WO2022076595A1 - Formulations for suprachoroidal administration such as gel formulations - Google Patents

Formulations for suprachoroidal administration such as gel formulations Download PDF

Info

Publication number
WO2022076595A1
WO2022076595A1 PCT/US2021/053818 US2021053818W WO2022076595A1 WO 2022076595 A1 WO2022076595 A1 WO 2022076595A1 US 2021053818 W US2021053818 W US 2021053818W WO 2022076595 A1 WO2022076595 A1 WO 2022076595A1
Authority
WO
WIPO (PCT)
Prior art keywords
days
pharmaceutical composition
hours
aav
administered
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/US2021/053818
Other languages
English (en)
French (fr)
Inventor
Jared BEE
Tristan James MARSHALL
Sherri VAN EVEREN
Stephen Joseph Pakola
Nicholas Alexander Piers Sascha BUSS
Anthony Ray O'berry
Jesse I. Yoo
Ewa BUDZYNSKI
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.)
Regenxbio Inc
Original Assignee
Regenxbio Inc
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 Regenxbio Inc filed Critical Regenxbio Inc
Priority to MX2023004005A priority Critical patent/MX2023004005A/es
Priority to JP2023521545A priority patent/JP2023545424A/ja
Priority to AU2021356645A priority patent/AU2021356645A1/en
Priority to CA3194861A priority patent/CA3194861A1/en
Priority to CN202180076844.2A priority patent/CN116635004A/zh
Priority to KR1020237014819A priority patent/KR20230106598A/ko
Priority to IL301947A priority patent/IL301947A/en
Priority to EP21801750.7A priority patent/EP4225380A1/en
Priority to US18/030,616 priority patent/US20230414788A1/en
Publication of WO2022076595A1 publication Critical patent/WO2022076595A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0075—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the delivery route, e.g. oral, subcutaneous
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0008—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition
    • A61K48/0025—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid
    • A61K48/0041—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'non-active' part of the composition delivered, e.g. wherein such 'non-active' part is not delivered simultaneously with the 'active' part of the composition wherein the non-active part clearly interacts with the delivered nucleic acid the non-active part being polymeric
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/0091—Purification or manufacturing processes for gene therapy compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/22—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • 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
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

Definitions

  • the rate of transduction at a site of injection after suprachoroidal administration is equal to or higher as compared to the rate of transduction at a site of injection after suprachoroidal administration of a reference pharmaceutical composition
  • the reference pharmaceutical composition comprises the recombinant AAV comprising the expression cassette encoding the transgene, wherein an amount of the recombinant AAV genome copies is the same when the pharmaceutical composition or the reference pharmaceutical composition is administered to the suprachoroidal space, and wherein the reference pharmaceutical composition has a lower viscosity and/or lower elastic modulus than the pharmaceutical composition at about 32-35°C.
  • the pharmaceutical composition is administered in an injection time of about 10-15 seconds. In some embodiments, the pharmaceutical composition is administered in an injection time of about 5-30 seconds.
  • FIG. 4 Gelation temperature as a function of formulation composition surface plot from design of experiments study.
  • FIG. 32 Viscosity versus shear rate at 5°C for Formulation B.
  • FIG. 33 Viscosity versus shear rate at 5°C for Formulation C.
  • FIG. 37 Differential Scanning Fluorometry Profiles of Control (S-0DGN) and
  • Formulations A S-ODGO
  • B S-0DGP
  • C S-0DGQ
  • a pharmaceutical composition provided herein has a viscosity of ⁇ 183 mPas at 20°C. In some embodiments, a pharmaceutical composition provided herein has a viscosity of ⁇ 183 mPas at 5°C. Because viscosity depends on shear rate, the “viscosity” of the pharmaceutical composition is the viscosity at any point between a shear rate of 0.01 s-1 to 100,000 s-1. In some embodiments, the unit for viscosity can be defined as cP or mPas. In some cases, cP and mPas are used interchangeably.
  • the pharmaceutical composition results in reduced vasodilation and/or vascular leakage when the pharmaceutical composition is administered in the SCS as compared to when the pharmaceutical composition is administered subretinally or intravitreously (see Section 4.2.4). In some embodiments, the pharmaceutical composition results in reduced vasodilation and/or vascular leakage when the pharmaceutical composition is administered in the SCS as compared to when a reference pharmaceutical composition is administered subretinally, intravitreously, or in the SCS (see Section 4.2.4). In some embodiments, the reference pharmaceutical composition includes the recombinant adeno- associated virus (AAV) vector comprising the expression cassette encoding the transgene.
  • AAV adeno- associated virus
  • a pharmaceutical composition that is more viscous and/or elastic and/or gelled at about 32-35°C has a viscosity value that is higher than the viscosity of water at about 32-35°C. In some embodiments, a pharmaceutical composition that is more viscous and gelled at about 32-35°C has a viscosity value and/or an elastic modulus value that is higher than the viscosity and/or elastic modulus of a solution normally used for subretinal injection at about 32-35°C.
  • the clearance time of the pharmaceutical composition after the pharmaceutical composition is administered to the SCS is equal to or higher than the clearance time of a reference pharmaceutical composition after the reference pharmaceutical composition is administered subretinally or intravitreously. In some embodiments, the clearance time of the pharmaceutical composition after the pharmaceutical composition is administered to the SCS is equal to or higher than the clearance time of a reference pharmaceutical composition after the reference pharmaceutical composition is administered to the SCS.
  • the thickness obtained at the site of injection after a pharmaceutical composition e.g., a pharmaceutical composition comprising an AAV comprising an expression cassette encoding a transgene
  • a pharmaceutical composition e.g., a pharmaceutical composition comprising an AAV comprising an expression cassette encoding a transgene
  • the thickness obtained at the site of injection after a pharmaceutical composition is greater than after the same pharmaceutical composition administered by subretinal administration or by intravitreous administration.
  • vectors delivered using a pharmaceutical composition that has medium to high viscosity and/or elastic modulus (G’) at about 32-35°C are more effective than vectors delivered using a pharmaceutical composition that has a low viscosity and/or elastic modulus (G’) at about 32-35°C (e.g., when administered in the SCS).
  • vectors delivered using a formulation that has medium to high viscosity and/or elastic modulus (G’) at about 32-35°C results in improved vision as compared to vectors delivered using a formulation which has low viscosity and/or elastic modulus (G’) at about 32-35°C.
  • the recombinant vectors provided herein comprise the following elements in the following order: a) a first ITR sequence, b) a first linker sequence, c) a constitutive or a hypoxia-inducible promoter sequence, d) a second linker sequence, e) an intron sequence, f) a third linker sequence, g) a first UTR sequence, h) a sequence encoding the transgene (e.g., an anti-VEGF antigen-binding fragment moiety), i) a second UTR sequence, j) a fourth linker sequence, k) a poly A sequence, 1) a fifth linker sequence, and m) a second ITR sequence.
  • the AAV (AAV viral vectors) provided herein comprise the following elements in the following order: a) a constitutive or a hypoxia-inducible promoter sequence, and b) a sequence encoding the transgene (e.g., an anti-VEGF antigen-binding fragment moiety).
  • the transgene is a fully human post-translationally modified (HuPTM) antibody against VEGF.
  • the fully human post- translationally modified antibody against VEGF is a fully human post-translationally modified antigen-binding fragment of a monoclonal antibody (mAb) against VEGF (“HuPTMFabVEGFi”).
  • the signal peptide is MYRMQLLLLIALSLALVTNS (SEQ ID NO: 55). In some embodiments, the signal peptide is derived from IL-2 signal sequence. In some embodiments, the viral vector comprises a signal peptide from any signal peptide disclosed in Table 1, such as MNFLLSWVHW SLALLLYLHH AKWSQA (VEGF-A signal peptide) (SEQ ID NO: 5); MERAAPSRRV PLPLLLLGGL ALLAAGVDA (Fibulin-1 signal peptide) (SEQ ID NO: 6); MAPLRPLLIL ALLAWVALA (Vitronectin signal peptide) (SEQ ID NO: 7); MRLLAKIICLMLWAICVA (Complement Factor H signal peptide) (SEQ ID NO: 8); MRLLAFLSLL ALVLQETGT (Opticin signal peptide) (SEQ ID NO: 9); MKWVTFISLLFLFSSAYS (Albumin signal peptide) (SEQ ID NO: 5
  • nucleic acids e.g., polynucleotides
  • nucleic acid sequences disclosed herein may be codon-optimized, for example, via any codon-optimization technique known to one of skill in the art (see, e.g., review by Quax et al., 2015, Mol Cell 59: 149-161).
  • AAV8 vectors comprising a viral genome comprising an expression cassette for expression of the transgene, under the control of regulatory elements and flanked by ITRs and a viral capsid that has the amino acid sequence of the AAV8 capsid protein or is at least 95%, 96%, 97%, 98%, 99% or 99.9% identical to the amino acid sequence of the AAV8 capsid protein (SEQ ID NO: 48) while retaining the biological function of the AAV8 capsid.
  • rAAV8-based or rAAV9-based viral vectors encoding human-alpha-sarcoglycan-gamma- sarcoglycan. In some embodiments, provided herein are rAAV8-based or rAAV9-based viral vectors encoding huFollistatin344. In some embodiments, provided herein are rAAV8-based or rAAV9-based viral vectors encoding human-alpha-sarcoglycan-gamma-sarcoglycan. In some embodiments, provided herein are rAAV8-based or rAAV9-based viral vectors encoding CLN2.
  • Antibody Prescreening at Animal Supplier blood (at least ImL) from about 90 female monkeys is collected from each animal via a femoral vein and placed into tubes containing no anticoagulant. Another vein may be used for collection, as needed. Animals are selected as study candidates based on the pre-screening results. Blood is allowed to clot at room temperature and centrifuged within 1 hour to obtain serum. Serum is divided into 2 aliquots and placed into cryovials and maintained on dry ice prior to storage at approximately -70°C. Samples are shipped overnight on dry ice for analysis. Samples are then analyzed for anti-AAV8 neutralizing antibodies (NAbs) by any acceptable method. Animals are selected for shipment based on anti-AAV8 Nab results.
  • NAbs anti-AAV8 neutralizing antibodies
  • Test Article 1 (gel) had an impact on delivery to the retina and choroid, compared to the Control formulation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Inorganic Chemistry (AREA)
  • Manufacturing & Machinery (AREA)
  • Neurosurgery (AREA)
  • Dermatology (AREA)
  • Zoology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
PCT/US2021/053818 2020-10-07 2021-10-06 Formulations for suprachoroidal administration such as gel formulations Ceased WO2022076595A1 (en)

Priority Applications (9)

Application Number Priority Date Filing Date Title
MX2023004005A MX2023004005A (es) 2020-10-07 2021-10-06 Formulaciones para administración supracoroidea tales como formulaciones de gel.
JP2023521545A JP2023545424A (ja) 2020-10-07 2021-10-06 ゲル製剤などの脈絡膜上投与用製剤
AU2021356645A AU2021356645A1 (en) 2020-10-07 2021-10-06 Formulations for suprachoroidal administration such as gel formulations
CA3194861A CA3194861A1 (en) 2020-10-07 2021-10-06 Formulations for suprachoroidal administration such as gel formulations
CN202180076844.2A CN116635004A (zh) 2020-10-07 2021-10-06 用于脉络膜上施用的制剂如凝胶制剂
KR1020237014819A KR20230106598A (ko) 2020-10-07 2021-10-06 겔 제형과 같은 맥락막위 투여용 제형
IL301947A IL301947A (en) 2020-10-07 2021-10-06 Formulations for suprachoroidal administration such as gel formulations
EP21801750.7A EP4225380A1 (en) 2020-10-07 2021-10-06 Formulations for suprachoroidal administration such as gel formulations
US18/030,616 US20230414788A1 (en) 2020-10-07 2021-10-06 Formulations for suprachoroidal administration such as gel formulations

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202063088886P 2020-10-07 2020-10-07
US63/088,886 2020-10-07
US202163147584P 2021-02-09 2021-02-09
US63/147,584 2021-02-09

Publications (1)

Publication Number Publication Date
WO2022076595A1 true WO2022076595A1 (en) 2022-04-14

Family

ID=78483535

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2021/053818 Ceased WO2022076595A1 (en) 2020-10-07 2021-10-06 Formulations for suprachoroidal administration such as gel formulations

Country Status (10)

Country Link
US (1) US20230414788A1 (https=)
EP (1) EP4225380A1 (https=)
JP (1) JP2023545424A (https=)
KR (1) KR20230106598A (https=)
AU (1) AU2021356645A1 (https=)
CA (1) CA3194861A1 (https=)
IL (1) IL301947A (https=)
MX (1) MX2023004005A (https=)
TW (1) TW202228646A (https=)
WO (1) WO2022076595A1 (https=)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11697801B2 (en) 2017-12-19 2023-07-11 Akouos, Inc. AAV-mediated delivery of therapeutic antibodies to the inner ear
WO2023196835A1 (en) * 2022-04-06 2023-10-12 Regenxbio Inc. Formulations for suprachoroidal administration such as gel formulations
WO2024073669A1 (en) 2022-09-30 2024-04-04 Regenxbio Inc. Treatment of ocular diseases with recombinant viral vectors encoding anti-vegf fab
WO2024238867A1 (en) 2023-05-16 2024-11-21 Regenxbio Inc. Vectorized anti-complement antibodies and administration thereof
US12365726B2 (en) 2020-12-01 2025-07-22 Akouos, Inc. Anti-VEGF antibody constructs

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3886946A1 (en) 2019-06-05 2021-10-06 Regeneron Pharmaceuticals, Inc. Devices and methods for precision dose delivery
US20240307553A1 (en) * 2021-04-01 2024-09-19 Pfizer Inc. Pharmaceutical compositions containing adeno-associated viral vector
CN116350801A (zh) * 2022-11-22 2023-06-30 四川至善唯新生物科技有限公司 一种重组腺相关病毒载体的药物组合物及其用途
USD1120314S1 (en) 2022-11-30 2026-03-24 Regeneron Pharmaceuticals, Inc. Dose delivery device

Citations (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6596535B1 (en) 1999-08-09 2003-07-22 Targeted Genetics Corporation Metabolically activated recombinant viral vectors and methods for the preparation and use
US7282199B2 (en) 2001-12-17 2007-10-16 The Trustees Of The University Of Pennsylvania Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor
US7456683B2 (en) 2005-06-09 2008-11-25 Panasonic Corporation Amplitude error compensating device and quadrature skew error compensating device
US7906111B2 (en) 2003-09-30 2011-03-15 The Trustees Of The University Of Pennsylvania Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses therefor
US7947267B2 (en) * 2004-10-08 2011-05-24 Potentia Pharmaceuticals, Inc. Viral complement control proteins for eye disorders
US20130224836A1 (en) 2010-10-27 2013-08-29 Jichi Medical University Adeno-Associated Virus Virion for Gene Transfer to Nervous System Cells
US8524446B2 (en) 2001-11-13 2013-09-03 The Trustees Of The University Of Pennsylvania Method for detecting adeno-associated virus
US8628966B2 (en) 2010-04-30 2014-01-14 City Of Hope CD34-derived recombinant adeno-associated vectors for stem cell transduction and systemic therapeutic gene transfer
US8734809B2 (en) 2009-05-28 2014-05-27 University Of Massachusetts AAV's and uses thereof
US8927514B2 (en) 2010-04-30 2015-01-06 City Of Hope Recombinant adeno-associated vectors for targeted treatment
US8999678B2 (en) 2005-04-07 2015-04-07 The Trustees Of The University Of Pennsylvania Method of increasing the function of an AAV vector
US20150126588A1 (en) 2012-05-09 2015-05-07 Oregon Health & Science University Adeno associated virus plasmids and vectors
US9169299B2 (en) 2011-08-24 2015-10-27 The Board Of Trustees Of The Leleand Stanford Junior University AAV capsid proteins for nucleic acid transfer
US9193956B2 (en) 2011-04-22 2015-11-24 The Regents Of The University Of California Adeno-associated virus virions with variant capsid and methods of use thereof
US20150374803A1 (en) 2013-03-13 2015-12-31 The Children's Hospital Of Philadelphia Adeno-associated virus vectors and methods of use thereof
GB2531910A (en) 2014-09-19 2016-05-04 Prec Ocular Ltd Ophthalmic delivery device
US20160215024A1 (en) 2013-10-11 2016-07-28 Massachusetts Eye & Ear Infirmary Methods of Predicting Ancestral Virus Sequences and Uses Thereof
US9409953B2 (en) 2011-02-10 2016-08-09 The University Of North Carolina At Chapel Hill Viral vectors with modified transduction profiles and methods of making and using the same
US20160310417A1 (en) * 2013-12-20 2016-10-27 Emory University Formulations and Methods For Targeted Ocular Delivery of Therapeutic Agents
US9585971B2 (en) 2013-09-13 2017-03-07 California Institute Of Technology Recombinant AAV capsid protein
US20170067908A1 (en) 2014-04-25 2017-03-09 Oregon Health & Science University Methods of viral neutralizing antibody epitope mapping
WO2017181021A1 (en) 2016-04-15 2017-10-19 Regenxbio Inc. Treatment of ocular diseases with fully-human post-translationally modified anti-vegf fab
US20170340756A1 (en) * 2014-12-05 2017-11-30 Exchange Imaging Technologies Gmbh Pharmaceutical formulation having reverse thermal gelation properties for local delivery of nanoparticles
WO2019173334A1 (en) * 2018-03-05 2019-09-12 The Schepens Eye Research Institute, Inc. Engineered vegf variants for retinal neuroprotection, promotion of axon growth and axon regeneration
CN111494305A (zh) * 2020-05-25 2020-08-07 海宁凤鸣叶绿素有限公司 一种叶黄素脂质体眼用温敏型原位凝胶制剂及其制备方法
US10912883B2 (en) 2017-11-04 2021-02-09 Altaviz, Llc Gas-powered fluid injection system

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140378401A1 (en) * 2013-06-21 2014-12-25 Gnt, Llc Ophthalmic Lipophilic and Hydrophilic Drug Delivery Vehicle Formulations
CN105147595B (zh) * 2015-08-18 2018-08-31 吉林大学 吡嘧司特钾温度敏感性水凝胶及其制备方法
CN107854424A (zh) * 2017-10-30 2018-03-30 沈小玲 一种阿奇霉素眼用原位凝胶及其制备方法

Patent Citations (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7125717B2 (en) 1999-08-09 2006-10-24 Targeted Genetics Corporation Metabolically activated recombinant viral vectors and methods for their preparation and use
US6596535B1 (en) 1999-08-09 2003-07-22 Targeted Genetics Corporation Metabolically activated recombinant viral vectors and methods for the preparation and use
US8524446B2 (en) 2001-11-13 2013-09-03 The Trustees Of The University Of Pennsylvania Method for detecting adeno-associated virus
US7282199B2 (en) 2001-12-17 2007-10-16 The Trustees Of The University Of Pennsylvania Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor
US7790449B2 (en) 2001-12-17 2010-09-07 The Trustees Of The University Of Pennsylvania Adeno-associated virus (AAV) serotype 8 sequences, vectors containing the same, and uses therefor
US8962332B2 (en) 2001-12-17 2015-02-24 The Trustees Of The University Of Pennsylvania Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor
US8318480B2 (en) 2001-12-17 2012-11-27 The Trustees Of The University Of Pennsylvania Adeno-associated virus (AAV) serotype 8 sequences, vectors containing same, and uses therefor
US7906111B2 (en) 2003-09-30 2011-03-15 The Trustees Of The University Of Pennsylvania Adeno-associated virus (AAV) clades, sequences, vectors containing same, and uses therefor
US7947267B2 (en) * 2004-10-08 2011-05-24 Potentia Pharmaceuticals, Inc. Viral complement control proteins for eye disorders
US8999678B2 (en) 2005-04-07 2015-04-07 The Trustees Of The University Of Pennsylvania Method of increasing the function of an AAV vector
US7456683B2 (en) 2005-06-09 2008-11-25 Panasonic Corporation Amplitude error compensating device and quadrature skew error compensating device
US9284357B2 (en) 2009-05-28 2016-03-15 University Of Massachusetts AAV's and uses thereof
US8734809B2 (en) 2009-05-28 2014-05-27 University Of Massachusetts AAV's and uses thereof
US8628966B2 (en) 2010-04-30 2014-01-14 City Of Hope CD34-derived recombinant adeno-associated vectors for stem cell transduction and systemic therapeutic gene transfer
US8927514B2 (en) 2010-04-30 2015-01-06 City Of Hope Recombinant adeno-associated vectors for targeted treatment
US20130224836A1 (en) 2010-10-27 2013-08-29 Jichi Medical University Adeno-Associated Virus Virion for Gene Transfer to Nervous System Cells
US9409953B2 (en) 2011-02-10 2016-08-09 The University Of North Carolina At Chapel Hill Viral vectors with modified transduction profiles and methods of making and using the same
US9587282B2 (en) 2011-04-22 2017-03-07 The Regents Of The University Of California Adeno-associated virus virions with variant capsid and methods of use thereof
US9193956B2 (en) 2011-04-22 2015-11-24 The Regents Of The University Of California Adeno-associated virus virions with variant capsid and methods of use thereof
US20160376323A1 (en) 2011-04-22 2016-12-29 The Regents Of The University Of California Adeno-associated virus virions with variant capsid and methods of use thereof
US9458517B2 (en) 2011-04-22 2016-10-04 The Regents Of The University Of California Adeno-associated virus virions with variant capsid and methods of use thereof
US9169299B2 (en) 2011-08-24 2015-10-27 The Board Of Trustees Of The Leleand Stanford Junior University AAV capsid proteins for nucleic acid transfer
US20150126588A1 (en) 2012-05-09 2015-05-07 Oregon Health & Science University Adeno associated virus plasmids and vectors
US20150374803A1 (en) 2013-03-13 2015-12-31 The Children's Hospital Of Philadelphia Adeno-associated virus vectors and methods of use thereof
US9585971B2 (en) 2013-09-13 2017-03-07 California Institute Of Technology Recombinant AAV capsid protein
US20160215024A1 (en) 2013-10-11 2016-07-28 Massachusetts Eye & Ear Infirmary Methods of Predicting Ancestral Virus Sequences and Uses Thereof
US20170051257A1 (en) 2013-10-11 2017-02-23 Massachusetts Eye And Ear Infirmary Methods of predicting ancestral virus sequences and uses thereof
US20160310417A1 (en) * 2013-12-20 2016-10-27 Emory University Formulations and Methods For Targeted Ocular Delivery of Therapeutic Agents
US20170067908A1 (en) 2014-04-25 2017-03-09 Oregon Health & Science University Methods of viral neutralizing antibody epitope mapping
GB2531910A (en) 2014-09-19 2016-05-04 Prec Ocular Ltd Ophthalmic delivery device
US20170340756A1 (en) * 2014-12-05 2017-11-30 Exchange Imaging Technologies Gmbh Pharmaceutical formulation having reverse thermal gelation properties for local delivery of nanoparticles
WO2017181021A1 (en) 2016-04-15 2017-10-19 Regenxbio Inc. Treatment of ocular diseases with fully-human post-translationally modified anti-vegf fab
US10912883B2 (en) 2017-11-04 2021-02-09 Altaviz, Llc Gas-powered fluid injection system
WO2019173334A1 (en) * 2018-03-05 2019-09-12 The Schepens Eye Research Institute, Inc. Engineered vegf variants for retinal neuroprotection, promotion of axon growth and axon regeneration
CN111494305A (zh) * 2020-05-25 2020-08-07 海宁凤鸣叶绿素有限公司 一种叶黄素脂质体眼用温敏型原位凝胶制剂及其制备方法

Non-Patent Citations (18)

* Cited by examiner, † Cited by third party
Title
"Global Data On Visual Impairments 2010", 2012, WORLD HEALTH ORGANIZATION
ALBA ET AL.: "Gutless adenovirus: last generation adenovirus for gene therapy", GENE THERAPY, vol. 12, 2005, pages S18 - S27, XP008102765, DOI: 10.1038/sj.gt.3302612
CAS , no. 9003-11-6
CHIANG, IOVS, vol. 58, no. 1, 2017, pages 545 - 554
CHITNIS, G.D. ET AL.: "A resistance-sensing mechanical injector for the precise delivery of liquids to target tissue", NATBIOMEDENG, vol. 3, 2019, pages 621 - 631, XP036854623, Retrieved from the Internet <URL:https://doi.org/10.1038/s41551-019-0350-2> DOI: 10.1038/s41551-019-0350-2
COURTOIS ET AL., MABS, vol. 8, 2016, pages 99 - 112
FRANCOIS ET AL., MOLECULAR THERAPY METHODS & CLINICAL DEVELOPMENT, vol. 10, 2018, pages 223 - 236
GONGALVES, VIROLOGY JOURNAL, vol. 2, 2005, pages 43
MCCARTY ET AL., GENE THERAPY, vol. 8, no. 16, 2001, pages 1248 - 1254
QUAX ET AL., MOL CELL, vol. 59, 2015, pages 149 - 161
SHI ET AL., SCI. ADV., vol. 6, 2020, pages eaaz3621
TAYLOR ET AL., GELS, vol. 3, no. 1, March 2017 (2017-03-01), pages 4
TKACOVA ET AL., MEASUREMENT 2011, PROCEEDINGS OF THE 8TH INTERNATIONAL CONFERENCE, SMOLENICE, SLOVAKIA, 2011
TSUI, T. Y. ET AL., HEPATOLOGY, vol. 42, 2005, pages 335 - 342
WU, HUMAN GENE THERAPY, vol. 18, no. 2, 2007, pages 171 - 82
XU L ET AL., INVEST. OPTHAL. VIS. SCI., vol. 54, 2013, pages 1616 - 1624
ZEINAB ET AL., EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol. 114, 2017, pages 119 - 13
ZINN ET AL., CELL REP., vol. 12, no. 6, 2015, pages 1056 - 1068

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11697801B2 (en) 2017-12-19 2023-07-11 Akouos, Inc. AAV-mediated delivery of therapeutic antibodies to the inner ear
US12077783B2 (en) 2017-12-19 2024-09-03 Akouos, Inc. AAV-mediated delivery of antibodies to the inner ear
US12275960B2 (en) 2017-12-19 2025-04-15 Akouos, Inc. AAV-mediated delivery of therapeutic antibodies to the inner ear
US12365726B2 (en) 2020-12-01 2025-07-22 Akouos, Inc. Anti-VEGF antibody constructs
WO2023196835A1 (en) * 2022-04-06 2023-10-12 Regenxbio Inc. Formulations for suprachoroidal administration such as gel formulations
WO2024073669A1 (en) 2022-09-30 2024-04-04 Regenxbio Inc. Treatment of ocular diseases with recombinant viral vectors encoding anti-vegf fab
WO2024238867A1 (en) 2023-05-16 2024-11-21 Regenxbio Inc. Vectorized anti-complement antibodies and administration thereof

Also Published As

Publication number Publication date
JP2023545424A (ja) 2023-10-30
CA3194861A1 (en) 2022-04-14
MX2023004005A (es) 2023-06-06
TW202228646A (zh) 2022-08-01
AU2021356645A9 (en) 2025-03-20
US20230414788A1 (en) 2023-12-28
IL301947A (en) 2023-06-01
EP4225380A1 (en) 2023-08-16
KR20230106598A (ko) 2023-07-13
AU2021356645A1 (en) 2023-05-25

Similar Documents

Publication Publication Date Title
AU2021356645A9 (en) Formulations for suprachoroidal administration such as gel formulations
WO2022076591A1 (en) Formulations for suprachoroidal administration such as formulations with aggregate formation
US20240024508A1 (en) Formulations for suprachoroidal administration such as high viscosity formulations
JP2023544797A5 (https=)
CA3148376A1 (en) Methods of treating retinal neovascular diseases using aav2 variants encoding aflibercept________________________________
CA3215855A1 (en) Methods of treating ocular diseases using aav2 variants encoding aflibercept
KR20240145489A (ko) 아플리베르셉트를 코딩하는 aav2 변이체를 사용하여 안구 신생혈관 질환을 치료하는 방법
TW202117016A (zh) 使用編碼阿柏西普(aflibercept)之aav2變異體治療眼睛新生血管性疾病的方法
US20250339555A1 (en) Formulations for suprachoroidal administration such as formulations with aggregate formation
WO2023196873A1 (en) Pharmaceutical composition comprising a recombinant adeno-associated virus vector with an expression cassette encoding a transgene forsuprachoidal administration
WO2023196835A1 (en) Formulations for suprachoroidal administration such as gel formulations
CN116635004A (zh) 用于脉络膜上施用的制剂如凝胶制剂
CN116546975A (zh) 用于脉络膜上施用的制剂诸如高粘度制剂
CN116601299A (zh) 用于脉络膜上施用的制剂诸如具有聚集体形成的制剂

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: 21801750

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 3194861

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2023521545

Country of ref document: JP

REG Reference to national code

Ref country code: BR

Ref legal event code: B01A

Ref document number: 112023006571

Country of ref document: BR

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2021801750

Country of ref document: EP

Effective date: 20230508

WWE Wipo information: entry into national phase

Ref document number: 202180076844.2

Country of ref document: CN

ENP Entry into the national phase

Ref document number: 2021356645

Country of ref document: AU

Date of ref document: 20211006

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 112023006571

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20230406