JPH10503362A - 増殖分化因子−12 - Google Patents
増殖分化因子−12Info
- Publication number
- JPH10503362A JPH10503362A JP7523725A JP52372595A JPH10503362A JP H10503362 A JPH10503362 A JP H10503362A JP 7523725 A JP7523725 A JP 7523725A JP 52372595 A JP52372595 A JP 52372595A JP H10503362 A JPH10503362 A JP H10503362A
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.実質的に純粋な増殖分化因子−12(GDF−12)およびその機能性断片 。 2.請求項1に記載のGDF−12ポリペプチドをコードする、単離されたポリ ヌクレオチド配列。 3.GDF−12が次のa〜c: a.TがUであり得る配列番号13; b.配列番号13に相補的な核酸配列;および c.長さが少なくとも15塩基であり、かつ配列番号14のGDF−12タンパク 質をコードするDNAに選択的にハイブリダイズする、上記aまたはbの断片 よりなる群から選ばれる、請求項2に記載のポリヌクレオチド。 4.ポリヌクレオチドが哺乳動物の細胞から単離される、請求項2に記載のポリ ヌクレオチド。 5.哺乳動物の細胞がマウス、ラットおよびヒトの細胞よりなる群から選ばれる 、請求項4に記載のポリヌクレオチド。 6.請求項2のポリヌクレオチドを含む発現ベクター。 7.ベクターがプラスミドである、請求項6に記載のベクター。 8.ベクターがウイルスである、請求項6に記載のベクター。 9.請求項6のベクターで安定に形質転換された宿主細胞。 10.細胞が原核細胞である、請求項9に記載の宿主細胞。 11.細胞が真核細胞である、請求項9に記載の宿主細胞。 12.請求項1のポリペプチドまたはその断片に結合する抗体。 13.抗体がポリクローナルである、請求項12に記載の抗体。 14.抗体がモノクローナルである、請求項12に記載の抗体。 15.請求項12の抗体を、GDF−12関連疾患の疑いがある被検体の検体と接触 させ、該抗体の結合を検出することを含んでなる、細胞増殖性疾患の検出方法。 16.細胞が肝細胞である、請求項15に記載の方法。 17.検出をin vivoで行う、請求項15に記載の方法。 18.抗体が検出可能に標識される、請求項17に記載の方法。 19.検出可能な標識が放射性同位元素、蛍光化合物、生物発光化合物および化学 発光化合物よりなる群から選ばれる、請求項18に記載の方法。 20.検出をin vitroで行う、請求項15に記載の方法。 21.抗体が検出可能に標識される、請求項20に記載の方法。 22.標識が放射性同位元素、蛍光化合物、生物発光化合物、化学発光化合物およ び酵素よりなる群から選ばれる、請求項21に記載の方法。 23.細胞を、GDF−12活性を抑制する試薬と接触させることを含んでなる、 GDF−12の発現と関連した細胞増殖性疾患の治療方法。 24.試薬が抗GDF−12抗体である、請求項23に記載の方法。 25.試薬がGDF−12アンチセンス配列である、請求項23に記載の方法。 26.細胞が肝細胞である、請求項23に記載の方法。 27.GDF−12活性を抑制する試薬がベクターを用いて細胞に導入される、請 求項23に記載の方法。 28.ベクターがコロイド分散系である、請求項27に記載の方法。 29.コロイド分散系がリポソームである、請求項28に記載の方法。 30.リポソームが本質的にターゲット特異性である、請求項29に記載の方法。 31.リポソームが解剖的にターゲッティングされる、請求項30に記載の方法。 32.リポソームが機械的にターゲッティングされる、請求項31に記載の方法。 33.機械的ターゲッティングが受動的である、請求項32に記載の方法。 34.機械的ターゲッティングが能動的である、請求項32に記載の方法。 35.リポソームが糖、糖脂質およびタンパク質よりなる群から選ばれる部分とカ ップリングすることにより能動的にターゲッティングされる、請求項34に記載の 方法。 36.タンパク質部分が抗体である、請求項35に記載の方法。 37.ベクターがウイルスである、請求項36に記載の方法。 38.ウイルスがRNAウイルスである、請求項37に記載の方法。 39.RNAウイルスがレトロウイルスである、請求項38に記載の方法。 40.レトロウイルスが本質的にターゲット特異性である、請求項39に記載の方法 。 41.ターゲット特異性部分がレトロウイルスゲノムに挿入されたポリヌクレオチ ドによりコードされる、請求項40に記載の方法。 42.ターゲット特異性部分が糖、糖脂質およびタンパク質よりなる群から選ばれ る、請求項40に記載の方法。 43.タンパク質が抗体である、請求項42に記載の方法。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/274,215 | 1994-07-13 | ||
US08/274,215 US5831054A (en) | 1994-07-13 | 1994-07-13 | Polynucleotide encoding growth differentiation factor-12 |
US31137094A | 1994-09-26 | 1994-09-26 | |
US08/311,370 | 1994-09-26 | ||
PCT/US1995/008745 WO1996002559A1 (en) | 1994-07-13 | 1995-07-12 | Growth differentiation factor-12 |
Publications (1)
Publication Number | Publication Date |
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JPH10503362A true JPH10503362A (ja) | 1998-03-31 |
Family
ID=26956672
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP7523725A Pending JPH10503362A (ja) | 1994-07-13 | 1995-07-12 | 増殖分化因子−12 |
Country Status (11)
Country | Link |
---|---|
US (1) | US5929213A (ja) |
EP (1) | EP0770089B1 (ja) |
JP (1) | JPH10503362A (ja) |
AT (1) | ATE196147T1 (ja) |
CA (1) | CA2195246A1 (ja) |
DE (1) | DE69518760T2 (ja) |
DK (1) | DK0770089T3 (ja) |
ES (1) | ES2151607T3 (ja) |
GR (1) | GR3034772T3 (ja) |
PT (1) | PT770089E (ja) |
WO (1) | WO1996002559A1 (ja) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5846770A (en) * | 1994-11-22 | 1998-12-08 | Genetics Institute, Inc. | DNA molecules encoding human chordin |
US5965403A (en) | 1996-09-18 | 1999-10-12 | Genetics Institute, Inc. | Nucleic acids encoding bone morphogenic protein-16 (BMP-16) |
US20020052026A1 (en) | 1997-10-08 | 2002-05-02 | Steven M. Vicik | Methods of refolding proteins |
US6027917A (en) | 1997-12-10 | 2000-02-22 | Genetics Institute, Inc. | Bone morphogenetic protein (BMP)-17 and BMP-18 compositions |
US6727224B1 (en) | 1999-02-01 | 2004-04-27 | Genetics Institute, Llc. | Methods and compositions for healing and repair of articular cartilage |
NZ519546A (en) * | 1999-12-15 | 2005-07-29 | Res Dev Foundation | Betaglycan as an inhibin receptor and uses thereof |
TWI267378B (en) | 2001-06-08 | 2006-12-01 | Wyeth Corp | Calcium phosphate delivery vehicles for osteoinductive proteins |
CN1878565B (zh) | 2003-09-12 | 2011-01-12 | 惠氏公司 | 用于递送成骨蛋白的注射型磷酸钙固体小棒剂和糊剂 |
AU2005247871A1 (en) | 2004-04-27 | 2005-12-08 | Research Development Foundation | Antagonism of TGF-beta superfamily receptor signaling |
US7473678B2 (en) | 2004-10-14 | 2009-01-06 | Biomimetic Therapeutics, Inc. | Platelet-derived growth factor compositions and methods of use thereof |
US8147860B2 (en) | 2005-12-06 | 2012-04-03 | Etex Corporation | Porous calcium phosphate bone material |
CA2641860C (en) | 2006-02-09 | 2015-07-14 | Biomimetic Therapeutics, Inc. | Compositions and methods for treating bone |
US9161967B2 (en) | 2006-06-30 | 2015-10-20 | Biomimetic Therapeutics, Llc | Compositions and methods for treating the vertebral column |
JP5484047B2 (ja) | 2006-06-30 | 2014-05-07 | バイオミメティック セラピューティクス, エルエルシー | 回旋筋腱板傷害を処置するためのpdgf−生体マトリックス組成物および方法 |
US8524265B2 (en) | 2006-08-17 | 2013-09-03 | Warsaw Orthopedic, Inc. | Medical implant sheets useful for tissue regeneration |
AU2009291828C1 (en) | 2008-09-09 | 2016-03-17 | Biomimetic Therapeutics, Llc | Platelet-derived growth factor compositions and methods for the treatment of tendon and ligament injuries |
US8609127B2 (en) | 2009-04-03 | 2013-12-17 | Warsaw Orthopedic, Inc. | Medical implant with bioactive material and method of making the medical implant |
WO2010144696A1 (en) | 2009-06-11 | 2010-12-16 | Burnham Institute For Medical Research | Directed differentiation of stem cells |
JP6144049B2 (ja) | 2010-02-22 | 2017-06-07 | バイオミメティック セラピューティクス,リミテッド ライアビリティ カンパニー | 腱障害を処置するための血小板由来成長因子組成物及び方法 |
US10034945B2 (en) | 2012-07-13 | 2018-07-31 | Trustees Of Tufts College | Silk powder compaction for production of constructs with high mechanical strength and stiffness |
JP7025021B2 (ja) | 2015-10-26 | 2022-02-24 | プレジデント アンド フェローズ オブ ハーバード カレッジ | 還元多糖および酸化多糖ならびにそれらの使用の方法 |
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CA2129820C (en) * | 1992-02-12 | 2003-06-17 | Helge Neidhardt | Dna sequences encoding novel growth/differentiation factors |
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1995
- 1995-07-12 PT PT95928062T patent/PT770089E/pt unknown
- 1995-07-12 EP EP95928062A patent/EP0770089B1/en not_active Expired - Lifetime
- 1995-07-12 WO PCT/US1995/008745 patent/WO1996002559A1/en active IP Right Grant
- 1995-07-12 AT AT95928062T patent/ATE196147T1/de not_active IP Right Cessation
- 1995-07-12 DE DE69518760T patent/DE69518760T2/de not_active Expired - Fee Related
- 1995-07-12 CA CA002195246A patent/CA2195246A1/en not_active Abandoned
- 1995-07-12 US US08/765,662 patent/US5929213A/en not_active Expired - Fee Related
- 1995-07-12 ES ES95928062T patent/ES2151607T3/es not_active Expired - Lifetime
- 1995-07-12 DK DK95928062T patent/DK0770089T3/da active
- 1995-07-12 JP JP7523725A patent/JPH10503362A/ja active Pending
-
2000
- 2000-11-07 GR GR20000402461T patent/GR3034772T3/el not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
ES2151607T3 (es) | 2001-01-01 |
DE69518760T2 (de) | 2001-05-23 |
EP0770089B1 (en) | 2000-09-06 |
EP0770089A4 (en) | 1997-06-18 |
GR3034772T3 (en) | 2001-02-28 |
DK0770089T3 (da) | 2000-10-23 |
PT770089E (pt) | 2001-02-28 |
CA2195246A1 (en) | 1996-02-01 |
DE69518760D1 (de) | 2000-10-12 |
EP0770089A1 (en) | 1997-05-02 |
WO1996002559A1 (en) | 1996-02-01 |
US5929213A (en) | 1999-07-27 |
ATE196147T1 (de) | 2000-09-15 |
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