KR890007724A - 약물-모노클로날 항체 결합체 - Google Patents

약물-모노클로날 항체 결합체 Download PDF

Info

Publication number
KR890007724A
KR890007724A KR1019880015383A KR880015383A KR890007724A KR 890007724 A KR890007724 A KR 890007724A KR 1019880015383 A KR1019880015383 A KR 1019880015383A KR 880015383 A KR880015383 A KR 880015383A KR 890007724 A KR890007724 A KR 890007724A
Authority
KR
South Korea
Prior art keywords
drug
group
substituted
monoclonal antibody
carbon atoms
Prior art date
Application number
KR1019880015383A
Other languages
English (en)
Other versions
KR910005887B1 (ko
Inventor
디. 센터 피터
Original Assignee
아이삭 자아코브스키
브리스톨-마이어즈 컴페니
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 아이삭 자아코브스키, 브리스톨-마이어즈 컴페니 filed Critical 아이삭 자아코브스키
Publication of KR890007724A publication Critical patent/KR890007724A/ko
Application granted granted Critical
Publication of KR910005887B1 publication Critical patent/KR910005887B1/ko

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • 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
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Abstract

내용 없음

Description

약물-모노클로날 항체 결합체
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제1도는 MMC를 그의 상응하는 전구약물로부터 방출시키는 경로를 도시한 도면,
제2도는 본 발명에 따른 대표적인 약물-모노클로날 항체 결합체의 합성을 도시한 도면.
제3도는 본 발명에 따른 전구약물로서의 유도체들의 HPLC비교 분석 결과를 도시한 도면.

Claims (6)

  1. 다음의 일반식을 갖는 항종양 약물-모노클로날 항체 결합체:
    상기 일반식 중, D는 항종양 약물 부분으로서 그의 기본 골격에 일반식R1NH-로 나타내지는 1차 아미노기, 일반식 R1R2N-으로 나타내지는 2차 아미노기, 및 일반식 R10-로 나타내지는 알코올기 중에서 유도된 화학 반응성 관능기를 부속적으로 가지고, 이에 의해 약물의 기본 골격이 디술파이드 벤질옥시카르보닐기에 결합되며; R1은 D가 1차 아미노기, 2차 아미노기, 및 알코올기중에서 유도되는 경우 상기 약물의 기본 골격을 이루며, 여기서 2차 아미노기의 경우, R1및R2는 독립적이고; R2는 R1과 R2가 독립적인 경우, 탄소원자를 1-3개 갖는 1-3개의 알콕시기와 1-3개의 할로기 중에서 선택된 치환체로 치환되거나 치환되지 않고, 측쇄를 갖거나 직쇄인 탄소원자1-10개의 알킬기; 탄소원자를 1-3개 갖는 1-개의 알킬기, 탄소원자를 1-3개 갖는 1-3개의 알콕시기, 및 1-3개의 할로기 중에서 선택된 치환체로 치환되거나 치환되지 않은 페닐; 및 치환되거나 치환되지 않은 페닐알킬로서 이때 페닐부분은 치환되는 경우, 상기 치환페닐의 경우 정의된 바와 같이 치환되고 알킬 부분은 탄소원자를 1-3개 갖는 폴리알킬렌기인 페닐알킬 중에서 선택되며; R1과 R2는 2차 아민으로부터 유도된 관능기에서 함께 취해질 경우, 상기 2차 아미노기를 구성하는 질소원자에 화학적으로 결합된 2가지를 가지며 약물 부분 D의 기본 골격을 나타내고; R3과 R4는 H 및 탄소원자를 1-3개 갖는 알콕시기 및 1-3개의 할로기 중에서 선택된 치환체로 치환되거나 치환되지 않고, 측쇄를 갖거나 직쇄인 탄소원자 1-10개를 갖는 알킬기; 탄소원자를 1-3개 갖는 1-3개의 알킬기, 탄소원자를 1-3개 갖는 1-3개의 알콕시기 및 1-3개의 할로기 중에서 선택된 치환체로 치환되거나 치환되지 않는 페닐; 및 치환되거나 치환되지 않은 페닐알킬로서, 이때 페닐 부분은 치환되는 경우, 상기 치환 페닐의 경우 정의된 바와 같이 치환되고 알킬 부분은 1-3개의탄소원자를 갖는 폴리알킬렌기인 페닐알킬 중에서 독립적으로 선택되며; m은 1에서 10까지의 정수중 하나이고; Ab는 부속 아미노기를 갖는 모노클로날 항체를 나타내며; 벤질카르바메이트 부분의 페닐 고리상의기의 치환 방향은 오르토-및 파라위치 중에서 선택된다.
  2. 제1항에 있어서, 약물 부분 D가, 1차 아민 함유 약물 및 2차 아민 함유 약물 중에서 선택됨을 특징으로 하는 항종양 약물-모노클로날 항체 결합체.
  3. 제2항에 있어서, 약물 부분D가 미토마이신-C, 미토마이신-A, 다우노마이신, 아드리아마이신, 아미노프테린, 악티노마이신, 블레오마이신 및 이들의 유도체 중에서 선택됨을 특징으로 하는 항종양 약물-모노클로날 항체 결합체.
  4. 제1항에 있어서, 약물 부분D가 알코올기 함유 약물인 것이 특징인 항종양 약물-모노클로날 항체 결합체.
  5. 제4항에 있어서, 약물 부분D가 에토포시드인 것이 특징인 항종양 약물-모노클로날 항체 결합체.
  6. (a) 제1항에 따른 항종양 약물-모노클로날 항체 결합체의 항종양 유효량을 포유동물에 투여하고, (b) (a)단계로부터의 항종양 약물-모노클로날 항체 결합체를 내인성 환원 조건에 접하게 하여 (c) 항종양 약물-모노클로날 항체를 환원적으로 분해시켜 이 결합체로부터 유리 약물을 방출시키는 단계로 이루어짐을 특징으로하는, NADH, NADPH 및 글로타치온중 적어도 하나를 포함하는 내인성 환원제를 높은 수준으로 갖는 포유동물의 종양세포 부위에, 일반식 R1NH-로 나타내지는 1차 아미노기, 일반식 R1R2N-으로 나타내지는 2차 아미노기, 일반식 R1O로 나타내지는 알코올기(이때 R1및 R2는 상기 정의된 바와 같음)중에서 선택된 화학 반응성 관능기를 그의 기본 골격에 부수적으로 갖는 활성 항종양 약물을 전달하는 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019880015383A 1987-11-23 1988-11-22 약물-모노클로날 항체 결합체 KR910005887B1 (ko)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US124,313 1987-11-23
US07/124,313 US4952394A (en) 1987-11-23 1987-11-23 Drug-monoclonal antibody conjugates
US124.313 1987-11-23

Publications (2)

Publication Number Publication Date
KR890007724A true KR890007724A (ko) 1989-07-05
KR910005887B1 KR910005887B1 (ko) 1991-08-06

Family

ID=22414122

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1019880015383A KR910005887B1 (ko) 1987-11-23 1988-11-22 약물-모노클로날 항체 결합체

Country Status (16)

Country Link
US (1) US4952394A (ko)
EP (1) EP0317957B1 (ko)
JP (1) JPH02111731A (ko)
KR (1) KR910005887B1 (ko)
AT (1) ATE81986T1 (ko)
AU (1) AU617380B2 (ko)
CA (1) CA1303524C (ko)
DE (1) DE3875700T2 (ko)
DK (1) DK651088A (ko)
FI (1) FI885361A (ko)
GR (1) GR3006211T3 (ko)
IL (1) IL88428A0 (ko)
NO (1) NO169958C (ko)
NZ (1) NZ226955A (ko)
PT (1) PT89062B (ko)
ZA (1) ZA886811B (ko)

Families Citing this family (73)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5149782A (en) * 1988-08-19 1992-09-22 Tanox Biosystems, Inc. Molecular conjugates containing cell membrane-blending agents
US5171563A (en) * 1988-09-30 1992-12-15 Neorx Corporation Cleavable linkers for the reduction of non-target organ retention of immunoconjugates
US5155210A (en) * 1990-09-11 1992-10-13 Brunswick Corporation Methods of conjugating actinomycin d
EP0510132B1 (en) * 1990-09-28 1997-05-14 Neorx Corporation Polymeric carriers for release of covalently linked agents
US5776458A (en) * 1990-12-05 1998-07-07 Pharmacia & Upjohn S.P.A. Anthracycline-conjugates
FR2676058B1 (fr) * 1991-04-30 1994-02-25 Hoechst Lab Prodrogues glycosylees, leur procede de preparation et leur utilisation dans le traitement des cancers.
ATE412769T1 (de) * 1994-04-05 2008-11-15 Morre D James Nadh-oxidase als zielmolekül in diagnose und therapie
US20030119724A1 (en) * 1995-11-22 2003-06-26 Ts`O Paul O.P. Ligands to enhance cellular uptake of biomolecules
EP0932390A1 (en) * 1996-10-11 1999-08-04 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method
US6207805B1 (en) 1997-07-18 2001-03-27 University Of Iowa Research Foundation Prostate cell surface antigen-specific antibodies
US7157418B1 (en) 1998-07-22 2007-01-02 Osprey Pharmaceuticals, Ltd. Methods and compositions for treating secondary tissue damage and other inflammatory conditions and disorders
US20030215421A1 (en) * 1999-07-21 2003-11-20 Mcdonald John R. Methods and compositions for treating secondary tissue damage and other inflammatory conditions and disorders
US6299860B1 (en) * 1998-10-15 2001-10-09 Fluoro Probe, Inc. Method for viewing diseased tissue located within a body cavity
US6652836B2 (en) 1998-10-15 2003-11-25 Fluoroprobe, Inc. Method for viewing tumor tissue located within a body cavity
US7303760B2 (en) 1999-04-23 2007-12-04 Alza Corporation Method for treating multi-drug resistant tumors
US7238368B2 (en) 1999-04-23 2007-07-03 Alza Corporation Releasable linkage and compositions containing same
MXPA01010750A (es) * 1999-04-23 2003-08-20 Alza Corp Conjugado que tiene un enlace dividible para utilizarse en un liposoma.
NZ514990A (en) * 1999-04-23 2004-01-30 Alza Corp Releasable linkage and compositions containing same
US7112337B2 (en) 1999-04-23 2006-09-26 Alza Corporation Liposome composition for delivery of nucleic acid
CN1110322C (zh) * 1999-07-21 2003-06-04 中国医学科学院医药生物技术研究所 单克隆抗体Fab'－平阳霉素偶联物及其抗肿瘤作用
AU2001227679A1 (en) * 2000-02-25 2001-09-03 General Atomics Mutant nucleic binding enzymes and use thereof in diagnostic, detection and purification methods
AU2001250898A1 (en) * 2000-03-17 2001-10-03 The Salk Institute For Biological Studies Compositions associated with complex formation
US6610504B1 (en) 2000-04-10 2003-08-26 General Atomics Methods of determining SAM-dependent methyltransferase activity using a mutant SAH hydrolase
EP1282714A2 (en) * 2000-05-10 2003-02-12 Bristol-Myers Squibb Company Modified inosine 5'-monophosphate dehydrogenase polypeptides and uses thereof
WO2002043771A2 (en) 2000-12-01 2002-06-06 Cell Works Inc. Conjugates of glycosylated/galactosylated peptide
WO2002092771A2 (en) 2001-05-11 2002-11-21 Ludwig Institute For Cancer Research Specific binding proteins and uses thereof
US20100056762A1 (en) 2001-05-11 2010-03-04 Old Lloyd J Specific binding proteins and uses thereof
KR20030033007A (ko) * 2001-05-31 2003-04-26 코울터 파머수티컬, 인코포레이티드 세포독소, 약물전구체, 링커 및 이에 유용한 안정화제
US7053188B2 (en) 2002-02-22 2006-05-30 Purdue Research Foundation Monoclonal antibodies specific for neoplasia-specific NADH:disulfide reductase
US7384760B2 (en) * 2004-04-30 2008-06-10 General Atomics Methods for assaying inhibitors of S-adenosylhomocysteine (SAH) hydrolase and S-adenosylmethionine (SAM)-dependent methyltransferase
CA2564076C (en) * 2004-05-19 2014-02-18 Medarex, Inc. Chemical linkers and conjugates thereof
US7691962B2 (en) * 2004-05-19 2010-04-06 Medarex, Inc. Chemical linkers and conjugates thereof
US7541330B2 (en) * 2004-06-15 2009-06-02 Kosan Biosciences Incorporated Conjugates with reduced adverse systemic effects
AU2005281359A1 (en) * 2004-08-26 2006-03-16 Apparao Satyam Prodrugs and codrugs containing novel bio-cleavable disulfide linkers
CN101124249B (zh) * 2005-02-18 2011-06-29 米德列斯公司 抗前列腺特异性膜抗原（psma）的人单克隆抗体
US7714016B2 (en) * 2005-04-08 2010-05-11 Medarex, Inc. Cytotoxic compounds and conjugates with cleavable substrates
BRPI0617546A2 (pt) * 2005-09-26 2011-07-26 Medarex Inc conjugado de fÁrmaco-anticorpo, formulaÇço farmacÊutica, mÉtodo para matar uma cÉlula de tumor, mÉtodo para retardar ou interromper o crescimento de um tumor em um sujeito mamÍfero e composto
CA2627046C (en) 2005-10-26 2015-09-15 Medarex, Inc. Methods and compounds for preparing cc-1065 analogs
CA2627190A1 (en) 2005-11-10 2007-05-24 Medarex, Inc. Duocarmycin derivatives as novel cytotoxic compounds and conjugates
TWI412367B (zh) 2006-12-28 2013-10-21 Medarex Llc 化學鏈接劑與可裂解基質以及其之綴合物
MX2009007987A (es) 2007-01-25 2010-03-01 Dana Farber Cancer Inst Inc Uso de anticuerpos anti-egfr en el tratamiento de enfermedad mediada por egfr mutante.
TW200900059A (en) * 2007-02-21 2009-01-01 Medarex Inc Chemical linkers with single amino acids and conjugates thereof
US9023356B2 (en) 2007-03-15 2015-05-05 Ludwig Institute For Cancer Research Ltd Treatment method using EGFR antibodies and SRC inhibitors and related formulations
EP2164875A4 (en) 2007-05-24 2011-11-30 Us Dept Veterans Affairs INTRANUCLEAR PROTEIN TRANSDUCTION THROUGH A NUCLEOSIDE SALVAGE PATHWAY
JP5532486B2 (ja) 2007-08-14 2014-06-25 ルードヴィッヒ インスティテュート フォー キャンサー リサーチ Ｅｇｆ受容体を標的とするモノクローナル抗体１７５ならびにその誘導体および用途
CA3128656A1 (en) 2007-08-22 2009-02-26 The Regents Of The University Of California Activatable binding polypeptides and methods of identification and use thereof
CA2699912A1 (en) * 2007-09-19 2009-03-26 Oncofluor, Inc. Method for imaging and treating organs and tissues
KR101666631B1 (ko) 2008-05-27 2016-10-17 젠자임 코포레이션 알파-멜라노사이트 자극 호르몬의 펩티드 유사체
NZ602824A (en) 2008-12-05 2014-05-30 Abraxis Bioscience Llc Sparc binding peptides and uses thereof
EP2385955B1 (en) 2009-01-12 2020-08-12 CytomX Therapeutics, Inc. Modified antibody compositions, methods of making and using thereof
WO2010096394A2 (en) 2009-02-17 2010-08-26 Redwood Biosciences, Inc. Aldehyde-tagged protein-based drug carriers and methods of use
AU2010215761B2 (en) 2009-02-23 2017-04-06 Cytomx Therapeutics, Inc Proproteins and methods of use thereof
US9155801B2 (en) 2009-05-28 2015-10-13 The United States Government As Represented By The Department Of Veterans Affairs Amino acid sequences which enhance peptide conjugate solubility
US8871744B2 (en) 2010-07-21 2014-10-28 B & G Partyers, LLC Compounds and methods for selectively targeting tumor-associated mucins
GB201012410D0 (en) 2010-07-23 2010-09-08 Medical Res Council Intracellular immunity
AU2012205301B2 (en) 2011-01-14 2017-01-05 Redwood Bioscience, Inc. Aldehyde-tagged immunoglobulin polypeptides and method of use thereof
GB201202268D0 (en) 2012-02-09 2012-03-28 Medical Res Council Intracellular immunity
JP6133431B2 (ja) 2012-11-24 2017-05-24 ハンジョウ ディーエーシー バイオテック シーオー．，エルティディ．Ｈａｎｇｚｈｏｕ Ｄａｃ Ｂｉｏｔｅｃｈ Ｃｏ．，Ｌｔｄ． 親水性連結体及び薬物分子と細胞結合分子との共役反応における親水性連結体の使用
US10464955B2 (en) 2014-02-28 2019-11-05 Hangzhou Dac Biotech Co., Ltd. Charged linkers and their uses for conjugation
JP6921743B2 (ja) 2014-11-05 2021-08-18 ナンヤン テクノロジカル ユニヴァーシティー 安定化かつ自律性抗体ｖｈドメイン
AU2015242213A1 (en) 2015-07-12 2018-03-08 Hangzhou Dac Biotech Co., Ltd Bridge linkers for conjugation of cell-binding molecules
US9839687B2 (en) 2015-07-15 2017-12-12 Suzhou M-Conj Biotech Co., Ltd. Acetylenedicarboxyl linkers and their uses in specific conjugation of a cell-binding molecule
AU2017257504A1 (en) 2016-04-26 2018-10-25 R.P. Scherer Technologies, Llc Antibody conjugates and methods of making and using the same
CA3027960C (en) 2016-06-15 2022-06-14 Yale University Antibody-mediated autocatalytic, targeted delivery of nanocarriers to tumors
US20190330317A1 (en) 2016-06-15 2019-10-31 Yale University Anti-guanosine antibody as a molecular delivery vehicle
KR20220147720A (ko) 2016-11-14 2022-11-03 항저우 디에이씨 바이오테크 씨오, 엘티디 결합 링커, 그러한 결합 링커를 함유하는 세포 결합 분자-약물 결합체, 링커를 갖는 그러한 결합체의 제조 및 사용
WO2019152806A1 (en) 2018-02-01 2019-08-08 Yale University Compositions and methods for enhancing nuclear translocation
WO2022013613A2 (en) 2020-07-17 2022-01-20 Onena Medicines S.L. Antibodies against lefty proteins
EP4079327A1 (en) * 2021-04-22 2022-10-26 Centaurus Polytherapeutics Payloads for drug-conjugates and their use for treating cancer
WO2023010060A2 (en) 2021-07-27 2023-02-02 Novab, Inc. Engineered vlrb antibodies with immune effector functions
WO2023056450A1 (en) 2021-09-30 2023-04-06 Yale University Compositions and methods for the treatment of autosomal dominant polycystic kidney disease and other diseases having upregulated mtor activity
WO2024050524A1 (en) 2022-09-01 2024-03-07 University Of Georgia Research Foundation, Inc. Compositions and methods for directing apolipoprotein l1 to induce mammalian cell death
WO2024064752A2 (en) 2022-09-20 2024-03-28 Yale University Compositions of wet adhesives derived from vibrio cholerae biofilm adhesins and methods thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4003792A (en) * 1967-07-01 1977-01-18 Miles Laboratories, Inc. Conjugates of acid polysaccharides and complex organic substances
AU8762982A (en) * 1981-07-02 1983-02-02 Walton, A.G. Glycosaminoglycan drug complexes
US4671958A (en) * 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
JPH0651643B2 (ja) * 1983-01-19 1994-07-06 帝人株式会社 殺細胞性修飾免疫グロブリン及びその製造方法
US4625014A (en) * 1984-07-10 1986-11-25 Dana-Farber Cancer Institute, Inc. Cell-delivery agent
DE3684887D1 (de) * 1985-11-29 1992-05-21 Biomatrix Inc Arzneistoffabgabesysteme auf basis von hyaluronan, dessen derivaten und salzen sowie verfahren zu deren herstellung.
GB8603537D0 (en) * 1986-02-13 1986-03-19 Parker D Conjugate compound

Also Published As

Publication number Publication date
AU2582488A (en) 1989-05-25
NO885199L (no) 1989-05-24
NO885199D0 (no) 1988-11-22
NZ226955A (en) 1991-11-26
US4952394A (en) 1990-08-28
KR910005887B1 (ko) 1991-08-06
AU617380B2 (en) 1991-11-28
NO169958B (no) 1992-05-18
FI885361A0 (fi) 1988-11-18
FI885361A (fi) 1989-05-24
EP0317957B1 (en) 1992-11-04
JPH02111731A (ja) 1990-04-24
EP0317957A3 (en) 1989-07-05
ATE81986T1 (de) 1992-11-15
GR3006211T3 (ko) 1993-06-21
PT89062A (pt) 1989-11-30
ZA886811B (en) 1989-07-26
IL88428A0 (en) 1989-06-30
DK651088A (da) 1989-05-24
NO169958C (no) 1992-08-26
CA1303524C (en) 1992-06-16
DE3875700D1 (de) 1992-12-10
EP0317957A2 (en) 1989-05-31
DK651088D0 (da) 1988-11-22
DE3875700T2 (de) 1993-03-18
PT89062B (pt) 1993-07-30

Similar Documents

Publication Publication Date Title
KR890007724A (ko) 약물-모노클로날 항체 결합체
CA2495795A1 (en) Cross-linkers with high reactivity and solubility and their use in the preparation of conjugates for targeted delivery of small molecule drugs
RU95112841A (ru) Полимерный конъюгат, способ его получения, производная 20-0-ациламинокамптотецина и способ ее получения, фармацевтическая композиция
DK1492526T3 (da) Konjugerede prodrugs af CC-1065-analoger
KR900002804A (ko) 세포독성 약물 결합체 및 이의 제조방법
CA2437983A1 (en) Transporters comprising spaced arginine moieties
KR920701200A (ko) 신규의 4h-3,1-벤조옥사진-4-온 유도체
CY1112527T1 (el) Συνθεσεις που περιεχουν αμιοdαrονε και sulfoalkyl ether cyclodextrin
WO2002088172B1 (en) Pentapeptide compounds and uses related thereto
CA2494049A1 (en) Dehydrophenylahistins and analogs thereof and the synthesis of dehydrophenylahistins and analogs thereof
DE60303961D1 (de) Modifizierte saccharide, deren konjugate sowie deren herstellung
ATE416186T1 (de) Phenylethylenamin-derivate
FR2765478B1 (fr) Nouvelles compositions cosmetiques comprenant un polymere filmogene
TR200101663T2 (tr) Pro-kollajen c-proteinaz inhibitörleri
FI952141A (fi) Molekyylimerkintä käyttäen 2-hydraninopyridiinijohdannaisia
KR910020034A (ko) 내인성 신경 전달 물질의 유도체, 이들의 염, 이들을 함유하는 조성물, 이들의 제조 방법 및 용도
PT96226A (pt) Processo para a preparacao de derivados morfolinilicos de doxorubicina e de composicoes farmaceuticas que os contem
KR880011112A (ko) 벤즈아제핀 설폰아미드 화합물
DK0696585T3 (da) Nyt bisoxadiazolidinderivat
KR910004557A (ko) 2,4,6-치환 페놀 유도체
CA2217026A1 (en) New antiviral substituted pyrimidinedione homocarbocyclic nucleoside derivatives and methods for the preparation thereof and compositions containing the same as active ingredients
DE69125707D1 (de) Anthracyclinkonjugate
FI940011A0 (fi) Mono- ja bis-alkyyliaminoantrasykliinit
IE800912L (en) Bis(4-demethoxydaunorubicin) dihydrazones
KR910000638A (ko) 피롤카르복시산 유도체

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
G160 Decision to publish patent application
E701 Decision to grant or registration of patent right
GRNT Written decision to grant
LAPS Lapse due to unpaid annual fee