Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
2.
Therapeutic Combinations of a BTK Inhibitor, a PI3K Inhibitor, a JAK-2 Inhibitor, and/or a BCL-2 Inhibitor
Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/529 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim forming part of bridged ring systems
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 47/64 - Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.
A61P 35/02 - Antineoplastic agents specific for leukemia
C07C 309/29 - Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton of non-condensed six-membered aromatic rings
C07D 239/54 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
Compounds having the structure of Formula (I):
4, and A are as defined in the specification; pharmaceutical compositions comprising such compounds and salts; use of such compounds and salts to treat or prevent Menin-mediated conditions; kits comprising such compounds and salts; and methods for manufacturing such compounds and salts.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
The present invention provides commercial processes for preparing 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid as well as intermediates thereof.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
Compounds having the structure of Formula (I):
Compounds having the structure of Formula (I):
Compounds having the structure of Formula (I):
and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and A are as defined in the specification; pharmaceutical compositions comprising such compounds and salts; use of such compounds and salts to treat or prevent Menin-mediated conditions; kits comprising such compounds and salts; and methods for manufacturing such compounds and salts.
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 31/4545 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
A61K 31/506 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
Compounds having the structure of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and A are as defined in the specification; pharmaceutical compositions comprising such compounds and salts; use of such compounds and salts to treat or prevent Menin-mediated conditions; kits comprising such compounds and salts; and methods for manufacturing such compounds and salts.
The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.
In certain embodiments, the invention includes therapeutic methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
12.
Crystal Forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)-pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-n-(pyridin-2-yl)benzamide
In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-α]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-α]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.
Therapeutic combinations of a CD 19 inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a CD 19 inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer, such as a hematological malignancy. A combination of a BTK inhibitor and a CD 19 inhibitor, such as a CD19-targeted antibody or a CD19-targeted chimeric antigen receptor expressing T cell or NK cell, and compositions and uses thereof are disclosed. Combinations of a BTK inhibitor and a CD 19 inhibitor with a programmed death-1 (PD-1) or PD-1 ligand (PD-L1) inhibitor and compositions and uses thereof are also disclosed.
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
14.
Methods of treating chronic lymphocytic leukemia and small lymphocytic leukemia using a BTK inhibitor
Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
15.
METHODS AND COMPOSITIONS FOR USE OF THERAPEUTIC T CELLS IN COMBINATION WITH KINASE INHIBITORS
The present disclosure relates to methods, compositions and uses involving immunotherapies and inhibitors of a target protein tyrosine kinase in which the kinase is not IL-2-inducible T cell kinase (ITK) and/or is selected from Bruton's tyrosine kinase (BTK), tec protein tyrosine kinase (TEC), BMX non-receptor tyrosine kinase (Etk), TXK tyrosine kinase (TXK) and/or receptor tyrosine-protein kinase ErbB4 (ErbB4). The provided methods, compositions and uses include administration of one or more such inhibitor with another agent, such as an immunotherapeutic agent targeting T cells and/or genetically engineered T cells, such as CAR-expressing T cells. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration, nucleic acids, articles of manufacture and kits. In some aspects, features of the methods and cells provide for improved activity, efficacy, persistence, expansion and/or proliferation of T cells for adoptive cell therapy or endogenous T cells recruited by immunotherapeutic agents.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
The present disclosure relates, in general, to: (a) solid pharmaceutical dosage forms comprising acalabrutinib maleate; (b) methods of using such pharmaceutical dosage forms to treat B-cell malignancies and/or other conditions; (c) kits comprising such pharmaceutical dosage forms and, optionally, a second pharmaceutical dosage form comprising another therapeutic agent; (d) methods for the preparation of such pharmaceutical dosage forms; and (e) pharmaceutical dosage forms prepared by such methods.
In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.
The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.
Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/4468 - Non-condensed piperidines, e.g. piperocaine having a nitrogen atom directly attached in position 4, e.g. clebopride, fentanyl
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
20.
Methods of treating chronic lymphocytic leukemia and small lymphocytic leukemia using a BTK inhibitor
Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
The present disclosure relates, in general, to: (a) solid pharmaceutical dosage forms comprising acalabrutinib maleate; (b) methods of using such pharmaceutical dosage forms to treat B-cell malignancies and/or other conditions; (c) kits comprising such pharmaceutical dosage forms and, optionally, a second pharmaceutical dosage form comprising another therapeutic agent; (d) methods for the preparation of such pharmaceutical dosage forms; and (e) pharmaceutical dosage forms prepared by such methods.
The present disclosure relates, in general, to: (a) solid pharmaceutical dosage forms comprising acalabrutinib maleate; (b) methods of using such pharmaceutical dosage forms to treat B-cell malignancies and/or other conditions; (c) kits comprising such pharmaceutical dosage forms and, optionally, a second pharmaceutical dosage form comprising another therapeutic agent; (d) methods for the preparation of such pharmaceutical dosage forms; and (e) pharmaceutical dosage forms prepared by such methods.
In some embodiments, the invention relates to a BTK inhibitor or a pharmaceutically acceptable salt, cocrystal, ester, prodrug, solvate, hydrate or derivative thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to imidazopyrazine compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.
In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.
The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.
The present disclosure relates, in general, to improved processes for the preparation of 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)-benzamide, particularly large-scale processes for manufacturing 4-{8-amino-3-[(2S)-1-(but-2-ynoyl)pyrrolidin-2-yl]imidazo[1,5-a]pyrazin-1-yl}-N-(pyridin-2-yl)benzamide and intermediates used in such processes.
In some embodiments, the invention relates to an interleukin-2- inducible T-cell kinase (ITK) inhibitor of formula (I) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in the treatment of ITK mediated disorders.
Therapeutic combinations of a MEK inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a MEK inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61P 35/02 - Antineoplastic agents specific for leukemia
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
29.
Imidazopyrazine inhibitors of Bruton's tyrosine kinase
In some embodiments, the invention relates to the compounds of Formula (I) and (II) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to the compounds of Formula (I) and (II), pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.
Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide for treating diffuse large B-cell lymphoma
In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.
The present disclosure relates to methods, compositions and uses involving immunotherapies and inhibitors of a target protein tyrosine kinase in which the kinase is not IL-2-inducible T cell kinase (ITK) and/or is selected from Bruton's tyrosine kinase (BTK), tec protein tyrosine kinase (TEC), BMX non-receptor tyrosine kinase (Etk), TXK tyrosine kinase (TXK) and/or receptor tyro-sine-protein kinase ErbB4 (ErbB4). The provided methods, compositions and uses include administration of one or more such inhibitor with another agent, such as an immunotherapeutic agent targeting T cells and/or genetically engineered T cells, such as CAR-expressing T cells. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration, nucleic acids, articles of manufacture and kits. In some aspects, features of the methods and cells provide for improved activity, efficacy, persistence, expansion and/or proliferation of T cells for adoptive cell therapy or endogenous T cells recruited by immunotherapeutic agents.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
A61K 9/00 - Medicinal preparations characterised by special physical form
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
32.
Methods of treating chronic lymphocytic leukemia and small lymphocytic leukemia using a BTK inhibitor
Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
33.
Imidazopyrazine inhibitors of Bruton's tyrosine kinase
In some embodiments, the invention relates to a BTK inhibitor or a pharmaceutically acceptable salt, cocrystal, ester, prodrug, solvate, hydrate or derivative thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to imidazopyrazine compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.
Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/4468 - Non-condensed piperidines, e.g. piperocaine having a nitrogen atom directly attached in position 4, e.g. clebopride, fentanyl
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/635 - Compounds containing para-N-benzene- sulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonohydrazide having a heterocyclic ring, e.g. sulfadiazine
35.
Pharmaceutical composition comprising a crystal form of (S)-4-(8-amino-3-(1-(but-2-ynoyl) pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide
In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.
In some embodiments, the invention relates to compositions, methods, and kits for assessment of drug target occupancy in Bruton's tyrosine kinase (BTK) in a selective and sensitive manner for use with BTK inhibitor therapy in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders, including cancers, inflammatory diseases, and immune and autoimmune diseases.
In some embodiments, the invention relates to the compounds of Formula (I) and (II) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to the compounds of Formula (I) and (II), pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.
In some embodiments, the invention relates to crystalline solid forms, including polymorphs and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5- a]pyrazin-1-yl)-2-methoxy-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the crystalline solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.
In some embodiments, the invention relates to the compounds of Formula (I) and (II) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to the compounds of Formula (I) and (II), pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
In some embodiments, the invention includes a therapeutic combination of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms, and a Bruton's tyrosine kinase (BTK) inhibitor. In some embodiments, the invention includes therapeutic methods of using a BTK inhibitor and a PI3K-δ inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
41.
THERAPEUTIC COMBINATIONS OF AN ANTIFOLATE AND A BTK INHIBITOR
Therapeutic combinations of an antifolate compound and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of an antifolate compound and a BTK inhibitor, and methods of treating a disease using an antifolate compound and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of an antifolate compound, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, and methods of treating a disease using an antifolate compound, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease.
A61K 39/00 - Medicinal preparations containing antigens or antibodies
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a PI3K-δ inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, PI3K-δ inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.
A61K 31/529 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim forming part of bridged ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
43.
IMIDAZOPYRAZINE INHIBITORS OF BRUTON'S TYROSINE KINASE
In some embodiments, the invention relates to a BTK inhibitor or a pharmaceutically acceptable salt, cocrystal, ester, prodrug, solvate, hydrate or derivative thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to imidazopyrazine compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of a hyperproliferative disorder, an inflammatory disorder, an immune disorder, or an autoimmune disorder.
Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
45.
THERAPEUTIC COMBINATIONS OF A CD19 INHIBITOR AND A BTK INHIBITOR
Therapeutic combinations of a CD 19 inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a CD 19 inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer, such as a hematological malignancy. A combination of a BTK inhibitor and a CD 19 inhibitor, such as a CD19-targeted antibody or a CD19-targeted chimeric antigen receptor expressing T cell or NK cell, and compositions and uses thereof are disclosed. Combinations of a BTK inhibitor and a CD 19 inhibitor with a programmed death- 1 (PD-1) or PD-1 ligand (PD-L1) inhibitor and compositions and uses thereof are also disclosed.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Therapeutic combinations of a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a BTK inhibitor, and methods of treating a disease using a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, and methods of treating a disease using a molecule selected from the group consisting of a GITR binding molecule, a 4-1BB agonist, an OX40 agonist, and combinations thereof, a PD-1 or a PD-L1 inhibitor, and a BTK inhibitor, in particular a cancer or an immune, autoimmune, or inflammatory disease.
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Therapeutic combinations of a MEK inhibitor and a Bruton's tyrosine kinase (BTK) inhibitor are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of a MEK inhibitor and a BTK inhibitor and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
In an embodiment, therapeutic methods and uses of Bruton's Tyrosine Kinase (BTK) inhibitors for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, including dermatoses, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
In some embodiments, the present invention relates to novel small molecule inhibitors that block the CXCR4-SDF-1 signaling pathway by directly inhibiting members of the Tec family of kinases, namely Bruton's tyrosine kinase (BTK), and their use in treating diseases in which pathogenesis is mediated by the CXCR4/SDF-1 signaling pathway.
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
In some embodiments, the invention relates to crystalline solid forms, including hydrates, polymorphs, and salt forms, of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention relates to amorphous solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-a]pyrazin-1-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents.
The present disclosure relates to crystalline solid forms of (S)-4-(8-amino-3-(1-(but-2-ynoyl)pyrrolidin-2-yl)imidazo[ 1,5-a ]pyrazin-1-yl)-N( pyridin-2-yl)benzamide, and hydrates and salts thereof. The present disclosure further relates to use of the crystalline solid forms of the present disclosure in the treatment of diseases.
In some embodiments, the invention relates to crystalline solid forms, including polymorphs, hydrates, and salt forms, of(S)-4-(8-amino-3-(1 -(but-2-ynoyl)pyrrolidin-2-yl)imidazo[1,5-α]pyrazin-l-yl)-N-(pyridin-2-yl)benzamide. In some embodiments, the invention also relates to pharmaceutical compositions containing the crystalline solid forms, and methods for treating conditions or disorders by administering to a subject a pharmaceutical composition that includes the forms, including pharmaceutical compositions and methods for overcoming the effects of acid reducing agents. Formula (I)
Therapeutic compositions and methods of using the compositions, including combinations of a Bruton's tyrosine kinase (BTK) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor, and/or a Janus kinase-2 (JAK- 2) inhibitor are described. In certain embodiments, the invention includes therapeutic methods of using a PD-1 monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-L1 monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-1 inhibitor, a BTK inhibitor, and a PI3K-δ inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-L1 inhibitor, a BTK inhibitor, and a PI3K-δ inhibitor.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
54.
COMPOSITIONS AND METHODS FOR TREATMENT OF CHRONIC LYMPHOCYTIC LEUKEMIA AND SMALL LYMPHOCYTIC LEUKEMIA USING A BTK INHIBITOR
Therapeutic methods and pharmaceutical compositions for treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes pharmaceutical compositions for treating hematological malignancies comprising a combination of a BTK inhibitor and an anti-CD20 antibody.
In certain embodiments, the invention includes therapeutic methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
In some embodiments, the invention relates to quinazoline and quinoline compounds of Formula I: (I) or a pharmaceutically acceptable salt thereof, or to pharmaceutical compositions comprising these compounds and to their use in therapy. In particular, in some embodiments, the present invention relates to quinazoline and quinoline compounds, pharmaceutical compositions thereof, and the use of the compounds and pharmaceutical compositions in the treatment of Bruton's tyrosine kinase (BTK) mediated disorders.
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
57.
BTK INHIBITORS TO TREAT SOLID TUMORS THROUGH MODULATION OF THE TUMOR MICROENVIRONMENT
In certain embodiments, the invention includes therapeutic methods of using a BTK inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ), a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a B-cell lymphoma-2 (BCL-2) inhibitor are described. In some embodiments, the invention provides therapeutic combinations of a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a BCL-2 and BTK inhibitor.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/437 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4468 - Non-condensed piperidines, e.g. piperocaine having a nitrogen atom directly attached in position 4, e.g. clebopride, fentanyl
59.
THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, A PD-1 INHIBITOR AND/OR A PD-L1 INHIBITOR
Therapeutic compositions and methods of using the compositions, including combinations of a Bruton's tyrosine kinase (BTK) inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor, and/or a Janus kinase-2 (JAK- 2) inhibitor are described. In certain embodiments, the invention includes therapeutic methods of using a PD-1 monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-L1 monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-1 inhibitor, a BTK inhibitor, and a PI3K-δ inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-L1 inhibitor, a BTK inhibitor, and a PI3K-δ inhibitor.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
60.
THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR AND/OR A CDK 4/6 INHIBITOR
Therapeutic combinations of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms (PI3K-γ,δ, PI3K-γ, and PI3K-δ, a Janus kinase-2 (JAK-2) inhibitor, a cyclin-dependent kinase- 4/6 (CDK4/6) inhibitor, and/or a Bruton's tyrosine kinase (BTK) inhibitor are described. In certain embodiments, the invention includes therapeutic combinations of a cyclin-dependent kinase-4/6 (CDK4/6) inhibitor and a BTK inhibitor, a PI3K-δ inhibitor and a BTK inhibitor, a JAK-2 and a BTK inhibitor, and a JAK-2, PI3K-δ, and BTK inhibitor.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
A61K 31/4439 - Non-condensed pyridinesHydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
61.
THERAPEUTIC COMBINATIONS OF A BTK INHIBITOR, A PI3K INHIBITOR, A JAK-2 INHIBITOR, A PD-1 INHIBITOR AND/OR A PD-L1 INHIBITOR
Therapeutic compositions and methods of using the compositions, including combinations of a Bruton's tyrosine kinase (BTK) inhibitor, a phosphomositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both y- and δ-isoforms (ΡΙ3Κ-γ,δ, ΡΙ3Κ-γ, and ΡΙ3Κ-δ, a programmed death 1 (PD-1) or programmed death ligand 1 (PD-Ll) inhibitor, and/or a Janus kinase-2 (JAK- 2) inhibitor are described. In certain embodiments, the invention includes therapeutic methods of using a PD-1 monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-Ll monoclonal antibody and a BTK inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-1 inhibitor, a BTK inhibitor, and a ΡΙ3Κ~δ inhibitor. In other embodiments, the invention includes therapeutic methods of using a PD-Ll inhibitor, a BTK inhibitor, and a ΡΙ3Κ~δ inhibitor.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/4155 - 1,2-Diazoles not condensed and containing further heterocyclic rings
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
62.
METHODS OF TREATING CANCERS, IMMUNE AND AUTOIMMUNE DISEASES, AND INFLAMMATORY DISEASES BASED ON BTK OCCUPANCY AND BTK RESYNTHESIS RATE
In an embodiment, therapeutic methods and use of a Bruton's Tyrosine Kinase (BTK) inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described. In an embodiment, dosing regimens for a BTK inhibitor for treatment of cancer, inflammation, immune disorders, and autoimmune disorders, and for transplantation prophylaxis, based on BTK occupancies and/or BTK resynthesis rates for B cells in various diseases, tissue compartments, including bone marrow and lymph nodes, are described.
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/522 - Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
A61P 37/06 - Immunosuppressants, e.g. drugs for graft rejection
Therapeutic combinations of a Janus kinase-2 (JAK-2) inhibitor, a Bruton's tyrosine kinase (BTK) inhibitor, and/or a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms, are described. In some embodiments, the invention provides pharmaceutical compositions comprising combinations of (1) a ΡΙ3Κ-δ inhibitor and a BTK inhibitor, (2) a JAK-2 inhibitor and a BTK inhibitor, or (3) a JAK-2 inhibitor, ΡΙ3Κ-δ inhibitor, and BTK inhibitor, and methods of using the pharmaceutical compositions for treating a disease, in particular a cancer.
In some embodiments, the present invention relates to novel small molecule inhibitors that block the CXCR4-SDF-1 signaling pathway by directly inhibiting members of the Tec family of kinases, namely bone marrow X kinase (BMX) (also known as epithelial and endothelial tyrosine kinase (ETK)), and their use in treating diseases in which pathogenesis is mediated by the CXCR4/SDF-1 signaling pathway.
In some embodiments, the present invention relates to novel small molecule inhibitors that block the CXCR4-SDF-1 signaling pathway by directly inhibiting members of the Tec family of kinases, namely Bruton's tyrosine kinase (BTK), and their use in treating diseases in which pathogenesis is mediated by the CXCR4/SDF-1 signaling pathway.
A61K 31/454 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
66.
BTK INHIBITOR FOR THE TREATMENT OF CHRONIC LYMPHOCYTIC AND SMALL LYMPHOCYTIC LEUKEMIA
Therapeutic methods of treating chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) are described. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating subtypes of CLL and SLL using a BTK inhibitor, including subtypes of CLL in patients sensitive to thrombosis and subtypes of CLL that increase monocytes and NK cells in peripheral blood after treatment with a BTK inhibitor. In certain embodiments, the invention includes therapeutic methods of treating CLL and SLL using a combination of a BTK inhibitor and an anti-CD20 antibody.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
In some embodiments, the invention includes a therapeutic combination of a phosphoinositide 3-kinase (PI3K) inhibitor, including PI3K inhibitors selective for the γ- and δ-isoforms and selective for both γ- and δ-isoforms, and a Bruton's tyrosine kinase (BTK) inhibitor. In some embodiments, the invention includes therapeutic methods of using a BTK inhibitor and a PI3K-δ inhibitor to treat solid tumor cancers by modulation of the tumor microenvironment, including macrophages, monocytes, mast cells, helper T cells, cytotoxic T cells, regulatory T cells, natural killer cells, myeloid-derived suppressor cells, regulatory B cells, neutrophils, dendritic cells, and fibroblasts.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
Methods to improve hematopoiesis and increase white blood cell counts in subjects and patients using pyrimidine-based inhibitors of Bruton's tyrosine kinase (Btk) are disclosed.
Compounds of the formula
1 are defined herein, inhibit the IGF-1R enzyme and are useful for the treatment and/or prevention of hyperproliferative diseases such as cancer, inflammation, psoriasis, allergy/asthma, disease and conditions of the immune system, disease and conditions of the central nervous system.
C07D 471/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups
C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
C07D 491/00 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or
C07D 495/00 - Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
C07D 497/00 - Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
patents
