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1.发明公开公开(公告)号：US20230265142A1
公开(公告)日：2023-08-24
申请号：US17943875
申请日：2022-09-13
发明人： Michael Blaber , Liam M. Longo
IPC分类号： C07K14/50
CPC分类号： C07K14/501
摘要： A synthetic foldable protein has a tertiary structure emulating the tertiary structure of a reference foldable protein. The reference foldable protein has a folding nucleus peptide sequence associated with folding the reference foldable protein. The synthetic foldable protein also has a peptide sequence including the folding nucleus peptide sequence and at least one repeat thereof.
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公开(公告)号：US20190192630A1
公开(公告)日：2019-06-27
申请号：US16295950
申请日：2019-03-07
发明人： Jae Myoung Suh , Michael Downes , Ronald M. Evans , Annette Atkins , Ruth T. Yu
IPC分类号： A61K38/18 , A61K31/4439 , A61K31/422 , A61K31/7088 , C07K14/50 , A61K45/06 , A61K31/421
CPC分类号： A61K38/1825 , A61K31/421 , A61K31/422 , A61K31/4439 , A61K31/7088 , A61K45/06 , C07K14/501 , A61K2300/00
摘要： The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a β-Klotho-binding protein, an FGFR1c-binding protein, a β-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.
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3.发明申请公开(公告)号：US20180228869A1
公开(公告)日：2018-08-16
申请号：US15952516
申请日：2018-04-13
发明人： Ronald M. Evans , Michael Downes , Annette Atkins , Ruth T. Yu
IPC分类号： A61K38/18 , A61P3/10 , A61K31/573 , A61K45/06
CPC分类号： A61K38/1825 , A61K31/573 , A61K31/7088 , A61K45/06 , A61P3/10 , C07K14/50 , C07K14/501 , C07K2319/70 , A61K2300/00
摘要： Methods of using FGF1 analogs, such as FGF1 mutant proteins having an N-terminal deletion, point mutation(s), or combinations thereof, to reduce blood glucose levels in subjects with steroid-induced diabetes, hypercortisolemia, or diabetes due to treatment with an antipsychotic agent, are provided. Such mutant FGF1 proteins can be part of a chimeric protein that includes a β-Klotho-binding protein, an FGFR1-binding protein, a β-Klotho-binding protein and a FGFR1-binding protein, a C-terminal region from FGF19 or FGF21.
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公开(公告)号：US09926356B2
公开(公告)日：2018-03-27
申请号：US15289544
申请日：2016-10-10
申请人： New York University
发明人： Moosa Mohammadi , Regina Goetz
CPC分类号： C07K14/50 , A61K38/1825 , A61K45/06 , C07K14/501 , C07K14/503 , C07K2319/00 , A61K2300/00
摘要： The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of the present invention.
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5.发明申请公开(公告)号：US20170362289A1
公开(公告)日：2017-12-21
申请号：US15698130
申请日：2017-09-07
发明人： Michael Blaber , Liam M. Longo
CPC分类号： C07K14/501
摘要： A method of making a synthetic foldable having a tertiary structure emulating the tertiary structure of a reference foldable protein is described. The method includes determining a folding nucleus peptide sequence associated with folding the reference foldable protein. The synthetic foldable protein is synthesized by including the determined folding nucleus peptide sequence and at least one repeat thereof in the peptide sequence of the synthetic foldable protein.
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6.发明授权公开(公告)号：US09783587B1
公开(公告)日：2017-10-10
申请号：US14707691
申请日：2015-05-08
发明人： Michael Blaber , Liam M. Longo
CPC分类号： C07K14/501
摘要： A method of making a synthetic foldable having a tertiary structure emulating the tertiary structure of a reference foldable protein is described. The method includes determining a folding nucleus peptide sequence associated with folding the reference foldable protein. The synthetic foldable protein is synthesized by including the determined folding nucleus peptide sequence and at least one repeat thereof in the peptide sequence of the synthetic foldable protein.
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7.发明申请公开(公告)号：US20170096465A1
公开(公告)日：2017-04-06
申请号：US15295833
申请日：2016-10-17
发明人： Michael Blaber , Jihun LEE
IPC分类号： C07K14/50
CPC分类号： C07K14/50 , A61K38/00 , A61K38/18 , A61K38/1825 , C07H21/00 , C07K14/501 , C07K2319/21
摘要： Mutant fibroblast growth factor (FGF) proteins having a polypeptide sequence with a high sequence identity to proteins encoded by members of the Fgf-1 subfamily of genes from a mammalian species, such as human, and with a specific amino acid substitution of an alanine at a position corresponding to amino acid position 66 of human FGF-1 with a cysteine and/or a specific amino acid substitution of a phenylalanine at a position corresponding to amino acid position 132 of human FGF-1 with a tryptophan (based on the 140 amino acid numbering scheme of human FGF-1) are provided. Other amino acid mutations or substitutions may be combined. Polynucleotide sequences encoding the mutant FGF proteins and host cells containing such polynucleotide sequences are provided. Methods of administering a mutant FGF protein to an individual to treat an ischemic condition or disease or a wound or tissue injury are also provided.
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8.发明申请公开(公告)号：US20170096464A1
公开(公告)日：2017-04-06
申请号：US15295804
申请日：2016-10-17
发明人： Michael Blaber , Jihun LEE
IPC分类号： C07K14/50
CPC分类号： C07K14/50 , A61K38/00 , A61K38/18 , A61K38/1825 , C07H21/00 , C07K14/501 , C07K2319/21
摘要： Mutant fibroblast growth factor (FGF) proteins having a polypeptide sequence with a high sequence identity to proteins encoded by members of the Fgf-1 subfamily of genes from a mammalian species, such as human, and with a specific amino acid substitution of an alanine at a position corresponding to amino acid position 66 of human FGF-1 with a cysteine and/or a specific amino acid substitution of a phenylalanine at a position corresponding to amino acid position 132 of human FGF-1 with a tryptophan (based on the 140 amino acid numbering scheme of human FGF-1) are provided. Other amino acid mutations or substitutions may be combined. Polynucleotide sequences encoding the mutant FGF proteins and host cells containing such polynucleotide sequences are provided. Methods of administering a mutant FGF protein to an individual to treat an ischemic condition or disease or a wound or tissue injury are also provided.
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9.发明授权公开(公告)号：US09469680B2
公开(公告)日：2016-10-18
申请号：US14593107
申请日：2015-01-09
发明人： Michael Blaber , Jihun Lee
CPC分类号： C07K14/50 , A61K38/00 , A61K38/18 , A61K38/1825 , C07H21/00 , C07K14/501 , C07K2319/21
摘要： Mutant fibroblast growth factor (FGF) proteins having a polypeptide sequence with a high sequence identity to proteins encoded by members of the Fgf-1 subfamily of genes from a mammalian species, such as human, and with a specific amino acid substitution of an alanine at a position corresponding to amino acid position 66 of human FGF-1 with a cysteine and/or a specific amino acid substitution of a phenylalanine at a position corresponding to amino acid position 132 of human FGF-1 with a tryptophan (based on the 140 amino acid numbering scheme of human FGF-1) are provided. Other amino acid mutations or substitutions may be combined. Polynucleotide sequences encoding the mutant FGF proteins and host cells containing such polynucleotide sequences are provided. Methods of administering a mutant FGF protein to an individual to treat an ischemic condition or disease or a wound or tissue injury are also provided.
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公开(公告)号：US09464126B2
公开(公告)日：2016-10-11
申请号：US13837880
申请日：2013-03-15
申请人： New York University
发明人： Moosa Mohammadi , Regina Goetz
CPC分类号： C07K14/50 , A61K31/00 , A61K38/1825 , A61K45/06 , C07K14/501 , C07K14/503 , C07K2319/00 , G01N2333/50 , G01N2500/02 , G01N2800/042 , A61K2300/00
摘要： The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor (“FGF”) and the C-terminus includes a C-terminal portion of an FGF21 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the βKlotho-FGF receptor complex involving the use of chimeric proteins of the present invention.
摘要翻译： 本发明涉及包含与C-末端偶联的N-末端的嵌合蛋白，其中N末端包括一部分旁分泌成纤维细胞生长因子（“FGF”），并且C-末端包括C末端 部分FGF21分子。 与没有修饰的部分相比，旁分泌FGF的部分被修饰以降低对肝素和/或硫酸乙酰肝素的结合亲和力。 本发明还涉及包含根据本发明的嵌合蛋白质的药物组合物，用于治疗患有糖尿病，肥胖或代谢综合征的受试者的方法，以及筛选具有增强的对βKlotho-FGF受体复合物的结合亲和力的化合物的方法，涉及 使用本发明的嵌合蛋白。
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