WO2009018386A1 - Multispecific epitope binding proteins and uses thereof - Google Patents

Multispecific epitope binding proteins and uses thereof Download PDF

Info

Publication number
WO2009018386A1
WO2009018386A1 PCT/US2008/071656 US2008071656W WO2009018386A1 WO 2009018386 A1 WO2009018386 A1 WO 2009018386A1 US 2008071656 W US2008071656 W US 2008071656W WO 2009018386 A1 WO2009018386 A1 WO 2009018386A1
Authority
WO
WIPO (PCT)
Prior art keywords
protein
region
terminus
epitope binding
chain
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2008/071656
Other languages
English (en)
French (fr)
Inventor
Herren Wu
Changshou Gao
Carl Hay
Nazzareno Dimasi
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.)
MedImmune LLC
Original Assignee
MedImmune LLC
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 MedImmune LLC filed Critical MedImmune LLC
Priority to JP2010520165A priority Critical patent/JP2010535032A/ja
Priority to EP08796901A priority patent/EP2069401A4/en
Priority to CA2694488A priority patent/CA2694488A1/en
Priority to AU2008282218A priority patent/AU2008282218A1/en
Priority to CN2008801010234A priority patent/CN101952312A/zh
Publication of WO2009018386A1 publication Critical patent/WO2009018386A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/522—CH1 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/55—Fab or Fab'
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/64—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising a combination of variable region and constant region components

Definitions

  • glycosylation of the Fc region can be modified to increase or decrease effector function (see for examples, Umana et al, 1999, Nat. Biotechnol 17:176-180; Davies et al., 2001, Biotechnol Bioeng 74:288-294; Shields et al, 2002, J Biol Chem 277:26733-26740; Shinkawa et al., 2003, J Biol Chem 278:3466-3473) U.S. Pat. No. 6,602,684; U.S. Ser. No. 10/277,370; U.S. Ser. No.
  • Ankrin repeats also known as DARpins
  • VASP polypeptides also known as DARpins
  • VASP polypeptides Avian pancreatic polypeptide (aPP)
  • Tetranectin based on CTLD3
  • Aff ⁇ lilin based on ⁇ B-crystallin/ubiquitin
  • Knottins SH3 domains, PDZ domains, Tendamistat, Neocarzinostatin, Protein A domains, Lipocalins, Transferrin, and Kunitz domains that specifically bind epitopes.
  • multispecific epitope binding proteins of the invention may comprise a CHl or a Ckappa/lambda region in the absence of an Fc region.
  • multispecific epitope binding proteins of the invention comprise at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8 or more CHl and or
  • the expression vector comprises a promoter, a polynucleotide sequence encoding a single chain diabody linked to the N-terminus of the Fc region, and a poly A tail.
  • the expression vector comprises a promoter, a polynucleotide sequence encoding multiple single chain diabodies linked to the N-terminus of the Fc region, and a poly A tail.
  • the expression vector comprises a promoter, a polynucleotide sequence encoding 1 , 2, 3, 4, 5, 6, 7, 8 or more single chain diabodies linked to the N-terminus of the Fc region and a poly A tail.
  • vectors of the invention comprise a promoter, a polynucleotide sequence encoding 3 scFvs linked to an Fc region, and a poly a tail.
  • vectors of the invention comprise a promoter, a polynucleotide sequence encoding 3 scFvs linked to an Fc region arranged N-terminus to C-terminus: scFv-scFv-Fc region-scFv, and a poly A tail (see Figure IA (inset a)).
  • vectors of the invention comprise a promoter, a polynucleotide sequence encoding an antibody heavy chain variable domain, a CHl, an antibody light chain variable domain, and a Ckappa/lambda arranged N- terminus to C-terminus in the following orientation:VH-CHl-VL-Ckappa/lambda, and a poly A tail (see Figure 4S, inset b).
  • the first and/or second polypeptide chain comprises multiple antibody variable regions linked to the N-terminus and C-terminus of the Fc region.
  • the epitope binding protein of the invention comprises a first and/or second chain with at least 1 , 2, 3, 4, 5, 6, 7, 8 or more antibody variable regions linked to the N-terminus and C- terminus of the Fc region.
  • the multispecific epitope binding protein comprises a first, a second, a third and a fourth polypeptide chain, wherein at least the first, the second, the third, or the fourth chain further comprises an epitope binding protein known in the art linked to the C-terminus of the CHl /Fc region, or Ckappa/lambda region.
  • the epitope binding protein of the invention comprises at least a first, a second, a third, or a fourth chain with multiple epitope binding domains known in the art linked to the C-terminus of the CHl /Fc region, or Ckappa/lambda region.
  • the epitope binding protein of the invention comprises at least a first, a second, a third, or a fourth chain with 1, 2, 3, 4, 5, 6, 7, 8 or more antibody variable regions linked to the N-terminus and C-terminus of the CHl /Fc region, or Ckappa/lambda region.
  • the multispecific epitope binding protein comprises a first, a second, a third and a fourth polypeptide chain, wherein at least the first, the second, the third, or the fourth chain further comprises an epitope binding protein known in the art linked to the N-terminus and C-terminus of the CHl /Fc region, or Ckappa/lambda region.
  • the epitope binding protein of the invention comprises at least a first, a second, a third, or a fourth chain with at least 1, 2, 3, 4, 5, 6, 7, 8 or more epitope binding domains known in the art, wherein the domains are selected from the group consisting of scFvs, single chain diabodies, antibody variable regions, or an epitope binding domain known in the art, linked to the N-terminus and C-terminus of the CHl /Fc region, or Ckappa/lambda region.
  • VECTIBIX® pascolizumab, pemtumomab (also known as THERAGYN®), pertuzumab (also known as 2C4, OMNITARG®), pexelizumab, pintumomab, priliximab, pritumumab, ranibizumab (also known as LUCENTIS®), raxibacumab, regaviramab, reslizumab, rituximab (also known as RITUXAN®, MabTHERA®), rovelizumab, ruplizumab, satumomab, sevirumab, sibrotuzumab, siplizumab (also known as MEDI-507), thankuzumab, stamulumab (also known as MYO-029), sulesomab (also known as LEUKOSCAN®), tacatuzumab tetraxetan, tadoc
  • the multispecific epitope binding proteins of the invention comprise at least one epitope binding domain that binds to the same antigen as the antibodies listed above. [0269] In other embodiments, the multispecific epitope binding proteins of the invention comprise at least one epitope binding domain that specifically binds to an antigen selected from: PDGFRalpha, PDGFRbeta, PDGF, VEGF, VEGF-A, VEGF-B, VEGF-C.
  • multispecific epitope binding proteins of the invention comprise scFvs, single chain diabodies, antibody variable regions or epitope binding domains known in the art which may share the same binding specificity with other scFvs, single chain diabodies, antibody variable regions or epitope binding domains known in the art within the protein.
  • multispecific epitope binding proteins of the invention comprise scFvs, single chain diabodies, antibody variable regions or epitope binding domains known in the art wherein at least 1, 2, 3, 4, 5, 6, 7, 8, or more share the same binding specificity.
  • multispecific epitope binding proteins of the invention comprise scFvs, single chain diabodies, antibody variable regions, or epitope binding domains known in the art, capable of binding epitopes concurrently
  • multispecific epitope binding proteins of the invention comprise scFvs, single chain diabodies, antibody variable regions, or epitope binding domains known in the art, with non-identical binding specificities, capable of binding epitopes concurrently.
  • an epitope binding domain of a multispecific epitope binding protein exhibits a binding affinity less than 99%, less than 95%, less than 90%, less than 80%, less than 70%, less than 60%, less than 50%, less than 40%, less than 30%, less than 20%, or less than 10% to a specific epitope than an identical functional isolated epitope binding domain as measured by any assay known in the art.
  • multispecific epitope binding proteins of the invention comprise 3 scFvs wherein the most N-terminal scFv has a lower binding affinity than the identical functional isolated scFvs, wherein the second most N-terminal scFv has a lower binding affinity than the identical functional isolated scFv and wherein the third most N- terminal scFv has a lower binding affinity than the identical functional isolated scFv .
  • multispecific epitope binding proteins of the invention may be administered to a patient in need thereof in conjunction with OX40 based therapies (OX40-Ig, Ox40 ligand), angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), corticosteroids, NSAIDS, and/or free radical scavengers
  • OX40-Ig Ox40 ligand
  • ACE angiotensin converting enzyme
  • ARBs angiotensin II receptor blockers
  • corticosteroids corticosteroids
  • NSAIDS and/or free radical scavengers
  • the multispecific epitope binding proteins of the invention may be used to first target an adjacent antigen and while binding, another binding domain may engage the cryptic antigen.
  • the invention also provides methods of targeting epitopes not present on the cell surface through the use of the multiple epitope binding domains. It is to be understood that the proteins of the invention are useful in delivering epitope binding domains to the interior of a cell. Using at least on epitope binding domain specific for a cell surface antigen, proteins of the invention may be targeted directly (through internalization of the bound antigen) or indirectly through membrane permeable structures of sequences (ie. intrabodies) present on the protein of the invention, hi such a scenario, it is possible to target intracellular targets with the proteins of the invention.
  • multispecific epitope binding proteins of the invention may utilize one or more uses described herein to accomplish the required task.
  • multispecific epitope binding proteins of the invention may block receptor dimerization and neutralize the cognate antigen concominantly.
  • multispecific epitope binding proteins of the invention may comprise at least one epitope directed against the IFNARl receptor to block dimerization which is required for activity, while using at least one other epitope binding domain to bind and neutralize the soluble interferon alpha subtypes that bind IFNARl .
  • the proteins of the invention provide methods of performing multiple tasks by the administration of multiple epitope binding domains directed at various properties of an interaction.
  • the proteins of the invention and compositions comprising the same are useful for many purposes, for example, as therapeutics against a wide range of chronic and acute diseases and disorders including, but not limited to, autoimmune and/or inflammatory disorders, which include Sjogren's syndrome, rheumatoid arthritis, lupus psoriasis, atherosclerosis, diabetic and other retinopathies, retrolental fibroplasia, age-related macular degeneration, neovascular glaucoma, hemangiomas, thyroid hyperplasias (including Grave's disease), corneal and other tissue transplantation, and chronic inflammation, sepsis, rheumatoid arthritis, peritonitis, Crohn's disease, reperfusion injury, septicemia, endotoxic shock, cystic fibrosis, endocarditis, psoriasis, arthritis (e.g., psoriatic arthritis), anaphylactic shock, organ ischemia, reperfusion injury,
  • inflammatory disorders include, but are not limited to, asthma, encephilitis, inflammatory bowel disease, chronic obstructive pulmonary disease (COPD), allergic disorders, septic shock, pulmonary fibrosis, undifferentitated spondyloarthropathy, undifferentiated arthropathy, arthritis, inflammatory osteolysis, and chronic inflammation resulting from chronic viral or bacteria infections.
  • COPD chronic obstructive pulmonary disease
  • the compositions and methods of the invention can be used with one or more conventional therapies that are used to prevent, manage or treat the above diseases.
  • the invention comprises compositions capable of treating chronic inflammation.
  • the compositions are useful in the targeting of immune cells for destruction or deactivation.
  • compositions of the invention are capable of inhibiting or reducing mast cell degranulation by at Ieast5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, or at least 100% or more as compared to untreated mast cells.
  • fungal pathogens include, but are not limited to: Absidia species ⁇ e.g., Absidia corymbifera and Absidia ramosd), Aspergillus species, ⁇ e.g., Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans, Aspergillus niger, and Aspergillus terreus), Basidiobolus ranarum, Blastomyces dermatitidis, Candida species ⁇ e.g., Candida albicans, Candida glabrata, Candida kerr, Candida krusei, Candida par apsilosis, Candida pseudotropicalis, Candida quillermondii, Candida rugosa, Candida stellatoidea, and Candida tropicalis), Coccidioides immitis, Conidiobolus species, Cryptococcus neoforms, Cunninghamella species, dermatophytes, Histoplasma capsulatum, Microsporum gypseum
  • the epitope binding proteins of the invention utilized to prevent, manage, treat or ameliorate cancer, autoimmune, inflammatory or infectious diseases or one or more symptoms or one or more symptoms thereof may or may not be conjugated or fused to a moiety (e.g., therapeutic agent or drug).
  • a moiety e.g., therapeutic agent or drug.
  • the invention provides methods for preventing, managing, treating or ameliorating cancer, autoimmune, inflammatory or infectious diseases or one or more symptoms or one or more symptoms thereof, said methods comprising administering to a subject in need thereof one or more epitope binding proteins of the invention in combination with one or more of therapeutic agents that are not cancer therapeutics (a.k.a., non-cancer therapies).
  • anti-emetic agents examples include, but are not limited to, anti-emetic agents, anti-fungal agents, antibacterial agents, such as antibiotics, anti-inflammatory agents, and anti-viral agents.
  • anti-emetic agents include metopimazin and metochlopramide.
  • antifungal agents include azole drugs, imidazole, triazoles, polyene, amphotericin and ryrimidine.
  • a multispecific epitope binding protein of the invention may be conjugated to a therapeutic moiety such as a cytotoxin, e.g., a cytostatic or cytocidal agent, a therapeutic agent or a radioactive metal ion, e.g., alpha-emitters such as, for example, Bi.
  • a cytotoxin or cytotoxic agent includes any agent that is detrimental to cells.
  • At least one epitope binding domain may be specific for a linker moiety, useful for conjugation to a variety of targets.
  • the user may "custom fit" the linker moiety with the cargo of choice and use the linker specific epitope binding domain to deliver the custom cargo to the cell.
  • Such approaches for traditional antibodies have been described previously in U.S. Patent No. 6,962,702, granted Nov 8, 2005 and which is hereby incorporated by reference in its entirety.
  • binding properties include but are not limited to, binding specificity, equilibrium dissociation constant (K D ), dissociation and association rates (k off and k on respectively), binding affinity and/or avidity. It is generally understood that a binding molecule (e.g., a Fc variant protein such as an antibody) with a low K D may be preferable to a binding molecule with a high K D . However, in some instances the value of the k on or k off may be more relevant than the value of the K D .
  • K D equilibrium dissociation constant
  • k off and k on respectively binding affinity and/or avidity.
  • the affinities and binding properties of an Fc region for its ligand may be determined by a variety of in vitro assay methods (biochemical or immunological based assays) known in the art for determining Fc-Fc ⁇ R interactions, i.e., specific binding of an Fc region to an Fc ⁇ R including but not limited to, equilibrium methods (e.g., enzyme-linked immunoabsorbent assay (ELISA), or radioimmunoassay (RIA)), or kinetics (e.g., BIACORE® analysis), and other methods such as indirect binding assays, competitive inhibition assays, fluorescence resonance energy transfer (FRET), gel electrophoresis and chromatography (e.g., gel filtration).
  • in vitro assay methods biochemical or immunological based assays
  • ELISA enzyme-linked immunoabsorbent assay
  • RIA radioimmunoassay
  • kinetics e.g., BIACORE® analysis
  • indirect binding assays e
  • the present invention provides an Fc variant, wherein the Fc region comprises at least one non naturally occurring amino acid residue selected from the group consisting of 234D, 234E, 234N, 234Q, 234T, 234H, 234Y, 2341, 234V, 234F, 235A, 235D, 235R, 235W, 235P, 235S, 235N, 235Q, 235T, 235H, 235Y, 2351, 235V, 235F, 236E, 239D, 239E, 239N, 239Q, 239F, 239T, 239H, 239Y, 2401, 240A, 240T, 240M, 241W, 241 L, 241 Y, 241E, 241 R.
  • the Fc region comprises at least one non naturally occurring amino acid residue selected from the group consisting of 234D, 234E, 234N, 234Q, 234T, 234H, 234Y, 2341, 234
  • the Fc variants of the present invention may be combined with other known Fc variants such as those disclosed in Ghetie et al., 1997, Nat Biotech. 15:637- 40; Duncan et al, 1988, Nature 332:563-564; Lund et al., 1991, J. Immunol 147:2657-2662; Lund et al, 1992, MoI Immunol 29:53-59; Alegre et al, 1994, Transplantation 57:1537-1543; Hutchins et al., 1995, ProcNatl. Acad Sci USA 92:11980-11984; Jefferis et al, 1995, Immunol Lett.
  • the invention also provides methods of producing the multispecific epitope binding proteins of the invention.
  • the multispecific epitope binding proteins may be expressed from a single vector, or from multiple vectors.
  • the arrangement of the binding domains within the vector can be varied.
  • the orientation of the Fc region (or CHl /Fc region) may be N-terminus or C-terminus to any of the binding domains contained within the multispecific epitope binding polypeptide chain, hi some embodiments, the epitope binding domains are present both N-terminal and C-terminal to the Fc region (or CHl /Fc region) within the polypeptide chain.
  • Methods which are known to those skilled in the art can be used to construct expression vectors containing protein coding sequences and appropriate transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination.
  • the invention thus, provides replicable vectors comprising a nucleotide sequence encoding an epitope binding protein molecule operably linked to a promoter.
  • the aggregation and/or fragmentation profile may be assessed by the use of analytical ultracentrifugation (AUC), size-exclusion chromatography (SEC), high- performance size-exclusion chromatography (HPSEC), melting temperature (T m ), polyacrylamide gel electrophoresis (PAGE), capillary gel electrophoresis (CGE), light scattering (SLS), Fourier Transform Infrared Spectroscopy (FTIR), circular dichroism (CD), urea-induced protein unfolding techniques, intrinsic tryptophan fluorescence, differential scanning calorimetry, or l-anilino-8-naphthalenesulfonic acid (ANS) protein binding techniques.
  • AUC analytical ultracentrifugation
  • SEC size-exclusion chromatography
  • HPSEC high- performance size-exclusion chromatography
  • T m melting temperature
  • PAGE polyacrylamide gel electrophoresis
  • CGE capillary gel electrophoresis
  • SLS light scattering
  • isotonic agents for example, sugars, polyalcohols such as mannitol, sorbitol, or sodium chloride in the composition.
  • Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent that delays absorption, for example, monostearate salts and gelatin.
  • endotoxin and pyrogen levels in the composition are less then about 10 EU/mg, or less then about 5 EU/mg, or less then about 1 EU/mg, or less then about 0.1 EU/mg, or less then about 0.01 EU/mg, or less then about 0.001 EU/mg.
  • Example 13 Examining binding epitopes displayed on the cell surface.
  • Results Presented in Figure 25 are the results from a competitive inhibition of binding experiment involving the proteins and soluble EphB family RTK ligand.
  • the tracings represent the residual binding of the proteins to MiaPaCa2 cells after being incubated with soluble ligand and then applied to the cells.
  • the P2 and Pl proteins contain EphB family RTK specific binding elements yet they remain bound to the cells, however the EB2 tracing represents a protein that has monospecificity for EphB family RTK and resembles the non-specific anti hu-Fc tracing. This suggests that the free ligand, EphB family RTK has completely saturated the ability to bind epitopes displayed on the cell surface.
  • EphB family receptors were immunoprecipitated with the 4G10 agarose (Upstate Cat. 16-199) and detected with a specific anti-EphB family antibody with goat anti-mouse IgG (Pierce Cat. 31437) was used as a secondary antibody.
  • EphA2 a specific EphA2 antibody (ICl) was used.
  • the trispecific epitope binding protein exhibits a predicted molecular weight of about 240 kDa which is more than the predicted molecular weigh of a traditional antibody represented by (a) run on a PAGE gel in non-denaturing conditions.
  • the trispecific epitope binding protein exhibits predicted molecular weights to about 75 kDa for the heavy chain and about 50 kDa for the light chain. These values are higher than the predicted molecular weights exhibited by a traditional antibody, including a heavy chain (b) and a light chain (c) run under similar conditions.
  • Example 30 Transient expression of multispecific epitope binding proteins [0544]
  • Purpose To transiently express various multispecific epitope binding protein formats [0545]
  • Methods All constructs were expressed in HEK293F cells cultivated in Invitrogen FreestyleTM media. The culture medium was collected 10 days post-transfection and all antibody formats were purified by standard protein A affinity chromatography in accordance with the manufacturer's protocol (GE Healthcare, Piscataway, NJ), and buffer exchanged into 25 mM Histidine-HCl pH 6.0. The purity of the constructs was analyzed using sodium dodecyl sulfate polyacrilamide gel electrophoresis (SDS-PAGE) under reducing and non- reducing conditions and using analytical size-exclusion chromatography.
  • SDS-PAGE sodium dodecyl sulfate polyacrilamide gel electrophoresis

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Rheumatology (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Hematology (AREA)
  • Transplantation (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
PCT/US2008/071656 2007-07-31 2008-07-30 Multispecific epitope binding proteins and uses thereof Ceased WO2009018386A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2010520165A JP2010535032A (ja) 2007-07-31 2008-07-30 多重特異性エピトープ結合性タンパク質およびその用途
EP08796901A EP2069401A4 (en) 2007-07-31 2008-07-30 MULTISPECIENT EPITOP BINDING PROTEINS AND THEIR USE
CA2694488A CA2694488A1 (en) 2007-07-31 2008-07-30 Multispecific epitope binding proteins and uses thereof
AU2008282218A AU2008282218A1 (en) 2007-07-31 2008-07-30 Multispecific epitope binding proteins and uses thereof
CN2008801010234A CN101952312A (zh) 2007-07-31 2008-07-30 多特异性表位结合蛋白及其应用

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US93519907P 2007-07-31 2007-07-31
US60/935,199 2007-07-31
US1265607P 2007-12-10 2007-12-10
US61/012,656 2007-12-10
US7433008P 2008-06-20 2008-06-20
US61/074,330 2008-06-20

Publications (1)

Publication Number Publication Date
WO2009018386A1 true WO2009018386A1 (en) 2009-02-05

Family

ID=40304858

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2008/071656 Ceased WO2009018386A1 (en) 2007-07-31 2008-07-30 Multispecific epitope binding proteins and uses thereof

Country Status (8)

Country Link
US (3) US20090155275A1 (https=)
EP (2) EP2626371A1 (https=)
JP (1) JP2010535032A (https=)
KR (1) KR20100058509A (https=)
CN (1) CN101952312A (https=)
AU (1) AU2008282218A1 (https=)
CA (1) CA2694488A1 (https=)
WO (1) WO2009018386A1 (https=)

Cited By (144)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010115551A1 (en) * 2009-04-07 2010-10-14 Roche Glycart Ag Bispecific anti-erbb-1/anti-c-met antibodies
WO2010115589A1 (en) * 2009-04-07 2010-10-14 Roche Glycart Ag Trivalent, bispecific antibodies
WO2011086091A1 (en) * 2010-01-12 2011-07-21 Ucb Pharma S.A. Multivalent antibodies
WO2011061492A3 (en) * 2009-11-17 2011-07-28 Ucb Pharma S.A. Multivalent antibodies
WO2011061246A3 (en) * 2009-11-19 2011-07-28 Ucb Pharma S.A. Multivalent antibodies
WO2012025525A1 (en) 2010-08-24 2012-03-01 Roche Glycart Ag Activatable bispecific antibodies
WO2012118903A2 (en) 2011-03-01 2012-09-07 Amgen Inc. Bispecific binding agents
WO2012172521A1 (en) * 2011-06-16 2012-12-20 Novartis Ag Soluble proteins for use as therapeutics
WO2013026831A1 (en) * 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific antigen binding molecules
WO2013026837A1 (en) * 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific t cell activating antigen binding molecules
WO2013026833A1 (en) * 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific t cell activating antigen binding molecules
JP2013513370A (ja) * 2009-12-09 2013-04-22 フリードリヒ−アレクサンダー−ウニベルジテート・エアランゲン−ニュルンベルク 急性骨髄性白血病に対する三重特異性治療剤
WO2013070565A1 (en) 2011-11-07 2013-05-16 Medimmune, Llc Multispecific and multivalent binding proteins and uses thereof
EP2464663A4 (en) * 2009-08-13 2013-05-29 Massachusetts Inst Technology MANIPULATED PROTEINS WITH MUTANT FIBRONECTIN DOMAINS
WO2013092001A1 (en) * 2011-12-19 2013-06-27 Synimmune Gmbh Bispecific antibody molecule
EP2643353A1 (en) * 2010-11-24 2013-10-02 Novartis AG Multispecific molecules
EP2596114A4 (en) * 2010-07-14 2014-01-08 Amgen Inc IMMUNOGLOBULIN WITH DOMAIN INSERTION
US8629246B2 (en) 2007-09-26 2014-01-14 Ucb Pharma S.A. Dual specificity antibody fusions
WO2014144722A3 (en) * 2013-03-15 2014-11-06 Amgen Inc. Bispecific bivalent scfv-fc molecules
US8981061B2 (en) 2001-03-20 2015-03-17 Novo Nordisk A/S Receptor TREM (triggering receptor expressed on myeloid cells) and uses thereof
US9000127B2 (en) 2012-02-15 2015-04-07 Novo Nordisk A/S Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
US9062120B2 (en) 2012-05-02 2015-06-23 Janssen Biotech, Inc. Binding proteins having tethered light chains
US9128101B2 (en) 2010-03-01 2015-09-08 Caris Life Sciences Switzerland Holdings Gmbh Biomarkers for theranostics
WO2015184203A1 (en) 2014-05-29 2015-12-03 Macrogenics, Inc. Tri-specific binding molecules and methods of use thereof
US9266967B2 (en) 2007-12-21 2016-02-23 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
US9273111B2 (en) 2004-11-29 2016-03-01 Universite De Lorraine Therapeutic TREM-1 peptides
EP2655415A4 (en) * 2010-12-22 2016-03-09 Abbvie Inc THREE VARIABLE DOMAIN LINK PROTEINS AND USES THEREOF
WO2016050867A1 (en) 2014-10-01 2016-04-07 Medimmune Limited Antibodies to ticagrelor and methods of use
WO2016054315A1 (en) 2014-10-01 2016-04-07 Medimmune, Llc Method of conjugating a polypeptide
JP2016054746A (ja) * 2010-08-02 2016-04-21 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｖｌドメインを含む結合タンパク質を作製するマウス
US9382323B2 (en) 2009-04-02 2016-07-05 Roche Glycart Ag Multispecific antibodies comprising full length antibodies and single chain fab fragments
CN105907760A (zh) * 2016-05-31 2016-08-31 东北师范大学 靶向沉默TKS4的shRNA
US9469876B2 (en) 2010-04-06 2016-10-18 Caris Life Sciences Switzerland Holdings Gmbh Circulating biomarkers for metastatic prostate cancer
WO2017011559A1 (en) 2015-07-14 2017-01-19 Medlmmune, Llc Compositions and methods for treating cancer
US9550830B2 (en) 2012-02-15 2017-01-24 Novo Nordisk A/S Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
WO2017019846A1 (en) 2015-07-30 2017-02-02 Macrogenics, Inc. Pd-1-binding molecules and methods use thereof
WO2017059243A2 (en) 2015-09-30 2017-04-06 Janssen Biotech, Inc. Agonistic antibodies specifically binding human cd40 and methods of use
US9631031B2 (en) 2011-07-07 2017-04-25 Centre National De La Recherche Scientifique Multispecific antigens binding fragments and multispecific antibodies derived therefrom comprising mutant CH1 and CL-κ domains
WO2017079112A1 (en) 2015-11-03 2017-05-11 Janssen Biotech, Inc. Antibodies specifically binding pd-1 and their uses
US9663568B2 (en) 2012-02-15 2017-05-30 Novo Nordisk A/S Antibodies that bind peptidoglycan recognition protein 1
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
WO2017106061A1 (en) 2015-12-14 2017-06-22 Macrogenics, Inc. Bispecific molecules having immunoreactivity with pd-1 and ctla-4, and methods of use thereof
US9688758B2 (en) 2012-02-10 2017-06-27 Genentech, Inc. Single-chain antibodies and other heteromultimers
WO2017132298A1 (en) 2016-01-27 2017-08-03 Medimmune, Llc Methods for preparing antibodies with a defined glycosylation pattern
WO2017142928A1 (en) 2016-02-17 2017-08-24 Macrogenics, Inc. Ror1-binding molecules, and methods of use thereof
WO2017180813A1 (en) 2016-04-15 2017-10-19 Macrogenics, Inc. Novel b7-h3 binding molecules, antibody drug conjugates thereof and methods of use thereof
EP2609111B1 (en) * 2010-08-24 2017-11-01 F. Hoffmann-La Roche AG Bispecific antibodies comprising a disulfide stabilized-fv fragment
WO2017193032A2 (en) 2016-05-06 2017-11-09 Medimmune, Llc Bispecific binding proteins and uses thereof
WO2018007314A1 (en) * 2016-07-04 2018-01-11 F. Hoffmann-La Roche Ag Novel antibody format
WO2018031258A1 (en) 2016-08-12 2018-02-15 Janssen Biotech, Inc. Engineered antibodies and other fc-domain containing molecules with enhanced agonism and effector functions
US9975952B2 (en) 2013-01-09 2018-05-22 Metis Precision Medicine Sb S.R.L. Antibody fragments, compositions and uses thereof
US9982036B2 (en) 2011-02-28 2018-05-29 Hoffmann-La Roche Inc. Dual FC antigen binding proteins
US9994646B2 (en) 2009-09-16 2018-06-12 Genentech, Inc. Coiled coil and/or tether containing protein complexes and uses thereof
WO2018119166A1 (en) 2016-12-23 2018-06-28 Macrogenics, Inc. Adam9-binding molecules, and methods of use thereof
WO2018118780A1 (en) * 2016-12-19 2018-06-28 Calico Biolabs, Inc. Monovalent and divalent binding proteins
US10106600B2 (en) 2010-03-26 2018-10-23 Roche Glycart Ag Bispecific antibodies
US10106612B2 (en) 2012-06-27 2018-10-23 Hoffmann-La Roche Inc. Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof
US10138293B2 (en) 2007-12-21 2018-11-27 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
US10179814B2 (en) 2014-07-17 2019-01-15 Novo Nordisk A/S Site directed mutagenesis of TREM-1 antibodies for decreasing viscosity
WO2019018770A1 (en) * 2017-07-21 2019-01-24 Trianni, Inc. SINGLE CHAIN VH-L1-CK1-L2-CH1 ANTIBODY
WO2019024979A1 (en) * 2017-07-31 2019-02-07 Institute For Research In Biomedicine FUNCTIONAL DOMAIN ANTIBODIES IN THE ELBOW REGION
US10266608B2 (en) 2013-12-30 2019-04-23 Epimab Biotherapeutics, Inc. Fabs-in-tandem immunoglobulin and uses thereof
US10323099B2 (en) 2013-10-11 2019-06-18 Hoffmann-La Roche Inc. Multispecific domain exchanged common variable light chain antibodies
US10407513B2 (en) 2008-09-26 2019-09-10 Ucb Biopharma Sprl Biological products
US10421816B2 (en) 2009-09-10 2019-09-24 Ucb Biopharma Sprl Multivalent antibodies
US10457748B2 (en) 2012-12-21 2019-10-29 Ucb Biopharma Sprl Single linker FabFv antibodies and methods of producing same
WO2019224718A2 (en) 2018-05-24 2019-11-28 Janssen Biotech, Inc. Psma binding agents and uses thereof
WO2019224713A2 (en) 2018-05-24 2019-11-28 Janssen Biotech, Inc. Monospecific and multispecific anti-tmeff2 antibodies and there uses
WO2019224717A2 (en) 2018-05-24 2019-11-28 Janssen Biotech, Inc. Anti-cd3 antibodies and uses thereof
US10501552B2 (en) 2015-01-26 2019-12-10 Macrogenics, Inc. Multivalent molecules comprising DR5-binding domains
US10611825B2 (en) 2011-02-28 2020-04-07 Hoffmann La-Roche Inc. Monovalent antigen binding proteins
US10633457B2 (en) 2014-12-03 2020-04-28 Hoffmann-La Roche Inc. Multispecific antibodies
WO2020097395A1 (en) * 2018-11-08 2020-05-14 The Regents Of The University Of California Systems and methods for targeting cancer cells
US10662247B2 (en) 2014-10-08 2020-05-26 Novartis Ag Compositions and methods of use for augmented immune response and cancer therapy
US10669337B2 (en) 2014-07-25 2020-06-02 Cytomx Therapeutics, Inc. Bispecific anti-CD3 antibodies, bispecific activatable anti-CD3 antibodies, and methods of using the same
US10787522B2 (en) 2014-03-21 2020-09-29 Regeneron Pharmaceuticals, Inc. VL antigen binding proteins exhibiting distinct binding characteristics
US20200319174A1 (en) * 2019-04-17 2020-10-08 Jiangnan University Method for Detecting Human Soluble Asialoglycoprotein Receptor
EP3752196A1 (en) 2018-02-15 2020-12-23 MacroGenics, Inc. Variant cd3-binding domains and their use in combination therapies for the treatment of disease
US10881085B2 (en) 2014-03-21 2021-01-05 Regeneron Pharmaceuticals, Inc. Non-human animals that make single domain binding proteins
US10946104B2 (en) 2012-01-13 2021-03-16 Apo-Tb.V. Aberrant cell-restricted immunoglobulins provided with a toxic moiety
US10995149B2 (en) 2017-06-05 2021-05-04 Janssen Biotech, Inc. Antibodies that specifically bind PD-1 and methods of use
US11072653B2 (en) 2015-06-08 2021-07-27 Macrogenics, Inc. LAG-3-binding molecules and methods of use thereof
US11072663B2 (en) 2013-10-14 2021-07-27 Janssen Biotech, Inc. Cysteine engineered fibronectin type III domain binding molecules
US11098115B2 (en) 2011-09-29 2021-08-24 Apo-T B.V. Multi-specific binding molecules targeting aberrant cells
US11111314B2 (en) 2015-03-19 2021-09-07 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
US11155618B2 (en) 2018-04-02 2021-10-26 Bristol-Myers Squibb Company Anti-TREM-1 antibodies and uses thereof
US11161906B2 (en) 2013-07-25 2021-11-02 Cytomx Therapeutics, Inc. Multispecific antibodies, multispecific activatable antibodies and methods of using the same
US11174315B2 (en) 2015-10-08 2021-11-16 Macrogenics, Inc. Combination therapy for the treatment of cancer
WO2022010798A1 (en) 2020-07-06 2022-01-13 Kiromic BioPharma, Inc. Mesothelin isoform binding molecules and chimeric pd1 receptor molecules, cells containing the same and uses thereof
US11286300B2 (en) 2015-10-01 2022-03-29 Hoffmann-La Roche Inc. Humanized anti-human CD19 antibodies and methods of use
WO2022108627A1 (en) 2020-11-18 2022-05-27 Kiromic Biopharma, Inc.Kiromic Biopharma, Inc. Gamma-delta t cell manufacturing processes and chimeric pd1 receptor molecules
US11345760B2 (en) 2014-06-25 2022-05-31 UCB Biopharma SRL Multispecific antibody constructs
US11359029B2 (en) 2016-08-12 2022-06-14 Janssen Biotech, Inc. FC engineered anti-TNFR superfamily member antibodies having enhanced agonistic activity and methods of using them
WO2022162518A2 (en) 2021-01-28 2022-08-04 Janssen Biotech, Inc. Psma binding proteins and uses thereof
US11421022B2 (en) 2012-06-27 2022-08-23 Hoffmann-La Roche Inc. Method for making antibody Fc-region conjugates comprising at least one binding entity that specifically binds to a target and uses thereof
US11421028B2 (en) 2016-02-06 2022-08-23 Epimab Biotherapeutics, Inc. Fabs-in-tandem immunoglobulin and uses thereof
WO2022189942A1 (en) 2021-03-09 2022-09-15 Janssen Biotech, Inc. Treatment of cancers lacking egfr-activating mutations
US11459394B2 (en) 2017-02-24 2022-10-04 Macrogenics, Inc. Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof
US11459391B2 (en) 2019-02-26 2022-10-04 Janssen Biotech, Inc. Combination therapies and patient stratification with bispecific anti-EGFR/c-Met antibodies
US11472889B2 (en) 2017-10-14 2022-10-18 Cytomx Therapeutics, Inc. Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof
WO2022243900A1 (en) 2021-05-18 2022-11-24 Janssen Biotech, Inc. Methods for identifying cancer patients for combination treatment
US11591395B2 (en) 2019-04-19 2023-02-28 Janssen Biotech, Inc. Methods of treating prostate cancer with an anti-PSMA/CD3 antibody
US11618790B2 (en) 2010-12-23 2023-04-04 Hoffmann-La Roche Inc. Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery
US11667712B2 (en) 2019-05-08 2023-06-06 Janssen Biotech, Inc. Materials and methods for modulating t cell mediated immunity
WO2023105479A1 (en) 2021-12-09 2023-06-15 Janssen Biotech, Inc. Use of amivantamab to treat colorectal cancer
EP4223319A2 (en) 2017-05-26 2023-08-09 MedImmune, LLC Method and molecules
WO2023148702A1 (en) 2022-02-07 2023-08-10 Janssen Biotech, Inc. Methods for reducing infusion-related reactions in patients treated with egfr/met bispecific antibodies
WO2023192850A1 (en) 2022-03-29 2023-10-05 Ngm Biopharmaceuticals, Inc. Ilt3 and cd3 binding agents and methods of use thereof
US11795226B2 (en) 2017-12-12 2023-10-24 Macrogenics, Inc. Bispecific CD16-binding molecules and their use in the treatment of disease
EP4054649A4 (en) * 2019-11-06 2023-12-06 Systimmune, Inc. GUIDANCE AND NAVIGATION REGULATORY PROTEINS AND METHODS OF PRODUCTION AND USE THEREOF
WO2024003837A1 (en) 2022-06-30 2024-01-04 Janssen Biotech, Inc. Use of anti-egfr/anti-met antibody to treat gastric or esophageal cancer
US11866507B2 (en) 2017-04-11 2024-01-09 Inhibrx, Inc. Multispecific polypeptide constructs having constrained CD3 binding and methods of using the same
US11879013B2 (en) 2019-05-14 2024-01-23 Janssen Biotech, Inc. Combination therapies with bispecific anti-EGFR/c-Met antibodies and third generation EGFR tyrosine kinase inhibitors
EP4114373A4 (en) * 2020-03-03 2024-05-01 Systimmune, Inc. ANTI-CD19 ANTIBODIES AND THEIR METHODS OF USE AND PREPARATION
WO2024089551A1 (en) 2022-10-25 2024-05-02 Janssen Biotech, Inc. Msln and cd3 binding agents and methods of use thereof
EP4121461A4 (en) * 2020-03-17 2024-08-07 Systimmune, Inc. Miniature guidance and navigation control (minignc) antibody-like proteins and methods of making and using thereof
US12060425B2 (en) 2018-05-03 2024-08-13 Shanghai Epimab Biotherapeutics Co., Ltd. High affinity antibodies to PD-1 and LAG-3 and bispecific binding proteins made therefrom
US12076413B2 (en) 2020-10-28 2024-09-03 Janssen Biotech, Inc. Compositions and methods for modulating delta gamma chain mediated immunity
WO2024189544A1 (en) 2023-03-13 2024-09-19 Janssen Biotech, Inc. Combination therapies with bi-specific anti-egfr/c-met antibodies and anti-pd-1 antibodies
WO2024241273A1 (en) 2023-05-23 2024-11-28 Janssen Biotech, Inc. Methods for treatment of non-small cell lung cancer (nsclc)
WO2024255841A1 (zh) 2023-06-16 2024-12-19 复旦大学 乙肝病毒表面抗体及其应用
US12195533B2 (en) 2018-07-24 2025-01-14 Inhibrx Biosciences, Inc. Multispecific polypeptide constructs containing a constrained CD3 binding domain and a receptor binding region and methods of using the same
US12215160B2 (en) 2020-02-12 2025-02-04 Janssen Biotech, Inc. Treatment of patients having c-met exon 14 skipping mutations
US12221481B2 (en) 2019-05-21 2025-02-11 Novartis Ag CD19 binding molecules and uses thereof
WO2025032508A1 (en) 2023-08-07 2025-02-13 Janssen Biotech, Inc. Enpp3 and cd3 binding agents and methods of use thereof
WO2025032510A1 (en) 2023-08-07 2025-02-13 Janssen Biotech, Inc. Stabilized cd3 antigen binding agents and methods of use thereof
RU2834996C1 (ru) * 2020-03-03 2025-02-20 Систиммьюн, Инк. Антитела против cd19 и способы их применения и получения
WO2025052273A1 (en) 2023-09-05 2025-03-13 Janssen Biotech, Inc. Methods of treating non-small cell lung cancer
WO2025079020A1 (en) 2023-10-12 2025-04-17 Janssen Biotech, Inc. First line treatment in egfr exon 20 insertion-mutated advanced non-small cell lung cancer
US12331132B2 (en) 2018-04-11 2025-06-17 Inhibrx Biosciences, Inc. Multispecific polypeptide constructs having constrained CD3 binding and related methods and uses
WO2025126102A1 (en) 2023-12-12 2025-06-19 Janssen Biotech, Inc. Enpp3 × cd3 bispecific antibodies and use thereof
US12365728B2 (en) 2018-10-11 2025-07-22 Inhibrx Biosciences, Inc. DLL3 single domain antibodies and therapeutic compositions thereof
WO2025153988A1 (en) 2024-01-16 2025-07-24 Janssen Biotech, Inc. Use of amivantamab to treat colorectal cancer
WO2025158277A1 (en) 2024-01-22 2025-07-31 Janssen Biotech, Inc. Use of amivantamab to treat head and neck cancer
US12398209B2 (en) 2018-01-22 2025-08-26 Janssen Biotech, Inc. Methods of treating cancers with antagonistic anti-PD-1 antibodies
WO2025191459A1 (en) 2024-03-11 2025-09-18 Janssen Biotech, Inc. Use of bispecific anti-egfr/c-met antibodies to treat solid tumors
US12460001B2 (en) 2020-05-27 2025-11-04 Janssen Biotech, Inc. Proteins comprising CD3 antigen binding domains and uses thereof
US12522661B2 (en) 2020-01-29 2026-01-13 Inhibrx Biosciences, Inc. CD28 single domain antibodies and multivalent and multispecific constructs thereof
US12528869B2 (en) 2020-08-25 2026-01-20 Janssen Biotech, Inc. Treatment of non-small cell lung cancer with EGFR mutations
WO2026038161A1 (en) 2024-08-13 2026-02-19 Janssen Biotech, Inc. Methods for reducing dermatologic adverse events in patients treated with egfr/met bispecific antibodies
WO2026038160A1 (en) 2024-08-13 2026-02-19 Janssen Biotech, Inc. Methods for reducing infusion-related reactions in patients treated with egfr/met bispecific antibodies
WO2026042017A1 (en) 2024-08-19 2026-02-26 Janssen Biotech, Inc. Amivantamab in combination with lazertinib for the treatment of non-small cell lung cancer (nsclc)
US12590169B2 (en) 2018-10-11 2026-03-31 Inhibrx Biosciences, Inc. 5T4 single domain antibodies and therapeutic compositions thereof
US12599606B2 (en) 2019-05-14 2026-04-14 Janssen Biotech, Inc. Therapies with 3rd generation EGFR tyrosine kinase inhibitors

Families Citing this family (203)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8712924B2 (en) * 2007-05-16 2014-04-29 Lynch Marks Llc Real-time pricing of shipping vendors
US8454960B2 (en) 2008-01-03 2013-06-04 The Scripps Research Institute Multispecific antibody targeting and multivalency through modular recognition domains
US8557243B2 (en) 2008-01-03 2013-10-15 The Scripps Research Institute EFGR antibodies comprising modular recognition domains
KR101658247B1 (ko) 2008-01-03 2016-09-22 더 스크립스 리서치 인스티튜트 모듈 인식 도메인을 통한 항체 표적화
US8574577B2 (en) 2008-01-03 2013-11-05 The Scripps Research Institute VEGF antibodies comprising modular recognition domains
US8557242B2 (en) 2008-01-03 2013-10-15 The Scripps Research Institute ERBB2 antibodies comprising modular recognition domains
US20100260668A1 (en) * 2008-04-29 2010-10-14 Abbott Laboratories Dual Variable Domain Immunoglobulins and Uses Thereof
SG190572A1 (en) * 2008-04-29 2013-06-28 Abbott Lab Dual variable domain immunoglobulins and uses thereof
TW201006485A (en) 2008-06-03 2010-02-16 Abbott Lab Dual variable domain immunoglobulins and uses thereof
CA2726087A1 (en) 2008-06-03 2009-12-10 Tariq Ghayur Dual variable domain immunoglobulins and uses thereof
CN102149825B (zh) * 2008-07-08 2015-07-22 Abbvie公司 前列腺素e2双重可变结构域免疫球蛋白及其用途
ES2610356T3 (es) 2009-02-03 2017-04-27 Amunix Operating Inc. Polipéptidos recombinantes extendidos y composiciones que comprenden los mismos
CA2755336C (en) 2009-03-20 2015-07-14 Amgen Inc. Carrier immunoglobulins and uses thereof
PE20120540A1 (es) * 2009-05-27 2012-05-09 Hoffmann La Roche Anticuerpos triespecificos o tetraespecificos
WO2011028811A2 (en) * 2009-09-01 2011-03-10 Abbott Laboratories Dual variable domain immunoglobulins and uses thereof
AU2010306774A1 (en) * 2009-10-14 2012-05-03 Merrimack Pharmaceuticals, Inc. Bispecific binding agents targeting IGF-1R and ErbB3 signalling and uses thereof
BR112012008833A2 (pt) * 2009-10-15 2015-09-08 Abbott Lab imunoglobulinas de dominio variavel duplo e usos das mesmas
UY32979A (es) * 2009-10-28 2011-02-28 Abbott Lab Inmunoglobulinas con dominio variable dual y usos de las mismas
WO2011060144A2 (en) * 2009-11-11 2011-05-19 Virginia Tech Intellectual Properties, Inc. Compositions and methods to protect cells by blocking entry of pathogen proteins
ES2717883T3 (es) * 2010-03-25 2019-06-26 Ucb Biopharma Sprl Moléculas de DVD-LG estabilizadas con disulfuro
ES2993140T3 (en) * 2010-04-02 2024-12-23 Amunix Pharmaceuticals Inc Binding fusion proteins, binding fusion protein-drug conjugates, xten-drug conjugates and methods of making and using same
US8557961B2 (en) 2010-04-02 2013-10-15 Amunix Operating Inc. Alpha 1-antitrypsin compositions and methods of making and using same
EP2556161A4 (en) * 2010-04-09 2013-11-06 Gen Hospital Corp METHOD FOR TREATING AUTOIMMUNE DISEASES
WO2012009705A1 (en) 2010-07-15 2012-01-19 Zyngenia, Inc. Ang-2 binding complexes and uses thereof
EP3252072A3 (en) 2010-08-03 2018-03-14 AbbVie Inc. Dual variable domain immunoglobulins and uses thereof
JP2013539364A (ja) 2010-08-26 2013-10-24 アッヴィ・インコーポレイテッド 二重可変ドメイン免疫グロブリンおよびその使用
MX360946B (es) 2010-09-22 2018-10-29 Amgen Inc Star Inmunoglobulinas portadoras y usos de las mismas.
US10844106B2 (en) * 2010-11-08 2020-11-24 The Board Of Trustees Of The Leland Stanford Junior University Fusion proteins comprising an engineered knottin peptide and uses thereof
WO2012158818A2 (en) * 2011-05-16 2012-11-22 Fabion Pharmaceuticals, Inc. Multi-specific fab fusion proteins and methods of use
EP2714738B1 (en) 2011-05-24 2018-10-10 Zyngenia, Inc. Multivalent and monovalent multispecific complexes and their uses
WO2013009843A1 (en) * 2011-07-11 2013-01-17 Camas Incorporated Compositions against bacterial toxins
BR112014003315A2 (pt) 2011-08-15 2017-03-01 Univ Chicago composições e métodos relacionados a anticorpos para a proteína a estafilocócica
WO2013026839A1 (en) * 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific antibodies specific for t-cell activating antigens and a tumor antigen and methods of use
CN104185642A (zh) * 2011-12-27 2014-12-03 财团法人生物技术开发中心 轻链桥连的双特异性抗体
TW201333035A (zh) 2011-12-30 2013-08-16 Abbvie Inc 針對ｉｌ－１３及／或ｉｌ－１７之雙特異性結合蛋白
EP2825553B1 (en) 2012-03-14 2018-07-25 Regeneron Pharmaceuticals, Inc. Multispecific antigen-binding molecules and uses thereof
JP6325463B2 (ja) 2012-03-16 2018-05-16 コヴァジェン アクチェン ゲゼルシャフト 抗腫瘍活性を有する新規結合分子
US10011660B2 (en) * 2012-04-30 2018-07-03 Medimmune, Llc Molecules with reduced effector function and extended half-lives, compositions, and uses thereof
AU2013259276B2 (en) 2012-05-10 2018-03-22 Bioatla Llc Multi-specific monoclonal antibodies
TW202037609A (zh) 2012-11-01 2020-10-16 美商艾伯維有限公司 抗-vegf/dll4雙重可變區域免疫球蛋白及其用途
CN102973191A (zh) * 2012-11-29 2013-03-20 李安平 药物纸巾制造方法
CN103013370B (zh) * 2012-12-14 2014-12-10 京东方科技集团股份有限公司 一种各向异性导电胶膜及电子装置
EP2934577A1 (en) * 2012-12-19 2015-10-28 Adimab, LLC Multivalent antibody analogs, and methods of their preparation and use
WO2014116846A2 (en) * 2013-01-23 2014-07-31 Abbvie, Inc. Methods and compositions for modulating an immune response
EP2961773B1 (en) * 2013-02-26 2019-03-20 Roche Glycart AG Bispecific t cell activating antigen binding molecules
JP2016514676A (ja) * 2013-03-15 2016-05-23 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ 四価二重特異性抗体
US10150800B2 (en) 2013-03-15 2018-12-11 Zyngenia, Inc. EGFR-binding modular recognition domains
WO2014144280A2 (en) 2013-03-15 2014-09-18 Abbvie Inc. DUAL SPECIFIC BINDING PROTEINS DIRECTED AGAINST IL-1β AND / OR IL-17
CN105377897A (zh) 2013-05-03 2016-03-02 俄亥俄州创新基金会 Cs1-特异性嵌合抗原受体工程化的免疫效应细胞
CN105683754B (zh) * 2013-05-30 2019-02-01 崔武铉 由重复链和单体的复合物交叉形成的超级复合物及其应用
WO2015048312A1 (en) 2013-09-26 2015-04-02 Costim Pharmaceuticals Inc. Methods for treating hematologic cancers
KR20160122127A (ko) * 2013-12-23 2016-10-21 자임워크스 인코포레이티드 C-말단의 경쇄 폴리펩타이드 연장부를 포함하는 항체 및 이의 컨쥬게이트 및 이들의 사용방법
PE20170255A1 (es) 2014-01-24 2017-03-22 Dana Farber Cancer Inst Inc Moleculas de anticuerpo que se unen a pd-1 y usos de las mismas
HUE045065T2 (hu) 2014-01-31 2019-12-30 Novartis Ag TIM-3 antitest molekulák és felhasználásaik
KR102442436B1 (ko) 2014-03-14 2022-09-15 노파르티스 아게 Lag-3에 대한 항체 분자 및 그의 용도
US20170335281A1 (en) 2014-03-15 2017-11-23 Novartis Ag Treatment of cancer using chimeric antigen receptor
SG11201608192SA (en) * 2014-04-11 2016-10-28 Medimmune Llc Bispecific her2 antibodies
CN104004092B (zh) * 2014-06-05 2015-07-29 深圳市第三人民医院 单基因编码的双或多价特异性抗hiv免疫粘附素
JP6822849B2 (ja) 2014-06-27 2021-01-27 イナート・ファルマ・ソシエテ・アノニムＩｎｎａｔｅ Ｐｈａｒｍａ Ｐｈａｒｍａ Ｓ．Ａ． 多重特異的ＮＫｐ４６結合タンパク質
WO2015197598A2 (en) * 2014-06-27 2015-12-30 Innate Pharma Multispecific antigen binding proteins
WO2016001810A1 (en) 2014-07-01 2016-01-07 Pfizer Inc. Bispecific heterodimeric diabodies and uses thereof
US11542488B2 (en) 2014-07-21 2023-01-03 Novartis Ag Sortase synthesized chimeric antigen receptors
TWI719942B (zh) 2014-07-21 2021-03-01 瑞士商諾華公司 使用ｃｄ３３嵌合抗原受體治療癌症
JP2017528433A (ja) 2014-07-21 2017-09-28 ノバルティス アーゲー 低い免疫増強用量のｍＴＯＲ阻害剤とＣＡＲの組み合わせ
BR112017001183A2 (pt) 2014-07-21 2017-11-28 Novartis Ag tratamento de câncer usando receptor de antígeno quimérico anti-bcma humanizado
EP4205749A1 (en) 2014-07-31 2023-07-05 Novartis AG Subset-optimized chimeric antigen receptor-containing cells
AU2015301460B2 (en) 2014-08-14 2021-04-08 Novartis Ag Treatment of cancer using GFR alpha-4 chimeric antigen receptor
MX2017002205A (es) 2014-08-19 2017-08-21 Novartis Ag Receptor quimerico de antigeno (car) anti-cd123 para uso en el tratamiento de cancer.
KR20170060042A (ko) 2014-09-13 2017-05-31 노파르티스 아게 Alk 억제제의 조합 요법
JP6839074B2 (ja) 2014-09-17 2021-03-03 ノバルティス アーゲー 養子免疫療法のためのキメラ受容体での細胞毒性細胞のターゲティング
EP4245376A3 (en) 2014-10-14 2023-12-13 Novartis AG Antibody molecules to pd-l1 and uses thereof
US20180334490A1 (en) 2014-12-03 2018-11-22 Qilong H. Wu Methods for b cell preconditioning in car therapy
US10093733B2 (en) 2014-12-11 2018-10-09 Abbvie Inc. LRP-8 binding dual variable domain immunoglobulin proteins
EP3240561A4 (en) * 2014-12-29 2018-07-11 Academia Sinica Method for treating influenza a virus infection
CA2973720A1 (en) * 2015-01-14 2016-07-21 Compass Therapeutics Llc Multispecific immunomodulatory antigen-binding constructs
WO2016134371A2 (en) * 2015-02-20 2016-08-25 Ohio State Innovation Foundation Bivalent antibody directed against nkg2d and tumor associated antigens
CN104804099B (zh) * 2015-04-01 2019-01-25 广州谱泰生物技术有限公司 一种重组h9n2亚型禽流感加强型多表位疫苗
US11045543B2 (en) 2015-04-06 2021-06-29 Cytoimmune Therapeutics, Inc. EGFR-directed car therapy for glioblastoma
JP6961490B2 (ja) 2015-04-08 2021-11-05 ノバルティス アーゲー Ｃｄ２０療法、ｃｄ２２療法、およびｃｄ１９キメラ抗原受容体（ｃａｒ）発現細胞との併用療法
EP3286211A1 (en) 2015-04-23 2018-02-28 Novartis AG Treatment of cancer using chimeric antigen receptor and protein kinase a blocker
TW201710286A (zh) 2015-06-15 2017-03-16 艾伯維有限公司 抗ｖｅｇｆ、ｐｄｇｆ及／或其受體之結合蛋白
AU2016284871B2 (en) 2015-06-23 2022-09-29 Innate Pharma Multispecific NK engager proteins
IL296285A (en) 2015-07-06 2022-11-01 Regeneron Pharma Multispecific antigen-binding molecules and uses thereof
HRP20211058T8 (hr) 2015-07-29 2021-11-26 Novartis Ag Kombinirane terapije koje sadrže molekule antitijela protiv lag-3
EP3328418A1 (en) 2015-07-29 2018-06-06 Novartis AG Combination therapies comprising antibody molecules to pd-1
EP3878465A1 (en) 2015-07-29 2021-09-15 Novartis AG Combination therapies comprising antibody molecules to tim-3
EP3307321A4 (en) 2015-08-26 2019-04-17 Bison Therapeutics Inc. MULTISPECIFIC ANTIBODY PLATFORM AND ASSOCIATED METHODS
CN105218679B (zh) * 2015-09-23 2018-01-12 天津市疾病预防控制中心 人偏肺病毒多表位抗原及其应用
US20200261573A1 (en) 2015-12-17 2020-08-20 Novartis Ag Combination of c-met inhibitor with antibody molecule to pd-1 and uses thereof
ES2986067T3 (es) 2015-12-17 2024-11-08 Novartis Ag Moléculas de anticuerpos frente a PD-1 y usos de las mismas
EP4643874A3 (en) 2015-12-22 2026-02-11 Novartis AG Mesothelin chimeric antigen receptor (car) and antibody against pd-l1 inhibitor for combined use in anticancer therapy
WO2017124002A1 (en) * 2016-01-13 2017-07-20 Compass Therapeutics Llc Multispecific immunomodulatory antigen-binding constructs
MA55746A (fr) 2016-01-21 2022-03-02 Novartis Ag Molécules multispécifiques ciblant cll-1
KR20180118175A (ko) 2016-03-04 2018-10-30 노파르티스 아게 다중 키메라 항원 수용체 (car) 분자를 발현하는 세포 및 그에 따른 용도
CN116284392A (zh) 2016-03-10 2023-06-23 艾科赛扬制药股份有限公司 活化素2型受体结合蛋白及其用途
US10765625B2 (en) * 2016-03-15 2020-09-08 The Board Of Trustees Of The Leland Stanford Junior University Knottin-drug conjugates and methods of using the same
EP3430058A4 (en) 2016-03-15 2019-10-23 Generon (Shanghai) Corporation Ltd. MULTISPECIFIC FAB FUSION PROTEINS AND USES THEREOF
EP3432924A1 (en) 2016-03-23 2019-01-30 Novartis AG Cell secreted minibodies and uses thereof
CN109715808A (zh) 2016-04-15 2019-05-03 诺华股份有限公司 用于选择性蛋白质表达的组合物和方法
WO2017185037A1 (en) 2016-04-22 2017-10-26 Acceleron Pharma Inc. Alk7 binding proteins and uses thereof
EP3448891A1 (en) 2016-04-28 2019-03-06 Regeneron Pharmaceuticals, Inc. Methods of making multispecific antigen-binding molecules
WO2017210617A2 (en) 2016-06-02 2017-12-07 Porter, David, L. Therapeutic regimens for chimeric antigen receptor (car)- expressing cells
SG11201900344YA (en) 2016-07-15 2019-02-27 Novartis Ag Treatment and prevention of cytokine release syndrome using a chimeric antigen receptor in combination with a kinase inhibitor
AU2017302668B9 (en) 2016-07-28 2023-06-22 Novartis Ag Combination therapies of chimeric antigen receptors and PD-1 inhibitors
BR112019002035A2 (pt) 2016-08-01 2019-05-14 Novartis Ag tratamento de câncer usando um receptor de antígeno quimérico em combinação com um inibidor de uma molécula pró-macrófago m2
US20190225701A1 (en) 2016-09-26 2019-07-25 The Brigham And Women's Hospital, Inc. Regulators of b cell-mediated immunosuppression
BR112019006781A2 (pt) 2016-10-07 2019-07-30 Novartis Ag receptores de antígeno quiméricos para o tratamento de câncer
KR102692708B1 (ko) 2016-12-20 2024-08-07 에프. 호프만-라 로슈 아게 항-cd20/항-cd3 이중특이성 항체 및 4-1bb(cd137) 작용물질의 병용 요법
ES2912408T3 (es) 2017-01-26 2022-05-25 Novartis Ag Composiciones de CD28 y métodos para terapia con receptores quiméricos para antígenos
WO2018160731A1 (en) 2017-02-28 2018-09-07 Novartis Ag Shp inhibitor compositions and uses for chimeric antigen receptor therapy
WO2018182935A1 (en) * 2017-03-31 2018-10-04 The Board Of Trustees Of The Leland Stanford Junior University Synthekine compositions and methods of use
US20200179511A1 (en) 2017-04-28 2020-06-11 Novartis Ag Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor
EP3615055A1 (en) 2017-04-28 2020-03-04 Novartis AG Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor
DK3635009T3 (da) 2017-06-07 2026-03-30 Regeneron Pharma Sammensætninger og fremgangsmåder til internalisering af enzymer
MY204117A (en) 2017-06-22 2024-08-08 Novartis Ag Antibody molecules to cd73 and uses thereof
CA3066747A1 (en) 2017-06-27 2019-01-03 Novartis Ag Dosage regimens for anti-tim-3 antibodies and uses thereof
AU2018301393B2 (en) 2017-07-11 2025-02-27 Compass Therapeutics Llc Agonist antibodies that bind human CD137 and uses thereof
CA3068956A1 (en) * 2017-07-19 2019-01-24 Novo Nordisk A/S Bifunctional compounds
JP2020527572A (ja) 2017-07-20 2020-09-10 ノバルティス アーゲー 抗ｌａｇ−３抗体の投薬量レジメンおよびその使用
US11918634B2 (en) * 2017-08-10 2024-03-05 Good T Cells, Inc. Method for activating T cells for cancer treatment
US20210179709A1 (en) 2017-10-31 2021-06-17 Novartis Ag Anti-car compositions and methods
WO2019089753A2 (en) 2017-10-31 2019-05-09 Compass Therapeutics Llc Cd137 antibodies and pd-1 antagonists and uses thereof
CN111655288A (zh) 2017-11-16 2020-09-11 诺华股份有限公司 组合疗法
EP3713961A2 (en) 2017-11-20 2020-09-30 Compass Therapeutics LLC Cd137 antibodies and tumor antigen-targeting antibodies and uses thereof
US12247060B2 (en) 2018-01-09 2025-03-11 Marengo Therapeutics, Inc. Calreticulin binding constructs and engineered T cells for the treatment of diseases
AU2019215031C1 (en) 2018-01-31 2026-02-26 Novartis Ag Combination therapy using a chimeric antigen receptor
EP3765517A1 (en) 2018-03-14 2021-01-20 Elstar Therapeutics, Inc. Multifunctional molecules that bind to calreticulin and uses thereof
US20210147547A1 (en) 2018-04-13 2021-05-20 Novartis Ag Dosage Regimens For Anti-Pd-L1 Antibodies And Uses Thereof
WO2019210153A1 (en) 2018-04-27 2019-10-31 Novartis Ag Car t cell therapies with enhanced efficacy
KR102871690B1 (ko) 2018-04-30 2025-10-16 리제너론 파마슈티칼스 인코포레이티드 Her2 및/또는 aplp2에 결합하는 항체 및 이중특이적 항원-결합 분자 및 접합체 그리고 이들의 용도
BR112020023145A2 (pt) 2018-05-17 2021-02-02 Regeneron Pharmaceuticals, Inc. anticorpo anti-cd63 ou fragmento de ligação ao antígeno do mesmo, molécula de ligação ao antígeno biespecífica, proteína terapêutica de múltiplos domínios, polinucleotídeo composição farmacêutica, e, composto
WO2019226658A1 (en) 2018-05-21 2019-11-28 Compass Therapeutics Llc Multispecific antigen-binding compositions and methods of use
CA3099308A1 (en) 2018-05-21 2019-11-28 Compass Therapeutics Llc Compositions and methods for enhancing the killing of target cells by nk cells
EP3801769A1 (en) 2018-05-25 2021-04-14 Novartis AG Combination therapy with chimeric antigen receptor (car) therapies
WO2019232244A2 (en) 2018-05-31 2019-12-05 Novartis Ag Antibody molecules to cd73 and uses thereof
TWI890660B (zh) 2018-06-13 2025-07-21 瑞士商諾華公司 Bcma 嵌合抗原受體及其用途
WO2019241216A1 (en) 2018-06-14 2019-12-19 Bioatla, Llc Multi-specific antibody constructs
CN112654394B (zh) 2018-06-19 2025-07-11 阿塔盖有限责任公司 针对补体成分5的抗体分子和其用途
CA3105448A1 (en) 2018-07-03 2020-01-09 Elstar Therapeutics, Inc. Anti-tcr antibody molecules and uses thereof
AR116109A1 (es) 2018-07-10 2021-03-31 Novartis Ag Derivados de 3-(5-amino-1-oxoisoindolin-2-il)piperidina-2,6-diona y usos de los mismos
JP2021531306A (ja) 2018-07-25 2021-11-18 アドバンスド アクセラレーター アプリケーションズ エスエー 神経内分泌腫瘍の処置の方法
EP3847196A4 (en) 2018-09-07 2023-01-04 ITabMed (HK) Limited BISPECIFIC ANTIGEN BINDING PROTEINS AND USES THEREOF
AU2019372673A1 (en) 2018-11-01 2021-05-27 Gracell Biotechnologies (Shanghai) Co., Ltd. Compositions and methods for T cell engineering
US11046769B2 (en) 2018-11-13 2021-06-29 Compass Therapeutics Llc Multispecific binding constructs against checkpoint molecules and uses thereof
KR20210106437A (ko) 2018-12-20 2021-08-30 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법 및 약학적 조합물
EP3897648B1 (en) 2018-12-20 2023-08-23 Novartis AG Extended low dose regimens for mdm2 inhibitors
WO2020132810A1 (en) 2018-12-24 2020-07-02 Generon (Shanghai) Corporation Ltd. Multispecific antigen binding proteins capable of binding cd19 and cd3, and use thereof
US10871640B2 (en) 2019-02-15 2020-12-22 Perkinelmer Cellular Technologies Germany Gmbh Methods and systems for automated imaging of three-dimensional objects
CA3123519A1 (en) 2019-02-15 2020-08-20 Novartis Ag Substituted 3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
CN113490528B (zh) 2019-02-15 2024-12-03 诺华股份有限公司 3-(1-氧代-5-(哌啶-4-基)异吲哚啉-2-基)哌啶-2,6-二酮衍生物及其用途
GB2599228B (en) 2019-02-21 2024-02-07 Marengo Therapeutics Inc Multifunctional molecules that bind to T cell related cancer cells and uses thereof
CN119039441A (zh) 2019-02-21 2024-11-29 马伦戈治疗公司 与nkp30结合的抗体分子及其用途
WO2020172553A1 (en) 2019-02-22 2020-08-27 Novartis Ag Combination therapies of egfrviii chimeric antigen receptors and pd-1 inhibitors
BR112021019337A2 (pt) 2019-03-29 2021-12-07 Atarga Llc Anticorpo anti-fgf23
US11840575B2 (en) 2019-05-07 2023-12-12 Gracell Biotechnologies (Shanghai) Co., Ltd. Engineered immune cells targeting BCMA and their uses thereof
WO2021022304A2 (en) 2019-07-30 2021-02-04 Qlsf Biotherapeutics, Inc. MULTISPECIFIC BINDING COMPOUNDS THAT BIND TO LRRC15 AND CD3ε
CN114929750B (zh) 2019-09-13 2024-11-22 芝加哥大学 用于治疗葡萄球菌感染的方法和组合物
BR112022007179A2 (pt) 2019-10-21 2022-08-23 Novartis Ag Inibidores de tim-3 e usos dos mesmos
CN114786679A (zh) 2019-10-21 2022-07-22 诺华股份有限公司 具有维奈托克和tim-3抑制剂的组合疗法
IL293215A (en) 2019-11-26 2022-07-01 Novartis Ag Chimeric antigen receptors that bind bcma and cd19 and their uses
US20230340119A1 (en) * 2019-12-05 2023-10-26 Arbele Corp Composition of triax antibodies and method of making and using thereof
BR112022011902A2 (pt) 2019-12-20 2022-09-06 Novartis Ag Terapias de combinação
AU2020416273A1 (en) 2020-01-03 2022-07-28 Marengo Therapeutics, Inc. Anti-TCR antibody molecules and uses thereof
WO2021146636A1 (en) 2020-01-17 2021-07-22 Becton, Dickinson And Company Methods and compositions for single cell secretomics
BR112022012310A2 (pt) 2020-01-17 2022-09-06 Novartis Ag Combinação compreendendo um inibidor de tim-3 e um agente hipometilante para uso no tratamento de síndrome mielodisplásica ou leucemia mielomonocítica crônica
CN115397460A (zh) 2020-02-27 2022-11-25 诺华股份有限公司 制备表达嵌合抗原受体的细胞的方法
KR20230027056A (ko) 2020-06-23 2023-02-27 노파르티스 아게 3-(1-옥소이소인돌린-2-일)피페리딘-2,6-디온 유도체를 포함하는 투약 요법
TW202216761A (zh) 2020-07-16 2022-05-01 瑞士商諾華公司 抗β細胞素抗體、其片段及多特異性結合分子
WO2022026592A2 (en) 2020-07-28 2022-02-03 Celltas Bio, Inc. Antibody molecules to coronavirus and uses thereof
JP7819176B2 (ja) 2020-08-03 2026-02-24 ノバルティス アーゲー ヘテロアリール置換３－（１－オキソイソインドリン－２－イル）ピペリジン－２，６－ジオン誘導体及びその使用
US12540188B2 (en) 2020-08-05 2026-02-03 Synthekine, Inc. IL10Rα/IL2Rγ synthetic cytokines
EP4204021A1 (en) 2020-08-31 2023-07-05 Advanced Accelerator Applications International S.A. Method of treating psma-expressing cancers
EP4204020A1 (en) 2020-08-31 2023-07-05 Advanced Accelerator Applications International S.A. Method of treating psma-expressing cancers
CN113416249B (zh) * 2020-10-21 2023-04-07 北京智仁美博生物科技有限公司 针对破伤风毒素的组合物
US20240002509A1 (en) 2020-11-06 2024-01-04 Novartis Ag ANTIBODY Fc VARIANTS
KR20230118573A (ko) * 2020-11-11 2023-08-11 에이치큐 한 액티빈/tgf-베타 및 rankl의 이작용성 길항제 및 이의 용도
CA3198447A1 (en) 2020-11-13 2022-05-19 Novartis Ag Combination therapies with chimeric antigen receptor (car)-expressing cells
US20240141060A1 (en) 2021-01-29 2024-05-02 Novartis Ag Dosage regimes for anti-cd73 and anti-entpd2 antibodies and uses thereof
US20240052359A1 (en) 2021-02-10 2024-02-15 Limagrain Europe Multiplex targeted recombinations for trait introgression applications
AU2022251523A1 (en) * 2021-03-31 2023-09-28 Hangzhou Exegenesis Bio Ltd. Fusion molecules targeting vegf and angiopoietin and uses thereof
TW202304979A (zh) 2021-04-07 2023-02-01 瑞士商諾華公司 抗ＴＧＦβ抗體及其他治療劑用於治療增殖性疾病之用途
AR125874A1 (es) 2021-05-18 2023-08-23 Novartis Ag Terapias de combinación
WO2023044483A2 (en) 2021-09-20 2023-03-23 Voyager Therapeutics, Inc. Compositions and methods for the treatment of her2 positive cancer
CA3176410A1 (en) * 2021-09-24 2023-03-24 Kashiv Biosciences, Llc An improved process for preparation of stable protein solution
US20250034559A1 (en) 2021-11-17 2025-01-30 Voyager Therapeutics, Inc. Compositions and methods for the treatment of tau-related disorders
TW202342548A (zh) 2022-02-07 2023-11-01 美商威特拉公司 抗獨特型(anti-idiotype)抗體分子及其用途
WO2023220695A2 (en) 2022-05-13 2023-11-16 Voyager Therapeutics, Inc. Compositions and methods for the treatment of her2 positive cancer
JP2025528068A (ja) 2022-08-03 2025-08-26 ボイジャー セラピューティクス インコーポレイテッド 血液脳関門を通過させるための組成物及び方法
CN120693395A (zh) * 2022-10-20 2025-09-23 北京三诺佳邑生物技术有限责任公司 特异性结合TRAIL或FasL的抗体组合以及双特异性抗体
TW202434306A (zh) 2022-11-24 2024-09-01 瑞士商百濟神州瑞士有限責任公司 抗ｃｅａ抗體藥物軛合物及使用方法
CN121293352A (zh) 2023-01-19 2026-01-09 广州百济神州生物制药有限公司 抗cmet抗体及使用方法
WO2024168061A2 (en) 2023-02-07 2024-08-15 Ayan Therapeutics Inc. Antibody molecules binding to sars-cov-2
AR132043A1 (es) 2023-03-03 2025-05-21 Beigene Switzerland Gmbh Anticuerpos muc1 y métodos de uso
JP2026506241A (ja) 2023-03-03 2026-02-20 ビーワン メディシンズ ワン ゲーエムベーハー Ｃｄ１６ａ抗体及び使用方法
EP4676975A1 (en) 2023-03-03 2026-01-14 Beone Medicines I GmbH Muc1 and cd16a antibodies and methods of use
TW202436345A (zh) 2023-03-06 2024-09-16 瑞士商百濟神州瑞士有限責任公司 抗ｃｄ３多特異性抗體及使用方法
WO2024184812A1 (en) 2023-03-06 2024-09-12 Beigene Switzerland Gmbh Anti-cldn6 antibodies and methods of use
WO2024184810A1 (en) 2023-03-06 2024-09-12 Beigene Switzerland Gmbh Anti-cldn6 and anti-cd3 multispecific antibodies and methods of use
EP4724490A2 (en) 2023-06-12 2026-04-15 Amgen Inc. Lymphotoxin beta receptor agonist binding proteins
WO2025122634A1 (en) 2023-12-05 2025-06-12 Voyager Therapeutics, Inc. Compositions and methods for the treatment of tau-related disorders
WO2026021476A1 (en) 2024-07-24 2026-01-29 Beone Guangzhou Biologics Manufacturing Co., Ltd. Anti-cmet and anti-egfr multispecific antibody drug conjugates
WO2026036047A1 (en) 2024-08-08 2026-02-12 Altus Enterprises, Inc. Antibody molecules to fixa and fx and uses thereof
WO2026058155A1 (en) 2024-09-11 2026-03-19 Novartis Ag Antibodies targeting il-31

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995009917A1 (en) * 1993-10-07 1995-04-13 The Regents Of The University Of California Genetically engineered bispecific tetravalent antibodies
US20040259156A1 (en) * 2000-05-24 2004-12-23 Zhenping Zhu Bispecific immunoglobulin-like antigen binding proteins and method of production

Family Cites Families (101)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2207308A (en) 1940-07-09 Electrolytic manufacture
EP0092918B1 (en) 1982-04-22 1988-10-19 Imperial Chemical Industries Plc Continuous release formulations
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4741900A (en) 1982-11-16 1988-05-03 Cytogen Corporation Antibody-metal ion complexes
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US5807715A (en) 1984-08-27 1998-09-15 The Board Of Trustees Of The Leland Stanford Junior University Methods and transformed mammalian lymphocyte cells for producing functional antigen-binding protein including chimeric immunoglobulin
US5128326A (en) 1984-12-06 1992-07-07 Biomatrix, Inc. Drug delivery systems based on hyaluronans derivatives thereof and their salts and methods of producing same
US5374548A (en) 1986-05-02 1994-12-20 Genentech, Inc. Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor
MX9203291A (es) 1985-06-26 1992-08-01 Liposome Co Inc Metodo para acoplamiento de liposomas.
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
JP3101690B2 (ja) 1987-03-18 2000-10-23 エス・ビィ・２・インコーポレイテッド 変性抗体の、または変性抗体に関する改良
US4880078A (en) 1987-06-29 1989-11-14 Honda Giken Kogyo Kabushiki Kaisha Exhaust muffler
US5677425A (en) 1987-09-04 1997-10-14 Celltech Therapeutics Limited Recombinant antibody
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
AU6430190A (en) 1989-10-10 1991-05-16 Pitman-Moore, Inc. Sustained release composition for macromolecular proteins
CA2071867A1 (en) 1989-11-06 1991-05-07 Edith Mathiowitz Method for producing protein microspheres
CA2109528A1 (en) 1991-05-01 1992-11-02 Gregory A. Prince A method for treating infectious respiratory diseases
EP1400536A1 (en) 1991-06-14 2004-03-24 Genentech Inc. Method for making humanized antibodies
US5637481A (en) * 1993-02-01 1997-06-10 Bristol-Myers Squibb Company Expression vectors encoding bispecific fusion proteins and methods of producing biologically active bispecific fusion proteins in a mammalian cell
MX9204374A (es) 1991-07-25 1993-03-01 Idec Pharma Corp Anticuerpo recombinante y metodo para su produccion.
US5714350A (en) 1992-03-09 1998-02-03 Protein Design Labs, Inc. Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region
US5912015A (en) 1992-03-12 1999-06-15 Alkermes Controlled Therapeutics, Inc. Modulated release from biocompatible polymers
CA2118508A1 (en) 1992-04-24 1993-11-11 Elizabeth S. Ward Recombinant production of immunoglobulin-like domains in prokaryotic cells
GB9221657D0 (en) * 1992-10-15 1992-11-25 Scotgen Ltd Recombinant bispecific antibodies
US5934272A (en) 1993-01-29 1999-08-10 Aradigm Corporation Device and method of creating aerosolized mist of respiratory drug
US5885573A (en) 1993-06-01 1999-03-23 Arch Development Corporation Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies
AU691811B2 (en) 1993-06-16 1998-05-28 Celltech Therapeutics Limited Antibodies
US6132764A (en) 1994-08-05 2000-10-17 Targesome, Inc. Targeted polymerized liposome diagnostic and treatment agents
ATE252894T1 (de) 1995-01-05 2003-11-15 Univ Michigan Oberflächen-modifizierte nanopartikel und verfahren für ihre herstellung und verwendung
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5641870A (en) * 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
US6019968A (en) 1995-04-14 2000-02-01 Inhale Therapeutic Systems, Inc. Dispersible antibody compositions and methods for their preparation and use
US6121022A (en) 1995-04-14 2000-09-19 Genentech, Inc. Altered polypeptides with increased half-life
WO1997007788A2 (en) 1995-08-31 1997-03-06 Alkermes Controlled Therapeutics, Inc. Composition for sustained release of an agent
ATE508733T1 (de) 1996-03-04 2011-05-15 Penn State Res Found Materialien und verfahren zur steigerung der zellulären internalisierung
AU5711196A (en) 1996-03-14 1997-10-01 Human Genome Sciences, Inc. Apoptosis inducing molecule i
JP4046354B2 (ja) 1996-03-18 2008-02-13 ボード オブ リージェンツ，ザ ユニバーシティ オブ テキサス システム 増大した半減期を有する免疫グロブリン様ドメイン
CA2248868A1 (en) 1996-03-22 1997-09-25 Human Genome Sciences, Inc. Apoptosis inducing molecule ii
US5855913A (en) 1997-01-16 1999-01-05 Massachusetts Instite Of Technology Particles incorporating surfactants for pulmonary drug delivery
US5985309A (en) 1996-05-24 1999-11-16 Massachusetts Institute Of Technology Preparation of particles for inhalation
US5874064A (en) 1996-05-24 1999-02-23 Massachusetts Institute Of Technology Aerodynamically light particles for pulmonary drug delivery
US6056973A (en) 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
CA2277801C (en) 1997-01-16 2002-10-15 Massachusetts Institute Of Technology Preparation of particles for inhalation
US6277375B1 (en) 1997-03-03 2001-08-21 Board Of Regents, The University Of Texas System Immunoglobulin-like domains with increased half-lives
US20020062010A1 (en) * 1997-05-02 2002-05-23 Genentech, Inc. Method for making multispecific antibodies having heteromultimeric and common components
EP1958962A3 (en) 1997-06-12 2013-05-01 Novartis International Pharmaceutical Ltd. Artificial antibody polypeptides
US5989463A (en) 1997-09-24 1999-11-23 Alkermes Controlled Therapeutics, Inc. Methods for fabricating polymer-based controlled release devices
SE512663C2 (sv) 1997-10-23 2000-04-17 Biogram Ab Inkapslingsförfarande för aktiv substans i en bionedbrytbar polymer
CA2309541C (en) 1997-11-03 2011-01-11 Human Genome Sciences, Inc. Vegi, an inhibitor of angiogenesis and tumor growth
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
US6528624B1 (en) 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
DK1071700T3 (da) 1998-04-20 2010-06-07 Glycart Biotechnology Ag Glykosylerings-modifikation af antistoffer til forbedring af antistofafhængig cellulær cytotoksicitet
US7112324B1 (en) 1998-04-21 2006-09-26 Micromet Ag CD 19×CD3 specific polypeptides and uses thereof
GB9809951D0 (en) 1998-05-08 1998-07-08 Univ Cambridge Tech Binding molecules
US6962702B2 (en) 1998-06-22 2005-11-08 Immunomedics Inc. Production and use of novel peptide-based agents for use with bi-specific antibodies
WO1999066903A2 (en) 1998-06-24 1999-12-29 Advanced Inhalation Research, Inc. Large porous particles emitted from an inhaler
PL209392B1 (pl) 1999-01-15 2011-08-31 Genentech Inc Przeciwciało, komórka gospodarza, sposób wytwarzania przeciwciała oraz zastosowanie przeciwciała
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
CA2704600C (en) 1999-04-09 2016-10-25 Kyowa Kirin Co., Ltd. A method for producing antibodies with increased adcc activity
US7527787B2 (en) 2005-10-19 2009-05-05 Ibc Pharmaceuticals, Inc. Multivalent immunoglobulin-based bioactive assemblies
EP1229125A4 (en) 1999-10-19 2005-06-01 Kyowa Hakko Kogyo Kk PROCESS FOR PREPARING A POLYPEPTIDE
HUP0204475A2 (en) 2000-02-11 2003-04-28 Merck Patent Gmbh Enhancing the circulating half-life of antibody-based fusion proteins
JP2003531588A (ja) 2000-04-11 2003-10-28 ジェネンテック・インコーポレーテッド 多価抗体とその用途
US6725230B2 (en) 2000-07-18 2004-04-20 Aegis Analytical Corporation System, method and computer program for assembling process data of multi-database origins using a hierarchical display
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
CA2953239A1 (en) 2000-10-06 2002-04-18 Kyowa Hakko Kirin Co., Ltd. Antibody composition-producing cell
CA2424977C (en) 2000-10-06 2008-03-18 Kyowa Hakko Kogyo Co., Ltd. Process for purifying antibody
US7083784B2 (en) 2000-12-12 2006-08-01 Medimmune, Inc. Molecules with extended half-lives, compositions and uses thereof
CN1294148C (zh) 2001-04-11 2007-01-10 中国科学院遗传与发育生物学研究所 环状单链三特异抗体
US20050048512A1 (en) 2001-04-26 2005-03-03 Avidia Research Institute Combinatorial libraries of monomer domains
US7053202B2 (en) * 2001-10-19 2006-05-30 Millennium Pharmaceuticals, Inc. Immunoglobulin DNA cassette molecules, monobody constructs, methods of production, and methods of use therefor
CA2463879C (en) 2001-10-25 2012-12-04 Genentech, Inc. Glycoprotein compositions
US20040002587A1 (en) 2002-02-20 2004-01-01 Watkins Jeffry D. Fc region variants
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
WO2003075957A1 (en) 2002-03-04 2003-09-18 Medimmune, Inc. The prevention or treatment of cancer using integrin alphavbeta3 antagonists in combination with other agents
JP3975850B2 (ja) 2002-07-25 2007-09-12 富士ゼロックス株式会社 画像処理装置
DK1534335T4 (en) 2002-08-14 2015-10-05 Macrogenics Inc FCGAMMARIIB-SPECIFIC ANTIBODIES AND PROCEDURES FOR USE THEREOF
EP1553975B8 (en) 2002-09-27 2023-04-12 Xencor, Inc. Optimized fc variants and methods for their generation
DK1562972T3 (da) 2002-10-15 2010-12-06 Facet Biotech Corp Modifikation af FcRn-bindingsaffiniteter eller serumhalveringstider for antistoffer ved mutagenese
CA2511013A1 (en) * 2002-12-20 2004-07-15 Biogen Idec Ma Inc. Multivalent lymphotoxin beta receptor agonists and therapeutic uses thereof
CA2512729C (en) 2003-01-09 2014-09-16 Macrogenics, Inc. Identification and engineering of antibodies with variant fc regions and methods of using same
KR20060041205A (ko) 2003-07-01 2006-05-11 이뮤노메딕스, 인코오포레이티드 양특이성 항체들의 다가 담체들
US20050226867A1 (en) 2003-10-08 2005-10-13 Kyowa Hakko Kogyo Co., Ltd. IL-5R-specific antibody composition
GB0324368D0 (en) 2003-10-17 2003-11-19 Univ Cambridge Tech Polypeptides including modified constant regions
US20050164301A1 (en) 2003-10-24 2005-07-28 Avidia Research Institute LDL receptor class A and EGF domain monomers and multimers
NZ547629A (en) 2003-11-26 2009-08-28 Max Planck Gesellschaft Antibodies binding to conformationally discriminating epitopes of human IGG Fc receptor IIb and IIb
SI1706424T1 (sl) 2004-01-12 2010-01-29 Applied Molecular Evolution Variante fc regij
DK1709081T3 (da) * 2004-01-16 2011-06-06 Regeneron Pharma Fusionspolypeptider, der kan aktivere receptorer
EP1737890A2 (en) 2004-03-24 2007-01-03 Xencor, Inc. Immunoglobulin variants outside the fc region
EP1786918A4 (en) 2004-07-17 2009-02-11 Imclone Systems Inc NEW BISPECIFIC ANTIBODY TETRAVALENT
AU2005274905B2 (en) 2004-08-04 2010-12-23 Mentrik Biotech, Llc Variant Fc regions
DK1791565T3 (en) 2004-09-23 2016-08-01 Genentech Inc Cysteingensplejsede antibodies and conjugates
AU2006218876A1 (en) * 2005-02-28 2006-09-08 Centocor, Inc. Heterodimeric protein binding compositions
PT1896071E (pt) 2005-06-30 2015-07-09 Janssen Biotech Inc Métodos e composições com melhorias na atividade terapêutica
US7612181B2 (en) * 2005-08-19 2009-11-03 Abbott Laboratories Dual variable domain immunoglobulin and uses thereof
NZ612578A (en) 2005-08-19 2014-11-28 Abbvie Inc Dual variable domain immunoglobin and uses thereof
CA2647524C (en) 2006-04-05 2019-11-26 The Rockefeller University Polypeptides with enhanced anti-inflammatory and decreased cytotoxic properties and relating methods
WO2008027236A2 (en) * 2006-08-30 2008-03-06 Genentech, Inc. Multispecific antibodies
GB0708585D0 (en) * 2007-05-03 2007-06-13 Queen Mary & Westfield College Novel antibody and use in diagnosis and therapy of arthropathies
US11392902B2 (en) 2017-06-06 2022-07-19 United Parcel Service Of America, Inc. Systems, methods, apparatuses and computer program products for providing notification of items for pickup and delivery

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995009917A1 (en) * 1993-10-07 1995-04-13 The Regents Of The University Of California Genetically engineered bispecific tetravalent antibodies
US20040259156A1 (en) * 2000-05-24 2004-12-23 Zhenping Zhu Bispecific immunoglobulin-like antigen binding proteins and method of production

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
LU ET AL.: "Fab-scFv fusion protein: an efficient approach to production of bispecific antibodyfragments", J. IMMUNOL. METHODS, vol. 267, no. 2, 15 September 2002 (2002-09-15), pages 213 - 226, XP004375842 *
See also references of EP2069401A4 *

Cited By (250)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8981061B2 (en) 2001-03-20 2015-03-17 Novo Nordisk A/S Receptor TREM (triggering receptor expressed on myeloid cells) and uses thereof
US9273111B2 (en) 2004-11-29 2016-03-01 Universite De Lorraine Therapeutic TREM-1 peptides
US10603357B2 (en) 2004-11-29 2020-03-31 Bristol-Myers Squibb Company Therapeutic TREM-1 peptides
US10100130B2 (en) 2007-09-26 2018-10-16 Ucb Biopharma Sprl Dual specificity antibody fusions
US9828438B2 (en) 2007-09-26 2017-11-28 Ucb Pharma S.A. Dual specificity antibody fusions
US9309327B2 (en) 2007-09-26 2016-04-12 Ucb Pharma S.A. Dual specificity antibody fusions
US11427650B2 (en) 2007-09-26 2022-08-30 UCB Biopharma SRL Dual specificity antibody fusions
US8629246B2 (en) 2007-09-26 2014-01-14 Ucb Pharma S.A. Dual specificity antibody fusions
US9266967B2 (en) 2007-12-21 2016-02-23 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
US10138293B2 (en) 2007-12-21 2018-11-27 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
US10927163B2 (en) 2007-12-21 2021-02-23 Hoffmann-La Roche, Inc. Bivalent, bispecific antibodies
US10407513B2 (en) 2008-09-26 2019-09-10 Ucb Biopharma Sprl Biological products
US9382323B2 (en) 2009-04-02 2016-07-05 Roche Glycart Ag Multispecific antibodies comprising full length antibodies and single chain fab fragments
US11993642B2 (en) 2009-04-07 2024-05-28 Hoffmann-La Roche Inc. Trivalent, bispecific antibodies
WO2010115551A1 (en) * 2009-04-07 2010-10-14 Roche Glycart Ag Bispecific anti-erbb-1/anti-c-met antibodies
WO2010115589A1 (en) * 2009-04-07 2010-10-14 Roche Glycart Ag Trivalent, bispecific antibodies
US9890204B2 (en) 2009-04-07 2018-02-13 Hoffmann-La Roche Inc. Trivalent, bispecific antibodies
JP2012522527A (ja) * 2009-04-07 2012-09-27 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
JP2014193181A (ja) * 2009-04-07 2014-10-09 Roche Glycart Ag 三価の二重特異性抗体
US9676845B2 (en) 2009-06-16 2017-06-13 Hoffmann-La Roche, Inc. Bispecific antigen binding proteins
US10640555B2 (en) 2009-06-16 2020-05-05 Hoffmann-La Roche Inc. Bispecific antigen binding proteins
US11673945B2 (en) 2009-06-16 2023-06-13 Hoffmann-La Roche Inc. Bispecific antigen binding proteins
EP2464663A4 (en) * 2009-08-13 2013-05-29 Massachusetts Inst Technology MANIPULATED PROTEINS WITH MUTANT FIBRONECTIN DOMAINS
US10421816B2 (en) 2009-09-10 2019-09-24 Ucb Biopharma Sprl Multivalent antibodies
US9994646B2 (en) 2009-09-16 2018-06-12 Genentech, Inc. Coiled coil and/or tether containing protein complexes and uses thereof
WO2011061492A3 (en) * 2009-11-17 2011-07-28 Ucb Pharma S.A. Multivalent antibodies
CN106243227A (zh) * 2009-11-17 2016-12-21 Ucb医药有限公司 多价抗体
US20130066054A1 (en) * 2009-11-17 2013-03-14 Ucb Pharma S.A. Multivalent antibodies
CN102639561A (zh) * 2009-11-17 2012-08-15 Ucb医药有限公司 多价抗体
JP2013510897A (ja) * 2009-11-17 2013-03-28 ユセベ ファルマ ソシエテ アノニム 多価抗体
JP2016094486A (ja) * 2009-11-17 2016-05-26 ユセベ ファルマ ソシエテ アノニム 多価抗体
EA023053B1 (ru) * 2009-11-17 2016-04-29 Юсб Фарма С.А. Поливалентные антитела
WO2011061246A3 (en) * 2009-11-19 2011-07-28 Ucb Pharma S.A. Multivalent antibodies
JP2013513370A (ja) * 2009-12-09 2013-04-22 フリードリヒ−アレクサンダー−ウニベルジテート・エアランゲン−ニュルンベルク 急性骨髄性白血病に対する三重特異性治療剤
WO2011086091A1 (en) * 2010-01-12 2011-07-21 Ucb Pharma S.A. Multivalent antibodies
US9128101B2 (en) 2010-03-01 2015-09-08 Caris Life Sciences Switzerland Holdings Gmbh Biomarkers for theranostics
US10106600B2 (en) 2010-03-26 2018-10-23 Roche Glycart Ag Bispecific antibodies
US9469876B2 (en) 2010-04-06 2016-10-18 Caris Life Sciences Switzerland Holdings Gmbh Circulating biomarkers for metastatic prostate cancer
EP2596114A4 (en) * 2010-07-14 2014-01-08 Amgen Inc IMMUNOGLOBULIN WITH DOMAIN INSERTION
JP2016054746A (ja) * 2010-08-02 2016-04-21 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｖｌドメインを含む結合タンパク質を作製するマウス
US10954310B2 (en) 2010-08-02 2021-03-23 Regeneran Pharmaceuticals, Inc. Mice that make VL binding proteins
US12486335B2 (en) 2010-08-02 2025-12-02 Regeneron Pharmaceuticals, Inc. Mice that make VL binding proteins
WO2012025525A1 (en) 2010-08-24 2012-03-01 Roche Glycart Ag Activatable bispecific antibodies
EP2609112B1 (en) * 2010-08-24 2017-11-22 Roche Glycart AG Activatable bispecific antibodies
US9879095B2 (en) 2010-08-24 2018-01-30 Hoffman-La Roche Inc. Bispecific antibodies comprising a disulfide stabilized-Fv fragment
EP2609111B1 (en) * 2010-08-24 2017-11-01 F. Hoffmann-La Roche AG Bispecific antibodies comprising a disulfide stabilized-fv fragment
EP2643353A1 (en) * 2010-11-24 2013-10-02 Novartis AG Multispecific molecules
EP2655415A4 (en) * 2010-12-22 2016-03-09 Abbvie Inc THREE VARIABLE DOMAIN LINK PROTEINS AND USES THEREOF
US11618790B2 (en) 2010-12-23 2023-04-04 Hoffmann-La Roche Inc. Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery
US9982036B2 (en) 2011-02-28 2018-05-29 Hoffmann-La Roche Inc. Dual FC antigen binding proteins
US10611825B2 (en) 2011-02-28 2020-04-07 Hoffmann La-Roche Inc. Monovalent antigen binding proteins
US10793621B2 (en) 2011-02-28 2020-10-06 Hoffmann-La Roche Inc. Nucleic acid encoding dual Fc antigen binding proteins
WO2012118903A2 (en) 2011-03-01 2012-09-07 Amgen Inc. Bispecific binding agents
WO2012172521A1 (en) * 2011-06-16 2012-12-20 Novartis Ag Soluble proteins for use as therapeutics
CN103635490A (zh) * 2011-06-16 2014-03-12 诺瓦提斯公司 用作治疗剂的可溶性蛋白
US10815310B2 (en) 2011-07-07 2020-10-27 Centre National De La Recherche Scientifique Multispecific antigen binding fragments and multispecific antibodies derived therefrom comprising mutant CH1 and CL-kappa domains
US9631031B2 (en) 2011-07-07 2017-04-25 Centre National De La Recherche Scientifique Multispecific antigens binding fragments and multispecific antibodies derived therefrom comprising mutant CH1 and CL-κ domains
US12378325B2 (en) 2011-07-07 2025-08-05 Centre National De La Recherche Scientifique Multispecific antigens binding fragments and multspecific antibodies
US11945879B2 (en) 2011-07-07 2024-04-02 Jean Kadouche Multispecific antigens binding fragments and multispecific antibodies
WO2013026831A1 (en) * 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific antigen binding molecules
WO2013026837A1 (en) * 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific t cell activating antigen binding molecules
RU2650775C2 (ru) * 2011-08-23 2018-04-17 Рош Гликарт Аг Биспецифические антигенсвязывающие молекулы
TWI633121B (zh) * 2011-08-23 2018-08-21 羅齊克雷雅公司 雙特異性活化ｔ細胞之抗原結合分子
WO2013026833A1 (en) * 2011-08-23 2013-02-28 Roche Glycart Ag Bispecific t cell activating antigen binding molecules
EA030147B1 (ru) * 2011-08-23 2018-06-29 Роше Гликарт Аг Биспецифические антигенсвязывающие молекулы, активирующие т-клетки
CN103764681A (zh) * 2011-08-23 2014-04-30 罗切格利卡特公司 双特异性抗原结合分子
EP3321286A1 (en) * 2011-08-23 2018-05-16 Roche Glycart AG Bispecific t cell activating antigen binding molecules
EP3892640A1 (en) * 2011-08-23 2021-10-13 Roche Glycart AG Bispecific t cell activating antigen binding molecules
US11098115B2 (en) 2011-09-29 2021-08-24 Apo-T B.V. Multi-specific binding molecules targeting aberrant cells
US9580509B2 (en) 2011-11-07 2017-02-28 Medimmune, Llc Multispecific and multivalent binding proteins and uses thereof
WO2013070565A1 (en) 2011-11-07 2013-05-16 Medimmune, Llc Multispecific and multivalent binding proteins and uses thereof
EP2776061A4 (en) * 2011-11-07 2015-06-10 Medimmune Llc MULTISPECIFIC AND MULTIVALENT BINDING PROTEINS AND USES THEREOF
CN103906533A (zh) * 2011-11-07 2014-07-02 米迪缪尼有限公司 多特异性和多价结合蛋白及其用途
US9718893B2 (en) 2011-12-19 2017-08-01 Synimmune Gmbh Bispecific antibody molecule
WO2013092001A1 (en) * 2011-12-19 2013-06-27 Synimmune Gmbh Bispecific antibody molecule
US10946104B2 (en) 2012-01-13 2021-03-16 Apo-Tb.V. Aberrant cell-restricted immunoglobulins provided with a toxic moiety
US9688758B2 (en) 2012-02-10 2017-06-27 Genentech, Inc. Single-chain antibodies and other heteromultimers
US10906975B2 (en) 2012-02-15 2021-02-02 Novo Nordisk A/S Methods of treating autoimmune disease or chronic inflammation with antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
US10906965B2 (en) 2012-02-15 2021-02-02 Novo Nordisk A/S Methods of treating autoimmune disease or chronic inflammation wtih antibodies that bind peptidoglycan recognition protein 1
US9550830B2 (en) 2012-02-15 2017-01-24 Novo Nordisk A/S Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
US10150809B2 (en) 2012-02-15 2018-12-11 Bristol-Myers Squibb Company Antibodies that bind peptidoglycan recognition protein 1
US9000127B2 (en) 2012-02-15 2015-04-07 Novo Nordisk A/S Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
US9663568B2 (en) 2012-02-15 2017-05-30 Novo Nordisk A/S Antibodies that bind peptidoglycan recognition protein 1
US10189904B2 (en) 2012-02-15 2019-01-29 Novo Nordisk A/S Antibodies that bind and block triggering receptor expressed on myeloid cells-1 (TREM-1)
US9062120B2 (en) 2012-05-02 2015-06-23 Janssen Biotech, Inc. Binding proteins having tethered light chains
US11421022B2 (en) 2012-06-27 2022-08-23 Hoffmann-La Roche Inc. Method for making antibody Fc-region conjugates comprising at least one binding entity that specifically binds to a target and uses thereof
US10106612B2 (en) 2012-06-27 2018-10-23 Hoffmann-La Roche Inc. Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof
US11407836B2 (en) 2012-06-27 2022-08-09 Hoffmann-La Roche Inc. Method for selection and production of tailor-made highly selective and multi-specific targeting entities containing at least two different binding entities and uses thereof
US10457748B2 (en) 2012-12-21 2019-10-29 Ucb Biopharma Sprl Single linker FabFv antibodies and methods of producing same
US11401349B2 (en) 2012-12-21 2022-08-02 UCB Biopharma SRL Single linker FabFv antibodies and methods of producing same
US10351628B2 (en) 2013-01-09 2019-07-16 Metis Precision Medicine Sb S.R.L. Antibody fragments, compositions and uses thereof
US9975952B2 (en) 2013-01-09 2018-05-22 Metis Precision Medicine Sb S.R.L. Antibody fragments, compositions and uses thereof
US11753475B2 (en) 2013-03-15 2023-09-12 Amgen Inc. Bispecific-Fc molecules
WO2014144722A3 (en) * 2013-03-15 2014-11-06 Amgen Inc. Bispecific bivalent scfv-fc molecules
US11161906B2 (en) 2013-07-25 2021-11-02 Cytomx Therapeutics, Inc. Multispecific antibodies, multispecific activatable antibodies and methods of using the same
US10323099B2 (en) 2013-10-11 2019-06-18 Hoffmann-La Roche Inc. Multispecific domain exchanged common variable light chain antibodies
US11702475B2 (en) 2013-10-14 2023-07-18 Janssen Biotech, Inc. Cysteine engineered fibronectin type III domain binding molecules
US11072663B2 (en) 2013-10-14 2021-07-27 Janssen Biotech, Inc. Cysteine engineered fibronectin type III domain binding molecules
US10266608B2 (en) 2013-12-30 2019-04-23 Epimab Biotherapeutics, Inc. Fabs-in-tandem immunoglobulin and uses thereof
US10519251B2 (en) 2013-12-30 2019-12-31 Epimab Biotherapeutics, Inc. Fabs-in-tandem immunoglobulin and uses thereof
US10787522B2 (en) 2014-03-21 2020-09-29 Regeneron Pharmaceuticals, Inc. VL antigen binding proteins exhibiting distinct binding characteristics
US10881085B2 (en) 2014-03-21 2021-01-05 Regeneron Pharmaceuticals, Inc. Non-human animals that make single domain binding proteins
US10633440B2 (en) 2014-05-29 2020-04-28 Macrogenics, Inc. Multi-chain polypeptide-containing tri-specific binding molecules that specifically bind to multiple cancer antigens
US11820818B2 (en) 2014-05-29 2023-11-21 Macrogenics, Inc. Multi-chain polypeptide-containing tri-specific binding molecules
US10647768B2 (en) 2014-05-29 2020-05-12 Macrogenics, Inc. Multi-chain polypeptide-containing tri-specific binding molecules
US11697684B2 (en) 2014-05-29 2023-07-11 Macrogenics, Inc. Tri-specific binding molecules that specifically bind to multiple cancer antigens
EP3954703A2 (en) 2014-05-29 2022-02-16 MacroGenics, Inc. Tri-specific binding molecules and methods of use thereof
WO2015184203A1 (en) 2014-05-29 2015-12-03 Macrogenics, Inc. Tri-specific binding molecules and methods of use thereof
US12428497B2 (en) 2014-06-25 2025-09-30 UCB Biopharma SRL Multispecific antibody constructs
US11345760B2 (en) 2014-06-25 2022-05-31 UCB Biopharma SRL Multispecific antibody constructs
US12116408B2 (en) 2014-07-17 2024-10-15 Novo Nordisk A/S Site directed mutagenesis of TREM-1 antibodies for decreasing viscosity
US11072654B2 (en) 2014-07-17 2021-07-27 Novo Nordisk A/S Site directed mutagenesis of TREM-1 antibodies for decreasing viscosity
US10179814B2 (en) 2014-07-17 2019-01-15 Novo Nordisk A/S Site directed mutagenesis of TREM-1 antibodies for decreasing viscosity
US10669337B2 (en) 2014-07-25 2020-06-02 Cytomx Therapeutics, Inc. Bispecific anti-CD3 antibodies, bispecific activatable anti-CD3 antibodies, and methods of using the same
US11802158B2 (en) 2014-07-25 2023-10-31 Cytomx Therapeutics, Inc. Bispecific anti-CD3 antibodies, bispecific activatable anti-CD3 antibodies, and methods of using the same
US9982061B2 (en) 2014-10-01 2018-05-29 Medimmune Limited Antibodies to ticagrelor and methods of use
US10954308B2 (en) 2014-10-01 2021-03-23 Medimmune Limited Antibodies to ticagrelor and methods of use
WO2016050867A1 (en) 2014-10-01 2016-04-07 Medimmune Limited Antibodies to ticagrelor and methods of use
US11773186B2 (en) 2014-10-01 2023-10-03 Medimmune Limited Antibodies to ticagrelor and methods of use
US10487154B2 (en) 2014-10-01 2019-11-26 Medimmune Limited Antibodies to ticagrelor and methods of use
WO2016054315A1 (en) 2014-10-01 2016-04-07 Medimmune, Llc Method of conjugating a polypeptide
US12391768B2 (en) 2014-10-01 2025-08-19 Medimmune Limited Antibodies to ticagrelor and methods of use
US10662247B2 (en) 2014-10-08 2020-05-26 Novartis Ag Compositions and methods of use for augmented immune response and cancer therapy
US10633457B2 (en) 2014-12-03 2020-04-28 Hoffmann-La Roche Inc. Multispecific antibodies
US11999801B2 (en) 2014-12-03 2024-06-04 Hoffman-La Roche Inc. Multispecific antibodies
US10501552B2 (en) 2015-01-26 2019-12-10 Macrogenics, Inc. Multivalent molecules comprising DR5-binding domains
US11111314B2 (en) 2015-03-19 2021-09-07 Regeneron Pharmaceuticals, Inc. Non-human animals that select for light chain variable regions that bind antigen
EP4303235A2 (en) 2015-06-08 2024-01-10 MacroGenics, Inc. Lag-3-binding moleculkes and methods of use thereof
US12600779B2 (en) 2015-06-08 2026-04-14 Macrogenics, Inc. LAG-3-binding molecules and methods of use thereof
US11858991B2 (en) 2015-06-08 2024-01-02 Macrogenics, Inc. LAG-3-binding molecules and methods of use thereof
US11072653B2 (en) 2015-06-08 2021-07-27 Macrogenics, Inc. LAG-3-binding molecules and methods of use thereof
WO2017011559A1 (en) 2015-07-14 2017-01-19 Medlmmune, Llc Compositions and methods for treating cancer
WO2017019846A1 (en) 2015-07-30 2017-02-02 Macrogenics, Inc. Pd-1-binding molecules and methods use thereof
US12534531B2 (en) 2015-07-30 2026-01-27 Macrogenics, Inc. PD-1-binding molecules and methods of use thereof
US11623959B2 (en) 2015-07-30 2023-04-11 Macrogenics, Inc. PD-1-binding molecules and methods of use thereof
EP3456346A1 (en) 2015-07-30 2019-03-20 MacroGenics, Inc. Pd-1 and lag-3 binding molecules and methods of use thereof
EP3981792A1 (en) 2015-07-30 2022-04-13 MacroGenics, Inc. Pd-1-binding molecules and methods of use thereof
US10577422B2 (en) 2015-07-30 2020-03-03 Macrogenics, Inc. PD-1-binding molecules and methods of use thereof
EP4450088A2 (en) 2015-07-30 2024-10-23 MacroGenics, Inc. Pd-1-binding molecules and methods of use thereof
WO2017059243A2 (en) 2015-09-30 2017-04-06 Janssen Biotech, Inc. Agonistic antibodies specifically binding human cd40 and methods of use
US11286300B2 (en) 2015-10-01 2022-03-29 Hoffmann-La Roche Inc. Humanized anti-human CD19 antibodies and methods of use
US11174315B2 (en) 2015-10-08 2021-11-16 Macrogenics, Inc. Combination therapy for the treatment of cancer
US10894830B2 (en) 2015-11-03 2021-01-19 Janssen Biotech, Inc. Antibodies specifically binding PD-1, TIM-3 or PD-1 and TIM-3 and their uses
WO2017079115A1 (en) 2015-11-03 2017-05-11 Janssen Biotech, Inc. Antibodies specifically binding tim-3 and their uses
WO2017079116A2 (en) 2015-11-03 2017-05-11 Janssen Biotech, Inc. Antibodies specifically binding pd-1 and tim-3 and their uses
US12173064B2 (en) 2015-11-03 2024-12-24 Janssen Biotech, Inc. Antibodies specifically binding PD-1, TIM-3 or PD-1 and TIM-3 and their uses
WO2017079112A1 (en) 2015-11-03 2017-05-11 Janssen Biotech, Inc. Antibodies specifically binding pd-1 and their uses
EP4046655A1 (en) 2015-11-03 2022-08-24 Janssen Biotech, Inc. Antibodies specifically binding pd-1 and their uses
WO2017106061A1 (en) 2015-12-14 2017-06-22 Macrogenics, Inc. Bispecific molecules having immunoreactivity with pd-1 and ctla-4, and methods of use thereof
US11840571B2 (en) 2015-12-14 2023-12-12 Macrogenics, Inc. Methods of using bispecific molecules having immunoreactivity with PD-1 and CTLA-4
US10954301B2 (en) 2015-12-14 2021-03-23 Macrogenics, Inc. Bispecific molecules having immunoreactivity with PD-1 and CTLA-4, and methods of use thereof
WO2017132298A1 (en) 2016-01-27 2017-08-03 Medimmune, Llc Methods for preparing antibodies with a defined glycosylation pattern
US11421028B2 (en) 2016-02-06 2022-08-23 Epimab Biotherapeutics, Inc. Fabs-in-tandem immunoglobulin and uses thereof
WO2017142928A1 (en) 2016-02-17 2017-08-24 Macrogenics, Inc. Ror1-binding molecules, and methods of use thereof
WO2017180813A1 (en) 2016-04-15 2017-10-19 Macrogenics, Inc. Novel b7-h3 binding molecules, antibody drug conjugates thereof and methods of use thereof
US10961311B2 (en) 2016-04-15 2021-03-30 Macrogenics, Inc. B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof
US11591400B2 (en) 2016-04-15 2023-02-28 Macrogenics, Inc. B7-H3 directed antibody drug conjugates
WO2017193032A2 (en) 2016-05-06 2017-11-09 Medimmune, Llc Bispecific binding proteins and uses thereof
CN105907760A (zh) * 2016-05-31 2016-08-31 东北师范大学 靶向沉默TKS4的shRNA
CN109415435A (zh) * 2016-07-04 2019-03-01 豪夫迈·罗氏有限公司 新型抗体形式
CN109415435B (zh) * 2016-07-04 2024-01-16 豪夫迈·罗氏有限公司 新型抗体形式
WO2018007314A1 (en) * 2016-07-04 2018-01-11 F. Hoffmann-La Roche Ag Novel antibody format
WO2018031258A1 (en) 2016-08-12 2018-02-15 Janssen Biotech, Inc. Engineered antibodies and other fc-domain containing molecules with enhanced agonism and effector functions
US11359029B2 (en) 2016-08-12 2022-06-14 Janssen Biotech, Inc. FC engineered anti-TNFR superfamily member antibodies having enhanced agonistic activity and methods of using them
WO2018118780A1 (en) * 2016-12-19 2018-06-28 Calico Biolabs, Inc. Monovalent and divalent binding proteins
US11242402B2 (en) 2016-12-23 2022-02-08 Macrogenics, Inc. ADAM9-binding molecules, and methods of use thereof
WO2018119166A1 (en) 2016-12-23 2018-06-28 Macrogenics, Inc. Adam9-binding molecules, and methods of use thereof
EP4653464A2 (en) 2016-12-23 2025-11-26 MacroGenics, Inc. Adam9-binding molecules, and methods of use thereof
EP4389226A2 (en) 2017-02-24 2024-06-26 MacroGenics, Inc. Bispecific binding molecules that are capable of binding cd137 and tumor antigens, and uses thereof
US11942149B2 (en) 2017-02-24 2024-03-26 Macrogenics, Inc. Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof
US11459394B2 (en) 2017-02-24 2022-10-04 Macrogenics, Inc. Bispecific binding molecules that are capable of binding CD137 and tumor antigens, and uses thereof
US11866507B2 (en) 2017-04-11 2024-01-09 Inhibrx, Inc. Multispecific polypeptide constructs having constrained CD3 binding and methods of using the same
EP4223319A2 (en) 2017-05-26 2023-08-09 MedImmune, LLC Method and molecules
US10995149B2 (en) 2017-06-05 2021-05-04 Janssen Biotech, Inc. Antibodies that specifically bind PD-1 and methods of use
US11746161B2 (en) 2017-06-05 2023-09-05 Janssen Biotech, Inc. Antibodies that specifically bind PD-1 and methods of use
CN111065650A (zh) * 2017-07-21 2020-04-24 特里安尼公司 单链VH-L1-Cκ-L2-CH1-抗体
US11414478B2 (en) 2017-07-21 2022-08-16 Trianni, Inc. Single chain VH and heavy chain antibodies
WO2019018770A1 (en) * 2017-07-21 2019-01-24 Trianni, Inc. SINGLE CHAIN VH-L1-CK1-L2-CH1 ANTIBODY
WO2019024979A1 (en) * 2017-07-31 2019-02-07 Institute For Research In Biomedicine FUNCTIONAL DOMAIN ANTIBODIES IN THE ELBOW REGION
AU2018311032B2 (en) * 2017-07-31 2025-01-23 Institute For Research In Biomedicine Antibodies with functional domains in the elbow region between variable and constant domain
WO2019025391A1 (en) * 2017-07-31 2019-02-07 Institute For Research In Biomedicine ANTIBODIES HAVING FUNCTIONAL DOMAINS IN THE ELBOW REGION BETWEEN A VARIABLE DOMAIN AND A CONSTANT DOMAIN
US12331108B2 (en) 2017-07-31 2025-06-17 Institute For Research In Biomedicine Antibodies with functional domains in the elbow region between variable and constant domain
US11859010B2 (en) 2017-10-14 2024-01-02 Cytomx Therapeutics, Inc. Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof
US12460017B2 (en) 2017-10-14 2025-11-04 Cytomx Therapeutics, Inc. Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof
US11472889B2 (en) 2017-10-14 2022-10-18 Cytomx Therapeutics, Inc. Antibodies, activatable antibodies, bispecific antibodies, and bispecific activatable antibodies and methods of use thereof
US11795226B2 (en) 2017-12-12 2023-10-24 Macrogenics, Inc. Bispecific CD16-binding molecules and their use in the treatment of disease
US12398209B2 (en) 2018-01-22 2025-08-26 Janssen Biotech, Inc. Methods of treating cancers with antagonistic anti-PD-1 antibodies
US11685781B2 (en) 2018-02-15 2023-06-27 Macrogenics, Inc. Variant CD3-binding domains and their use in combination therapies for the treatment of disease
EP3752196A1 (en) 2018-02-15 2020-12-23 MacroGenics, Inc. Variant cd3-binding domains and their use in combination therapies for the treatment of disease
US11155618B2 (en) 2018-04-02 2021-10-26 Bristol-Myers Squibb Company Anti-TREM-1 antibodies and uses thereof
US11919954B2 (en) 2018-04-02 2024-03-05 Bristol-Myers Squibb Company Anti-TREM-1 antibodies and uses thereof
US11952420B2 (en) 2018-04-02 2024-04-09 Bristol-Myers Squibb Company Nucleic acids encoding anti-TREM-1 antibodies
US12331132B2 (en) 2018-04-11 2025-06-17 Inhibrx Biosciences, Inc. Multispecific polypeptide constructs having constrained CD3 binding and related methods and uses
US12060425B2 (en) 2018-05-03 2024-08-13 Shanghai Epimab Biotherapeutics Co., Ltd. High affinity antibodies to PD-1 and LAG-3 and bispecific binding proteins made therefrom
WO2019224718A2 (en) 2018-05-24 2019-11-28 Janssen Biotech, Inc. Psma binding agents and uses thereof
WO2019224713A2 (en) 2018-05-24 2019-11-28 Janssen Biotech, Inc. Monospecific and multispecific anti-tmeff2 antibodies and there uses
US11603405B2 (en) 2018-05-24 2023-03-14 Janssen Biotech, Inc. Anti-CD3 antibodies and uses thereof
US11746157B2 (en) 2018-05-24 2023-09-05 Janssen Biotech, Inc. PSMA binding agents and uses thereof
US11866499B2 (en) 2018-05-24 2024-01-09 Janssen Biotech, Inc. Monospecific and multispecific anti-TMEFF2 antibodies and their uses
WO2019224717A2 (en) 2018-05-24 2019-11-28 Janssen Biotech, Inc. Anti-cd3 antibodies and uses thereof
US12195533B2 (en) 2018-07-24 2025-01-14 Inhibrx Biosciences, Inc. Multispecific polypeptide constructs containing a constrained CD3 binding domain and a receptor binding region and methods of using the same
US12365728B2 (en) 2018-10-11 2025-07-22 Inhibrx Biosciences, Inc. DLL3 single domain antibodies and therapeutic compositions thereof
US12590169B2 (en) 2018-10-11 2026-03-31 Inhibrx Biosciences, Inc. 5T4 single domain antibodies and therapeutic compositions thereof
WO2020097395A1 (en) * 2018-11-08 2020-05-14 The Regents Of The University Of California Systems and methods for targeting cancer cells
US12466892B2 (en) 2018-11-08 2025-11-11 The Regents Of The University Of California Systems and methods for targeting cancer cells
US11459391B2 (en) 2019-02-26 2022-10-04 Janssen Biotech, Inc. Combination therapies and patient stratification with bispecific anti-EGFR/c-Met antibodies
US12215161B2 (en) 2019-02-26 2025-02-04 Janssen Biotech, Inc. Combination therapies and patient stratification with bispecific anti-EGFR/c-Met antibodies
US20200319174A1 (en) * 2019-04-17 2020-10-08 Jiangnan University Method for Detecting Human Soluble Asialoglycoprotein Receptor
US11591395B2 (en) 2019-04-19 2023-02-28 Janssen Biotech, Inc. Methods of treating prostate cancer with an anti-PSMA/CD3 antibody
US11667712B2 (en) 2019-05-08 2023-06-06 Janssen Biotech, Inc. Materials and methods for modulating t cell mediated immunity
US12599606B2 (en) 2019-05-14 2026-04-14 Janssen Biotech, Inc. Therapies with 3rd generation EGFR tyrosine kinase inhibitors
US12448455B2 (en) 2019-05-14 2025-10-21 Janssen Biotech, Inc. Combination therapies with bispecific anti-EGFR/c-met antibodies and third generation EGFR tyrosine kinase inhibitors
US11879013B2 (en) 2019-05-14 2024-01-23 Janssen Biotech, Inc. Combination therapies with bispecific anti-EGFR/c-Met antibodies and third generation EGFR tyrosine kinase inhibitors
US12221481B2 (en) 2019-05-21 2025-02-11 Novartis Ag CD19 binding molecules and uses thereof
US12617870B2 (en) 2019-09-20 2026-05-05 SFJ Pharmaceutical X, LTD. Methods of reversing ticagrelor activity
EP4054649A4 (en) * 2019-11-06 2023-12-06 Systimmune, Inc. GUIDANCE AND NAVIGATION REGULATORY PROTEINS AND METHODS OF PRODUCTION AND USE THEREOF
US12522661B2 (en) 2020-01-29 2026-01-13 Inhibrx Biosciences, Inc. CD28 single domain antibodies and multivalent and multispecific constructs thereof
US12215160B2 (en) 2020-02-12 2025-02-04 Janssen Biotech, Inc. Treatment of patients having c-met exon 14 skipping mutations
EP4114373A4 (en) * 2020-03-03 2024-05-01 Systimmune, Inc. ANTI-CD19 ANTIBODIES AND THEIR METHODS OF USE AND PREPARATION
RU2834996C1 (ru) * 2020-03-03 2025-02-20 Систиммьюн, Инк. Антитела против cd19 и способы их применения и получения
EP4121458A4 (en) * 2020-03-17 2024-10-16 Systimmune, Inc. Guidance and navigation control (gnc) antibody-like proteins and methods of making and using thereof
EP4121461A4 (en) * 2020-03-17 2024-08-07 Systimmune, Inc. Miniature guidance and navigation control (minignc) antibody-like proteins and methods of making and using thereof
RU2838544C1 (ru) * 2020-03-17 2025-04-21 Систиммьюн, Инк. МИНИАТЮРНЫЕ АНТИТЕЛОПОДОБНЫЕ БЕЛКИ УПРАВЛЕНИЯ И НАВИГАЦИОННОГО КОНТРОЛЯ (miniGNC) И СПОСОБЫ ИХ ПОЛУЧЕНИЯ И ПРИМЕНЕНИЕ
US12460001B2 (en) 2020-05-27 2025-11-04 Janssen Biotech, Inc. Proteins comprising CD3 antigen binding domains and uses thereof
WO2022010798A1 (en) 2020-07-06 2022-01-13 Kiromic BioPharma, Inc. Mesothelin isoform binding molecules and chimeric pd1 receptor molecules, cells containing the same and uses thereof
US12528869B2 (en) 2020-08-25 2026-01-20 Janssen Biotech, Inc. Treatment of non-small cell lung cancer with EGFR mutations
US12076413B2 (en) 2020-10-28 2024-09-03 Janssen Biotech, Inc. Compositions and methods for modulating delta gamma chain mediated immunity
WO2022108627A1 (en) 2020-11-18 2022-05-27 Kiromic Biopharma, Inc.Kiromic Biopharma, Inc. Gamma-delta t cell manufacturing processes and chimeric pd1 receptor molecules
WO2022162518A2 (en) 2021-01-28 2022-08-04 Janssen Biotech, Inc. Psma binding proteins and uses thereof
WO2022189942A1 (en) 2021-03-09 2022-09-15 Janssen Biotech, Inc. Treatment of cancers lacking egfr-activating mutations
WO2022243900A1 (en) 2021-05-18 2022-11-24 Janssen Biotech, Inc. Methods for identifying cancer patients for combination treatment
WO2023105479A1 (en) 2021-12-09 2023-06-15 Janssen Biotech, Inc. Use of amivantamab to treat colorectal cancer
WO2023148702A1 (en) 2022-02-07 2023-08-10 Janssen Biotech, Inc. Methods for reducing infusion-related reactions in patients treated with egfr/met bispecific antibodies
WO2023192850A1 (en) 2022-03-29 2023-10-05 Ngm Biopharmaceuticals, Inc. Ilt3 and cd3 binding agents and methods of use thereof
WO2024003837A1 (en) 2022-06-30 2024-01-04 Janssen Biotech, Inc. Use of anti-egfr/anti-met antibody to treat gastric or esophageal cancer
WO2024089551A1 (en) 2022-10-25 2024-05-02 Janssen Biotech, Inc. Msln and cd3 binding agents and methods of use thereof
WO2024189544A1 (en) 2023-03-13 2024-09-19 Janssen Biotech, Inc. Combination therapies with bi-specific anti-egfr/c-met antibodies and anti-pd-1 antibodies
WO2024241273A1 (en) 2023-05-23 2024-11-28 Janssen Biotech, Inc. Methods for treatment of non-small cell lung cancer (nsclc)
WO2024255841A1 (zh) 2023-06-16 2024-12-19 复旦大学 乙肝病毒表面抗体及其应用
WO2025032508A1 (en) 2023-08-07 2025-02-13 Janssen Biotech, Inc. Enpp3 and cd3 binding agents and methods of use thereof
WO2025032510A1 (en) 2023-08-07 2025-02-13 Janssen Biotech, Inc. Stabilized cd3 antigen binding agents and methods of use thereof
WO2025052273A1 (en) 2023-09-05 2025-03-13 Janssen Biotech, Inc. Methods of treating non-small cell lung cancer
WO2025079020A1 (en) 2023-10-12 2025-04-17 Janssen Biotech, Inc. First line treatment in egfr exon 20 insertion-mutated advanced non-small cell lung cancer
WO2025126102A1 (en) 2023-12-12 2025-06-19 Janssen Biotech, Inc. Enpp3 × cd3 bispecific antibodies and use thereof
WO2025153988A1 (en) 2024-01-16 2025-07-24 Janssen Biotech, Inc. Use of amivantamab to treat colorectal cancer
WO2025158277A1 (en) 2024-01-22 2025-07-31 Janssen Biotech, Inc. Use of amivantamab to treat head and neck cancer
WO2025191459A1 (en) 2024-03-11 2025-09-18 Janssen Biotech, Inc. Use of bispecific anti-egfr/c-met antibodies to treat solid tumors
WO2026038161A1 (en) 2024-08-13 2026-02-19 Janssen Biotech, Inc. Methods for reducing dermatologic adverse events in patients treated with egfr/met bispecific antibodies
WO2026038160A1 (en) 2024-08-13 2026-02-19 Janssen Biotech, Inc. Methods for reducing infusion-related reactions in patients treated with egfr/met bispecific antibodies
WO2026042017A1 (en) 2024-08-19 2026-02-26 Janssen Biotech, Inc. Amivantamab in combination with lazertinib for the treatment of non-small cell lung cancer (nsclc)

Also Published As

Publication number Publication date
KR20100058509A (ko) 2010-06-03
EP2626371A1 (en) 2013-08-14
AU2008282218A1 (en) 2009-02-05
EP2069401A1 (en) 2009-06-17
JP2010535032A (ja) 2010-11-18
US20100233173A1 (en) 2010-09-16
US20090155275A1 (en) 2009-06-18
CN101952312A (zh) 2011-01-19
CA2694488A1 (en) 2009-02-05
US20130295098A1 (en) 2013-11-07
EP2069401A4 (en) 2011-02-23

Similar Documents

Publication Publication Date Title
EP2626371A1 (en) Multispecific epitope binding proteins and uses thereof
JP7165175B2 (ja) 部位特異的コンジュゲーションのための操作された抗体定常領域、ならびにそのための方法および使用
AU2010270979B2 (en) Engineered Fc regions for site-specific conjugation
JP6014596B2 (ja) 均一コンジュゲーションのための抗体足場
AU2015243380B2 (en) Conjugated compounds comprising cysteine-engineered antibodies
JP2020522266A (ja) 非対称なｃｈ２−ｃｈ３領域の変異を有する、操作された多重特異性抗体及び他の多量体タンパク質
WO2015173756A2 (en) Bispecific antibodies
AU2015205870A1 (en) ENGINEERED Fc REGIONS FOR SITE-SPECIFIC CONJUGATION
HK1196090A (en) Engineered fc regions for site-specific conjugation

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200880101023.4

Country of ref document: CN

WWE Wipo information: entry into national phase

Ref document number: 2008796901

Country of ref document: EP

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08796901

Country of ref document: EP

Kind code of ref document: A1

WWE Wipo information: entry into national phase

Ref document number: 2008282218

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 491/DELNP/2010

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2694488

Country of ref document: CA

ENP Entry into the national phase

Ref document number: 2008282218

Country of ref document: AU

Date of ref document: 20080730

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2010520165

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 20107004171

Country of ref document: KR

Kind code of ref document: A