WO2015173824A1 - Improved polyethyleneimine polyethyleneglycol vectors - Google Patents

Improved polyethyleneimine polyethyleneglycol vectors Download PDF

Info

Publication number
WO2015173824A1
WO2015173824A1 PCT/IL2015/050514 IL2015050514W WO2015173824A1 WO 2015173824 A1 WO2015173824 A1 WO 2015173824A1 IL 2015050514 W IL2015050514 W IL 2015050514W WO 2015173824 A1 WO2015173824 A1 WO 2015173824A1
Authority
WO
WIPO (PCT)
Prior art keywords
polyplex
cancer
peg
lpei
alkylene
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/IL2015/050514
Other languages
English (en)
French (fr)
Inventor
Alex Levitzki
Salim Joubran
Alexei Shir
Maya ZIGLER
Alaa TALHAMI
Yael Langut
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alex Levitzki Management And Holdings Ltd
Original Assignee
Alex Levitzki Management And Holdings Ltd
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 to CA2949017A priority Critical patent/CA2949017A1/en
Priority to NZ727092A priority patent/NZ727092A/en
Priority to PH1/2016/502258A priority patent/PH12016502258B1/en
Priority to MX2016014881A priority patent/MX377654B/es
Priority to AU2015260725A priority patent/AU2015260725B2/en
Priority to CN202310954498.4A priority patent/CN116966310A/zh
Priority to KR1020167033997A priority patent/KR102472590B1/ko
Priority to CN201580025099.3A priority patent/CN106687121A/zh
Priority to KR1020227041535A priority patent/KR102589295B1/ko
Priority to RU2016146389A priority patent/RU2771104C2/ru
Priority to SG11201609442YA priority patent/SG11201609442YA/en
Priority to CN202310955550.8A priority patent/CN116966311A/zh
Priority to EP15793532.1A priority patent/EP3142673A4/en
Application filed by Alex Levitzki Management And Holdings Ltd filed Critical Alex Levitzki Management And Holdings Ltd
Priority to US15/310,735 priority patent/US10278991B2/en
Priority to IL287206A priority patent/IL287206B2/en
Priority to JP2017512466A priority patent/JP6753843B2/ja
Priority to BR112016026581-5A priority patent/BR112016026581B1/pt
Publication of WO2015173824A1 publication Critical patent/WO2015173824A1/en
Priority to IL248890A priority patent/IL248890B/en
Anticipated expiration legal-status Critical
Priority to ZA2016/08042A priority patent/ZA201608042B/en
Priority to US16/296,117 priority patent/US11298376B2/en
Priority to US16/297,133 priority patent/US10543232B2/en
Priority to AU2021203336A priority patent/AU2021203336C1/en
Priority to US17/653,221 priority patent/US20220339189A1/en
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • 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
    • 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
    • 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
    • A61P35/00—Antineoplastic agents
    • 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
    • C12N15/117—Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/17—Immunomodulatory nucleic acids
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/35—Nature of the modification
    • C12N2310/351—Conjugate
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/50—Physical structure
    • C12N2310/53—Physical structure partially self-complementary or closed

Definitions

  • FIG. 2 shows 1H-NMR analysis of the two di-conjugates, LPEI-PEG 2k -OPSS (di- conjugate 1: 1) and LPEI-(PEG 2 k-OPSS)3 (di-conjugate 1:3).
  • the coupling of PEG groups to LPEI was indicated by the presence of the chemical shifts that correlate to ethylene glycol hydrogens (a) at 3.7 ppm and ethyleneimine hydrogens at -3.0 ppm (b) .
  • the integral values of these peaks provide molar ratios of PEG to LPEI, from which the illustrated structures of di-conjugate 1 : 1 (A) and di-conjugate 1 :3 (B) were deduced.
  • Figure 3 shows a scheme for conjugation of the co-polymeric networks (di-conjugate 1: 1 and di-conjugate 1:3) to the affibody ("Her- 2") through disulfide exchange, resulting in the generation of two differently PEGylated tri-conjugates [20].
  • the tri-conjugate polyplexes conjugated to affibodies had lower surface charge than the di-conjugate polyplexes, showing that the Her-2 affibody (which itself has slight positive charge) also reduced the surface charge of the particles.
  • Her-2 affibody changes the topography of the particle with more targeting moieties masking the charge on the surface, leading to a decrease in surface charge.
  • R4 is selected from (Ci-C 8 )alkylene, (C 2 -C 8 )alkenylene, (C 2 -C 8 ) alkynylene, (Ci- C 8 )alkylene-(C3-C 8 )cycloalkylene, (C 2 -C 8 )alkenylene-(C 3 -C 8 )cycloalkylene, (C 2 -C 8 ) alkynylene-(C 3 -C 8 )cycloalkylene, (C 6 -Cio)arylene-diyl, heteroarylenediyl, (Ci-C 8 )alkylene- (C 6 -Cio)arylene-diyl, or (Ci-C 8 )alkylene -heteroarylenediyl;
  • Polylnosine/PolyCytosine has strong anti-tumor activity.
  • Breast cancer cell lines overexpressing Her-2 were found to be strongly inhibited by a complex of PEI-PEG- Her2Affibody with PolylC. Strong inhibition was observed also of trastuzumab resistant Her2 overexpressing breast cancer cell lines.
  • the purified LPEI-PEG-hEGF or LPEI-PEG-mEGF triconjugate was analyzed by HPLC and quantified by a "copper assay” and an EGF photometric assay to measure [LPEI] and [EGF] concentrations, correspondingly.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Genetics & Genomics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cell Biology (AREA)
  • Hematology (AREA)
  • Developmental Biology & Embryology (AREA)
  • Virology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Other Resins Obtained By Reactions Not Involving Carbon-To-Carbon Unsaturated Bonds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
PCT/IL2015/050514 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors Ceased WO2015173824A1 (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
EP15793532.1A EP3142673A4 (en) 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors
PH1/2016/502258A PH12016502258B1 (en) 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors
MX2016014881A MX377654B (es) 2014-05-14 2015-05-14 Vectores mejorados de polietilenimina polietilenglicol.
AU2015260725A AU2015260725B2 (en) 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors
CN202310954498.4A CN116966310A (zh) 2014-05-14 2015-05-14 改善的聚乙烯亚胺聚乙二醇载体
KR1020167033997A KR102472590B1 (ko) 2014-05-14 2015-05-14 개선된 폴리에틸렌이민 폴리에틸렌글리콜 벡터
CN201580025099.3A CN106687121A (zh) 2014-05-14 2015-05-14 改善的聚乙烯亚胺聚乙二醇载体
KR1020227041535A KR102589295B1 (ko) 2014-05-14 2015-05-14 개선된 폴리에틸렌이민 폴리에틸렌글리콜 벡터
NZ727092A NZ727092A (en) 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors
SG11201609442YA SG11201609442YA (en) 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors
US15/310,735 US10278991B2 (en) 2014-05-14 2015-05-14 Polyethyleneimine polyethyleneglycol vectors
CA2949017A CA2949017A1 (en) 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors
RU2016146389A RU2771104C2 (ru) 2014-05-14 2015-05-14 Улучшенные полиэтилениминовые полиэтиленгликолевые векторы
CN202310955550.8A CN116966311A (zh) 2014-05-14 2015-05-14 改善的聚乙烯亚胺聚乙二醇载体
IL287206A IL287206B2 (en) 2014-05-14 2015-05-14 Improved vectors containing polyethyleneimine-polyethyleneglycol
JP2017512466A JP6753843B2 (ja) 2014-05-14 2015-05-14 改善されたポリエチレンイミンポリエチレングリコールベクター
BR112016026581-5A BR112016026581B1 (pt) 2014-05-14 2015-05-14 Poliplexo de um rna de fita dupla (dsrna) e um conjugado polimérico, uso do poliplexo e composições farmacêuticas que o compreendem
IL248890A IL248890B (en) 2014-05-14 2016-11-10 Improved vectors containing polyethyleneimine-polyethyleneglycol
ZA2016/08042A ZA201608042B (en) 2014-05-14 2016-11-21 Improved polyethyleneimine polyethyleneglycol vectors
US16/296,117 US11298376B2 (en) 2014-05-14 2019-03-07 Method of treating cancer
US16/297,133 US10543232B2 (en) 2014-05-14 2019-03-08 Polyplex of double-stranded RNA and polymeric conjugate
AU2021203336A AU2021203336C1 (en) 2014-05-14 2021-05-24 Improved polyethyleneimine polyethyleneglycol vectors
US17/653,221 US20220339189A1 (en) 2014-05-14 2022-03-02 Method of treating cancer

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201461993110P 2014-05-14 2014-05-14
US61/993,110 2014-05-14

Related Child Applications (3)

Application Number Title Priority Date Filing Date
US15/310,735 A-371-Of-International US10278991B2 (en) 2014-05-14 2015-05-14 Polyethyleneimine polyethyleneglycol vectors
US16/296,117 Division US11298376B2 (en) 2014-05-14 2019-03-07 Method of treating cancer
US16/297,133 Continuation US10543232B2 (en) 2014-05-14 2019-03-08 Polyplex of double-stranded RNA and polymeric conjugate

Publications (1)

Publication Number Publication Date
WO2015173824A1 true WO2015173824A1 (en) 2015-11-19

Family

ID=54479412

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IL2015/050514 Ceased WO2015173824A1 (en) 2014-05-14 2015-05-14 Improved polyethyleneimine polyethyleneglycol vectors

Country Status (16)

Country Link
US (4) US10278991B2 (https=)
EP (1) EP3142673A4 (https=)
JP (3) JP6753843B2 (https=)
KR (2) KR102589295B1 (https=)
CN (3) CN116966311A (https=)
AU (2) AU2015260725B2 (https=)
CA (1) CA2949017A1 (https=)
IL (2) IL287206B2 (https=)
MA (1) MA39970A (https=)
MX (2) MX377654B (https=)
NZ (1) NZ727092A (https=)
PH (1) PH12016502258B1 (https=)
RU (1) RU2771104C2 (https=)
SG (2) SG11201609442YA (https=)
WO (1) WO2015173824A1 (https=)
ZA (1) ZA201608042B (https=)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017085228A1 (en) 2015-11-17 2017-05-26 Bioncotech Therapeutics, S.L Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
WO2018210439A1 (en) 2017-05-17 2018-11-22 Bioncotech Therapeutics Sl Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
CN109071419A (zh) * 2016-03-07 2018-12-21 韩美药品株式会社 聚乙二醇衍生物及其用途
WO2019063705A1 (en) 2017-09-27 2019-04-04 Targimmune Therapeutics Ag CANCER OF THE PROSTATE RESISTANT TO CASTRATION
WO2020201568A1 (en) 2019-04-03 2020-10-08 Targimmune Therapeutics Ag Immunotherapy for the treatment of cancer
WO2020263782A1 (en) * 2019-06-24 2020-12-30 North Carolina State University Methods and compositions for modifying nucleic acids and for killing cells
WO2021001417A1 (en) * 2019-07-02 2021-01-07 Biontech Rna Pharmaceuticals Gmbh Rna formulations suitable for therapy
JP2021516056A (ja) * 2018-03-08 2021-07-01 ターグイミューン セラピューティクス アーゲー 二本鎖ｒｎａ結合ドメインを含む組換えタンパク質
WO2022074152A1 (en) 2020-10-08 2022-04-14 Targimmune Therapeutics Ag Immunotherapy for the treatment of cancer
WO2023079142A2 (en) 2021-11-05 2023-05-11 Targimmune Therapeutics Ag Targeted linear conjugates comprising polyethyleneimine and polyethylene glycol and polyplexes comprising the same
WO2024100046A1 (en) * 2022-11-07 2024-05-16 Targimmune Therapeutics Ag Targeted linear conjugates comprising polyethyleneimine and polyethylene glycol and polyplexes comprising the same
WO2024100040A1 (en) 2022-11-07 2024-05-16 Targimmune Therapeutics Ag Psma-targeting linear conjugates comprising polyethyleneimine and polyethylene glycol and polyplexes comprising the same
WO2024100044A1 (en) 2022-11-07 2024-05-16 Targimmune Therapeutics Ag Polyplexes of nucleic acids and targeted conjugates comprising polyethyleneimine and polyethylene glycol
WO2025238236A1 (en) 2024-05-16 2025-11-20 Targimmune Therapeutics Ag Polyplexes of nucleic acids and targeted conjugates comprising polyethyleneimine and polyethylene glycol

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR102589295B1 (ko) 2014-05-14 2023-10-13 타르그이뮨 테라퓨틱스 아게 개선된 폴리에틸렌이민 폴리에틸렌글리콜 벡터
BR112019004017A2 (pt) 2016-09-04 2019-06-25 Targimmune Therapeutics Ag proteínas quiméricas para direcionar dsrna
CN109893657B (zh) * 2019-02-28 2022-04-29 中国人民解放军军事科学院军事医学研究院 基因递送载体、药物复合物、抗肺纤维化药物及应用
US20240091348A1 (en) * 2022-09-20 2024-03-21 Highlight Therapeutics, S.L. Novel compositions based on polyinosinic-polycytidylic acid

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004045491A2 (en) 2002-11-18 2004-06-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem Targeted double stranded rna mediated cell killing
WO2010073247A2 (en) 2008-12-22 2010-07-01 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Egfr-homing double-stranded rna vector for systemic cancer treatment

Family Cites Families (76)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE59106279D1 (de) 1990-05-18 1995-09-21 Genentech Inc Neue protein-polykation-konjugate.
DE4104186A1 (de) 1991-02-12 1992-08-13 Genentech Inc Neue, ueber endozytose in hoehere eukaryotische zellen aufnehmbare, nukleinsaeure enthaltende komplexe
IL103059A0 (en) 1991-09-30 1993-02-21 Boehringer Ingelheim Int Conjugates for introducing nucleic acid into higher eucaryotic cells
NZ244306A (en) 1991-09-30 1995-07-26 Boehringer Ingelheim Int Composition for introducing nucleic acid complexes into eucaryotic cells, complex containing nucleic acid and endosomolytic agent, peptide with endosomolytic domain and nucleic acid binding domain and preparation
DE19726186A1 (de) 1997-06-20 1998-12-24 Boehringer Ingelheim Int Komplexe für den Transport von Nukleinsäure in höhere eukaryotische Zellen
WO1999061032A1 (en) 1998-05-25 1999-12-02 Nippon Shinyaku Co., Ltd. Process for producing composite preparation containing nucleic acid
US6652886B2 (en) 2001-02-16 2003-11-25 Expression Genetics Biodegradable cationic copolymers of poly (alkylenimine) and poly (ethylene glycol) for the delivery of bioactive agents
US20040043030A1 (en) 2001-07-31 2004-03-04 Immunomedics, Inc. Polymeric delivery systems
GB0119346D0 (en) 2001-08-08 2001-10-03 Bioclones Proprietary Ltd Process for the maturation of dendritic cells
US7060498B1 (en) 2001-11-28 2006-06-13 Genta Salus Llc Polycationic water soluble copolymer and method for transferring polyanionic macromolecules across biological barriers
KR20030043780A (ko) 2001-11-28 2003-06-02 주식회사 바이오폴리메드 생체적합성 비항원성 공중합체와 그 결합체 및 이들의제조방법
WO2003072636A1 (en) 2002-02-28 2003-09-04 Jong Sang Park Cationic highly branched polyaminoester
CN1720257A (zh) 2002-08-06 2006-01-11 因特拉迪格姆公司 通过导入干扰rna在体内下调靶基因表达的方法
US8969543B2 (en) 2003-04-03 2015-03-03 Bioneer Corporation SiRNA-hydrophilic polymer conjugates for intracellular delivery of siRNA and method thereof
US8324365B2 (en) 2003-04-03 2012-12-04 Korea Advanced Institute Of Science And Technology Conjugate for gene transfer comprising oligonucleotide and hydrophilic polymer, polyelectrolyte complex micelles formed from the conjugate, and methods for preparation thereof
US7727969B2 (en) 2003-06-06 2010-06-01 Massachusetts Institute Of Technology Controlled release nanoparticle having bound oligonucleotide for targeted delivery
US20050118718A1 (en) 2003-09-22 2005-06-02 University Of Utah Research Foundation Stabilization and controlled delivery of ionic biopharmaceuticals
US20050277575A1 (en) 2004-03-24 2005-12-15 Alexandre Semov Therapeutic compositions and methods for treating diseases that involve angiogenesis
CA2587676A1 (en) 2004-11-19 2006-05-26 Institut Gustave Roussy Improved treatment of cancer by double-stranded rna
US7893244B2 (en) 2005-04-12 2011-02-22 Intradigm Corporation Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases
CN101287500A (zh) * 2005-08-19 2008-10-15 恩多塞特公司 多药物配体缀合物
US20090011004A1 (en) 2005-12-30 2009-01-08 Philadelphia Health & Education Corp., D/B/A/ Drexel University Of College Of Medicine Improved carriers for delivery of nucleic acid agents to cells and tissues
US20070231392A1 (en) 2006-01-23 2007-10-04 Ernst Wagner CHEMICALLY MODIFIED POLYCATION POLYMER FOR siRNA DELIVERY
US20070225213A1 (en) 2006-03-23 2007-09-27 Kosak Matthew K Nucleic acid carriers for delivery of therapeutic agents
ES2776100T3 (es) 2006-03-31 2020-07-29 Massachusetts Inst Technology Sistema para el suministro dirigido de agentes terapéuticos
EP2136788B1 (en) 2007-03-30 2011-10-26 Bind Biosciences, Inc. Cancer cell targeting using nanoparticles
WO2008124634A1 (en) 2007-04-04 2008-10-16 Massachusetts Institute Of Technology Polymer-encapsulated reverse micelles
EP4464384A3 (en) 2007-08-17 2025-01-08 Purdue Research Foundation Psma binding ligand-linker conjugates and methods for using
WO2009030254A1 (en) * 2007-09-04 2009-03-12 Curevac Gmbh Complexes of rna and cationic peptides for transfection and for immunostimulation
EP2630966B1 (en) 2007-10-12 2017-04-19 Massachusetts Institute of Technology Vaccine nanotechnology
US20110027172A1 (en) 2007-12-10 2011-02-03 Zhuang Wang Drug delivery system for pharmaceuticals and radiation
US20110038888A1 (en) 2008-01-10 2011-02-17 Peter Emtage Adjuvant compositions comprising poly-ic and a cationic polymer
WO2009131435A1 (en) 2008-04-23 2009-10-29 Erasmus University Medical Center Rotterdam Linker containing bungarotoxin and a binding peptide
EP2113257A1 (en) 2008-04-30 2009-11-04 Consorzio per il Centro di Biomedica Moleculare Scrl Polyelectrolyte with positive net charge for use as medicament and diagnostic for cancer
EP2123304A1 (en) 2008-05-23 2009-11-25 Freie Universität Berlin Compounds suited as nanocarriers for active agents and their use
WO2009151539A1 (en) 2008-05-24 2009-12-17 Sirnaomics, Inc. COMPOSITIONS AND METHODS USING siRNA MOLECULES FOR TREATMENT OF GLIOMAS
WO2010005740A2 (en) 2008-06-16 2010-01-14 Bind Biosciences, Inc. Methods for the preparation of targeting agent functionalized diblock copolymers for use in fabrication of therapeutic targeted nanoparticles
WO2010088927A1 (en) 2009-02-09 2010-08-12 Curevac Gmbh Use of pei for the improvement of endosomal release and expression of transfected nucleic acids, complexed with cationic or polycationic compounds
US20100266642A1 (en) 2009-02-20 2010-10-21 Bind Biosciences, Inc. Modified cells for targeted cell trafficking and uses thereof
ES2588183T3 (es) 2009-03-31 2016-10-31 Japan As Represented By Director-General Of National Institute Of Infectious Diseases Procedimiento para la prevención de la gripe utilizando una vacuna para administración intranasal
WO2010127159A2 (en) 2009-04-30 2010-11-04 Intezyne Technologies, Incorporated Polymeric micelles for polynucleotide encapsulation
ES2368963B1 (es) 2009-07-04 2012-10-10 Fundación Centro Nacional De Investigaciones Oncológicas Carlos Iii Procedimiento de identificación de agentes terapéuticos contra el melanoma y uso de agente identificado.
CN101638484A (zh) * 2009-08-24 2010-02-03 中国科学院长春应用化学研究所 聚乙二醇单甲醚-聚2-甲基-2-羧基碳酸丙烯酯接枝聚乙烯亚胺共聚物与制法及应用
CA2781717C (en) 2009-12-09 2017-09-12 Ibc Pharmaceuticals, Inc. Dock-and-lock (dnl) complexes for delivery of interference rna
JP6175237B2 (ja) 2009-12-15 2017-08-02 ファイザー・インク コルチコステロイドを含む治療用ポリマーナノ粒およびそれを製造かつ使用する方法
ES2780156T3 (es) 2009-12-15 2020-08-24 Pfizer Composiciones terapéuticas de nanopartículas poliméricas con alta temperatura de transición vítrea o copolímeros de alto peso molecular
JP5898627B2 (ja) 2009-12-15 2016-04-06 バインド セラピューティックス インコーポレイテッド エポチロンを含む治療用ポリマーナノ粒子ならびにそれを製造および使用する方法
DK2539451T3 (da) 2010-02-24 2016-04-04 Arrowhead Res Corp Sammensætninger til målrettet tilførsel af siRNA
ES2631458T3 (es) 2010-03-04 2017-08-31 Interna Technologies B.V. Molécula de ARNmi definida por su fuente y sus usos terapéuticos en el cáncer asociado a la EMT
US20110256227A1 (en) 2010-04-14 2011-10-20 Intezyne Technologies, Inc. Controlled polyplex assembly
WO2011154331A1 (en) 2010-06-10 2011-12-15 F. Hoffmann-La Roche Ag Polymers for delivery of nucleic acids
EP2395041A1 (en) 2010-06-10 2011-12-14 F. Hoffmann-La Roche AG Polymers for delivery of nucleic acids
NZ704322A (en) 2010-07-06 2016-07-29 Interna Technologies Bv Mirna and its diagnostic and therapeutic uses in diseases or conditions associated with melanoma, or in diseases or conditions associated with activated braf pathway
US20120207795A1 (en) 2010-07-13 2012-08-16 The Regents Of The University Of California Cationic polymer coated mesoporous silica nanoparticles and uses thereof
WO2012016188A2 (en) 2010-07-30 2012-02-02 Alnylam Pharmaceuticals, Inc. Methods and compositions for delivery of active agents
FR2963350B1 (fr) 2010-07-30 2013-11-01 Univ D Evry Val D Essonne Nouveaux copolymeres a bloc et leurs utilisations pour delivrer une substance active dans une cellule.
US8461224B2 (en) 2011-03-04 2013-06-11 National Health Research Institutes Single monomer derived linear-like copolymer comprising polyethylenimine and poly(ethylene glycol) for nucleic acid delivery
US10029023B2 (en) 2011-03-31 2018-07-24 The Johns Hopkins University Theranostic imaging agents and methods of use
WO2012166923A2 (en) 2011-05-31 2012-12-06 Bind Biosciences Drug loaded polymeric nanoparticles and methods of making and using same
EP3272868A1 (en) 2012-05-02 2018-01-24 Arrowhead Pharmaceuticals, Inc. Organic compositions to treat kras-related diseases
EP2852668B1 (en) 2012-07-12 2016-04-27 ProQR Therapeutics II B.V. Oligonucleotides for making a change in the sequence of a target rna molecule present in a living cell
CA2912975A1 (en) 2012-10-16 2014-04-24 William Marsh Rice University An improved nanovector based drug delivery system for overcoming drug resistance
US10201556B2 (en) 2012-11-06 2019-02-12 Interna Technologies B.V. Combination for use in treating diseases or conditions associated with melanoma, or treating diseases or conditions associated with activated B-raf pathway
BR112015011118B1 (pt) 2012-11-15 2022-12-13 Endocyte, Inc Conjugado; composição farmacêutica; e uso de um conjugado
EP2930180B1 (en) 2012-12-06 2021-11-10 Kyowa Hakko Bio Co., Ltd. Double-stranded ribonucleic acid for adjuvants
EP3013964B1 (en) 2013-06-28 2020-05-06 ethris GmbH Compositions for introducing rna into cells
CN104341488A (zh) 2013-08-02 2015-02-11 复旦大学 c(LyP-1)多肽及其构建的纳米递药系统和应用
WO2015065773A1 (en) 2013-11-04 2015-05-07 Northeastern University System for co-delivery of polynucleotides and drugs into protease-expressing cells
JP2017505104A (ja) 2013-11-08 2017-02-16 デイナ ファーバー キャンサー インスティチュート，インコーポレイテッド インビボにおける薬剤送達のための核酸ナノ構造体
MA39734B1 (fr) 2014-03-14 2019-07-31 Pfizer Nanoparticules thérapeutiques comportant un agent thérapeutique, et leurs procédés de fabrication et d'utilisation
EP3126501A1 (en) 2014-03-24 2017-02-08 RiboxX GmbH Double-stranded rna conjugates and their use
JP7348708B2 (ja) 2014-04-30 2023-09-21 プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ 組み合わせワクチン装置および癌細胞を殺滅する方法
KR102589295B1 (ko) 2014-05-14 2023-10-13 타르그이뮨 테라퓨틱스 아게 개선된 폴리에틸렌이민 폴리에틸렌글리콜 벡터
US20180016352A1 (en) 2015-02-05 2018-01-18 The University Of Queensland Targeting constructs for delivery of payloads
US20160331845A1 (en) 2015-05-14 2016-11-17 The Johns Hopkins University Compositions of nucleic acid-containing nanoparticles for in vivo delivery
HUE047172T2 (hu) 2015-11-17 2020-04-28 Bioncotech Therapeutics S L Újfajta gyógyszerészeti készítmény, mely egy kétszálú poli-ribonukleotid és egy polialkilén-imin egy komplexét tartalmazó részecskéket tartalmaz

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004045491A2 (en) 2002-11-18 2004-06-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem Targeted double stranded rna mediated cell killing
WO2010073247A2 (en) 2008-12-22 2010-07-01 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Egfr-homing double-stranded rna vector for systemic cancer treatment

Non-Patent Citations (44)

* Cited by examiner, † Cited by third party
Title
AGUILAR, Z. ET AL.: "Biologic effects of heregulin/neu differentiation factor on normal and malignant human breast and ovarian epithelial cells", ONCOGENE, vol. 18, no. 44, 1999, pages 6050 - 62, XP037733054, DOI: 10.1038/sj.onc.1202993
BEHR, J.P.: "The proton sponge: A trick to enter cells the viruses did not exploit", CHIMIA, vol. 51, no. 1-2, 1997, pages 34 - 36, XP002067584
BOUSSIF, O. ET AL.: "A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimine", PROC NATL ACAD SCI U S A, vol. 92, no. 16, 1995, pages 7297 - 301, XP002006502, DOI: 10.1073/pnas.92.16.7297
BRAGONZI, A. ET AL.: "Comparison between cationic polymers and lipids in mediating systemic gene delivery to the lungs", GENE THER, vol. 6, no. 12, 1999, pages 1995 - 2004, XP037770634, DOI: 10.1038/sj.gt.3301039
BRISSAULT, B. ET AL.: "Synthesis, characterization, and gene transfer application of poly(ethylene glycol-b-ethylenimine) with high molar mass polyamine block", BIOMACROMOLECULES, vol. 7, no. 10, 2006, pages 2863 - 70, XP002509813, DOI: 10.1021/bm060499a
CHAMPION, J.A.Y.K. KATARES. MITRAGOTRI: "Particle shape: a new design parameter for micro- and nanoscale drug delivery carriers.", J CONTROL RELEASE, vol. 121, no. 1-2, 2007, pages 3 - 9, XP002716774, DOI: 10.1016/j.jconrel.2007.03.022
CHOLLET, P. ET AL.: "Side-effects of a systemic injection of linear polyethylenimine-DNA complexes.", J GENE MED, vol. 4, no. 1, 2002, pages 84 - 91
DAVIS, M.E.Z.G. CHEND.M. SHIN: "Nanoparticle therapeutics: an emerging treatment modality for cancer", NAT REV DRUG DISCOV, vol. 7, no. 9, 2008, pages 771 - 82, XP055801549, DOI: 10.1038/nrd2614
DENT, M.F ET AL.: "The methylene blue colorimetric microassay for determining cell line response to growth factors", CYTOTECHNOLOGY, vol. 17, no. 1, 1995, pages 27 - 33
EIGENBROT, C. ET AL.: "Structural basis for high-affinity HER2 receptor binding by an engineered protein.", PROC NATL ACAD SCI U S A, vol. 107, no. 34, 2010, pages 15039 - 44, XP009148172, DOI: 10.1073/pnas.1005025107
GEBHART, C.L. ET AL.: "Design and formulation of polyplexes based on pluronic-polyethyleneimine conjugates for gene transfer.", BIOCONJUG CHEM, vol. 13, no. 5, 2002, pages 937 - 44
GOULA, D. ET AL.: "Polyethylenimine-based intravenous delivery of transgenes to mouse lung", GENE THER, vol. 5, no. 9, 1998, pages 1291 - 5, XP037772106, DOI: 10.1038/sj.gt.3300717
HOBEL, S. ET AL.: "Maltose- and maltotriose-modified, hyperbranched poly(ethylene imine)s (OM-PEIs): Physicochemical and biological properties of DNA and siRNA complexes", J CONTROL RELEASE, vol. 149, no. 2, 2011, pages 146 - 58, XP027595350, DOI: 10.1016/j.jconrel.2010.10.008
JAGER, M. ET AL.: "Branched and linear poly(ethylene imine)-based conjugates: synthetic modification, characterization, and application", CHEM SOC REV, vol. 41, no. 13, 2012, pages 4755 - 67, XP055497987, DOI: 10.1039/c2cs35146c
JEONG, G.J. ET AL.: "Biodistribution and tissue expression kinetics of plasmid DNA complexed with polyethylenimines of different molecular weight and structure", J CONTROL RELEASE, vol. 118, no. 1, 2007, pages 118 - 25, XP005903639, DOI: 10.1016/j.jconrel.2006.12.009
KAWAKAMI, S. ET AL.: "Evaluation of proinflammatory cytokine production induced by linear and branched polyethylenimine/plasmid DNA complexes in mice", J PHARMACOL EXP THER, vol. 317, no. 3, 2006, pages 1382 - 90, XP055048457, DOI: 10.1124/jpet.105.100669
KIRCHEIS, R. ET AL.: "Polyethylenimine/DNA complexes shielded by transferrin target gene expression to tumors after systemic application", GENE THER, vol. 8, no. 1, 2001, pages 28 - 40, XP037774103, DOI: 10.1038/sj.gt.3301351
KLEEMANN, E. ET AL.: "Nano-carriers for DNA delivery to the lung based upon a TAT-derived peptide covalently coupled to PEG-PEI.", J CONTROL RELEASE, vol. 109, no. 1-3, 2005, pages 299 - 316, XP005204221, DOI: 10.1016/j.jconrel.2005.09.036
KLOECKNER, J ET AL.: "Photochemically enhanced gene delivery of EGF receptor-targeted DNA polyplexes.", J DRUG TARGET, vol. 12, no. 4, 2004, pages 205 - 13
LEE, K. ET AL., MACROMOL BIOSCI, vol. 10, no. 3, 2010, pages 239 - 45
LITTLE, S.R ET AL.: "Poly-beta amino ester-containing microparticles enhance the activity of nonviral genetic vaccines", PROC NATL ACAD SCI U S A, vol. 101, no. 26, 2004, pages 9534 - 9, XP055768641, DOI: 10.1073/pnas.0403549101
LIU, Y. ET AL.: "The shape of things to come: importance of design in nanotechnology for drug delivery.", THER DELIV, vol. 3, no. 2, 2012, pages 181 - 94
LOFBLOM, J. ET AL.: "Affibody molecules: engineered proteins for therapeutic, diagnostic and biotechnological applications.", FEBS LETT, vol. 584, no. 12, 2010, pages 2670 - 80
NILSSON, B. ET AL.: "A synthetic IgG-binding domain based on staphylococcal protein A", PROTEIN ENG, vol. 1, no. 2, 1987, pages 107 - 13, XP093187558, DOI: 10.1093/protein/1.2.107
OGRIS, M. ET AL.: "DNA/polyethylenimine transfection particles: influence of ligands, polymer size, and PEGylation on internalization and gene expression", AAPS PHARMSCI, 2001
OGRIS, M. ET AL.: "PEGylated DNA/transferrin-PEI complexes: reduced interaction with blood components, extended circulation in blood and potential for systemic gene delivery", GENE THER, vol. 6, no. 4, 1999, pages 595 - 605, XP037771172, DOI: 10.1038/sj.gt.3300900
OGRIS, M. ET AL.: "The size of DNA/transferrin-PEI complexes is an important factor for gene expression in cultured cells", GENE THER, vol. 5, no. 10, 1998, pages 1425 - 33, XP037771503, DOI: 10.1038/sj.gt.3300745
PARK, J.W. ET AL.: "Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery.", CLIN CANCER RES, vol. 8, no. 4, 2002, pages 1172 - 81
PETERSEN, H. ET AL.: "Polyethylenimine-graft-poly(ethylene glycol) copolymers: influence of copolymer block structure on DNA complexation and biological activities as gene delivery system", BIOCONJUG CHEM, vol. 13, no. 4, 2002, pages 845 - 54, XP055329074, DOI: 10.1021/bc025529v
RABENSTEIN, D.L.: "Heparin and heparan sulfate: structure and function", NAT PROD REP, vol. 19, no. 3, 2002, pages 312 - 31, XP009047723
REJMAN, J.A. BRAGONZIM. CONESE: "Role of clathrin- and caveolae-mediated endocytosis in gene transfer mediated by lipo- and polyplexes.", MOL THER, vol. 12, no. 3, 2005, pages 468 - 74, XP005472381, DOI: 10.1016/j.ymthe.2005.03.038
REMY, J.S. ET AL.: "Targeted gene transfer into hepatoma cells with lipopolyamine-condensed DNA particles presenting galactose ligands: a stage toward artificial viruses", PROC NATL ACAD SCI U S A, vol. 92, no. 5, 1995, pages 1744 - 8, XP000601443, DOI: 10.1073/pnas.92.5.1744
RUDOLPH, C. ET AL.: "Nonviral gene delivery to the lung with copolymer-protected and transferrin-modified polyethylenimine", BIOCHIM BIOPHYS ACTA, vol. 1573, no. 1, 2002, pages 75 - 83, XP004386975, DOI: 10.1016/S0304-4165(02)00334-3
SALIM JOUBRAN ET AL.: "Optimization of Liganded Polyethylenimine Polyethylene Glycol Vector for Nucleic Acid Delivery.", B IOCONJUGATE CHEMISTRY, vol. 25, no. 9, 14 August 2014 (2014-08-14), pages 1644 - 1654, XP055236354 *
SCH?FER, A. ET AL.: "Disconnecting the yin and yang relation of epidermal growth factor receptor (EGFR)-mediated delivery: a fully synthetic, EGFR-targeted gene transfer system avoiding receptor activation.", HUMAN GENE THERAPY, vol. 22, no. 12, 31 December 2011 (2011-12-31), pages 1463 - 1473, XP055236352 *
SCHAFFERT, D. ET AL.: "Poly (I: C)-mediated tumor growth suppression in EGF-receptor overexpressing tumors using EGF-polyethylene glycol-linear polyethylenimine as carrier.", PHARMACEUTICAL RESEARCH, vol. 28, no. 4, 6 August 2010 (2010-08-06), pages 731 - 741, XP055236351 *
SCHAFFERT, D. ET AL.: "Poly(I:C)-mediated tumor growth suppression in EGF-receptor overexpressing tumors using EGF-polyethylene glycol-linear polyethylenimine as carrier", PHARM RES, vol. 28, no. 4, 2011, pages 731 - 41, XP055236351, DOI: 10.1007/s11095-010-0225-4
See also references of EP3142673A4
SEIB, F.PA.T. JONESR. DUNCAN: "Comparison of the endocytic properties of linear and branched PEls, and cationic PAMAM dendrimers in B16f10 melanoma cells", J CONTROL RELEASE, vol. 117, no. 3, 2007, pages 291 - 300
SUH, JH.J. PAIKB.K. HWANG: "Ionization of Poly(Ethylenimine) and Poly(Allylamine) at Various Phs.", BIOORGANIC CHEMISTRY, vol. 22, no. 3, 1994, pages 318 - 327, XP024023080, DOI: 10.1006/bioo.1994.1025
UNGARO, F. ET AL.: "Spectrophotometric determination of polyethylenimine in the presence of an oligonucleotide for the characterization of controlled release formulations", J PHARM BIOMED ANAL, vol. 31, no. 1, 2003, pages 143 - 9
WAGNER, E. ET AL.: "Transferrin-polycation-DNA complexes: the effect of polycations on the structure of the complex and DNA delivery to cells", PROC NATL ACAD SCI U S A, vol. 88, no. 10, 1991, pages 4255 - 9, XP002001450, DOI: 10.1073/pnas.88.10.4255
ZHENG, M. ET AL.: "Poly(ethylene oxide) grafted with short polyethylenimine gives DNA polyplexes with superior colloidal stability, low cytotoxicity, and potent in vitro gene transfection under serum conditions.", BIOMACROMOLECULES, vol. 13, no. 3, 2012, pages 881 - 8, XP055778953, DOI: 10.1021/bm2017965
ZIEBARTH, J.D.Y. WANG: "Understanding the protonation behavior of linear polyethylenimine in solutions through Monte Carlo simulations", BIOMACROMOLECULES, 2010

Cited By (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107920993B (zh) * 2015-11-17 2020-11-20 拜昂科技医疗公司 包含含有双链聚核糖核苷酸与聚亚烷基亚胺的复合物的粒子的医药组合物
CN107920993A (zh) * 2015-11-17 2018-04-17 拜昂科技医疗公司 包含含有双链聚核糖核苷酸与聚亚烷基亚胺的复合物的粒子的新颖医药组合物
GB2555364A (en) * 2015-11-17 2018-04-25 Grund IP Group Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and polyalkyleneimine
DE202016008594U1 (de) 2015-11-17 2018-08-23 Bioncotech Therapeutics S.L Neue pharmazeutische Zusammensetzung umfassend Partikel umfassend einen Komplex eines doppelsträngigen Polyribonukleotids und eines Polyalkylenimins
DE112016003047B4 (de) 2015-11-17 2022-10-27 Highlight Therapeutics, S.L. Neue pharmazeutische zusammensetzung umfassend partikel umfassend einen komplex eines doppelsträngigen polyribonukleotids und eines polyalkylenimins
EP4183386A1 (en) 2015-11-17 2023-05-24 Highlight Therapeutics, S.L. Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
US12419967B2 (en) 2015-11-17 2025-09-23 Highlight Therapeutics, S.L. Polyinosinic—polycytidylic acid compositions and methods of making same
EA037117B1 (ru) * 2015-11-17 2021-02-09 Хайлайт Терапьютикс, С.Л. Новая фармацевтическая композиция, содержащая частицы, содержащие комплекс двухнитевого полирибонуклеотида и полиалкиленимина
ES2715251R1 (es) * 2015-11-17 2019-11-28 Bioncotech Therapeutics S L Novedosa composicion farmaceutica que comprende particulas que comprenden un complejo de un polirribonucleotido de doble cadena y una polialquilenimina
US10568971B2 (en) 2015-11-17 2020-02-25 Bioncotech Therapeutics, S.L. Pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
EP3639811A1 (en) 2015-11-17 2020-04-22 Bioncotech Therapeutics, S.L Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
WO2017085228A1 (en) 2015-11-17 2017-05-26 Bioncotech Therapeutics, S.L Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
CN109071419A (zh) * 2016-03-07 2018-12-21 韩美药品株式会社 聚乙二醇衍生物及其用途
US12139455B2 (en) 2016-03-07 2024-11-12 Hanmi Pharm. Co., Ltd. Polyethylene glycol derivative and use thereof
EP3428147A4 (en) * 2016-03-07 2019-08-28 Hanmi Pharm. Co., Ltd. Polyethylene glycol derivative and use thereof
US11603346B2 (en) 2016-03-07 2023-03-14 Hanmi Pharm. Co., Ltd. Polyethylene glycol derivative and use thereof
US11896606B2 (en) 2016-11-17 2024-02-13 Highlight Therapeutics, S.L. Pharmaceutical composition comprising particles and methods of making same
US10849921B2 (en) 2017-05-17 2020-12-01 Bioncotech Therapeutics Sl Pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
US11883424B2 (en) 2017-05-17 2024-01-30 Highlight Therapeutics, S.L. Methods of making novel pharmaceutical compositions
US12383575B2 (en) 2017-05-17 2025-08-12 Highlight Therapeutics, S.L. Polyinosinic—polycytidylic acid compositions
EP4122449A1 (en) 2017-05-17 2023-01-25 Highlight Therapeutics, S.L. Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
WO2018210439A1 (en) 2017-05-17 2018-11-22 Bioncotech Therapeutics Sl Novel pharmaceutical composition comprising particles comprising a complex of a double-stranded polyribonucleotide and a polyalkyleneimine
IL273195B1 (en) * 2017-09-27 2023-12-01 Targimmune Therapeutics Ag Castration-resistant prostate cancer
WO2019063705A1 (en) 2017-09-27 2019-04-04 Targimmune Therapeutics Ag CANCER OF THE PROSTATE RESISTANT TO CASTRATION
AU2018342909B2 (en) * 2017-09-27 2023-06-08 Targimmune Therapeutics Ag Castration resistant prostate cancer
US11679160B2 (en) 2017-09-27 2023-06-20 Targimmune Therapeutics Ag Castration resistant prostate cancer
CN111164093A (zh) * 2017-09-27 2020-05-15 塔尔格免疫治疗有限公司 去势抵抗性前列腺癌
IL273195B2 (en) * 2017-09-27 2024-04-01 Targimmune Therapeutics Ag Castration-resistant prostate cancer
JP2021516056A (ja) * 2018-03-08 2021-07-01 ターグイミューン セラピューティクス アーゲー 二本鎖ｒｎａ結合ドメインを含む組換えタンパク質
WO2020201568A1 (en) 2019-04-03 2020-10-08 Targimmune Therapeutics Ag Immunotherapy for the treatment of cancer
WO2020263782A1 (en) * 2019-06-24 2020-12-30 North Carolina State University Methods and compositions for modifying nucleic acids and for killing cells
WO2021001417A1 (en) * 2019-07-02 2021-01-07 Biontech Rna Pharmaceuticals Gmbh Rna formulations suitable for therapy
WO2021001023A1 (en) * 2019-07-02 2021-01-07 Biontech Rna Pharmaceuticals Gmbh Rna formulations suitable for therapy
WO2022074152A1 (en) 2020-10-08 2022-04-14 Targimmune Therapeutics Ag Immunotherapy for the treatment of cancer
CN116348142A (zh) * 2020-10-08 2023-06-27 塔尔格免疫治疗有限公司 用于治疗癌症的免疫疗法
WO2023079142A3 (en) * 2021-11-05 2023-06-22 Targimmune Therapeutics Ag Targeted linear conjugates comprising polyethyleneimine and polyethylene glycol and polyplexes comprising the same
WO2023079142A2 (en) 2021-11-05 2023-05-11 Targimmune Therapeutics Ag Targeted linear conjugates comprising polyethyleneimine and polyethylene glycol and polyplexes comprising the same
WO2024100046A1 (en) * 2022-11-07 2024-05-16 Targimmune Therapeutics Ag Targeted linear conjugates comprising polyethyleneimine and polyethylene glycol and polyplexes comprising the same
WO2024100040A1 (en) 2022-11-07 2024-05-16 Targimmune Therapeutics Ag Psma-targeting linear conjugates comprising polyethyleneimine and polyethylene glycol and polyplexes comprising the same
WO2024100044A1 (en) 2022-11-07 2024-05-16 Targimmune Therapeutics Ag Polyplexes of nucleic acids and targeted conjugates comprising polyethyleneimine and polyethylene glycol
WO2025238236A1 (en) 2024-05-16 2025-11-20 Targimmune Therapeutics Ag Polyplexes of nucleic acids and targeted conjugates comprising polyethyleneimine and polyethylene glycol

Also Published As

Publication number Publication date
US20170072063A1 (en) 2017-03-16
JP6753843B2 (ja) 2020-09-16
JP2020196739A (ja) 2020-12-10
CN116966311A (zh) 2023-10-31
IL248890B (en) 2021-10-31
EP3142673A1 (en) 2017-03-22
BR112016026581A2 (pt) 2017-10-31
EP3142673A4 (en) 2018-01-03
IL287206A (en) 2021-12-01
US20190192563A1 (en) 2019-06-27
JP2024028995A (ja) 2024-03-05
KR20170005052A (ko) 2017-01-11
JP2017521090A (ja) 2017-08-03
IL287206B1 (en) 2023-10-01
US11298376B2 (en) 2022-04-12
US20220339189A1 (en) 2022-10-27
RU2771104C2 (ru) 2022-04-26
CN116966310A (zh) 2023-10-31
JP7406475B2 (ja) 2023-12-27
CA2949017A1 (en) 2015-11-19
KR102472590B1 (ko) 2022-11-30
US20190262395A1 (en) 2019-08-29
AU2015260725A1 (en) 2016-12-22
RU2016146389A3 (https=) 2018-12-26
MX2020012698A (es) 2021-02-15
CN106687121A (zh) 2017-05-17
PH12016502258A1 (en) 2017-02-27
AU2021203336C1 (en) 2025-05-08
KR102589295B1 (ko) 2023-10-13
IL287206B2 (en) 2024-02-01
IL248890A0 (en) 2017-01-31
KR20220163536A (ko) 2022-12-09
MX2016014881A (es) 2017-05-01
SG10201911695SA (en) 2020-01-30
PH12016502258B1 (en) 2022-08-03
AU2021203336A1 (en) 2021-06-24
ZA201608042B (en) 2018-11-28
RU2016146389A (ru) 2018-06-15
AU2015260725B2 (en) 2021-02-25
SG11201609442YA (en) 2016-12-29
NZ764423A (en) 2021-08-27
AU2021203336B2 (en) 2024-11-07
NZ727092A (en) 2021-07-30
US10278991B2 (en) 2019-05-07
MX377654B (es) 2025-03-11
MA39970A (fr) 2015-11-19
US10543232B2 (en) 2020-01-28

Similar Documents

Publication Publication Date Title
AU2021203336B2 (en) Improved polyethyleneimine polyethyleneglycol vectors
KR102052225B1 (ko) 관능성 pla-peg 공중합체, 그의 나노입자, 그의 제조법, 및 표적화 약물 전달 및 영상화를 위한 용도
US8697667B2 (en) Cyclodextrin-modified polyamines for delivery of therapeutic molecules
WO2021134026A2 (en) Compositions and methods for nucleic acid delivery
Yu et al. Improved method for synthesis of low molecular weight protamine–siRNA conjugate
Luo et al. Artificial peptides for antitumoral siRNA delivery
WO2008070141A2 (en) Compositions for delivery of therapeutic agents
NZ764423B2 (en) Improved polyethyleneimine polyethyleneglycol vectors
EP2388016A1 (en) Non-viral nucleic acid molecules delivery systems
BR112016026581B1 (pt) Poliplexo de um rna de fita dupla (dsrna) e um conjugado polimérico, uso do poliplexo e composições farmacêuticas que o compreendem
WO2025238236A1 (en) Polyplexes of nucleic acids and targeted conjugates comprising polyethyleneimine and polyethylene glycol
WO2023247781A1 (en) Peptides for intracellular delivery
WO2024190929A1 (ja) タンパク質送達用ｐＨ応答性担体
Hamilton Advanced drug delivery systems from tailored building blocks: Controlled intracellular delivery of bioactive cargo

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: 15793532

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 248890

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2017512466

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 15310735

Country of ref document: US

Ref document number: 12016502258

Country of ref document: PH

ENP Entry into the national phase

Ref document number: 2949017

Country of ref document: CA

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: MX/A/2016/014881

Country of ref document: MX

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112016026581

Country of ref document: BR

ENP Entry into the national phase

Ref document number: 20167033997

Country of ref document: KR

Kind code of ref document: A

REEP Request for entry into the european phase

Ref document number: 2015793532

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2015793532

Country of ref document: EP

ENP Entry into the national phase

Ref document number: 2016146389

Country of ref document: RU

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 2015260725

Country of ref document: AU

Date of ref document: 20150514

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 112016026581

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20161111