RS59700B1 - Monoklonalna antitela za faktor 15 (gdf-15) rasta i diferencijacije, i njihove upotrebe u lečenju kancerske kaheksije i kancera - Google Patents

Monoklonalna antitela za faktor 15 (gdf-15) rasta i diferencijacije, i njihove upotrebe u lečenju kancerske kaheksije i kancera

Info

Publication number
RS59700B1
RS59700B1 RS20191652A RSP20191652A RS59700B1 RS 59700 B1 RS59700 B1 RS 59700B1 RS 20191652 A RS20191652 A RS 20191652A RS P20191652 A RSP20191652 A RS P20191652A RS 59700 B1 RS59700 B1 RS 59700B1
Authority
RS
Serbia
Prior art keywords
group
mixture according
silicone
peg
cosmetic
Prior art date
Application number
RS20191652A
Other languages
English (en)
Serbian (sr)
Inventor
Jörg Wischhusen
Markus Junker
Tina Schäfer
Dirk Pühringer
Original Assignee
Univ Wuerzburg J Maximilians
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
Priority claimed from GB1405477.9A external-priority patent/GB2524553C/en
Priority claimed from GB1405475.3A external-priority patent/GB2524552B/en
Application filed by Univ Wuerzburg J Maximilians filed Critical Univ Wuerzburg J Maximilians
Publication of RS59700B1 publication Critical patent/RS59700B1/sr

Links

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
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • 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
    • 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
    • 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
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • 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
    • 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
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • 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
    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Cosmetics (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
RS20191652A 2014-03-26 2015-03-26 Monoklonalna antitela za faktor 15 (gdf-15) rasta i diferencijacije, i njihove upotrebe u lečenju kancerske kaheksije i kancera RS59700B1 (sr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB1405477.9A GB2524553C (en) 2014-03-26 2014-03-26 Monoclonal antibodies to growth and differentiation factor 15 (GDF-15), and uses thereof for treating cancer cachexia
GB1405475.3A GB2524552B (en) 2014-03-26 2014-03-26 Monoclonal antibodies to growth and differentiation factor 15 (GDF-15), and use thereof for treating cancer
PCT/EP2015/056654 WO2015144855A1 (en) 2014-03-26 2015-03-26 Monoclonal antibodies to growth and differentiation factor 15 (gdf-15), and uses thereof for treating cancer cachexia and cancer
EP15712629.3A EP3122775B1 (en) 2014-03-26 2015-03-26 Monoclonal antibodies to growth and differentiation factor 15 (gdf-15), and uses thereof for treating cancer cachexia and cancer

Publications (1)

Publication Number Publication Date
RS59700B1 true RS59700B1 (sr) 2020-01-31

Family

ID=52745885

Family Applications (1)

Application Number Title Priority Date Filing Date
RS20191652A RS59700B1 (sr) 2014-03-26 2015-03-26 Monoklonalna antitela za faktor 15 (gdf-15) rasta i diferencijacije, i njihove upotrebe u lečenju kancerske kaheksije i kancera

Country Status (22)

Country Link
US (5) US20170204174A1 (cg-RX-API-DMAC7.html)
EP (3) EP3653644B1 (cg-RX-API-DMAC7.html)
JP (3) JP6865585B2 (cg-RX-API-DMAC7.html)
KR (1) KR102520978B1 (cg-RX-API-DMAC7.html)
CN (1) CN106536553B (cg-RX-API-DMAC7.html)
AU (2) AU2015238264B2 (cg-RX-API-DMAC7.html)
BR (1) BR122023027559A2 (cg-RX-API-DMAC7.html)
CY (1) CY1122456T1 (cg-RX-API-DMAC7.html)
DK (2) DK3653644T5 (cg-RX-API-DMAC7.html)
ES (2) ES2965626T3 (cg-RX-API-DMAC7.html)
FI (1) FI3653644T3 (cg-RX-API-DMAC7.html)
HR (2) HRP20200034T1 (cg-RX-API-DMAC7.html)
HU (2) HUE047398T2 (cg-RX-API-DMAC7.html)
IL (2) IL248038B (cg-RX-API-DMAC7.html)
LT (2) LT3653644T (cg-RX-API-DMAC7.html)
NZ (1) NZ724649A (cg-RX-API-DMAC7.html)
PL (2) PL3122775T3 (cg-RX-API-DMAC7.html)
PT (2) PT3122775T (cg-RX-API-DMAC7.html)
RS (1) RS59700B1 (cg-RX-API-DMAC7.html)
SI (1) SI3122775T1 (cg-RX-API-DMAC7.html)
SM (1) SMT202000064T1 (cg-RX-API-DMAC7.html)
WO (1) WO2015144855A1 (cg-RX-API-DMAC7.html)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LT3653644T (lt) 2014-03-26 2024-01-25 Julius-Maximilians-Universität Würzburg Monokloniniai antikūnai prieš augimo ir diferenciacijos faktorių 15 (gdf- 15), ir jų panaudojimas taikant vėžio kacheksijos ir vėžio gydymą
WO2016049470A1 (en) 2014-09-25 2016-03-31 Aveo Pharmaceuticals, Inc. Methods of reversing cachexia and prolonging survival comprising administering a gdf15 modulator and an anti-cancer agent
US11262360B2 (en) 2015-10-02 2022-03-01 Julius-Maximilians-Universität Würzburg GDF-15 as a diagnostic marker to predict the clinical outcome of a treatment with immune checkpoint blockers
GB201517528D0 (en) * 2015-10-02 2015-11-18 Julius Maximillians Universitãt Würzburg GDF-15 as a diagnosis marker for melanoma
HRP20221530T1 (hr) * 2015-10-02 2023-03-17 Julius-Maximilians-Universität Würzburg Kombinirana terapija uporabom inhibitora ljudskog rasta i faktora diferencijacije 15 (gdf-15) te blokatora imunološke kontrolne točke
JP7138567B2 (ja) * 2016-04-27 2022-09-16 ノバルティス アーゲー 成長分化因子１５に対する抗体およびそれらの使用
WO2018007950A1 (en) * 2016-07-06 2018-01-11 National Research Council Of Canada Humanized antibodies transmigrating the blood-brain barrier and uses thereof
EP3526346A1 (en) * 2016-10-12 2019-08-21 Janssen Biotech, Inc. Methods for screening for modulators of gdf15-like biological activity
EP3551214B1 (en) * 2016-12-06 2024-03-13 St Vincent's Hospital Sydney Limited Treatment of obesity and eating disorders
KR102715542B1 (ko) 2018-08-20 2024-10-08 화이자 인코포레이티드 항-gdf15 항체, 조성물 및 사용 방법
EP4243928A1 (en) * 2020-11-10 2023-09-20 CatalYm GmbH Anti-gdf15 antibody and a dosage regimen for the treatment of cancer
JP2024511853A (ja) 2021-03-31 2024-03-15 カイマブ・リミテッド Ｇｄｆ１５シグナル伝達の治療的阻害剤
IL310535A (en) 2021-08-10 2024-03-01 Byomass Inc Anti-gdf15 antibodies, compositions and uses thereof
WO2023122213A1 (en) 2021-12-22 2023-06-29 Byomass Inc. Targeting gdf15-gfral pathway cross-reference to related applications
WO2023217068A1 (zh) 2022-05-09 2023-11-16 舒泰神（北京）生物制药股份有限公司 特异性识别gdf15的抗体及其应用
CN116462757A (zh) * 2023-03-24 2023-07-21 科兴生物制药股份有限公司 Gdf15的单域抗体及其应用
CN118878677A (zh) * 2024-09-29 2024-11-01 江苏凯基生物技术股份有限公司 一种IgM亚型单克隆抗体及其制备方法和应用

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0953639A1 (en) * 1998-04-30 1999-11-03 Boehringer Ingelheim International GmbH FAPalpha-specific antibody with improved producibility
US6455677B1 (en) * 1998-04-30 2002-09-24 Boehringer Ingelheim International Gmbh FAPα-specific antibody with improved producibility
US6465181B2 (en) 1999-03-25 2002-10-15 Abbott Laboratories Reagents and methods useful for detecting diseases of the prostate
CA2372119A1 (en) 1999-05-17 2000-11-23 Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Und Zum Vertrie B Von Pharmaka Mbh Neuroprotective properties of gdf-15, a novel member of the tgf-.beta. superfamily
US7141661B2 (en) 2000-09-08 2006-11-28 The United States Of America As Represented By The Department Of Health And Human Services Non-steroidal anti-inflammatory drug activated gene with anti-tumorigenic properties
BRPI0506726B8 (pt) * 2004-01-07 2021-05-25 Chiron Corp anticorpo monoclonal específico para m-csf e usos deste
CA2905125C (en) 2004-04-13 2017-02-07 Samuel Norbert Breit Use of mic-1 or modulating agent thereof to modulate appetite or body weight
WO2009021293A1 (en) * 2007-08-16 2009-02-19 St Vincent's Hospital Sydney Limited Agents and methods for modulating macrophage inhibitory cytokine (mic-1) activity
JP2011502106A (ja) * 2007-10-09 2011-01-20 セントビンセンツ ホスピタル シドニー リミテッド マクロファージ阻害性サイトカイン−１を除去又は不活性化して悪液質を治療する方法
WO2010034443A1 (en) 2008-09-29 2010-04-01 F. Hoffmann-La Roche Ag Antibodies against human il 17 and uses thereof
WO2011050407A1 (en) 2009-10-28 2011-05-05 St Vincent's Hospital Sydney Limited Methods of diagnosing and prognosing colonic polyps
US9212221B2 (en) * 2010-03-03 2015-12-15 Detroit R & D, Inc. Form-specific antibodies for NAG-1 (MIC-1, GDF-15), H6D and other TGF-β subfamily and heart disease and cancer diagnoses
CN103298937B (zh) * 2010-11-17 2016-05-25 中外制药株式会社 具有代替凝血因子viii的功能的功能的多特异性抗原结合分子
US8790651B2 (en) * 2011-07-21 2014-07-29 Zoetis Llc Interleukin-31 monoclonal antibody
CN102321173B (zh) 2011-08-12 2013-04-03 中国医学科学院肿瘤研究所 人源化巨噬细胞抑制因子1单克隆抗体及其应用
EP2565262A1 (en) 2011-08-31 2013-03-06 VTU Holding GmbH Protein expression
MX2014009129A (es) 2012-01-26 2014-11-21 Amgen Inc Polipeptidos de factor 15 de diferenciacion de crecimiento (gdf-15).
KR101838786B1 (ko) * 2012-09-26 2018-03-15 율리우스-막시밀리안스 우니버지태트 뷔르츠부르크 성장 및 분화 인자 15 (gdf-15)에 대한 모노클로날 항체
JP6758832B2 (ja) * 2012-12-21 2020-09-30 アベオ ファーマシューティカルズ， インコーポレイテッド 抗ｇｄｆ１５抗体
LT3653644T (lt) 2014-03-26 2024-01-25 Julius-Maximilians-Universität Würzburg Monokloniniai antikūnai prieš augimo ir diferenciacijos faktorių 15 (gdf- 15), ir jų panaudojimas taikant vėžio kacheksijos ir vėžio gydymą

Also Published As

Publication number Publication date
PL3122775T3 (pl) 2020-05-18
ES2763859T3 (es) 2020-06-01
US10604565B2 (en) 2020-03-31
AU2020260440A1 (en) 2020-11-26
DK3653644T3 (da) 2023-12-18
KR20160139005A (ko) 2016-12-06
US20180298091A1 (en) 2018-10-18
JP6865585B2 (ja) 2021-04-28
PL3653644T3 (pl) 2024-03-04
SI3122775T1 (sl) 2020-02-28
US20200308265A1 (en) 2020-10-01
PT3122775T (pt) 2019-12-26
ES2965626T3 (es) 2024-04-16
EP4316596A3 (en) 2024-04-17
WO2015144855A1 (en) 2015-10-01
IL248038B (en) 2020-08-31
HRP20200034T1 (hr) 2020-03-20
BR122023027559A2 (pt) 2024-01-30
US20230382987A1 (en) 2023-11-30
IL276405B (en) 2021-07-29
SMT202000064T1 (it) 2020-03-13
EP3653644B1 (en) 2023-11-15
EP3122775B1 (en) 2019-11-13
CY1122456T1 (el) 2021-01-27
EP4316596A2 (en) 2024-02-07
DK3122775T3 (da) 2020-02-03
US20170204174A1 (en) 2017-07-20
US20200308264A1 (en) 2020-10-01
BR112016022013A2 (pt) 2017-10-31
DK3653644T5 (da) 2024-08-26
CA2943694A1 (en) 2015-10-01
EP3653644A1 (en) 2020-05-20
EP3122775A1 (en) 2017-02-01
NZ724649A (en) 2022-07-01
JP2023098966A (ja) 2023-07-11
US11760795B2 (en) 2023-09-19
JP7607498B2 (ja) 2024-12-27
IL276405A (en) 2020-09-30
HRP20231514T1 (hr) 2024-03-01
AU2015238264A1 (en) 2016-10-20
HUE064573T2 (hu) 2024-03-28
JP2017508475A (ja) 2017-03-30
HUE047398T2 (hu) 2020-04-28
PT3653644T (pt) 2023-12-19
LT3653644T (lt) 2024-01-25
IL248038A0 (en) 2016-11-30
LT3122775T (lt) 2020-02-10
JP2021119138A (ja) 2021-08-12
AU2015238264B2 (en) 2020-09-03
CN106536553A (zh) 2017-03-22
KR102520978B1 (ko) 2023-04-11
US11634482B2 (en) 2023-04-25
AU2020260440B2 (en) 2024-03-21
CN106536553B (zh) 2021-03-12
FI3653644T3 (fi) 2023-12-12

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