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 PDFInfo
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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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- Prior art keywords
- aicd2
- bab
- mab
- bispecific antibody
- antibody
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- 239000000427 antigen Substances 0.000 title claims abstract 10
- 102000036639 antigens Human genes 0.000 title claims abstract 10
- 108091007433 antigens Proteins 0.000 title claims abstract 10
- 206010028980 Neoplasm Diseases 0.000 title claims abstract 6
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 title 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 title 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims abstract 7
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims abstract 7
- 210000004698 lymphocyte Anatomy 0.000 claims abstract 3
- 210000004881 tumor cell Anatomy 0.000 claims 7
- 238000000034 method Methods 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 238000009472 formulation Methods 0.000 claims 3
- 239000000203 mixture Substances 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 2
- 238000002955 isolation Methods 0.000 claims 2
- 125000003396 thiol group Chemical class [H]S* 0.000 claims 2
- 210000001744 T-lymphocyte Anatomy 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000010322 bone marrow transplantation Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000003776 cleavage reaction Methods 0.000 claims 1
- 238000001212 derivatisation Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 238000004090 dissolution Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000006911 enzymatic reaction Methods 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 230000002934 lysing effect Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 238000000746 purification Methods 0.000 claims 1
- 230000007017 scission Effects 0.000 claims 1
- 229940126585 therapeutic drug Drugs 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
Classifications
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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
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (14)
- 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.
- 제1항에 있어서, X가 모노클론 항체 MAb 425, MAb 361 또는 MAb 15로부터 유도되는 항체 결정기인 이특이적 항체 분자.
- 제1항 또는 제2항에 있어서, Y가 F(ab′)2 분자인 이특이적 항체 분자.
- 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.
- 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.
- 제5항에 있어서, MAb 425, MAb 361 또는 MAb 15를 종양 세포를 인식하는 항체로 사용함을 특징으로 하는 방법.
- 세포주 1H 10(국제 기탁번호 DSM ACC2118)로부터 단리하여 얻어질 수 있는, 항원 CD2를 인식하는 모노클론 항체 AICD2.M1.
- 세포주 7D 3(국제 기탁번호 DSM ACC2119)로부터 단리하여 얻어질 수 있는, 항원 CD2를 인식하는 모노클론 항체 AICD2.M2.
- 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.
- 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.
- 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.
- 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.
- 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.
- 사람의 종양 치료 약물을 제조하기 위한, 제1항 내지 제4항중 어느 한 항에 따른 이특이적 항체 단편의 용도.※참고사항:최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP93112330 | 1993-08-02 | ||
EP93112330.1 | 1993-08-02 |
Publications (2)
Publication Number | Publication Date |
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KR950005327A true KR950005327A (ko) | 1995-03-20 |
KR100347465B1 KR100347465B1 (ko) | 2003-03-03 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1019940018956A KR100347465B1 (ko) | 1993-08-02 | 1994-08-01 | 임파구항원cd2및종양항원을인식하는이특이적트리거분자 |
Country Status (20)
Country | Link |
---|---|
US (1) | US5798229A (ko) |
EP (1) | EP0637593B1 (ko) |
JP (2) | JP3822653B2 (ko) |
KR (1) | KR100347465B1 (ko) |
AT (1) | ATE199378T1 (ko) |
AU (1) | AU683659B2 (ko) |
CA (1) | CA2129183C (ko) |
CZ (1) | CZ291071B6 (ko) |
DE (1) | DE69426743T2 (ko) |
DK (1) | DK0637593T3 (ko) |
ES (1) | ES2156587T3 (ko) |
GR (1) | GR3035926T3 (ko) |
HU (1) | HU218100B (ko) |
NO (1) | NO942850L (ko) |
PL (1) | PL176761B1 (ko) |
PT (1) | PT637593E (ko) |
RU (1) | RU2203319C2 (ko) |
SK (1) | SK283133B6 (ko) |
UA (1) | UA40577C2 (ko) |
ZA (1) | ZA945753B (ko) |
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EP0260880A3 (en) * | 1986-09-11 | 1990-03-07 | Dana-Farber Cancer Institute, Inc. | Turning on of cytotoxicity |
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AU6290090A (en) * | 1989-08-29 | 1991-04-08 | University Of Southampton | Bi-or trispecific (fab)3 or (fab)4 conjugates |
CZ282603B6 (cs) * | 1991-03-06 | 1997-08-13 | Merck Patent Gesellschaft Mit Beschränkter Haftun G | Humanizované a chimerické monoklonální protilátky |
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NO942850L (no) | 1995-02-03 |
JP3822653B2 (ja) | 2006-09-20 |
PT637593E (pt) | 2001-08-30 |
GR3035926T3 (en) | 2001-08-31 |
SK283133B6 (sk) | 2003-03-04 |
CA2129183C (en) | 2006-05-16 |
US5798229A (en) | 1998-08-25 |
CZ291071B6 (cs) | 2002-12-11 |
DE69426743D1 (de) | 2001-04-05 |
UA40577C2 (uk) | 2001-08-15 |
HUT71309A (en) | 1995-11-28 |
PL304510A1 (en) | 1995-02-06 |
ATE199378T1 (de) | 2001-03-15 |
DK0637593T3 (da) | 2001-06-25 |
HU218100B (hu) | 2000-06-28 |
JP2005336207A (ja) | 2005-12-08 |
JP4231862B2 (ja) | 2009-03-04 |
CA2129183A1 (en) | 1995-02-03 |
PL176761B1 (pl) | 1999-07-30 |
CZ180294A3 (en) | 1995-02-15 |
AU683659B2 (en) | 1997-11-20 |
EP0637593A1 (en) | 1995-02-08 |
SK91294A3 (en) | 1996-11-06 |
DE69426743T2 (de) | 2001-08-16 |
JPH0789873A (ja) | 1995-04-04 |
KR100347465B1 (ko) | 2003-03-03 |
ES2156587T3 (es) | 2001-07-01 |
HU9402220D0 (en) | 1994-10-28 |
RU2203319C2 (ru) | 2003-04-27 |
RU94028282A (ru) | 1996-07-20 |
ZA945753B (en) | 1995-03-15 |
NO942850D0 (ko) | 1994-08-01 |
AU6869894A (en) | 1995-02-09 |
EP0637593B1 (en) | 2001-02-28 |
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