[go: up one dir, main page]

WO2022166949A1 - Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation - Google Patents

Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation Download PDF

Info

Publication number
WO2022166949A1
WO2022166949A1 PCT/CN2022/075348 CN2022075348W WO2022166949A1 WO 2022166949 A1 WO2022166949 A1 WO 2022166949A1 CN 2022075348 W CN2022075348 W CN 2022075348W WO 2022166949 A1 WO2022166949 A1 WO 2022166949A1
Authority
WO
WIPO (PCT)
Prior art keywords
amino acid
acid sequence
seq
aav2
monoclonal antibody
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/CN2022/075348
Other languages
English (en)
Chinese (zh)
Inventor
丁莉丹
邹江波
史敏龙
陈晖�
武波
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.)
Nanjing Jinsirui Science and Technology Biology Corp
Original Assignee
Nanjing Jinsirui Science and Technology Biology Corp
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 Nanjing Jinsirui Science and Technology Biology Corp filed Critical Nanjing Jinsirui Science and Technology Biology Corp
Priority to CN202280013675.2A priority Critical patent/CN116917314A/zh
Publication of WO2022166949A1 publication Critical patent/WO2022166949A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/08—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from viruses
    • 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
    • C12N7/00—Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof

Definitions

  • the present application belongs to the field of downstream detection of monoclonal antibodies, and relates to a monoclonal antibody for anti-AAV2 ELISA and Western Blot (WB) applications.
  • the present application also relates to the preparation method and use of the anti-AAV2 monoclonal antibody.
  • AAV Addeno-associated virus
  • the diameter is about 20-25nM
  • the genome is single-stranded DNA
  • the length is about 4.7kb
  • the two ends of the genome are composed of two ITRs (inverted terminal repeats).
  • the core elements of AAV are mainly composed of four non-structural proteins (Rep78, Rep68, Rep52 and Rep40) and three structural proteins (VP1, VP2 and VP3).
  • VP1, VP2, and VP3 interact and assemble approximately 1:1:10 to form an approximately icosahedral structure.
  • AAV has been widely used in gene therapy, and a number of AAV drugs have been launched.
  • large-scale production of AAV has been supported in several ways, including early stage process development and GMP-grade production.
  • due to the specificity of AAV about 40%-70% of individuals have been infected with AAV, which leads to a certain amount of AAV antibodies in the human body. The presence of these antibodies has a major impact on the durable efficacy of AAV.
  • AAV has a variety of serotypes, and at least 10 different serotypes of AAV have been found, including AAV1-9 and AAV-DJ.
  • the main difference between different serotypes of AAV is the difference in their capsid proteins, which also leads to different AAVs' infectivity to different tissues and cell types.
  • AAV2 has very low immunogenicity, is not easily rejected by the body's immune system, and has the ability to infect dividing and non-dividing cells. It has been reported that it has a more permanent expression of heterologous genes, therefore, AAV2 is the most widely studied.
  • the transformation of AAV vectors mainly focuses on the coat protein. In the transformation process, both the detection of the wild type and the characterization of new AAV vectors are required, which requires AAV with very good specificity and affinity. Antibody.
  • the present application provides an anti-AAV2 monoclonal antibody or a functional fragment thereof, the antibody or functional fragment thereof comprising a heavy chain variable region and a light chain variable region, wherein: (a) the heavy chain can be The variable region comprises HCDR1, HCDR2 and HCDR3 comprising an amino acid sequence selected from the group consisting of the amino acid sequence shown in SEQ ID NO: 3 or a variant of the amino acid sequence shown comprising up to three (eg, one, two or three) amino acid mutations
  • the HCDR2 comprises a variant of the amino acid sequence shown in SEQ ID NO: 4 or a variant of the amino acid sequence comprising at most three amino acid mutations
  • the HCDR3 comprises an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID NO: 5 or the amino acid sequence shown in SEQ ID NO: 5
  • the light chain variable region comprises LCDR1, LCDR2 and LCDR3, and the LCDR1 sequence comprises an amino acid sequence selected from the group consisting of the amino
  • the HCDR1 sequence comprises an amino acid sequence selected from SEQ ID NO: 3, the HCDR2 sequence comprises an amino acid sequence selected from SEQ ID NO: 4, and the HCDR3 sequence comprises SEQ ID NO: 4 The amino acid sequence shown in ID NO: 5; and the LCDR1 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 6, the LCDR2 sequence comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 7, the LCDR3 The sequence comprises an amino acid sequence selected from those shown in SEQ ID NO:8.
  • the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from the following sequences: the amino acid sequences of the HCDR1, HCDR2, and HCDR3 are set forth in SEQ ID NOs: 3, 4, and 5, respectively, and LCDR1, The amino acid sequences of LCDR2 and LCDR3 are shown in SEQ ID NOs: 6, 7 and 8, respectively.
  • the heavy chain variable region sequence comprises an amino acid sequence that is at least 80% identical to the amino acid sequence set forth in SEQ ID NO: 1; and the light chain variable region sequence comprises the same as SEQ ID NO:
  • the amino acid sequences shown in 2 have amino acid sequences that are at least 80% identical.
  • the heavy chain variable region sequence comprises at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87% of the amino acid sequence set forth in SEQ ID NO: 1 , 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical amino acid sequences; the light chain variable region sequence Comprising at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92 with the amino acid sequence shown in SEQ ID NO: 2 %, 93%, 94%, 95%, 96%, 97%, 98% or 99% identical amino acid sequences.
  • the heavy chain variable region sequence comprises the amino acid sequence set forth in SEQ ID NO:1; the light chain variable region sequence comprises the amino acid sequence set forth in SEQ ID NO:2.
  • the heavy chain variable region and the light chain variable region are selected from the following sequences: the amino acid sequence of the heavy chain variable region is shown in SEQ ID NO: 1, the light chain variable region The amino acid sequence of the region is shown in SEQ ID NO:2.
  • the present application provides isolated polynucleotides encoding the above-described anti-AAV2 monoclonal antibodies or functional fragments thereof.
  • the polynucleotide comprises a nucleotide sequence encoding the heavy chain variable region of the above-mentioned anti-AAV2 monoclonal antibody or a functional fragment thereof, and a nucleotide sequence encoding the anti-AAV2 monoclonal antibody or a functional fragment thereof Nucleotide sequence of light chain variable region.
  • the application provides an expression vector comprising the polynucleotide.
  • the present application provides a host cell or cell-free expression system comprising the expression vector.
  • the present application provides an antibody for ELISA and WB detection, the detection antibody comprising the monoclonal antibody or a functional fragment thereof.
  • the present application provides the application of the anti-AAV2 monoclonal antibody or its functional fragment in detecting AAV2 by ELISA and WB detection methods.
  • the AAV2 virus is recombinantly expressed AAV2 after purification.
  • the present application provides a method for preparing an anti-AAV2 monoclonal antibody or a functional fragment thereof, comprising: (1) immunizing an animal with purified AAV2, and generating an immune response against AAV2 in the animal; (2) ) Take the hybridoma cells obtained by fusing the spleen cells of the animal with myeloma cells, and screen them to obtain a positive clone that specifically recognizes AAV2; (3) subcloning the positive parent clone to obtain a stable hybrid tumor cell line; (4) performing gene sequencing on the hybridoma cell line to obtain the variable region coding sequences of the anti-AAV2 heavy chain and light chain; (5) using the stable hybridoma cell line for antibody production or The coding sequence of the variable region was used for recombinant antibody production to obtain a functional anti-AAV2 monoclonal antibody.
  • the monoclonal antibody is murine, chimeric, humanized or fully human.
  • Fig. 1 is the result graph of the detection result of mouse serum titer after immunization shown in some embodiments of the present application;
  • Fig. 2 is a graph showing the results of SDS-PAGE identification after purification of monoclonal antibodies shown in some embodiments of the present application;
  • Fig. 3 is according to the WB detection result diagram of monoclonal antibody shown in some embodiments of the present application and different titers of AAV2;
  • FIG. 4 is a graph showing the results of WB detection of monoclonal antibodies and different serotypes of AAV according to some embodiments of the present application.
  • AAV Addeno-associated virus
  • the diameter is about 20-25nM
  • the genome is single-stranded DNA
  • the length is about 4.7kb
  • the two ends of the genome are composed of two ITRs (inverted terminal repeats).
  • antibody is intended to refer to an immunoglobulin molecule consisting of four polypeptide chains (wherein two heavy (H) and two light (L) chains are connected to each other by disulfide bonds (ie "complete antibody molecule")) , and multimers thereof (eg, IgM) or antigen-binding fragments thereof.
  • Each heavy chain consists of a heavy chain variable region ("HCVR” or “VH”) and a heavy chain constant region (consisting of the domains CH1, CH2 and CH3).
  • Each light chain consists of a light chain variable region (“LCVR” or “VL”) and a light chain constant region (CL).
  • VH and VL regions can be further subdivided into hypervariable regions called complementarity determining regions (CDRs) with more conserved regions interposed therebetween called framework regions (FRs).
  • CDRs complementarity determining regions
  • FRs framework regions
  • Each VH and VL consists of three CDRs and four FRs, arranged from amino terminus to hydroxyl terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.
  • the FRs of the antibody may be identical to human germline sequences or may be naturally or artificially modified.
  • the term "monoclonal antibody” refers to a uniform antibody directed against only a particular epitope. Each monoclonal antibody is directed against a single epitope on an antigen, in contrast to typical polyclonal antibody preparations that include different antibodies directed against different antigenic determinants (epitopes).
  • the modifier "monoclonal” denotes a uniform characteristic of an antibody and is not to be construed as requiring that the antibody be produced by any particular method.
  • the monoclonal antibodies of the present application are preferably produced by recombinant DNA methods, or obtained by screening methods described elsewhere in this application.
  • mutation refers to a monoclonal antibody or functional fragment thereof comprising an alteration of one or more (several) amino acid residues at one or more (several) positions, ie, a substitution, insertion and/or deletion of a polypeptide.
  • a substitution refers to replacing an amino acid occupying a position with a different amino acid;
  • a deletion refers to removing an amino acid occupying a position; and
  • an insertion refers to adding 1-3 amino acids adjacent to and after the amino acid occupying a position.
  • isolated polynucleotide refers to a polynucleotide that is not in a naturally occurring state in nature, including polynucleotides isolated from nature (including in vivo) by biological techniques, as well as artificially synthesized polynucleotides.
  • An isolated polynucleotide can be genomic DNA, cDNA, mRNA, or other synthetic RNA, or a combination thereof. It should be pointed out that those skilled in the art can design the provided nucleotide sequences with different nucleotide sequences according to the amino acid sequences of the heavy chain variable region and light chain variable region provided herein and based on the degeneracy of codons. nucleotide sequences, but both encode the same amino acid sequence. These altered nucleotide sequences are also included within the scope of this application.
  • vector when referring to a polynucleotide refers to any molecule (eg, nucleic acid, plasmid or virus, etc.) used to transfer information encoded by a nucleotide into a host cell.
  • expression vector or “expression cassette” refers to a vector suitable for expressing a gene of interest (nucleotide sequence to be expressed) in a host cell, usually including parts of the gene of interest, promoter, terminator, marker gene and the like.
  • hybrida cell refers to a cell that can sustainably expand and stably secrete monoclonal antibodies.
  • antibody functional fragment means antigen-binding fragments and antibody analogs of antibodies, which typically include at least a portion of the antigen-binding or variable regions (eg, one or more CDRs) of the parental antibody. Antibody fragments retain at least some of the binding specificity of the parent antibody.
  • antibody fragments capable of binding AAV2 or a portion thereof include, but are not limited to, sdAbs (single domain antibodies), Fab (eg, antibodies obtained by papain digestion), F(ab')2 (eg, obtained by pepsin digestion) ), Fv or scFv (eg obtained by molecular biology techniques).
  • amino acid substitution refers to the replacement of existing amino acid residues with different amino acid residues in a predetermined (original) amino acid sequence.
  • amino acid substitutions are preferably made in accordance with the substitutions shown in Table 1:
  • Percent (%) amino acid sequence identity with respect to antibody sequences is defined as comparing sequences and introducing gaps where necessary to obtain maximum percent sequence identity, and without considering any conservative substitutions as part of sequence identity, among candidate sequences The percentage of amino acid residues that are identical to amino acid residues in a particular peptide or polypeptide sequence. Alignment of sequences to determine percent amino acid sequence identity can be performed in a variety of ways that are within the skill in the art, eg, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to obtain maximal alignment over the full length of the sequences being compared.
  • TKARA Lenti-X 293T
  • FBS FBS
  • Virus harvesting was performed after culturing for 72 h, and 1/80 (V/V) 0.5M EDTA (pH 8) was added to the medium supernatant and mixed. Place at room temperature for 10min. Collect the digested cells into a 50 mL centrifuge tube, centrifuge at 1750 g for 10 min at 4°C. Collect the centrifuged supernatant into a new centrifuge tube. The centrifuge tube containing cells was re-centrifuged at 1750g and 4°C for about 1-2 min, and the supernatant was collected. At this point, the supernatant and cells have been collected separately for the next experiment.
  • the virus supernatant obtained in Example 1 was purified according to the kit instructions (TAKARA Cat: 6232), and the specific steps were as follows:
  • Example 2 2.1 Transfer the supernatant of Example 1 to a new 50 mL centrifuge tube, and add 1/100 volume of Cryonase Cold-Active Nuclease (TAKARA Cat: 6232). Incubate for 1 h at 37°C.
  • TAKARA Cat Cryonase Cold-Active Nuclease
  • the AAV virus was eluted with 3 mL of eluent and collected in a fresh tube, and a total of 3 mL of virus was collected.
  • the purified virus was concentrated to 1 mL through a filter.
  • the animal immunization antigen adopts the recombinant virus purified in Example 2.
  • C57BL/6 mice were immunized with 10 11 VG of AAV2 virus by intramuscular immunization. Subsequently, the immunization was repeated every 2 to 3 weeks, so that the experimental mice were boosted 3 times in total.
  • the serum titers of 2 mice No.: 3839 and 3840 reached more than 10 5 after 3 immunizations (Fig. 1).
  • the spleen of the experimental mouse numbered 3839 was selected 4 days after the last immunization for subsequent antibody discovery.
  • the mouse spleen in Example 3 was prepared as a single cell suspension, and at the same time a single cell suspension of myeloma cells (SP2/0) was prepared. 5.35 ⁇ 10 7 splenocytes were fused with 2.675 ⁇ 10 7 SP2/0 mouse myeloma cells using electrofusion. Resuspend the fused cells in 150 mL of DMEM + 10% FBS medium containing the hybridoma cell selection agents thymidine, hypoxanthine, and aminopterin, and pipette to 15 cells at a volume of 100 ⁇ L/well. in a 96-well plate. The cells in the 96-well plate were incubated in a 37°C, 5% CO2 incubator. After 7 days of incubation, the presence of antibodies to AAV2 was tested using the ELISA binding described below.
  • Indirect ELISA was used to assess the binding ability of antibodies to AAV2 in the supernatant.
  • ELISA plates were coated with 50 ⁇ L/well of 5 ⁇ 10 8 AAV2 in PBS overnight at 4°C. Plates were washed with PBS-T (0.05% Tween) and blocked with 150 [mu]L/well of PBST containing 1% BSA for 1 hour at 37[deg.]C. The blocking solution was then discarded, and 100 ⁇ L of hybridoma cell culture supernatant was added to each well, followed by incubation at 37° C. for 1 hour.
  • Subcloning was performed using limiting dilution. Determine the number of cells using a hemocytometer and serial dilutions of cells in DMEM + 10% FBS medium containing the hybridoma cell selection agents thymidine, hypoxanthine, and aminopterin until the cell density reaches 5-15 cells/mL. For each hybridoma, pipette 200 ⁇ L of the cell solution into 96 wells at a density of 1-3 cells/well.
  • the filtered supernatant was incubated with the protein A column for 2 hours at room temperature, and after washing the column with 1 ⁇ the above buffer, IgG was eluted with sterile 0.1 M sodium citrate (pH 3.5), and the eluate was collected and washed with one-ninth Neutralize with a volume of sterile 1M Tris-HCl (pH 9). Under sterile conditions, the product was buffer exchanged to PBS (pH 7.4) to remove elution buffer.
  • the purified antibody 12C10A6 was analyzed by SDS-PAGE using a BioRad electrophoresis system using 10% precast gels (GenScript, M42012C). The gel was stained with Estain 2.0 (GenScript, L00687R) and molecular size and purity were estimated by comparing the stained bands with Protein Ladder (Takara, 3452), as shown in Figure 2, the antibody was 99% pure.
  • Murine immunoglobulin heavy and light chain V-region fragments were subsequently amplified by RACE PCR (GenScript) and the resulting PCR fragments were subcloned into the pMD18-T vector system (Takara) and inserted using vector-specific primer pairs Fragments are sequenced. Finally, the unique V-region protein amino acid sequences of 12C10A6 were obtained: 12C10A6 heavy chain variable region amino acid sequence (SEQ ID NO: 1) and 12C10A6 light chain variable region amino acid sequence (SEQ ID NO: 2).
  • Example 7 Binding of recombinant monoclonal antibody supernatants to different serotypes of AAV
  • ELISA plates were coated with 50 ⁇ L/well of 5 ⁇ 10 8 AAV1, AAV5, AAV6, AAV9, AAV2 serotype virus particles in PBS overnight at 4°C. Plates were washed with PBS-T (0.05% Tween) and blocked with 150 [mu]L/well of PBST containing 1% BSA for 1 hour at 37[deg.]C. The blocking solution was then discarded, and 100 ⁇ L of hybridoma cell culture supernatant was added to each plate, followed by incubation at 37° C. for 1 hour.
  • C represents a purchased commercial positive control antibody (CREATIVE DIAGNOSTICS, CABT-B9062), and K represents blank control PBS. It is generally judged that the absorbance is 2.1 times that of the blank control. It can be seen from Table 5 that the binding of the antibody secreted by the 12C10A6 cell line to AAV2 is 16 times that of the blank control, indicating that the antibody secreted by the 12C10A6 cell line can be specific. Sex Recognition AAV2. At the same time, it can be seen from Table 5 that the binding of the antibody secreted by the 12C10A6 cell line to AAV2 is 2.5 times that of the commercial antibody, and the binding capacity is also significantly higher than that of the commercial antibody.
  • C represents a purchased commercial positive control antibody (CREATIVE DIAGNOSTICS, CABT-B9062)
  • K represents blank control PBS. It is generally judged that the absorbance is 2.1 times that of the blank control. It can be seen from Table 5 that the binding of the antibody secreted by the 12C10A
  • the anti-AAV2 monoclonal antibody disclosed in this application and its preparation method and application may bring beneficial effects including but not limited to: 1.
  • the anti-AAV2 monoclonal antibody can specifically bind to AAV2.
  • the binding ability of AAV2 monoclonal antibody to AAV2 is obviously better than that of commercial antibodies, which provides possibility and convenience for ELISA and WB detection of AAV2.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Virology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne un anticorps monoclonal anti-AAV2, son procédé de préparation et son utilisation. L'anticorps monoclonal anti-AAV2 peut se lier de manière spécifique à AAV2, et la capacité de liaison est significativement meilleure que celle d'anticorps disponibles dans le commerce. A la fois des possibilités et une commodité sont proposées pour la détection ELISA et WB de AAV2.
PCT/CN2022/075348 2021-02-07 2022-02-07 Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation Ceased WO2022166949A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202280013675.2A CN116917314A (zh) 2021-02-07 2022-02-07 抗aav2单克隆抗体及其制备方法和应用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN202110174898.4 2021-02-07
CN202110174898 2021-02-07

Publications (1)

Publication Number Publication Date
WO2022166949A1 true WO2022166949A1 (fr) 2022-08-11

Family

ID=82740922

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2022/075348 Ceased WO2022166949A1 (fr) 2021-02-07 2022-02-07 Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation

Country Status (2)

Country Link
CN (1) CN116917314A (fr)
WO (1) WO2022166949A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116199773A (zh) * 2022-12-22 2023-06-02 北京因诺惟康医药科技有限公司 一种可结合多种aav血清型的纳米抗体及其应用
CN116589564A (zh) * 2023-03-30 2023-08-15 恺佧生物科技(上海)有限公司 抗aav5抗体及快速aav5滴度测定elisa试剂盒
CN117229393A (zh) * 2023-11-10 2023-12-15 北京百普赛斯生物科技股份有限公司 特异性结合腺相关病毒5的抗体及其应用
WO2024140628A1 (fr) * 2022-12-26 2024-07-04 南京金斯瑞生物科技有限公司 Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation
WO2024140627A1 (fr) * 2022-12-26 2024-07-04 南京金斯瑞生物科技有限公司 Anticorps monoclonal dirigé contre des protéines capsidiques de multiples sérotypes de vaa, son procédé de préparation et son utilisation

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180179265A1 (en) * 2015-04-27 2018-06-28 The Trustees Of The University Of Pennsylvania Engineered human anti-aav antibodies and uses thereof
CN108794622A (zh) * 2017-05-02 2018-11-13 广州医科大学附属第医院 一种人3型腺病毒的中和性人源化单克隆抗体及其制备方法和应用

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180179265A1 (en) * 2015-04-27 2018-06-28 The Trustees Of The University Of Pennsylvania Engineered human anti-aav antibodies and uses thereof
CN108794622A (zh) * 2017-05-02 2018-11-13 广州医科大学附属第医院 一种人3型腺病毒的中和性人源化单克隆抗体及其制备方法和应用

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
C. E. WOBUS, GLE-D BARBARA H, RR, GIROD ANNE, PETERSEN GABRIELE, HALLEK MICHAEL, AND J, RGEN A, KLEINSCHMIDT, FORSCHUNGSSCHWERPUNK: "Monoclonal Antibodies against the Adeno-Associated Virus Type 2 (AAV-2) Capsid: Epitope Mapping and Identification of Capsid Domains Involved in AAV-2-Cell Interaction and Neutralization of AAV-2 Infection", JOURNAL OF VIROLOGY, vol. 74, no. 19, 1 October 2000 (2000-10-01), US , pages 9281 - 9293, XP055233477, ISSN: 0022-538X, DOI: 10.1128/JVI.74.19.9281-9293.2000 *
DATABASE Protein 18 March 2009 (2009-03-18), ANONYMOUS: "Igh protein [Mus musculus]", XP055956457, retrieved from Genbank Database accession no. AAH18535 *
DATABASE Protein 27 April 1993 (1993-04-27), ANONYMOUS : "IgMk light chain precursor, partial [Mus musculus]", XP055956454, retrieved from Genbank Database accession no. AAA38844 *
DUSTIN M. MCCRAW; JASON K. O DONNELL; KENNETH A. TAYLOR; SCOTT M. STAGG; MICHAEL S. CHAPMAN;: "Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20", VIROLOGY, vol. 431, no. 1, 7 May 2012 (2012-05-07), AMSTERDAM, NL , pages 40 - 49, XP028493855, ISSN: 0042-6822, DOI: 10.1016/j.virol.2012.05.004 *
GILES APRIL R., CALCEDO ROBERTO, TRETIAKOVA ANNA P., WILSON JAMES M.: "Isolating Human Monoclonal Antibodies Against Adeno-Associated Virus From Donors With Pre-existing Immunity", FRONTIERS IN IMMUNOLOGY, vol. 11, 7 July 2020 (2020-07-07), Lausanne, CH , pages 1 - 15, XP055887612, ISSN: 1664-3224, DOI: 10.3389/fimmu.2020.01135 *
TAN SHU-PING ,YUAN ZHEN-HUA ,TIAN WEN-HONG ,DONG XIAO-YAN ,WU XIAO-BING: "The Preparation of Monoclonal Antibodies against AAV2 and Study on Their Characterizations", CHINESE JOURNAL OF VIROLOGY, vol. 25, no. 4, 5 July 2009 (2009-07-05), pages 267 - 273, XP055956450, ISSN: 1000-8721, DOI: 10.13242/j.cnki.bingduxuebao.002016 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN116199773A (zh) * 2022-12-22 2023-06-02 北京因诺惟康医药科技有限公司 一种可结合多种aav血清型的纳米抗体及其应用
CN116199773B (zh) * 2022-12-22 2023-08-25 北京因诺惟康医药科技有限公司 一种可结合多种aav血清型的纳米抗体及其应用
WO2024140628A1 (fr) * 2022-12-26 2024-07-04 南京金斯瑞生物科技有限公司 Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation
WO2024140627A1 (fr) * 2022-12-26 2024-07-04 南京金斯瑞生物科技有限公司 Anticorps monoclonal dirigé contre des protéines capsidiques de multiples sérotypes de vaa, son procédé de préparation et son utilisation
CN116589564A (zh) * 2023-03-30 2023-08-15 恺佧生物科技(上海)有限公司 抗aav5抗体及快速aav5滴度测定elisa试剂盒
CN116589564B (zh) * 2023-03-30 2024-01-09 恺佧生物科技(上海)有限公司 抗aav5抗体及快速aav5滴度测定elisa试剂盒
CN117229393A (zh) * 2023-11-10 2023-12-15 北京百普赛斯生物科技股份有限公司 特异性结合腺相关病毒5的抗体及其应用
CN117229393B (zh) * 2023-11-10 2024-01-30 北京百普赛斯生物科技股份有限公司 特异性结合腺相关病毒5的抗体及其应用

Also Published As

Publication number Publication date
CN116917314A (zh) 2023-10-20

Similar Documents

Publication Publication Date Title
WO2022166949A1 (fr) Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation
Tseng et al. Mapping the AAV capsid host antibody response toward the development of second generation gene delivery vectors
CN116199773B (zh) 一种可结合多种aav血清型的纳米抗体及其应用
CN112812178B (zh) PCV3 Cap蛋白抗原表位肽、抗PCV3 Cap蛋白的单克隆抗体及其制备方法和应用
CN112074605B (zh) 抗fam19a5抗体的腺相关病毒（aav）递送
US20180179265A1 (en) Engineered human anti-aav antibodies and uses thereof
CN116589564B (zh) 抗aav5抗体及快速aav5滴度测定elisa试剂盒
CN116239679B (zh) 一种可结合多种aav血清型的纳米抗体及其应用
WO2021110181A2 (fr) Polypeptide pouvant se lier à cd47 et son utilisation
CN113004413B (zh) 猪IgG3的单克隆抗体、该单克隆抗体特异性识别的抗原表位肽及其应用
CN119529074B (zh) 抗诺如病毒vp1蛋白抗体及其应用
CN117129675B (zh) 用于人博卡病毒型别特异性检测或诊断的试剂或试剂盒
CN117126269B (zh) 一种1型人博卡病毒型别特异性抗体及其应用
WO2024140627A1 (fr) Anticorps monoclonal dirigé contre des protéines capsidiques de multiples sérotypes de vaa, son procédé de préparation et son utilisation
WO2024140628A1 (fr) Anticorps monoclonal anti-aav2, son procédé de préparation et son utilisation
CN120435494A (zh) 抗aav8的单克隆抗体及其制备方法和用途
WO2024107451A1 (fr) Procédés de détection et d'évaluation de virus et de particules de type viral
CN112279913B (zh) 一种抗人il-6单克隆抗体及应用
CN117186212A (zh) 宽pH下用于纯化不同AAV的纳米抗体
CN118085066B (zh) 一种抗aav的单克隆抗体及其用途
CN117126270B (zh) 一种2型人博卡病毒型别特异性抗体及其应用
CN118359719B (zh) 人抗人pla2r抗体标准品及其应用
WO2025008323A1 (fr) Protéines capsidiques d'aav modifiées
US20250074971A1 (en) Single-domain antibody against sva and uses thereof
CN115724953A (zh) 一种全分子IgG抗体及其制备方法和应用

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: 22749228

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 202280013675.2

Country of ref document: CN

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 22749228

Country of ref document: EP

Kind code of ref document: A1