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1. 发明申请

US20200348286A1 OLIGONUCLEOTIDES FOR INDUCING PATERNAL UBE3A EXPRESSION 审中-公开
公开(公告)号：US20200348286A1
公开(公告)日：2020-11-05
申请号：US16933445
申请日：2020-07-20
申请人： ROCHE INNOVATION CENTER COPENHAGEN A/S , HOFFMANN-LA ROCHE INC.
发明人： Veronica Costa , Maj HEDTJÄRN , Marius Hoener , Ravi Jagasia , Mads Aaboe Jensen , Christoph Patsch , Lykke Pedersen , Søren Vestergaard Rasmussen
IPC分类号： G01N33/50 , C12N5/0797 , C12N15/11 , C12N15/113 , C12N5/0793 , C12N5/00 , C12N5/074
摘要： The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

2. 发明申请

US20160326150A1 N-PHENYL-LACTAM DERIVATIVES CAPABLE OF STIMULATING NEUROGENESIS AND THEIR USE IN THE TREATMENT OF NEUROLOGICAL DISORDERS 有权
标题翻译：刺激神经细胞的N-PHENYL-LACTAM衍生物及其在治疗神经疾病中的应用
公开(公告)号：US20160326150A1
公开(公告)日：2016-11-10
申请号：US15213622
申请日：2016-07-19
申请人： Hoffmann-La Roche Inc.
发明人： Roland Jakob-Roetne , Juergen Wichmann , Jens-Uwe Peters , Ravi Jagasia
IPC分类号： C07D413/10 , C07D401/10 , C07D401/14 , C07D403/10
CPC分类号： C07D413/10 , C07D401/10 , C07D401/14 , C07D403/10
摘要： The present invention relates to compounds of the general formula I wherein Het, R1, R2, W and X are as defined herein. Compounds of formula I are useful for treating neuropsychiatric disorders.

3. 发明授权

US09440962B2 Benzisoxazoles 有权
标题翻译：苯并恶唑
公开(公告)号：US09440962B2
公开(公告)日：2016-09-13
申请号：US14602541
申请日：2015-01-22
申请人： Hoffmann-La Roche Inc.
发明人： Simona M. Ceccarelli , Ravi Jagasia , Roland Jakob-Roetne , Juergen Wichmann
IPC分类号： A61K31/41 , C07D413/14 , C07D413/04 , C07D231/12 , C07D401/04
CPC分类号： C07D413/14 , C07D231/12 , C07D401/04 , C07D413/04
摘要： The present invention relates to compounds of general formula wherein Ar1/Ar2 are phenyl or a 5 or 6-membered heteroaryl; R1/R2 is hydrogen, halogen, lower alkyl, CF3 or lower alkoxy; n,m are 1 or 2; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof, with the exception of the compound 2,1-benzisoxazole, 3-(4-chlorophenyl)-5-(1-phenyl-1H-pyrazol-5 -yl)-. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.
摘要翻译：这些化合物可用于治疗精神分裂症，强迫症人格障碍，重症抑郁症，双相障碍，焦虑症，正常老化，癫痫，视网膜变性，创伤性脑损伤，脊髓损伤，创伤后应激障碍，恐慌症，帕金森病，痴呆，阿尔茨海默病，轻度认知障碍，化疗诱导的认知功能障碍，唐氏综合征，自闭症谱系障碍，听力损失，耳鸣，脊髓小脑共济失调，肌萎缩性侧索硬化，多发性硬化，亨廷顿氏病，中风，放射治疗，慢性压力，滥用神经活性药物，如酒精，阿片剂，甲基苯丙胺，苯环利定和可卡因。

4. 发明申请

US20160251355A1 PYRIDO[4,3-B]PYRAZINE-2-CARBOXAMIDES AS NEUROGENIC AGENTS FOR THE TREATMENT OF NEURODEGENERATIVE DISORDERS 有权
标题翻译：吡咯并[4,3-B]吡嗪-2-羧酰胺作为治疗神经细胞增生性疾病的神经病原体
公开(公告)号：US20160251355A1
公开(公告)日：2016-09-01
申请号：US15151698
申请日：2016-05-11
申请人： Hoffmann-La Roche Inc.
发明人： Ravi Jagasia , Roland Jakob-Roetne , Jens-Uwe Peters , Juergen Wichmann
IPC分类号： C07D471/04
CPC分类号： C07D471/04
摘要： The present invention relates to compounds of general formula I wherein R1, R2 and R3 are as defined herein which may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, cognitive impairment, chemotherapy-induced cognitive dysfunction (“chemobrain”), Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, and disturbances due to radiation therapy, chronic stress, optic neuropathy or macular degeneration, or abuse of neuro-active drugs, selected from alcohol, opiates, methamphetamine, phencyclidine and cocaine.
摘要翻译：本发明涉及通式I的化合物，其中R 1，R 2和R 3如本文所定义，其可用于治疗精神分裂症，强迫症人格障碍，重性抑郁症，双相性精神障碍，焦虑症，正常衰老，癫痫，视网膜变性，创伤性脑损伤，脊髓损伤，创伤后应激障碍，恐慌症，帕金森病，痴呆，阿尔茨海默病，认知障碍，化疗诱发的认知功能障碍（“chemobrain”），唐氏综合征，自闭症谱系障碍，听力损失，耳鸣，脊髓小脑性共济失调，肌萎缩性侧索硬化，多发性硬化，亨廷顿舞蹈病，中风以及由放射治疗引起的干扰，慢性应激，视神经病变或黄斑变性，或滥用神经活性药物，选自酒精，阿片剂，甲基苯丙胺，苯环利定和可卡因。

5. 发明授权

US11320421B2 Oligonucleotides for inducing paternal UBE3A expression 有权
公开(公告)号：US11320421B2
公开(公告)日：2022-05-03
申请号：US16933445
申请日：2020-07-20
申请人： HOFFMANN-LA ROCHE INC.
发明人： Veronica Costa , Maj Hedtjärn , Marius Hoener , Ravi Jagasia , Mads Aaboe Jensen , Christoph Patsch , Lykke Pedersen , Søren Vestergaard Rasmussen
IPC分类号： C12N15/113 , C12N15/11 , G01N33/50 , C12N5/0797 , C12N5/0793 , C12N5/00 , C12N5/074
摘要： The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

6. 发明授权

US10739332B2 Oligonucleotides for inducing paternal UBE3A expression 有权
公开(公告)号：US10739332B2
公开(公告)日：2020-08-11
申请号：US16388714
申请日：2019-04-18
申请人： ROCHE INNOVATION CENTER COPENHAGEN A/S , HOFFMANN-LA ROCHE INC.
发明人： Veronica Costa , Maj Hedtjärn , Marius Hoener , Ravi Jagasia , Mads Aaboe Jensen , Christoph Patsch , Lykke Pedersen , Søren Vestergaard Rasmussen
IPC分类号： A61K48/00 , C12N15/11 , C07H21/02 , C07H21/04 , G01N33/50 , C12N5/0797 , C12N15/113 , C12N5/0793 , C12N5/00 , C12N5/074
摘要： The present invention relates to oligonucleotides that are capable of inducing expression of ubiquitin-protein ligase E3A (UBE3A) from the paternal allele in animal or human neurons. The oligonucleotides target the suppressor of the UBE3A paternal allele by hybridization to SNHG14 long non-coding RNA downstream of SNORD109B. The present invention further relates to pharmaceutical compositions and methods for treatment of Angelman syndrome.

7. 发明授权

US09714239B2 N-phenyl-lactam derivatives capable of stimulating neurogenesis and their use in the treatment of neurological disorders 有权
公开(公告)号：US09714239B2
公开(公告)日：2017-07-25
申请号：US15213622
申请日：2016-07-19
申请人： Hoffmann-La Roche Inc.
发明人： Roland Jakob-Roetne , Juergen Wichmann , Jens-Uwe Peters , Ravi Jagasia
IPC分类号： C07D413/10 , C07D401/10 , C07D403/10 , C07D401/14
CPC分类号： C07D413/10 , C07D401/10 , C07D401/14 , C07D403/10
摘要： The present invention relates to compounds of the general formula I wherein Het, R1, R2, W and X are as defined herein. Compounds of formula I are useful for treating neuropsychiatric disorders.

8. 发明申请

US20160369234A1 CONVERSION OF SOMATIC CELLS TO INDUCED REPROGRAMMED NEURAL STEM CELLS (IRNSCS) 审中-公开
标题翻译：诱导的神经干细胞（IRNSCS）诱导的神经细胞转化
公开(公告)号：US20160369234A1
公开(公告)日：2016-12-22
申请号：US15046885
申请日：2016-02-18
申请人： Hoffmann-La Roche Inc.
发明人： Klaus Christensen , Martin Graf , Roberto Iacone , Ravi Jagasia
IPC分类号： C12N5/0797 , A61K35/30
CPC分类号： C12N5/0623 , A61K35/30 , C12N15/86 , C12N2501/11 , C12N2501/115 , C12N2501/119 , C12N2501/13 , C12N2501/405 , C12N2501/60 , C12N2501/602 , C12N2501/727 , C12N2506/1307 , C12N2510/00
摘要： This application relates to a method for converting somatic cells to Neural Stem Cells (NSCs). Moreover this application relates to a method for converting human fibroblasts, keratinocytes or adipocytes to neural stem cells based on linked steps of genes transduction and chemically defined medium induction.
摘要翻译：本申请涉及将体细胞转化为神经干细胞（NSCs）的方法。此外，本申请涉及基于基因转导和化学上确定的培养基诱导的连接步骤将人成纤维细胞，角质形成细胞或脂肪细胞转化为神经干细胞的方法。

9. 发明申请

US20150259334A1 BENZISOXAZOLES 有权
标题翻译：苯唑沙司
公开(公告)号：US20150259334A1
公开(公告)日：2015-09-17
申请号：US14602541
申请日：2015-01-22
申请人： Hoffmann-La Roche Inc.
发明人： Simona M. Ceccarelli , Ravi Jagasia , Roland Jakob-Roetne , Juergen Wichmann
IPC分类号： C07D413/14 , C07D231/12 , C07D401/04 , C07D413/04
CPC分类号： C07D413/14 , C07D231/12 , C07D401/04 , C07D413/04
摘要： The present invention relates to compounds of general formula wherein Ar1/Ar2 are phenyl or a 5 or 6-membered heteroaryl; R1/R2 is hydrogen, halogen, lower alkyl, CF3 or lower alkoxy; n,m are 1 or 2; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof, with the exception of the compound 2,1-benzisoxazole, 3-(4-chlorophenyl)-5-(1-phenyl-1H-pyrazol-5 -yl)-. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.
摘要翻译：本发明涉及通式的化合物，其中Ar 1 / Ar 2是苯基或5或6元杂芳基; R1 / R2是氢，卤素，低级烷基，CF3或低级烷氧基; n，m为1或2; 或其药学上可接受的酸加成盐与外消旋混合物或其相应的对映异构体和/或光学异构体反应，除了化合物2,1-苯并异恶唑，3-（4-氯苯基）-5-（1- 苯基-1H-吡唑-5-基） - 。这些化合物可用于治疗精神分裂症，强迫症人格障碍，重性抑郁症，双相障碍，焦虑症，正常老化，癫痫，视网膜变性，创伤性脑损伤，脊髓损伤，创伤后应激障碍，恐慌症，帕金森病，痴呆，阿尔茨海默病，轻度认知障碍，化疗诱导的认知功能障碍，唐氏综合征，自闭症谱系障碍，听力损失，耳鸣，脊髓小脑共济失调，肌萎缩性侧索硬化，多发性硬化，亨廷顿氏病，中风，放射治疗，慢性压力，滥用神经活性药物，如酒精，阿片剂，甲基苯丙胺，苯环利定和可卡因。

10. 发明申请

US20150203472A1 BENZIMIDAZOLES AS CNS ACTIVE AGENTS 有权
标题翻译：苯并咪唑作为CNS活性剂
公开(公告)号：US20150203472A1
公开(公告)日：2015-07-23
申请号：US14675404
申请日：2015-03-31
申请人： HOFFMANN-LA ROCHE INC.
发明人： Simona M. Ceccarelli , Ravi Jagasia , Roland Jakob-Roetne , Juergen Wichmann
IPC分类号： C07D403/04 , C07D401/14
CPC分类号： C07D403/04 , C07D401/14
摘要： The present invention relates to compounds of general formula wherein R1 hydrogen, lower alkyl, halogen or lower alkyl substituted by halogen; R2 is hydrogen or halogen; X1 is N or CH; X2 is N or CH; with the proviso that only one of X1 or X2 is N; X3 is C(R) or N; and R is hydrogen, lower alkyl, halogen, lower alkyl substituted by halogen, lower alkoxy or SO2-lower alkyl; or to a pharmaceutically acceptable acid addition salt, to a racemic mixture or to its corresponding enantiomer and/or optical isomers thereof. The compounds may be used for the treatment of schizophrenia, obsessive-compulsive personality disorder, major depression, bipolar disorders, anxiety disorders, normal aging, epilepsy, retinal degeneration, traumatic brain injury, spinal cord injury, post-traumatic stress disorder, panic disorder, Parkinson's disease, dementia, Alzheimer's disease, mild cognitive impairment, chemotherapy-induced cognitive dysfunction, Down syndrome, autism spectrum disorders, hearing loss, tinnitus, spinocerebellar ataxia, amyotrophic lateral sclerosis, multiple sclerosis, Huntington's disease, stroke, radiation therapy, chronic stress, abuse of neuro-active drugs, such as alcohol, opiates, methamphetamine, phencyclidine and cocaine.
摘要翻译：本发明涉及通式的化合物，其中R 1为氢，低级烷基，卤素或被卤素取代的低级烷基; R2是氢或卤素; X1是N或CH; X2是N或CH; 条件是X1或X2中仅有一个为N; X3是C（R）或N; R为氢，低级烷基，卤素，被卤素取代的低级烷基，低级烷氧基或SO 2 - 低级烷基; 或其药学上可接受的酸加成盐与外消旋混合物或其相应的对映体和/或光学异构体反应。这些化合物可用于治疗精神分裂症，强迫症人格障碍，重性抑郁症，双相障碍，焦虑症，正常老化，癫痫，视网膜变性，创伤性脑损伤，脊髓损伤，创伤后应激障碍，恐慌症，帕金森病，痴呆，阿尔茨海默病，轻度认知障碍，化疗诱导的认知功能障碍，唐氏综合征，自闭症谱系障碍，听力损失，耳鸣，脊髓小脑共济失调，肌萎缩性侧索硬化，多发性硬化，亨廷顿氏病，中风，放射治疗，慢性压力，滥用神经活性药物，如酒精，阿片剂，甲基苯丙胺，苯环利定和可卡因。

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