HRP20192192T1 - 5-bromo-2,6-di-(1h-pyrazol-l-yl)pyrimidin-4-amine for use in the treatment of cancer - Google Patents

5-bromo-2,6-di-(1h-pyrazol-l-yl)pyrimidin-4-amine for use in the treatment of cancer Download PDF

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HRP20192192T1
HRP20192192T1 HRP20192192TT HRP20192192T HRP20192192T1 HR P20192192 T1 HRP20192192 T1 HR P20192192T1 HR P20192192T T HRP20192192T T HR P20192192TT HR P20192192 T HRP20192192 T HR P20192192T HR P20192192 T1 HRP20192192 T1 HR P20192192T1
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amino acid
acid sequence
cancer
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HRP20192192TT
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Sanela Bilic
Juan Alberto Camacho Gomez
John Scott CAMERON
Julio Cesar Castro-Palomino Laria
Danny Roland Howard
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Novartis Ag
Palobiofarma, S.L.
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Priority claimed from PCT/IB2016/054834 external-priority patent/WO2017025918A1/en
Application filed by Novartis Ag, Palobiofarma, S.L. filed Critical Novartis Ag
Publication of HRP20192192T1 publication Critical patent/HRP20192192T1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
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    • A—HUMAN NECESSITIES
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    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
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    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [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
    • C07K16/2818—Immunoglobulins [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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [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
    • C07K16/2827—Immunoglobulins [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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding

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  • Health & Medical Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Claims (17)

1. Kombinirani proizvod, naznačen time, što sadrži spoj formule (I): ili njegovu farmaceutski prihvatljivu sol ili kokristal, i jedno ili više imunoterapeutskih sredstava odabranih iz skupine koja se sastoji od sljedećih: anti-CTLA4 protutijelo, anti-PD-1 protutijelo i anti-PD-L1 protutijelo. 1. Combined product, characterized in that it contains a compound of formula (I): or a pharmaceutically acceptable salt or cocrystal thereof, and one or more immunotherapeutic agents selected from the group consisting of anti-CTLA4 antibody, anti-PD-1 antibody, and anti-PD-L1 antibody. 2. Spoj, naznačen time, što je predstavljen Formulom (I): ili njegova farmaceutski prihvatljiva sol ili kokristal; ili kombinirani proizvod prema patentnom zahtjevu 1, te time, da služe za upotrebu u liječenju raka.2. Compound, indicated by the fact that it is represented by Formula (I): or a pharmaceutically acceptable salt or cocrystal thereof; or the combined product according to patent claim 1, and thus, to serve for use in the treatment of cancer. 3. Spoj ili kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, naznačen time, što rak je rak pluća (npr., rak pluća ne-malih stanica (NSCLC) (npr., NSCLC sa skvamoznom i/ili ne-skvamoznom histologijom, ili NSCLC adenokarcinom)), melanom (npr., uznapredovali melanom), rak bubrega (npr., karcinom bubrežnih stanica), rak jetre, mijelom (npr., multipli mijelom), rak prostate, rak dojke (npr., rak dojke koji ne eksprimira jedan, dva ili sve od sljedećih: estrogenski receptor, progesteronski receptor, ili Her2/neu, npr., trostruki negativni rak dojke), kolorektalni rak, rak gušterače, rak glave i vrata (npr., planocelularni karcinom glave i vrata (HNSCC), analni rak, gastroezofagealni rak, rak štitnjače, rak grlića maternice, limfoproliferativna bolest (npr., limfoproliferativna bolest nakon transplantacije) ili hematološki rak, limfom T-stanice, limfom B-stanice, ne-Hodgkinov limfom, ili leukemija (npr., mijeloična leukemija ili limfoidna leukemija).3. A compound or combination product for use according to claim 2, wherein the cancer is lung cancer (eg, non-small cell lung cancer (NSCLC) (eg, NSCLC with squamous and/or non-squamous histology) , or NSCLC adenocarcinoma)), melanoma (eg, advanced melanoma), kidney cancer (eg, renal cell carcinoma), liver cancer, myeloma (eg, multiple myeloma), prostate cancer, breast cancer (eg, breast cancer that does not express one, two, or all of the following: estrogen receptor, progesterone receptor, or Her2/neu (eg, triple-negative breast cancer), colorectal cancer, pancreatic cancer, head and neck cancer (eg, squamous cell carcinoma of the head and neck (HNSCC), anal cancer, gastroesophageal cancer, thyroid cancer, cervical cancer, lymphoproliferative disease (eg, post-transplant lymphoproliferative disease) or hematologic cancer, T-cell lymphoma, B-cell lymphoma, non-Hodgkin's lymphoma, or leukemia ( eg, myeloid leukemia or lymphoid leukemia). 4. Spoj ili kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, naznačen time, što rak je rak pluća (skvamozan), rak pluća (adenokarcinom), rak glave i vrata, rak grlića maternice (skvamozan), rak želuca, rak štitnjače, melanom, rak nazofarinksa ili rak dojke.4. A compound or combined product for use according to claim 2, characterized in that the cancer is lung cancer (squamous), lung cancer (adenocarcinoma), head and neck cancer, cervical cancer (squamous), stomach cancer, thyroid cancer , melanoma, nasopharyngeal cancer or breast cancer. 5. Spoj ili kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, naznačen time, što rak je rak pluća ili rak pluća ne-malih stanica.5. A compound or combined product for use according to claim 2, characterized in that the cancer is lung cancer or non-small cell lung cancer. 6. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, 3, 4 ili 5, naznačen time, što je imunoterapeutsko sredstvo odabrano iz skupine koja se sastoji od sljedećih: ipilimumab, tremelimumab, nivolumab, pembrolizumab, CT-011, AMP-224, MPDL3280A, MEDI4736 i MDX-1105.6. Combined product for use according to claim 2, 3, 4 or 5, characterized in that the immunotherapeutic agent is selected from the group consisting of the following: ipilimumab, tremelimumab, nivolumab, pembrolizumab, CT-011, AMP-224 , MPDL3280A, MEDI4736 and MDX-1105. 7. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, 3, 4 ili 5, naznačen time, što je imunoterapeutsko sredstvo odabrano iz skupine koja se sastoji od sljedećih: MPDL3280A, MEDI4736 i MDX-1105.7. Combination product for use according to claim 2, 3, 4 or 5, characterized in that the immunotherapeutic agent is selected from the group consisting of the following: MPDL3280A, MEDI4736 and MDX-1105. 8. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, 3, 4 ili 5, naznačen time, što je imunoterapeutsko sredstvo odabrano iz skupine koja se sastoji od sljedećih: nivolumab, pembrolizumab, pidilizumab i AMP-224.8. Combined product for use according to claim 2, 3, 4 or 5, characterized in that the immunotherapeutic agent is selected from the group consisting of the following: nivolumab, pembrolizumab, pidilizumab and AMP-224. 9. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, 3, 4 ili 5, naznačen time, što imunoterapeutsko sredstvo je anti-PD-1 protutijelo.9. Combined product for use according to claim 2, 3, 4 or 5, characterized in that the immunotherapeutic agent is an anti-PD-1 antibody. 10. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 9, naznačen time, što anti-PD-1 protutijelo obuhvaća: (a) varijabilnu regiju teškog lanca (VH) koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 4, VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 5, i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 3; i varijabilnu regiju lakog lanca (VL) koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 13, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 14, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 33; (b) VH koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 1; VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 2; i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 3; i VL koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 10, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 11, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 32; (c) VH koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 224, VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 5, i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 3; i VL koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 13, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 14, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 33; ili (d) VH koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 224; VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 2; i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 3; i VL koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 10, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 11, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 32.10. Combined product for use according to claim 9, characterized in that the anti-PD-1 antibody comprises: (a) a variable heavy chain (VH) region comprising the VHCDR1 amino acid sequence of SEQ ID NO: 4, the VHCDR2 amino acid sequence of SEQ ID NO: 5, and the VHCDR3 amino acid sequence of SEQ ID NO: 3; and a variable light chain (VL) region comprising the VLCDR1 amino acid sequence of SEQ ID NO: 13, the VLCDR2 amino acid sequence of SEQ ID NO: 14, and the VLCDR3 amino acid sequence of SEQ ID NO: 33; (b) VH comprising the VHCDR1 amino acid sequence of SEQ ID NO: 1; VHCDR2 amino acid sequence from SEQ ID NO: 2; and the VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising the VLCDR1 amino acid sequence of SEQ ID NO: 10, the VLCDR2 amino acid sequence of SEQ ID NO: 11, and the VLCDR3 amino acid sequence of SEQ ID NO: 32; (c) a VH comprising the VHCDR1 amino acid sequence of SEQ ID NO: 224, the VHCDR2 amino acid sequence of SEQ ID NO: 5, and the VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising the VLCDR1 amino acid sequence of SEQ ID NO: 13, the VLCDR2 amino acid sequence of SEQ ID NO: 14, and the VLCDR3 amino acid sequence of SEQ ID NO: 33; or (d) a VH comprising the VHCDR1 amino acid sequence of SEQ ID NO: 224; VHCDR2 amino acid sequence from SEQ ID NO: 2; and the VHCDR3 amino acid sequence of SEQ ID NO: 3; and a VL comprising the VLCDR1 amino acid sequence of SEQ ID NO: 10, the VLCDR2 amino acid sequence of SEQ ID NO: 11, and the VLCDR3 amino acid sequence of SEQ ID NO: 32. 11. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 9 ili 10, naznačen time, što anti-PD-1 protutijelo sadrži varijabilnu domenu teškog lanca koja obuhvaća sekvencu aminokiseline iz SEQ ID NO: 38 i varijabilnu domenu lakog lanca koja obuhvaća sekvencu aminokiseline iz SEQ ID NO: 70.11. Combined product for use according to claim 9 or 10, characterized in that the anti-PD-1 antibody contains a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO: 38 and a light chain variable domain comprising the amino acid sequence of SEQ ID NO: 70. 12. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 9, 10 ili 11, naznačen time, što anti-PD-1 protutijelo sadrži: teški lanac koji sadrži sekvencu aminokiseline iz SEQ ID NO: 91 i laki lanac koji sadrži sekvencu aminokiseline iz SEQ ID NO: 72.12. Combined product for use according to claim 9, 10 or 11, characterized in that the anti-PD-1 antibody contains: a heavy chain containing the amino acid sequence from SEQ ID NO: 91 and a light chain containing the amino acid sequence from SEQ ID NO: 72. 13. Kombinirani proizvod za uporabu prema bilo kojem od patentnih zahtjeva 9 do 12, naznačen time, što se molekula anti-PD-1 protutijela daje u dozi od oko 300 mg jednom svaka tri tjedna, ili time, da se molekula anti-PD-1 protutijela daje u dozi od oko 400 mg jednom svaka četiri tjedna.13. Combined product for use according to any one of claims 9 to 12, characterized in that the anti-PD-1 antibody molecule is given in a dose of about 300 mg once every three weeks, or in that the anti-PD- 1 antibody is given in a dose of about 400 mg once every four weeks. 14. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 2, 3, 4 ili 5, naznačen time, što je imunoterapeutsko sredstvo jedno anti-PD-L1 protutijelo.14. Combined product for use according to claim 2, 3, 4 or 5, characterized in that the immunotherapeutic agent is an anti-PD-L1 antibody. 15. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 14, naznačen time, što molekula anti-PD-L1 protutijela obuhvaća: (a) varijabilnu regiju teškog lanca (VH) koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 228, VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 229, i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 227; i varijabilnu regiju lakog lanca (VL) koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 233, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 234, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 235; (b) VH koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 225; VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 226; i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 227; i VL koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 230, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 231, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 232; (c) VH koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 244, VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 229, i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 227; i VL koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 233, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 234, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 235; ili (d) VH koja sadrži VHCDR1 sekvencu aminokiseline iz SEQ ID NO: 244; VHCDR2 sekvencu aminokiseline iz SEQ ID NO: 226; i VHCDR3 sekvencu aminokiseline iz SEQ ID NO: 227; i VL koja sadrži VLCDR1 sekvencu aminokiseline iz SEQ ID NO: 230, VLCDR2 sekvencu aminokiseline iz SEQ ID NO: 231, i VLCDR3 sekvencu aminokiseline iz SEQ ID NO: 232.15. Combined product for use according to claim 14, characterized in that the anti-PD-L1 antibody molecule comprises: (a) a variable heavy chain (VH) region comprising the VHCDR1 amino acid sequence of SEQ ID NO: 228, the VHCDR2 amino acid sequence of SEQ ID NO: 229, and the VHCDR3 amino acid sequence of SEQ ID NO: 227; and a variable light chain (VL) region comprising the VLCDR1 amino acid sequence of SEQ ID NO: 233, the VLCDR2 amino acid sequence of SEQ ID NO: 234, and the VLCDR3 amino acid sequence of SEQ ID NO: 235; (b) VH comprising the VHCDR1 amino acid sequence of SEQ ID NO: 225; VHCDR2 amino acid sequence from SEQ ID NO: 226; and the VHCDR3 amino acid sequence of SEQ ID NO: 227; and a VL comprising the VLCDR1 amino acid sequence of SEQ ID NO: 230, the VLCDR2 amino acid sequence of SEQ ID NO: 231, and the VLCDR3 amino acid sequence of SEQ ID NO: 232; (c) a VH comprising the VHCDR1 amino acid sequence of SEQ ID NO: 244, the VHCDR2 amino acid sequence of SEQ ID NO: 229, and the VHCDR3 amino acid sequence of SEQ ID NO: 227; and a VL comprising the VLCDR1 amino acid sequence of SEQ ID NO: 233, the VLCDR2 amino acid sequence of SEQ ID NO: 234, and the VLCDR3 amino acid sequence of SEQ ID NO: 235; or (d) VH comprising the VHCDR1 amino acid sequence of SEQ ID NO: 244; VHCDR2 amino acid sequence from SEQ ID NO: 226; and the VHCDR3 amino acid sequence of SEQ ID NO: 227; and a VL comprising the VLCDR1 amino acid sequence of SEQ ID NO: 230, the VLCDR2 amino acid sequence of SEQ ID NO: 231, and the VLCDR3 amino acid sequence of SEQ ID NO: 232. 16. Kombinirani proizvod za uporabu u skladu s patentnim zahtjevom 14 ili 15, naznačen time, što molekula anti-PD-L1 protutijela obuhvaća varijabilnu domenu teškog lanca koja sadrži sekvencu aminokiseline iz SEQ ID NO: 236 i varijabilnu domenu lakog lanca koja sadrži sekvencu aminokiseline iz SEQ ID NO: 239.16. Combined product for use according to claim 14 or 15, characterized in that the anti-PD-L1 antibody molecule comprises a heavy chain variable domain containing the amino acid sequence from SEQ ID NO: 236 and a light chain variable domain containing the amino acid sequence from SEQ ID NO: 239. 17. Kombinirani proizvod za uporabu prema bilo kojem od patentnih zahtjeva 2-16, naznačen time, što se kombinacija imunoterapeutskog sredstva daje zajedno u jednom pripravku ili se daje odvojeno u dva ili više različitih oblika pripravaka; ili time, da se imunoterapeutsko sredstvo primjenjuje istovremeno, prethodno ili naknadno u odnosu na spoj Formule (I).17. Combined product for use according to any one of patent claims 2-16, characterized in that the combination of the immunotherapeutic agent is given together in one preparation or is given separately in two or more different forms of preparations; or whereby the immunotherapeutic agent is applied simultaneously, before or after the compound of Formula (I).
HRP20192192TT 2015-08-11 2019-12-04 5-bromo-2,6-di-(1h-pyrazol-l-yl)pyrimidin-4-amine for use in the treatment of cancer HRP20192192T1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP15382425 2015-08-11
US201662335984P 2016-05-13 2016-05-13
PCT/IB2016/054834 WO2017025918A1 (en) 2015-08-11 2016-08-10 5-bromo-2,6-di-(lh-pyrazol-l-yl)pyrimidin-4-amine for use in the treatment of cancer
EP16766384.8A EP3334431B9 (en) 2015-08-11 2016-08-10 5-bromo-2,6-di-(1h-pyrazol-l-yl)pyrimidin-4-amine for use in the treatment of cancer

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