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公开(公告)号：WO1994024148A1
公开(公告)日：1994-10-27
申请号：PCT/US1994004069
申请日：1994-04-13
Applicant: WASHINGTON UNIVERSITY
Inventor： WASHINGTON UNIVERSITY , BOIME, Irving
IPC: C07K03/00
CPC classification number: C07K14/59 , A61K38/00 , C07K2319/75
Abstract: "Partial" and "complete" CTP units are used to modify biologically active proteins and peptides to alter their clearance patterns. "Complete" CTP units have the amino acid sequence found at positions 112-118 to position 145 of the beta -subunit of human chorionic gonadotropin; "partial" CTP units are missing at least one amino acid in the region of position 118-145 inclusive. Variants of these CTP units contain 1-5 conservative amino acid substitutions which do not destroy activity. Suitable peptides or proteins which may be modified in this manner include various hormones and cytokines.
Abstract translation: “部分”和“完整”CTP单位用于修饰生物活性蛋白质和肽以改变其清除模式。 “完全”CTP单元具有在人绒毛膜促性腺激素的β亚基的位置112-118至位置145处发现的氨基酸序列; “部分”CTP单位在118-145位置区域中缺少至少一个氨基酸。 这些CTP单元的变体含有1-5个保守氨基酸取代，其不破坏活性。 可以以这种方式修饰的合适的肽或蛋白质包括各种激素和细胞因子。
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公开(公告)号：EP0461200A1
公开(公告)日：1991-12-18
申请号：EP90905115.0
申请日：1990-02-20
Applicant: WASHINGTON UNIVERSITY
Inventor： BOIME, Irving , MATZUK, Martin, M. , KEENE, Jeffrey, L.
CPC classification number: C07K14/59 , A61K38/00 , C07K2319/00 , C07K2319/75 , C07K2319/91
Abstract: L'invention concerne des formes natives et mutéines de recombinaison d'hormones de reproduction humaines présentant des configurations de glycosilation caractéristiques et influençant l'activité métabolique de la protéine. L'invention concerne également des formes mutantes de recombinaison de la sous-unité alpha humaine commune à FSH, LH, CG et TSH, permettant d'obtenir des hormones présentant également des configurations de glycosilation uniques. Elle concerne en outre des matières de recombinaison permettant de produire ces sous-unités séparément ou ensemble, afin d'obtenir des hormones hétérodimères complètes dont la configuration et l'activité de glycosilation sont régulées. Des formes modifiées de sous-unités bêta LH et FSH augmentant la vitesse de dimérisation et de secrétion des dimères ou de chaînes individuelles sont décrites.
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公开(公告)号：WO1996005224A1
公开(公告)日：1996-02-22
申请号：PCT/US1995009664
申请日：1995-08-01
Applicant: WASHINGTON UNIVERSITY
Inventor： WASHINGTON UNIVERSITY , BOIME, Irving
IPC: C07K14/59
CPC classification number: C07K14/59 , A61K38/00 , C07K14/575 , C07K2319/00
Abstract: Single-chain forms of the glycoprotein hormone quartet, at least some members of which are found in most vertebrates, are disclosed. In one embodiment of these single-chain forms, the alpha and beta subunits of the wild-type heterodimers or their variants are covalently linked, optionally through a linker moiety. A drug may further be included within the linker moiety to be targeted to receptors for these hormones. Some of the single-chain forms are agonists and others antagonists of the glycoprotein hormone activity. Another embodiment of the single-chain compounds of the invention comprises two beta subunits of the glycoprotein hormones, which beta subunits are the same or different. These "two- beta " forms are antagonists of glycoprotein hormone activity.
Abstract translation: 公开了在大多数脊椎动物中发现的至少一些成员的糖链蛋白激素四重奏的单链形式。 在这些单链形式的一个实施方案中，野生型异二聚体或其变体的α和β亚基任选地通过连接体部分共价连接。 接头部分中还可以包含药物以靶向这些激素的受体。 一些单链形式是激动剂和糖蛋白激素活性的其它拮抗剂。 本发明的单链化合物的另一个实施方案包含糖蛋白激素的两个β亚基，β亚单位是相同或不同的。 这些“双β”形式是糖蛋白激素活性的拮抗剂。
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公开(公告)号：WO1993021947A1
公开(公告)日：1993-11-11
申请号：PCT/US1993004051
申请日：1993-04-30
Applicant: WASHINGTON UNIVERSITY
Inventor： WASHINGTON UNIVERSITY , BOIME, Irving
IPC: A61K37/38
CPC classification number: C07K14/59
Abstract: Improved methods for recombinant production of human reproductive hormones are disclosed. These methods involve the use of animal-derived cells that contain regulated secretory granules as host cells for expression systems capable of expressing DNA encoding human reproductive hormones or their beta subunits.
Abstract translation: 公开了用于重组生产人生殖激素的改进方法。 这些方法涉及使用含有调节分泌颗粒的动物来源的细胞作为能够表达编码人生殖激素或其β亚基的DNA的表达系统的宿主细胞。
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公开(公告)号：WO1993006844A1
公开(公告)日：1993-04-15
申请号：PCT/US1992008424
申请日：1992-10-02
Applicant: WASHINGTON UNIVERSITY
Inventor： WASHINGTON UNIVERSITY , BOIME, Irving
IPC: A61K37/02
CPC classification number: C07K16/26 , A61K38/00 , C07K14/59 , C07K2319/00 , C07K2319/75 , Y10S930/11 , Y10S930/141
Abstract: The invention provides peptide and protein pharmaceuticals with extended half-lives. The modified peptides and proteins of the invention contain at least two tandem extensions at their C-terminus comprising the carboxy terminal portion of human chorionic gonadotropin. These "CTP units" consist essentially of the native HCG- beta sequence from position 112-118 to position 145 or conservative modifications thereof.
Abstract translation: 本发明提供具有延长半衰期的肽和蛋白质药物。 本发明的修饰的肽和蛋白质在其包含人绒毛膜促性腺激素的羧基末端的C末端含有至少两个串联延伸。 这些“CTP单元”基本上由位置112-118到位置145的天然HCG-β序列或其保守修饰组成。
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Patent Agency Ranking
公开(公告)号：WO2001081406A3
公开(公告)日：2001-11-01
申请号：PCT/US2001/013190
申请日：2001-04-24
Applicant: WASHINGTON UNIVERSITY
Inventor： BOIME, Irving
IPC: C07K14/59
Abstract: Glycosylated or nonglycosylated proteins of the formula FSHβ-(linker 1 ) n 1 -LHβ(1-X)-(linker 2 ) n 2 -α, wherein FSHß is a vertebrate follicle stimulating hormone β subunit or a variant thereof; LHβ(1-X) refers to a β subunit of a vertebrate luteinizing hormone containing positions 1-X where X is an integer of 114-121 or a variant thereof; each "linker" is a hydrophilic, flexible amino acid sequence containing 1-100 amino acid residue; each n is a 0 or 1; and α is the α subunit of a vertebrate glycoprotein hormone or a variant thereof are useful in protocols to enhance fertility in humans and in animals.
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公开(公告)号：WO1990009800A1
公开(公告)日：1990-09-07
申请号：PCT/US1990001037
申请日：1990-02-20
Applicant: WASHINGTON UNIVERSITY
Inventor： WASHINGTON UNIVERSITY , BOIME, Irving , MATZUK, Martin, M. , KEENE, Jeffrey, L.
IPC: C12P21/00
CPC classification number: C07K14/59 , A61K38/00 , C07K2319/00 , C07K2319/75 , C07K2319/91
Abstract: The invention provides recombinant native and mutein forms of human reproductive hormones with characteristic glycosylation patterns which are influential in the metabolic activity of the protein. The invention also provides recombinant mutant forms of the human alpha subunit common to FSH, LH, CG, and TSH, to obtain hormones which also have unique glycosylation patterns. Also provided are recombinant materials to produce these subunits separately or together to obtain complete heterodimeric hormones of regulated glycosylation pattern and activity. Modified forms of LH and FSH beta subunits which enhance the rate of dimerization and secretion of the dimers or individual chains are also disclosed.
Abstract translation: 本发明提供具有特征性糖基化模式的人类生殖激素的重组天然和突变蛋白形式，其在蛋白质的代谢活性中是有影响的。 本发明还提供FSH，LH，CG和TSH共同的人α亚基的重组突变体形式，以获得也具有独特糖基化模式的激素。 还提供了分别或一起产生这些亚单位以获得调节的糖基化模式和活性的完全异二聚体激素的重组材料。 还公开了增强二聚体或单链的二聚化和分泌速率的LH和FSHβ亚基的修饰形式。
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8.发明授权
公开(公告)号：EP1276765B1
公开(公告)日：2011-06-08
申请号：EP01928808.3
申请日：2001-04-24
Applicant: Washington University
Inventor： BOIME, Irving
CPC classification number: C07K14/59 , C07K14/575 , C07K2319/00
Abstract: Glycosylated or nonglycosylated proteins of the formula FSHβ-(linker1)n1-LHβ(1-X)-(linker2)n2-α, wherein FSHß is a vertebrate follicle stimulating hormone β subunit or a variant thereof; LHβ(1-X) refers to a β subunit of a vertebrate luteinizing hormone containing positions 1-X where X is an integer of 114-121 or a variant thereof; each 'linker' is a hydrophilic, flexible amino acid sequence containing 1-100 amino acid residue; each n is a 0 or 1; and α is the α subunit of a vertebrate glycoprotein hormone or a variant thereof are useful in protocols to enhance fertility in humans and in animals.
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公开(公告)号：EP1032688B1
公开(公告)日：2008-07-23
申请号：EP98956662.5
申请日：1998-11-09
Applicant: Washington University
Inventor： BOIME, Irving , BEN-MENAHEM, David
CPC classification number: C07K14/59 , A61K38/00 , C07K2319/00
Abstract: Single-chain agonists and/or antagonists of the glycoprotein hormones are disclosed. These proteins are of the formulae: (1) beta -(linker )m- alpha -(linker )n- beta ; or (2) beta -(linker )m- beta -(linker )n- alpha ; or (3) alpha -(linker )m- beta -(linker )n- beta , wherein each of beta and beta has the amino acid sequence of the beta subunit of a vertebrate glycoprotein hormone or a variant thereof; " alpha " designates the alpha subunit of a vertebrate glycoprotein hormone or a variant thereof; "linker" refers to a covalently linked moiety that the spaces beta and beta subunits at distances from the alpha subunit and from each other effective to retain said activity, and each of m and n is independently 0 or 1.
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公开(公告)号：EP0607297B1
公开(公告)日：2003-09-03
申请号：EP92921759.4
申请日：1992-10-02
Applicant: WASHINGTON UNIVERSITY
Inventor： BOIME, Irving
CPC classification number: C07K16/26 , A61K38/00 , C07K14/59 , C07K2319/00 , C07K2319/75 , Y10S930/11 , Y10S930/141
Abstract: The invention provides peptide and protein pharmaceuticals with extended half-lives. The modified peptides and proteins of the invention contain at least two tandem extensions at their C-terminus comprising the carboxy terminal portion of human chorionic gonadotropin. These "CTP units" consist essentially of the native HCG- beta sequence from position 112-118 to position 145 or conservative modifications thereof.
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