Patent application EP15306978A (EP), filed 2015-12-10
Publication number: EP3178487A1
Title: A METHOD FOR OBTAINING HEMATOPOETIC CELL POPULATION CONTAINING REGULATORY T CELLS (TREGS) SPECIFIC FOR AN IRRELEVANT ANTIGEN
Abstract: [0001]    The invention relates to the field of immunology and cell therapy. The invention relates to anin vitroorex vivomethod for obtaining hematopoietic cell population containing regulatory T cells (Tregs) specific for an irrelevant antigen, to a hematopoietic cell population obtained by said method, to a pharmaceutical composition and a product containing said hematopoietic cell population and therapeutic use thereof.
IPC codes: A61K  39/    00            A I
C12N   5/  0783            A I
Claims: number: 1
text: Anin vitro orex vivo method for obtaining a population of regulatory T cells (Tregs) specific for an irrelevant antigen from a PBMC population, comprising the steps of:
number: 2
text: The method of claim 1, wherein step a) comprises the further steps of:
number: 3
text: The method of claim 2, further comprising adding an antibody directed against CD127 and recovering the cells not bound by said antibody.
number: 4
text: The method of claim 3, wherein said antibody directed against CD127 is added to the PBMC population of step i) or to the cells recovered in step ii).
number: 5
text: The method of any one of the previous claims, wherein said irrelevant antigen is selected from non-pathogenic exogenous antigen or irrelevant pathogenic antigen, preferably said irrelevant antigen is Keyhole Limpet Hemocyanin (KLH).
number: 6
text: The method of any one of the previous claims, wherein the antigen of step b) is presented by antigen-presenting cells (APCs).
number: 7
text: The method of any one of the previous claims, wherein step d) comprises growing said Tregs in the presence of APC presenting said irrelevant antigen.
number: 8
text: The method any one of the previous claims, wherein the APCs have been previously irradiated.
number: 9
text: The method of claim 7, wherein said Tregs are grown in step d) for at least 2 generation times.
number: 10
text: The method of any one of the previous claims, wherein selection is performed by magnetic activated cells sorting.
number: 11
text: A population of Tregs obtained by the method of any one of claims 1 to 10.
number: 12
text: A pharmaceutical composition comprising at least one population of Tregs of claim 11 with one or more pharmaceutically acceptable carrier.
number: 13
text: The population of Tregs of claim 11 for use as a drug.
number: 14
text: The population of Tregs according to claim 11 for use in the treatment or the prevention of a disease caused by pathological T cells.
number: 15
text: The population of Tregs for use according to claim 14, wherein said use further comprises the administration to said patient of the irrelevant antigen used in step b), simultaneously, separately or sequentially.
number: 16
text: A product comprising a) an irrelevant antigen and b) the population of T cells activated by said antigen of claim 11, as a combined preparation for simultaneous, separate or sequential use for preventing or treating disease caused by pathological T cells.
Office action: search_report, dated 2017-06-14
Rejection reasons: novelty_epc_54
inventive_step_epc_56
Prior art cited: ref_id: WO2013076268A1
ref_type: patent
severity: background
ref_id: - WAN; FLAVELL, J MOL CELL BIOL., vol. 1, no. 1, 2009, pages 20 - 36
ref_type: npl
severity: background
ref_id: - C. GATSOGIANNIS; J. MARKL: "Keyhole limpet hemocyanin: 9-A CryoEM structure and molecular model of the KLH1 didecamer reveal the interfaces and intricate topology of the 160 functional units", JOURNAL OF MOL. BIOL., vol. 385, no. 3, 2009, pages 963 - 983, XP025940924, DOI: doi:10.1016/j.jmb.2008.10.080
ref_type: npl
severity: background
ref_id: - MILTENYI, S. ET AL., CYTOMETRY, vol. 11, 1990, pages 231 - 238
ref_type: npl
severity: background
ref_id: - KOHLER; MILSTEIN, NATURE, vol. 256, 1975, pages 495 - 497
ref_type: npl
severity: background
ref_id: - KOZBOR ET AL., LMMUNOL TODAY, vol. 4, 1983, pages 72 - 79
ref_type: npl
severity: background
ref_id: - COLE ET AL., METHODS ENZYMOL, vol. 121, 1986, pages 140 - 167
ref_type: npl
severity: background
ref_id: - HUSE ET AL., SCIENCE, vol. 246, 1989, pages 1275 - 1281
ref_type: npl
severity: background
ref_id: - RAULF-HEIMSOTH: "T cell - primary culture from peripheral blood", METHODS MOL MED., vol. 138, 2008, pages 17 - 30
ref_type: npl
severity: background
ref_id: - ELPEK ET AL.: "Ex vivo expansion of CD4+CD25+FoxP3+ T regulatory cells based on synergy between IL-2 and 4-1 BB signaling", J LMMUNOL., vol. 179, no. 11, 2007, pages 7295 - 7304
ref_type: npl
severity: background
ref_id: - STRAUSS ET AL.: "Differential responses of human regulatory T cells (Treg) and effector T cells to rapamycin", PLOS ONE, vol. 4, no. 6, 2009, pages E5994
ref_type: npl
severity: background
ref_id: - "Remington's Pharmaceutical Science", 1985, MACK PUBLISHING COMPANY
ref_type: npl
severity: background
ref_id: - BACHER; SCHEFFOLD, CYTOMETRY A, vol. 83, no. 8, August 2013 (2013-08-01), pages 692 - 701
ref_type: npl
severity: background
ref_id: - BACHER ET AL., MUCOSAL LMMUNOL,, vol. 7, no. 4, July 2014 (2014-07-01), pages 916 - 28
ref_type: npl
severity: background
ref_id: - BATTAGLIA; RANCAROLO, EUR J LMMUNOL., vol. 39, no. 12, December 2009 (2009-12-01), pages 3296 - 300
ref_type: npl
severity: background
ref_id: - BRUNSTEIN, C.G. ET AL.: "Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics", BLOOD, 2011
ref_type: npl
severity: background
ref_id: - COHEN, J. L.; TRENADO, A.; VASEY, D.; KLATZMANN, D.; SALOMON, B .L: "CD4(+)CD25(+) immunoregulatory T Cells: new therapeutics for graft- versus-host disease", J EXP MED, vol. 196, 2002, pages 401 - 6
ref_type: npl
severity: background
ref_id: - DI LANNI, M. ET AL.: "Tregs prevent GVHD and promote immune reconstitution in HL haploidentical transplantation", BLOOD, vol. 117, 2011, pages 3921 - 8
ref_type: npl
severity: background
ref_id: - FERRARA, J.L.; LEVINE, J.E.; REDDY, P; HOLLER, E: "Graft-versus-host disease", LANCET, vol. 373, 2009, pages 1550 - 61
ref_type: npl
severity: background
ref_id: - NOYAN ET AL., EUR. J. IMMUNOL., vol. 44, 2014, pages 2592 - 2602
ref_type: npl
severity: background
ref_id: - SAGOO, P. ET AL.: "Human regulatory T cells with alloantigen specificity are more potent inhibitors of alloimmune skin graft damage than polyclonal regulatory T cells", SCI TRANSL MED, vol. 3, 2011, pages 83RA42
ref_type: npl
severity: background
ref_id: - TANG, Q ET AL.: "et al. In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes", J EXP MED, vol. 199, 2004, pages 1455 - 65
ref_type: npl
severity: background
ref_id: - TRENADO, A. ET AL.: "Recipient-type specific CD4+CD25+ regulatory T cells favor immune reconstitution and control graft-versus-host disease while maintaining graft-versus-leukemia", J CLIN INVEST, vol. 112, 2003, pages 1688 - 96, XP009127461
ref_type: npl
severity: background
ref_id: WO2013076268A1
ref_type: patent
severity: background
ref_id: EP2518504A1
ref_type: patent
severity: background
ref_id: WO2013076181A1
ref_type: patent
severity: background
ref_id: - P. SAGOO ET AL: "Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells", SCIENCE TRANSLATIONAL MEDICINE, vol. 3, no. 83, 18 May 2011 (2011-05-18), Washington, DC, pages 83ra42 - 83ra42, XP055279145, ISSN: 1946-6234, DOI: 10.1126/scitranslmed.3002076
ref_type: npl
severity: background
ref_id: - KELI L HIPPEN ET AL: "Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity", SCIENCE TRANSLATIONAL MEDICINE, 18 May 2011 (2011-05-18), United States, pages 83ra41, XP055279124, Retrieved from the Internet <URL:http://stm.sciencemag.org/content/scitransmed/3/83/83ra41.full.pdf>
ref_type: npl
severity: background
ref_id: EP2518504
ref_type: patent
severity: obviousness
ref_id: WO2013076268
ref_type: patent
severity: novelty_destroying
ref_id: WO2013076181
ref_type: patent
severity: obviousness
ref_id: - P. SAGOO ET AL, "Human Regulatory T Cells with Alloantigen Specificity Are More Potent Inhibitors of Alloimmune Skin Graft Damage than Polyclonal Regulatory T Cells", SCIENCE TRANSLATIONAL MEDICINE, Washington, DC, (20110518), vol. 3, no. 83, doi:10.1126/scitranslmed.3002076, ISSN 1946-6234, pages 83ra42 - 83ra42, XP055279145 [T] * the whole document *
ref_type: npl
severity: background
ref_id: - Keli L Hippen ET AL, "Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity", Science translational medicine, United States, (20110518), page 83ra41, URL: http://stm.sciencemag.org/content/scitransmed/3/83/83ra41.full.pdf, XP055279124
ref_type: npl
severity: background
Final disposition: pending (2017-06-14)