Title:
FUSOKINES INVOLVING CYTOKINES WITH STRONGLY REDUCED RECEPTOR BINDING AFFINITIES
Document Type and Number:
WIPO Patent Application WO/2015/007536
Kind Code:
A3
Abstract:
The present invention relates to a fusion protein comprising at least two cytokines, of which at least one is a modified cytokine with a strongly reduced binding affinity to its receptor, or to one of its receptors. Preferably, both cytokines are connected by a linker, preferably a GGS linker. The invention relates further to said fusion protein for use in treatment of diseases.
Inventors:
TAVERNIER JAN (BE)
BULTINCK JENNYFER (BE)
GERLO SARAH (BE)
UZÉ GILLES (FR)
PAUL FRANCIANE (FR)
BORDAT YANN (FR)
BULTINCK JENNYFER (BE)
GERLO SARAH (BE)
UZÉ GILLES (FR)
PAUL FRANCIANE (FR)
BORDAT YANN (FR)
Application Number:
PCT/EP2014/064227
Publication Date:
March 19, 2015
Filing Date:
July 03, 2014
Export Citation:
Assignee:
VIB VZW (BE)
UNIV GENT (BE)
CENTRE NAT RECH SCIENT (FR)
UNIVERSITÉ MONTPELLIER 2 (FR)
CT HOSPITALIER REGIONAL UNIVERSITAIRE MONTPELLIER (FR)
UNIV GENT (BE)
CENTRE NAT RECH SCIENT (FR)
UNIVERSITÉ MONTPELLIER 2 (FR)
CT HOSPITALIER REGIONAL UNIVERSITAIRE MONTPELLIER (FR)
International Classes:
C12N15/62; A61K38/19; A61K38/20; A61K38/21; C07K14/52; C07K14/525; C07K14/545; C07K14/56; C07K14/575
Domestic Patent References:
| WO2008124086A2 | 2008-10-16 | |||
| WO2009039409A1 | 2009-03-26 | |||
| WO1991002754A1 | 1991-03-07 | |||
| WO2008014612A1 | 2008-02-07 | |||
| WO2013107791A1 | 2013-07-25 |
Other References:
H WEBER ET AL: "Single amino acid changes that render human IFN-oa2 biologically active on mouse cells", THE EMBO JOURNAL, 1 January 1987 (1987-01-01), pages 591 - 598, XP055142112, Retrieved from the Internet [retrieved on 20140926]
ROISMAN L C ET AL: "Structure of the interferon-receptor complex determined by distance constraints from double-mutant cycles and flexible docking", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 98, no. 23, 6 November 2001 (2001-11-06), pages 13231 - 13236, XP002242615, ISSN: 0027-8424, DOI: 10.1073/PNAS.221290398
RAFEI M; BERCHICHE YA; BIRMAN E; BOIVIN MN; YOUNG YK; WU JH; HEVEKER N; GALIPEAU J.: "An engineered GM-CSF-CCL2 fusokine is a potent inhibitor of CCR2-driven inflammation as demonstrated in a murine model of inflammatory arthritis", J IMMUNOL., vol. 183, 2009, pages 1759 - 66, XP002730450
ACRES B; GANTZER M; REMY C; FUTIN N; ACCART N; CHALOIN O; HOEBEKE J; BALLOUL JM; PAUL S.: "Fusokine interleukin-2/interleukin-18, a novel potent innate and adaptive immune stimulator with decreased toxicity", CANCER RES., vol. 65, 2005, pages 9536 - 46, XP002730451
PENAFUERTE C; BAUTISTA-LOPEZ N; BOULASSEL MR; ROUTY JP; GALIPEAU J: "The human ortholog of granulocyte macrophage colony-stimulating factor and interleukin-2 fusion protein induces potent ex vivo natural killer cell activation and maturation", CANCER RES, vol. 69, 2009, pages 9020 - 9028, XP002730452
MOUTIH RAFEI ET AL: "A MCP1 fusokine with CCR2-specific tumoricidal activity", MOLECULAR CANCER, BIOMED CENTRAL, LONDON, GB, vol. 10, no. 1, 24 September 2011 (2011-09-24), pages 121, XP021110637, ISSN: 1476-4598, DOI: 10.1186/1476-4598-10-121
BABA M ET AL: "IDENTIFICATION OF CCR6, THE SPECIFIC RECEPTOR FOR A NOVEL LYMPHOCYTE-DIRECTED CC CHEMOKINE LARC", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 272receptor for LARC = CCL20, no. 23, 6 September 1997 (1997-09-06), pages 14893 - 14898, XP002055488, ISSN: 0021-9258, DOI: 10.1074/JBC.272.23.14893
GENEVIÈVE GARCIN ET AL: "High efficiency cell-specific targeting of cytokine activity", NATURE COMMUNICATIONS, vol. 5, 8 January 2014 (2014-01-08), XP055142158, DOI: 10.1038/ncomms4016
DIJKMANS R ET AL: "Murine interferon-gamma/interleukin-1 fusion proteins used as antigens for the generation of hybridomas producing monoclonal anti-interleukin-1 antibodies", CYTOKINE, ACADEMIC PRESS LTD, PHILADELPHIA, PA, US, vol. 3, no. 2, 1 March 1991 (1991-03-01), pages 134 - 140, XP022967632, ISSN: 1043-4666, [retrieved on 19910301], DOI: 10.1016/1043-4666(91)90034-B
SCHUTYSER E ET AL: "The CC chemokine CCL20 and its receptor CCR6", CYTOKINE AND GROWTH FACTOR REVIEWS, ELSEVIER LTD, GB, vol. 14, no. 5, 1 October 2003 (2003-10-01), pages 409 - 426, XP002984466, ISSN: 1359-6101, DOI: 10.1016/S1359-6101(03)00049-2
CAMACHO N P ET AL: "STRUCTURE OF AN INTERLEUKIN-1 MUTANT WITH REDUCED BIOACTIVITY SHOWS MULTIPLE SUBTLE CHANGES IN CONFORMATION THAT AFFECT PROTEIN-PROTEIN RECOGNITION", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 32, no. 34, 31 August 1993 (1993-08-31), pages 8749 - 8757, XP000387592, ISSN: 0006-2960, DOI: 10.1021/BI00085A005
ROISMAN L C ET AL: "Structure of the interferon-receptor complex determined by distance constraints from double-mutant cycles and flexible docking", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, vol. 98, no. 23, 6 November 2001 (2001-11-06), pages 13231 - 13236, XP002242615, ISSN: 0027-8424, DOI: 10.1073/PNAS.221290398
RAFEI M; BERCHICHE YA; BIRMAN E; BOIVIN MN; YOUNG YK; WU JH; HEVEKER N; GALIPEAU J.: "An engineered GM-CSF-CCL2 fusokine is a potent inhibitor of CCR2-driven inflammation as demonstrated in a murine model of inflammatory arthritis", J IMMUNOL., vol. 183, 2009, pages 1759 - 66, XP002730450
ACRES B; GANTZER M; REMY C; FUTIN N; ACCART N; CHALOIN O; HOEBEKE J; BALLOUL JM; PAUL S.: "Fusokine interleukin-2/interleukin-18, a novel potent innate and adaptive immune stimulator with decreased toxicity", CANCER RES., vol. 65, 2005, pages 9536 - 46, XP002730451
PENAFUERTE C; BAUTISTA-LOPEZ N; BOULASSEL MR; ROUTY JP; GALIPEAU J: "The human ortholog of granulocyte macrophage colony-stimulating factor and interleukin-2 fusion protein induces potent ex vivo natural killer cell activation and maturation", CANCER RES, vol. 69, 2009, pages 9020 - 9028, XP002730452
MOUTIH RAFEI ET AL: "A MCP1 fusokine with CCR2-specific tumoricidal activity", MOLECULAR CANCER, BIOMED CENTRAL, LONDON, GB, vol. 10, no. 1, 24 September 2011 (2011-09-24), pages 121, XP021110637, ISSN: 1476-4598, DOI: 10.1186/1476-4598-10-121
BABA M ET AL: "IDENTIFICATION OF CCR6, THE SPECIFIC RECEPTOR FOR A NOVEL LYMPHOCYTE-DIRECTED CC CHEMOKINE LARC", JOURNAL OF BIOLOGICAL CHEMISTRY, AMERICAN SOCIETY FOR BIOCHEMISTRY AND MOLECULAR BIOLOGY, US, vol. 272receptor for LARC = CCL20, no. 23, 6 September 1997 (1997-09-06), pages 14893 - 14898, XP002055488, ISSN: 0021-9258, DOI: 10.1074/JBC.272.23.14893
GENEVIÈVE GARCIN ET AL: "High efficiency cell-specific targeting of cytokine activity", NATURE COMMUNICATIONS, vol. 5, 8 January 2014 (2014-01-08), XP055142158, DOI: 10.1038/ncomms4016
DIJKMANS R ET AL: "Murine interferon-gamma/interleukin-1 fusion proteins used as antigens for the generation of hybridomas producing monoclonal anti-interleukin-1 antibodies", CYTOKINE, ACADEMIC PRESS LTD, PHILADELPHIA, PA, US, vol. 3, no. 2, 1 March 1991 (1991-03-01), pages 134 - 140, XP022967632, ISSN: 1043-4666, [retrieved on 19910301], DOI: 10.1016/1043-4666(91)90034-B
SCHUTYSER E ET AL: "The CC chemokine CCL20 and its receptor CCR6", CYTOKINE AND GROWTH FACTOR REVIEWS, ELSEVIER LTD, GB, vol. 14, no. 5, 1 October 2003 (2003-10-01), pages 409 - 426, XP002984466, ISSN: 1359-6101, DOI: 10.1016/S1359-6101(03)00049-2
CAMACHO N P ET AL: "STRUCTURE OF AN INTERLEUKIN-1 MUTANT WITH REDUCED BIOACTIVITY SHOWS MULTIPLE SUBTLE CHANGES IN CONFORMATION THAT AFFECT PROTEIN-PROTEIN RECOGNITION", BIOCHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 32, no. 34, 31 August 1993 (1993-08-31), pages 8749 - 8757, XP000387592, ISSN: 0006-2960, DOI: 10.1021/BI00085A005
Attorney, Agent or Firm:
VIB VZW (Gent, BE)
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