Patent application EP20154732A (EP), filed 2020-01-30
Publication number: EP3689905A2
Title: LTBP COMPLEX-SPECIFIC INHIBITORS OF TGF-BETA AND USES THEREOF
Abstract: [0001]    Disclosed herein are inhibitors, such as antibodies, and antigen-binding portions thereof, that selectively bind complexes of LTBP1-TGFβ and/or LTBP3-TGFβ. The application also provides methods of use of these inhibitors for, for example, inhibiting TGFβ activation, and treating subjects suffering from TGFβ-related disorders, such as fibrotic conditions. Methods of selecting a context-dependent or context-independent isoform-specific TGFβ inhibitor for a subject in need thereof are also provided.
IPC codes: A61P  43/    00            A I
C07K  16/    22            A I
C07K  16/    28            A I
Claims: number: 1
text: An antibody which is:
number: 2
text: The antibody according to claim 1(A)-(C), wherein the antibody comprises:
number: 3
text: The antibody, or antigen-binding fragment thereof, according to claim 1(C) or 2, wherein the up to three amino acid changes comprises up to two amino acid changes.
number: 4
text: The antibody, or antigen-binding fragment thereof, according to any one of claims 1(A)-(C), 2 and 3, wherein the antibody is specific for:
number: 5
text: The antibody, or antigen-binding fragment thereof, according to claim 1(D), wherein:
number: 6
text: The antibody, or antigen-binding fragment thereof, according to claim 1(D) or 5(b), wherein:
number: 7
text: The antibody, or antigen-binding fragment thereof, according to any one of claims 1(D), 5 and 6, which:
number: 8
text: The antibody, or antigen-binding fragment thereof, according to any one of claims 1(D), 1(E) and 5-7:
number: 9
text: The antibody, or antigen-binding fragment thereof, according to any one of the preceding claims:
number: 10
text: The antibody, or antigen-binding fragment thereof, according to any one of the preceding claims, wherein the antibody is a human IgG4 or IgG1 subtype, optionally wherein the antibody is a human IgG4 subtype and comprises a backbone substitution of Ser to Pro that produces an IgG1-like hinge.
number: 11
text: A pharmaceutical composition comprising the antibody of any one of the preceding claims and a pharmaceutically acceptable excipient; optionally wherein the composition is prepared for intravenous administration or subcutaneous administration.
number: 12
text: A composition comprising:
number: 13
text: The composition of any one of claims 11-12 for use in a method for the treatment of a fibrotic condition in a human subject, wherein the treatment comprises administration of the composition to the subject in an amount effective to treat the fibrotic disorder.
number: 14
text: The composition for use according to claim 13, wherein:
number: 15
text: A method for making a composition of any one of claims 11 or 12, comprising an antibody, or antigen-binding fragment thereof, that specifically binds a human LTBP1-proTGFβ complex and/or a human LTBP3-proTGFβ complex, the method comprising steps of:
number: 16
text: The method of claim 15, further comprising the step(s) of:
Office action: search_report, dated 2020-08-05
Rejection reasons: novelty_epc_54
Prior art cited: ref_id: WO2016161410A2
ref_type: patent
severity: background
ref_id: WO2006116002A2
ref_type: patent
severity: background
ref_id: WO2018158727A1
ref_type: patent
severity: background
ref_id: WO2018029367A1
ref_type: patent
severity: background
ref_id: WO2018129331A1
ref_type: patent
severity: background
ref_id: WO2018134681A1
ref_type: patent
severity: background
ref_id: WO2017156500A1
ref_type: patent
severity: background
ref_id: WO2018129329A1
ref_type: patent
severity: background
ref_id: WO2019023661A1
ref_type: patent
severity: background
ref_id: WO2014074532A2
ref_type: patent
severity: background
ref_id: WO2014182676A2
ref_type: patent
severity: background
ref_id: US2017021972W
ref_type: patent
severity: background
ref_id: US2019041373W
ref_type: patent
severity: background
ref_id: US6291158B1
ref_type: patent
severity: background
ref_id: US6582915B1
ref_type: patent
severity: background
ref_id: US6593081B1
ref_type: patent
severity: background
ref_id: US6172197B1
ref_type: patent
severity: background
ref_id: US6696245B2
ref_type: patent
severity: background
ref_id: US5786464A
ref_type: patent
severity: background
ref_id: US6114148A
ref_type: patent
severity: background
ref_id: US5223409A
ref_type: patent
severity: background
ref_id: WO9218619A1
ref_type: patent
severity: background
ref_id: WO9117271A1
ref_type: patent
severity: background
ref_id: WO9220791A1
ref_type: patent
severity: background
ref_id: WO9215679A1
ref_type: patent
severity: background
ref_id: WO9301288A1
ref_type: patent
severity: background
ref_id: WO9201047A1
ref_type: patent
severity: background
ref_id: WO9209690A2
ref_type: patent
severity: background
ref_id: WO9002809A1
ref_type: patent
severity: background
ref_id: US7700302B2
ref_type: patent
severity: background
ref_id: US8877688B2
ref_type: patent
severity: background
ref_id: US4816567A
ref_type: patent
severity: background
ref_id: US4816397A
ref_type: patent
severity: background
ref_id: EP0171496A2
ref_type: patent
severity: background
ref_id: EP0173494A2
ref_type: patent
severity: background
ref_id: GB2177096B
ref_type: patent
severity: background
ref_id: US4485045A
ref_type: patent
severity: background
ref_id: US4544545A
ref_type: patent
severity: background
ref_id: US5013556A
ref_type: patent
severity: background
ref_id: US3773919A
ref_type: patent
severity: background
ref_id: US2018012601W
ref_type: patent
severity: background
ref_id: US6492497B1
ref_type: patent
severity: background
ref_id: US7151169B2
ref_type: patent
severity: background
ref_id: US7723486B2
ref_type: patent
severity: background
ref_id: US2011008364A1
ref_type: patent
severity: background
ref_id: WO2017218592A1
ref_type: patent
severity: background
ref_id: WO2016098357A1
ref_type: patent
severity: background
ref_id: WO2020014473A1
ref_type: patent
severity: background
ref_id: US8198412B2
ref_type: patent
severity: background
ref_id: WO2018015872A1
ref_type: patent
severity: background
ref_id: WO2020014460A1
ref_type: patent
severity: background
ref_id: WO2018013939A1
ref_type: patent
severity: background
ref_id: US62503785P
ref_type: patent
severity: background
ref_id: - ANDERTON ET AL., TOXICOLOGY PATHOLOGY, vol. 39, 2011, pages 916 - 24
ref_type: npl
severity: background
ref_id: - FRAZIER ET AL., TOXICOLOGY PATHOLOGY, vol. 35, 2007, pages 284 - 295
ref_type: npl
severity: background
ref_id: - STAUBER ET AL., J. CLIN. PRACTICE, vol. 4, 2014, pages 3
ref_type: npl
severity: background
ref_id: - LONNING ET AL., CURRENT PHARMACEUTICAL BIOTECHNOLOGY, vol. 12, 2011, pages 2176 - 89
ref_type: npl
severity: background
ref_id: - LACOUTURE ET AL., CANCER IMMUNOL IMMUNOTHER, vol. 64, 2015, pages 437 - 46
ref_type: npl
severity: background
ref_id: - STEVENSON ET AL., ONCOLMMUNOLOGY, vol. 2, no. 8, 2013, pages e26218
ref_type: npl
severity: background
ref_id: - BRENNAN ET AL., MABS, vol. 10, no. 1, 2018, pages 1 - 17
ref_type: npl
severity: background
ref_id: - SHOUKRY ET AL., J IMMUNOL, vol. 198, no. 1, 2017
ref_type: npl
severity: background
ref_id: - RICHERT-SPUHLERLUND, PROG MOL BIOL TRANSL SCI., vol. 136, 2015, pages 217 - 243
ref_type: npl
severity: background
ref_id: - BIRD ET AL., SCIENCE, vol. 242, 1988, pages 423 - 426
ref_type: npl
severity: background
ref_id: - HUSTON ET AL., PROC. NAT'L. ACAD. SCI. USA, vol. 85, 1988, pages 5879 - 5883
ref_type: npl
severity: background
ref_id: - WARD ET AL., NATURE, vol. 341, 1989, pages 544 - 546
ref_type: npl
severity: background
ref_id: - CLACKSON ET AL., NATURE, vol. 352, 1991, pages 624 - 628
ref_type: npl
severity: background
ref_id: - KULKARNI, A.B. ET AL., PROC NATL ACAD SCI USA, vol. 90, no. 8, 1993, pages 3710 - 4
ref_type: npl
severity: background
ref_id: - SHULL, M.M. ET AL., NATURE, vol. 359, no. 6397, 1992, pages 693 - 9
ref_type: npl
severity: background
ref_id: - FENG, X.H.R. DERYNCK, ANNU REV CELL DEV BIOL, vol. 21, 2005, pages 659 - 93
ref_type: npl
severity: background
ref_id: - MASSAGUE, J., ANNU REV BIOCHEM, vol. 67, 1998, pages 753 - 91
ref_type: npl
severity: background
ref_id: - MASSAGUE, J.J. SEOANED. WOTTON, GENES DEV, vol. 19, no. 23, 2005, pages 2783 - 810
ref_type: npl
severity: background
ref_id: - DERYNCK, R.Y.E. ZHANG, NATURE, vol. 425, no. 6958, 2003, pages 577 - 84
ref_type: npl
severity: background
ref_id: - HOLM, T.M. ET AL., SCIENCE, vol. 332, no. 6027, 2011, pages 358 - 61
ref_type: npl
severity: background
ref_id: - JANSSENS, K. ET AL., J MED GENET, vol. 43, no. 1, 2006, pages 1 - 11
ref_type: npl
severity: background
ref_id: - VAN LAER, L.H. DIETZB. LOEYS, ADV EXP MED BIOL, vol. 802, 2014, pages 95 - 105
ref_type: npl
severity: background
ref_id: - RICE, L.M. ET AL., J CLIN INVEST, vol. 125, no. 7, 2015, pages 2795 - 807
ref_type: npl
severity: background
ref_id: - TRACHTMAN, H. ET AL., KIDNEY INT, vol. 79, no. 11, 2011, pages 1236 - 43
ref_type: npl
severity: background
ref_id: - MORRIS, J.C. ET AL., PLOS ONE, vol. 9, no. 3, 2014, pages e90353
ref_type: npl
severity: background
ref_id: - YUNG, L.M. ET AL., A AM J RESPIR CRIT CARE MED, vol. 194, no. 9, 2016, pages 1140 - 1151
ref_type: npl
severity: background
ref_id: - YUNG, L.M. ET AL., AM J RESPIR CRIT CARE MED, vol. 194, no. 9, 2016, pages 1140 - 1151
ref_type: npl
severity: background
ref_id: - ANDERTON, M.J. ET AL., TOXICOL PATHOL, vol. 39, no. 6, 2011, pages 916 - 24
ref_type: npl
severity: background
ref_id: - STAUBER, A. ET AL., CLINICAL TOXICOLOGY, vol. 4, no. 3, 2014, pages 1 - 10
ref_type: npl
severity: background
ref_id: - HERBERTZ, S. ET AL., DRUG DES DEVEL THER, vol. 9, 2015, pages 4479 - 99
ref_type: npl
severity: background
ref_id: - SHI, M. ET AL., NATURE, vol. 474, no. 7351, 2011, pages 343 - 9
ref_type: npl
severity: background
ref_id: - ROBERTSON, I.B. ET AL., MATRIX BIOL, vol. 47, 2015, pages 44 - 53
ref_type: npl
severity: background
ref_id: - WANG, R. ET AL., MOL BIOL CELL, vol. 23, no. 6, 2012, pages 1129 - 39
ref_type: npl
severity: background
ref_id: - T.A. SPRINGER, INT. BMP CONFERENCE, 2016
ref_type: npl
severity: background
ref_id: - REED, N.I. ET AL., SCI TRANSL MED, vol. 7, no. 288, 2015, pages 288ra79
ref_type: npl
severity: background
ref_id: - TRAVIS, M.A.D. SHEPPARD, ANNU REV IMMUNOL, vol. 32, 2014, pages 51 - 82
ref_type: npl
severity: background
ref_id: - MUNGER, J.S. ET AL., CELL, vol. 96, no. 3, 1999, pages 319 - 28
ref_type: npl
severity: background
ref_id: - DONG, X. ET AL., NAT STRUCT MOL BIOL, vol. 21, no. 12, 2014, pages 1091 - 6
ref_type: npl
severity: background
ref_id: - YANG, Z. ET AL., J CELL BIOL, vol. 176, no. 6, 2007, pages 787 - 93
ref_type: npl
severity: background
ref_id: - ALUWIHARE, P. ET AL., J CELL SCI, vol. 122, 2009, pages 227 - 32
ref_type: npl
severity: background
ref_id: - HORAN, G.S. ET AL., AM J RESPIR CRIT CARE MED, vol. 177, no. 1, 2008, pages 56 - 65
ref_type: npl
severity: background
ref_id: - EZZIE, M.E. ET AL., AM J RESPIR CELL MOL BIOL, vol. 44, no. 4, 2011, pages 556 - 61
ref_type: npl
severity: background
ref_id: - WORTHINGTON, J.J.J.E. KLEMENTOWICZM.A. TRAVIS, TRENDS BIOCHEM SCI, vol. 36, no. 1, 2011, pages 47 - 54
ref_type: npl
severity: background
ref_id: - CHAKRAVARTHY ET AL.: "TGF-p-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure", NATURE COMMUNICATIONS, vol. 9, 2018, pages 4692
ref_type: npl
severity: background
ref_id: - TAKAHASHI ET AL., NAT METAB., vol. 1, no. 2, 2019, pages 291 - 303
ref_type: npl
severity: background
ref_id: - SAHARINEN, J.J. KESKI-OJA, MOL BIOL CELL, vol. 11, no. 8, 2000, pages 2691 - 704
ref_type: npl
severity: background
ref_id: - CHEN, Y. ET AL., J MOL BIOL, vol. 345, no. 1, 2005, pages 175 - 86
ref_type: npl
severity: background
ref_id: - URBAN, Z. ET AL., AM J HUM GENET, vol. 85, no. 5, 2009, pages 593 - 605
ref_type: npl
severity: background
ref_id: - DABOVIC, B. ET AL., J CELL PHYSIOL, vol. 230, no. 1, 2015, pages 226 - 36
ref_type: npl
severity: background
ref_id: - HARLOWLANE: "Using Antibodies, a Laboratory Manual", 1999, COLD SPRING HARBOR LABORATORY PRESS
ref_type: npl
severity: background
ref_id: - KARLINALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 87, 1990, pages 2264 - 68
ref_type: npl
severity: background
ref_id: - KARLINALTSCHUL, PROC. NATL. ACAD. SCI. USA, vol. 90, 1993, pages 5873 - 77
ref_type: npl
severity: background
ref_id: - ALTSCHUL ET AL., J. MOL. BIOL., vol. 215, 1990, pages 403 - 10
ref_type: npl
severity: background
ref_id: - ALTSCHUL ET AL., NUCLEIC ACIDS RES., vol. 25, no. 17, 1997, pages 3389 - 3402
ref_type: npl
severity: background
ref_id: - DASCH, J.R. ET AL., J IMMUNOL, vol. 142, no. 5, 1989, pages 1536 - 41
ref_type: npl
severity: background
ref_id: - ANGAL ET AL.: "A single amino acid substitution abolishes the heterogeneity of chimeric mouse/human (IgG4) antibody", MOL IMMUNOL, vol. 30, 1993, pages 105 - 108, XP023683005, DOI: 10.1016/0161-5890(93)90432-B
ref_type: npl
severity: background
ref_id: - KOHLERMILSTEIN, NATURE, vol. 256, 1975, pages 495 - 499
ref_type: npl
severity: background
ref_id: - SMITH, SCIENCE, vol. 228, 1985, pages 1315 - 1317
ref_type: npl
severity: background
ref_id: - MARKS ET AL., J. MOL. BIOL., vol. 222, 1991, pages 581 - 597
ref_type: npl
severity: background
ref_id: - GRAM H., PROC. NATL. ACAD. SCI. U.S.A., vol. 89, 1992, pages 3576 - 3580
ref_type: npl
severity: background
ref_id: - HAWKINS R. E. ET AL., J. MOL. BIOL., vol. 226, 1992, pages 889 - 896
ref_type: npl
severity: background
ref_id: - YANG W. P. ET AL., J. MOL. BIOL., vol. 254, 1995, pages 392 - 403
ref_type: npl
severity: background
ref_id: - HO M. ET AL., J. BIOL. CHEM., vol. 280, 2005, pages 607 - 617
ref_type: npl
severity: background
ref_id: - HO M. ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 103, 2006, pages 9637 - 9642
ref_type: npl
severity: background
ref_id: - BOWERS P. M. ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 108, 2011, pages 20455 - 20460
ref_type: npl
severity: background
ref_id: - MARKS ET AL., NATURE BIOTECH, vol. 10, 1992, pages 779 - 78
ref_type: npl
severity: background
ref_id: - SCHIER ET AL., J. MOL. BIOL., vol. 255, 1996, pages 28 - 43
ref_type: npl
severity: background
ref_id: - PARK ET AL., BBRC, vol. 275, 2000, pages 553 - 557
ref_type: npl
severity: background
ref_id: - CHAMES ET AL., J. IMMUNOL, 2002, pages 1110 - 1118
ref_type: npl
severity: background
ref_id: - MORRISON ET AL., PROC. NATL. ACAD. SCI. U.S.A., vol. 81, 1985, pages 6851
ref_type: npl
severity: background
ref_id: - TAKEDA ET AL., NATURE, vol. 314, 1985, pages 452
ref_type: npl
severity: background
ref_id: - "Antibodies: A Laboratory Manual", 1988, COLD SPRING HARBOR LABORATORY
ref_type: npl
severity: background
ref_id: - BEYCHOK: "Cells of Immunoglobulin Synthesis", 1979, ACADEMIC PRESS
ref_type: npl
severity: background
ref_id: - SCOPES: "Protein Purification", 1982, SPRINGER VERLAG
ref_type: npl
severity: background
ref_id: - STRAUBER ET AL.: "Nonclinical safety evaluation of a Transforming Growth Factor (3 receptor I kinase inhibitor in Fischer 344 rats and beagle dogs", J. CLIN. PRACT, vol. 4, no. 3, 2014, pages 1000196
ref_type: npl
severity: background
ref_id: - SUNTHARALINGAM G ET AL., N ENGL J MED., vol. 355, no. 10, 7 September 2006 (2006-09-07), pages 1018 - 28
ref_type: npl
severity: background
ref_id: - ISHITOBI, M. ET AL., NEUROREPORT, vol. 11, no. 18, 2000, pages 4033 - 5
ref_type: npl
severity: background
ref_id: - EPSTEIN ET AL., PROC. NATL. ACAD. SCI. USA, vol. 82, 1985, pages 3688
ref_type: npl
severity: background
ref_id: - HWANG ET AL., PROC. NATL. ACAD. SCI. USA, vol. 77, 1980, pages 4030
ref_type: npl
severity: background
ref_id: - SOU: "Advanced drug carriers targeting bone marrow", RESEARCHGATE PUBLICATION, 2012
ref_type: npl
severity: background
ref_id: - CHEN, Y.W. ET AL., NEUROLOGY, vol. 65, no. 17, 2005, pages 1309 - 34
ref_type: npl
severity: background
ref_id: - JAMSHIDIAN ET AL., J NEUROIMMUNOL, vol. 262, no. 1-2, 2013, pages 106 - 12
ref_type: npl
severity: background
ref_id: - MCGUIRE, AM J RESPIR CRIT CARE MED, vol. 191, no. 8, 2015, pages 866 - 8
ref_type: npl
severity: background
ref_id: - ZHUANG ET AL., SCIENTIFIC REPORTS, vol. 7, 2017, pages 40141
ref_type: npl
severity: background
ref_id: - DOMINGUEZ-VILLEARHALER, NATURE IMMUNOLOGY, vol. 19, 2018, pages 665 - 673
ref_type: npl
severity: background
ref_id: - LO ET AL., AM. J. TRANSPLANT., vol. 13, 2013, pages 3085 - 3093
ref_type: npl
severity: background
ref_id: - DIDIASOVA ET AL., INT. J. MOL. SCI, vol. 15, 2014, pages 21229 - 21252
ref_type: npl
severity: background
ref_id: - PHILIPS ET AL., CANCER RES., vol. 71, no. 21, 1 November 2011 (2011-11-01), pages 6676 - 83
ref_type: npl
severity: background
ref_id: - CHOONG ET AL., CLIN. ORTHOP. RELAT. RES., vol. 415S, 2003, pages S46 - S58
ref_type: npl
severity: background
ref_id: - HORIGUCHI ET AL., JBIOCHEM., vol. 152, no. 4, October 2012 (2012-10-01), pages 321 - 9
ref_type: npl
severity: background
ref_id: - SANTIBANEZ, JUAN F., ISRN DERMATOLOGY, vol. 2013, pages 597927
ref_type: npl
severity: background
ref_id: - D. Q. SEETOO ET AL., JOURNAL OF SURGICAL ONCOLOGY, vol. 82, no. 3, 2003, pages 184 - 193
ref_type: npl
severity: background
ref_id: - N. HARBECK ET AL., CLINICAL BREAST CANCER, vol. 5, no. 5, 2004, pages 348 - 352
ref_type: npl
severity: background
ref_id: - LAMPIREINHART-KING: "Targeting extracellular matrix stiffness to attenuate disease: From molecular mechanisms to clinical trials", SCI TARNSL MED, vol. 10, no. 422, 2018, pages eaao0475
ref_type: npl
severity: background
ref_id: - SHIGA ET AL.: "Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth", CANCERS, vol. 7, 2015, pages 2443 - 2458, XP002793767, DOI: 10.3390/cancers7040902
ref_type: npl
severity: background
ref_id: - CAJA ET AL., INT. J. MOL. SCI., vol. 19, 2018, pages 1294
ref_type: npl
severity: background
ref_id: - KIM, K.K. ET AL., COLD SPRING HARB. PERSPECT. BIOL., 2017
ref_type: npl
severity: background
ref_id: - OKABE, H., HISTOL. HISTOPHATHOL., vol. 31, 2016, pages 141 - 148
ref_type: npl
severity: background
ref_id: - LI, C ET AL., NAT COMMUN., vol. 7, 2016, pages 11455
ref_type: npl
severity: background
ref_id: - FABREGAT ET AL., FEBS J., vol. 283, 2016, pages 2219 - 2232
ref_type: npl
severity: background
ref_id: - MENG ET AL., NAT. REV. NEPHROL., vol. 12, 2016, pages 325 - 338
ref_type: npl
severity: background
ref_id: - KULKARNI ET AL., AM. J. RESPIR. CELL MOL. BIOL., vol. 54, 2016, pages 751 - 760
ref_type: npl
severity: background
ref_id: - BUSNADIEGO ET AL., MOL. CELL. BIOL., vol. 33, 2013, pages 2388 - 2401
ref_type: npl
severity: background
ref_id: - BARBAS-FILHO ET AL., J. CLIN. PATHOL., vol. 54, 2001, pages 132 - 138
ref_type: npl
severity: background
ref_id: - WANG ET AL., DEV. DYN., vol. 247, 2017, pages 492 - 508
ref_type: npl
severity: background
ref_id: - MURRAY ET AL., INT. J. BIOCHEM. CELL BIOL., vol. 43, 2011, pages 154 - 162
ref_type: npl
severity: background
ref_id: - DEWIDAR ET AL., CELLS, vol. 8, 2019, pages 1419
ref_type: npl
severity: background
ref_id: - ZHANG ET AL.: "reported that persistence of liver cirrhosis is maintained by intrahepatic regulatory T cells that inhibit the process of fibrosis resolution", TRANSL RES., vol. 169, 2016, pages 67 - 79.el,2
ref_type: npl
severity: background
ref_id: - KOBAYASHI ET AL.: "suggested that Tregs are involved in the progression of liver fibrosis into hepatocellular carcinoma (HCC), a process referred to as hepatocarcinogenesis", CLIN CANCER RES., vol. 13, no. 3, 2007, pages 902 - 911
ref_type: npl
severity: background
ref_id: - JENNIE KA CHING LAU ET AL., J PATHOL, vol. 241, 2017, pages 36 - 44
ref_type: npl
severity: background
ref_id: - TAG ET AL., J VIS EXP., vol. 96, 2015, pages 52438
ref_type: npl
severity: background
ref_id: - ALLEN, R.E., J CELL PHYSIOL, vol. 133, no. 3, 1987, pages 567 - 72
ref_type: npl
severity: background
ref_id: - BRENNAN, T.J. ET AL., PROC NATL ACAD SCI USA, vol. 88, no. 9, 1991, pages 3822 - 6
ref_type: npl
severity: background
ref_id: - MASSAGUE, J. ET AL., PROC NATL ACAD SCI USA, vol. 83, no. 21, 1986, pages 8206 - 10
ref_type: npl
severity: background
ref_id: - OLSON, E.N. ET AL., J CELL BIOL, vol. 103, no. 5, 1986, pages 1799 - 805
ref_type: npl
severity: background
ref_id: - LI, Y. ET AL., AM J PATHOL, vol. 164, no. 3, 2004, pages 1007 - 19
ref_type: npl
severity: background
ref_id: - MENDIAS, C.L. ET AL., MUSCLE NERVE, vol. 45, no. 1, 2012, pages 55 - 9
ref_type: npl
severity: background
ref_id: - NELSON, C.A. ET AL., AM J PATHOL, vol. 178, no. 6, 2011, pages 2611 - 21
ref_type: npl
severity: background
ref_id: - LEMOS, D.R. ET AL., NAT MED, vol. 21, no. 7, 2015, pages 786 - 94
ref_type: npl
severity: background
ref_id: - VILLALTA, S.A. ET AL., SCI TRANSL MED, vol. 6, no. 259, 2014, pages 259ral44
ref_type: npl
severity: background
ref_id: - WANG, X. ET AL., J IMMUNOL, vol. 197, no. 12, 2016, pages 4750 - 4761
ref_type: npl
severity: background
ref_id: - BERNASCONI, P. ET AL., J CLIN INVEST, vol. 96, no. 2, 1995, pages 1137 - 44
ref_type: npl
severity: background
ref_id: - ZHOU, L. ET AL., NEUROMUSCUL DISORD, vol. 16, no. 1, 2006, pages 32 - 8
ref_type: npl
severity: background
ref_id: - PESSINA, P. ET AL., STEM CELL REPORTS, vol. 4, no. 6, 2015, pages 1046 - 60
ref_type: npl
severity: background
ref_id: - BUSHBY, K. ET AL., LANCET NEUROL, vol. 9, no. 1, 2010, pages 77 - 93
ref_type: npl
severity: background
ref_id: - DELLORUSSO, C. ET AL., J MUSCLE RES CELL MOTIL, vol. 22, no. 5, 2001, pages 467 - 75
ref_type: npl
severity: background
ref_id: - PRATT, S.J. ET AL., CELL MOL LIFE SCI, vol. 72, no. 1, 2015, pages 153 - 64
ref_type: npl
severity: background
ref_id: - MCDONALD, C.M. ET AL., MUSCLE NERVE, vol. 48, no. 3, 2013, pages 343 - 56
ref_type: npl
severity: background
ref_id: - KLINGLER, W. ET AL., ACTA MYOL, vol. 31, no. 3, 2012, pages 184 - 95
ref_type: npl
severity: background
ref_id: - COLEY, W.D. ET AL., HUM MOL GENET, vol. 25, no. 1, 2016, pages 130 - 45
ref_type: npl
severity: background
ref_id: - HEYDEMANN, A. ET AL., J CLIN INVEST, vol. 119, no. 12, 2009, pages 3703 - 12
ref_type: npl
severity: background
ref_id: - FLANIGAN, K.M. ET AL., ANN NEUROL, vol. 73, no. 4, 2013, pages 481 - 8
ref_type: npl
severity: background
ref_id: - VAN DEN BERGEN, J.C. ET AL., J NEUROL NEUROSURG PSYCHIATRY, vol. 86, no. 10, 2015, pages 1060 - 5
ref_type: npl
severity: background
ref_id: - HINCK ET AL., COLD SPRING HARB. PERSPECT. BIOL, vol. 8, no. 12, 2016
ref_type: npl
severity: background
ref_id: - TANNER, J.W.KHALIL, A.HILL, J.FRANTI, M.MACDONNELL, S.M.: "Fibrosis: From Basic Mechanisms to Targeted therapies", 2016, KEYSTONE, article "Growth Differentiation Factor 11 Potentiates Myofibroblast Activation"
ref_type: npl
severity: background
ref_id: - ANDREETTA, F. ET AL., J NEUROIMMUNOL, vol. 175, no. 1-2, 2006, pages 77 - 86
ref_type: npl
severity: background
ref_id: - GUMUCIO, J.P. ET AL., J APPL PHYSIOL, vol. 115, no. 4, 1985, pages 539 - 45
ref_type: npl
severity: background
ref_id: - ACCORNERO, F. ET AL., HUM MOL GENET, vol. 23, no. 25, 2014, pages 6903 - 15
ref_type: npl
severity: background
ref_id: - LI, Y. ET AL., MOL THER, vol. 15, no. 9, 2007, pages 1616 - 22
ref_type: npl
severity: background
ref_id: - GOSSELIN, L.E. ET AL., MUSCLE NERVE, vol. 30, no. 5, 2004, pages 645 - 53
ref_type: npl
severity: background
ref_id: - SPURNEY, C.F. ET AL., J CARDIOVASC PHARMACOL THER, vol. 16, no. 1, 2011, pages 87 - 95
ref_type: npl
severity: background
ref_id: - TANIGUTI, A.P. ET AL., MUSCLE NERVE, vol. 43, no. 1, 2011, pages 82 - 7
ref_type: npl
severity: background
ref_id: - BEDAIR, H.S. ET AL., AM J SPORTS MED, vol. 36, no. 8, 2008, pages 1548 - 54
ref_type: npl
severity: background
ref_id: - COHN, R.D. ET AL., NAT MED, vol. 13, no. 2, 2007, pages 204 - 10
ref_type: npl
severity: background
ref_id: - HOSANG, M., J CELL BIOCHEM, vol. 29, no. 3, 1985, pages 265 - 73
ref_type: npl
severity: background
ref_id: - OLIVIER, S. ET AL., EUR J CANCER, vol. 26, no. 8, 1990, pages 867 - 71
ref_type: npl
severity: background
ref_id: - SCHER, H.I.W.D. HESTON, CANCER TREAT RES, vol. 59, 1992, pages 131 - 51
ref_type: npl
severity: background
ref_id: - MIURA, T. ET AL., BIOCHEM BIOPHYS RES COMMUN, vol. 340, no. 2, 2006, pages 675 - 80
ref_type: npl
severity: background
ref_id: - BRANDAN, E.C. CABELLO-VERRUGIOC. VIAL, MATRIX BIOL, vol. 27, no. 8, 2008, pages 700 - 8
ref_type: npl
severity: background
ref_id: - ZHU, J. ET AL., J BIOL CHEM, vol. 282, no. 35, 2007, pages 25852 - 63
ref_type: npl
severity: background
ref_id: - BURKS, T.N. ET AL., SCI TRANSL MED, vol. 3, no. 82, 2011, pages 82ra37
ref_type: npl
severity: background
ref_id: - SABHARWAL, R.M.W. CHAPLEAU, EXP PHYSIOL, vol. 99, no. 4, 2014, pages 627 - 31
ref_type: npl
severity: background
ref_id: - MCINTYRE, M. ET AL., PHARMACOL THER, vol. 74, no. 2, 1997, pages 181 - 94
ref_type: npl
severity: background
ref_id: - COXERLER: "Molecular pathways: connecting fibrosis and solid tumor metastasis", CLINICAL CANCER RESEARCH, vol. 20, no. 14, 2014, pages 3637 - 43
ref_type: npl
severity: background
ref_id: - SHIGA ET AL.: "Cancer-associated fibroblasts: their characteristics and their roles in tumor growth", CANCERS, vol. 7, 2015, pages 2443 - 2458, XP002793767, DOI: 10.3390/cancers7040902
ref_type: npl
severity: background
ref_id: - WYNNBARRON: "Macrophages: master regulators of inflammation and fibrosis", SEMIN. LIVER DIS., vol. 30, no. 3, 2010, pages 245 - 257
ref_type: npl
severity: background
ref_id: - SMITH: "Chemotactic cytokines mediate leukocyte recruitment in fibrotic lung disease", BIOL SIGNALS, vol. 5, no. 4, July 1996 (1996-07-01), pages 223 - 31
ref_type: npl
severity: background
ref_id: - MRUGACZ ET AL., J INTERFERON CYTOKINE RES., vol. 27, no. 6, June 2007 (2007-06-01), pages 491 - 5
ref_type: npl
severity: background
ref_id: - ABE ET AL., ANAL BIOCHEM., vol. 216, no. 2, 1994, pages 276 - 84
ref_type: npl
severity: background
ref_id: - TAVARE ET AL., PNAS, vol. 111, no. 3, 2014, pages 1108 - 1113
ref_type: npl
severity: background
ref_id: - TAVARE ET AL., J NUCL MED, vol. 56, no. 8, 2015, pages 1258 - 1264
ref_type: npl
severity: background
ref_id: - RASHIDIAN ET AL., J EXP MED, vol. 214, no. 8, 2017, pages 2243 - 2255
ref_type: npl
severity: background
ref_id: - BECKFORD VERA ET AL., PLOS ONE, vol. 13, no. 3, 2018, pages e0193832
ref_type: npl
severity: background
ref_id: - TAVARE ET AL., CANCER RES, vol. 76, no. 1, 2015, pages 73 - 82
ref_type: npl
severity: background
ref_id: - MATSUMOTO, INT J EXP PATHOL., vol. 94, no. 2, April 2013 (2013-04-01), pages 93 - 103
ref_type: npl
severity: background
ref_id: - HAHM ET AL., THE AMERICAN JOURNAL OF PATHOLOGY, vol. 170, no. 1, 2007, pages 110 - 125
ref_type: npl
severity: background
ref_id: WO2011102483
ref_type: patent
severity: background
ref_id: WO2014182676
ref_type: patent
severity: background
ref_id: WO2017156500
ref_type: patent
severity: background
ref_id: WO2018129329
ref_type: patent
severity: background
ref_id: WO2019023661
ref_type: patent
severity: novelty_destroying
ref_id: - RUDIKOFF S ET AL, "Single amino acid substitution altering antigen-binding specificity", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, NATIONAL ACADEMY OF SCIENCES, (19820301), vol. 79, no. 6, doi:10.1073/PNAS.79.6.1979, ISSN 0027-8424, pages 1979 - 1983, XP002986051 [A] 1-10 * the whole document *
ref_type: npl
severity: background
Final disposition: pending (2020-08-05)