JPH03504645A - 架橋抗体およびその製造方法 - Google Patents
架橋抗体およびその製造方法Info
- Publication number
- JPH03504645A JPH03504645A JP2503355A JP50335590A JPH03504645A JP H03504645 A JPH03504645 A JP H03504645A JP 2503355 A JP2503355 A JP 2503355A JP 50335590 A JP50335590 A JP 50335590A JP H03504645 A JPH03504645 A JP H03504645A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- cross
- conjugate
- chain
- zygote
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1093—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody conjugates with carriers being antibodies
-
- 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
-
- 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
- A61K47/6875—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 the antibody being a hybrid immunoglobulin
- A61K47/6877—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 the antibody being a hybrid immunoglobulin the antibody being an immunoglobulin containing regions, domains or residues from different species
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/10—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody
- A61K51/1084—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody the antibody being a hybrid immunoglobulin
- A61K51/1087—Antibodies or immunoglobulins; Fragments thereof, the carrier being an antibody, an immunoglobulin or a fragment thereof, e.g. a camelised human single domain antibody or the Fc fragment of an antibody the antibody being a hybrid immunoglobulin the immunoglobulin comprises domains from different animal species, e.g. chimeric immunoglobulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Abstract
Description
Claims (1)
- 【特許請求の範囲】 (1)少なくとも1個の非ジスルフイド性鎖間架橋を有する標識抗体分子からな り、その架橋は抗体の抗原結合ドメインの外側に位置する1個または2個以上の 架橋部位で各鎖に結合している架橋抗体接合体。 (2)架橋部位はアミノ酸残基の側鎖に存在するアミノ、スルフヒドリル、カル ボキシル、フェノールまたは他の芳香族もしくは異項環芳香族官能基である請求 項(1)記載の接合体。 (3)架橋部位はシステイン残差の側鎖に存在するスルフヒドリル基である請求 項121記載の接合体。 (4)システイン残基は蝶番領域における各重鎖中に存在する請求項(3)記載 の接合体。 (5)システイン残基は蝶番領域に存在する唯一のシステイン残基である請求項 (4)記載の接合体。 (6)抗体は組換え抗体である請求項(1)〜(5)のいずれかに記載の接合体 。 (7)抗体は抗体フラグメントである請求項(1)〜(6)のいずれかに記載の 接合体。 (8)フラグメントはF(ab′)2フラグメントである請求項(7)記載の接 合体。 (9)非ジスルフィド性鎖間架橋は同種または異種官能性架橋剤の残基である請 求項(1)〜(8)のいずれかに記載の接合体。 (10)標識抗体分子は、レポーターまたはエフェクター基が結合している抗体 分子である請求項(1)〜(9)のいずれかに記載の接合体。 (11)レポーターまたはエフェクター基は、放射性核種、キレート化金属、螢 光化合物、NMRもしくはESRで検出できる化合物、薬理学的物質、酵素また はホルモンである請求項(10)記載の接合体。 (12)レポーターまたはエフェクター基は、放射性核種またはキレート化金属 である請求項(11)記載の接合体。 (13)放射性核種は放射性ヨウ素である請求項(12)記載の接合体。 (14)キレート化金属は、配位数2から8までの二価または三価陽性金属と多 座キレート剤のキレートである請求項(12)記載の接合体。 (15)多座キレート剤は、非環式もしくは環式ポリアミン、ポリエーテル、ポ リアミド、ポルフイリンまたは炭素環式誘導体である請求項(14)記載の接合 体。 (16)非環式ポリアミンはポリアミノカルボン酸である請求項(15)記載の 接合体。 (17)環式ポリアミンは環式トリアザまたはテトラアザ誘導体である請求項( 15)記載の接合体。 (18)少なくとも1個の非ジスルフイド性鎖間架橋を有する標識抗体分子であ って、その架橋は抗体の抗原結合ドメインの外側に位置する1個または2個以上 の架橋部位で各鎖に結合している抗体と、1種または2種以上の医薬的に許容さ れる担体または賦形剤からなる医薬組成物。 (19)少なくとも1個の非ジスルフイド性鎖間架橋を有する標識抗体分子から なり、その架橋に抗体の抗原結合ドメインの外側に位置する1個または2個以上 の架橋部位で各鎖に結合している抗体接合体を製造するにあたり、架橋剤を抗体 と反応させる方法。 (20)抗体は架橋剤に対して過剰濃度で存在させる請求項(19)記載の方法 。 (21)少なくとも1個の非ジスルフイド性鎖間架橋を有する標識抗体分子から なり、その架橋は抗体の抗原結合ドメインの外側に位置する1個または2個以上 の架橋部位で各鎖に結合している、ヒトまたは動物対象の処置またに診断方法に 使用するための抗体接合体。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8903021.7 | 1989-02-10 | ||
GB898903021A GB8903021D0 (en) | 1989-02-10 | 1989-02-10 | Chemical compounds |
Publications (2)
Publication Number | Publication Date |
---|---|
JPH03504645A true JPH03504645A (ja) | 1991-10-09 |
JP2975677B2 JP2975677B2 (ja) | 1999-11-10 |
Family
ID=10651471
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2503355A Expired - Lifetime JP2975677B2 (ja) | 1989-02-10 | 1990-02-12 | 架橋抗体およびその製造方法 |
Country Status (15)
Country | Link |
---|---|
EP (1) | EP0385601B1 (ja) |
JP (1) | JP2975677B2 (ja) |
KR (1) | KR910700076A (ja) |
AT (1) | ATE123653T1 (ja) |
AU (1) | AU636872B2 (ja) |
CA (1) | CA2026313A1 (ja) |
DE (1) | DE69020007T2 (ja) |
GB (2) | GB8903021D0 (ja) |
HU (1) | HUT56289A (ja) |
IE (1) | IE67448B1 (ja) |
IL (1) | IL93346A0 (ja) |
NO (1) | NO904368L (ja) |
NZ (1) | NZ232489A (ja) |
WO (1) | WO1990009196A1 (ja) |
ZA (1) | ZA90982B (ja) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5010176A (en) * | 1988-11-10 | 1991-04-23 | Eli Lilly And Company | Antibody-drug conjugates |
US5194594A (en) * | 1990-09-07 | 1993-03-16 | Techniclone, Inc. | Modified antibodies |
GB9422383D0 (en) * | 1994-11-05 | 1995-01-04 | Wellcome Found | Antibodies |
US5922618A (en) * | 1996-03-04 | 1999-07-13 | Matsushita Electric Industrial Co., Ltd. | Dye-labeled antibody conjugate and preparation method thereof |
US5990286A (en) * | 1996-12-18 | 1999-11-23 | Techniclone, Inc. | Antibodies with reduced net positive charge |
US6306393B1 (en) * | 1997-03-24 | 2001-10-23 | Immunomedics, Inc. | Immunotherapy of B-cell malignancies using anti-CD22 antibodies |
DE19911329A1 (de) * | 1998-03-27 | 2000-09-21 | Benes Ivan Friedrich | Humantherapeutisch anwendbares Radioimmunkonjugat und Verfahren zu seiner Herstellung |
GB9809951D0 (en) | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
US9770517B2 (en) | 2002-03-01 | 2017-09-26 | Immunomedics, Inc. | Anti-Trop-2 antibody-drug conjugates and uses thereof |
US9707302B2 (en) | 2013-07-23 | 2017-07-18 | Immunomedics, Inc. | Combining anti-HLA-DR or anti-Trop-2 antibodies with microtubule inhibitors, PARP inhibitors, bruton kinase inhibitors or phosphoinositide 3-kinase inhibitors significantly improves therapeutic outcome in cancer |
US10058621B2 (en) | 2015-06-25 | 2018-08-28 | Immunomedics, Inc. | Combination therapy with anti-HLA-DR antibodies and kinase inhibitors in hematopoietic cancers |
US9757458B2 (en) | 2011-12-05 | 2017-09-12 | Immunomedics, Inc. | Crosslinking of CD22 by epratuzumab triggers BCR signaling and caspase-dependent apoptosis in hematopoietic cancer cells |
CA2853138A1 (en) | 2011-12-05 | 2013-06-13 | Immunomedics, Inc. | Therapeutic use of anti-cd22 antibodies for inducing trogocytosis |
US9931417B2 (en) | 2012-12-13 | 2018-04-03 | Immunomedics, Inc. | Antibody-SN-38 immunoconjugates with a CL2A linker |
PT2900277T (pt) | 2012-12-13 | 2022-05-25 | Immunomedics Inc | Doses de imunoconjugados de anticorpos e sn-38 para melhorar a eficácia e diminuir a toxicidade |
US10744129B2 (en) | 2012-12-13 | 2020-08-18 | Immunomedics, Inc. | Therapy of small-cell lung cancer (SCLC) with a topoisomerase-I inhibiting antibody-drug conjugate (ADC) targeting Trop-2 |
US9492566B2 (en) | 2012-12-13 | 2016-11-15 | Immunomedics, Inc. | Antibody-drug conjugates and uses thereof |
US10206918B2 (en) | 2012-12-13 | 2019-02-19 | Immunomedics, Inc. | Efficacy of anti-HLA-DR antiboddy drug conjugate IMMU-140 (hL243-CL2A-SN-38) in HLA-DR positive cancers |
US10137196B2 (en) | 2012-12-13 | 2018-11-27 | Immunomedics, Inc. | Dosages of immunoconjugates of antibodies and SN-38 for improved efficacy and decreased toxicity |
ES2819573T3 (es) | 2012-12-13 | 2021-04-16 | Immunomedics Inc | Método para producir inmunoconjugados de anticuerpo-SN-38 con un enlazador CL2A |
US10413539B2 (en) | 2012-12-13 | 2019-09-17 | Immunomedics, Inc. | Therapy for metastatic urothelial cancer with the antibody-drug conjugate, sacituzumab govitecan (IMMU-132) |
US11253606B2 (en) | 2013-07-23 | 2022-02-22 | Immunomedics, Inc. | Combining anti-HLA-DR or anti-Trop-2 antibodies with microtubule inhibitors, PARP inhibitors, Bruton kinase inhibitors or phosphoinositide 3-kinase inhibitors significantly improves therapeutic outcome in cancer |
CA2981543A1 (en) | 2015-04-22 | 2016-10-27 | Immunomedics, Inc. | Isolation, detection, diagnosis and/or characterization of circulating trop-2-positive cancer cells |
US10195175B2 (en) | 2015-06-25 | 2019-02-05 | Immunomedics, Inc. | Synergistic effect of anti-Trop-2 antibody-drug conjugate in combination therapy for triple-negative breast cancer when used with microtubule inhibitors or PARP inhibitors |
CA3011372A1 (en) | 2016-02-10 | 2017-08-17 | Immunomedics, Inc. | Combination of abcg2 inhibitors with sacituzumab govitecan (immu-132) overcomes resistance to sn-38 in trop-2 expressing cancers |
CN109310385A (zh) | 2016-04-27 | 2019-02-05 | 免疫医疗公司 | 抗trop-2-sn-38抗体药物缀合物用于检查点抑制剂复发/难治的肿瘤的疗法的功效 |
EP3600283A4 (en) | 2017-03-27 | 2020-12-16 | Immunomedics, Inc. | TREATMENT OF TROP-2 EXPRESSIVE TRIPLE NEGATIVE BREAST CANCER WITH SACITUZUMAB GOVITECAN AND A RAD51 INHIBITOR |
CN110352201A (zh) | 2017-04-03 | 2019-10-18 | 免疫医疗公司 | 用于癌症疗法的抗体药物缀合物的皮下施用 |
CN111876460A (zh) * | 2020-08-17 | 2020-11-03 | 郑州伊美诺生物技术有限公司 | 鼠单抗IgG2a F(ab`)2的制备方法 |
CN117466980A (zh) * | 2023-11-02 | 2024-01-30 | 浙江普罗亭健康科技有限公司 | 基于多肽链骨架应用于金属抗体标记的负载金属缀合物及其应用 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4751286A (en) * | 1985-11-19 | 1988-06-14 | The Johns Hopkins University | Protein label and drug delivery system |
GB8603537D0 (en) * | 1986-02-13 | 1986-03-19 | Parker D | Conjugate compound |
GB8720833D0 (en) * | 1987-09-04 | 1987-10-14 | Celltech Ltd | Recombinant dna product |
-
1989
- 1989-02-10 GB GB898903021A patent/GB8903021D0/en active Pending
-
1990
- 1990-02-09 ZA ZA90982A patent/ZA90982B/xx unknown
- 1990-02-11 IL IL93346A patent/IL93346A0/xx unknown
- 1990-02-12 AT AT90301442T patent/ATE123653T1/de not_active IP Right Cessation
- 1990-02-12 NZ NZ232489A patent/NZ232489A/en unknown
- 1990-02-12 EP EP90301442A patent/EP0385601B1/en not_active Expired - Lifetime
- 1990-02-12 WO PCT/GB1990/000214 patent/WO1990009196A1/en active Application Filing
- 1990-02-12 IE IE49390A patent/IE67448B1/en not_active IP Right Cessation
- 1990-02-12 KR KR1019900702232A patent/KR910700076A/ko not_active Application Discontinuation
- 1990-02-12 HU HU901927A patent/HUT56289A/hu unknown
- 1990-02-12 DE DE69020007T patent/DE69020007T2/de not_active Expired - Lifetime
- 1990-02-12 JP JP2503355A patent/JP2975677B2/ja not_active Expired - Lifetime
- 1990-02-12 CA CA002026313A patent/CA2026313A1/en not_active Abandoned
- 1990-02-12 AU AU50810/90A patent/AU636872B2/en not_active Ceased
- 1990-10-09 NO NO90904368A patent/NO904368L/no unknown
- 1990-10-09 GB GB9021895A patent/GB2236529B/en not_active Revoked
Also Published As
Publication number | Publication date |
---|---|
AU636872B2 (en) | 1993-05-13 |
ZA90982B (en) | 1991-10-30 |
AU5081090A (en) | 1990-09-05 |
ATE123653T1 (de) | 1995-06-15 |
NO904368L (no) | 1990-12-10 |
IE900493L (en) | 1990-08-10 |
DE69020007T2 (de) | 1995-11-23 |
IE67448B1 (en) | 1996-04-03 |
HUT56289A (en) | 1991-08-28 |
HU901927D0 (en) | 1991-03-28 |
WO1990009196A1 (en) | 1990-08-23 |
NZ232489A (en) | 1992-09-25 |
EP0385601B1 (en) | 1995-06-14 |
EP0385601A2 (en) | 1990-09-05 |
IL93346A0 (en) | 1990-11-29 |
GB9021895D0 (en) | 1990-11-21 |
JP2975677B2 (ja) | 1999-11-10 |
DE69020007D1 (de) | 1995-07-20 |
GB2236529A (en) | 1991-04-10 |
CA2026313A1 (en) | 1990-08-11 |
GB2236529B (en) | 1993-03-31 |
NO904368D0 (no) | 1990-10-09 |
GB8903021D0 (en) | 1989-03-30 |
EP0385601A3 (en) | 1990-11-14 |
KR910700076A (ko) | 1991-03-13 |
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