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1. 发明申请

WO2011080103A1 DOUBLE-ACYLATED GLP-1 DERIVATIVES 审中-公开
标题翻译：双酚A-GLP-1衍生物
公开(公告)号：WO2011080103A1
公开(公告)日：2011-07-07
申请号：PCT/EP2010/069932
申请日：2010-12-16
申请人： NOVO NORDISK A/S , GARIBAY, Patrick, William , SPETZLER, Jane , KODRA, János, Tibor , LINDEROTH, Lars , LAU, Jesper , SAUERBERG, Per
发明人： GARIBAY, Patrick, William , SPETZLER, Jane , KODRA, János, Tibor , LINDEROTH, Lars , LAU, Jesper , SAUERBERG, Per
IPC分类号： C07K14/605 , A61K47/48
CPC分类号： C07K14/65 , A61K38/00 , A61K47/542 , A61K47/60 , C07K14/605 , G01N2333/605
摘要： The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1 (7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1 (7-37), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37), wherein the first K residue is designated K 37 , and the second K residue is designated K 26 , which derivative comprises two albumin binding moieties attached to K 26 and K 37 , respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: Chem. 1 : HOOC-(CH 2 ) X -CO-* Chem. 2: HOOC-C 6 H 4 -O-(CH 2 ) y -CO-* Chem. 3: R 1 -C 6 H 4 -(CH 2 ) Z -CO-* Chem. 4: HOOC-C 4 SH 2 -(CH 2 ) W -CO-* in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1 -5, R 1 is a group having a molar mass not higher than 150 Da, and w is an integer in the range of 6-18; with the proviso that when the protracting moiety is Chem. 1, the albumin binding moiety further comprises a linker of formula Chem. 5: *-NH-(CH 2 ) 2 -(O-(CH 2 ) 2 ) k -O-(CH 2 ) n -CO-*, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.
摘要翻译：本发明涉及GLP-1类似物的衍生物，其类似物包含在对应于GLP-1（7-37）（SEQ ID NO：1）的第37位的位置处的第一个K残基，相对于GLP-1（7-37）的位置26的位置和与GLP-1（7-37）相比最多10个氨基酸修饰，其中第一个K残基指定为K37，第二个K残基是命名为K26，该衍生物分别包含与K26和K37连接的两个白蛋白结合部分，其中白蛋白结合部分包含选自下列的伸长部分： 1：HOOC-（CH2）X-CO- * Chem。 2：HOOC-C6H4-O-（CH2）y-CO- * 3：R1-C6H4-（CH2）Z-CO- * Chem。 4：HOOC-C4SH2-（CH2）W-CO- *，其中x是6-18的整数，y是3-17的整数，z是1〜 5，R1是摩尔质量不高于150Da的基团，w是6-18的整数; 条件是当伸长部分是Chem。如图1所示，白蛋白结合部分还包含式Chem的接头。 5：* -NH-（CH2）2-（O-（CH2）2）kO-（CH2）n-CO- *，其中k是1-5的整数，n是范围1-5; 或其药学上可接受的盐，酰胺或酯。本发明还涉及其药物用途，例如用于治疗和/或预防所有形式的糖尿病和相关疾病，以及相应的新型肽和侧链中间体。该衍生物适合口服给药。

2. 发明申请

WO2012062803A1 DOUBLE-ACYLATED GLP-1 DERIVATIVES 审中-公开
标题翻译：双取代的GLP-1衍生物
公开(公告)号：WO2012062803A1
公开(公告)日：2012-05-18
申请号：PCT/EP2011/069738
申请日：2011-11-09
申请人： NOVO NORDISK A/S , MADSEN, Alice Ravn , WIECZOREK, Birgit , KOFOED, Jacob , LAU, Jesper , SPETZLER, Jane , KODRA, János Tibor , LINDEROTH, Lars , GARIBAY, Patrick William , SAUERBERG, Per , KRUSE, Thomas
发明人： MADSEN, Alice Ravn , WIECZOREK, Birgit , KOFOED, Jacob , LAU, Jesper , SPETZLER, Jane , KODRA, János Tibor , LINDEROTH, Lars , GARIBAY, Patrick William , SAUERBERG, Per , KRUSE, Thomas
IPC分类号： A61K47/48 , C07K14/605 , A61P3/10
CPC分类号： C07K14/605 , A61K47/542
摘要： The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 18 of GLP-1 (7-37) (SEQ ID NO: 1 ), a second K residue at another position, and a maximum of twelve amino acid changes as compared to GLP-1 (7-37); which derivative comprises two protracting moieties attached to said first and second K residue, respectively, via a linker, wherein the protracting moiety is selected from Chem. 1, Chem. 2, and Chem. 3: Chem. : HOOC-(CH 2 ) x -CO-* Chem. 2: HOOC-C 6 H 4 -0-(CH 2 ) y -CO-* Chem. 3: R 2 -C 6 H 4 -(CH 2 ) z -CO-*, in which x is an integer in the range of 6-18, y is an integer in the range of 3-17, z is an integer in the range of 1 -5, and R 2 is a group having a molar mass not higher than 150 Da; and the linker comprises Chem. 4: *-NH-(CH 2 ) 2 -(0-(CH 2 ) 2 ) k -0-(CH 2 ) n -CO-*. wherein k is an integer in the range of 1 -5, and n is an integer in the range of 1 -5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel peptides and side chain intermediates. The derivatives are suitable for oral administration.
摘要翻译：本发明涉及GLP-1类似物的衍生物，其类似物包含在对应于GLP-1（7-37）（SEQ ID NO：1）的第18位的位置处的第一个K残基，另一个的第二个K残基位置和与GLP-1（7-37）相比最多12个氨基酸变化; 该衍生物分别包含通过接头分别连接到所述第一和第二K残基的两个伸长部分，其中伸长部分选自Chem。 1，Chem。 2和Chem。 3：Chem。：HOOC-（CH2）x-CO- * Chem。 2：HOOC-C6H4-0-（CH2）y-CO- * Chem。 3：R2-C6H4-（CH2）z-CO- *，其中x是6-18的整数，y是3-17的整数，z是1的整数 -5和R2是摩尔质量不高于150Da的基团; 连接体包括Chem。 4：* -NH-（CH 2）2 - （O-（CH 2）2）k -O-（CH 2）n -CO- *。其中k是1-5的整数，n是1-5的整数; 或其药学上可接受的盐，酰胺或酯。本发明还涉及其药物用途，例如用于治疗和/或预防所有形式的糖尿病和相关疾病，以及相应的新型肽和侧链中间体。该衍生物适用于口服给药。

3. 发明申请

WO2009030774A1 TRUNCATED GLP-1 DERIVATIVES AND THEIR THERAPEUTICAL USE 审中-公开
标题翻译：截短的GLP-1衍生物及其治疗用途
公开(公告)号：WO2009030774A1
公开(公告)日：2009-03-12
申请号：PCT/EP2008/061833
申请日：2008-09-05
申请人： NOVO NORDISK A/S , SPETZLER, Jane , SCHÄFFER, Lauge , LAU, Jesper , KODRA, János Tibor , MADSEN, Kjeld , GARIBAY, Patrick William , KOFOED, Jacob , RUNGE, Steffen , THØGERSEN, Henning , PETTERSSON, Ingrid
发明人： SPETZLER, Jane , SCHÄFFER, Lauge , LAU, Jesper , KODRA, János Tibor , MADSEN, Kjeld , GARIBAY, Patrick William , KOFOED, Jacob , RUNGE, Steffen , THØGERSEN, Henning , PETTERSSON, Ingrid
IPC分类号： C07K14/605 , A61K38/26 , C07K14/575 , A61K38/22
CPC分类号： C07K14/605 , A61K38/00
摘要： The invention relates to truncated GLP-1 analogues, in particular a GLP-1 analogue which is a modified GLP-1(7-35) (SEQ ID No 1) having : i) a total of 2, 3, 4, 5 6, 7, 8, or 9 amino acid substitutions as compared to GLP-1(7-35), including a) a GIu residue at a position equivalent to position 22 of GLP-1(7-35), and b) an Arg residue at a position equivalent to position 26 of GLP-1(7-35); as well as derivatives thereof, and therapeutic uses and compositions. These analogues and derivatives are highly potent, have a good binding affinity to the GLP-1 receptor, also to the extracellular domain of the GLP-1 receptor, which is of potential relevance achieving long-acting, stable GLP-1 compounds with a potential for once weekly administration.
摘要翻译：本发明涉及截短的GLP-1类似物，特别是GLP-1类似物，其是修饰的GLP-1（7-35）（SEQ ID No.1），其具有：i）总共2,3,4,5,6 ，7,8或9个氨基酸取代，其包括a）在等同于GLP-1（7-35）的位置22的位置处的Glu残基，和b）Arg 在等同于GLP-1（7-35）的第26位的位置上的残基; 以及其衍生物，以及治疗用途和组合物。这些类似物和衍生物是高度有效的，对GLP-1受体以及GLP-1受体的细胞外结构域具有良好的结合亲和力，这与具有潜在的长效，稳定的GLP-1化合物具有潜在的相关性每周一次行政。

4. 发明申请

WO2011080102A2 GLP-1 ANALOGUES AND DERIVATIVES 审中-公开
标题翻译： GLP-1类似物和衍生物
公开(公告)号：WO2011080102A2
公开(公告)日：2011-07-07
申请号：PCT/EP2010/069931
申请日：2010-12-16
申请人： NOVO NORDISK A/S , KALTHOFF, Christoph , LAU, Jesper , SPETZLER, Jane , GARIBAY, Patrick, William , KOFOED, Jacob , LINDEROTH, Lars
发明人： KALTHOFF, Christoph , LAU, Jesper , SPETZLER, Jane , GARIBAY, Patrick, William , KOFOED, Jacob , LINDEROTH, Lars
IPC分类号： C07K14/605
CPC分类号： C07K14/65 , A61K38/00 , A61K47/542 , A61K47/60 , C07K14/605 , G01N2333/605
摘要： The invention relates to a GLP-1 analogue which comprises a histidine (H) residue at a position corresponding to position 31 of GLP-1(7-37) (SEQ ID NO: 1), a glutamine (Q) residue at a position corresponding to position 34 of GLP-1 (7-37) (SEQ I D NO: 1), and a maximum of ten amino acid modifications as compared to GLP-1 (7-37) (SEQ ID NO: 1); wherein the H residue is designated H 31 , and the Q residue is designated Q 34 ; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to derivatives thereof, as well as the pharmaceutical use of these analogues and derivatives, for example in the treatment and/or prevention of all forms of diabetes and related diseases. The invention furthermore relates to corresponding novel side chain intermediates. The derivatives are suitable for oral administration.
摘要翻译：本发明涉及GLP-1类似物，其在对应于GLP-1（7-37）（SEQ ID NO：1）的位置31的位置包含组氨酸（H）残基，（7-37）（SEQ ID NO：1）的位置34处的谷氨酰胺（Q）残基，和与GLP-1（7-37）（SEQ ID NO：1）相比最多10个氨基酸修饰 ID NO：1）; 其中H残基命名为H 31，Q残基命名为Q 34。或其药学上可接受的盐，酰胺或酯。本发明还涉及其衍生物，以及这些类似物和衍生物的药物用途，例如用于治疗和/或预防所有形式的糖尿病和相关疾病。本发明还涉及相应的新型侧链中间体。这些衍生物适合口服给药。

5. 发明申请

WO2009030771A1 PEPTIDES DERIVATIZED WITH A-B-C-D- AND THEIR THERAPEUTICAL USE 审中-公开
标题翻译：用A-B-C-D及其治疗用途衍生的肽
公开(公告)号：WO2009030771A1
公开(公告)日：2009-03-12
申请号：PCT/EP2008/061830
申请日：2008-09-05
申请人： NOVO NORDISK A/S , SPETZLER, Jane , SCHÄFFER, Lauge , LAU, Jesper , KRUSE, Thomas , GARIBAY, Patrick William , ØSTERGAARD, Søren , RUNGE, Steffen , THØGERSEN, Henning
发明人： SPETZLER, Jane , SCHÄFFER, Lauge , LAU, Jesper , KRUSE, Thomas , GARIBAY, Patrick William , ØSTERGAARD, Søren , RUNGE, Steffen , THØGERSEN, Henning
IPC分类号： A61K38/22 , A61K38/26 , A61K47/48 , C07K14/575 , C07K14/605
CPC分类号： C07K14/001 , A61K38/00 , A61K38/16 , A61K38/17 , A61K38/22 , A61K38/26 , A61K47/50 , A61K47/51 , A61K47/54 , A61K47/542 , A61K47/543 , A61K47/545 , A61K47/56 , A61K47/60 , C07K14/00 , C07K14/575 , C07K14/57563 , C07K14/605
摘要： The invention relates to protracted peptide derivatives such as Glucagon-Like Peptide-1 (GLP-1), exendin-4, and analogues thereof, as well as therapeutic uses thereof.The peptide derivative of the invention comprises a peptide wherein at least one amino acid residue is derivatized with A-B-C-, or A-B-C-D-. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, have a low ratio of binding affinity to the GLP-1 receptor in the presence of high/low albumin concentrations, have long half-lives, and have a high affinity of binding to albumin, all of which is of potential relevance for the overall aim of achieving long- acting, stable and active GLP-1 derivatives with a potential for once weekly administration.
摘要翻译：本发明涉及延长的肽衍生物，例如胰高血糖素样肽-1（GLP-1），毒蜥外泌肽-4及其类似物，以及其治疗用途。本发明的肽衍生物包含肽，其中至少一个氨基酸残基用ABC-或ABCD-衍生化。这些化合物可用于治疗或预防2型糖尿病和相关疾病。该化合物是有效的，在高/低白蛋白浓度存在下具有低的GLP-1受体结合亲和力比，具有长的半衰期，并且具有与白蛋白结合的高亲和力，所有这些都是潜在的对于实现长效，稳定和活性的GLP-1衍生物的总体目标的相关性，具有每周施用一次的潜力。

6. 发明申请

WO2009030738A1 GLUCAGON-LIKE PEPTIDE-1 DERIVATIVES AND THEIR PHARMACEUTICAL USE 审中-公开
标题翻译： GLUCAGON-LIKE PEPTIDE-1衍生物及其药物用途
公开(公告)号：WO2009030738A1
公开(公告)日：2009-03-12
申请号：PCT/EP2008/061755
申请日：2008-09-05
申请人： NOVO NORDISK A/S , PETTERSSON, Ingrid , SPETZLER, Jane , SCHÄFFER, Lauge , LAU, Jesper , KRUSE, Thomas , GARIBAY, Patrick William , RUNGE, Steffen , THØGERSEN, Henning
发明人： SPETZLER, Jane , SCHÄFFER, Lauge , LAU, Jesper , KRUSE, Thomas , GARIBAY, Patrick William , RUNGE, Steffen , THØGERSEN, Henning
IPC分类号： C07K14/605 , A61K38/26
CPC分类号： C07K14/605 , A61K38/26
摘要： The invention relates to protracted Glucagon-Like Peptide-1 (GLP-1) derivatives and therapeutic uses thereof. The GLP-1 derivative of the invention comprises a modified GLP-1(7-37) sequence having a total of 2-12 amino acid modifications, including Glu22 and Arg26, and being derivatised with an albumin binding residue or pegylated in position 18, 20, 23, 30, 31, 34, 36, 37, or 39. These compounds are useful in the treatment or prevention of diabetes type 2 and related diseases. The compounds are potent, stable, have long half-lives, a high affinity of binding to albumin, and/or a high affinity of binding to the extracellular domain of the GLP-1 receptor (GLP-1R), all of which is of potential relevance for the overall aim of achieving long-acting, stable and active GLP-1 derivatives with a potential for once weekly administration.
摘要翻译：本发明涉及长效的胰高血糖素样肽-1（GLP-1）衍生物及其治疗用途。本发明的GLP-1衍生物包含具有总共2-12个氨基酸修饰的修饰的GLP-1（7-37）序列，包括Glu22和Arg26，并用白蛋白结合残基衍生或在18位聚乙二醇化， 20,23,30,31,34,36,37或39.这些化合物可用于治疗或预防2型糖尿病和相关疾病。该化合物是有效的，稳定的，具有长的半衰期，与白蛋白结合的高亲和力，和/或与GLP-1受体（GLP-1R）细胞外结构域结合的高亲和力，所有这些都是对于实现长效，稳定和活性的GLP-1衍生物的总体目标的潜在相关性，具有每周一次行政的潜力。

7. 发明申请

WO2012140117A1 DOUBLE-ACYLATED GLP-1 DERIVATIVES 审中-公开
标题翻译：双取代的GLP-1衍生物
公开(公告)号：WO2012140117A1
公开(公告)日：2012-10-18
申请号：PCT/EP2012/056642
申请日：2012-04-12
申请人： NOVO NORDISK A/S , WIECZOREK, Birgit , SPETZLER, Jane , KRUSE, Thomas , LINDEROTH, Lars , KOFOED, Jacob
发明人： WIECZOREK, Birgit , SPETZLER, Jane , KRUSE, Thomas , LINDEROTH, Lars , KOFOED, Jacob
IPC分类号： A01N43/90 , A01N61/00 , A01P3/00 , A61K38/26 , C07K14/065
CPC分类号： C07K14/605 , A61K38/00 , A61K38/26 , A61K47/542 , A61K47/60
摘要： The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 27 of GLP-1(7-37) (SEQ ID NO: 1 ); a second K residue at a position corresponding to position T of GLP-1(7-37), where T is an integer in the range of 7-37 except 18 and 27; and a maximum of ten amino acid changes as compared to GLP-1(7-37); wherein the first K residue is designated K 27 , and the second K residue is designated K T ; which derivative comprises two albumin binding moieties attached to K 27 and K T , respectively, via a linker, wherein the albumin binding moiety comprises a protracting moiety selected from HOOC-(CH 2 ) x -CO- and HOOC-C 6 H 4 -0-(CH 2 ) y -CO-; in which x is an integer in the range of 6-16, and y is an integer in the range of 3-17; wherein the linker comprises an element of the formula -NH-(CH 2 ) 2 -(O-(CH 2 ) 2 ) k -O-(CH 2 ) n -CO-, wherein k is an integer in the range of 1-5, and n is an integer in the range of 1-5; or a pharmaceutically acceptable salt, amide, or ester thereof. The invention also relates to the pharmaceutical use thereof, for example in the treatment and/or prevention of all forms of diabetes and related diseases, as well as to corresponding novel GLP-1 analogues. The derivatives are suitable for oral administration.
摘要翻译：本发明涉及GLP-1类似物的衍生物，其类似物包含在对应于GLP-1（7-37）（SEQ ID NO：1）的位置27的位置处的第一个K残基; 在对应于GLP-1（7-37）的位置T的位置处的第二个K残基，其中T是除了18和27之外的7-37范围内的整数; 与GLP-1（7-37）相比最多10个氨基酸变化; 其中第一K残基指定为K27，第二K残基指定为KT; 该衍生物通过接头分别包含与K27和KT连接的两个白蛋白结合部分，其中白蛋白结合部分包含选自HOOC-（CH 2）x -CO-和HOOC-C 6 H 4 O-（CH 2）y -CO-; 其中x是6-16的整数，y是3-17的整数; 其中所述接头包含式-NH-（CH 2）2 - （O-（CH 2）2）kO-（CH 2）n -CO-的元素，其中k是1-5的整数，n 是1-5的整数; 或其药学上可接受的盐，酰胺或酯。本发明还涉及其药物用途，例如用于治疗和/或预防所有形式的糖尿病和相关疾病，以及相应的新型GLP-1类似物。该衍生物适用于口服给药。

8. 发明申请

WO2008023050A1 ACYLATED EXENDIN-4 COMPOUNDS 审中-公开
标题翻译：酰化的EXENDIN-4化合物
公开(公告)号：WO2008023050A1
公开(公告)日：2008-02-28
申请号：PCT/EP2007/058789
申请日：2007-08-24
申请人： NOVO NORDISK A/S , LAU, Jesper , HANSEN, Thomas Kruse , CHRISTENSEN, Leif , MADSEN, Kjeld , SCHÄFFER, Lauge , SPETZLER, Jane
发明人： LAU, Jesper , HANSEN, Thomas Kruse , CHRISTENSEN, Leif , MADSEN, Kjeld , SCHÄFFER, Lauge , SPETZLER, Jane
IPC分类号： C07K14/605 , A61K38/26 , A61P3/08 , A61P5/48
CPC分类号： C07K14/57563 , A61K38/00 , A61K38/26 , A61K47/48038 , A61K47/48046 , A61K47/48061 , A61K47/48215 , A61K47/542 , A61K47/543 , A61K47/545 , A61K47/60 , C07K14/605
摘要： This invention provides new therapeutic peptides, i.e. new protracted Exendin-4 compounds, pharmaceutical compositions and the use of such.
摘要翻译：本发明提供了新的治疗肽，即新的延长的毒蜥外泌肽-4化合物，药物组合物及其用途。

9. 发明申请

WO2006097536A2 DIMERIC PEPTIDE AGONISTS OF THE GLP-1 RECEPTOR 审中-公开
标题翻译： GLP-1受体的二肽拮抗剂
公开(公告)号：WO2006097536A2
公开(公告)日：2006-09-21
申请号：PCT/EP2006/060854
申请日：2006-03-20
申请人： NOVO NORDISK A/S , CHRISTENSEN, Leif , LAU, Jesper , SPETZLER, Jane , HANSEN, Thomas Kruse
发明人： CHRISTENSEN, Leif , LAU, Jesper , SPETZLER, Jane , HANSEN, Thomas Kruse
IPC分类号： A61K47/48 , C07K14/605 , A61K38/26 , A61P3/10
CPC分类号： C07K14/605 , A61K38/00 , A61K47/60 , A61K47/65 , C07K14/57563
摘要： Dimerization of GLP-1 agonists and therapeutic uses thereof.
摘要翻译： GLP-1激动剂的二聚化及其治疗用途。

10. 发明申请

WO2011104378A1 PEPTIDES FOR TREATMENT OF OBESITY 审中-公开
标题翻译：治疗肥胖症的肽
公开(公告)号：WO2011104378A1
公开(公告)日：2011-09-01
申请号：PCT/EP2011/052909
申请日：2011-02-28
申请人： NOVO NORDISK A/S , FRIEBOES, Kilian Waldemar Conde , SPETZLER, Jane , SENSFUSS, Ulrich , WULFF, Birgitte Schjellerup , THØGERSEN, Henning , NORRILD, Jens Chr.
发明人： FRIEBOES, Kilian Waldemar Conde , SPETZLER, Jane , SENSFUSS, Ulrich , WULFF, Birgitte Schjellerup , THØGERSEN, Henning , NORRILD, Jens Chr.
IPC分类号： C07K14/68 , A61K38/34
CPC分类号： C07K14/68
摘要： The present invention relates to novel peptide compounds which are effective in modulating one or more melanocortin receptor types, to the use of the compounds in therapy, to methods of treatment comprising administration of the compounds to patients in need thereof, and to the use of the compounds in the manufacture of medicaments. The compounds of the invention are of particular interest in relation to the treatment of obesity as well as a variety of diseases or conditions associated with obesity.
摘要翻译：本发明涉及有效调节一种或多种黑皮素受体类型的新型肽化合物，该化合物在治疗中的用途，治疗方法，包括将化合物给予需要的患者并涉及这些化合物在制造药物中的用途。本发明的化合物在治疗肥胖以及与肥胖相关的多种疾病或病症方面特别有意义。

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