1H 10(국제 기탁번호 DSM ACC2118)로부터 단리하여 얻어질 수 있는, 항원 CD2를 인식하는 모노클론 항체 AICD2.M1.
  8. 세포주 7D 3(국제 기탁번호 DSM ACC2119)로부터 단리하여 얻어질 수 있는, 항원 CD2를 인식하는 모노클론 항체 AICD2.M2.
  9. 하나 또는 그 이상의 약학적으로 허용가능한 담체, 부형제 또는 희석제와 함께, 제1항 내지 제4항 중 어느 한 항에 따른 하나 이상의 이특이적 항체 단편을 활성 성분으로서 포함하는 약학 제제.
  10. 이특이적 항체 단편 BAb<X, AICD2.M2>Y를 포함하는 제9항에 따른 제1약학 제제(I) 및 MAb AICD2.M1 또는 MAb<AICD2.M2>Y 또는 BAb<X, AICD2.M1>Y(여기서, X 및 Y는 제1항에서 정의한 바와 같다)를 포함하는 별도의 제2약학제제를 포함하는 약학적 킷트.
  11. 이특이적 항체 단편 BAb<X, AICD2.M1>Y를 포함하는 제9항에 따른 제1약학 제제 및 MAb AICD2.M2 또는 MAb<AICD2.M2>Y 또는 BAb<X, AICD2.M2>Y(여기서, X 및 Y는 제1항에서 정의한 바와 같다)를 포함하는 별도의 제2약학제제를 포함하는 약학적 킷트.
  12. 제11항에 있어서, 제제(I)이 이특이적 항체 단편 BAb<425, AICD2.M1>F(ab′)2 또는 BAb<361, AICD2.M1>F(ab′)2 또는 BAb<15, AICD2.M1>F(ab′)2를 포함하고, 제제(II)가 MAb<AICD2.M2>F(ab′)2를 포함하는 약학적 킷트.
  13. 부가적인 T-임파구의 임의적 존재하에 제10항 내지 제12항중 어느 한 항에 따른 약학적 킷트를 이용하여 종양 세포를 제제 (I)으로 처리한 후 제제(II)로 처리한 다음, 임의적으로 기존의 정제단계를 수행하는, 자가유래 골수 이식에서 생체의 종양 세포의 정화방법.
  14. 사람의 종양 치료 약물을 제조하기 위한, 제1항 내지 제4항중 어느 한 항에 따른 이특이적 항체 단편의 용도.
    ※참고사항:최초출원 내용에 의하여 공개하는 것임.
KR1019940018956A 1993-08-02 1994-08-01 임파구항원cd2및종양항원을인식하는이특이적트리거분자 KR100347465B1 (ko)

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