JPH10502523A - 変異型rドメインを有するジフテリア毒素ワクチン - Google Patents
変異型rドメインを有するジフテリア毒素ワクチンInfo
- Publication number
- JPH10502523A JPH10502523A JP8501159A JP50115996A JPH10502523A JP H10502523 A JPH10502523 A JP H10502523A JP 8501159 A JP8501159 A JP 8501159A JP 50115996 A JP50115996 A JP 50115996A JP H10502523 A JPH10502523 A JP H10502523A
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- diphtheria toxin
- cells
- domain
- wild
- 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
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.変異型ジフテリア毒素Rドメインを含むポリペプチドであって、該Rドメイン が野生型ジフテリア毒素(図1、配列番号:1)のLys516、Lys526、Phe530、また はLys534のうちの少なくとも一つまたは複数の位置に変異を含むポリペプチド。 2.Lys516、Lys526、またはLys534のうちの少なくとも一つまたは複数がCysま たはPheのいずれかで置換されている、請求の範囲1のポリペプチド。 3.Phe530がGlu、Lys、またはGlnで置換されている、請求の範囲1のポリペプチ ド。 4.野生型ジフテリア毒素(図1;配列番号:1)のアミノ酸379〜535位を有さな いジフテリア毒素フラグメントBの少なくとも一部をさらに含む、請求の範囲1〜 3のいずれかのポリペプチド。 5.ジフテリア毒素フラグメントAの少なくとも一部を含む、請求の範囲1〜3の いずれかのポリペプチド。 6.ジフテリア毒素フラグメントAの少なくとも一部を含む、請求の範囲4のポリ ペプチド。 7.ジフテリア毒素フラグメントAの全部を含む、請求の範囲4のポリペプチド。 8.請求の範囲1〜3のいずれかのポリペプチドの実質的に純粋な調製物。 9.請求の範囲4のポリペプチドの実質的に純粋な調製物。 10.請求の範囲5のポリペプチドの実質的に純粋な調製物。 11.請求の範囲1〜3のいずれかのポリペプチドをコードする核酸を含む細胞。 12.請求の範囲4のポリペプチドをコードする核酸を含む細胞。 13.請求の範囲5のポリペプチドをコードする核酸を含む細胞。 14.枯草菌(B.subtilis)、BCG、サルモネラ種(Salmonella sp.)、コレラ 菌(Vibrio cholerae)リステリエ(Listeriae)、エルシニエ(Yersiniae)、 ストレプトコッキ(Streptococci)、コリネバクテリウム・ジフテリエ(Coryne bacterium diphtheriae)、または大腸菌の細胞である、請求の範囲11の細胞。 15.枯草菌(B.subtilis)、BCG、サルモネラ種(Salmonella sp.)、コレラ 菌(Vibrio cholerae)リステリエ(Listeriae)、エルシニエ(Yersiniae)、 ストレプトコッキ(Streptococci)、コリネバクテリウム・ジフテリエ(Coryne ba cterium diphtheriae)、または大腸菌の細胞である、請求の範囲12の細胞。 16.枯草菌(B.subtilis)、BCG、サルモネラ種(Salmonella sp.)、コレラ 菌(Vibrio cholerae)リステリエ(Listeriae)、エルシニエ(Yersiniae)、 ストレプトコッキ(Streptococci)、コリネバクテリウム・ジフテリエ(Coryne bacterium diphtheriae)、または大腸菌の細胞である、請求の範囲13の細胞。 17.請求の範囲1〜3のいずれかのポリペプチドを含む生理学的に許容される混 合物を含むワクチン。 18.請求の範囲4のポリペプチドを含む生理学的に許容される混合物を含むワ クチン。 19.請求の範囲5のポリペプチドを含む生理学的に許容される混合物を含むワ クチン。 20.請求の範囲14の細胞を含む生ワクチン株。 21.請求の範囲15の細胞を含む生ワクチン株。 22.請求の範囲16の細胞を含む生ワクチン株。 23.ポリペプチドを調製する方法であって、請求の範囲14の細胞を準備し、該 ポリペプチドを発現する細胞群を生成するために培地中で該細胞を培養し、該細 胞群または該培地から該ポリペプチドを得ることを含む、方法。 24.ポリペプチドを調製する方法であって、請求の範囲15の細胞を準備し、該 ポリペプチドを発現する細胞群を生成するために培地中で該細胞を培養し、該細 胞群または該培地から該ポリペプチドを得ることを含む、方法。 25.ポリペプチドを調製する方法であって、請求の範囲16の細胞を準備し、該 ポリペプチドを発現する細胞群を生成するために培地中で該細胞を培養し、該細 胞群または該培地から該ポリペプチドを得ることを含む、方法。 26.生ワクチン細胞として動物体内へ導入するのに適当な細胞が増殖するよう な条件下で、請求の範囲14の細胞を培養することを含むワクチンを製造する方法 。 27.生ワクチン細胞として動物体内へ導入するのに適当な細胞が増殖するよう な条件下で、請求の範囲15の細胞を培養することを含むワクチンを製造する方法 。 28.生ワクチン細胞として動物体内へ導入するのに適当な細胞が増殖するよう な条件下で、請求の範囲16の細胞を培養することを含むワクチンを製造する方法 。 29.免疫量の請求の範囲17のワクチンを哺乳類へ導入することを含む、野生型 ジフテリア毒素に対して哺乳類を免疫する方法。 30.免疫量の請求の範囲18のワクチンを哺乳類へ導入することを含む、野生型 ジフテリア毒素に対して哺乳類を免疫する方法。 31.免疫量の請求の範囲19のワクチンを哺乳類へ導入することを含む、野生型 ジフテリア毒素に対して哺乳類を免疫する方法。 32.哺乳類がヒトである、請求の範囲29の方法。 33.哺乳類がヒトである、請求の範囲30の方法。 34.哺乳類がヒトである、請求の範囲31の方法。 35.ペプチド結合により第二のポリペプチドに結合した請求の範囲1〜3のいず れかのポリペプチドを含む融合ポリペプチド。 36.ペプチド結合により第二のポリペプチドに結合した請求の範囲4のポリペ プチドを含む融合ポリペプチド。 37.ペプチド結合により第二のポリペプチドに結合した請求の範囲5のポリペ プチドを含む融合ポリペプチド。 38.変異型ジフテリア毒素Rドメインをコードする配列を含むDNA分子であって 、天然のジフテリア毒素(図1、配列番号:1)のLys516、Lys526、Phe530、また はLys534のうちの少なくとも一つに対応するコドンに相補的なDNA配列が変異し ている、DNA分子。 39.Lys516、Lys526、またはLys534のうちの少なくとも一つに対応するコドン に相補的な変異型DNA配列がCysまたはPheをコードする、請求の範囲38のDNA分子 。 40.Phe530に対応するコドンに相補的な変異型DNA配列がGlu、Lys、またはGln をコードする、請求の範囲38のDNA分子。 41.アミノ酸379〜535位を有さないジフテリア毒素フラグメントBの少なくと も一部をコードする、請求の範囲38〜40のいずれかのDNA分子。 42.ジフテリア毒素フラグメントAの少なくとも一部をコードする、請求の範 囲38〜40のいずれかのDNA分子。 43.ジフテリア毒素フラグメントAの少なくとも一部をコードする、請求の範 囲41のDNA分子。 44.ジフテリア毒素フラグメントAの全部をコードする、請求の範囲42のDNA分 子。 45.フラグメントBが野生型ジフテリア毒素のGlu349、Asp352、またはIle364 のうちのいずれかの位置に変異を含む、請求の範囲41のDNA分子。 46.フラグメントAが野生型ジフテリア毒素のHis21、Glu22、Lys39、Gly52、G ly79、Gly128、Ala158、Gly162、Glu142、Val147、Glu148の位置に変異を含む、 請求の範囲42のDNA分子。 47.図2に示されるDNA配列(配列番号:2)によりコードされるポリペプチド をコードするDNA配列。 48.哺乳類にジフテリア毒素Rドメインを注入することにより作製されたポリ クローナル抗体。 49.ジフテリア毒素レセプター結合領域に結合することができるモノクローナ ル抗体。 50.変異型Rドメインを含むポリペプチドであって、該Rドメインがアミノ酸37 9〜535(配列番号:1)の間に少なくとも一つの変異を含み、該ポリペプチドが 野生型ジフテリア毒素よりも低い親和性で感受性細胞に結合し、野生型ジフテリ ア毒素のRドメインを特異的に認識する抗体と免疫複合体を形成することができ る、ポリペプチド。 51.379〜535位の間の少なくとも一つアミノ酸(配列番号:1)に対応するコ ドンに相補的なDNA配列が変異している、変異型ジフテリア毒素Rドメインをコー ドする配列を含むDNA分子。
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US08/257,781 US5917017A (en) | 1994-06-08 | 1994-06-08 | Diphtheria toxin vaccines bearing a mutated R domain |
US08/257,781 | 1994-06-08 | ||
PCT/US1995/006857 WO1995033481A1 (en) | 1994-06-08 | 1995-05-31 | Diphtheria toxin vaccines bearing a mutated r domain |
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JPH10502523A true JPH10502523A (ja) | 1998-03-10 |
JP3755773B2 JP3755773B2 (ja) | 2006-03-15 |
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JP50115996A Expired - Fee Related JP3755773B2 (ja) | 1994-06-08 | 1995-05-31 | 変異型rドメインを有するジフテリア毒素ワクチン |
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EP (1) | EP0762892B1 (ja) |
JP (1) | JP3755773B2 (ja) |
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US4709017A (en) * | 1985-06-07 | 1987-11-24 | President And Fellows Of Harvard College | Modified toxic vaccines |
US6099842A (en) * | 1990-12-03 | 2000-08-08 | The United States Of America As Represented By The Department Of Health And Human Services | Recombinant immunotoxin composed of a single chain antibody reacting with the human transferrin receptor and diptheria toxin |
DE69324487T2 (de) * | 1992-05-06 | 1999-08-12 | Harvard College | Rezeptorbindende region des diphtherietoxius |
EP0652758B1 (en) * | 1992-06-18 | 2000-01-05 | The President And Fellows Of Harvard College | Diphtheria toxin vaccines |
US5733726A (en) * | 1995-06-07 | 1998-03-31 | Emory University | Cytotoxicity-based genetic selection system (TOXSEL) |
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1994
- 1994-06-08 US US08/257,781 patent/US5917017A/en not_active Expired - Fee Related
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1995
- 1995-05-31 DE DE69534786T patent/DE69534786T2/de not_active Expired - Fee Related
- 1995-05-31 PT PT95921528T patent/PT762892E/pt unknown
- 1995-05-31 WO PCT/US1995/006857 patent/WO1995033481A1/en active IP Right Grant
- 1995-05-31 AT AT95921528T patent/ATE317701T1/de not_active IP Right Cessation
- 1995-05-31 CA CA002191239A patent/CA2191239A1/en not_active Abandoned
- 1995-05-31 ES ES95921528T patent/ES2258768T3/es not_active Expired - Lifetime
- 1995-05-31 EP EP95921528A patent/EP0762892B1/en not_active Expired - Lifetime
- 1995-05-31 JP JP50115996A patent/JP3755773B2/ja not_active Expired - Fee Related
- 1995-05-31 DK DK95921528T patent/DK0762892T3/da active
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2003508010A (ja) * | 1999-02-16 | 2003-03-04 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | 多数変異型ジフテリア毒素ワクチン |
JP2005509399A (ja) * | 2000-11-14 | 2005-04-14 | モーフオテク・インコーポレーテツド | 遺伝的に改変された抗原の生成法 |
JP2015512382A (ja) * | 2012-03-20 | 2015-04-27 | コミッサリア ア レネルジ アトミック エ オー エネルジ アルターネイティブスCommissariat A L’Energie Atomique Et Aux Energies Alternatives | Hb−egf/egfr経路の活性化に関連する疾患の処置のためのジフテリア毒素のrドメイン由来のhb−egf阻害物質 |
Also Published As
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CA2191239A1 (en) | 1995-12-14 |
JP3755773B2 (ja) | 2006-03-15 |
US5917017A (en) | 1999-06-29 |
ATE317701T1 (de) | 2006-03-15 |
EP0762892B1 (en) | 2006-02-15 |
PT762892E (pt) | 2006-07-31 |
EP0762892A4 (en) | 1999-06-02 |
DK0762892T3 (da) | 2006-06-19 |
EP0762892A1 (en) | 1997-03-19 |
DE69534786T2 (de) | 2006-11-09 |
WO1995033481A1 (en) | 1995-12-14 |
ES2258768T3 (es) | 2006-09-01 |
DE69534786D1 (de) | 2006-04-20 |
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