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公开(公告)号:US06451762B1
公开(公告)日:2002-09-17
申请号:US09227774
申请日:1999-01-08
IPC分类号: A61K3828
CPC分类号: A61K38/28 , Y10S514/866
摘要: The present invention relates-to protracted acting, water-soluble aggregates of derivatives of human insulin, derivatives of human insulin capable of forming such aggregates, pharmaceutical compositions containing them, and to the use of such aggregates in the treatment of diabetes.
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公开(公告)号:US5750497A
公开(公告)日:1998-05-12
申请号:US400256
申请日:1995-03-08
IPC分类号: C12N15/09 , A61K38/00 , A61K38/28 , A61P3/08 , A61P3/10 , C07K14/62 , C12N1/19 , C12N1/21 , C12P21/02 , C12R1/19 , C12R1/865
CPC分类号: C07K14/62 , A61K38/00 , Y10S514/866
摘要: The present invention relates to human insulin derivatives having a protracted profile of action in which the A21 and B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; Phe.sup.B1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the E-amino group of Lys.sup.B29 ; (b) any amino acid residue which can be coded by the genetic code except Lys, Arg and Cys, in which case a lipophilic substituent is bound to the E-amino group of Lys.sup.B29 ; or (c) deleted, in which case a lipophilic substituent is bound to the E-amino group of LyS.sup.B29 ; and any Zn.sup.2+ complexes thereof; provided that when the B30 amino acid residue is Thr or Ala, the A21 and B3 amino acid residues are both Asn and Phe.sup.B1 is present, then the insulin derivative is a Zn.sup.2 + complex.
摘要翻译: 本发明涉及具有延长的作用曲线的人胰岛素衍生物,其中A21和B3氨基酸残基独立地是可由除Lys,Arg和Cys之外的遗传密码编码的任何氨基酸残基; PheB1可能被删除; B30氨基酸残基是(a)具有10-24个碳原子的非可编码的亲脂性氨基酸,在这种情况下,具有至多5个碳原子的羧酸的酰基与LysB29的E-氨基结合 ; (b)除了Lys,Arg和Cys之外可以通过遗传密码编码的任何氨基酸残基,在这种情况下,亲油性取代基与LysB29的E氨基结合; 或(c)缺失,在这种情况下,亲油取代基与LySB29的E氨基结合; 及其任何Zn2 +配合物; 条件是当B30氨基酸残基是Thr或Ala时,A21和B3氨基酸残基都是Asn和PheB1,则胰岛素衍生物是Zn 2+络合物。
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公开(公告)号:US08796205B2
公开(公告)日:2014-08-05
申请号:US12297914
申请日:2007-05-08
摘要: Novel human insulin derivatives are described which are soluble at physiological pH values and have a prolonged profile of action.
摘要翻译: 描述了新的人胰岛素衍生物,其在生理pH值下可溶,并具有延长的作用特征。
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公开(公告)号:US07595172B2
公开(公告)日:2009-09-29
申请号:US10205110
申请日:2002-07-24
申请人: Ib Jonassen , Michi Egel-Mitani , Per Balschmidt , Jan Markussen , Ivan Diers , Thomas Borglum Kjeldsen
发明人: Ib Jonassen , Michi Egel-Mitani , Per Balschmidt , Jan Markussen , Ivan Diers , Thomas Borglum Kjeldsen
IPC分类号: A61K38/00
CPC分类号: C07K1/006 , C07K1/1077
摘要: The present invention related to a method of producing polypeptides in transformed host cells by expressing a precursor molecule of the desired polypeptide which are to be acylated in a subsequent in vitro step. The invention is also related to DNA-sequences, vectors and transformed host cells for use in the claimed method. Further, the present invention is related to certain precursors of the desired polypeptides and certain acylation methods. The invention provides a method for making polypeptides being preferentially acylated in certain lysine ε-amino groups.
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公开(公告)号:US07576059B2
公开(公告)日:2009-08-18
申请号:US09772607
申请日:2001-01-30
IPC分类号: C07K14/00 , C07K14/575
CPC分类号: A61K38/08 , A61K38/2242 , A61K38/26 , A61K38/31 , A61K47/64 , C07K14/575 , C07K14/665
摘要: A pharmacologically active peptide hormone derivative in which the parent peptide hormone has been modified by introducing either a lipophilic substituent, W, in the N-terminal amino acid or a lipophilic substituent, Z, in the C-terminal amino acid of the parent peptide hormone or an analogue thereof, said lipophilic substituent having from 8 to 40 carbon atoms, has a protracted profile of action.
摘要翻译: 通过在母体肽激素的C-末端氨基酸中的N-末端氨基酸或亲脂性取代基Z中引入亲油性取代基W而修饰了母体肽激素的药理活性肽激素衍生物 或其类似物,所述具有8至40个碳原子的亲油取代基具有延长的作用曲线。
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公开(公告)号:US06869930B1
公开(公告)日:2005-03-22
申请号:US09398365
申请日:1999-09-17
CPC分类号: C07K14/62 , A61K38/00 , Y10S514/866
摘要: The present invention relates to protracted human insulin derivatives in which the A21 and the B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; PheB1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms, in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the ε-amino group of LysB29; or (b) the B30 amino acid residue is deleted or is any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys, in any of which cases the ε-amino group of LysB29 has a lipophilic substituent; and any Zn2+ complexes thereof with the proviso that when B30 is Thr or Ala and A21 and B3 are both Asn, and PheB1 is present, then the insulin derivative is always present as a Zn2+ complex.
摘要翻译: 本发明涉及延长的人胰岛素衍生物,其中A21和B3氨基酸残基独立地是可由遗传密码编码的除Lys,Arg和Cys之外的任何氨基酸残基; Phe
可能被删除; B30氨基酸残基是(a)具有10-24个碳原子的不可编码的亲脂性氨基酸,在这种情况下,具有至多5个碳原子的羧酸的酰基与ε-氨基的ε-氨基结合 Lys ; 或(b)B30氨基酸残基被缺失,或者是任何氨基酸残基,其可以通过除Lys,Arg和Cys之外的遗传密码进行编码,在这些情况下,Lys 的ε-氨基具有 亲油取代基; 和任何Zn 2+络合物,条件是当B30是Thr或Ala,A21和B3都是Asn和Phe 时,胰岛素衍生物总是作为Zn 2+络合物存在 。 -
公开(公告)号:US06620780B2
公开(公告)日:2003-09-16
申请号:US09861687
申请日:2001-05-21
申请人: Jan Markussen , Ib Jonassen , Svend Havelund , Jakob Brandt , Peter Kurtzhals , Per Hertz Hansen , Niels Christian Kaarsholm
发明人: Jan Markussen , Ib Jonassen , Svend Havelund , Jakob Brandt , Peter Kurtzhals , Per Hertz Hansen , Niels Christian Kaarsholm
IPC分类号: C07K1462
CPC分类号: C07K14/62 , Y10S514/866
摘要: The present invention relates to insulin derivatives in which a lipophilic group having from 12 to 40 carbon atoms is attached to the &agr;-amino group of the N-terminal amino acid in the B-chain or to the carboxy group of the C-terminal amino acid in the B-chain have a protracted profile of action.
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公开(公告)号:US6011007A
公开(公告)日:2000-01-04
申请号:US975365
申请日:1997-11-20
CPC分类号: C07K14/62 , A61K38/00 , Y10S514/866
摘要: The present invention relates to protracted human insulin derivatives in which the A21 and the B3 amino acid residues are, independently, any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys; Phe.sup.B1 may be deleted; the B30 amino acid residue is (a) a non-codable, lipophilic amino acid having from 10 to 24 carbon atoms, in which case an acyl group of a carboxylic acid with up to 5 carbon atoms is bound to the .epsilon.-amino group of Lys.sup.B29 ; or (b) the B30 amino acid residue is deleted or is any amino acid residue which can be coded for by the genetic code except Lys, Arg and Cys, in any of which cases the .epsilon.-amino group of Lys.sup.B29 has a lipophilic substituent; and any Zn.sup.2+ complexes thereof with the proviso that when B30 is Thr or Ala and A21 and B3 are both Asn, and Phe.sup.B1 is present, then the insulin derivative is always present as a Zn.sup.2+ complex.
摘要翻译: 本发明涉及延长的人胰岛素衍生物,其中A21和B3氨基酸残基独立地是可由遗传密码编码的除Lys,Arg和Cys之外的任何氨基酸残基; PheB1可能被删除; B30氨基酸残基是(a)具有10至24个碳原子的非可编码的亲脂性氨基酸,在这种情况下,具有至多5个碳原子的羧酸的酰基与ε-氨基的ε-氨基结合 LysB29; 或(b)B30氨基酸残基被缺失或者是任何氨基酸残基,其可以通过除Lys,Arg和Cys之外的遗传密码进行编码,在这些情况下,LysB29的ε-氨基具有亲脂性取代基; 和任何Zn 2+配合物,条件是当B30是Thr或Ala,A21和B3都是Asn和PheB1时,胰岛素衍生物总是作为Zn 2+络合物存在。
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39.
公开(公告)号:US5324641A
公开(公告)日:1994-06-28
申请号:US952696
申请日:1992-09-23
申请人: Ib Jonassen , Ib G. Clausen , Ejner B. Jensen , Allan Svendsen
发明人: Ib Jonassen , Ib G. Clausen , Ejner B. Jensen , Allan Svendsen
IPC分类号: C12N15/09 , A61K38/00 , C07K14/575 , C07K14/62 , C12N15/17 , C12P21/02 , C12R1/865 , C12N15/00 , C12N1/08 , C12P21/06
摘要: DNA molecule and process for producing insulin precursors having the formula B(1-29) -H.sub.1 --X.sub.2 --Y.sub.2 --Y.sub.1 --A(1-21), wherein B(1-29) are the 29 first amino acid residues of the B chain of human insulin starting from the N-terminus, A(1-21) are the 21 amino acid residues of the A chain of human insulin, X.sub.1 represents a peptide bond or one naturally-occurring alpha-amino acid acid residues, X.sub.2 represents Glu or Asp, and Y.sub.1 and Y.sub.2 each represent Lys or Arg, the positions A6 and A11, A7 and B7 and A20 and B19, respectively, are connected through sulphur bridges, and, if desired, one or more of the glutamic acid residues in positions A4, A17, B13 and B21 are substituted by another naturally-occurring alpha-amino acid residue having an uncharged side chain, are provided. The insulin precursors are prepared by culturing a yeast strain transformed with a replicable plasmid comprising a DNA sequence encoding an insulin precursor of the above formula in a suitable medium and isolating the insulin precursor thus formed from the culture medium. The insulin precursor can be converted into human insulin or insulin analogues by enzymatic treatment in a manner known per se.
摘要翻译: DNA分子和具有式B(1-29)-H1-X2-Y2-Y1-A(1-21)的胰岛素前体的制备方法,其中B(1-29)是B的第一个氨基酸残基 A(1-21)是人胰岛素A链的21个氨基酸残基,X1表示肽键或一个天然存在的α-氨基酸酸残基,X2表示 Glu或Asp,Y1和Y2各自表示Lys或Arg,位置A6和A11,A7和B7和A20和B19分别通过硫桥连接,如果需要,一个或多个谷氨酸残基在 位置A4,A17,B13和B21被另一个具有不带电侧链的天然存在的α-氨基酸残基所取代。 通过在合适的培养基中培养用包含编码上式胰岛素前体的DNA序列的可复制质粒转化的酵母菌株并分离由培养基形成的胰岛素前体来制备胰岛素前体。 胰岛素前体可以通过本身已知的方式通过酶处理转化为人胰岛素或胰岛素类似物。
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