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1. 发明授权

US5786327A Bone stimulating factor, methods of isolating same, and methods of increasing bone growth comprising administering same 失效
标题翻译：骨刺激因子，其分离方法和增加骨生长的方法，包括施用它
公开(公告)号：US5786327A
公开(公告)日：1998-07-28
申请号：US302485
申请日：1994-09-12
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： G01N33/53 , A61K35/12 , A61K35/16 , A61K38/00 , A61P19/08 , A61P43/00 , C07H21/04 , C07K1/16 , C07K1/18 , C07K1/26 , C07K7/06 , C07K14/51 , C07K14/52 , C07K14/575 , C07K16/22 , C12N15/09 , C12N15/12 , C12P21/02 , C12P21/08 , C07K1/14 , A61K38/18
CPC分类号： C07K14/522 , C07K14/51 , A61K38/00
摘要： A polypepide substance isolated from rat serum which, upon administration to rats incapable of producing PTH (parathyroidectomized rats), produces an increase in the observed bone mineral apposition rate. The substance bas been isolated in two forms, a first larger polypeptide having a molecular weight about twice that of a second smaller polypeptide. The first eleven amino acids of the sequence of the smaller polypepeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile (SEQ ID NO:3). The first seven amino acids of the larger polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu (SEQ ID NO:2). The larger polypeptide might be the dimer of the smaller peptide. A nucleic acid probe, based on the amino acid sequence of the rat peptide was used to screen a human liver cDNA fetal library. A polypeptide was thus chemically synthesized according to the sequence Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO: 11). The bone apposition rate in rats increases in a dose dependent fashion upon administration of this chemically synthesized compound. A modified polypeptide containing a cysteine.fwdarw.alanine substitution was carried synthesized: Glr Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gin Asn Gin Pro (SEQ ID NO: 13). Some of the bone stimulatory effects of the normal polypeptide were found for the modified polypeptide.
摘要翻译：从大鼠血清中分离的多肽物质，当给予不能产生PTH（甲状旁腺切除的大鼠）的大鼠时，观察到的骨矿物质配合率增加。物质基本分离成两种形式，第一种较大的多肽具有约二倍于第二较小多肽的分子量。已经确定较小多肽的序列的前11个氨基酸为Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile（SEQ ID NO：3）。已确定较大多肽的前7个氨基酸为Gly Pro Gly Gly Ala Gly Glu（SEQ ID NO：2）。较大的多肽可能是较小肽的二聚体。使用基于大鼠肽的氨基酸序列的核酸探针筛选人肝脏cDNA胎儿文库。因此，根据序列化学合成多肽Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro（SEQ ID NO ：11）。在施用该化学合成的化合物时，大鼠的骨配合率以剂量依赖性方式增加。合成了含有半胱氨酸 - >丙氨酸取代的修饰多肽：Glr Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gin Asn Gin Pro （SEQ ID NO：13）。针对修饰的多肽发现一些正常多肽的骨刺激作用。

2. 发明授权

US5880094A Polypeptides that stimulate bone growth 失效
标题翻译：刺激骨骼生长的多肽
公开(公告)号：US5880094A
公开(公告)日：1999-03-09
申请号：US487074
申请日：1995-06-07
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： G01N33/53 , A61K38/00 , A61P19/10 , A61P43/00 , C07K14/51 , C07K16/22 , C12N15/09 , C12N15/12 , C12P21/02 , C12Q1/68 , A61K38/04 , C07K7/08
CPC分类号： C07K14/51 , A61K38/00 , C07K2319/00
摘要： Polypeptides which stimulate bone growth are described based on the sequences: (a) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val; (b) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala; (c) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu; and (d) Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile. The associated nucleotide sequences, methods of preparation and use, and antibodies and kits based upon them are described, as well.
摘要翻译：基于以下序列描述刺激骨生长的多肽：（a）Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val; （b）Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala; （c）Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu; 和（d）Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile。还描述了相关的核苷酸序列，制备和使用方法，以及基于它们的抗体和试剂盒。

3. 发明授权

US06693081B2 Bone stimulating factor 失效
标题翻译：骨刺激因子
公开(公告)号：US06693081B2
公开(公告)日：2004-02-17
申请号：US09229304
申请日：1999-01-13
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： A61K3808
CPC分类号： C07K7/06 , A61K38/00 , C07K7/08 , C07K14/51 , C07K14/52
摘要： Polypeptides which increase or promote mammalian bone growth, related nucleotide sequences, antibodies, diagnostic kits and treatments. Subsequences of the polypeptide (SEQ ID NO:2)Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser Leu Glu Val Ile Gly Lys Gly Thr His Cys Asn Gln Val Glu Val Ile Ala Thr Leu Lys Asp Gly Arg Lys Ile Cys Leu Asp Pro Asp Ala Pro Arg Ile Lys Lys Ile Val Gln Lys Lys Leu Ala Gly Asp Glu Ser Ala Asp have been shown to promote growth. Subsequences include (SEQ ID NO:11) Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser (SEQ ID NO:12); Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Glu Ser (SEQ ID NO:13); Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser and (SEQ ID NO:19) TTSGIHPK.
摘要翻译：增加或促进哺乳动物骨生长的多肽，相关核苷酸序列，抗体，诊断试剂盒和治疗。多肽的亚序列（SEQ ID NO：2）Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser Leu Glu Val Ile Gly Lys Gly Thr His Cys Asn Gln Val Glu Val Ile Ala Thr Leu Lys Asp Gly Arg Lys Ile Cys Leu Asp Pro Asp Ala Pro Arg Ile Lys Lys Ile Val Gln Lys Lys Leu Ala Gly Asp Glu Ser Ala Asp已显示促进生长。子序列包括（SEQ ID NO：11）Asp Ser Asp Leu Tyr Ala Glu Leu Arg Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser（SEQ ID NO：12）; Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Glu Ser（SEQ ID NO：13）; Cys Met Cys Ile Lys Thr Thr Ser Gly Ile His Pro Lys Asn Ile Gln Ser和（SEQ ID NO：19）TTSGIHPK。

4. 发明授权

US06352973B1 Bone stimulating factor 失效
标题翻译：骨刺激因子
公开(公告)号：US06352973B1
公开(公告)日：2002-03-05
申请号：US08986627
申请日：1997-12-08
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： A61K3816
CPC分类号： C07K14/51 , A61K38/00 , C07K2319/00
摘要： Polypeptides which stimulate bone growth, associated nucleotide sequences, methods of preparation and use, antibodies and kits are disclosed.
摘要翻译：公开了刺激骨生长的多肽，相关核苷酸序列，制备和使用方法，抗体和试剂盒。

5. 发明授权

US06815421B1 Polypeptides for use in ameliorating effects of aging in mammals 失效
标题翻译：用于改善哺乳动物衰老作用的多肽
公开(公告)号：US06815421B1
公开(公告)日：2004-11-09
申请号：US10103132
申请日：2002-03-22
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： A61K3800
CPC分类号： A61K38/08
摘要： Method of ameliorating effects of aging in an animal, the method comprising administering to the animal an effective amount of a synthetic polypeptide comprising an amino acid sequence that has 10+q amino acids, wherein, under physiological conditions, residues numbered n, n+4, n+9 are positively charged amino acids, residues numbered n+3, n+7 are negatively charged amino acids, wherein the remaining amino acids are nonpolar amino acids or uncharged polar amino acids, wherein n is an integer from 1 to 1+q and q is a whole number greater than or equal to zero. Experiments demonstrating the effect were performed with a polypeptide having the sequence Arg-Thr-Gln-Glu-His-Thr-Ala-Glu-Cys-Lys.
摘要翻译：一种改善动物衰老作用的方法，所述方法包括向动物施用有效量的包含具有10 + q个氨基酸的氨基酸序列的合成多肽，其中在生理条件下，编号为n，n + 4的残基，n + 9是带正电荷的氨基酸，n + 3，n + 7的残基是带负电荷的氨基酸，其中剩余的氨基酸是非极性氨基酸或不带电极性氨基酸，其中n是1至1的整数， q和q是大于或等于零的整数。用具有Arg-Thr-Gln-Glu-His-Thr-Ala-Glu-Cys-Lys序列的多肽进行证明该效果的实验。

6. 发明授权

US06596498B1 Bone stimulating factor 失效
标题翻译：骨刺激因子
公开(公告)号：US06596498B1
公开(公告)日：2003-07-22
申请号：US09728484
申请日：2000-12-04
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： G01N3348
CPC分类号： C07K14/522 , A61K38/00 , C07K14/51
摘要： A polypeptide substance isolate from rat serum which, upon administration to rats incapable of producing PTH (parathyroidectomized rats), produces an increase in the observed bone mineral apposition rate. The substance has been isolated in two forms, a first layer polypeptide having a molecular weight about twice that of a second smaller polypeptide. The first eleven amino acids of the sequence of the smaller polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile (SEQ ID NO:3). The first seven amino acids of the larger polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu (SEQ ID NO:2). The lager polypeptide might be the dimer of the smaller peptide. A nucleic acid probe, based on the amino acid sequence of the rat peptide was used to screen a human liver cDNA fetal library. A polypeptide was thus chemically synthesized according to the sequence Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Pro (SEQ ID NO:11). The bone apposition rate in rats increases in a dose dependent fashion upon administration of this chemically synthesized compound. A modified polypeptide containing a cysteine→alaine substinition was carried synthesized: Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:13). Some of the bone stimulatory effects of the normal polypeptide were found for the modified polypeptide.
摘要翻译：从大鼠血清分离的多肽物质，当给予不能产生PTH（甲状旁腺切除的大鼠）的大鼠时，观察到的骨矿物质配合率增加。该物质已被分离成两种形式，第一层多肽的分子量约为第二较小多肽的分子量的两倍。已经确定较小多肽的序列的前11个氨基酸为Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile（SEQ ID NO：3）。已确定较大多肽的前7个氨基酸为Gly Pro Gly Gly Ala Gly Glu（SEQ ID NO：2）。较大的多肽可能是较小肽的二聚体。使用基于大鼠肽的氨基酸序列的核酸探针筛选人肝脏cDNA胎儿文库。因此，根据序列化学合成多肽Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Pro（SEQ ID NO： 11）。在施用该化学合成的化合物时，大鼠的骨配合率以剂量依赖性方式增加。合成了含有半胱氨酸 - > alaine取代基的修饰多肽：Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Met Val Leu Asp Gln Asn Gln Pro SEQ ID NO：13）。针对修饰的多肽发现一些正常多肽的骨刺激作用。

7. 发明授权

US06274702B1 Bone stimulating factor 失效
标题翻译：骨刺激因子
公开(公告)号：US06274702B1
公开(公告)日：2001-08-14
申请号：US09044098
申请日：1998-03-19
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： C07K14435
CPC分类号： C07K14/522 , A61K38/00 , C07K14/51
摘要： A polypeptide substance isolated from rat serum which, upon administration to rats incapable of producing PTH (parathyroidectomized rats), produces an increase in the observed bone mineral apposition rate. The substance has been isolated in two forms, a first larger polypeptide having a molecular weight twice that of a second smaller polypeptide. The first eleven amino acids of the sequence of the smaller polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile (SEQ ID NO:3). The first seven amino acids of the larger polypeptide have been determined to be Gly Pro Gly Gly Ala Gly Glu (SEQ ID NO:2). The larger polypeptide might be the dimer of the smaller peptide. A nucleic acid probe, based on the amino acid sequence of the rat peptide was used to screen a human liver cDNA fetal library. A polypeptide was thus chemically synthesized according to the sequence Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:11). The bone apposition rate in rats increases in a dose dependent fashion upon administration of this chemically synthesized compound. A modified polypeptide containing a cysteine alanine substitution was carried synthesized: Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:13). Some of the bone stimulatory effects of the normal polypeptide were found for the modified polypeptide.
摘要翻译：从大鼠血清中分离出的多肽物质，当给予不能产生PTH（甲状旁腺切除的大鼠）的大鼠时，观察到的骨矿物结合率增加。该物质已经被分离成两种形式，第一种较大的多肽的分子量是第二较小多肽的两倍。已经确定较小多肽的序列的前11个氨基酸为Gly Pro Gly Gly Ala Gly Glu Thr Lys Pro Ile（SEQ ID NO：3）。已确定较大多肽的前7个氨基酸为Gly Pro Gly Gly Ala Gly Glu（SEQ ID NO：2）。较大的多肽可能是较小肽的二聚体。使用基于大鼠肽的氨基酸序列的核酸探针筛选人肝脏cDNA胎儿文库。因此，根据序列化学合成多肽Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro（SEQ ID NO ：11）。在施用该化学合成的化合物时，大鼠的骨配合率以剂量依赖性方式增加。合成了含有半胱氨酸丙氨酸取代基的修饰多肽：Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Ala Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro（SEQ ID NO： ID NO：13）。针对修饰的多肽发现一些正常多肽的骨刺激作用。

8. 发明授权

US06117839A Bone stimulating factor 失效
标题翻译：骨刺激因子
公开(公告)号：US06117839A
公开(公告)日：2000-09-12
申请号：US763458
申请日：1996-12-11
申请人： Cherk Shing Tam
发明人： Cherk Shing Tam
IPC分类号： G01N33/53 , A61K38/00 , A61P19/10 , A61P43/00 , C07K14/51 , C07K16/22 , C12N15/09 , C12N15/12 , C12N15/18 , C12P21/02 , C12Q1/68 , A61K38/13 , C07K14/00
CPC分类号： C07K14/51 , A61K38/00 , C07K2319/00
摘要： Polypeptides which stimulate bone growth: Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro (SEQ ID NO:1) and subsequences, particularly Arg Thr Asn Glu His Thr Ala Asp Cys Lys (SEQ ID NO:9) and associated nucleotide sequences, methods of preparation and use, antibodies and kits.
摘要翻译：刺激骨生长的多肽：Gly Ile Gly Lys Arg Thr Asn Glu His Thr Ala Asp Cys Lys Ile Lys Pro Asn Thr Leu His Lys Lys Ala Ala Glu Thr Leu Met Val Leu Asp Gln Asn Gln Pro（SEQ ID NO：1）和子序列，特别是Arg Thr Asn Glu His Thr Ala Asp Cys Lys（SEQ ID NO：9）和相关核苷酸序列，制备和使用方法，抗体和试剂盒。

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