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1. 发明授权

US10420738B2 Compounds as modulators of a mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction 有权
公开(公告)号：US10420738B2
公开(公告)日：2019-09-24
申请号：US14969598
申请日：2015-12-15
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Norbert Odolczyk , Piotr Zielenkiewicz , Grzegorz Wieczorek , Aleksander Edelman , Danielle Tondelier , Janine Fritsch
IPC分类号： C07C233/65 , A61K31/194 , C07D219/10 , C07D473/30 , C07F9/30 , C07C235/84 , C07D401/12 , C07D473/22 , A61K31/496 , A61K31/663 , A61K31/52
摘要： An exemplary embodiment relates to novel protein modulators capable of altering function of the mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. The invention provides compositions, pharmaceutical preparations and methods of correcting the cellular alteration of a mutant CFTR protein wherein the CFTR mutation is a mutation ΔF508-CFTR, or another mutation of class II.

2. 发明授权

US09505806B2 DNA vaccine, method of inducing the immune response, method of immunisation, antibodies specifically recognising the H5 haemagglutinin of an influenza virus and use of the DNA vaccine 有权
标题翻译： DNA疫苗，诱导免疫应答的方法，免疫方法，特异性识别流感病毒的H5血凝素的抗体和使用DNA疫苗
公开(公告)号：US09505806B2
公开(公告)日：2016-11-29
申请号：US14346664
申请日：2012-09-21
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Agnieszka Sirko , Anna Góra-Sochacka , Włodzimierz Zagórski-Ostoja , Anna Stachyra , Róza Sawicka , Bogusław Szewczyk , Beata Gromadzka , Violetta Sączyńska , Katarzyna Florys , Zenon Minta , Krzysztof Śmietanka
IPC分类号： A61K39/145 , C07K14/005 , A61K39/12 , A61K39/39 , C07K16/10 , A61K39/00
CPC分类号： C07K14/005 , A61K39/12 , A61K39/145 , A61K39/39 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/552 , A61K2039/55522 , A61K2039/55533 , A61K2039/55555 , C07K16/1018 , C12N2760/16122 , C12N2760/16134
摘要： The object of the invention is a DNA vaccine, method of inducing the immune response, antibodies specifically recognizing the haemagglutinin H5 of an influenza virus and application of the DNA vaccine. According to the invention, one or two-fold immunization of hens with DNA vaccine containing a cDNA encoding the modified H5 haemagglutinin HA protein, i.e. with the deletion of the cleavage site between HA subunits (this provides for greater safety of the vaccines). Moreover, the encoding region of the HA is modified in such a way that protein production in the bird cells should achieve maximal yield. The main modification is codon optimization for the hens and deletion of the site of proteolytic cleavage between subunits HA1 and HA2.
摘要翻译：本发明的目的是DNA疫苗，诱导免疫应答的方法，特异性识别流感病毒的血凝素H5的抗体和DNA疫苗的应用。根据本发明，用含有编码修饰的H5血凝素HA蛋白的cDNA的DNA疫苗进行一次或两次免疫，即在HA亚基之间缺失切割位点（这提供了疫苗的更大的安全性）。此外，HA的编码区域以使鸟类细胞中的蛋白质产生达到最大产量的方式被修饰。主要修饰是母鸡的密码子优化和亚基HA1和HA2之间的蛋白水解切割位点的缺失。

3. 发明申请

US20140255343A1 DNA VACCINE, METHOD OF INDUCING THE IMMUNE RESPONSE, METHOD OF IMMUNISATION, ANTIBODIES SPECIFICALLY RECOGNISING THE H5 HAEMAGGLUTININ OF AN INFLUENZA VIRUS AND USE OF THE DNA VACCINE 有权
标题翻译： DNA疫苗，诱导免疫应答的方法，免疫方法，特异性识别流感病毒的H5 HAEMAGGLUTININ的抗体和DNA疫苗的使用
公开(公告)号：US20140255343A1
公开(公告)日：2014-09-11
申请号：US14346664
申请日：2012-09-21
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Agnieszka Sirko , Anna Gora-Sochacka , Wlodzimierz Zagorski-Ostoja , Anna Stachyra , Roza Sawicka , Boguslaw Szewczyk , Beata Gromadzka , Violetta Saczynska , Katarzyna Florys , Zenon Minta , Krzysztof Smietanka
IPC分类号： C07K14/005 , C07K16/10 , A61K39/145 , A61K39/39
CPC分类号： C07K14/005 , A61K39/12 , A61K39/145 , A61K39/39 , A61K2039/53 , A61K2039/54 , A61K2039/545 , A61K2039/552 , A61K2039/55522 , A61K2039/55533 , A61K2039/55555 , C07K16/1018 , C12N2760/16122 , C12N2760/16134
摘要： The object of the invention is a DNA vaccine, method of inducing the immune response, antibodies specifically recognising the haemagglutinin H5 of an influenza virus and application of the DNA vaccine. According to the invention, one or two-fold immunisation of hens with DNA vaccine containing a cDNA encoding the modified H5 haemagglutinin HA protein, i.e. with the deletion of the cleavage site between HA subunits (this provides for greater safety of the vaccines). Moreover, the encoding region of the HA is modified in such a way that protein production in the bird cells should achieve maximal yield. The main modification is codon optimisation for the hens and deletion of the site of proteolytic cleavage between subunits HA1 and HA2.
摘要翻译：本发明的目的是DNA疫苗，诱导免疫应答的方法，特异性识别流感病毒的血凝素H5的抗体和DNA疫苗的应用。根据本发明，用含有编码修饰的H5血凝素HA蛋白的cDNA的DNA疫苗进行一次或两次免疫，即在HA亚基之间缺失切割位点（这提供了疫苗的更大的安全性）。此外，HA的编码区域以使鸟类细胞中的蛋白质产生达到最大产量的方式被修饰。主要修饰是母鸡的密码子优化和亚基HA1和HA2之间的蛋白水解切割位点的缺失。

4. 发明授权

US10463639B2 Compounds as modulators of a mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction 有权
公开(公告)号：US10463639B2
公开(公告)日：2019-11-05
申请号：US14969609
申请日：2015-12-15
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Norbert Odolczyk , Piotr Zielenkiewicz , Grzegorz Wieczorek , Aleksander Edelman , Danielle Tondelier , Janine Fritsch
IPC分类号： C07D473/30 , A61K31/194 , C07C233/65 , C07D219/10 , C07F9/30 , C07C235/84 , C07D401/12 , C07D473/22 , A61K31/496 , A61K31/663 , A61K31/52
摘要： An exemplary embodiment relates to novel protein modulators capable of altering function of the mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. The invention provides compositions, pharmaceutical preparations and methods of correcting the cellular alteration of a mutant CFTR protein wherein the CFTR mutation is a mutation ΔF508-CFTR, or another mutation of class II.

5. 发明公开

US20230152333A1 METHOD OF DIFFERENTIATING OF A CHRONIC KIDNEY DISEASE OR GLOMERULOPATHY, METHOD OF MONITORING A RESPONSE TO TREATMENT OF A CHRONIC KIDNEY DISEASE OR GLOMERULOP ATHY IN A SUBJECT AND A METHOD OF TREATMENT OF A CHRONIC KIDNEY DISEASE OR GLOMERULOPATHY 审中-公开
公开(公告)号：US20230152333A1
公开(公告)日：2023-05-18
申请号：US17906914
申请日：2020-11-10
申请人： WARSZAWSKI UNIWERSYTET MEDYCZNY , INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Krzysztof MUCHA , Radoslaw ZAGOZDZON , Bartosz FORONCEWICZ , Leszek PACZEK , Barbara MOSZCZUK , Natalia KRATA , Dominik CYSEWSKI , Dominik DOMANSKI , Michal DADLEZ , Michal BURDUKIEWICZ
IPC分类号： G01N33/68
CPC分类号： G01N33/6893 , G01N2800/347 , G01N2800/56
摘要： The object of the present invention is a method of diagnosis of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: (a) determination of the level of at least five, or at least six or at least seven protein markers selected from the group consisting of Ig gamma-2 chain C region (IGHG2), serum albumin (ALB), ceruloplasmin (CP), thrombin (F2), haptoglobin beta chain (HP), alpha-1-antitrypsin (SERPINA1), Ig kappa chain V-1 region HK102 (IGKV1-5), myoglobin (MB), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin(TF), alpha-1 B-glycoprotein (A1 BG), Igkappa chain V-I region Daudi (P04432), ganglioside GM2 activator (GM2A), alpha-1-acid glycoprotein 2 (ORM2), zinc-alpha-2-glycoprotein (AZGP1), afamin (AFM), NHL repeat-containing protein 3 (NHLC3), inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2); wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from said subject and (b) assigning a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy based on the results of the assay of step (a), wherein this involves: (i) determining the probability of the patient having a particular glomerulopathy based on the level of a first marker one of the markers determined in step (a), the probability being estimated based on the levels of said first marker determined in subjects known to have the particular glomerulopathy; (ii) determining the probability of the patient having a particular glomerulopathy based on the level of a second marker one of the markers determined in step (a), the probability being estimated based on the levels of said second marker determined in subjects known to have the particular glomerulopathy; (iii) conducting the calculations of (i) as required for further markers determined in step (a); (iv) determining the probability of the subject, providing the urine sample tested in step (a), having or being at a risk of each of the assessed glomerulopathies as a multiplication product of the corresponding probabilities obtained from each marker in (i)-(iii). A further object of the present invention is a method of monitoring a response to treatment, comprising the following steps: (a) determination of the level, at a first point in time, of at least five, or at least six or at least seven protein markers selected from the group consisting of Ig gamma-2 chain C region (IGHG2), serum albumin (ALB), ceruloplasmin (CP), thrombin (F2), haptoglobin beta chain (HP), alpha-1-antitrypsin (SERPINA1), Ig kappa chain V-1 region HK102 (IGKV1-5), myoglobin (MB), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF), alpha-1 B-glycoprotein (A1 BG), Ig kappa chain V-I region Daudi (P04432), ganglioside GM2 activator (GM2A), alpha-1-acid glycoprotein 2 (ORM2), zinc-alpha-2-glycoprotein (AZGP1), afamin (AFM), NHL repeat-containing protein 3 (NHLC3), inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2); wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from a subject; (b) repeating the assay of step (a) at a later point in time after a period wherein the subject was undergoing a treatment; (c) assessing a response to said treatment by comparing the results of the assays of steps (a) and (b), wherein lower marker levels after treatment are indicative of a positive response to treatment. A further object of the present invention is a method of treatment of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: (a) determination of the level of at least five, or at least six or at least seven protein markers selected from the group consisting of Ig gamma-2 chain C region (IGHG2), serum albumin (ALB), ceruloplasmin (CP), thrombin (F2), haptoglobin beta chain (HP), alpha-1-antitrypsin (SERPINA1), Ig kappa chain V-1 region HK102 (IGKV1-5), myoglobin (MB), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF), alpha-1 B-glycoprotein (A1 BG), Ig kappa chain V-I region Daudi (P04432), ganglioside GM2 activator (GM2A), alpha-1-acid glycoprotein 2 (ORM2), zinc-alpha-2-glycoprotein (AZGP1), afamin (AFM), NHL repeat-containing protein 3 (NHLC3), inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2); wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from said subject and (b) assigning a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy based on the results of the assay of step (a), wherein this involves: (i) determining the probability of the patient having a particular glomerulopathy based on the level of a first marker one of the markers determined in step (a), the probability being estimated based on the levels of said first marker determined in subjects known to have the particular glomerulopathy; (ii) determining the probability of the patient having a particular glomerulopathy based on the level of a second marker one of the markers determined in step (a), the probability being estimated based on the levels of said second marker determined in subjects known to have the particular glomerulopathy; (iii) conducting the calculations of (i) as required for further markers determined in step (a); (iv) determining the probability of the subject, providing the urine sample tested in step (a), having or being at a risk of each of the assessed glomerulopathies as a multiplication product of the corresponding probabilities obtained from each marker in (i)-(iii); (c) administering treatment against a chronic kidney disease (CKD) or glomerulopathy in the subject evaluated in step (b) as having or being at a risk of chronic kidney disease or glomerulopathy, according to the particular glomerulopathy determined in step (b) (iv).

6. 发明申请

US20230137242A1 METHOD OF SCREENING FOR A CHRONIC KIDNEY DISEASE OR GLOMERULOPATHY METHOD OF MONITORING A RESPONSE TO TREATMENT OF A CHRONIC KIDNEY DISEASE OR GLOMERULOPATHY IN A SUBJECT AND A METHOD OF TREATMENT OF A CHRONIC KIDNEY DISEASE OR GLOMERULOPATHY 有权
公开(公告)号：US20230137242A1
公开(公告)日：2023-05-04
申请号：US17906922
申请日：2020-11-10
申请人： WARSZAWSKI UNIWERSYTET MEDYCZNY , INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Krzysztof MUCHA , Radoslaw ZAGOZDZON , Bartosz FORONCEWICZ , Leszek PACZEK , Barbara MOSZCZUK , Natalia KRATA , Dominik CYSEWSKI , Dominik DOMANSKI , Michal DADLEZ , Michal BURDUKIEWICZ
IPC分类号： G01N33/68
摘要： The object of the present invention is a method of diagnosis of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: (a) determination of the level of at least three or four or five protein markers selected from the group consisting of serum albumin (ALB), alpha-1-antitrypsin (serpinal), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF) and trefoil factor 1 (TFF), wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from said subject and (b) assigning a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy or not having nor being at a risk thereof based on the results of the assay of step (a), wherein this involves estimating a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy or not having nor being at a risk thereof based on the level of each of the marker levels determined in (a)), the probability being estimated based on the levels of each of the markers as determined in subjects known to suffer from a glomerulopathy or a chronic kidney disease; and determining the probability of the subject, providing the urine sample tested in step (a), having or being at a risk of a glomerulopathy or a chronic kidney disease or not having nor being at a risk thereof as a product of the corresponding probabilities obtained from each marker. A further object of the present invention is a method of monitoring a response to treatment of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: a) measurement of the level, at a first point in time, for three or four or five of the markers selected from a group consisting of serum albumin (ALB), alpha-1-antitrypsin (serpinal), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF) and trefoil factor 1 (TFF), wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from a subject; b) repeating the assay of step (a) at a later point in time after a period wherein the subject was undergoing a treatment; c) assessing a response to said treatment by comparing the results of the assays of steps (a) and (b), wherein lower marker levels after treatment are indicative of a positive response to treatment. A further object of the present invention is a method of treatment of a chronic kidney disease (CKD) or glomerulopathy in a subject, comprising the following steps: (a) determination of the level of at least three or four or five protein markers selected from the group consisting of serum albumin (ALB), alpha-1-antitrypsin (serpinal), alpha-1-acid glycoprotein 1 (ORM1), serotransferrin (TF) and trefoil factor 1 (TFF), wherein said markers also comprise the non-full-length fragments thereof, in a urine sample from said subject and (b) assigning a probability of the subject having or being at a risk of chronic kidney disease or glomerulopathy based on the results of the assay of step (a); (c) administering treatment against a chronic kidney disease (CKD) or glomerulopathy in the subject evaluated in step (b) as having or being at a risk of chronic kidney disease or glomerulopathy.

7. 发明授权

US10398665B2 Compounds as modulators of a mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction 有权
公开(公告)号：US10398665B2
公开(公告)日：2019-09-03
申请号：US14969573
申请日：2015-12-15
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Norbert Odolczyk , Piotr Zielenkiewicz , Grzegorz Wieczorek , Aleksander Edelman , Danielle Tondelier , Janine Fritsch
IPC分类号： A61K31/663 , A61K31/194 , C07C233/65 , C07D219/10 , C07D473/30 , C07F9/30 , C07C235/84 , C07D401/12 , C07D473/22 , A61K31/496 , A61K31/52
摘要： An exemplary embodiment relates to novel protein modulators capable of altering function of the mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. An exemplary embodiment provides compositions, pharmaceutical preparations and methods of correcting the cellular alteration of a mutant CFTR protein wherein the CFTR mutation is a mutation ΔF508-CFTR, or another mutation of class II.

8. 发明申请

US20160101107A1 COMPOUNDS AS MODULATORS OF A MUTANT CFTR PROTEIN AND THEIR USE FOR TREATING DISEASES ASSOCIATED WITH CFTR PROTEIN MALFUNCTION 有权
标题翻译：作为突变型CFTR蛋白的调节剂的化合物及其用于治疗与CFTR蛋白质功能相关的疾病的用途
公开(公告)号：US20160101107A1
公开(公告)日：2016-04-14
申请号：US14969598
申请日：2015-12-15
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Norbert Odolczyk , Piotr ZIELENKIEWICZ , Grzegorz WIECZOREK , Aleksander EDELMAN , Danielle TONDELIER , Janine FRITSCH
IPC分类号： A61K31/52
摘要： An exemplary embodiment relates to novel protein modulators capable of altering function of the mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. The invention provides compositions, pharmaceutical preparations and methods of correcting the cellular alteration of a mutant CFTR protein wherein the CFTR mutation is a mutation ΔF508-CFTR, or another mutation of class II.
摘要翻译：示例性实施方案涉及能够改变突变CFTR蛋白的功能的新型蛋白质调节剂及其用于治疗与CFTR蛋白质功能障碍相关的疾病的用途。本发明提供了组合物，药物制剂和校正突变CFTR蛋白质的细胞改变的方法，其中CFTR突变是突变，Dgr; F508-CFTR或II类的另一个突变。

9. 发明申请

US20160272966A1 Method of using a miR172 Molecule for Decreasing Inflammation 审中-公开
标题翻译：使用miR172分子减少炎症的方法
公开(公告)号：US20160272966A1
公开(公告)日：2016-09-22
申请号：US14913650
申请日：2014-08-13
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN , UNIWERSYTET IM. ADAMA MICKIEWICZA W POZNANIU
发明人： Anna Lukasik , Piotr Zielenkiewicz , Zofia Szweykowska-Kulinska , Leszek Paczek , Maria Nowaczyk
IPC分类号： C12N15/113
CPC分类号： C12N15/113 , C12N2310/141
摘要： An exemplary embodiment relates to a method of using a plant-derived miR172 molecule or its synthetic equivalent, selected from amongst miR172a or miR172b, for decreasing inflammatory processes in an organism, a method of decreasing B and T lymphocyte proliferation, as well as a method of reducing protein FAN (Factor Associated with Neutral Sphingomyelinase Activation) level. Exemplary embodiments provide a novel therapeutic method based on miRNA molecules, which through the interaction with mRNA encoding FAN protein, negatively regulate its expression and decrease the inflammatory response of the organism.
摘要翻译：示例性实施方案涉及使用植物来源的miR172分子或其选自miR172a或miR172b的合成等同物以减少生物体内炎症过程的方法，降低B和T淋巴细胞增殖的方法，以及方法的降低蛋白质FAN（与中性鞘磷脂酶激活相关的因子）水平。示例性实施方案提供了基于miRNA分子的新型治疗方法，其通过与编码FAN蛋白的mRNA的相互作用负调节其表达并降低生物体的炎症反应。

10. 发明申请

US20160113896A1 COMPOUNDS AS MODULATORS OF A MUTANT CFTR PROTEIN AND THEIR USE FOR TREATING DISEASES ASSOCIATED WITH CFTR PROTEIN MALFUNCTION 审中-公开
公开(公告)号：US20160113896A1
公开(公告)日：2016-04-28
申请号：US14969609
申请日：2015-12-15
申请人： INSTYTUT BIOCHEMII I BIOFIZYKI PAN
发明人： Norbert Odolczyk , Piotr ZIELENKIEWICZ , Grzegorz WIECZOREK , Aleksander EDELMAN , Danielle TONDELIER , Janine FRITSCH
IPC分类号： A61K31/194
摘要： An exemplary embodiment relates to novel protein modulators capable of altering function of the mutant CFTR protein and their use for treating diseases associated with CFTR protein malfunction. The invention provides compositions, pharmaceutical preparations and methods of correcting the cellular alteration of a mutant CFTR protein wherein the CFTR mutation is a mutation ΔF508-CFTR, or another mutation of class II.

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