JP2015163631A - 肺癌治療剤 - Google Patents
肺癌治療剤 Download PDFInfo
- Publication number
- JP2015163631A JP2015163631A JP2015095990A JP2015095990A JP2015163631A JP 2015163631 A JP2015163631 A JP 2015163631A JP 2015095990 A JP2015095990 A JP 2015095990A JP 2015095990 A JP2015095990 A JP 2015095990A JP 2015163631 A JP2015163631 A JP 2015163631A
- Authority
- JP
- Japan
- Prior art keywords
- antibody
- cells
- lung cancer
- therapeutic agent
- cancer
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
Links
Images
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1774—Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
-
- 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
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
- A61P33/06—Antimalarials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
- C07K14/70521—CD28, 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
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
- C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
- G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
- G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
- A61K2039/507—Comprising a combination of two or more separate antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- 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
- C07K2317/73—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Description
1.PD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質を含有してなる免疫賦活組成物、
2.PD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質を含有してなる癌治療組成物、
3.癌転移を抑制する組成物である前項2記載の癌治療組成物、
4.PD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質を含有してなる感染症治療組成物、
5.免疫賦活を介して作用することを特徴とする前項2または3記載の癌治療組成物、
6.免疫賦活を介して作用することを特徴とする前項4記載の感染症治療組成物、
7.PD−1とPD−L1若しくはPD−1とPD−L2の相互作用阻害物質、PD−1の細胞内シグナル阻害物質、およびPD−1、PD−L1若しくはPD−L2の産生阻害物質から選択される一以上の免疫抑制シグナル阻害物質である前項1乃至6のいずれかに記載の組成物、
8.PD−1抗体、PD−L1抗体、可溶化PD−1、および可溶化PD−L1から選択される一以上のPD−1とPD−L1の相互作用阻害物質である前項7記載の組成物、
9.国際受託番号FERM BP-8392で識別されるハイブリドーマが産生する抗ヒトPD−1抗体、非ヒト抗体をヒト化させた抗PD−1抗体、および完全ヒト型抗ヒトPD−1抗体から選択されるPD−1抗体である前項8記載の組成物、
10.遺伝子改変によりPD−1発現が阻害されたリンパ球細胞が、免疫抑制シグナル阻害物質である前項1乃至6のいずれかに記載の組成物、
11.PD−1とPD−L1若しくはPD−1とPD−L2の相互作用阻害物質、PD−1の細胞内シグナル阻害物質、またはPD−1、PD−L1若しくはPD−L2の産生阻害物質が、タンパク質、ポリペプチド若しくはペプチド、ポリヌクレオチド若しくはポリヌクレオシド、抗体若しくはそれらの誘導体、有機合成化合物、無機化合物、および天然物から選択される一以上の物質である前項7記載の組成物、
12.PD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質を投与することからなる免疫賦活方法、
13.PD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質を投与することからなる癌治療方法、
14.癌転移を抑制する前項13記載の癌治療方法、
15.PD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質を投与することからなる感染症治療方法、
16.免疫賦活を介して作用することを特徴とする前項13または14記載の癌治療方法、
17.免疫賦活を介して作用することを特徴とする前項15記載の感染症治療方法、
18.PD−1とPD−L1若しくはPD−1とPD−L2の相互作用阻害物質、PD−1の細胞内シグナル阻害物質、およびPD−1、PD−L1若しくはPD−L2の産生阻害物質から選択される一以上の免疫抑制シグナル阻害物質である前項12乃至17のいずれかに記載の方法、
19.PD−1抗体、PD−L1抗体、可溶化PD−1、および可溶化PD−L1から選択される一以上のPD−1とPD−L1の相互作用阻害物質である前項18記載の方法、20.国際受託番号FERM BP-8392で識別されるハイブリドーマが産生する抗ヒトPD−1抗体、非ヒト抗体をヒト化させたPD−1抗体、および完全ヒト型抗ヒトPD−1抗体から選択されるPD−1抗体である前項19記載の方法、
21.遺伝子改変によりPD−1発現が阻害されたリンパ球細胞が、免疫抑制シグナル阻害物質である前項12乃至17のいずれかに記載の方法、
22.PD−1とPD−L1若しくはPD−1とPD−L2の相互作用阻害物質、PD−1の細胞内シグナル阻害物質、またはPD−1、PD−L1若しくはPD−L2の産生阻害物質が、タンパク質、ポリペプチド若しくはペプチド、ポリヌクレオチド若しくはポリヌクレオシド、抗体若しくはそれらの誘導体、有機合成化合物、無機化合物、および天然物から選択される1つ以上の物質である前項18記載の方法、
23.免疫賦活組成物を製造するためのPD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質の使用、
24.癌治療組成物を製造するためのPD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質の使用、
25.癌治療組成物が、癌転移抑制組成物である前項24記載の物質の使用、
26.感染症治療組成物を製造するためのPD−1、PD−L1、またはPD−L2の免疫抑制シグナル阻害物質の使用、
27.PD−L1またはPD−L2を発現するように形質転換されたスクリーニング用癌細胞株、
28.前項27記載の細胞、リンパ球細胞および被験物質を接触させて、前項27記載の細胞へのリンパ球細胞の免疫反応に対する被験物質の増強作用を評価することを特徴とする免疫賦活物質のスクリーニング方法、
29.癌細胞である前項27記載の細胞、リンパ球細胞および被験物質を接触させて、その癌細胞へのリンパ球細胞の免疫反応に対する被験物質の増強作用またはその腫瘍細胞の増殖に対する阻害作用を評価することを特徴とする癌治療物質のスクリーニング方法、
30.病原体を感染させた前項27記載の細胞またはPD−L1若しくはPD−L2を発現する細胞、リンパ球細胞および被験物質を接触させて、その感染細胞へのリンパ球細胞の免疫反応に対する被験物質の増強作用または病原体増殖に対する阻害作用を評価することを特徴とする感染症治療物質のスクリーニング方法、
31.前項27記載の癌細胞株を移植して作出した哺乳動物、
32.前項31記載の哺乳動物に被験物質を投与し、被験物質による移植癌細胞の増殖に対する抑制率またはその被移植哺乳動物の生存率を評価することを特徴とする癌治療物質の選別方法に関する。
モノクローナル抗体産生細胞の作製は、抗原で免疫された動物から抗体価の認められた個体を選択し、最終免疫の2〜5日後に脾臓またはリンパ節を採取し、それらに含まれる抗体産生細胞を同種または異種動物の骨髄腫細胞と融合させることにより、継代培養可能なモノクローナル抗体産生ハイブリドーマを作製することにより行なうことができる。抗原タンパク質の投与は、抗体産生が可能な部位にそれ自体あるいは担体、希釈剤と共に行なう。投与には、抗体産生能を高めるため、完全フロイントアジュバントや不完全フロイントアジュバントを投与するのが一般的である。また、“DNA免疫”と呼ばれる方法によっても、動物を免疫することができる。この方法は、免疫動物の後足前脛骨筋にカルジオトキシン(Cardiotoxin)を処置し、さらに抗原タンパク質を発現するベクターを導入した後、組織修復の過程でベクターが筋細胞に取りこまれ、タンパク質を発現する現象を利用した方法である(Nature Immunology,2001年,第2巻,第3号,p.261〜267)。
マウスPD−L1発現ベクターの作製は、マウスPD-L1cDNA(Journal of Experimental Medicine,2000年,第19巻,第7号,p.1027〜1034)を制限酵素EcoRIで消化して、発現ベクターpApuroXS(The EMBO Journal,1994年,第13巻,第6号,p.1341〜1349)に挿入し、連結させることによって行った。作製した発現ベクターpApuroXS-PD-L1のP815細胞への導入は、エレクトロポーレーション法(360V、500μF)で行った。P815細胞の培養は、FCS(10%)、2−メルカプトエタノール(10-5M)、各種抗生物質含RPMI-1640培地で培養できるが、さらに、抗生物質ピューロマイシン(Puromycin;3μg/ml)を含んだ培地の培養に対して耐性の同細胞株を継代培養することによって、マウスPD−L1を安定的に発現する形質転換P815細胞株を取得した。PD−L1の発現は、フローサイトメトリー解析にて確認した。図1(A)にH−2Ld特異的2C CTLクローンのPD−1発現(i)と、P815(肥満細胞種由来細胞株)のPD−L1発現安定形質転換株でのPD−L1発現(ii)を示すフローサイトメトリーを示す。
同様の方法で、PD−L1を安定的に発現する形質転換B16細胞株(B16/PD−L1)を取得した(図1(A)(iii)〜(v)参照)。ここでは発現ベクターとして同様の方法で作製したpEFBOSneo-PD-L1(Nucleic Acid Research,1990年,第18巻,第17号,p.5322)を用い、細胞株の選択培養にはG418(0.5mg/ml)を使用した。
全長マウスPD-L1cDNAの3'末端側に6個のヒスチジンがタンデムに並んだペプチドタグ(His-Tag)を連結させたタンパク質をコードするcDNAを制限酵素EcoRIおよびNotIで消化して、発現ベクターpVL1393(商品名:Clontechより購入)に挿入させた。続いて、この発現ベクターをSF9昆虫細胞(Invitrogenより購入)に導入して、封入体を回収した。この封入体ウイルスをHiFive昆虫細胞(Invitrogenより購入)に2日間、27℃下で培養することによって感染させた。溶解緩衝液(Tris-HCl(50mM,pH7,含1%TritonX-100)、EDTA(10mM)、NaCl(150mM)、各種プロテアーゼ阻害剤)で溶解させた細胞溶解液を、Ni−セファロースカラムクロマトグラフィーで処理することによって、抗原となる精製PD−L1タンパク質を取得した。
透析した同PD−L1タンパク質を完全フロイントアジュバンドと共に8週令メスWhisterラット(SLC Japanより購入)に免疫して、数日後、末梢リンパ節から回収した2×108細胞を、PEG1500(Amershamより購入)を用いて同数のSP2/0細胞と細胞融合させた。さらに、RPMI1640培地(HAT(Sigmaより購入)、Origen(10%,Igenより購入)、FCS(10%)、2−メルカプトエタノール(10-5M)、各種抗生物質)で培養することによって選択し、産生抗体の存在をフローサイトメトリー解析にて確認した。これによって樹立されたハイブリドーマ(国際受託番号:FERM BP-8396で認識されるハイブリドーマ)をBalb/C nu/nuマウスに移入して、後に腹水からの回収液をプロテインGセファロースカラムクロマトグラフィーで精製することによって、PD−L1に対するモノクローナル抗体(1−111)を取得した。フローサイトメトリー等で使用される抗体は、Sulfo-NHS-LC-biotin(商品名:Pierceより購入)を用いてビオチン化したものを用いた。
また、同様の方法に従い、抗ヒトPD−1抗体(国際受託番号:FERM BP-8392で認識されるハイブリドーマから産生されるモノクローナル抗体)を作製した。
細胞傷害性アッセイは、51Cr(クロム)遊離アッセイによって行った。
2C細胞(Journal of Immunology,1996年,第157巻,第2号,p.670〜678)は、2CトランスジェニックB6マウス由来の(H−2L)dアロ反応性の細胞傷害性T細胞である。図1(B)に、2C細胞(E:エフェクター)を51Crラベル化したP815細胞(T:ターゲット)と共に(○)または3つのPD−L1発現P815細胞株(P815/PD−L1)(□、◇、△)と共にあるいはさらに10mg/mlラットanti-PD-L1F(ab')2IgG存在下(▲)を、さまざまなE/T比で混合して、4時間で遊離される51Crを測定した結果を示す。
抗PD−L1抗体(anti-PD-L1F(ab')2)は、細胞傷害性Tリンパ球細胞の低下した細胞傷害活性を回復させた。これらの結果から、PD−L1の機能を阻害することによるPD−1およびPD−L1シグナルの阻害は、癌細胞に対する細胞傷害活性を増強させることができると考えられる。
1×106細胞のP815細胞(n=6)またはP815/PD−L1細胞(n=6)を同系DBA/2マウスの皮下にそれぞれ移入し、腫瘍増殖とマウスの生存率を評価した。その結果を図2(A)に示す。図中、○はP815細胞株移植群、□、△はPD−L1発現P815細胞株移植群である。さらにP815/PD−L1細胞を移入した群の組織学的解析を行った。移入20日後のマウスの腹壁ならびに腹膜腔の組織切片を、10%ホルムアルデヒドで固定、パラフィンで砲架して、ヘマトキシリン、エオジンで染色して得られた染色像を図2(B)に示す。図中、aは腹壁および腹膜への腫瘍細胞の浸潤を示す40倍像、bは同じく400倍像であり、cは脾臓への転移、dは肝臓への転移を示す。
P815細胞を移植した群では、P815細胞の増殖は抑えられており、6〜7週目では30%が生存したのに対して、PD−L1を発現するP815細胞(P815/PD−L1)を移植した群では、癌細胞の増殖は著しく、2〜4週目までに全例が死亡した(図2(A))。P815/PD−L1は、腹膜腔、さらに、腹腔へ浸潤しており、また、肝および脾臓への転移が認められた(図2(B)a〜d参照)。
P815細胞を移入し免疫したマウスから細胞傷害性T細胞CTLを調整し、2×106個数のCTL細胞と、5×106個数のP815細胞またはP815/PD−L1細胞のみ、あるいはanti-PD-L1F(ab')2IgG(10mg/ml)存在下でP815/PD−L1細胞をそれぞれ混合培養し、24時間後の培養上清中のIFN−γをELISAキット(Bioscienceから購入)で測定した。その結果を図3(A)に示す。
また、図3(B)に、3×106個数のP815/PD−L1細胞を皮下移入した同系DBA/2マウス(n=10)に、ラットIgG(□)あるいはanti-PD-L1F(ab')2IgG(0.1mg/一匹)(○)を、細胞移入後1、3、5、7日後にそれぞれ腹腔内投与し、腫瘍増殖とマウスの生存率を評価した結果を示す。
抗PD−L1抗体は、P815/PD−L1により抑制された細胞傷害性Tリンパ球細胞からのIFN−γ産生を回復させた(図3(A))。抗PD−L1抗体の投与は、癌細胞増殖を抑制し、明確な生存効果を示した(図3(B))。この結果は、抗PD−L1抗体の投与が癌治療に有効であることを示している。
1×106個数のB16メラノーマ(n=6)またはB16/PD−L1細胞(n=6)をB6マウスにはそれぞれ皮下移入し、同数のB16/PD−L1細胞をPD−1トランスジェニックB6マウス(n=5)およびPD−1遺伝子ホモ欠損B6マウス(PD−1-/-(n=4))(Science,2001年,291巻,5502号,p.319〜332)に移入し、以後25日までそれぞれの腫瘍増殖を測定した。その結果を図4に示す。
2.5×108個数のJ558Lミエローマ細胞を皮下移入した同系Balb/Cマウス(n=9)に、ラットIgGあるいはanti-PD-L1F(ab')2IgG(0.1mg/一匹)を細胞移入後3、5、7日後にそれぞれ腹腔内投与し、腫瘍増殖を評価した(図5(B))。また、同様にJ558Lミエローマ細胞を皮下移入したPD−1ホモ欠損マウスとBalb/C(n=4)での腫瘍増殖を比較した(図5(C))。
抗PD−L1抗体の投与は、PD−L1を発現しているJ558癌細胞(図5(A)に各種ミエローマ細胞株でのPD−L1発現を示すフローサイトメトリーを示す。)の増殖を抑制した(図5(B))。また、J558細胞を移植したPD−1欠損マウスでは移植癌細胞の増殖は完全に阻害された(図5(C))。これらの結果は、PD−L1もしくはPD−1の阻害が癌治療に有効であることを示している。
血管内皮細胞(以下、ECsと略す。)をマレリーバーグの方法(Journal Immunology Methods,2000年,第244巻,第1-2号,p.205〜215)により、マウス心臓から取得した。具体的には、心臓組織をコラゲナーゼで消化した後、マウスIgとともに前培養、さらに、FITC修飾した抗CD31抗体、同修飾抗CD105抗体、同修飾抗isolectinB4抗体、および、抗FITCビーズを添加して培養した。この血管内皮細胞をMagnetic-activated cell-sorting separation columns(商品名:Miltenyi Biotecより購入)を用いて、ポジティブ選択によって精製した。
取得した血管内皮細胞でのPD−L1、PD−L2の発現を、フローサイトメトリーで確認した。同細胞の標識には、抗PD−L1抗体(抗体名:1−111)、抗PD−L2抗体(抗体名:#122)および蛍光標識した2次抗体を用いて行った(図6(A))。解析はCellQuestソフトウェア(Dickinsonより購入)を使用したFacscalibur(機器名:Becton Dickinsonより購入)で、1万回イベントで解析した。PD−L1あるいはPD−L2の発現は、開口曲線で示され、コントロールIgは充填曲線で示される。
マウス各組織でのPD−L1発現の確認を組織染色によって行った。各組織サンプリング1時間前に100μgビオチン標識化抗PD−L1抗体(1−111)を溶解した100μlPBSをマウスに静脈投与した。続いて、5μm凍結切片を4%パラホルムアルデヒド(PFA)で固定して、Streptavidin-FITCで染色した。さらに、各切片をPhalloidinで対比染色した(図6(B)、(a)眼球、(b)顎下腺、(c)心臓、(d)肺、(e)肝臓、(f)腎臓でのPD−L1の発現を示す。図中、Chは脈絡膜、CVは中心静脈、Glは糸球体、Reは網膜を示す。各矢印は、血管内皮細胞を示す。各染色像は40倍拡大像である。)。PD−L1は、心臓、肺、腎臓、胃、小腸、顎下腺、眼球、肝臓の血管内皮で認められた。肝臓での発現は、肝臓洞様毛細血管に局在していた。
肝臓非実質細胞(以下、LNPCsと略記する。)でのPD−L1発現を組織染色(図7(A))ならびにフローサイトメトリー(図7(B))で確認した。組織染色は、3%PFAで固定した5μm肝臓凍結切片をラット血清で前処理し、ビオチン標識化抗PD−L1抗体(1−111)あるいはビオチン標識化抗ICAM−1抗体(商品名:BD Pharmingenより購入)にて1時間、室温下で抗体反応を行ない、ビオチン抗体をtyramide signal amplification(TSA)fluorescence system(機器名:PerkinElmer Life Sciencesより購入)にて視覚化した(図7(A):ICAM−1の発現、同図(B):PD−L1の発現、CV:中心静脈を示す。各染色像は40倍拡大像である。)。
LNPCsは、pronaseE法(Experimental Cell Research,1976年,第99巻,p.444〜449)によってマウス肝臓より単離した。具体的には、LNPCsは、肝臓をpronaseE溶液(Merck)にて還流、培養し、密度勾配遠心法にて分離した。その細胞懸濁液中のクップファー細胞(Kupffer Cells)(CD54+、CD11bhigh)の相対的分布は20〜25%であり、肝臓類洞周囲腔内皮細胞(以下、LSECsと略記する。)(CD54+、CD11bhigh)は、75〜80%である。
クップファー細胞とLSECsを、FITC標識化抗CD11b抗体およびICAM−1、PD−L1、B7−1、B7−2に対するそれぞれのビオチン化モノクローナル抗体、それに続くPE標識化Streptavidinにて、それぞれ二重染色した。クップファー細胞とLSECsは、それぞれCD11bhighとCD11blow細胞としてゲートされる(図8)。
PD−L1は、クップファー細胞では、ICAM−1、B7−1、B7−2を共発現しているが、LSECsではその発現は弱いものであった(図8)。
PD−1遺伝子ホモ欠損マウス(PD−1-/-)あるいは野生型C57BL/6マウス(wt)の脾臓ならびにリンパ組織から、T-cell enrichment column(商品名:Genzymeより購入)を用いたネガティブ選別によって、ナイーブT細胞(精製度90%以上)を精製した。同細胞を10μg/ml抗CD3モノクローナル抗体(2C11)とともに48時間培養して活性化させた。
上記方法によって活性化したナイーブT細胞を、FITC標識化抗CD4抗体あるいはAPC標識化抗CD8抗体ならびにPE標識化抗CD25抗体、PE標識化抗CD44抗体、PE標識化抗CD69抗体、PE標識化抗CTLA−4抗体、ビオチン標識化抗B7−1(CD80)抗体、ビオチン標識化抗B7−2(CD86)抗体、抗PD−1抗体(抗体名:J43、国際受託番号FERM BP-8118で認識されるハイブリドーマから産生されるモノクローナル抗体)、抗PD−L1抗体(1−111)で二重染色して、フローサイトメトリーにてそれぞれの分子の発現を解析した(図9、図10)。
なお、国際受託番号FERM BP-8118で識別されるハイブリドーマは、2001年5月30日付で日本国茨城県つくば市東1丁目1番地1 中央第6(郵便番号305-8566)、独立行政法人産業技術総合研究所特許生物寄託センターに受託番号FERM P-18356で寄託され、2002年7月16日付で国際寄託に移管されている。
PD−1遺伝子ホモ欠損マウス(PD−1-/-)あるいは野生型マウス(wt)のナイーブT細胞の活性化は、上記実施例8に記載の方法で行った。活性化後の同細胞の増殖をBrdU取りこみ法によって測定した(図11(A))。BrdUを48時間の最後の6時間に添加して細胞を標識し、これをProliferation ELISA kit(商品名:Rocheより購入)を用いる測定によって細胞増殖を決定した。また、この時のIFN−γ産生量をELISA Kit(商品名:Genzymeより購入)にて測定した(図12(A))。
PD−1遺伝子ホモ欠損マウス(PD−1-/-)あるいは野生型マウス(wt)由来のT細胞を上記実施例8で記載の方法であらかじめ活性化させた。続いて、既に活性化しているT細胞に対して、野生型マウスからのマイトマイシンC処理LNPCsの存在あるいは非存在下で、さらに、30μg/ml抗PD−L1抗体(1−111)(コントロールとしたラットIgG)、20μg/mlCTLA4-Ig(Genzyme)(コントロールとしたヒトIgG)の存在あるいは非存在下でそれぞれ60時間培養して、最後の12時間の同細胞の増殖をBrdU取りこみ法によって測定した(図11(B))。また、48時間時点でのIFN−γ産生量も測定した(図12(B))。
ナイーブT細胞の活性化時におけるIFN−γ産生量は、PD−1-/-と野生型マウスの違いによる有意な差異は認められなかった。一方、既に活性化されたT細胞においては、野生型マウス由来のT細胞のIFN−γ産生量は、PD−1-/-由来のものに比べ有意に低かった(図12)。このことから、既に活性化しているT細胞に対するPD−1の抑制作用の効果は、ナイーブT細胞の活性化に対する効果よりも高いことが示唆された。
野生型マウス由来の活性化したT細胞は、LNPCsとの共培養では、T細胞の細胞増殖およびIFN−γ産生量に有意な変化は認められないが、PD−1-/-由来の活性化したT細胞は、LNPCsとの共培養によって、その細胞増殖に有意な増加が認められた(図11(B)、図12(B))。また、野生型マウス由来の活性化したT細胞とLNPCsとの共培養への抗PD−L1抗体の添加によって、T細胞の細胞増殖の増加が認められた(図11(B))。これらの結果は、LNPCsのPD−1あるいはPD−L1が、活性化T細胞の抑制に関与しており、PD−1の欠如あるいはPD−1とPD−L1間の相互作用の阻害が、T細胞を活性化することを示すものである。
PD−1遺伝子ホモ欠損マウス(PD−1-/-)あるいは野生型マウス(wt)の活性化T細胞を、5μM CFSE(5-(6)-carboxy-fluorescein diacetate succinimidyl diester)(商品名:Molecular probesより購入)で標識して、LNPCsとともに48時間共培養した。この時の細胞分裂を、FACSを用いたCFSE活性測定によって決定した(図12(C))。
活性化T細胞の細胞増殖抑制は、細胞分裂の停止に起因しており、PD−1シグナルがT細胞の細胞分裂を抑制することが示唆された(図12(C))。
PD−1遺伝子ホモ欠損マウス(PD−1-/-)あるいは野生型マウス(wt)(3匹/群)に109-1010PFU(plaque-forming units)Ad-lacZを静脈内投与して、マウスをアデノウイルスに感染させた。ここで使用したAd-lacZは、E1およびE3領域に欠損を有し、さらに、lacZ遺伝子を持った5型アデノウイルスであり、293細胞で増殖させた後、塩化セシウム密度勾配遠心分離(Nucleic Acid Research,1995年,第234巻,第19号,p.3816〜3821)の記載によって精製したものである。
感染後0日日あるいは7日目に、同マウスに対して屠殺1時間前に0.5mg BrdU(商品名:Sigmaより購入)を静脈内投与して、採取した脾臓細胞および肝臓内リンパ球を抗BrdU抗体および抗CD19抗体あるいは抗CD3抗体で二重標識した(図13)。
さらに、感染後7日目の同細胞に対しては、抗BrdU抗体、抗CD19抗体、抗CD3抗体、抗CD4抗体、抗CD8抗体で二重標識した(図14(B)、それぞれの棒グラフはBrdU陽性細胞の割合を示す。)。
アデノウイルス感染したPD−1-/-マウスの肝臓では、同様に感染した野生型マウスの肝臓に比較して、増殖性(BrdU陽性)の各リンパ球(CD19陽性、CD3陽性、CD4陽性、CD8陽性)の割合が増加していた。一方、このような現象が脾臓では認められなかったことから、PD−1は、炎症を起した組織でのT細胞の増殖を阻害することが示唆された(図14(B))。
PD−1遺伝子ホモ欠損マウス(PD−1-/-)あるいは野生型マウス(wt)(3匹/群)に109-1010PFU Ad-lacZを静脈内投与して、マウスをアデノウイルスに感染させ、さらに、感染後0日目あるいは7日目の屠殺1時間前に0.5mg BrdU(商品名:Sigmaより購入)を静脈内投与して、採取した肝臓切片を抗BrdU抗体で標識した(図15(a)〜(d))、20倍拡大像)。感染後7日目のPD−1遺伝子ホモ欠損マウス(PD−1-/-)の肝臓切片に対しては、抗BrdU抗体および抗CD4抗体あるいは抗CD8抗体で二重標識した(図15(e)、(f)、40倍拡大像)。
感染後30日目の野生型マウスの肝臓では、洞様毛細血管および非実質領域への中程度の局所的な細胞浸潤が認められたが、PD−1-/-マウスでは、肝炎を示す症状は認められなかった(図16(h)、(i)および(j)、(n))。
感染後7日目あるいは30日目のPD−1遺伝子ホモ欠損マウス(PD−1-/-)あるいは野生型マウス(wt)の肝臓切片に対して、ヘマトキシリン&エオジン染色(図16(g)〜(j),20倍拡大像、(k)〜(n),40倍拡大像)およびX−Gal染色を行った(図16(o)〜(r),40倍拡大像)。
感染後7日目および30日目の野生型マウスの肝臓では、X−Gal染色像が示すアデノウイルスの感染が認められたが、PD−1-/-マウスでは、その感染は、30日目にはほぼ排除されていた(図16(o)、(p)および(q)、(r))。これらの結果から、PD−1シグナルが、ウイルス感染による炎症組織におけるエフェクターT細胞の細胞増殖を誘導することによるウイルスの排除に関与することが示された。
マウスPD−L1を強制発現させたP−815/PD−L1細胞は、5μg/mL puromycin(Sigmaより購入)を含む通常培地(以下、選択培地と略す。)を用いて、培養フラスコに播種し、37℃、5%CO2/95%airの条件で50%〜90%コンフルエントになるまで培養した。マウスcytotoxic T lymphocyte 2C細胞は、MMC(Mitomycin C)処理したP−815細胞およびConA刺激ラット脾細胞培養上清とともに通常培地中で数日継代培養した。回収したP−815/PD−L1細胞にDELFIA EuTDA Cytotoxicity Reagents(PerkinElmerより購入)のBATDA Reagentを3μL加え、15分間培養した。さらに、PBSで洗浄した。2C細胞は、P−815細胞を加えて継代した5〜8日目の細胞を用いた。
被検物質である抗マウスPD−1抗体(図17中、anti-mPD-1Ab(J43))、抗マウスPD−L1抗体(同図中、anti-mPD-L1Ab(1−111))、マウスPD−1Fc(同図中、mPD−1Fc)、ヒトPD−1Fc(同図中、hPD−1Fc)、マウスIgG2aκ(同図中、ControlIg)またはPBSを96well plateに20μL(10ng/mL)ずつ分注し、P−815/PD−L1細胞または通常培地を50μLずつ加えた。さらに2C細胞、通常培地または1%TritonX100を含む通常培地を50μLずつ加えた。通常培地を添加したウェルの上清50μLをバックグラウンド用として回収し、その他の上清を回収するまで、37℃で保存した。残りの細胞は4時間培養した。続いて、同96well plateを遠心し、上清を回収した。回収した上清にCytotoxicity Reagents(PerkinElmerより購入)のDELFIA Europium Solutionを200μL添加して15分間振とうした。振とう後、ARVOsxマルチラベルカウンター(WALLAC)にて時間分解蛍光測定を行った。なお、1%TritonX100を含む通常培地を添加したウェルの上清を高コントロール、通常培地を添加したウェルの上清を低コントロールとした。
評価群の組成は、被検物質、P−815/PD−L1細胞及び2C細胞、高コントロール群の組成は、PBS、P−815/PD−L1細胞および1%TritonX100を含む通常培地、低コントロール群の組成は、PBS、P−815/PD−L1細胞および通常培地、2C細胞コントロール群の組成は、PBS、通常培地および2C細胞、バックグラウンド群の組成は、PBS、P−815/PD−L1細胞及び通常培地である。CTL活性(%)は、以下の式にて算出した。すべての値は、バックグランドで得た平均値を引いたものを使用した。
B16メラノーマ細胞を脾臓に移入したC57BL/6マウスに、抗マウスPD−1モノクローナル抗体を2日おきに腹腔内に投与して、移入後18日目の肝臓重量を測定することによって、癌転移に対する抗PD−1抗体の抑制効果を評価した。
コントロールIgGのみを投与したコントロール群に比べ、抗PD−1抗体投与群では、肝臓重量増加が有意に抑制された(肝臓重量/癌細胞非移入群:1.3g、コントロール群:6.8gから抗PD−1抗体投与群:3.5gへ減少)。この重量増加の抑制は、B16メラノーマ細胞の転移を抑制することを示すものである。
Claims (16)
- PD−1の免疫抑制シグナルを阻害する抗PD−1抗体を有効成分として含む肺癌治療剤。
- 抗PD−1抗体が、PD−1およびPD−L1の相互作用を阻害する請求項1記載の肺癌治療剤。
- 抗PD−1抗体が、キメラ抗体、ヒト化抗体または完全ヒト型抗体である請求項1または2記載の肺癌治療剤。
- 肺癌が、肺扁平上皮癌または肺腺癌である請求項1〜3のいずれか1項記載の肺癌治療剤。
- 肺癌が、PD−L1を発現する癌である請求項1〜4のいずれか1項記載の肺癌治療剤。
- 肺癌患者に対する外科的処置後に投与される請求項1〜5のいずれか1項記載の肺癌治療剤。
- さらに、免疫賦活剤または抗癌剤と組み合わせることを特徴とする請求項1〜6のいずれか1項記載の肺癌治療剤。
- 免疫賦活剤が、サイトカインまたは癌抗原である請求項7記載の肺癌治療剤。
- サイトカインが、GM−CSF、M−CSF、G−CSF、インターフェロン−α、インターフェロン−β、インターフェロン−γ、IL−1、IL−2、IL−3またはIL−12である請求項8記載の肺癌治療剤。
- 癌抗原が、MAGE−1もしくはMAGE−3由来のHLA−A1またはHLA−A2拘束ペプチド、MART−1、gp100、HER2/neuペプチド、MUC−1ペプチドおよびNY−ESO−1から選択される一または二以上の癌抗原である請求項8記載の肺癌治療剤。
- 免疫賦活剤が、抗CTLA−4抗体である請求項7記載の肺癌治療剤。
- さらに、化学療法剤と組み合わせることを特徴とする請求項1〜6のいずれか1項記載の肺癌治療剤。
- 化学療法剤が、アルキル化剤、ニトロソウレア剤、代謝拮抗剤、抗癌性抗生物質、植物由来アルカロイド、トポイソメラーゼ阻害剤、ホルモン療法剤、ホルモン拮抗剤、アロマターゼ阻害剤、P糖蛋白阻害剤および白金錯体誘導体から選択される一または二以上の化学療法剤である請求項12記載の肺癌治療剤。
- さらに、白血球減少症治療薬、血小板減少症治療薬、制吐剤または癌性疼痛治療薬から選択される一または二以上と組み合わせることを特徴とする請求項1〜6のいずれか1項記載の肺癌治療剤。
- インビボにおいて癌細胞の増殖を抑制する作用を有する請求項1記載の肺癌治療剤。
- PD−1の免疫抑制シグナルを阻害する抗PD−1抗体の有効量を患者に投与することを特徴とする肺癌治療方法。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015095990A JP6035372B2 (ja) | 2002-07-03 | 2015-05-08 | 肺癌治療剤 |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002194491 | 2002-07-03 | ||
JP2002194491 | 2002-07-03 | ||
JP2003029846 | 2003-02-06 | ||
JP2003029846 | 2003-02-06 | ||
JP2015095990A JP6035372B2 (ja) | 2002-07-03 | 2015-05-08 | 肺癌治療剤 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2014007941A Division JP5885764B2 (ja) | 2002-07-03 | 2014-01-20 | 癌治療剤 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016184782A Division JP6258428B2 (ja) | 2002-07-03 | 2016-09-21 | 肺癌治療剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2015163631A true JP2015163631A (ja) | 2015-09-10 |
JP6035372B2 JP6035372B2 (ja) | 2016-11-30 |
Family
ID=30117379
Family Applications (9)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004519238A Expired - Lifetime JP4409430B2 (ja) | 2002-07-03 | 2003-07-02 | 免疫賦活組成物 |
JP2009203514A Expired - Lifetime JP5159730B2 (ja) | 2002-07-03 | 2009-09-03 | モノクローナル抗体 |
JP2012197861A Expired - Lifetime JP5701266B2 (ja) | 2002-07-03 | 2012-09-07 | 感染症治療剤 |
JP2014007941A Expired - Lifetime JP5885764B2 (ja) | 2002-07-03 | 2014-01-20 | 癌治療剤 |
JP2015095990A Expired - Lifetime JP6035372B2 (ja) | 2002-07-03 | 2015-05-08 | 肺癌治療剤 |
JP2016184782A Expired - Lifetime JP6258428B2 (ja) | 2002-07-03 | 2016-09-21 | 肺癌治療剤 |
JP2017219349A Expired - Lifetime JP6559207B2 (ja) | 2002-07-03 | 2017-11-14 | 癌治療剤 |
JP2019018057A Pending JP2019094340A (ja) | 2002-07-03 | 2019-02-04 | 癌治療剤 |
JP2021036417A Pending JP2021080301A (ja) | 2002-07-03 | 2021-03-08 | 癌治療剤 |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2004519238A Expired - Lifetime JP4409430B2 (ja) | 2002-07-03 | 2003-07-02 | 免疫賦活組成物 |
JP2009203514A Expired - Lifetime JP5159730B2 (ja) | 2002-07-03 | 2009-09-03 | モノクローナル抗体 |
JP2012197861A Expired - Lifetime JP5701266B2 (ja) | 2002-07-03 | 2012-09-07 | 感染症治療剤 |
JP2014007941A Expired - Lifetime JP5885764B2 (ja) | 2002-07-03 | 2014-01-20 | 癌治療剤 |
Family Applications After (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016184782A Expired - Lifetime JP6258428B2 (ja) | 2002-07-03 | 2016-09-21 | 肺癌治療剤 |
JP2017219349A Expired - Lifetime JP6559207B2 (ja) | 2002-07-03 | 2017-11-14 | 癌治療剤 |
JP2019018057A Pending JP2019094340A (ja) | 2002-07-03 | 2019-02-04 | 癌治療剤 |
JP2021036417A Pending JP2021080301A (ja) | 2002-07-03 | 2021-03-08 | 癌治療剤 |
Country Status (15)
Country | Link |
---|---|
US (10) | US7595048B2 (ja) |
EP (4) | EP2206517B1 (ja) |
JP (9) | JP4409430B2 (ja) |
AT (1) | ATE481985T1 (ja) |
AU (1) | AU2003281200A1 (ja) |
DE (2) | DE60334303D1 (ja) |
DK (2) | DK1537878T3 (ja) |
ES (2) | ES2654064T3 (ja) |
FI (1) | FI2206517T3 (ja) |
FR (2) | FR15C0088I1 (ja) |
HU (3) | HUE10161767T1 (ja) |
LU (2) | LU92905I2 (ja) |
PT (2) | PT1537878E (ja) |
SI (1) | SI2206517T1 (ja) |
WO (1) | WO2004004771A1 (ja) |
Families Citing this family (679)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PT1210428E (pt) | 1999-08-23 | 2015-07-21 | Genetics Inst Llc | Pd-1, um recetor para b7-4 e suas utilizações |
CA2392477A1 (en) | 1999-11-30 | 2001-06-07 | Mayo Foundation For Medical Education And Research | B7-h1, a novel immunoregulatory molecule |
US7030219B2 (en) * | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
JP4409430B2 (ja) | 2002-07-03 | 2010-02-03 | 小野薬品工業株式会社 | 免疫賦活組成物 |
EP2277532A1 (en) | 2002-09-11 | 2011-01-26 | Genentech, Inc. | Novel composition and methods for the treatment of immune related diseases |
US7432351B1 (en) | 2002-10-04 | 2008-10-07 | Mayo Foundation For Medical Education And Research | B7-H1 variants |
MX2007004176A (es) | 2004-10-06 | 2007-06-15 | Mayo Foundation | B7-h1 y metodos de diagnosis, prognosis, y tratamiento de cancer. |
CN109485727A (zh) | 2005-05-09 | 2019-03-19 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及使用抗pd-1抗体来治疗癌症的方法 |
WO2006124667A2 (en) | 2005-05-12 | 2006-11-23 | Zymogenetics, Inc. | Compositions and methods for modulating immune responses |
BRPI0611766A2 (pt) | 2005-06-08 | 2011-12-20 | Dana Farber Cancer Inst Inc | métodos e composições para o tratamento de infecções persistentes e cáncer por inibição da rota de morte celular programada |
AU2012204032B2 (en) * | 2005-06-08 | 2014-01-16 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for the treatment of persistent infections and cancer by inhibiting the programmed cell death 1 (PD-1) pathway |
DK1907424T3 (en) * | 2005-07-01 | 2015-11-09 | Squibb & Sons Llc | HUMAN MONOCLONAL ANTIBODIES TO PROGRAMMED death ligand 1 (PD-L1) |
AU2006276083B2 (en) * | 2005-07-26 | 2012-04-19 | Cms Peptides Patent Holding Company Limited | Novel biologically active peptides and their new uses |
EP1777523A1 (en) * | 2005-10-19 | 2007-04-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | An in vitro method for the prognosis of progression of a cancer and of the outcome in a patient and means for performing said method |
US20090215084A1 (en) * | 2006-01-05 | 2009-08-27 | Mayo Foundation For Medical Education And Research | B7-h1 and b7-h4 in cancer |
US20100015642A1 (en) * | 2006-01-05 | 2010-01-21 | Kwon Eugene D | B7-h1 and survivin in cancer |
US8216996B2 (en) | 2006-03-03 | 2012-07-10 | Ono Pharmaceutical Co., Ltd. | Multimer of extracellular domain of cell surface functional molecule |
WO2007124361A2 (en) * | 2006-04-20 | 2007-11-01 | Mayo Foundation For Medical Education And Research | Soluble b7-h1 |
DK2772535T3 (da) | 2006-05-31 | 2022-07-04 | Childrens Medical Center | ABC5-positive mesenkymale stamceller som immunmodulatorer |
WO2008085562A2 (en) * | 2006-09-20 | 2008-07-17 | The Johns Hopkins University | Combinatorieal therapy of cancer and infectious diseases with anti-b7-h1 antibodies |
SI2486941T1 (sl) | 2006-10-02 | 2017-08-31 | E. R. Squibb & Sons, L.L.C. | Humana protitelesa, ki vežejo CXCR4 in njihova uporaba |
CA3045637A1 (en) * | 2006-12-27 | 2008-07-10 | Emory University | Compositions and methods for the treatment of infections and tumors |
SI2644205T1 (sl) | 2007-04-12 | 2018-11-30 | The Brigham And Women's Hospital, Inc. | Ciljanje ABCB5 za zdravljenje raka |
ES2437327T3 (es) | 2007-06-18 | 2014-01-10 | Merck Sharp & Dohme B.V. | Anticuerpos para el receptor PD-1 humano de muerte programada |
EP2514762B1 (en) | 2007-07-13 | 2015-04-08 | The Johns Hopkins University | B7-DC variants |
US8747847B2 (en) | 2008-02-11 | 2014-06-10 | Curetech Ltd. | Monoclonal antibodies for tumor treatment |
WO2009111315A2 (en) * | 2008-02-29 | 2009-09-11 | Mayo Foundation For Medical Education And Research | Methods for reducing granulomatous inflammation |
EP2262837A4 (en) * | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
EP2279412B1 (en) | 2008-04-09 | 2017-07-26 | Genentech, Inc. | Novel compositions and methods for the treatment of immune related diseases |
ES2741730T3 (es) | 2008-05-19 | 2020-02-12 | Advaxis Inc | Sistema de administración doble para antígenos heterólogos que comprende una cepa de Listeria recombinante atenuada por la mutación de dal/dat y la deleción de ActA que comprende una molécula de ácido nucleico que codifica una proteína de fusión de listeriolisina O - antígeno prostático específico |
US9650639B2 (en) | 2008-05-19 | 2017-05-16 | Advaxis, Inc. | Dual delivery system for heterologous antigens |
US9017660B2 (en) | 2009-11-11 | 2015-04-28 | Advaxis, Inc. | Compositions and methods for prevention of escape mutation in the treatment of Her2/neu over-expressing tumors |
JP5945096B2 (ja) * | 2008-07-04 | 2016-07-05 | 小野薬品工業株式会社 | 抗ヒトpd−1抗体の癌に対する治療効果を最適化するための判定マーカーの使用 |
AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
PE20110435A1 (es) | 2008-08-25 | 2011-07-20 | Amplimmune Inc | Composiciones antagonistas del pd-1 |
US20110223188A1 (en) * | 2008-08-25 | 2011-09-15 | Solomon Langermann | Targeted costimulatory polypeptides and methods of use to treat cancer |
KR101050829B1 (ko) | 2008-10-02 | 2011-07-20 | 서울대학교산학협력단 | 항 pd-1 항체 또는 항 pd-l1 항체를 포함하는 항암제 |
WO2010056332A1 (en) * | 2008-11-14 | 2010-05-20 | The Brigham And Women's Hospital, Inc. | Therapeutic and diagnostic methods relating to cancer stem cells |
US11542328B2 (en) | 2008-11-14 | 2023-01-03 | The Brigham And Women's Hospital, Inc. | Therapeutic and diagnostic methods relating to cancer stem cells |
WO2010063011A2 (en) | 2008-11-28 | 2010-06-03 | Emory University | Methods for the treatment of infections and tumors |
BRPI0917592B1 (pt) * | 2008-12-09 | 2021-08-17 | Genentech, Inc | Anticorpo anti-pd-l1, composição, artigos manufaturados e usos de uma composição |
WO2010101249A1 (ja) * | 2009-03-06 | 2010-09-10 | 国立大学法人三重大学 | T細胞の機能増強方法 |
EP3375791A1 (en) * | 2009-09-30 | 2018-09-19 | Memorial Sloan Kettering Cancer Center | Combination immunotherapy for the treatment of cancer |
US10016617B2 (en) | 2009-11-11 | 2018-07-10 | The Trustees Of The University Of Pennsylvania | Combination immuno therapy and radiotherapy for the treatment of Her-2-positive cancers |
RS56469B1 (sr) * | 2009-11-24 | 2018-01-31 | Medimmune Ltd | Ciljano vezujući agensi usmereni na b7-h1 |
CA2791930A1 (en) | 2010-03-11 | 2011-09-15 | Kerry Louise Tyson | Pd-1 antibody |
TW201134488A (en) * | 2010-03-11 | 2011-10-16 | Ucb Pharma Sa | PD-1 antibodies |
US10745467B2 (en) | 2010-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | VISTA-Ig for treatment of autoimmune, allergic and inflammatory disorders |
EP3153521B1 (en) | 2010-03-26 | 2019-09-04 | Trustees of Dartmouth College | Vista regulatory t cell mediator protein, vista binding agents and use thereof |
US20150231215A1 (en) | 2012-06-22 | 2015-08-20 | Randolph J. Noelle | VISTA Antagonist and Methods of Use |
JP2013532153A (ja) | 2010-06-18 | 2013-08-15 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッド | 慢性免疫病に対する免疫治療のためのtim−3およびpd−1に対する二重特異性抗体 |
US8907053B2 (en) | 2010-06-25 | 2014-12-09 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
US9783578B2 (en) | 2010-06-25 | 2017-10-10 | Aurigene Discovery Technologies Limited | Immunosuppression modulating compounds |
CN107412756A (zh) | 2010-10-01 | 2017-12-01 | 宾夕法尼亚大学理事会 | 李斯特菌疫苗载体用于在寄生虫感染的个体中扭转免疫无应答的用途 |
EP2625292B1 (en) | 2010-10-07 | 2018-12-05 | The General Hospital Corporation | Biomarkers of cancer |
CN103687611A (zh) | 2011-03-11 | 2014-03-26 | 阿德瓦希斯公司 | 基于李斯特菌属的佐剂 |
KR101970025B1 (ko) | 2011-04-20 | 2019-04-17 | 메디뮨 엘엘씨 | B7-h1 및 pd-1과 결합하는 항체 및 다른 분자들 |
CN102250910B (zh) * | 2011-05-31 | 2013-01-30 | 苏州大学 | 一种人可溶性b7-dc定量检测试剂盒 |
US9096642B2 (en) | 2011-06-08 | 2015-08-04 | Aurigene Discovery Technologies Limited | Therapeutic compounds for immunomodulation |
HUE052198T2 (hu) | 2011-07-21 | 2021-04-28 | Sumitomo Dainippon Pharma Oncology Inc | Heterociklusos protein kináz inhibitorok |
US11951157B2 (en) | 2011-10-11 | 2024-04-09 | Universitat Zurich | Methods of treating malignant tumour with IL-12 and anti-PD-1 antibody |
EP2766035B1 (en) | 2011-10-11 | 2018-03-28 | Universität Zürich Prorektorat MNW | Combination medicament comprising il-12 and an agent for blockade of t-cell inhibitory molecules for tumour therapy |
JP6259763B2 (ja) * | 2011-10-17 | 2018-01-10 | ヘルレフ ホスピタルHerlev Hospital | Pd−l1に基づく免疫療法 |
US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
ES2527544T1 (es) | 2011-10-21 | 2015-01-26 | Abbvie Inc. | Tratamiento mono (PSI-7977) o de combinación con AAD para su uso en el tratamiento del VHC |
GB2506086A (en) | 2011-10-21 | 2014-03-19 | Abbvie Inc | Methods for treating HCV comprising at least two direct acting antiviral agent, ribavirin but not interferon |
DK2785375T3 (da) | 2011-11-28 | 2020-10-12 | Merck Patent Gmbh | Anti-pd-l1-antistoffer og anvendelser deraf |
GB201120779D0 (en) | 2011-12-02 | 2012-01-11 | Immodulon Therapeutics Ltd | Cancer therapy |
US20150004175A1 (en) * | 2011-12-13 | 2015-01-01 | Yale University | Compositions and Methods for Reducing CTL Exhaustion |
CA2861927C (en) | 2012-01-20 | 2021-01-26 | Vib Vzw | Targeted mutant alpha-helical bundle cytokines |
CA2863695C (en) | 2012-02-16 | 2023-01-17 | Vlp Therapeutics, Llc | Virus like particle composition |
WO2013132317A1 (en) | 2012-03-07 | 2013-09-12 | Aurigene Discovery Technologies Limited | Peptidomimetic compounds as immunomodulators |
AU2013232291B8 (en) | 2012-03-12 | 2016-07-21 | Advaxis, Inc. | Suppressor cell function inhibition following listeria vaccine treatment |
RU2014143443A (ru) | 2012-03-29 | 2016-05-20 | Ориджин Дискавери Текнолоджиз Лимитед | Иммуномодулирующие циклические соединения |
WO2013155493A1 (en) | 2012-04-12 | 2013-10-17 | Yale University | Methods of treating inflammatory and autoimmune diseases and disorders |
WO2013173223A1 (en) * | 2012-05-15 | 2013-11-21 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
EP3279315A3 (en) * | 2012-05-25 | 2018-02-28 | Cellectis | Use of pre t alpha or functional variant thereof for expanding tcr alpha deficient t cells |
WO2014039983A1 (en) * | 2012-09-07 | 2014-03-13 | The Trustees Of Dartmouth College | Vista modulators for diagnosis and treatment of cancer |
US9890215B2 (en) * | 2012-06-22 | 2018-02-13 | King's College London | Vista modulators for diagnosis and treatment of cancer |
UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
CN112587658A (zh) * | 2012-07-18 | 2021-04-02 | 博笛生物科技有限公司 | 癌症的靶向免疫治疗 |
US9657082B2 (en) | 2013-01-31 | 2017-05-23 | Thomas Jefferson University | PD-L1 and PD-L2-based fusion proteins and uses thereof |
WO2014122271A1 (en) | 2013-02-07 | 2014-08-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the survival time of patients suffering from diffuse large b-cell lymphomas |
US20150368316A1 (en) * | 2013-02-07 | 2015-12-24 | Albert Einstein College Of Medicine Of Yeshiva University | A selective high-affinity immune stimulatory reagent and uses thereof |
DK2958588T3 (da) | 2013-02-22 | 2017-11-20 | Curevac Ag | Kombination af vaccination og hæmning af PD-1-reaktionsvejen |
US9302005B2 (en) | 2013-03-14 | 2016-04-05 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
KR20150139955A (ko) | 2013-04-09 | 2015-12-14 | 보스톤 바이오메디칼, 인크. | 암 치료에 사용하기 위한 2-아세틸나프토[2,3-b]푸란-4,9-디온 |
BR112015026823A2 (pt) | 2013-05-02 | 2017-09-05 | Anaptysbio Inc | Polipeptídeo de cadeia pesada de imunoglobulina isolada, polipeptídeo de cadeia leve de imunoglobulina isolada, sequência de ácido nucleico isolada ou purificada, vetor, agente de ligação de proteína de morte-1 programada (pd-1) isolada, célula isolada, composição, e uso do agente de ligação da pd-1 isolada |
CN103242448B (zh) * | 2013-05-27 | 2015-01-14 | 郑州大学 | 一种全人源化抗pd-1单克隆抗体及其制备方法和应用 |
WO2014194293A1 (en) | 2013-05-30 | 2014-12-04 | Amplimmune, Inc. | Improved methods for the selection of patients for pd-1 or b7-h4 targeted therapies, and combination therapies thereof |
CN111423511B (zh) * | 2013-05-31 | 2024-02-23 | 索伦托药业有限公司 | 与pd-1结合的抗原结合蛋白 |
CN104250302B (zh) | 2013-06-26 | 2017-11-14 | 上海君实生物医药科技股份有限公司 | 抗pd‑1抗体及其应用 |
TWI676636B (zh) | 2013-07-12 | 2019-11-11 | Vlp醫療股份有限公司 | 包含pd-1抗原或pd-1配體抗原的類病毒粒子 |
ES2819209T3 (es) | 2013-07-16 | 2021-04-15 | Hoffmann La Roche | Procedimientos de tratamiento del cáncer usando antagonistas de unión al eje de PD-1 e inhibidores de TIGIT |
EP3041468B1 (en) | 2013-09-06 | 2018-06-13 | Aurigene Discovery Technologies Limited | Cyclic peptidomimetic compounds as immunomodulators |
AU2014316682B2 (en) | 2013-09-06 | 2018-11-22 | Aurigene Discovery Technologies Limited | 1,2,4-oxadiazole derivatives as immunomodulators |
ES2682040T3 (es) | 2013-09-06 | 2018-09-18 | Aurigene Discovery Technologies Limited | Derivados de 1,3,4-oxadiazol y 1,3,4-tiadiazol como inmunomoduladores |
PL3702373T3 (pl) | 2013-09-13 | 2022-12-05 | Beigene Switzerland Gmbh | Przeciwciała anty-PD1 i ich zastosowanie jako środki terapeutyczne i diagnostyczne |
EP3178849B1 (en) | 2013-09-20 | 2019-03-20 | Bristol-Myers Squibb Company | Combination of anti-lag-3 antibodies and anti-pd-1 antibodies to treat tumors |
EP3757130A1 (en) | 2013-09-26 | 2020-12-30 | Costim Pharmaceuticals Inc. | Methods for treating hematologic cancers |
US10259875B2 (en) | 2013-10-01 | 2019-04-16 | Mayo Foundation For Medical Education And Research | Methods for treating cancer in patients with elevated levels of BIM |
RU2672055C2 (ru) | 2013-11-01 | 2018-11-09 | Йейл Юниверсити | Модульные частицы для иммунотерапии |
DK3081576T3 (da) | 2013-12-12 | 2019-10-21 | Shanghai hengrui pharmaceutical co ltd | Pd-1-antistof, antigenbindende fragment deraf og medicinsk anvendelse deraf |
GB201322626D0 (en) | 2013-12-19 | 2014-02-05 | Immutep S A | Combined preparations for the treatment of cancer |
JP6622703B2 (ja) | 2013-12-20 | 2019-12-18 | インターベット インターナショナル ベー. フェー. | アンタゴニストの、抗イヌpd−1抗体 |
GB201322725D0 (en) | 2013-12-20 | 2014-02-05 | Immodulon Therapeutics Ltd | Cancer therapy |
CN106661107B (zh) | 2013-12-24 | 2021-12-24 | 杨森制药公司 | 抗vista抗体及片段 |
US11014987B2 (en) | 2013-12-24 | 2021-05-25 | Janssen Pharmaceutics Nv | Anti-vista antibodies and fragments, uses thereof, and methods of identifying same |
CA2936377A1 (en) | 2014-01-10 | 2015-07-16 | Shanghai Birdie Biotech, Inc. | Compounds and compositions for treating egfr expressing tumors |
HUE057917T2 (hu) * | 2014-01-15 | 2022-06-28 | Kadmon Corp Llc | Immunmodulátor szerek |
TWI680138B (zh) | 2014-01-23 | 2019-12-21 | 美商再生元醫藥公司 | 抗pd-l1之人類抗體 |
TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對pd-1的人類抗體 |
JOP20200094A1 (ar) | 2014-01-24 | 2017-06-16 | Dana Farber Cancer Inst Inc | جزيئات جسم مضاد لـ pd-1 واستخداماتها |
JOP20200096A1 (ar) | 2014-01-31 | 2017-06-16 | Children’S Medical Center Corp | جزيئات جسم مضاد لـ tim-3 واستخداماتها |
JP2017508785A (ja) | 2014-02-04 | 2017-03-30 | インサイト・コーポレイションIncyte Corporation | 癌を治療するためのpd−1アンタゴニストおよびido1阻害剤の組み合わせ |
CA2937521C (en) | 2014-02-04 | 2023-08-29 | Pfizer, Inc. | Combination of a pd-1 antagonist and a vegfr inhibitor for treating cancer |
US10899840B2 (en) | 2014-02-04 | 2021-01-26 | Pfizer Inc. | Combination of a PD-1 antagonist and a 4-1BB agonist for treating cancer |
GB201403775D0 (en) | 2014-03-04 | 2014-04-16 | Kymab Ltd | Antibodies, uses & methods |
US10618963B2 (en) | 2014-03-12 | 2020-04-14 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
US9394365B1 (en) | 2014-03-12 | 2016-07-19 | Yeda Research And Development Co., Ltd | Reducing systemic regulatory T cell levels or activity for treatment of alzheimer's disease |
US10307472B2 (en) | 2014-03-12 | 2019-06-04 | Curevac Ag | Combination of vaccination and OX40 agonists |
US10519237B2 (en) | 2014-03-12 | 2019-12-31 | Yeda Research And Development Co. Ltd | Reducing systemic regulatory T cell levels or activity for treatment of disease and injury of the CNS |
NZ747418A (en) | 2014-03-12 | 2023-05-26 | Yeda Res & Dev | Reducing systemic regulatory t cell levels or activity for treatment of disease and injury of the cns |
WO2015179654A1 (en) | 2014-05-22 | 2015-11-26 | Mayo Foundation For Medical Education And Research | Distinguishing antagonistic and agonistic anti b7-h1 antibodies |
JP2017516779A (ja) | 2014-05-28 | 2017-06-22 | アイデニクス・ファーマシューティカルズ・エルエルシー | 癌治療のためのヌクレオシド誘導体 |
LT3148579T (lt) | 2014-05-28 | 2021-05-25 | Agenus Inc. | Anti-gitr antikūnai ir jų panaudojimo būdai |
JP6997619B2 (ja) | 2014-06-11 | 2022-01-17 | キャシー・エイ・グリーン | 液性免疫の抑制または増進のための、vistaアゴニスト及びvistaアンタゴニストの使用 |
TWI693232B (zh) | 2014-06-26 | 2020-05-11 | 美商宏觀基因股份有限公司 | 與pd-1和lag-3具有免疫反應性的共價結合的雙抗體和其使用方法 |
KR102003754B1 (ko) | 2014-07-03 | 2019-07-25 | 베이진 엘티디 | Pd-l1 항체와 이를 이용한 치료 및 진단 |
TWI727427B (zh) | 2014-07-09 | 2021-05-11 | 英屬開曼群島商博笛生物科技有限公司 | 用於治療腫瘤的抗pd-1組合 |
US10280223B2 (en) | 2014-07-09 | 2019-05-07 | Nippon Zenyaku Kogyo Co., Ltd. | Anti-canine PD-1 antibody or anti-canine PD-L1 antibody |
CN105440135A (zh) | 2014-09-01 | 2016-03-30 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-pd-l1结合物 |
CA2955084C (en) | 2014-07-16 | 2023-08-29 | Transgene Sa | Combination of oncolytic virus with immune checkpoint modulators |
DK3169341T3 (da) | 2014-07-16 | 2019-08-05 | Transgene Sa | Onkolytisk virus til ekspression af immun-checkpoint-modulatorer |
SG11201701149SA (en) | 2014-07-18 | 2017-04-27 | Advaxis Inc | Combination of a pd-1 antagonist and a listeria-based vaccine for treating prostate cancer |
CA2955788C (en) | 2014-07-22 | 2024-01-16 | Ziyong Sun | Anti-pd-1 antibodies |
WO2016014148A1 (en) | 2014-07-23 | 2016-01-28 | Mayo Foundation For Medical Education And Research | Targeting dna-pkcs and b7-h1 to treat cancer |
EP3936145A1 (en) * | 2014-07-31 | 2022-01-12 | The University Of Western Australia | A method for the identification of immunotherapy-drug combinations using a network approach |
CN105296433B (zh) | 2014-08-01 | 2018-02-09 | 中山康方生物医药有限公司 | 一种ctla4抗体、其药物组合物及其用途 |
WO2016022630A1 (en) | 2014-08-05 | 2016-02-11 | Jiping Zha | Anti-pd-l1 antibodies |
JP6629321B2 (ja) | 2014-08-05 | 2020-01-15 | マブクエスト エスエーMabQuest SA | 免疫学的試薬 |
US9982052B2 (en) | 2014-08-05 | 2018-05-29 | MabQuest, SA | Immunological reagents |
EP3178484B1 (en) * | 2014-08-07 | 2019-07-24 | Hyogo College Of Medicine | Therapeutic agent for cancer which comprises combination of il-18 and molecule-targeting antibody |
US10385101B2 (en) | 2014-08-08 | 2019-08-20 | Vlp Therapeutics, Llc | Virus like particle comprising modified envelope protein E3 |
TWI720946B (zh) | 2014-08-08 | 2021-03-11 | 美商Vlp醫療股份有限公司 | 包含改質套膜蛋白質e3之類病毒粒子 |
JP6629211B2 (ja) * | 2014-08-19 | 2020-01-15 | 国立大学法人 岡山大学 | 免疫細胞の機能増強方法及び免疫細胞の多機能性評価方法 |
WO2016032927A1 (en) | 2014-08-25 | 2016-03-03 | Pfizer Inc. | Combination of a pd-1 antagonist and an alk inhibitor for treating cancer |
EP3191589A4 (en) | 2014-09-11 | 2018-05-09 | VLP Therapeutics, LLC | Flavivirus virus like particle |
EP3191097B1 (en) | 2014-09-13 | 2019-10-23 | Novartis AG | Combination therapies |
CN112851816B (zh) | 2014-09-30 | 2024-03-08 | 英特维特国际股份有限公司 | 结合犬pd-l1的pd-l1抗体 |
US10039564B2 (en) | 2014-09-30 | 2018-08-07 | Ethicon Llc | Surgical devices having power-assisted jaw closure and methods for compressing and sensing tissue |
AU2015330731B2 (en) | 2014-10-10 | 2020-07-09 | Idera Pharmaceuticals, Inc. | Treatment of cancer using TLR9 agonist with checkpoint inhibitors |
MX2017004810A (es) | 2014-10-14 | 2017-10-16 | Novartis Ag | Moleculas de anticuerpo que se unen a pd-l1 y usos de las mismas. |
US11236139B2 (en) | 2014-11-05 | 2022-02-01 | The Regents Of The University Of California | Combination immunotherapy |
AU2015355137A1 (en) * | 2014-12-02 | 2017-06-08 | Celgene Corporation | Combination therapies |
WO2016089797A1 (en) | 2014-12-05 | 2016-06-09 | Merck Sharp & Dohme Corp. | Novel tricyclic compounds as inhibitors of mutant idh enzymes |
EP3226689B1 (en) | 2014-12-05 | 2020-01-15 | Merck Sharp & Dohme Corp. | Novel tricyclic compounds as inhibitors of mutant idh enzymes |
AU2015357463B2 (en) | 2014-12-05 | 2021-10-07 | Immunext, Inc. | Identification of VSIG8 as the putative vista receptor and its use thereof to produce vista/VSIG8 modulators |
US10086000B2 (en) | 2014-12-05 | 2018-10-02 | Merck Sharp & Dohme Corp. | Tricyclic compounds as inhibitors of mutant IDH enzymes |
US11220545B2 (en) * | 2014-12-08 | 2022-01-11 | Dana-Farber Cancer Institute, Inc. | Methods for upregulating immune responses using combinations of anti-RGMb and anti-PD-1 agents |
RS61218B1 (sr) * | 2014-12-09 | 2021-01-29 | Regeneron Pharma | Životinja koja nije čovek sa humanizovanim klasterom diferencijacije 274 gena |
TWI595006B (zh) | 2014-12-09 | 2017-08-11 | 禮納特神經系統科學公司 | 抗pd-1抗體類和使用彼等之方法 |
JP6767096B2 (ja) * | 2014-12-11 | 2020-10-14 | リティックス バイオファーマ エイエス | 免疫チェックポイント阻害剤の組み合わせ |
US10849862B2 (en) | 2014-12-26 | 2020-12-01 | Theravalues Corporation | Formulation of curcumin and anti-PD-1 antibody |
EP3240801B1 (en) | 2014-12-31 | 2021-01-20 | Checkmate Pharmaceuticals, Inc. | Combination tumor immunotherapy |
GB201500319D0 (en) * | 2015-01-09 | 2015-02-25 | Agency Science Tech & Res | Anti-PD-L1 antibodies |
GB201500374D0 (en) | 2015-01-09 | 2015-02-25 | Immutep S A | Combined preparations for the treatment of cancer |
MA41414A (fr) | 2015-01-28 | 2017-12-05 | Centre Nat Rech Scient | Protéines de liaison agonistes d' icos |
EP3252469A4 (en) * | 2015-01-29 | 2017-12-06 | Konica Minolta, Inc. | Method for simultaneous detection of blood cells having interacting molecules |
MA41460A (fr) | 2015-02-03 | 2017-12-12 | Oncomed Pharm Inc | Agents de liaison à la tnfrsf et leurs utilisations |
US11491139B2 (en) * | 2015-02-12 | 2022-11-08 | The Johns Hopkins University | Inhibition of YAP for breaking tumor immune tolerance |
US10800846B2 (en) | 2015-02-26 | 2020-10-13 | Merck Patent Gmbh | PD-1/PD-L1 inhibitors for the treatment of cancer |
AR103726A1 (es) * | 2015-02-27 | 2017-05-31 | Merck Sharp & Dohme | Cristales de anticuerpos monoclonales anti-pd-1 humanos |
RU2737216C2 (ru) | 2015-03-04 | 2020-11-26 | Мерк Шарп Энд Дохме Корп. | Комбинация антагониста pd-1 и эрибулина для лечения рака |
CA2978226A1 (en) | 2015-03-04 | 2016-09-09 | Merck Sharpe & Dohme Corp. | Combination of a pd-1 antagonist and a vegfr/fgfr/ret tyrosine kinase inhibitor for treating cancer |
PL3267984T3 (pl) | 2015-03-10 | 2022-05-02 | Aurigene Discovery Technologies Limited | Związki 1,2,4-oksadiazolu i tiadiazolu jako immunomodulatory |
IL292449B2 (en) | 2015-03-13 | 2024-02-01 | Cytomx Therapeutics Inc | Nucleic acids encoding antibodies against PDL1 and methods for their preparation |
RU2742241C2 (ru) | 2015-03-23 | 2021-02-04 | Джоунс Терапьютикс, Инк. | Антитела к icos |
JP6901400B2 (ja) | 2015-04-03 | 2021-07-14 | ゾーマ テクノロジー リミテッド | TGF−β及びPD−1の阻害物質を使用する癌の治療法 |
SG10201912035YA (en) | 2015-04-17 | 2020-02-27 | Bristol Myers Squibb Co | Compositions comprising a combination of an anti-pd-1 antibody and another antibody |
EP3988571A1 (en) | 2015-04-28 | 2022-04-27 | Bristol-Myers Squibb Company | Treatment of pd-l1-negative melanoma using an anti-pd-1 antibody and an anti-ctla-4 antibody |
US10815264B2 (en) | 2015-05-27 | 2020-10-27 | Southern Research Institute | Nucleotides for the treatment of cancer |
AU2016271018A1 (en) | 2015-05-29 | 2017-11-30 | Dynavax Technologies Corporation | Combination of a PD-1 antagonist and CPG-C type oligonucleotide for treating cancer |
WO2016196389A1 (en) | 2015-05-29 | 2016-12-08 | Bristol-Myers Squibb Company | Treatment of renal cell carcinoma |
CN113603784A (zh) | 2015-05-29 | 2021-11-05 | 艾吉纳斯公司 | 抗-ctla-4抗体及其使用方法 |
DK3302502T3 (da) * | 2015-05-29 | 2019-10-28 | Dynavax Tech Corp | Intrapulmonal administration af polynukleotid-agonister af toll-lignende receptor-9 til behandling af lungecancer |
EA201792623A1 (ru) | 2015-06-03 | 2018-04-30 | Бостон Биомедикал, Инк. | Композиции, содержащие ингибитор стволовости рака и иммунотерапевтический агент, для применения в лечении рака |
TWI773646B (zh) | 2015-06-08 | 2022-08-11 | 美商宏觀基因股份有限公司 | 結合lag-3的分子和其使用方法 |
TW201709929A (zh) | 2015-06-12 | 2017-03-16 | 宏觀基因股份有限公司 | 治療癌症的聯合療法 |
KR20180017152A (ko) | 2015-06-12 | 2018-02-20 | 매카이 메디컬 파운데이션 더 프레즈비티리언 처치 인 타이완 매카이 메모리얼 호스피탈 | 면역반응의 조절을 위한 방법 및 항체 |
CA2989586A1 (en) | 2015-06-16 | 2016-12-22 | Pfizer, Inc. | Pd-l1 antagonist combination treatments |
CN107922497B (zh) | 2015-06-24 | 2022-04-12 | 詹森药业有限公司 | 抗vista抗体和片段 |
CN114344462A (zh) * | 2015-06-24 | 2022-04-15 | 英摩杜伦治疗学公司 | 用于癌症治疗的检查点抑制剂和全细胞分枝杆菌 |
GB201511790D0 (en) | 2015-07-06 | 2015-08-19 | Iomet Pharma Ltd | Pharmaceutical compound |
KR20180040138A (ko) | 2015-07-13 | 2018-04-19 | 싸이톰스 테라퓨틱스, 인크. | 항pd-1 항체, 활성화 가능한 항pd-1 항체, 및 이들의 사용 방법 |
US10544224B2 (en) | 2015-07-14 | 2020-01-28 | Bristol-Myers Squibb Company | Method of treating cancer using immune checkpoint inhibitor |
US10682390B2 (en) | 2015-07-16 | 2020-06-16 | Biokine Therapeutics Ltd. | Compositions and methods for treating cancer |
MD3456346T2 (ro) | 2015-07-30 | 2021-11-30 | Macrogenics Inc | Molecule de legare la PD-1 și LAG-3 și metode de utilizare a acestora |
CA2994241A1 (en) | 2015-07-31 | 2017-02-09 | University Of Florida Research Foundation, Inc. | Hematopoietic stem cells in combinatorial therapy with immune checkpoint inhibitors against cancer |
EP3331918A1 (en) | 2015-08-04 | 2018-06-13 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
CA2994635A1 (en) | 2015-08-04 | 2017-02-09 | Glaxosmithkline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
AU2016306597A1 (en) | 2015-08-07 | 2018-02-22 | Pieris Pharmaceuticals Gmbh | Novel fusion polypeptide specific for LAG-3 and PD-1 |
EP3331919A1 (en) | 2015-08-07 | 2018-06-13 | GlaxoSmithKline Intellectual Property Development Limited | Combination therapy comprising anti ctla-4 antibodies |
WO2017024465A1 (en) | 2015-08-10 | 2017-02-16 | Innovent Biologics (Suzhou) Co., Ltd. | Pd-1 antibodies |
MX2018001644A (es) | 2015-08-11 | 2018-11-09 | Wuxi Biologics Cayman Inc | Anticuerpos anti-pd-1 novedosos. |
US11453697B1 (en) | 2015-08-13 | 2022-09-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
CR20180101A (es) | 2015-08-13 | 2018-04-12 | Merck Sharp & Dohme | Compuestos di-nucleóticos cíclicos como agonistas de sting |
AR105654A1 (es) | 2015-08-24 | 2017-10-25 | Lilly Co Eli | Anticuerpos pd-l1 (ligando 1 de muerte celular programada) |
BR112018003186A2 (pt) | 2015-09-01 | 2018-09-25 | Agenus Inc. | anticorpos anti-pd-1 e seus métodos de uso |
CA2997240C (en) | 2015-09-03 | 2024-04-02 | Ono Pharmaceutical Co., Ltd. | Immunity enhancing agent for cancer by allergin-1 antagonist |
US11124569B2 (en) * | 2015-09-18 | 2021-09-21 | Dana-Farber Cancer Institute, Inc. | Methods of reducing liver PD-1-expressing CD8+ T cells using PD-1 Fc fusion proteins that bind Fc receptors |
WO2017053250A1 (en) * | 2015-09-21 | 2017-03-30 | Merck Sharp & Dohme Corp. | Antibody that binds to human programmed death ligand 2 (pd-l2) and uses thereof |
CA2999756A1 (en) * | 2015-09-24 | 2017-03-30 | The University Of North Carolina At Chapel Hill | Methods and compositions for reducing metastases |
CN108290946B (zh) | 2015-09-25 | 2021-09-28 | 豪夫迈·罗氏有限公司 | 抗tigit抗体和使用方法 |
RU2722451C1 (ru) * | 2015-09-29 | 2020-06-01 | Шанхай Чжанцзян Биотекнолоджи Ко., Лтд. | Pd-1 антитела и их применение. |
ES2839212T3 (es) | 2015-09-29 | 2021-07-05 | Inst Nat Sante Rech Med | Métodos para determinar el estado metabólico de linfomas B |
AU2016332725A1 (en) | 2015-09-29 | 2018-03-22 | Celgene Corporation | PD-1 binding proteins and methods of use thereof |
KR102072317B1 (ko) | 2015-10-02 | 2020-01-31 | 에프. 호프만-라 로슈 아게 | 항-pd1 항체 및 사용 방법 |
MY192202A (en) | 2015-10-02 | 2022-08-06 | Hoffmann La Roche | Bispecific antibodies specific for pd1 and tim3 |
RU2731202C2 (ru) | 2015-10-08 | 2020-08-31 | Макродженикс, Инк. | Комбинированная терапия для лечения рака |
CN108135934A (zh) | 2015-10-19 | 2018-06-08 | 永恒生物科技股份有限公司 | 通过组合疗法治疗实体或淋巴肿瘤的方法 |
CA2998208A1 (en) | 2015-10-22 | 2017-04-27 | Jounce Therapeutics, Inc. | Gene signatures for determining icos expression |
WO2017074774A1 (en) * | 2015-10-28 | 2017-05-04 | Yale University | Humanized anti-dkk2 antibody and uses thereof |
WO2017075045A2 (en) | 2015-10-30 | 2017-05-04 | Mayo Foundation For Medical Education And Research | Antibodies to b7-h1 |
JP2019500892A (ja) | 2015-11-03 | 2019-01-17 | ヤンセン バイオテツク,インコーポレーテツド | Tim−3に特異的に結合する抗体及びその使用 |
EP3371311B1 (en) | 2015-11-06 | 2021-07-21 | Orionis Biosciences BV | Bi-functional chimeric proteins and uses thereof |
AU2016352572B2 (en) * | 2015-11-12 | 2023-10-19 | Hookipa Biotech Gmbh | Arenavirus particles as cancer vaccines |
WO2017087870A1 (en) | 2015-11-18 | 2017-05-26 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-pd-1 antibody and an anti-ctla-4 antibody |
WO2017093942A1 (en) | 2015-12-01 | 2017-06-08 | Glaxosmithkline Intellectual Property Development Limited | Combination treatments and uses and methods thereof |
KR20180083944A (ko) | 2015-12-02 | 2018-07-23 | 아게누스 인코포레이티드 | 항체 및 이의 사용 방법 |
RU2020113165A (ru) | 2015-12-03 | 2020-06-09 | Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед | Циклические пуриновые динуклеотиды в качестве модуляторов sting |
WO2017098421A1 (en) | 2015-12-08 | 2017-06-15 | Glaxosmithkline Intellectual Property Development Limited | Benzothiadiazine compounds |
UA125611C2 (uk) | 2015-12-14 | 2022-05-04 | Макродженікс, Інк. | Біспецифічні молекули, що мають імунореактивність відносно pd-1 і ctla-4, і способи їх застосування |
WO2017106062A1 (en) | 2015-12-15 | 2017-06-22 | Merck Sharp & Dohme Corp. | Novel compounds as indoleamine 2,3-dioxygenase inhibitors |
GB201522309D0 (en) | 2015-12-17 | 2016-02-03 | Photocure Asa | Use |
GB201522311D0 (en) | 2015-12-17 | 2016-02-03 | Photocure Asa | Use |
US10392442B2 (en) | 2015-12-17 | 2019-08-27 | Bristol-Myers Squibb Company | Use of anti-PD-1 antibody in combination with anti-CD27 antibody in cancer treatment |
US11091556B2 (en) | 2015-12-18 | 2021-08-17 | Intervet Inc. | Caninized human antibodies to human IL-4R alpha |
WO2017118634A1 (en) | 2016-01-04 | 2017-07-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of pd-1 and tim-3 as a measure for cd8+ cells in predicting and treating renal cell carcinoma |
CN106943596A (zh) | 2016-01-07 | 2017-07-14 | 博笛生物科技(北京)有限公司 | 用于治疗肿瘤的抗-cd20组合 |
CN106943598A (zh) | 2016-01-07 | 2017-07-14 | 博笛生物科技(北京)有限公司 | 用于治疗肿瘤的抗-her2组合 |
CN115252792A (zh) | 2016-01-07 | 2022-11-01 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-egfr组合 |
MA43590A (fr) | 2016-01-08 | 2018-11-14 | Taiho Pharmaceutical Co Ltd | Agent antitumoral contenant un immunomodulateur et un amplificateur d'effet antitumoral |
CN109195988B (zh) | 2016-01-10 | 2023-12-01 | 尼奥克斯医疗有限公司 | 用于增强超抗原介导的癌症免疫疗法效力的方法和组合物 |
US11214617B2 (en) | 2016-01-22 | 2022-01-04 | MabQuest SA | Immunological reagents |
EP3964529A1 (en) | 2016-01-22 | 2022-03-09 | Mabquest SA | Non-blocking pd1 specific antibodies |
US11661455B2 (en) | 2016-02-05 | 2023-05-30 | Orionis Biosciences BV | Chimeric protein comprising an interferon alpha 2mutant and a PD-L1 binding moiety |
CA3013551A1 (en) | 2016-02-05 | 2017-08-10 | Orionis Biosciences Nv | Clec9a binding agents and use thereof |
EP3413910A1 (en) | 2016-02-12 | 2018-12-19 | Janssen Pharmaceutica NV | Anti-vista (b7h5) antibodies |
US10358496B2 (en) | 2016-03-01 | 2019-07-23 | Ralf Kleef | Low dose immune checkpoint blockade in metastatic cancer |
US11883404B2 (en) | 2016-03-04 | 2024-01-30 | Taiho Pharmaceuticals Co., Ltd. | Preparation and composition for treatment of malignant tumors |
US20170252417A1 (en) | 2016-03-07 | 2017-09-07 | Massachusetts Institute Of Technology | Protein-chaperoned t-cell vaccines |
WO2017153402A1 (en) | 2016-03-07 | 2017-09-14 | Vib Vzw | Cd20 binding single domain antibodies |
US11497781B2 (en) | 2016-03-10 | 2022-11-15 | Cg Oncology, Inc. | Methods of treating bladder cancer by combination therapy comprising the oncolytic adenovirus CG0070 and an immune checkpoint inhibitor |
WO2017153952A1 (en) | 2016-03-10 | 2017-09-14 | Glaxosmithkline Intellectual Property Development Limited | 5-sulfamoyl-2-hydroxybenzamide derivatives |
WO2017160599A1 (en) | 2016-03-14 | 2017-09-21 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Use of cd300b antagonists to treat sepsis and septic shock |
EP3430141B1 (en) | 2016-03-14 | 2020-12-30 | H. Hoffnabb-La Roche Ag | Oligonucleotides for reduction of pd-l1 expression |
CN109310885B (zh) | 2016-03-15 | 2022-05-31 | 梅尔莎纳医疗公司 | NaPi2b靶向抗体-药物缀合物及其使用方法 |
KR102646979B1 (ko) * | 2016-03-30 | 2024-03-13 | 마이크로바이오 컴퍼니 엘티디. | 면역 체크포인트 조절제 및 공생 미생물군에 의한 발효 산물로의 병용 암 치료법 |
US20190046638A1 (en) | 2016-04-01 | 2019-02-14 | Checkmate Pharmaceuticals, Inc. | Fc RECEPTOR-MEDIATED DRUG DELIVERY |
WO2017176925A1 (en) | 2016-04-05 | 2017-10-12 | Bristol-Myers Squibb Company | Cytokine profiling analysis for predicting prognosis of a patient in need of an anti-cancer treatment |
SG11201808708RA (en) | 2016-04-07 | 2018-11-29 | Glaxosmithkline Ip Dev Ltd | Heterocyclic amides useful as protein modulators |
WO2017175147A1 (en) | 2016-04-07 | 2017-10-12 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides useful as protein modulators |
UA125382C2 (uk) | 2016-04-15 | 2022-03-02 | Імьюнекст Інк. | Антитіла проти людського vista та їх застосування |
WO2017189978A1 (en) | 2016-04-28 | 2017-11-02 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
JP2019516685A (ja) | 2016-05-05 | 2019-06-20 | グラクソスミスクライン、インテレクチュアル、プロパティー、(ナンバー2)、リミテッドGlaxosmithkline Intellectual Property (No.2) Limited | Zesteホモログ2阻害剤のエンハンサー |
TWI822521B (zh) | 2016-05-13 | 2023-11-11 | 美商再生元醫藥公司 | 藉由投予pd-1抑制劑治療皮膚癌之方法 |
EP3243832A1 (en) | 2016-05-13 | 2017-11-15 | F. Hoffmann-La Roche AG | Antigen binding molecules comprising a tnf family ligand trimer and pd1 binding moiety |
WO2017194783A1 (en) | 2016-05-13 | 2017-11-16 | Orionis Biosciences Nv | Targeted mutant interferon-beta and uses thereof |
CA3023881A1 (en) | 2016-05-13 | 2017-11-16 | Orionis Biosciences Nv | Therapeutic targeting of non-cellular structures |
WO2017201043A1 (en) * | 2016-05-16 | 2017-11-23 | Concert Pharmaceuticals, Inc. | Combination therapy for treating cancer |
TWI781934B (zh) | 2016-05-27 | 2022-11-01 | 美商艾吉納斯公司 | 抗-tim-3抗體及其使用方法 |
RU2732572C2 (ru) | 2016-05-31 | 2020-09-21 | Тайхо Фармасьютикал Ко., Лтд. | Сульфонамидное соединение или его соль |
KR20190008962A (ko) | 2016-06-02 | 2019-01-25 | 브리스톨-마이어스 스큅 컴퍼니 | 림프종 치료에서의 항-cd30 항체와 조합된 항-pd-1 항체의 용도 |
LT3463457T (lt) | 2016-06-02 | 2023-09-11 | Bristol-Myers Squibb Company | Pd-1 blokada su nivolumabu gydant atsparią hodžkino limfomą |
ES2897964T3 (es) | 2016-06-03 | 2022-03-03 | Bristol Myers Squibb Co | Uso del anticuerpo anti-PD-1 en el tratamiento de pacientes con cáncer colorrectal |
JP2019517498A (ja) | 2016-06-03 | 2019-06-24 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 再発性小細胞肺癌の処置方法において使用するための抗pd−1抗体 |
AU2017279029A1 (en) | 2016-06-08 | 2018-12-20 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds as ATF4 pathway inhibitors |
EP3468948A1 (en) | 2016-06-08 | 2019-04-17 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds |
CN109715196A (zh) | 2016-06-13 | 2019-05-03 | 转矩医疗股份有限公司 | 用于促进免疫细胞功能的组合物和方法 |
US9567399B1 (en) * | 2016-06-20 | 2017-02-14 | Kymab Limited | Antibodies and immunocytokines |
RU2769282C2 (ru) | 2016-06-20 | 2022-03-30 | Кимаб Лимитед | Анти-PD-L1 и IL-2 цитокины |
EP3476865B1 (en) | 2016-06-28 | 2023-09-13 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Method for constructing pd-1 gene-modified humanized animal model and use thereof |
CA3029426A1 (en) | 2016-06-30 | 2018-01-04 | Oncorus, Inc. | Pseudotyped oncolytic viral delivery of therapeutic polypeptides |
WO2018007885A1 (en) | 2016-07-05 | 2018-01-11 | Beigene, Ltd. | COMBINATION OF A PD-l ANTAGONIST AND A RAF INHIBITOR FOR TREATING CANCER |
CN109789135A (zh) | 2016-07-20 | 2019-05-21 | 葛兰素史密斯克莱知识产权发展有限公司 | 作为perk抑制剂的异喹啉衍生物 |
US11649289B2 (en) * | 2016-08-04 | 2023-05-16 | Glaxosmithkline Intellectual Property Development Limited | Anti-ICOS and anti-PD-1 antibody combination therapy |
JP7198752B2 (ja) | 2016-08-09 | 2023-01-04 | カイマブ・リミテッド | 抗icos抗体 |
TWI739887B (zh) | 2016-08-19 | 2021-09-21 | 英屬開曼群島商百濟神州有限公司 | 使用包含btk抑制劑的組合產品治療癌症 |
WO2018039131A1 (en) * | 2016-08-22 | 2018-03-01 | Protiva Biotherapeutics, Inc. | Anti-pd-1 antibodies, or fragments thereof, for treating hepatitis b |
WO2018035710A1 (en) | 2016-08-23 | 2018-03-01 | Akeso Biopharma, Inc. | Anti-ctla4 antibodies |
US10372100B2 (en) * | 2016-08-29 | 2019-08-06 | Ge Healthcare Bio-Sciences Corp. | Manufacturing system for biopharmaceutical products |
JP7045378B2 (ja) | 2016-09-01 | 2022-03-31 | キメラ・バイオエンジニアリング,インコーポレーテッド | Gold最適化CAR T細胞 |
PE20191102A1 (es) | 2016-09-14 | 2019-08-23 | Abbvie Biotherapeutics Inc | Anticuerpos anti-pd-1 y sus usos |
WO2018053434A1 (en) | 2016-09-16 | 2018-03-22 | The Johns Hopkins University | Protein nanocages with enhanced mucus penetration for targeted tissue and intracellular delivery |
WO2018053405A1 (en) | 2016-09-19 | 2018-03-22 | Celgene Corporation | Methods of treating immune disorders using pd-1 binding proteins |
JP2019534859A (ja) | 2016-09-19 | 2019-12-05 | セルジーン コーポレイション | Pd−1結合タンパク質を使用して白斑を治療する方法 |
RU2759334C2 (ru) | 2016-09-21 | 2021-11-12 | Нексткьюр, Инк. | Антитела против siglec-15 и способы их применения |
CA3037008A1 (en) | 2016-09-27 | 2018-04-05 | Oncologie, Inc. | Methods for treating cancer with bavituximab based on levels of .beta.2-glycoprotein 1, and assays therefor |
JOP20190070B1 (ar) | 2016-10-04 | 2023-09-17 | Merck Sharp And Dohme Llc | مركبات بنزو[b] ثيوفين كناهضات محفزة لبروتين جينات الإنترفيرون |
IL265762B2 (en) | 2016-10-06 | 2024-04-01 | Merck Patent Gmbh | Dosing regimen of avolumab for cancer treatment |
TW202246349A (zh) | 2016-10-11 | 2022-12-01 | 美商艾吉納斯公司 | 抗lag-3抗體及其使用方法 |
US20190263927A1 (en) | 2016-10-14 | 2019-08-29 | Merck Sharp & Dohme Corp. | Combination of a pd-1 antagonist and eribulin for treating urothelial cancer |
WO2018077893A1 (en) | 2016-10-24 | 2018-05-03 | Orionis Biosciences Nv | Targeted mutant interferon-gamma and uses thereof |
JP7420335B2 (ja) | 2016-10-26 | 2024-01-23 | デンカ株式会社 | 変異型ヒトDNAポリメラーゼε |
SG11201903835WA (en) | 2016-11-01 | 2019-05-30 | Anaptysbio Inc | Antibodies directed against programmed death- 1 (pd-1) |
TW201829462A (zh) | 2016-11-02 | 2018-08-16 | 英商葛蘭素史克智慧財產(第二)有限公司 | 結合蛋白 |
HUE057559T2 (hu) | 2016-11-02 | 2022-06-28 | Jounce Therapeutics Inc | PD-1 elleni antitestek és alkalmazásaik |
US11779604B2 (en) | 2016-11-03 | 2023-10-10 | Kymab Limited | Antibodies, combinations comprising antibodies, biomarkers, uses and methods |
WO2018089688A1 (en) | 2016-11-09 | 2018-05-17 | Jinjun Shi | Restoration of tumor suppression using mrna-based delivery system |
WO2018094275A1 (en) | 2016-11-18 | 2018-05-24 | Tolero Pharmaceuticals, Inc. | Alvocidib prodrugs and their use as protein kinase inhibitors |
EP3541825A1 (en) | 2016-11-21 | 2019-09-25 | Idenix Pharmaceuticals LLC. | Cyclic phosphate substituted nucleoside derivatives for the treatment of liver diseases |
WO2018098352A2 (en) | 2016-11-22 | 2018-05-31 | Jun Oishi | Targeting kras induced immune checkpoint expression |
US11135307B2 (en) | 2016-11-23 | 2021-10-05 | Mersana Therapeutics, Inc. | Peptide-containing linkers for antibody-drug conjugates |
CA3045306A1 (en) | 2016-11-29 | 2018-06-07 | Boston Biomedical, Inc. | Naphthofuran derivatives, preparation, and methods of use thereof |
BR112019010943A8 (pt) | 2016-11-30 | 2023-02-07 | Oncomed Pharm Inc | Usos de um anticorpo que se liga especificamente ao domínio extracelular de tigit humano para a inibição do crescimento do tumor, composição que compreende o dito anticorpo, polinucleotídeo, vetor e célula |
BR112019011370A2 (pt) | 2016-12-01 | 2019-10-15 | Glaxosmithkline Ip Dev Ltd | terapia de combinação |
AU2017369994A1 (en) | 2016-12-01 | 2019-06-13 | Glaxosmithkline Intellectual Property Development Limited | Combination therapy |
MD3551660T2 (ro) | 2016-12-07 | 2024-03-31 | Agenus Inc | Anticorpi anti-CTLA-4 și procedee de utilizare a acestora |
BR112019011582A2 (pt) | 2016-12-07 | 2019-10-22 | Agenus Inc. | anticorpos e métodos de utilização dos mesmos |
WO2018112364A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Combination therapies for treating melanoma |
WO2018112360A1 (en) | 2016-12-16 | 2018-06-21 | Evelo Biosciences, Inc. | Combination therapies for treating cancer |
WO2018123999A1 (ja) | 2016-12-28 | 2018-07-05 | 学校法人近畿大学 | 免疫チェックポイント阻害剤の投与対象となる個体の選択方法 |
SG11201906192SA (en) | 2017-01-09 | 2019-08-27 | Tesaro Inc | Methods of treating cancer with anti-pd-1 antibodies |
JP2020503883A (ja) | 2017-01-13 | 2020-02-06 | アジェナス インコーポレイテッド | Ny−eso−1に結合するt細胞受容体およびその使用方法 |
WO2018134279A1 (en) | 2017-01-18 | 2018-07-26 | Pieris Pharmaceuticals Gmbh | Novel fusion polypeptides specific for lag-3 and pd-1 |
EP3573989A4 (en) | 2017-01-25 | 2020-11-18 | Beigene, Ltd. | CRYSTALLINE FORMS OF (S) -7- (1- (BUT-2-YNOYL) -PIPERIDINE-4-YL) -2- (4-PHENOXYPHENYL) -4,5,6,7-TETRAHYDROPYRAZOLO [1,5-A ] PYRIMIDINE-3-CARBOXAMIDE, MANUFACTURING AND USES THEREOF |
JP2020505955A (ja) | 2017-02-06 | 2020-02-27 | オリオンズ バイオサイエンス インコーポレイテッド | 標的化改変型インターフェロン及びその使用 |
AU2018216032B2 (en) | 2017-02-06 | 2022-04-07 | Orionis Biosciences BV | Targeted chimeric proteins and uses thereof |
CA3050601A1 (en) | 2017-02-07 | 2018-08-16 | Vib Vzm | Immune-cell targeted bispecific chimeric proteins and uses thereof |
EP3582855A1 (en) | 2017-02-15 | 2019-12-25 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatment for cancer |
CA3052767A1 (en) | 2017-02-27 | 2018-08-30 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides as kinase inhibitors |
WO2018160538A1 (en) | 2017-02-28 | 2018-09-07 | Mersana Therapeutics, Inc. | Combination therapies of her2-targeted antibody-drug conjugates |
UY37621A (es) | 2017-02-28 | 2018-09-28 | Sanofi Sa | Arn terapéutico que codifica citoquinas |
US20200239579A1 (en) | 2017-03-09 | 2020-07-30 | Genmab A/S | Antibodies against pd-l1 |
EP3596469A1 (en) | 2017-03-12 | 2020-01-22 | Yeda Research and Development Co., Ltd. | Methods of diagnosing and prognosing cancer |
WO2018167780A1 (en) | 2017-03-12 | 2018-09-20 | Yeda Research And Development Co. Ltd. | Methods of prognosing and treating cancer |
US20210186982A1 (en) | 2017-03-24 | 2021-06-24 | Universite Nice Sophia Antipolis | Methods and compositions for treating melanoma |
US11352408B2 (en) | 2017-03-31 | 2022-06-07 | Toagosei Co., Ltd. | Antitumor peptide having PD-1 signal sequence and utilization thereof |
AU2018249493A1 (en) | 2017-04-03 | 2019-09-19 | Oncxerna Therapeutics, Inc. | Methods for treating cancer using PS-targeting antibodies with immuno-oncology agents |
MX2019011770A (es) | 2017-04-03 | 2020-01-09 | Hoffmann La Roche | Inmunoconjugados de un anticuerpo anti-pd-1 con un mutante il-2 o con il-15. |
CN116375876A (zh) | 2017-04-05 | 2023-07-04 | 豪夫迈·罗氏有限公司 | 特异性结合pd1和lag3的双特异性抗体 |
US11603407B2 (en) | 2017-04-06 | 2023-03-14 | Regeneron Pharmaceuticals, Inc. | Stable antibody formulation |
TW201841942A (zh) | 2017-04-13 | 2018-12-01 | 美商艾吉納斯公司 | 抗cd137抗體及其使用方法 |
EP3612201B1 (en) | 2017-04-21 | 2023-10-25 | Sillajen, Inc. | Oncolytic vaccinia virus and checkpoint inhibitor combination therapy |
CN108794467A (zh) | 2017-04-27 | 2018-11-13 | 博笛生物科技有限公司 | 2-氨基-喹啉衍生物 |
AR111651A1 (es) | 2017-04-28 | 2019-08-07 | Novartis Ag | Conjugados de anticuerpos que comprenden agonistas del receptor de tipo toll y terapias de combinación |
RS64576B1 (sr) | 2017-05-01 | 2023-10-31 | Agenus Inc | Anti-tigit antitela i postupci njihove primene |
CA3060581A1 (en) | 2017-05-02 | 2018-11-08 | Merck Sharp & Dohme Corp. | Formulations of anti-lag3 antibodies and co-formulations of anti-lag3 antibodies and anti-pd-1 antibodies |
JOP20190260A1 (ar) | 2017-05-02 | 2019-10-31 | Merck Sharp & Dohme | صيغ ثابتة لأجسام مضادة لمستقبل الموت المبرمج 1 (pd-1) وطرق استخدامها |
EP3621624B1 (en) | 2017-05-12 | 2023-08-30 | Merck Sharp & Dohme LLC | Cyclic di-nucleotide compounds as sting agonists |
JP2020520923A (ja) | 2017-05-17 | 2020-07-16 | ボストン バイオメディカル, インコーポレイテッド | がんを処置するための方法 |
MX2019013755A (es) | 2017-05-18 | 2020-07-20 | Tesaro Inc | Terapias de combinación para el tratamiento del cáncer. |
MX2019014104A (es) | 2017-05-26 | 2020-02-07 | Taiho Pharmaceutical Co Ltd | Compuesto novedoso de bifenilo o sal del mismo. |
TWI727173B (zh) | 2017-05-26 | 2021-05-11 | 日商大鵬藥品工業股份有限公司 | 使用有新穎聯苯化合物之抗腫瘤效果增強劑 |
US11723975B2 (en) | 2017-05-30 | 2023-08-15 | Bristol-Myers Squibb Company | Compositions comprising an anti-LAG-3 antibody or an anti-LAG-3 antibody and an anti-PD-1 or anti-PD-L1 antibody |
CN110720039A (zh) | 2017-05-30 | 2020-01-21 | 百时美施贵宝公司 | Lag-3阳性肿瘤的治疗 |
JOP20190279A1 (ar) | 2017-05-31 | 2019-11-28 | Novartis Ag | الصور البلورية من 5-برومو -2، 6-داي (1h-بيرازول -1-يل) بيريميدين -4- أمين وأملاح جديدة |
AU2018278327B2 (en) | 2017-06-01 | 2023-03-16 | Cytomx Therapeutics, Inc. | Activatable anti-pdl1 antibodies and methods of use thereof |
EP3630126A4 (en) | 2017-06-02 | 2021-03-17 | The Penn State Research Foundation | CERAMIDE NANOLIPOSOMES, COMPOSITIONS AND METHODS OF USE FOR IMMUNOTHERAPY |
WO2018225093A1 (en) | 2017-06-07 | 2018-12-13 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds as atf4 pathway inhibitors |
CN110869049A (zh) | 2017-06-09 | 2020-03-06 | 葛兰素史克知识产权开发有限公司 | 组合疗法 |
AU2018281830B2 (en) | 2017-06-09 | 2023-11-02 | Agonox, Inc. | Utilization of CD39 and CD103 for identification of human tumor reactive cells for treatment of cancer |
WO2018232230A1 (en) | 2017-06-15 | 2018-12-20 | Cancer Advances Inc. | Compositions and methods for inducing humoral and cellular immunities against tumors and cancer |
WO2018229715A1 (en) | 2017-06-16 | 2018-12-20 | Novartis Ag | Compositions comprising anti-cd32b antibodies and methods of use thereof |
GB201709808D0 (en) | 2017-06-20 | 2017-08-02 | Kymab Ltd | Antibodies |
CN110785187B (zh) | 2017-06-22 | 2024-04-05 | 诺华股份有限公司 | 针对cd73的抗体分子及其用途 |
WO2018235056A1 (en) | 2017-06-22 | 2018-12-27 | Novartis Ag | IL-1BETA BINDING ANTIBODIES FOR USE IN THE TREATMENT OF CANCER |
US20190048072A1 (en) | 2017-06-22 | 2019-02-14 | Novartis Ag | USE OF IL-1beta BINDING ANTIBODIES |
US20200172628A1 (en) | 2017-06-22 | 2020-06-04 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
AU2017419352A1 (en) | 2017-06-23 | 2019-12-12 | Birdie Biopharmaceuticals, Inc. | Pharmaceutical compositions |
CA3066518A1 (en) | 2017-06-26 | 2019-01-03 | Beigene, Ltd. | Immunotherapy for hepatocellular carcinoma |
JP2020525483A (ja) | 2017-06-27 | 2020-08-27 | ノバルティス アーゲー | 抗tim−3抗体のための投与レジメンおよびその使用 |
MX2020000150A (es) | 2017-06-30 | 2020-07-22 | Taiho Pharmaceutical Co Ltd | Quimioterapia para el cáncer usando el compuesto azabiciclo. |
US20210145771A1 (en) | 2017-07-03 | 2021-05-20 | Glaxosmithkline Intellectual Property Development Limited | N-(3-(2-(4-chlorophenoxy)acetamido)bicyclo[1.1.1] pentan-1-yl)-2-cyclobutane-1- carboxamide derivatives and related compounds as atf4 inhibitors for treating cancer and other diseases |
EP3649108A1 (en) | 2017-07-03 | 2020-05-13 | GlaxoSmithKline Intellectual Property Development Limited | 2-(4-chlorophenoxy)-n-((1 -(2-(4-chlorophenoxy)ethynazetidin-3-yl)methyl)acetamide derivatives and related compounds as atf4 inhibitors for treating cancer and other diseases |
AU2018302283A1 (en) | 2017-07-20 | 2020-02-06 | Novartis Ag | Dosage regimens of anti-LAG-3 antibodies and uses thereof |
WO2019021208A1 (en) | 2017-07-27 | 2019-01-31 | Glaxosmithkline Intellectual Property Development Limited | USEFUL INDAZOLE DERIVATIVES AS PERK INHIBITORS |
EP3661499A4 (en) | 2017-08-04 | 2021-04-21 | Merck Sharp & Dohme Corp. | COMBINATIONS OF PD-1 ANTAGONISTS AND BENZO [B] |
AU2018309339A1 (en) | 2017-08-04 | 2020-02-20 | BioNTech SE | Binding agents binding to PD-L1 and CD137 and use thereof |
JP2020530838A (ja) | 2017-08-04 | 2020-10-29 | メルク・シャープ・アンド・ドーム・コーポレーションMerck Sharp & Dohme Corp. | がん治療のためのベンゾ[b]チオフェンSTINGアゴニスト |
WO2019032663A1 (en) | 2017-08-09 | 2019-02-14 | Orionis Biosciences Inc. | PD-1 AND PD-L1 BINDING AGENTS |
CN111511763A (zh) | 2017-08-09 | 2020-08-07 | 奥里尼斯生物科学有限公司 | Cd8结合剂 |
SG11202001441WA (en) | 2017-08-18 | 2020-03-30 | Tragara Pharmaceuticals Inc | Polymorphic form of tg02 |
SG11202001319QA (en) | 2017-09-04 | 2020-03-30 | Agenus Inc | T cell receptors that bind to mixed lineage leukemia (mll)-specific phosphopeptides and methods of use thereof |
TW201922721A (zh) | 2017-09-07 | 2019-06-16 | 英商葛蘭素史克智慧財產發展有限公司 | 化學化合物 |
KR20200045520A (ko) | 2017-09-07 | 2020-05-04 | 오거스타 유니버시티 리서치 인스티튜트, 인크. | 프로그래밍된 세포사 단백질 1에 대한 항체 |
US11497756B2 (en) | 2017-09-12 | 2022-11-15 | Sumitomo Pharma Oncology, Inc. | Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib |
WO2019053617A1 (en) | 2017-09-12 | 2019-03-21 | Glaxosmithkline Intellectual Property Development Limited | CHEMICAL COMPOUNDS |
WO2019061324A1 (en) | 2017-09-29 | 2019-04-04 | Curis Inc. | CRYSTALLINE FORMS OF IMMUNOMODULATORS |
AU2018338901A1 (en) | 2017-09-30 | 2020-05-07 | Tesaro, Inc. | Combination therapies for treating cancer |
WO2019069269A1 (en) | 2017-10-05 | 2019-04-11 | Glaxosmithkline Intellectual Property Development Limited | INTERFERON GENE STIMULATOR MODULATORS USEFUL IN THE TREATMENT OF HIV |
WO2019069270A1 (en) | 2017-10-05 | 2019-04-11 | Glaxosmithkline Intellectual Property Development Limited | GENERATOR STIMULATOR MODULATORS (STING) INTERFERON |
AU2018346688A1 (en) | 2017-10-06 | 2020-04-23 | Tesaro, Inc. | Combination therapies and uses thereof |
AU2018348350A1 (en) | 2017-10-11 | 2020-04-02 | Aurigene Oncology Limited | Crystalline forms of 3-substituted 1,2,4-oxadiazole |
WO2019072241A1 (en) | 2017-10-13 | 2019-04-18 | Beijing Biocytogen Co., Ltd | NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC |
CN111247169A (zh) | 2017-10-15 | 2020-06-05 | 百时美施贵宝公司 | 治疗肿瘤的方法 |
US20210040205A1 (en) | 2017-10-25 | 2021-02-11 | Novartis Ag | Antibodies targeting cd32b and methods of use thereof |
WO2019089753A2 (en) | 2017-10-31 | 2019-05-09 | Compass Therapeutics Llc | Cd137 antibodies and pd-1 antagonists and uses thereof |
US20210179607A1 (en) | 2017-11-01 | 2021-06-17 | Merck Sharp & Dohme Corp. | Novel substituted tetrahydroquinolin compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
CN111372584A (zh) | 2017-11-03 | 2020-07-03 | 奥瑞基尼探索技术有限公司 | Tim-3和pd-1途径的双重抑制剂 |
CN111386128A (zh) | 2017-11-06 | 2020-07-07 | 奥瑞基尼探索技术有限公司 | 用于免疫调节的联合疗法 |
EP3709021A4 (en) * | 2017-11-07 | 2021-07-21 | J-Pharma Co., Ltd. | METHOD FOR PREDICTING THE EFFECTIVENESS OF ANTI-PD-1 ANTIBODY OR ANTI-PD-L1 ANTIBODY THERAPY, METHOD OF EVALUATING THE LEVEL OF CANCER AND METHOD OF IMPROVING THE EFFECTIVENESS OF ANTI-BODY THERAPY ANTI-PD-1 OR ANTI-PD-L1 ANTIBODY |
CN111344287B (zh) | 2017-11-14 | 2023-12-19 | 默沙东有限责任公司 | 作为吲哚胺2,3-双加氧酶(ido)抑制剂的新型取代的联芳基化合物 |
WO2019099294A1 (en) | 2017-11-14 | 2019-05-23 | Merck Sharp & Dohme Corp. | Novel substituted biaryl compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
WO2019104289A1 (en) | 2017-11-27 | 2019-05-31 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
US11786529B2 (en) | 2017-11-29 | 2023-10-17 | Beigene Switzerland Gmbh | Treatment of indolent or aggressive B-cell lymphomas using a combination comprising BTK inhibitors |
TW201925782A (zh) | 2017-11-30 | 2019-07-01 | 瑞士商諾華公司 | 靶向bcma之嵌合抗原受體及其用途 |
MY181242A (en) | 2017-12-01 | 2020-12-21 | Sbi Pharmaceuticals Co Ltd | Pharmaceutical composition for enhancing antitumor effect by immune checkpoint inhibitor |
US11946094B2 (en) | 2017-12-10 | 2024-04-02 | Augusta University Research Institute, Inc. | Combination therapies and methods of use thereof |
WO2019122882A1 (en) | 2017-12-19 | 2019-06-27 | Kymab Limited | Bispecific antibody for icos and pd-l1 |
AU2018388791A1 (en) | 2017-12-19 | 2020-07-16 | The Rockefeller University | Human IgG Fc domain variants with improved effector function |
US11685761B2 (en) | 2017-12-20 | 2023-06-27 | Merck Sharp & Dohme Llc | Cyclic di-nucleotide compounds as sting agonists |
CN111757757A (zh) | 2017-12-21 | 2020-10-09 | 梅尔莎纳医疗公司 | 吡咯并苯并二氮呯抗体共轭物 |
EP3731850A4 (en) | 2017-12-29 | 2021-12-01 | Oncorus, Inc. | ONCOLYTIC VIRUS DELIVERY OF THERAPEUTIC POLYPEPTIDES |
US20210072244A1 (en) | 2018-01-04 | 2021-03-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma resistant |
US11324774B2 (en) | 2018-01-05 | 2022-05-10 | Augusta University Research Institute, Inc. | Compositions of oral alkaline salts and metabolic acid inducers and uses thereof |
EP3737408A1 (en) | 2018-01-08 | 2020-11-18 | Novartis AG | Immune-enhancing rnas for combination with chimeric antigen receptor therapy |
KR20200112913A (ko) | 2018-01-23 | 2020-10-05 | 넥스트큐어 인코포레이티드 | B7-h4 항체 및 그 사용 방법 |
WO2019149716A1 (en) | 2018-01-31 | 2019-08-08 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising an antigen-binding site binding to lag3 |
WO2019152660A1 (en) | 2018-01-31 | 2019-08-08 | Novartis Ag | Combination therapy using a chimeric antigen receptor |
EP4317972A3 (en) | 2018-02-06 | 2024-03-13 | The General Hospital Corporation | Repeat rna as biomarkers of tumor immune response |
WO2019160956A1 (en) | 2018-02-13 | 2019-08-22 | Novartis Ag | Chimeric antigen receptor therapy in combination with il-15r and il15 |
EP3756012A1 (en) | 2018-02-21 | 2020-12-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of sk1 as biomarker for predicting response to immunecheckpoint inhibitors |
KR102608723B1 (ko) | 2018-02-23 | 2023-12-01 | 유큐(베이징) 바이오파마 코., 엘티디 | 항―pd-1 항체 및 그의 용도 |
US20210002373A1 (en) | 2018-03-01 | 2021-01-07 | Nextcure, Inc. | KLRG1 Binding Compositions and Methods of Use Thereof |
EP3765524A4 (en) | 2018-03-14 | 2021-12-22 | Surface Oncology, Inc. | Antibodies for binding CD39 and uses thereof |
CA3094431C (en) | 2018-03-19 | 2023-06-27 | Taiho Pharmaceutical Co., Ltd. | Pharmaceutical composition including sodium alkyl sulfate |
US11332524B2 (en) | 2018-03-22 | 2022-05-17 | Surface Oncology, Inc. | Anti-IL-27 antibodies and uses thereof |
EP3774765A4 (en) | 2018-04-03 | 2021-12-29 | Merck Sharp & Dohme Corp. | Aza-benzothiophene compounds as sting agonists |
MA52189A (fr) | 2018-04-03 | 2021-02-17 | Merck Sharp & Dohme | Benzothiophènes et composés associés utilisés en tant qu'agonistes de sting |
WO2019193541A1 (en) | 2018-04-06 | 2019-10-10 | Glaxosmithkline Intellectual Property Development Limited | Bicyclic aromatic ring derivatives of formula (i) as atf4 inhibitors |
WO2019193540A1 (en) | 2018-04-06 | 2019-10-10 | Glaxosmithkline Intellectual Property Development Limited | Heteroaryl derivatives of formula (i) as atf4 inhibitors |
US20210147547A1 (en) | 2018-04-13 | 2021-05-20 | Novartis Ag | Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof |
AU2019256383A1 (en) | 2018-04-17 | 2020-11-26 | Celldex Therapeutics, Inc. | Anti-CD27 and anti-PD-L1 antibodies and bispecific constructs |
CN112105733A (zh) | 2018-04-19 | 2020-12-18 | 查美特制药公司 | 合成rig-i样受体激动剂 |
US11542505B1 (en) | 2018-04-20 | 2023-01-03 | Merck Sharp & Dohme Llc | Substituted RIG-I agonists: compositions and methods thereof |
CA3096909A1 (en) | 2018-04-26 | 2019-10-31 | Agenus Inc. | Heat shock protein-binding peptide compositions and methods of use thereof |
CN112384624A (zh) | 2018-05-15 | 2021-02-19 | 杜克大学 | 用于对阿克曼菌进行基因操纵的系统和方法 |
GB201807924D0 (en) | 2018-05-16 | 2018-06-27 | Ctxt Pty Ltd | Compounds |
TW202015726A (zh) | 2018-05-30 | 2020-05-01 | 瑞士商諾華公司 | Entpd2抗體、組合療法、及使用該等抗體和組合療法之方法 |
WO2019232244A2 (en) | 2018-05-31 | 2019-12-05 | Novartis Ag | Antibody molecules to cd73 and uses thereof |
WO2019232319A1 (en) | 2018-05-31 | 2019-12-05 | Peloton Therapeutics, Inc. | Compositions and methods for inhibiting cd73 |
WO2019231870A1 (en) | 2018-05-31 | 2019-12-05 | Merck Sharp & Dohme Corp. | Novel substituted [1.1.1] bicyclo compounds as indoleamine 2,3-dioxygenase inhibitors |
EP3802611A2 (en) | 2018-06-01 | 2021-04-14 | Novartis AG | Binding molecules against bcma and uses thereof |
US20210253528A1 (en) | 2018-07-09 | 2021-08-19 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds |
AU2019301070A1 (en) | 2018-07-09 | 2021-01-21 | Precigen, Inc. | Fusion constructs and methods of using thereof |
AR116109A1 (es) | 2018-07-10 | 2021-03-31 | Novartis Ag | Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos |
IL278951B (en) | 2018-07-10 | 2022-08-01 | Novartis Ag | History of 3-(5-hydroxy-1-oxoisoindolin-2-yl)piperidine-6,2-dione and their use in the treatment of ikzf2-dependent diseases |
EP3827020A1 (en) | 2018-07-24 | 2021-06-02 | Amgen Inc. | Combination of lilrb1/2 pathway inhibitors and pd-1 pathway inhibitors |
WO2020021061A1 (en) | 2018-07-26 | 2020-01-30 | Pieris Pharmaceuticals Gmbh | Humanized anti-pd-1 antibodies and uses thereof |
WO2020030571A1 (en) | 2018-08-06 | 2020-02-13 | Glaxosmithkline Intellectual Property Development Limited | Combinations of a pd-1 antibody and a tlr4 modulator and uses thereof |
WO2020031107A1 (en) | 2018-08-08 | 2020-02-13 | Glaxosmithkline Intellectual Property Development Limited | Chemical compounds |
CA3106881A1 (en) | 2018-08-27 | 2020-03-05 | Pieris Pharmaceuticals Gmbh | Combination therapies comprising cd137/her2 bispecific agents and pd-1 axis inhibitors and uses thereof |
WO2020044206A1 (en) | 2018-08-29 | 2020-03-05 | Glaxosmithkline Intellectual Property Development Limited | Heterocyclic amides as kinase inhibitors for use in the treatment cancer |
US20210340279A1 (en) | 2018-08-31 | 2021-11-04 | Yale University | Compositions and methods of using cell-penetrating antibodies in combination with immune checkpoint modulators |
WO2020067170A1 (ja) | 2018-09-25 | 2020-04-02 | 国立研究開発法人国立循環器病研究センター | 抗腫瘍効果増強剤 |
EP3865141A4 (en) | 2018-10-09 | 2022-06-08 | Biocomo Incorporation | ANTI-CANCER AGENT, PHARMACEUTICAL COMPOSITION FOR CANCER TREATMENT AND KIT |
JP2022504468A (ja) | 2018-10-17 | 2022-01-13 | バイオラインアールエックス・リミテッド | 転移性膵臓腺癌の処置 |
WO2020086479A1 (en) | 2018-10-22 | 2020-04-30 | Glaxosmithkline Intellectual Property Development Limited | Dosing |
MX2021004906A (es) | 2018-10-29 | 2021-09-10 | Mersana Therapeutics Inc | Conjugados de anticuerpo modificado con cisteína-fármaco con enlazadores que contienen péptidos. |
WO2020089811A1 (en) | 2018-10-31 | 2020-05-07 | Novartis Ag | Dc-sign antibody drug conjugates |
US20210395240A1 (en) | 2018-11-01 | 2021-12-23 | Merck Sharp & Dohme Corp. | Novel substituted pyrazole compounds as indoleamine 2,3-dioxygenase inhibitors |
US20210403469A1 (en) | 2018-11-06 | 2021-12-30 | Merck Sharp & Dohme Corp. | Novel substituted tricyclic compounds as indoleamine 2,3-dioxygenase inhibitors |
KR20210124959A (ko) | 2018-11-06 | 2021-10-15 | 젠맵 에이/에스 | 항체 제제 |
SG11202104864QA (en) | 2018-11-13 | 2021-06-29 | Compass Therapeutics Llc | Multispecific binding constructs against checkpoint molecules and uses thereof |
TW202028222A (zh) | 2018-11-14 | 2020-08-01 | 美商Ionis製藥公司 | Foxp3表現之調節劑 |
JP2022513029A (ja) | 2018-11-14 | 2022-02-07 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | 皮膚がんを治療するためのpd-1阻害剤の病変内投与 |
EP3880202A2 (en) | 2018-11-16 | 2021-09-22 | ArQule, Inc. | Pharmaceutical combination for treatment of cancer |
CN113227142B (zh) | 2018-11-19 | 2022-11-29 | 百奥赛图(北京)医药科技股份有限公司 | 抗pd-1抗体及其用途 |
EP3883576A4 (en) | 2018-11-20 | 2022-06-22 | Merck Sharp & Dohme Corp. | SUBSTITUTED AMINOTRIAZOLOPYRIMIDINES AND AMINO-TRIAZOLOPYRAZINE ADENOSINE RECEPTOR ANTAGONISTS, PHARMACEUTICAL COMPOSITIONS AND THEIR USE |
WO2020106558A1 (en) | 2018-11-20 | 2020-05-28 | Merck Sharp & Dohme Corp. | Substituted amino triazolopyrimidine and amino triazolopyrazine adenosine receptor antagonists, pharmaceutical compositions and their use |
WO2020104479A1 (en) | 2018-11-20 | 2020-05-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers and resistant cancers with anti transferrin receptor 1 antibodies |
WO2020104496A1 (en) | 2018-11-20 | 2020-05-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Bispecific antibody targeting transferrin receptor 1 and soluble antigen |
WO2020112581A1 (en) | 2018-11-28 | 2020-06-04 | Merck Sharp & Dohme Corp. | Novel substituted piperazine amide compounds as indoleamine 2, 3-dioxygenase (ido) inhibitors |
JP7406556B2 (ja) | 2018-11-30 | 2023-12-27 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | Hiv療法に有用な化合物 |
KR102653800B1 (ko) | 2018-11-30 | 2024-04-01 | 머크 샤프 앤드 돔 엘엘씨 | 아데노신 수용체 길항제로서의 9-치환된 아미노 트리아졸로 퀴나졸린 유도체, 제약 조성물 및 그의 용도 |
CN113490499A (zh) | 2018-12-04 | 2021-10-08 | 大日本住友制药肿瘤公司 | 用作治疗癌症的活性剂的cdk9抑制剂及其多晶型物 |
WO2020115261A1 (en) | 2018-12-07 | 2020-06-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
BR112021011224A2 (pt) | 2018-12-11 | 2021-08-24 | Theravance Biopharma R&D Ip, Llc | Inibidores de alk5 |
WO2020120592A1 (en) | 2018-12-12 | 2020-06-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for predicting and treating melanoma |
GB201820547D0 (en) | 2018-12-17 | 2019-01-30 | Oxford Univ Innovation | Modified antibodies |
EP3898699A1 (en) | 2018-12-19 | 2021-10-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers by immuno-modulation using antibodies against cathespin-d |
MX2021007392A (es) | 2018-12-20 | 2021-08-24 | Novartis Ag | Regimen de dosificacion y combinacion farmaceutica que comprende derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona. |
JP2022514087A (ja) | 2018-12-21 | 2022-02-09 | ノバルティス アーゲー | IL-1β結合抗体の使用 |
WO2020127885A1 (en) | 2018-12-21 | 2020-06-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Compositions for treating cancers and resistant cancers |
CA3124408A1 (en) | 2018-12-21 | 2020-06-25 | Aim Immunotech Inc. | Compositions and methods for cancer therapy |
AU2019408408A1 (en) | 2018-12-21 | 2021-06-03 | Valerio Therapeutics | New conjugated nucleic acid molecules and their uses |
US20220025036A1 (en) | 2018-12-21 | 2022-01-27 | Novartis Ag | Use of il-1beta binding antibodies |
SG11202104699TA (en) | 2018-12-21 | 2021-07-29 | Novartis Ag | Use of il-1 beta antibodies in the treatment or prevention of myelodysplastic syndrome |
WO2020128637A1 (en) | 2018-12-21 | 2020-06-25 | Novartis Ag | Use of il-1 binding antibodies in the treatment of a msi-h cancer |
CN109593135B (zh) * | 2018-12-29 | 2021-01-15 | 百奥赛图江苏基因生物技术有限公司 | 抗人pd-l1单克隆抗体及其应用 |
CN111423510B (zh) | 2019-01-10 | 2024-02-06 | 迈威(上海)生物科技股份有限公司 | 重组抗人pd-1抗体及其应用 |
JP2022518207A (ja) | 2019-01-17 | 2022-03-14 | ジョージア テック リサーチ コーポレイション | 酸化コレステロールを含有する薬物送達システム |
KR20200089645A (ko) | 2019-01-17 | 2020-07-27 | 오토텔릭바이오 주식회사 | 암 치료용 조성물 |
EP3918332A1 (en) | 2019-01-30 | 2021-12-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for identifying whether a subject suffering from a cancer will achieve a response with an immune-checkpoint inhibitor |
CN113924317A (zh) | 2019-02-01 | 2022-01-11 | 葛兰素史克知识产权开发有限公司 | 贝兰他单抗莫福汀与派姆单抗组合用于治疗癌症 |
WO2020161083A1 (en) | 2019-02-04 | 2020-08-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for modulating blood-brain barrier |
JP2022520361A (ja) | 2019-02-12 | 2022-03-30 | スミトモ ダイニッポン ファーマ オンコロジー, インコーポレイテッド | 複素環式タンパク質キナーゼ阻害剤を含む製剤 |
EP3924520A1 (en) | 2019-02-13 | 2021-12-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for selecting a cancer treatment in a subject suffering from cancer |
KR20210129672A (ko) | 2019-02-15 | 2021-10-28 | 노파르티스 아게 | 치환된 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체 및 이의 용도 |
JP2022520811A (ja) | 2019-02-15 | 2022-04-01 | ノバルティス アーゲー | 3-(1-オキソ-5-(ピペリジン-4-イル)イソインドリン-2-イル)ピペリジン-2,6-ジオン誘導体及びその使用 |
US20220107320A1 (en) | 2019-02-15 | 2022-04-07 | Incelldx, Inc. | Assaying Bladder-Associated Samples, Identifying and Treating Bladder-Associated Neoplasia, and Kits for Use Therein |
CN113490529A (zh) | 2019-02-28 | 2021-10-08 | 瑞泽恩制药公司 | 用于治疗皮肤癌的pd-1抑制剂的施用 |
CA3129963A1 (en) | 2019-03-06 | 2020-09-10 | Regeneron Pharmaceuticals, Inc. | Il-4/il-13 pathway inhibitors for enhanced efficacy in treating cancer |
WO2020183011A1 (en) | 2019-03-14 | 2020-09-17 | Institut Curie | Htr1d inhibitors and uses thereof in the treatment of cancer |
WO2020191326A1 (en) | 2019-03-20 | 2020-09-24 | Sumitomo Dainippon Pharma Oncology, Inc. | Treatment of acute myeloid leukemia (aml) with venetoclax failure |
AU2020245437A1 (en) | 2019-03-22 | 2021-09-30 | Sumitomo Pharma Oncology, Inc. | Compositions comprising PKM2 modulators and methods of treatment using the same |
KR20220009941A (ko) | 2019-03-26 | 2022-01-25 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | Stat3의 저분자 분해제 |
CN113767115A (zh) | 2019-03-28 | 2021-12-07 | 奥里尼斯生物科学股份有限公司 | 治疗性干扰素α1蛋白 |
EP3947403A1 (en) | 2019-03-29 | 2022-02-09 | The Regents Of The University Of Michigan | Stat3 protein degraders |
EP3946424A1 (en) | 2019-03-29 | 2022-02-09 | Institut Curie | Interleukin-2 variants with modified biological activity |
US20220177465A1 (en) | 2019-04-04 | 2022-06-09 | Merck Sharp & Dohme Corp. | Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes |
EP3725370A1 (en) | 2019-04-19 | 2020-10-21 | ImmunoBrain Checkpoint, Inc. | Modified anti-pd-l1 antibodies and methods and uses for treating a neurodegenerative disease |
US20220220565A1 (en) | 2019-04-30 | 2022-07-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
US20220213194A1 (en) | 2019-05-15 | 2022-07-07 | Neotx Therapeutics Ltd. | Cancer treatment |
EP3969452A1 (en) | 2019-05-16 | 2022-03-23 | Stingthera, Inc. | Benzo[b][1,8]naphthyridine acetic acid derivatives and methods of use |
JP2022533390A (ja) | 2019-05-16 | 2022-07-22 | スティングセラ インコーポレイテッド | オキソアクリジニル酢酸誘導体および使用方法 |
EP3976090A1 (en) | 2019-05-24 | 2022-04-06 | Pfizer Inc. | Combination therapies using cdk inhibitors |
US20220226291A1 (en) | 2019-05-29 | 2022-07-21 | Taiho Pharmaceutical Co., Ltd. | Combination Treatment of Cancer Using Sulfonamide Compound and Immune Regulator |
US11246906B2 (en) | 2019-06-11 | 2022-02-15 | Alkermes Pharma Ireland Limited | Compositions and methods for subcutaneous administration of cancer immunotherapy |
CA3141405A1 (en) | 2019-06-12 | 2020-12-17 | H. Charles Manning | Amino acid transport inhibitors and the uses thereof |
EP3983377A1 (en) | 2019-06-12 | 2022-04-20 | Vanderbilt University | Dibenzylamines as amino acid transport inhibitors |
US20220233685A1 (en) | 2019-06-18 | 2022-07-28 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis b virus (hbv) vaccines and anti-pd-1 antibody |
AU2020295012A1 (en) | 2019-06-18 | 2022-02-17 | Janssen Sciences Ireland Unlimited Company | Combination of hepatitis B virus (HBV) vaccines and anti-PD-1 or anti-PD-L1 antibody |
JP7329173B2 (ja) | 2019-06-25 | 2023-08-18 | 東亞合成株式会社 | 抗腫瘍ペプチドおよびその利用 |
JP2022539178A (ja) | 2019-06-26 | 2022-09-07 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッド | Il1rap結合タンパク質 |
EP3990635A1 (en) | 2019-06-27 | 2022-05-04 | Rigontec GmbH | Design method for optimized rig-i ligands |
CA3145864A1 (en) | 2019-07-03 | 2021-01-07 | Sumitomo Dainippon Pharma Oncology, Inc. | Tyrosine kinase non-receptor 1 (tnk1) inhibitors and uses thereof |
US20220356255A1 (en) * | 2019-07-15 | 2022-11-10 | Capella Bioscience Ltd | Anti-pd-l1 antibodies |
CN114127073A (zh) | 2019-07-16 | 2022-03-01 | 美国密歇根州立大学试剂中心 | 作为eed抑制剂的咪唑并嘧啶和其用途 |
GB201910304D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
GB201910305D0 (en) | 2019-07-18 | 2019-09-04 | Ctxt Pty Ltd | Compounds |
US11083705B2 (en) | 2019-07-26 | 2021-08-10 | Eisai R&D Management Co., Ltd. | Pharmaceutical composition for treating tumor |
AU2020324388A1 (en) | 2019-08-02 | 2022-02-24 | Mersana Therapeutics, Inc. | Bis-[N-((5-carbamoyl)-1H-benzo[d]imidazol-2-yl)-pyrazol-5-carboxamide] derivatives and related compounds as STING (Stimulator of Interferon Genes) agonists for the treatment of cancer |
EP4011389A1 (en) | 2019-08-09 | 2022-06-15 | Riken | Combined use of artificial adjuvant vector cells and an immunostimulant |
CA3151824A1 (en) | 2019-08-27 | 2021-03-04 | The Regents Of The University Of Michigan | Cereblon e3 ligase inhibitors |
JP2022545741A (ja) | 2019-08-30 | 2022-10-28 | アジェナス インコーポレイテッド | 抗cd96抗体およびその使用方法 |
WO2021043961A1 (en) | 2019-09-06 | 2021-03-11 | Glaxosmithkline Intellectual Property Development Limited | Dosing regimen for the treatment of cancer with an anti icos agonistic antibody and chemotherapy |
WO2021048292A1 (en) | 2019-09-11 | 2021-03-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
BR112022002351A2 (pt) | 2019-09-16 | 2022-07-19 | Surface Oncology Inc | Composições e métodos de anticorpo anti-cd39 |
AU2020349516A1 (en) | 2019-09-17 | 2022-03-17 | Bial-R&D Investments, S.A. | Substituted imidazole carboxamides and their use in the treatment of medical disorders |
CN114901652A (zh) | 2019-09-17 | 2022-08-12 | 比亚尔R&D投资股份公司 | 用于治疗医学病症的经取代的饱和和不饱和n-杂环甲酰胺及相关化合物 |
CA3151022A1 (en) | 2019-09-17 | 2021-03-25 | Bial - R&D Investments, S.A. | Substituted n-heterocyclic carboxamides as acid ceramidase inhibitors and their use as medicaments |
US20220348651A1 (en) | 2019-09-18 | 2022-11-03 | Novartis Ag | Entpd2 antibodies, combination therapies, and methods of using the antibodies and combination therapies |
TW202124446A (zh) | 2019-09-18 | 2021-07-01 | 瑞士商諾華公司 | 與entpd2抗體之組合療法 |
WO2021055756A1 (en) | 2019-09-19 | 2021-03-25 | The Regents Of The University Of Michigan | Spirocyclic androgen receptor protein degraders |
EP4034559A1 (en) | 2019-09-25 | 2022-08-03 | Surface Oncology, Inc. | Anti-il-27 antibodies and uses thereof |
CA3155173A1 (en) | 2019-09-27 | 2021-04-01 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins |
EP4037714A1 (en) | 2019-10-03 | 2022-08-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for modulating macrophages polarization |
EP4045686A1 (en) | 2019-10-17 | 2022-08-24 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods for diagnosing nasal intestinal type adenocarcinomas |
CN114786679A (zh) | 2019-10-21 | 2022-07-22 | 诺华股份有限公司 | 具有维奈托克和tim-3抑制剂的组合疗法 |
TW202128191A (zh) | 2019-10-21 | 2021-08-01 | 瑞士商諾華公司 | Tim-3抑制劑及其用途 |
US20220401539A1 (en) | 2019-10-22 | 2022-12-22 | Institut Curie | Immunotherapy Targeting Tumor Neoantigenic Peptides |
MX2022004825A (es) | 2019-10-23 | 2022-10-10 | Regeneron Pharma | Agonistas sintéticos del receptor similar a rig i. |
EP4053124A1 (en) | 2019-10-28 | 2022-09-07 | Shanghai Institute of Materia Medica, Chinese Academy of Sciences | Five-membered heterocyclic oxocarboxylic acid compound and medical use thereof |
WO2021083959A1 (en) | 2019-10-29 | 2021-05-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating uveal melanoma |
EP4051278A1 (en) | 2019-10-29 | 2022-09-07 | Eisai R&D Management Co., Ltd. | Combination of a pd-1 antagonist, a vegfr/fgfr/ret tyrosine kinase inhibitor and a cbp/beta-catenin inhibitor for treating cancer |
IL291748A (en) | 2019-11-07 | 2022-06-01 | Oncxerna Therapeutics Inc | Classification of growth microenvironments |
WO2021102343A1 (en) | 2019-11-22 | 2021-05-27 | Sumitomo Dainippon Pharma Oncology, Inc. | Solid dose pharmaceutical composition |
EP3824954A1 (en) | 2019-11-22 | 2021-05-26 | Centre National de la Recherche Scientifique | Device, apparatus and method for minibeam radiation therapy |
TW202132297A (zh) | 2019-11-22 | 2021-09-01 | 美商施萬生物製藥研發Ip有限責任公司 | 經取代吡啶及使用方法 |
WO2021108025A1 (en) | 2019-11-26 | 2021-06-03 | Massachusetts Institute Of Technology | Cell-based cancer vaccines and cancer therapies |
WO2021113679A1 (en) | 2019-12-06 | 2021-06-10 | Mersana Therapeutics, Inc. | Dimeric compounds as sting agonists |
US11897950B2 (en) | 2019-12-06 | 2024-02-13 | Augusta University Research Institute, Inc. | Osteopontin monoclonal antibodies |
AU2020408198A1 (en) | 2019-12-19 | 2022-07-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and vaccine compositions to treat cancers |
WO2021123902A1 (en) | 2019-12-20 | 2021-06-24 | Novartis Ag | Combination of anti tim-3 antibody mbg453 and anti tgf-beta antibody nis793, with or without decitabine or the anti pd-1 antibody spartalizumab, for treating myelofibrosis and myelodysplastic syndrome |
WO2021144426A1 (en) | 2020-01-17 | 2021-07-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
IL293752A (en) | 2020-01-17 | 2022-08-01 | Novartis Ag | A combination containing a tim-3 inhibitor and a substance that causes hypomethylation for use in the treatment of myeloplastic syndrome or chronic myelomonocytic leukemia |
CA3161513A1 (en) | 2020-01-28 | 2021-08-05 | Irwin DAVIDSON | Antisense oligonucleotide targeting linc00518 for treating melanoma |
CN115038466A (zh) | 2020-01-28 | 2022-09-09 | 葛兰素史密斯克莱知识产权发展有限公司 | 联合治疗及其用途和方法 |
KR20220137054A (ko) | 2020-02-04 | 2022-10-11 | 젠맵 에이/에스 | 요법에 사용하기 위한 항체 |
WO2021156360A1 (en) | 2020-02-05 | 2021-08-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for discontinuing a treatment with a tyrosine kinase inhibitor (tki) |
US20230113705A1 (en) | 2020-02-28 | 2023-04-13 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for diagnosing, prognosing and managing treatment of breast cancer |
JP2023517011A (ja) | 2020-03-05 | 2023-04-21 | ネオティーエックス セラピューティクス リミテッド | 免疫細胞を用いて癌を治療するための方法および組成物 |
US20230159573A1 (en) | 2020-03-26 | 2023-05-25 | The Regents Of The University Of Michigan | Small molecule stat protein degraders |
CN115443269A (zh) | 2020-03-31 | 2022-12-06 | 施万生物制药研发Ip有限责任公司 | 经取代的嘧啶和使用方法 |
WO2021209358A1 (en) | 2020-04-14 | 2021-10-21 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer based upon an icos antibody and a pd-l1 antibody tgf-beta-receptor fusion protein |
EP4136112A1 (en) | 2020-04-14 | 2023-02-22 | GlaxoSmithKline Intellectual Property Development Limited | Combination treatment for cancer |
AU2021256652A1 (en) | 2020-04-14 | 2022-11-03 | Glaxosmithkline Intellectual Property Development Limited | Combination treatment for cancer involving anti-ICOS and anti-PD1 antibodies, optionally further involving anti-tim3 antibodies |
WO2021216488A1 (en) | 2020-04-21 | 2021-10-28 | Regeneron Pharmaceuticals, Inc. | Il-2 variants with reduced binding to il-2 receptor alpha and uses thereof |
TW202206100A (zh) | 2020-04-27 | 2022-02-16 | 美商西健公司 | 癌症之治療 |
EP4137156A1 (en) | 2020-05-01 | 2023-02-22 | The University of Tokyo | Prophylactic or therapeutic agent for at least one type of cancer selected from group consisting of pancreatic cancer, lung cancer, colorectal cancer, biliary tract cancer and liver cancer, prophylactic or therapeutic agent for said cancer which is used in combination drug in combination with said agent, combination drug comprising said agents, and method for screening for prophylactic or therapeutic agent for cancer |
WO2021224186A1 (en) | 2020-05-04 | 2021-11-11 | Institut Curie | New pyridine derivatives as radiosensitizers |
IL297781A (en) | 2020-05-06 | 2022-12-01 | Merck Sharp & Dohme Llc | il4i1 inhibitors and methods of use |
CN116323647A (zh) | 2020-05-13 | 2023-06-23 | 博纳姆治疗公司 | 蛋白质复合物的组合物及其使用方法 |
AU2021270750A1 (en) | 2020-05-13 | 2022-12-08 | Massachusetts Institute Of Technology | Compositions of polymeric microdevices and their use in cancer immunotherapy |
EP4153628A1 (en) | 2020-05-20 | 2023-03-29 | Institut Curie | Single domain antibodies and their use in cancer therapies |
JP7240512B2 (ja) | 2020-05-26 | 2023-03-15 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Pd-1阻害剤を投与することにより子宮頸がんを処置する方法 |
US11767353B2 (en) | 2020-06-05 | 2023-09-26 | Theraly Fibrosis, Inc. | Trail compositions with reduced immunogenicity |
EP4165041A1 (en) | 2020-06-10 | 2023-04-19 | Theravance Biopharma R&D IP, LLC | Naphthyridine derivatives useful as alk5 inhibitors |
TW202214857A (zh) | 2020-06-19 | 2022-04-16 | 法商昂席歐公司 | 新型結合核酸分子及其用途 |
JP2023531676A (ja) | 2020-06-23 | 2023-07-25 | ノバルティス アーゲー | 3-(1-オキソイソインドリン-2-イル)ピぺリジン-2,6-ジオン誘導体を含む投与レジメン |
WO2021260675A1 (en) | 2020-06-24 | 2021-12-30 | Yeda Research And Development Co. Ltd. | Agents for sensitizing solid tumors to treatment |
JP2023531493A (ja) | 2020-06-26 | 2023-07-24 | アムジエン・インコーポレーテツド | Il-10突然変異タンパク質及びその融合タンパク質 |
WO2022011205A1 (en) | 2020-07-10 | 2022-01-13 | The Regents Of The University Of Michigan | Androgen receptor protein degraders |
US20230257365A1 (en) | 2020-07-10 | 2023-08-17 | The Regents Of The University Of Michigan | Small molecule androgen receptor protein degraders |
EP4189395A1 (en) | 2020-07-28 | 2023-06-07 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods and compositions for preventing and treating a cancer |
JP2023536164A (ja) | 2020-08-03 | 2023-08-23 | ノバルティス アーゲー | ヘテロアリール置換3-(1-オキソイソインドリン-2-イル)ピペリジン-2,6-ジオン誘導体及びその使用 |
MX2023002123A (es) | 2020-08-26 | 2023-03-15 | Regeneron Pharma | Metodos de tratamiento de cancer mediante la administracion de un inhibidor de pd-1. |
JP2023540490A (ja) | 2020-09-02 | 2023-09-25 | ファーマブシン インコーポレイテッド | がん患者を治療するためのpd-1拮抗薬及びvegfr-2拮抗薬の併用療法 |
WO2022051448A1 (en) | 2020-09-03 | 2022-03-10 | Regeneron Pharmaceuticals, Inc. | Methods of treating cancer pain by administering a pd-1 inhibitor |
CN111920948B (zh) * | 2020-09-25 | 2021-02-02 | 安可瑞(山西)生物细胞有限公司 | 包含免疫细胞的药物组合物用于治疗癌症 |
WO2022079270A1 (en) | 2020-10-16 | 2022-04-21 | Université D'aix-Marseille | Anti-gpc4 single domain antibodies |
EP4232453A1 (en) | 2020-10-20 | 2023-08-30 | Institut Curie | Metallic trans-(n-heterocyclic carbene)-amine-platinum complexes and uses thereof for treating cancer |
WO2022084531A1 (en) | 2020-10-23 | 2022-04-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating glioma |
TW202233185A (zh) | 2020-10-28 | 2022-09-01 | 日商衛材R&D企管股份有限公司 | 腫瘤治療用醫藥組合物 |
EP4240491A1 (en) | 2020-11-06 | 2023-09-13 | Novartis AG | Cd19 binding molecules and uses thereof |
EP4244392A1 (en) | 2020-11-16 | 2023-09-20 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and compositions for predicting and treating uveal melanoma |
EP4244391A1 (en) | 2020-11-16 | 2023-09-20 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for predicting and treating uveal melanoma |
JP2023550402A (ja) | 2020-11-18 | 2023-12-01 | アンスティテュ・クリー | ビグアニジンの二量体及びその治療的使用 |
CA3200895A1 (en) | 2020-12-07 | 2022-06-16 | Ugur Sahin | Antibody and taxane combination therapy |
TW202237119A (zh) | 2020-12-10 | 2022-10-01 | 美商住友製藥腫瘤公司 | Alk﹘5抑制劑和彼之用途 |
WO2022130206A1 (en) | 2020-12-16 | 2022-06-23 | Pfizer Inc. | TGFβr1 INHIBITOR COMBINATION THERAPIES |
JP2024505428A (ja) | 2021-01-14 | 2024-02-06 | アンスティテュ キュリー | Her2単一ドメイン抗体バリアントおよびそのcar |
EP4284510A1 (en) | 2021-01-29 | 2023-12-06 | Novartis AG | Dosage regimes for anti-cd73 and anti-entpd2 antibodies and uses thereof |
TW202241508A (zh) | 2021-01-29 | 2022-11-01 | 美商艾歐凡斯生物治療公司 | 細胞介素相關之腫瘤浸潤性淋巴球組合物及方法 |
WO2022165403A1 (en) | 2021-02-01 | 2022-08-04 | Yale University | Chemotherapeutic bioadhesive particles with immunostimulatory molecules for cancer treatment |
IL305427A (en) | 2021-03-02 | 2023-10-01 | Glaxosmithkline Ip Dev Ltd | Substituted pyridines as DNMT1 inhibitors |
WO2022187419A1 (en) | 2021-03-03 | 2022-09-09 | The Regents Of The University Of Michigan | Small molecule degraders of androgen receptor |
WO2022187423A1 (en) | 2021-03-03 | 2022-09-09 | The Regents Of The University Of Michigan | Cereblon ligands |
WO2022189618A1 (en) | 2021-03-12 | 2022-09-15 | Institut Curie | Nitrogen-containing heterocycles as radiosensitizers |
EP4308118A1 (en) | 2021-03-17 | 2024-01-24 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods and compositions for treating melanoma |
JP2024511373A (ja) | 2021-03-18 | 2024-03-13 | ノバルティス アーゲー | がんのためのバイオマーカーおよびその使用 |
JP2024511106A (ja) | 2021-03-23 | 2024-03-12 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | Pd-1阻害剤を投与することにより免疫抑制または免疫不全患者におけるがんを処置する方法 |
AU2022245322A1 (en) | 2021-03-25 | 2023-10-05 | Oncxerna Therapeutics, Inc. | Targeted therapies in cancer |
CN117858719A (zh) | 2021-03-29 | 2024-04-09 | 朱诺治疗学股份有限公司 | 使用检查点抑制剂疗法和car t细胞疗法的组合进行给药和治疗的方法 |
WO2022208353A1 (en) | 2021-03-31 | 2022-10-06 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins and combinations thereof |
TW202304979A (zh) | 2021-04-07 | 2023-02-01 | 瑞士商諾華公司 | 抗TGFβ抗體及其他治療劑用於治療增殖性疾病之用途 |
AU2022254104A1 (en) | 2021-04-08 | 2023-10-26 | Nurix Therapeutics, Inc. | Combination therapies with cbl-b inhibitor compounds |
TW202309022A (zh) | 2021-04-13 | 2023-03-01 | 美商努法倫特公司 | 用於治療具egfr突變之癌症之胺基取代雜環 |
WO2022223791A1 (en) | 2021-04-23 | 2022-10-27 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cell senescence accumulation related disease |
WO2022227015A1 (en) | 2021-04-30 | 2022-11-03 | Merck Sharp & Dohme Corp. | Il4i1 inhibitors and methods of use |
EP4334348A1 (en) | 2021-05-07 | 2024-03-13 | Surface Oncology, LLC | Anti-il-27 antibodies and uses thereof |
WO2022238386A1 (en) | 2021-05-10 | 2022-11-17 | Institut Curie | Methods for the treatment of cancer, inflammatory diseases and autoimmune diseases |
AR125874A1 (es) | 2021-05-18 | 2023-08-23 | Novartis Ag | Terapias de combinación |
WO2022251853A1 (en) | 2021-05-25 | 2022-12-01 | Edelweiss Immune Inc | C-x-c motif chemokine receptor 6 (cxcr6) binding molecules, and methods of using the same |
WO2022251359A1 (en) | 2021-05-26 | 2022-12-01 | Theravance Biopharma R&D Ip, Llc | Bicyclic inhibitors of alk5 and methods of use |
TW202313117A (zh) | 2021-06-03 | 2023-04-01 | 美商欣爍克斯公司 | 包含il-2接合物及西妥昔單抗(cetuximab)之頭頸癌組合療法 |
GB202107994D0 (en) | 2021-06-04 | 2021-07-21 | Kymab Ltd | Treatment of cancer |
WO2022261018A1 (en) | 2021-06-07 | 2022-12-15 | Providence Health & Services - Oregon | Cxcr5, pd-1, and icos expressing tumor reactive cd4 t cells and their use |
KR20240043747A (ko) | 2021-07-02 | 2024-04-03 | 예일 유니버시티 | 암을 치료하기 위한 조성물 및 방법 |
US20230139492A1 (en) | 2021-07-19 | 2023-05-04 | Regeneron Pharmaceuticals, Inc. | Combination of checkpoint inhibitors and an oncolytic virus for treating cancer |
WO2023010080A1 (en) | 2021-07-30 | 2023-02-02 | Seagen Inc. | Treatment for cancer |
WO2023012147A1 (en) | 2021-08-03 | 2023-02-09 | F. Hoffmann-La Roche Ag | Bispecific antibodies and methods of use |
CA3227880A1 (en) | 2021-08-05 | 2023-02-09 | Marios SOTIROPOULOS | Scanning dynamic device for minibeams production |
CA3229448A1 (en) | 2021-08-23 | 2023-03-02 | Immunitas Therapeutics, Inc. | Anti-cd161 antibodies and uses thereof |
WO2023026881A1 (ja) | 2021-08-25 | 2023-03-02 | 東亞合成株式会社 | 抗pd-1シグナルペプチド抗体とその利用 |
AU2022340804A1 (en) | 2021-08-31 | 2024-03-21 | Gennao Bio, Inc. | Compositions and methods for treating cancers |
WO2023041744A1 (en) | 2021-09-17 | 2023-03-23 | Institut Curie | Bet inhibitors for treating pab1 deficient cancer |
WO2023057882A1 (en) | 2021-10-05 | 2023-04-13 | Pfizer Inc. | Combinations of azalactam compounds with a pd-1 axis binding antagonist for the treatment of cancer |
CA3233512A1 (en) | 2021-10-06 | 2023-04-13 | Alexander Muik | Multispecific binding agents against pd-l1 and cd137 in combination with anti pd-1 antibodies for treating cancers |
CA3234647A1 (en) | 2021-10-06 | 2023-04-13 | Genmab A/S | Multispecific binding agents against pd-l1 and cd137 in combination therapy |
WO2023078900A1 (en) | 2021-11-03 | 2023-05-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating triple negative breast cancer (tnbc) |
WO2023079428A1 (en) | 2021-11-03 | 2023-05-11 | Pfizer Inc. | Combination therapies using tlr7/8 agonist |
WO2023089032A1 (en) | 2021-11-19 | 2023-05-25 | Institut Curie | Methods for the treatment of hrd cancer and brca-associated cancer |
WO2023099763A1 (en) | 2021-12-03 | 2023-06-08 | Institut Curie | Sirt6 inhibitors for use in treating resistant hrd cancer |
WO2023111203A1 (en) | 2021-12-16 | 2023-06-22 | Onxeo | New conjugated nucleic acid molecules and their uses |
WO2023122573A1 (en) | 2021-12-20 | 2023-06-29 | Synthorx, Inc. | Head and neck cancer combination therapy comprising an il-2 conjugate and pembrolizumab |
WO2023118165A1 (en) | 2021-12-21 | 2023-06-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating melanoma |
WO2023147488A1 (en) | 2022-01-28 | 2023-08-03 | Iovance Biotherapeutics, Inc. | Cytokine associated tumor infiltrating lymphocytes compositions and methods |
WO2023159102A1 (en) | 2022-02-17 | 2023-08-24 | Regeneron Pharmaceuticals, Inc. | Combinations of checkpoint inhibitors and oncolytic virus for treating cancer |
WO2023174210A1 (en) | 2022-03-14 | 2023-09-21 | Laekna Limited | Combination treatment for cancer |
WO2023180552A1 (en) | 2022-03-24 | 2023-09-28 | Institut Curie | Immunotherapy targeting tumor transposable element derived neoantigenic peptides in glioblastoma |
WO2023187024A1 (en) | 2022-03-31 | 2023-10-05 | Institut Curie | Modified rela protein for inducing interferon expression and engineered immune cells with improved interferon expression |
WO2023194607A1 (en) | 2022-04-07 | 2023-10-12 | Institut Curie | Myeloid cells modified by chimeric antigen receptor with cd40 and uses thereof for anti-cancer therapy |
WO2023194608A1 (en) | 2022-04-07 | 2023-10-12 | Institut Curie | Myeloid cells modified by chimeric antigen receptor and uses thereof for anti-cancer therapy |
WO2023213764A1 (en) | 2022-05-02 | 2023-11-09 | Transgene | Fusion polypeptide comprising an anti-pd-l1 sdab and a member of the tnfsf |
WO2023213763A1 (en) | 2022-05-02 | 2023-11-09 | Transgene | Poxvirus encoding a binding agent comprising an anti- pd-l1 sdab |
WO2023214325A1 (en) | 2022-05-05 | 2023-11-09 | Novartis Ag | Pyrazolopyrimidine derivatives and uses thereof as tet2 inhibitors |
WO2023230554A1 (en) | 2022-05-25 | 2023-11-30 | Pfizer Inc. | Combination of a braf inhibitor, an egfr inhibitor, and a pd-1 antagonist for the treatment of braf v600e-mutant, msi-h/dmmr colorectal cancer |
WO2023230541A1 (en) | 2022-05-27 | 2023-11-30 | Viiv Healthcare Company | Piperazine derivatives useful in hiv therapy |
WO2024003353A1 (en) | 2022-07-01 | 2024-01-04 | Transgene | Fusion protein comprising a surfactant-protein-d and a member of the tnfsf |
WO2024033399A1 (en) | 2022-08-10 | 2024-02-15 | Institut National de la Santé et de la Recherche Médicale | Sigmar1 ligand for the treatment of pancreatic cancer |
WO2024033400A1 (en) | 2022-08-10 | 2024-02-15 | Institut National de la Santé et de la Recherche Médicale | Sk2 inhibitor for the treatment of pancreatic cancer |
WO2024040264A1 (en) | 2022-08-19 | 2024-02-22 | Massachusetts Institute Of Technology | Compositions and methods for targeting dendritic cell lectins |
WO2024056716A1 (en) | 2022-09-14 | 2024-03-21 | Institut National de la Santé et de la Recherche Médicale | Methods and pharmaceutical compositions for the treatment of dilated cardiomyopathy |
WO2024068617A1 (en) | 2022-09-26 | 2024-04-04 | Institut Curie | Myeloid cells expressing il-2 and uses thereof for quick anticancer therapy |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001014557A1 (en) * | 1999-08-23 | 2001-03-01 | Dana-Farber Cancer Institute, Inc. | Pd-1, a receptor for b7-4, and uses therefor |
JP5159730B2 (ja) * | 2002-07-03 | 2013-03-13 | 小野薬品工業株式会社 | モノクローナル抗体 |
Family Cites Families (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE555319A (ja) | 1956-03-21 | 1900-01-01 | ||
US3095355A (en) | 1961-10-12 | 1963-06-25 | Revlon | Aerosol composition |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
JP3454275B2 (ja) | 1992-06-05 | 2003-10-06 | 佑 本庶 | プログラムされた細胞死に関連した新規なポリペプチドおよびそれをコードするdna |
US5260074A (en) | 1992-06-22 | 1993-11-09 | Digestive Care Inc. | Compositions of digestive enzymes and salts of bile acids and process for preparation thereof |
EP0749475A4 (en) * | 1992-08-26 | 1997-05-07 | Harvard College | USE OF THE CYTOKIN IP-10 AS AN ANTI-TUMOR AGENCY |
IL108501A (en) | 1994-01-31 | 1998-10-30 | Mor Research Applic Ltd | Antibodies and pharmaceutical compositions containing them |
JPH07291996A (ja) | 1994-03-01 | 1995-11-07 | Yuu Honshiyo | ヒトにおけるプログラムされた細胞死に関連したポリペプチド、それをコードするdna、そのdnaからなるベクター、そのベクターで形質転換された宿主細胞、そのポリペプチドの抗体、およびそのポリペプチドまたはその抗体を含有する薬学的組成物 |
DE4431401A1 (de) * | 1994-08-24 | 1996-02-29 | Max Delbrueck Centrum | Lebendvakzine gegen Tumorerkrankungen |
US6051227A (en) * | 1995-07-25 | 2000-04-18 | The Regents Of The University Of California, Office Of Technology Transfer | Blockade of T lymphocyte down-regulation associated with CTLA-4 signaling |
US6632976B1 (en) | 1995-08-29 | 2003-10-14 | Kirin Beer Kabushiki Kaisha | Chimeric mice that are produced by microcell mediated chromosome transfer and that retain a human antibody gene |
EP0843961B1 (en) | 1995-08-29 | 2007-01-24 | Kirin Beer Kabushiki Kaisha | Chimeric animal and method for constructing the same |
EP2311490A3 (en) * | 1998-07-13 | 2011-05-04 | Board of Regents, The University of Texas System | Uses of antibodies to aminophospholipids for cancer treatment |
DE69938871D1 (de) * | 1998-12-03 | 2008-07-17 | Univ California | Stimulierung von T-Zellen gegen Selbstantigene unter Verwendung von CTLA-4 inhibierenden Wirkstoffen |
US7041474B2 (en) | 1998-12-30 | 2006-05-09 | Millennium Pharmaceuticals, Inc. | Nucleic acid encoding human tango 509 |
EP1053751A1 (en) * | 1999-05-17 | 2000-11-22 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Compositions and methods for treating cell proliferation disorders |
FR2794025A1 (fr) * | 1999-05-25 | 2000-12-01 | Transgene Sa | Composition destinee a la mise en oeuvre d'un traitement antitumoral ou antiviral chez un mammifere |
IL148021A0 (en) | 1999-08-23 | 2002-09-12 | Dana Farber Cancer Inst Inc | Novel b7-4 molecules and uses therefor |
EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
GB9927328D0 (en) * | 1999-11-18 | 2000-01-12 | Lorantis Ltd | Immunotherapy |
US6803192B1 (en) | 1999-11-30 | 2004-10-12 | Mayo Foundation For Medical Education And Research | B7-H1, a novel immunoregulatory molecule |
CA2392477A1 (en) | 1999-11-30 | 2001-06-07 | Mayo Foundation For Medical Education And Research | B7-h1, a novel immunoregulatory molecule |
JP3904374B2 (ja) * | 2000-02-29 | 2007-04-11 | 独立行政法人科学技術振興機構 | キラー活性を増強したリンパ球 |
US7030219B2 (en) | 2000-04-28 | 2006-04-18 | Johns Hopkins University | B7-DC, Dendritic cell co-stimulatory molecules |
AU7309601A (en) * | 2000-06-28 | 2002-01-08 | Genetics Inst | Pd-l2 molecules: novel pd-1 ligands and uses therefor |
EP1368061B1 (en) * | 2000-10-20 | 2008-12-24 | Tsuneya Ohno | Fusion cells and cytokine compositions for treatment of disease |
US7132109B1 (en) * | 2000-10-20 | 2006-11-07 | University Of Connecticut Health Center | Using heat shock proteins to increase immune response |
JP2002194491A (ja) | 2000-12-27 | 2002-07-10 | Daido Steel Co Ltd | ばね用鋼材 |
CA2442066C (en) | 2001-04-02 | 2005-11-01 | Wyeth | Pd-1, a receptor for b7-4, and uses therefor |
AR036993A1 (es) * | 2001-04-02 | 2004-10-20 | Wyeth Corp | Uso de agentes que modulan la interaccion entre pd-1 y sus ligandos en la submodulacion de respuestas inmunologicas |
US7794710B2 (en) * | 2001-04-20 | 2010-09-14 | Mayo Foundation For Medical Education And Research | Methods of enhancing T cell responsiveness |
JP2003029846A (ja) | 2001-07-11 | 2003-01-31 | Sanyo Electric Co Ltd | 流量調整器および流量調整器を備えた飲料供給装置 |
WO2003006636A1 (de) | 2001-07-12 | 2003-01-23 | Genethor Gmbh | Reduktion der stimulationsfähigkeit von antigen präsentierenden zellen |
US20040241745A1 (en) | 2001-07-31 | 2004-12-02 | Tasuku Honjo | Substance specific to pd-1 |
IL145926A0 (en) | 2001-10-15 | 2002-07-25 | Mor Research Applic Ltd | Peptide epitopes of mimotopes useful in immunomodulation |
EP1456652A4 (en) | 2001-11-13 | 2005-11-02 | Dana Farber Cancer Inst Inc | IMMUNOCELL ACTIVATION MODULATING SUBSTANCES AND USE METHOD THEREFOR |
IL149820A0 (en) | 2002-05-23 | 2002-11-10 | Curetech Ltd | Humanized immunomodulatory monoclonal antibodies for the treatment of neoplastic disease or immunodeficiency |
WO2004000221A2 (en) | 2002-06-20 | 2003-12-31 | The Regents Of The University Of California | Compositions and methods for modulating lymphocyte activity |
CN1753912B (zh) * | 2002-12-23 | 2011-11-02 | 惠氏公司 | 抗pd-1抗体及其用途 |
JP4532409B2 (ja) | 2003-01-23 | 2010-08-25 | 小野薬品工業株式会社 | ヒトpd−1に対し特異性を有する物質 |
US7465446B2 (en) | 2003-05-30 | 2008-12-16 | Medarex, Inc. | Surrogate therapeutic endpoint for anti-CTLA4-based immunotherapy of disease |
EP1591627A1 (de) | 2004-04-27 | 2005-11-02 | Siemens Aktiengesellschaft | Regeleinrichtung für einen Kompressor sowie Verwendung eines Bragg-Gitter-Sensors bei einer Regeleinrichtung |
WO2006021955A2 (en) | 2004-08-23 | 2006-03-02 | Mor Research Applications Ltd. | Use of bat monoclonal antibody for immunotherapy |
US7423128B2 (en) | 2004-11-03 | 2008-09-09 | Amgen Fremont Inc. | Anti-properdin antibodies, and methods for making and using same |
CN109485727A (zh) | 2005-05-09 | 2019-03-19 | 小野药品工业株式会社 | 程序性死亡-1(pd-1)的人单克隆抗体及使用抗pd-1抗体来治疗癌症的方法 |
WO2006124269A2 (en) | 2005-05-16 | 2006-11-23 | Amgen Fremont Inc. | Human monoclonal antibodies that bind to very late antigen-1 for the treatment of inflammation and other disorders |
DK1907424T3 (en) | 2005-07-01 | 2015-11-09 | Squibb & Sons Llc | HUMAN MONOCLONAL ANTIBODIES TO PROGRAMMED death ligand 1 (PD-L1) |
WO2013173223A1 (en) | 2012-05-15 | 2013-11-21 | Bristol-Myers Squibb Company | Cancer immunotherapy by disrupting pd-1/pd-l1 signaling |
-
2003
- 2003-07-02 JP JP2004519238A patent/JP4409430B2/ja not_active Expired - Lifetime
- 2003-07-02 FI FIEP10161767.8T patent/FI2206517T3/fi active
- 2003-07-02 DK DK03741154.3T patent/DK1537878T3/da active
- 2003-07-02 PT PT03741154T patent/PT1537878E/pt unknown
- 2003-07-02 EP EP10161767.8A patent/EP2206517B1/en not_active Expired - Lifetime
- 2003-07-02 DE DE60334303T patent/DE60334303D1/de not_active Expired - Lifetime
- 2003-07-02 DK DK10161767.8T patent/DK2206517T3/da active
- 2003-07-02 ES ES10161767T patent/ES2654064T3/es not_active Expired - Lifetime
- 2003-07-02 AU AU2003281200A patent/AU2003281200A1/en not_active Abandoned
- 2003-07-02 DE DE10161767.8T patent/DE10161767T1/de active Pending
- 2003-07-02 WO PCT/JP2003/008420 patent/WO2004004771A1/ja active Search and Examination
- 2003-07-02 AT AT03741154T patent/ATE481985T1/de active
- 2003-07-02 EP EP20100172772 patent/EP2243493A1/en not_active Withdrawn
- 2003-07-02 US US10/519,925 patent/US7595048B2/en active Active
- 2003-07-02 EP EP03741154A patent/EP1537878B1/en not_active Expired - Lifetime
- 2003-07-02 PT PT101617678T patent/PT2206517T/pt unknown
- 2003-07-02 EP EP17196173.3A patent/EP3287144A1/en active Pending
- 2003-07-02 HU HUE10161767A patent/HUE10161767T1/hu unknown
- 2003-07-02 ES ES03741154T patent/ES2350687T3/es not_active Expired - Lifetime
- 2003-07-02 SI SI200332625T patent/SI2206517T1/sl unknown
-
2009
- 2009-08-10 US US12/538,698 patent/US8168179B2/en active Active
- 2009-09-03 JP JP2009203514A patent/JP5159730B2/ja not_active Expired - Lifetime
-
2010
- 2010-12-02 US US12/959,307 patent/US8728474B2/en active Active
-
2012
- 2012-09-07 JP JP2012197861A patent/JP5701266B2/ja not_active Expired - Lifetime
-
2014
- 2014-01-20 JP JP2014007941A patent/JP5885764B2/ja not_active Expired - Lifetime
- 2014-04-04 US US14/245,692 patent/US9402899B2/en not_active Expired - Lifetime
- 2014-11-21 US US14/550,585 patent/US9073994B2/en not_active Expired - Lifetime
-
2015
- 2015-03-04 US US14/638,985 patent/US9067999B1/en not_active Expired - Lifetime
- 2015-05-08 JP JP2015095990A patent/JP6035372B2/ja not_active Expired - Lifetime
- 2015-12-10 LU LU92905C patent/LU92905I2/xx unknown
- 2015-12-15 HU HUS1500066C patent/HUS1500066I1/hu unknown
- 2015-12-15 FR FR15C0088C patent/FR15C0088I1/fr active Active
-
2016
- 2016-01-06 LU LU92940C patent/LU92940I2/xx unknown
- 2016-01-06 FR FR16C0001C patent/FR16C0001I1/fr active Active
- 2016-01-07 HU HUS1600004C patent/HUS1600004I1/hu unknown
- 2016-01-19 US US15/000,863 patent/US9393301B2/en not_active Expired - Lifetime
- 2016-01-19 US US15/000,869 patent/US9439962B2/en not_active Expired - Lifetime
- 2016-08-02 US US15/226,848 patent/US20170051060A1/en not_active Abandoned
- 2016-09-21 JP JP2016184782A patent/JP6258428B2/ja not_active Expired - Lifetime
-
2017
- 2017-11-14 JP JP2017219349A patent/JP6559207B2/ja not_active Expired - Lifetime
-
2019
- 2019-02-04 JP JP2019018057A patent/JP2019094340A/ja active Pending
- 2019-07-01 US US16/459,392 patent/US20200062846A1/en not_active Abandoned
-
2021
- 2021-03-08 JP JP2021036417A patent/JP2021080301A/ja active Pending
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001014557A1 (en) * | 1999-08-23 | 2001-03-01 | Dana-Farber Cancer Institute, Inc. | Pd-1, a receptor for b7-4, and uses therefor |
JP5159730B2 (ja) * | 2002-07-03 | 2013-03-13 | 小野薬品工業株式会社 | モノクローナル抗体 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6559207B2 (ja) | 癌治療剤 | |
KR102235202B1 (ko) | T 세포 수용체 베타 불변 영역에 대한 항원 결합 도메인을 갖는 키메라 항원 수용체(car) | |
US7148329B1 (en) | Composition and method for modulating dendritic cell-t cell interaction | |
JP2023090710A (ja) | B7-h3に対するモノクローナル抗体および細胞治療におけるその使用 | |
US20190284262A1 (en) | T cell receptor-like antibodies specific for foxp3-derived peptides | |
WO2022089557A1 (zh) | Itpripl1的调节剂在制备调节免疫反应或抗肿瘤的药物中的用途 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20150605 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150625 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160524 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160628 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160921 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20161025 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20161031 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6035372 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
EXPY | Cancellation because of completion of term |