SG11201901271VA - Uses of pd-1/pd-l1 inhibitors and/or ctla-4 inhibitors with a biologic containing multiple cytokine components to treat cancer - Google Patents

Uses of pd-1/pd-l1 inhibitors and/or ctla-4 inhibitors with a biologic containing multiple cytokine components to treat cancer

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Publication number
SG11201901271VA
SG11201901271VA SG11201901271VA SG11201901271VA SG11201901271VA SG 11201901271V A SG11201901271V A SG 11201901271VA SG 11201901271V A SG11201901271V A SG 11201901271VA SG 11201901271V A SG11201901271V A SG 11201901271VA SG 11201901271V A SG11201901271V A SG 11201901271VA
Authority
SG
Singapore
Prior art keywords
antagonist
international
ctla
inhibitors
pct
Prior art date
Application number
SG11201901271VA
Inventor
John Hadden
Neil Berinstein
James Egan
Original Assignee
Brooklyn Immunotherapeutics Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Brooklyn Immunotherapeutics Llc filed Critical Brooklyn Immunotherapeutics Llc
Publication of SG11201901271VA publication Critical patent/SG11201901271VA/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404Indoles, e.g. pindolol
    • A61K31/405Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/66Phosphorus compounds
    • A61K31/675Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00Medicinal preparations containing inorganic active ingredients
    • A61K33/24Heavy metals; Compounds thereof
    • A61K33/30Zinc; Compounds thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/191Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2006IL-1
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2013IL-2
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/204IL-6
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/20Interleukins [IL]
    • A61K38/2053IL-8
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19Cytokines; Lymphokines; Interferons
    • A61K38/21Interferons [IFN]
    • A61K38/217IFN-gamma
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/04Antineoplastic agents specific for metastasis
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/52Cytokines; Lymphokines; Interferons
    • C07K14/525Tumour necrosis factor [TNF]
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2827Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against B7 molecules, e.g. CD80, CD86
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/505Medicinal preparations containing antigens or antibodies comprising antibodies
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/545Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2818Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152

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Abstract

INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property 1111111011111111101 1111111111011111010011111101111111111111111111111111111111110111111 Organization International Bureau (10) International Publication Number (43) International Publication Date ......0\"\"1 WO 2018/035395 Al 22 February 2018 (22.02.2018) WIP0 I PCT — (51) (21) (22) (25) Filing Language: (26) (30) (71) (72) International Patent Classification: (74) Agent: GATES, Edward, R. et al.; Wolf, Greenfield & A61K 38/19 (2006.01) A61K 39/395 (2006.01) Sacks, P.C., 600 Atlantic Avenue, Boston, MA 02210-2206 A61K 38/20 (2006.01) CO7K 16/28 (2006.01) (US). International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US2017/047477 kind of national protection available): AE, AG, AL, AM, International Filing Date: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, 18 August 2017 (18.08.2017) CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, English HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, Publication Language: English KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, Priority Data: OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, 62/377,051 19 August 2016 (19.08.2016) US SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. Applicant: IRX THERAPEUTICS, INC. [US/US]; 654 Madison Avenue, Suite 1601, New York, NY 10065 (US). (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, Inventors: HADDEN, John, W.; 25 East 86th St, New GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, York, NY 10028 (US). BERINSTEIN, Neil, L.; 2075 UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, Bayview Avenue, Toronto, ON M4N 3M5 (CA). EGAN, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, James, E.; 2 Cedar Hill Road, Stony Brook, NY 11790 EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, (US). MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, = = the CTLA-4 Title: USES OF PD-1/PD-L1 INHIBITORS AND/OR CTLA-4 INHIBITORS WITH A BIOLOGIC CONTAINING MULTIPLE COMPONENTS TO TREAT CANCER Difference in Mean Membrane Intensity of PD-L1 Expression After Treatment CYTOKINE -L1) of = (54) = = = = 1.2 a) _ at 1 18 0.8 ,_.4 0.6 ,...., &, -' 0.4 -,- ct r.:1 . = = _ = = — -derived programmed (1.) 0 0 ct -0.2 U -0.4 FIG. 2 : Aspects of the disclosure relate to methods for treating cancer, e.g., by administering to a subject having cancer a primary biologic with multiple cytokine components in combination with an antagonist of programmed cell death-ligand 1 (PD cell death 1 (PD-1) and/or with an antagonist of cytotoxic T-lymphocyte- associated protein 4 (CTLA-4). Other aspects disclosure relate to methods of identifying a subject for treatment with an antagonist of PD-L1 or PD-1 and/or an antagonist or assessing the likelihood that a subject will be responsive to an antagonist of PD-Ll or PD-1 and/or an antagonist of CTLA-4. = _ 1-1 kin tz . M in (57) en cell --.., © or GC of C 1-1 ei O [Continued on next page] WO 2018/035395 Al MIDEDIMOMMIDIREIHRIMIOMEHINIMEMOVOIS TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG). Published: — with international search report (Art. 21(3)) — with sequence listing part of description (Rule 5.2(a))
SG11201901271VA 2016-08-19 2017-08-18 Uses of pd-1/pd-l1 inhibitors and/or ctla-4 inhibitors with a biologic containing multiple cytokine components to treat cancer SG11201901271VA (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662377051P 2016-08-19 2016-08-19
PCT/US2017/047477 WO2018035395A1 (en) 2016-08-19 2017-08-18 Uses of pd-1/pd-l1 inhibitors and/or ctla-4 inhibitors with a biologic containing multiple cytokine components to treat cancer

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SG11201901271VA true SG11201901271VA (en) 2019-03-28

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US (1) US20200330557A1 (en)
EP (1) EP3500290A4 (en)
JP (2) JP2019524887A (en)
KR (1) KR20190082192A (en)
CN (1) CN109890405A (en)
AU (1) AU2017312121A1 (en)
BR (1) BR112019003248A2 (en)
CA (1) CA3034266A1 (en)
EA (1) EA201990530A1 (en)
MX (1) MX2019002023A (en)
PH (1) PH12019550027A1 (en)
SG (1) SG11201901271VA (en)
WO (1) WO2018035395A1 (en)
ZA (1) ZA201901258B (en)

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SG10201609131YA (en) 2016-11-01 2018-06-28 Xylonix Ip Holdings Pte Ltd Zinc-pga compositions and methods for treating cancer
JP7165717B2 (en) 2017-03-15 2022-11-04 パンディオン・オペレーションズ・インコーポレイテッド target immune tolerance
US10676516B2 (en) 2017-05-24 2020-06-09 Pandion Therapeutics, Inc. Targeted immunotolerance
US10174091B1 (en) 2017-12-06 2019-01-08 Pandion Therapeutics, Inc. IL-2 muteins
US10946068B2 (en) 2017-12-06 2021-03-16 Pandion Operations, Inc. IL-2 muteins and uses thereof
WO2019245458A1 (en) * 2018-06-22 2019-12-26 Xylonix Ip Holdings Pte. Ltd. Oncology treatments using zinc agents
TW202110885A (en) 2019-05-20 2021-03-16 美商潘迪恩治療公司 Madcam targeted immunotolerance
CN110746493A (en) * 2019-09-06 2020-02-04 中国药科大学 PD-L1 antagonist polypeptide and application thereof
EP3995144A4 (en) * 2019-10-11 2023-06-14 Kyungpook National University Industry-Academic Cooperation Foundation Composition comprising inhibitor against expression of exosomal pd-l1 as active ingredient for enhancing anticancer effect
EP4107187A4 (en) 2020-02-21 2024-07-03 Pandion Operations Inc Tissue targeted immunotolerance with a cd39 effector
CN113450877B (en) * 2021-06-28 2022-04-08 深圳裕泰抗原科技有限公司 Biomarker analysis method based on multiple immunohistochemical technology and application thereof

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EP2429585B1 (en) * 2009-05-15 2018-04-18 IRX Therapeutics, Inc. Vaccine immunotherapy
DK2619576T3 (en) * 2010-09-24 2020-09-07 Niels Grabe MEASURES AND METHODS FOR PREDICTING A TREATMENT RESPONSE IN A CANCER PATIENT
CN107106687A (en) * 2014-10-03 2017-08-29 诺华股份有限公司 Combined therapy
MA40035A (en) * 2014-10-14 2016-04-21 Dana Farber Cancer Inst Inc PD-L1 ANTIBODY MOLECULES AND THEIR USES

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MX2019002023A (en) 2019-11-18
JP2019524887A (en) 2019-09-05
BR112019003248A2 (en) 2019-10-01
US20200330557A1 (en) 2020-10-22
EA201990530A1 (en) 2019-07-31
KR20190082192A (en) 2019-07-09
EP3500290A1 (en) 2019-06-26
WO2018035395A1 (en) 2018-02-22
AU2017312121A1 (en) 2019-03-21
EP3500290A4 (en) 2020-04-29
PH12019550027A1 (en) 2019-07-24
CN109890405A (en) 2019-06-14
JP2023116576A (en) 2023-08-22
CA3034266A1 (en) 2018-02-22

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