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1. 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。

2. 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。

3. 发明授权

US5958737A Single-chain .beta. subunit dimers of the glycoprotein hormones and recombinant materials related thereto 失效
标题翻译：糖链蛋白激素的单链β亚基二聚体和与其相关的重组材料
公开(公告)号：US5958737A
公开(公告)日：1999-09-28
申请号：US806772
申请日：1997-02-26
申请人： Irving Boime , David Ben-Menahem
发明人： Irving Boime , David Ben-Menahem
IPC分类号： A61K38/00 , C07K14/575 , C07K14/59 , C12N20060101 , C12N15/16 , C07H21/00
CPC分类号： C07K14/59 , C07K14/575 , A61K38/00 , C07K2319/00
摘要： 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.
摘要翻译：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。

4. 发明授权

US5883073A Single-chain double-alpha peptide 失效
标题翻译：单链双α肽
公开(公告)号：US5883073A
公开(公告)日：1999-03-16
申请号：US834802
申请日：1997-04-03
申请人： Irving Boime , David Ben-Menahem
发明人： Irving Boime , David Ben-Menahem
IPC分类号： A61K38/00 , C07K14/59 , A61K38/24
CPC分类号： C07K14/59 , A61K38/00 , C07K2319/00 , Y10S930/11 , Y10S930/13 , Y10S930/31
摘要： The invention is directed to a glycosylated or nonglycosylated protein which is composed of the amino acid sequence of a first .alpha. subunit common to the glycoprotein hormones linked covalently, optionally through a linker moiety, to the amino acid sequence of a second .alpha. subunit of said hormones, wherein said first and second .alpha. subunits consist of the native amino acid sequences or variants of said amino acid sequences. These proteins are useful as agonists or antagonists of glycoprotein hormone activity.
摘要翻译：本发明涉及糖基化或非糖基化蛋白质，其由通过共价连接的任选地通过连接体部分与所述激素的第二个α亚基的氨基酸序列共价连接的糖蛋白激素共有的第一个α亚基的氨基酸序列组成其中所述第一和第二α亚基由所述氨基酸序列的天然氨基酸序列或变体组成。这些蛋白质可用作糖蛋白激素活性的激动剂或拮抗剂。

5. 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.

6. 发明授权

US6103501A Single chain glycoprotein hormones comprising two .beta. and one .alpha. subunits and recombinant production thereof 失效
标题翻译：包含两个β和一个α亚基的单链糖蛋白激素及其重组产生
公开(公告)号：US6103501A
公开(公告)日：2000-08-15
申请号：US971439
申请日：1997-11-17
申请人： Irving Boime , David Ben Menahem
发明人： Irving Boime , David Ben Menahem
IPC分类号： C12N15/09 , A61K38/00 , A61K38/22 , A61K38/24 , C07K14/59 , C07K16/26 , C07K19/00 , C12N5/10 , C12N15/16 , C12N15/62 , C12N15/85 , C12P21/02
CPC分类号： C07K14/59 , A61K38/00 , C07K2319/00
摘要： Single-chain agonists and/or antagonists of the glycoprotein hormones are disclosed. These proteins are of the formula.beta..sup.1 -(linker.sup.1).sub.m -.alpha.-(linker.sup.2).sub.n -.beta..sup.2 (1);or.beta..sup.1 -(linker.sup.1).sub.m -.beta..sup.2 -(linker.sup.2).sub.n -.alpha. (2);or.alpha.-(linker.sup.1).sub.m -.beta..sup.1 -(linker.sup.2).sub.n - .beta..sup.2 (3)wherein each of .beta..sup.1 and .beta..sup.2 has the amino acid sequence of the .beta. subunit of a vertabrate glycoprotein hormone or a variant thereof; ".alpha." designates the .alpha. subunit of a vertabrate glycoprotein hormone or a variant thereof; "linker" refers to a covalently linked moiety that spaces the .beta..sup.1 and .beta..sup.2 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.
摘要翻译：公开了糖蛋白激素的单链激动剂和/或拮抗剂。这些蛋白质具有式β1-（接头1）m-α-（接头2）n-β2（1）或β1-（接头1）m-β2-（接头2）n-α（2）;或 α - （接头1）m-β1-（接头2）n-β2（3），其中β1和β2中的每一个具有转氨酶糖蛋白激素或其变体的β亚基的氨基酸序列; “α”表示高糖糖蛋白激素或其变体的α亚单位; “接头”是指共价连接的部分，其与β亚基和β2亚基在距离α亚基的距离处相互间隔并且有效保留所述活性，并且m和n中的每一个独立地为0或1。

7. 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。

8. 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。

9. 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。

10. 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。

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