US20180230215A1 - Anti-human cd19 antibodies with high affinity - Google Patents

Anti-human cd19 antibodies with high affinity Download PDF

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US20180230215A1
US20180230215A1 US15/941,519 US201815941519A US2018230215A1 US 20180230215 A1 US20180230215 A1 US 20180230215A1 US 201815941519 A US201815941519 A US 201815941519A US 2018230215 A1 US2018230215 A1 US 2018230215A1
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antibody
amino acid
seq
cdr
acid sequence
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Thomas Hofer
Claudia Ferrara Koller
Ekkehard Moessner
Mi He
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Hoffmann La Roche Inc
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Hoffmann La Roche Inc
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Priority to US18/052,526 priority patent/US20230312710A1/en
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C07K16/3061—Blood cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Definitions

  • Human CD19 is a 95 kDa transmembrane protein (B-cell co-receptor) exclusively expressed on B-cells and on follicular dendritic cells.
  • CD 19 is found in association with CD21 and CD81.
  • CD19 and CD21 are required for normal B-cell differentiation (Carter, R. H., et al., Immunol. Res. 26 (2002) 45-54).
  • Antibodies against CD19 have been used in several clinical trials (see e. g. Hekman, A., et al., Cancer Immunol. Immunother. 32 (191) 364-372; Vlasfeld, L. T., et al., Cancer Immunol. Immunother. 40 (1995) 37-47; Conry, R. M., et al., J. Immunother. Emphasis Tumor Immunol. 18 (1995) 231-241; Manzke, O., et al., Int. J. Cancer 91 (2001) 516-522).
  • the antibody of the invention or the pharmaceutical composition of the invention, for use as a medicament.
  • the antibody of the invention, or the pharmaceutical composition of the invention for use in the treatment of a disease in an individual in need thereof.
  • the antibody of the invention, or the pharmaceutical composition of the invention for use in the treatment of cancer.
  • the antibody of the invention, or the pharmaceutical composition of the invention for use in the treatment autoimmune diseases, rheumatoid arthritis, lupus, psoriasis, or a bone disease.
  • FIG. 3 shows the alignment of the parental anti-CD19 clone 8B8 with the selected affinity-matured binders. Shown are the sequences of clone 8B8 and all selected affinity-matured binders. CDRs of both heavy and light chains are framed.
  • antibody herein is used in the broadest sense and encompasses various antibody structures, including but not limited to monoclonal antibodies, polyclonal antibodies, monospecific and multispecific antibodies (e.g., bispecific antibodies), and antibody fragments so long as they exhibit the desired antigen-binding activity.
  • bispecific antibody denotes an antibody that has one or more binding sites each of which bind to the same epitope of the same antigen.
  • bispecific means that the antigen binding molecule is able to specifically bind to at least two distinct antigenic determinants.
  • a bispecific antigen binding molecule comprises two antigen binding sites, each of which is specific for a different antigenic determinant.
  • the bispecific antigen binding molecule is capable of simultaneously binding two antigenic determinants, particularly two antigenic determinants expressed on two distinct cells.
  • An affibody is a scaffold derived from Protein A of Staphylococcus aureus which can be engineered to bind to antigen.
  • the domain consists of a three-helical bundle of approximately 58 amino acids. Libraries have been generated by randomization of surface residues. For further details see Protein Eng. Des. Sel. 17, 455-462 (2004) and EP 1641818A1.
  • Peptide aptamers are combinatorial recognition molecules that consist of a constant scaffold protein, typically thioredoxin (TrxA) which contains a constrained variable peptide loop inserted at the active site.
  • TrxA thioredoxin
  • Microbodies are derived from naturally occurring microproteins of 25-50 amino acids in length which contain 3-4 cysteine bridges—examples of microproteins include KalataBl and conotoxin and knottins.
  • the microproteins have a loop which can beengineered to include upto 25 amino acids without affecting the overall fold of the microprotein.
  • knottin domains see WO2008098796.
  • affinity matured in the context of antigen binding molecules (e.g., antibodies) refers to an antigen binding molecule that is derived from a reference antigen binding molecule, e.g., by mutation, binds to the same antigen, preferably binds to the same epitope, as the reference antibody; and has a higher affinity for the antigen than that of the reference antigen binding molecule.
  • Affinity maturation generally involves modification of one or more amino acid residues in one or more CDRs of the antigen binding molecule.
  • the affinity matured antigen binding molecule binds to the same epitope as the initial reference antigen binding molecule.
  • tyrosine or tryptophan tyrosine or tryptophan.
  • Compensatory cavities of identical or similar size to the protuberances are created in the interface of the second polypeptide by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine).
  • the protuberance and cavity can be made by altering the nucleic acid encoding the polypeptides, e.g. by site-specific mutagenesis, or by peptide synthesis.
  • a knob modification comprises the amino acid substitution T366W in one of the two subunits of the Fc domain
  • the hole modification comprises the amino acid substitutions T366S, L368A and Y407V in the other one of the two subunits of the Fc domain.
  • the subunit of the Fc domain comprising the knob modification additionally comprises the amino acid substitution S354C
  • the subunit of the Fc domain comprising the hole modification additionally comprises the amino acid substitution Y349C.
  • an “activating Fc receptor” is an Fc receptor that following engagement by an Fc region of an antibody elicits signaling events that stimulate the receptor-bearing cell to perform effector functions. Activating Fc receptors include Fc ⁇ RIIIa (CD16a), Fc ⁇ RI (CD64), Fc ⁇ RIIa (CD32), and Fc ⁇ RI (CD89). A particular activating Fc receptor is human Fc ⁇ RIIIa (see UniProt accession no. P08637, version 141).
  • a residue or group of target residues e.g., charged residues such as Arg, Asp, His, Lys, and Glu
  • a neutral or negatively charged amino acid e.g., alanine or polyalanine
  • Further substitutions may be introduced at the amino acid locations demonstrating functional sensitivity to the initial substitutions.
  • a crystal structure of an antigen-antigen binding molecule complex to identify contact points between the antibody and antigen. Such contact residues and neighboring residues may be targeted or eliminated as candidates for substitution.
  • Variants may be screened to determine whether they contain the desired properties.
  • “Conservative substitutions” are provided in Table B under the heading “Preferred Substitutions” and further described below in reference to amino acid side chain classes (1) to (6). Amino acid substitutions may be introduced into the molecule of interest and the products screened for a desired activity, e.g., retained/improved antigen binding, decreased immunogenicity, or improved ADCC or CDC.
  • cysteine engineered variants of the antigen binding molecule of the invention e.g., “thioMAbs,” in which one or more residues of the molecule are substituted with cysteine residues.
  • the substituted residues occur at accessible sites of the molecule.
  • reactive thiol groups are thereby positioned at accessible sites of the antibody and may be used to conjugate the antibody to other moieties, such as drug moieties or linker-drug moieties, to create an immunoconjugate.
  • Polyethylene glycol propionaldehyde may have advantages in manufacturing due to its stability in water.
  • the polymer may be of any molecular weight, and may be branched or unbranched.
  • the number of polymers attached to the antibody may vary, and if more than one polymer is attached, they can be the same or different molecules. In general, the number and/or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the particular properties or functions of the antibody to be improved, whether the antibody derivative will be used in a therapy under defined conditions, etc.
  • conjugates of an antibody and non-proteinaceous moiety that may be selectively heated by exposure to radiation are provided.
  • an antibody that specifically binds to human CD19 wherein the antibody comprises
  • a further aspect of the present invention is the provision an antibody as disclosed herein that specifically binds to CD19.
  • the antibody as disclosed herein specifically binds to human CD19.
  • the antibody as disclosed herein specifically binds to cynomolgus CD19.
  • the antibodies as disclosed have cross species reactivity.
  • VH domain comprising an amino acid sequence of SEQ ID NO:111 and a VL domain comprising an amino acid sequence of SEQ ID NO:112,
  • the antibodies are engineered to have enhanced binding affinity according to, for example, the methods disclosed in PCT publication WO 2012/020006 (see Examples relating to affinity maturation) or U.S. Pat. Appl. Publ. No. 2004/0132066.
  • the ability of the antigen binding molecules of the invention to bind to a specific antigenic determinant can be measured either through an enzyme-linked immunosorbent assay (ELISA) or other techniques familiar to one of skill in the art, e.g., surface plasmon resonance technique (Liljeblad, et al., Glyco J 17, 323-329 (2000)), and traditional binding assays (Heeley, Endocr Res 28, 217-229 (2002)).
  • ELISA enzyme-linked immunosorbent assay
  • Antibodies of the invention prepared as described herein may be purified by art-known techniques such as high performance liquid chromatography, ion exchange chromatography, gel electrophoresis, affinity chromatography, size exclusion chromatography, and the like.
  • the actual conditions used to purify a particular protein will depend, in part, on factors such as net charge, hydrophobicity, hydrophilicity etc., and will be apparent to those having skill in the art.
  • affinity chromatography purification an antibody, ligand, receptor or antigen can be used to which the TNF ligand trimer-containing antigen binding molecule binds.
  • a matrix with protein A or protein G may be used for affinity chromatography purification of fusion proteins of the invention.
  • compositions are lyophilized formulations or aqueous solutions.
  • pharmaceutically acceptable excipient includes any and all solvents, buffers, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents), isotonic agents, salts, stabilizers and combinations thereof, as would be known to one of ordinary skill in the art.
  • the fusion proteins may also be formulated as a depot preparation. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection.
  • the fusion proteins may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
  • composition herein may also contain more than one active ingredients as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other.
  • active ingredients are suitably present in combination in amounts that are effective for the purpose intended.
  • CD19 is expressed on most B-cells (pan-B-cell marker) with the exception of stem cells and plasma cells, and is frequently expressed on most human B-cell malignancies (tumor associated antigen), such as lymphoma and leukemias except for multiple myeloma, e.g. in non-Hodgkin lymphoma and acute lymphoblastic leukemia.
  • Desired gene segments were either generated by PCR using appropriate templates or were synthesized by Geneart AG (Regensburg, Germany) from synthetic oligonucleotides and PCR products by automated gene synthesis. In cases where no exact gene sequence was available, oligonucleotide primers were designed based on sequences from closest homologues and the genes were isolated by RT-PCR from RNA originating from the appropriate tissue. The gene segments flanked by singular restriction endonuclease cleavage sites were cloned into standard cloning/sequencing vectors. The plasmid DNA was purified from transformed bacteria and concentration determined by UV spectroscopy. The DNA sequence of the subcloned gene fragments was confirmed by DNA sequencing. Gene segments were designed with suitable restriction sites to allow sub-cloning into the respective expression vectors. All constructs were designed with a 5′-end DNA sequence coding for a leader peptide which targets proteins for secretion in eukaryotic cells.
  • Proteins were purified from filtered cell culture supernatants referring to standard protocols. In brief, antibodies were applied to a Protein A Sepharose column (GE healthcare) and washed with PBS. Elution of antibodies was achieved at pH 2.8 followed by immediate neutralization of the sample. Aggregated protein was separated from monomeric antibodies by size exclusion chromatography (Superdex 200, GE Healthcare) in PBS or in 20 mM Histidine, 150 mM NaCl pH 6.0. Monomeric antibody fractions were pooled, concentrated (if required) using e.g., a MILLIPORE Amicon Ultra (30 MWCO) centrifugal concentrator, frozen and stored at ⁇ 20° C. or ⁇ 80° C. Part of the samples were provided for subsequent protein analytics and analytical characterization e.g. by SDS-PAGE, size exclusion chromatography (SEC) or mass spectrometry.
  • SEC size exclusion chromatography
  • the NuPAGE® Pre-Cast gel system (Invitrogen) was used according to the manufacturer's instruction. In particular, 10% or 4-12% NuPAGE® Novex® Bis-TRIS Pre-Cast gels (pH 6.4) and a NuPAGE® MES (reduced gels, with NuPAGE® Antioxidant running buffer additive) or MOPS (non-reduced gels) running buffer was used.
  • Binding of the generated antibodies to the respective antigens is investigated by surface plasmon resonance using a BIACORE instrument (GE Healthcare Biosciences AB, Uppsala, Sweden). Briefly, for affinity measurements Goat-Anti-Human IgG, JIR 109-005-098 antibodies are immobilized on a CMS chip via amine coupling for presentation of the antibodies against the respective antigen. Binding is measured in HBS buffer (HBS-P (10 mM HEPES, 150 mM NaCl, 0.005% Tween 20, ph 7.4), 25° C. (or alternatively at 37° C.). Antigen (R&D Systems or in house purified) was added in various concentrations in solution.
  • HBS buffer HBS-P (10 mM HEPES, 150 mM NaCl, 0.005% Tween 20, ph 7.4
  • Antigen R&D Systems or in house purified
  • the pH of collected fractions was adjusted by adding 1/40 (v/v) of 2M Tris, pH8.0.
  • the protein was concentrated and filtered prior to loading on a HiLoad Superdex 200 column (GE Healthcare) equilibrated with 2 mM MOPS, 150 mM sodium chloride, 0.02% (w/v) sodium azide solution of pH 7.4.
  • Table 3 summarizes the yield and final monomer content of monomeric human and cynomolgus CD19 Fc(kih) fusion protein.
  • Neutravidin plates were washed with 5 ⁇ PBS/Tween20 and 5 ⁇ PBS.
  • the neutravidin plate was incubated overnight in 2 liters PBS for an “off-rate” selection before phage was eluted from the plate.
  • cynomolgus CD19-Fc protein was used in round 2 in order to enrich cross-reactive binders.
  • Clones that were ELISA-positive on recombinant human CD19 were further tested in a cell-based ELISA using cells that were transiently transfected with the human CD19 ECD-containing expression plasmid (SEQ ID NO: 227).
  • This analysis was performed as follows: 48 h after transfection, HEK cells were harvested and centrifuged at 250 ⁇ g for 5 min. Cells were then re suspended in ice-cold PBS BSA 2% to 4 ⁇ 10 6 cells/ml and incubated for 20 min on ice to block unspecific binding sites. 4 ⁇ 10 5 cells in 100 ul were distributed to each well of a 96 well plate and centrifuged at 250 ⁇ g and 4° C. for 3 min.
  • variable regions of heavy and light chain DNA sequences of the selected anti-CD19 binders were subcloned in frame with either the constant heavy chain or the constant light chain of human IgG1.
  • Pro329Gly, Leu234Ala and Leu235Ala mutations have been introduced in order to abrogate binding to Fc gamma receptors according to the method described in International Patent Appl. Publ. No. WO 2012/130831 A1.
  • the cDNA and amino acid sequences of the anti-CD19 IgGs are shown in Table 9 and Table 10, respectively. All antibody-encoding sequences were cloned into an expression vector, which drives transcription of the insert with a chimeric MPSV promoter and contains a synthetic polyA signal sequence located at the 3′ end of the CDS. In addition, the vector contains an EBV OriP sequence for episomal maintenance of the plasmid.
  • the Affinity (K D ) of the parental antibody 8B8 as well as it derivatives was measured by SPR using a ProteOn XPR36 instrument (Biorad) at 25° C. 7000 RU of polyclonal anti-human Fab antibody were immobilized on all 6 channels of a GLM chip by Amine coupling (NaAcetate pH4.5, 25 ul/min, 240 s) (vertical orientation).
  • a human IgG Fc fragment (150 nM) was injected in channel 5 as a negative control for specific binding to monomeric CD19-Fc.
  • Buffer (PBST) was injected along the sixth channel to provide an “in-line” blank for referencing.
  • FIGS. 4A to 4H An overview of the respective sensorgrams is shown in FIGS. 4A to 4H . Regeneration was performed by two pulses of 10 mM glycine pH 1.5 and 50 mM NaOH for 30 s at 90 ul/min (vertical orientation). Association rate constants (k on ) and dissociation rate constants (k off ) were calculated using a simple one-to-one Langmuir binding model in ProteOn Manager v3.1 software by simultaneously fitting the association and dissociation sensorgrams.

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US16/689,880 US20200317774A1 (en) 2015-10-02 2019-11-20 Anti-human cd19 antibodies with high affinity
US18/052,526 US20230312710A1 (en) 2015-10-02 2022-11-03 Anti-human cd19 antibodies with high affinity

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EP15188262.8 2015-10-02
EP16167893 2016-05-02
EP16167893.3 2016-05-02
PCT/EP2016/073062 WO2017055328A1 (fr) 2015-10-02 2016-09-28 Anticorps anti-humain cd19 à affinité élevée

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US20200254021A1 (en) * 2016-09-05 2020-08-13 Ucl Business Ltd Chimeric Antigen Receptor
US11242396B2 (en) 2018-10-01 2022-02-08 Hoffmann-La Roche Inc. Bispecific antigen binding molecules comprising anti-FAP clone 212
US11267903B2 (en) 2014-11-14 2022-03-08 Hofmann-La Roche Inc. Antigen-binding molecules comprising a tumor necrosis factor (TNF) family ligand trimer
US11286300B2 (en) 2015-10-01 2022-03-29 Hoffmann-La Roche Inc. Humanized anti-human CD19 antibodies and methods of use
US11447558B2 (en) 2017-01-03 2022-09-20 Hoffmann-La Roche Inc. Bispecific antigen binding molecules comprising anti-4-1BB clone 20H4.9
US11608376B2 (en) 2018-12-21 2023-03-21 Hoffmann-La Roche Inc. Tumor-targeted agonistic CD28 antigen binding molecules
US11639394B2 (en) 2017-03-29 2023-05-02 Hoffmann-La Roche Inc. Bispecific antigen binding molecule for a costimulatory TNF receptor
US11718680B2 (en) 2016-12-20 2023-08-08 Hoffmann-La Roche Inc. Combination therapy of anti-CD20/anti-CD3 bispecific antibodies and 4-1BB (CD137) agonists
US11780919B2 (en) 2020-04-01 2023-10-10 Hoffmann-La Roche Inc. Bispecific antigen binding molecules targeting OX40 and FAP
US11780920B2 (en) 2020-06-19 2023-10-10 Hoffmann-La Roche Inc. Antibodies binding to CD3 and CD19

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WO2017189959A1 (fr) 2016-04-29 2017-11-02 Voyager Therapeutics, Inc. Compositions pour le traitement de maladies
WO2017189964A2 (fr) 2016-04-29 2017-11-02 Voyager Therapeutics, Inc. Compositions pour le traitement de maladies
BR112020005402A2 (pt) * 2017-09-21 2020-09-29 WuXi Biologics Ireland Limited anticorpos, sequências de polinucleotídeo e de ácido nucleico, vetores, célula hospedeira, métodos de expressar o anticorpo e de modulação conjugado, composição farmacêutica, métodos para tratar uma doença, para detectar, para diagnosticar e para estimular uma resposta imune, método in vivo ou in vitro, uso, receptor de antígeno quimérico e célula t
JP2021500902A (ja) 2017-11-01 2021-01-14 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト 新規ｔｎｆファミリーリガンド三量体含有抗原結合分子
US11891426B2 (en) 2017-12-15 2024-02-06 Aleta Biotherapeutics Inc. CD19 variants
CN108047332B (zh) * 2018-01-15 2021-08-24 阿思科力(苏州)生物科技有限公司 以cd19为靶点的特异性抗体、car-nk细胞及其制备和应用
JP2021528988A (ja) 2018-07-04 2021-10-28 エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト 新規の二重特異性アゴニスト４−１ｂｂ抗原結合分子
EP3931212A1 (fr) 2019-03-01 2022-01-05 Universität für Bodenkultur Wien Domaine extracellulaire stabilisé de cd19
WO2021067598A1 (fr) 2019-10-04 2021-04-08 Ultragenyx Pharmaceutical Inc. Procédés pour une utilisation thérapeutique améliorée d'aav recombinant
WO2021119551A1 (fr) * 2019-12-11 2021-06-17 Cullinan Oncology, Inc. Anticorps anti-cd19 et protéines de liaison multi-spécifiques
CN115916816A (zh) * 2019-12-11 2023-04-04 库利南肿瘤股份有限公司 抗血清白蛋白抗体
EP4240491A1 (fr) * 2020-11-06 2023-09-13 Novartis AG Molécules de liaison à cd19 et utilisations associées

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008022152A2 (fr) * 2006-08-14 2008-02-21 Xencor, Inc. Anticorps optimisés ciblant cd19
WO2016075278A1 (fr) * 2014-11-14 2016-05-19 F. Hoffmann-La Roche Ag Molécules de liaison à l'antigène comprenant un ligand trimèrique de la famille du tnf

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2283368T3 (es) * 2001-11-14 2007-11-01 Affimed Therapeutics Ag Anticuerpos biespecificos anti-cd19 y anti-cd16 y usos de los mismos.
JP5651285B2 (ja) * 2005-02-15 2015-01-07 デューク ユニバーシティ 抗ｃｄ１９抗体および腫瘍学における使用
CN101233156B (zh) * 2005-06-20 2012-06-27 米德列斯公司 Cd19抗体及其用途
MX2009002414A (es) * 2006-09-08 2009-05-20 Medimmune Llc Anticuerpos anti-cd19 humanizados y su uso en el tratamiento de oncologia, transplante y enfermedad autoinmunitaria.
WO2011147834A1 (fr) * 2010-05-26 2011-12-01 Roche Glycart Ag Anticorps contre cd19 et utilisations associées
EP2409993A1 (fr) * 2010-07-19 2012-01-25 International-Drug-Development-Biotech Anticorps Anti-CD19 doté d'une fonction ADCC et d'un profil de glycosylation amélioré
SG193554A1 (en) * 2011-03-29 2013-11-29 Roche Glycart Ag Antibody fc variants
JP6996979B2 (ja) * 2015-03-31 2022-02-04 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 三量体ｔｎｆファミリーリガンドを含む抗原結合分子

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008022152A2 (fr) * 2006-08-14 2008-02-21 Xencor, Inc. Anticorps optimisés ciblant cd19
WO2016075278A1 (fr) * 2014-11-14 2016-05-19 F. Hoffmann-La Roche Ag Molécules de liaison à l'antigène comprenant un ligand trimèrique de la famille du tnf

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11267903B2 (en) 2014-11-14 2022-03-08 Hofmann-La Roche Inc. Antigen-binding molecules comprising a tumor necrosis factor (TNF) family ligand trimer
US11306154B2 (en) 2014-11-14 2022-04-19 Hoffmann-La Roche Inc. Methods of treating cancer by administering antigen-binding molecules comprising a TNF family ligand trimer
US11286300B2 (en) 2015-10-01 2022-03-29 Hoffmann-La Roche Inc. Humanized anti-human CD19 antibodies and methods of use
US20200254021A1 (en) * 2016-09-05 2020-08-13 Ucl Business Ltd Chimeric Antigen Receptor
US11718680B2 (en) 2016-12-20 2023-08-08 Hoffmann-La Roche Inc. Combination therapy of anti-CD20/anti-CD3 bispecific antibodies and 4-1BB (CD137) agonists
US11447558B2 (en) 2017-01-03 2022-09-20 Hoffmann-La Roche Inc. Bispecific antigen binding molecules comprising anti-4-1BB clone 20H4.9
US11639394B2 (en) 2017-03-29 2023-05-02 Hoffmann-La Roche Inc. Bispecific antigen binding molecule for a costimulatory TNF receptor
US11242396B2 (en) 2018-10-01 2022-02-08 Hoffmann-La Roche Inc. Bispecific antigen binding molecules comprising anti-FAP clone 212
US11608376B2 (en) 2018-12-21 2023-03-21 Hoffmann-La Roche Inc. Tumor-targeted agonistic CD28 antigen binding molecules
US11780919B2 (en) 2020-04-01 2023-10-10 Hoffmann-La Roche Inc. Bispecific antigen binding molecules targeting OX40 and FAP
US11780920B2 (en) 2020-06-19 2023-10-10 Hoffmann-La Roche Inc. Antibodies binding to CD3 and CD19

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UA125685C2 (uk) 2022-05-18
WO2017055328A1 (fr) 2017-04-06
MX2018003827A (es) 2018-06-22
CN108137698A (zh) 2018-06-08
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PH12018500707A1 (en) 2018-10-15
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US20200317774A1 (en) 2020-10-08
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EP3356405A1 (fr) 2018-08-08
US20230312710A1 (en) 2023-10-05
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