JP6283030B2 - 高度に多様なコンビナトリアル抗体ライブラリ - Google Patents
高度に多様なコンビナトリアル抗体ライブラリ Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/005—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies constructed by phage libraries
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
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- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
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- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
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Description
(1.発明の分野)
本発明は、概して、ラクダ種から得られる抗体ライブラリに、より詳細には、野生型ヒト抗体において使用されるものに相当する鎖のファミリーを含有するラクダ抗体ライブラリに関する。
リボソームディスプレイ、ファージディスプレイ、及び細胞表面ディスプレイなどのディスプレイ法の出現によって、抗体ライブラリは、抗体の研究及び開発のための、ますます重要な手立てとなりつつある。抗体ライブラリは、設計、及び構築の手段の点で違いがある。最も重要なライブラリは、治療用抗体の特定及び単離のために開発されたものである。概要は、Ponselらの文献「高親和性、発展性、及び機能的規模:コンビナトリアル抗体ライブラリ産生の聖杯(High Affinity, Developability and Functional Size: The Holy Grail of Combinatorial Antibody Library Generation)」, Molecules 2011, 16, 3675-3700によって提供されている。
本発明は、ラクダ種に由来する抗体ライブラリであって、以下のヒト抗体鎖ファミリーのうちの少なくとも1つに属する抗体鎖を含有する前記ライブラリに関する:VH6;Vκ3;及びVλ6。好ましいのは、ヒトVλ6ファミリーに属する抗体鎖を含有する抗体ライブラリである。
以下は、発明の詳細な説明である。
「抗体」(Ab)及び「免疫グロブリン」(Ig)は、(標的)抗原に対する結合特異性を発揮する糖タンパク質である。ラクダ種は、2つの異なる型の抗体;旧来又は「従来の」抗体と重鎖抗体を有することが公知である。
a)従来のラクダ抗体のVH及び/又はVLドメインをコードする核酸分子の領域を増幅して、増幅された遺伝子断片(各遺伝子断片は、従来のラクダ抗体のVHドメインをコードするヌクレオチドの配列又はVLドメインをコードするヌクレオチドの配列を含有する)を得ること;及び
b)a)で得られた遺伝子断片を、各発現ベクターが、VHドメインをコードする遺伝子断片及び/又はVLドメインをコードする遺伝子断片を少なくとも含有するように、発現ベクターにクローン化し、それによって発現ベクターのライブラリを得ること。
(プライマー配列を含む増幅プロトコルの説明)
免疫化、PBL単離、RNA抽出、及びcDNA調製を、Dreierらの米国特許出願公開第2011/0300140号に開示されている通りに行った。
表1.ラクダVH遺伝子の増幅のためのFR1プライマー
S-G又はC
M-A又はC
Y-T又はC
K-G又はT
W-A又はT
R-G又はA
N-A、C、T、G、不明、その他
Claims (16)
- ラクダ種から得られる抗体ライブラリであって、少なくとも7種の異なるヒト抗体鎖ファミリーに属する抗体鎖を含有する前記ライブラリ。
- 少なくとも2つの異なる遺伝子によって発現される1つのヒト抗体鎖ファミリー内の抗体鎖を含む、請求項1記載の抗体ライブラリ。
- ラマから得られる、請求項1記載の抗体ライブラリ。
- 少なくとも10種の異なるヒト抗体鎖ファミリーに属する抗体鎖を含有する、請求項1記載の抗体ライブラリ。
- 少なくとも12種の異なるヒト抗体鎖ファミリーに属する抗体鎖を含有する、請求項1記載の抗体ライブラリ。
- 少なくとも15種の異なるヒト抗体鎖ファミリーに属する抗体鎖を含有する、請求項1記載の抗体ライブラリ。
- 以下のヒト抗体鎖ファミリーのうちの少なくとも1つの抗体鎖を含有する、請求項1記載の抗体ライブラリ:VH6;Vκ3;及びVλ6。
- ヒト抗体鎖ファミリーVH3、Vκ1、及びVλ6のメンバーを含む、請求項1記載の抗体ライブラリ。
- ヒト抗体鎖ファミリーVH1、VH3、Vκ1、及びVλ6のメンバーを含む、請求項8記載の抗体ライブラリ。
- ヒト抗体鎖ファミリーVH1、VH3、Vκ1、Vλ1、及びVλ6のメンバーを含む、請求項9記載の抗体ライブラリ。
- ヒト抗体鎖ファミリーVH1、VH3、Vκ1、Vλ1、Vλ2、及びVλ6のメンバーを含む、請求項11記載の抗体ライブラリ。
- ヒト抗体鎖ファミリーVH1、VH3、Vκ1、Vλ1、Vλ2、及びVλ6のメンバーを含む、請求項11記載の抗体ライブラリ。
- ヒト抗体鎖ファミリーVH1、VH3、Vκ1、Vκ2、Vλ1、Vλ2、及びVλ6のメンバーを含む、請求項12記載の抗体ライブラリ。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201261695819P | 2012-08-31 | 2012-08-31 | |
US61/695,819 | 2012-08-31 | ||
PCT/EP2013/068110 WO2014033304A2 (en) | 2012-08-31 | 2013-09-02 | Highly diverse combinatorial antibody libraries |
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JP2015526495A JP2015526495A (ja) | 2015-09-10 |
JP6283030B2 true JP6283030B2 (ja) | 2018-02-21 |
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JP2015529046A Active JP6283030B2 (ja) | 2012-08-31 | 2013-09-02 | 高度に多様なコンビナトリアル抗体ライブラリ |
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Country | Link |
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US (1) | US10040870B2 (ja) |
EP (1) | EP2890709A2 (ja) |
JP (1) | JP6283030B2 (ja) |
CN (1) | CN104583236A (ja) |
AU (1) | AU2013310839B2 (ja) |
CA (1) | CA2879834A1 (ja) |
IL (1) | IL236524B (ja) |
IN (1) | IN2015DN00138A (ja) |
WO (1) | WO2014033304A2 (ja) |
Families Citing this family (18)
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KR101997241B1 (ko) | 2015-05-21 | 2019-07-09 | 하푼 테라퓨틱스, 인크. | 삼중특이성 결합 단백질 및 사용 방법 |
US11623958B2 (en) | 2016-05-20 | 2023-04-11 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
US10100106B2 (en) | 2016-05-20 | 2018-10-16 | Harpoon Therapeutics, Inc. | Single domain serum albumin binding protein |
US10544221B2 (en) | 2016-05-20 | 2020-01-28 | Harpoon Therapeutics, Inc. | Single chain variable fragment CD3 binding proteins |
JP2019525772A (ja) | 2016-07-08 | 2019-09-12 | スターテン・バイオテクノロジー・ベー・フェー | 抗apoc3抗体およびその使用方法 |
WO2018098354A1 (en) | 2016-11-23 | 2018-05-31 | Harpoon Therapeutics, Inc. | Prostate specific membrane antigen binding protein |
BR112019010602A2 (pt) * | 2016-11-23 | 2019-12-17 | Harpoon Therapeutics Inc | proteínas trispecíficas para psma e métodos de uso |
CN110139952B (zh) * | 2016-12-09 | 2022-11-25 | 深圳华大生命科学研究院 | 骆驼科抗体可变区免疫组库构建的引物组合及应用 |
WO2018160754A2 (en) | 2017-02-28 | 2018-09-07 | Harpoon Therapeutics, Inc. | Inducible monovalent antigen binding protein |
WO2018193427A1 (en) | 2017-04-21 | 2018-10-25 | Staten Biotechnology B.V. | Anti-apoc3 antibodies and methods of use thereof |
US10730954B2 (en) | 2017-05-12 | 2020-08-04 | Harpoon Therapeutics, Inc. | MSLN targeting trispecific proteins and methods of use |
US10543271B2 (en) | 2017-05-12 | 2020-01-28 | Harpoon Therapeutics, Inc. | Mesothelin binding proteins |
PE20201183A1 (es) | 2017-10-13 | 2020-11-03 | Harpoon Therapeutics Inc | Proteinas trispecificas y metodos de uso |
US10927180B2 (en) | 2017-10-13 | 2021-02-23 | Harpoon Therapeutics, Inc. | B cell maturation antigen binding proteins |
US10538583B2 (en) | 2017-10-31 | 2020-01-21 | Staten Biotechnology B.V. | Anti-APOC3 antibodies and compositions thereof |
MA50516A (fr) | 2017-10-31 | 2020-09-09 | Staten Biotechnology B V | Anticorps anti-apoc3 et leurs procédés d'utilisation |
IL297931A (en) | 2018-09-25 | 2023-01-01 | Harpoon Therapeutics Inc | dll3 binding proteins and methods of use |
JP2023527609A (ja) | 2020-02-21 | 2023-06-30 | ハープーン セラピューティクス,インク. | Flt3結合タンパク質および使用方法 |
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GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
GB2461546B (en) * | 2008-07-02 | 2010-07-07 | Argen X Bv | Antigen binding polypeptides |
US8444976B2 (en) | 2008-07-02 | 2013-05-21 | Argen-X B.V. | Antigen binding polypeptides |
US8921281B2 (en) * | 2009-05-20 | 2014-12-30 | Novimmune S.A. | Synthetic polypeptide libraries and methods for generating naturally diversified polypeptide variants |
GB2476681B (en) * | 2010-01-04 | 2012-04-04 | Argen X Bv | Humanized camelid VH, VK and VL immunoglobulin domains |
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- 2013-09-02 JP JP2015529046A patent/JP6283030B2/ja active Active
- 2013-09-02 US US14/419,881 patent/US10040870B2/en active Active
- 2013-09-02 AU AU2013310839A patent/AU2013310839B2/en active Active
- 2013-09-02 CN CN201380044638.9A patent/CN104583236A/zh active Pending
- 2013-09-02 EP EP13758830.7A patent/EP2890709A2/en not_active Withdrawn
- 2013-09-02 CA CA2879834A patent/CA2879834A1/en not_active Abandoned
- 2013-09-02 WO PCT/EP2013/068110 patent/WO2014033304A2/en active Application Filing
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Publication number | Publication date |
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IN2015DN00138A (ja) | 2015-06-12 |
WO2014033304A2 (en) | 2014-03-06 |
AU2013310839B2 (en) | 2017-06-01 |
AU2013310839A1 (en) | 2015-01-29 |
CA2879834A1 (en) | 2014-03-06 |
IL236524B (en) | 2019-01-31 |
CN104583236A (zh) | 2015-04-29 |
WO2014033304A3 (en) | 2014-05-01 |
JP2015526495A (ja) | 2015-09-10 |
EP2890709A2 (en) | 2015-07-08 |
US10040870B2 (en) | 2018-08-07 |
US20150166680A1 (en) | 2015-06-18 |
IL236524A0 (en) | 2015-02-26 |
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