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1. 发明申请

US20100120677A1 ACTIVITY OF RECOMBINANT EQUINE FOLLICLE STIMULATING HORMONE 有权
标题翻译：重组体激活刺激激素的活性
公开(公告)号：US20100120677A1
公开(公告)日：2010-05-13
申请号：US12325084
申请日：2008-11-28
申请人： Mark COLGIN , Irving Boime , Janet Roser , Kory Niswender
发明人： Mark COLGIN , Irving Boime , Janet Roser , Kory Niswender
IPC分类号： A61K38/24 , C07K14/575 , C07H21/04 , C12N15/63 , C12N5/10 , A61P15/00
CPC分类号： C07K14/59 , A61K38/00
摘要： The present invention provides methods of producing biologically active recombinant eFSH analogs and methods of increasing reproduction in mammals, particularly equine, using recombinant eFSH analogs. Also provided are methods of producing biologically active single chain recombinant eFSH. The recombinant eFSH analogs of the present invention increase superovulation, follicular development, embryo development, and reproductive efficiency in horses, cattle and other ungulates.
摘要翻译：本发明提供使用重组eFSH类似物生产生物活性重组eFSH类似物的方法和增加哺乳动物尤其是马的繁殖的方法。还提供了生产生物活性单链重组eFSH的方法。本发明的重组eFSH类似物增加了马，牛和其他有蹄类动物的超排卵，卵泡发育，胚胎发育和繁殖效率。

2. 发明授权

US08835386B2 Activity of recombinant equine follicle stimulating hormone 有权
标题翻译：重组马刺激素的活性
公开(公告)号：US08835386B2
公开(公告)日：2014-09-16
申请号：US12325084
申请日：2008-11-28
申请人： Mark Colgin , Kory Niswender , Irving Boime , Janet Roser
发明人： Mark Colgin , Kory Niswender , Irving Boime , Janet Roser
IPC分类号： A61K38/24 , C07K14/575 , C07K14/59
CPC分类号： C07K14/59 , A61K38/00
摘要： The present invention provides methods of producing biologically active recombinant eFSH analogs and methods of increasing reproduction in mammals, particularly equine, using recombinant eFSH analogs. Also provided are methods of producing biologically active single chain recombinant eFSH. The recombinant eFSH analogs of the present invention increase superovulation, follicular development, embryo development, and reproductive efficiency in horses, cattle and other ungulates.
摘要翻译：本发明提供使用重组eFSH类似物生产生物活性重组eFSH类似物的方法和增加哺乳动物尤其是马的繁殖的方法。还提供了生产生物活性单链重组eFSH的方法。本发明的重组eFSH类似物增加了马，牛和其他有蹄类动物的超排卵，卵泡发育，胚胎发育和繁殖效率。

3. 发明授权

US06693074B1 Cystine depleted glycoprotein hormones 失效
标题翻译：胱氨酸消耗的糖蛋白激素
公开(公告)号：US06693074B1
公开(公告)日：2004-02-17
申请号：US08933693
申请日：1997-09-19
申请人： Irving Boime , David Ben Menahem
发明人： Irving Boime , David Ben Menahem
IPC分类号： A61K3824
CPC分类号： A61K38/24
摘要： Single-chain forms of the glycoprotein hormones LH, FSH, TSH or CG which are lacking at least one disulfide bridge in the sequence representing the &agr; and/or &bgr; subunit are useful as agonists or antagonists of the native glycoprotein hormones.
摘要翻译：在代表α和/或β亚基的序列中缺少至少一个二硫桥的糖蛋白激素LH，FSH，TSH或CG的单链形式可用作天然糖蛋白激素的激动剂或拮抗剂。

4. 发明授权

US5585345A CTP extended form of glycoprotein hormones 失效
标题翻译： CTP延长形式的糖蛋白激素
公开(公告)号：US5585345A
公开(公告)日：1996-12-17
申请号：US239256
申请日：1994-05-06
申请人： Irving Boime
发明人： Irving Boime
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61K38/24 , A61K38/27 , A61P13/02 , A61P15/00 , C07K14/00 , C07K14/575 , C07K14/59 , C07K19/00 , C12N5/10 , C12N15/06 , C12N15/16 , C12P21/02 , C12R1/91
CPC分类号： C07K14/59 , A61K38/00 , C07K2319/00 , C07K2319/75 , C07K2319/91
摘要： Extended forms of beta subunits of human glycoproteins wherein the amino acid sequence of a carboxy terminal peptide (CTP) representing positions from about 112-118 to 145 of the human CG-beta subunit or a variant form thereof is appended to the C-terminus are disclosed. Recombinant materials for the production of these extended human glycoprotein beta subunits and production of the modified hormones containing the extended beta subunits are also described. Pharmaceutical compositions containing the modified forms of these hormones are useful in pharmacological applications analogous to those of the unmodified forms.
摘要翻译：人类糖蛋白的β亚基的延伸形式，其中代表位于人CG-β亚基的约112-118至145位或其变体形式的羧基末端肽（CTP）的氨基酸序列附加到C末端是披露还描述了用于生产这些延伸的人类糖蛋白β亚基的重组材料和含有延伸的β亚单位的修饰的激素的生产。含有这些激素修饰形式的药物组合物可用于类似于未修饰形式的药理学应用。

5. 发明授权

US5177193A Modified forms of reproductive hormones 失效
标题翻译：生殖激素的修饰形式
公开(公告)号：US5177193A
公开(公告)日：1993-01-05
申请号：US532254
申请日：1990-06-01
申请人： Irving Boime , Martin M. Matzuk
发明人： Irving Boime , Martin M. Matzuk
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61K38/24 , A61K38/27 , A61P13/02 , A61P15/00 , C07K14/00 , C07K14/575 , C07K14/59 , C07K19/00 , C12N5/10 , C12N15/06 , C12N15/16 , C12P21/02 , C12R1/91
CPC分类号： C07K14/59 , A61K38/00 , C07K2319/00 , C07K2319/75 , C07K2319/91
摘要： 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.
摘要翻译：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基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。

6. 发明授权

US06689365B1 Single-chain fertility hormones with fsh and LH activity 有权
标题翻译：单链生育激素与fsh和LH活性
公开(公告)号：US06689365B1
公开(公告)日：2004-02-10
申请号：US09565930
申请日：2000-05-05
申请人： Irving Boime
发明人： Irving Boime
IPC分类号： C12N1516
CPC分类号： C07K14/575 , C07K14/59 , C07K2319/00
摘要： Glycosylated or nonglycosylated proteins of the formula FSH&bgr;-(linker1)n1-LH&bgr;(1-X)-(linker2)n2-&agr; wherein FSH&bgr; is a vertebrate follicle stimulating hormone &bgr; subunit or a variant thereof; LH&bgr;(1-X) refer's to a &bgr; 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 residues; each n is a 0 or 1; and &agr; is the &agr; subunit of a vertebrate glycoprotein hormone or a variant thereof are useful in protocols to enhance fertility in humans and in animals.
摘要翻译： FSHbeta的糖基化或非糖基化蛋白质是脊椎动物刺激素β亚基或其变体; LHbeta（1-X）是指含有1-X位置的X的整数为114位的脊椎动物黄体生成激素的β亚基， 121或其变体;每个“接头”是含有1-100个氨基酸残基的亲水性柔性氨基酸序列;每个n是0或1; andalpha是脊椎动物糖蛋白激素的α亚基或其变体，可用于增强人和动物的生育力。

7. 发明授权

US06635256B1 Glycoprotein hormone compositions comprising two &bgr; subunits and methods of use thereof 有权
标题翻译：包含两个β亚基的糖蛋白激素组合物及其使用方法
公开(公告)号：US06635256B1
公开(公告)日：2003-10-21
申请号：US09175017
申请日：1998-10-19
申请人： Irving Boime , David Ben-Menahem
发明人： Irving Boime , David Ben-Menahem
IPC分类号： A61K3824
CPC分类号： C07K14/59 , A61K38/00 , A61K38/24 , C07K2319/00
摘要： Forms of differentially acting glycoprotein hormones are disclosed. These compositions are of the formula &bgr;1-(linker1)m-&agr;-(linker2)n-&bgr;2 (1); &bgr;1-(linker1)m-&bgr;2-(linker2)n-&agr; (2); &agr;-(linker1)m-&bgr;1-(linker2)n-&bgr;2 (3); &bgr;2≈&agr;-(linker)m-&bgr;1 (4); or &bgr;1-(linker)m-&agr;≈&bgr;2 (5) wherein each of &bgr;1 and &bgr;2 has the amino acid sequence of the &bgr; subunit of a vertebrate glycoprotein hormone or a variant of said amino acid sequence as variants are defined herein. “&agr;” designates the a subunit of a vertebrate glycoprotein hormone or a variant thereof; “linker” refers to a covalently linked moiety that spaces the &bgr;1 and &bgr;2 subunits at appropriate distances from the &agr; subunit and from each other. “≈” is a noncovalent link. Each of m and n is independently 0 or 1.
摘要翻译：公开了差异作用的糖蛋白激素的形式。这些组合物是β1和β2中的每一个具有脊椎动物糖蛋白激素的β亚基的氨基酸序列或作为变体的所述氨基酸序列的变体的定义。 “α”表示脊椎动物糖蛋白激素的a亚基或其变体; “接头”是指共价连接的部分，其在α亚基和彼此之间的适当距离处使β1和β2亚基间隔开。 “≈”是一个非共价链接。 m和n各自独立地为0或1。

8. 发明授权

US06306654B1 Follicle stimulating hormone-glycosylation analogs 失效
标题翻译：促卵泡激素 - 糖基化类似物
公开(公告)号：US06306654B1
公开(公告)日：2001-10-23
申请号：US08155102
申请日：1993-11-19
申请人： Irving Boime , Martin M. Matzuk , Jeffrey L. Keene
发明人： Irving Boime , Martin M. Matzuk , Jeffrey L. Keene
IPC分类号： C12N1506
CPC分类号： C07K14/59 , A61K38/00 , C07K2319/00 , C07K2319/75 , C07K2319/91
摘要： Recombinant materials are provided for the production of the &agr;-glycoprotein hormone subunit. These muteins have utility as antagonists and in altering pharmacokinetic activity of these hormones.
摘要翻译：提供重组材料用于生产α-糖蛋白激素亚基。这些突变蛋白具有作为拮抗剂的作用并改变这些激素的药代动力学活性。

9. 发明授权

US5338835A CTP-extended form of FSH 失效
标题翻译： CTP扩展形式的FSH
公开(公告)号：US5338835A
公开(公告)日：1994-08-16
申请号：US950801
申请日：1992-09-24
申请人： Irving Boime
发明人： Irving Boime
IPC分类号： A61K38/00 , C07K14/59 , C07K13/00 , A61K37/38
CPC分类号： C07K14/59 , A61K38/00 , C07K2319/75
摘要： 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.
摘要翻译：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基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。

10. 发明授权

US07442376B2 Glycoprotein hormone compositions containing two β subunits 失效
公开(公告)号：US07442376B2
公开(公告)日：2008-10-28
申请号：US10647088
申请日：2003-08-21
申请人： Irving Boime , David Ben-Menahem
发明人： Irving Boime , David Ben-Menahem
IPC分类号： C07K14/59
CPC分类号： C07K14/59 , A61K38/00 , A61K38/24 , C07K2319/00
摘要： Forms of differentially acting glycoprotein hormones are disclosed. These compositions are of the formula β1-(linker1)m-α-(linker2)n-β2; (1) β1-(linker1)m-β2-(linker2)n-α; (2) α-(linker1)m-β1-(linker2)n-β2; (3) β2≈α-(linker)m-β1; or (4) β1-(linker)m-α≈β2 (5) wherein each of β1 and β2 has the amino acid sequence of the β subunit of a vertebrate glycoprotein hormone or a variant of said amino acid sequence, as variants are defined herein. “α” designates the α subunit of a vertebrate glycoprotein hormone or a variant thereof, “linker” refers to a covalently linked moiety that spaces the β1 and β2 subunits at appropriate distances from the α subunit and from each other. “≈” is a noncovalent link. Each of m and n is independently 0 or 1.

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