JPH04504365A - 異種抗体の生成 - Google Patents
異種抗体の生成Info
- Publication number
- JPH04504365A JPH04504365A JP3503394A JP50339491A JPH04504365A JP H04504365 A JPH04504365 A JP H04504365A JP 3503394 A JP3503394 A JP 3503394A JP 50339491 A JP50339491 A JP 50339491A JP H04504365 A JPH04504365 A JP H04504365A
- Authority
- JP
- Japan
- Prior art keywords
- locus
- mouse
- human
- primate
- heavy chain
- 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.)
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Abstract
Description
Claims (25)
- 1.哺乳類で非霊長類の宿主において異種の霊長類抗血清または抗体アナログを 生産する方法で、ある免疫原に対する免疫応答を刺激する条件下、該免疫原で該 宿主を免疫化し、それにより該宿主が該免疫原に対する免疫応答を獲得し該免疫 原に特異的な表面免疫グロブリンおよび該免疫原に特異的な抗体を有する血漿細 胞、B細胞を生産させることを含み、かつ該非霊長類宿主が(1)内在性免疫グ ロブリン重鎖、および(2)少なくとも1つの内在性軽鎖を実質的に発現し得ず 、かつ外来性霊長類重鎖および経鎖またはそのアナログを発現し得ることを特徴 とするものである方法。
- 2.前記宿主がマウスである請求の範囲1記載の方法。
- 3.前記アナログが免疫グロブリン不変部以外のペプチドにペプチド結合で連結 した可変部を含む請求の範囲1記載の方法。
- 4.前記抗血清がヒト抗血清である請求の範囲1記載の方法。
- 5.モノクローナル抗体の生産を目的として前記B細胞を不朽化するステップを 含む請求の範囲1記載の方法。
- 6.前記宿主が外来性可変部および少なくとも1つのヒト不変部を含む機能性免 疫グロブリン遺伝子座を有するB細胞を含む請求の範囲1記載の方法。
- 7.前記宿主が少なくとも重鎖に関するヒト免疫グロブリン遺伝子座の機能的部 分および重鎖2コピーおよび少なくとも1タイプの軽鎖2コピーに関する不活性 化内在性遺伝子座を含み、その結果実質的に内在性抗体サブユニットを発現し得 ない請求の範囲1記載の方法。
- 8.非霊長類のトランスジェニック哺乳動物で、少なくとも重鎖ドメインの少な くとも1部および軽鎖ドメインに関するヒト免疫グロブリン遺伝子座の機能性部 分および重鎖2コピーおよび少なくとも1タイプの軽鎖2コピーに閲する不活性 化内在性遺伝子座を含むゲノムを有し、その結果実質的に内在性抗体ユニットを 発現し得ない動物。
- 9.前記ヒト免疫グロブリン遺伝子座が類似する内在性遺伝子座に存在する請求 の範囲8記載の非霊長類トランスジェニック哺乳動物。
- 10.前記ヒト免疫グロブリン遺伝子座が類似する内在性遺伝子座以外に存在す る請求の範囲8記載の非霊長類トランスジェニック哺乳動物。
- 11.前記哺乳動物がマウスである請求の範囲8記載の非霊長類トランスジェニ ック哺乳動物。
- 12.前記重鎖ドメインの少なくとも一部が少なくとも1個の不変部を含む請求 の範囲8記載の非霊長類トランスジェニック哺乳動物。
- 13.前記重鎖ドメインの少なくとも一部が不変部以外のペプチド鎖を含む請求 の範囲8記載の非霊長類トランスジェニック哺乳動物。
- 14.少なくとも1つの欠失または挿入の結果免疫グロブリン重鎖の両コピーお よび少なくとも1タイプの軽鎖2コピーからなる不活性化遺伝子座および重鎖お よび軽鎖に関するヒト免疫グロブリンの少なくとも機能性部分を含むゲノムを有 するトランスジェニックマウス。
- 15.前記少なくとも機能性部分が可変部の一部のみを請求の範囲14記載のト ランスジェニックマウス。
- 16.少なくとも1つの欠失または挿入の結果免疫グロブリン重鎖両コピーおよ び少なくとも1タイプの軽鎖2コピーからなる不活性遺伝子座および重鎖および 軽鎖に関するヒト免疫グロブリン遺伝子座の少なくとも機能性部分で、該重鎖お よび該軽鎖の少なくとも1つの不変部が該不変部配列以外の配列を含むゲノムを 有するトランスジェニックマウス。
- 17.重鎖および怪鎖の少なくとも一部に関するヒト免疫グロブリン遺伝子座の 少なくとも機能性部分および該遺伝子座における重鎖2コピーおよび少なくとも 1ウイブの怪鎖2コピーに関する相同組換えによる不活性な内在性遺伝子座を含 み、その結果実質的に内在性抗体ユニットを発現し得ないゲノムを有する非霊長 類トランスジェニック哺乳動物。
- 18.前記哺乳動物がマウスであり、かつ前記ヒト免疫グロブリン重鎖および経 鎖遺伝子座が各々マウス免疫グロブリン重鎖および軽鎖遺伝子座に存在する請求 の範囲17記載の非霊長類トランスジェニック哺乳動物。
- 19.1つの免疫グロブリン遺伝子座のJ領域に障害を有し免疫グロブリンの機 能性サブユニットに再配列する能力を持たない非霊長類胚幹細胞。
- 20.前記サブユニットが重鎖である請求の範囲19記載の幹細胞。
- 21.前記非霊長類がマウスである請求の範囲20記載の幹細胞。
- 22.前記障害が挿入である請求の範囲19記載の幹細胞。
- 23.前記挿入が選択可能なマーカーである請求の範囲22記載の幹細胞。
- 24.前記障害が欠失である請求の範囲19記載の幹細胞。
- 25.前記非霊長類がマウスである請求の範囲19記載の幹細胞。
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Application Number | Priority Date | Filing Date | Title |
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US46600890A | 1990-01-12 | 1990-01-12 | |
US466,008 | 1990-01-12 | ||
US61051590A | 1990-11-08 | 1990-11-08 | |
US610,515 | 1990-11-08 | ||
PCT/US1991/000245 WO1991010741A1 (en) | 1990-01-12 | 1991-01-11 | Generation of xenogeneic antibodies |
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JP9147795A Division JP3068506B2 (ja) | 1990-01-12 | 1997-06-05 | 異種抗体の生成 |
JP9147805A Division JP3068507B2 (ja) | 1990-01-12 | 1997-06-05 | 異種抗体の生成 |
JP10352238A Division JPH11262386A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352239A Division JPH11262388A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
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JPH04504365A true JPH04504365A (ja) | 1992-08-06 |
JP3068180B2 JP3068180B2 (ja) | 2000-07-24 |
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JP03503394A Expired - Lifetime JP3068180B2 (ja) | 1990-01-12 | 1991-01-11 | 異種抗体の生成 |
JP9147805A Expired - Lifetime JP3068507B2 (ja) | 1990-01-12 | 1997-06-05 | 異種抗体の生成 |
JP9147795A Expired - Lifetime JP3068506B2 (ja) | 1990-01-12 | 1997-06-05 | 異種抗体の生成 |
JP10352238A Withdrawn JPH11262386A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352241A Pending JPH11262396A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352240A Pending JPH11239490A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352243A Withdrawn JPH11243973A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352242A Pending JPH11239491A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352239A Pending JPH11262388A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP2006035101A Withdrawn JP2006204301A (ja) | 1990-01-12 | 2006-02-13 | 異種抗体の生成 |
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JP9147805A Expired - Lifetime JP3068507B2 (ja) | 1990-01-12 | 1997-06-05 | 異種抗体の生成 |
JP9147795A Expired - Lifetime JP3068506B2 (ja) | 1990-01-12 | 1997-06-05 | 異種抗体の生成 |
JP10352238A Withdrawn JPH11262386A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352241A Pending JPH11262396A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352240A Pending JPH11239490A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352243A Withdrawn JPH11243973A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352242A Pending JPH11239491A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP10352239A Pending JPH11262388A (ja) | 1990-01-12 | 1998-12-11 | 異種抗体の生成 |
JP2006035101A Withdrawn JP2006204301A (ja) | 1990-01-12 | 2006-02-13 | 異種抗体の生成 |
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AU (1) | AU633698B2 (ja) |
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