Patent application EP19305140A (EP), filed 2019-02-06
Publication number: EP3693063A1
Title: METHODS AND COMPOSITIONS FOR TREATING CANCER
Abstract: The present invention relates to compositions and methods for treating cancers in a subject in need thereof. The invention more particularly relates to methods of treating cancers by inhibiting PLA2GIB in a subject in need thereof.
IPC codes: A61K  39/   395            A I
A61P  35/    00            A I
C07K  16/    40            A I
Claims: number: 1
text: A compound which inhibits PLA2-GIB for use for treating cancer or neoplasia in a subject in need thereof.
number: 2
text: The compound for use according to claim 1, wherein the compound is an antibody or a fragment or derivative thereof which binds PLA2-GIB.
number: 3
text: The compound for use according to claim 2, wherein the compound is a monoclonal antibody.
number: 4
text: The compound for use according to claim 3, wherein the monoclonal antibody is human or humanized.
number: 5
text: The compound for use according to claim 1, wherein the compound is 3-(2-amino-1,2-dioxoethyl)-2-ethyl-1-(phenylmethyl)-1H-indol-4-yl)oxy)acetic acid or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, such as a sodium salt thereof.
number: 6
text: The compound for use according to claim 1, wherein the compound is a vaccine against PLA2-GIB.
number: 7
text: The compound for use according to claim 1, wherein the compound is a cyclic peptide selected from FLSYK, FLSYR and (2NapA)LS(2NapA)R.
number: 8
text: The compound for use according to anyone of claims 1 to 7, wherein the compound is administered in combination with a further anticancer agent, vaccine, or treatment.
number: 9
text: The compound for use according to claim 8, wherein the compound is administered in combination with chemotherapy or hormonotherapy.
number: 10
text: The compound for use according to claim 8, wherein the compound is administered in combination with radiotherapy, ultrasound therapy or nanoparticle therapy.
number: 11
text: The compound for use according to claim 8, wherein the compound is administered in combination with check-point inhibitors, immunotherapy or anti-cancer vaccines.
number: 12
text: The compound for use according to claim 8, wherein the compound is administered in combination with an inhibitor of a cofactor of PLA2-GIB.
number: 13
text: The compound for use according to claim 12, wherein the inhibitor is an antagonist of a PLA2-GIB cofactor, or a cytostatic or cytotoxic agent or a vaccine against a PLA2-GIB cofactor or against a prokaryotic or eukaryotic cell or virus expressing a PLA2-GIB cofactor.
number: 14
text: The compound for use according to anyone of claims 1 to 13, wherein the compound is administered prior to, during or after surgery.
number: 15
text: The compound for use according to anyone of claims 1 to 14, wherein the compound is administered repeatedly.
number: 16
text: The compound for use according to anyone of the preceding claims, wherein the cancer is a solid cancer.
number: 17
text: The compound for use according to anyone of claims 1 to 16, wherein a PLA2-GIB cofactor or a prokaryotic or eukaryotic cell or virus expressing PLA2-GIB cofactor is present in said subject.
number: 18
text: The compound for use according to anyone of claims 1 to 17, wherein PLA2-GIB or a PLA2-GIB cofactor is present in the cancer microenvironment or blood.
number: 19
text: The compound for use according to anyone of claims 1 to 18, wherein the subject has a PLA2GIB-related CD4 T cell deficiency.
number: 20
text: The compound for use according to claim 16, wherein the cancer is selected from pancreatic cancer, melanoma, lung, oesophageal or pharyngeal cancer, retinoblastoma, liver, breast, ovary, renal, gastric, duodenum, uterine, cervical, thyroid, bladder, prostate, bone, brain or colorectal cancer.
number: 21
text: The compound for use according to claim 20, wherein the cancer is pancreatic cancer.
number: 22
text: The compound for use according to claim 21, wherein the cancer is selected from pancreatic adenocarcinoma, neuroendocrine tumor, intraductal papillary-mucinous neoplasama, mucinous cystic neoplasm, and serious cystic neoplasm.
number: 23
text: The compound for use according to claim 1, wherein the cancer is inducing gastrointestinal and metabolic pathologies.
number: 24
text: The compound for use according to anyone of claims 1 to 23, for preventing cancer or reducing the rate of cancer occurrence.
number: 25
text: The compound for use according to anyone of claims 1 to 23, for reducing the rate of cancer progression.
number: 26
text: The compound for use according to anyone of claims 1 to 23, for reducing or preventing or treating cancer metastasis.
number: 27
text: The compound for use according to anyone of claims 1 to 23, for killing cancer cells.
number: 28
text: The compound for use according to anyone of claims 1 to 23, for treating risk factors for cancer, particularly oro-gastro-intestinal inflammations or infections, such as pancreatitis.
number: 29
text: The compound for use according to anyone of claims 1 to 28, wherein the subject is a human.
number: 30
text: The compound for use according to anyone of claims 1 to 29, wherein the level of PLA2-GIB or PLA2-GIB cofactor in the tumor or in body fluids is measured to guide therapeutic regimen.
Office action: search_report, dated 2020-08-12
Rejection reasons: novelty_epc_54
inventive_step_epc_56
Prior art cited: ref_id: WO2015097140A1
ref_type: patent
severity: background
ref_id: US4376110A
ref_type: patent
severity: background
ref_id: US4486530A
ref_type: patent
severity: background
ref_id: USRE32011E
ref_type: patent
severity: background
ref_id: US4902614A
ref_type: patent
severity: background
ref_id: US4543439A
ref_type: patent
severity: background
ref_id: US4411993A
ref_type: patent
severity: background
ref_id: GB2272440A
ref_type: patent
severity: background
ref_id: US5569825A
ref_type: patent
severity: background
ref_id: US5545806A
ref_type: patent
severity: background
ref_id: WO8702671A1
ref_type: patent
severity: background
ref_id: EP0184187A2
ref_type: patent
severity: background
ref_id: EP0171496A2
ref_type: patent
severity: background
ref_id: EP0173494A2
ref_type: patent
severity: background
ref_id: WO8601533A1
ref_type: patent
severity: background
ref_id: US4816567A
ref_type: patent
severity: background
ref_id: EP0125023A1
ref_type: patent
severity: background
ref_id: US5225539A
ref_type: patent
severity: background
ref_id: WO9201047A1
ref_type: patent
severity: background
ref_id: WO9607754A1
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: WO9209690A2
ref_type: patent
severity: background
ref_id: WO9002809A1
ref_type: patent
severity: background
ref_id: EP18305229A
ref_type: patent
severity: background
ref_id: US7521541B2
ref_type: patent
severity: background
ref_id: WO2017060405A1
ref_type: patent
severity: background
ref_id: WO2017037041A1
ref_type: patent
severity: background
ref_id: WO0212562A2
ref_type: patent
severity: background
ref_id: - SMITH; WATERMAN, J MOL BIOL, vol. 147, 1981, pages 195 - 197
ref_type: npl
severity: background
ref_id: - THOMPSON ET AL., NUCLEIC ACIDS RES, vol. 22, 1994, pages 4673 - 4680
ref_type: npl
severity: background
ref_id: - ALTSCHUL ET AL., NUCLEIC ACIDS RES, vol. 25, 1997, pages 3389 - 3402
ref_type: npl
severity: background
ref_id: - "Genbank", Database accession no. NP_000919
ref_type: npl
severity: background
ref_id: - SCATCHARD ET AL., ANN. N.Y. ACAD. SCI., vol. 51, 1949, pages 660
ref_type: npl
severity: background
ref_id: - "Antibodies: A Laboratory Manual", 1988, COLD SPRING HARBOR LABORATORY PRESS
ref_type: npl
severity: background
ref_id: - "Monoclonal Antibodies, Hybridomas: A New Dimension in Biological Analyses", 1980, PLENUM PRESS
ref_type: npl
severity: background
ref_id: - ALTING-MEES ET AL.: "Monoclonal Antibody Expression Libraries: A Rapid Alternative to Hybridomas", STRATEGIES IN MOLECULAR BIOLOGY, vol. 3, 1990, pages 1 - 9, XP001538956
ref_type: npl
severity: background
ref_id: - LARRICK ET AL., BIOTECHNOLOGY, vol. 7, 1989, pages 394
ref_type: npl
severity: background
ref_id: - RIECHMANN ET AL., NATURE, vol. 332, 1988, pages 323
ref_type: npl
severity: background
ref_id: - LIU ET AL., PNAS, vol. 84, 1987, pages 3439
ref_type: npl
severity: background
ref_id: - LARRICK ET AL., BIO/TECHNOLOGY, vol. 7, 1989, pages 934
ref_type: npl
severity: background
ref_id: - WINTER; HARRIS, TIPS, vol. 14, May 1993 (1993-05-01), pages 139
ref_type: npl
severity: background
ref_id: - BETTER ET AL., SCIENCE, vol. 240, 1988, pages 1041 1043
ref_type: npl
severity: background
ref_id: - LIU ET AL., PNAS, vol. 84, 1987, pages 3439 3443
ref_type: npl
severity: background
ref_id: - LIU ET AL., J. IMMUNOL., vol. 139, 1987, pages 3521 3526
ref_type: npl
severity: background
ref_id: - SUN ET AL., PNAS, vol. 84, 1987, pages 214 218
ref_type: npl
severity: background
ref_id: - NISHIMURA ET AL., CANC. RES., vol. 47, 1987, pages 999 1005
ref_type: npl
severity: background
ref_id: - WOOD ET AL., NATURE, vol. 314, 1985, pages 446 449
ref_type: npl
severity: background
ref_id: - SHAW ET AL., J. NATL. CANCER INST., vol. 80, 1988, pages 1553 1559
ref_type: npl
severity: background
ref_id: - MORRISON, S. L., SCIENCE, vol. 229, 1985, pages 1202 1207
ref_type: npl
severity: background
ref_id: - OI ET AL., BIOTECHNIQUES, vol. 4, 1986, pages 214
ref_type: npl
severity: background
ref_id: - JONES ET AL., NATURE, vol. 321, 1986, pages 552 525
ref_type: npl
severity: background
ref_id: - VERHOEYAN ET AL., SCIENCE, vol. 239, 1988, pages 1534
ref_type: npl
severity: background
ref_id: - BEIDLER ET AL., J. IMMUNOL., vol. 141, 1988, pages 4053 4060
ref_type: npl
severity: background
ref_id: - JAKOBOVITS ET AL., ANN NY ACAD SCI, vol. 764, 1995, pages 525 - 535
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: - GRIFFTHS ET AL., EMBO J, vol. 12, 1993
ref_type: npl
severity: background
ref_id: - BARBAS ET AL., PROC. NAT'L ACAD. SCI. USA, vol. 89, 1992, pages 4457 4461
ref_type: npl
severity: background
ref_id: - FUCHS ET AL., BIO/TECHNOLOGY, vol. 9, 1991, pages 1370 1372
ref_type: npl
severity: background
ref_id: - HAY ET AL., HUM ANTIBOD HYBRIDOMAS, vol. 3, 1992, pages 81 85
ref_type: npl
severity: background
ref_id: - HUSE ET AL., SCIENCE, vol. 246, 1989, pages 1275 1281
ref_type: npl
severity: background
ref_id: - HAWKINS ET AL., J MOL BIOL, vol. 226, 1992, pages 889 896
ref_type: npl
severity: background
ref_id: - CLACKSON ET AL., NATURE, vol. 352, 1991, pages 624 628
ref_type: npl
severity: background
ref_id: - GRAM ET AL., PNAS, vol. 89, 1992, pages 3576 3580
ref_type: npl
severity: background
ref_id: - GARRAD ET AL., BIO/TECHNOLOGY, vol. 9, 1991, pages 1373 1377
ref_type: npl
severity: background
ref_id: - HOOGENBOOM ET AL., NUC ACID RES, vol. 19, 1991, pages 4133 4137
ref_type: npl
severity: background
ref_id: - BARBAS ET AL., PNAS, vol. 88, 1991, pages 7978 7982
ref_type: npl
severity: background
ref_id: - E. KABAT ET AL.: "Sequences of Proteins of Immunological Interest", 1983, U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
ref_type: npl
severity: background
ref_id: - WRIGHT ET AL., TIBTECH, vol. 15, 1997, pages 26 - 32
ref_type: npl
severity: background
ref_id: - OKAZAKI ET AL., J. MOL. BIOL., vol. 336, 2004, pages 1239 - 1249
ref_type: npl
severity: background
ref_id: - YAMANE-OHNUKI N; SATOH M, MABS, vol. 1, 2009, pages 230 - 236
ref_type: npl
severity: background
ref_id: - RIPKA ET AL., ARCH. BIOCHEM. BIOPHYS., vol. 249, 1986, pages 533 - 545
ref_type: npl
severity: background
ref_id: - YAMANE-OHNUKI ET AL., BIOTECH. BIOENG., vol. 87, 2004, pages 614
ref_type: npl
severity: background
ref_id: - KANDA, Y. ET AL., BIOTECHNOL. BIOENG., vol. 94, no. 4, 2006, pages 680 - 688
ref_type: npl
severity: background
ref_id: - CHARI ET AL., CANCER RES., vol. 52, 1992, pages 127 - 131
ref_type: npl
severity: background
ref_id: - FLATMAN ET AL., J. CHROMATOGR. B, vol. 848, 2007, pages 79 - 87
ref_type: npl
severity: background
ref_id: - SAMBROOK J; RUSSELL D, MOLECULAR CLONING: A LABORATORY MANUAL, 2001
ref_type: npl
severity: background
ref_id: - ZHANG DENGHONG ET AL: "The inhibitory effect of saPLI[gamma], a snake sourced PLA2inhibitor on carrageenan-induced inflammation in mice", TOXICON, ELMSFORD, NY, US, vol. 151, 9 July 2018 (2018-07-09), pages 89 - 95, XP085439818, ISSN: 0041-0101, DOI: 10.1016/J.TOXICON.2018.07.002
ref_type: npl
severity: background
ref_id: - CLARK J D ET AL: "Potential therapeutic uses of phospholipase A2 inhibitors", EXPERT OPINION ON THERAPEUTIC PATENTS,, vol. 14, no. 7, 1 January 2004 (2004-01-01), pages 937 - 950, XP002405708, ISSN: 1354-3776, DOI: 10.1517/13543776.14.7.937
ref_type: npl
severity: background
ref_id: - SCHEWE MATTHIAS ET AL: "Secreted Phospholipases A2 Are Intestinal Stem Cell Niche Factors with Distinct Roles in Homeostasis, Inflammation, and Cancer", CELL STEM CELL, vol. 19, no. 1, pages 38 - 51, XP029631424, ISSN: 1934-5909, DOI: 10.1016/J.STEM.2016.05.023
ref_type: npl
severity: background
ref_id: - TSUJI SHOHEI ET AL: "Temozolomide has anti-tumor effects through the phosphorylation of cPLA2 on glioblastoma cells", BRAIN RESEARCH, ELSEVIER, AMSTERDAM, NL, vol. 1723, 20 August 2019 (2019-08-20), XP085838886, ISSN: 0006-8993, [retrieved on 20190820], DOI: 10.1016/J.BRAINRES.2019.146396
ref_type: npl
severity: background
ref_id: - MISAKI A ET AL: "PRODUCTION AND CHARACTERIZATION OF MONOCLONAL ANTIBODIES AGAINST HUMAN PANCREATIC PHOSPHOLIPASE A2", JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION, TOKYO, JP, vol. 11, no. 2, 1 January 1991 (1991-01-01), pages 79 - 89, XP000872202, ISSN: 0912-0009
ref_type: npl
severity: background
ref_id: - CASH J G ET AL: "Pancreatic acinar cell-specific overexpression of group 1B phospholipase A(2) exacerbates diet-induced obesity and insulin resistance in mice", INTERNATIONAL JOURNAL OF OBESITY, vol. 35, no. 6, June 2011 (2011-06-01), pages 877 - 881, ISSN: 0307-0565
ref_type: npl
severity: background
ref_id: - ANJA PUCER ET AL: "Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival", MOLECULAR CANCER, BIOMED CENTRAL, LONDON, GB, vol. 12, no. 1, 27 September 2013 (2013-09-27), pages 111, XP021164223, ISSN: 1476-4598, DOI: 10.1186/1476-4598-12-111
* abstract *
ref_type: npl
severity: background
ref_id: WO2015097140A1
ref_type: patent
severity: background
ref_id: WO2017037041A1
ref_type: patent
severity: background
ref_id: WO2004064822A1
ref_type: patent
severity: background
ref_id: WO9941278A1
ref_type: patent
severity: background
ref_id: EP3530282A1
ref_type: patent
severity: background
ref_id: EP3533460A1
ref_type: patent
severity: background
ref_id: - PEDADA SRINIVASA RAO ET AL: "Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, vol. 112, 10 February 2016 (2016-02-10), pages 289 - 297, XP029450368, ISSN: 0223-5234, DOI: 10.1016/J.EJMECH.2016.02.025
ref_type: npl
severity: background
ref_id: - QUACH NHAT D ET AL: "Secretory phospholipase A2enzymes as pharmacological targets for treatment of disease", BIOCHEMICAL PHARMACOLOGY, ELSEVIER, US, vol. 90, no. 4, 4 June 2014 (2014-06-04), pages 338 - 348, XP029036571, ISSN: 0006-2952, DOI: 10.1016/J.BCP.2014.05.022
ref_type: npl
severity: background
ref_id: - MURAKAMI MAKOTO ET AL: "Emerging roles of secreted phospholipase A(2) enzymes: Lessons from transgenic and knockout mice", BIOCHIMIE, MASSON, PARIS, FR, vol. 92, no. 6, Sp. Iss. SI, 1 June 2010 (2010-06-01), pages 561 - 582, XP002623635, ISSN: 0300-9084, [retrieved on 20100327], DOI: 10.1016/J.BIOCHI.2010.03.015
ref_type: npl
severity: background
ref_id: WO9941278
ref_type: patent
severity: obviousness
ref_id: WO2004064822
ref_type: patent
severity: obviousness
ref_id: WO2015097140
ref_type: patent
severity: obviousness
ref_id: WO2017037041
ref_type: patent
severity: obviousness
ref_id: EP3530282
ref_type: patent
severity: novelty_destroying
ref_id: EP3533460
ref_type: patent
severity: novelty_destroying
ref_id: - PEDADA SRINIVASA RAO ET AL, "Synthesis of new secretory phospholipase A2-inhibitory indole containing isoxazole derivatives as anti-inflammatory and anticancer agents", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, ELSEVIER, AMSTERDAM, NL, (20160210), vol. 112, doi:10.1016/J.EJMECH.2016.02.025, ISSN 0223-5234, pages 289 - 297, XP029450368 [I] 5,8-15 * page  290  - page  292 * [Y] 1-15
ref_type: npl
severity: obviousness
ref_id: - QUACH NHAT D ET AL, "Secretory phospholipase A2enzymes as pharmacological targets for treatment of disease", BIOCHEMICAL PHARMACOLOGY, ELSEVIER, US, (20140604), vol. 90, no. 4, doi:10.1016/J.BCP.2014.05.022, ISSN 0006-2952, pages 338 - 348, XP029036571 [A] 1-15 * page  339  - page  340 * * table 2 *
ref_type: npl
severity: background
ref_id: - MURAKAMI MAKOTO ET AL, "Emerging roles of secreted phospholipase A(2) enzymes: Lessons from transgenic and knockout mice", BIOCHIMIE, MASSON, PARIS, FR, vol. 92, no. 6, Sp. Iss. SI, doi:10.1016/J.BIOCHI.2010.03.015, ISSN 0300-9084, (20100601), pages 561 - 582, (20100327), XP002623635 [A] 1-15 * page  570  - page  573 *
ref_type: npl
severity: background
Final disposition: pending (2020-08-12)