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1. 发明授权

US10532068B2 Dual molecular delivery of oligonucleotides and peptide containing conjugates 有权
公开(公告)号：US10532068B2
公开(公告)日：2020-01-14
申请号：US15974135
申请日：2018-05-08
申请人： Merck Sharp & Dohme Corp.
发明人： Steven L. Colletti , Thomas J. Tucker , David M. Tellers , Boyoung Kim , Rob Burke , Kathleen B. Calati , Matthew G. Stanton , Rubina G. Parmar , Jeffrey G. Aaronson , Weimin Wang
IPC分类号： C12N15/87 , A61K31/713 , A61K38/10 , A61K38/16 , C12N15/11 , C12N15/113 , A61K31/7125
摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

2. 发明授权

US10010562B2 Dual molecular delivery of oligonucleotides and peptide containing conjugates 有权
公开(公告)号：US10010562B2
公开(公告)日：2018-07-03
申请号：US15033715
申请日：2014-11-03
申请人： Merck Sharp & Dohme Corp.
发明人： Steven L. Colletti , Thomas J. Tucker , David M. Tellers , Boyoung Kim , Rob Burke , Kathleen B. Calati , Matthew G. Stanton , Rubina G. Parmar , Jeffrey G. Aaronson , Weimin Wang
IPC分类号： A61K31/713 , C12N15/113 , C07H15/203 , A61K31/7125 , A61K38/10 , A61K38/16
CPC分类号： A61K31/7125 , A61K31/713 , A61K38/10 , A61K38/16 , C07K2319/10 , C12N15/111 , C12N15/113 , C12N15/87 , C12N2310/14 , C12N2310/351 , C12N2320/31
摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

3. 发明申请

US20170189441A1 DUAL MOLECULAR DELIVERY OF OLIGONUCLEOTIDES AND PEPTIDE CONTAINING CONJUGATES 有权
公开(公告)号：US20170189441A1
公开(公告)日：2017-07-06
申请号：US15033715
申请日：2014-11-03
申请人： Steven L. COLLETTI , Thomas J. TUCKER , David M. TELLERS , Boyoung KIM , Rob BURKE , Kathleen B. CALATI , Matthew G. STANTON , Rubina G. PARMAR , Jeffrey G. AARONSON , Weimin WANG , MERCK SHARP & DOHME CORP.
发明人： Steven L. Colletti , Thomas J. Tucker , David M. Tellers , Boyoung Kim , Rob Burke , Kathleen B. Calati , Matthew G. Stanton , Rubina G. Parmar , Jeffery G. Aaronson , Weimin Wang
IPC分类号： A61K31/7125 , A61K38/10 , A61K38/16 , A61K31/713
CPC分类号： A61K31/7125 , A61K31/713 , A61K38/10 , A61K38/16 , C07K2319/10 , C12N15/111 , C12N15/113 , C12N15/87 , C12N2310/14 , C12N2310/351 , C12N2320/31
摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

4. 发明申请

US20130324588A1 RNA Interference Mediated Inhibition of Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) Gene Expression Using Short Interfering Nucleic Acid (siNA) 有权
标题翻译： RNA干扰介导的使用短干扰核酸（siNA）的联蛋白（Cadherin相关蛋白），β1（CTNNB1）基因表达的抑制作用
公开(公告)号：US20130324588A1
公开(公告)日：2013-12-05
申请号：US13937412
申请日：2013-08-06
申请人： Merck Sharp & Dohme Corp.
发明人： Duncan Brown , James J. Cunningham , Marian Gindy , Victoria Pickering , Matthew G. Stanton , Steven M. Stirdivant , Walter R. Strapps
IPC分类号： C12N15/113
CPC分类号： C12N15/1138 , C12N15/113 , C12N2310/14 , C12N2310/315 , C12N2310/321 , C12N2310/332 , C12N2310/346 , C12N2310/3521 , C12N2320/32
摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against CTNNB1 gene expression.
摘要翻译：本发明涉及用于研究，诊断和治疗对CTNNB1基因表达和/或活性的调节作用和/或调节β-连环蛋白基因表达途径的性状，疾病和病症的化合物，组合物和方法。具体地说，本发明涉及包括小核酸分子，如短干扰核酸（siNA），短干扰RNA（siRNA），双链RNA（dsRNA），微RNA（miRNA）等双链核酸分子，和能够介导或介导针对CTNNB1基因表达的RNA干扰（RNAi）的短发夹RNA（shRNA）分子。

5. 发明申请

US20130131041A1 SPIROCYCLIC COMPOUNDS 有权
标题翻译：螺环化合物
公开(公告)号：US20130131041A1
公开(公告)日：2013-05-23
申请号：US13719999
申请日：2012-12-19
申请人： Merck Sharp & Dohme Corp.
发明人： Scott C. Berk , Joshua Close , Christopher Hamblett , Richard W. Heidebrecht , Solomon D. Kattar , Laura T. Kliman , Dawn M. Mampreian Hoffman , Joey L. Methot , Thomas Miller , David L. Soloman , Matthew G. Stanton , Paul Tempest , Anna Z. Zabierek
IPC分类号： C07D471/10 , C07D498/10 , C07D491/107 , C07D487/10
CPC分类号： C07D471/10 , C07D487/10 , C07D491/10 , C07D491/107 , C07D498/10
摘要： The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.
摘要翻译：本发明涉及一类新的取代的螺环化合物。这些化合物可以抑制组蛋白脱乙酰酶，适用于选择性诱导终末分化，阻止肿瘤细胞的细胞生长和/或细胞凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性，过敏性和炎性疾病，以及预防和/或治疗中枢神经系统（CNS）的疾病，例如神经退行性疾病本发明进一步提供包含本发明化合物和易于遵循的这些药物组合物的安全给药方案的药物组合物，并且其在体内导致治疗有效量的这些化合物。

6. 发明申请

US20190015442A1 DUAL MOLECULAR DELIVERY OF OLIGONUCLEOTIDES AND PEPTIDE CONTAINING CONJUGATES 审中-公开
公开(公告)号：US20190015442A1
公开(公告)日：2019-01-17
申请号：US15974135
申请日：2018-05-08
申请人： Merck Sharp & Dohme Corp.
发明人： Steven L. Colletti , Thomas J. Tucker , David M. Tellers , Boyoung Kim , Rob Burke , Kathleen B. Calati , Matthew G. Stanton , Rubina G. Parmar , Jeffrey G. Aaronson , Weimin Wang
IPC分类号： A61K31/7125 , C12N15/113 , C12N15/87 , A61K38/16 , A61K38/10 , A61K31/713 , C12N15/11
CPC分类号： A61K31/7125 , A61K31/713 , A61K38/10 , A61K38/16 , C07K2319/10 , C12N15/111 , C12N15/113 , C12N15/87 , C12N2310/14 , C12N2310/351 , C12N2320/31
摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurance of L is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurance of P is independently selected from Table 2; L is a linker and each occurance of L is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.

7. 发明授权

US08686020B2 Spirocyclic compounds 有权
标题翻译：螺环化合物
公开(公告)号：US08686020B2
公开(公告)日：2014-04-01
申请号：US13719999
申请日：2012-12-19
申请人： Merck Sharp & Dohme Corp.
发明人： Christopher Hamblett , Joey L. Methot , Thomas Miller , David L. Sloman , Matthew G. Stanton , Paul Tempest , Anna A. Zabierek
IPC分类号： A61K31/40 , C07D487/00
CPC分类号： C07D471/10 , C07D487/10 , C07D491/10 , C07D491/107 , C07D498/10
摘要： The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.
摘要翻译：本发明涉及一类新的取代的螺环化合物。这些化合物可以抑制组蛋白脱乙酰酶，适用于选择性诱导终末分化，阻止肿瘤细胞的细胞生长和/或细胞凋亡，从而抑制这些细胞的增殖。因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性，过敏性和炎性疾病，以及预防和/或治疗中枢神经系统（CNS）的疾病，例如神经退行性疾病本发明进一步提供包含本发明化合物和易于遵循的这些药物组合物的安全给药方案的药物组合物，并且其在体内导致治疗有效量的这些化合物。

8. 发明授权

US10239957B2 Peptide containing conjugates for dual molecular delivery of oligonucleotides 有权
公开(公告)号：US10239957B2
公开(公告)日：2019-03-26
申请号：US15033731
申请日：2014-11-03
申请人： Merck Sharp & Dohme Corp.
发明人： Steven L. Colletti , Thomas J. Tucker , David M. Tellers , Boyoung Kim , Rob Burke , Kathleen B. Calati , Matthew G. Stanton , Rubina G. Parmar , Jeffery G. Aaronson , Weimin Wang
IPC分类号： C07K19/00 , C12N15/62 , C12N15/113 , A61K38/14
摘要： Disclosed herein is a peptide containing conjugate comprising (P)c-(L)d-(G)e, wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L)a-(G)b, wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.

9. 发明申请

US20170081425A1 PEPTIDE CONTAINING CONJUGATES FOR DUAL MOLECULAR DELIVERY OF OLIGONUCLEOTIDES 审中-公开
公开(公告)号：US20170081425A1
公开(公告)日：2017-03-23
申请号：US15033731
申请日：2014-11-03
申请人： Merck Sharp & Dohme Corp.
发明人： Steven L. Colletti , Thomas J. Tucker , David M. Tellers , Boyoung Kim , Rob Burke , Kathleen B. Calati , Matthew G. Stanton , Rubina G. Parmar , Jeffery G. Aaronson , Weimin Wang
IPC分类号： C07K19/00 , C12N15/113
CPC分类号： C07K19/00 , A61K38/14 , C07K2319/00 , C07K2319/01 , C12N15/113 , C12N15/62 , C12N2310/14 , C12N2310/3513
摘要： Disclosed herein is a peptide containing conjugate comprising (P)c-(L)d-(G)e, wherein P is a peptide and each occurance of P is independently selected from Table 2; L is an optional linker and each occurance of L, if present, is independently selected from Table 3; G is a targeting ligand and each occurance of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. The conjugate can be administered to a subject either alone or in combination with a composition comprising R-(L)a-(G)b, wherein R is an oligonucleotide as defined herein, to inhibit expression of a gene of the subject.

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