CL2015001124A1 - Combinacion de anticuerpo anti-cd20 e inhibidor selectivo de kinasa p13 - Google Patents

Combinacion de anticuerpo anti-cd20 e inhibidor selectivo de kinasa p13

Info

Publication number
CL2015001124A1
CL2015001124A1 CL2015001124A CL2015001124A CL2015001124A1 CL 2015001124 A1 CL2015001124 A1 CL 2015001124A1 CL 2015001124 A CL2015001124 A CL 2015001124A CL 2015001124 A CL2015001124 A CL 2015001124A CL 2015001124 A1 CL2015001124 A1 CL 2015001124A1
Authority
CL
Chile
Prior art keywords
antibody
selective
combination
kinase inhibitor
phosfoinositide
Prior art date
Application number
CL2015001124A
Other languages
English (en)
Spanish (es)
Inventor
Michael Weiss
Hari Miskin
Peter Sportelli
Swaroop K V S Vakkalanka
Original Assignee
Tg Therapeutics Inc
Rhizen Pharmaceuticals Sa
Lab Francais Du Fractionnement
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=54264181&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=CL2015001124(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Tg Therapeutics Inc, Rhizen Pharmaceuticals Sa, Lab Francais Du Fractionnement filed Critical Tg Therapeutics Inc
Publication of CL2015001124A1 publication Critical patent/CL2015001124A1/es

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/395Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/02Nasal agents, e.g. decongestants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00Drugs for skeletal disorders
    • A61P19/02Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K16/00Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2887Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/20Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2317/00Immunoglobulins specific features
    • C07K2317/70Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Endocrinology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Otolaryngology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CL2015001124A 2012-11-02 2015-04-29 Combinacion de anticuerpo anti-cd20 e inhibidor selectivo de kinasa p13 CL2015001124A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN4595CH2012 2012-11-02
US201361771812P 2013-03-02 2013-03-02

Publications (1)

Publication Number Publication Date
CL2015001124A1 true CL2015001124A1 (es) 2016-01-08

Family

ID=54264181

Family Applications (1)

Application Number Title Priority Date Filing Date
CL2015001124A CL2015001124A1 (es) 2012-11-02 2015-04-29 Combinacion de anticuerpo anti-cd20 e inhibidor selectivo de kinasa p13

Country Status (22)

Country Link
US (3) US9694071B2 (https=)
EP (3) EP3756686A1 (https=)
JP (1) JP6437441B2 (https=)
KR (2) KR102185175B1 (https=)
CN (2) CN105073197B (https=)
AU (3) AU2013337733B2 (https=)
BR (1) BR112015009879A8 (https=)
CA (1) CA2890176C (https=)
CL (1) CL2015001124A1 (https=)
CY (1) CY1123938T1 (https=)
DK (1) DK3150256T3 (https=)
EA (1) EA030745B1 (https=)
IL (1) IL238564B (https=)
LT (1) LT3150256T (https=)
MX (2) MX375325B (https=)
NZ (1) NZ708249A (https=)
PL (1) PL3150256T3 (https=)
RS (1) RS60844B1 (https=)
SG (2) SG11201503393SA (https=)
SI (1) SI3150256T1 (https=)
SM (1) SMT202000543T1 (https=)
WO (1) WO2014071125A1 (https=)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3613743B1 (en) 2008-01-04 2022-03-16 Intellikine, LLC Processes for the preparation of 1h-pyrazolo[3,4-d]pyrimidin-4-amine derivatives
US8193182B2 (en) 2008-01-04 2012-06-05 Intellikine, Inc. Substituted isoquinolin-1(2H)-ones, and methods of use thereof
TWI674262B (zh) 2011-01-10 2019-10-11 美商英菲尼提製藥股份有限公司 製備異喹啉酮之方法及異喹啉酮之固體形式
US8828998B2 (en) 2012-06-25 2014-09-09 Infinity Pharmaceuticals, Inc. Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors
EP2914296B2 (en) 2012-11-01 2021-09-29 Infinity Pharmaceuticals, Inc. Treatment of cancers using pi3 kinase isoform modulators
US20150320754A1 (en) 2014-04-16 2015-11-12 Infinity Pharmaceuticals, Inc. Combination therapies
WO2015160975A2 (en) 2014-04-16 2015-10-22 Infinity Pharmaceuticals, Inc. Combination therapies
WO2016004221A1 (en) * 2014-07-01 2016-01-07 Mayo Foundation For Medical Education And Research Methods and materials for identifying and treating mammals resistant to proteasome inhibitor treatments
KR102499191B1 (ko) 2016-03-18 2023-02-13 프레드 허친슨 캔서 센터 Cd20 면역요법을 위한 조성물 및 방법
AU2017268839A1 (en) 2016-05-27 2018-11-29 Laboratoire Francais Du Fractionnement Et Des Biotechnologies Combination of anti-CD20 antibody, P13 kinase-delta selective inhibitor, and BTK inhibitor to treat B-cell proliferative disorders
RU2754507C2 (ru) 2016-06-24 2021-09-02 Инфинити Фармасьютикалз, Инк. Комбинированная терапия
CN110191720A (zh) * 2016-09-09 2019-08-30 Tg治疗有限公司 用于治疗血液学癌症的抗-CD20抗体、PI 3激酶-δ抑制剂以及抗-PD-1或抗-PD-L1抗体的组合
US10610104B2 (en) 2016-12-07 2020-04-07 Progenity, Inc. Gastrointestinal tract detection methods, devices and systems
US20210138213A1 (en) 2017-03-30 2021-05-13 Progenity, Inc. Treatment of a disease of the gastrointestinal tract with an immune modulatory agent released using an ingestible device
KR20200041358A (ko) * 2017-08-14 2020-04-21 메이 파마, 아이엔씨. 병용 요법
WO2019246312A1 (en) 2018-06-20 2019-12-26 Progenity, Inc. Treatment of a disease of the gastrointestinal tract with an immunomodulator
US12227565B2 (en) 2018-06-20 2025-02-18 Biora Therapeutics, Inc. Method of formulating a pharmaceutical composition comprising administering an immune modulator to the small intestine
US20220249814A1 (en) 2018-11-19 2022-08-11 Progenity, Inc. Methods and devices for treating a disease with biotherapeutics
CN121197633A (zh) 2019-12-13 2025-12-26 比特比德科有限责任公司 用于将治疗剂递送至胃肠道的可摄取装置
WO2021164789A1 (zh) * 2020-02-21 2021-08-26 南京明德新药研发有限公司 一种吡唑并嘧啶类化合物的晶型及其应用
CN114891005B (zh) * 2022-03-30 2024-01-19 武汉九州钰民医药科技有限公司 一种乌帕利斯对甲苯磺酸盐的制备工艺
CN119654341A (zh) * 2022-06-01 2025-03-18 Tg疗法有限公司 抗cd20抗体组合物
US11965032B1 (en) 2022-06-01 2024-04-23 Tg Therapeutics, Inc. Anti-CD20 antibody compositions
US11807689B1 (en) * 2022-06-01 2023-11-07 Tg Therapeutics, Inc. Anti-CD20 antibody compositions
US11884740B1 (en) 2022-06-01 2024-01-30 Tg Therapeutics, Inc. Anti-CD20 antibody compositions
US11814439B1 (en) 2022-06-01 2023-11-14 Tg Therapeutics, Inc. Anti-CD20 antibody compositions
KR20250125901A (ko) * 2024-02-13 2025-08-22 연세대학교 산학협력단 항-CD20 항체 및 PIKfyve의 억제제를 유효성분으로 포함하는 림프종의 예방 또는 치료용 조성물

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5225539A (en) 1986-03-27 1993-07-06 Medical Research Council Recombinant altered antibodies and methods of making altered antibodies
US5530101A (en) 1988-12-28 1996-06-25 Protein Design Labs, Inc. Humanized immunoglobulins
US5639641A (en) 1992-09-09 1997-06-17 Immunogen Inc. Resurfacing of rodent antibodies
US5736137A (en) 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
WO1999004705A1 (en) 1997-07-25 1999-02-04 Tsui Ban C H Devices, systems and methods for determining proper placement of epidural catheters
FR2807767B1 (fr) 2000-04-12 2005-01-14 Lab Francais Du Fractionnement Anticorps monoclonaux anti-d
FR2844455B1 (fr) 2002-09-13 2007-12-14 Lab Francais Du Fractionnement Traitement des pathologies echappant a la reponse immune par des anticorps optimises
EP3263596A1 (en) 2002-12-16 2018-01-03 Genentech, Inc. Immunoglobulin variants and uses thereof
FR2858235B1 (fr) 2003-07-31 2006-02-17 Lab Francais Du Fractionnement Utilisation d'anticorps optimises en adcc pour traiter les patients faibles repondeurs
FR2879204B1 (fr) * 2004-12-15 2007-02-16 Lab Francais Du Fractionnement Anticorps cytotoxique dirige contre les proliferations hematopoietiques lymphoides de type b.
JPWO2007102200A1 (ja) * 2006-03-07 2009-07-23 国立大学法人大阪大学 抗cd20モノクローナル抗体
AR064106A1 (es) * 2006-12-05 2009-03-11 Bayer Schering Pharma Ag Derivados de 2,3-dihidroimidazo [1,2-c] quinazolina sustituida utiles para el tratamiento de enfermedades y trastornos hiper-proliferativos asociados con la angiogenesis
FR2915398B1 (fr) * 2007-04-25 2012-12-28 Lab Francais Du Fractionnement "ensemble de moyens pour le traitement d'une pathologie maligne, d'une maladie auto-immune ou d'une maladie infectieuse"
US20110280913A1 (en) * 2008-07-31 2011-11-17 The Ohio State University Methods and Compositions for Delivering Therapeutic Agents in the Treatment of B-Cell Related Disorders
FR2939314A1 (fr) * 2008-12-04 2010-06-11 Univ Victor Segalen Bordeaux 2 Nouvelles compositions et methodes pour la potentialisation des signaux d'apoptose dans les cellules tumorales
CN102369011A (zh) * 2009-03-12 2012-03-07 健泰科生物技术公司 用于治疗造血恶性肿瘤的磷酸肌醇3-激酶抑制剂化合物与化学治疗剂的组合
PH12012500901A1 (en) 2009-11-05 2016-08-05 Rhizen Pharmaceuticals Sa Novel benzopyran kinase modulators
CN109970742A (zh) * 2012-07-04 2019-07-05 理森制药股份公司 选择性PI3Kδ抑制剂

Also Published As

Publication number Publication date
BR112015009879A2 (https=) 2014-05-08
RS60844B1 (sr) 2020-10-30
JP2016505515A (ja) 2016-02-25
AU2018203579A1 (en) 2018-06-14
SMT202000543T1 (it) 2020-11-10
CY1123938T1 (el) 2022-03-24
US20200323981A1 (en) 2020-10-15
DK3150256T3 (da) 2020-08-24
EP2914343A1 (en) 2015-09-09
KR20200136498A (ko) 2020-12-07
AU2020203417A1 (en) 2020-06-11
CN105073197A (zh) 2015-11-18
EP3756686A1 (en) 2020-12-30
SG11201503393SA (en) 2015-06-29
CA2890176C (en) 2021-12-14
KR102185175B1 (ko) 2020-12-02
WO2014071125A1 (en) 2014-05-08
US9694071B2 (en) 2017-07-04
CN110269941A (zh) 2019-09-24
EP3150256A1 (en) 2017-04-05
EA030745B1 (ru) 2018-09-28
AU2013337733A1 (en) 2015-06-04
SI3150256T1 (sl) 2021-03-31
BR112015009879A8 (pt) 2019-09-17
SG10201704511RA (en) 2017-07-28
EP3150256B1 (en) 2020-07-15
US20150290317A1 (en) 2015-10-15
KR102341275B1 (ko) 2021-12-21
JP6437441B2 (ja) 2018-12-12
US20170304441A1 (en) 2017-10-26
IL238564A0 (en) 2015-06-30
AU2013337733B2 (en) 2018-03-08
KR20150084885A (ko) 2015-07-22
MX2015005555A (es) 2015-11-30
MX2020009919A (es) 2020-10-14
US10729768B2 (en) 2020-08-04
IL238564B (en) 2020-11-30
EP2914343B1 (en) 2019-03-06
LT3150256T (lt) 2020-11-10
MX375325B (es) 2025-03-06
EA201590866A1 (ru) 2015-12-30
AU2018203579B2 (en) 2020-02-27
CA2890176A1 (en) 2014-05-08
NZ708249A (en) 2019-03-29
PL3150256T3 (pl) 2021-02-08
CN105073197B (zh) 2019-06-28

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