JP2898003B2 - ミルクにおける蛋白の発現 - Google Patents

ミルクにおける蛋白の発現

Info

Publication number
JP2898003B2
JP2898003B2 JP63505800A JP50580088A JP2898003B2 JP 2898003 B2 JP2898003 B2 JP 2898003B2 JP 63505800 A JP63505800 A JP 63505800A JP 50580088 A JP50580088 A JP 50580088A JP 2898003 B2 JP2898003 B2 JP 2898003B2
Authority
JP
Japan
Prior art keywords
milk
recombinant protein
promoter
protein
sequence
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.)
Expired - Lifetime
Application number
JP63505800A
Other languages
English (en)
Other versions
JPH02500798A (ja
Inventor
ミード，ハリー
ロンバーグ，ニルス
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
FUAAMINGU BV
Original Assignee
FUAAMINGU BV
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=22066571&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP2898003(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by FUAAMINGU BV filed Critical FUAAMINGU BV
Publication of JPH02500798A publication Critical patent/JPH02500798A/ja
Application granted granted Critical
Publication of JP2898003B2 publication Critical patent/JP2898003B2/ja
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
    • A01K67/027—New breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Humanized animals, e.g. knockin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4732—Casein
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6456—Plasminogen activators
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/103—Ovine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
    • C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/44—Vectors comprising a special translation-regulating system being a specific part of the splice mechanism, e.g. donor, acceptor
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/827—Proteins from mammals or birds
    • Y10S530/832—Milk; colostrum
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/827—Proteins from mammals or birds
    • Y10S530/833—Whey; cheese

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Environmental Sciences (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Animal Husbandry (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Dairy Products (AREA)

Description

【発明の詳細な説明】 ［発明の技術分野］ 本発明は、哺乳動物のミルクにおける組換蛋白の産生
に関するものである。特に本発明は、信号ペプチドおよ
び所望の組換蛋白生産物をコードするDNA配列に作用結
合した少なくとも１種のミルク特異性蛋白プロモータか
らなる発現系に関するものである。この種の系を哺乳動
物中にトランスジェニック的（transgenically）に組込
むと、授乳期のトランスジェニック哺乳動物のミルクに
組換蛋白が発現される。さらに本発明は、所望の組換生
産物をミルク中に産生するトランスジェニック哺乳動物
に関するものである。本発明の発現系およびトランスジ
ェニック改変した哺乳動物により産生される組換生産物
は、慣用の組換蛋白産生技術によるよりも顕著に低いコ
ストで製造することができる。
［従来の技術］ 組換DNA技術は、医学上および産業上重要な蛋白およ
びグリコ蛋白をコードする遺伝子のクローン化および発
現を可能にした。この種の生産物はたとえばインシュリ
ン、成長ホルモン、成長ホルモン放出因子、ソマトスタ
チン、組織プラスミノーゲン賦活物質、腫瘍壊死因子、
リポコルチン、凝集因子VIIIおよびIX、インターフェロ
ン、コロニー刺戟因子、インターロイキンおよびウロキ
ナーゼを包含する。
しかしながら、これら重要な蛋白の多くは大分子（30
Kdを越える分子量）で分泌され、適正な折畳みを維持す
るにはスルフヒドリル結合を必要とし、グリコシル化さ
れておりかつプロテアーゼに対し感受性である。その結
果、原核細胞におけるこの種の生産物の組換産生は、所
望の組換蛋白が不適正に処理され、適正なグリルシル化
を欠如し、或いは不適正に折畳まれるので、満足しうる
ものでないことが判明している。したがって、これらの
組換蛋白は培養された真核細胞にて産生させねばならな
かった。この技術は、細胞培養法の変動に基づき高価と
なりかつしばしば信頼性がないと判明した。たとえば、
平均収率は培地１当たり組換蛋白10mgであり、その結
果コストは典型的には組換蛋白1g当たり1000ドルを越え
る。したがって、これら組換蛋白は培養された真核細胞
にて産生させねばならなかった。
［発明の開示］ 本発明は、トランスジェニック改変された哺乳動物の
ミルクにて多量の組換蛋白生産物を産生する効率的手段
を提供することにより、これらの問題を解決する。本発
明によれば、所望の蛋白をコードするDNA配列は、発現
系においてミルク特異性蛋白プロモータ或いは乳房組織
にて特異的に賦活される任意のプロモータ配列に、信号
（シグナル）ペプチドをコードするDNA配列を介して作
用可能に結合され、この信号ペプチドは乳房組織にて所
望蛋白の分泌および成熟を可能にする。より好ましく
は、発現系は所望の組換蛋白をコードするDNA配列の下
流に３′非翻訳領域をも含む。この非翻訳領域は、発現
系のrDNA転写産物を安定化させることができる。必要に
応じ発現系は、信号ペプチドをコードするDNA配列の上
流に５′非翻訳領域をも含む。
この発現系は標準的なトランスジェニック（transgen
ic）技術により宿主ゲノム中にトランスジェニック的に
導入される。その結果、構造物もしくは系の１つもしく
はそれ以上のコピーがトランスジェニック哺乳動物のゲ
ノムに組込まれる。発現系の存在は、雌哺乳動物が組換
蛋白生産物を産生すると共にミルク中へまたはミルクと
一緒に分泌することを可能にする。この種の方法は、所
望蛋白の低コストかつ高レベルの製造を可能にする。
［図面の簡単な説明］ 第１図は本発明のプラスミド、pCAS1151の構成を示
す。
［定義］ 本明細書に使用する組換蛋白および作用可能に結合と
いう用語は次の意味を有する： 作用可能に結合：所望蛋白をコードするDNA配列の発
現および所望蛋白の産生を可能にすると共に制御するよ
うな、ミルク特異性プロモータまたは乳房組織で特異的
に、賦活されるプロモータの、上記DNA配列への結合。
組換蛋白：本発明に従い蛋白又はペプチドがそのミル
ク中に産生されるところの哺乳動物の天然ゲノムに対し
内生でないDNA配列によりコードされる蛋白もしくはペ
プチド、或いは蛋白又はペプチドがそのミルク中に産生
されるところの哺乳動物の天然ゲノムに対し内生である
ならば、そのミルク中での該蛋白もしくはペプチドの産
生を、本発明のトランスジェニック哺乳動物がそのミル
ク中にて産生するのと同じレベルではもたらさないとこ
ろのDNA配列によりコードされる蛋白又はペプチド。
［発明の詳細な説明］ 本発明は、組換蛋白を製造するための方法、DNA配
列、組成物およびトランスジェニック哺乳動物に関する
ものである。より詳細には本発明は、乳房組織にて所望
の組換蛋白の分泌および成熟を可能にするような信号ペ
プチドをコードするDNA配列を介し、所望の組換蛋白を
コードするDNA配列に作用可能に結合したミルク特異性
蛋白プロモータ或いは乳房組織にて特異的に賦活される
プロモータ配列を含む構造物の１つもしくはそれ以上の
コピーをトランスジェニック的に組込むことに関する。
この構造物は哺乳動物の胚中にトランスジェニック的に
組込まれ、次いで組換蛋白生産物を発現して授乳期のト
ランスジェニック哺乳動物のミルク中にまたはミルクと
共に分泌される。
本発明には、任意の哺乳動物を有効に用いることがで
きる。好ましくは、多量のミルクを産生しかつ長い授乳
期間を有する哺乳動物が好適である。好適哺乳動物は
牛、羊、山羊、ネズミ、牛属動物、ラクダおよび豚であ
る。勿論、これら哺乳動物のそれぞれは本発明の所定の
発現配列に関し互いに同じ効果を有するものでない。た
とえば、特定のミルク特異性プロモータまたは信号配列
は、或る種の哺乳動物において他の哺乳動物におけるよ
りも効果が大である。しかしながら、当業者は本発明の
教示にしたがってこの種の選択を容易に行なうことがで
きる。
本発明の各具体例において有用なミルク特異性蛋白プ
ロモータとしては、カゼインプロモータおよびβ−ラク
トグロブリンプロモータがある。たとえばガゼインプロ
モータはα−カゼインプロモータ、β−カゼインプロモ
ータまたはκ−カゼインプロモータから選択することが
できる。好ましくは、カゼインプロモータは牛由来のも
のであり、かつαＳ−１カゼインプロモータである。乳
房組織で特異的に賦活されかつしたがって本発明に有用
であるプロモータとしては、マウス乳房腫瘍ウィルス
（MMTV）の長い末端反復配列（LTR）プロモータがあ
る。乳房組織にて特異的に賦活されるミルク特異性蛋白
プロモータは、cDNA配列またはゲノム配列のいずれかか
ら誘導することができる。好ましくは、これらは性質上
ゲノム性である。
本発明に有用な信号ペプチドとしては、真核および原
核蛋白の分泌および成熟に有用なミルク特異性信号ペプ
チドまたはその他の信号ペプチドがある。好ましくは、
信号ペプチドはミルク特異性信号ペプチドまたは必要に
応じ所望の組換蛋白生産物の信号ペプチドから選択され
る。特に好ましくは、ミルク特異性信号ペプチドは本発
明の発現系に使用されるミルク特異性プロモータに関連
する。信号ペプチドの大きさは、本発明にとって臨界的
でない。唯一の必要とされることは、乳房組織で発現さ
れる所望の組換蛋白の分泌および成熟を行なうのに充分
な大きさをペプチドが有することである。
本発明の方法により産生させうる蛋白生産物は、たと
えば凝集因子VIIIおよびIX、ヒトもしくは動物血清アル
ブミン、組織プラスミノーゲン賦活物質（TPA）、ウロ
キナーゼ、α−１アンチトリプシン、動物成長ホルモ
ン、ミュラー氏阻止物質（MIS）、細胞表面蛋白、イン
シュリン、インターフェロン、インターロイキン、ミル
クリパーゼ、抗ウィルス蛋白、ペプチドホルモン、免疫
グロブリン、リポコルチン、並びにその他の組換蛋白生
産物を包含する。
所望の組換蛋白は、所望のまたは天然の蛋白の他にア
ミノ酸を含有する融合蛋白として産生することもでき
る。たとえば、本発明の所望の組換蛋白は、この所望の
蛋白を安定化させ或いはミルクからの精製をより容易化
しかつ迅速にするため大型組換蛋白の１部として産生す
ることができる。次いで、融合を破壊しかつ所望の蛋白
を分離する。或いは、所望の組換蛋白は天然蛋白の断片
もしくは誘導体として産生させることもでき、或いは天
然蛋白と類似したアミノ酸配列を有するよう産生させる
こともできる。これら代案のそれぞれは、単に適正なDN
A配列を選択することにより容易に実施される。
好ましくは、本発明の発現系はもしくは構造物は、所
望の組換蛋白をコードするDNA配列の下流に３′非翻訳
領域をも含む。この領域は明らかに発現系のRNA転写を
安定化させ、したがって発現系からの所望蛋白の収率を
増大させる。本発明の構造物に有用な３′非翻訳領域と
しては、ポリＡ信号を備える配列がある。この種の配列
は、たとえばSV40小型ｔ抗原、カゼイン３′非翻訳領域
またはその他の当業界で周知された３′非翻訳領域配列
から得ることができる。好ましくは、３′非翻訳領域は
ミルク特異性蛋白から誘導される。３′非翻訳領域の長
さは臨界的でないが、そのポリＡ転写産物の安定化作用
が発現配列のRNAを安定化させるのに重要であると思わ
れる。
必要に応じ、本発明の発現制御配列はさらにプロモー
タと信号ペプチドをコードするDNA配列との間に５′非
翻訳領域をも含む。この種の非翻訳領域は、好ましくは
プロモータに関連する。しかしながら、これらは他の合
成、半合成および天然の供給源から誘導することもでき
る。この場合も、特定長さは重要でないが、これらは発
現レベルを向上させるのに有用であると思われる。
上記発現系は、当業界で周知された方法を用いて作成
することができる。たとえば、慣用のリンカー、制限部
位等を用いる各種の結合技術を使用して良好な作用をう
ることができる。好ましくは、本発明の発現系は大型プ
ラスミドの１部として作成される。この種の作成は、当
業界で周知されたように適正な構成のクローン化および
選択を効率的に可能にする。特に好ましくは、本発明の
発現系は、所望の哺乳動物に組込むため残余のプラスミ
ド配列から容易に分離しうるよう、プラスミド上の便利
な制限部位の間に位置する。
このような分離および精製の後、本発明の発現系もし
くは構成物をトランスジェニック改変させるべき哺乳動
物の遺伝子プールに添加する。たとえば、この構成物の
１個もしくは数個のコピーを、標準的トランスジェニッ
ク技術により哺乳動物胚のゲノムに組込むことができ
る。
哺乳動物をトランスジェニック改変させる１つの技術
は、受精した哺乳動物卵の前核中に構成物をマイクロイ
ンジェクトして、構成物の１つもしくはそれ以上のコピ
ーを成長哺乳動物の細胞に保持させることである。一般
に、注入した卵から成長する哺乳動物の少なくとも40％
は体組織中に少なくとも１個のクローン化構成物のコピ
ーを含有し、これらの「トランスジェニック哺乳動物」
は一般に遺伝子を生殖細胞系を介して次の世代に伝達す
る。トランスジェニック的に処理された胚の成長体を組
織のセグメントのサウザン・ブロット分析により構成物
の存在につき試験することができる。外生クローン化構
成物の１つもしくはそれ以上のコピーがこの種のトラン
スジェニック胚のゲノムに安定に一体化され続ければ、
トランスジェニック改変した構成物を有する永久的なト
ランスジェニック哺乳動物ラインを確立することができ
る。
トランスジェニック改変した哺乳動物の同腹子を出産
後に子孫のゲノム中への構成物の組込みにつき分析する
ことができる。好ましくは、この分析は、所望組換蛋白
生産物をコードするDNA配列またはその断片に対応する
プローブを子孫からの染色体物質にハイブリッド化させ
て行なわれる。ゲノム中に構成物の少なくとも１個のコ
ピーを含有することが判明した哺乳動物の子孫を成熟さ
せる。これら子孫の雌は、そのミルク中に或いはミルク
と共に所望の蛋白を産生する。或いは、トランスジェニ
ック哺乳動物を育種して、ミルク中に所望蛋白を産生さ
せるのに有用な他のトランスジェニック子孫を得ること
もできる。
実施例 実施例 1:牛αＳ−１カゼイン 牛αＳ−１カゼインを、コスミドベクターHC79（ベー
リンガー・マンハイム社から供給）にてB.ホーンおよび
J.コリンスによりジーン、第11巻、第291〜98頁（198
0）に記載されたように牛胸腺DNAのコスミド保存物とク
ローン化した。胸腺は屠殺所から入手し、かつDNAを当
業界で周知された標準技術［T.マニアチス等、「モレキ
ュラ・クローニング：ラボラトリー・マューアル」、コ
ールド・スプリング・ハーバー・ラボラトリー、第271
頁（1982）］により分離した。コスミド保存物は、標準
技術［F.グロスベルト等、ジーン、第13巻、第227〜31
頁（1982）］を用いて分離した。牛胸腺DNAをSau3A（ニ
ュー・イングランド・ビオ・ラブス社から入手）で部分
的に切断し、かつこれを塩濃度勾配で処理して30〜40kb
断片を増加させた。次いで、部分切断されたDNA断片をB
amH I切断されたHC79コスミドベクターと結合させ、次
いで製造業者の推奨に従いλ抽出物（アメルシャム社）
でインビトロパッケージングした。次いで、インビトロ
パッケージングされた物質を用いてイー・コリＫ−12菌
株HB101に感染させ、次いで50μg/mlのアンピシリン
（シグマ社）を含有するLBプレートで選択した。
45塩基対オリゴヌクレオチドプローブ、すなわちCAS
−１を用いて、この保存物をスクリーニングした。この
CSA−１配列、すなわち５′ CATGGCTTGATCTTCAGTTGATT
CACTCCCAATATCCTTGCTCAG ３′は、I.M.ウィルス等によ
りDNA、第１巻、第375〜86頁（1982）に記載されたよう
にαＳ−１カゼインの部分cDNA配列から得られた。この
配列は成熟牛カゼインのアミノ酸20〜35に相当する。
このスクリーニングの結果、３種のコスミド（C9、D4
およびE1）が分離された。C9の部分サブクローン化およ
び配列決定は、このコスミドがαＳ−１カゼイン遺伝子
のゲノム配列の１部であることを示した。
次いで、開示された配列［A.F.スチュワート等、ヌク
レイック・アシッド・リサーチ、第12巻、第3895頁（19
84）;M.ナガオ等、アグリカルチャル・バイオロジカル
・ケミストリー、第48巻、第1663〜67頁（1984）］に基
づきカゼインcDNAの領域に相当する数種のオリゴヌクレ
オチドプローブを合成した。制限マッピングおよびサウ
ザン・ブロット分析［E.サウザン、ジャーナル・モレキ
ュラ・バイオロジー、第98巻、第503頁（1975）］は、
コスミドD4およびE1が構造遺伝子および上述の9kbまた
は５′フランキング配列を有することを確認した。C9コ
スミドはカゼイン構造遺伝子および下流の8kbもしくは
３′配列（第１図参照）を含有した。カゼイン構造配列
の転写開始に相当する領域におけるコスミドE1およびD4
を配列決定して、この配列がL.L.ユーリー等、ヌクレイ
ック・アシッド・リサーチ、第14巻、第1883〜1902頁
（1986）に記載されたと同じ領域の配列に相当すること
を確認した。
αＳ−１カゼインの制御領域は転写開始部の上流に位
置すると思われる。配列決定後、40bpエクソンＩが存在
することを確認すると共に、成熟CASの最初の２種のア
ミノ酸（アルギニンおよびグルタミン）をコードする配
列と一緒にCASの信号配列がエクソンIIに存在すること
も確認した。
CASプロモータプラスミドを次のように作成した：第
１図のゲノム地図は、制御領域もしくはプロモータ領域
がエクソンＩおよびIIと一緒に9kb Kpn I−BamH I断片
としてクローン化されうることを示している。したがっ
て、E1コスミドをKpn IおよびBamH Iで切断し、次いで
これを予めKpn IおよびBamH Iで切断されているpUC19
（ベセスダ・リサーチ・ラブス社）に結合させた。得ら
れたプラスミドpCAS1134（第１図参照）は、CASプロモ
ータとクローニングに適するBamH I部位を持った信号配
列とを含有した。
真核宿主にてゲノム構成物を機能させ、すなわちトラ
ンスジェニック作業を行なってDNAを前核中に注入する
には、原核配列を最初に除去せねばならない。原核配列
を除去するべく用いた１つの方法は、Sal I部位が真核D
NAに隣接するようにpCAS1134を改変することである。CA
Sプロモータの上流に位置するKpn I部位を、CAS−11リ
ンカー５′ GGT CGA CCG TAC ３′を用いてSal I
部位に変化させ、これをKpn Iで切断した後にプラスミ
ドに結合させた。得られたプラスミドpCAS1141（第１図
参照）は、CASプロモータに隣接するSal I部位とBamH I
クローン化部位とを含有した。
実施例 2:CAS−組換生産物の作成 本発明の方法により産生しうる１種の組換蛋白は組織
プラスミノーゲン賦活物質、すなわちTPAである。下記
するように、カゼイン信号ペプチドを用いて、本発明に
よる構成物を有するトランスジェニック・マウスの乳腺
からTPAの分泌を直接指令した。この構成おいて、カゼ
イン信号ペプチドのヌクレオチド配列をRNA処理（プロ
セッシング）により成熟TPAの配列に融合させた。TPAの
配列はD.ペニカ等によりネイチャー、第301巻、第214〜
21頁（1983）に記載されている。TPA遺伝子においてはC
AS遺伝子におけると同様に、成熟配列から信号ペプチド
を分離するイントロンIIにBamH I部位が存在する［R.フ
ッシャー等、ジャーナル・バイオロジカル・ケミストリ
ー、第260巻、第11223〜30頁（1985）］。TPAのcDNA
は、成熟TPAのアミノ酸No.3にてエクソンIII中にBgl II
部位を示す。
TPAのゲノムクローン［R.フィッシャー等、上記］か
らの1.7kb断片を、BamH I−Bgl IIを用いてサブクロー
ン化した。この1.7kb断片はイントロンIIの１部と３′
スプライスアクセプタ部位とBgl II部位までのエクソン
IIIとを含有した。この1.7kb断片を用いて、TPAのcDNA
クローンに見られるTPA信号配列を置換し、BamH Iカセ
ットを得た。実施例１に示したように、成熟蛋白の配列
からカゼイン信号ペプチドのための配列を分離するイン
トロンIIに位置するBamH I部位が存在する。CASプロモ
ータプラスミドpCAS1141をBamH Iで切断し、かつTPAを
含有するBamH Iカセットを第１図に示したように切断プ
ラスミドに結合させてプラスミドpCAS1151を生ぜしめ、
これはTPAのcDNA配列の上流にCASプロモータを有する。
この構成物は、TPA構造配列がRNA処理によりカゼイン信
号配列を受入れることを可能にする。
次いで、哺乳動物をトランスジェニック改変させるた
めに使用するDNAを分離した。pCAS1151DNAをSal Iで完
全に切断した。１％アガロースTBE［マニアチス等、上
記］における電気泳動の後、真核配列に相当する13kb断
片をゲルから切除し、かつDNAを電気溶出させた。次い
で、DNAを平衡CsCl濃度勾配にて１晩遠心分離した。DNA
バンドを除去しかつ緩衝剤TNE（5mMトリス（pH7.4）5mM
NaClおよび0.1m EDTA（pH8））に対し徹底的に透析
した。
実施例3:マウス中への構成物のトランスジェニック組込
み 成長しているマウス胚中へ所望の遺伝子情報をトラン
スジェニック的に組込む方法は当業界で確立されている
［B.ホーガン等、「マウス胚の処理；ラボラトリー・マ
ュニアル」、コールド・スプリング・ハーバー・ラボラ
トリー（1986）］。C57B1とCB6との間のF1世代［スロー
ン・ケタリング）交配を用いた［ジャクソン・ラボラト
リース社］。６週令の雌を、ゲスチル（妊娠雌マウス血
清）の注射に続き２日後のヒトコリオゴナドトロピンの
注射により排卵過多にした。処理した雌を24時間後にC5
7B1雄マウスと交配させた。移植前受精した胚を、DNAの
マイクロインジェクションおよび疑妊娠雌への移植のた
め交配してから12時間以内に取出した。
卵を包囲する卵丘細胞をヒマルロニターゼで先す最初
に切断することにより、構成物を注入した。構成物は、
寸法が30％〜50％膨潤するまで胚の前核中に注入した。
次いで、注入した胚（262個）を疑妊娠F1雌の卵管に移
植した。注入されかつ移植された262個の胚のうち、23
匹の子供が生まれた。これらのテールブロットを行な
い、かつニック翻訳されたpCAS1151DNAで試験して、そ
の５匹がCAS配列を有することを示した。雌GO子孫のう
ち２匹を６週間で雄に交配して、G1世代を得た。pCAS11
51配列につき、これら交配体の子孫をテールブロットに
より試験した。次いで、分娩後に得られた雌を育成しか
つ授乳させた。pCAS1151DNA配列を有するこれらの雌マ
ウスはそのミルク中にTPAを産生したのに対し、比較は
産生しなかった。
トランスジェニック雄GOマウスを比較雌と交配させ
た。テールプロットによりG1子孫を試験し、かつpCAS11
52配列を有する雌を搾乳用に育成した。G1子孫はそのミ
ルク中に0.2〜0.5μg/mlのTPAを産生した。次いで、こ
れらの雌を野生型F1と交配させた。pCAS1151DNA配列を
有する子孫は同レベルのTPAを産生したのに対し、この
配列を持たない子孫はそのミルク中にTPAを産生しなか
った。
実施例 4:大型哺乳動物中へのヒトTPA配列のトランス
ジェニック組込み 少なくとも１回の事前の発情期間の後、羊を胚ドナー
とする前に排卵過多にした。より詳細には、発情サイク
ルのほぼ10日目に、各羊にプロゲスタゲンで含浸した腟
内スポンジ（各スポンジは60mgの６α−メチル−17−α
−アセトキシプロゲステロンを含有する）を移植した。
このスポンジを12日間にわたり移植状態に保持した。ス
ポンジを取出す前の３日間および取出した翌日まで、各
動物にゴナドトロピン処理を施し、この処理は毎日２回
の筋肉内注射により2.5mgの豚卵胞刺戟ホルモンを投与
して行なった。発情の開始時点で、羊を受精可能なラム
に交配させるか或いは１頭当たり0.2mlの洗浄したラム
精子を子宮に受精させた。スポンジ除去してから72時間
以内に、１細胞受精胚および分裂胚を、麻酔された羊の
生殖管から外科的に採取し、その際各卵管のカニューレ
挿入した漏斗管端部を介し子宮−卵管接合部から得られ
た熱失活胎児牛血清10％を含有する約6mlのハムスＦ−1
0媒体で逆行洗浄した。洗浄液を集め、かつ胚を解剖用
顕微鏡の下で剔出した。
次いで、この胎芽を10％の胎児牛血清を含有する新鮮
なハムスＦ−10に移し、かつマイクロマニピュレータを
装着した倒立顕微鏡の台に載せた。次いで、各胚には、
たとえばR.L.ブリンスター等、セル、第27巻、第223〜3
1頁（1981）に示された方法により、pCAS1151のような
複数の構成物をマイクロインジェクトした。次いで、胚
を10mlのハムスＦ−10と共にガラスピペット先端に吸引
し、かつ同期された受容体羊における卵管の房状端部に
１〜3cm排出された。次いで、これらの羊を適当な時間
にわたり妊娠させ、かつその子孫をTPAをコードするDNA
配列の組込みにつき試験した。これらトランスジェニッ
ク子孫の雌は、そのミルク中にTPAを産生した。
プラスミドpCAS1151を含有する本発明の構成物は1987
年６月23日付でメリーランド州、ロックビル在、アメリ
カン・タイプ・カルチャー・コレクションに寄託されか
つLE392/pCAS1151として同定された培養物により代表さ
れ、ここでpCAS1151はイー・コリK12中に存在する。こ
れは、受託番号ATCC67450が付与されている。
以上、本発明の多くの実施例につき説明したが、この
基本的構成を変化させて本発明の方法および構成物を用
いる他の具体例も与えうることが了解されよう。したが
って、本発明の範囲は実施例として上記に説明した特定
実施例のみに限定されないことが了解されよう。
フロントページの続き (56)参考文献 特開 昭63−309192（ＪＰ，Ａ) 特開 昭63−291（ＪＰ，Ａ) 特表 平１−500162（ＪＰ，Ａ) Ｊｏｕｒｎａｌ ｏｆ Ｃｅｌｌ Ｂ ｉｏｌｏｇｙ，Ｖｏｌ．103，Ｎｏ．５, Ｐａｒｔ．２（1986）ｐ．313ａ Ｃｅｌｌ，Ｏ Ｖｏｌ．49（1987．Ｍ ａｙ）ｐ465−475 Ｐｒｏｃ．Ｎａｆｌ．Ａｃａｄ，Ｓｃ ｉ，ＵＳＡ，Ｖｏｌ．84（1987．Ｍａ ｒ）ｐ1299−1303 Ｊｏｕｒｎａｌ ｏｆ Ｃｅｌｕｌａ ｒ Ｂｉｏｃｈｅｍｉｓｔｒｙ，Ｓｕｐ ｐｌ，11Ｃ（1987．Ａｐｒ）ｐ．153 Ｔｒｅｎｄｓ ｉｎ Ｂｉｏｆｅｃｈ ｎｏｌｏｇｙ，Ｖｏ５．Ｎｏ．１ （1987．Ｊａｎ）ｐ20−24 (58)調査した分野(Int.Cl.6，ＤＢ名) C12N 15/85 C12P 21/00 A01K 67/027 ＢＩＯＳＩＳ（ＤＩＡＬＯＧ) ＷＰＩ（ＤＩＡＬＯＧ)

Claims (5)

    (57)【特許請求の範囲】
  1. 【請求項１】乳房組織にて組換蛋白を分泌しかつ成熟さ
    せるのに有効な信号ペプチドをコードするDNA配列を介
    して組換蛋白をコードするDNA配列に作用可能に結合さ
    れたαＳ−１カゼインプロモーターを含む発現系を特徴
    とするトランスジェニック哺乳動物からミルクを集め、
    そして該ミルクから組換蛋白を分離することを特徴とす
    る組換蛋白の製造方法。
  2. 【請求項２】発現系が、組換蛋白をコードするDNA配列
    の下流に３′非翻訳領域をさらに含む請求の範囲第１項
    記載の方法。
  3. 【請求項３】発現系が、プロモータと信号ペプチドをコ
    ードするDNA配列との間に５′非翻訳領域をさらに含む
    請求の範囲第１項記載の方法。
  4. 【請求項４】乳房組織にて組換蛋白を分泌しかつ成熟さ
    せるのに有効な信号ペプチドをコードするDNA配列を介
    して組換蛋白をコードするDNA配列に作用可能に結合さ
    れたαＳ−１カゼインプロモーターを含むトランスジー
    ンを含む、非ヒトトランスジェニック哺乳動物。
  5. 【請求項５】プロモーターがウシのαＳ−１プロモータ
    ーである請求の範囲第１項記載の方法。
JP63505800A 1987-06-23 1988-06-23 ミルクにおける蛋白の発現 Expired - Lifetime JP2898003B2 (ja)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US65994 1987-06-23
US07/065,994 US4873316A (en) 1987-06-23 1987-06-23 Isolation of exogenous recombinant proteins from the milk of transgenic mammals

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP10357018A Division JPH11253097A (ja) 1998-12-02 1998-12-02 非ヒト哺乳動物のミルク

Publications (2)

Publication Number Publication Date
JPH02500798A JPH02500798A (ja) 1990-03-22
JP2898003B2 true JP2898003B2 (ja) 1999-05-31

Family

ID=22066571

Family Applications (1)

Application Number Title Priority Date Filing Date
JP63505800A Expired - Lifetime JP2898003B2 (ja) 1987-06-23 1988-06-23 ミルクにおける蛋白の発現

Country Status (6)

Country Link
US (3) US4873316A (ja)
EP (1) EP0347431B1 (ja)
JP (1) JP2898003B2 (ja)
AT (1) ATE128625T1 (ja)
DE (1) DE3854555T2 (ja)
WO (1) WO1988010118A1 (ja)

Families Citing this family (720)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE122007000007I2 (de) 1986-04-09 2010-12-30 Genzyme Corp Genetisch transformierte Tiere, die ein gewünschtes Protein in Milch absondern
US5322775A (en) * 1986-06-30 1994-06-21 Pharmaceutical Proteins Ltd. Peptide production
EP0832981A1 (en) * 1987-02-17 1998-04-01 Pharming B.V. DNA sequences to target proteins to the mammary gland for efficient secretion
US6284492B1 (en) * 1988-02-26 2001-09-04 Large Scale Biology Corporation Recombinant animal viral nucleic acids
US6054566A (en) * 1988-02-26 2000-04-25 Biosource Technologies, Inc. Recombinant animal viral nucleic acids
US20030150019A1 (en) * 1988-02-26 2003-08-07 Large Scale Biology Corporation Monopartite RNA virus transformation vectors
US5316931A (en) * 1988-02-26 1994-05-31 Biosource Genetics Corp. Plant viral vectors having heterologous subgenomic promoters for systemic expression of foreign genes
US5997859A (en) * 1988-03-21 1999-12-07 Chiron Corporation Method for treating a metastatic carcinoma using a conditionally lethal gene
US6020015A (en) * 1988-09-22 2000-02-01 Gaull; Gerald E. Infant formula compositions and nutrition containing genetically engineered human milk proteins
GB8823869D0 (en) * 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
GB8826446D0 (en) * 1988-11-11 1988-12-14 Agricultural & Food Res Peptide production
US5650503A (en) * 1988-11-11 1997-07-22 Ppl Therapeutics (Scotland) Limited Genetic construct of which protein coding DNA comprises introns and is designed for protein production in transgenic animals
EP0370813A3 (en) * 1988-11-25 1991-06-19 Exemplar Corporation Rapid screening mutagenesis and teratogenesis assay
US5215904A (en) * 1989-01-27 1993-06-01 Wisconsin Alumni Research Foundation Method for producing a recombinant mammal in vivo
JPH02261386A (ja) * 1989-03-31 1990-10-24 Kyowa Hakko Kogyo Co Ltd 組換えベクター
CA2065866A1 (en) * 1989-09-11 1991-03-12 Vermuri B. Reddy Production of growth hormone in transgenic animal milk
EP0497922B1 (en) * 1989-10-24 2002-01-30 Chiron Corporation Infective protein delivery system
US5633076A (en) * 1989-12-01 1997-05-27 Pharming Bv Method of producing a transgenic bovine or transgenic bovine embryo
DE69027683T2 (de) * 1989-12-01 1997-02-13 Pharming Bv Herstellung rekombinanter polypeptide durch rinder und transgene methoden
AU652355B2 (en) * 1990-02-22 1994-08-25 Gene Pharming Europe Bv Improved expression of polypeptides
US5674898A (en) * 1990-03-05 1997-10-07 Genzyme Corporation Methods and therapeutic compositions for treating cystic fibrosis
JPH04365487A (ja) * 1990-04-11 1992-12-17 Consortium Elektrochem Ind Gmbh 組換ｄｎａ−構造体、組換ベクター、トランスゲン動物の乳からの蛋白質の取得法、トランスゲン動物の製法及びトランスゲン動物の乳
WO1992006104A1 (en) * 1990-09-28 1992-04-16 The Dana-Farber Cancer Institute Adipocyte-specific dna sequences and use for the production of transgenic animals exhibiting altered fat metabolism
US5831141A (en) * 1991-01-11 1998-11-03 United States Of America As Represented By The Department Of Health And Human Services Expression of a heterologous polypeptide in mammary tissue of transgenic non-human mammals using a long whey acidic protein promoter
US5965789A (en) * 1991-01-11 1999-10-12 American Red Cross Engineering protein posttranslational modification by PACE/furin in transgenic non-human mammals
ATE211177T1 (de) * 1991-01-11 2002-01-15 American Nat Red Cross Expression von aktivem menschlichem protein c im milchdrüsengewebe transgener tiere
US6984772B1 (en) * 1994-02-18 2006-01-10 Virginia Tech Intellectual Properties, Inc. Transgenic non-human mammals producing fibrinogen in their milk
US6262336B1 (en) 1991-01-11 2001-07-17 American Red Cross Expression of a heterologous protein C in mammary tissue of transgenic animals using a long whey acidic protein promoter
US5965788A (en) * 1992-06-12 1999-10-12 Institut National De La Recherche Agronomique Transgenic non-human mammal comprising a rabbit WAP promoter
US6268545B1 (en) 1991-06-12 2001-07-31 Institut National De La Recherche Agronomique Transgenic non-human mammal comprising a rabbit WAP promoter, uses thereof, and a DNA construct comprising the rabbit WAP promoter
WO1993003164A1 (en) * 1991-07-31 1993-02-18 Rhone-Poulenc Rorer International (Holdings) Inc. Transgenic protein production
GB9119338D0 (en) 1991-09-10 1991-10-23 Inst Of Animal Physiology And Control of gene expression
US6448469B1 (en) * 1991-10-02 2002-09-10 Genzyme Corporation Production of membrane proteins in the milk of transgenic nonhuman mammals
US5298422A (en) * 1991-11-06 1994-03-29 Baylor College Of Medicine Myogenic vector systems
DK8892D0 (da) * 1992-01-23 1992-01-23 Symbicom Ab Humant proteingen
HRP930935A2 (en) * 1992-06-11 1994-12-31 Astra Ab New dna sequences
AU4537393A (en) * 1992-06-15 1994-01-04 Gene Pharming Europe Bv Production of recombinant polypeptides by bovine species and transgenic methods
EP0672136B1 (en) * 1992-07-08 2000-03-08 N.V. Innogenetics S.A. Polypeptides, derived from endonexin 2, having hepatitis b virus receptor activity and their use in diagnostic and pharmaceutical compositions
DE4233152A1 (de) * 1992-10-02 1994-04-07 Behringwerke Ag Antikörper-Enzym-Konjugate zur Prodrug-Aktivierung
US5667839A (en) * 1993-01-28 1997-09-16 Collagen Corporation Human recombinant collagen in the milk of transgenic animals
EP0804070B1 (en) * 1993-03-09 2000-05-24 Genzyme Corporation Process of isolation of proteins from milk
DK75393D0 (da) * 1993-06-24 1993-06-24 Symbicom Ab Production of protein
EP0724628A4 (en) * 1993-07-22 1997-07-02 Merck & Co Inc TRANSGENIC ANIMAL MODEL FOR COGNITIVE DISEASES
EP0710283A4 (en) * 1993-07-22 1997-07-02 Merck & Co Inc THE EXPRESSION OF HUMAN INTERLEUKIN-1-g (b) IN A TRANSGENIC ANIMAL
US5856178A (en) * 1993-08-30 1999-01-05 Utah State University DNA cassettes for expression of lytic peptides in mammalian cells and transgenic organisms containing same
RU2025487C1 (ru) * 1993-10-18 1994-12-30 Товарищество с ограниченной ответственностью "БиоПрогресс" Способ направленной генетической трансформации молочной железы животного и устройство для введения генетического материала в молочный проток молочной железы животного
US5750367A (en) * 1993-11-08 1998-05-12 Baylor College Of Medicine Human and mouse very low density lipoprotein receptors and methods for use of such receptors
US5827690A (en) * 1993-12-20 1998-10-27 Genzyme Transgenics Corporatiion Transgenic production of antibodies in milk
AU5657800A (en) * 1993-12-20 2000-11-23 Gtc Biotherapeutics, Inc. Transgenic production of antibodies in milk
US5639940A (en) 1994-03-03 1997-06-17 Pharmaceutical Proteins Ltd. Production of fibrinogen in transgenic animals
US5888814A (en) * 1994-06-06 1999-03-30 Chiron Corporation Recombinant host cells encoding TNF proteins
US6713662B1 (en) * 1994-07-27 2004-03-30 Pharming Intellectual Property B.V. Production of collagen in the milk of transgenic mammals
US5959171A (en) * 1994-08-17 1999-09-28 Pharming B.V. Method for the production of biologically active polypeptides in a mammal's
US6518482B2 (en) 1994-09-13 2003-02-11 American National Red Cross Transgenic non-human mammals expressing human coagulation factor VIII and von Willebrand factor
US5880327A (en) * 1994-09-21 1999-03-09 American National Red Cross Transgenic mammals expressing human coagulation factor VIII
WO1996012792A1 (en) * 1994-10-20 1996-05-02 Merck & Co., Inc. INTERLEUKIN-1β DEFICIENT TRANSGENIC ANIMALS
US5780009A (en) * 1995-01-20 1998-07-14 Nexia Biotechnologies, Inc. Direct gene transfer into the ruminant mammary gland
US5843705A (en) * 1995-02-21 1998-12-01 Genzyme Transgenic Corporation Transgenically produced antithrombin III
JPH11511979A (ja) * 1995-09-06 1999-10-19 ババリアン・ノルディック・リサーチ・インスティテュート・アクティーゼルスカブ ヒト乳癌細胞を含むヒト乳腺細胞を標的として、連結された異種性遺伝子を発現させるためのｗａｐまたはｍｍｔｖ制御配列の使用
US5907080A (en) * 1995-11-30 1999-05-25 Nexia Biotechnologies, Inc. Method for development of transgenic dwarf goats
US7632922B1 (en) * 1995-12-22 2009-12-15 Amgen, Inc. Osteoprotegerin
US6613544B1 (en) * 1995-12-22 2003-09-02 Amgen Inc. Osteoprotegerin
SE9601091L (sv) * 1996-03-21 1997-09-22 Joyce Carlson Användning av en proteinsubstans för bindning av steroid-liknande molekyler
US6025155A (en) * 1996-04-10 2000-02-15 Chromos Molecular Systems, Inc. Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes
US6077697A (en) 1996-04-10 2000-06-20 Chromos Molecular Systems, Inc. Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes
US20030033617A1 (en) * 1996-04-10 2003-02-13 Gyula Hadlaczky Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes
US20020160970A1 (en) * 1996-04-10 2002-10-31 Gyula Hadlaczky Artificial chromosomes, uses thereof and methods for preparing artificial chromosomes
EP0959907A4 (en) * 1996-07-24 2002-01-09 Univ Maryland BUTYROPHILIN GENE PROMOTER AND USES THEREOF
US6478969B2 (en) 1996-09-06 2002-11-12 Pall Corporation Shear separation method and system
EP0971724B1 (en) * 1997-02-14 2010-01-20 American Red Cross Expression of active human factor ix in mammary tissue of transgenic animals
EP1793000A1 (en) * 1997-02-25 2007-06-06 GTC Biotherapeutics, Inc. Transgenically produced non-secreted proteins
EP0973934A4 (en) * 1997-02-25 2003-02-05 Genzyme Transgenics Corp NON-SECRETED PROTEINS PRODUCED TRANSGENICALLY
DE69842225D1 (de) 1997-04-16 2011-05-26 Millennium Pharm Inc Zusammensetzung, umfassend einen Antikörper, der selektiv an ein cysteinreiches sekretiertes Protein (CRSP) bindet
US6210736B1 (en) 1997-06-17 2001-04-03 Genzyme Transgenics Corporation Transgenically produced prolactin
US6087166A (en) 1997-07-03 2000-07-11 Basf Aktiengesellschaft Transcriptional activators with graded transactivation potential
US6323008B1 (en) 1997-08-14 2001-11-27 Neose Technologies, Inc. Methods for producing sialyloligosaccharides in a dairy source
WO1999009816A1 (de) * 1997-08-22 1999-03-04 Roche Diagnostics Gmbh Verfahren zur gewinnung von insulin precursorproteinen
KR20010031210A (ko) * 1997-10-20 2001-04-16 추후보정 세포계내의 ｍＲＮＡ량 및 단백질 발현을 증가시키는 방법및 변형 핵산 서열
US7157615B2 (en) 1998-03-17 2007-01-02 Nexia Biotechnologies, Inc. Production of biofilaments in transgenic animals
US6733991B1 (en) * 1998-05-08 2004-05-11 Osi Pharmaceuticals, Inc. AGS proteins and nucleic acid molecules and uses therefor
US6746852B1 (en) 1998-05-08 2004-06-08 Osi Pharmaceuticals, Inc. AGS proteins and nucleic acid molecules and uses thereof
CN1107445C (zh) * 1998-05-08 2003-05-07 上海市儿童医院上海医学遗传研究所 一种转基因羊的制备方法
US7700353B2 (en) * 1998-07-22 2010-04-20 E-P Therapeutics, Inc. Compositions and methods for inducing apoptosis in tumor cells
US20030027998A1 (en) * 1998-10-30 2003-02-06 Holtzman Douglas A. Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses
US20060205034A1 (en) * 1998-10-30 2006-09-14 Millennium Pharmaceuticals, Inc. Novel genes encoding proteins having prognostic, diagnostic, preventive, therapeutic, and other uses
JP2002534077A (ja) 1999-01-06 2002-10-15 アトランティック バイオファーマシューティカルズ インコーポレイティッド トランスジェニック動物における分泌型ヒトアルファ−フェト蛋白質の発現
US7208576B2 (en) * 1999-01-06 2007-04-24 Merrimack Pharmaceuticals, Inc. Non-glycosylated human alpha-fetoprotein, methods of production, and uses thereof
EP1162934A4 (en) * 1999-02-22 2005-01-26 Eric F Bernstein COMPOSITIONS AND METHODS FOR PREVENTING PHOTOVAGENING
EP2301947A3 (en) 1999-02-26 2011-11-23 Millennium Pharmaceuticals, Inc. Secreted proteins and uses thereof
AR022952A1 (es) 1999-03-19 2002-09-04 Smithkline Beecham Corp ANTICUERPO MONOCLONAL DE ROEDOR ESPECIFICAMENTE NEUTRALIZANTE PARA LA INTERLEUQUINA-18 HUMANA , UN FRAGMENTO FAB NEUTRALIZANTE o FRAGMENTO F(AB')2, UNA REGION DE COMPLEMENTARIEDAD DE CADENA LIGERA DE INMONOGLOBULINA(CDR), UNA MOLECULA DE ACIDO NUCLEICO, COMPOSICION FARMACEUTICA QUE LO COMPRENDE, EL
NZ514792A (en) * 1999-04-14 2004-02-27 Gtc Biotherapeutics Inc Method of expression of protein in milk of transgenic mammal
US20040023874A1 (en) * 2002-03-15 2004-02-05 Burgess Catherine E. Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US6974684B2 (en) * 2001-08-08 2005-12-13 Curagen Corporation Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20040229779A1 (en) * 1999-05-14 2004-11-18 Ramesh Kekuda Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US6774120B1 (en) * 1999-06-01 2004-08-10 Sarah Ferber Methods of inducing regulated pancreatic hormone production in non-pancreatic islet tissues
US20040067490A1 (en) * 2001-09-07 2004-04-08 Mei Zhong Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US6183803B1 (en) 1999-06-11 2001-02-06 Biosante Pharmaceuticals, Inc. Method for processing milk
TR200103706T2 (tr) 1999-06-25 2002-10-21 Basf Aktiengesellschaft Karbon metabolizma ve enerji üretimindeki proteinleri kodlayan corynebacterium glutamicum genleri.
US7291714B1 (en) 1999-06-30 2007-11-06 Millennium Pharmaceuticals, Inc. Glycoprotein VI and uses thereof
PL359501A1 (en) 1999-07-01 2004-08-23 Basf Aktiengesellschaft Orynebacterium glutamicum
DE1246922T1 (de) 1999-07-01 2003-03-20 Basf Ag Für proteine des phosphoenolpyruvat:zucker phosphotransferase systems kodierende gene aus corynebacterium glutamicum
CA2378953A1 (en) * 1999-07-27 2001-02-01 Abgenix, Inc. Methods and compositions for inhibiting polypeptide accumulation associated with neurological disorders
AU6913600A (en) * 1999-08-19 2001-03-13 Us Transgenics, Inc. Transgenic prothrombin and related thrombin precursors and transgenics, methods,compositions, uses and the like relating thereto
PT1210428E (pt) 1999-08-23 2015-07-21 Genetics Inst Llc Pd-1, um recetor para b7-4 e suas utilizações
AT411997B (de) 1999-09-14 2004-08-26 Baxter Ag Faktor ix/faktor ixa aktivierende antikörper und antikörper-derivate
US6855806B1 (en) * 1999-10-15 2005-02-15 Curagen Corporation Thymosin beta 10-like proteins and nucleic acids encoding same
WO2001029071A2 (en) * 1999-10-19 2001-04-26 Curagen Corporation Genes associated with obesity and methods for using the same
US7820878B2 (en) * 1999-11-19 2010-10-26 Kyowa Hakko Kirin Co., Ltd. Production of ungulates, preferably bovines that produce human immunoglobulins
US7074983B2 (en) 1999-11-19 2006-07-11 Kirin Beer Kabushiki Kaisha Transgenic bovine comprising human immunoglobulin loci and producing human immunoglobulin
US7414170B2 (en) * 1999-11-19 2008-08-19 Kirin Beer Kabushiki Kaisha Transgenic bovines capable of human antibody production
AU1777301A (en) * 1999-11-19 2001-05-30 Hematech, Llc Production of ungulates, preferably bovines that produce human immunoglobulins
US20030157592A1 (en) * 1999-12-16 2003-08-21 Jens Lerchl Moss genes from physcomitrella patens encoding proteins involved in the synthesis of tocopherols and carotenoids
EP1254169B1 (en) 1999-12-30 2007-05-09 President And Fellows of Harvard College Methods relating to modulation of th2 cell subset activity by modulation of xbp-1 activity
DK1254238T3 (da) 2000-02-09 2009-11-30 Basf Se Nyt elongasegen og fremgangsmåde til fremstilling af flerumættede fedtsyrer
EP2143796A3 (en) 2000-02-29 2010-03-17 Millennium Pharmaceuticals, Inc. 1983, 52881, 2398, 45449, 50289, and 52872, G protein-coupled receptors and uses therefor
EP1261712B1 (en) * 2000-03-03 2006-12-13 Curagen Corporation Proteins named fctrx and nucleic acids encoding same
US8697137B2 (en) 2000-03-24 2014-04-15 Biosphere Medical, Inc. Methods of using microspheres for active embolization
US20030212022A1 (en) * 2001-03-23 2003-11-13 Jean-Marie Vogel Compositions and methods for gene therapy
DE10016877A1 (de) * 2000-04-05 2001-10-18 Scintec Diagnostics Gmbh Zug (Glyko-)Proteine mit hoher Immunreaktivität sowie ein Verfahren zu ihrer Herstellung
US6720477B2 (en) 2000-04-07 2004-04-13 Basf Plant Science Gmbh Signal transduction stress-related proteins and methods of use in plants
US20040005554A1 (en) * 2000-05-08 2004-01-08 Tayar Nabil El Novel glycoproteins and methods of use thereof
US20030219786A1 (en) * 2000-08-11 2003-11-27 Applied Research Systems Ars Holding N.V. Novel glycoproteins and methods of use thereof
EP1714661A3 (en) 2000-05-19 2012-03-14 The Center for Blood Research, INC. Methods for diagnosing and treating hemostatic disorders by modulating p-selectin activity
US20040034193A1 (en) * 2001-06-13 2004-02-19 Samy Ashkar Biosynthetic oncolytic molecules and uses therefor
US20050048614A1 (en) * 2000-06-13 2005-03-03 Children's Medical Center Corporation Biosynthetic oncolytic molecules and uses therefor
CA2414331C (en) 2000-06-28 2011-11-29 Genetics Institute, Llc. Pd-l2 molecules: novel pd-1 ligands and uses therefor
AU2001280639A1 (en) 2000-07-18 2002-01-30 Millennium Pharmaceuticals, Inc. 13237,18480,2245 or 16228 human protein kinase molecules and uses therefor
US6924412B1 (en) * 2000-07-21 2005-08-02 Arriwan Holding B.V. Means and methods for raising antibody concentration in compartments of the body of a non-human animal
US20040023259A1 (en) * 2000-07-26 2004-02-05 Luca Rastelli Therapeutic polypeptides, nucleic acids encoding same, and methods of use
UA81743C2 (uk) 2000-08-07 2008-02-11 Центокор, Инк. МОНОКЛОНАЛЬНЕ АНТИТІЛО ЛЮДИНИ, ЩО СПЕЦИФІЧНО ЗВ'ЯЗУЄТЬСЯ З ФАКТОРОМ НЕКРОЗУ ПУХЛИН АЛЬФА (ФНПα), ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ, ЩО ЙОГО МІСТИТЬ, ТА СПОСІБ ЛІКУВАННЯ РЕВМАТОЇДНОГО АРТРИТУ
US6902734B2 (en) 2000-08-07 2005-06-07 Centocor, Inc. Anti-IL-12 antibodies and compositions thereof
US7288390B2 (en) 2000-08-07 2007-10-30 Centocor, Inc. Anti-dual integrin antibodies, compositions, methods and uses
AU2001284948A1 (en) * 2000-08-15 2002-02-25 Board Of Trustees Of The University Of Illinois Animals expressing exogenous igf-i in their milk
CA2417432C (en) 2000-09-01 2010-11-02 The Center For Blood Research, Inc. Modified polypeptides stabilized in a desired conformation and methods for producing same
PL204888B1 (pl) 2000-09-13 2010-02-26 Novo Nordisk Healthcare Ag Wariant polipeptydu czynnika VII, konstrukcja kwasu nukleinowego, rekombinowana komórka gospodarza, zwierzę transgeniczne, sposób wytwarzania wariantu polipeptydu czynnika VII, kompozycja farmaceutyczna i zastosowanie wariantu polipeptydu czynnika VII
US20030176344A1 (en) * 2000-09-14 2003-09-18 Decode Genetics Ehf. Human osteoporosis gene
UA83458C2 (uk) 2000-09-18 2008-07-25 Байоджен Айдек Ма Інк. Виділений поліпептид baff-r (рецептор фактора активації в-клітин сімейства tnf)
CA2421267C (en) * 2000-09-28 2009-01-06 Bioriginal Food & Science Corporation Fad4, fad5, fad5-2, and fad6, novel fatty acid desaturase family members and uses thereof
EP2174954B1 (en) 2000-10-18 2016-03-23 Robert Sackstein Hematopoietic cell e-selectin/l-selectin ligand polypeptides and methods of use thereof
BR0115728A (pt) 2000-11-28 2003-09-23 Wyeth Corp Análise da expressão de ácidos nucléicos kiaa e polipeptìdeos úteis no diagnóstico e tratamento de cáncer de próstata
AU2002241524A1 (en) 2000-11-28 2002-06-11 Wyeth Expression analysis of FKBP nucleic acids and polypeptides useful in the diagnosis and treatment of prostate cancer
CA2431861A1 (en) 2000-12-08 2002-06-13 Curagen Corporation Method of detecting and treating tuberous sclerosis complex associated disorders
US7247704B2 (en) * 2000-12-18 2007-07-24 Arriva Pharmaceuticals, Inc. Multifunctional protease inhibitors and their use in treatment of disease
AU2002231736A1 (en) 2000-12-22 2002-07-08 Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. Use of repulsive guidance molecule (rgm) and its modulators
US20020142397A1 (en) * 2000-12-22 2002-10-03 Philippe Collas Methods for altering cell fate
US7491534B2 (en) 2000-12-22 2009-02-17 Kirin Holdings Kabushiki Kaisha Methods for altering cell fate to generate T-cells specific for an antigen of interest
NZ525607A (en) 2000-12-22 2005-05-27 Aurox Llc Methods for cloning mammals using reprogrammed donor chromatin or donor cells
US6964849B2 (en) 2001-01-11 2005-11-15 Curagen Corporation Proteins and nucleic acids encoding same
US20040043928A1 (en) * 2001-08-02 2004-03-04 Ramesh Kekuda Therapeutic polypeptides, nucleic acids encoding same, and methods of use
GB0103174D0 (en) * 2001-02-08 2001-03-28 Smithkline Beecham Plc Novel method of treatment
US20040133930A1 (en) * 2002-03-11 2004-07-08 Cooper Julian D. Production of high levels of transgenic factor ix without gene rescue, and its therapeutic uses
CA2342376C (en) * 2001-03-20 2013-11-12 Marco Colonna A receptor trem (triggering receptor expressed on myeloid cells) and uses thereof
US8231878B2 (en) * 2001-03-20 2012-07-31 Cosmo Research & Development S.P.A. Receptor trem (triggering receptor expressed on myeloid cells) and uses thereof
US8981061B2 (en) 2001-03-20 2015-03-17 Novo Nordisk A/S Receptor TREM (triggering receptor expressed on myeloid cells) and uses thereof
US20090081199A1 (en) * 2001-03-20 2009-03-26 Bioxell S.P.A. Novel receptor trem (triggering receptor expressed on myeloid cells) and uses thereof
JP2005508608A (ja) 2001-03-22 2005-04-07 アボット ゲーエムベーハー ウント カンパニー カーゲー 問題遺伝子に対して特異的な抗体を発現するトランスジェニック動物及びその使用
ES2432967T3 (es) 2001-03-22 2013-12-05 Novo Nordisk Health Care Ag Derivados del Factor VII de coagulación
GB0107510D0 (en) * 2001-03-26 2001-05-16 Univ Bristol New elongase gene and a process for the production of -9-polyunsaturated fatty acids
CA2442066C (en) 2001-04-02 2005-11-01 Wyeth Pd-1, a receptor for b7-4, and uses therefor
WO2002083855A2 (en) 2001-04-16 2002-10-24 Wyeth Holdings Corporation Novel streptococcus pneumoniae open reading frames encoding polypeptide antigens and uses thereof
IL159015A0 (en) * 2001-05-25 2004-05-12 Genset Sa Polypeptides, their preparation and use
US20070015144A9 (en) * 2001-05-25 2007-01-18 Genset, S.A. Human cDNAs and proteins and uses thereof
PL370139A1 (en) * 2001-06-07 2005-05-16 Wyeth A g-protein coupled receptor and uses therefor
US20030129613A1 (en) * 2001-07-05 2003-07-10 Fernandes Elma R. Novel human proteins and polynucleotides encoding them
US20030087274A1 (en) * 2001-07-05 2003-05-08 Anderson David W. Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20040029790A1 (en) * 2001-07-05 2004-02-12 Meera Patturajan Novel human proteins, polynucleotides encoding them and methods of using the same
US20040030096A1 (en) * 2001-08-02 2004-02-12 Linda Gorman Novel human proteins, polynucleotides encoding them and methods of using the same
US7220718B2 (en) * 2001-08-03 2007-05-22 United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Oral treatment of hemophilia
US7285631B2 (en) 2001-08-10 2007-10-23 Serono Genetics Institute S.A. Human cDNAs and proteins and uses thereof
CA2459961A1 (en) 2001-09-05 2003-03-13 Basf Plant Science Gmbh Protein phosphatase stress-related polypeptides and methods of use in plants
US20060068405A1 (en) * 2004-01-27 2006-03-30 Alex Diber Methods and systems for annotating biomolecular sequences
US20040142325A1 (en) * 2001-09-14 2004-07-22 Liat Mintz Methods and systems for annotating biomolecular sequences
WO2003045304A2 (en) * 2001-09-26 2003-06-05 Mayo Foundation For Medical Education And Research Mutable vaccines
ATE532858T1 (de) 2001-09-27 2011-11-15 Novo Nordisk Healthcare Ag Menschliche gerinnungsfaktor-vii-polypeptide
US20030199442A1 (en) * 2001-10-09 2003-10-23 Alsobrook John P. Therapeutic polypeptides, nucleic acids encoding same, and methods of use
US20050124022A1 (en) * 2001-10-30 2005-06-09 Maithreyan Srinivasan Novel sulfurylase-luciferase fusion proteins and thermostable sulfurylase
US6902921B2 (en) 2001-10-30 2005-06-07 454 Corporation Sulfurylase-luciferase fusion proteins and thermostable sulfurylase
US6956114B2 (en) 2001-10-30 2005-10-18 '454 Corporation Sulfurylase-luciferase fusion proteins and thermostable sulfurylase
DE10154270A1 (de) 2001-11-05 2003-05-15 Basf Ag Gene die für Kohlenstoffmetabolismus- und Energieproduktion-Proteine codieren
DE10154180A1 (de) 2001-11-05 2003-05-15 Basf Ag gene die für genetische Stabilitäts-, genexpressions-und Faltungsproteine codieren
EP1525323B1 (en) 2001-11-09 2015-01-21 Dana-Farber Cancer Institute, Inc. Pgc-1beta, a novel pgc-1 homologue and uses therefor
US7220585B2 (en) 2001-11-09 2007-05-22 Basf Plant Science Gmbh Transcription factor stress-related polypeptides and methods of use in plants
DE10155505A1 (de) 2001-11-13 2003-05-22 Basf Ag Gene die für Glucose-6-Phosphat-Dehydrogenase Proteine codieren
JP2007528691A (ja) 2001-11-14 2007-10-18 セントカー・インコーポレーテツド 抗ｉｌ−６抗体、組成物、方法および使用
AU2002364169A1 (en) * 2001-12-14 2003-06-30 President And Fellows Of Harvard College Dual inhibition of sister chromatide separation at metaphase
EP1455815A4 (en) * 2001-12-19 2006-11-02 Millennium Pharm Inc MEMBERS OF THE DIACYLGLYCEROL-ACYLTRANSFERASES FAMILY 2 (DGAT2) AND USES THEREOF
EP1458860A2 (en) * 2001-12-21 2004-09-22 Nexia Biotechnologies, Inc. Production of butyrylcholinesterases in transgenic mammals
US20060253913A1 (en) * 2001-12-21 2006-11-09 Yue-Jin Huang Production of hSA-linked butyrylcholinesterases in transgenic mammals
US20070016969A1 (en) * 2002-01-18 2007-01-18 Animal Technology Institute Taiwan Expression vector for hirudin and transformed cells and transgenic animals containing said vector
US7781396B2 (en) * 2002-01-31 2010-08-24 Tel Aviv University Future Technology Development L.P. Peptides directed for diagnosis and treatment of amyloid-associated disease
US20040052928A1 (en) * 2002-09-06 2004-03-18 Ehud Gazit Peptides and methods using same for diagnosing and treating amyloid-associated diseases
US20050215478A1 (en) * 2002-02-07 2005-09-29 Ben-Sasson Shmuel A Amino acid sequences capable of facilitating penetration across a biological barrier
EP1472351B1 (en) 2002-02-07 2007-06-20 Yissum Research Development Company Of The Hebrew University Of Jerusalem Amino acid sequences capable of facilitating penetration across a biological barrier
US20040117862A1 (en) * 2002-03-11 2004-06-17 Cooper Julian D. Production of high levels of transgenic factor VII with engineered stability and its therapeutic uses
NZ548701A (en) 2002-04-09 2008-03-28 Biogen Idec Inc Methods for treating tweak-related conditions
EP1572950B1 (en) 2002-06-17 2012-10-10 Thrasos, Inc. Single domain tdf-related compounds and analogs thereof
AU2003280130B2 (en) 2002-06-28 2009-06-11 Centocor, Inc. Mammalian CH1 deleted mimetibodies, compositions, methods and uses
JP2005532053A (ja) * 2002-07-01 2005-10-27 ウエイン・ステイト・ユニバーシテイ 抗生物質耐性を起こしやすくない抗生物質の同定のための方法および組成物
US7250551B2 (en) * 2002-07-24 2007-07-31 President And Fellows Of Harvard College Transgenic mice expressing inducible human p25
AR040778A1 (es) 2002-08-06 2005-04-20 Glaxo Group Ltd Anticuerpos alterados o fragmentos funcionales que se unen a mag (glicoproteina asociada a mielina).
DE10238433A1 (de) * 2002-08-16 2004-03-04 Justus-Liebig-Universität Giessen Verfahren zur Bestimmung des allelischen Zustandes des 5'-Ende des alpha-S1-Kaseingenes
AU2003265556A1 (en) 2002-08-20 2004-03-11 Millenium Pharmaceuticals, Inc. Compositions, kits, and methods for identification, assessment, prevention, and therapy of cervical cancer
CA2502490A1 (en) * 2002-11-08 2004-05-27 Hematech, Llc Transgenic ungulates having reduced prion protein activity and uses thereof
US20060009378A1 (en) * 2002-11-14 2006-01-12 Itshak Golan Novel galectin sequences and compositions and methods utilizing same for treating or diagnosing arthritis and other chronic inflammatory diseases
EP2112229A3 (en) 2002-11-25 2009-12-02 Sequenom, Inc. Methods for identifying risk of breast cancer and treatments thereof
US7491699B2 (en) * 2002-12-09 2009-02-17 Ramot At Tel Aviv University Ltd. Peptide nanostructures and methods of generating and using the same
AU2003299441A1 (en) * 2002-12-19 2004-07-14 Centre National De La Recherche Scientifique - Cnrs Nf-hev compositions and methods of use
EP2058275A1 (en) 2003-01-07 2009-05-13 Ramot at Tel-Aviv University Ltd. Peptide nanostructures encapsulating a foreign material and method of manufacturing same
DE602004030546D1 (de) 2003-03-04 2011-01-27 Aspenbio Pharma Inc LH zur Verwendung der Erhaltung einer oder mehreren Schwangerschaften durch Induktion der Bildung des sekundären Gelbkörpers.
EP2319857A3 (en) 2003-03-04 2012-06-27 Yeda Research And Development Co., Ltd. Pon polypeptides, polynucleotides encoding same and compositions and methods utilizing same
JP2007524371A (ja) * 2003-03-04 2007-08-30 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ レラキシン３−ｇｐｃｒ１３５複合体ならびにそれらの生産及び使用
WO2004083421A1 (en) 2003-03-18 2004-09-30 Novo Nordisk Health Care Ag Method for the production of gla-residue containing serine proteases
GB0306309D0 (en) * 2003-03-19 2003-04-23 Glaxo Group Ltd Method of treatment
DK2330132T3 (da) 2003-04-04 2013-11-04 Yeda Res & Dev Antistoffer mod MMP2 eller MMP9 og farmaceutiske sammensætninger deraf til hæmning af deres metalloproteinaktivitet
AU2004227204B2 (en) 2003-04-08 2010-06-03 Yeda Research And Development Co. Ltd Stem cells having increased sensitivity to SDF-1 and methods of generating and using same
FR2853551B1 (fr) 2003-04-09 2006-08-04 Lab Francais Du Fractionnement Formulation stabilisante pour compositions d'immunoglobulines g sous forme liquide et sous forme lyophilisee
US9708410B2 (en) 2003-05-30 2017-07-18 Janssen Biotech, Inc. Anti-tissue factor antibodies and compositions
EP1638517A4 (en) 2003-06-30 2010-01-06 Univ Tel Aviv Future Tech Dev PEPTIDES, ANTIBODIES AGAINST DISEASES ASSOCIATED WITH AMYLOID AND METHODS OF USE FOR THE DIAGNOSIS AND TREATMENT OF THESE DISEASES
ES2359473T3 (es) 2003-07-21 2011-05-23 Transgene S.A. Citoquinas multifuncionales.
US20050059089A1 (en) * 2003-08-07 2005-03-17 Chester Kuei Complexes of GPCR142 and relaxin3 or INSL5, and their production and use
EP2520654B8 (en) 2003-08-26 2017-04-19 The Regents of the University of Colorado, a body corporate Inhibitors of serine protease activity and their use in methods and compositions for treatment of bacterial infections
EP1660659A2 (en) * 2003-09-05 2006-05-31 Licentia, Ltd. Gdnf-related neuropeptides
US7550263B2 (en) * 2003-09-05 2009-06-23 Gtc Biotherapeutics, Inc. Method for the production of fusion proteins in transgenic mammal milk
ES2381110T3 (es) 2003-09-09 2012-05-23 Novo Nordisk Health Care Ag Polipéptidos de factor VII de coagulación
US7297336B2 (en) 2003-09-12 2007-11-20 Baxter International Inc. Factor IXa specific antibodies displaying factor VIIIa like activity
US20050136103A1 (en) * 2003-09-17 2005-06-23 Ben-Sasson Shmuel A. Compositions capable of facilitating penetration across a biological barrier
CA2539432A1 (en) * 2003-09-23 2005-04-07 Favrille, Inc. Altering a b cell pathology using self-derived antigens in conjunction with specific-binding cytoreductive agent
UA89481C2 (uk) 2003-09-30 2010-02-10 Центокор, Инк. Еритропоетинові міметичні шарнірно-серцевинні міметитіла людини, композиції, способи та застосування
US7625707B2 (en) 2003-10-02 2009-12-01 Ramot At Tel Aviv University Ltd. Antibacterial agents and methods of identifying and utilizing same
KR20060120652A (ko) 2003-10-07 2006-11-27 밀레니엄 파머슈티컬스 인코퍼레이티드 난소암의 확인, 평가, 예방 및 치료를 위한 핵산 분자 및단백질
US7418396B2 (en) * 2003-10-14 2008-08-26 Broadcom Corporation Reduced memory implementation technique of filterbank and block switching for real-time audio applications
WO2005040377A2 (en) 2003-10-24 2005-05-06 Selexis S.A. High efficiency gene transfer and expression in mammalian cells by a multiple transfection procedure of matrix attachment region sequences
IL158868A0 (en) 2003-11-13 2004-05-12 Yeda Res & Dev Methods of generating and using stem cells enriched with immature primitive progenitor
US20050125914A1 (en) * 2003-11-18 2005-06-16 Gerard Malle Hair shaping composition comprising at least one- non-hydroxide base
JP4412989B2 (ja) * 2003-12-15 2010-02-10 株式会社日立製作所 複数の記憶システムを有するデータ処理システム
DE10359661A1 (de) * 2003-12-18 2005-07-28 Basf Ag Genvarianten die für Proteine aus dem Stoffwechselweg von Feinchemikalien codieren
CA2487098A1 (en) * 2003-12-22 2005-06-22 F. Hoffmann-La Roche Ag Novel targets for obesity from fat tissue
US8007847B2 (en) 2004-01-13 2011-08-30 Eytan Biderman Feeding formula appliance
AU2005206389A1 (en) * 2004-01-27 2005-08-04 Compugen Ltd. Methods of identifying putative gene products by interspecies sequence comparison and biomolecular sequences uncovered thereby
US20050186608A1 (en) * 2004-02-19 2005-08-25 Olsen Byron V. Method for the production of transgenic proteins useful in the treatment of obesity and diabetes
US20050197496A1 (en) * 2004-03-04 2005-09-08 Gtc Biotherapeutics, Inc. Methods of protein fractionation using high performance tangential flow filtration
CA2563379A1 (en) * 2004-03-31 2005-10-20 Centocor, Inc. Human glp-1 mimetibodies, compositions, methods and uses
CA2563064A1 (en) * 2004-04-22 2005-11-10 Kirin Beer Kabushiki Kaisha Transgenic animals and uses thereof
US20050245444A1 (en) * 2004-04-30 2005-11-03 Yann Echelard Method of using recombinant human antithrombin for neurocognitive disorders
KR100646222B1 (ko) 2004-06-03 2006-11-23 대한민국 돼지 유선특이 발현벡터 및 이를 이용한 형질전환 동물 유선에서 유전자 발현방법
CA2571218C (en) 2004-06-17 2015-11-03 William D. Carlson Tdf-related compounds and analogs thereof
US7288385B2 (en) * 2004-06-25 2007-10-30 The Salk Institute For Biological Studies Increasing life span by modulation of Smek
US8680062B2 (en) 2004-07-06 2014-03-25 Deliversir Ltd. System for delivering therapeutic agents into living cells and cells nuclei
WO2006006172A2 (en) * 2004-07-15 2006-01-19 Ramot At Tel Aviv University Ltd. Use of anti-amyloid agents for treating and typing pathogen infections
US8568637B2 (en) * 2004-08-02 2013-10-29 Ramot At Tel-Aviv University Ltd. Method of forming a fiber made of peptide nanostructures
US7510858B2 (en) * 2004-08-02 2009-03-31 Janssen Pharmaceutica N.V. IRAK 1c splice variant and its use
US7893197B2 (en) * 2004-08-25 2011-02-22 Janssen Pharmaceutica N.V. Relaxin-3 chimeric polypeptides and their preparation and use
US7393662B2 (en) 2004-09-03 2008-07-01 Centocor, Inc. Human EPO mimetic hinge core mimetibodies, compositions, methods and uses
US7786086B2 (en) 2004-09-08 2010-08-31 Ramot At Tel-Aviv University Ltd. Peptide nanostructures containing end-capping modified peptides and methods of generating and using the same
US20060063187A1 (en) * 2004-09-15 2006-03-23 Hotamisligil Gokhan S Modulation of XBP-1 activity for treatment of metabolic disorders
US20080124741A1 (en) * 2004-10-12 2008-05-29 Heng Dai Canine Cholecystokinin 1 Receptor Materials And Their Use
JP4271122B2 (ja) * 2004-10-15 2009-06-03 財団法人 ひろしま産業振興機構 カイコでの組換えタンパク質製造のためのポリヌクレオチド
WO2007001423A2 (en) 2004-10-21 2007-01-04 Wyeth Immunogenic compositions of staphylococcus epidermidis polypeptide and polynucleotide antigens
GB0426146D0 (en) 2004-11-29 2004-12-29 Bioxell Spa Therapeutic peptides and method
US20060121004A1 (en) * 2004-12-07 2006-06-08 Yann Echelard Methods of reducing the incidence of rejection in tissue transplantation through the use of recombinant human antithrombin
US20060130159A1 (en) * 2004-12-09 2006-06-15 Nick Masiello Method of purifying recombinant MSP 1-42 derived from Plasmodium falciparum
CN1274829C (zh) 2004-12-10 2006-09-13 四川大学华西医院 抗eb病毒所致肿瘤多肽及其应用与制备方法
US20060154285A1 (en) * 2004-12-29 2006-07-13 Robishaw Janet D Zebrafish heterotrimer G-protein gamma 2 subunit (GNG2)
JP2008529325A (ja) * 2005-01-16 2008-07-31 ズランゴー リミテッド 通信ネットワークシステムおよびそれを使用するための方法
WO2006075334A2 (en) * 2005-01-16 2006-07-20 Zlango Ltd. Iconic communication
US8019818B2 (en) * 2005-01-18 2011-09-13 Zlango Ltd. Communications network system and methods for using same
US20080019905A9 (en) * 2005-02-18 2008-01-24 Strome Scott E Method of using an anti-CD137 antibody as an agent for radioimmunotherapy or radioimmunodetection
PE20061324A1 (es) 2005-04-29 2007-01-15 Centocor Inc Anticuerpos anti-il-6, composiciones, metodos y usos
ES2568782T3 (es) 2005-05-09 2016-05-04 Biosphere Medical, S.A. Composiciones y métodos de uso de microesferas y agentes de contraste no iónicos
JP2008544744A (ja) 2005-05-11 2008-12-11 ウエイン・ステイト・ユニバーシテイ 抗生物質耐性に対し感受性でない抗生物質の同定のための新規標的
WO2006122224A1 (en) 2005-05-11 2006-11-16 Wayne State University Methods and compositions for the identification of antibiotics that are not susceptible to antibiotic resistance in pseudomonas aeruginosa
MX2007014474A (es) 2005-05-17 2008-02-07 Univ Connecticut Composiciones y metodos para inmunomodulacion en un organismo.
CA2612016A1 (en) 2005-06-17 2006-12-21 Basf Plant Science Gmbh Lecitin-like protein kinase stress-related polypeptides and methods of use in plants
US20070056050A1 (en) * 2005-06-29 2007-03-08 Clokie Cameron M L PRODUCTION OF BONE MORPHOGENIC PROTEINS (BMPs) IN TRANSGENIC MAMMALS
TR201902033T4 (tr) 2005-06-30 2019-03-21 Janssen Biotech Inc Anti-IL-23 antikorları, bileşimleri, yöntemleri ve kullanımları.
WO2007007317A1 (en) * 2005-07-07 2007-01-18 Yissum Research Development Company Of The Hebrew University Of Jerusalem Nucleic acid agents for downregulating h19, and methods of using same
AU2006292827B2 (en) 2005-08-09 2013-02-14 Revivicor, Inc. Transgenic ungulates expressing CTLA4-IG and uses thereof
US20090055942A1 (en) 2005-09-14 2009-02-26 Novo Nordisk Healthcare A/G Human Coagulation Factor VII Polypeptides
PT2497780E (pt) 2005-09-20 2015-08-20 Thrasos Innovation Inc Compostos relacionados com tdf e seus análogos
WO2007039256A2 (de) 2005-09-30 2007-04-12 Abbott Gmbh & Co. Kg Bindungsdomänen von proteinen der repulsive guidance molecule (rgm) proteinfamilie und funktionale fragmente davon sowie deren verwendung
CA2624662A1 (en) 2005-09-30 2007-04-12 The Government Of The United States Of America, As Represented By The Se Cretary Of Health And Human Services Methods and compositions for modulating immune tolerance
IL172297A (en) 2005-10-03 2016-03-31 Compugen Ltd Soluble vegfr-1 variants for the diagnosis of preeclampsia
US10004828B2 (en) * 2005-10-11 2018-06-26 Romat at Tel-Aviv University Ltd. Self-assembled Fmoc-ff hydrogels
US8021867B2 (en) 2005-10-18 2011-09-20 Duke University Rationally-designed meganucleases with altered sequence specificity and DNA-binding affinity
AU2006304886B2 (en) * 2005-10-21 2012-04-12 Genzyme Corporation Antibodies with enhanced antibody-dependent cellular cytoxicity activity, methods of their production and use
US20090291437A1 (en) * 2005-11-02 2009-11-26 O'brien Sean Methods for targeting quadruplex sequences
US7879212B2 (en) * 2005-11-03 2011-02-01 Ramot At Tel-Aviv University Ltd. Peptide nanostructure-coated electrodes
US7767420B2 (en) 2005-11-03 2010-08-03 Momenta Pharmaceuticals, Inc. Heparan sulfate glycosaminoglycan lyase and uses thereof
US20070161546A1 (en) * 2005-12-15 2007-07-12 Colm King Methods and compositions for treatment of cancer
GB0525662D0 (en) 2005-12-16 2006-01-25 Glaxo Group Ltd Immunoglobulins
MX2008008621A (es) 2005-12-29 2008-11-27 Centocor Inc Anticuerpos anti-il-23 humanos, composiciones, metodos y usos.
IL173104A0 (en) 2006-01-12 2006-06-11 Yeda Res & Dev Siva and ubiquintination
EP2216339A1 (en) 2006-01-16 2010-08-11 Compugen Ltd. Novel nucleotide and amino acid sequences, and methods of use thereof for diagnosis
US8775526B2 (en) 2006-01-16 2014-07-08 Zlango Ltd. Iconic communication
US9458444B2 (en) 2006-02-03 2016-10-04 Opko Biologics Ltd. Long-acting coagulation factors and methods of producing same
US8048848B2 (en) 2006-02-03 2011-11-01 Prolor Biotech Ltd. Long-acting interferons and derivatives thereof and methods thereof
US10221228B2 (en) 2006-02-03 2019-03-05 Opko Biologics Ltd. Long-acting polypeptides and methods of producing and administering same
US10351615B2 (en) 2006-02-03 2019-07-16 Opko Biologics Ltd. Methods of treatment with long-acting growth hormone
US8946155B2 (en) 2006-02-03 2015-02-03 Opko Biologics Ltd. Long-acting polypeptides and methods of producing and administering same
US20140113860A1 (en) 2006-02-03 2014-04-24 Prolor Biotech Ltd. Long-acting polypeptides and methods of producing and administering same
US8476234B2 (en) 2006-02-03 2013-07-02 Prolor Biotech Inc. Long-acting coagulation factors and methods of producing same
US8048849B2 (en) 2006-02-03 2011-11-01 Modigene, Inc. Long-acting polypeptides and methods of producing same
US9249407B2 (en) 2006-02-03 2016-02-02 Opko Biologics Ltd. Long-acting coagulation factors and methods of producing same
US8759292B2 (en) 2006-02-03 2014-06-24 Prolor Biotech, Llc Long-acting coagulation factors and methods of producing same
US8450269B2 (en) 2006-02-03 2013-05-28 Prolor Biotech Ltd. Long-acting growth hormone and methods of producing same
US20150038413A1 (en) 2006-02-03 2015-02-05 Opko Biologics Ltd. Long-acting polypeptides and methods of producing and administering same
US7553941B2 (en) 2006-02-03 2009-06-30 Modigene Inc Long-acting polypeptides and methods of producing same
US20090221072A1 (en) * 2006-02-15 2009-09-03 Chen Thomas T Compositions and methods for modulating cell differentiation
US7531632B2 (en) * 2006-02-16 2009-05-12 Gtc Biotherapeutics, Inc. Clarification of transgenic milk using depth filtration
EP1991268A4 (en) 2006-03-03 2009-08-26 Univ Southern California POLYMORPHISMS OF THE GENES OF THE PATH OF ANGIOGENESIS FOR CHOICE OF THERAPY
US20100034819A1 (en) * 2006-03-31 2010-02-11 Centocor Inc. Human epo mimetic hinge core mimetibodies, compositions, methods and uses for preventing or treating glucose intolerance related conditions on renal disease associated anemia
WO2007127151A2 (en) * 2006-04-24 2007-11-08 The Cleveland Clinic Foundation Non-human model of autoimmune disease
EP2537934A3 (en) * 2006-05-15 2013-04-10 Paratek Pharmaceuticals, Inc. Methods of regulating expression of genes or of gene products using substituted tetracycline compounds
US8153369B2 (en) 2006-06-05 2012-04-10 Cancer Care Ontario Assessment of risk for colorectal cancer
US8124831B2 (en) * 2006-07-06 2012-02-28 Duke University Transgenic mice carrying functional single nucleotide polymorphisms in brain-specific tryptophan hydroxylase
EP2471809B1 (en) 2006-07-11 2015-09-02 University Of Medicine And Dentistry Of New Jersey Proteins, nucleic acids encoding the same and associated methods of use
WO2008019036A2 (en) * 2006-08-04 2008-02-14 Pharmathene Inc. Long half-life recombinant butyrylcholinesterase
US9277737B2 (en) 2006-09-21 2016-03-08 Probiodrug Ag Mouse models carrying a knock-out mutation of the QPCTL-gene
WO2008060776A2 (en) 2006-10-03 2008-05-22 University Of Medicine And Dentistry Of New Jersey Atap peptides, nucleic acids encoding the same and associated methods of use
US9018440B2 (en) * 2006-10-27 2015-04-28 Stowers Institute For Medical Research Fluorescent mouse model
UY30820A1 (es) * 2006-12-21 2008-07-03 Centocor Inc Uso de agonistas del receptor de glp-1 de accion prolongada para mejorar la sensibilidad a la insulina y los perfiles lipidicos
EP2111450A2 (en) * 2007-01-16 2009-10-28 Yissum Research Development Company of the Hebrew University of Jerusalem Nucleic acid constructs and methods for specific silencing of h19
WO2008088861A2 (en) * 2007-01-18 2008-07-24 University Of Southern California Gene polymorphisms predictive for dual tki therapy
US20120070444A1 (en) 2007-01-19 2012-03-22 Probiodrug Ag IN VIVO SCREENING MODELS FOR TREATMENT OF isoQC-RELATED DISORDERS
ES2372229T3 (es) 2007-01-19 2012-01-17 Probiodrug Ag Modelos de selección in vivo para el tratamiento de la enfermedad de alzheimer y otros trastornos relacionados con qpct.
US20100196403A1 (en) * 2007-01-29 2010-08-05 Jacob Hochman Antibody conjugates for circumventing multi-drug resistance
AU2008222563A1 (en) 2007-03-05 2008-09-12 Cancer Care Ontario Assessment of risk for colorectal cancer
EP2134365B1 (en) 2007-03-21 2019-03-13 Effat Emamian Compositions and methods for inhibiting tumor cell growth
US9156865B2 (en) 2007-04-23 2015-10-13 Deliversir Ltd System for delivering therapeutic agents into living cells and cells nuclei
US9556210B2 (en) 2007-04-23 2017-01-31 Sabag-Rfa Ltd. System for delivering therapeutic agents into living cells and cells nuclei
PT2144633E (pt) * 2007-04-23 2014-10-27 Deliversir Ltd Um sistema para a administração de agentes terapêuticos em células vivas e núcleos de células
ES2614735T3 (es) 2007-07-23 2017-06-01 Janssen Biotech, Inc. Métodos y composiciones para tratar los trastornos relacionados con fibrosis usando antagonistas de la IL-17
PL2769729T3 (pl) 2007-09-04 2019-09-30 Compugen Ltd. Polipeptydy i polinukleotydy i ich zastosowanie jako cel dla leków do wytwarzania leków i środków biologicznych
CA2696934A1 (en) * 2007-09-12 2010-02-16 Probiodrug Ag Transgenic mice
EP3824902A1 (en) 2007-09-28 2021-05-26 Portola Pharmaceuticals, Inc. Antidotes for factor xa inhibitors and methods of using the same
EP2214708A4 (en) 2007-10-26 2011-01-12 Centocor Ortho Biotech Inc VECTORS, HOST CELLS, METHODS OF PRODUCTION AND USES
AU2008318430A1 (en) * 2007-10-31 2009-05-07 Precision Biosciences, Inc. Rationally-designed single-chain meganucleases with non-palindromic recognition sequences
US20110008345A1 (en) 2007-11-30 2011-01-13 Claire Ashman Antigen-binding constructs
US8501449B2 (en) 2007-12-04 2013-08-06 Proteon Therapeutics, Inc. Recombinant elastase proteins and methods of manufacturing and use thereof
KR100912038B1 (ko) 2007-12-31 2009-08-12 전남대학교산학협력단 돼지 β-카제인 게놈 ＤＮＡ, 및 이를 포함하는 재조합벡터 및 형질전환체
JP2011511622A (ja) * 2008-01-14 2011-04-14 プロビオドルグ エージー グルタミニルシクラーゼ遺伝子のノックアウト変異を有するマウスモデル
US20110052501A1 (en) * 2008-01-31 2011-03-03 Liat Dassa Polypeptides and polynucleotides, and uses thereof as a drug target for producing drugs and biologics
US8962803B2 (en) 2008-02-29 2015-02-24 AbbVie Deutschland GmbH & Co. KG Antibodies against the RGM A protein and uses thereof
AU2009223671B2 (en) 2008-03-11 2014-11-27 Sequenom, Inc. Nucleic acid-based tests for prenatal gender determination
WO2009134389A2 (en) * 2008-05-01 2009-11-05 Gtc Biotherapeutics, Inc. An anti-cd137 antibody as an agent in the treatment of inflammatory conditions
WO2009155484A2 (en) 2008-06-20 2009-12-23 Wyeth Compositions and methods of use of orf1358 from beta-hemolytic streptococcal strains
WO2010002160A2 (ko) * 2008-06-30 2010-01-07 조아제약주식회사 돼지의 알파에스 1 카제인 유전자, 그 프로모터 및 그의 용도
US8420388B2 (en) * 2008-06-30 2013-04-16 Cho-A Pharm. Co., Ltd. Gene of porcine beta casein, a promoter of the same and the use thereof
US8999661B2 (en) * 2008-07-30 2015-04-07 Dana-Farber Cancer Institute, Inc. Compositions for detecting cell death and methods of use thereof
NZ590816A (en) 2008-08-14 2013-02-22 Cephalon Australia Pty Ltd Anti-il-12/il-23 antibodies
WO2010029537A1 (en) 2008-09-10 2010-03-18 Ben Gurion University Of The Negev Research And Development Authority Antinecrotic activity of alpha 1-antitrypsin
US8476013B2 (en) 2008-09-16 2013-07-02 Sequenom, Inc. Processes and compositions for methylation-based acid enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
US8962247B2 (en) 2008-09-16 2015-02-24 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non invasive prenatal diagnoses
AU2009296392B2 (en) 2008-09-26 2016-06-02 Dana-Farber Cancer Institute, Inc. Human anti-PD-1, PD-L1, and PD-L2 antibodies and uses therefor
LT3335728T (lt) 2008-10-10 2020-03-10 Children`S Medical Center Corporation Biocheminiu požiūriu stabilizuota živ-1 env trimero vakcina
WO2010061393A1 (en) 2008-11-30 2010-06-03 Compugen Ltd. He4 variant nucleotide and amino acid sequences, and methods of use thereof
WO2010064231A1 (en) 2008-12-02 2010-06-10 Tel Hashomer Medical Research Infrastructure And Services Ltd. Methods of analyzing a-i rna editing and nucleic acid constructs capable of same
US8734759B2 (en) 2008-12-05 2014-05-27 Yeda Research And Development Co. Ltd. Methods of diagnosing and treating motor neuron diseases
WO2010080985A1 (en) 2009-01-08 2010-07-15 Dana-Farber Cancer Institute, Inc. Compositions and methods for induced brown fat differentiation
US8530629B2 (en) 2009-01-30 2013-09-10 Ab Biosciences, Inc. Lowered affinity antibodies and uses therefor
US8362203B2 (en) * 2009-02-10 2013-01-29 Wayne State University Non-natural peptides as models for the development of antibiotics
US20110305694A1 (en) 2009-02-24 2011-12-15 Paul Andrew Hamblin Multivalent and/or multispecific rankl-binding constructs
JP2012518398A (ja) 2009-02-24 2012-08-16 グラクソ グループ リミテッド 抗原結合性構築物
JP2012518399A (ja) 2009-02-24 2012-08-16 グラクソ グループ リミテッド 抗原結合性構築物
EP2414517B1 (en) 2009-03-30 2016-09-21 Portola Pharmaceuticals, Inc. Antidotes for factor xa inhibitors and methods of using the same
JP2012522749A (ja) 2009-04-01 2012-09-27 グラクソ グループ リミテッド 抗ｉｌ−２３免疫グロブリン
EP2421611A1 (en) 2009-04-24 2012-02-29 Glaxo Group Limited Fgfr1c antibody combinations
US9023767B2 (en) * 2009-05-07 2015-05-05 Memorial Sloan-Kettering Cancer Center γ-Secretase substrates and methods of use
SG176164A1 (en) * 2009-05-19 2011-12-29 Probiodrug Ag Mouse models carrying a knock-out mutation of the qpctl-gene
US20100304873A1 (en) * 2009-05-28 2010-12-02 Lipa Markowitz Bowling Ball and Football Game Controller
US8268550B2 (en) * 2009-06-26 2012-09-18 Massachusetts Institute Of Technology Compositions and methods for identification of PARP function, inhibitors, and activators
US8435961B2 (en) * 2009-06-26 2013-05-07 Massachusetts Institute Of Technology Methods and compositions for increasing the activity of inhibitory RNA
US20110097329A1 (en) 2009-06-26 2011-04-28 Massachusetts Institute Of Technology Compositions and methods for treating cancer and modulating stress granule formation
US9663778B2 (en) 2009-07-09 2017-05-30 OPKO Biologies Ltd. Long-acting coagulation factors and methods of producing same
JP6163304B2 (ja) 2009-07-15 2017-07-12 ポートラ ファーマシューティカルズ， インコーポレイテッド 第Ｘａ因子インヒビターの解毒剤の単位用量処方物およびその使用方法
AU2010272483B2 (en) * 2009-07-17 2016-07-21 Omeros Corporation MASP isoforms as inhibitors of complement activation
CN106619515A (zh) 2009-08-27 2017-05-10 工业研究与发展基金会有限公司 脂质体组合物及其用途
EP2496246B1 (en) 2009-11-03 2018-06-27 Grifols Therapeutics LLC Composition, method, and kit for alpha-1 proteinase inhibitor
US8968740B2 (en) 2009-11-13 2015-03-03 Dana-Farber Cancer Institute, Inc. Compositions, kits, and methods for the diagnosis, prognosis, monitoring, treatment and modulation of post-transplant lymphoproliferative disorders and hypoxia associated angiogenesis disorders using galectin-1
CA2781120C (en) 2009-11-24 2015-01-27 Jianxin Guo Lyophilization methods, compositions, and kits
CN102656190A (zh) 2009-12-08 2012-09-05 雅培股份有限两合公司 用于在视网膜神经纤维层变性治疗中使用的针对rgm a蛋白质的单克隆抗体
WO2011084145A2 (en) 2009-12-21 2011-07-14 Pharmathene, Inc. Recombinant butyrylcholinesterases and truncates thereof
EP3660165B1 (en) 2009-12-22 2023-01-04 Sequenom, Inc. Processes and kits for identifying aneuploidy
WO2011088163A1 (en) 2010-01-14 2011-07-21 President And Fellows Of Harvard College Methods for modulating skeletal remodeling and patterning by modulating shn2 activity, shn3 activity, or shn2 and shn3 activity in combination
US10429384B2 (en) 2010-01-22 2019-10-01 Dana-Farber Cancer Institute, Inc. Compositions, kits, and methods for identification, assessment, prevention, and therapy of metabolic disorders
US8697078B2 (en) 2010-01-27 2014-04-15 Yeda Research And Development Co. Ltd. Antibodies that inhibit metalloproteins
WO2011094593A2 (en) 2010-01-28 2011-08-04 Ab Biosciences, Inc. Novel lowered affinity antibodies and methods of marking the same
TWI518325B (zh) 2010-02-04 2016-01-21 自治醫科大學 對ａｌｋ抑制劑具有先抗性或後抗性癌症的識別、判斷和治療
AU2011215900A1 (en) 2010-02-10 2012-07-26 Immunogen, Inc. CD20 antibodies and uses thereof
WO2011104708A2 (en) 2010-02-24 2011-09-01 Ben Gurion University Of The Negev Research And Development Authority Methods for inhibiting necrosis
JP6148013B2 (ja) 2010-03-05 2017-06-14 リグショスピタレト 補体活性化のキメラ抑制分子
US20150231215A1 (en) 2012-06-22 2015-08-20 Randolph J. Noelle VISTA Antagonist and Methods of Use
US10745467B2 (en) 2010-03-26 2020-08-18 The Trustees Of Dartmouth College VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders
EP2552947A4 (en) 2010-03-26 2013-11-13 Dartmouth College VISTA REGULATORY T CELL MEDIATOR PROTEIN, VISTA BINDING ACTIVE SUBSTANCES AND USE THEREOF
WO2011133288A1 (en) 2010-04-19 2011-10-27 The Trustees Of The University Of Pennsylvania Microrna induction of pluripotential stem cells and uses thereof
KR101834026B1 (ko) 2010-06-19 2018-03-02 메모리얼 슬로안-케터링 캔서 센터 항-ｇｄ2 항체
WO2016030888A1 (en) 2014-08-26 2016-03-03 Compugen Ltd. Polypeptides and uses thereof as a drug for treatment of autoimmune disorders
EP2588123A2 (en) 2010-06-30 2013-05-08 Compugen Ltd. C1orf32 for the treatment of multiple sclerosis, rheumatoid arthritis and other autoimmune disorders
US9632088B2 (en) 2010-09-07 2017-04-25 Memorial Sloan-Kettering Cancer Center Methods and compositions for gamma-secretase assay
WO2012046238A2 (en) 2010-10-06 2012-04-12 Ramot At Tel-Aviv University Ltd. Erythropoietin receptor antagonists
WO2012051301A1 (en) 2010-10-12 2012-04-19 President And Fellows Of Harvard College Methods for identifying modulators of triglyceride metabolism, for modulating triglyceride metabolism and for identifying subjects at risk for abnormal triglyceride metabolism
WO2012052878A1 (en) 2010-10-19 2012-04-26 Vascular Biogenics Ltd. Isolated polynucleotides and nucleic acid constructs for directing expression of a gene-of-interest in cells
US9539427B2 (en) 2010-11-08 2017-01-10 The Johns Hopkins University Methods for improving heart function
TW201225972A (en) 2010-11-15 2012-07-01 Univ Ramot Dipeptide analogs for treating conditions associated with amyloid fibril formation
MY170404A (en) 2010-11-23 2019-07-27 Glaxo Group Ltd Antigen binding proteins
EP2643351A1 (en) 2010-11-24 2013-10-02 Glaxo Group Limited Multispecific antigen binding proteins targeting hgf
AU2011352205B2 (en) 2010-12-31 2016-06-16 Bioatla, Llc Express humanization of antibodies
US9956236B2 (en) 2011-02-07 2018-05-01 Cornell University Methods for increasing immune responses using agents that directly bind to and activate IRE-1
US8974782B2 (en) 2011-02-07 2015-03-10 Glaxo Group Limited Treatment of stroke comprising anti-MAG antibodies
CN102643852B (zh) 2011-02-28 2015-04-08 华东理工大学 光可控的基因表达系统
US9409987B2 (en) 2011-04-15 2016-08-09 Compugen Ltd Polypeptides and polynucleotides, and uses thereof for treatment of immune related disorders and cancer
AU2012249531B2 (en) 2011-04-29 2017-06-29 Sequenom, Inc. Quantification of a minority nucleic acid species
WO2012156976A1 (en) 2011-05-16 2012-11-22 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Methods of producing artemisinin in non-host plants and vectors for use in same
EP2710130B1 (en) 2011-05-19 2022-06-29 Fundación Pública Andaluza Progreso Y Salud Highly inducible dual-promoter lentiviral tet-on system
AU2012260601B2 (en) 2011-05-25 2018-02-01 Innate Pharma, S.A. Anti-KIR antibodies for the treatment of inflammatory disorders
RS64791B1 (sr) 2011-05-27 2023-11-30 Glaxo Group Ltd Bcma (cd269/tnfrsf17) - vezujući proteini
WO2013001517A1 (en) 2011-06-30 2013-01-03 Compugen Ltd. Polypeptides and uses thereof for treatment of autoimmune disorders and infection
US9499612B2 (en) 2011-07-27 2016-11-22 Glaxo Group Limited Antigen binding constructs
EP2742062A2 (en) 2011-08-12 2014-06-18 Probiodrug AG In vivo screening models for treatment of qc-related disorders
SG2014012728A (en) 2011-08-23 2014-06-27 Foundation Medicine Inc Novel kif5b-ret fusion molecules and uses thereof
US8969519B2 (en) 2011-09-13 2015-03-03 Dana-Farber Cancer Institute, Inc. Compositions and methods for brown fat induction and activity using FNDC5
WO2013055911A1 (en) 2011-10-14 2013-04-18 Dana-Farber Cancer Institute, Inc. Znf365/zfp365 biomarker predictive of anti-cancer response
ES2894724T3 (es) 2011-12-02 2022-02-15 Rhode Island Hospital Vacuna contra la malaria falciparum
US9636398B2 (en) 2011-12-14 2017-05-02 AbbVie Deutschland GmbH & Co. KG Composition and method for the diagnosis and treatment of iron-related disorders
EP2791173B1 (en) 2011-12-14 2020-07-29 AbbVie Deutschland GmbH & Co. KG Composition and method for the diagnosis and treatment of iron-related disorders
CA2858825A1 (en) * 2011-12-19 2013-06-27 Lfb Usa, Inc. Recombinant human alpha-1-antitrypsin for the treatment of inflammatory disorders
IL305223A (en) 2012-01-27 2023-10-01 Abbvie Inc The composition and method for the diagnosis and treatment of diseases related to the degeneration of nerve cells
WO2013114363A2 (en) 2012-01-30 2013-08-08 Yeda Research And Development Co.Ltd. Antimicrobial agents
BR112014018481A2 (pt) 2012-02-01 2017-07-04 Compugen Ltd anticorpo monoclonal ou policlonal ou um fragmento de ligação a antígeno do mesmo, polinucleotídeo, anticorpo monoclonal, vetor, hibridoma, anticorpo, hibridoma 5166-2 e/ou 5166-9, anticorpo ou fragmento de ligação a antígeno, composição farmacêutica, uso do anticorpo ou fragmento de ligação a anticorpo, método para tratar câncer, método para diagnosticar câncer em um indivíduo, anticorpo, método, composição ou uso
US11787844B2 (en) 2012-02-09 2023-10-17 Var2 Pharmaceuticals Aps Targeting of chondroitin sulfate glycans
KR102310704B1 (ko) 2012-02-14 2021-10-08 옵코 바이오로직스 리미티드 장기 작용 응고 인자들 및 이를 생산하는 방법들
US9663568B2 (en) 2012-02-15 2017-05-30 Novo Nordisk A/S Antibodies that bind peptidoglycan recognition protein 1
US9550830B2 (en) 2012-02-15 2017-01-24 Novo Nordisk A/S Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
ES2640268T3 (es) 2012-02-15 2017-11-02 Novo Nordisk A/S Anticuerpos que se unen a y bloquean un receptor desencadenante expresado en células mieloides 1 (TREM-1)
EP2820129A1 (en) 2012-03-02 2015-01-07 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
US9228006B2 (en) 2012-03-16 2016-01-05 University Health Network Methods and compositions for modulating Toso activity
US9494597B2 (en) 2012-04-02 2016-11-15 Ab Biosciences, Inc. Human control antibodies and uses therefor
CN104487082A (zh) 2012-04-19 2015-04-01 奥普科生物制品有限公司 长效胃泌酸调节素变体及其生产方法
US9920361B2 (en) 2012-05-21 2018-03-20 Sequenom, Inc. Methods and compositions for analyzing nucleic acid
JP5868549B2 (ja) 2012-05-24 2016-02-24 マウントゲイト グループ リミテッド 狂犬病感染の予防および治療に関する組成物および方法
AU2013277051B2 (en) 2012-06-22 2018-06-07 King's College London Novel VISTA-Ig constructs and the use of VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders
US9890215B2 (en) 2012-06-22 2018-02-13 King's College London Vista modulators for diagnosis and treatment of cancer
US20140093873A1 (en) 2012-07-13 2014-04-03 Sequenom, Inc. Processes and compositions for methylation-based enrichment of fetal nucleic acid from a maternal sample useful for non-invasive prenatal diagnoses
US9511087B2 (en) 2012-08-03 2016-12-06 Revo Biologics, Inc. Use of antithrombin in extracorporeal membrane oxygenation
WO2014029752A1 (en) 2012-08-22 2014-02-27 Glaxo Group Limited Anti lrp6 antibodies
AU2013312211B2 (en) 2012-09-07 2018-03-29 King's College London VISTA modulators for diagnosis and treatment of cancer
JP2015532307A (ja) 2012-10-15 2015-11-09 ノヴォ・ノルディスク・ヘルス・ケア・アーゲー 凝固因子ｖｉｉポリペプチド
CN104918639B (zh) 2012-10-22 2018-01-26 萨拜格Rfa公司 用于将治疗剂递送到活细胞和细胞核中的系统
EP2912069B1 (en) 2012-10-23 2019-07-31 Emory University Gm-csf and il-4 conjugates, compositions, and methods related thereto
WO2014071358A2 (en) 2012-11-05 2014-05-08 Foundation Medicine, Inc. Novel ntrk1 fusion molecules and uses thereof
BR122020018510B1 (pt) 2012-11-20 2023-03-14 Opko Biologics Ltd Método para aumentar incrementalmente o tamanho hidrodinâmico de um fator de coagulação ativado viia
ES2576128T3 (es) 2012-12-12 2016-07-05 The Broad Institute, Inc. Modificación por tecnología genética y optimización de sistemas, métodos y composiciones para la manipulación de secuencias con dominios funcionales
WO2014093694A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
EP2931899A1 (en) 2012-12-12 2015-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
ES2658401T3 (es) 2012-12-12 2018-03-09 The Broad Institute, Inc. Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas
EP2931892B1 (en) 2012-12-12 2018-09-12 The Broad Institute, Inc. Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
EP4234696A3 (en) 2012-12-12 2023-09-06 The Broad Institute Inc. Crispr-cas component systems, methods and compositions for sequence manipulation
PT2921557T (pt) 2012-12-12 2016-10-19 Massachusetts Inst Technology Engenharia de sistemas, métodos e composições guia otimizadas para a manipulação de sequências
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
PL2784162T3 (pl) 2012-12-12 2016-01-29 Broad Inst Inc Opracowanie systemów, metod oraz zoptymalizowanych kompozycji przewodnikowych do manipulacji sekwencyjnej
DK2898075T3 (en) 2012-12-12 2016-06-27 Broad Inst Inc CONSTRUCTION AND OPTIMIZATION OF IMPROVED SYSTEMS, PROCEDURES AND ENZYME COMPOSITIONS FOR SEQUENCE MANIPULATION
EP2945652B1 (en) 2013-01-18 2021-07-07 Foundation Medicine, Inc. Methods of treating cholangiocarcinoma
MX2015009433A (es) 2013-01-28 2015-10-09 Solae Llc Polipeptidos novedosos que tienen actividad liberadora de hormonas de la saciedad.
EP2956003A2 (en) 2013-02-13 2015-12-23 Laboratoire Français du Fractionnement et des Biotechnologies Proteins with modified glycosylation and methods of production thereof
MX2015010427A (es) 2013-02-13 2016-03-17 Lab Francais Du Fractionnement Anticuerpos anti-tnf-alfa altamente galactosilados y sus usos.
EP2971100A1 (en) 2013-03-13 2016-01-20 Sequenom, Inc. Primers for dna methylation analysis
AU2014230741B2 (en) 2013-03-15 2017-04-13 Glaxosmithkline Intellectual Property Development Limited Anti-LAG-3 binding proteins
US9469686B2 (en) 2013-03-15 2016-10-18 Abbott Laboratories Anti-GP73 monoclonal antibodies and methods of obtaining the same
EP2968545B1 (en) 2013-03-15 2019-03-06 Memorial Sloan Kettering Cancer Center High affinity anti-gd2 antibodies
US10183988B2 (en) 2013-06-07 2019-01-22 Duke University Anti-Complement factor H antibodies
DK3011032T3 (da) 2013-06-17 2020-01-20 Broad Inst Inc Fremføring, modificering og optimering af systemer, fremgangsmåder og sammensætninger til målretning mod og modellering af sygdomme og forstyrrelser i postmitotiske celler
WO2014204725A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
WO2014204727A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
ES2777217T3 (es) 2013-06-17 2020-08-04 Broad Inst Inc Suministro, modificación y optimización de sistemas de guía en tándem, métodos y composiciones para la manipulación de secuencias
KR20160030187A (ko) 2013-06-17 2016-03-16 더 브로드 인스티튜트, 인코퍼레이티드 간의 표적화 및 치료를 위한 ＣＲＩＳＰＲ­Ｃａｓ 시스템, 벡터 및 조성물의 전달 및 용도
EP3011034B1 (en) 2013-06-17 2019-08-07 The Broad Institute, Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
US9163284B2 (en) 2013-08-09 2015-10-20 President And Fellows Of Harvard College Methods for identifying a target site of a Cas9 nuclease
US9228207B2 (en) 2013-09-06 2016-01-05 President And Fellows Of Harvard College Switchable gRNAs comprising aptamers
DK3049521T3 (en) 2013-09-25 2019-04-23 Univ Cornell Compounds for inducing antitumor immunity and methods thereof
DK3060239T3 (da) 2013-10-21 2020-08-03 Opko Biologics Ltd Langtidsvirkende polypeptider og fremgangsmåder til fremstilling og indgivelse heraf
US20150158926A1 (en) 2013-10-21 2015-06-11 Opko Biologics, Ltd. Long-acting polypeptides and methods of producing and administering same
WO2015065964A1 (en) 2013-10-28 2015-05-07 The Broad Institute Inc. Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof
EP2876114A1 (en) 2013-11-25 2015-05-27 Consejo Superior De Investigaciones Científicas Antibodies against CCR9 and applications thereof
MX2016007324A (es) 2013-12-12 2017-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapeuticas de los sistemas y composiciones crispr-cas para actuar sobre hbv y trastornos y enfermedades virales.
WO2015089486A2 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems
MX2016007327A (es) 2013-12-12 2017-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapeuticas de sistemas y composiciones crispr-cas para dirigirlos a trastornos y enfermedades usando componentes para suministro de particulas.
WO2015089354A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
WO2015089364A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Crystal structure of a crispr-cas system, and uses thereof
WO2015089473A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
KR20160089527A (ko) 2013-12-12 2016-07-27 더 브로드 인스티튜트, 인코퍼레이티드 게놈 편집을 위한 ｃｒｉｓｐｒ-ｃａｓ 시스템 및 조성물의 전달, 용도 및 치료적 응용
WO2015097536A2 (en) 2013-12-24 2015-07-02 Janssen Pharmaceutical Nv Anti-vista antibodies and fragments
US11014987B2 (en) 2013-12-24 2021-05-25 Janssen Pharmaceutics Nv Anti-vista antibodies and fragments, uses thereof, and methods of identifying same
KR20160125409A (ko) 2014-02-07 2016-10-31 메디뮨 엘엘씨 인간 페리오스틴을 검출하기 위한 신규 검정법
AU2015225867B2 (en) 2014-03-07 2020-02-06 University Health Network Methods and compositions for modifying the immune response
EP3736344A1 (en) 2014-03-13 2020-11-11 Sequenom, Inc. Methods and processes for non-invasive assessment of genetic variations
CA2944903A1 (en) 2014-04-24 2015-10-29 Dana-Farber Cancer Institute, Inc. Tumor suppressor and oncogene biomarkers predictive of anti-immune checkpoint inhibitor response
US10428305B2 (en) 2014-05-15 2019-10-01 National University Of Singapore Modified natural killer cells that express IL15 and uses thereof
ES2769030T3 (es) 2014-05-16 2020-06-24 Univ Pennsylvania Inducción por microARN de la regeneración cardíaca
AU2015274504B2 (en) 2014-06-11 2021-02-04 Kathy A. Green Use of VISTA agonists and antagonists to suppress or enhance humoral immunity
CA2952697A1 (en) 2014-06-16 2015-12-23 The Johns Hopkins University Compositions and methods for the expression of crispr guide rnas using the h1 promoter
KR20240029114A (ko) 2014-07-17 2024-03-05 노보 노르디스크 에이/에스 점도를 감소시키기 위한 trem-1 항체의 부위 지정 돌연변이유발
US10077453B2 (en) 2014-07-30 2018-09-18 President And Fellows Of Harvard College CAS9 proteins including ligand-dependent inteins
EP3180426B1 (en) 2014-08-17 2019-12-25 The Broad Institute, Inc. Genome editing using cas9 nickases
WO2016049251A1 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling mutations in leukocytes
WO2016049024A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling competition of multiple cancer mutations in vivo
WO2016049163A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Use and production of chd8+/- transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder
WO2016049258A2 (en) 2014-09-25 2016-03-31 The Broad Institute Inc. Functional screening with optimized functional crispr-cas systems
WO2016057367A1 (en) 2014-10-06 2016-04-14 Dana-Farber Cancer Institute, Inc. Angiopoietin-2 biomarkers predictive of anti-immune checkpoint response
AU2015357463B2 (en) 2014-12-05 2021-10-07 Immunext, Inc. Identification of VSIG8 as the putative vista receptor and its use thereof to produce vista/VSIG8 modulators
CN107438623B (zh) 2014-12-10 2023-07-14 Opko生物科学有限公司 长效的ctp修饰的生长激素多肽的制备方法
EP3985115A1 (en) 2014-12-12 2022-04-20 The Broad Institute, Inc. Protected guide rnas (pgrnas)
WO2016094872A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Dead guides for crispr transcription factors
WO2016094880A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs)
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
EP3234192B1 (en) 2014-12-19 2021-07-14 The Broad Institute, Inc. Unbiased identification of double-strand breaks and genomic rearrangement by genome-wide insert capture sequencing
WO2016106236A1 (en) 2014-12-23 2016-06-30 The Broad Institute Inc. Rna-targeting system
CA2970370A1 (en) 2014-12-24 2016-06-30 Massachusetts Institute Of Technology Crispr having or associated with destabilization domains
MA41296A (fr) 2014-12-30 2017-11-07 Orgenesis Ltd Procédés de transdifférenciation et procédés d'utilisation de ceux-ci
WO2016108926A1 (en) 2014-12-30 2016-07-07 The Broad Institute Inc. Crispr mediated in vivo modeling and genetic screening of tumor growth and metastasis
WO2016144673A1 (en) 2015-03-06 2016-09-15 Dana-Farber Cancer Institute, Inc. Pd-l2 biomarkers predictive of pd-1 pathway inhibitor responses in esophagogastric cancers
AU2016233309B2 (en) 2015-03-17 2021-11-18 Memorial Sloan Kettering Cancer Center Anti-MUC16 antibodies and uses thereof
US20180064748A1 (en) 2015-03-27 2018-03-08 Yeda Research And Development Co. Ltd. Methods of treating motor neuron diseases
US20180161300A1 (en) 2015-05-11 2018-06-14 Yeda Research And Development Co., Ltd. Citrin inhibitors for the treatment of cancer
WO2016185457A1 (en) 2015-05-19 2016-11-24 Yeda Research And Development Co. Ltd. Methods of promoting lymphangiogenesis
NL2014935B1 (en) 2015-06-08 2017-02-03 Applied Immune Tech Ltd T cell receptor like antibodies having fine specificity.
WO2016205728A1 (en) 2015-06-17 2016-12-22 Massachusetts Institute Of Technology Crispr mediated recording of cellular events
WO2016205745A2 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Cell sorting
WO2016205749A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
CA3012631A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
WO2016203482A2 (en) 2015-06-19 2016-12-22 Opko Biologics Ltd. Long-acting coagulation factors and methods of producing same
BR112017027870A2 (pt) 2015-06-24 2018-08-28 Janssen Pharmaceutica Nv anticorpos e fragmentos anti-vista
US10287338B2 (en) 2015-07-10 2019-05-14 Miran NERSISSIAN Factor VIII protein compositions and methods of treating of hemophilia A
JP2018528763A (ja) 2015-07-31 2018-10-04 リサーチ インスティチュート アット ネイションワイド チルドレンズ ホスピタル バイオフィルムの除去のためのペプチドおよび抗体
WO2017024317A2 (en) 2015-08-06 2017-02-09 Dana-Farber Cancer Institute, Inc. Methods to induce targeted protein degradation through bifunctional molecules
WO2017025963A1 (en) 2015-08-10 2017-02-16 The Medical Research, Infrastructure and Health Services Fund of the Tel Aviv Medical Center Methods and pharmaceutical compositions for improving wound healing using cd24
KR20180042412A (ko) 2015-09-02 2018-04-25 이뮤텝 에스.에이.에스. 항-lag-3 항체
EP3365027B1 (en) 2015-10-14 2022-03-30 Research Institute at Nationwide Children's Hospital Hu specific antibodies and their use in inhibiting biofilm
US20170211142A1 (en) 2015-10-22 2017-07-27 The Broad Institute, Inc. Novel crispr enzymes and systems
EP3365357B1 (en) 2015-10-23 2024-02-14 President and Fellows of Harvard College Evolved cas9 proteins for gene editing
US20210106661A1 (en) 2015-10-29 2021-04-15 Dana-Farber Cancer Institute, Inc. Methods for identification, assessment, prevention, and treatment of metabolic disorders using pm20d1 and n-lipidated amino acids
IL289849B2 (en) 2015-11-10 2024-01-01 Nat Inst Biotechnology Negev Ltd Means and methods for reducing the tumorigenicity of cancer stem cells
US20190233814A1 (en) 2015-12-18 2019-08-01 The Broad Institute, Inc. Novel crispr enzymes and systems
US10465003B2 (en) 2016-02-05 2019-11-05 Janssen Biotech, Inc. Anti-TNF antibodies, compositions, methods and use for the treatment or prevention of type 1 diabetes
US10899836B2 (en) 2016-02-12 2021-01-26 Janssen Pharmaceutica Nv Method of identifying anti-VISTA antibodies
WO2017138008A2 (en) 2016-02-14 2017-08-17 Yeda Research And Development Co. Ltd. Methods of modulating protein exocytosis and uses of same in therapy
EP3436477A2 (en) 2016-03-29 2019-02-06 Janssen Biotech, Inc. Method of treating psoriasis with increased interval dosing of anti-il12 and/or -23 antibody
EP3436076A1 (en) 2016-03-30 2019-02-06 Regentis Biomaterials Ltd. Treatments utilizing a polymer-protein conjugate
WO2017175058A1 (en) 2016-04-07 2017-10-12 Janssen Pharmaceutica Nv Anti-vista antibodies and fragments, uses thereof, and methods of identifying same
CA3020848A1 (en) 2016-04-15 2017-10-19 Janssen Pharmaceuticals, Inc. Anti-human vista antibodies and use thereof
CA3026112A1 (en) 2016-04-19 2017-10-26 The Broad Institute, Inc. Cpf1 complexes with reduced indel activity
EP3445848A1 (en) 2016-04-19 2019-02-27 The Broad Institute, Inc. Novel crispr enzymes and systems
CN109790551A (zh) 2016-06-16 2019-05-21 奥斯陆大学医院Hf 改进的基因编辑
JP7267013B2 (ja) 2016-06-17 2023-05-01 ザ・ブロード・インスティテュート・インコーポレイテッド Ｖｉ型ｃｒｉｓｐｒオルソログ及び系
WO2018005873A1 (en) 2016-06-29 2018-01-04 The Broad Institute Inc. Crispr-cas systems having destabilization domain
MX2019000251A (es) 2016-07-05 2019-10-09 Univ Johns Hopkins Composiciones y metodos que comprenden mejoras de los arn guias de crispr usando el promotor h1.
HUE064463T2 (hu) 2016-07-11 2024-03-28 Opko Biologics Ltd Hosszantartó hatású VII. koagulációs faktor és az elõállítására vonatkozó eljárások
WO2018011803A1 (en) 2016-07-11 2018-01-18 The National Institute for Biotechnology in the Negev Ltd. Fusion proteins with extended serum half life
WO2018013720A1 (en) 2016-07-12 2018-01-18 Washington University Incorporation of internal polya-encoded poly-lysine sequence tags and their variations for the tunable control of protein synthesis in bacterial and eukaryotic cells
AU2017306676B2 (en) 2016-08-03 2024-02-22 President And Fellows Of Harvard College Adenosine nucleobase editors and uses thereof
AU2017308889B2 (en) 2016-08-09 2023-11-09 President And Fellows Of Harvard College Programmable Cas9-recombinase fusion proteins and uses thereof
CN110312799A (zh) 2016-08-17 2019-10-08 博德研究所 新型crispr酶和系统
US11352647B2 (en) 2016-08-17 2022-06-07 The Broad Institute, Inc. Crispr enzymes and systems
US11542509B2 (en) 2016-08-24 2023-01-03 President And Fellows Of Harvard College Incorporation of unnatural amino acids into proteins using base editing
WO2018047154A1 (en) 2016-09-07 2018-03-15 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Anti-nkp46 antibodies and therapeutic use of same
WO2018057618A1 (en) 2016-09-20 2018-03-29 Dana-Farber Cancer Institute, Inc. Compositions and methods for identification, assessment, prevention, and treatment of aml using usp10 biomarkers and modulators
EP3519049A4 (en) 2016-09-30 2020-05-27 Janssen Biotech, Inc. SAFE AND EFFICIENT METHOD FOR TREATING PSORIASIS WITH ANTI-IL23-SPECIFIC ANTIBODY
BR112019006710A2 (pt) 2016-10-03 2019-06-25 Abbott Lab métodos aprimorados para avaliação do estado da uch-l1 em amostras de pacientes
SG11201903089RA (en) 2016-10-14 2019-05-30 Harvard College Aav delivery of nucleobase editors
WO2018074979A1 (en) 2016-10-17 2018-04-26 Nanyang Technological University Truncated crispr-cas proteins for dna targeting
WO2018093841A1 (en) 2016-11-16 2018-05-24 Janssen Biotech, Inc. Method of treating psoriasis with anti-il-23 specific antibody
US11542508B2 (en) 2016-11-28 2023-01-03 Yeda Research And Development Co. Ltd. Isolated polynucleotides and polypeptides and methods of using same for expressing an expression product of interest
WO2018119359A1 (en) 2016-12-23 2018-06-28 President And Fellows Of Harvard College Editing of ccr5 receptor gene to protect against hiv infection
AU2018206560A1 (en) 2017-01-04 2019-07-18 Research Institute At Nationwide Children's Hospital Antibody fragments for the treatment of biofilm-related disorders
WO2018129078A1 (en) 2017-01-04 2018-07-12 Research Institute At Nationwide Children's Hospital Dnabii vaccines and antibodies with enhanced activity
JP7194324B2 (ja) 2017-01-05 2022-12-22 カール メディカル リミテッド ＳＩＲＰα－４１ＢＢＬ融合タンパク質およびその使用方法
EP3565579B9 (en) 2017-01-05 2023-10-04 KAHR Medical Ltd. A pd1-41bbl fusion protein and methods of use thereof
EP3574012A1 (en) 2017-01-27 2019-12-04 Memorial Sloan Kettering Cancer Center Bispecific her2 and cd3 binding molecules
CN110234351A (zh) 2017-01-30 2019-09-13 詹森生物科技公司 用于治疗活动性银屑病关节炎的抗tnf抗体、组合物和方法
CN110418652A (zh) 2017-02-07 2019-11-05 詹森生物科技公司 用于治疗活动性强直性脊柱炎的抗tnf抗体、组合物和方法
WO2018165504A1 (en) 2017-03-09 2018-09-13 President And Fellows Of Harvard College Suppression of pain by gene editing
US11542496B2 (en) 2017-03-10 2023-01-03 President And Fellows Of Harvard College Cytosine to guanine base editor
JP2020513808A (ja) 2017-03-15 2020-05-21 リサーチ インスティチュート アット ネイションワイド チルドレンズ ホスピタル 付随する炎症のない細菌バイオフィルムの破壊のための組成物および方法
KR102185464B1 (ko) 2017-03-15 2020-12-03 매사추세츠 인스티튜트 오브 테크놀로지 신규 cas13b 오르소로그 crispr 효소 및 시스템
IL306092A (en) 2017-03-23 2023-11-01 Harvard College Nucleic base editors that include nucleic acid programmable DNA binding proteins
US11016092B2 (en) 2017-03-23 2021-05-25 Abbott Laboratories Methods for aiding in the diagnosis and determination of the extent of traumatic brain injury in a human subject using the early biomarker ubiquitin carboxy-terminal hydrolase L1
US11840711B2 (en) 2017-04-12 2023-12-12 The Broad Institute, Inc. Type VI CRISPR orthologs and systems
WO2018191531A1 (en) 2017-04-15 2018-10-18 Abbott Laboratories Methods for aiding in the hyperacute diagnosis and determination of traumatic brain injury in a human subject using early biomarkers
BR112019022476A2 (pt) 2017-04-28 2020-05-12 Abbott Laboratories Métodos para o auxílio no diagnóstico e determinação hiperagudos de lesão cerebral traumática usando biomarcadores iniciais em pelo menos duas amostras a partir do mesmo ser humano
US10865238B1 (en) 2017-05-05 2020-12-15 Duke University Complement factor H antibodies
SG11201911256UA (en) 2017-05-08 2020-01-30 Orgenesis Ltd Transdifferentiated cell populations and methods of use thereof
US20210278416A1 (en) 2017-05-09 2021-09-09 The Broad Institute, Inc. Gut microbiome function predicts response to anti-integrin biologic therapy in inflammatory bowel diseases
WO2018209320A1 (en) 2017-05-12 2018-11-15 President And Fellows Of Harvard College Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation
CA3078725A1 (en) 2017-05-25 2018-11-29 Abbott Laboratories Methods for aiding in the determination of whether to perform imaging on a human subject who has sustained or may have sustained an injury to the head using early biomarkers
BR112019025313A2 (pt) 2017-05-30 2020-06-23 Abbott Laboratories Métodos para auxílio no diagnóstico e avaliação de uma lesão cerebral traumática leve em um indivíduo humano usando troponina cardíaca i
EP3634496A4 (en) 2017-06-06 2021-09-08 Dana-Farber Cancer Institute, Inc. METHOD FOR RISING AWARENESS IN CANCER CELLS AGAINST T-CELL-MEDIATED KILLING BY MODULATING MOLECULAR SIGNAL PATHS
AU2018290843A1 (en) 2017-06-26 2020-01-16 Massachusetts Institute Of Technology CRISPR/Cas-adenine deaminase based compositions, systems, and methods for targeted nucleic acid editing
EP3649474A1 (en) 2017-07-03 2020-05-13 Abbott Laboratories Improved methods for measuring ubiquitin carboxy-terminal hydrolase l1 levels in blood
JP2020534795A (ja) 2017-07-28 2020-12-03 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 ファージによって支援される連続的進化（ｐａｃｅ）を用いて塩基編集因子を進化させるための方法および組成物
WO2019139645A2 (en) 2017-08-30 2019-07-18 President And Fellows Of Harvard College High efficiency base editors comprising gam
CN111511388A (zh) 2017-09-21 2020-08-07 博德研究所 用于靶向核酸编辑的系统、方法和组合物
TW201922780A (zh) 2017-09-25 2019-06-16 美商健生生物科技公司 以抗ｉｌ１２／ｉｌ２３抗體治療狼瘡之安全且有效之方法
US11795443B2 (en) 2017-10-16 2023-10-24 The Broad Institute, Inc. Uses of adenosine base editors
WO2019089803A1 (en) 2017-10-31 2019-05-09 The Broad Institute, Inc. Methods and compositions for studying cell evolution
CA3082365A1 (en) 2017-11-09 2019-05-16 Pinteon Therapeutics Inc. Methods and compositions for the generation and use of humanized conformation-specific phosphorylated tau antibodies
EP3710039A4 (en) 2017-11-13 2021-08-04 The Broad Institute, Inc. METHODS AND COMPOSITIONS FOR CANCER TREATMENT BY TARGETING THE CLEC2D-KLRB1 PATH
US11016105B2 (en) 2017-12-09 2021-05-25 Abbott Laboratories Methods for aiding in diagnosing and evaluating a traumatic brain injury in a human subject using a combination of GFAP and UCH-L1
EP3721233A2 (en) 2017-12-09 2020-10-14 Abbott Laboratories Methods for aiding in the diagnosis and evaluation of a subject who has sustained an orthopedic injury and that has or may have sustained an injury to the head, such as mild traumatic brain injury (tbi), using glial fibrillary acidic protein (gfap) and/or ubiquitin carboxy-terminal hydrolase l1 (uch-l1)
EP3732489A1 (en) 2017-12-29 2020-11-04 Abbott Laboratories Novel biomarkers and methods for diagnosing and evaluating traumatic brain injury
WO2019150309A1 (en) 2018-02-02 2019-08-08 Hammack Scott Modulators of gpr68 and uses thereof for treating and preventing diseases
KR20200129125A (ko) 2018-03-05 2020-11-17 얀센 바이오테크 인코포레이티드 항-il23 특이적 항체로 크론병을 치료하는 방법
EP3765523A1 (en) 2018-03-12 2021-01-20 Memorial Sloan Kettering Cancer Center Bispecific binding agents and uses thereof
AR117566A1 (es) 2018-04-02 2021-08-18 Bristol Myers Squibb Co Anticuerpos anti-trem-1 y sus usos
US10968257B2 (en) 2018-04-03 2021-04-06 The Broad Institute, Inc. Target recognition motifs and uses thereof
WO2019209807A1 (en) 2018-04-23 2019-10-31 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Compositions and methods for modulating endoplasmic reticulum-associated degradation
WO2019211842A1 (en) 2018-04-30 2019-11-07 Opko Biologics Ltd. Long-acting human growth hormone-antagonists and methods of producing the same
US20210239700A1 (en) 2018-05-04 2021-08-05 Abbott Laboratories Hbv diagnostic, prognostic, and therapeutic methods and products
MA52590A (fr) 2018-05-11 2021-03-17 Janssen Biotech Inc Méthodes de traitement de la dépression à l'aide d'anticorps il-23
EP3797160A1 (en) 2018-05-23 2021-03-31 The Broad Institute Inc. Base editors and uses thereof
WO2019244107A1 (en) 2018-06-21 2019-12-26 Daiichi Sankyo Company, Limited Compositions including cd3 antigen binding fragments and uses thereof
US11873322B2 (en) 2018-06-25 2024-01-16 Yeda Research And Development Co. Ltd. Systems and methods for increasing efficiency of genome editing
CN112543773A (zh) 2018-07-11 2021-03-23 卡尔医学有限公司 SIRPα-4-1BBL变体融合蛋白及其使用方法
CN112789504A (zh) 2018-07-13 2021-05-11 瓦克特诊断有限责任公司 使用重组疟疾蛋白var2csa分离胎儿来源的循环细胞
JP2021530697A (ja) 2018-07-18 2021-11-11 ヤンセン バイオテツク，インコーポレーテツド 抗ｉｌ２３特異的抗体で治療した後の持続応答予測因子
WO2020033601A1 (en) 2018-08-07 2020-02-13 The Broad Institute, Inc. Novel cas12b enzymes and systems
WO2020041380A1 (en) 2018-08-20 2020-02-27 The Broad Institute, Inc. Methods and compositions for optochemical control of crispr-cas9
US11548938B2 (en) 2018-08-21 2023-01-10 Quidel Corporation DbpA antibodies and uses thereof
KR20230148273A (ko) 2018-09-24 2023-10-24 얀센 바이오테크 인코포레이티드 항-il12/il23 항체로 궤양성 결장염을 치료하는 안전하고 효과적인 방법
US20210338783A1 (en) 2018-10-05 2021-11-04 Research Institute At Nationwide Children's Hospital Compositions and methods for enzymatic disruption of bacterial biofilms
US20210363509A1 (en) 2018-10-22 2021-11-25 University Of Rochester Genome Editing by Directed Non-Homologous DNA Insertion Using a Retroviral Integrase-Cas9 Fusion Protein
BR112021008200A2 (pt) 2018-10-29 2021-12-14 Spin Therapeutics Llc Composições e métodos para distúrbios de alfa-1-antitripsina
WO2020102659A1 (en) 2018-11-15 2020-05-22 The Broad Institute, Inc. G-to-t base editors and uses thereof
MA55149A (fr) 2018-11-20 2021-09-29 Janssen Biotech Inc Procédé sûr et efficace de traitement du psoriasis avec un anticorps spécifique anti-il-23
US20200197517A1 (en) 2018-12-18 2020-06-25 Janssen Biotech, Inc. Safe and Effective Method of Treating Lupus with Anti-IL12/IL23 Antibody
MX2021008487A (es) 2019-01-14 2021-11-12 Univ Rochester Escisión y poliadenilación del arn nuclear dirigido con crispr-cas.
JP2022518208A (ja) 2019-01-15 2022-03-14 ヤンセン バイオテツク，インコーポレーテツド 若年性特発性関節炎の治療のための抗ｔｎｆ抗体、組成物、及び方法
WO2020152544A1 (en) 2019-01-23 2020-07-30 Janssen Biotech, Inc. Anti-tnf antibody compositions for use in methods for the treatment of psoriatic arthritis
WO2020181180A1 (en) 2019-03-06 2020-09-10 The Broad Institute, Inc. A:t to c:g base editors and uses thereof
WO2020181202A1 (en) 2019-03-06 2020-09-10 The Broad Institute, Inc. A:t to t:a base editing through adenine deamination and oxidation
WO2020181193A1 (en) 2019-03-06 2020-09-10 The Broad Institute, Inc. T:a to a:t base editing through adenosine methylation
WO2020181178A1 (en) 2019-03-06 2020-09-10 The Broad Institute, Inc. T:a to a:t base editing through thymine alkylation
WO2020181195A1 (en) 2019-03-06 2020-09-10 The Broad Institute, Inc. T:a to a:t base editing through adenine excision
CN113825765A (zh) 2019-03-14 2021-12-21 詹森生物科技公司 用于制备抗il12/il23抗体组合物的制造方法
MA55283A (fr) 2019-03-14 2022-01-19 Janssen Biotech Inc Procédés de production de compositions d'anticorps anti-tnf
GB201903520D0 (en) 2019-03-14 2019-05-01 Tropic Biosciences Uk Ltd Modifying the specificity of non-coding rna molecules for silencing genes in eukaryotic cells
CA3133388A1 (en) 2019-03-14 2020-09-17 Janssen Biotech, Inc. Methods for producing anti-tnf antibody compositions
KR20210142002A (ko) 2019-03-14 2021-11-23 얀센 바이오테크 인코포레이티드 항-tnf 항체 조성물을 생성하기 위한 제조 방법
GB201903519D0 (en) 2019-03-14 2019-05-01 Tropic Biosciences Uk Ltd Introducing silencing activity to dysfunctional rna molecules and modifying their specificity against a gene of interest
WO2020191102A1 (en) 2019-03-18 2020-09-24 The Broad Institute, Inc. Type vii crispr proteins and systems
EA202192459A1 (ru) 2019-03-18 2021-11-25 Янссен Байотек, Инк. Способ лечения псориаза антителом к il12/il23 у субъектов детского возраста
JP2022526908A (ja) 2019-03-19 2022-05-27 ザ ブロード インスティテュート，インコーポレーテッド 編集ヌクレオチド配列を編集するための方法および組成物
IL265486A (en) 2019-03-19 2020-09-30 Yeda Res & Dev Bistable type ii opsins and uses thereof
WO2020214842A1 (en) 2019-04-17 2020-10-22 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
US20220143131A1 (en) 2019-05-16 2022-05-12 Ceva Sante Animale Compositions and Methods for increasing Reproduction Performance in Non Human Mammals Using Recombinant Luteinizing Hormone
US20220220469A1 (en) 2019-05-20 2022-07-14 The Broad Institute, Inc. Non-class i multi-component nucleic acid targeting systems
US11780911B2 (en) 2019-05-23 2023-10-10 Janssen Biotech, Inc. Method of treating inflammatory bowel disease with a combination therapy of antibodies to IL-23 and TNF alpha
MX2021014882A (es) 2019-06-03 2022-03-25 Janssen Biotech Inc Anticuerpos anti-tnf, composiciones y métodos para el tratamiento de la espondilitis anquilosante activa.
CN113939531A (zh) 2019-06-03 2022-01-14 詹森生物科技公司 用于治疗银屑病关节炎的抗tnf抗体组合物和方法
CN114222760A (zh) 2019-06-26 2022-03-22 葛兰素史密斯克莱知识产权发展有限公司 Il1rap结合蛋白
AU2020311897A1 (en) 2019-07-08 2022-02-03 Research Institute At Nationwide Children's Hospital Antibody compositions for disrupting biofilms
CA3146248A1 (en) 2019-07-11 2021-01-14 Kahr Medical Ltd. Heterodimers and methods of use thereof
WO2021005604A1 (en) 2019-07-11 2021-01-14 Opko Biologics Ltd. Long-acting igf-1 or igf-1 variants and methods of producing same
EP4004206A1 (en) 2019-07-23 2022-06-01 University of Rochester Targeted rna cleavage with crispr-cas
WO2021030666A1 (en) 2019-08-15 2021-02-18 The Broad Institute, Inc. Base editing by transglycosylation
WO2021028752A1 (en) 2019-08-15 2021-02-18 Janssen Biotech, Inc. Anti-tfn antibodies for treating type i diabetes
EP4028064A1 (en) 2019-09-12 2022-07-20 The Broad Institute, Inc. Engineered adeno-associated virus capsids
WO2021091539A1 (en) 2019-11-05 2021-05-14 Versiti Blood Research Institute Foundation, Inc. A murine model of fetal/neonatal alloimmune thrombocytopenia
US11266129B2 (en) 2019-11-05 2022-03-08 Versiti Blood Research Institute Foundation, Inc. Murine model of fetal/neonatal alloimmune thrombocytopenia
AU2020384953A1 (en) 2019-11-11 2022-06-23 Ibi-Ag Innovative Bio Insecticides Ltd. Insect control nanobodies and uses thereof
WO2021108717A2 (en) 2019-11-26 2021-06-03 The Broad Institute, Inc Systems and methods for evaluating cas9-independent off-target editing of nucleic acids
JP2023507083A (ja) 2019-12-19 2023-02-21 クイデル コーポレーション モノクローナル抗体融合物
IL271656A (en) 2019-12-22 2021-06-30 Yeda Res & Dev System and methods for identifying cells that have undergone genome editing
EP4100519A2 (en) 2020-02-05 2022-12-14 The Broad Institute, Inc. Adenine base editors and uses thereof
WO2021195519A1 (en) 2020-03-27 2021-09-30 University Of Rochester Targeted destruction of viral rna by crispr-cas13
EP4127170A1 (en) 2020-03-27 2023-02-08 University of Rochester Crispr-cas13 crrna arrays
EP4136459A1 (en) 2020-04-13 2023-02-22 Abbott Laboratories Methods, complexes and kits for detecting or determining an amount of a ss-coronavirus antibody in a sample
AU2021267940A1 (en) 2020-05-08 2022-12-08 President And Fellows Of Harvard College Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence
JP2023534464A (ja) 2020-07-15 2023-08-09 ユニバーシティ オブ ロチェスター ｄＣａｓ１３－ＲＮａｓｅ融合タンパク質による標的ＲＮＡの切断
EP4182458A2 (en) 2020-07-20 2023-05-24 Dana-Farber Cancer Institute, Inc. Methods and compositions for treatment and prevention of coronavirus infection
KR20230042301A (ko) 2020-08-04 2023-03-28 애벗트 라보라토리이즈 샘플에서 sars-cov-2 단백질을 검출하기 위한 개선된 방법 및 키트
WO2022034374A2 (en) 2020-08-11 2022-02-17 University Of Oslo Improved gene editing
IL278401A (en) 2020-10-29 2022-05-01 Yeda Res & Dev Polynucleotides for editing RNA and a method for using them
WO2023102384A1 (en) 2021-11-30 2023-06-08 Abbott Laboratories Use of one or more biomarkers to determine traumatic brain injury (tbi) in a subject having received a head computerized tomography scan that is negative for a tbi
WO2022119841A1 (en) 2020-12-01 2022-06-09 Abbott Laboratories Use of one or more biomarkers to determine traumatic brain injury (tbi) in a subject having received a head computerized tomography scan that is negative for a tbi
EP4271998A1 (en) 2020-12-30 2023-11-08 Abbott Laboratories Methods for determining sars-cov-2 antigen and anti-sars-cov-2 antibody in a sample
JP2024503658A (ja) 2021-01-13 2024-01-26 メモリアル スローン－ケタリング キャンサー センター 抗ｄｌｌ３抗体－薬物コンジュゲート
WO2022153194A1 (en) 2021-01-13 2022-07-21 Memorial Sloan Kettering Cancer Center Antibody-pyrrolobenzodiazepine derivative conjugate
BR112023018353A2 (pt) 2021-03-12 2024-02-06 Janssen Biotech Inc Método seguro e eficaz para tratamento da artrite psoriática com anticorpo específico anti-il23
IL305836A (en) 2021-03-12 2023-11-01 Janssen Biotech Inc A method for treating psoriatic arthritis patients with insufficient response to TNF therapy with a specific anti-IL23 antibody
KR20240000580A (ko) 2021-04-23 2024-01-02 유니버시티 오브 로체스터 레트로바이러스 인테그라제-Cas 융합 단백질을 이용한 직접 비상동 DNA 삽입에 의한 게놈 편집 및 치료 방법
US20220381796A1 (en) 2021-05-18 2022-12-01 Abbott Laboratories Methods of evaluating brain injury in a pediatric subject
CA3220618A1 (en) 2021-05-20 2022-11-24 Janssen Biotech, Inc. Method of treating inflammatory bowel disease with a combination therapy of antibodies to il-23 and tnf alpha
WO2022261183A2 (en) 2021-06-08 2022-12-15 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating and/or identifying an agent for treating intestinal cancers
WO2022261509A1 (en) 2021-06-11 2022-12-15 The Broad Institute, Inc. Improved cytosine to guanine base editors
EP4356129A1 (en) 2021-06-14 2024-04-24 Abbott Laboratories Methods of diagnosing or aiding in diagnosis of brain injury caused by acoustic energy, electromagnetic energy, an over pressurization wave, and/or blast wind
AU2022306973A1 (en) 2021-07-09 2024-02-22 Janssen Biotech, Inc. Manufacturing methods for producing anti-il12/il23 antibody compositions
WO2023281462A1 (en) 2021-07-09 2023-01-12 Janssen Biotech, Inc. Manufacturing methods for producing anti-tnf antibody compositions
CN117957251A (zh) 2021-07-09 2024-04-30 詹森生物科技公司 用于制备抗tnf抗体组合物的制造方法
WO2023004367A2 (en) 2021-07-20 2023-01-26 The Broad Institute, Inc. Engineered targeting compositions for endothelial cells of the central nervous system vasculature and methods of use thereof
WO2023028186A1 (en) 2021-08-27 2023-03-02 Abbott Laboratories Methods for detecting immunoglobulin g, subclass 4 (igg4) in a biological sample
CA3230038A1 (en) 2021-08-31 2023-03-09 Hongwei Zhang Methods and systems of diagnosing brain injury
AU2022354059A1 (en) 2021-09-30 2024-03-28 Abbott Laboratories Methods and systems of diagnosing brain injury
WO2023073615A1 (en) 2021-10-29 2023-05-04 Janssen Biotech, Inc. Methods of treating crohn's disease with anti-il23 specific antibody
US20230151087A1 (en) 2021-11-15 2023-05-18 Janssen Biotech, Inc. Methods of Treating Crohn's Disease with Anti-IL23 Specific Antibody
WO2023095000A1 (en) 2021-11-23 2023-06-01 Janssen Biotech, Inc. Method of treating ulcerative colitis with anti-il23 specific antibody
WO2023097119A2 (en) 2021-11-29 2023-06-01 Dana-Farber Cancer Institute, Inc. Methods and compositions to modulate riok2
WO2023114978A1 (en) 2021-12-17 2023-06-22 Abbott Laboratories Systems and methods for determining uch-l1, gfap, and other biomarkers in blood samples
US20230213536A1 (en) 2021-12-28 2023-07-06 Abbott Laboratories Use of biomarkers to determine sub-acute traumatic brain injury (tbi) in a subject having received a head computerized tomography (ct) scan that is negative for a tbi or no head ct scan
WO2023150652A1 (en) 2022-02-04 2023-08-10 Abbott Laboratories Lateral flow methods, assays, and devices for detecting the presence or measuring the amount of ubiquitin carboxy-terminal hydrolase l1 and/or glial fibrillary acidic protein in a sample
US20230312703A1 (en) 2022-03-30 2023-10-05 Janssen Biotech, Inc. Method of Treating Psoriasis with IL-23 Specific Antibody
WO2023196802A1 (en) 2022-04-04 2023-10-12 The Broad Institute, Inc. Cas9 variants having non-canonical pam specificities and uses thereof
US20230374122A1 (en) 2022-05-18 2023-11-23 Janssen Biotech, Inc. Method for Evaluating and Treating Psoriatic Arthritis with IL23 Antibody
WO2023240137A1 (en) 2022-06-08 2023-12-14 The Board Institute, Inc. Evolved cas14a1 variants, compositions, and methods of making and using same in genome editing
WO2024006876A1 (en) 2022-06-29 2024-01-04 Abbott Laboratories Magnetic point-of-care systems and assays for determining gfap in biological samples
WO2024016003A2 (en) 2022-07-14 2024-01-18 The Broad Institute, Inc. Aav capsids that enable cns-wide gene delivery through interactions with the transferrin receptor
WO2024040083A1 (en) 2022-08-16 2024-02-22 The Broad Institute, Inc. Evolved cytosine deaminases and methods of editing dna using same
WO2024047587A1 (en) 2022-08-31 2024-03-07 Regel Therapeutics, Inc. Cas-phi compositions and methods of use
WO2024059708A1 (en) 2022-09-15 2024-03-21 Abbott Laboratories Biomarkers and methods for differentiating between mild and supermild traumatic brain injury
WO2024059692A1 (en) 2022-09-15 2024-03-21 Abbott Laboratories Hbv diagnostic, prognostic, and therapeutic methods and products
WO2024081245A1 (en) 2022-10-10 2024-04-18 Therapeutics By Design, LLC Tissue differentiation factor related polypeptides (tdfrps) for the treatment of myocardial injury

Family Cites Families (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2239208B1 (ja) * 1973-07-31 1977-10-07 Nestle Sa
US4229342A (en) * 1977-05-18 1980-10-21 Rhone-Poulenc Industries Process for extracting proteins from milk using silica and anion exchange resins
US4396601A (en) * 1980-03-26 1983-08-02 The Regents Of The University Of Calif. Gene transfer in intact mammals
US4376072A (en) * 1980-11-17 1983-03-08 New Zealand Milk Products, Inc. Method of producing milk protein isolates and milk protein/vegetable protein isolates and compositions of same
IE56716B1 (en) * 1983-01-19 1991-11-20 Genentech Inc Method for producing human tpa and expression vectors therefor
US4462932A (en) * 1983-06-22 1984-07-31 Purdue Research Foundation Isolation of native casein by cryodestabilization
US4736866A (en) * 1984-06-22 1988-04-12 President And Fellows Of Harvard College Transgenic non-human mammals
DE3432718C1 (de) * 1984-09-06 1986-05-22 Biotest Pharma GmbH, 6000 Frankfurt Verfahren zur Herstellung einer Loesung von Milch- und/oder Kolostralimmunglobulinen
DE122007000007I2 (de) * 1986-04-09 2010-12-30 Genzyme Corp Genetisch transformierte Tiere, die ein gewünschtes Protein in Milch absondern
DE3752347T2 (de) * 1986-05-20 2002-09-26 Gen Hospital Corp Verfahren zur pharmakokinetischen Studie der Insulin-Expression mit nicht-menschlichem Transgen-Säugetier
GB8615942D0 (en) * 1986-06-30 1986-08-06 Animal & Food Research Council Peptide production
WO1988001648A1 (en) * 1986-08-28 1988-03-10 Immunex Corporation Expression of heterologous proteins by transgenic lactating mammals
EP0832981A1 (en) * 1987-02-17 1998-04-01 Pharming B.V. DNA sequences to target proteins to the mammary gland for efficient secretion

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
Ｃｅｌｌ，Ｏ Ｖｏｌ．４９（１９８７．Ｍａｙ）ｐ４６５−４７５
Ｊｏｕｒｎａｌ ｏｆ Ｃｅｌｌ Ｂｉｏｌｏｇｙ，Ｖｏｌ．１０３，Ｎｏ．５，Ｐａｒｔ．２（１９８６）ｐ．３１３ａ
Ｊｏｕｒｎａｌ ｏｆ Ｃｅｌｕｌａｒ Ｂｉｏｃｈｅｍｉｓｔｒｙ，Ｓｕｐｐｌ，１１Ｃ（１９８７．Ａｐｒ）ｐ．１５３
Ｐｒｏｃ．Ｎａｆｌ．Ａｃａｄ，Ｓｃｉ，ＵＳＡ，Ｖｏｌ．８４（１９８７．Ｍａｒ）ｐ１２９９−１３０３
Ｔｒｅｎｄｓ ｉｎ Ｂｉｏｆｅｃｈｎｏｌｏｇｙ，Ｖｏ５．Ｎｏ．１（１９８７．Ｊａｎ）ｐ２０−２４

Also Published As

Publication number Publication date
DE3854555T2 (de) 1996-04-04
EP0347431A4 (en) 1991-10-16
EP0347431A1 (en) 1989-12-27
WO1988010118A1 (en) 1988-12-29
ATE128625T1 (de) 1995-10-15
JPH02500798A (ja) 1990-03-22
US4873316A (en) 1989-10-10
US20040250300A1 (en) 2004-12-09
DE3854555D1 (de) 1995-11-09
EP0347431B1 (en) 1995-10-04
US20020129387A1 (en) 2002-09-12

Similar Documents

Publication Publication Date Title
JP2898003B2 (ja) ミルクにおける蛋白の発現
US5750172A (en) Transgenic non human mammal milk
Shani et al. Expression of human serum albumin in the milk of transgenic mice
Devinoy et al. High level production of human growth hormone in the milk of transgenic mice: the upstream region of the rabbit whey acidic protein (WAP) gene targets transgene expression to the mammary gland
JP3670003B2 (ja) ウシ種による組み換えポリペプチドの製造及びトランスジェニック法
AU663101B2 (en) DNA sequence encoding bovine alpha-lactalbumin and methods of use
CA2286366C (en) Transgenic expression in genital tract and sexual accessory glands
US5648243A (en) Human serum albumin expression construct
US20130131317A1 (en) Expression of secreted human alpha-fetoprotein in transgenic animals
JPH04505710A (ja) ポリペプチドの改良された発現
EP0771874B1 (en) Transgenic protein production
JP2000300115A (ja) 非ヒト哺乳動物のミルク
Besenfelder et al. Generation and application of transgenic rabbits
JPH11253097A (ja) 非ヒト哺乳動物のミルク
Lee et al. Integration and Expression of Goat ${\beta}-Casein/hGH $ Hybrid Gene in a Transgenic Goat
CA1316851C (en) Transgenic animals incorporating exogenous grf genes
US20050043530A1 (en) Seminal vesicle tissue-specific promoters and uses thereof

Legal Events

Date Code Title Description
R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20090312

Year of fee payment: 10

EXPY Cancellation because of completion of term
FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20090312

Year of fee payment: 10