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11. 发明申请

WO2004056865A3 METHOD OF MODULATION OF INTERACTION BETWEEN RECEPTOR AND LIGAND 审中-公开
标题翻译：受体和配体之间相互作用的调节方法
公开(公告)号：WO2004056865A3
公开(公告)日：2005-02-24
申请号：PCT/DK0300901
申请日：2003-12-18
申请人： ENKAM PHARMACEUTICALS AS , BEREZIN VLADIMIR , ALBRECHTSEN MORTEN , BOCK ELISABETH
发明人： BEREZIN VLADIMIR , ALBRECHTSEN MORTEN , BOCK ELISABETH
IPC分类号： A61K38/00 , C07K7/06 , C07K7/08 , C07K16/22 , G01N33/566 , G01N33/74 , C07K7/00
CPC分类号： C07K7/06 , A61K38/00 , C07K7/08 , C07K16/22 , G01N33/566 , G01N33/74 , G01N2333/50
摘要： The present invention relates to a method for modulating the interaction between at least two proteins, wherein at least one of the two proteins is a functional cell-surface receptor and the other protein is the receptor ligand. The invention features a binding site of said functional cell-surface receptor on the receptor ligand and discloses a series of amino acid sequences, which are part of the structure of said binding site and/or involved in the interaction between the receptor and the ligand. Moreover, the present invention features methods for molecular design and screening of a candidate compound capable of modulating the interaction between the functional cell-surface receptor and receptor ligand through the described binding site, and provides a screening assay for identification of such a compound. The invention further describes an antibody capable of binding to the above binding site and/or to an epitope comprising an amino acid sequence essential for executing the receptor ligand interaction through said binding site. The invention also concerns a variety of uses of the disclosed methods, peptide sequences and antibodies. The invention in preferred embodiments concerns the binding site of the fibroblast growth factor receptor (FGFR) on FGFR ligands, compounds capable of modulating the receptor ligand interaction through said binding site, and antibody capable of recognition of said binding site.
摘要翻译：本发明涉及调节至少两种蛋白质之间的相互作用的方法，其中两种蛋白质中的至少一种是功能性细胞表面受体，而另一种蛋白质是受体配体。本发明的特征在于所述功能性细胞表面受体在受体配体上的结合位点，并公开了一系列氨基酸序列，其是所述结合位点结构的一部分和/或参与受体和配体之间的相互作用。此外，本发明的特征在于分子设计和筛选能够通过所述结合位点调节功能性细胞表面受体和受体配体之间的相互作用的候选化合物的方法，并提供了鉴定这种化合物的筛选试验。本发明还描述了能够结合上述结合位点和/或包含通过所述结合位点执行受体配体相互作用所必需的氨基酸序列的表位的抗体。本发明还涉及所公开的方法，肽序列和抗体的各种用途。本发明在优选实施方案中涉及成纤维细胞生长因子受体（FGFR）对FGFR配体的结合位点，能够通过所述结合位点调节受体配体相互作用的化合物和能够识别所述结合位点的抗体。

12. 发明申请

WO03016351B1 N - CAM RELATED COMPOUNDS MODULATING CELL GROTH 审中-公开
标题翻译： N - CAM相关化合物调节细胞培养
公开(公告)号：WO03016351B1
公开(公告)日：2004-05-06
申请号：PCT/DK0200541
申请日：2002-08-19
申请人： ENKAM PHARMACEUTICALS AS , KISELYOV VLADISLAV V , SKLADCHIKOVA GALINA , BEREZIN VLADIMIR , BOCK ELISABETH
发明人： KISELYOV VLADISLAV V , SKLADCHIKOVA GALINA , BEREZIN VLADIMIR , BOCK ELISABETH
IPC分类号： A61K38/00 , A61P1/18 , A61P3/10 , A61P9/10 , A61P13/12 , A61P17/02 , A61P21/00 , A61P21/04 , A61P25/00 , A61P25/02 , A61P25/14 , A61P25/16 , A61P25/24 , A61P25/28 , A61P35/00 , C07K7/06 , C07K7/08 , C07K14/705 , C07K14/78 , A61K38/04 , A61K38/17 , C07K7/00
CPC分类号： C07K14/70503 , A61K38/00 , C07K2319/00
摘要： The present invention relates to a compound comprising the third Immunoglobulin (Ig3) module, and/or the fourth Immunoglobulin (Ig4) module, and/or the fifth Immunoglobulin (Ig5) module, and/or the first Fibronectin III (Fn3, 1) module, and/or the second Fibronectin III (Fn3, 2) module of neural cell adhesion molecule (NCAM), or a fragment, or a variant thereof, capable of interacting with a Fibroblast Growth Factor (FGF) receptor and/or Adenosine-Tri-Phosphate (ATP) and/or L1, and thereby the compounds are capable of inducing differentiation, modulating proliferation, stimulate regeneration, neuronal plasticity and/or survival of cells. Further, the present invention relates to a pharmaceutical composition comprising said compound, a process of producing a pharmaceutical composition and the use of said compound.
摘要翻译：本发明涉及包含第三免疫球蛋白（Ig3）模块和/或第四免疫球蛋白（Ig4）模块和/或第五免疫球蛋白（Ig5）模块和/或第一纤连蛋白III（Fn3,1）和/或能够与成纤维细胞生长因子（FGF）受体和/或腺苷-3-磷酸结合蛋白相互作用的片段或变体的神经细胞粘附分子（NCAM）的第二纤连蛋白III（Fn3,2）模块，三磷酸（ATP）和/或L1，并且由此所述化合物能够诱导分化，调节增殖，刺激再生，神经元可塑性和/或细胞存活。此外，本发明涉及包含所述化合物的药物组合物，制备药物组合物的方法以及所述化合物的用途。

13. 发明申请

WO2007115571A8 ERBB RECEPTOR-DERIVED PEPTIDE FRAGMENTS 审中-公开
标题翻译： ERBB受体衍生的肽片段
公开(公告)号：WO2007115571A8
公开(公告)日：2008-11-20
申请号：PCT/DK2007000171
申请日：2007-04-03
申请人： ENKAM PHARMACEUTICALS AS , BOCK ELISABETH , BEREZIN VLADIMIR , POVLSEN GRO KLITGAARD
发明人： BOCK ELISABETH , BEREZIN VLADIMIR , POVLSEN GRO KLITGAARD
IPC分类号： C07K14/71 , A61K38/04
CPC分类号： C07K14/71
摘要： The invention relates to new peptide compounds capable of modulating cell proliferation, differentiation, survival and/or motility. The peptide compounds of the invention comprise short peptide fragments of the ErbB receptor and are capable of binding to ErbB and modulating activity of the receptor. The invention also relates to antibodies capable of binding to an epitope comprising a peptide sequence of the invention, pharmaceutical compositions comprising the peptide sequences and/or antibodies and uses thereof for treatment of conditions wherein modulating activity of ErbB is needed.
摘要翻译：本发明涉及能够调节细胞增殖，分化，存活和/或运动的新的肽化合物。本发明的肽化合物包含ErbB受体的短肽片段，并且能够结合ErbB并调节受体的活性。本发明还涉及能够结合包含本发明的肽序列的表位的抗体，包含肽序列和/或抗体的药物组合物及其用于治疗需要调节ErbB活性的病症的用途。

14. 发明申请

WO2007115571A3 ERBB RECEPTOR-DERIVED PEPTIDE FRAGMENTS 审中-公开
标题翻译： ERBB受体衍生的肽片段
公开(公告)号：WO2007115571A3
公开(公告)日：2008-07-17
申请号：PCT/DK2007000171
申请日：2007-04-03
申请人： ENKAM PHARMACEUTICALS AS , BOCK ELISABETH , BEREZIN VLADIMIR , POVLSEN GRO KLITGAARD
发明人： BOCK ELISABETH , BEREZIN VLADIMIR , POVLSEN GRO KLITGAARD
IPC分类号： C07K14/71 , A61K38/04
CPC分类号： C07K14/71
摘要： The invention relates to new peptide compounds capable of modulating cell proliferation, differentiation, survival and/or motility. The peptide compounds of the invention comprise short peptide fragments of the ErbB receptor and are capable of binding to ErbB and modulating activity of the receptor. The invention also relates to antibodies capable of binding to an epitope comprising a peptide sequence of the invention, pharmaceutical compositions comprising the peptide sequences and/or antibodies and uses thereof for treatment of conditions wherein modulating activity of ErbB is needed.
摘要翻译：本发明涉及能够调节细胞增殖，分化，存活和/或运动性的新肽化合物。本发明的肽化合物包含ErbB受体的短肽片段，并且能够与ErbB结合并调节受体的活性。本发明还涉及能够结合包含本发明肽序列的表位的抗体，包含所述肽序列和/或抗体的药物组合物及其用于治疗需要调节ErbB活性的病症的用途。

15. 发明申请

WO2008022645A3 NCAM FIBRONECTIN TYPE 3 BINDING PEPTIDES 审中-公开
标题翻译： NCAM纤连蛋白3型结合肽
公开(公告)号：WO2008022645A3
公开(公告)日：2008-04-17
申请号：PCT/DK2007050112
申请日：2007-08-21
申请人： ENKAM PHARMACEUTICALS AS , BEREZIN VLADIMIR , BOCK ELISABETH
发明人： BEREZIN VLADIMIR , BOCK ELISABETH
IPC分类号： C07K14/705 , A61K38/00 , C07K7/06 , G01N33/68
CPC分类号： C07K14/70503 , A61K38/00 , C07K7/06
摘要： The present invention discloses the discovery of a new class of NCAM binding peptides, which has a beneficial mode of modulating NCAM function which differs from previously identified NCAM binding compounds. One aspect of the present invention is to provide a compound which binds to a fibronectin type 3 module of NCAM, wherein said compound is capable of modulating NCAM signaling. The invention also relates to pharmaceutical compositions comprising the peptide sequences and uses thereof for treatment of conditions wherein NCAM play a prominent role.
摘要翻译：本发明公开了一类新的NCAM结合肽的发现，其具有调节NCAM功能的有益模式，该模式不同于先前鉴定的NCAM结合化合物。本发明的一个方面是提供与NCAM的3型纤连蛋白模块结合的化合物，其中所述化合物能够调节NCAM信号传导。本发明还涉及包含肽序列的药物组合物及其用于治疗其中NCAM发挥显着作用的病症的用途。

16. 发明申请

WO2007110079A8 TARGETED DELIVERY OF FGFR LIGANDS INTO THE BRAIN 审中-公开
标题翻译：将FGFR配体定向送入脑
公开(公告)号：WO2007110079A8
公开(公告)日：2007-12-13
申请号：PCT/DK2007000152
申请日：2007-03-28
申请人： ENKAM PHARMACEUTICALS AS , BOCK ELISABETH , BEREZIN VLADIMIR , KISELYOV VLADISLAV V
发明人： BOCK ELISABETH , BEREZIN VLADIMIR , KISELYOV VLADISLAV V
IPC分类号： C07K14/43
CPC分类号： C07K14/825
摘要： The present invention relates to a compound consisting of metallothionein (MT) and a peptide sequence, wherein said peptide sequence and metallotionein are bound to each other via a non-covalent bond. A peptide sequence comprised by the compound is a biologically active short peptide sequence which comprises at most 25 amino acid residues. The peptide sequence is capable of binding to and modulating activity of a functional cell receptor, in particular fibroblast growth factor receptor (FGFR). The invention relates to pharmaceutical compositions comprising such compound or such peptide sequence and use of the compound, peptide sequence and pharmaceutical composition for treatment of conditions and diseases where modulating activity of FGFR is beneficial for treatment. In preferred embodiments the use is for treatment of conditions and diseases of the brain including conditions requiring stimulating brain cell proliferation, differentiation and/or survival, stimulating neural plasticity associated with learning and memory, modulating adhesion and motility of cells, in particular cancer cells. The compound of the invention is capable of penetrating the blood brain barrier (BBB).
摘要翻译：本发明涉及由金属硫蛋白（MT）和肽序列组成的化合物，其中所述肽序列和金属蛋白酶通过非共价键彼此结合。由化合物组成的肽序列是包含至多25个氨基酸残基的生物活性短肽序列。肽序列能够结合并调节功能性细胞受体，特别是成纤维细胞生长因子受体（FGFR）的活性。本发明涉及包含这种化合物或这种肽序列的药物组合物，以及该化合物，肽序列和药物组合物用于治疗调节FGFR活性对治疗有利的病症和疾病的用途。在优选的实施方案中，用于治疗脑的病症和疾病包括需要刺激脑细胞增殖，分化和/或存活的条件，刺激与学习和记忆相关的神经可塑性，调节细胞特别是癌细胞的粘附和运动性。本发明的化合物能够穿透血脑屏障（BBB）。

17. 发明申请

WO2007045243A3 NOVEL FGF RECEPTOR BINDING COMPOUNDS COMPRISING PEPTIDE FRAGMENTS OF NEURAL CELL ADHESION MOLECULE L1 审中-公开
标题翻译：包含神经细胞粘附分子的肽片段的新型FGF受体结合化合物
公开(公告)号：WO2007045243A3
公开(公告)日：2007-10-18
申请号：PCT/DK2006000580
申请日：2006-10-16
申请人： ENKAM PHARMACEUTICALS AS , BEREZIN VLADIMIR , BOCK ELISABETH
发明人： BEREZIN VLADIMIR , BOCK ELISABETH
IPC分类号： C07K14/705 , A61P25/00 , C07K7/06 , C07K7/08
CPC分类号： C07K14/70503 , C07K14/78
摘要： The present invention relates to novel peptide compounds capable of interacting with Fibroblast Growth Factor Receptor (FGFR) comprising an amino acid sequence of 5 to 105 amino acid residues which comprises an amino acid motif of the formula x'-(x) n -x p -(x) n -x', wherein x' is a basic amino acid residue, x p is a hydrophobic amino acid residue and (x) n is a sequence of any amino acid residues, wherein n is an integer from 0 to 3. Preferably, the compounds of the invention comprise a fragment of neural cell adhesion molecule L1. The invention also relates to uses of the compounds for treatment and/or prevention of different pathological conditions wherein FGFR and /or L1 play a role in pathology and/or recovery from the disease. Accordingly, pharmaceutical compositions comprising the compounds of the invention are also concerned.
摘要翻译：本发明涉及能够与成纤维细胞生长因子受体（FGFR）相互作用的新型肽化合物，其包含5至105个氨基酸残基的氨基酸序列，其包含式x' - （x）n的氨基酸基序其中x'为碱性氨基酸残基，x为p为 - （x）n 疏水性氨基酸残基和（x）N是任何氨基酸残基的序列，其中n是0至3的整数。优选地，本发明的化合物包含神经细胞粘附的片段分子L1。本发明还涉及该化合物用于治疗和/或预防不同病理状况的用途，其中FGFR和/或L1在疾病的病理学和/或恢复中发挥作用。因此，也涉及包含本发明化合物的药物组合物。

18. 发明申请

WO2008086813A3 PEPTIDES DERIVED FROM PROTEINS OF THE INSULIN SUPER-FAMILY 审中-公开
标题翻译：从胰岛素超家族蛋白衍生的肽
公开(公告)号：WO2008086813A3
公开(公告)日：2008-12-04
申请号：PCT/DK2008050009
申请日：2008-01-18
申请人： UINV KOBENHAVNS , BOCK ELISABETH , BEREZIN VLADIMIR
发明人： BOCK ELISABETH , BEREZIN VLADIMIR
IPC分类号： C07K14/65 , A61K38/30 , A61K39/395 , C07K7/04 , C12N15/09
CPC分类号： C07K14/62 , A61K38/00 , C07K7/06 , C07K7/08 , C07K14/65
摘要： The present invention relates to peptides derived from members of the insulin super-family. The peptides preferably bind and modify the activation status of receptors of proteins of the insulin super-family. The invention also relates to a pharmaceutical composition containing a compound comprising one or more of the peptides capable of promoting cell differentiation and/or modulating neuronal plasticity and/or proliferation of neural cells, and/or modulating survival and/or regeneration of cells expressing a receptor of a protein of the insulin super-family. The peptides may further be used to treat conditions affecting the peripheral and/or the central nervous system and/or muscles and other tissues or for treatment of normal, degenerated or damaged cells which express receptors of one or more proteins of the insulin super-family.
摘要翻译：本发明涉及衍生自胰岛素超家族成员的肽。肽优选结合并修饰胰岛素超家族的蛋白质的受体的活化状态。本发明还涉及包含一种或多种能够促进神经细胞的神经元可塑性和/或神经细胞增殖的调节和/或调节神经细胞的可塑性和/或增殖的一种或多种肽的化合物的药物组合物，和/或调节表达细胞的细胞的存活和/或再生胰岛素超家族蛋白的受体。肽可以进一步用于治疗影响外周和/或中枢神经系统和/或肌肉和其他组织的病症，或用于治疗表达胰岛素超家族的一种或多种蛋白质的受体的正常，退化或损伤的细胞。

19. 发明申请

WO2007071248A8 NEURITOGENIC AND NEURONAL SURVIVAL PROMOTING PEPTIDES DERIVED FROM THE FAMILY OF S-100 PROTEINS 审中-公开
标题翻译：从S-100蛋白家族衍生的神经生长因子和神经营养促进肽
公开(公告)号：WO2007071248A8
公开(公告)日：2007-09-13
申请号：PCT/DK2006000730
申请日：2006-12-20
申请人： COPENHAGEN UNIVERSITY , BOCK ELISABETH , BEREZIN VLADIMIR , KIRYUSHKO DARYA
发明人： BOCK ELISABETH , BEREZIN VLADIMIR , KIRYUSHKO DARYA
IPC分类号： C07K14/43 , A61K38/17 , C07K14/47
CPC分类号： C07K14/4728 , A61K38/00
摘要： The present invention relates to peptide fragments derived from proteins of the S-100 family promoting neural cell survival, differentiation and proliferation. The invention further relates to pharmaceutical compositions comprising said peptide fragments and uses thereof for treatment of diseases and conditions where the effects of stimulating neural cell proliferation, differentiation and/or survival, and/or stimulating neural plasticity associated with learning and memory are beneficial for treatment.
摘要翻译：本发明涉及衍生自S-100家族蛋白质的肽片段，促进神经细胞存活，分化和增殖。本发明还涉及包含所述肽片段的药物组合物及其用于治疗刺激神经细胞增殖，分化和/或存活和/或刺激与学习和记忆相关的神经可塑性的效果有益于治疗的疾病和病症的用途。

20. 发明申请

WO2010136031A1 FIBROBLAST GROWTH FACTOR RECEPTOR-DERIVED PEPTIDES BINDING TO NCAM 审中-公开
标题翻译：纤维母细胞生长因子受体衍生肽与NCAM结合
公开(公告)号：WO2010136031A1
公开(公告)日：2010-12-02
申请号：PCT/DK2009050119
申请日：2009-05-27
申请人： UNIV KOEBENHAVN , BEREZIN VLADIMIR , BOCK ELISABETH , KOCHOYAN ARTHUR
发明人： BEREZIN VLADIMIR , BOCK ELISABETH , KOCHOYAN ARTHUR
IPC分类号： C07K14/71
CPC分类号： C07K16/42 , A61K38/179 , C07K2317/70
摘要： The present invention relates to the use of peptides that are capable of binding to, and modulating the activity of NCAM. The peptides are peptide fragments of FGFRs. They are derived from two distinct binding sites for binding of the immunoglobulin-like module 2 of FGFR to NCAM F3 modules 1-2. The invention further relates to use of said peptides for the production of a medicament for the treatment of different pathological conditions, wherein NCAM and/or FGFRs play a prominent role.
摘要翻译：本发明涉及能够结合并调节NCAM活性的肽的用途。肽是FGFR的肽片段。它们衍生自用于结合FGFR的免疫球蛋白样模块2与NCAM F3模块1-2的两个不同的结合位点。本发明还涉及所述肽在生产用于治疗不同病理状况的药物中的用途，其中NCAM和/或FGFRs起着重要作用。

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