MX2019006432A - Conjugados que comprenden un agonista dual de glp-1/glucagon, un enlazador y acido hialuronico. - Google Patents
Conjugados que comprenden un agonista dual de glp-1/glucagon, un enlazador y acido hialuronico.Info
- Publication number
- MX2019006432A MX2019006432A MX2019006432A MX2019006432A MX2019006432A MX 2019006432 A MX2019006432 A MX 2019006432A MX 2019006432 A MX2019006432 A MX 2019006432A MX 2019006432 A MX2019006432 A MX 2019006432A MX 2019006432 A MX2019006432 A MX 2019006432A
- Authority
- MX
- Mexico
- Prior art keywords
- glp
- linker
- receptor agonist
- conjugates
- glucagon receptor
- Prior art date
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- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
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- 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
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- 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
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- 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
- A61K38/22—Hormones
- A61K38/26—Glucagons
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6903—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel
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- 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
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- 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
- A61K9/10—Dispersions; Emulsions
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
- C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
- C07K1/113—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides without change of the primary structure
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- 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
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- 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
- C07K14/575—Hormones
- C07K14/605—Glucagons
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Dermatology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Marine Sciences & Fisheries (AREA)
- Toxicology (AREA)
- Inorganic Chemistry (AREA)
- Analytical Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
La presente invención se refiere a un conjugado, o una de sus sales farmacéuticamente aceptables, que comprende un agonista del receptor de GLP-1/glucagón, un enlazador y un hidrogel de ácido hialurónico que porta grupos -L1-L2-L-Y-R20, en donde Y representa una porción agonista del receptor de GLP-1/glucagón; y -L es una porción enlazadora de fórmula (la), (ver Fórmula) en donde la línea discontinua indica la unión a uno de los grupos amino del agonista del receptor de GLP-1/glucagón a través de la formación de un enlace amida. La invención se refiere además a composiciones farmacéuticas que comprenden dicho conjugado, así como a su uso como medicamente para tratar o prevenir enfermedades o trastornos que pueden ser tratados mediante un agonista del receptor de GLP-1/glucagón.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP16306613 | 2016-12-02 | ||
PCT/EP2017/081217 WO2018100174A1 (en) | 2016-12-02 | 2017-12-01 | Conjugates comprising an glp-1/glucagon dual agonist, a linker and hyaluronic acid |
Publications (1)
Publication Number | Publication Date |
---|---|
MX2019006432A true MX2019006432A (es) | 2019-08-21 |
Family
ID=57542941
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
MX2019006432A MX2019006432A (es) | 2016-12-02 | 2017-12-01 | Conjugados que comprenden un agonista dual de glp-1/glucagon, un enlazador y acido hialuronico. |
Country Status (23)
Country | Link |
---|---|
US (2) | US10792367B2 (es) |
EP (1) | EP3548090A1 (es) |
JP (1) | JP2020503278A (es) |
KR (1) | KR20190091482A (es) |
CN (1) | CN110022902A (es) |
AR (1) | AR110299A1 (es) |
AU (1) | AU2017369723A1 (es) |
BR (1) | BR112019011139A8 (es) |
CA (1) | CA3045483A1 (es) |
CL (1) | CL2019001466A1 (es) |
CO (1) | CO2019006912A2 (es) |
CR (1) | CR20190312A (es) |
DO (1) | DOP2019000038A (es) |
EA (1) | EA201991316A1 (es) |
EC (1) | ECSP19046865A (es) |
IL (1) | IL266973A (es) |
MA (1) | MA46996A (es) |
MX (1) | MX2019006432A (es) |
PE (1) | PE20191472A1 (es) |
PH (1) | PH12019501215A1 (es) |
TW (1) | TW201832783A (es) |
UY (1) | UY37505A (es) |
WO (1) | WO2018100174A1 (es) |
Families Citing this family (13)
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AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
US20200276276A1 (en) | 2016-03-01 | 2020-09-03 | Ascendis Pharma Bone Diseases A/S | PTH Prodrugs |
FI3518960T3 (fi) | 2016-09-29 | 2023-10-04 | Ascendis Pharma Bone Diseases As | Annostusohjelma kontrolloidusti vapautuvalle PTH-yhdisteelle |
MX2019003182A (es) | 2016-09-29 | 2019-08-05 | Ascendis Pharma Bone Diseases As | Compuestos de hormona paratiroidea con bajas relaciones pico - valle. |
AR110299A1 (es) | 2016-12-02 | 2019-03-13 | Sanofi Sa | Conjugados que comprenden un agonista dual de glp-1 / glucagón, un conector y ácido hialurónico |
CA3055985A1 (en) | 2017-03-22 | 2018-09-27 | Genentech, Inc. | Hydrogel cross-linked hyaluronic acid prodrug compositions and methods |
US11352405B2 (en) | 2017-08-09 | 2022-06-07 | Sanofi | GLP-1/glucagon receptor agonists in the treatment of fatty liver disease and steatohepatitis |
TW202015735A (zh) | 2018-05-30 | 2020-05-01 | 法商賽諾菲公司 | 包含glp-1/升糖素/gip三重受體促效劑、連接子及透明質酸之接合物 |
FR3084586B1 (fr) * | 2018-08-03 | 2020-11-06 | Adocia | Compositions sous forme d'une solution aqueuse injectable comprenant de l'amyline, un agoniste au recepteur de l'amyline ou un analogue d'amyline et un compose amphiphile porteur de radicaux hydrophobes |
US11813312B2 (en) | 2020-04-24 | 2023-11-14 | Boehringer Ingelheim International Gmbh | Glucagon analogues as long-acting GLP-1/glucagon receptor agonists in the treatment of fatty liver disease and steatohepatitis |
KR102225971B1 (ko) * | 2020-05-19 | 2021-03-10 | 주식회사 차메디텍 | 펩타이드 가교제를 이용한 히알루론산 기반의 하이드로겔 및 이의 제조 방법 |
KR20240043778A (ko) | 2021-07-30 | 2024-04-03 | 베링거 인겔하임 인터내셔날 게엠베하 | 장시간-작용하는 glp1/글루카곤 수용체 작용제를 위한 용량 용법 |
CN114470170B (zh) * | 2022-02-22 | 2023-09-19 | 广州新济药业科技有限公司 | 一种司美格鲁肽可溶性微针组合物及其制备方法 |
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HUE042585T2 (hu) | 2011-06-17 | 2019-07-29 | Hanmi Science Co Ltd | Oxintomodulint és immunglobulin-fragmentumot tartalmazó konjugátum és alkalmazása |
WO2014000056A1 (en) | 2012-06-29 | 2014-01-03 | University Of South Australia | Fluid connection ports |
UA116217C2 (uk) * | 2012-10-09 | 2018-02-26 | Санофі | Пептидна сполука як подвійний агоніст рецепторів glp1-1 та глюкагону |
MA38276B1 (fr) | 2012-12-21 | 2018-03-30 | Sanofi Sa | Dérivés de l'exendine 4 pour l’utilisation dans le traitement des troubles du syndrome metabolique, y compris le diabete et l'obesite, ainsi que la reduction de l'apport alimentaire excessif. |
JP2017503474A (ja) | 2013-11-06 | 2017-02-02 | ジーランド ファーマ アクティーゼルスカブ | グルカゴン−glp−1−gipトリプルアゴニスト化合物 |
TW201609798A (zh) * | 2013-12-13 | 2016-03-16 | 賽諾菲公司 | Exendin-4胜肽類似物 |
EP3080149A1 (en) | 2013-12-13 | 2016-10-19 | Sanofi | Dual glp-1/glucagon receptor agonists |
WO2015086731A1 (en) | 2013-12-13 | 2015-06-18 | Sanofi | Exendin-4 peptide analogues as dual glp-1/glucagon receptor agonists |
TW201625669A (zh) | 2014-04-07 | 2016-07-16 | 賽諾菲公司 | 衍生自艾塞那肽-4(Exendin-4)之肽類雙重GLP-1/升糖素受體促效劑 |
US10188759B2 (en) * | 2015-01-07 | 2019-01-29 | Endocyte, Inc. | Conjugates for imaging |
AR105319A1 (es) | 2015-06-05 | 2017-09-27 | Sanofi Sa | Profármacos que comprenden un conjugado agonista dual de glp-1 / glucagón conector ácido hialurónico |
AR110299A1 (es) | 2016-12-02 | 2019-03-13 | Sanofi Sa | Conjugados que comprenden un agonista dual de glp-1 / glucagón, un conector y ácido hialurónico |
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2017
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- 2017-11-30 TW TW106141763A patent/TW201832783A/zh unknown
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- 2017-12-01 EP EP17822168.5A patent/EP3548090A1/en active Pending
- 2017-12-01 KR KR1020197018576A patent/KR20190091482A/ko active Search and Examination
- 2017-12-01 WO PCT/EP2017/081217 patent/WO2018100174A1/en unknown
- 2017-12-01 UY UY0001037505A patent/UY37505A/es not_active Application Discontinuation
- 2017-12-01 CR CR20190312A patent/CR20190312A/es unknown
- 2017-12-01 MX MX2019006432A patent/MX2019006432A/es unknown
- 2017-12-01 MA MA046996A patent/MA46996A/fr unknown
- 2017-12-01 CN CN201780074647.0A patent/CN110022902A/zh active Pending
- 2017-12-01 BR BR112019011139A patent/BR112019011139A8/pt not_active IP Right Cessation
- 2017-12-01 PE PE2019001081A patent/PE20191472A1/es unknown
- 2017-12-01 JP JP2019529643A patent/JP2020503278A/ja not_active Abandoned
- 2017-12-01 CA CA3045483A patent/CA3045483A1/en not_active Abandoned
- 2017-12-01 AU AU2017369723A patent/AU2017369723A1/en not_active Abandoned
- 2017-12-01 EA EA201991316A patent/EA201991316A1/ru unknown
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2019
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- 2019-05-31 PH PH12019501215A patent/PH12019501215A1/en unknown
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- 2019-07-01 EC ECSENADI201946865A patent/ECSP19046865A/es unknown
- 2019-10-28 US US16/665,785 patent/US11141489B2/en active Active
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US20180154005A1 (en) | 2018-06-07 |
EP3548090A1 (en) | 2019-10-09 |
JP2020503278A (ja) | 2020-01-30 |
CL2019001466A1 (es) | 2019-10-11 |
CN110022902A (zh) | 2019-07-16 |
CR20190312A (es) | 2019-09-11 |
MA46996A (fr) | 2019-10-09 |
PH12019501215A1 (en) | 2019-08-19 |
CO2019006912A2 (es) | 2020-04-24 |
TW201832783A (zh) | 2018-09-16 |
CA3045483A1 (en) | 2018-06-07 |
IL266973A (en) | 2019-07-31 |
US20200155688A1 (en) | 2020-05-21 |
DOP2019000038A (es) | 2019-05-31 |
EA201991316A1 (ru) | 2019-10-31 |
ECSP19046865A (es) | 2019-07-31 |
WO2018100174A1 (en) | 2018-06-07 |
BR112019011139A8 (pt) | 2020-03-24 |
US11141489B2 (en) | 2021-10-12 |
PE20191472A1 (es) | 2019-10-16 |
BR112019011139A2 (pt) | 2019-10-01 |
UY37505A (es) | 2018-06-29 |
AR110299A1 (es) | 2019-03-13 |
KR20190091482A (ko) | 2019-08-06 |
AU2017369723A1 (en) | 2019-07-18 |
US10792367B2 (en) | 2020-10-06 |
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