KR930702029A - Homozygous Immunoglobulins - Google Patents

Homozygous Immunoglobulins

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Publication number
KR930702029A
KR930702029A KR1019930700605A KR930700605A KR930702029A KR 930702029 A KR930702029 A KR 930702029A KR 1019930700605 A KR1019930700605 A KR 1019930700605A KR 930700605 A KR930700605 A KR 930700605A KR 930702029 A KR930702029 A KR 930702029A
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antibody
pharmaceutical composition
homozygous
antigen
monoclonal antibody
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KR1019930700605A
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Korean (ko)
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에디쓰 앤 울프
하워드 브이 래프
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스티븐 체스노프
브리스톨-마이어즈 스퀴브 캄파니
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Publication of KR930702029A publication Critical patent/KR930702029A/en

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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
    • C07K16/30—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
    • C07K16/3015—Breast
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6881—Cluster-antibody conjugates, i.e. the modifying agent consists of a plurality of antibodies covalently linked to each other or of different antigen-binding fragments covalently linked to each other
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734—Complement-dependent cytotoxicity [CDC]

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
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  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
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  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

항원에 대한 높은 결합 활성을 갖는 동종접합된 항체는 치료 활성을 증가시키고, 제약 및 진단 조성물에 이용된다. 동일한 항원 결정 인자에 결합하는 IgG군 단일 클론 항체로부터 통상적으로 제조된 동종접합체는 합성 가교에 의해 공유적으로 결합된다. 동종접합체는 선택된 항원에 대해 4가, 6가 이상의 IgG 유사분자를 제공하기 위하여 2개 이상의 면역 글로불린 단량체로 이루어진다.Homoconjugated antibodies with high binding activity to the antigen increase the therapeutic activity and are used in pharmaceutical and diagnostic compositions. Homozygotes commonly prepared from IgG group monoclonal antibodies that bind to the same antigenic determinants are covalently linked by synthetic crosslinking. Homozygotes consist of two or more immunoglobulin monomers to provide tetravalent, hexavalent or higher IgG analog molecules for the selected antigen.

동종접합체는 태반을 통과할 수 있다. 또한 이러한 동종접합체를 사용하는 치료방법이 제공된다.Homozygotes can cross the placenta. Also provided are methods of treatment using such homozygotes.

Description

동종접합된 면역 글로불린Homozygous Immunoglobulins

본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음Since this is an open matter, no full text was included.

제1도는 x축은 체류시간이고 y축은 A280인, IgG동종접합 혼합물의 FPLC프로필의 크로마토그램을 나타내고, A,B및 C로 표시된 피크는 각각 삼량체, 이량체 및 단량체 분획물을 표시한다. 제2도는 B군연쇄상구균의 탄수화물 군에 결합하는 인체의 IgG단일 클론 항체인 단일 클론 항체 D3의 초기 단량체에 비교한 동종 접합체(이량체 또는 삼량체)의 EIA에 있어서 증가된 결합 활성을 나타낸 것이다. 제3도는 이. 콜리 K1의 캡슐 탄수화물에 결합하는 인체의 IgG단일 클론 항체인 단일 클론 항체 5E1－G의 초기 단량체에 비교한 동종접합체(이량체 또는 삼량체)의 증가된 결합 활성을 나타낸 것이다. 제4도는 인체의 유방 종양에 관련된 항원에 결합하는 쥐의 단일 클론 항체인 BR64의 초기 단량체의 비교한 동종접합체(이량체)의 EIA에서의 증가된 결합 활성을 나타낸 것이다.FIG. 1 shows the chromatogram of FPLCpropyl of an IgG homozygous mixture, where the x axis is the retention time and the y axis is A 280 , and the peaks labeled A, B and C represent the trimer, dimer and monomer fractions, respectively. FIG. 2 shows increased binding activity in the EIA of homologous conjugates (dimers or trimers) compared to the initial monomer of monoclonal antibody D3, a human IgG monoclonal antibody that binds to the carbohydrate group of group B streptococci. . Third is this. It shows the increased binding activity of homozygotes (dimers or trimers) compared to the initial monomer of monoclonal antibody 5E1-G, the human IgG monoclonal antibody that binds to the capsular carbohydrate of Colli K1. Figure 4 shows the increased binding activity in EIA of the comparative homozygotes (dimer) of the initial monomers of BR64, a mouse monoclonal antibody that binds to antigens associated with human breast tumors.

Claims (23)

동일한 항원 결정인자에 결합하는 2개 이상의 IgG항체 분자를 갖는 공유 가교되어 동종접합된 단일 클론항체, 및 제약학적으로 허용 가능한 담체로 이루어지는 제약 조성물.A pharmaceutical composition comprising a covalently crosslinked homozygous monoclonal antibody having two or more IgG antibody molecules that bind to the same antigenic determinant, and a pharmaceutically acceptable carrier. 제1항에 있어서, 동종접합된 단일 클론 항체가 2개의 항체 분자를 갖는 제약 조성물.The pharmaceutical composition of claim 1, wherein the homozygous monoclonal antibody has two antibody molecules. 제1항에 있어서, 동종접합된 단일 클론 항체가 3개의 항체 분자를 갖는 제약 조성물.The pharmaceutical composition of claim 1, wherein the homozygous monoclonal antibody has three antibody molecules. 제1항에 있어서, 항체가 이황화 결합에 의해 가교된 제약 조성물.The pharmaceutical composition of claim 1, wherein the antibody is crosslinked by disulfide bonds. 제1항에 있어서, 항체가 인체의 항체인 제약 조성물.The pharmaceutical composition of claim 1, wherein the antibody is an antibody of a human body. 제1항에 있어서, 항체 분자가 쥐의 항체인 제약 조성물.The pharmaceutical composition of claim 1, wherein the antibody molecule is a mouse antibody. 제1항에 있어서, 항체 분자가 쥐－인간 키메라(chimera)항체인 제약 조성물.The pharmaceutical composition of claim 1, wherein the antibody molecule is a murine-human chimera antibody. 제5항에 있어서, 인체의 항체 중쇄가 IgG1인 제약 조성물.The pharmaceutical composition of claim 5, wherein the antibody heavy chain of the human body is IgG 1 . 제1항에 있어서, 이. 콜리(E. coli) K1에 의한 감염에 대해 보호적인 제약 조성물.The method of claim 1, wherein: Pharmaceutical compositions that are protective against infection by E. coli K1. 제1항에 있어서, B군 연쇄상구균에 의한 감염에 대해 보호적인 제약 조성물.The pharmaceutical composition according to claim 1, which is protective against infection by Group B streptococci. 제1항에 있어서, 동종접합된 단일 클론 항체가 종양 관련 항원에 결합하고, 유방 종양 세포의 성장을 억제하는 제약 조성물.The pharmaceutical composition of claim 1, wherein the homozygous monoclonal antibody binds to tumor associated antigens and inhibits the growth of breast tumor cells. 제1항에 있어서, 동종접합된 단일 클론 항체가 태반을 통과할 수 있는 제약 조성물.The pharmaceutical composition of claim 1, wherein the homozygous monoclonal antibody can cross the placenta. 제1항에 있어서, 항체 분자의 경쇄 및 중쇄의 일정 영역이 인체의 것인 제약 조성물.The pharmaceutical composition of claim 1, wherein the regions of the light and heavy chains of the antibody molecule are of the human body. 제1항에 있어서, 가교된 항체가 동일한 세포주로부터 유도된 제약 조성물.The pharmaceutical composition of claim 1, wherein the crosslinked antibody is derived from the same cell line. 동일한 항원 결정 인자에 결합하는 2개 이상의 공유 가교된 IgG항체 분자를 포함하는 동종접합된 단일 클론 항체의 치료학적 유효량을 환자에게 투여하는 것으로 이루어지는, 항원에 관련된 질병을 앓고 있는 환자의 치료방법.A method of treating a patient suffering from a disease associated with an antigen, comprising administering to the patient a therapeutically effective amount of a homozygous monoclonal antibody comprising two or more covalently crosslinked IgG antibody molecules that bind to the same antigenic determinant. 제15항에 있어서, 항원 관련 질병이 B군 연쇄상구균 감염인 방법.The method of claim 15, wherein the antigen related disease is Group B streptococcal infection. 제15항에 있어서, 항원 관련 질병이 이. 콜리 K1 감염인 방법.The method of claim 15, wherein the antigen related disease is E. coli. How is Collie K1 infection. 제15항에 있어서, 동종접합된 단일 클론 항체를 임산부 환자에게 투여하고, 동종접합체가 태반을 통해 태아의 순환계로 통과할 수 있는 방법.The method of claim 15, wherein the homozygous monoclonal antibody is administered to the pregnant patient and the homozygous can pass through the placenta into the fetal circulation. 제18항에 있어서, 동종접합된 단일 클론 항체가 태아의 항원 관련 질병을 치료할 수 있는 방법.The method of claim 18, wherein the homozygous monoclonal antibody can treat an antigen related disease of the fetus. 제19항에 있어서, 항원 관련 질병이 B군 연쇄상구균 또는 이. 콜리 K1에 의한 감염인 방법.The method of claim 19, wherein the antigen-associated disease is Group B streptococci or E. coli. The method is infection with Colli K1. 제15항에 있어서, 항원 관련 질병이 유방 종양이고, 동종접합된 단일 클론 항체가 유방종양 관련 항원에 결합하는 방법.The method of claim 15, wherein the antigen-associated disease is a breast tumor and the homozygous monoclonal antibody binds to a breast tumor-associated antigen. 항원 관련 질병의 치료를 위해 단일 클론 항체를 치료적 투여하는 방법에 있어서, 항원의 동일한 항원결정 인자에 결합하는 2개 이상의 공유 가교된 IgG항체 분자를 포함하는 동종접합된 단일 항체를 환자에게 투여하는 것으로 이루어지는 개선된 방법.A method of therapeutically administering a monoclonal antibody for the treatment of an antigen related disease, comprising administering to a patient a homozygous single antibody comprising two or more covalently crosslinked IgG antibody molecules that bind to the same antigenic determinant of the antigen. Improved method. ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.※ Note: The disclosure is based on the initial application.
KR1019930700605A 1990-08-31 1991-08-29 Homozygous Immunoglobulins KR930702029A (en)

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Application Number Priority Date Filing Date Title
US57572590A 1990-08-31 1990-08-31
US575,725 1990-08-31
US74866291A 1991-08-26 1991-08-26
US748,662 1991-08-26
PCT/US1991/006195 WO1992004053A1 (en) 1990-08-31 1991-08-29 Homoconjugated immunoglobulins

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AU (1) AU8506991A (en)
CA (1) CA2090317A1 (en)
FI (1) FI930846A (en)
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EP3089758B1 (en) 2014-01-03 2021-01-27 F.Hoffmann-La Roche Ag Covalently linked helicar-anti-helicar antibody conjugates and uses thereof
AR100978A1 (en) 2014-06-26 2016-11-16 Hoffmann La Roche ANTI-Tau HUMANIZED ANTIBODY BRAIN LAUNCHERS (pS422) AND USES OF THE SAME
WO2016087416A1 (en) 2014-12-03 2016-06-09 F. Hoffmann-La Roche Ag Multispecific antibodies
PL3313877T3 (en) 2015-06-24 2020-11-02 F. Hoffmann-La Roche Ag Humanized anti-tau(ps422) antibodies and methods of use
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