JP2003530852A5 - - Google Patents
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- JP2003530852A5 JP2003530852A5 JP2001577463A JP2001577463A JP2003530852A5 JP 2003530852 A5 JP2003530852 A5 JP 2003530852A5 JP 2001577463 A JP2001577463 A JP 2001577463A JP 2001577463 A JP2001577463 A JP 2001577463A JP 2003530852 A5 JP2003530852 A5 JP 2003530852A5
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- 230000000295 complement Effects 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000001225 therapeutic Effects 0.000 description 4
- 102100001249 ALB Human genes 0.000 description 2
- 101710027066 ALB Proteins 0.000 description 2
- 229940050528 albumin Drugs 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 102000037240 fusion proteins Human genes 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 102100007493 CNTF Human genes 0.000 description 1
- 102100006400 CSF2 Human genes 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- QIVBCDIJIAJPQS-SECBINFHSA-N D-tryptophane Chemical compound C1=CC=C2C(C[C@@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-SECBINFHSA-N 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- -1 IL -11 Proteins 0.000 description 1
- 102100013277 IRF1 Human genes 0.000 description 1
- 101700001416 IRF1 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108010002386 Interleukin-3 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108010002335 Interleukin-9 Proteins 0.000 description 1
- 102100011646 LIF Human genes 0.000 description 1
- 101700037605 LIF Proteins 0.000 description 1
- 102100019388 SOAT1 Human genes 0.000 description 1
- 101700025022 SOAT1 Proteins 0.000 description 1
- 102000036902 Thrombopoietin Human genes 0.000 description 1
- 108010041111 Thrombopoietin Proteins 0.000 description 1
- 102000004965 antibodies Human genes 0.000 description 1
- 108090001123 antibodies Proteins 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 102000003675 cytokine receptors Human genes 0.000 description 1
- 108010057085 cytokine receptors Proteins 0.000 description 1
- 125000000267 glycino group Chemical group [H]N([*])C([H])([H])C(=O)O[H] 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 108091008007 nuclear receptors type I Proteins 0.000 description 1
- 101710028406 satA Proteins 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
Description
好ましい実施形態においては、治療用タンパク質と特異的に結合し、アルブミン融合タンパク質の治療用タンパク質部分に対応する、抗体のフラグメントもしくは変異体は、(Gly４Ser)３などのペプチドリンカーによって治療用タンパク質のVLドメインと連結された、治療用タンパク質のVHドメインを含んでなるscFvを含んでなるか、またはそのscFvから構成されている(配列番号72)。
天然に存在するシグナル配列を用いて本発明のアルブミン融合タンパク質を産生する場合、pC4は第2のシグナルペプチドを必要としない。このほか、天然に存在するシグナル配列を使用しない場合には、ベクターは異種シグナル配列が含まれるように改変することができる。(たとえば、国際公開WO 96/34891号を参照されたい)
ヒトIgG Fc領域:
GGGATCCGGAGCCCAAATCTTCTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAATTCGAGGGTGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACTCCTGAGGTCACATGCGTGGTGGTGGACGTAAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAACCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCAAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGAGTGCGACGGCCGCGACTCTAGAGGAT (配列番号81)
ヒトIgG Fc領域:
GGGATCCGGAGCCCAAATCTTCTGACAAAACTCACACATGCCCACCGTGCCCAGCACCTGAATTCGAGGGTGCACCGTCAGTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACTCCTGAGGTCACATGCGTGGTGGTGGACGTAAGCCACGAAGACCCTGAGGTCAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAGCAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACTGGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAACCCCCATCGAGAAAACCATCTCCAAAGCCAAAGGGCAGCCCCGAGAACCACAGGTGTACACCCTGCCCCCATCCCGGGATGAGCTGACCAAGAACCAGGTCAGCCTGACCTGCCTGGTCAAAGGCTTCTATCCAAGCGACATCGCCGTGGAGTGGGAGAGCAATGGGCAGCCGGAGAACAACTACAAGACCACGCCTCCCGTGCTGGACTCCGACGGCTCCTTCTTCCTCTACAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACGTCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAGCCTCTCCCTGTCTCCGGGTAAATGAGTGCGACGGCCGCGACTCTAGAGGAT (配列番号81)
Jakは、以下の表によりまとめられる多種多様な受容体によって活性化される。(Schidler and Darnell, Ann. Rev. Biochem. 64:621-51(1995)によるレビューから抜粋編集)。Jakを活性化しうるサイトカイン受容体ファミリーは、2つのグループに分けられる：(a)クラス1は、IL-2、IL-3、IL-4、IL-6、IL-7、IL-9、IL-11、IL-12、IL-15、Epo、PRL、GH、G-CSF、GM-CSF、LIF、CNTF、およびトロンボポエチンに対する受容体を含み;そして(b)クラス2は、IFN-a、IFN-g、およびIL-10を含む。クラス1受容体は、保存されたシステインモチーフ(4つの保存されたシステインおよび1つのトリプトファンのセット)およびWSXWSモチーフ(Trp-Ser-Xaa-Trp-Ser(配列番号82)をコードする膜近接領域)を共有する。
実施例32〜33に記載の生物学的アッセイに使用されるプロモーターエレメント含有合成GASを構築するために、PCRに基づくストラテジーを利用してGAS-SV40プロモーター配列を作製する。5'プライマーには、IRF1プロモーター中に見いだされ、一定範囲のサイトカインによる誘導を受けるとSTATに結合することが既に実証されている、GAS結合部位の4つのタンデムコピーが含まれるが(Rothman et al., Immunity 1:457-468(1994))、他のGASまたはISREエレメントを代わりに使用することもできる。5'プライマーはまた、SV40初期プロモーター配列に相補的な18bpの配列を含み、そしてXhoI部位でフランキングされている。5'プライマーの配列は次のとおりである。
5’:GCGCCTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAG:3’ (配列番号83)
5’:GCGCCTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAG:3’ (配列番号83)
下流プライマーは、SV40プロモーターに相補的であり、そしてHindIII部位でフランキングされている： 5':GCGGCAAGCTTTTTGCAAAGCCTAGGC:3' (配列番号84)。
Clontechから入手したB-gal:プロモータープラスミド中に存在するSV40プロモーター鋳型を用いてPCR増幅を行う。得られたPCR断片をXhoI/Hind IIIで消化させ、そしてBLSK2-.(Stratagene)中にサブクローン化する。フォワードおよびリバースプライマーを用いる配列決定により、インサートが以下の配列を含有することを確認する。
5’:CTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTT:3' (配列番号85)
5’:CTCGAGATTTCCCCGAAATCTAGATTTCCCCGAAATGATTTCCCCGAAATGATTTCCCCGAAATATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTT:3' (配列番号85)
5’ GCGCTCGAGGGATGACAGCGATAGAACCCCGG-3' (配列番号86)
5’ GCGAAGCTTCGCGACTCCCCGGATCCGCCTC-3' (配列番号87)
5’ GCGAAGCTTCGCGACTCCCCGGATCCGCCTC-3' (配列番号87)
NF-KBプロモーターエレメントを含むベクターを構築するために、PCRに基づいたストラテジーを利用する。上流プライマーは、NF-KB結合部位(GGGGACTTTCCC)(配列番号88)の4つのタンデムコピー、SV40初期プロモーター配列の5'末端に相補的な18bpの配列を含み、そしてXhoI部位でフランキングされている。
5’:GCGGCCTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGACTTTCCATCCTGCCATCTCAATTAG:3’ (配列番号89)
下流プライマーは、SV40プロモーターの3'末端に相補的であり、そしてHindIII部位でフランキングされている。
5’:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3’ (配列番号84)
5’:GCGGCCTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGACTTTCCATCCTGCCATCTCAATTAG:3’ (配列番号89)
下流プライマーは、SV40プロモーターの3'末端に相補的であり、そしてHindIII部位でフランキングされている。
5’:GCGGCAAGCTTTTTGCAAAGCCTAGGC:3’ (配列番号84)
Clontechから入手したpB-gal:プロモータープラスミドに存在するSV40プロモーター鋳型を使用して、PCR増幅を行う。得られたPCR断片をXhoIおよびHindIIIで消化し、BLSK2-(Stratagene)にサブクローン化する。T7およびT3プライマーを用いる配列決定により、インサートが以下の配列を含むことを確認する。
5’:CTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGACTTTCCATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTT:3’ (配列番号90)
5’:CTCGAGGGGACTTTCCCGGGGACTTTCCGGGGACTTTCCGGGACTTTCCATCTGCCATCTCAATTAGTCAGCAACCATAGTCCCGCCCCTAACTCCGCCCATCCCGCCCCTAACTCCGCCCAGTTCCGCCCATTCTCCGCCCCATGGCTGACTAATTTTTTTTATTTATGCAGAGGCCGAGGCCGCCTCGGCCTCTGAGCTATTCCAGAAGTAGTGAGGAGGCTTTTTTGGAGGCCTAGGCTTTTGCAAAAAGCTT:3’ (配列番号90)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US22935800P | 2000-04-12 | 2000-04-12 | |
| US60/229,358 | 2000-04-12 | ||
| US19938400P | 2000-04-25 | 2000-04-25 | |
| US60/199,384 | 2000-04-25 | ||
| US25693100P | 2000-12-21 | 2000-12-21 | |
| US60/256,931 | 2000-12-21 | ||
| PCT/US2001/011991 WO2001079480A1 (en) | 2000-04-12 | 2001-04-12 | Albumin fusion proteins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003530852A JP2003530852A (ja) | 2003-10-21 |
| JP2003530852A5 true JP2003530852A5 (ja) | 2006-03-23 |
Family
ID=27394014
Family Applications (9)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001576855A Pending JP2003530838A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001577428A Pending JP2003530847A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001577426A Pending JP2003531590A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001577463A Pending JP2003530852A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001575607A Pending JP2004506407A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001577427A Pending JP2003530846A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001576866A Pending JP2003530839A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2011109620A Pending JP2011217750A (ja) | 2000-04-12 | 2011-05-16 | アルブミン融合タンパク質 |
| JP2013216509A Pending JP2014057589A (ja) | 2000-04-12 | 2013-10-17 | アルブミン融合タンパク質 |
Family Applications Before (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001576855A Pending JP2003530838A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001577428A Pending JP2003530847A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001577426A Pending JP2003531590A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001575607A Pending JP2004506407A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001577427A Pending JP2003530846A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2001576866A Pending JP2003530839A (ja) | 2000-04-12 | 2001-04-12 | アルブミン融合タンパク質 |
| JP2011109620A Pending JP2011217750A (ja) | 2000-04-12 | 2011-05-16 | アルブミン融合タンパク質 |
| JP2013216509A Pending JP2014057589A (ja) | 2000-04-12 | 2013-10-17 | アルブミン融合タンパク質 |
Country Status (10)
| Country | Link |
|---|---|
| US (23) | US6905688B2 (ja) |
| EP (21) | EP2298355A3 (ja) |
| JP (9) | JP2003530838A (ja) |
| AU (7) | AU2001259066A1 (ja) |
| BE (1) | BE2016C059I2 (ja) |
| CA (8) | CA2405709A1 (ja) |
| DK (2) | DK2216409T3 (ja) |
| ES (2) | ES2529300T3 (ja) |
| FR (1) | FR16C0043I2 (ja) |
| WO (7) | WO2001079258A1 (ja) |
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2001
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