公开(公告)号：US06835544B2

公开(公告)日：2004-12-28

申请号：US09742684

申请日：2000-12-19

申请人： Lawrence W. Mathews ,  Wylie W. Vale, Jr. ,  Kunihiro Tsuchida

发明人： Lawrence W. Mathews ,  Wylie W. Vale, Jr. ,  Kunihiro Tsuchida

IPC分类号： G01N3353

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein: an extracellular, ligand-binding domain, a hydrophobic, trans-membrane domain, and an intracellular, receptor domain having serine kinase-like activity. The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-&bgr; superfamily of polypeptide growth factors such that concentrations of ≦10 nM of said polypeptide growth factor occupy ≧50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-&bgr;, and other non-activin-like proteins. DNA sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed.

摘要翻译： 根据本发明，提供了新的受体蛋白，其特征在于具有以下结构域，从所述蛋白质的N-末端读取：细胞外，配体结合结构域，疏水性，跨膜结构域和细胞内， 受体结构域具有丝氨酸激酶样活性。本发明受体任选地还包含在其氨基末端的第二疏水结构域。 本发明受体蛋白的进一步特征在于对多肽生长因子的激活素/ TGF-β超家族的至少一个成员具有足够的结合亲和力，使得所述多肽生长因子的<= 10nM的浓度占结合物的50％ 所述受体蛋白的位点。 本发明目前优选的受体超家族成员特异性结合激活素，优于抑制素，转化生长因子-β和其他非激活素样蛋白。 还公开了编码这种受体的DNA序列，使用其的测定法，以及由其衍生的抗体。

公开(公告)号：US6162896A

公开(公告)日：2000-12-19

申请号：US476123

申请日：1995-06-07

申请人： Lawrence W. Mathews ,  Wylie W. Vale, Jr. ,  Kunihiro Tsuchida

发明人： Lawrence W. Mathews ,  Wylie W. Vale, Jr. ,  Kunihiro Tsuchida

IPC分类号： A61K38/00 ,  C07K14/71 ,  C12N15/12

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein:an extracellular, ligand-binding domain,a hydrophobic, trans-membrane domain, andan intracellular, receptor domain having serine kinase-like activity.The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-.beta. superfamily of polypeptide growth factors such that concentrations of .ltoreq.10 nM of said polypeptide growth factor occupy .gtoreq.50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factory-.beta., and other non-activin-like proteins. DNA sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed.

摘要翻译： 根据本发明，提供了新的受体蛋白，其特征在于具有以下结构域，从所述蛋白质的N-末端读取：细胞外，配体结合结构域，疏水性，跨膜结构域和细胞内 ，具有丝氨酸激酶样活性的受体结构域。 本发明受体任选地还包含在其氨基末端的第二疏水结构域。 本发明受体蛋白的进一步特征在于对多肽生长因子的激活素/ TGF-β超家族的至少一个成员具有足够的结合亲和力，使得所述多肽生长因子的10nM的浓度占所述多肽生长因子的10％ 所述受体蛋白的结合位点。 本发明目前优选的受体超家族成员特异性结合激活素，优于抑制素，转化生长工厂-β和其他非激活素样蛋白。 还公开了编码这种受体的DNA序列，使用其的测定法，以及由其衍生的抗体。

公开(公告)号：US07893213B2

公开(公告)日：2011-02-22

申请号：US11747869

申请日：2007-05-11

申请人： Lawrence S. Mathews ,  Wylie W. Vale, Jr. ,  Kunihiro Tsuchida

发明人： Lawrence S. Mathews ,  Wylie W. Vale, Jr. ,  Kunihiro Tsuchida

IPC分类号： C07K16/18 ,  A61K39/395

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein: an extracellular, ligand-binding domain, a hydrophobic, trans-membrane domain, and an intracellular, receptor domain having serine kinase-like activity. The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-β superfamily of polypeptide growth factors such that concentrations of ≦10 nM of said polypeptide growth factor occupy ≧50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-β, and other non-activin-like proteins. DNA sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed.

摘要翻译： 根据本发明，提供了新的受体蛋白，其特征在于具有以下结构域，从所述蛋白质的N-末端读取：细胞外，配体结合结构域，疏水性，跨膜结构域和细胞内 ，具有丝氨酸激酶样活性的受体结构域。 本发明受体任选地还包含在其氨基末端的第二疏水结构域。 本发明受体蛋白的进一步特征在于对活化素/ TGF-β1的至少一个成员具有足够的结合亲和力; 多肽生长因子的超家族，使得所述多肽生长因子的浓度为10nM占所述受体蛋白质结合位点的≥50％。 本发明目前优选的受体超家族成员特异性结合激活素，优于抑制素，转化生长因子-β和其它非激活素样蛋白。 还公开了编码这种受体的DNA序列，使用其的测定法，以及由其衍生的抗体。

公开(公告)号：US20100016558A1

公开(公告)日：2010-01-21

申请号：US11747869

申请日：2007-05-11

申请人： Lawrence S. Mathews ,  Wylie W. Vale, JR. ,  Kunihiro Tsuchida

发明人： Lawrence S. Mathews ,  Wylie W. Vale, JR. ,  Kunihiro Tsuchida

IPC分类号： C07K16/00

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein: an extracellular, ligand-binding domain, a hydrophobic, trans-membrane domain, and an intracellular, receptor domain having serine kinase-like activity. The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-β superfamily of polypeptide growth factors such that concentrations of ≦10 nM of said polypeptide growth factor occupy ≧50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-β, and other non-activin-like proteins. DNA sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed.

摘要翻译： 根据本发明，提供了新的受体蛋白，其特征在于具有以下结构域，从所述蛋白质的N-末端读取：细胞外，配体结合结构域，疏水性，跨膜结构域和细胞内 ，具有丝氨酸激酶样活性的受体结构域。 本发明受体任选地还包含在其氨基末端的第二疏水结构域。 本发明受体蛋白的进一步特征在于对多肽生长因子的激活素/ TGF-β超家族的至少一个成员具有足够的结合亲和力，使得所述多肽生长因子的<= 10nM的浓度占结合物的50％ 所述受体蛋白的位点。 本发明目前优选的受体超家族成员特异性结合激活素，优于抑制素，转化生长因子-β和其他非激活素样蛋白。 还公开了编码这种受体的DNA序列，使用其的测定法，以及由其衍生的抗体。

公开(公告)号：US20050186593A1

公开(公告)日：2005-08-25

申请号：US11007077

申请日：2004-12-07

申请人： Lawrence Mathews ,  Wylie Vale ,  Kunihiro Tsuchida

发明人： Lawrence Mathews ,  Wylie Vale ,  Kunihiro Tsuchida

IPC分类号： A61K38/00 ,  C07K14/71 ,  C12Q1/68 ,  C07H21/04 ,  C07K14/705

CPC分类号： C07K14/71 ,  A61K38/00 ,  C07K2319/00

摘要： In accordance with the present invention, there are provided novel receptor proteins characterized by having the following domains, reading from the N-terminal end of said protein: an extracellular, ligand-binding domain, a hydrophobic, trans-membrane domain, and an intracellular, receptor domain having serine kinase-like activity. The invention receptors optionally further comprise a second hydrophobic domain at the amino terminus thereof. The invention receptor proteins are further characterized by having sufficient binding affinity for at least one member of the activin/TGF-β superfamily of polypeptide growth factors such that concentrations of ≦10 nM of said polypeptide growth factor occupy ≦50% of the binding sites of said receptor protein. A presently preferred member of the invention superfamily of receptors binds specifically to activins, in preference to inhibins, transforming growth factor-β, and other non-activin-like proteins. DNA sequences encoding such receptors, assays employing same, as well as antibodies derived therefrom, are also disclosed.

摘要翻译： 根据本发明，提供了新的受体蛋白，其特征在于具有以下结构域，从所述蛋白质的N-末端读取：细胞外，配体结合结构域，疏水性，跨膜结构域和细胞内 ，具有丝氨酸激酶样活性的受体结构域。 本发明受体任选地还包含在其氨基末端的第二疏水结构域。 本发明受体蛋白的进一步特征在于对多肽生长因子的活化素/ TGF-β超家族的至少一个成员具有足够的结合亲和力，使得所述多肽生长因子的<= 10nM的浓度占结合物的<50％ 所述受体蛋白的位点。 本发明目前优选的受体超家族成员特异性结合激活素，优于抑制素，转化生长因子-β和其他非激活素样蛋白。 还公开了编码这种受体的DNA序列，使用其的测定法，以及由其衍生的抗体。

公开(公告)号：US07867973B2

公开(公告)日：2011-01-11

申请号：US11578408

申请日：2005-04-15

申请人： Kunihiro Tsuchida ,  Tatsuya Murakami

发明人： Kunihiro Tsuchida ,  Tatsuya Murakami

IPC分类号： C12P21/04 ,  A61K38/18 ,  C07K14/475

CPC分类号： C07K14/4703 ,  A61K38/00

摘要： The object of the present invention is to provide a follistatin variant capable of specifically inhibiting GDF-8 activity without inhibiting activin activity. The present invention provides a follistatin variant polypeptide, which (a) comprises follistatin domain I; (b) does not comprise an amino acid sequence that is represented by formula (I): Cys-(X1)a-Cys-(X2)b-Cys-(X3)c-Cys-(X4)d-Cys-(X5)e-Cys-(X6)f-Cys-(X7)g-Cys-(X8)h-Cys-(X9)i-Cys (SEQ ID NO: 30) wherein X1, X2, X3, X4, X5, X6, X7, X8, and X9 each independently represents the same or a different naturally occurring amino acid residue other than cysteine, “a” represents an integer between 2 and 6, “b” represents an integer between 3 and 7, “c” represents an integer between 7 and 11, “d” represents an integer between 0 and 4, “e” represents an integer between 1 and 6, “f” and “g” represent integers between 8 and 12, “h” represents an integer between 4 and 8, and “i” represents an integer between 11 and 15) and has 50% or more homology with the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 29; and (c) selectively inhibits GDF-8 activity as compared with its inhibition of activin activity.

摘要翻译： 本发明的目的是提供能够抑制GDF-8活性而不抑制激活素活性的卵泡抑素变异体。 本发明提供了一种卵泡抑素变体多肽，其（a）包含卵泡抑素结构域I; （C） - （X 4）d-Cys-（X）的Cys-（X1）a-Cys-（X2）b-Cys- X5）e-Cys-（X6）f-Cys-（X7）g-Cys-（X8）h-Cys-（X9）i-Cys（SEQ ID NO：30）其中X1，X2，X3，X4，X5 ，X6，X7，X8和X9各自独立地表示除半胱氨酸以外的相同或不同的天然存在的氨基酸残基，“a”表示2至6之间的整数，“b”表示3至7之间的整数，“c “表示7到11之间的整数，”d“表示0和4之间的整数，”e“表示1和6之间的整数，”f“和”g“表示8和12之间的整数，”h“表示 4〜8之间的整数，“i”表示11〜15的整数），与SEQ ID NO：2或SEQ ID NO：29的氨基酸序列具有50％以上的同源性。 和（c）与其抑制活化素活性相比，选择性地抑制GDF-8活性。

公开(公告)号：US20080090755A1

公开(公告)日：2008-04-17

申请号：US11578408

申请日：2005-04-15

申请人： Kunihiro Tsuchida ,  Tatsuya Murakami

发明人： Kunihiro Tsuchida ,  Tatsuya Murakami

IPC分类号： A61K38/17 ,  A01K67/00 ,  A61K48/00 ,  A61P21/00 ,  A61P3/00 ,  A61P37/00 ,  C07H21/00 ,  C07K14/435 ,  C12N1/21 ,  C12N15/63 ,  C12P21/00 ,  C12Q1/66

CPC分类号： C07K14/4703 ,  A61K38/00

摘要： The object of the present invention is to provide a follistatin variant capable of specifically inhibiting GDF-8 activity without inhibiting activin activity. The present invention provides a follistatin variant polypeptide, which (a) comprises follistatin domain I; (b) does not comprise an amino acid sequence that is represented by formula (I): Cys-(X1)a-Cys-(X2)b-Cys-(X3)c-Cys-(X4)d-Cys-(X5)e-Cys-(X6)f-Cys-(X7)g-Cys-(X8)h-Cys-(X9)i-Cys (SEQ ID NO: 30) wherein X1, X2, X3, X4, X5, X6, X7, X8, and X9 each independently represents the same or a different naturally occurring amino acid residue other than cysteine, “a” represents an integer between 2 and 6, “b” represents an integer between 3 and 7, “c” represents an integer between 7 and 11, “d” represents an integer between 0 and 4, “e” represents an integer between 1 and 6, “f” and “g” represent integers between 8 and 12, “h” represents an integer between 4 and 8, and “i” represents an integer between 11 and 15) and has 50% or more homology with the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 29; and (c) selectively inhibits GDF-8 activity as compared with its inhibition of activin activity.

摘要翻译： 本发明的目的是提供能够抑制GDF-8活性而不抑制激活素活性的卵泡抑素变异体。 本发明提供了一种卵泡抑素变体多肽，其（a）包含卵泡抑素结构域I; （B）不包含由式（I）表示的氨基酸序列：Cys-（X 1）S a - （X 2） （S-S）S-C（X S） C 6 - （X 5）5 - （X 6） -C≡-（X S>）Cys-（X S>）-Sys-（X < SEQ ID NO：30，其中X 1，X 2，X 2，...， X 4，X 4，X 5，X 6，X 7，X 6， 8和X 9各自独立地表示除半胱氨酸以外的相同或不同的天然存在的氨基酸残基，“a”表示2至6之间的整数，“b”表示整数 在3和7之间，“c”表示7和11之间的整数，“d”表示0和4之间的整数，“e”表示1和6之间的整数，“f”和“g”表示8和 12中，“h”表示4〜8的整数，“i”表示11 a之间的整数 d 15），并且与SEQ ID NO：2或SEQ ID NO：29的氨基酸序列具有50％以上的同源性; 和（c）与其抑制活化素活性相比，选择性地抑制GDF-8活性。