JPH08508158A - 骨刺激因子 - Google Patents
骨刺激因子Info
- Publication number
- JPH08508158A JPH08508158A JP6518447A JP51844794A JPH08508158A JP H08508158 A JPH08508158 A JP H08508158A JP 6518447 A JP6518447 A JP 6518447A JP 51844794 A JP51844794 A JP 51844794A JP H08508158 A JPH08508158 A JP H08508158A
- Authority
- JP
- Japan
- Prior art keywords
- polypeptide
- lys
- thr
- gly
- ala
- 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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- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys- Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn- Gln-Pro-Co2Hのアミノ酸配列を有することを特徴とするポリペプチド。 2.各ポリペプチド単量体がNH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Al a-Asp-Cys-Lys-Ile-Lys-Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Me t-Val-Leu-Asp-Gln-Asn-Gln-Pro-Co2Hのアミノ酸配列を有し、該単量体同士が各 アミノ酸配列のシステイン残基間で二硫酸塩架橋により結合されていることを特 徴とする正方晶系ポリペプチド。 3.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys- Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn- Gln-Pro-Co2Hのアミノ酸配列を有する単量体とその二量体とからなるポリペプチ ドであって、該単量体同士が各アミノ酸配列のシステイン残基間で二硫酸塩架橋 により結合されていることを特徴とする哺乳動物において骨剌激活性を示すポリ ペプチド。 4.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys- Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn- Gln-Pro-Co2Hのアミノ酸配列の一部又は全部に相当する配列を有するポリペプチ ド、上記配列の三次元構造によって発揮される哺乳動物における骨刺激活性が保 持される限りにおいて上記配列中のアミノ酸を加除又は変更した同等物、又は上 記ポリペプチド又はその同等物の結合物からなることを特徴とする哺乳動物にお いて骨剌激活性を示すポリペプチド。 5.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys- Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn- Gln-Pro-Co2Hのアミノ酸配列の一部又は全部に相当する配列を有するペプチドの 二量体であって、上記ペプチド同士が各ペプチドのシステイン残基間で二硫酸塩 架橋により結合されており、しかも上記ペプチドは上記配列の三次元構造によっ て発揮される哺乳動物における骨刺激活性が保持される限りにおいて上記配列中 のアミノ酸を加除又は変更した同等物、又は上記ポリペプチド又はその同等物の 結合物であり得ることを特徴とする哺乳動物において骨剌激活性を示すポリペプ チド。 6.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys- Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn- Gln-Pro-Co2Hのアミノ酸配列の一部又は全部に相当する配列を有する単量体から なるポリペプチドであって、上記単量体同士が各アミノ酸配列のシステイン残基 間で二硫酸塩架橋により結合されており、しかも上記ペプチドは上記配列の三次 元構造によって発揮される哺乳動物における骨刺激活性が保持される限りにおい て上記配列中のアミノ酸を加除又は変更した同等物、又は上記ポリペプチド又は その同等物の結合物であり得ることを特徴とする哺乳動物において骨剌激活性を 示すポリペプチド。 7.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys- Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn- Gln-Pro-Co2Hのアミノ酸配列、及び上記アミノ酸配列の三次元構造によって発揮 される哺乳動物における骨剌激活性が上記アミノ酸配列を有するポリペプチドに おいて保持される限りにおいて上記配列中のアミノ酸を加除又は変更した同等物 をエンコードしていることを特徴とするDNA配列。 8.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys- Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn- Gln-Pro-Co2Hのアミノ酸配列、及び上記アミノ酸配列の三次元構造によって発揮 される哺乳動物における骨剌激活性が上記アミノ酸配列を有するポリペプチドに おいて保持される限りにおいて上記配列中のアミノ酸を加除又は変更した同等物 、及び哺乳動物において骨剌激活性を示すポリペプチドのアミノ酸配列をエンコ ードする配列をエンコードしていることを特徴とするDNA配列。 9.請求項7のDNAからなるベクター。 10.請求項8のDNAからなるベクター。 11.(a)哺乳動物の血清から分子量が30,000ダルトン未満で3,000ダルトン よりも大きいポリペプチド及びタンパク質を単離し、(b)得られた単離物から 約9のpIを有するポリペプチドを除去することにより所望のポリペプチドを得 ることを特徴とする骨成長率増進作用を有するポリペプチドの製造方法。 12.上記哺乳動物の血清がヒトの血清であり、上記工程(b)がアニオン交換 クロマトグラフィ手段により所望のポリペプチドを分離することからなることを 特徴とする請求項11の方法。 13.上記工程(b)で収集されたポリペプチドをゲル電気泳動により分子量に 従って溶解させる工程をさらに有することを特徴とする請求項12の方法。 14.溶解したポリペプチドから分子量約8000ダルトンのペプチドを単離する工 程をさらに有することを特徴とする請求項13の方法。 15.上記ペプチド単離工程が、溶解したポリペプチドをポリマー膜に移し、分 子量約8000ダルトンのペプチドを含む膜部分を分離し、該膜部分からペプチドを 除去することによって行われることを特徴とする請求項14の方法。 16.上記工程(a)がサンプルを濾過することからなる請求項11の方法。 17.請求項11の方法によって得られるポリペプチド。 18.請求項12の方法によって得られるポリペプチド。 19.請求項13の方法によって得られるポリペプチド。 20.請求項14の方法によって得られるポリペプチド。 21.請求項15の方法によって得られるポリペプチド。 22.請求項16の方法によって得られるポリペプチド。 23.請求項1のポリペプチドに対して抗原反応を示すタンパク質。 24.請求項2のポリペプチドに対して抗原反応を示すタンパク質。 25.請求項3のポリペプチドに対して抗原反応を示すタンパク質。 26.請求項4のポリペプチドに対して抗原反応を示すタンパク質。 27.請求項5のポリペプチドに対して抗原反応を示すタンパク質。 28.請求項6のポリペプチドに対して抗原反応を示すタンパク質。 29.請求項11のポリペプチドに対して抗原反応を示すタンパク質。 30.請求項4のポリペプチドの存在を確認するための装置であって、レポータ ーシステムに結合されたポリペプチドに対する抗体を含み、該レポーターシステ ムは所定量のポリペプチドと抗体との結合が行われたときに検出可能な反応を示 すことを特徴とする装置。 31.請求項11の方法によって得られるポリペプチドの存在を確認するための 装置であって、レポーターシステムに結合されたポリペプチドに対する抗体を含 み、該レポーターシステムは所定量のポリペプチドと抗体との結合が行われたと きに検出可能な反応を示すことを特徴とする装置。 32.上記レポーターシステムが上記反応とポリペプチドの上記所定量とを関連 付ける手段を有してなることを特徴とする請求項30の装置。 33.上記レポーターシステムが上記反応とポリペプチドの上記所定量とを関連 付ける手段を有してなることを特徴とする請求項31の装置。 34.(a)哺乳動物の血清から分子量が30,000ダルトン未満で3,000ダルトン よりも大きいポリペプチド及びタンパク質を単離し、(b)得られた単離物から 約9のpIを有するポリペプチドを除去することにより所望のポリペプチド、ア ミノ酸配列の三次元構造によって発揮される哺乳動物における骨刺激活性が保持 される限りにおいて上記配列中のアミノ酸を加除又は変更した同等物、及び上記 ペプチド又は同等物の結合体を得る方法によって得られることを特徴とする骨成 長率増進作用を有するポリペプチド。 35.骨成長率増大効果を有する精製タンパク質の製造方法であって、(a)GG G ATC GGA AAA CGA ACA AAT GAA CAT ACG GCA GAT TGT AAA ATT AAA CCG AAC AC C TTG CAT AAA AAA GCT GCA GAG ACT TTA ATG GTC CTT GAC CAA AAT CAA CCAの DNA配列でトランスフォームされた細胞を適当な培地で培養し、(b)上記培 地から上記タンパク質を単離精製することを特徴とする方法。 36.骨成長率増大効果を有する精製タンパク質の製造方法であって、(a)NH2 -Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys-Pro-As n-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn-Gln-Pr o-Co2Hのアミノ酸配列をエンコードするDNA配列でトランスフォームされた細 胞を適当な培地で培養し、(b)上記培地から上記タンパク質を単離精製するこ とを特徴とする方法。 37.請求項7のDNAでトランスフォームされた宿主細胞。 38.請求項8のDNAでトランスフォームされた宿主細胞。 39.哺乳動物において骨剌激活性を示すタンパク質の存在を検出する方法であ って、哺乳動物から血清サンプルを採取し、該サンプルの少なくとも一部をレポ ーターシステムに結合した抗体に作用させる工程よりなり、上記抗体はNH2-Gly- Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys-Pro-Asn-Thr- Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn-Gln-Pro-Co2H のアミノ酸配列を有するポリペプチドに結合する能力を持ち、これら抗体とタン パク質との結合を上記レポーターシステムが検出することを特徴とするタンパク 質検出方法。 40.NH2-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Ly s-Pro-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-As n-Gln-Pro-Co2Hのアミノ酸配列を有するポリペプチドの有効量を投与することに より骨の成長を促進させる方法。 41.SEQ ID NO.11に記述したものと十分に複製可能なアミノ酸配列を有し、ネ ズミ等の哺乳動物への投与により骨の成長を促進させる効果を有するタンパク質 。 42.SEQ ID NO.11に記述したものと少なくとも50%ホモロジーであるタンパク 質。 43.SEQ ID NO.11に記述したものと十分に複製可能なアミノ酸配列を有し、SE Q ID NO.11に記述したタンパク質をエンコードするDNAと交雑するDNAによ りタンパク質をエンコードすることによって上記複製が可能であることを特徴と するタンパク質。 44.SEQ ID NO.11に記述したアミノ酸配列またはその一部を有する骨剌激因子 。 45.血清から単離される実質的に純粋な循環性ポリペプチドであって、該ポリ ペプチドは(a)骨成長率の増大をもたらすと共に(b)Gly-Pro-Gly-Gly-Ala- Gly-Glu-Thr-Lys-Pro-Ileで示されるN-末端アミノ酸配列を有することを特徴と するポリペプチド。 46.ネズミの血清から単離される請求項45のポリペプチド。 47.約5,000ダルトンの分子量を持ち、ダイマー又はポリマーあるいはそれら の結合体である請求項45のポリペプチド。 48.サンプル中に骨成長率増進誘発性ポリペプチドが存在することを確認する ための装置であって、レポーターシステムに結合されたGly-Pro-Gly-Gly-Ala-Gl y-Glu-Thr-Lys-Pro-Ileで示されるN-末端アミノ酸配列を有するポリペプチドに 対する抗体を含み、該該レポーターシステムは所定量のポリペプチドと抗体との 結合が行われたときに検出可能な反応を示すことを特徴とする装置。 49.上記レポーターシステムが上記反応とポリペプチドの上記所定量とを関連 付ける手段を有してなることを特徴とする請求項48の装置。 50.Gly-Pro-Gly-Gly-Ala-Gly-Glu-Thr-Lys-Pro-Ileで示されるN-末端アミノ 酸配列を有するポリペプチドに対して抗原反応を示すタンパク質。 51.血清からタンパク質画分を採取し、該画分から分子量約30,000ダルトンよ りも大きなタンパク質を除去することを特徴とする、Gly-Pro-Gly-Gly-Ala-Gly- Glu-Thr-Lys-Pro-Ileで示されるN-末端アミノ酸配列を有するポリペプチドを製 造する方法。 52.逆相高性能液体クロマトグラフィのコラムからタンパク質を回収すること により上記ポリペプチドを単離することを特徴とする請求項51の方法。 53.3個の炭素鎖側基を有するシリカゾルを充填した逆相高性能液体クロマト グラフィのコラムから少なくとも約62〜63のアセトニトリルを有する希釈溶剤で 希釈することにより上記タンパク質を回収することを特徴とする請求項52の方 法。 54.哺乳動物の血清から単離された分子量約5,000GダルトンでGly-Pro-Gly-Gl y-Ala-Gly-Glu-Thr-Lys-Pro-Ileで示されるN-末端アミノ酸配列を有するポリペ プチドを有効量投与することによりヒトの骨成長を促進させる方法。 55.(a)哺乳動物の血清中のポリペプチドレベルを増大させるためにカルシ ウム欠乏餌で動物を飼育し、(b)該哺乳動物の血清サンプルを抽出し、(c) 該血清サンプルからGly-Pro-Gly-Gly-Ala-Gly-Glu-Thr-Lys-Pro-Ileで示されるN -末端アミノ酸配列を有するポリペプチドを実施的に純粋な形態で回収すること を特徴とする哺乳動物の骨成長率誘発性ポリペプチドの回収方法。 56.血清から単離される実質的に純粋な循環性ポリペプチドであって、該ポリ ペプチドは(a)骨成長率の増大をもたらすと共に(b)分子量約3,000ダルト ンのダイマー又はポリマー或いはそれらの結合体よりなることを特徴とするポリ ペプチド。 57.骨粗鬆症のような疾患を治療する方法であって、哺乳動物から血清サンプ ルを採取し、該血清サンプル中の骨成長増進誘発性ポリペプチドの量が所定レベ ルを越えているか否かを測定し、該ポリペプチド量が該所定レベルに達しないと きに疾患を示すことを特徴とする方法。 58.上記ポリペプチドの抗体にレポーターシステムを結合し、上記検出工程が 上記サンプルの少なくとも一部を上記抗体に晒すことによりポリペプチドと抗体 との結合を上記レポーターシステムが検出することからなることを特徴とする請 求項57の方法。 59.上記血清サンプルからタンパク質画分を単離し、約30,000ダルトンよりも 大きな分子量のタンパク質を除去することにより上記ポリペプチドの量を測定す ることを特徴とする請求項57の方法。 60.ATG ACT GCT CAA AAT ACA GAC CTT AAC CAA CTA TCC AAC AGT TTC ACT TT A GGG ATC GGA AAA CGA ACA AAT GAA CAT ACG GCA GAT TGT AAA ATT AAA CCG AA C ACC TTG CAT AAA AAA GCT GCA GAG ACT TTA ATG GTC CTT GAC CAA AAT CAA CC A の核酸配列を有することを特徴とするDNA。 61.NH2-Met-Thr-Ala-Gln-Asn-Thr-Asp Leu-Asn-Gln-Leu-Ser-Asn-Ser-Phe-Th r-Leu-Gly-Ile-Gly-Lys-Arg-Thr-Asn-Glu-His-Thr-Ala-Asp-Cys-Lys-Ile-Lys-Pr o-Asn-Thr-Leu-His-Lys-Lys-Ala-Ala-Glu-Thr-Leu-Met-Val-Leu-Asp-Gln-Asn-Gl n-Pro-CO2Hのアミノ酸配列をエンコードするDNA配列。 62.請求項60の核酸配列によってエンコードされるポリペプチド。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002538775A (ja) * | 1999-01-13 | 2002-11-19 | オステオファーム インコーポレイテッド | 骨刺激因子 |
JP2010513460A (ja) * | 2006-12-21 | 2010-04-30 | ヌーマット・アーエス | 共通ペプチド |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5786327A (en) | 1993-03-12 | 1998-07-28 | Gensci Regeneration Sciences Inc. | Bone stimulating factor, methods of isolating same, and methods of increasing bone growth comprising administering same |
US5880094A (en) * | 1995-06-07 | 1999-03-09 | Osteopharm Limited | Polypeptides that stimulate bone growth |
US6352973B1 (en) | 1995-06-07 | 2002-03-05 | Osteopharm Inc. | Bone stimulating factor |
US6117839A (en) * | 1995-06-07 | 2000-09-12 | Gensci Regeneration Sciences, Inc. | Bone stimulating factor |
EP1015565B1 (en) | 1997-09-19 | 2006-04-12 | Metabolix, Inc. | Biological systems for manufacture of polyhydroxyalkanoate polymers containing 4-hydroxyacids |
DE19906096A1 (de) | 1999-02-13 | 2000-08-17 | Walter Sebald | Protein mit einem Heparin-bindenden Epitop |
WO2000075185A1 (en) * | 1999-06-02 | 2000-12-14 | Osteopharm Inc. | Bone stimulating factor |
BR0014150A (pt) | 1999-08-30 | 2002-05-14 | Interleukin Genetics Inc | Diagnósticos e terapêuticos para osteoporose |
US6815421B1 (en) | 2001-03-22 | 2004-11-09 | Osteopharm Inc. | Polypeptides for use in ameliorating effects of aging in mammals |
CA2534365A1 (en) | 2003-08-08 | 2005-02-17 | Interleukin Genetics, Inc. | Diagnostic and therapeutics for osteoporosis |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
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EP0128041A3 (en) * | 1983-06-06 | 1986-12-03 | David Jeston Baylink | Polypeptides exhibiting skeletal growth factor activity |
CA2020729A1 (en) * | 1989-07-19 | 1991-01-20 | Michael C. Kiefer | Bone morphogenetic protein |
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1994
- 1994-03-11 IL IL10894794A patent/IL108947A0/xx unknown
- 1994-03-14 CA CA002157901A patent/CA2157901A1/en not_active Abandoned
- 1994-03-14 BR BR9406447A patent/BR9406447A/pt not_active Application Discontinuation
- 1994-03-14 KR KR1019950703855A patent/KR960701201A/ko not_active Application Discontinuation
- 1994-03-14 NZ NZ262352A patent/NZ262352A/en unknown
- 1994-03-14 AU AU61797/94A patent/AU678441B2/en not_active Ceased
- 1994-03-14 EP EP94908917A patent/EP0688360B1/en not_active Expired - Lifetime
- 1994-03-14 WO PCT/CA1994/000144 patent/WO1994020615A1/en not_active Application Discontinuation
- 1994-03-14 JP JP51844794A patent/JP3733381B2/ja not_active Expired - Fee Related
- 1994-03-14 AT AT94908917T patent/ATE208818T1/de not_active IP Right Cessation
- 1994-03-14 CZ CZ952342A patent/CZ234295A3/cs unknown
- 1994-03-14 PL PL94310617A patent/PL182236B1/pl unknown
- 1994-03-14 CN CN94191456A patent/CN1119457A/zh active Pending
- 1994-03-14 DE DE69429082T patent/DE69429082T2/de not_active Expired - Fee Related
- 1994-03-14 ES ES94908917T patent/ES2168295T3/es not_active Expired - Lifetime
- 1994-03-14 HU HU9502659A patent/HUT73297A/hu unknown
- 1994-03-21 TW TW083102552A patent/TW385314B/zh not_active IP Right Cessation
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1995
- 1995-08-22 NO NO953286A patent/NO953286L/no not_active Application Discontinuation
- 1995-09-11 FI FI954252A patent/FI954252A/fi unknown
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002538775A (ja) * | 1999-01-13 | 2002-11-19 | オステオファーム インコーポレイテッド | 骨刺激因子 |
JP2010513460A (ja) * | 2006-12-21 | 2010-04-30 | ヌーマット・アーエス | 共通ペプチド |
Also Published As
Publication number | Publication date |
---|---|
TW385314B (en) | 2000-03-21 |
ES2168295T3 (es) | 2002-06-16 |
CA2157901A1 (en) | 1994-09-15 |
AU6179794A (en) | 1994-09-26 |
BR9406447A (pt) | 1996-02-13 |
IL108947A0 (en) | 1994-06-24 |
KR960701201A (ko) | 1996-02-24 |
HU9502659D0 (en) | 1995-11-28 |
CN1119457A (zh) | 1996-03-27 |
CZ234295A3 (en) | 1996-04-17 |
HUT73297A (en) | 1996-07-29 |
AU678441B2 (en) | 1997-05-29 |
EP0688360B1 (en) | 2001-11-14 |
NO953286D0 (no) | 1995-08-22 |
FI954252A0 (fi) | 1995-09-11 |
FI954252A (fi) | 1995-09-11 |
DE69429082D1 (de) | 2001-12-20 |
DE69429082T2 (de) | 2002-07-25 |
ATE208818T1 (de) | 2001-11-15 |
NZ262352A (en) | 1997-10-24 |
PL310617A1 (en) | 1995-12-27 |
WO1994020615A1 (en) | 1994-09-15 |
JP3733381B2 (ja) | 2006-01-11 |
NO953286L (no) | 1995-10-25 |
PL182236B1 (pl) | 2001-11-30 |
EP0688360A1 (en) | 1995-12-27 |
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