Title:
BCMA-TARGETED CAR-T CELL THERAPY FOR MULTIPLE MYELOMA
Document Type and Number:
WIPO Patent Application WO/2023/077343
Kind Code:
A1
Abstract:
Provided herein are methods of treating a subject who has multiple myeloma and has received prior treatment and has limited treatment options. Infusions of chimeric antigen receptor (CAR)-T cells comprising an anti-BCMA CAR comprising a polypeptide are administered to the subject. In certain embodiments, the dose of CAR-T cells administered to the subject is from 1.0 x 105 to 5.0 x 106 of CAR-T cells per kilogram of the subject's mass. The method of treatment is effective in obtaining and maintaining minimal residual disease negativity status, as well as other beneficial clinical outcomes related to efficacy and safety.
Inventors:
AKRAM MUHAMMAD (US)
DEBRAGANCA KEVIN (US)
FAN XIAOHU (CA)
GENG DONG (US)
NESHEIWAT TONIA (US)
PACAUD LIDA (US)
SCHECTER JORDAN (US)
VARSOS HELEN (US)
ZUDAIRE ENRIQUE (US)
DEBRAGANCA KEVIN (US)
FAN XIAOHU (CA)
GENG DONG (US)
NESHEIWAT TONIA (US)
PACAUD LIDA (US)
SCHECTER JORDAN (US)
VARSOS HELEN (US)
ZUDAIRE ENRIQUE (US)
Application Number:
PCT/CN2021/128578
Publication Date:
May 11, 2023
Filing Date:
November 04, 2021
Export Citation:
Assignee:
JANSSEN BIOTECH INC (US)
NANJING LEGEND BIOTECH CO LTD (CN)
NANJING LEGEND BIOTECH CO LTD (CN)
International Classes:
C07K16/28; A61K39/00; A61P35/00; C07K14/725; C12N5/0783
Domestic Patent References:
| WO2020020359A1 | 2020-01-30 | |||
| WO2020014333A1 | 2020-01-16 | |||
| WO1992008796A1 | 1992-05-29 | |||
| WO1994028143A1 | 1994-12-08 | |||
| WO2018028647A1 | 2018-02-15 |
Foreign References:
| EP3475307A1 | 2019-05-01 | |||
| US20070004909A1 | 2007-01-04 | |||
| US20090060910A1 | 2009-03-05 | |||
| US20090093024A1 | 2009-04-09 | |||
| US5464758A | 1995-11-07 | |||
| US5814618A | 1998-09-29 | |||
| US7112715B2 | 2006-09-26 | |||
| US5885827A | 1999-03-23 | |||
| US5122464A | 1992-06-16 | |||
| US5770359A | 1998-06-23 | |||
| US5545806A | 1996-08-13 | |||
| US5569825A | 1996-10-29 | |||
| US5714352A | 1998-02-03 | |||
| US20020197266A1 | 2002-12-26 | |||
| US6265150B1 | 2001-07-24 | |||
| US20180230225A1 | 2018-08-16 | |||
| CN2020133598W | 2020-12-03 | |||
| US4235871A | 1980-11-25 | |||
| US4501728A | 1985-02-26 | |||
| US4837028A | 1989-06-06 | |||
| US5019369A | 1991-05-28 |
Other References:
ANONYMOUS: "A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-cell Maturation Antigen (BCMA) in Participants With Multiple Myeloma - Full Text View - ClinicalTrials.gov", 21 October 2019 (2019-10-21), XP055913141, Retrieved from the Internet [retrieved on 20220415]
COHEN YAEL C ET AL: "Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Lenalidomide-Refractory Patients with Progressive Multiple", BLOOD, vol. 138, 5 November 2021 (2021-11-05), pages 3866 - 3868, XP055913140, Retrieved from the Internet [retrieved on 20220415]
KLAUS PODAR ET AL: "Current and developing synthetic pharmacotherapy for treating relapsed/refractory multiple myeloma", EXPERT OPIN PHARMACOTHER, vol. 18, no. 11, 5 July 2017 (2017-07-05), London, UK, pages 1061 - 1079, XP055530635, ISSN: 1465-6566, DOI: 10.1080/14656566.2017.1340942
ALANAZI FEHAID ET AL: "New generation drugs for treatment of multiple myeloma", DRUG DISCOVERY TODAY, ELSEVIER, AMSTERDAM, NL, vol. 25, no. 2, 22 November 2019 (2019-11-22), pages 367 - 379, XP086060426, ISSN: 1359-6446, [retrieved on 20191122], DOI: 10.1016/J.DRUDIS.2019.11.008
DURER CEREN ET AL: "Treatment of relapsed multiple myeloma: Evidence-based recommendations", BLOOD REVIEWS, CHURCHILL LIVINGSTONE, AMSTERDAM, NL, vol. 39, 31 August 2019 (2019-08-31), XP085988534, ISSN: 0268-960X, [retrieved on 20190831], DOI: 10.1016/J.BLRE.2019.100616
WUKABAT, J. EXP. MED., vol. 132, 1970, pages 211 - 50
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", vol. 7, 1991, NATIONAL INSTITUTE OF HEALTH
CHOTHIALESK, MOL. BIOL., vol. 196, 1987, pages 901 - 17
LEFRANC ET AL., DEV. COMPARAT. IMMUNOL., vol. 27, 2003, pages 55 - 77
HAMERS-CASTERMAN ET AL., NATURE, vol. 363, 1993, pages 446 - 8
GREENBERG ET AL., NATURE, vol. 374, 1995, pages 168 - 73
HASSANZADEH-GHASSABEH ET AL., NANOMEDICINE (LOND, vol. 8, 2013, pages 1013 - 26
HOLLIGER ET AL., NAT. BIOTECH., vol. 23, no. 9, 2005, pages 126 - 1129
BIRD ET AL., SCIENCE, vol. 242, 1988, pages 423 - 426
HUSTON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 85, 1988, pages 5879 - 5883
OSBOURN ET AL., NAT. BIOTECHNOL, vol. 16, 1998, pages 778
JOHNSTON, NATURE, vol. 346, 1990, pages 776 - 777
NO ET AL., PROC. NATL. ACAD. SCI., vol. 93, 1996, pages 3346 - 3351
INDRA ET AL., NUC. ACID. RES., vol. 27, 1999, pages 4324 - 4327
NUC. ACID. RES., vol. 28, 2000, pages e99
KRAMERFUSSENEGGER, METHODS MOL. BIOL, vol. 308, 2005, pages 123 - 144
"Fundamental Immunology", 1993, RAVEN PRESS, pages: 353 - 363
WIGLER ET AL., PROC. NATL. ACAD. SCI. USA, vol. 77, 1980, pages 3567
O'HARE ET AL., PROC. NATL. ACAD. SCI. USA, vol. 78, 1981, pages 2072
COLBERRE-GARAPIN ET AL., J. MOL. BIOL., vol. 150, 1981, pages 1
SANTERRE ET AL., GENE, vol. 30, 1984, pages 147
KENT ET AL., SCIENCE, vol. 237, 1987, pages 901 - 903
WIGLER ET AL., CELL, IP, 1977, pages 223
SZYBALSKASZYBALSKI, PROC. NATL. ACAD. SCI. USA, vol. 48, 1962, pages 2026
LOWY ET AL., CELL, vol. 22, 1980, pages 817
CONESE ET AL., GENE THERAPY, vol. 11, 2004, pages 1735 - 1742
SAMBROOK ET AL.: "Molecular Cloning: A Laboratory Manual", 2001, COLD SPRING HARBOR PRESS
BRASH ET AL., MOL. CELL BIOL., vol. 7, 1987, pages 2031 - 2034
KOHLERMILSTEIN, EUR. J. IMMUNOL., vol. 5, 1976, pages 511 - 519
"Antibodies: A Laboratory Manual", 1988, CSH PRESS
HASKARDARCHER, J. IMMUNOL. METHODS, vol. 74, no. 2, 1984, pages 361 - 67
RODER ET AL., METHODS ENZYMOL., vol. 121, 1986, pages 140 - 67
HUSE ET AL., SCIENCE, vol. 246, 1989, pages 1275 - 81
CHAN ET AL.: "Fmoc Solid Phase Peptide Synthesis", 2000, OXFORD UNIVERSITY PRESS
AUSUBEL ET AL.: "Current Protocols in Molecular Biology", 1994, GREENE PUBLISHING ASSOCIATES AND JOHN WILEY & SONS
RESTIFO, BLOOD, vol. 124, no. 4, 2014, pages 476 - 77
JOSHI ET AL., J. IMMUNOL., vol. 180, no. 3, 2008, pages 1309 - 15
GATTINONI ET AL., NAT. MED., vol. 17, 2011, pages 1290 - 7
FLYNN ET AL., CLIN. TRANSLAT. IMMUNOL., vol. 3, 2014, pages e20
SZOKA ET AL., ANN. REV. BIOPHYS. BIOENG., vol. 9, 1980, pages 467
KOCHENDERFER ET AL., J. IMMUNOTHERAPY, vol. 32, no. 7, 2009, pages 689 - 702
HERMAN ET AL., J. IMMUNOLOGICAL METHODS, vol. 285, no. 1, 2004, pages 25 - 40
COHEN YAEL C ET AL: "Efficacy and Safety of Ciltacabtagene Autoleucel (Cilta-cel), a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor (CAR) T-Cell Therapy, in Lenalidomide-Refractory Patients with Progressive Multiple", BLOOD, vol. 138, 5 November 2021 (2021-11-05), pages 3866 - 3868, XP055913140, Retrieved from the Internet
KLAUS PODAR ET AL: "Current and developing synthetic pharmacotherapy for treating relapsed/refractory multiple myeloma", EXPERT OPIN PHARMACOTHER, vol. 18, no. 11, 5 July 2017 (2017-07-05), London, UK, pages 1061 - 1079, XP055530635, ISSN: 1465-6566, DOI: 10.1080/14656566.2017.1340942
ALANAZI FEHAID ET AL: "New generation drugs for treatment of multiple myeloma", DRUG DISCOVERY TODAY, ELSEVIER, AMSTERDAM, NL, vol. 25, no. 2, 22 November 2019 (2019-11-22), pages 367 - 379, XP086060426, ISSN: 1359-6446, [retrieved on 20191122], DOI: 10.1016/J.DRUDIS.2019.11.008
DURER CEREN ET AL: "Treatment of relapsed multiple myeloma: Evidence-based recommendations", BLOOD REVIEWS, CHURCHILL LIVINGSTONE, AMSTERDAM, NL, vol. 39, 31 August 2019 (2019-08-31), XP085988534, ISSN: 0268-960X, [retrieved on 20190831], DOI: 10.1016/J.BLRE.2019.100616
WUKABAT, J. EXP. MED., vol. 132, 1970, pages 211 - 50
KABAT ET AL.: "Sequences of Proteins of Immunological Interest", vol. 7, 1991, NATIONAL INSTITUTE OF HEALTH
CHOTHIALESK, MOL. BIOL., vol. 196, 1987, pages 901 - 17
LEFRANC ET AL., DEV. COMPARAT. IMMUNOL., vol. 27, 2003, pages 55 - 77
HAMERS-CASTERMAN ET AL., NATURE, vol. 363, 1993, pages 446 - 8
GREENBERG ET AL., NATURE, vol. 374, 1995, pages 168 - 73
HASSANZADEH-GHASSABEH ET AL., NANOMEDICINE (LOND, vol. 8, 2013, pages 1013 - 26
HOLLIGER ET AL., NAT. BIOTECH., vol. 23, no. 9, 2005, pages 126 - 1129
BIRD ET AL., SCIENCE, vol. 242, 1988, pages 423 - 426
HUSTON ET AL., PROC. NATL. ACAD. SCI. USA, vol. 85, 1988, pages 5879 - 5883
OSBOURN ET AL., NAT. BIOTECHNOL, vol. 16, 1998, pages 778
JOHNSTON, NATURE, vol. 346, 1990, pages 776 - 777
NO ET AL., PROC. NATL. ACAD. SCI., vol. 93, 1996, pages 3346 - 3351
INDRA ET AL., NUC. ACID. RES., vol. 27, 1999, pages 4324 - 4327
NUC. ACID. RES., vol. 28, 2000, pages e99
KRAMERFUSSENEGGER, METHODS MOL. BIOL, vol. 308, 2005, pages 123 - 144
"Fundamental Immunology", 1993, RAVEN PRESS, pages: 353 - 363
WIGLER ET AL., PROC. NATL. ACAD. SCI. USA, vol. 77, 1980, pages 3567
O'HARE ET AL., PROC. NATL. ACAD. SCI. USA, vol. 78, 1981, pages 2072
COLBERRE-GARAPIN ET AL., J. MOL. BIOL., vol. 150, 1981, pages 1
SANTERRE ET AL., GENE, vol. 30, 1984, pages 147
KENT ET AL., SCIENCE, vol. 237, 1987, pages 901 - 903
WIGLER ET AL., CELL, IP, 1977, pages 223
SZYBALSKASZYBALSKI, PROC. NATL. ACAD. SCI. USA, vol. 48, 1962, pages 2026
LOWY ET AL., CELL, vol. 22, 1980, pages 817
CONESE ET AL., GENE THERAPY, vol. 11, 2004, pages 1735 - 1742
SAMBROOK ET AL.: "Molecular Cloning: A Laboratory Manual", 2001, COLD SPRING HARBOR PRESS
BRASH ET AL., MOL. CELL BIOL., vol. 7, 1987, pages 2031 - 2034
KOHLERMILSTEIN, EUR. J. IMMUNOL., vol. 5, 1976, pages 511 - 519
"Antibodies: A Laboratory Manual", 1988, CSH PRESS
HASKARDARCHER, J. IMMUNOL. METHODS, vol. 74, no. 2, 1984, pages 361 - 67
RODER ET AL., METHODS ENZYMOL., vol. 121, 1986, pages 140 - 67
HUSE ET AL., SCIENCE, vol. 246, 1989, pages 1275 - 81
CHAN ET AL.: "Fmoc Solid Phase Peptide Synthesis", 2000, OXFORD UNIVERSITY PRESS
AUSUBEL ET AL.: "Current Protocols in Molecular Biology", 1994, GREENE PUBLISHING ASSOCIATES AND JOHN WILEY & SONS
RESTIFO, BLOOD, vol. 124, no. 4, 2014, pages 476 - 77
JOSHI ET AL., J. IMMUNOL., vol. 180, no. 3, 2008, pages 1309 - 15
GATTINONI ET AL., NAT. MED., vol. 17, 2011, pages 1290 - 7
FLYNN ET AL., CLIN. TRANSLAT. IMMUNOL., vol. 3, 2014, pages e20
SZOKA ET AL., ANN. REV. BIOPHYS. BIOENG., vol. 9, 1980, pages 467
KOCHENDERFER ET AL., J. IMMUNOTHERAPY, vol. 32, no. 7, 2009, pages 689 - 702
HERMAN ET AL., J. IMMUNOLOGICAL METHODS, vol. 285, no. 1, 2004, pages 25 - 40
Attorney, Agent or Firm:
CHINA PATENT AGENT (H.K.) LTD. (CN)
Download PDF: