Title:
THERAPEUTIC AGENT FOR PROGRESSIVE DISEASE CAUSED BY INCREASE IN EOMES-POSITIVE CD4-POSITIVE T CELLS
Document Type and Number:
WIPO Patent Application WO/2022/097287
Kind Code:
A1
Abstract:
The present invention provides a therapeutic agent for a progressive disease caused by an increase in Eomes-positive CD4-positive T cells, said therapeutic agent comprising a compound represented by general formula (I) or a salt thereof as an active ingredient. In the formula: R1 represents an aldopyranose residue; R2 represents a hydrogen atom or a hydroxyl group; R3 represents -CH2-, -CH(OH)-CH2- or -CH=CH-; R4 represents a hydrogen atom or CH3; x is 0-35; and y and z are integers satisfying the relationship 0≤y+z≤3.
Inventors:
YAMAMURA TAKASHI (JP)
OKI SHINJI (JP)
RAVENEY BENJAMIN JOSEPH EDWARD (JP)
SATO WAKIRO (JP)
OKAMOTO TOMOKO (JP)
OKI SHINJI (JP)
RAVENEY BENJAMIN JOSEPH EDWARD (JP)
SATO WAKIRO (JP)
OKAMOTO TOMOKO (JP)
Application Number:
PCT/JP2020/041603
Publication Date:
May 12, 2022
Filing Date:
November 06, 2020
Export Citation:
Assignee:
NAT CENTER NEUROLOGY & PSYCHIATRY (JP)
International Classes:
A61K31/7032; A61P25/00
Foreign References:
| JP2004501165A | 2004-01-15 |
Other References:
MIYAMOTO, KATSUICHI ET AL.: "A synthetic glycolipid prevents autoimmune encephalomyelitis by inducing TH 2 bias of natural killer T cells", NATURE, vol. 413, 4 October 2001 (2001-10-04), pages 531 - 534, XP002303730, Retrieved from the Internet DOI: 10.1038/35097097
ARAKI MANABU, TAKAYUKI KONDO, JENNY E GUMPERZ, MICHAEL B BRENNER, SACHIKO MIYAKE, : "Th2 bias of CD 4 NKT cells derived from multiple sclerosis in remissio n", INTERNATIONAL IMMUNOLOGY, vol. 15, no. 2, 1 January 2003 (2003-01-01), pages 279 - 298, XP055938577
RAVENEY BEN J. E., OKI SHINJI, HOHJOH HIROHIKO, NAKAMURA MASAKAZU, SATO WAKIRO, MURATA MIHO, YAMAMURA TAKASHI: "Eomesodermin-expressing T-helper cells are essential for chronic neuroinflammation", NATURE COMMUNICATIONS, NATURE PUBLISHING GROUP, vol. 6, no. 1, 15 October 2015 (2015-10-15), pages 8437, XP055938584, DOI: 10.1038/ncomms9437
ZHANG CHENYANG, ZHANG CHENYANG, RAVENEY BEN J. E., HOHJOH HIROHIKO, TOMI CHIHARU, OKI SHINJI, YAMAMURA TAKASHI: "Extrapituitary prolactin promotes generation of Eomes-positive helper T cells mediating neuroinflammation", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 116, no. 42, 15 October 2019 (2019-10-15), pages 21131 - 21139, XP055938587, ISSN: 0027-8424, DOI: 10.1073/pnas.1906438116
DOI YOSHIMITSU, OKI SHINJI, OZAWA TOMOKO, HOHJOH HIROHIKO, MIYAKE SACHIKO, YAMAMURA TAKASHI: "Orphan nuclear receptor NR4A2 expressed in T cells from multiple sclerosis mediates production of inflammatory cytokines", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 105, no. 24, 17 June 2008 (2008-06-17), pages 8381 - 8386, XP055939190, ISSN: 0027-8424, DOI: 10.1073/pnas.0803454105
TAKAHASHI, SHUJI HASHIMOTO, TAKASHI YAMAMURA: "Natural killer type 2 bias in remission of multiple sclerosis", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 107, no. 5, 1 January 2001 (2001-01-01), pages R23 - R29, XP055939195, DOI: https://doi.org/10.1172/JCI11819.
MATSUI MAKOTO: "Progress in unravelling the etiology of multiple sclerosis?", CLINICAL NEUROLOGY., SOCIETAS NEUROLOGICA JAPONICA., JP, vol. 48, no. 11, 1 January 2008 (2008-01-01), JP , pages 849 - 852, XP055939198, ISSN: 0009-918X, DOI: 10.5692/clinicalneurol.48.849
CUI YU, QI WAN: "NKT Cells in Neurological Diseases", FRONTIERS IN CELLULAR NEUROSCIENCE, vol. 13, 29 May 2019 (2019-05-29), pages 245, XP055939210, DOI: https:// doi.org/10.3389/fncel.2019.00245
VAN KAER, LUC ET AL.: "Natural killer T cells in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis", IMMUNOLOGY, vol. 146, 2015, pages 1 - 10, XP071276630, DOI: https://doi.org/10.1111/imm.12485
SEKIYA TAKASHI, IKKOU KASHIWAGI, NAOKO INOUE, RIMPEI MORITA, SHOHEI HORI, HERMAN WALDMANN, ALEXANDER Y. RUDENSKY, HIROSHI ICHINOS: "The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD 4 T cells", NATURE COMMUNICATIONS, vol. 2, 5 April 2011 (2011-04-05), pages 269, XP055939219
SAKUISHI, KAORI ET AL.: "Role of NK Cells and Invariant NKT Cells in Multiple Sclerosis", RESULTS AND PROBLEMS IN CELL DIFFERENTIATION, vol. 51, 2010, pages 127 - 147, DOI: https://doi.org/10.1007/400200911
ANONYMOUS: "NKT cell-targeted glycolipids for patients with recurrent multiple sclerosis Current status and issues of OCH–NCNP1 Phase II doctor-led clinical trial", PMDA JOINT SYMPOSIUM. TREATMENT DEVELOPMENT FOR RARE NEUROLOGICAL DISEASES: CURRENT STATUS AND ISSUES – 4, vol. 37, no. 6, 1 January 2020 (2020-01-01), pages S93, XP055939322
"efficacy and safety of OCH-NCNP1 in patients with relapsing 1-4 X multiple sclerosis", JAPANESE SOCIETY OF NEUROLOGICAL THERAPEUTICS WEBSITE, 4 December 2019 (2019-12-04), Retrieved from the Internet
ANONYMOUS: "Phase II Clinical Trial of OCH-NCNP1", CLINICALTRIALS.GOV NCT04211740, 26 December 2019 (2019-12-26), XP055939326, Retrieved from the Internet [retrieved on 20220706]
ARAKI MANABU, TAKAYUKI KONDO, JENNY E GUMPERZ, MICHAEL B BRENNER, SACHIKO MIYAKE, : "Th2 bias of CD 4 NKT cells derived from multiple sclerosis in remissio n", INTERNATIONAL IMMUNOLOGY, vol. 15, no. 2, 1 January 2003 (2003-01-01), pages 279 - 298, XP055938577
RAVENEY BEN J. E., OKI SHINJI, HOHJOH HIROHIKO, NAKAMURA MASAKAZU, SATO WAKIRO, MURATA MIHO, YAMAMURA TAKASHI: "Eomesodermin-expressing T-helper cells are essential for chronic neuroinflammation", NATURE COMMUNICATIONS, NATURE PUBLISHING GROUP, vol. 6, no. 1, 15 October 2015 (2015-10-15), pages 8437, XP055938584, DOI: 10.1038/ncomms9437
ZHANG CHENYANG, ZHANG CHENYANG, RAVENEY BEN J. E., HOHJOH HIROHIKO, TOMI CHIHARU, OKI SHINJI, YAMAMURA TAKASHI: "Extrapituitary prolactin promotes generation of Eomes-positive helper T cells mediating neuroinflammation", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 116, no. 42, 15 October 2019 (2019-10-15), pages 21131 - 21139, XP055938587, ISSN: 0027-8424, DOI: 10.1073/pnas.1906438116
DOI YOSHIMITSU, OKI SHINJI, OZAWA TOMOKO, HOHJOH HIROHIKO, MIYAKE SACHIKO, YAMAMURA TAKASHI: "Orphan nuclear receptor NR4A2 expressed in T cells from multiple sclerosis mediates production of inflammatory cytokines", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 105, no. 24, 17 June 2008 (2008-06-17), pages 8381 - 8386, XP055939190, ISSN: 0027-8424, DOI: 10.1073/pnas.0803454105
TAKAHASHI, SHUJI HASHIMOTO, TAKASHI YAMAMURA: "Natural killer type 2 bias in remission of multiple sclerosis", THE JOURNAL OF CLINICAL INVESTIGATION, vol. 107, no. 5, 1 January 2001 (2001-01-01), pages R23 - R29, XP055939195, DOI: https://doi.org/10.1172/JCI11819.
MATSUI MAKOTO: "Progress in unravelling the etiology of multiple sclerosis?", CLINICAL NEUROLOGY., SOCIETAS NEUROLOGICA JAPONICA., JP, vol. 48, no. 11, 1 January 2008 (2008-01-01), JP , pages 849 - 852, XP055939198, ISSN: 0009-918X, DOI: 10.5692/clinicalneurol.48.849
CUI YU, QI WAN: "NKT Cells in Neurological Diseases", FRONTIERS IN CELLULAR NEUROSCIENCE, vol. 13, 29 May 2019 (2019-05-29), pages 245, XP055939210, DOI: https:// doi.org/10.3389/fncel.2019.00245
VAN KAER, LUC ET AL.: "Natural killer T cells in multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis", IMMUNOLOGY, vol. 146, 2015, pages 1 - 10, XP071276630, DOI: https://doi.org/10.1111/imm.12485
SEKIYA TAKASHI, IKKOU KASHIWAGI, NAOKO INOUE, RIMPEI MORITA, SHOHEI HORI, HERMAN WALDMANN, ALEXANDER Y. RUDENSKY, HIROSHI ICHINOS: "The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD 4 T cells", NATURE COMMUNICATIONS, vol. 2, 5 April 2011 (2011-04-05), pages 269, XP055939219
SAKUISHI, KAORI ET AL.: "Role of NK Cells and Invariant NKT Cells in Multiple Sclerosis", RESULTS AND PROBLEMS IN CELL DIFFERENTIATION, vol. 51, 2010, pages 127 - 147, DOI: https://doi.org/10.1007/400200911
ANONYMOUS: "NKT cell-targeted glycolipids for patients with recurrent multiple sclerosis Current status and issues of OCH–NCNP1 Phase II doctor-led clinical trial", PMDA JOINT SYMPOSIUM. TREATMENT DEVELOPMENT FOR RARE NEUROLOGICAL DISEASES: CURRENT STATUS AND ISSUES – 4, vol. 37, no. 6, 1 January 2020 (2020-01-01), pages S93, XP055939322
"efficacy and safety of OCH-NCNP1 in patients with relapsing 1-4 X multiple sclerosis", JAPANESE SOCIETY OF NEUROLOGICAL THERAPEUTICS WEBSITE, 4 December 2019 (2019-12-04), Retrieved from the Internet
ANONYMOUS: "Phase II Clinical Trial of OCH-NCNP1", CLINICALTRIALS.GOV NCT04211740, 26 December 2019 (2019-12-26), XP055939326, Retrieved from the Internet
Attorney, Agent or Firm:
HASEGAWA Yoshiki et al. (JP)
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