UY34419A - Profármaco de adrenomedulina basado en polietilenglicol y el uso del mismo - Google Patents

Profármaco de adrenomedulina basado en polietilenglicol y el uso del mismo

Info

Publication number
UY34419A
UY34419A UY0001034419A UY34419A UY34419A UY 34419 A UY34419 A UY 34419A UY 0001034419 A UY0001034419 A UY 0001034419A UY 34419 A UY34419 A UY 34419A UY 34419 A UY34419 A UY 34419A
Authority
UY
Uruguay
Prior art keywords
adrenomedulin
polyethylene glycol
propharm
diseases
prevention
Prior art date
Application number
UY0001034419A
Other languages
English (en)
Spanish (es)
Inventor
Wunder Dr Frank
Knorr Dr Andreas
Redlich Dr Gorden
Griebenow Dr Nils
Flamme Dr Ingo
Koebberling Dr Johannes
Lerchen Dr Hans-Georg
Schohe-Loop Dr Rudolf
Wittrock Dr Sven
Koellnberger Maria
Marley Dr July
Pritchard Dr Iain
Original Assignee
Bayer Pharma AG
Bayer Ip Gmbh
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
Application filed by Bayer Pharma AG, Bayer Ip Gmbh filed Critical Bayer Pharma AG
Priority to UY0001037922A priority Critical patent/UY37922A/es
Publication of UY34419A publication Critical patent/UY34419A/es

Links

Classifications

    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • 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
    • A61K38/23—Calcitonins
    • 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
    • A61K47/50—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
    • 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
    • A61K47/59—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 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—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 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • 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
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
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    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • 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
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/04—Antipruritics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/10—Antioedematous agents; Diuretics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pulmonology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Immunology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Otolaryngology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Toxicology (AREA)
  • Dispersion Chemistry (AREA)
  • Obesity (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Communicable Diseases (AREA)
  • Dermatology (AREA)
UY0001034419A 2011-11-03 2012-10-29 Profármaco de adrenomedulina basado en polietilenglicol y el uso del mismo UY34419A (es)

Priority Applications (1)

Application Number Priority Date Filing Date Title
UY0001037922A UY37922A (es) 2011-11-03 2012-10-29 Composiciones farmacéuticas que comprenden un profármaco deadrenomedulina basado en polietilenglicol

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP11187735 2011-11-03

Publications (1)

Publication Number Publication Date
UY34419A true UY34419A (es) 2013-05-31

Family

ID=47146369

Family Applications (2)

Application Number Title Priority Date Filing Date
UY0001034419A UY34419A (es) 2011-11-03 2012-10-29 Profármaco de adrenomedulina basado en polietilenglicol y el uso del mismo
UY0001037922A UY37922A (es) 2011-11-03 2012-10-29 Composiciones farmacéuticas que comprenden un profármaco deadrenomedulina basado en polietilenglicol

Family Applications After (1)

Application Number Title Priority Date Filing Date
UY0001037922A UY37922A (es) 2011-11-03 2012-10-29 Composiciones farmacéuticas que comprenden un profármaco deadrenomedulina basado en polietilenglicol

Country Status (45)

Country Link
US (3) US9603936B2 (forum.php)
EP (2) EP3075395B1 (forum.php)
JP (2) JP5995984B2 (forum.php)
KR (2) KR102004668B1 (forum.php)
CN (2) CN107412740B (forum.php)
AR (2) AR088582A1 (forum.php)
AU (2) AU2012331244B2 (forum.php)
BR (1) BR112014010708B1 (forum.php)
CA (1) CA2854134C (forum.php)
CL (1) CL2014000948A1 (forum.php)
CO (1) CO7020863A2 (forum.php)
CR (1) CR20140184A (forum.php)
CU (1) CU24184B1 (forum.php)
CY (2) CY1117354T1 (forum.php)
DK (2) DK2773376T3 (forum.php)
DO (2) DOP2014000078A (forum.php)
EA (2) EA025631B1 (forum.php)
EC (2) ECSP14013326A (forum.php)
ES (2) ES2659195T3 (forum.php)
GT (1) GT201400085A (forum.php)
HR (2) HRP20160285T1 (forum.php)
HU (2) HUE036535T2 (forum.php)
IL (3) IL232037B (forum.php)
IN (1) IN2014CN03290A (forum.php)
JO (2) JOP20190001B1 (forum.php)
LT (1) LT3075395T (forum.php)
MA (1) MA35618B1 (forum.php)
ME (1) ME02379B (forum.php)
MX (2) MX350341B (forum.php)
MY (2) MY173372A (forum.php)
NO (1) NO3075395T3 (forum.php)
PE (2) PE20141219A1 (forum.php)
PH (1) PH12014500998A1 (forum.php)
PL (2) PL2773376T3 (forum.php)
PT (1) PT3075395T (forum.php)
RS (2) RS54623B1 (forum.php)
SG (2) SG11201400924TA (forum.php)
SI (2) SI3075395T1 (forum.php)
TN (1) TN2014000185A1 (forum.php)
TR (1) TR201802124T4 (forum.php)
TW (2) TWI653051B (forum.php)
UA (1) UA111098C2 (forum.php)
UY (2) UY34419A (forum.php)
WO (1) WO2013064508A1 (forum.php)
ZA (1) ZA201600434B (forum.php)

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EP2896400A1 (en) * 2014-01-17 2015-07-22 Université Catholique De Louvain Method for increasing the bioavailability of inhaled compounds
WO2015141819A1 (ja) * 2014-03-20 2015-09-24 国立大学法人宮崎大学 長時間作用型アドレノメデュリン誘導体
EA201790699A1 (ru) 2014-09-26 2017-10-31 Байер Фарма Акциенгезельшафт Стабилизированные производные адреномедуллина и их применение
AU2016324119B2 (en) 2015-09-18 2019-11-14 Himuka AM Australia Pty Ltd. Long-acting adrenomedullin derivative
CN110678550B (zh) 2017-03-29 2023-11-14 国立大学法人宫崎大学 长效肾上腺髓质素衍生物
GB201707938D0 (en) 2017-05-17 2017-06-28 Univ Sheffield Compounds
JP2022537369A (ja) 2019-06-18 2022-08-25 バイエル アクチェンゲゼルシャフト 長期安定化のためのアドレノメデュリン－類似体およびその使用
EP4031185A2 (en) * 2019-09-21 2022-07-27 Ixaka France Dmso-free synthesis of oligopeptide-modified poly(beta-amino ester)s and their use in nanoparticle delivery systems
JP7498882B2 (ja) * 2019-12-05 2024-06-13 国立大学法人 宮崎大学 異常タンパク質蓄積性神経変性疾患の治療剤
EP4126062A1 (en) 2020-04-03 2023-02-08 Bayer Aktiengesellschaft Liquid pharmaceutical formulations polyethylene glycol-based prodrugs of adrenomedullin and use
CN115666654A (zh) 2020-04-03 2023-01-31 拜耳公司 药物制剂聚乙二醇基肾上腺髓质素前药和用途
AU2021341508A1 (en) 2020-09-10 2023-05-25 Precirix N.V. Antibody fragment against fap
CN112457218B (zh) * 2020-11-05 2022-08-09 宁夏医科大学 2,4-二氨基丁酸衍生物的合成方法
US20240391873A1 (en) 2021-08-20 2024-11-28 Bayer Aktiengesellschaft Process for the preparation of pegylated adrenomedullin, its intermediates and use thereof
WO2023203135A1 (en) 2022-04-22 2023-10-26 Precirix N.V. Improved radiolabelled antibody
WO2023213801A1 (en) 2022-05-02 2023-11-09 Precirix N.V. Pre-targeting
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WO2025133225A1 (en) 2023-12-22 2025-06-26 Pam Theragnostics Gmbh Pharmaceutical combination of peptide-gly and peptidylglycine alpha-amidating monooxygenase (pam)

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