US20030175884A1 - Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity - Google Patents

Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity Download PDF

Info

Publication number
US20030175884A1
US20030175884A1 US10/211,554 US21155402A US2003175884A1 US 20030175884 A1 US20030175884 A1 US 20030175884A1 US 21155402 A US21155402 A US 21155402A US 2003175884 A1 US2003175884 A1 US 2003175884A1
Authority
US
United States
Prior art keywords
antibody
human
host cell
cell
region
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.)
Abandoned
Application number
US10/211,554
Other languages
English (en)
Inventor
Pablo Umana
Joel Jean-Mairet
James Bailey
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.)
Roche Glycart AG
Original Assignee
Roche Glycart AG
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 Roche Glycart AG filed Critical Roche Glycart AG
Priority to US10/211,554 priority Critical patent/US20030175884A1/en
Assigned to GLYCART BIOTECHNOLOGY AG reassignment GLYCART BIOTECHNOLOGY AG ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BAILEY, JAMES E. (DECEASED)-BY HIS LEGAL REPRESENTATIVE, JEAN-MAIRET, JOEL, UMANA, PABLO
Publication of US20030175884A1 publication Critical patent/US20030175884A1/en
Priority to US11/199,232 priority patent/US8021856B2/en
Priority to US13/196,724 priority patent/US8999324B2/en
Assigned to ROCHE GLYCART AG reassignment ROCHE GLYCART AG CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: GLYCART BIOTECHNOLOGY AG
Priority to US14/665,191 priority patent/US9321843B2/en
Priority to US15/080,020 priority patent/US9631023B2/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • 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
    • C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
    • A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
    • A61K49/10—Organic compounds
    • A61K49/14—Peptides, e.g. proteins
    • A61K49/16—Antibodies; Immunoglobulins; Fragments thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • 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
    • 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
    • C07K16/3038—Kidney, bladder
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1048—Glycosyltransferases (2.4)
    • C12N9/1051—Hexosyltransferases (2.4.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/005—Glycopeptides, glycoproteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/10—Immunoglobulins specific features characterized by their source of isolation or production
    • C07K2317/14—Specific host cells or culture conditions, e.g. components, pH or temperature
    • 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
    • C07K2317/40—Immunoglobulins specific features characterized by post-translational modification
    • C07K2317/41—Glycosylation, sialylation, or fucosylation
    • 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
    • C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts

Definitions

  • the present invention relates to the field of glycosylation engineering of proteins. More particularly, the present invention relates to glycosylation engineering to generate proteins with improved therapeutic properties, including antibodies with increased antibody-dependent cellular cytotoxicity.
  • Glycoproteins mediate many essential functions in human beings, other eukaryotic organisms, and some prokaryotes, including catalysis, signaling, cell-cell communication, and molecular recognition and association. They make up the majority of non-cytosolic proteins in eukaryotic organisms. (Lis et al., Eur. J. Biochem. 218:1-27 (1993)). Many glycoproteins have been exploited for therapeutic purposes, and during the last two decades, recombinant versions of naturally-occurring, secreted glycoproteins have been a major product of the biotechnology industry.
  • EPO erythropoietin
  • therapeutic mAbs therapeutic monoclonal antibodies
  • tPA tissue plasminogen activator
  • IFN- ⁇ interferon- ⁇
  • GM-CSF granulocyte-macrophage colony stimulating factor
  • hCG human chorionic gonadotrophin
  • the oligosaccharide component can significantly affect properties relevant to the efficacy of a therapeutic glycoprotein, including physical stability, resistance to protease attack, interactions with the immune system, pharmacokinetics, and specific biological activity. Such properties may depend not only on the presence or absence, but also on the specific structures, of oligosaccharides. Some generalizations between oligosaccharide structure and glycoprotein function can be made. For example, certain oligosaccharide structures mediate rapid clearance of the glycoprotein from the bloodstream through interactions with specific carbohydrate binding proteins, while others can be bound by antibodies and trigger undesired immune reactions. (Jenkins et al., Nature Biotechnol. 14:975-81 (1996)).
  • Mammalian cells are the preferred hosts for production of therapeutic glycoproteins, due to their capability to glycosylate proteins in the most compatible form for human application. (Cumming et al., Glycobiology 1:115-30 (1991); Jenkins et al., Nature Biotechnol. 14:975-81 (1996)). Bacteria very rarely glycosylate proteins, and like other types of common hosts, such as yeasts, filamentous fungi, insect and plant cells, yield glycosylation patterns associated with rapid clearance from the bloodstream, undesirable immune interactions, and in some specific cases, reduced biological activity. Among mammalian cells, Chinese hamster ovary (CHO) cells have been most commonly used during the last two decades.
  • these cells allow consistent generation of genetically stable, highly productive clonal cell lines. They can be cultured to high densities in simple bioreactors using serum-free media, and permit the development of safe and reproducible bioprocesses.
  • Other commonly used animal cells include baby hamster kidney (BHK) cells, NS0- and SP2/0-mouse myeloma cells. More recently, production from transgenic animals has also been tested. (Jenkins et al., Nature Biotechnol. 14:975-81 (1996)).
  • All antibodies contain carbohydrate structures at conserved positions in the heavy chain constant regions, with each isotype possessing a distinct array of N-linked carbohydrate structures, which variably affect protein assembly, secretion or functional activity.
  • N-linked carbohydrate structures which variably affect protein assembly, secretion or functional activity.
  • the structure of the attached N-linked carbohydrate varies considerably, depending on the degree of processing, and can include high-mannose, multiply-branched as well as biantennary complex oligosaccharides. (Wright, A., and Morrison, S. L., Trends Biotech. 15:26-32 (1997)).
  • Unconjugated monoclonal antibodies can be useful medicines for the treatment of cancer, as demonstrated by the U.S. Food and Drug Administration's approval of Rituximab (RituxanTM; IDEC Pharmaceuticals, San Diego, Calif., and Genentech Inc., San Francisco, Calif.), for the treatment of CD20 positive B-cell, low-grade or follicular Non-Hodgkin's lymphoma, and Trastuzumab (HerceptinTM; Genentech Inc,) for the treatment of advanced breast cancer (Grillo-Lopez, A. -J., et al., Semin. Oncol. 26:66-73 (1999); Goldenberg, M. M., Clin. Ther.
  • IgGl type antibodies the most commonly used antibodies in cancer immunotherapy, are glycoproteins that have a conserved N-linked glycosylation site at Asn297 in each CH2 domain.
  • ADCC antibody dependent cellular cytotoxicity
  • the present inventors showed previously that over expression in Chinese hamster ovary (CHO) cells of ⁇ (1,4)-N-acetylglucosaminyltransferase III (GnTIII), a glycosyltransferase catalyzing the formation of bisected oligosaccharides, significantly increases the in vitro ADCC activity of an anti-neuroblastoma chimeric monoclonal antibody (chCE7) produced by the engineered CHO cells.
  • GnTIII Chinese hamster ovary
  • the antibody chCE7 belongs to a large class of unconjugated mAbs which have high tumor affinity and specificity, but have too little potency to be clinically useful when produced in standard industrial cell lines lacking the GnTIII enzyme (Umana, P., et al., Nature Biotechnol. 17:176-180 (1999)). That study was the first to show that large increases of maximal in vitro ADCC activity could be obtained by increasing the proportion of constant region (Fc)-associated, bisected oligosaccharides above the levels found in naturally occurring antibodies.
  • Fc constant region
  • the present inventors have applied this technology to Rituximab, the anti-CD20, IDEC-C2B8 chimeric antibody.
  • the present inventors have likewise applied the technology to the unconjugated anti-cancer mAb chG250.
  • the present inventors have now generated new glycosylation variants of the anti-CD20 monoclonal antibody (mAb) IDEC-C2B8 (Rituximab) and the anti-cancer mAb chG250 using genetically engineered mAb-producing cell lines that overexpress N-acetylglucosaminyltransferase III (GnTIII; EC 2.1.4.144) in a tetracycline regulated fashion.
  • GnTIII is required for the synthesis of bisected oligosaccharides, which are found at low to intermediate levels in naturally-occurring human antibodies but are missing in mAbs produced in standard industrial cell lines.
  • MabtheraTM the version of Rixtuximab marketed in Europe
  • ADCC mouse-myeloma derived chG250 in biological activity.
  • the variant carrying the highest levels of bisected oligosaccharides mediated significant ADCC activity at a 125-fold lower concentration than that required to detect even low ADCC activity by the unmodified control chG250.
  • the claimed invention is directed to a host cell engineered to produce a polypeptide having increased Fc-mediated cellular cytotoxicity by expression of at least one nucleic acid encoding ⁇ (1,4)-N-acetylglucosaminyltransferase III (GnT III), wherein the polypeptide produced by the host cell is selected from the group consisting of a whole antibody molecule, an antibody fragment, and a fusion protein which includes a region equivalent to the Fc region of an immunoglobulin, and wherein the GnT III is expressed in an amount sufficient to increase the proportion of said polypeptide carrying bisected hybrid oligosaccharides or galactosylated complex oligosaccharides or mixtures thereof in the Fc region relative to polypeptides carrying bisected complex oligosaccharides in the Fc region.
  • GnT III ⁇ (1,4)-N-acetylglucosaminyltransferase III
  • the polypeptide is IgG or a fragment thereof, most preferably, IgG1 or a fragment thereof.
  • the polypeptide is a fusion protein that includes a region equivalent to the Fc region of a human IgG.
  • a nucleic acid molecule comprising at least one gene encoding GnTIII has been introduced into the host cell.
  • at least one gene encoding GnTIII has been introduced into the host cell chromosome.
  • the host cell has been engineered such that an endogenous GnT III gene is activated, for example, by insertion of a DNA element which increases gene expression into the host chromosome.
  • the endogenous GnTIII has been activated by insertion of a promoter, an enhancer, a transcription factor binding site, a transposon, or a retroviral element or combinations thereof into the host cell chromosome.
  • the host cell has been selected to carry a mutation triggering expression of an endogenous GnTIII.
  • the host cell is the CHO cell mutant lec 10.
  • the at least one nucleic acid encoding a GnTIII is operably linked to a constitutive promoter element.
  • the host cell is a CHO cell, a BHK cell, a NSO cell, a SP2/0 cell, or a hybridoma cell, a YO myeloma cell, a P3X63 mouse myeloma cell, a PER cell or a PER.C6 cell and said polypeptide is an anti-CD20 antibody.
  • the host cell is a SP2/0 cell and the polypeptide is the monoclonal antibody chG250.
  • the claimed invention is directed to a host cell that further comprises at least one transfected nucleic acid encoding an antibody molecule, an antibody fragment, or a fusion protein that includes a region equivalent to the Fc region of an immunoglobulin.
  • the host cell comprises at least one transfected nucleic acid encoding an anti-CD20 antibody, the chimeric anti-human neuroblastoma monoclonal antibody chCE7, the chimeric anti-human renal cell carcinoma monoclonal antibody chG250, the chimeric anti-human colon, lung, and breast carcinoma monoclonal antibody ING-1, the humanized anti-human 17-1A antigen monoclonal antibody 3622W94, the humanized anti-human colorectal tumor antibody A33, the anti-human melanoma antibody directed against GD3 ganglioside R24, or the chimeric anti-human squamous-cell carcinoma monoclonal antibody SF-25, an anti-human EGFR antibody, an anti-human EGFRvIII antibody, an anti-human PSMA antibody, and anti-human PSCA antibody, an anti-human CD22 antibody, an anti-human CD30 antibody, an anti-human CD33 antibody, an anti-human CD38 antibody, an anti-human CD40 antibody,
  • the claimed invention is directed to a method for producing a polypeptide in a host cell comprising culturing any of the above-described the host cells under conditions which permit the production of said polypeptide having increased Fc-mediated cellular cytotoxicity.
  • the method further comprises isolating said polypeptide having increased Fc-mediated cellular cytotoxicity.
  • the host cell comprises at least one nucleic acid encoding a fusion protein comprising a region equivalent to a glycosylated Fc region of an immunoglobulin.
  • the proportion of bisected oligosaccharides in the Fc region of said polypeptides is greater than 50%, more preferably, greater than 70%.
  • the proportion of bisected hybrid oligosaccharides or galactosylated complex oligosaccharides or mixtures thereof in the Fc region is greater than the proportion of bisected complex oligosaccharides in the Fc region of said polypeptide.
  • the polypeptide is an anti-CD20 antibody and the anti-CD20 antibodies produced by said host cell have a glycosylation profile, as analyzed by MALDI/TOF-MS, that is substantially equivalent to that shown in FIG. 2E.
  • the polypeptide is the chG250 monoclonal antibody and the chG250 antibodies produced by said host cell have a glycosylaton profile, as analyzed by MALDI/TOF-MS, that is substantially equivalent to that shown in FIG. 7D.
  • the claimed invention is directed to an antibody having increased antibody dependent cellular cytotoxicity (ADCC) produced by any of the methods described above.
  • ADCC antibody dependent cellular cytotoxicity
  • the antibody is selected from the group consisting of an anti-CD20 antibody, chCE7, ch-G250, a humanized anti-HER2 monoclonal antibody, ING-1, 3622W94, SF-25, A33, and R24.
  • the polypeptide can be an antibody fragment that includes a region equivalent to the Fc region of an immunoglobulin, having increased Fc-mediated cellular cytotoxicity produced by any of the methods described above.
  • the claimed invention is directed to a fusion protein that includes a region equivalent to the Fe region of an immunoglobulin and having increased Fc-mediated cellular cytotoxicity produced by any of the methods described above.
  • the claimed invention is directed to a pharmaceutical composition
  • a pharmaceutical composition comprising the antibody, antibody fragment, or fusion protein of the invention and a pharmaceutically acceptable carrier.
  • the claimed invention is directed to a method for the treatment of cancer comprising administering a therapeutically effective amount of said pharmaceutical composition to a patient in need thereof.
  • the invention is directed to an improved method for treating an autoimmune disease produced in whole or in part by pathogenic autoantibodies based on B-cell depletion comprising administering a therapeutically effective amount of immunologically active antibody to a human subject in need thereof, the improvement comprising administering a therapeutically effective amount of an antibody having increased ADCC prepared as described above.
  • the antibody is an anti-CD20 antibody.
  • autoimmune diseases or disorders include, but are not limited to, immune-mediated thrombocytopenias, such as acute idiopathic thrombocytopenic purpurea and chronic idiopathic thrombocytopenic purpurea, dermatomyositis, Sydenham's chorea, lupus nephritis, rheumatic fever, polyglandular syndromes, Henoch-Schonlein purpura, post-streptococcal nephritis, erythema nodosum, Takayasu's arteritis, Addison's disease, erythema multiform, polyarteritis nodosa, ankylosing spondylitis, Goodpasture's syndrome, thromboangitis ubiterans, primary biliary cirrhosis, Hashimoto's thyroiditis, thyrotoxicosis, chronic active hepatitis, polymyositis/der
  • atopic dermatitis atopic dermatitis
  • systemic scleroderma and sclerosis responses associated with inflammatory bowel disease (such as Crohn's disease and ulcerative colitis); respiratory distress syndrome (including adult respiratory distress syndrome; ARDS); dermatitis; meningitis; encephalitis; uveitis; colitis; glomerulonephritis; allergic conditions such as eczema and asthma and other conditions involving infiltration of T cells and chronic inflammatory responses; atherosclerosis; leukocyte adhesion deficiency; rheumatoidarthritis; systemic lupus erythematosus (SLE); diabetes mellitus (e.g.
  • FIG. 1 Indirect immunofluorescence assay showing the reactivity of the antibody preparation C2B8-25t to CD20 positive SB cells. Negative controls, including the HSB CD20 negative cell line and cells treated only with the secondary FITC-conjugated anti-human Fc polyclonal antibody are not shown.
  • FIG. 2A-2E MALDI/TOF-MS spectra of the oligosaccharides derived from MabtheraTM (FIG. 2A), C2B8-nt (FIG. 2B), C2B8-2000t (FIG. 2C), C2B8-50t (FIG. 2D), and C2B8-25t (FIG. 2E) antibody samples. Oligosaccharides appear as [M+Na + ] and [M+K + ] ions.
  • FIG. 3A and 3B Illustration of a typical human IgG Fc-associated oligosaccharide structure (A) and partial N-linked glycosylation pathway (B).
  • FIG. 3A The core of the oligosaccharide is composed of three mannose (M) and two N-acetylglucosamine (Gn) monosaccharide residues attached to Asn 297 .
  • Galactose (G), fucose (F), and bisecting N-acetylglucosamine (Gn, boxed) can be present or absent. Terminal N-acetylneuraminic acid may be also present but it is not included in the figure.
  • FIG. 3B Partial N-linked glycosylation pathway leading to the formation of the major oligosaccharide classes (dotted frames). Bisecting N-acetylglucosamine is denoted as Gn b . Subscript numbers indicate how many monosaccharide residues are present in each oligosaccharide. Each structure appears together with its sodium-associated [M+Na + ] mass. The mass of those structures that contain fucose (f) are also included.
  • FIG. 4A and 4B ADCC activities of Rituximab glycosylation variants. The percentage of cytotoxicity was measured via lysis of 51 Cr labeled CD20-positive SB cells by human lymphocytes (E:T ratio of 100:1) mediated by different mAb concentrations.
  • FIG. 4A Activity of C2B8 samples derived from a single cell line but produced at increasing GnTIII expression levels (i.e., decreasing tetracycline concentrations). The samples are C2B8-2000t, C2B8-50t, C2B8-25t, and C2B8-nt (control mAb derived from a clone that does not express GnTIII
  • FIG. 4B ADCC activity of C2B8-50t and C2B8-25t compared to MabtheraTM.
  • FIG. 5 Western blot analysis of the seven GnTIII expressing clones and the wild type. 30 ⁇ g of each sample were loaded on a 8.75% SDS gel, transferred to a PVDF membrane and probed with the anti-c-myc monoclonal antibody (9E10). WT refers to wt-chG250-SP2/0 cells.
  • FIG. 6 SDS polyacrylamide gel electrophoresis of resolved purified antibody samples.
  • FIG. 7A- 7 D MALDI/TOF-MS spectra of neutral oligosaccharide mixtures from chG250 mAb samples produced by clones expressing different GnTIII levels and wt-chG250-SP2/0 cells: WT (FIG. 7A), 2F1 (FIG. 7B), 3D3 (FIG. 7C), 4E6 (FIG. 7D).
  • FIG. 8A- 8 D MALDI/TOF-MS spectra of neutral oligosaccharide mixtures from chG250 mAb samples produced by clones expressing different GnTIII levels: 4E8, (FIG. 8A); 5G2, (FIG. 8B); 4G3, (FIG. 8C); 5H12, (FIG. 8D).
  • FIG. 9 In vitro ADCC assay of antibody samples derived from control wt-chG250-SP2/-cells and GnTIII transected clones 3D3 and 5H12.
  • antibody is intended to include whole antibody molecules, antibody fragments, or fusion proteins that include a region equivalent to the Fc region of an immunoglobulin.
  • region equivalent to the Fc region of an immunoglobulin is intended to include naturally occurring allelic variants of the Fc region of an immunoglobulin as well as variants having alterations which produce substitutions, additions, or deletions but which do not decrease substantially the ability of the immunoglobulin to mediate antibody dependent cellular cytotoxicity.
  • one or more amino acids can be deleted from the N-terminus or C-terminus of the Fc region of an immunoglobulin without substantial loss of biological function.
  • variants can be selected according to general rules known in the art so as to have minimal effect on activity. (See, e.g., Bowie, J. U. et al., Science 247:1306-10 (1990).
  • glycoprotein-modifying glycosyl transferase refers to ⁇ (1,4)-N-acetylglucosaminyltransferase III (GnTIII).
  • glycosylation engineering is considered to include any manipulation of the glycosylation pattern of a naturally occurring polypeptide or fragment thereof.
  • Glycosylation engineering includes metabolic engineering of the glycosylation machinery of a cell, including genetic manipulations of the oligosaccharide synthesis pathways to achieve altered glycosylation of glycoproteins expressed in cells.
  • glycosylation engineering includes the effects of mutations and cell environment on glycosylation.
  • the term host cell covers any kind of cellular system which can be engineered to generate modified glycoforms of proteins, protein fragments, or peptides of interest, including antibodies and antibody fragments.
  • the host cells have been manipulated to express optimized levels of GnT III.
  • Host cells include cultured cells, e.g., mammalian cultured cells, such as CHO cells, BHK cells, NSO cells, SP2/0 cells, YO myeloma cells, P3X63 mouse myeloma cells, PER cells, PER. C6 cells or hybridoma cells, yeast cells, and insect cells, to name only a few, but also cells comprised within a transgenic animal or cultured tissue.
  • Fc-mediated cellular cytotoxicity includes antibody-dependent cellular cytotoxicity and cellular cytotoxicity mediated by a soluble Fc-fusion protein containing a human Fc-region. It is an immune mechanism leading to the lysis of“antibody-targeted cells” by “human immune effector cells”, wherein:
  • the “human immune effector cells” are a population of leukocytes that display Fc receptors on their surface through which they bind to the Fc-region of antibodies or of Fc-fusion proteins and perform effector functions. Such a population may include, but is not limited to, peripheral blood mononuclear cells (PBMC) and/or natural killer (NK) cells.
  • PBMC peripheral blood mononuclear cells
  • NK natural killer
  • the “antibody-targeted cells” are cells bound by the antibodies or Fc-fusion proteins.
  • the antibodies or Fc fusion-proteins bind to target cells via the protein part N-terminal to the Fc region.
  • the term increased Fc-mediated cellular cytotoxicity is defined as either an increase in the number of “antibody-targeted cells” that are lysed in a given time, at a given concentration of antibody, or of Fc-fusion protein, in the medium surrounding the target cells, by the mechanism of Fc-mediated cellular cytotoxicity defined above, and/or a reduction in the concentration of antibody, or of Fc-fusion protein, in the medium surrounding the target cells, required to achieve the lysis of a given number of “antibody-targeted cells”, in a given time, by the mechanism of Fc -mediated cellular cytotoxicity.
  • Fc-mediated cellular cytotoxicity is relative to the cellular cytotoxicity mediated by the same antibody, or Fc-fusion protein, produced by the same type of host cells, using the same standard production, purification, formulation and storage methods, which are known to those skilled in the art, but that has not been produced by host cells engineered to express the glycosyltransferase GnTIII by the methods described herein.
  • ADCC antibody dependent cellular cytotoxicity
  • the assay uses target cells that are known to express the target antigen recognized by the antigen-binding region of the antibody;
  • the assay uses human peripheral blood mononuclear cells (PBMCs), isolated from blood of a randomly chosen healthy donor, as effector cells;
  • PBMCs peripheral blood mononuclear cells
  • the PBMCs are isolated using standard density centriftigation procedures and are suspended at 5 ⁇ 10 6 cells/ml in RPMI cell culture medium;
  • the target cells are grown by standard tissue culture methods, harvested from the exponential growth phase with a viability higher than 90%, washed in RPMI cell culture medium, labelled with 100 micro-Curies of 51 Cr, washed twice with cell culture medium, and resuspended in cell culture medium at a density of 10 5 cells/ml;
  • the antibody is serially-diluted from 4000 ng/ml to 0.04 ng/ml in cell culture medium and 50 microliters of the resulting antibody solutions are added to the target cells in the 96-well microtiter plate, testing in triplicate various antibody concentrations covering the whole concentration range above;
  • x) the percentage of specific lysis is calculated for each antibody concentration according to the formula (ER-MR)/(MR-SR) ⁇ 100, where ER is the average radioactivity quantified (see point ix above) for that antibody concentration, MR is the average radioactivity quantified (see point ix above) for the MR controls (see point v above), and SR is the average radioactivity quantified (see point ix above) for the SR controls (see point vi above);
  • “increased ADCC” is defined as either an increase in the maximum percentage of specific lysis observed within the antibody concentration range tested above, and/or a reduction in the concentration of antibody required to achieve one half of the maximum percentage of specific lysis observed within the antibody concentration range tested above.
  • the increase in ADCC is relative to the ADCC, measured with the above assay, mediated by the same antibody, produced by the same type of host cells, using the same standard production, purification, formulation and storage methods, which are known to those skilled in the art, but that has not been produced by host cells engineered to overexpress the glycosyltransferase GnTIII.
  • anti-CD20 antibody is intended to mean an antibody which specifically recognizes a cell surface non-glycosylated phosphoprotein of 35,000 Daltons, typically designated as the human B lymphocyte restricted differentiation antigen Bp35, commonly referred to as CD20.
  • the present invention provides methods for the generation and use of host cell systems for the production of glycoforms of antibodies or antibody fragments or fusion proteins which include antibody fragments with increased antibody-dependent cellular cytotoxicity. Identification of target epitopes and generation of antibodies having potential therapeutic value, for which modification of the glycosylation pattern is desired, and isolation of their respective coding nucleic acid sequence is within the scope of the invention.
  • antibodies to target epitopes of interest include but are not limited to polyclonal, monoclonal, chimeric, single chain, Fab fragments and fragments produced by an Fab expression library. Such antibodies may be useful, e.g., as diagnostic or therapeutic agents. As therapeutic agents, neutralizing antibodies, i.e., those which compete for binding with a ligand, substrate or adapter molecule, are of especially preferred interest.
  • various host animals are immunized by injection with the target protein of interest including, but not limited to, rabbits, mice, rats, etc.
  • Various adjuvants may be used to increase the immunological response, depending on the host species, including but not limited to Freund's (complete and incomplete), mineral gels such as aluminum hydroxide, surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, saponin, oil emulsions, keyhole limpet hemocyanin, dinitrophenol, and potentially useful human adjuvants such as BCG (bacille Calmette-Guerin) and Corynebacterium parvum.
  • BCG Bacille Calmette-Guerin
  • Monoclonal antibodies to the target of interest may be prepared using any technique which provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique originally described by Kohler and Milstein, Nature 256:495-97 (1975), the human B-cell hybridoma technique (Kosbor et al., Immunology Today 4:72 (1983); Cote et al., Proc. Natl. Acad. Sci. U.S.A. 80:2026-30 (1983 ) and the EBV-hybridoma technique (Cole et al., Monoclonal Antibodies and Cancer Therapy 77-96 (Alan R. Liss, Inc., 1985)).
  • Antibody fragments which contain specific binding sites of the target protein of interest may be generated by known techniques.
  • fragments include, but are not limited to, F(ab′) 2 fragments which can be produced by pepsin digestion of the antibody molecule and the Fab fragments which can be generated by reducing the disulfide bridges of the F(ab′) 2 fragments.
  • Fab expression libraries may be constructed (Huse et al., Science 246:1275-81 (1989) to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity to the target protein of interest.
  • the present invention provides host cell expression systems for the generation of proteins having modified glycosylation patterns.
  • the present invention provides host cell systems for the generation of glycoforms of proteins having an improved therapeutic value. Therefore, the invention provides host cell expression systems selected or engineered to increase the expression of a glycoprotein-modifying glycosyltransferase, namely ⁇ (1,4)-N-acetylglucosaminyltransferase III (GnTIID).
  • GnTIID glycoprotein-modifying glycosyltransferase
  • such host cell expression systems may be engineered to comprise a recombinant nucleic acid molecule encoding GnTIII, operatively linked to a constitutive or regulated promoter system.
  • host cell expression systems may be employed that naturally produce, are induced to produce, and/or are selected to produce GnTIII.
  • the present invention provides a host cell that has been engineered to express at least one nucleic acid encoding GnTIII.
  • the host cell is transformed or transfected with a nucleic acid molecule comprising at least one gene encoding GnTIII.
  • the host cell has been engineered and/or selected in such way that endogenous GnTIII is activated.
  • the host cell may be selected to carry a mutation triggering expression of endogenous GnTIII.
  • the host cell is a CHO lec 10 mutant.
  • the host cell may be engineered such that endogenous GnTIII is activated.
  • the host cell is engineered such that endogenous GnTIII has been activated by insertion of a constitutive promoter element, a transposon, or a retroviral element into the host cell chromosome.
  • any type of cultured cell line can be used as a background to engineer the host cell lines of the present invention.
  • CHO cells, BHK cells, NS0 cells, SP2/0 cells, YO myeloma cells, P3X63 mouse myeloma cells, PER cells, PER.C6 cells or hybridoma cells, yeast cells, or insect cells are used as the background cell line to generate the engineered host cells of the invention.
  • the invention is contemplated to encompass any engineered host cells expressing GnTIII as defined herein.
  • One or several nucleic acids encoding GnTIII may be expressed under the control of a constitutive promoter or, alternately, a regulated expression system.
  • Suitable regulated expression systems include, but are not limited to, a tetracycline-regulated expression system, an ecdysone-inducible expression system, a lac-switch expression system, a glucocorticoid-inducible expression system, a temperature-inducible promoter system, and a metallothionein metal-inducible expression system.
  • nucleic acids encoding GnTIII are comprised within the host cell system, some of them may be expressed under the control of a constitutive promoter, while others are expressed under the control of a regulated promoter.
  • the maximal expression level is considered to be the highest possible level of stable GnTIII expression that does not have a significant adverse effect on cell growth rate, and will be determined using routine experimentation
  • Expression levels are determined by methods generally known in the art, including Western blot analysis using a GnTIII specific antibody, Northern blot analysis using a GnTIII specific nucleic acid probe, or measurement of enzymatic activity.
  • a lectin may be employed which binds to biosynthetic products of the GnTIII, for example, E 4 -PHA lectin.
  • the nucleic acid may be operatively linked to a reporter gene; the expression levels of the GnTIII are determined by measuring a signal correlated with the expression level of the reporter gene.
  • the reporter gene may transcribed together with the nucleic acid(s) encoding said GnTIII as a single mRNA molecule; their respective coding sequences may be linked either by an internal ribosome entry site (IRES) or by a cap-independent translation enhancer (CITE).
  • the reporter gene may be translated together with at least one nucleic acid encoding said GnTIII such that a single polypeptide chain is formed.
  • the nucleic acid encoding the GnTIII may be operatively linked to the reporter gene under the control of a single promoter, such that the nucleic acid encoding the GnTIII and the reporter gene are transcribed into an RNA molecule which is alternatively spliced into two separate messenger RNA (mRNA) molecules; one of the resulting mRNAs is translated into said reporter protein, and the other is translated into said GnTIII.
  • mRNA messenger RNA
  • nucleic acids encoding GnTIII may be arranged in such way that they are transcribed as one or as several mRNA molecules. If they are transcribed as a single mRNA molecule, their respective coding sequences may be linked either by an internal ribosome entry site (IRES) or by a cap-independent translation enhancer (CITE). They may be transcribed from a single promoter into an RNA molecule which is alternatively spliced into several separate messenger RNA (mRNA) molecules, which then are each translated into their respective encoded GnTIII.
  • IRS internal ribosome entry site
  • CITE cap-independent translation enhancer
  • the present invention provides host cell expression systems for the generation of therapeutic antibodies, having an increased antibody-dependent cellular cytotoxicity, and cells which display the IgG Fc region on the surface to promote Fc-mediated cytotoxicity.
  • the host cell expression systems have been engineered and/or selected to express nucleic acids encoding the antibody for which the production of altered glycoforms is desired, along with at least one nucleic acid encoding GnTIII.
  • the host cell system is transfected with at least one gene encoding GnTIII.
  • the transfected cells are selected to identify and isolate clones that stably express the GnTIII.
  • the host cell has been selected for expression of endogenous GnTIII.
  • cells may be selected carrying mutations which trigger expression of otherwise silent GnTIII.
  • CHO cells are known to carry a silent GnT III gene that is active in certain mutants, e.g., in the mutant Lec10.
  • methods known in the art may be used to activate silent GnTIII, including the insertion of a regulated or constitutive promoter, the use of transposons, retroviral elements, etc.
  • gene knockout technologies or the use of ribozyme methods may be used to tailor the host cell's GnTIII expression level, and is therefore within the scope of the invention.
  • any type of cultured cell line can be used as background to engineer the host cell lines of the present invention.
  • CHO cells, BHK cells, NS0 cells, SP2/0 cells, YO myeloma cells, P3X63 mouse myeloma cells, PER cells, PER.C6 cells or hybridoma cells, yeast cell, or insect cells may be used.
  • such cell lines are engineered to further comprise at least one transfected nucleic acid encoding a whole antibody molecule, an antibody fragment, or a fusion protein that includes a region equivalent to the Fc region of an immunoglobulin.
  • a hybridoma cell line expressing a particular antibody of interest is used as background cell line to generate the engineered host cells of the invention.
  • At least one nucleic acid in the host cell system encodes GnT III.
  • One or several nucleic acids encoding GnTIII may be expressed under the control of a constitutive promoter, or alternately, a regulated expression system
  • Suitable regulated expression systems include, but are not limited to, a tetracycline-regulated expression system, an ecdysone-inducible expression system, a lac-switch expression system, a glucocorticoid-inducible expression system, a temperature-inducible promoter system, and a metallothionein metal-inducible expression system.
  • nucleic acids encoding GnTIII are comprised within the host cell system, some of them may be expressed under the control of a constitutive promoter, while others are expressed under the control of a regulated promoter.
  • the maximal expression level is considered to be the highest possible level of stable GnTIII expression that does not have a significant adverse effect on cell growth rate, and will be determined using routine experimentation. Expression levels are determined by methods generally known in the art, including Western blot analysis using a GnTIII specific antibody, Northern blot analysis using a GnTIII specific nucleic acid probe, or measurement of GnTIII enzymatic activity.
  • a lectin may be employed which binds to biosynthetic products of GnTIII, for example, E 4 -PHA lectin.
  • the nucleic acid may be operatively linked to a reporter gene; the expression levels of the glycoprotein-modifying glycosyl transferase are determined by measuring a signal correlated with the expression level of the reporter gene.
  • the reporter gene may transcribed together with the nucleic acid(s) encoding said glycoprotein-modifying glycosyl transferase as a single mRNA molecule; their respective coding sequences may be linked either by an internal ribosome entry site (IRES) or by a cap-independent translation enhancer (CITE).
  • the reporter gene may be translated together with at least one nucleic acid encoding GnTIII such that a single polypeptide chain is formed.
  • the nucleic acid encoding the GnTIII may be operatively linked to the reporter gene under the control of a single promoter, such that the nucleic acid encoding the GnTIII and the reporter gene are transcribed into an RNA molecule which is alternatively spliced into two separate messenger RNA (mRNA) molecules; one of the resulting mRNAs is translated into said reporter protein, and the other is translated into said GnTIII.
  • mRNA messenger RNA
  • nucleic acids encoding a GnTIII may be arranged in such way that they are transcribed as one or as several mRNA molecules. If they are transcribed as single mRNA molecule, their respective coding sequences may be linked either by an internal ribosome entry site (IRES) or by a cap-independent translation enhancer (CITE). They may be transcribed from a single promoter into an RNA molecule which is alternatively spliced into several separate messenger RNA (mRNA) molecules, which then are each translated into their respective encoded GnTIII.
  • IRS internal ribosome entry site
  • CITE cap-independent translation enhancer
  • Methods which are well known to those skilled in the art can be used to construct expression vectors containing the coding sequence of the protein of interest and the coding sequence of the GnTIII and appropriate transcriptional/translational control signals. These methods include in vitro recombinant DNA techniques, synthetic techniques and in vivo recombination/genetic recombination. See, for example, the techniques described in Maniatis et al., Molecular Cloning A Laboratory Manual, Cold Spring Harbor Laboratory, N.Y. (1989) and Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates and Wiley Interscience, N.Y (1989).
  • a variety of host-expression vector systems maybe utilized to express the coding sequence of the protein of interest and the coding sequence of the GnTIII.
  • mammalian cells are used as host cell systems transfected with recombinant plasmid DNA or cosmid DNA expression vectors containing the coding sequence of the protein of interest and the coding sequence of the GnTIII.
  • CHO cells, ByIK cells, NS0 cells, SP2/0 cells, YO myeloma cells, P3X63 mouse myeloma cells, PER cells, PER. C6 cells or hybridoma cells, yeast cells, or insect cells are used as host cell system.
  • yeast cells transformed with recombinant yeast expression vectors containing the coding sequence of the protein of interest and the coding sequence of the GnTIII include, yeast cells transformed with recombinant yeast expression vectors containing the coding sequence of the protein of interest and the coding sequence of the GnTIII; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing the coding sequence of the protein of interest and the coding sequence of the GnTIII; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing the coding sequence of the protein of interest and the coding sequence of the GnTIII; or animal cell systems infected with recombinant virus expression vectors (e.g., adenovirus, vaccinia virus) including cell lines engineered to contain multiple copies
  • stable expression is generally preferred to transient expression because it typically achieves more reproducible results and also is more amenable to large scale production.
  • host cells can be transformed with the respective coding nucleic acids controlled by appropriate expression control elements (e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker.
  • appropriate expression control elements e.g., promoter, enhancer, sequences, transcription terminators, polyadenylation sites, etc.
  • engineered cells may be allowed to grow for 1-2 days in an enriched media, and then are switched to a selective media.
  • the selectable marker in the recombinant plasmid confers resistance to the selection and allows selection of cells which have stably integrated the plasmid into their chromosomes and grow to form foci which in turn can be cloned and expanded into cell lines.
  • a number of selection systems may be used, including, but not limited to, the herpes simplex virus thymidine kinase (Wigler et al., Cell 11:223 (1977)), hypoxanthine-guaninephosphoribosyltransferase (Szybalska & Szybalski, Proc. Natl. Acad. Sci.
  • trpB which allows cells to utilize indole in place of tryptophan
  • hisD which allows cells to utilize histinol in place of histidine
  • ODC ornithine decarboxylase
  • DFMO 2-(difluoromethyl)-DL- ornithine
  • the host cells which contain the coding sequence and which express the biologically active gene products may be identified by at least four general approaches; (a) DNA-DNA or DNA-RNA hybridization; (b) the presence or absence of “marker” gene functions; (c) assessing the level of transcription as measured by the expression of the respective mRNA transcripts in the host cell; and (d) detection of the gene product as measured by immunoassay or by its biological activity.
  • the presence of the coding sequence of the protein of interest and the coding sequence of the GnTIII inserted in the expression vector can be detected by DNA-DNA or DNA-RNA hybridization using probes comprising nucleotide sequences that are homologous to the respective coding sequences, respectively, or portions or derivatives thereof
  • the recombinant expression vector/host system can be identified and selected based upon the presence or absence of certain “marker” gene functions (e.g., thymidine kinase activity, resistance to antibiotics, resistance to methotrexate, transformation phenotype, occlusion body formation in baculovirus, etc.).
  • certain “marker” gene functions e.g., thymidine kinase activity, resistance to antibiotics, resistance to methotrexate, transformation phenotype, occlusion body formation in baculovirus, etc.
  • a marker gene can be placed in tandem with the coding sequences under the control of the same or different promoter used to control the expression of the coding sequences. Expression of the marker in response to induction or selection indicates expression of the coding sequence of the protein of interest and the coding sequence of the GnTIII.
  • transcriptional activity for the coding region of the protein of interest and the coding sequence of the GnTIII can be assessed by hybridization assays.
  • RNA can be isolated and analyzed by Northern blot using a probe homologous to the coding sequences of the protein of interest and the coding sequence of the GnTIII or particular portions thereof
  • total nucleic acids of the host cell may be extracted and assayed for hybridization to such probes.
  • the expression of the protein products of the protein of interest and the coding sequence of the GnTIII can be assessed immunologically, for example by Western blots, immunoassays such as radioimmuno-precipitation, enzyme-linked immunoassays and the like.
  • the ultimate test of the success of the expression system involves the detection of the biologically active gene products.
  • the present invention provides glycoforms of antibodies and antibody fragments having increased antibody-dependent cellular cytotoxicity.
  • ADCC a lytic attack on antibody-targeted cells, is triggered upon binding of leukocyte receptors to the constant region (Fc) of antibodies. Deo et al., Immunology Today 18:127 (1997)
  • Fc ⁇ Rs lymphocyte receptors
  • Protein engineering studies have shown that Fc ⁇ Rs interact with the lower hinge region of the IgG CH2 domain. Lund et al., J. Immunol. 157:4963-69 (1996). However, Fc ⁇ R binding also requires the presence of oligosaccharides covalently attached at the conserved Asn 297 in the CH2 region. Lund et al., J. Immunol. 157:4963-69 (1996); Wright and Morrison, Trends Biotech.
  • An IgG molecule carries two N-linked oligosaccharides in its Fc region, one on each heavy chain.
  • an antibody is produced as a population of glycoforms which share the same polypeptide backbone but have different oligosaccharides attached to the glycosylation sites.
  • the oligosaccharides normally found in the Fc region of serum IgG are of complex bi-antennary type (Wormald et al., Biochemistry 36:130-38 (1997), with low level of terminal sialic acid and bisecting N-acetylglucosamine (GIcNAc), and a variable degree of terminal galactosylation and core fucosylation.
  • the mouse- or hamster-derived cell lines used in industry and academia for production of unconjugated therapeutic mAbs normally attach the required oligosaccharide determinants to Fc sites.
  • IgGs expressed in these cell lines lack, however, the bisecting GIcNAc found in low amounts in serum IgGs. Lifely et al., Glycobiology 318:813-22 (1995).
  • CAMPATH-1H humanized IgG1
  • the rat cell-derived antibody reached a similar in vitro ADCC activity as CAMPATH-1H antibodies produced in standard cell lines, but at significantly lower antibody concentrations.
  • the CAMPATH antigen is normally present at high levels on lymphoma cells, and this chimeric mAb has high ADCC activity in the absence of a bisecting GlcNAc. Lifely et al., Glycobiology 318:813-22 (1995). In the N-linked glycosylation pathway, a bisecting GlcNAc is added by the enzyme ⁇ (1,4)-N-acetylglucosaminyltransferase III (GnT III). Schachter, Biochem. Cell Biol. 64:163-81 (1986).
  • the present inventors used a single antibody-producing CHO cell line, that was previously engineered to express, in an externally-regulated fashion, different levels of a cloned GnT III gene. This approach established for the first time a rigorous correlation between expression of GnTIII and the ADCC activity of the modified antibody.
  • C2B8 antibody modified according to the disclosed method had an about sixteen-fold higher ADCC activity than the standard, unmodified C2B8 antibody produced under identical cell culture and purification conditions.
  • a C2B8 antibody sample expressed in CHO-tTA-C2B8 cells that do not have GnTIII expression showed a cytotoxic activity of about 31% (at 1 ⁇ g/ml antibody concentration), measured as in vitro lysis of SB cells (CD20+) by human lymphocytes.
  • C2B8 antibody derived from a CHO cell culture expressing GnT III at a basal, largely repressed level showed at 1 ⁇ g/ml antibody concentration a 33% increase in ADCC activity against the control at the same antibody concentration.
  • increasing the expression of GnT III produced a large increase of almost 80% in the maximal ADCC activity (at 1 ⁇ g/ml antibody concentration) compared to the control at the same antibody concentration.
  • antibodies of the invention having increased antibody-dependent cellular cytotoxicity include, but are not limited to, anti-human neuroblastoma monoclonal antibody (chCE7) produced by the methods of the invention, a chimeric anti-human renal cell carcinoma monoclonal antibody (ch-G250) produced by the methods of the invention, a humanized anti-HER2 monoclonal antibody (e.g., Trastuzumab (HERCEPTIN)) produced by the methods of the invention, a chimeric anti-human colon, lung, and breast carcinoma monoclonal antibody (ING-1) produced by the methods of the invention, a humanized anti-human 17-1A antigen monoclonal antibody (3622W94) produced by the methods of the invention, a humanized anti-human colorectal tumor antibody (A33) produced by the methods of the invention, an anti-human melanoma antibody (R24) directed against GD3 ganglioside produced by the methods of the invention, and a chimeric anti-human squam
  • the present invention relates to a method for increasing the ADCC activity of therapeutic antibodies. This is achieved by engineering the glycosylation pattern of the Fc region of such antibodies, in particular by maximizing the proportion of antibody molecules carrying bisected complex oligosaccharides and bisected hybrid oligosaccharides N-linked to the conserved glycosylation sites in their Fc regions.
  • This strategy can be applied to increase Fc-mediated cellular cytotoxicity against undesirable cells mediated by any molecule carrying a region that is an equivalent to the Fc region of an immunoglobulin, not only by therapeutic antibodies, since the changes introduced by the engineering of glycosylation affect only the Fc region and therefore its interactions with the Fc receptors on the surface of effector cells involved in the ADCC mechanism.
  • Fc-containing molecules to which the presently disclosed methods can be applied include, but are not limited to, (a) soluble fusion proteins made of a targeting protein domain fused to the N-terminus of an Fc-region (Chamov and Ashkenazi, Trends Biotech. 14: 52 (1996) and (b) plasma membrane-anchored fusion proteins made of a type II transmembrane domain that localizes to the plasma membrane fused to the N-terminus of an Fc region (Stumble, P. F., Nature Biotech. 16: 1357 (1998)).
  • the targeting domain directs binding of the fusion protein to undesirable cells such as cancer cells, i.e., in an analogous fashion to therapeutic antibodies.
  • undesirable cells such as cancer cells
  • the application of presently disclosed method to enhance the Fc-mediated cellular cytotoxic activity mediated by these molecules would therefore be identical to the method applied to therapeutic antibodies.
  • the undesirable cells in the body have to express the gene encoding the fusion protein.
  • This can be achieved either by gene therapy approaches, i.e., by transfecting the cells in vivo with a plasmid or viral vector that directs expression of the fusion protein-encoding gene to undesirable cells, or by implantation in the body of cells genetically engineered to express the fusion protein on their surface.
  • the later cells would normally be implanted in the body inside a polymer capsule (encapsulated cell therapy) where they cannot be destroyed by an Fc-mediated cellular cytotoxicity mechanism. However should the capsule device fail and the escaping cells become undesirable, then they can be eliminated by Fc-mediated cellular cytotoxicity.
  • the presently disclosed method would be applied either by incorporating into the gene therapy vector an additional gene expression cassette directing adequate or maximal expression levels of GnT III or by engineering the cells to be implanted to express adequate or maximal levels of GnT III.
  • the aim of the disclosed method is to increase or maximize the proportion of surface-displayed Fc regions carrying bisected complex oligosaccharides and/or bisected hybrid oligosaccharides.
  • VL and VH cDNA fragments were subcloned into pBluescriptIIKS(+), sequenced and directly joined by ligation to the human constant light (Ig ⁇ ) and heavy (IgG1) chain cDNAs, respectively, using unique restriction sites introduced at the variable and constant region junctions without altering the original amino acid residue sequence (Umana, P., et al., Nat Biotechnol. 17:176-180 (1999); Reff, M. E., et al., Blood 83:435-445 (1994)).
  • Each cell line was cotranfected with vectors pC2B8L, pC2B8H, and pZeoSV2(+) (for Zeocin resistance; Invitrogen, Leek, The Netherlands) using a calcium phosphate method.
  • Zeocin resistant clones were transferred to a 96-well plate and assayed for IDEC-C2B8 production using an ELISA assay specific for the human constant region (4).
  • Three IDEC-C2B8 samples were obtained from parallel cultures of a selected clone (CHO-tet-GnTIII-C2B8), differing only in the tetracycline concentration added to the medium (25, 50 and 2000 ng/mL respectively).
  • CD20-positive cells SB cells; ATCC deposit no. ATCC CCL120
  • HSB cells CD20-negative cells
  • HBSSB bovine serum albumin fraction V
  • Oligosaccharide profiling by MALDI/TOF-MS were derived from C2B8 antibody samples, MabTheraTM (European counterpart of Rituximab; kind gift from R. Stahel, Universit ⁇ dot over (a) ⁇ tspital, Switzerland), C2B8-25t, C2B8-50t, C2B8-2000t, and C2B8-nt, (100 ⁇ g each) as previously described (Umana, P., et al., Nat Biotechnol. 17:176-180 (1999)).
  • the antibody samples were first treated with Arthrobacter ureafaciens sialidase (Oxford Glycosciences, Abingson, UK) to remove any sialic acid monosaccharide residues.
  • Neutral N-linked oligosaccharides were then released from the desialylated antibody samples using peptide-N-glycosidase F (Oxford Glycosciences), purified using micro-columns, and analyzed by MALDI/TOF-MS in an Elite Voyager 400 spectrometer (Perseptive Biosystems, Farmingham, Mass.).
  • PBMC Peripheral blood mononuclear cells
  • a C2B8-producing, control cell line that does not express GnTIII was also established and cultured under the same conditions as for the three parallel cultures of CHO-tet-GnTIII. After Protein A-affinity chromatography, mAb purity was estimated to be higher than 95% by SDS-PAGE and Coomassie-blue staining.
  • Sample C2B8-25t showed specific antigen binding by indirect immunofluorescence using CD20-positive and CD20-negative cells (FIG. 1), indicating that the synthesized VL and VH gene fragments were functionally correct.
  • Oligosaccharide profiling with MALDI/TOF-MS The glycosylation profile of each antibody sample was analyzed by MALDI/TOF-MS of the released, neutral oligosaccharide mix. In this technique, oligosaccharides of different mass appear as separate peaks in the spectrum and their proportions are quantitatively reflected by the relative peak heights (Harvey, D. J., Rapid Common Mass Spectrom. 7:614-619 (1993); Harvey, D. J., et al., Glycoconj J. 15:333-338(1998)).
  • Oligosaccharide structures were assigned to different peaks based on their expected molecular masses, previous structural data for oligosaccharides derived from IgGI mAbs produced in the same host, and information on the N-linked oligosaccharide biosynthetic pathway.
  • GnTIII expression levels i.e., tetracycline concentration
  • the amount of bisected oligosaccharides derived from the different antibody samples did not carry bisected oligosaccharides (FIGS. 2A and 2B).
  • bisected structures amounted up to approximately 35% of the oligosaccharides pool in sample C2B8-2000t, i.e, at a basal level of GnTIII expression.
  • ADCC activity of IDEC-C2B8 glycosylated variants Different C2B8 mAb glycosylation variants were compared for ADCC activity, measured as in vitro lysis of CD20-positive SB cells.
  • sample C2B8-50t carried approximately equal levels of bisected and non-bisected oligosaccharides, but did not mediate significantly higher target-cell lysis.
  • sample C2B8-25t which contained up to 80% of bisected oligosaccharide structures, was significantly more active than the rest of the samples in the whole antibody concentration range. It reached the maximal level of ADCC activity of sample C2B8-nt at a 10-fold lower antibody concentration (FIG. 4A).
  • Sample C2B8-25t also showed a significant increase in the maximal ADCC activity with respect to the control (50% vs. 30% lysis).
  • Sample C2B8-50t showed a slight increase in activity whereas sample C2B8-25t clearly out performed MabtheraTM at all antibody concentrations.
  • SP2/0 mouse myeloma cells producing chG250 chimeric mAb were grown in standard cell culture medium supplemented with 1:100 (v/v) penicillin/streptomycin/antimycotic solution (SIGMA, Buchs, Switzerland). Cells were cultured at 37° C. in a 5% CO 2 humidified atmosphere in Tissue Culture Flasks. Medium was changed each 3-4 days. Cells were frozen in culture medium containing 10% DMSO.
  • wt-chG250-SP2/0 myeloma cells were transfected by electroporation with a vector for constitutive expression of GnTIII operatively linked via an IRES to a puromycin resistance gene. 24 hours before electroporation culture medium was changed and cells were seeded at 5 ⁇ 10 5 cells/ml. Seven million cells were centrifuged for 4 min at 1300 rpm at 4° C. Cells were washed with 3 mL new medium and centrifuged again. Cells were resuspended in a volume of 0.3-0.5 ml of reaction mix, containing 1.25% (v/v) DMSO and 20-30 ⁇ g DNA in culture medium.
  • the electroporation mix was then transferred to a 0.4 cm cuvette and pulsed at low voltage (250-300 V) and high capacitance (960 ⁇ F) using Gene Pulser from Bio Rad. After electroporation cells were quickly transferred to 6 mL 1.25% (v/v) DMSO culture medium in a T25 culture flask and incubated at 37° C. Stable integrants were selected by applying 2 ⁇ g/mL puromycin to the medium two days after electroporation. After 2-3 weeks a stable, puromycin-resitant mixed population was obtained. Single-cell derived clones were obtained via FACS and were subsequently expanded and maintained under puromycin selection.
  • Clones 2F1, 3D3, 4E6, 4E8, 4G3, 5G2, 5H12 and the wild type were seeded at 3 ⁇ 10 5 cells/mL in a total volume of 130 ml culture medium, and cultivated in single Triple-flasks. Cells used for seeding were all in full exponential growth phase, therefore cells were considered to be at the same growth state when the production batches started. Cells were cultivated for 4 days. Supernatants containing the antibody were collected in the late exponential growth phase to ensure reproducibility . The chG250 monoclonal antibody was purified in two chromatographic steps.
  • Culture supernatants containing the chG250 monoclonal antibody derived from each batch were first purified using a HiTrap Protein A affinity chromatography. Protein A is highly specific for the human IgG F c region. Pooled samples from the protein A eluate were buffer exchanged to PBS by cation-exchange chromatography on a Resource S 1 ml column (Amersham Pharmacia Biotech). Final purity was judged to be higher than 95% from SDS-staining and Coomassie blue staining (FIG. 6). The concentration of each sample was determined with a standard calibration curve using wild type antibody with known concentration.
  • Oligosaccharide profiles were obtained by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF-MS), which accurately provides the molecular masses of the different oligosaccharide structures.
  • MALDI/TOF-MS matrix-assisted laser desorption/ionization time of flight mass spectrometry
  • This technique allows a quantitative analysis of proportions between different oligosacchaiide structures within a mixture.
  • Neutral oligosaccharides appeared predominantly as [M+Na + ] ions, however sometimes they were accompanied by smaller [M+K + ] ions, leading to an increase in mass of m/z of 16.
  • the percentage of the structure appearing as potassium ion adducts depends on the content of the matrix and may thus vary between samples.
  • a mixture of neutral N-linked oligosaccharides derived from each antibody preparation was analyzed using a 2,5-dehydrobenzoic acid (2,5-DHB) as matrix.
  • 2,5-DHB 2,5-dehydrobenzoic acid
  • Some of the peaks in the spectra were unequivocally assigned to specific oligosaccharide structures, because of known monosaccharide composition and unique mass. However, sometimes multiple structures could be assigned to a particular mass.
  • MALDI enables the determination of the mass and cannot distinguish between isomers.
  • Knowledge of the biosynthetic pathway and previous structural data enable, in most cases, the assignment of an oligosaccharide structure to a peak in the spectrum.
  • GCTIII generated bisected Fc-associated oligosaccharide structures of two types: complex or hybrid.
  • Complex bisected oligosaccharides were unequivocally assigned to peaks at m/z 1543, 1689, 1705, 1851 and 1867 ([M+K + ] adduct).
  • the increase in bisected oligosaccharides was accompanied by a concomitant reduction of peaks m/z 1486 and 1648, that correspond to nonbisected complex oligosaccharides.
  • the main substrate of GnTIII m/z 1486) decreased dramatically.
  • the percentage of the nonbisected complex oligosaccharide type assigned to peak at m/z 1648, had the lowest values for the clones expressing the highest GnTIII levels (clones 4E6, 4E8, 5G2 and 5H12). These two peaks decreased in favor of the accumulation of bisected complex and bisected hybrid type oligosaccharides (FIGS. 7 A- 7 D and 8 A- 8 D). The percentage of bisected complex oligosaccharides was higher for the samples derived from the clones expressing lower amounts of GnTIII. This is consistent with the fact that a higher GnTIII expression level probably shifts the biosynthetic flux to bisected hybrid structures, thereby decreasing the relative proportions of complex and complex bisected compound.
  • Peaks m/z 1664, 1680, 1810 and 1826 can be assigned to either bisected hybrid type, to galactosylated complex oligosaccharides, or a mixture of them. Due to the fact that the wt-antibody preparation had a relatively low percentage of peak 1664, it was assumed that this peak, appearing in significant amounts in the antibody samples derived from the different clones, corresponded entirely to bisected hybrid structures (FIGS. 7 A- 7 D and 8 A- 8 D).
  • the Calcein-AM retention method of measuring cytotoxicity measures the dye fluorescence remaining in the cells after incubation with the antibody.
  • Four million G250 antigen-positive cells (target) were labelled with 10 ⁇ M Calcein-AM (Molecular Probes, Eugene, Oreg.) in 1.8 mL RPMI-1640 cell culture medium (GIBCO BRL, Basel, Switzerland) supplemented with 10% fetal calf serum for 30 min at 37° C. in a 5% CO 2 humidified atmosphere.
  • the cells were washed twice in culture medium and resuspended in 12 mL AIMV serum free medium (GIBCO BRL, Basel, Switzerland).
  • PBMC Peripheral blood mononuclear cells
  • 96-well plate was centrifuged at 700 ⁇ g for 5 min and the supernatants were discarded.
  • the cell pellets were washed twice with Hank's balanced salt solution (HBSS) and lysed in 200 ⁇ L 0.05M sodium borate, pH 9, 0.1% Triton X-100. Retention of the fluorescent dye in the target cells was measured with a FLUO star microplate reader (BMG Lab Technologies, Offenburg, Germany).
  • the specific lysis was calculated relative to a total lysis control, resulting from exposure of the target cells to saponin (200 ⁇ g/mL in AIMV; SIGMA, Buchs, Switzerland) instead of exposure to antibody.
  • F med represents the fluorescence of target cells treated with medium alone and considers unspecific lysis by PMBCs
  • F exp represents the fluorescence of cells treated with antibody
  • F det represents the fluorescence of cells treated with saponin instead of antibody.
  • Unmodified chG250 antibody did not mediate significant ADCC activity over the entire concentration range used in the assay (the activity was not significantly different from background).
  • Augmented ADCC activity (close to 20%, see FIG. 9) at 2 ⁇ g/mL was observed with the antibody sample derived from clone 3D3, which expressed intermediate GnTIII levels.
  • the cytotoxic activity of this antibody samples did not grow at higher antibody concentrations.
  • the antibody preparation derived from clone 5H12 showed a striking increase over samples 3D3 and unmodified antibody in its ability to mediate ADCC against target cells.
  • the maximal ADCC activity of this antibody preparation was around 50% andwas remarkable in mediating significant ADCC activity at 125-fold less concentrated when comparing with the unmodified control sample.
  • Immune-mediated, acquired pure red cell aplasia is a rare disorder frequently associated with other autoimmune phenomena.
  • an anti-CD20 chimeric monoclonal antibody prepared by the methods of the present invention and having increased ADCC is administered to the subject as described in Zecca, M. et al., Blood 12:3995-97 (1997) (the entire contents of which are hereby incorporated by reference).
  • a subject with PRCA and autoimmune hemolytic anemia is given two doses of antibody, 375 mg/m 2 , per week.
  • substitutive treatment with intravenous immunoglobulin is initiated. This treatment produces a marked depletion of B cells and a significant rise in reticulocyte count accompanied by increased hemoglobin levels.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Radiology & Medical Imaging (AREA)
  • Epidemiology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
US10/211,554 1998-04-20 2002-08-05 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity Abandoned US20030175884A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US10/211,554 US20030175884A1 (en) 2001-08-03 2002-08-05 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US11/199,232 US8021856B2 (en) 1998-04-20 2005-08-09 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US13/196,724 US8999324B2 (en) 1998-04-20 2011-08-02 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US14/665,191 US9321843B2 (en) 1998-04-20 2015-03-23 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US15/080,020 US9631023B2 (en) 1998-04-20 2016-03-24 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US30951601P 2001-08-03 2001-08-03
US10/211,554 US20030175884A1 (en) 2001-08-03 2002-08-05 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
US10/633,697 Continuation-In-Part US7517670B2 (en) 1998-04-20 2003-08-05 Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US11/199,232 Continuation US8021856B2 (en) 1998-04-20 2005-08-09 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity

Publications (1)

Publication Number Publication Date
US20030175884A1 true US20030175884A1 (en) 2003-09-18

Family

ID=23198536

Family Applications (5)

Application Number Title Priority Date Filing Date
US10/211,554 Abandoned US20030175884A1 (en) 1998-04-20 2002-08-05 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US11/199,232 Expired - Fee Related US8021856B2 (en) 1998-04-20 2005-08-09 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US13/196,724 Expired - Fee Related US8999324B2 (en) 1998-04-20 2011-08-02 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US14/665,191 Expired - Fee Related US9321843B2 (en) 1998-04-20 2015-03-23 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US15/080,020 Expired - Fee Related US9631023B2 (en) 1998-04-20 2016-03-24 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity

Family Applications After (4)

Application Number Title Priority Date Filing Date
US11/199,232 Expired - Fee Related US8021856B2 (en) 1998-04-20 2005-08-09 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US13/196,724 Expired - Fee Related US8999324B2 (en) 1998-04-20 2011-08-02 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US14/665,191 Expired - Fee Related US9321843B2 (en) 1998-04-20 2015-03-23 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US15/080,020 Expired - Fee Related US9631023B2 (en) 1998-04-20 2016-03-24 Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity

Country Status (15)

Country Link
US (5) US20030175884A1 (da)
EP (2) EP1423510A4 (da)
JP (2) JP2005524379A (da)
KR (2) KR20040054669A (da)
CN (1) CN1555411A (da)
AU (1) AU2002339845B2 (da)
CA (2) CA2838062C (da)
HU (1) HUP0700103A3 (da)
IL (2) IL160170A0 (da)
MX (1) MXPA04001072A (da)
NO (1) NO332457B1 (da)
NZ (5) NZ603111A (da)
PL (1) PL217751B1 (da)
RU (1) RU2321630C2 (da)
WO (1) WO2003011878A2 (da)

Cited By (142)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1071700A1 (en) * 1998-04-20 2001-01-31 GlycArt Biotechnology AG Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US20030003097A1 (en) * 2001-04-02 2003-01-02 Idec Pharmaceutical Corporation Recombinant antibodies coexpressed with GnTIII
US20040132101A1 (en) * 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US20050208617A1 (en) * 2000-06-28 2005-09-22 Piotr Bobrowicz N-acetylglucosamintransferase III expression in lower eukaryotes
US20050244403A1 (en) * 2004-03-24 2005-11-03 Xencor, Inc. Immunoglobulin variants outside the Fc region
US20050249723A1 (en) * 2003-12-22 2005-11-10 Xencor, Inc. Fc polypeptides with novel Fc ligand binding sites
US20050272128A1 (en) * 1998-04-20 2005-12-08 Glycart Biotechnology Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US20060002930A1 (en) * 2004-04-16 2006-01-05 Genentech, Inc. Treatment of disorders
US20060074225A1 (en) * 2004-09-14 2006-04-06 Xencor, Inc. Monomeric immunoglobulin Fc domains
US20060173170A1 (en) * 2004-11-12 2006-08-03 Xencor, Inc. Fc variants with altered binding to FcRn
US20060177898A1 (en) * 2000-06-28 2006-08-10 Glycofi, Inc. Methods for producing modified glycoproteins
US20060210555A1 (en) * 2001-12-21 2006-09-21 Antigenics, Inc. Compositions comprising immunoreactive reagents and saponins, and methods of use thereof
US20060223096A1 (en) * 2005-03-25 2006-10-05 Glycart Biotechnology Ag Antigen binding molecules directed to MCSP and having increased Fc receptor binding affinity and effector function
US20060235208A1 (en) * 2002-09-27 2006-10-19 Xencor, Inc. Fc variants with optimized properties
US20060269545A1 (en) * 2005-02-07 2006-11-30 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20060275282A1 (en) * 2005-01-12 2006-12-07 Xencor, Inc. Antibodies and Fc fusion proteins with altered immunogenicity
US20070003546A1 (en) * 2002-03-01 2007-01-04 Xencor, Inc. Optimized Fc variants and methods for their generation
US20070037248A1 (en) * 2000-06-28 2007-02-15 Piotr Bobrowicz Production of modified glycoproteins having multiple antennary structures
US20070071745A1 (en) * 2005-08-26 2007-03-29 Pablo Umana Modified antigen binding molecules with altered cell signaling activity
US20070087005A1 (en) * 2005-10-14 2007-04-19 Lazar Gregory A Anti-glypican-3 antibody
US20070111281A1 (en) * 2005-05-09 2007-05-17 Glycart Biotechnology Ag Antigen binding molecules having modified Fc regions and altered binding to Fc receptors
US20070148171A1 (en) * 2002-09-27 2007-06-28 Xencor, Inc. Optimized anti-CD30 antibodies
US20070219133A1 (en) * 2002-03-01 2007-09-20 Xencor, Inc. CD52 OPTIMIZED Fc VARIANTS AND METHODS FOR THEIR GENERATION
US20070237767A1 (en) * 2003-03-03 2007-10-11 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRllla
US20070275460A1 (en) * 2003-03-03 2007-11-29 Xencor.Inc. Fc Variants With Optimized Fc Receptor Binding Properties
US20080057056A1 (en) * 2003-03-03 2008-03-06 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIC
US20080095770A1 (en) * 2006-08-09 2008-04-24 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20080206867A1 (en) * 2005-10-03 2008-08-28 Desjarlais John R Fc variants with optimized Fc receptor binding properties
US20080254027A1 (en) * 2002-03-01 2008-10-16 Bernett Matthew J Optimized CD5 antibodies and methods of using the same
US20080260731A1 (en) * 2002-03-01 2008-10-23 Bernett Matthew J Optimized antibodies that target cd19
US20080267976A1 (en) * 2005-10-06 2008-10-30 Gregory Alan Lazar Optimized Anti-Cd30 Antibodies
WO2008070569A3 (en) * 2006-12-01 2008-11-20 Medarex Inc Human antibodies that bind cd22 and uses thereof
US20080313379A1 (en) * 2007-06-15 2008-12-18 United Memories, Inc. Multiple bus charge sharing
US20090169550A1 (en) * 2007-12-21 2009-07-02 Genentech, Inc. Therapy of rituximab-refractory rheumatoid arthritis patients
US20090209024A1 (en) * 2000-06-28 2009-08-20 Gerngross Tillman U Combinatorial DNA library for producing modified N-glycans in lower eukaryotes
US20090208500A1 (en) * 2005-06-03 2009-08-20 Genentech, Inc. Method of producing antibodies with improved function
US20090263318A1 (en) * 2003-01-24 2009-10-22 Agensys, Inc. Nucleic acids and corresponding proteins entitled 254p1d6b useful in treatment and detection of cancer
US20090269339A1 (en) * 2008-04-29 2009-10-29 Genentech, Inc. Responses to immunizations in rheumatoid arthritis patients treated with a cd20 antibody
US20100028951A1 (en) * 2007-03-07 2010-02-04 Stephen Hamilton Production of glycoproteins with modified fucosylation
US20100104557A1 (en) * 2006-09-18 2010-04-29 Xencor, Inc. Optimized Antibodies that Target HM1.24
US20100135987A1 (en) * 2008-10-20 2010-06-03 Hickman Robert K Isolation and purification of antibodies using protein a affinity chromatography
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
US7776343B1 (en) 1999-02-17 2010-08-17 Csl Limited Immunogenic complexes and methods relating thereto
US20100248359A1 (en) * 2004-07-09 2010-09-30 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody
US20100272723A1 (en) * 2006-08-14 2010-10-28 Xencor, Inc. Optimized Antibodies that Target CD19
WO2010146059A2 (en) 2009-06-16 2010-12-23 F. Hoffmann-La Roche Ag Biomarkers for igf-1r inhibitor therapy
US20110033452A1 (en) * 2004-10-26 2011-02-10 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody Having Modified Sugar Chain
WO2011019619A1 (en) 2009-08-11 2011-02-17 Genentech, Inc. Production of proteins in glutamine-free cell culture media
WO2011023787A1 (en) 2009-08-31 2011-03-03 Roche Glycart Ag Affinity-matured humanized anti cea monoclonal antibodies
US7923011B2 (en) 2006-10-12 2011-04-12 Genentech, Inc. Antibodies to lymphotoxin-alpha
WO2011100403A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
WO2011101328A2 (en) 2010-02-18 2011-08-25 Roche Glycart Ag Treatment with a humanized igg class anti egfr antibody and an antibody against insulin like growth factor 1 receptor
US8084582B2 (en) 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
WO2012020006A2 (en) 2010-08-13 2012-02-16 Roche Glycart Ag Anti-fap antibodies and methods of use
WO2012020038A1 (en) 2010-08-13 2012-02-16 Roche Glycart Ag Anti-tenascin-c a2 antibodies and methods of use
US8188231B2 (en) 2002-09-27 2012-05-29 Xencor, Inc. Optimized FC variants
WO2012107416A2 (en) 2011-02-10 2012-08-16 Roche Glycart Ag Improved immunotherapy
US20120251533A1 (en) * 2005-02-18 2012-10-04 Medarex, Inc. Monoclonal antibodies against cd30 lacking in fucosyl residues
WO2012146628A1 (en) 2011-04-29 2012-11-01 Roche Glycart Ag Novel immunoconjugates
US8318907B2 (en) 2004-11-12 2012-11-27 Xencor, Inc. Fc variants with altered binding to FcRn
WO2013026832A1 (en) 2011-08-23 2013-02-28 Roche Glycart Ag Anti-mcsp antibodies
WO2013026831A1 (en) 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific antigen binding molecules
EP2586788A1 (en) 2007-07-09 2013-05-01 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
WO2013113641A1 (en) 2012-01-31 2013-08-08 Roche Glycart Ag Use of nkp46 as a predictive biomarker for cancer treatment with adcc- enhanced antibodies
WO2013127465A1 (en) 2012-03-02 2013-09-06 Roche Glycart Ag Predicitive biomarker for cancer treatment with adcc enhanced antibodies
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
US20130310273A1 (en) * 2011-01-27 2013-11-21 Torsten Witte Methods and Means for Diagnosing Vasculitis
US8642742B2 (en) 2011-03-02 2014-02-04 Roche Glycart Ag Anti-CEA antibodies
WO2014023679A1 (en) 2012-08-07 2014-02-13 Roche Glycart Ag Composition comprising two antibodies engineered to have reduced and increased effector function
WO2014114595A1 (en) 2013-01-23 2014-07-31 Roche Glycart Ag Predictive biomarker for cancer treatment with adcc-enhanced antibodies
US8802820B2 (en) 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
WO2014131715A1 (en) 2013-02-26 2014-09-04 Roche Glycart Ag Anti-mcsp antibodies
US8883980B2 (en) 2003-11-05 2014-11-11 Roche Glycart Ag Antigen binding molecules with increased Fc receptor binding affinity and effector function
US8906646B2 (en) 2006-09-13 2014-12-09 Abbvie Inc. Fed-batch method of making human anti-TNF-alpha antibody
US8911964B2 (en) 2006-09-13 2014-12-16 Abbvie Inc. Fed-batch method of making human anti-TNF-alpha antibody
US8921526B2 (en) 2013-03-14 2014-12-30 Abbvie, Inc. Mutated anti-TNFα antibodies and methods of their use
US8946395B1 (en) 2013-10-18 2015-02-03 Abbvie Inc. Purification of proteins using hydrophobic interaction chromatography
US8986949B2 (en) 2003-02-20 2015-03-24 Glycofi, Inc. Endomannosidases in the modification of glycoproteins in eukaryotes
US9017687B1 (en) 2013-10-18 2015-04-28 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same using displacement chromatography
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
US9062106B2 (en) 2011-04-27 2015-06-23 Abbvie Inc. Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US9067990B2 (en) 2013-03-14 2015-06-30 Abbvie, Inc. Protein purification using displacement chromatography
US9085618B2 (en) 2013-10-18 2015-07-21 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9109010B2 (en) 2008-10-20 2015-08-18 Abbvie Inc. Viral inactivation during purification of antibodies cross reference to related applications
US9150645B2 (en) 2012-04-20 2015-10-06 Abbvie, Inc. Cell culture methods to reduce acidic species
US9181337B2 (en) 2013-10-18 2015-11-10 Abbvie, Inc. Modulated lysine variant species compositions and methods for producing and using the same
US9181572B2 (en) 2012-04-20 2015-11-10 Abbvie, Inc. Methods to modulate lysine variant distribution
US9193787B2 (en) 2012-04-20 2015-11-24 Abbvie Inc. Human antibodies that bind human TNF-alpha and methods of preparing the same
US9206390B2 (en) 2012-09-02 2015-12-08 Abbvie, Inc. Methods to control protein heterogeneity
US9234033B2 (en) 2012-09-02 2016-01-12 Abbvie, Inc. Methods to control protein heterogeneity
US9249182B2 (en) 2012-05-24 2016-02-02 Abbvie, Inc. Purification of antibodies using hydrophobic interaction chromatography
US9266938B2 (en) 2011-02-10 2016-02-23 Roche Glycart Ag Mutant interleukin-2 polypeptides
US9403855B2 (en) 2010-05-10 2016-08-02 Academia Sinica Zanamivir phosphonate congeners with anti-influenza activity and determining oseltamivir susceptibility of influenza viruses
US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity
US9499614B2 (en) 2013-03-14 2016-11-22 Abbvie Inc. Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides
EP3095463A2 (en) 2008-09-16 2016-11-23 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
US9547009B2 (en) 2012-08-21 2017-01-17 Academia Sinica Benzocyclooctyne compounds and uses thereof
US9550826B2 (en) 2013-11-15 2017-01-24 Abbvie Inc. Glycoengineered binding protein compositions
US9598667B2 (en) 2013-10-04 2017-03-21 Abbvie Inc. Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins
WO2017053906A1 (en) 2015-09-24 2017-03-30 Abvitro Llc Hiv antibody compositions and methods of use
US9695454B2 (en) 2012-05-23 2017-07-04 Glykos Finland Oy Production of fucosylated glycoproteins
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
US9759726B2 (en) 2014-03-27 2017-09-12 Academia Sinica Reactive labelling compounds and uses thereof
US9782476B2 (en) 2013-09-06 2017-10-10 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
US9816981B2 (en) 2007-03-23 2017-11-14 Academia Sinica Alkynyl sugar analogs for labeling and visualization of glycoconjugates in cells
WO2017194441A1 (en) 2016-05-11 2017-11-16 F. Hoffmann-La Roche Ag Modified anti-tenascin antibodies and methods of use
EP3252078A1 (en) 2016-06-02 2017-12-06 F. Hoffmann-La Roche AG Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer
US9879042B2 (en) 2014-09-08 2018-01-30 Academia Sinica Human iNKT cell activation using glycolipids
US9914956B2 (en) 2012-08-18 2018-03-13 Academia Sinica Cell-permeable probes for identification and imaging of sialidases
US9975966B2 (en) 2014-09-26 2018-05-22 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing theraputic agent
US9975965B2 (en) 2015-01-16 2018-05-22 Academia Sinica Compositions and methods for treatment and detection of cancers
US9982041B2 (en) 2014-01-16 2018-05-29 Academia Sinica Compositions and methods for treatment and detection of cancers
US9981030B2 (en) 2013-06-27 2018-05-29 Academia Sinica Glycan conjugates and use thereof
US10005847B2 (en) 2014-05-27 2018-06-26 Academia Sinica Anti-HER2 glycoantibodies and uses thereof
US10023892B2 (en) 2014-05-27 2018-07-17 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US10034921B2 (en) 2013-02-13 2018-07-31 Laboratoire Français Du Fractionnement Et Des Biotechnologies Proteins with modified glycosylation and methods of production thereof
US10087236B2 (en) 2009-12-02 2018-10-02 Academia Sinica Methods for modifying human antibodies by glycan engineering
US10086054B2 (en) 2013-06-26 2018-10-02 Academia Sinica RM2 antigens and use thereof
WO2018201096A1 (en) 2017-04-27 2018-11-01 Tesaro, Inc. Antibody agents directed against lymphocyte activation gene-3 (lag-3) and uses thereof
US10118969B2 (en) 2014-05-27 2018-11-06 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US10130714B2 (en) 2012-04-14 2018-11-20 Academia Sinica Enhanced anti-influenza agents conjugated with anti-inflammatory activity
WO2018220099A1 (en) 2017-06-02 2018-12-06 F. Hoffmann-La Roche Ag Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer
US10150818B2 (en) 2014-01-16 2018-12-11 Academia Sinica Compositions and methods for treatment and detection of cancers
US10174110B2 (en) 2013-02-13 2019-01-08 Laboratoire Français Du Fractionnement Et Des Biotechnologies Highly galactosylated anti-TNF-α antibodies and uses thereof
US10274488B2 (en) 2008-07-15 2019-04-30 Academia Sinica Glycan arrays on PTFE-like aluminum coated glass slides and related methods
US10336784B2 (en) 2016-03-08 2019-07-02 Academia Sinica Methods for modular synthesis of N-glycans and arrays thereof
US10338069B2 (en) 2010-04-12 2019-07-02 Academia Sinica Glycan arrays for high throughput screening of viruses
US10342858B2 (en) 2015-01-24 2019-07-09 Academia Sinica Glycan conjugates and methods of use thereof
US10495645B2 (en) 2015-01-16 2019-12-03 Academia Sinica Cancer markers and methods of use thereof
WO2019234576A1 (en) 2018-06-03 2019-12-12 Lamkap Bio Beta Ltd. Bispecific antibodies against ceacam5 and cd47
US10513724B2 (en) 2014-07-21 2019-12-24 Glykos Finland Oy Production of glycoproteins with mammalian-like N-glycans in filamentous fungi
US10525137B2 (en) 2015-12-30 2020-01-07 Genentech, Inc. Formulations with reduced degradation of polysorbate
US10538592B2 (en) 2016-08-22 2020-01-21 Cho Pharma, Inc. Antibodies, binding fragments, and methods of use
EP3831849A1 (en) 2019-12-02 2021-06-09 LamKap Bio beta AG Bispecific antibodies against ceacam5 and cd47
US11332523B2 (en) 2014-05-28 2022-05-17 Academia Sinica Anti-TNF-alpha glycoantibodies and uses thereof
US11377485B2 (en) 2009-12-02 2022-07-05 Academia Sinica Methods for modifying human antibodies by glycan engineering
EP4026848A1 (en) 2015-12-09 2022-07-13 F. Hoffmann-La Roche AG Type ii anti-cd20 antibody for reducing the cytokine release syndrome
US11401348B2 (en) 2009-09-02 2022-08-02 Xencor, Inc. Heterodimeric Fc variants
US11820830B2 (en) 2004-07-20 2023-11-21 Xencor, Inc. Optimized Fc variants
US11884739B2 (en) 2014-05-27 2024-01-30 Academia Sinica Anti-CD20 glycoantibodies and uses thereof
US11932685B2 (en) 2007-10-31 2024-03-19 Xencor, Inc. Fc variants with altered binding to FcRn

Families Citing this family (795)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6136311A (en) 1996-05-06 2000-10-24 Cornell Research Foundation, Inc. Treatment and diagnosis of cancer
ES2558160T3 (es) 1998-12-09 2016-02-02 Phyton Holdings, Llc Glicoproteínas que tienen glicosilación de tipo humano
NZ518532A (en) 1999-10-26 2004-02-27 Plant Res Internat B Transgenic plant expressing mammalian beta-1,4- galactosyltransferase
US7416726B2 (en) * 2000-04-13 2008-08-26 The Rockefeller University Enhancement of antibody-mediated immune responses
ZA200306406B (en) 2001-01-19 2004-09-06 Dow Chemical Co Method for secretory production of glycoprotein having human-type sugar chain using plant cell.
JP5350573B2 (ja) 2002-03-19 2013-11-27 スティヒティング ディーンスト ランドバウクンディフ オンデルズーク 植物におけるｇｎｔｉｉｉ発現
AU2003219418B2 (en) 2002-03-19 2008-02-28 Stichting Dienst Landbouwkundig Onderzoek Optimizing glycan processing in plants
AR042145A1 (es) 2002-11-27 2005-06-08 Dow Agrociences Llc Produccion de inmunoglobulinas en plantas con una fucocilacion reducida
AR044388A1 (es) 2003-05-20 2005-09-07 Applied Molecular Evolution Moleculas de union a cd20
EP2168986A3 (en) 2004-02-19 2010-07-28 Genentech, Inc. CDR-repaired antibodies
AR048098A1 (es) * 2004-03-15 2006-03-29 Wyeth Corp Conjugados de caliqueamicina
KR20070029733A (ko) 2004-06-04 2007-03-14 제넨테크, 인크. 다발성 경화증의 치료 방법
CA2573505C (en) 2004-07-14 2013-06-25 Igeneon Krebs-Immuntherapie Forschungs-Und Entwicklungs-Ag N-glycosylated antibody
BRPI0516297A (pt) 2004-10-05 2008-09-02 Genentech Inc métodos de tratamento de vasculite e artigos de fabricação
JO3000B1 (ar) 2004-10-20 2016-09-05 Genentech Inc مركبات أجسام مضادة .
TWI441646B (zh) 2005-01-21 2014-06-21 Genentech Inc 帕妥珠單抗(pertuzumab)用於製備治療人類病患癌症之藥物的用途
ES2440481T3 (es) 2005-02-23 2014-01-29 Genentech, Inc. Prolongación del tiempo hasta la progresión de la enfermedad o supervivencia en pacientes de cáncer de ovario usando pertuzumab
JO3058B1 (ar) 2005-04-29 2017-03-15 Applied Molecular Evolution Inc الاجسام المضادة لمضادات -اي ال-6,تركيباتها طرقها واستعمالاتها
AU2006252733A1 (en) * 2005-06-02 2006-12-07 Astrazeneca Ab Antibodies directed to CD20 and uses thereof
HUE042561T2 (hu) 2005-06-30 2019-07-29 Janssen Biotech Inc Anti-IL-23-ellenanyagok, készítmények, eljárások és alkalmazások
CA2615846A1 (en) 2005-07-21 2007-01-25 Genmab A/S Potency assays for antibody drug substance binding to an fc receptor
US20070041979A1 (en) * 2005-08-19 2007-02-22 Raju T S Proteolysis resistant antibody preparations
MY149159A (en) 2005-11-15 2013-07-31 Hoffmann La Roche Method for treating joint damage
AU2006342792A1 (en) 2005-12-02 2007-11-08 Genentech, Inc. Compositions and methods for the treatment of diseases and disorders associated with cytokine signaling involving antibodies that bind to IL-22 and IL-22R
ES2517420T3 (es) 2005-12-29 2014-11-03 Janssen Biotech, Inc. Anticuerpos anti-IL-23 humanos, composiciones, procedimientos y usos
DK1973950T3 (da) 2006-01-05 2014-12-15 Genentech Inc Anti-ephb4-antistoffer og fremgangsmåder ved anvendelse af samme
MX2008009220A (es) 2006-01-17 2008-10-10 Biolex Therapeutics Inc Composiciones y metodos para la humanizacion y optimizacion de n-glicanos en plantas.
US20070166306A1 (en) * 2006-01-17 2007-07-19 Fey Georg H M Anti-CD19 antibody composition and method
EP1987068B1 (en) * 2006-02-10 2018-08-08 Life Technologies Corporation Oligosaccharide modification and labeling of proteins
AR059851A1 (es) 2006-03-16 2008-04-30 Genentech Inc Anticuerpos de la egfl7 y metodos de uso
US8940871B2 (en) 2006-03-20 2015-01-27 The Regents Of The University Of California Engineered anti-prostate stem cell antigen (PSCA) antibodies for cancer targeting
MX2008015132A (es) 2006-05-30 2008-12-10 Genentech Inc Anticuerpos e inmunoconjugados y sus usos.
KR20090027227A (ko) 2006-06-06 2009-03-16 제넨테크, 인크. 항-ｄｌｌ4 항체 및 이의 사용 방법
MX2009000476A (es) 2006-07-14 2009-01-28 Ac Immune Sa Anticuerpo humanizado contra beta amiloide.
ME01758B (me) 2006-07-14 2014-09-20 Genentech Inc Humanizirano protutijelo protiv amiloida beta
EP2046809B1 (en) 2006-07-19 2016-12-07 The Trustees Of The University Of Pennsylvania Wsx-1/il-27 as a target for anti-inflammatory responses
EP2061814B1 (en) 2006-10-27 2012-06-06 Genentech, Inc. Antibodies and immunoconjugates and uses therefor
CA2676766A1 (en) 2007-02-09 2008-08-21 Genentech, Inc. Anti-robo4 antibodies and uses therefor
WO2008109440A2 (en) 2007-03-02 2008-09-12 Genentech, Inc. Predicting response to a her dimerisation inhibitor based on low her3 expression
KR101460953B1 (ko) 2007-04-17 2014-11-13 스티칭 디엔스트 랜드보위쿤디그 온데조에크 비-포유동물 글리코실트랜스퍼라제의 발현에 의한 식물에서의 포유동물형 글리코실화
NO3072525T3 (da) 2007-05-14 2018-06-30
ES2417148T3 (es) 2007-06-08 2013-08-06 Genentech, Inc. Marcadores de expresión génica de la resistencia tumoral al tratamiento con inhibidor de HER2
PL2170389T3 (pl) 2007-06-12 2015-03-31 Ac Immune Sa Humanizowane przeciwciało przeciw amyloidowi beta
RU2499053C2 (ru) * 2007-06-15 2013-11-20 Медикаго Инк. Способ синтеза белка с модифицированным профилем n-гликозилирования в растениях
JP6126773B2 (ja) 2007-09-04 2017-05-10 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア 癌のターゲッティングおよび検出のための高親和性抗前立腺幹細胞抗原（ｐｓｃａ）抗体
ES2566957T3 (es) 2007-09-26 2016-04-18 Chugai Seiyaku Kabushiki Kaisha Región constante de anticuerpo modificado
BRPI0818623A2 (pt) 2007-10-05 2017-05-23 Ac Immune Sa composição farmacêutica, e, métodos para reduzir a carga da placa na camada de célula de gânglio retinal de um animal, para reduzir a quantidade de placas na camada de célula de gânglio retinal de um animal, para diminuir a quantidade total de amilóide-beta solúvel na camada de célula de gânglio retinal de um animal, para prevenir, tratar e/ou aliviar os efeitos de uma doença ocular associada com anormalidades patológicas/mudanças no tecido do sistema visual, para monitorar doença ocular residual mínima associada com anormalidades patológicas/mudanças nos tecidos do sistema visual, para predizer responsividade de um paciente, e para reter ou diminuir a pressão ocular nos olhos de um animal
MX2010005108A (es) 2007-11-07 2010-05-27 Genentech Inc Composiciones y metodos para el tratamiento de trastornos microbianos.
AR069501A1 (es) 2007-11-30 2010-01-27 Genentech Inc Anticuerpos anti- vegf (factor de crecimiento endotelial vascular)
JP5990365B2 (ja) * 2007-12-26 2016-09-14 バイオテスト・アクチエンゲゼルシヤフト Ｃｄ１３８を標的とする剤及びその使用
WO2009080831A1 (en) * 2007-12-26 2009-07-02 Biotest Ag Method of decreasing cytotoxic side-effects and improving efficacy of immunoconjugates
JP5817034B2 (ja) 2007-12-26 2015-11-18 バイオテスト・アクチエンゲゼルシヤフト Ｃｄ１３８を標的とする免疫複合体及びその使用
MX2010007101A (es) * 2007-12-26 2011-07-01 Biotest Ag Metodos y agentes para mejorar el reconocimiento de celulas de tumor que expresan cd138.
TWI472339B (zh) 2008-01-30 2015-02-11 Genentech Inc 包含結合至ｈｅｒ２結構域ii之抗體及其酸性變異體的組合物
KR101054362B1 (ko) * 2008-07-03 2011-08-05 재단법인 목암생명공학연구소 재조합 단백질의 푸코스 함량을 감소시키는 방법
JP2012503656A (ja) * 2008-09-26 2012-02-09 エウレカ セラピューティクス，インコーポレイテッド 変異体グリコシル化パターンを有する細胞株およびタンパク質
CN110317272A (zh) 2008-10-14 2019-10-11 霍夫曼-拉罗奇有限公司 免疫球蛋白变体及其用途
HUE024872T2 (en) 2008-11-22 2016-02-29 Hoffmann La Roche Use of anti-vegf antibody in combination with chemotherapy to treat breast cancer
UY32341A (es) 2008-12-19 2010-07-30 Glaxo Group Ltd Proteínas de unión antígeno novedosas
EP3318573A1 (en) 2008-12-23 2018-05-09 F. Hoffmann-La Roche AG Mmunoglobulin variants with altered binding to protein a
ES2712732T3 (es) 2009-02-17 2019-05-14 Cornell Res Foundation Inc Métodos y kits para el diagnóstico de cáncer y la predicción de valor terapéutico
WO2010098865A1 (en) * 2009-02-26 2010-09-02 Gt Life Sciences, Inc. Mammalian cell line models and related methods
CN104447995A (zh) 2009-03-20 2015-03-25 霍夫曼-拉罗奇有限公司 双特异性抗-her抗体
PE20120770A1 (es) 2009-03-25 2012-07-10 Genentech Inc ANTICUERPOS ANTI alfa5ß1 CON ACTIVIDAD SOBRE GLIOBLASTOMAS
SI3702371T1 (sl) 2009-03-25 2023-01-31 Genentech, Inc. Protitelesa proti FGFR3 in postopki za uporabo le-teh
JP5616428B2 (ja) 2009-04-07 2014-10-29 ロシュ グリクアート アクチェンゲゼルシャフト 三価の二重特異性抗体
NZ596807A (en) * 2009-05-06 2013-09-27 Biotest Ag Uses of immunoconjugates targeting cd138
WO2010138184A2 (en) 2009-05-27 2010-12-02 Synageva Biopharma Corp. Avian derived antibodies
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
WO2011014457A1 (en) 2009-07-27 2011-02-03 Genentech, Inc. Combination treatments
KR20120089253A (ko) 2009-07-31 2012-08-09 제넨테크, 인크. Ｂｖ８? 또는 ｇ?ｃｓｆ?길항제를 이용한 종양 전이의 억제
BR112012003346A2 (pt) 2009-08-15 2016-11-16 Genentech Inc metodo de tratamento de um paciente diagnostico com cancer de mama metastico previamente tratado kit para tratamento de cancer de mama metastatico previamente tratado em um paciente humano metodo para instruir um paciente humano com cancer metodo promocional e metodo comercial
TWI412375B (zh) * 2009-08-28 2013-10-21 Roche Glycart Ag 人類化抗ｃｄｃｐ１抗體
EP2473522B1 (en) 2009-09-02 2016-08-17 Genentech, Inc. Mutant smoothened and methods of using the same
EP2491059B1 (en) 2009-10-22 2015-02-25 F.Hoffmann-La Roche Ag Anti-hepsin antibodies and methods using same
WO2011056502A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Bone morphogenetic protein receptor type ii compositions and methods of use
WO2011056497A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Activin receptor type iib compositions and methods of use
WO2011056494A1 (en) 2009-10-26 2011-05-12 Genentech, Inc. Activin receptor-like kinase-1 antagonist and vegfr3 antagonist combinations
US20120316071A1 (en) 2009-11-04 2012-12-13 Vaughn Smider Methods for affinity maturation-based antibody optimization
BR112012010153B1 (pt) 2009-11-05 2022-05-03 Genentech, Inc Método de produção de um anticorpo
EP2506876B1 (en) 2009-12-02 2016-10-12 Imaginab, Inc. J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (psma) and methods for their use
US8486397B2 (en) 2009-12-11 2013-07-16 Genentech, Inc. Anti-VEGF-C antibodies and methods using same
CA2784385A1 (en) 2009-12-23 2011-06-30 Genentech, Inc. Anti-bv8 antibodies and uses thereof
US8940303B2 (en) 2010-01-28 2015-01-27 Glaxo Group Limited CD127 binding proteins
CN102834413A (zh) 2010-02-09 2012-12-19 葛兰素集团有限公司 代谢障碍的治疗
CN102892779B (zh) 2010-02-18 2016-12-21 基因泰克公司 神经调节蛋白拮抗剂及其在治疗癌症中的用途
CA2787952C (en) 2010-02-23 2016-07-26 Genentech, Inc. Anti-angiogenesis therapy for the treatment of ovarian cancer
UA108227C2 (xx) 2010-03-03 2015-04-10 Антигензв'язуючий білок
AU2011232514A1 (en) 2010-03-24 2012-08-30 Genentech, Inc. Anti-LRP6 antibodies
EP2374816B1 (en) 2010-04-07 2016-09-28 Agency For Science, Technology And Research Binding molecules against Chikungunya virus and uses thereof
US9441032B2 (en) 2010-04-07 2016-09-13 Agency For Science, Technology And Research Binding molecules against Chikungunya virus and uses thereof
WO2011146568A1 (en) 2010-05-19 2011-11-24 Genentech, Inc. Predicting response to a her inhibitor
WO2011147834A1 (en) 2010-05-26 2011-12-01 Roche Glycart Ag Antibodies against cd19 and uses thereof
WO2011153243A2 (en) 2010-06-02 2011-12-08 Genentech, Inc. Anti-angiogenesis therapy for treating gastric cancer
AR081556A1 (es) 2010-06-03 2012-10-03 Glaxo Group Ltd Proteinas de union al antigeno humanizadas
MX336109B (es) 2010-06-03 2016-01-08 Genentech Inc Formacion de imagenes inmuno-tep de anticuerpos e inmunoconjugados y usos de lo mismo.
MX336001B (es) 2010-06-18 2016-01-07 Genentech Inc Anticuerpos anti-axl y metodos de uso.
WO2011161119A1 (en) 2010-06-22 2011-12-29 F. Hoffmann-La Roche Ag Antibodies against insulin-like growth factor i receptor and uses thereof
WO2011161189A1 (en) 2010-06-24 2011-12-29 F. Hoffmann-La Roche Ag Anti-hepsin antibodies and methods of use
CA2803792A1 (en) 2010-07-09 2012-01-12 Genentech, Inc. Anti-neuropilin antibodies and methods of use
EP2409993A1 (en) 2010-07-19 2012-01-25 International-Drug-Development-Biotech Anti-CD19 antibody having ADCC function with improved glycosylation profile
EP2409712A1 (en) 2010-07-19 2012-01-25 International-Drug-Development-Biotech Anti-CD19 antibody having ADCC and CDC functions and improved glycosylation profile
EP2409989A1 (en) 2010-07-19 2012-01-25 International-Drug-Development-Biotech Method to improve glycosylation profile for antibody
WO2012010582A1 (en) 2010-07-21 2012-01-26 Roche Glycart Ag Anti-cxcr5 antibodies and methods of use
JP2013538191A (ja) 2010-07-23 2013-10-10 トラスティーズ オブ ボストン ユニバーシティ 病的血管新生および腫瘍細胞侵襲性の阻害のための治療法としてならびに分子イメージングおよび標的化送達のための抗ＤＥｓｕｐＲ阻害剤
CN103153341B (zh) 2010-08-03 2015-05-27 霍夫曼-拉罗奇有限公司 慢性淋巴细胞性白血病(cll)生物标志物
CA2805564A1 (en) 2010-08-05 2012-02-09 Stefan Jenewein Anti-mhc antibody anti-viral cytokine fusion protein
CN103080132B (zh) 2010-08-25 2016-06-08 弗·哈夫曼-拉罗切有限公司 抗il-18r1的抗体及其用途
AU2011295919A1 (en) 2010-08-31 2013-03-07 Genentech, Inc. Biomarkers and methods of treatment
DK2625197T3 (da) 2010-10-05 2016-10-03 Genentech Inc Smoothened-mutant og fremgangsmåder til anvendelse af samme
EP4029881A1 (en) 2010-11-08 2022-07-20 F. Hoffmann-La Roche AG Subcutaneously administered anti-il-6 receptor antibody
US8772457B2 (en) 2010-11-10 2014-07-08 Genentech, Inc. BACE1 antibodies
JP6351973B2 (ja) 2010-11-23 2018-07-04 グラクソ グループ リミテッドＧｌａｘｏ Ｇｒｏｕｐ Ｌｉｍｉｔｅｄ 抗原結合タンパク質
BR112013013003A2 (pt) 2010-11-24 2016-08-09 Glaxo Group Ltd proteína de ligação de antígeno, e, composição farmacêutica
US20120171120A1 (en) 2010-11-30 2012-07-05 Genentech, Inc. Low affinity blood brain barrier receptor antibodies and uses therefor
CN105175542B (zh) 2010-12-16 2018-12-18 弗·哈夫曼-拉罗切有限公司 与th2抑制相关的诊断和治疗
PE20141114A1 (es) 2010-12-20 2014-09-15 Genentech Inc Anticuerpos anti-mesotelina e inmunoconjugados
MX2013007168A (es) 2010-12-22 2013-11-04 Genentech Inc Anticuerpo anti-pcsk9 y metodos de uso.
WO2012092539A2 (en) 2010-12-31 2012-07-05 Takeda Pharmaceutical Company Limited Antibodies to dll4 and uses thereof
AR085403A1 (es) 2011-02-28 2013-09-25 Hoffmann La Roche Proteinas monovalentes que se unen a antigenos
WO2012116926A1 (en) 2011-02-28 2012-09-07 F. Hoffmann-La Roche Ag Antigen binding proteins
JP2014516511A (ja) 2011-04-07 2014-07-17 ジェネンテック， インコーポレイテッド 抗ｆｇｆｒ４抗体及び使用方法
WO2012146630A1 (en) 2011-04-29 2012-11-01 F. Hoffmann-La Roche Ag N-terminal acylated polypeptides, methods for their production and uses thereof
CA2833212C (en) 2011-05-12 2020-06-09 Genentech, Inc. Multiple reaction monitoring lc-ms/ms method to detect therapeutic antibodies in animal samples using framework signature peptides
RS56090B1 (sr) 2011-05-16 2017-10-31 Hoffmann La Roche Fgfr1 agonisti i načini primene
DK3415531T3 (da) 2011-05-27 2023-09-18 Glaxo Group Ltd Bcma (cd269/tnfrsf17)-bindende proteiner
BR112013032235A2 (pt) 2011-06-15 2016-11-22 Hoffmann La Roche anticorpos do receptor de epo anti-humano e métodos de uso
AR086982A1 (es) 2011-06-22 2014-02-05 Hoffmann La Roche Eliminacion de celulas diana por parte de celulas t citotoxicas especificas de virus utilizando complejos que comprenden mhc de clase i
US20130004484A1 (en) 2011-06-30 2013-01-03 Genentech, Inc. Anti-c-met antibody formulations
US20130022551A1 (en) 2011-07-22 2013-01-24 Trustees Of Boston University DEspR ANTAGONISTS AND AGONISTS AS THERAPEUTICS
AU2012288846B2 (en) 2011-07-27 2016-05-19 Glaxo Group Limited Anti-VEGF single variable domains fused to fc domains
BR112014003431A2 (pt) 2011-08-17 2017-06-13 Genentech Inc anticorpo, ácido nucleico, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica, agente farmacêutico, uso do anticorpo, método de tratamento de um indivíduo que tem câncer e método de aumento de tempo para recorrência de tumor
RU2014109985A (ru) 2011-08-17 2015-09-27 Дженентек, Инк. Ингибирование ангиогенеза в рефрактерных опухолях
JP2014533927A (ja) 2011-09-15 2014-12-18 ジェネンテック， インコーポレイテッド 分化を促進する方法
AR087918A1 (es) 2011-09-19 2014-04-23 Genentech Inc Tratamientos combinados que comprenden antagonistas de c-met y antagonistas de b-raf
AU2012319150B2 (en) 2011-10-05 2017-08-17 Genentech, Inc. Methods of treating liver conditions using Notch2 antagonists
JP6532678B2 (ja) 2011-10-14 2019-06-19 ジェネンテック， インコーポレイテッド 抗ＨｔｒＡ１抗体及び使用方法
WO2013057078A1 (en) 2011-10-19 2013-04-25 Roche Glycart Ag Separation method for fucosylated antibodies
WO2013059531A1 (en) 2011-10-20 2013-04-25 Genentech, Inc. Anti-gcgr antibodies and uses thereof
MX2014004991A (es) 2011-10-28 2014-05-22 Genentech Inc Combinaciones terapeuticas y metodos para tratar el melanoma.
JP2014533700A (ja) 2011-11-21 2014-12-15 ジェネンテック， インコーポレイテッド 抗ｃ−ＭＥＴ抗体の精製
EP2788024A1 (en) 2011-12-06 2014-10-15 F.Hoffmann-La Roche Ag Antibody formulation
MX358680B (es) 2011-12-08 2018-08-31 Biotest Ag Usos de inmunoconjugados dirigidos a cd138.
KR102080356B1 (ko) 2011-12-22 2020-02-24 에프. 호프만-라 로슈 아게 발현 벡터 구성, 신규한 생산 세포 생성 방법 및 폴리펩티드의 재조합 생산을 위한 그의 용도
CA3149402A1 (en) 2011-12-22 2013-06-27 F. Hoffman-La Roche Ag Expression vector element combinations, novel production cell generation methods and their use for the recombinant production of polypeptides
CN104011080B (zh) 2011-12-22 2017-10-20 弗·哈夫曼-拉罗切有限公司 用于真核细胞的全长抗体展示系统及其用途
WO2013096791A1 (en) 2011-12-23 2013-06-27 Genentech, Inc. Process for making high concentration protein formulations
WO2013101771A2 (en) 2011-12-30 2013-07-04 Genentech, Inc. Compositions and method for treating autoimmune diseases
JP2015509091A (ja) 2012-01-09 2015-03-26 ザ スクリプス リサーチ インスティテュート ヒト化抗体
WO2013106485A2 (en) 2012-01-09 2013-07-18 The Scripps Research Institute Ultralong complementarity determining regions and uses thereof
EP2804629A1 (en) 2012-01-18 2014-11-26 Genentech, Inc. Anti-lrp5 antibodies and methods of use
JP2015506944A (ja) 2012-01-18 2015-03-05 ジェネンテック， インコーポレイテッド Ｆｇｆ１９修飾薬を使用する方法
RU2014133069A (ru) 2012-02-11 2016-04-10 Дженентек, Инк. Транслокации r-спондина и способы с их использованием
MX360352B (es) 2012-02-15 2018-10-30 Hoffmann La Roche Cromatografia de afinidad basada en receptores fc.
JP2015514710A (ja) 2012-03-27 2015-05-21 ジェネンテック， インコーポレイテッド Ｈｅｒ３阻害剤に関する診断及び治療
AR090549A1 (es) 2012-03-30 2014-11-19 Genentech Inc Anticuerpos anti-lgr5 e inmunoconjugados
CA2867824A1 (en) 2012-05-01 2013-11-07 Genentech, Inc. Anti-pmel17 antibodies and immunoconjugates
WO2013170191A1 (en) 2012-05-11 2013-11-14 Genentech, Inc. Methods of using antagonists of nad biosynthesis from nicotinamide
SG10201709555SA (en) 2012-05-18 2017-12-28 Genentech Inc High-concentration monoclonal antibody formulations
TW201400132A (zh) 2012-05-21 2014-01-01 Genentech Inc 改善血腦屏障運送之安全性之方法
CN104335047B (zh) 2012-05-23 2017-08-15 弗·哈夫曼-拉罗切有限公司 治疗剂的选择方法
CN103463633B (zh) * 2012-06-07 2016-03-30 复旦大学 一种靶向的嵌合乙肝核心抗原治疗性疫苗及其用途
BR112014031310A2 (pt) 2012-06-15 2017-07-25 Genentech Inc anticorpos anti-pcsk9, formulações, dosagem e métodos de uso
US20140004121A1 (en) 2012-06-27 2014-01-02 Amgen Inc. Anti-mesothelin binding proteins
HUE029435T2 (en) 2012-07-04 2017-02-28 Hoffmann La Roche Anti-theophylline antibodies and methods of their application
EP3339328A1 (en) 2012-07-04 2018-06-27 F. Hoffmann-La Roche AG Anti-biotin antibodies and methods of use
CN107973856B (zh) 2012-07-04 2021-11-23 弗·哈夫曼-拉罗切有限公司 共价连接的抗原-抗体缀合物
RU2670491C2 (ru) 2012-07-05 2018-10-23 Дженентек, Инк. Система экспрессии и секреции
MA37840B1 (fr) 2012-07-09 2020-05-29 Genentech Inc Immunoconjugués comprenant des anticorps anti-cd79b
CA2873889A1 (en) 2012-07-09 2014-01-16 Genentech, Inc. Anti-cd22 antibodies and immunoconjugates
AR091701A1 (es) 2012-07-09 2015-02-25 Genentech Inc Anticuerpos anti-cd22 e inmunoconjugados
CN104411337A (zh) 2012-07-09 2015-03-11 基因泰克公司 包含抗cd79b抗体的免疫偶联物
HRP20211641T1 (hr) 2012-07-13 2022-02-04 Roche Glycart Ag Bispecifična protutijela anti-vegf/anti-ang-2 i njihova primjena u liječenju vaskularnih očnih bolesti
NZ630363A (en) 2012-07-25 2018-09-28 Celldex Therapeutics Inc Anti-kit antibodies and uses thereof
WO2014029752A1 (en) 2012-08-22 2014-02-27 Glaxo Group Limited Anti lrp6 antibodies
SG11201500583PA (en) 2012-08-29 2015-04-29 Hoffmann La Roche Blood brain barrier shuttle
WO2014039855A1 (en) 2012-09-07 2014-03-13 Genentech, Inc. Combination therapy of a type ii anti-cd20 antibody with a selective bcl-2 inhibitor
PL2766048T3 (pl) 2012-10-12 2015-05-29 Medimmune Ltd Pirolobenzodiazepiny i ich koniugaty
EP3666285A3 (en) 2012-10-29 2020-06-24 The University of North Carolina at Chapel Hill Compositions and methods for inhibiting pathogen infection
AU2013337277B2 (en) 2012-11-05 2018-03-08 Foundation Medicine, Inc. Novel NTRK1 fusion molecules and uses thereof
EP2917243B1 (en) 2012-11-08 2018-03-14 F.Hoffmann-La Roche Ag Her3 antigen binding proteins binding to the beta-hairpin of her3
MX2015005860A (es) 2012-11-13 2015-08-10 Genentech Inc Anticuerpos de antihemaglutinina y metodo de uso.
WO2014096015A1 (en) 2012-12-21 2014-06-26 F. Hoffmann-La Roche Ag Disulfide-linked multivalent mhc class i comprising multi-function proteins
WO2014113729A2 (en) 2013-01-18 2014-07-24 Foundation Mecicine, Inc. Methods of treating cholangiocarcinoma
WO2014116749A1 (en) 2013-01-23 2014-07-31 Genentech, Inc. Anti-hcv antibodies and methods of using thereof
BR112015018418A2 (pt) 2013-02-22 2017-07-18 Hoffmann La Roche métodos para tratar câncer, para aumentar a eficácia de um tratamento, para adiar e/ou prevenir o desenvolvimento de câncer, para aumentar a sensibilidade a um terapêutico direcionado, para estender o período de sensibilidade, para estender a duração de resposta a um terapêutico direcionado e produto farmacêutico
CN105246511A (zh) 2013-03-06 2016-01-13 豪夫迈·罗氏有限公司 治疗和预防癌症药物抗性的方法
US20160031887A1 (en) 2013-03-13 2016-02-04 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
EP2968540A2 (en) 2013-03-14 2016-01-20 Genentech, Inc. Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use
US9562099B2 (en) 2013-03-14 2017-02-07 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
JP2016516046A (ja) 2013-03-14 2016-06-02 ジェネンテック， インコーポレイテッド がんの治療方法及びがん薬物耐性を阻止する方法
MX2015010777A (es) 2013-03-14 2016-04-25 Genentech Inc Anticuerpos e inmunoconjugados anti-b7-h4.
EP2970476A1 (en) 2013-03-15 2016-01-20 F. Hoffmann-La Roche AG Compositions and methods for diagnosis and treatment of hepatic cancers
EP3385277A1 (en) 2013-03-15 2018-10-10 F. Hoffmann-La Roche AG Il-22 polypeptides and il-22 fc fusion proteins and methods of use
RU2661111C2 (ru) 2013-03-15 2018-07-11 Ац Иммуне С.А. Антитела к тау и способы применения
KR20230070054A (ko) 2013-03-15 2023-05-19 제넨테크, 인크. Pd-1 및 pd-l1 관련 상태를 치료하기 위한 바이오마커 및 방법
JP6224739B2 (ja) 2013-03-15 2017-11-01 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ 抗ｌａｇ−３結合タンパク質
MX2015012326A (es) 2013-03-15 2016-03-08 Genentech Inc Anticuerpos anti-crth2 y su uso.
KR20150130451A (ko) 2013-03-15 2015-11-23 제넨테크, 인크. 암 치료 방법 및 항암제 내성 예방을 위한 방법
UA118028C2 (uk) 2013-04-03 2018-11-12 Рош Глікарт Аг Біспецифічне антитіло, специфічне щодо fap і dr5, антитіло, специфічне щодо dr5, і спосіб їх застосування
KR20210094669A (ko) 2013-04-29 2021-07-29 에프. 호프만-라 로슈 아게 인간 fcrn-결합 변형된 항체 및 사용 방법
EP3327034A1 (en) 2013-04-29 2018-05-30 F. Hoffmann-La Roche AG Fcrn-binding abolished anti-igf-1r antibodies and their use in the treatment of vascular eye diseases
CA2904805A1 (en) 2013-04-29 2014-11-06 F. Hoffmann-La Roche Ag Fc-receptor binding modified asymmetric antibodies and methods of use
US9708406B2 (en) 2013-05-20 2017-07-18 Genentech, Inc. Anti-transferrin receptor antibodies and methods of use
WO2015017146A2 (en) 2013-07-18 2015-02-05 Fabrus, Inc. Antibodies with ultralong complementarity determining regions
CN111518199A (zh) 2013-07-18 2020-08-11 图鲁斯生物科学有限责任公司 具有超长互补决定区的人源化抗体
HUE043815T2 (hu) 2013-08-01 2019-09-30 Five Prime Therapeutics Inc Fukózmentes FGFR2IIIB elleni antitestek
KR20180021234A (ko) 2013-08-12 2018-02-28 제넨테크, 인크. 보체-연관 상태의 치료를 위한 조성물 및 방법
KR20160055252A (ko) 2013-09-17 2016-05-17 제넨테크, 인크. 항-lgr5 항체의 사용 방법
RU2016117978A (ru) 2013-10-11 2017-11-17 Дженентек, Инк. Ингибиторы nsp4 и способы их применения
ES2960807T3 (es) 2013-10-11 2024-03-06 Us Health Anticuerpos contra TEM8 y su uso
CA2922912A1 (en) 2013-10-11 2015-04-16 F. Hoffmann-La Roche Ag Multispecific domain exchanged common variable light chain antibodies
BR112016008477A2 (pt) 2013-10-18 2017-10-03 Genentech Inc Corpos, ácido nucleico, célula hospedeira, método de produção de um anticorpo, imunoconjugado, formulação farmacêutica e usos do anticorpo
CA2924873A1 (en) 2013-10-23 2015-04-30 Genentech, Inc. Methods of diagnosing and treating eosinophilic disorders
EP3783020A1 (en) 2013-11-21 2021-02-24 F. Hoffmann-La Roche AG Anti-alpha-synuclein antibodies and methods of use
BR112016013109B1 (pt) 2013-12-09 2021-05-11 Allakos Inc. anticorpo anti-siglec-8, ácido nucleico, vetor, célula hospedeira, composição farmancêutica, seu método de produção e seus usos
US20160333063A1 (en) 2013-12-13 2016-11-17 The General Hospital Corporation Soluble high molecular weight (hmw) tau species and applications thereof
EA201691214A1 (ru) 2013-12-13 2016-12-30 Дженентек, Инк. Антитела к cd33 и иммуноконъюгаты
CN112353943A (zh) 2013-12-17 2021-02-12 豪夫迈·罗氏有限公司 用pd-1轴结合拮抗剂和紫杉烷治疗癌症的方法
CN105899535A (zh) 2013-12-17 2016-08-24 豪夫迈·罗氏有限公司 用pd-1轴结合拮抗剂和抗cd20抗体治疗癌症的方法
ES2811923T3 (es) 2013-12-17 2021-03-15 Genentech Inc Anticuerpos anti-CD3 y métodos de uso
EP3527587A1 (en) 2013-12-17 2019-08-21 F. Hoffmann-La Roche AG Combination therapy comprising ox40 binding agonists and pd-l1 binding antagonists
TWI670283B (zh) 2013-12-23 2019-09-01 美商建南德克公司 抗體及使用方法
MX368804B (es) 2013-12-24 2019-10-17 Univ Texas Antagonistas fcrn y metodos de uso.
PL3089996T3 (pl) 2014-01-03 2021-12-13 F. Hoffmann-La Roche Ag Dwuswoiste przeciwciała przeciw haptenowi/przeciw receptorowi występującemu w barierze krew-mózg, ich kompleksy i ich zastosowanie jako przenośniki wahadłowe występujące w barierze krew-mózg
WO2015103549A1 (en) 2014-01-03 2015-07-09 The United States Of America, As Represented By The Secretary Department Of Health And Human Services Neutralizing antibodies to hiv-1 env and their use
CA2930046A1 (en) 2014-01-03 2015-07-09 F. Hoffmann-La Roche Ag Covalently linked polypeptide toxin-antibody conjugates
MX2016008189A (es) 2014-01-03 2016-09-29 Hoffmann La Roche Conjugados helicoidales-anticuerpo anti-helicoidal unidos covalentemente y usos de los mismos.
KR102381685B1 (ko) 2014-01-06 2022-04-01 에프. 호프만-라 로슈 아게 1가 혈액 뇌 장벽 셔틀 모듈
CN110903398B (zh) 2014-01-15 2023-08-15 豪夫迈·罗氏有限公司 具有修饰的FCRN和保持的蛋白A结合性质的Fc区变体
RU2016130349A (ru) 2014-01-24 2018-03-01 Дженентек, Инк. Способы применения антител против steap1 и иммуноконъюгатов
WO2015120075A2 (en) 2014-02-04 2015-08-13 Genentech, Inc. Mutant smoothened and methods of using the same
KR20160111039A (ko) 2014-02-08 2016-09-23 제넨테크, 인크. 알츠하이머 질환을 치료하는 방법
MX2016010237A (es) 2014-02-08 2017-04-27 Genentech Inc Metodos de tratamiento de enfermedad de alzheimer.
CA2936565C (en) 2014-02-12 2020-08-11 Genentech, Inc. Anti-jagged1 antibodies and methods of use
CA2937556A1 (en) 2014-02-21 2015-08-27 Genentech, Inc. Anti-il-13/il-17 bispecific antibodies and uses thereof
EP3110446B1 (en) 2014-02-28 2021-12-01 Allakos Inc. Methods and compositions for treating siglec-8 associated diseases
CA2941687A1 (en) 2014-03-14 2015-09-17 Genentech, Inc. Methods and compositions for secretion of heterologous polypeptides
US20170107294A1 (en) 2014-03-21 2017-04-20 Nordlandssykehuset Hf Anti-cd14 antibodies and uses thereof
RU2016141385A (ru) 2014-03-24 2018-04-28 Дженентек, Инк. Лечение рака антагонистами с-мет и их корреляция с экспрессией hgf
CA2943262A1 (en) 2014-03-31 2015-10-08 Genentech, Inc. Anti-ox40 antibodies and methods of use
BR112016022345A2 (pt) 2014-03-31 2017-10-10 Genentech Inc terapia de combinação compreendendo agentes antiangiogênese e agonistas de ligação de ox40
WO2015164615A1 (en) 2014-04-24 2015-10-29 University Of Oslo Anti-gluten antibodies and uses thereof
CN106414499A (zh) 2014-05-22 2017-02-15 基因泰克公司 抗gpc3抗体和免疫偶联物
JP2017524371A (ja) 2014-05-23 2017-08-31 ジェネンテック， インコーポレイテッド Ｍｉｔバイオマーカーとその使用方法
CN106459202A (zh) 2014-06-11 2017-02-22 豪夫迈·罗氏有限公司 抗LgR5抗体及其用途
CN107073121A (zh) 2014-06-13 2017-08-18 基因泰克公司 治疗及预防癌症药物抗性的方法
WO2015197736A1 (en) 2014-06-26 2015-12-30 F. Hoffmann-La Roche Ag Anti-brdu antibodies and methods of use
US20160009805A1 (en) 2014-07-11 2016-01-14 Genentech, Inc. Anti-pd-l1 antibodies and diagnostic uses thereof
JP2017526641A (ja) 2014-07-11 2017-09-14 ジェネンテック， インコーポレイテッド Ｎｏｔｃｈ経路阻害
PE20170289A1 (es) 2014-08-19 2017-04-05 Merck Sharp & Dohme Anticuerpos anti tigit
TWI751102B (zh) 2014-08-28 2022-01-01 美商奇諾治療有限公司 對ｃｄ１９具專一性之抗體及嵌合抗原受體
US20170260261A1 (en) 2014-08-28 2017-09-14 Bioatla, Llc Conditionally Active Chimeric Antigen Receptors for Modified T-Cells
EP3193940A1 (en) 2014-09-10 2017-07-26 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
CA2958479A1 (en) 2014-09-12 2016-03-17 Genentech, Inc. Anti-cll-1 antibodies and immunoconjugates
US10059768B2 (en) 2014-09-12 2018-08-28 Genentech, Inc. Anti-B7-H4 antibodies and immunoconjugates
TWI758784B (zh) 2014-09-12 2022-03-21 美商建南德克公司 抗her2抗體及免疫結合物
CN107124870A (zh) 2014-09-17 2017-09-01 基因泰克公司 包含抗her2抗体和吡咯并苯并二氮杂*的免疫缀合物
PT3262071T (pt) 2014-09-23 2020-06-16 H Hoffnabb La Roche Ag Métodos de utilização de imunoconjugados anti-cd79b
WO2016059602A2 (en) 2014-10-16 2016-04-21 Glaxo Group Limited Methods of treating cancer and related compositions
CN107074938A (zh) 2014-10-16 2017-08-18 豪夫迈·罗氏有限公司 抗‑α‑突触核蛋白抗体和使用方法
EP3223865A4 (en) 2014-10-31 2018-10-03 Jounce Therapeutics, Inc. Methods of treating conditions with antibodies that bind b7-h4
MX2017005751A (es) 2014-11-03 2018-04-10 Genentech Inc Métodos y biomarcadores para predecir la eficacia y evaluación de un tratamiento con agonista de ox40.
EP3215850B1 (en) 2014-11-03 2019-07-03 F. Hoffmann-La Roche AG Assays for detecting t cell immune subsets and methods of use thereof
MX2017003478A (es) 2014-11-05 2018-02-01 Genentech Inc Anticuerpos anti-fgfr2/3 y metodos para su uso.
WO2016073282A1 (en) 2014-11-06 2016-05-12 Genentech, Inc. Combination therapy comprising ox40 binding agonists and tigit inhibitors
JP6576456B2 (ja) 2014-11-06 2019-09-18 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 修飾されたＦｃＲｎ結合特性およびプロテインＡ結合特性を有するＦｃ領域変種
PL3215528T3 (pl) 2014-11-06 2020-01-31 F.Hoffmann-La Roche Ag Warianty regionu Fc ze zmodyfikowanym wiązaniem FcRn i sposoby stosowania
CR20170240A (es) 2014-11-10 2018-04-03 Genentech Inc Anticuerpos anti-interleucina-33 y sus usos
CN107105632A (zh) 2014-11-10 2017-08-29 豪夫迈·罗氏有限公司 肾病动物模型及其治疗剂
HUE049982T2 (hu) 2014-11-14 2020-11-30 Hoffmann La Roche TNF-családba tartozó ligandum-trimert tartalmazó antigénkötõ molekulák
EP3875481A1 (en) 2014-11-14 2021-09-08 The U.S.A. as represented by the Secretary, Department of Health and Human Services Neutralizing antibodies to ebola virus glycoprotein and their use
MX2017006320A (es) 2014-11-17 2017-08-10 Genentech Inc Terapia combinada que comprende agonistas de unión de ox40 y antagonistas de unión del eje de pd-1.
RU2730668C2 (ru) 2014-11-19 2020-08-24 Аксон Ньюросайенс Се Гуманизированные тау-антитела при болезни альцгеймера
CN107001473B (zh) 2014-11-19 2021-07-09 豪夫迈·罗氏有限公司 抗-运铁蛋白受体抗体及使用方法
JP6993228B2 (ja) 2014-11-19 2022-03-03 ジェネンテック， インコーポレイテッド 抗トランスフェリン受容体／抗ｂａｃｅ１多重特異性抗体および使用方法
JP6859259B2 (ja) 2014-11-19 2021-04-14 ジェネンテック， インコーポレイテッド ＢＡＣＥｌに対する抗体及び神経疾患免疫療法のためのその使用
PL3221355T3 (pl) 2014-11-20 2021-03-08 F. Hoffmann-La Roche Ag Terapia skojarzona składająca się z dwuswoistych aktywujących limfocyty T cząsteczek wiążących antygen CD3 i receptor folianowy 1 (FolR1) oraz antagonistów wiązania osi PD-1
CN107001482B (zh) 2014-12-03 2021-06-15 豪夫迈·罗氏有限公司 多特异性抗体
BR112017011326A2 (pt) 2014-12-05 2018-07-31 Genentech, Inc. anticorpo, ácido nucleico, vetor, célula hospedeira, método para produzir o anticorpo, imunoconjugado, composição farmacêutica, usos do anticorpo, métodos para tratar ou retardar a progressão de distúrbio proliferativo celular e para intensificar a função imune
BR112017011234A2 (pt) 2014-12-10 2018-03-27 Genentech Inc anticorpos contra receptor da barreira hematoencefálica e métodos de uso
CN113045650A (zh) 2014-12-19 2021-06-29 中外制药株式会社 抗-c5抗体及使用方法
US20160200815A1 (en) 2015-01-05 2016-07-14 Jounce Therapeutics, Inc. Antibodies that inhibit tim-3:lilrb2 interactions and uses thereof
TWI718118B (zh) 2015-01-16 2021-02-11 美商奇諾治療有限公司 針對ｒｏｒ１之特異性抗體及嵌合抗原受體
CN107428823B (zh) 2015-01-22 2021-10-26 中外制药株式会社 两种以上抗-c5抗体的组合与使用方法
EP3250927B1 (en) 2015-01-28 2020-02-19 H. Hoffnabb-La Roche Ag Gene expression markers and treatment of multiple sclerosis
CA2975875A1 (en) 2015-02-04 2016-08-11 Genentech, Inc. Mutant smoothened and methods of using the same
EA201791754A1 (ru) 2015-02-05 2019-01-31 Чугаи Сейяку Кабусики Кайся АНТИТЕЛА, СОДЕРЖАЩИЕ ЗАВИСЯЩИЙ ОТ КОНЦЕНТРАЦИИ ИОНОВ АНТИГЕНСВЯЗЫВАЮЩИЙ ДОМЕН, ВАРИАНТЫ Fc-ОБЛАСТИ, IL-8-СВЯЗЫВАЮЩИЕ АНТИТЕЛА И ИХ ПРИМЕНЕНИЯ
KR20170140180A (ko) 2015-02-24 2017-12-20 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 중동 호흡기 증후군 코로나 바이러스 면역원, 항체 및 그 용도
SG10201908259WA (en) 2015-03-09 2019-10-30 Argenx Bvba Methods of reducing serum levels of fc-containing agents using fcrn antagonsits
CA2977285A1 (en) 2015-03-16 2016-09-22 F. Hoffmann-La Roche Ag Methods of detecting and quantifying il-13 and uses in diagnosing and treating th2-associated diseases
WO2016146833A1 (en) 2015-03-19 2016-09-22 F. Hoffmann-La Roche Ag Biomarkers for nad(+)-diphthamide adp ribosyltransferase resistance
PL3271389T3 (pl) 2015-03-20 2020-08-10 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Neutralizujące przeciwciała wiążące się z gp120 i ich stosowanie
EA037621B1 (ru) 2015-03-23 2021-04-22 Джаунс Терапьютикс, Инк. Антитела к icos
CN107743495B (zh) 2015-03-23 2021-05-14 拜耳制药股份公司 抗ceacam6抗体及其用途
MX2017012352A (es) 2015-04-03 2018-01-26 Eureka Therapeutics Inc Construccion dirigida a complejos de peptido de alfa-fetoproteina/complejo principal de histocompatibilidad (afp/cph) y usos de los mismos.
JP7044553B2 (ja) 2015-04-24 2022-03-30 ジェネンテック， インコーポレイテッド 結合ポリペプチドを含む細菌を特定する方法
JP2018520642A (ja) 2015-05-01 2018-08-02 ジェネンテック， インコーポレイテッド マスク抗ｃｄ３抗体及びその使用方法
WO2016179194A1 (en) 2015-05-04 2016-11-10 Jounce Therapeutics, Inc. Lilra3 and method of using the same
US10259882B2 (en) 2015-05-07 2019-04-16 Agenus Inc. Anti-OX40 antibodies
EP3294771A1 (en) 2015-05-11 2018-03-21 H. Hoffnabb-La Roche Ag Compositions and methods of treating lupus nephritis
HRP20201900T4 (hr) 2015-05-12 2024-06-07 F. Hoffmann - La Roche Ag Terapeutski i dijagnostički postupci kod raka
JP6884111B2 (ja) 2015-05-29 2021-06-09 ジェネンテック， インコーポレイテッド 癌におけるｐｄ−ｌ１プロモーターのメチル化
WO2016196343A1 (en) 2015-05-29 2016-12-08 Genentech, Inc. Humanized anti-ebola virus glycoprotein antibodies and methods of use
WO2016196298A1 (en) 2015-05-29 2016-12-08 Genentech, Inc. Therapeutic and diagnolstic methods for cancer
CN107810012A (zh) 2015-06-02 2018-03-16 豪夫迈·罗氏有限公司 使用抗il‑34抗体治疗神经疾病的组合物和方法
WO2016196975A1 (en) 2015-06-03 2016-12-08 The United States Of America, As Represented By The Secretary Department Of Health & Human Services Neutralizing antibodies to hiv-1 env and their use
MX2017015700A (es) 2015-06-04 2018-11-09 Ospedale San Raffaele Srl Igfbp3 y sus usos.
MX367312B (es) 2015-06-04 2019-08-14 Ospedale San Raffaele Srl Inhibidor del eje igrbp3/tmem219 y diabetes.
AU2016270858B2 (en) 2015-06-05 2022-04-28 Ac Immune Sa Anti-Tau antibodies and methods of use
WO2016200835A1 (en) 2015-06-08 2016-12-15 Genentech, Inc. Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists
WO2016200836A1 (en) 2015-06-08 2016-12-15 Genentech, Inc. Methods of treating cancer using anti-ox40 antibodies
WO2016205176A1 (en) 2015-06-15 2016-12-22 Genentech, Inc. Antibodies and immunoconjugates
RU2748943C2 (ru) 2015-06-16 2021-06-02 Дженентек, Инк. ГУМАНИЗИРОВАННЫЕ АНТИТЕЛА И АНТИТЕЛА С СОЗРЕВШЕЙ АФФИННОСТЬЮ ПРОТИВ FcRH5 И СПОСОБЫ ИХ ПРИМЕНЕНИЯ
EP3310811B1 (en) 2015-06-16 2021-06-16 Genentech, Inc. Anti-cd3 antibodies and methods of use
TW201718647A (zh) 2015-06-16 2017-06-01 建南德克公司 抗-cll-1抗體及使用方法
CA2986263A1 (en) 2015-06-17 2016-12-22 Genentech, Inc. Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes
JP2018524312A (ja) 2015-06-17 2018-08-30 ジェネンテック， インコーポレイテッド 抗ｈｅｒ２抗体及び使用方法
EP3310385A4 (en) 2015-06-17 2018-12-19 Allakos Inc. Methods and compositions for treating fibrotic diseases
CR20170562A (es) 2015-06-24 2018-02-01 Hoffmann La Roche Anticuerpos anti-receptor de transferrina con afinidad diseñada.
CN108473573A (zh) 2015-06-29 2018-08-31 豪夫迈·罗氏有限公司 Ii型抗cd20抗体用于器官移植中
CA3162586A1 (en) 2015-06-29 2017-01-05 Ventana Medical Systems, Inc. Materials and methods for performing histochemical assays for human pro-epiregulin and amphiregulin
RU2611685C2 (ru) * 2015-07-20 2017-02-28 Илья Владимирович Духовлинов Гуманизированное моноклональное антитело, специфичное к синдекану-1
EP4137158A1 (en) 2015-08-07 2023-02-22 Imaginab, Inc. Antigen binding constructs to target molecules
CN105384825B (zh) 2015-08-11 2018-06-01 南京传奇生物科技有限公司 一种基于单域抗体的双特异性嵌合抗原受体及其应用
CN108026180B (zh) 2015-08-28 2022-06-07 豪夫迈·罗氏有限公司 抗羟腐胺赖氨酸抗体及其用途
PT3344654T (pt) 2015-09-02 2021-01-26 Immutep Sas Anticorpos anti-lag-3
JP6904947B2 (ja) 2015-09-22 2021-07-21 スプリング バイオサイエンス コーポレーション 抗ｏｘ４０抗体及びその診断用途
CN116987187A (zh) 2015-09-23 2023-11-03 豪夫迈·罗氏有限公司 抗-vegf抗体的优化的变体
CA2994858C (en) 2015-09-25 2024-01-23 Genentech, Inc. Anti-tigit antibodies and methods of use
WO2017058944A1 (en) 2015-09-29 2017-04-06 Amgen Inc. Asgr inhibitors
AR106188A1 (es) 2015-10-01 2017-12-20 Hoffmann La Roche Anticuerpos anti-cd19 humano humanizados y métodos de utilización
EP3150636A1 (en) 2015-10-02 2017-04-05 F. Hoffmann-La Roche AG Tetravalent multispecific antibodies
MX2018003820A (es) 2015-10-02 2018-12-10 F Hoffmann ­La Roche Ag Anticuerpos biespecificos especificos para un receptor de tnf coestimulador.
MA43345A (fr) 2015-10-02 2018-08-08 Hoffmann La Roche Conjugués anticorps-médicaments de pyrrolobenzodiazépine et méthodes d'utilisation
EP3356406A1 (en) 2015-10-02 2018-08-08 H. Hoffnabb-La Roche Ag Bispecific anti-human cd20/human transferrin receptor antibodies and methods of use
AR106189A1 (es) 2015-10-02 2017-12-20 Hoffmann La Roche ANTICUERPOS BIESPECÍFICOS CONTRA EL A-b HUMANO Y EL RECEPTOR DE TRANSFERRINA HUMANO Y MÉTODOS DE USO
MY192202A (en) 2015-10-02 2022-08-06 Hoffmann La Roche Bispecific antibodies specific for pd1 and tim3
KR20180075537A (ko) 2015-10-06 2018-07-04 제넨테크, 인크. 다발성 경화증을 치료하기 위한 방법
JP7074665B2 (ja) 2015-10-07 2022-05-24 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 共刺激ｔｎｆ受容体に対する四価の二重特異性抗体発明の分野
WO2017062748A1 (en) 2015-10-07 2017-04-13 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Il-7r-alpha specific antibodies for treating acute lymphoblastic leukemia
US10604577B2 (en) 2015-10-22 2020-03-31 Allakos Inc. Methods and compositions for treating systemic mastocytosis
WO2017070423A1 (en) 2015-10-22 2017-04-27 Jounce Therapeutics, Inc. Gene signatures for determining icos expression
IL295756A (en) 2015-10-29 2022-10-01 Hoffmann La Roche Antibodies against fc-variable region and methods of use
EP3184547A1 (en) 2015-10-29 2017-06-28 F. Hoffmann-La Roche AG Anti-tpbg antibodies and methods of use
JO3555B1 (ar) 2015-10-29 2020-07-05 Merck Sharp & Dohme جسم مضاد يبطل فعالية فيروس الالتهاب الرئوي البشري
JP2018534930A (ja) 2015-10-30 2018-11-29 ジェネンテック， インコーポレイテッド 抗ｄ因子抗体及びコンジュゲート
ES2870141T3 (es) 2015-10-30 2021-10-26 Hoffmann La Roche Anticuerpos anti-HtrA1 y procedimientos de uso de los mismos
US11236152B2 (en) 2015-11-03 2022-02-01 The United States of America, as represented by the Sectetary, Department of Health and Human Services Neutralizing antibodies to HIV-1 GP41 and their use
CN108602884B (zh) 2015-11-08 2024-06-25 豪夫迈·罗氏有限公司 筛选多特异性抗体的方法
TWI791422B (zh) 2015-11-23 2023-02-11 美商戊瑞治療有限公司 用於癌症治療之單獨fgfr2抑制劑或與免疫刺激劑組合
CR20180364A (es) 2015-12-18 2018-08-22 Chugai Pharmaceutical Co Ltd Anticuerpos anti-c5 y métodos de uso
AU2017205089B2 (en) 2016-01-08 2023-10-05 F. Hoffmann-La Roche Ag Methods of treating CEA-positive cancers using PD-1 axis binding antagonists and anti-CEA/anti-CD3 bispecific antibodies
EP3405489A1 (en) 2016-01-20 2018-11-28 Genentech, Inc. High dose treatments for alzheimer's disease
JP6991978B2 (ja) 2016-01-27 2022-02-03 メディミューン，エルエルシー 定められるグリコシル化パターンを有する抗体を調製するための方法
CA3019952A1 (en) 2016-02-04 2017-08-10 Curis, Inc. Mutant smoothened and methods of using the same
WO2017145166A1 (en) * 2016-02-25 2017-08-31 B. G. Negev Technologies And Applications Ltd., At Ben-Gurion University Composition and method for treating amyotrophic lateral sclerosis
MX2018010361A (es) 2016-02-29 2019-07-08 Genentech Inc Métodos terapéuticos y de diagnóstico para el cáncer.
JP6430025B2 (ja) 2016-03-15 2018-11-28 中外製薬株式会社 Ｐｄ−１系結合アンタゴニストおよび抗ｇｐｃ３抗体を使用して癌を治療する方法
JP6943872B2 (ja) 2016-03-25 2021-10-06 ジェネンテック， インコーポレイテッド 多重全抗体及び抗体複合体化薬物定量化アッセイ
US10765724B2 (en) 2016-03-29 2020-09-08 Janssen Biotech, Inc. Method of treating psoriasis with increased interval dosing of anti-IL12/23 antibody
EP3439698A1 (en) 2016-04-05 2019-02-13 GlaxoSmithKline Intellectual Property Development Ltd Inhibition of tgfbeta in immunotherapy
EP3443004A1 (en) 2016-04-14 2019-02-20 H. Hoffnabb-La Roche Ag Anti-rspo3 antibodies and methods of use
JP2019515670A (ja) 2016-04-15 2019-06-13 ジェネンテック， インコーポレイテッド がんをモニタリングし治療するための方法
CN109563164A (zh) 2016-04-15 2019-04-02 生物蛋白有限公司 抗axl抗体、抗体片段和它们的免疫缀合物以及其用途
EP3443350B1 (en) 2016-04-15 2020-12-09 H. Hoffnabb-La Roche Ag Methods for monitoring and treating cancer
WO2017192589A1 (en) 2016-05-02 2017-11-09 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Neutralizing antibodies to influenza ha and their use and identification
KR102523682B1 (ko) 2016-05-02 2023-04-19 에프. 호프만-라 로슈 아게 콘톨스바디 - 단쇄 표적 결합제
EP3243836A1 (en) 2016-05-11 2017-11-15 F. Hoffmann-La Roche AG C-terminally fused tnf family ligand trimer-containing antigen binding molecules
JP7285076B2 (ja) 2016-05-11 2023-06-01 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト Ｔｎｆファミリーリガンドトリマーとテネイシン結合部分とを含む抗原結合分子
HRP20221298T1 (hr) 2016-05-13 2022-12-23 Bioatla, Inc. Anti-ror2 protutijela, fragmenti protutijela, njihovi imunokonjugati i njihove uporabe
EP3243832A1 (en) 2016-05-13 2017-11-15 F. Hoffmann-La Roche AG Antigen binding molecules comprising a tnf family ligand trimer and pd1 binding moiety
PL3458101T3 (pl) 2016-05-20 2021-05-31 F. Hoffmann-La Roche Ag Koniugaty PROTAC-przeciwciało i sposoby ich stosowania
JP7022080B2 (ja) 2016-05-27 2022-02-17 ジェネンテック， インコーポレイテッド 部位特異的抗体－薬物複合体の特徴付けのための生化学分析的方法
CN116143918A (zh) 2016-06-24 2023-05-23 豪夫迈·罗氏有限公司 抗聚泛素多特异性抗体
JP6983824B2 (ja) 2016-07-04 2021-12-17 エフ.ホフマン−ラ ロシュ アーゲーF. Hoffmann−La Roche Aktiengesellschaft 新規抗体フォーマット
WO2018014260A1 (en) 2016-07-20 2018-01-25 Nanjing Legend Biotech Co., Ltd. Multispecific antigen binding proteins and methods of use thereof
KR20230107408A (ko) 2016-07-29 2023-07-14 주노 쎄러퓨티크스 인코퍼레이티드 항-cd19 항체에 대한 항-이디오타입 항체
CA3027018A1 (en) 2016-07-29 2018-02-01 Chugai Seiyaku Kabushiki Kaisha Bispecific antibody exhibiting increased alternative fviii-cofactor-function activity
NL2017270B1 (en) 2016-08-02 2018-02-09 Aduro Biotech Holdings Europe B V New anti-hCTLA-4 antibodies
CA3026050A1 (en) 2016-08-05 2018-02-08 Chugai Seiyaku Kabushiki Kaisha Composition for prophylaxis or treatment of il-8 related diseases
CN109476748B (zh) 2016-08-08 2023-05-23 豪夫迈·罗氏有限公司 用于癌症的治疗和诊断方法
CA3035081A1 (en) 2016-09-02 2018-03-08 Dana-Farber Cancer Institute, Inc. Composition and methods of treating b cell disorders
WO2018049083A1 (en) 2016-09-07 2018-03-15 The Regents Of The University Of California Antibodies to oxidation-specific epitopes
SG10201607778XA (en) 2016-09-16 2018-04-27 Chugai Pharmaceutical Co Ltd Anti-Dengue Virus Antibodies, Polypeptides Containing Variant Fc Regions, And Methods Of Use
CN116731197A (zh) 2016-09-19 2023-09-12 豪夫迈·罗氏有限公司 基于补体因子的亲和层析
WO2018057849A1 (en) 2016-09-23 2018-03-29 Genentech, Inc. Uses of il-13 antagonists for treating atopic dermatitis
JOP20190055A1 (ar) 2016-09-26 2019-03-24 Merck Sharp & Dohme أجسام مضادة ضد cd27
CA3037961A1 (en) 2016-09-30 2018-04-05 Janssen Biotech, Inc. Safe and effective method of treating psoriasis with anti-il23 specific antibody
CN110139873A (zh) 2016-10-03 2019-08-16 朱诺治疗学股份有限公司 Hpv特异性结合分子
WO2018065501A1 (en) 2016-10-05 2018-04-12 F. Hoffmann-La Roche Ag Methods for preparing antibody drug conjugates
AU2017339517B2 (en) 2016-10-06 2024-03-14 Foundation Medicine, Inc. Therapeutic and diagnostic methods for cancer
WO2018068201A1 (en) 2016-10-11 2018-04-19 Nanjing Legend Biotech Co., Ltd. Single-domain antibodies and variants thereof against ctla-4
CN109862919A (zh) 2016-10-11 2019-06-07 免疫医疗有限公司 抗体-药物缀合物联合免疫介导的治疗剂
EP3532091A2 (en) 2016-10-29 2019-09-04 H. Hoffnabb-La Roche Ag Anti-mic antibidies and methods of use
WO2018085358A1 (en) 2016-11-02 2018-05-11 Jounce Therapeutics, Inc. Antibodies to pd-1 and uses thereof
CN109923128A (zh) 2016-11-15 2019-06-21 基因泰克公司 用于用抗cd20/抗cd3双特异性抗体进行治疗的给药
JP2020502261A (ja) 2016-11-16 2020-01-23 ヤンセン バイオテツク，インコーポレーテツド 抗ｉｌ２３特異的抗体で乾癬を治療する方法
JOP20190100A1 (ar) 2016-11-19 2019-05-01 Potenza Therapeutics Inc بروتينات ربط مولد ضد مضاد لـ gitr وطرق استخدامها
KR102221364B1 (ko) 2016-11-21 2021-03-04 쿠레아브 게엠베하 항-gp73　항체　및　면역접합체
US10759855B2 (en) 2016-12-02 2020-09-01 Rigel Pharmaceuticals, Inc. Antigen binding molecules to TIGIT
KR20240035636A (ko) 2016-12-07 2024-03-15 제넨테크, 인크. 항-타우 항체 및 이의 이용 방법
TW202328181A (zh) 2016-12-07 2023-07-16 美商建南德克公司 抗-tau抗體及使用方法
JP7106538B2 (ja) 2016-12-07 2022-07-26 アジェナス インコーポレイテッド 抗体およびその使用方法
TW201827076A (zh) 2016-12-12 2018-08-01 美商建南德克公司 使用抗pd-l1抗體及抗雄激素治療癌症之方法
JP7125400B2 (ja) 2016-12-19 2022-08-24 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト 標的化４－１ｂｂ（ｃｄ１３７）アゴニストとの併用療法
PL3559034T3 (pl) 2016-12-20 2021-04-19 F. Hoffmann-La Roche Ag Terapia skojarzona dwuswoistymi przeciwciałami anty-CD20/anty-CD3 i agonistami 4-1BB (CD137)
JOP20190134A1 (ar) 2016-12-23 2019-06-02 Potenza Therapeutics Inc بروتينات رابطة لمولد ضد مضادة لنيوروبيلين وطرق استخدامها
MX2019007795A (es) 2017-01-03 2019-08-16 Hoffmann La Roche Moleculas de union a antigeno biespecificas que comprenden el clon 20h4.9 anti-4-1bb.
TW201825515A (zh) 2017-01-04 2018-07-16 美商伊繆諾金公司 Ｍｅｔ抗體以及其免疫結合物及用途
WO2018132597A1 (en) 2017-01-12 2018-07-19 Eureka Therapeutics, Inc. Constructs targeting histone h3 peptide/mhc complexes and uses thereof
WO2018147960A1 (en) 2017-02-08 2018-08-16 Imaginab, Inc. Extension sequences for diabodies
US11021535B2 (en) 2017-02-10 2021-06-01 The United States Of America As Represented By The Secretary, Department Of Health And Human Services Neutralizing antibodies to plasmodium falciparum circumsporozoite protein and their use
WO2018148585A1 (en) 2017-02-10 2018-08-16 Genentech, Inc. Anti-tryptase antibodies, compositions thereof, and uses thereof
KR20190134631A (ko) 2017-03-01 2019-12-04 제넨테크, 인크. 암의 진단 및 치료 방법
CN110612124B (zh) 2017-03-22 2024-04-16 豪夫迈·罗氏有限公司 用于治疗眼部病症的优化的抗体组合物
TW202400231A (zh) 2017-03-28 2024-01-01 美商建南德克公司 治療神經退化性疾病之方法
EP3601346A1 (en) 2017-03-29 2020-02-05 H. Hoffnabb-La Roche Ag Bispecific antigen binding molecule for a costimulatory tnf receptor
CN110573528B (zh) 2017-03-29 2023-06-09 豪夫迈·罗氏有限公司 针对共刺激性tnf受体的双特异性抗原结合分子
JOP20190203A1 (ar) 2017-03-30 2019-09-03 Potenza Therapeutics Inc بروتينات رابطة لمولد ضد مضادة لـ tigit وطرق استخدامها
SG11201909218RA (en) 2017-04-03 2019-11-28 Hoffmann La Roche Antibodies binding to steap-1
CA3053358A1 (en) 2017-04-04 2018-10-11 F. Hoffmann-La Roche Ag Novel bispecific antigen binding molecules capable of specific binding to cd40 and to fap
US11285207B2 (en) 2017-04-05 2022-03-29 Hoffmann-La Roche Inc. Bispecific antibodies specifically binding to PD1 and LAG3
CN110392698B (zh) 2017-04-05 2022-01-25 豪夫迈·罗氏有限公司 抗lag3抗体
TW201839400A (zh) 2017-04-14 2018-11-01 美商建南德克公司 用於癌症之診斷及治療方法
JP7248588B2 (ja) 2017-04-21 2023-03-29 ジェネンテック， インコーポレイテッド 疾患の治療のためのｋｌｋ５アンタゴニストの使用
AU2018258049A1 (en) 2017-04-26 2019-12-12 Eureka Therapeutics, Inc. Constructs specifically recognizing glypican 3 and uses thereof
JP2020518638A (ja) 2017-05-05 2020-06-25 アラコス インコーポレイテッド アレルギー性眼疾患を処置するための方法および組成物
JP7299842B2 (ja) 2017-05-16 2023-06-28 ファイヴ プライム セラピューティクス インク がん治療における化学療法剤と組み合わせた抗ｆｇｆｒ２抗体
CN110945028B (zh) 2017-07-10 2023-09-08 国际药物发展生物技术公司 用非岩藻糖基化促凋亡抗cd19抗体与抗cd20抗体或化疗剂联合治疗b细胞恶性肿瘤
AU2018304458B2 (en) 2017-07-21 2021-12-09 Foundation Medicine, Inc. Therapeutic and diagnostic methods for cancer
WO2019023347A1 (en) 2017-07-26 2019-01-31 Forty Seven, Inc. ANTI-SIRP-ALPHA ANTIBODIES AND ASSOCIATED METHODS
CN111094352A (zh) 2017-08-25 2020-05-01 戊瑞治疗有限公司 B7-h4抗体及其使用方法
EP3684413A1 (en) 2017-09-20 2020-07-29 Chugai Seiyaku Kabushiki Kaisha Dosage regimen for combination therapy using pd-1 axis binding antagonists and gpc3 targeting agent
TW201922780A (zh) 2017-09-25 2019-06-16 美商健生生物科技公司 以抗ｉｌ１２／ｉｌ２３抗體治療狼瘡之安全且有效之方法
WO2019070541A1 (en) 2017-10-03 2019-04-11 Juno Therapeutics, Inc. HPV-SPECIFIC BINDING MOLECULES
WO2019075090A1 (en) 2017-10-10 2019-04-18 Tilos Therapeutics, Inc. ANTI-LAP ANTIBODIES AND USES THEREOF
EP3694890A4 (en) 2017-10-12 2021-11-03 Immunowake Inc. LIGHT CHAIN ANTIBODY FUSION PROTEIN WITH VEGFR
BR112020008323A2 (pt) 2017-11-01 2020-11-03 Juno Therapeutics Inc anticorpos e receptores de antígenos quiméricos específicos para antígeno de maturação de células b
KR20200079492A (ko) 2017-11-01 2020-07-03 에프. 호프만-라 로슈 아게 이중특이성 2+1 컨터체
BR112020007630A2 (pt) 2017-11-01 2020-11-17 F. Hoffmann-La Roche Ag anticorpo biespecífico ox40, produto farmacêutico, composição farmacêutica e anticorpos biespecíficos anti-fap/ anti-ox40
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
EP3707510B1 (en) 2017-11-06 2024-06-26 F. Hoffmann-La Roche AG Diagnostic and therapeutic methods for cancer
KR20200092328A (ko) 2017-12-01 2020-08-03 화이자 인코포레이티드 항-cxcr5 항체 및 그의 조성물 및 용도
MX2020005981A (es) 2017-12-08 2020-08-24 Argenx Bvba Uso de antagonistas del fcrn para el tratamiento de la miastenia gravis generalizada.
WO2019118937A1 (en) 2017-12-15 2019-06-20 Juno Therapeutics, Inc. Anti-cct5 binding molecules and methods of use thereof
BR112020011469A2 (pt) 2017-12-21 2020-11-24 F. Hoffmann-La Roche Ag anticorpos, molécula de ligação ao antígeno biespecífica, um ou mais polinucleotídeos isolados, um ou mais vetores, célula hospedeira, método para produzir um anticorpo, composição farmacêutica, uso do anticorpo, método de tratamento de uma doença e invenção
EP3502140A1 (en) 2017-12-21 2019-06-26 F. Hoffmann-La Roche AG Combination therapy of tumor targeted icos agonists with t-cell bispecific molecules
WO2019126472A1 (en) 2017-12-22 2019-06-27 Genentech, Inc. Use of pilra binding agents for treatment of a disease
SG11202004806SA (en) 2017-12-22 2020-06-29 Jounce Therapeutics Inc Antibodies to lilrb2
WO2019129211A1 (en) 2017-12-28 2019-07-04 Nanjing Legend Biotech Co., Ltd. Antibodies and variants thereof against pd-l1
EP3732202A4 (en) 2017-12-28 2022-06-15 Nanjing Legend Biotech Co., Ltd. SINGLE DOMAIN ANTIBODIES AND VARIANTS THEREOF AGAINST TIGIT
JP2021508471A (ja) 2017-12-29 2021-03-11 エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ 抗ｖｅｇｆ抗体のｖｅｇｆ受容体遮断選択性を改善する方法
WO2019136029A1 (en) 2018-01-02 2019-07-11 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Neutralizing antibodies to ebola virus glycoprotein and their use
AU2019205090A1 (en) 2018-01-05 2020-08-06 Ac Immune Sa Misfolded TDP-43 binding molecules
EP3508499A1 (en) 2018-01-08 2019-07-10 iOmx Therapeutics AG Antibodies targeting, and other modulators of, an immunoglobulin gene associated with resistance against anti-tumour immune responses, and uses thereof
KR20200120641A (ko) 2018-01-15 2020-10-21 난징 레전드 바이오테크 씨오., 엘티디. Pd-1에 대한 단일-도메인 항체 및 이의 변이체
WO2019143636A1 (en) 2018-01-16 2019-07-25 Lakepharma, Inc. Bispecific antibody that binds cd3 and another target
TWI835773B (zh) 2018-01-26 2024-03-21 美商建南德克公司 組合物及使用方法
CN111655717A (zh) 2018-01-26 2020-09-11 豪夫迈·罗氏有限公司 IL-22 Fc融合蛋白及使用方法
AU2019214183B2 (en) 2018-02-01 2022-04-07 Innovent Biologics (Suzhou) Co., Ltd. Fully human anti-B cell maturation antigen (BCMA) single chain variable fragment, and application thereof
US11866498B2 (en) 2018-02-08 2024-01-09 Genentech, Inc. Bispecific antigen-binding molecules and methods of use
TWI829667B (zh) 2018-02-09 2024-01-21 瑞士商赫孚孟拉羅股份公司 結合gprc5d之抗體
JP7418337B2 (ja) 2018-02-09 2024-01-19 ジェネンテック， インコーポレイテッド マスト細胞媒介性炎症性疾患の治療法及び診断法
WO2019158645A1 (en) 2018-02-14 2019-08-22 Abba Therapeutics Ag Anti-human pd-l2 antibodies
MX2020008736A (es) 2018-02-21 2020-12-07 Five Prime Therapeutics Inc Formulaciones de anticuerpos b7-h4.
RU2020130795A (ru) 2018-02-21 2022-03-21 Дзе Юнайтед Стэйтс Оф Америка, Эс Репрезентед Бай Дзе Секретэри, Департмент Оф Хелт Энд Хьюман Сервисиз Нейтрализующие антитела к env вич-1 и их применение
CA3091161A1 (en) 2018-02-21 2019-08-29 Five Prime Therapeutics, Inc. B7-h4 antibody dosing regimens
MA51907A (fr) 2018-02-21 2021-05-26 Hoffmann La Roche Posologie pour un traitement avec des protéines de fusion il-22 fc
CA3092108A1 (en) 2018-02-26 2019-08-29 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
WO2019169212A1 (en) 2018-03-02 2019-09-06 Five Prime Therapeutics, Inc. B7-h4 antibodies and methods of use thereof
CA3092551A1 (en) 2018-03-05 2019-09-12 Janssen Biotech, Inc. Methods of treating crohn's disease with anti-il23 specific antibody
CN111683961A (zh) 2018-03-13 2020-09-18 豪夫迈·罗氏有限公司 4-1bb激动剂与抗cd20抗体的治疗剂组合
EP3765501A1 (en) 2018-03-13 2021-01-20 F. Hoffmann-La Roche AG Combination therapy with targeted 4-1bb (cd137) agonists
SG11202006217YA (en) 2018-03-14 2020-07-29 Beijing Xuanyi Pharmasciences Co Ltd Anti-claudin 18.2 antibodies
US20200040103A1 (en) 2018-03-14 2020-02-06 Genentech, Inc. Anti-klk5 antibodies and methods of use
EP3765494A4 (en) 2018-03-15 2022-03-23 Chugai Seiyaku Kabushiki Kaisha ANTI-DENGUE VIRUS ANTIBODIES WITH CROSS-REACTIVITY AGAINST ZIKA VIRUS AND METHODS OF USE
CA3092589A1 (en) 2018-03-21 2019-09-26 Five Prime Therapeutics, Inc. Antibodies binding to vista at acidic ph
KR20200135510A (ko) 2018-03-29 2020-12-02 제넨테크, 인크. 포유류 세포들에서 젖분비자극 활성의 조절
CA3093034A1 (en) 2018-03-30 2019-10-03 Nanjing Legend Biotech Co., Ltd. Single-domain antibodies against lag-3 and uses thereof
TW202011029A (zh) 2018-04-04 2020-03-16 美商建南德克公司 偵測及定量fgf21之方法
US11471489B2 (en) 2018-04-05 2022-10-18 Juno Therapeutics, Inc. T cell receptors and engineered cells expressing same
TW202012440A (zh) 2018-04-13 2020-04-01 瑞士商赫孚孟拉羅股份公司 包含4-1bbl之靶向her2的抗原結合分子
JP2021523138A (ja) 2018-05-11 2021-09-02 ヤンセン バイオテツク，インコーポレーテツド Ｉｌ−２３抗体を使用してうつを治療する方法
SG11202011349PA (en) 2018-05-14 2020-12-30 Werewolf Therapeutics Inc Activatable interleukin-2 polypeptides and methods of use thereof
EP3794022A1 (en) 2018-05-14 2021-03-24 Werewolf Therapeutics, Inc. Activatable cytokine polypeptides and methods of use thereof
CN113286616A (zh) 2018-05-23 2021-08-20 Adc治疗有限公司 分子佐剂
US11987629B2 (en) 2018-06-01 2024-05-21 Tayu Huaxia Biotech Medical Group Co., Ltd. Compositions and uses thereof for treating disease or condition
JP7372237B2 (ja) 2018-06-04 2023-10-31 中外製薬株式会社 細胞質内での半減期が変化した抗原結合分子
US11993661B2 (en) 2018-06-18 2024-05-28 Eureka Therapeutics, Inc. Constructs targeting prostate-specific membrane antigen (PSMA) and uses thereof
AU2019288728A1 (en) 2018-06-23 2021-01-14 Genentech, Inc. Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor
TW202035447A (zh) 2018-07-04 2020-10-01 瑞士商赫孚孟拉羅股份公司 新穎雙特異性促效性4-1bb抗原結合分子
EP3820904A2 (en) 2018-07-09 2021-05-19 Five Prime Therapeutics, Inc. Antibodies binding to ilt4
WO2020014306A1 (en) 2018-07-10 2020-01-16 Immunogen, Inc. Met antibodies and immunoconjugates and uses thereof
SG11202100102VA (en) 2018-07-11 2021-02-25 Five Prime Therapeutics Inc Antibodies binding to vista at acidic ph
WO2020016838A2 (en) 2018-07-18 2020-01-23 Janssen Biotech, Inc. Sustained response predictors after treatment with anti-il23 specific antibody
BR112021000673A2 (pt) 2018-07-18 2021-04-20 Genentech, Inc. métodos para tratar um indivíduo com câncer de pulmão, kits, anticorpo anti-pd-l1 e composições
MX2021000745A (es) 2018-07-20 2021-03-26 Surface Oncology Inc Composiciones anti-cd112r y metodos.
US20220195045A1 (en) 2018-08-03 2022-06-23 Chugai Seiyaku Kabushiki Kaisha Antigen-binding molecule containing two antigen-binding domains that are linked to each other
EP3608674A1 (en) 2018-08-09 2020-02-12 Regeneron Pharmaceuticals, Inc. Methods for assessing binding affinity of an antibody variant to the neonatal fc receptor
SG11202003531WA (en) 2018-08-10 2020-05-28 Chugai Pharmaceutical Co Ltd Anti-cd137 antigen-binding molecule and utilization thereof
KR20210057053A (ko) 2018-08-23 2021-05-20 씨젠 인크. 항-tigit 항체
GB201814281D0 (en) 2018-09-03 2018-10-17 Femtogenix Ltd Cytotoxic agents
MX2021003214A (es) 2018-09-19 2021-05-12 Genentech Inc Metodos terapeuticos y de diagnostico para el cancer de vejiga.
EP4249917A3 (en) 2018-09-21 2023-11-08 F. Hoffmann-La Roche AG Diagnostic methods for triple-negative breast cancer
EP3853249A4 (en) 2018-09-21 2022-06-22 The University of North Carolina at Chapel Hill SYNTHETIC BINDERS TO LIMIT PERMEATION THROUGH MUCUS
DK3883606T5 (da) 2018-09-24 2024-01-02 Janssen Biotech Inc Sikker og effektiv fremgangsmåde til behandling af colitis ulcerosa med anti-il12/il23-antistof
JP7479383B2 (ja) 2018-09-27 2024-05-08 エクシリオ デベロップメント， インコーポレイテッド マスクされたサイトカインポリペプチド
EP3861025A1 (en) 2018-10-01 2021-08-11 F. Hoffmann-La Roche AG Bispecific antigen binding molecules with trivalent binding to cd40
KR20210069675A (ko) 2018-10-01 2021-06-11 에프. 호프만-라 로슈 아게 항-fap 클론 212를 포함하는 이중특이적 항원 결합 분자
EP3632929A1 (en) 2018-10-02 2020-04-08 Ospedale San Raffaele S.r.l. Antibodies and uses thereof
JP2022503886A (ja) 2018-10-05 2022-01-12 ファイブ プライム セラピューティクス， インコーポレイテッド 抗ｆｇｆｒ２抗体製剤
EP3863722A2 (en) 2018-10-10 2021-08-18 Tilos Theapeutics, Inc. Anti-lap antibody variants and uses thereof
CA3114955A1 (en) 2018-10-15 2020-04-23 Five Prime Therapeutics, Inc. Combination therapy for cancer
WO2020081493A1 (en) 2018-10-16 2020-04-23 Molecular Templates, Inc. Pd-l1 binding proteins
CN113196061A (zh) 2018-10-18 2021-07-30 豪夫迈·罗氏有限公司 肉瘤样肾癌的诊断和治疗方法
US20210395390A1 (en) 2018-10-31 2021-12-23 Bayer Aktiengesellschaft Reversal agents for neutralizing the therapeutic activity of anti-fxia antibodies
BR112021009373A2 (pt) 2018-11-16 2021-08-17 Memorial Sloan Kettering Cancer Center anticorpos para mucina-16 e métodos de uso dos mesmos
KR20210093973A (ko) 2018-11-20 2021-07-28 얀센 바이오테크 인코포레이티드 항-il23 특이적 항체로 건선을 치료하는 안전하고 효과적인 방법
CA3121265A1 (en) 2018-12-05 2020-06-11 Genentech, Inc. Diagnostic methods and compositions for cancer immunotherapy
US20220025051A1 (en) 2018-12-07 2022-01-27 Ono Pharmaceutical Co., Ltd. Immunosuppresive agent
CN113227119A (zh) 2018-12-10 2021-08-06 基因泰克公司 用于与含Fc的蛋白质进行位点特异性缀合的光交联肽
WO2020128864A1 (en) 2018-12-18 2020-06-25 Janssen Biotech, Inc. Safe and effective method of treating lupus with anti-il12/il23 antibody
WO2020132214A2 (en) 2018-12-20 2020-06-25 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Ebola virus glycoprotein-specific monoclonal antibodies and uses thereof
EP3898667A2 (en) 2018-12-20 2021-10-27 F. Hoffmann-La Roche AG Modified antibody fcs and methods of use
SG11202106198YA (en) 2018-12-21 2021-07-29 Hoffmann La Roche Antibody that binds to vegf and il-1beta and methods of use
MY194642A (en) 2018-12-21 2022-12-09 Hoffmann La Roche Antibodies binding to cd3
CN113286822A (zh) 2018-12-21 2021-08-20 豪夫迈·罗氏有限公司 靶向肿瘤的超激动性cd28抗原结合分子
EP3898682A1 (en) 2018-12-21 2021-10-27 F. Hoffmann-La Roche AG Tumor-targeted agonistic cd28 antigen binding molecules
JP2022516503A (ja) 2018-12-26 2022-02-28 シティ・オブ・ホープ 活性化可能なマスクされた抗ｃｔｌａ４結合タンパク質
CN113272327A (zh) 2018-12-30 2021-08-17 豪夫迈·罗氏有限公司 抗兔cd19抗体及其使用方法
CN115120716A (zh) 2019-01-14 2022-09-30 健泰科生物技术公司 用pd-1轴结合拮抗剂和rna疫苗治疗癌症的方法
CN113330030A (zh) 2019-01-17 2021-08-31 拜耳公司 确定受试者是否适于用可溶性鸟苷酸环化酶(sGC)的激动剂治疗的方法
US20220089770A1 (en) 2019-01-24 2022-03-24 Chugai Seiyaku Kabushiki Kaisha Novel cancer antigens and antibodies of said antigens
GB201901197D0 (en) 2019-01-29 2019-03-20 Femtogenix Ltd G-A Crosslinking cytotoxic agents
US20220096651A1 (en) 2019-01-29 2022-03-31 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for receptor tyrosine kinase like orphan receptor 1 (ror1)
KR20210133237A (ko) 2019-02-27 2021-11-05 제넨테크, 인크. 항-tigit 및 항-cd20 또는 항-cd38 항체로 치료를 위한 투약
EP3935385A1 (en) 2019-03-08 2022-01-12 F. Hoffmann-La Roche AG Methods for detecting and quantifying membrane-associated proteins on extracellular vesicles
AU2020236015A1 (en) 2019-03-14 2021-09-09 Genentech, Inc. Treatment of cancer with HER2XCD3 bispecific antibodies in combination with anti-HER2 MAB
EP3938384A4 (en) 2019-03-14 2022-12-28 Janssen Biotech, Inc. METHODS OF MANUFACTURING FOR PRODUCING ANTI-IL12/IL23 ANTIBODY COMPOSITIONS
BR112021018441A2 (pt) 2019-03-18 2023-02-28 Janssen Biotech Inc Método para tratamento de psoríase em indivíduos pediátricos com anticorpo anti-il12/il23
GB2589049C (en) 2019-04-11 2024-02-21 argenx BV Anti-IgE antibodies
JP7301155B2 (ja) 2019-04-12 2023-06-30 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト リポカリンムテインを含む二重特異性抗原結合分子
CA3134522A1 (en) 2019-04-19 2020-10-22 Genentech, Inc. Anti-mertk antibodies and their methods of use
AU2020257748A1 (en) 2019-04-19 2021-11-18 Chugai Seiyaku Kabushiki Kaisha Chimeric receptor recognizing modification site of antibody
US20220227853A1 (en) 2019-05-03 2022-07-21 The United States Of America,As Represented By The Secretary,Department Of Health And Human Services Neutralizing antibodies to plasmodium falciparum circumsporozoite protein and their use
KR20220004744A (ko) 2019-05-03 2022-01-11 제넨테크, 인크. 항-pd-l1 항체를 이용하여 암을 치료하는 방법
CA3137512A1 (en) 2019-05-14 2020-11-19 Werewolf Therapeutics, Inc. Separation moieties and methods and use thereof
BR112021022815A2 (pt) 2019-05-14 2021-12-28 Genentech Inc Métodos para tratar linfoma folicular, kits, imunoconjugados e polatuzumabe vedotina
US20230085439A1 (en) 2019-05-21 2023-03-16 University Of Georgia Research Foundation, Inc. Antibodies that bind human metapneumovirus fusion protein and their use
WO2020234473A1 (en) 2019-05-23 2020-11-26 Ac Immune Sa Anti-tdp-43 binding molecules and uses thereof
MX2021014302A (es) 2019-05-23 2022-01-04 Janssen Biotech Inc Metodo para tratar la enfermedad inflamatoria del intestino con una terapia de combinacion de anticuerpos contra il-23 y tnf alfa.
WO2020245420A1 (en) 2019-06-07 2020-12-10 Argenx Bvba PHARMACEUTICAL FORMULATIONS OF FcRn INHIBITORS SUITABLE FOR SUBCUTANEOUS ADMINISTRATION
BR112021026293A2 (pt) 2019-06-26 2022-03-03 Hoffmann La Roche Moléculas de ligação, anticorpos humanizados, ácido nucleico isolado, célula hospedeira, métodos para produzir a molécula de ligação ao antígeno, para tratar um indivíduo e suprarregular ou prolongar a atividade de células t citotóxicas, composição farmacêutica e uso da molécula
WO2020260326A1 (en) 2019-06-27 2020-12-30 F. Hoffmann-La Roche Ag Novel icos antibodies and tumor-targeted antigen binding molecules comprising them
CN114269783B (zh) 2019-07-02 2024-03-26 美国政府(由卫生和人类服务部的部长所代表) 结合egfrviii的单克隆抗体及其应用
WO2021005009A1 (en) 2019-07-05 2021-01-14 Iomx Therapeutics Ag Antibodies binding igc2 of igsf11 (vsig3) and uses thereof
AR119382A1 (es) 2019-07-12 2021-12-15 Hoffmann La Roche Anticuerpos de pre-direccionamiento y métodos de uso
JPWO2021010326A1 (da) 2019-07-12 2021-01-21
AR119393A1 (es) 2019-07-15 2021-12-15 Hoffmann La Roche Anticuerpos que se unen a nkg2d
CA3145278A1 (en) 2019-07-26 2021-02-04 Vanderbilt University Human monoclonal antibodies to enterovirus d68
JP2022543551A (ja) 2019-07-31 2022-10-13 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト Ｇｐｒｃ５ｄに結合する抗体
PE20220394A1 (es) 2019-07-31 2022-03-18 Hoffmann La Roche Anticuerpos que se fijan a gprc5d
EP4007773A1 (en) 2019-08-06 2022-06-08 Aprinoia Therapeutics Limited Antibodies that bind to pathological tau species and uses thereof
EP4028054A1 (en) 2019-09-12 2022-07-20 Genentech, Inc. Compositions and methods of treating lupus nephritis
AU2020349509A1 (en) 2019-09-18 2022-03-31 Genentech, Inc. Anti-KLK7 antibodies, anti-KLK5 antibodies, multispecific anti-KLK5/KLK7 antibodies, and methods of use
EP4031575A1 (en) 2019-09-19 2022-07-27 Bristol-Myers Squibb Company Antibodies binding to vista at acidic ph
AU2020348393A1 (en) 2019-09-20 2022-02-24 Genentech, Inc. Dosing for anti-tryptase antibodies
WO2021062085A1 (en) 2019-09-27 2021-04-01 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
EP4045090A1 (en) 2019-10-18 2022-08-24 Genentech, Inc. Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma
CN115066613A (zh) 2019-11-06 2022-09-16 基因泰克公司 用于治疗血液癌症的诊断和治疗方法
BR112022008629A2 (pt) 2019-11-15 2022-07-19 Enthera S R L Anticorpo isolado ou fragmento de ligação de antígeno do mesmo, polinucleotídeo isolado, vetor, célula isolada, composição farmacêutica, uso dos mesmos e método para inibir a ligação de igfbp3 ao receptor tmem219
EP3822288A1 (en) 2019-11-18 2021-05-19 Deutsches Krebsforschungszentrum, Stiftung des öffentlichen Rechts Antibodies targeting, and other modulators of, the cd276 antigen, and uses thereof
US20230039165A1 (en) 2019-11-21 2023-02-09 Enthera S.R.L. Igfbp3 antibodies and therapeutic uses thereof
KR20220122656A (ko) 2019-12-06 2022-09-02 주노 쎄러퓨티크스 인코퍼레이티드 Ｇｐｒｃ5ｄ-표적화 결합 도메인에 대한 항-이디오타입 항체 및 관련 조성물 및 방법
CN115916817A (zh) 2019-12-06 2023-04-04 朱诺治疗学股份有限公司 针对bcma靶向结合结构域的抗独特型抗体及相关组合物和方法
AU2020403145A1 (en) 2019-12-13 2022-07-07 Genentech, Inc. Anti-Ly6G6D antibodies and methods of use
BR112022011854A2 (pt) 2019-12-18 2022-09-06 Hoffmann La Roche Anticorpos, polinucleotídeo isolado, célula hospedeira, métodos para produzir um anticorpo e para tratar uma doença, composição farmacêutica, usos do anticorpo e invenção
CN113045655A (zh) 2019-12-27 2021-06-29 高诚生物医药(香港)有限公司 抗ox40抗体及其用途
JP7373588B2 (ja) 2019-12-27 2023-11-02 中外製薬株式会社 抗ｃｔｌａ－４抗体およびその使用
MX2022008320A (es) 2020-01-08 2022-10-21 argenx BV Métodos para tratar trastornos de pénfigo.
WO2021140130A1 (en) 2020-01-09 2021-07-15 F. Hoffmann-La Roche Ag New 4-1bbl trimer-containing antigen binding molecules
CN110818795B (zh) 2020-01-10 2020-04-24 上海复宏汉霖生物技术股份有限公司 抗tigit抗体和使用方法
WO2021194481A1 (en) 2020-03-24 2021-09-30 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
WO2022050954A1 (en) 2020-09-04 2022-03-10 Genentech, Inc. Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies
AU2021212197A1 (en) 2020-01-31 2022-08-04 BioNTech SE Methods of inducing neoepitope-specific T cells with a PD-1 axis binding antagonist and an RNA vaccine
AU2021214795A1 (en) 2020-01-31 2022-08-18 The Cleveland Clinic Foundation Anti-Müllerian Hormone Receptor 2 antibodies and methods of use
IL295310A (en) 2020-02-11 2022-10-01 Univ Vanderbilt Human monoclonal antibodies to severe acute respiratory syndrome coronavirus 2 (sars-cov-2)
TW202144395A (zh) 2020-02-12 2021-12-01 日商中外製藥股份有限公司 用於癌症之治療的抗cd137抗原結合分子
WO2021163064A2 (en) 2020-02-14 2021-08-19 Jounce Therapeutics, Inc. Antibodies and fusion proteins that bind to ccr8 and uses thereof
EP4093762A1 (en) 2020-02-20 2022-11-30 The United States of America, as represented by the Secretary, Department of Health and Human Services Epstein-barr virus monoclonal antibodies and uses thereof
EP3868396A1 (en) 2020-02-20 2021-08-25 Enthera S.R.L. Inhibitors and uses thereof
EP4112642A4 (en) 2020-02-28 2024-06-26 Shanghai Henlius Biotech, Inc. ANTI-CD137 CONSTRUCTION AND ITS USE
WO2021170071A1 (en) 2020-02-28 2021-09-02 Shanghai Henlius Biotech, Inc. Anti-cd137 constructs, multispecific antibody and uses thereof
US20230126689A1 (en) 2020-03-06 2023-04-27 Go Therapeutics, Inc. Anti-glyco-cd44 antibodies and their uses
WO2021183849A1 (en) 2020-03-13 2021-09-16 Genentech, Inc. Anti-interleukin-33 antibodies and uses thereof
MX2022011455A (es) 2020-03-19 2022-10-03 Genentech Inc Anticuerpos anti-tgf-beta con selectividad de isoforma y metodos de uso.
EP4107184A1 (en) 2020-03-23 2022-12-28 Genentech, Inc. Method for treating pneumonia, including covid-19 pneumonia, with an il6 antagonist
EP4107185A1 (en) 2020-03-23 2022-12-28 Genentech, Inc. Biomarkers for predicting response to il-6 antagonist in covid-19 pneumonia
WO2021194860A1 (en) 2020-03-23 2021-09-30 Genentech, Inc. Tocilizumab and remdesivir combination therapy for covid-19 pneumonia
WO2021194913A1 (en) 2020-03-24 2021-09-30 Genentech, Inc. Tie2-binding agents and methods of use
MX2022011892A (es) 2020-03-26 2022-10-18 Univ Vanderbilt Anticuerpos monoclonales humanos dirigidos contra el coronavirus 2 del sindrome respiratorio agudo grave (sars-cov-2).
WO2021195385A1 (en) 2020-03-26 2021-09-30 Vanderbilt University HUMAN MONOCLONAL ANTIBODIES TO SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-GoV-2)
CN115315512A (zh) 2020-03-26 2022-11-08 基因泰克公司 具有降低的宿主细胞蛋白质的经修饰的哺乳动物细胞
AR121706A1 (es) 2020-04-01 2022-06-29 Hoffmann La Roche Moléculas de unión a antígeno biespecíficas dirigidas a ox40 y fap
WO2021202959A1 (en) 2020-04-03 2021-10-07 Genentech, Inc. Therapeutic and diagnostic methods for cancer
WO2021207449A1 (en) 2020-04-09 2021-10-14 Merck Sharp & Dohme Corp. Affinity matured anti-lap antibodies and uses thereof
WO2021207662A1 (en) 2020-04-10 2021-10-14 Genentech, Inc. Use of il-22fc for the treatment or prevention of pneumonia, acute respiratory distress syndrome, or cytokine release syndrome
CA3175530A1 (en) 2020-04-24 2021-10-28 Genentech, Inc. Methods of using anti-cd79b immunoconjugates
EP4143225A4 (en) 2020-04-27 2024-05-15 The Regents of the University of California ISOFORM-INDEPENDENT ANTIBODIES AGAINST LIPOPROTEIN(A)
WO2021222167A1 (en) 2020-04-28 2021-11-04 Genentech, Inc. Methods and compositions for non-small cell lung cancer immunotherapy
CN116963782A (zh) 2020-05-03 2023-10-27 联宁（苏州）生物制药有限公司 包含抗trop-2抗体的抗体药物偶联物
JP2023528235A (ja) 2020-05-17 2023-07-04 アストラゼネカ・ユーケイ・リミテッド ＳＡＲＳ－ＣｏＶ－２抗体、並びにこれを選択及び使用する方法
US20230220057A1 (en) 2020-05-27 2023-07-13 Staidson (Beijing) Biopharmaceuticals Co., Ltd. Antibodies specifically recognizing nerve growth factor and uses thereof
EP4157462A1 (en) 2020-06-02 2023-04-05 Dynamicure Biotechnology LLC Anti-cd93 constructs and uses thereof
CN116529260A (zh) 2020-06-02 2023-08-01 当康生物技术有限责任公司 抗cd93构建体及其用途
PE20240080A1 (es) 2020-06-08 2024-01-16 Hoffmann La Roche Anticuerpos anti-hbv y metodos de uso
CN115698719A (zh) 2020-06-12 2023-02-03 基因泰克公司 用于癌症免疫疗法的方法和组合物
IL299039A (en) 2020-06-16 2023-02-01 Genentech Inc Methods and preparations for the treatment of triple-negative breast cancer
WO2021257124A1 (en) 2020-06-18 2021-12-23 Genentech, Inc. Treatment with anti-tigit antibodies and pd-1 axis binding antagonists
WO2021255146A1 (en) 2020-06-19 2021-12-23 F. Hoffmann-La Roche Ag Antibodies binding to cd3 and cea
AU2021291011A1 (en) 2020-06-19 2023-01-05 F. Hoffmann-La Roche Ag Antibodies binding to CD3 and CD19
JP2023531625A (ja) 2020-06-19 2023-07-25 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト ＣＤ３及びＦｏｌＲ１に結合する抗体
WO2021255142A1 (en) 2020-06-19 2021-12-23 F. Hoffmann-La Roche Ag Antibodies binding to cd3
KR20230016206A (ko) 2020-06-23 2023-02-01 에프. 호프만-라 로슈 아게 Her2를 표적으로 하는 작용성 CD28 항원 결합 분자
US20220041672A1 (en) 2020-06-24 2022-02-10 Genentech, Inc. Apoptosis resistant cell lines
WO2021260064A1 (en) 2020-06-25 2021-12-30 F. Hoffmann-La Roche Ag Anti-cd3/anti-cd28 bispecific antigen binding molecules
EP4175668A1 (en) 2020-07-06 2023-05-10 iOmx Therapeutics AG Antibodies binding igv of igsf11 (vsig3) and uses thereof
CR20230076A (es) 2020-07-10 2023-03-13 Hoffmann La Roche Anticuerpos que se unen a células cancerosas y dirigen radionucleótidos a dichas células
PE20231300A1 (es) 2020-07-17 2023-08-24 Genentech Inc Anticuerpos anti-notch2 y metodos de uso
GB2597532A (en) 2020-07-28 2022-02-02 Femtogenix Ltd Cytotoxic compounds
AU2021315665A1 (en) 2020-07-29 2023-03-16 Dynamicure Biotechnology Llc Anti-CD93 constructs and uses thereof
EP4189121A1 (en) 2020-08-03 2023-06-07 Genentech, Inc. Diagnostic and therapeutic methods for lymphoma
WO2022029660A1 (en) 2020-08-05 2022-02-10 Juno Therapeutics, Inc. Anti-idiotypic antibodies to ror1-targeted binding domains and related compositions and methods
EP4192854A1 (en) 2020-08-07 2023-06-14 Genentech, Inc. Flt3 ligand fusion proteins and methods of use
BR112023002234A2 (pt) 2020-08-10 2023-03-07 Astrazeneca Uk Ltd Anticorpos sars-cov-2 para tratamento e prevenção de covid-19
US20230322908A1 (en) 2020-08-14 2023-10-12 Ac Immune Sa Humanized Anti-TDP-43 Binding Molecules and Uses Thereof
WO2022043517A2 (en) 2020-08-27 2022-03-03 Cureab Gmbh Anti-golph2 antibodies for macrophage and dendritic cell differentiation
TW202227625A (zh) 2020-08-28 2022-07-16 美商建南德克公司 宿主細胞蛋白質之ＣＲＩＳＰＲ／Ｃａｓ９多重剔除
KR20230061458A (ko) 2020-09-04 2023-05-08 에프. 호프만-라 로슈 아게 Vegf-a 및 ang2에 결합하는 항체 및 사용 방법
MX2023002984A (es) 2020-09-15 2023-04-10 Bayer Ag Nuevos anticuerpos anti-a2ap y usos de los mismos.
CN116685351A (zh) 2020-09-17 2023-09-01 基因泰克公司 Empacta的结果：一项用于评估托珠单抗在患有covid-19肺炎的住院患者中的功效和安全性的随机、双盲、安慰剂对照、多中心研究
CA3193952A1 (en) 2020-10-05 2022-04-14 Bernard Martin Fine Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
WO2022079211A1 (en) 2020-10-16 2022-04-21 Adc Therapeutics Sa Glycoconjugates
WO2022084400A1 (en) 2020-10-20 2022-04-28 Kantonsspital St. Gallen Antibodies or antigen-binding fragments specifically binding to gremlin-1 and uses thereof
AR123855A1 (es) 2020-10-20 2023-01-18 Genentech Inc Anticuerpos anti-mertk conjugados con peg y métodos de uso
WO2022084210A1 (en) 2020-10-20 2022-04-28 F. Hoffmann-La Roche Ag Combination therapy of pd-1 axis binding antagonists and lrrk2 inhitibors
WO2022093981A1 (en) 2020-10-28 2022-05-05 Genentech, Inc. Combination therapy comprising ptpn22 inhibitors and pd-l1 binding antagonists
JP2023547507A (ja) 2020-11-03 2023-11-10 ドイチェス クレブスフォルシュンクスツェントルム スチフトゥング デス エッフェントリヒェン レヒツ 標的細胞限定的で共刺激性の二重特異性かつ２価の抗ｃｄ２８抗体
WO2022098638A2 (en) 2020-11-04 2022-05-12 Genentech, Inc. Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies
TW202225191A (zh) 2020-11-04 2022-07-01 美商建南德克公司 抗ｃｄ２０／抗ｃｄ３雙特異性抗體之皮下給藥
US20220153842A1 (en) 2020-11-04 2022-05-19 Genentech, Inc. Dosing for treatment with anti-cd20/anti-cd3 bispecific antibodies and anti-cd79b antibody drug conjugates
EP4244254A1 (en) 2020-11-16 2023-09-20 F. Hoffmann-La Roche AG Combination therapy with fap-targeted cd40 agonists
IL303134A (en) 2020-12-02 2023-07-01 Glaxosmithkline Ip Dev Ltd IL-7 binding proteins and their use in medical treatment
TW202237638A (zh) 2020-12-09 2022-10-01 日商武田藥品工業股份有限公司 烏苷酸環化酶ｃ（ｇｃｃ）抗原結合劑之組成物及其使用方法
TW202237639A (zh) 2020-12-09 2022-10-01 日商武田藥品工業股份有限公司 鳥苷酸環化酶ｃ（ｇｃｃ）抗原結合劑之組成物及其使用方法
WO2022132904A1 (en) 2020-12-17 2022-06-23 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Human monoclonal antibodies targeting sars-cov-2
MX2023007846A (es) 2021-01-06 2023-07-07 Hoffmann La Roche Tratamiento conjunto que usa un anticuerpo biespecifico contra pd1-lag3 y un anticuerpo biespecifico de linfocitos t cd20.
AU2022207615A1 (en) 2021-01-12 2023-07-13 F. Hoffmann-La Roche Ag Split antibodies which bind to cancer cells and target radionuclides to said cells
KR20230131205A (ko) 2021-01-13 2023-09-12 에프. 호프만-라 로슈 아게 병용 요법
WO2022162587A1 (en) 2021-01-27 2022-08-04 Centre Hospitalier Universitaire Vaudois (C.H.U.V.) Anti-sars-cov-2 antibodies and use thereof in the treatment of sars-cov-2 infection
CN117120084A (zh) 2021-01-28 2023-11-24 维肯芬特有限责任公司 用于调节b细胞介导的免疫应答的方法和手段
WO2022162203A1 (en) 2021-01-28 2022-08-04 Vaccinvent Gmbh Method and means for modulating b-cell mediated immune responses
WO2022162201A1 (en) 2021-01-28 2022-08-04 Vaccinvent Gmbh Method and means for modulating b-cell mediated immune responses
EP4288458A1 (en) 2021-02-03 2023-12-13 Genentech, Inc. Multispecific binding protein degrader platform and methods of use
CN117396502A (zh) 2021-02-09 2024-01-12 佐治亚大学研究基金会有限公司 针对肺炎球菌抗原的人类单克隆抗体
MX2023009244A (es) 2021-02-09 2023-09-11 Us Health Anticuerpos contra la proteina espicular de coronavirus.
AU2022219373A1 (en) 2021-02-15 2023-08-24 Takeda Pharmaceutical Company Limited Cell therapy compositions and methods for modulating tgf-b signaling
GB202102396D0 (en) 2021-02-19 2021-04-07 Adc Therapeutics Sa Molecular adjuvant
WO2022180172A1 (en) 2021-02-26 2022-09-01 Bayer Aktiengesellschaft Inhibitors of il-11 or il-11ra for use in the treatment of abnormal uterine bleeding
TW202317612A (zh) 2021-03-01 2023-05-01 美商艾希利歐發展股份有限公司 用於治療癌症的ｃｔｌａ４及ｐｄ１／ｐｄｌ１抗體之組合
US20220340662A1 (en) 2021-03-01 2022-10-27 Xilio Development, Inc. Combination of masked ctla4 and pd1/pdl1 antibodies for treating cancer
CN117440832A (zh) 2021-03-03 2024-01-23 索伦托药业有限公司 包括抗bcma抗体的抗体-药物缀合物
WO2022187591A1 (en) 2021-03-05 2022-09-09 Go Therapeutics, Inc. Anti-glyco-cd44 antibodies and their uses
TW202302646A (zh) 2021-03-05 2023-01-16 美商當康生物科技有限公司 抗vista構築體及其用途
EP4305062A1 (en) 2021-03-12 2024-01-17 Janssen Biotech, Inc. Method of treating psoriatic arthritis patients with inadequate response to tnf therapy with anti-il23 specific antibody
WO2022192647A1 (en) 2021-03-12 2022-09-15 Genentech, Inc. Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use
US20220298236A1 (en) 2021-03-12 2022-09-22 Janssen Biotech, Inc. Safe and Effective Method of Treating Psoriatic Arthritis with Anti-IL23 Specific Antibody
CA3213599A1 (en) 2021-03-15 2022-09-22 Genentech, Inc. Compositions and methods of treating lupus nephritis
WO2022197877A1 (en) 2021-03-19 2022-09-22 Genentech, Inc. Methods and compositions for time delayed bio-orthogonal release of cytotoxic agents
US20240150466A1 (en) 2021-03-25 2024-05-09 Dynamicure Biotechnology Llc Anti-igfbp7 constructs and uses thereof
EP4314047A1 (en) 2021-03-30 2024-02-07 Bayer Aktiengesellschaft Anti-sema3a antibodies and uses thereof
AR125344A1 (es) 2021-04-15 2023-07-05 Chugai Pharmaceutical Co Ltd Anticuerpo anti-c1s
CA3215965A1 (en) 2021-04-19 2022-10-27 Amy Shen Modified mammalian cells
JP2024514281A (ja) 2021-04-23 2024-04-01 エフ・ホフマン－ラ・ロシュ・アクチェンゲゼルシャフト Ｎｋ細胞係合剤関連の有害作用の防止または軽減
TW202243689A (zh) 2021-04-30 2022-11-16 瑞士商赫孚孟拉羅股份公司 抗ｃｄ２０／抗ｃｄ３雙特異性抗體及抗ｃｄ７８ｂ抗體藥物結合物的組合治療之給藥
WO2022241446A1 (en) 2021-05-12 2022-11-17 Genentech, Inc. Methods of using anti-cd79b immunoconjugates to treat diffuse large b-cell lymphoma
TW202306993A (zh) 2021-05-14 2023-02-16 美商建南德克公司 Ｔｒｅｍ２之促效劑
WO2022243261A1 (en) 2021-05-19 2022-11-24 F. Hoffmann-La Roche Ag Agonistic cd40 antigen binding molecules targeting cea
JP2024521107A (ja) 2021-05-21 2024-05-28 ジェネンテック， インコーポレイテッド 目的の組換え産物を産生するための修飾細胞
CA3220227A1 (en) 2021-05-28 2022-12-01 Matthew Bruce Combination therapies for treating cancer
AR126009A1 (es) 2021-06-02 2023-08-30 Hoffmann La Roche Moléculas agonistas de unión al antígeno cd28 que se dirigen a epcam
WO2022255440A1 (en) 2021-06-04 2022-12-08 Chugai Seiyaku Kabushiki Kaisha Anti-ddr2 antibodies and uses thereof
WO2022258600A1 (en) 2021-06-09 2022-12-15 F. Hoffmann-La Roche Ag Combination of a particular braf inhibitor (paradox breaker) and a pd-1 axis binding antagonist for use in the treatment of cancer
CA3221924A1 (en) 2021-06-11 2022-12-15 Genentech, Inc. Method for treating chronic obstructive pulmonary disease with an st2 antagonist
WO2022263638A1 (en) 2021-06-17 2022-12-22 Centre Hospitalier Universitaire Vaudois (C.H.U.V.) Anti-sars-cov-2 antibodies and use thereof in the treatment of sars-cov-2 infection
EP4355785A1 (en) 2021-06-17 2024-04-24 Amberstone Biosciences, Inc. Anti-cd3 constructs and uses thereof
CN117616123A (zh) 2021-06-25 2024-02-27 中外制药株式会社 抗ctla-4抗体
CA3220353A1 (en) 2021-06-25 2022-12-29 Chugai Seiyaku Kabushiki Kaisha Use of anti-ctla-4 antibody
WO2023283611A1 (en) 2021-07-08 2023-01-12 Staidson Biopharma Inc. Antibodies specifically recognizing tnfr2 and uses thereof
CN117916260A (zh) 2021-07-09 2024-04-19 詹森生物科技公司 用于制备抗il12/il23抗体组合物的制造方法
EP4370545A1 (en) 2021-07-12 2024-05-22 Genentech, Inc. Structures for reducing antibody-lipase binding
CN115812082A (zh) 2021-07-14 2023-03-17 舒泰神（北京）生物制药股份有限公司 特异性识别cd40的抗体及其应用
TW202309097A (zh) 2021-07-14 2023-03-01 美商建南德克公司 抗ｃ－ｃ模體趨化因子受體８（ｃｃｒ８）抗體及其使用方法
EP4373576A1 (en) 2021-07-22 2024-05-29 Genentech, Inc. Brain targeting compositions and methods of use thereof
EP4373859A1 (en) 2021-07-22 2024-05-29 F. Hoffmann-La Roche AG Heterodimeric fc domain antibodies
WO2023012147A1 (en) 2021-08-03 2023-02-09 F. Hoffmann-La Roche Ag Bispecific antibodies and methods of use
CA3228178A1 (en) 2021-08-05 2023-02-09 Go Therapeutics, Inc. Anti-glyco-muc4 antibodies and their uses
TW202337499A (zh) 2021-08-07 2023-10-01 美商建南德克公司 使用抗ｃｄ７９ｂ免疫結合物治療瀰漫性大ｂ細胞淋巴瘤之方法
EP4384224A1 (en) 2021-08-13 2024-06-19 GlaxoSmithKline Intellectual Property Development Limited Cytotoxicity targeting chimeras
WO2023019239A1 (en) 2021-08-13 2023-02-16 Genentech, Inc. Dosing for anti-tryptase antibodies
IL310698A (en) 2021-08-13 2024-04-01 Glaxosmithkline Ip Dev Ltd Cytotoxic targeting chimeras for CCR2-expressing cells
CN117858905A (zh) 2021-08-19 2024-04-09 豪夫迈·罗氏有限公司 多价抗变体fc区抗体及使用方法
WO2023028501A1 (en) 2021-08-23 2023-03-02 Immunitas Therapeutics, Inc. Anti-cd161 antibodies and uses thereof
KR20240049296A (ko) 2021-08-27 2024-04-16 제넨테크, 인크. 타우 병증을 치료하는 방법
TW202325727A (zh) 2021-08-30 2023-07-01 美商建南德克公司 抗聚泛素多特異性抗體
AU2022339819A1 (en) 2021-09-03 2024-04-11 Go Therapeutics, Inc. Anti-glyco-lamp1 antibodies and their uses
TW202328188A (zh) 2021-09-03 2023-07-16 美商Ｇｏ治療公司 抗醣化-cmet抗體及其用途
CA3232223A1 (en) 2021-09-17 2023-03-23 Ying Fu Synthetic humanized llama nanobody library and use thereof to identify sars-cov-2 neutralizing antibodies
WO2023056403A1 (en) 2021-09-30 2023-04-06 Genentech, Inc. Methods for treatment of hematologic cancers using anti-tigit antibodies, anti-cd38 antibodies, and pd-1 axis binding antagonists
WO2023057893A1 (en) 2021-10-05 2023-04-13 Glaxosmithkline Intellectual Property Development Limited Combination therapies for treating cancer
JPWO2023058723A1 (da) 2021-10-08 2023-04-13
KR20240099352A (ko) 2021-10-29 2024-06-28 얀센 바이오테크 인코포레이티드 항-il23 특이적 항체로 크론병을 치료하는 방법
WO2023078279A1 (zh) * 2021-11-04 2023-05-11 澄交生物科技股份有限公司 免疫原性组合物及其用途
TW202342095A (zh) 2021-11-05 2023-11-01 英商阿斯特捷利康英國股份有限公司 用於治療和預防ｃｏｖｉｄ—１９之組成物
AU2022379952A1 (en) 2021-11-05 2024-05-16 American Diagnostics & Therapy, Llc (Adxrx) Monoclonal antibodies against carcinoembryonic antigens, and their uses
WO2023086807A1 (en) 2021-11-10 2023-05-19 Genentech, Inc. Anti-interleukin-33 antibodies and uses thereof
AU2022388887A1 (en) 2021-11-15 2024-07-04 Janssen Biotech, Inc. Methods of treating crohn's disease with anti-il23 specific antibody
WO2023091887A1 (en) 2021-11-16 2023-05-25 Genentech, Inc. Methods and compositions for treating systemic lupus erythematosus (sle) with mosunetuzumab
WO2023088959A1 (en) 2021-11-16 2023-05-25 Ac Immune Sa Novel molecules for therapy and diagnosis
US20230159633A1 (en) 2021-11-23 2023-05-25 Janssen Biotech, Inc. Method of Treating Ulcerative Colitis with Anti-IL23 Specific Antibody
WO2023094569A1 (en) 2021-11-26 2023-06-01 F. Hoffmann-La Roche Ag Combination therapy of anti-tyrp1/anti-cd3 bispecific antibodies and tyrp1-specific antibodies
AR127887A1 (es) 2021-12-10 2024-03-06 Hoffmann La Roche Anticuerpos que se unen a cd3 y plap
AU2022411573A1 (en) 2021-12-17 2024-06-27 Shanghai Henlius Biologics Co., Ltd. Anti-ox40 antibodies and methods of use
CA3240585A1 (en) 2021-12-17 2023-06-22 Wenfeng Xu Anti-ox40 antibodies, multispecific antibodies and methods of use
AR128031A1 (es) 2021-12-20 2024-03-20 Hoffmann La Roche Anticuerpos agonistas anti-ltbr y anticuerpos biespecíficos que los comprenden
TW202337904A (zh) 2022-01-07 2023-10-01 美商壯生和壯生企業創新公司 ＩＬ－１β結合蛋白之材料及方法
US20230322958A1 (en) 2022-01-19 2023-10-12 Genentech, Inc. Anti-Notch2 Antibodies and Conjugates and Methods of Use
WO2023154824A1 (en) 2022-02-10 2023-08-17 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Human monoclonal antibodies that broadly target coronaviruses
WO2023156549A1 (en) 2022-02-16 2023-08-24 Ac Immune Sa Humanized anti-tdp-43 binding molecules and uses thereof
TW202342520A (zh) 2022-02-18 2023-11-01 美商樂天醫藥生技股份有限公司 抗計畫性死亡配體１（ｐｄ—ｌ１）抗體分子、編碼多核苷酸及使用方法
WO2023161875A1 (en) 2022-02-25 2023-08-31 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for prostate specific membrane antigen-expressing cells
WO2023161874A1 (en) 2022-02-25 2023-08-31 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for c-c chemokine receptor 2-expressing cells
WO2023161879A1 (en) 2022-02-25 2023-08-31 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for fibroblast activation protein-expressing cells
WO2023161881A1 (en) 2022-02-25 2023-08-31 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for ccr2-expressing cells
WO2023161877A1 (en) 2022-02-25 2023-08-31 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for integrin avb6-expressing cells
WO2023161878A1 (en) 2022-02-25 2023-08-31 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for folate receptor-expressing cells
WO2023161876A1 (en) 2022-02-25 2023-08-31 Glaxosmithkline Intellectual Property Development Limited Cytotoxicity targeting chimeras for cxcr3-expressing cells
WO2023173026A1 (en) 2022-03-10 2023-09-14 Sorrento Therapeutics, Inc. Antibody-drug conjugates and uses thereof
TW202346365A (zh) 2022-03-23 2023-12-01 瑞士商赫孚孟拉羅股份公司 抗ｃｄ２０／抗ｃｄ３雙特異性抗體及化學療法之組合治療
WO2023192827A1 (en) 2022-03-26 2023-10-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Bispecific antibodies to hiv-1 env and their use
WO2023192881A1 (en) 2022-03-28 2023-10-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Neutralizing antibodies to hiv-1 env and their use
WO2023186756A1 (en) 2022-03-28 2023-10-05 F. Hoffmann-La Roche Ag Interferon gamma variants and antigen binding molecules comprising these
WO2023187707A1 (en) 2022-03-30 2023-10-05 Janssen Biotech, Inc. Method of treating mild to moderate psoriasis with il-23 specific antibody
GB202204813D0 (en) 2022-04-01 2022-05-18 Bradcode Ltd Human monoclonal antibodies and methods of use thereof
WO2023191816A1 (en) 2022-04-01 2023-10-05 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
WO2023194565A1 (en) 2022-04-08 2023-10-12 Ac Immune Sa Anti-tdp-43 binding molecules
TW202408562A (zh) 2022-04-13 2024-03-01 美商建南德克公司 治療性蛋白質之醫藥組成物及使用方法
WO2023198727A1 (en) 2022-04-13 2023-10-19 F. Hoffmann-La Roche Ag Pharmaceutical compositions of anti-cd20/anti-cd3 bispecific antibodies and methods of use
WO2023203177A1 (en) 2022-04-20 2023-10-26 Kantonsspital St. Gallen Antibodies or antigen-binding fragments pan-specifically binding to gremlin-1 and gremlin-2 and uses thereof
WO2023209177A1 (en) 2022-04-29 2023-11-02 Astrazeneca Uk Limited Sars-cov-2 antibodies and methods of using the same
US20230348604A1 (en) 2022-04-29 2023-11-02 23Andme, Inc. Antigen binding proteins
TW202406934A (zh) 2022-05-03 2024-02-16 美商建南德克公司 抗Ｌｙ６Ｅ抗體、免疫結合物及其用途
WO2023217933A1 (en) 2022-05-11 2023-11-16 F. Hoffmann-La Roche Ag Antibody that binds to vegf-a and il6 and methods of use
WO2023219613A1 (en) 2022-05-11 2023-11-16 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
WO2023223265A1 (en) 2022-05-18 2023-11-23 Janssen Biotech, Inc. Method for evaluating and treating psoriatic arthritis with il23 antibody
WO2023227641A1 (en) 2022-05-27 2023-11-30 Glaxosmithkline Intellectual Property Development Limited Use of tnf-alpha binding proteins and il-7 binding proteins in medical treatment
WO2023235699A1 (en) 2022-05-31 2023-12-07 Jounce Therapeutics, Inc. Antibodies to lilrb4 and uses thereof
WO2023240058A2 (en) 2022-06-07 2023-12-14 Genentech, Inc. Prognostic and therapeutic methods for cancer
WO2023237706A2 (en) 2022-06-08 2023-12-14 Institute For Research In Biomedicine (Irb) Cross-specific antibodies, uses and methods for discovery thereof
WO2024015897A1 (en) 2022-07-13 2024-01-18 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
WO2024020432A1 (en) 2022-07-19 2024-01-25 Genentech, Inc. Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies
WO2024020407A1 (en) 2022-07-19 2024-01-25 Staidson Biopharma Inc. Antibodies specifically recognizing b- and t-lymphocyte attenuator (btla) and uses thereof
WO2024020564A1 (en) 2022-07-22 2024-01-25 Genentech, Inc. Anti-steap1 antigen-binding molecules and uses thereof
WO2024020579A1 (en) 2022-07-22 2024-01-25 Bristol-Myers Squibb Company Antibodies binding to human pad4 and uses thereof
WO2024030829A1 (en) 2022-08-01 2024-02-08 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Monoclonal antibodies that bind to the underside of influenza viral neuraminidase
WO2024028731A1 (en) 2022-08-05 2024-02-08 Janssen Biotech, Inc. Transferrin receptor binding proteins for treating brain tumors
WO2024028732A1 (en) 2022-08-05 2024-02-08 Janssen Biotech, Inc. Cd98 binding constructs for treating brain tumors
WO2024042112A1 (en) 2022-08-25 2024-02-29 Glaxosmithkline Intellectual Property Development Limited Antigen binding proteins and uses thereof
WO2024044779A2 (en) 2022-08-26 2024-02-29 Juno Therapeutics, Inc. Antibodies and chimeric antigen receptors specific for delta-like ligand 3 (dll3)
WO2024049949A1 (en) 2022-09-01 2024-03-07 Genentech, Inc. Therapeutic and diagnostic methods for bladder cancer
WO2024054929A1 (en) 2022-09-07 2024-03-14 Dynamicure Biotechnology Llc Anti-vista constructs and uses thereof
WO2024054822A1 (en) 2022-09-07 2024-03-14 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Engineered sars-cov-2 antibodies with increased neutralization breadth
WO2024064826A1 (en) 2022-09-22 2024-03-28 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Neutralizing antibodies to plasmodium falciparum circumsporozoite protein and their use
WO2024068996A1 (en) 2022-09-30 2024-04-04 Centre Hospitalier Universitaire Vaudois (C.H.U.V.) Anti-sars-cov-2 antibodies and use thereof in the treatment of sars-cov-2 infection
WO2024077239A1 (en) 2022-10-07 2024-04-11 Genentech, Inc. Methods of treating cancer with anti-c-c motif chemokine receptor 8 (ccr8) antibodies
WO2024091991A1 (en) 2022-10-25 2024-05-02 Genentech, Inc. Therapeutic and diagnostic methods for multiple myeloma
US20240165227A1 (en) 2022-11-04 2024-05-23 Gilead Sciences, Inc. Anticancer therapies using anti-ccr8 antibody, chemo and immunotherapy combinations
WO2024102734A1 (en) 2022-11-08 2024-05-16 Genentech, Inc. Compositions and methods of treating childhood onset idiopathic nephrotic syndrome
WO2024100200A1 (en) 2022-11-09 2024-05-16 Cis Pharma Ag Anti-l1-cam antibodies and their uses for diagnostic and therapeutic applications
WO2024100170A1 (en) 2022-11-11 2024-05-16 F. Hoffmann-La Roche Ag Antibodies binding to hla-a*02/foxp3
WO2024108053A1 (en) 2022-11-17 2024-05-23 Sanofi Ceacam5 antibody-drug conjugates and methods of use thereof
WO2024110898A1 (en) 2022-11-22 2024-05-30 Janssen Biotech, Inc. Method of treating ulcerative colitis with anti-il23 specific antibody
WO2024137381A1 (en) 2022-12-19 2024-06-27 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Monoclonal antibodies for treating sars-cov-2 infection
WO2024133940A2 (en) 2022-12-23 2024-06-27 Iomx Therapeutics Ag Cross-specific antigen binding proteins (abp) targeting leukocyte immunoglobulin-like receptor subfamily b1 (lilrb1) and lilrb2, combinations and uses thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6602684B1 (en) * 1998-04-20 2003-08-05 Glycart Biotechnology Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4215051A (en) * 1979-08-29 1980-07-29 Standard Oil Company (Indiana) Formation, purification and recovery of phthalic anhydride
KR850004274A (ko) * 1983-12-13 1985-07-11 원본미기재 에리트로포이에틴의 제조방법
US4946778A (en) 1987-09-21 1990-08-07 Genex Corporation Single polypeptide chain binding molecules
US4978745A (en) * 1987-11-23 1990-12-18 Centocor, Inc. Immunoreactive heterochain antibodies
US5047335A (en) * 1988-12-21 1991-09-10 The Regents Of The University Of Calif. Process for controlling intracellular glycosylation of proteins
ATE243713T1 (de) * 1989-05-25 2003-07-15 Sloan Kettering Inst Cancer Antiidiotypischer antikörper, der ein immunantwort gegen ein glykosphingolipid induziert und seine verwendung
DE4028800A1 (de) 1990-09-11 1992-03-12 Behringwerke Ag Gentechnische sialylierung von glykoproteinen
WO1994004574A1 (en) 1991-08-22 1994-03-03 Nissin Shokuhin Kabushiki Kaisha Hiv immunotherapeutics
US5753229A (en) * 1991-09-25 1998-05-19 Mordoh; Jose Monoclonal antibodies reactive with tumor proliferating cells
US5958403A (en) * 1992-02-28 1999-09-28 Beth Israel Hospital Association Methods and compounds for prevention of graft rejection
US5736137A (en) * 1992-11-13 1998-04-07 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human B lymphocyte restricted differentiation antigen for treatment of B cell lymphoma
NZ258392A (en) * 1992-11-13 1997-09-22 Idec Pharma Corp Chimeric and radiolabelled antibodies to the b lymphocyte cellsurface antigen bp35 (cd-20) and their use in the treatment of b cell lymphona
DE69419721T2 (de) 1993-01-12 2000-04-27 Biogen Inc Rekombinante anti-vla4 antikörpermoleküle
NZ279676A (en) 1994-03-09 1998-04-27 Abbott Lab Humanized milk produced by non-human transgenic mammal transformed with a heterologous gene coding for human enzyme producing human oligosaccharides and glycoconjugates
US5811524A (en) * 1995-06-07 1998-09-22 Idec Pharmaceuticals Corporation Neutralizing high affinity human monoclonal antibodies specific to RSV F-protein and methods for their manufacture and therapeutic use thereof
JP3606536B2 (ja) * 1995-11-17 2005-01-05 タカラバイオ株式会社 ウイルス複製抑制剤
GB9603256D0 (en) * 1996-02-16 1996-04-17 Wellcome Found Antibodies
WO1998006835A2 (en) 1996-08-16 1998-02-19 The Texas A & M University System Modifying insect cell gylcosylation pathways with baculovirus expression vectors
US6306393B1 (en) 1997-03-24 2001-10-23 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
US6183744B1 (en) * 1997-03-24 2001-02-06 Immunomedics, Inc. Immunotherapy of B-cell malignancies using anti-CD22 antibodies
US5952203A (en) * 1997-04-11 1999-09-14 The University Of British Columbia Oligosaccharide synthesis using activated glycoside derivative, glycosyl transferase and catalytic amount of nucleotide phosphate
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
EP1383800A4 (en) * 2001-04-02 2004-09-22 Idec Pharma Corp RECOMBINANT ANTIBODIES CO-EXPRESSED WITH GNTIII
CA2838062C (en) 2001-08-03 2015-12-22 Roche Glycart Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
AU2004205802B2 (en) 2003-01-22 2009-11-05 Roche Glycart Ag Fusion constructs and use of same to produce antibodies with increased Fc receptor binding affinity and effector function
WO2005044859A2 (en) 2003-11-05 2005-05-19 Glycart Biotechnology Ag Cd20 antibodies with increased fc receptor binding affinity and effector function
AR052285A1 (es) 2005-02-07 2007-03-07 Glycart Biotechnology Ag Moleculas de union al antigeno que fijan egfr, vectores que las codifican y usos de las mismas
BRPI0615397B1 (pt) 2005-08-26 2023-10-03 Roche Glycart Ag Anticorpo anti-cd20, composição farmacêutica que o contém e uso do mesmo
AR062223A1 (es) 2006-08-09 2008-10-22 Glycart Biotechnology Ag Moleculas de adhesion al antigeno que se adhieren a egfr, vectores que los codifican, y sus usos de estas
PE20121552A1 (es) 2009-08-31 2012-11-26 Roche Glycart Ag Anticuerpos monoclonales anti cea humanizados de afinidad madura

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6602684B1 (en) * 1998-04-20 2003-08-05 Glycart Biotechnology Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity

Cited By (338)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110142825A1 (en) * 1998-04-20 2011-06-16 Roche Glycart Ag Glycosylation Engineering of Antibodies for Improving Antibody-Dependent Cellular Cytotoxicity
US20050079605A1 (en) * 1998-04-20 2005-04-14 Glycart Biotechnology Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US7906329B2 (en) 1998-04-20 2011-03-15 Glycart Biotechnology Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US9068005B2 (en) 1998-04-20 2015-06-30 Roche Glycart Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US20080280322A9 (en) * 1998-04-20 2008-11-13 Glycart Biotechnology Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US8623644B2 (en) 1998-04-20 2014-01-07 Roche Glycart Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US8021856B2 (en) 1998-04-20 2011-09-20 Roche Glycart Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US9631023B2 (en) 1998-04-20 2017-04-25 Roche Glycart Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US20050272128A1 (en) * 1998-04-20 2005-12-08 Glycart Biotechnology Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US8629248B2 (en) 1998-04-20 2014-01-14 Roche Glycart Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US20040072290A1 (en) * 1998-04-20 2004-04-15 Glycart Biotechnology Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US7517670B2 (en) 1998-04-20 2009-04-14 Glycart Biotechnology Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US8999324B2 (en) 1998-04-20 2015-04-07 Roche Glycart Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
US20090304690A1 (en) * 1998-04-20 2009-12-10 Glycart Biotechnology Ag Glycosylation Engineering of Antibodies for Improving Antibody-Dependent Cellular Cytotoxicity
EP1071700B1 (en) * 1998-04-20 2010-02-17 GlycArt Biotechnology AG Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US9718885B2 (en) 1998-04-20 2017-08-01 Roche Glycart Ag Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US9139654B2 (en) 1998-04-20 2015-09-22 Roche GlyeArt AG Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US9321843B2 (en) 1998-04-20 2016-04-26 Roche Glycart Ag Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
EP1071700A1 (en) * 1998-04-20 2001-01-31 GlycArt Biotechnology AG Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
US8173141B2 (en) 1999-02-17 2012-05-08 Csl Limited Immunogenic complexes and methods relating thereto
US7776343B1 (en) 1999-02-17 2010-08-17 Csl Limited Immunogenic complexes and methods relating thereto
US8211691B2 (en) 2000-06-28 2012-07-03 Glycofi, Inc. Methods for producing modified glycoproteins
US20080274498A1 (en) * 2000-06-28 2008-11-06 Glycofi, Inc. Methods for producing modified glycoproteins
US20090209024A1 (en) * 2000-06-28 2009-08-20 Gerngross Tillman U Combinatorial DNA library for producing modified N-glycans in lower eukaryotes
US8067551B2 (en) 2000-06-28 2011-11-29 Glycofi, Inc. Combinatorial DNA library for producing modified N-glycans in lower eukaryotes
US7598055B2 (en) 2000-06-28 2009-10-06 Glycofi, Inc. N-acetylglucosaminyltransferase III expression in lower eukaryotes
US20050208617A1 (en) * 2000-06-28 2005-09-22 Piotr Bobrowicz N-acetylglucosamintransferase III expression in lower eukaryotes
US7981660B2 (en) 2000-06-28 2011-07-19 Glycofi, Inc. Methods for producing modified glycoproteins
US20060177898A1 (en) * 2000-06-28 2006-08-10 Glycofi, Inc. Methods for producing modified glycoproteins
US20070037248A1 (en) * 2000-06-28 2007-02-15 Piotr Bobrowicz Production of modified glycoproteins having multiple antennary structures
US8877462B2 (en) 2000-06-28 2014-11-04 Glycofi, Inc. Combinatorial DNA library for producing modified N-glycans in lower eukaryotes
US7923430B2 (en) 2000-06-28 2011-04-12 Glycofi, Inc. Methods for producing modified glycoproteins
US8445227B2 (en) 2000-06-28 2013-05-21 Merck Sharp & Dohme N-acetylglucosaminyltransferase III expression in lower eukaryotes
US7935513B2 (en) 2000-06-28 2011-05-03 Glycofi, Inc. Combinatorial DNA library for producing modified N-glycans in lower eukaryotes
US8883483B2 (en) 2000-06-28 2014-11-11 Glycofi, Inc. Combinatorial DNA library for producing modified N-glycans in lower eukaryotes
US20100021991A1 (en) * 2000-06-28 2010-01-28 Glycofi, Inc. Methods for Producing Modified Glycoproteins
US8697394B2 (en) 2000-06-28 2014-04-15 Glycofi, Inc. Production of modified glycoproteins having multiple antennary structures
US20100016555A1 (en) * 2000-06-28 2010-01-21 Glycofi, Inc. N-Acetylglucosaminyltransferase III Expression in Lower Eukaryotes
US20100016561A1 (en) * 2000-06-28 2010-01-21 Glycofi, Inc. N-Acetylglucosaminyltransferase III Expression in Lower Eukaryotes
US20030003097A1 (en) * 2001-04-02 2003-01-02 Idec Pharmaceutical Corporation Recombinant antibodies coexpressed with GnTIII
US8808692B2 (en) 2001-12-21 2014-08-19 Csl Limited Compositions comprising immunoreactive reagents and saponins, and methods of use thereof
US20060210555A1 (en) * 2001-12-21 2006-09-21 Antigenics, Inc. Compositions comprising immunoreactive reagents and saponins, and methods of use thereof
US20110064749A1 (en) * 2001-12-21 2011-03-17 Csl Limited Compositions comprising immunoreactive reagents and saponins, and methods of use thereof
US20090142340A1 (en) * 2002-03-01 2009-06-04 Xencor, Inc. Optimized Fc Variants and Methods for Their Generation
US7317091B2 (en) 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
US7662925B2 (en) 2002-03-01 2010-02-16 Xencor, Inc. Optimized Fc variants and methods for their generation
US8093357B2 (en) 2002-03-01 2012-01-10 Xencor, Inc. Optimized Fc variants and methods for their generation
US20080181890A1 (en) * 2002-03-01 2008-07-31 Xencor, Inc. Optimized Fc Variants and Methods for Their Generation
US20080260731A1 (en) * 2002-03-01 2008-10-23 Bernett Matthew J Optimized antibodies that target cd19
US20070003546A1 (en) * 2002-03-01 2007-01-04 Xencor, Inc. Optimized Fc variants and methods for their generation
US20070224189A1 (en) * 2002-03-01 2007-09-27 Xencor, Inc. CD20 OPTIMIZED Fc VARIANTS AND METHODS FOR THEIR GENERATION
US20070219133A1 (en) * 2002-03-01 2007-09-20 Xencor, Inc. CD52 OPTIMIZED Fc VARIANTS AND METHODS FOR THEIR GENERATION
US20090068175A1 (en) * 2002-03-01 2009-03-12 Xencor, Inc. Optimized FC Variants and Methods for Their Generation
US20080254027A1 (en) * 2002-03-01 2008-10-16 Bernett Matthew J Optimized CD5 antibodies and methods of using the same
US8124731B2 (en) 2002-03-01 2012-02-28 Xencor, Inc. Optimized Fc variants and methods for their generation
US8734791B2 (en) 2002-03-01 2014-05-27 Xencor, Inc. Optimized fc variants and methods for their generation
US8383109B2 (en) 2002-09-27 2013-02-26 Xencor, Inc. Optimized Fc variants and methods for their generation
US8753629B2 (en) 2002-09-27 2014-06-17 Xencor, Inc. Optimized Fc variants
US20090092599A1 (en) * 2002-09-27 2009-04-09 Xencor, Inc. Optimized Fc variants and methods for their generation
US20090081208A1 (en) * 2002-09-27 2009-03-26 Xencor, Inc. Optimized Fc variants and methods for their generation
US20040132101A1 (en) * 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
US10183999B2 (en) 2002-09-27 2019-01-22 Xencor, Inc. Optimized Fc variants and methods for their generation
US10184000B2 (en) 2002-09-27 2019-01-22 Xencor, Inc. Optimized Fc variants and methods for their generation
US8039592B2 (en) 2002-09-27 2011-10-18 Xencor, Inc. Optimized Fc variants and methods for their generation
US8093359B2 (en) 2002-09-27 2012-01-10 Xencor, Inc. Optimized Fc variants and methods for their generation
US8735547B2 (en) 2002-09-27 2014-05-27 Xencor, Inc. Optimized Fc Variants
US9353187B2 (en) 2002-09-27 2016-05-31 Xencor, Inc. Optimized FC variants and methods for their generation
US8858937B2 (en) 2002-09-27 2014-10-14 Xencor, Inc. Optimized Fc variants and methods for their generation
US8809503B2 (en) 2002-09-27 2014-08-19 Xencor, Inc. Optimized Fc variants and methods for their generation
US20060235208A1 (en) * 2002-09-27 2006-10-19 Xencor, Inc. Fc variants with optimized properties
US8188231B2 (en) 2002-09-27 2012-05-29 Xencor, Inc. Optimized FC variants
US8802823B2 (en) 2002-09-27 2014-08-12 Xencor, Inc. Optimized Fc variants
US9193798B2 (en) 2002-09-27 2015-11-24 Xencor, Inc. Optimized Fc variants and methods for their generation
US8753628B2 (en) 2002-09-27 2014-06-17 Xencor, Inc. Optimized Fc variants
US20070148171A1 (en) * 2002-09-27 2007-06-28 Xencor, Inc. Optimized anti-CD30 antibodies
US8460881B2 (en) * 2003-01-24 2013-06-11 Agensys, Inc. Nucleic acids and corresponding proteins entitled 254P1D6B useful in treatment and detection of cancer
US20090263318A1 (en) * 2003-01-24 2009-10-22 Agensys, Inc. Nucleic acids and corresponding proteins entitled 254p1d6b useful in treatment and detection of cancer
US8986949B2 (en) 2003-02-20 2015-03-24 Glycofi, Inc. Endomannosidases in the modification of glycoproteins in eukaryotes
US10584176B2 (en) 2003-03-03 2020-03-10 Xencor, Inc. Fc variants with increased affinity for FcγRIIc
US20070248603A1 (en) * 2003-03-03 2007-10-25 Xencor, Inc. Fc Variants with Increased Affinity for FcyRlla
US20070238665A1 (en) * 2003-03-03 2007-10-11 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRIIc
US8084582B2 (en) 2003-03-03 2011-12-27 Xencor, Inc. Optimized anti-CD20 monoclonal antibodies having Fc variants
US20070237767A1 (en) * 2003-03-03 2007-10-11 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRllla
US9657106B2 (en) 2003-03-03 2017-05-23 Xencor, Inc. Optimized Fc variants
US20070237766A1 (en) * 2003-03-03 2007-10-11 Xencor, Inc. Fc Variants Having Increased Affinity for FcyRllla
US10113001B2 (en) 2003-03-03 2018-10-30 Xencor, Inc. Fc variants with increased affinity for FcyRIIc
US20110021755A1 (en) * 2003-03-03 2011-01-27 Xencor, Inc. Optimized Fc Variants
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
US8735545B2 (en) 2003-03-03 2014-05-27 Xencor, Inc. Fc variants having increased affinity for fcyrllc
US20070243188A1 (en) * 2003-03-03 2007-10-18 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRlla
US20080057056A1 (en) * 2003-03-03 2008-03-06 Xencor, Inc. Fc Variants with Increased Affinity for FcyRIIC
US9663582B2 (en) 2003-03-03 2017-05-30 Xencor, Inc. Optimized Fc variants
US20070275460A1 (en) * 2003-03-03 2007-11-29 Xencor.Inc. Fc Variants With Optimized Fc Receptor Binding Properties
US20070237765A1 (en) * 2003-03-03 2007-10-11 Xencor, Inc. Fc Variants Having Increased Affinity for FcyRl
US20070248602A1 (en) * 2003-03-03 2007-10-25 Xencor, Inc. Fc Variants Having Increased Affinity for FcyRllc
US9051373B2 (en) 2003-05-02 2015-06-09 Xencor, Inc. Optimized Fc variants
US9714282B2 (en) 2003-09-26 2017-07-25 Xencor, Inc. Optimized Fc variants and methods for their generation
US9296820B2 (en) 2003-11-05 2016-03-29 Roche Glycart Ag Polynucleotides encoding anti-CD20 antigen binding molecules with increased Fc receptor binding affinity and effector function
US8883980B2 (en) 2003-11-05 2014-11-11 Roche Glycart Ag Antigen binding molecules with increased Fc receptor binding affinity and effector function
EA036531B1 (ru) * 2003-11-05 2020-11-19 Роше Гликарт Аг Гуманизированное антитело типа ii к cd20 (варианты), фармацевтическая композиция, содержащая эти варианты антитела, и их применение
US20050249723A1 (en) * 2003-12-22 2005-11-10 Xencor, Inc. Fc polypeptides with novel Fc ligand binding sites
US20100093979A1 (en) * 2003-12-22 2010-04-15 Gregory Alan Lazar Fc Polypeptides With Novel Fc Ligand Binding Sites
US7276585B2 (en) 2004-03-24 2007-10-02 Xencor, Inc. Immunoglobulin variants outside the Fc region
US20080248028A1 (en) * 2004-03-24 2008-10-09 Xencor, Inc. Immunoglobulin Variants Outside the Fc Region
US20050244403A1 (en) * 2004-03-24 2005-11-03 Xencor, Inc. Immunoglobulin variants outside the Fc region
US20110064727A9 (en) * 2004-03-24 2011-03-17 Xencor, Inc. Immunoglobulin Variants Outside the Fc Region
US20060002930A1 (en) * 2004-04-16 2006-01-05 Genentech, Inc. Treatment of disorders
US20070031331A1 (en) * 2004-04-16 2007-02-08 Genentech, Inc. Treatment of Disorders
US20100248359A1 (en) * 2004-07-09 2010-09-30 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody
US11820830B2 (en) 2004-07-20 2023-11-21 Xencor, Inc. Optimized Fc variants
US20060074225A1 (en) * 2004-09-14 2006-04-06 Xencor, Inc. Monomeric immunoglobulin Fc domains
US8101720B2 (en) 2004-10-21 2012-01-24 Xencor, Inc. Immunoglobulin insertions, deletions and substitutions
US20110033452A1 (en) * 2004-10-26 2011-02-10 Chugai Seiyaku Kabushiki Kaisha Anti-Glypican 3 Antibody Having Modified Sugar Chain
TWI468514B (zh) * 2004-10-26 2015-01-11 Chugai Pharmaceutical Co Ltd Sugar chain modified phosphatidylinositol glyphosyl 3 antibody
US11198739B2 (en) 2004-11-12 2021-12-14 Xencor, Inc. Fc variants with altered binding to FcRn
US8324351B2 (en) 2004-11-12 2012-12-04 Xencor, Inc. Fc variants with altered binding to FcRn
US9803023B2 (en) 2004-11-12 2017-10-31 Xencor, Inc. Fc variants with altered binding to FcRn
US8318907B2 (en) 2004-11-12 2012-11-27 Xencor, Inc. Fc variants with altered binding to FcRn
US8802820B2 (en) 2004-11-12 2014-08-12 Xencor, Inc. Fc variants with altered binding to FcRn
US20060173170A1 (en) * 2004-11-12 2006-08-03 Xencor, Inc. Fc variants with altered binding to FcRn
US8546543B2 (en) 2004-11-12 2013-10-01 Xencor, Inc. Fc variants that extend antibody half-life
US8883973B2 (en) 2004-11-12 2014-11-11 Xencor, Inc. Fc variants with altered binding to FcRn
US10336818B2 (en) 2004-11-12 2019-07-02 Xencor, Inc. Fc variants with altered binding to FcRn
US8852586B2 (en) 2004-11-12 2014-10-07 Xencor, Inc. Fc variants with altered binding to FcRn
US8367805B2 (en) 2004-11-12 2013-02-05 Xencor, Inc. Fc variants with altered binding to FcRn
US8338574B2 (en) 2004-11-12 2012-12-25 Xencor, Inc. FC variants with altered binding to FCRN
US9200079B2 (en) 2004-11-12 2015-12-01 Xencor, Inc. Fc variants with altered binding to FcRn
US20060275282A1 (en) * 2005-01-12 2006-12-07 Xencor, Inc. Antibodies and Fc fusion proteins with altered immunogenicity
US20080279858A9 (en) * 2005-02-07 2008-11-13 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US9957326B2 (en) 2005-02-07 2018-05-01 Roche Glycart Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US8614065B2 (en) 2005-02-07 2013-12-24 Roche Glycart Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
EP2404937A1 (en) 2005-02-07 2012-01-11 GlycArt Biotechnology AG Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20060269545A1 (en) * 2005-02-07 2006-11-30 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US8097436B2 (en) 2005-02-07 2012-01-17 Roche Glycart Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US7722867B2 (en) 2005-02-07 2010-05-25 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
EP3660049A1 (en) 2005-02-07 2020-06-03 Roche Glycart AG Antigen binding molecules that bind egfr, vectors encoding same, and uses thereof
EP2402374A1 (en) 2005-02-07 2012-01-04 GlycArt Biotechnology AG Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US9309317B2 (en) 2005-02-07 2016-04-12 Roche Glycart Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US7846432B2 (en) 2005-02-07 2010-12-07 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20120251533A1 (en) * 2005-02-18 2012-10-04 Medarex, Inc. Monoclonal antibodies against cd30 lacking in fucosyl residues
US8491898B2 (en) * 2005-02-18 2013-07-23 Medarex, L.L.C. Monoclonal antibodies against CD30 lacking in fucosyl residues
US20060223096A1 (en) * 2005-03-25 2006-10-05 Glycart Biotechnology Ag Antigen binding molecules directed to MCSP and having increased Fc receptor binding affinity and effector function
US20070111281A1 (en) * 2005-05-09 2007-05-17 Glycart Biotechnology Ag Antigen binding molecules having modified Fc regions and altered binding to Fc receptors
US20090208500A1 (en) * 2005-06-03 2009-08-20 Genentech, Inc. Method of producing antibodies with improved function
US20070071745A1 (en) * 2005-08-26 2007-03-29 Pablo Umana Modified antigen binding molecules with altered cell signaling activity
US20100249382A1 (en) * 2005-10-03 2010-09-30 Xencor, Inc. MODIFIED Fc MOLECULES
US9040041B2 (en) 2005-10-03 2015-05-26 Xencor, Inc. Modified FC molecules
US20080206867A1 (en) * 2005-10-03 2008-08-28 Desjarlais John R Fc variants with optimized Fc receptor binding properties
US20080267976A1 (en) * 2005-10-06 2008-10-30 Gregory Alan Lazar Optimized Anti-Cd30 Antibodies
US9574006B2 (en) 2005-10-06 2017-02-21 Xencor, Inc. Optimized anti-CD30 antibodies
US7973136B2 (en) 2005-10-06 2011-07-05 Xencor, Inc. Optimized anti-CD30 antibodies
US20080267979A1 (en) * 2005-10-14 2008-10-30 Gregory Alan Lazar Anti-Glypican-3 Antibody
US9102739B2 (en) 2005-10-14 2015-08-11 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody
US10118959B2 (en) 2005-10-14 2018-11-06 Chugai Seiyaku Kabushiki Kaisha Anti-glypican-3 antibody
US20070087005A1 (en) * 2005-10-14 2007-04-19 Lazar Gregory A Anti-glypican-3 antibody
US20090232817A9 (en) * 2006-08-09 2009-09-17 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20080095770A1 (en) * 2006-08-09 2008-04-24 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20080286277A1 (en) * 2006-08-09 2008-11-20 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US9074008B2 (en) 2006-08-09 2015-07-07 Roche Glycart Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US7727741B2 (en) 2006-08-09 2010-06-01 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US7662377B2 (en) 2006-08-09 2010-02-16 Glycart Biotechnology Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20100233080A1 (en) * 2006-08-09 2010-09-16 Umana Pablo Antigen Binding Molecules that Bind EGFR, Vectors Encoding Same, and Uses Thereof
US8273328B2 (en) 2006-08-09 2012-09-25 Roche Glycart Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
EP2444422A2 (en) 2006-08-09 2012-04-25 GlycArt Biotechnology AG Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US8088380B2 (en) 2006-08-09 2012-01-03 Roche Glycart Ag Antigen binding molecules that bind EGFR, vectors encoding same, and uses thereof
US20100272723A1 (en) * 2006-08-14 2010-10-28 Xencor, Inc. Optimized Antibodies that Target CD19
US9803020B2 (en) 2006-08-14 2017-10-31 Xencor, Inc. Optimized antibodies that target CD19
US10626182B2 (en) 2006-08-14 2020-04-21 Xencor, Inc. Optimized antibodies that target CD19
US11618788B2 (en) 2006-08-14 2023-04-04 Xencor, Inc. Optimized antibodies that target CD19
US8524867B2 (en) 2006-08-14 2013-09-03 Xencor, Inc. Optimized antibodies that target CD19
US8906646B2 (en) 2006-09-13 2014-12-09 Abbvie Inc. Fed-batch method of making human anti-TNF-alpha antibody
US9284371B2 (en) 2006-09-13 2016-03-15 Abbvie Inc. Methods of producing adalimumab
US9090867B2 (en) 2006-09-13 2015-07-28 Abbvie Inc. Fed-batch method of making anti-TNF-alpha antibody
US8911964B2 (en) 2006-09-13 2014-12-16 Abbvie Inc. Fed-batch method of making human anti-TNF-alpha antibody
US9073988B2 (en) 2006-09-13 2015-07-07 Abbvie Inc. Fed batch method of making anti-TNF-alpha antibodies
US10119118B2 (en) 2006-09-13 2018-11-06 Abbvie Inc. Modified serum-free cell culture medium
US9234032B2 (en) 2006-09-13 2016-01-12 Abbvie Inc. Fed-batch methods for producing adalimumab
US20100104557A1 (en) * 2006-09-18 2010-04-29 Xencor, Inc. Optimized Antibodies that Target HM1.24
US9040042B2 (en) 2006-09-18 2015-05-26 Xencor, Inc. Optimized antibodies that target HM1.24
US8394374B2 (en) 2006-09-18 2013-03-12 Xencor, Inc. Optimized antibodies that target HM1.24
US8216807B2 (en) 2006-10-12 2012-07-10 Genentech, Inc. Antibodies to lymphotoxin-α
US20110150865A1 (en) * 2006-10-12 2011-06-23 Genentech, Inc. Antibodies to lymphotoxin-alpha
US8642740B2 (en) 2006-10-12 2014-02-04 Genentech, Inc. Antibodies to lymphotoxin-alpha
US7923011B2 (en) 2006-10-12 2011-04-12 Genentech, Inc. Antibodies to lymphotoxin-alpha
US8541552B2 (en) 2006-10-12 2013-09-24 Genetech, Inc. Antibodies to lymphotoxin-α
US20110208673A1 (en) * 2006-10-12 2011-08-25 Genentech, Inc. Antibodies to lymphotoxin-alpha
WO2008070569A3 (en) * 2006-12-01 2008-11-20 Medarex Inc Human antibodies that bind cd22 and uses thereof
US8481683B2 (en) 2006-12-01 2013-07-09 Medarex, Inc. Human antibodies that bind CD22 and uses thereof
US20100143368A1 (en) * 2006-12-01 2010-06-10 David John King Human Antibodies That Bind Cd22 And Uses Thereof
US9499632B2 (en) 2006-12-01 2016-11-22 E.R. Squibb & Sons, L.L.C. Human antibodies that bind CD22 and uses thereof
US20100028951A1 (en) * 2007-03-07 2010-02-04 Stephen Hamilton Production of glycoproteins with modified fucosylation
US10317393B2 (en) 2007-03-23 2019-06-11 Academia Sinica Alkynyl sugar analogs for labeling and visualization of glycoconjugates in cells
US9816981B2 (en) 2007-03-23 2017-11-14 Academia Sinica Alkynyl sugar analogs for labeling and visualization of glycoconjugates in cells
US20080313379A1 (en) * 2007-06-15 2008-12-18 United Memories, Inc. Multiple bus charge sharing
EP4365189A2 (en) 2007-07-09 2024-05-08 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP2586788A1 (en) 2007-07-09 2013-05-01 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP4219522A2 (en) 2007-07-09 2023-08-02 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP3327026A1 (en) 2007-07-09 2018-05-30 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP4335863A2 (en) 2007-07-09 2024-03-13 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
EP4245766A2 (en) 2007-07-09 2023-09-20 Genentech, Inc. Prevention of disulfide bond reduction during recombinant production of polypeptides
US11932685B2 (en) 2007-10-31 2024-03-19 Xencor, Inc. Fc variants with altered binding to FcRn
US20090169550A1 (en) * 2007-12-21 2009-07-02 Genentech, Inc. Therapy of rituximab-refractory rheumatoid arthritis patients
US20090269339A1 (en) * 2008-04-29 2009-10-29 Genentech, Inc. Responses to immunizations in rheumatoid arthritis patients treated with a cd20 antibody
US10274488B2 (en) 2008-07-15 2019-04-30 Academia Sinica Glycan arrays on PTFE-like aluminum coated glass slides and related methods
US9683047B2 (en) 2008-09-16 2017-06-20 Genentech, Inc. Methods for treating progressive multiple sclerosis
EP3095463A2 (en) 2008-09-16 2016-11-23 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
US9994642B2 (en) 2008-09-16 2018-06-12 Genentech, Inc. Methods for treating progressive multiple sclerosis
EP3747464A1 (en) 2008-09-16 2020-12-09 F. Hoffmann-La Roche AG Methods for treating progessive multiple sclerosis using an anti-cd20 antibody
EP4364800A2 (en) 2008-09-16 2024-05-08 F. Hoffmann-La Roche AG Methods for treating progressive multiple sclerosis
US20100135987A1 (en) * 2008-10-20 2010-06-03 Hickman Robert K Isolation and purification of antibodies using protein a affinity chromatography
US9109010B2 (en) 2008-10-20 2015-08-18 Abbvie Inc. Viral inactivation during purification of antibodies cross reference to related applications
US9018361B2 (en) 2008-10-20 2015-04-28 Abbvie Inc. Isolation and purification of antibodies using protein a affinity chromatography
US8895709B2 (en) 2008-10-20 2014-11-25 Abbvie Inc. Isolation and purification of antibodies using protein A affinity chromatography
WO2010075249A2 (en) 2008-12-22 2010-07-01 Genentech, Inc. A method for treating rheumatoid arthritis with b-cell antagonists
WO2010146059A2 (en) 2009-06-16 2010-12-23 F. Hoffmann-La Roche Ag Biomarkers for igf-1r inhibitor therapy
WO2011019619A1 (en) 2009-08-11 2011-02-17 Genentech, Inc. Production of proteins in glutamine-free cell culture media
EP3760712A1 (en) 2009-08-11 2021-01-06 F. Hoffmann-La Roche AG Production of proteins in glutamine-free cell culture media
US20110104148A1 (en) * 2009-08-31 2011-05-05 Roche Glycart Ag Antibodies to Carcinoembryonic Antigen (CEA), Methods of Making Same, and Uses Thereof
WO2011023787A1 (en) 2009-08-31 2011-03-03 Roche Glycart Ag Affinity-matured humanized anti cea monoclonal antibodies
US9068008B2 (en) 2009-08-31 2015-06-30 Roche Glycart Ag Antibodies to carcinoembryonic antigen (CEA), methods of making same, and uses thereof
US11401348B2 (en) 2009-09-02 2022-08-02 Xencor, Inc. Heterodimeric Fc variants
US11377485B2 (en) 2009-12-02 2022-07-05 Academia Sinica Methods for modifying human antibodies by glycan engineering
US10087236B2 (en) 2009-12-02 2018-10-02 Academia Sinica Methods for modifying human antibodies by glycan engineering
US11267870B2 (en) 2009-12-02 2022-03-08 Academia Sinica Methods for modifying human antibodies by glycan engineering
US9475881B2 (en) 2010-01-19 2016-10-25 Xencor, Inc. Antibody variants with enhanced complement activity
WO2011100403A1 (en) 2010-02-10 2011-08-18 Immunogen, Inc Cd20 antibodies and uses thereof
WO2011101328A2 (en) 2010-02-18 2011-08-25 Roche Glycart Ag Treatment with a humanized igg class anti egfr antibody and an antibody against insulin like growth factor 1 receptor
US10338069B2 (en) 2010-04-12 2019-07-02 Academia Sinica Glycan arrays for high throughput screening of viruses
US9403855B2 (en) 2010-05-10 2016-08-02 Academia Sinica Zanamivir phosphonate congeners with anti-influenza activity and determining oseltamivir susceptibility of influenza viruses
US9874562B2 (en) 2010-05-10 2018-01-23 Academia Sinica Zanamivir phosphonate congeners with anti-influenza activity and determining oseltamivir susceptibility of influenza viruses
WO2012020006A2 (en) 2010-08-13 2012-02-16 Roche Glycart Ag Anti-fap antibodies and methods of use
WO2012020038A1 (en) 2010-08-13 2012-02-16 Roche Glycart Ag Anti-tenascin-c a2 antibodies and methods of use
EP3333194A1 (en) 2010-08-13 2018-06-13 Roche Glycart AG Anti-fap antibodies and methods of use
US20130310273A1 (en) * 2011-01-27 2013-11-21 Torsten Witte Methods and Means for Diagnosing Vasculitis
US9915667B2 (en) * 2011-01-27 2018-03-13 Medizinische Hochschule Hannover Methods and means for diagnosing vasculitis
WO2012107416A2 (en) 2011-02-10 2012-08-16 Roche Glycart Ag Improved immunotherapy
US9266938B2 (en) 2011-02-10 2016-02-23 Roche Glycart Ag Mutant interleukin-2 polypeptides
US10323098B2 (en) 2011-02-10 2019-06-18 Roche Glycart Ag Mutant interleukin-2 polypeptides
US11111312B2 (en) 2011-02-10 2021-09-07 Roche Glycart Ag Mutant interleukin-2 polypeptides
US10184009B2 (en) 2011-02-10 2019-01-22 Roche Glycart Ag Mutant interleukin-2 polypeptides
US9206260B2 (en) 2011-03-02 2015-12-08 Roche Glycart Ag Anti-CEA antibodies
US8642742B2 (en) 2011-03-02 2014-02-04 Roche Glycart Ag Anti-CEA antibodies
US9255143B2 (en) 2011-04-27 2016-02-09 Abbvie Inc. Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US9505834B2 (en) 2011-04-27 2016-11-29 Abbvie Inc. Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US9090688B2 (en) 2011-04-27 2015-07-28 Abbvie Inc. Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US9365645B1 (en) 2011-04-27 2016-06-14 Abbvie, Inc. Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US9062106B2 (en) 2011-04-27 2015-06-23 Abbvie Inc. Methods for controlling the galactosylation profile of recombinantly-expressed proteins
US11130822B2 (en) 2011-04-29 2021-09-28 Roche Glycart Ag Immunoconjugates
US10316104B2 (en) 2011-04-29 2019-06-11 Roche Glycart Ag Immunoconjugates
US10202464B2 (en) 2011-04-29 2019-02-12 Roche Glycart Ag Immunoconjugates
US9447159B2 (en) 2011-04-29 2016-09-20 Roche Glycart Ag Immunoconjugates
WO2012146628A1 (en) 2011-04-29 2012-11-01 Roche Glycart Ag Novel immunoconjugates
WO2013026831A1 (en) 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific antigen binding molecules
WO2013026832A1 (en) 2011-08-23 2013-02-28 Roche Glycart Ag Anti-mcsp antibodies
WO2013113641A1 (en) 2012-01-31 2013-08-08 Roche Glycart Ag Use of nkp46 as a predictive biomarker for cancer treatment with adcc- enhanced antibodies
WO2013127465A1 (en) 2012-03-02 2013-09-06 Roche Glycart Ag Predicitive biomarker for cancer treatment with adcc enhanced antibodies
US10130714B2 (en) 2012-04-14 2018-11-20 Academia Sinica Enhanced anti-influenza agents conjugated with anti-inflammatory activity
US9193787B2 (en) 2012-04-20 2015-11-24 Abbvie Inc. Human antibodies that bind human TNF-alpha and methods of preparing the same
US9505833B2 (en) 2012-04-20 2016-11-29 Abbvie Inc. Human antibodies that bind human TNF-alpha and methods of preparing the same
US9181572B2 (en) 2012-04-20 2015-11-10 Abbvie, Inc. Methods to modulate lysine variant distribution
US9957318B2 (en) 2012-04-20 2018-05-01 Abbvie Inc. Protein purification methods to reduce acidic species
US9150645B2 (en) 2012-04-20 2015-10-06 Abbvie, Inc. Cell culture methods to reduce acidic species
US9683033B2 (en) 2012-04-20 2017-06-20 Abbvie, Inc. Cell culture methods to reduce acidic species
US9708400B2 (en) 2012-04-20 2017-07-18 Abbvie, Inc. Methods to modulate lysine variant distribution
US9334319B2 (en) 2012-04-20 2016-05-10 Abbvie Inc. Low acidic species compositions
US9346879B2 (en) 2012-04-20 2016-05-24 Abbvie Inc. Protein purification methods to reduce acidic species
US9359434B2 (en) 2012-04-20 2016-06-07 Abbvie, Inc. Cell culture methods to reduce acidic species
US9695454B2 (en) 2012-05-23 2017-07-04 Glykos Finland Oy Production of fucosylated glycoproteins
US9249182B2 (en) 2012-05-24 2016-02-02 Abbvie, Inc. Purification of antibodies using hydrophobic interaction chromatography
EP3434695A1 (en) 2012-08-07 2019-01-30 Roche Glycart AG Improved immunotherapy
WO2014023679A1 (en) 2012-08-07 2014-02-13 Roche Glycart Ag Composition comprising two antibodies engineered to have reduced and increased effector function
US10214765B2 (en) 2012-08-18 2019-02-26 Academia Sinica Cell-permeable probes for identification and imaging of sialidases
US9914956B2 (en) 2012-08-18 2018-03-13 Academia Sinica Cell-permeable probes for identification and imaging of sialidases
US9547009B2 (en) 2012-08-21 2017-01-17 Academia Sinica Benzocyclooctyne compounds and uses thereof
US9512214B2 (en) 2012-09-02 2016-12-06 Abbvie, Inc. Methods to control protein heterogeneity
US9234033B2 (en) 2012-09-02 2016-01-12 Abbvie, Inc. Methods to control protein heterogeneity
US9290568B2 (en) 2012-09-02 2016-03-22 Abbvie, Inc. Methods to control protein heterogeneity
US9206390B2 (en) 2012-09-02 2015-12-08 Abbvie, Inc. Methods to control protein heterogeneity
WO2014114595A1 (en) 2013-01-23 2014-07-31 Roche Glycart Ag Predictive biomarker for cancer treatment with adcc-enhanced antibodies
US10034921B2 (en) 2013-02-13 2018-07-31 Laboratoire Français Du Fractionnement Et Des Biotechnologies Proteins with modified glycosylation and methods of production thereof
US10174110B2 (en) 2013-02-13 2019-01-08 Laboratoire Français Du Fractionnement Et Des Biotechnologies Highly galactosylated anti-TNF-α antibodies and uses thereof
WO2014131715A1 (en) 2013-02-26 2014-09-04 Roche Glycart Ag Anti-mcsp antibodies
US9067990B2 (en) 2013-03-14 2015-06-30 Abbvie, Inc. Protein purification using displacement chromatography
US9708399B2 (en) 2013-03-14 2017-07-18 Abbvie, Inc. Protein purification using displacement chromatography
US8921526B2 (en) 2013-03-14 2014-12-30 Abbvie, Inc. Mutated anti-TNFα antibodies and methods of their use
US9499614B2 (en) 2013-03-14 2016-11-22 Abbvie Inc. Methods for modulating protein glycosylation profiles of recombinant protein therapeutics using monosaccharides and oligosaccharides
US10086054B2 (en) 2013-06-26 2018-10-02 Academia Sinica RM2 antigens and use thereof
US9981030B2 (en) 2013-06-27 2018-05-29 Academia Sinica Glycan conjugates and use thereof
US10918714B2 (en) 2013-09-06 2021-02-16 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
US9782476B2 (en) 2013-09-06 2017-10-10 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
US10111951B2 (en) 2013-09-06 2018-10-30 Academia Sinica Human iNKT cell activation using glycolipids with altered glycosyl groups
US9598667B2 (en) 2013-10-04 2017-03-21 Abbvie Inc. Use of metal ions for modulation of protein glycosylation profiles of recombinant proteins
US9315574B2 (en) 2013-10-18 2016-04-19 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9017687B1 (en) 2013-10-18 2015-04-28 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same using displacement chromatography
US9181337B2 (en) 2013-10-18 2015-11-10 Abbvie, Inc. Modulated lysine variant species compositions and methods for producing and using the same
US9266949B2 (en) 2013-10-18 2016-02-23 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9522953B2 (en) 2013-10-18 2016-12-20 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9085618B2 (en) 2013-10-18 2015-07-21 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9200069B2 (en) 2013-10-18 2015-12-01 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9200070B2 (en) 2013-10-18 2015-12-01 Abbvie, Inc. Low acidic species compositions and methods for producing and using the same
US9688752B2 (en) 2013-10-18 2017-06-27 Abbvie Inc. Low acidic species compositions and methods for producing and using the same using displacement chromatography
US9499616B2 (en) 2013-10-18 2016-11-22 Abbvie Inc. Modulated lysine variant species compositions and methods for producing and using the same
US8946395B1 (en) 2013-10-18 2015-02-03 Abbvie Inc. Purification of proteins using hydrophobic interaction chromatography
US9550826B2 (en) 2013-11-15 2017-01-24 Abbvie Inc. Glycoengineered binding protein compositions
US9982041B2 (en) 2014-01-16 2018-05-29 Academia Sinica Compositions and methods for treatment and detection of cancers
US10150818B2 (en) 2014-01-16 2018-12-11 Academia Sinica Compositions and methods for treatment and detection of cancers
US9759726B2 (en) 2014-03-27 2017-09-12 Academia Sinica Reactive labelling compounds and uses thereof
US10119972B2 (en) 2014-03-27 2018-11-06 Academia Sinica Reactive labelling compounds and uses thereof
US10005847B2 (en) 2014-05-27 2018-06-26 Academia Sinica Anti-HER2 glycoantibodies and uses thereof
US11319567B2 (en) 2014-05-27 2022-05-03 Academia Sinica Fucosidase from bacteroides and methods using the same
US10023892B2 (en) 2014-05-27 2018-07-17 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US10618973B2 (en) 2014-05-27 2020-04-14 Academia Sinica Anti-HER2 glycoantibodies and uses thereof
US11884739B2 (en) 2014-05-27 2024-01-30 Academia Sinica Anti-CD20 glycoantibodies and uses thereof
US10118969B2 (en) 2014-05-27 2018-11-06 Academia Sinica Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
US11332523B2 (en) 2014-05-28 2022-05-17 Academia Sinica Anti-TNF-alpha glycoantibodies and uses thereof
US10513724B2 (en) 2014-07-21 2019-12-24 Glykos Finland Oy Production of glycoproteins with mammalian-like N-glycans in filamentous fungi
US9879042B2 (en) 2014-09-08 2018-01-30 Academia Sinica Human iNKT cell activation using glycolipids
US10533034B2 (en) 2014-09-08 2020-01-14 Academia Sinica Human iNKT cell activation using glycolipids
US9975966B2 (en) 2014-09-26 2018-05-22 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing theraputic agent
US11001643B2 (en) 2014-09-26 2021-05-11 Chugai Seiyaku Kabushiki Kaisha Cytotoxicity-inducing therapeutic agent
US9975965B2 (en) 2015-01-16 2018-05-22 Academia Sinica Compositions and methods for treatment and detection of cancers
US10495645B2 (en) 2015-01-16 2019-12-03 Academia Sinica Cancer markers and methods of use thereof
US10342858B2 (en) 2015-01-24 2019-07-09 Academia Sinica Glycan conjugates and methods of use thereof
WO2017053906A1 (en) 2015-09-24 2017-03-30 Abvitro Llc Hiv antibody compositions and methods of use
EP3662930A1 (en) 2015-09-24 2020-06-10 AbVitro LLC Hiv antibody compositions and methods of use
EP4026848A1 (en) 2015-12-09 2022-07-13 F. Hoffmann-La Roche AG Type ii anti-cd20 antibody for reducing the cytokine release syndrome
US10933141B2 (en) 2015-12-30 2021-03-02 Genentech, Inc. Formulations with reduced degradation of polysorbate
US10525137B2 (en) 2015-12-30 2020-01-07 Genentech, Inc. Formulations with reduced degradation of polysorbate
US10336784B2 (en) 2016-03-08 2019-07-02 Academia Sinica Methods for modular synthesis of N-glycans and arrays thereof
WO2017194441A1 (en) 2016-05-11 2017-11-16 F. Hoffmann-La Roche Ag Modified anti-tenascin antibodies and methods of use
EP3252078A1 (en) 2016-06-02 2017-12-06 F. Hoffmann-La Roche AG Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer
US10538592B2 (en) 2016-08-22 2020-01-21 Cho Pharma, Inc. Antibodies, binding fragments, and methods of use
WO2018201096A1 (en) 2017-04-27 2018-11-01 Tesaro, Inc. Antibody agents directed against lymphocyte activation gene-3 (lag-3) and uses thereof
WO2018220099A1 (en) 2017-06-02 2018-12-06 F. Hoffmann-La Roche Ag Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer
US11555071B2 (en) 2018-06-03 2023-01-17 Lamkap Bio Beta Ltd. Bispecific antibodies against CEACAM5 and CD47
WO2019234576A1 (en) 2018-06-03 2019-12-12 Lamkap Bio Beta Ltd. Bispecific antibodies against ceacam5 and cd47
WO2021110647A1 (en) 2019-12-02 2021-06-10 Lamkap Bio Beta Ag Bispecific antibodies against ceacam5 and cd47
EP3831849A1 (en) 2019-12-02 2021-06-09 LamKap Bio beta AG Bispecific antibodies against ceacam5 and cd47

Also Published As

Publication number Publication date
US20110293609A1 (en) 2011-12-01
NZ592087A (en) 2012-11-30
CA2838062A1 (en) 2003-02-13
EP1423510A2 (en) 2004-06-02
NO20040453L (no) 2004-03-30
RU2321630C2 (ru) 2008-04-10
US8999324B2 (en) 2015-04-07
WO2003011878A2 (en) 2003-02-13
NO332457B1 (no) 2012-09-24
NZ603111A (en) 2014-05-30
JP2005524379A (ja) 2005-08-18
PL217751B1 (pl) 2014-08-29
WO2003011878A3 (en) 2003-11-06
KR20100018071A (ko) 2010-02-16
CA2455365C (en) 2014-07-29
RU2004106559A (ru) 2005-05-10
KR20040054669A (ko) 2004-06-25
CA2455365A1 (en) 2003-02-13
MXPA04001072A (es) 2005-02-17
HUP0700103A3 (en) 2012-09-28
US20080280322A9 (en) 2008-11-13
EP2180044A1 (en) 2010-04-28
IL160170A (en) 2009-05-04
US9321843B2 (en) 2016-04-26
US20050272128A1 (en) 2005-12-08
US8021856B2 (en) 2011-09-20
US20160272719A1 (en) 2016-09-22
CA2838062C (en) 2015-12-22
NZ531219A (en) 2007-07-27
HUP0700103A2 (en) 2007-05-02
CN1555411A (zh) 2004-12-15
JP2009114201A (ja) 2009-05-28
AU2002339845B2 (en) 2009-03-26
EP1423510A4 (en) 2005-06-01
NZ581474A (en) 2011-04-29
PL374178A1 (en) 2005-10-03
IL160170A0 (en) 2004-07-25
US20150274837A1 (en) 2015-10-01
NZ571596A (en) 2010-11-26
US9631023B2 (en) 2017-04-25

Similar Documents

Publication Publication Date Title
US9631023B2 (en) Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
AU2002339845A1 (en) Antibody glycosylation variants having increased antibody-dependent cellular cytotoxicity
EP2248892B1 (en) Fusion constructs and use of same to produce antibodies with increased FC receptor binding affinity and effector function

Legal Events

Date Code Title Description
AS Assignment

Owner name: GLYCART BIOTECHNOLOGY AG, SWITZERLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:UMANA, PABLO;JEAN-MAIRET, JOEL;BAILEY, JAMES E. (DECEASED)-BY HIS LEGAL REPRESENTATIVE;REEL/FRAME:013893/0119

Effective date: 20030131

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

AS Assignment

Owner name: ROCHE GLYCART AG, SWITZERLAND

Free format text: CHANGE OF NAME;ASSIGNOR:GLYCART BIOTECHNOLOGY AG;REEL/FRAME:026883/0831

Effective date: 20100628