WO2016133372A3 - 지속형 인슐린 또는 이의 아날로그 결합체 - Google Patents

지속형 인슐린 또는 이의 아날로그 결합체 Download PDF

Info

Publication number
WO2016133372A3
WO2016133372A3 PCT/KR2016/001628 KR2016001628W WO2016133372A3 WO 2016133372 A3 WO2016133372 A3 WO 2016133372A3 KR 2016001628 W KR2016001628 W KR 2016001628W WO 2016133372 A3 WO2016133372 A3 WO 2016133372A3
Authority
WO
WIPO (PCT)
Prior art keywords
insulin
long
complex
analogue complex
insulin analogue
Prior art date
Application number
PCT/KR2016/001628
Other languages
English (en)
French (fr)
Other versions
WO2016133372A2 (ko
Inventor
허용호
이종수
박성희
김대진
정성엽
권세창
Original Assignee
한미약품 주식회사
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 한미약품 주식회사 filed Critical 한미약품 주식회사
Priority to US15/551,489 priority Critical patent/US10894089B2/en
Priority to JP2017543742A priority patent/JP2018508504A/ja
Priority to CN201680022070.4A priority patent/CN107810202A/zh
Priority to EP16752702.7A priority patent/EP3260139A4/en
Publication of WO2016133372A2 publication Critical patent/WO2016133372A2/ko
Publication of WO2016133372A3 publication Critical patent/WO2016133372A3/ko

Links

Classifications

    • 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
    • A61K47/68—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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
    • A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
    • A61K47/6811—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates the drug being a protein or peptide, e.g. transferrin or bleomycin
    • 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
    • A61K38/28—Insulins
    • 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
    • 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
    • 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
    • C07K14/62—Insulins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/67—General methods for enhancing the expression
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/522—CH1 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/524—CH2 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/528—CH4 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
    • C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Diabetes (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Immunology (AREA)
  • Toxicology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Emergency Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

본 발명은 인슐린 및/또는 이의 아날로그(insulin analog)와 면역글로불린 Fc 영역을 연결하여, 생체 내 지속성 및 안정성이 향상된 인슐린 및/또는 이의 아날로그 결합체 및 그 이용에 관한 것이다. 본 발명의 인슐린 및/또는 이의 아날로그 결합체는 생체 내에서 인슐린과 유사한 활성을 나타내고, 혈중 반감기가 현저히 증가된 인슐린 및/또는 이의 아날로그의 지속형 제형으로 인슐린 치료의 단점인 저 혈당을 유도하지 않는 획기적인 인슐린 및/또는 이의 아날로그 결합체를 제공한다.
PCT/KR2016/001628 2015-02-17 2016-02-17 지속형 인슐린 또는 이의 아날로그 결합체 WO2016133372A2 (ko)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US15/551,489 US10894089B2 (en) 2015-02-17 2016-02-17 Long-acting insulin or insulin analogue conjugate
JP2017543742A JP2018508504A (ja) 2015-02-17 2016-02-17 持続型インスリンまたはインスリンアナログ結合体
CN201680022070.4A CN107810202A (zh) 2015-02-17 2016-02-17 长效胰岛素或胰岛素类似物复合物
EP16752702.7A EP3260139A4 (en) 2015-02-17 2016-02-17 Long-acting insulin or insulin analogue complex

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
KR10-2015-0024091 2015-02-17
KR20150024091 2015-02-17

Publications (2)

Publication Number Publication Date
WO2016133372A2 WO2016133372A2 (ko) 2016-08-25
WO2016133372A3 true WO2016133372A3 (ko) 2016-10-13

Family

ID=56692355

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2016/001628 WO2016133372A2 (ko) 2015-02-17 2016-02-17 지속형 인슐린 또는 이의 아날로그 결합체

Country Status (6)

Country Link
US (1) US10894089B2 (ko)
EP (1) EP3260139A4 (ko)
JP (1) JP2018508504A (ko)
KR (1) KR20160101702A (ko)
CN (1) CN107810202A (ko)
WO (1) WO2016133372A2 (ko)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR105616A1 (es) 2015-05-07 2017-10-25 Lilly Co Eli Proteínas de fusión
EP3303380B1 (en) 2015-06-02 2020-01-15 Novo Nordisk A/S Insulins with polar recombinant extensions
MA43348A (fr) 2015-10-01 2018-08-08 Novo Nordisk As Conjugués de protéines
GB201607918D0 (en) 2016-05-06 2016-06-22 Arecor Ltd Novel formulations
HUE055417T2 (hu) 2016-12-09 2021-11-29 Akston Biosciences Corp Inzulin-Fc fúziók és alkalmazási eljárások
EP3606560A2 (en) * 2017-04-05 2020-02-12 Novo Nordisk A/S Oligomer extended insulin-fc conjugates
KR20190036956A (ko) * 2017-09-28 2019-04-05 한미약품 주식회사 지속형 단쇄 인슐린 아날로그 및 이의 결합체
KR20190114907A (ko) * 2018-03-30 2019-10-10 한미약품 주식회사 뇌 표적 지속성 단백질 결합체, 이의 제조 방법, 및 이를 포함하는 조성물
US11267862B2 (en) 2018-06-29 2022-03-08 Akston Biosciences Corporation Ultra-long acting insulin-Fc fusion proteins and methods of use
HRP20240408T1 (hr) 2018-06-29 2024-06-07 Akston Biosciences Corporation Inzulin-fc fuzijski proteini ultradugog djelovanja i metode uporabe
KR102646845B1 (ko) * 2018-08-08 2024-03-14 주식회사 대웅제약 클로스트리파인을 이용한 지속형 인슐린 아날로그 복합체의 활성형 제조방법
KR102666154B1 (ko) * 2018-08-08 2024-05-20 주식회사 대웅제약 지속형 인슐린 아날로그 및 그 복합체
EP3863680A1 (en) * 2018-10-10 2021-08-18 Novo Nordisk A/S Oligomer extended insulin-fc conjugates and their medical use
KR20220115975A (ko) 2019-12-19 2022-08-19 악스톤 바이오사이언시스 코퍼레이션 초-장기 작용 인슐린-fc 융합 단백질 및 사용 방법
US11186623B2 (en) 2019-12-24 2021-11-30 Akston Bioscience Corporation Ultra-long acting insulin-Fc fusion proteins and methods of use
US11192930B2 (en) 2020-04-10 2021-12-07 Askton Bioscences Corporation Ultra-long acting insulin-Fc fusion protein and methods of use
SI3972987T1 (sl) 2020-04-10 2023-10-30 Akston Biosciences Corporation Antigen-specifična imunoterapija za covid-19 fuzijske proteine in postopki za uporabo
US11198719B2 (en) 2020-04-29 2021-12-14 Akston Biosciences Corporation Ultra-long acting insulin-Fc fusion protein and methods of use
KR20220073454A (ko) * 2020-11-26 2022-06-03 한미약품 주식회사 신규한 뇌 표적 지속형 단백질 결합체 및 이의 제조방법
US11667689B2 (en) 2021-07-23 2023-06-06 Akston Biosciences Corporation Insulin-Fc fusion proteins and methods of use to treat cancer

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009015345A1 (en) * 2007-07-25 2009-01-29 Amgen Inc. Pharmaceutical compositions comprising fc fusion proteins
KR20110111267A (ko) * 2010-04-02 2011-10-10 한미홀딩스 주식회사 면역글로불린 단편을 이용한 인슐린 약물 결합체
EP1366067B1 (en) * 2001-03-07 2012-09-26 Merck Patent GmbH Expression technology for proteins containing a hybrid isotype antibody moiety
CN103509118A (zh) * 2012-06-15 2014-01-15 郭怀祖 胰岛素-Fc融合蛋白
KR20150008012A (ko) * 2013-07-12 2015-01-21 한미약품 주식회사 수용체-매개 제거가 감소된, 생리활성 폴리펩타이드 단량체-면역글로불린 Fc 단편 결합체 및 이의 제조방법

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6096871A (en) 1995-04-14 2000-08-01 Genentech, Inc. Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life
WO1997034631A1 (en) 1996-03-18 1997-09-25 Board Of Regents, The University Of Texas System Immunoglobin-like domains with increased half lives
US7601516B2 (en) * 2004-01-28 2009-10-13 Syntomix Pharmaceuticals, Inc. Heterodimeric follicle stimulating hormone-Fc (FSH-Fc) fusion proteins for the treatment of infertility
WO2010107520A1 (en) * 2009-03-20 2010-09-23 Smartcells, Inc. Soluble non-depot insulin conjugates and uses thereof
WO2013096386A1 (en) 2011-12-20 2013-06-27 Indiana University Research And Technology Corporation Ctp-based insulin analogs for treatment of diabetes
AR091902A1 (es) 2012-07-25 2015-03-11 Hanmi Pharm Ind Co Ltd Formulacion liquida de un conjugado de insulina de accion prolongada
MX361083B (es) * 2013-02-26 2018-11-27 Hanmi Pharma Co Ltd Conjugado de insulina específico de sitio.
SG11201506095TA (en) * 2013-02-26 2015-09-29 Hanmi Pharm Ind Co Ltd Novel insulin analog and use thereof

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1366067B1 (en) * 2001-03-07 2012-09-26 Merck Patent GmbH Expression technology for proteins containing a hybrid isotype antibody moiety
WO2009015345A1 (en) * 2007-07-25 2009-01-29 Amgen Inc. Pharmaceutical compositions comprising fc fusion proteins
KR20110111267A (ko) * 2010-04-02 2011-10-10 한미홀딩스 주식회사 면역글로불린 단편을 이용한 인슐린 약물 결합체
CN103509118A (zh) * 2012-06-15 2014-01-15 郭怀祖 胰岛素-Fc融合蛋白
KR20150008012A (ko) * 2013-07-12 2015-01-21 한미약품 주식회사 수용체-매개 제거가 감소된, 생리활성 폴리펩타이드 단량체-면역글로불린 Fc 단편 결합체 및 이의 제조방법

Also Published As

Publication number Publication date
US20180161448A1 (en) 2018-06-14
US10894089B2 (en) 2021-01-19
CN107810202A (zh) 2018-03-16
EP3260139A4 (en) 2018-09-05
KR20160101702A (ko) 2016-08-25
JP2018508504A (ja) 2018-03-29
WO2016133372A2 (ko) 2016-08-25
EP3260139A2 (en) 2017-12-27

Similar Documents

Publication Publication Date Title
WO2016133372A3 (ko) 지속형 인슐린 또는 이의 아날로그 결합체
WO2017106346A3 (en) Human immunodeficiency virus neutralizing antibodies
CL2018002825A1 (es) Vacuna contra vrs
WO2015106269A3 (en) Rapid action insulin formulations and pharmaceutical delivery systems
CL2015003655A1 (es) Polipéptidos f de prefusión del virus sincicial respiratorio (rsv) solubles y estabilizados
WO2015179351A3 (en) Heart assist systems and methods
WO2016014342A3 (en) Ang-(1-7) derviative oligopeptides and methods for using and producing the same
WO2015105981A3 (en) Nutritional composition comprising hmb for increasing or maintaining lean body mass in subjects having reduced leucine to hmb conversion efficiency or undergoing diabetic treatment
WO2016057529A3 (en) Biphasic single-chain insulin analogues
EP3645044A4 (en) USE OF ANTI-FAMILY WITH SEQUENCE SIMILARITY 19, ELEMENT A5 ANTIBODIES TO TREAT GLAUCOMA
WO2016012420A3 (de) Deodorantzubereitungen umfassend polyquaternium-6-polymere
WO2014139952A3 (en) Prolonged delivery of certain fragrance components from personal care compositions
EP3277338A4 (en) Cannula system with sterile connector, blood pump, and patient harness
BR112019004911A2 (pt) oligonucleotídeos modificados e métodos de uso
PH12017501290A1 (en) Treatment of pediatric type 2 diabetes mellitus patients with lixisenatide
WO2016020880A3 (en) Angiopoietin-like 4 antibodies and methods of use
WO2015107506A3 (en) Collapsible tip re-entry catheter
WO2014141126A3 (en) Oblique stent
WO2016064266A3 (en) Wearable injection device
WO2018013825A3 (en) Infusion catheter with high pressure capabilities
MY193042A (en) Protector-attached medical needle
WO2013120825A3 (de) Stabile wasser in öl emulsionen mit verbesserter sensorik
GB201508958D0 (en) Process for the preparation of a topography for improved blood coagulation and/or cell attachment on a body made of titanium or a titanium alloy
WO2018129511A3 (en) Ang-(1-7) and derivative oligopeptides for the treatment of traumatic brain injury and other cognitive impairments
Raja et al. Cardiac Autonomic Modulation in Psychologically Stressed Subjects as reflected by Heart Rate Variability

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16752702

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 15551489

Country of ref document: US

ENP Entry into the national phase

Ref document number: 2017543742

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

REEP Request for entry into the european phase

Ref document number: 2016752702

Country of ref document: EP

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16752702

Country of ref document: EP

Kind code of ref document: A2