WO2005061547A2 - Bispecific antibodies - Google Patents
Bispecific antibodies Download PDFInfo
- Publication number
- WO2005061547A2 WO2005061547A2 PCT/EP2004/014643 EP2004014643W WO2005061547A2 WO 2005061547 A2 WO2005061547 A2 WO 2005061547A2 EP 2004014643 W EP2004014643 W EP 2004014643W WO 2005061547 A2 WO2005061547 A2 WO 2005061547A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antigen
- bispecific antibody
- human
- antibody
- cell
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
- A01K67/027—New breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0276—Knockout animals
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- 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
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70567—Nuclear receptors, e.g. retinoic acid receptor [RAR], RXR, nuclear orphan receptors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2809—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against the T-cell receptor (TcR)-CD3 complex
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/07—Animals genetically altered by homologous recombination
- A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/0306—Animal model for genetic diseases
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0362—Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
-
- 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
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
-
- 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
- C07K2319/00—Fusion polypeptide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
- C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/48—Vector systems having a special element relevant for transcription regulating transport or export of RNA, e.g. RRE, PRE, WPRE, CTE
Definitions
- the invention relates to the field of antibodies. Specifically, the invention relates to a bispecific antibody comprising two antibody variable domains on a single polypeptide chain. The invention further relates to the use of such a bispecific antibody for the preparation of a pharmaceutical composition. The invention further relates to a method for the prevention, treatment or amelioration of a disease comprising administration of an effective amount of such a bispecific antibody. Finally, the invention relates to a kit comprising such a bispecific antibody.
- bispecific antibodies Unifying two antigen binding sites of different specificity into a single construct, bispecific antibodies have the ability to bring together two discreet antigens with extraordinar specificity and therefore have great potential as therapeutic agents. This potential was recognized early on, leading to a number of approaches for obtaining such bispecific antibodies.
- Bispecific antibodies were originally made by fusing two hybridomas, each capable of producing a different immunoglobulin. The resulting hybrid-hybridoma, or quadroma, was capable of producing antibodies bearing the antigen specificity of the first parent hybridoma as well as that of the second parent hybridoma (Milstein et al., 1983. Nature 305, 537). However, the antibodies resulting from quadromas often exhibited undesired properties due to the presence of an Fc antibody portion.
- Each scFv unit in such constructs was made up of one variable domain from each of the heavy (NH) and light (NL) antibody chains, joined with one another via a synthetic polypeptide linker, the latter often being genetically engineered so as to be minimally immuno genie while remaining maximally resistant to proteolysis.
- Respective scFv units were joined by a number of techniques including incorporation of a short (usually less than 10 amino acids) polypeptide spacer bridging the two scFv units, thereby creating a bispecific single chain antibody.
- the resulting bispecific single chain antibody is therefore a species containing two VH/VL pairs of different specificity on a single polypeptide chain, wherein the NH and NL domains in a respective scFv unit are separated by a polypeptide linker long enough to allow intramolecular association between these two domains, and wherein the thusly formed scFv units are contiguously tethered to one another through a polypeptide spacer kept short enough to prevent unwanted association between, for example, the NH domain of one scFv unit and the NL of the other scFv unit.
- Bispecific single chain antibodies of the general form described above have the advantage that the nucleotide sequence encoding the four N-domains, two linkers and one spacer can be incorporated into a suitable host expression organism under the control of a single promoter. This increases the flexibility with which these constructs can be designed as well as the degree of experimenter control during their production.
- one scFv unit is capable of activating cytotoxic cells, for example cytotoxic T cells, within the immune system by specifically binding to an antigen on the cytotoxic cells, while the other scFv unit specifically binds an antigen on a malignant cell intended for destruction.
- cytotoxic cells for example cytotoxic T cells
- the other scFv unit specifically binds an antigen on a malignant cell intended for destruction.
- bispecific single chain antibodies must fulfil additional requirements. Ixi order to achieve the desired activity, each scFv unit of a bispecific single chain antibody should remain properly folded, something which often proves unrealisable in conventional bacterial expression systems such as E.coli.
- the need to use less conventional, more cumbersome and more costly eukaryotic - even mammalian - expression systems often complicates the production of bispecific single chain antibodies and/or reduces the amount of product obtainable to levels lower than desired for therapeutic application.
- bispecific antibody In the event that a bispecific antibody is intended for therapeutic use, it is desirable to produce high amounts of this antibody solubly and in the desired functional form.
- the production of functionally active antibody becomes especially critical when producing bispecific antibodies of which one portion is able to activate and recruit the cytotoxic potential of human immune effector cells.
- a produced antibody devoid of functional activity will not lead to the desired activation of human immune effector cells
- a bispecific antibody which is functionally active albeit not in the desired manner, as for example may be the case when the bispecific antibody is produced in a heterogeneous form containing multiple isomers, may activate and recruit the cytotoxic potential of human immune effector cells in unforeseeable and/or unintended manners.
- bispecific antibody constructs can be of great therapeutic use in redirecting the powerful potential of the body's own immune system to achieve the destruction of diseased cells.
- the activation of such a powerful means of eradicating or neutralizing unwanted cells requires that this power be controlled as precisely as possible so that the cytotoxic potential of the immune system is recruited and applied only in the direction intended and no other.
- bispecific single chain antibody when one specific binding arm of a bispecific single chain antibody is to recruit the activity of a human immune effector cell, for example a cytotoxic T cell, there exists an especially heightened and, as yet, unmet need for bispecific single chain antibodies which overcome limitations as described above.
- a bispecific antibody comprising two antibody variable domains on a single polypeptide chain, wherein a first portion of the bispecific antibody is capable of recruiting the activity of a human immune effector cell by specifically binding to an effector antigen located on the human immune effector cell, said first portion consisting of one antibody variable domain, and a second portion of the bispecific antibody is capable of specifically binding to a target antigen other than the effector antigen, said target antigen being located on a target cell other than said human immune effector cell, and said second portion comprising an antibody variable domain (first aspect of the present invention).
- the second portion, of the bispecific antibody ' comprises two antibody variable domains.
- the second portion of the bispecific antibody comprises one antibody variable domain.
- the second aspect of the invention provides a bispecific antibody comprising two antibody variable domains on a single polypeptide chain, wherein a first portion of the bispecific antibody is capable of recruiting the activity of a human immune effector cell by specifically binding to an effector antigen located on the human immune effector cell, said first portion comprising an antibody variable domain, and a second portion of the bispecific antibody is capable of specifically binding to a target antigen other than the effector antigen, said target antigen being located on a target cell other than said human immune effector cell, and said second portion consisting of one antibody variable domain.
- the first portion of the bispecific antibody comprises two antibody variable domains.
- the total number of antibody variable regions in the bispecific antibody according to the invention is thus only two.
- the bispecific antibody of the invention is thus approximately half the size of conventional bispecific single chain antibodies containing four antibody variable domains.
- the greater simplicity in molecular design of the bispecific antibody of the invention conelates to greater possible simplicity in the host expression system used for its production in functionally active form.
- the small size of the inventive bispecific antibody opens up avenues of production hitherto closed to conventional bispecific single chain antibodies with four antibody variable domains.
- the bispecific antibody of the invention may be easily produced in conventional, well understood and cheap bacterial expression systems such as E.coli in amounts which are desired for therapeutic applications.
- Increased productivity has at least two highly advantageous effects.
- larger amounts of the bispecific antibody of the invention can be produced in functional form per batch than previously possible for single chain bispecific antibodies with four antibody variable domains, allowing greater efficiency and, ultimately, economy in production.
- Second, a greater number of constructs in the format of the bispecific antibody of the invention may now be considered as therapeutic candidates since a low cytotoxic activity of a bispecific construct with four antibody variable domains may now be offset by higher amounts of available therapeutic agent using the bispecific antibody of the invention.
- the palette of possible therapeutic applications for the bispecific antibody of the invention is thereby expanded relative to that of single chain bispecific antibodies with four antibody variable domains.
- the bispecific antibody of the invention can be produced more homogeneously than possible for single chain antibody formats with four antibody variable domains.
- product heterogeneity may threaten the therapeutic prognosis and/or product safety profile which can be expected from a bispecific antibody capable of binding to an immune effector cell.
- Decreasing the number of antibody variable domains in the bispecific antibody of the invention decreases the number of potential partners for intermolecular association. This eliminates pathways by which intermolecular association can take place.
- a bispecific antibody is thus obtained which retains the intended therapeutic profile while minimizing or even abolishing formation of intermolecular association products which might mobilize the host immune response in unintended manners.
- the two antibody variable domains are a NH- and NL-domain which are associated with one another.
- the two antibody variable domains comprised in either the second or the first portion may be two NH domains or two VL regions which are associated with one another.
- the two antibody variable domains may be designed as an scFv fragment, meaning that the two domains are separated from one another by a peptide linker long enough to allow intermolecular association between these two domains.
- linkers suitable for this purpose is described in the prior art, for example in the granted patents EP 623679 BI, US 5258498, EP 573551 BI and US 5525491.
- a bispecific antibody according to this embodiment of the invention is a construct with a total of three antibody variable domains.
- one antibody variable domain specifically binds alone, i.e. without being paired with another antibody variable domain (a) either to a human immune effector cell by specifically binding to an effector antigen on the human immune effector cell or to a target cell, while the remaining two antibody variable domains together specifically bind (b) either to the target antigen on the target cell or to a human immune effector cell by specifically binding to an effector antigen on the human immune effector cell, respectively.
- an scFv exhibiting the desired binding specificity for a target antigen is already known and optimized, and omitting one of its two antibody variable domains would abolish or at least attenuate its binding characteristics.
- Such an scFv may make up part of the bispecific antibody according to the present embodiment of the invention.
- such a three-domain antibody may advantageously comprise an entire scFv as either its effector antigen- or target antigen-conferring portion.
- the present embodiment of the invention allows a bispecific antibody to be formed starting from a desired scFv by simple incorporation of only one additional antibody variable domain into the same polypeptide chain as the scFv, wherein the one additional antibody variable domain incorporated has an antigen binding specificity different than that of the scFv.
- a bispecific antibody according to this embodiment of the invention and including no more than three antibody variable domains would represent trie upper limit in number of antibody variable domains for which high yielding, homogeneous production is possible while still allowing the researcher to employ preexisting binding molecules such as scFv constructs.
- the molecular architecture according to this embodiment allows for savings in research time and resources while still conferring the advantages associated with the bispecific antibody of the invention in its minimal form.
- the first and second portions of the bispecific antibody according to the invention or according to any of the above embodiments of the invention may be separated from one another by a synthetic polypeptide spacer moiety, which covalently (i.e. peptidically) links either the C-terminus of the first portion with the N- terminus of the second portion, or the C-terminus of the second portion with the N-terminus of the first portion.
- the portions of the bispecific antibody according to this embodiment may be ananged, as either N-(first portion)-(second portion)-C or N-(second portion)-(first portion)-C.
- human immune effector cell refers to a cell within the natural repertoire of cells in the human immune system which, when activated, is able to bring about a change in the viability of a target cell.
- viability of a target cell may refer within the scope of the invention to the target cell's ability to survive, proliferate and/or interact with other cells. Such interaction may be either direct, for example when the target cell contacts another cell, or indirect, for example when the target cell secretes substances which have an influence on the functioning of another distant cell.
- the target cell may be either native or foreign to humans. In the event that the cell is native to humans, the target cell is advantageously a cell which has undergone transformation to become a malignant cell.
- the native cell may additionally be a pathologically modified native cell, for example a native cell infected with an organism such as a virus, a plasmodium or a bacterium.
- the target cell is advantageously an invading pathogen, for example an invading bacterium or plasmodium.
- the antibody variable domains of the first and/or second portions may be derived from identical or separate animal species. This has the advantage that for each portion of the bispecific antibody, optimal antibody variable domain/s can be chosen to be derived from the animal species known to yield the best antibodies against a particular effector and/or target antigen. In this way, this embodiment allows the researcher to capitalize on already known, developed and/or optimized specificities such that the efficiency of workflow in developing bispecific antibodies as described herein is maximized.
- the first and/or second portion of the bispecific antibody are/is independently derived from an antibody produced in primate, rodent, tylopoda or cartilaginous fish.
- the first and/or second portion of a bispecific antibody according to this embodiment may be either naturally occurring or genetically engineered. Alternatively, it is within the scope of the present embodiment that part of a naturally occurring antibody is used as a substrate on which further genetic engineering is performed, to finally yield a derivative of the naturally occurring part of the antibody for use in the first or second portion of a bispecific antibody according to this embodiment.
- first and/or second portion of the bispecific antibody are/is derived from rodent
- said first and/or second portion may advantageously be derived independently from mouse or rat antibodies.
- one seeking to develop and/or optimize bispecific antibodies according to this embodiment of the invention can benefit from the preexisting and highly diverse palette of known murine and rat antibody sequences which bind relevant human antigens.
- a primate antibody is used as a basis for the first and/or second portion of the bispecific antibody
- said first and/or second portion are/is advantageously derived independently from human antibodies.
- use of human antibody variable domains entails the fiirther advantage that the resulting bispecific antibodies will elicit little to no immunogenic response when administered as part of a therapeutic regimen in human patients.
- Such bispecific antibodies are thus especially suitable as therapeutic agents for use in humans.
- a tylopoda-derived antibody variable domain is used in the first and/or second portion of a bispecific antibody according to this embodiment of the invention
- said first and/or second portion may advantageously be derived independently from camel, llama or/and dromedary.
- This use of such "camelid" antibodies allows the researcher seeking to develop or optimize bispecific antibodies according to this embodiment of the invention to capitalize on the unique types of antibodies known to be produced by these species. These species are namely known to produce high affinity antibodies of only a single variable domain.
- a tylopoda antibody is used as the source for the antibody variable domain in the first and/or second portion of the bispecific antibody, it is advantageous to use the NHH domain or a modified variant thereof.
- NHH denotes a variable region of a heavy chain of a so-called “camelid” antibody.
- Camelid antibodies comprise a heavy chain, but lack a light chain.
- a NHH region from such a camelid antibody represents the minimal structural element required to specifically bind to an antigen of interest in these species.
- Camelid NHH domains have been found to bind to antigen with high affinity (Desmyter et al. 2001. J Biol Chem 276, 26285-90) and possess high stability in solution (Ewert et al. 2002. Biochemistry 41, 3628-36).
- said cartilaginous fish is advantageously a shark.
- a rodent or primate antibody is used as the source for the antibody variable domain in the first and/or second portion of a bispecific antibody according to this embodiment of the invention, it is advantageous to use the NH domain or a modified variant thereof.
- the NH domain of antibodies in these species is known to contribute significantly to the binding specificity and affinity observed for a given antibody.
- the bispecific antibody may be subjected to an alteration to render it less immunogenic when administered to a human.
- an alteration may comprise one or more of the techniques commonly known as chimerization, humanization, CDR-grafting, deimmunization and/or mutation of framework region amino acids to correspond to the closest human germline sequence (germlining).
- Subjecting the bispecific antibody of the invention to such an alteration/s has the advantage that a bispecific antibody which would otherwise elicit a host immune response is rendered more, or completely "invisible" to the host immune system, so that such an immune response does not occur or is reduced.
- Bispecific antibodies which have been altered as described according to this embodiment will therefore remain administrable for a longer period of time with reduced or no immune response-related side effects than corresponding bispecific antibodies which have not undergone any such alteration(s).
- One of ordinary skill in the art will understand how to determine whether, and to what degree an antibody must be altered in order to prevent it from eliciting an unwanted host immune response.
- the human immune effector cell is a member of the human lymphoid cell lineage
- the effector cell may advantageously be a human T cell, a human B cell or a human natural killer (N ) cell.
- such cells will have either a cytotoxic or an apoptotic effect on the target cell.
- the human lymphoid cell is a cytotoxic T cell which, when activated, exerts a cytotoxic effect on the target cell.
- the recruited activity of the human effector cell is this cell's cytotoxic activity.
- activation of the cytotoxic T cell may occur via binding of the CD3 antigen as effector antigen on the surface of the cytotoxic T cell by a bispecific antibody of this embodiment of the invention.
- the human CD3 antigen is present on both helper T cells and cytotoxic T cells.
- Human CD3 denotes an antigen which is expressed on T cells as part of the multimolecular T cell complex and which comprises three different chains: CD3-epsilon, CD3-delta and CD3-gamma.
- TCR T cell receptor
- MHC major histocompatibility complex
- variable TCR binds foreign antigen as outlined above, signaling to the T cell that this binding has taken place depends on the presence of other, invariant, signaling proteins associated with the TCR. These signaling proteins in associated form are collectively refened to as the CD3 complex, here collectively refened to as the CD3 antigen.
- T cell cytotoxicity normally depends first on the binding of the TCR with an MHC protein, itself bound to foreign antigen, located on a separate cell. Only when this initial TCR-MHC binding has taken place can the CD3-dependent signaling cascade responsible for T cell clonal expansion and, ultimately, T cell cytotoxicity ensue.
- T cells may be cytotoxically activated in a clonally independent fashion, i.e. in a manner which is independent of the specific TCR clone carried by the T cell. This allows an activation of the entire T cell compartment rather than only specific T cells of a certain clonal identity.
- an especially prefened embodiment of the invention provides a bispecific antibody in which the effector antigen is the human CD3 antigen.
- the bispecific antibody according to this embodiment of the invention may have a total of either two or three antibody variable domains.
- lymphoid cell-associated effector antigens bound by a bispecific antibody of the invention may be the human CD 16 antigen, the human NKG2D antigen, the human NKp46 antigen, the human CD2 antigen, the human CD28 antigen or the human CD25 antigen.
- the human effector cell is a member of the human myeloid lineage.
- the effector cell may be a human monocyte, a human neutrophilic granulocyte or a human dendritic cell.
- such cells will have either a cytotoxic or an apoptotic effect on the target cell.
- Advantageous antigens within this embodiment which may be bound by a bispecific antibody of the invention may be the human CD64 antigen or the human CD89 antigen.
- the target antigen is an antigen which is uniquely expressed on a target cell in a disease condition, but which remains either non- expressed, expressed at a low level or non-accessible in a healthy condition.
- target antigens which might be specifically bound by a bispecific antibody of the invention may advantageously be selected from EpCAM, CCR5, CD19, HER-2 neu, HER-3, HER-4, EGFR, PSMA, CEA, MUC-1 (mucin), MUC2, MUC3, MUC4, MUC5 A c, MUC5 B , MUC7, DhCG, Lewis-Y, CD20 CD33, CD30, ganglioside GD3, 9-O-Acetyl-GD3, GM2, Globo H, fucosyl GM1, Poly SA, GD2, Carboanhydrase IX (MN/CA DC), CD44v6, Sonic Hedgehog (Shh), Wue- 1, Plasma Cell Antigen, (membrane-bound) IgE, Mel
- the target antigen specifically bound by a bispecific antibody may be a cancer-related antigen, that is an antigen related to a malignant condition.
- an antigen is either expressed or accessible on a malignant cell, whereas the antigen is either not present, not significantly present, or is not accessible on a non-malignant cell.
- a bispecific antibody according to this embodiment of the invention is a bispecific antibody which recruits the activity of a human immune effector cell against the malignant target cell bearing the target antigen, or rendering the target antigen accessible.
- the bispecific antibody specifically binds to the human CD3 antigen as effector antigen and to the human CD 19 antigen as target antigen.
- the human CD 19 antigen is expressed in the whole human B lineage from the pro B cell to the mature B cell, it is not shed, is uniformly expressed on all lymphoma cells, and is absent from stem cells.
- a bispecific antibody according to this embodiment namely one which specifically binds to the human CD3 antigen as effector antigen and to the human CD 19 antigen as target antigen, is of great potential value as a therapeutic for the eradication of malignant B cells.
- a bispecific antibody according to this embodiment consists of two or three antibody variable domains, separated by spacer and possibly linker polypeptides as described above.
- the bispecific antibody specifically binds to the human CD3 antigen as effector antigen and to the human EpCAM antigen as target antigen.
- EpCAM Epidermal cell adhesion molecule
- 17-1A antigen KSA, EGP40, GA733-2, ksl-4 or esa
- EpCAM has been shown in various studies to be beneficial in diagnosis and therapy of various carcinomas. Furthermore, in many cases, tumor cells were observed to express EpCAM to a much higher degree than their parental epithelium or less aggressive forms of said cancers.
- a bispecific antibody according to this embodiment namely one which specifically binds to the human CD3 antigen as effector antigen and to the human EpCAM antigen as target antigen is of great potential value as a therapeutic for the eradication of malignant epithelial cells.
- a bispecific antibody according to this embodiment consists of two or three antibody variable domains, separated by spacer and possibly linker polypeptides as described above.
- An anti-CD3 x anti-EpCAM bispecific antibody according to this latter embodiment may advantageously have the amino acid sequence as set out in SEQ ID NO: 1.
- a bispecific antibody according to this embodiment has as its first portion a murine-derived NH specifically binding the human CD3 antigen as effector antigen and, as its second portion, an scFv unit specifically binding the human EpCAM antigen as target antigen.
- SEQ ID NO: 1 represents a bispecific antibody with three antibody variable domains.
- a further aspect of the invention provides a use of a bispecific antibody as disclosed hereinabove for the preparation of a pharmaceutical composition for the prevention, treatment or amelioration of a proliferative disease, a tumorous disease, an inflammatory disease, an immunological disorder, an autoimmune disease, an infectious disease, a viral disease, an allergic reaction, a parasitic reaction, a graft-versus-host disease or a host-versus-graft disease.
- a further aspect of the invention provides a method for the prevention, treatment or amelioration a proliferative disease, a tumorous disease, an inflammatory disease, an immunological disorder, an autoimmune disease, an infectious disease, a viral disease, an allergic reaction, a parasitic reaction, a graft-versus-host disease or a host-versus-graft disease in a subject in the need thereof, said method comprising the step of administration of an effective amount of a bispecific antibody as disclosed hereinabove.
- the prevention, treatment or amelioration occurs in a human.
- the tumorous disease is preferably selected from the group of B cell disorders, for example a lymphoma, a B cell lymphoma and a Hodgkin lymphoma.
- the B cell lymphoma is a non-Hodgkin lymphoma.
- the autoimmune disease is selected from rheumatoid arthritis, multiple sclerosis, type 1 diabetes mellitus, inflammatory bowel disease, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.
- any administration of a bispecific antibody as described hereinabove may advantageously be coupled with the administration of a proteinaceous compound capable of providing an activation signal for immune effector cells.
- a proteinaceous compound capable of providing an activation signal for immune effector cells.
- Such a proteinaceous compound may advantageously be administered simultaneously or non- simultaneously with the bispecific antibody.
- a further aspect of the invention is a kit comprising a bispecific antibody as disclosed hereinabove.
- Fig. 1 Cytotoxic activity of an anti-EpCAM x anti-CD3 antibody comprising three variable domains
- Example 1 Design, prokaryotic expression and purification of a bispecific antibody with three antibody variable domains
- the DNA encoding an anti-EpCAM x anti-CD3 bispecific antibody with a VL and NH in the anti-EpCAM portion of the molecule and only one antibody variable domain (NH) in the anti CD3 portion of the molecule are cloned in the multiple cloning site (MCS) of pET-20b(+) vector ( ⁇ ovagen).
- MCS multiple cloning site
- the expression of the bispecific antibody with a Histidine (x6) tag is induced with rPTG.
- the choice of the vector facilitates the transport of the recombinant proteins into the periplasm.
- Other cloning vectors such as pBAD-glll (Invitrogen), pET-32 series (+) vector ( ⁇ ovagen) may also be used.
- arabinose is used to induce recombinant gene expression instead of IPTG.
- the D ⁇ A encoding the bispecific antibody is cloned in- frame with the sequence encoding the signal peptide (e.g. PelB, OmpA) that mediates the transport of the recombinant protein into the periplasm.
- the pET-20b (+) containing the D ⁇ A encoding the anti-EpCAM x anti-CD3 bispecific antibody described above is cloned and propagated in the bacterial host strain DH5.
- the recombinant bispecific antibody is expressed using the BL21 (DE3) bacterial host strain ( ⁇ ovagen).
- the Rosetta (DE3) bacterial host strain ( ⁇ ovagen) works when using a pET vector as described above.
- the pBAD-glll vector may be used with the TOP 10 E.coli strain (Invitrogen).
- a single colony of host cell transformed with the vector pET-20b(+) containing D ⁇ A encoding the anti-EpCAM x anti-CD3 bispecific antibody described above is selected and inoculated into 50ml LB containing the essential antibiotics.
- Cells are grown and harvested according to the supplier's instruction manual. The culture is incubated at 37°C until an OD600 of 0.4 to 1.0 is reached (0.6 is an ideal value), followed by induction of expression by addition of appropriate amounts of IPTG. The incubation is continued for an additional 2-3 h.
- Cultures as described are harvested by centrifugation.
- the cell pellet is suspended in 30 ml of 30 mM Tris-HCl pH 8, 20% sucrose.
- 60 ⁇ l of EDTA 0.5 M, pH 8 is added to a final concentration of 1 mM.
- the cells are collected by centrifugation and the cell-pellet is subjected to shock by re-suspending the pellet thoroughly for 10 min in the cold with chilled MgSO 4 (5mM, 30ml) solution.
- the shocked cells are subjected to centrifugation in order to separate the periplasmic (supernatant) and cellular (pellet) fractions.
- the supernatant is then further analysed by SDS-PAGE and is also checked for activity.
- Bispecific antibody produced as described above with a His tag is purified using a Ni-NTA spin column kit (Qiagen, Catalog Number 31314) following the protocol provided in the Qiagen instruction manual.
- Ni-NTA magnetic agarose beads Qiagen, cat n. 36113 can also be used.
- the polypeptide thus purified may be described as bispecific antibody with three antibody variable domains located on the same polypeptide chain.
- the bispecific single chain antibody contains the following elements: anti-human EpCAM VL; 15 amino acid linker of sequence (Gly 4 Ser) 3 ; anti-human EpCAM NH; 5 amino acid spacer of sequence Gly 4 Ser; anti-human CD3 NH; His 6 .
- the sequence is as set out in SEQ ID NO: 1.
- the ability of the bispecific antibody with the sequence set out in SEQ ID NO: 1 to recruit the cytotoxic potential of human cytotoxic T cells to effect the killing of cells bearing the human EpCAM antigen was measured in a cytotoxicity assay as follows.
- CHO cells from the American Type Cell Culture Collection (ATCC, USA) were transfected to express, human epithelial cell adhesion molecule (EpCAM) as the target antigen.
- EpCAM epithelial cell adhesion molecule
- Cells cultured from the resulting cell clone, refened to as CHO-EpCAM cells, were subsequently used in the cytotoxicity experiments as the target cells.
- the human cell line MC15 was used as a source of effector cells bearing the effector antigen CD3.
- the cell clone was derived from the cell clone CB15, which is a CD4-positive human T cell clone kindly provided by Dr. Fickenscher at the University of Er Weg/N ⁇ rnberg, Germany. Cells were cultured as recommended by the respective suppliers.
- 1.5xl0 7 target cells were washed twice with phosphate-buffered saline (PBS) and were labeled with PKH26 dye (Sigma-Aldrich Co.) according to the manufacturer's instractions. After staining, the cells were washed two times with 20ml of PBS. Labeled CHO-EpCAM cells (target cells) and MC15 cells (effector cells) were mixed together in a ratio of 1:5, respectively. The resulting cell suspension contained 400,000 target and 2 x 10 6 effector cells per ml. BiTEs were diluted to different concentrations in alpha MEM/10% FCS-medium.
- each reaction (of volume lOO ⁇ l) contained a mixture of 20,000 target cells, 1 x 10 5 effector cells and a specific concentration of the bispecific antibody set out as in SEQ ID NO:l. Measurements at each concentration of bispecific antibody were performed in triplicate. Reactions were incubated for about 20h at 37°C / 5% CO 2 .
- Propidium iodide was added to a final concentration of 1 ⁇ g/ml. Propidium iodide stains dead cells.
- the reaction samples were analyzed by flow cytometry (e.g. FACS-Calibur Becton Dickinson).
- the population of PKH26-labeled target cells was gated in an FSC versus FL-2 plot and subsequent analysis of cells was carried out only with the cell population identified within this gate.
- the percent of dead cells (propidium iodide stained) was determined in an FSC (forward scatter) versus FL-3 plot. Mean values were plotted against concentrations of bispecific antibody on a logarithmic scale, resulting in a typical dose response curve (see Fig.l).
- the EC 50 (the concentration of bispecific antibody required to elicit a half-maximal cytotoxic response) values were obtained after non-linear fitting of the data obtained with the GraphPad Prism software.
- the bispecific antibody with the sequence as set out in SEQ ID NO: 1 showed activity as a recruiter of cytotoxic T cells. This follows from the fact that the target cells are efficiently killed (with an EC 50 value of about 12 ng/ml) in a manner depending on the concentration of bispecific antibody added to a respective reaction mixture in the presence of cytotoxic T cells.
Abstract
Description
Claims
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AT04804237T ATE479710T1 (en) | 2003-12-22 | 2004-12-22 | BISPECIFIC ANTIBODIES |
EP04804237A EP1697421B1 (en) | 2003-12-22 | 2004-12-22 | Bispecific antibodies |
SI200431500T SI1697421T1 (en) | 2003-12-22 | 2004-12-22 | Bispecific antibodies |
DE602004028957T DE602004028957D1 (en) | 2003-12-22 | 2004-12-22 | BISPECIFIC ANTIBODIES |
MXPA06005592A MXPA06005592A (en) | 2003-12-22 | 2004-12-22 | Bispecific antibodies. |
JP2006546068A JP5376759B2 (en) | 2003-12-22 | 2004-12-22 | Bispecific antibody |
DK04804237.8T DK1697421T3 (en) | 2003-12-22 | 2004-12-22 | Bispecific antibodies |
AU2004303510A AU2004303510B2 (en) | 2003-12-22 | 2004-12-22 | Bispecific antibodies |
CA2544562A CA2544562C (en) | 2003-12-22 | 2004-12-22 | Bispecific antibodies |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/743,697 US7235641B2 (en) | 2003-12-22 | 2003-12-22 | Bispecific antibodies |
US10/743,697 | 2003-12-22 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US11/454,784 Continuation US7869934B2 (en) | 2003-12-19 | 2006-06-19 | Determination of an expected speed level |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2005061547A2 true WO2005061547A2 (en) | 2005-07-07 |
WO2005061547A3 WO2005061547A3 (en) | 2005-11-24 |
Family
ID=34678708
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2004/014643 WO2005061547A2 (en) | 2003-12-22 | 2004-12-22 | Bispecific antibodies |
Country Status (12)
Country | Link |
---|---|
US (2) | US7235641B2 (en) |
EP (1) | EP1697421B1 (en) |
JP (1) | JP5376759B2 (en) |
AT (1) | ATE479710T1 (en) |
AU (1) | AU2004303510B2 (en) |
CA (1) | CA2544562C (en) |
DE (1) | DE602004028957D1 (en) |
DK (1) | DK1697421T3 (en) |
ES (1) | ES2350935T3 (en) |
MX (1) | MXPA06005592A (en) |
SI (1) | SI1697421T1 (en) |
WO (1) | WO2005061547A2 (en) |
Cited By (176)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2007048849A1 (en) * | 2005-10-28 | 2007-05-03 | Novo Nordisk A/S | Fusion proteins that bind effector lymphocytes and target cells |
WO2007042261A3 (en) * | 2005-10-11 | 2007-12-21 | Micromet Ag | Compositions comprising cross-species-specific antibodies and uses thereof |
WO2008119565A2 (en) * | 2007-04-03 | 2008-10-09 | Micromet Ag | Cross-species-specific binding domain |
WO2008119566A3 (en) * | 2007-04-03 | 2009-01-08 | Micromet Ag | Cross-species-specific bispecific binders |
WO2008119567A3 (en) * | 2007-04-03 | 2009-01-08 | Micromet Ag | Cross-species-specific cd3-epsilon binding domain |
JP2010524435A (en) * | 2007-04-03 | 2010-07-22 | マイクロメット アーゲー | Species-specific bispecific binder |
EP2303859A2 (en) * | 2008-06-20 | 2011-04-06 | Metabolex Inc. | Aryl gpr119 agonists and uses thereof |
WO2011079283A1 (en) * | 2009-12-23 | 2011-06-30 | Bioalliance C.V. | Anti-epcam antibodies that induce apoptosis of cancer cells and methods using same |
WO2011109400A2 (en) | 2010-03-04 | 2011-09-09 | Macrogenics,Inc. | Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof |
EP2459729A2 (en) * | 2009-07-29 | 2012-06-06 | Abbott Laboratories | Dual variable domain immunoglobulins and uses thereof |
WO2012122528A1 (en) * | 2011-03-10 | 2012-09-13 | Hco Antibody, Inc. | Bispecific three-chain antibody-like molecules |
WO2012162067A2 (en) | 2011-05-21 | 2012-11-29 | Macrogenics, Inc. | Cd3-binding molecules capable of binding to human and non-human cd3 |
US8410127B2 (en) | 2009-10-01 | 2013-04-02 | Metabolex, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
US8409577B2 (en) | 2006-06-12 | 2013-04-02 | Emergent Product Development Seattle, Llc | Single chain multivalent binding proteins with effector function |
US8658765B2 (en) | 2009-12-31 | 2014-02-25 | Avidbiotics Corp. | Non-natural MIC proteins |
US8716450B2 (en) | 2009-10-15 | 2014-05-06 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US8722855B2 (en) | 2009-10-28 | 2014-05-13 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US8772459B2 (en) | 2009-12-02 | 2014-07-08 | Imaginab, Inc. | J591 minibodies and Cys-diabodies for targeting human prostate specific membrane antigen (PSMA) and methods for their use |
US8796420B2 (en) | 2009-12-31 | 2014-08-05 | Avidbiotics Corp. | Non-natural MIC proteins |
US8822645B2 (en) | 2008-07-08 | 2014-09-02 | Abbvie Inc. | Prostaglandin E2 dual variable domain immunoglobulins and uses thereof |
US8846675B2 (en) | 2007-07-19 | 2014-09-30 | Cymabay Therapeutics, Inc. | N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
WO2014159940A1 (en) | 2013-03-14 | 2014-10-02 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor |
US8853366B2 (en) | 2001-01-17 | 2014-10-07 | Emergent Product Development Seattle, Llc | Binding domain-immunoglobulin fusion proteins |
US8921350B2 (en) | 2006-12-28 | 2014-12-30 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US8951737B2 (en) | 1996-05-06 | 2015-02-10 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
US8987418B2 (en) | 2013-03-15 | 2015-03-24 | Abbvie Inc. | Dual specific binding proteins directed against IL-1β and/or IL-17 |
RU2547600C2 (en) * | 2008-10-01 | 2015-04-10 | Эмджен Рисерч (Мьюник) Гмбх | Pscaxcd3, cd19xcd3, c-metxcd3, endosialin xcd3, epcamxcd3, igf-1rxcd3 or fap-alpha xcd3 bispecific single-chain antibody with inter-species specificity |
US9029508B2 (en) | 2008-04-29 | 2015-05-12 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US9035027B2 (en) | 2008-06-03 | 2015-05-19 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US9045551B2 (en) | 2012-11-01 | 2015-06-02 | Abbvie Inc. | Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof |
US9046513B2 (en) | 2010-08-26 | 2015-06-02 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
WO2015095410A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Methods of treating cancer using pd-1 axis binding antagonists and an anti-cd20 antibody |
WO2015095418A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
US9085622B2 (en) | 2010-09-03 | 2015-07-21 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins |
US9101609B2 (en) | 2008-04-11 | 2015-08-11 | Emergent Product Development Seattle, Llc | CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
US9109026B2 (en) | 2008-06-03 | 2015-08-18 | Abbvie, Inc. | Dual variable domain immunoglobulins and uses thereof |
US9120870B2 (en) | 2011-12-30 | 2015-09-01 | Abbvie Inc. | Dual specific binding proteins directed against IL-13 and IL-17 |
WO2015184203A1 (en) | 2014-05-29 | 2015-12-03 | Macrogenics, Inc. | Tri-specific binding molecules and methods of use thereof |
US9241924B2 (en) | 2010-06-23 | 2016-01-26 | Cymabay Therapeutics, Inc. | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
WO2016073794A1 (en) | 2014-11-05 | 2016-05-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
WO2016073791A1 (en) | 2014-11-05 | 2016-05-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
US9358282B2 (en) | 2011-03-17 | 2016-06-07 | The University Of Birmingham | Re-directed immunotherapy |
WO2016154585A1 (en) | 2015-03-26 | 2016-09-29 | Charles Sentman | Anti-mica antigen binding fragments, fusion molecules, cells which express and methods of using |
US9493560B2 (en) | 2010-08-03 | 2016-11-15 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
WO2016196381A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Pd-l1 promoter methylation in cancer |
WO2016205320A1 (en) | 2015-06-17 | 2016-12-22 | Genentech, Inc. | Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes |
WO2017025033A1 (en) * | 2015-08-10 | 2017-02-16 | 中山大学 | Bispecific nano-antibody used for treating cea positive expression tumour |
US9650445B2 (en) | 2012-02-28 | 2017-05-16 | The University Of Birmingham | Immunotherapeutic molecules and uses |
EP3178848A1 (en) | 2015-12-09 | 2017-06-14 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody for reducing formation of anti-drug antibodies |
US9695236B2 (en) | 2008-04-02 | 2017-07-04 | Macrogenics, Inc. | BCR-complex-specific antibodies and methods of using same |
WO2017127499A1 (en) | 2016-01-22 | 2017-07-27 | Janssen Biotech, Inc. | Anti-ror1 antibodies, ror1 x cd3 bispecific antibodies, and methods of using the same |
EP3252078A1 (en) | 2016-06-02 | 2017-12-06 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer |
US9840554B2 (en) | 2015-06-15 | 2017-12-12 | Abbvie Inc. | Antibodies against platelet-derived growth factor (PDGF) |
CN107586340A (en) * | 2011-08-23 | 2018-01-16 | 罗切格利卡特公司 | To T cell activation antigen and the bispecific antibody and application method of specific for tumour antigen |
WO2018011421A1 (en) | 2016-07-14 | 2018-01-18 | Genmab A/S | Multispecific antibodies against cd40 and cd137 |
WO2018027204A1 (en) | 2016-08-05 | 2018-02-08 | Genentech, Inc. | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
US9896508B2 (en) | 2010-03-04 | 2018-02-20 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
WO2018114754A1 (en) | 2016-12-19 | 2018-06-28 | F. Hoffmann-La Roche Ag | Combination therapy with targeted 4-1bb (cd137) agonists |
WO2018114748A1 (en) | 2016-12-20 | 2018-06-28 | F. Hoffmann-La Roche Ag | Combination therapy of anti-cd20/anti-cd3 bispecific antibodies and 4-1bb (cd137) agonists |
US10035856B2 (en) | 2015-11-19 | 2018-07-31 | Revitope Limited | Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells |
WO2018162749A1 (en) | 2017-03-09 | 2018-09-13 | Genmab A/S | Antibodies against pd-l1 |
US10093733B2 (en) | 2014-12-11 | 2018-10-09 | Abbvie Inc. | LRP-8 binding dual variable domain immunoglobulin proteins |
WO2018184966A1 (en) | 2017-04-03 | 2018-10-11 | F. Hoffmann-La Roche Ag | Antibodies binding to steap-1 |
US10100115B2 (en) | 2014-02-14 | 2018-10-16 | Macrogenics, Inc. | Methods for the treatment of vascularizing cancers |
WO2018191502A2 (en) | 2017-04-13 | 2018-10-18 | Agenus Inc. | Anti-cd137 antibodies and methods of use thereof |
US10113003B2 (en) | 2015-06-23 | 2018-10-30 | Innate Pharma | Multispecific NK engager proteins |
WO2018204363A1 (en) | 2017-05-01 | 2018-11-08 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
US10143748B2 (en) | 2005-07-25 | 2018-12-04 | Aptevo Research And Development Llc | B-cell reduction using CD37-specific and CD20-specific binding molecules |
WO2018220099A1 (en) | 2017-06-02 | 2018-12-06 | F. Hoffmann-La Roche Ag | Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer |
US10160806B2 (en) | 2014-06-26 | 2018-12-25 | Macrogenics, Inc. | Covalently bonded diabodies having immunoreactivity with PD-1 and LAG-3, and methods of use thereof |
WO2019025545A1 (en) | 2017-08-04 | 2019-02-07 | Genmab A/S | Binding agents binding to pd-l1 and cd137 and use thereof |
WO2019086497A2 (en) | 2017-11-01 | 2019-05-09 | F. Hoffmann-La Roche Ag | Combination therapy with targeted ox40 agonists |
US10292983B2 (en) | 2016-08-03 | 2019-05-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
WO2019122052A2 (en) | 2017-12-21 | 2019-06-27 | F. Hoffmann-La Roche Ag | Antibodies binding to hla-a2/wt1 |
WO2019126634A2 (en) | 2017-12-22 | 2019-06-27 | Genentech, Inc. | Targeted integration of nucleic acids |
EP3505537A1 (en) | 2012-05-07 | 2019-07-03 | Trustees of Dartmouth College | Anti-b7-h6 antibody, fusion proteins, and methods of using the same |
WO2019149715A1 (en) | 2018-01-31 | 2019-08-08 | F. Hoffmann-La Roche Ag | Stabilized immunoglobulin domains |
WO2019149716A1 (en) | 2018-01-31 | 2019-08-08 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising an antigen-binding site binding to lag3 |
WO2019154890A1 (en) | 2018-02-09 | 2019-08-15 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
EP2780374B1 (en) | 2011-11-15 | 2019-08-21 | Amgen Research (Munich) GmbH | Binding molecules for bcma and cd3 |
WO2019175125A1 (en) | 2018-03-13 | 2019-09-19 | F. Hoffmann-La Roche Ag | Combination therapy with targeted 4-1bb (cd137) agonists |
WO2019175071A1 (en) | 2018-03-13 | 2019-09-19 | F. Hoffmann-La Roche Ag | Therapeutic combination of 4-1 bb agonists with anti-cd20 antibodies |
WO2019191552A1 (en) | 2018-03-29 | 2019-10-03 | Genentech, Inc. | Modulating lactogenic activity in mammalian cells |
US10441649B2 (en) | 2015-02-02 | 2019-10-15 | The University Of Birmingham | Targeting moiety peptide epitope complexes having a plurality of T-cell epitopes |
WO2019202041A1 (en) | 2018-04-18 | 2019-10-24 | F. Hoffmann-La Roche Ag | Multispecific antibodies and use thereof |
US10517969B2 (en) | 2009-02-17 | 2019-12-31 | Cornell University | Methods and kits for diagnosis of cancer and prediction of therapeutic value |
US10519234B2 (en) | 2014-06-27 | 2019-12-31 | Innate Pharma | NKp46 binding proteins |
WO2020061349A1 (en) | 2018-09-21 | 2020-03-26 | Genentech, Inc. | Diagnostic methods for triple-negative breast cancer |
WO2020058297A1 (en) | 2018-09-18 | 2020-03-26 | F. Hoffmann-La Roche Ag | Use of a cathepsin s inhibitor against the formation of anti-drug antibodies |
US10633443B2 (en) | 2014-09-26 | 2020-04-28 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD19 and CD3, and uses thereof |
WO2020094744A1 (en) | 2018-11-06 | 2020-05-14 | Genmab A/S | Antibody formulation |
WO2020096959A1 (en) | 2018-11-05 | 2020-05-14 | Genentech, Inc. | Methods of producing two chain proteins in prokaryotic host cells |
WO2020127619A1 (en) | 2018-12-21 | 2020-06-25 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 |
WO2020132165A1 (en) | 2018-12-21 | 2020-06-25 | Genentech, Inc. | Targeted integration of nucleic acids |
US10717778B2 (en) | 2014-09-29 | 2020-07-21 | Duke University | Bispecific molecules comprising an HIV-1 envelope targeting arm |
WO2020154410A1 (en) | 2019-01-23 | 2020-07-30 | Genentech, Inc. | Methods of producing multimeric proteins in eukaryotic host cells |
WO2021018925A1 (en) | 2019-07-31 | 2021-02-04 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
WO2021018859A2 (en) | 2019-07-31 | 2021-02-04 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
WO2021042019A1 (en) | 2019-08-30 | 2021-03-04 | Agenus Inc. | Anti-cd96 antibodies and methods of use thereof |
WO2021055577A2 (en) | 2019-09-18 | 2021-03-25 | Genentech, Inc. | Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use |
US10961311B2 (en) | 2016-04-15 | 2021-03-30 | Macrogenics, Inc. | B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof |
WO2021084104A1 (en) | 2019-10-30 | 2021-05-06 | Bioinvent International Ab | Tetravalent antibody molecules |
WO2021122875A1 (en) | 2019-12-18 | 2021-06-24 | F. Hoffmann-La Roche Ag | Antibodies binding to hla-a2/mage-a4 |
WO2021133723A2 (en) | 2019-12-23 | 2021-07-01 | Genentech, Inc. | Apolipoprotein l1-specific antibodies and methods of use |
US11066483B2 (en) | 2010-11-30 | 2021-07-20 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
EP3862365A1 (en) | 2016-01-08 | 2021-08-11 | F. Hoffmann-La Roche AG | Methods of treating cea-positive cancers using pd-1 axis binding antagonists and anti-cea/anti-cd3 bispecific antibodies |
WO2021156258A1 (en) | 2020-02-04 | 2021-08-12 | BioNTech SE | Treatment involving antigen vaccination and binding agents binding to pd-l1 and cd137 |
WO2021178896A1 (en) | 2020-03-06 | 2021-09-10 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
WO2021185934A1 (en) | 2020-03-18 | 2021-09-23 | Genmab A/S | Antibodies binding to b7h4 |
WO2021195464A2 (en) | 2020-03-26 | 2021-09-30 | Genentech, Inc. | Modified mammalian cells |
WO2021214277A1 (en) | 2020-04-24 | 2021-10-28 | F. Hoffmann-La Roche Ag | Enzyme and pathway modulation with sulfhydryl compounds and their derivatives |
WO2021249990A2 (en) | 2020-06-08 | 2021-12-16 | Hoffmann-La Roche Inc. | Anti-hbv antibodies and methods of use |
WO2021255143A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and folr1 |
WO2021255142A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 |
WO2021255146A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and cea |
WO2021257503A1 (en) | 2020-06-16 | 2021-12-23 | Genentech, Inc. | Methods and compositions for treating triple-negative breast cancer |
WO2021255155A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and cd19 |
US11208480B2 (en) | 2014-06-27 | 2021-12-28 | Innate Pharma | Multispecific antigen binding proteins |
WO2021262798A1 (en) | 2020-06-24 | 2021-12-30 | Genentech, Inc. | Targeted integration of nucleic acids |
WO2021262783A1 (en) | 2020-06-24 | 2021-12-30 | Genentech, Inc. | Apoptosis resistant cell lines |
WO2022016037A1 (en) | 2020-07-17 | 2022-01-20 | Genentech, Inc. | Anti-notch2 antibodies and methods of use |
WO2022029011A1 (en) | 2020-08-06 | 2022-02-10 | BioNTech SE | Binding agents for coronavirus s protein |
US11254744B2 (en) | 2015-08-07 | 2022-02-22 | Imaginab, Inc. | Antigen binding constructs to target molecules |
WO2022047222A2 (en) | 2020-08-28 | 2022-03-03 | Genentech, Inc. | Crispr/cas9 multiplex knockout of host cell proteins |
US11266745B2 (en) | 2017-02-08 | 2022-03-08 | Imaginab, Inc. | Extension sequences for diabodies |
US11286300B2 (en) | 2015-10-01 | 2022-03-29 | Hoffmann-La Roche Inc. | Humanized anti-human CD19 antibodies and methods of use |
US11352426B2 (en) | 2015-09-21 | 2022-06-07 | Aptevo Research And Development Llc | CD3 binding polypeptides |
WO2022129120A1 (en) | 2020-12-17 | 2022-06-23 | F. Hoffmann-La Roche Ag | Anti-hla-g antibodies and use thereof |
EP4026848A1 (en) | 2015-12-09 | 2022-07-13 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody for reducing the cytokine release syndrome |
US11390681B2 (en) | 2020-04-29 | 2022-07-19 | TeneoTwo, Inc. | Multispecific heavy chain antibodies with modified heavy chain constant regions |
WO2022169825A1 (en) | 2021-02-03 | 2022-08-11 | Mozart Therapeutics, Inc. | Binding agents and methods of using the same |
WO2022169872A1 (en) | 2021-02-03 | 2022-08-11 | Genentech, Inc. | Multispecific binding protein degrader platform and methods of use |
US11434299B2 (en) | 2016-12-21 | 2022-09-06 | Teneobio, Inc. | Anti-BCMA heavy chain-only antibodies |
WO2022187591A1 (en) | 2021-03-05 | 2022-09-09 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
WO2022192647A1 (en) | 2021-03-12 | 2022-09-15 | Genentech, Inc. | Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use |
WO2022217022A1 (en) | 2021-04-10 | 2022-10-13 | Profoundbio Us Co. | Folr1 binding agents, conjugates thereof and methods of using the same |
WO2022225880A1 (en) | 2021-04-19 | 2022-10-27 | Genentech, Inc. | Modified mammalian cells |
WO2022226317A1 (en) | 2021-04-23 | 2022-10-27 | Profoundbio Us Co. | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
US11485790B2 (en) | 2014-04-07 | 2022-11-01 | Chugai Seiyaku Kabushiki Kaisha | Immunoactivating antigen-binding molecule |
WO2022228705A1 (en) | 2021-04-30 | 2022-11-03 | F. Hoffmann-La Roche Ag | Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate |
WO2022228706A1 (en) | 2021-04-30 | 2022-11-03 | F. Hoffmann-La Roche Ag | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibody |
US11492409B2 (en) | 2018-06-01 | 2022-11-08 | Novartis Ag | Binding molecules against BCMA and uses thereof |
WO2022234146A1 (en) | 2021-05-07 | 2022-11-10 | Genmab A/S | PHARMACEUTICAL COMPOSITIONS COMPRISING BISPECIFIC ANTIBODIES BINDING TO B7H4 and CD3 |
US11505606B2 (en) | 2016-09-14 | 2022-11-22 | Teneobio, Inc. | CD3 binding antibodies |
US11505605B2 (en) | 2014-05-13 | 2022-11-22 | Chugai Seiyaku Kabushiki Kaisha | T cell-redirected antigen-binding molecule for cells having immunosuppression function |
WO2022242644A1 (en) | 2021-05-18 | 2022-11-24 | 赛斯尔擎生物技术(上海)有限公司 | Method for modifying cell |
WO2022246259A1 (en) | 2021-05-21 | 2022-11-24 | Genentech, Inc. | Modified cells for the production of a recombinant product of interest |
US11530274B2 (en) | 2018-07-02 | 2022-12-20 | Amgen Inc. | Anti-STEAP1 antigen-binding protein |
WO2022268740A1 (en) | 2021-06-21 | 2022-12-29 | Genmab A/S | Combination dosage regime of cd137 and pd-l1 binding agents |
WO2023280227A2 (en) | 2021-07-06 | 2023-01-12 | Profoundbio Us Co. | Linkers, drug linkers and conjugates thereof and methods of using the same |
WO2023287663A1 (en) | 2021-07-13 | 2023-01-19 | Genentech, Inc. | Multi-variate model for predicting cytokine release syndrome |
WO2023001884A1 (en) | 2021-07-22 | 2023-01-26 | F. Hoffmann-La Roche Ag | Heterodimeric fc domain antibodies |
WO2023012147A1 (en) | 2021-08-03 | 2023-02-09 | F. Hoffmann-La Roche Ag | Bispecific antibodies and methods of use |
WO2023014863A1 (en) | 2021-08-05 | 2023-02-09 | Go Therapeutics, Inc. | Anti-glyco-muc4 antibodies and their uses |
US11578139B1 (en) | 2022-06-08 | 2023-02-14 | Zhejiang Shimai Pharmaceutical Co., Ltd. | Antibodies against ENPP3 and uses thereof |
WO2023025207A1 (en) | 2021-08-24 | 2023-03-02 | 赛斯尔擎生物技术(上海)有限公司 | T cell product and use thereof |
WO2023025208A1 (en) | 2021-08-24 | 2023-03-02 | 赛斯尔擎生物技术(上海)有限公司 | Method for modifying cell |
WO2023034569A1 (en) | 2021-09-03 | 2023-03-09 | Go Therapeutics, Inc. | Anti-glyco-cmet antibodies and their uses |
WO2023034571A1 (en) | 2021-09-03 | 2023-03-09 | Go Therapeutics, Inc. | Anti-glyco-lamp1 antibodies and their uses |
US11613572B2 (en) | 2016-06-21 | 2023-03-28 | Teneobio, Inc. | CD3 binding antibodies |
WO2023057571A1 (en) | 2021-10-08 | 2023-04-13 | Genmab A/S | Antibodies binding to cd30 and cd3 |
WO2023076876A1 (en) | 2021-10-26 | 2023-05-04 | Mozart Therapeutics, Inc. | Modulation of immune responses to viral vectors |
US11649293B2 (en) | 2015-11-18 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for enhancing humoral immune response |
US11660340B2 (en) | 2015-11-18 | 2023-05-30 | Chugai Seiyaku Kabushiki Kaisha | Combination therapy using T cell redirection antigen binding molecule against cell having immunosuppressing function |
WO2023104938A1 (en) | 2021-12-10 | 2023-06-15 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and plap |
WO2023141445A1 (en) | 2022-01-19 | 2023-07-27 | Genentech, Inc. | Anti-notch2 antibodies and conjugates and methods of use |
WO2023174521A1 (en) | 2022-03-15 | 2023-09-21 | Genmab A/S | Binding agents binding to epcam and cd137 |
WO2023180353A1 (en) | 2022-03-23 | 2023-09-28 | F. Hoffmann-La Roche Ag | Combination treatment of an anti-cd20/anti-cd3 bispecific antibody and chemotherapy |
WO2023198727A1 (en) | 2022-04-13 | 2023-10-19 | F. Hoffmann-La Roche Ag | Pharmaceutical compositions of anti-cd20/anti-cd3 bispecific antibodies and methods of use |
US11845805B2 (en) | 2020-09-10 | 2023-12-19 | Genmab A/S | Bispecific antibody against CD3 and CD20 in combination therapy for treating diffuse large B-cell lymphoma |
US11858995B2 (en) | 2020-09-10 | 2024-01-02 | Genmab A/S | Bispecific antibodies against CD3 and CD20 for treating chronic lymphocytic leukemia |
WO2024020564A1 (en) | 2022-07-22 | 2024-01-25 | Genentech, Inc. | Anti-steap1 antigen-binding molecules and uses thereof |
WO2024030956A2 (en) | 2022-08-03 | 2024-02-08 | Mozart Therapeutics, Inc. | Cd39-specific binding agents and methods of using the same |
US11905326B2 (en) | 2019-06-14 | 2024-02-20 | Teneobio, Inc. | Multispecific heavy chain antibodies binding to CD22 and CD3 |
WO2024069165A1 (en) | 2022-09-27 | 2024-04-04 | Coding Bio Limited | Cll1 binding molecules |
Families Citing this family (161)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6765087B1 (en) * | 1992-08-21 | 2004-07-20 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
US20100311954A1 (en) * | 2002-03-01 | 2010-12-09 | Xencor, Inc. | Optimized Proteins that Target Ep-CAM |
US20090162382A1 (en) * | 2002-03-01 | 2009-06-25 | Bernett Matthew J | Optimized ca9 antibodies and methods of using the same |
US9453251B2 (en) | 2002-10-08 | 2016-09-27 | Pfenex Inc. | Expression of mammalian proteins in Pseudomonas fluorescens |
RU2401843C2 (en) | 2003-10-16 | 2010-10-20 | Микромет Аг | Multispecific deimmunising cd3-binders |
WO2005077065A2 (en) * | 2004-02-09 | 2005-08-25 | The Regents Of The University Of California | Selective high-affinity polydentate ligands and methods of making such |
EP2412816B1 (en) | 2004-07-26 | 2014-12-03 | Pfenex Inc. | Process for improved protein expression by strain engineering |
CA2652434A1 (en) | 2005-07-08 | 2007-01-18 | Xencor, Inc. | Optimized proteins that target ep-cam |
LT1976880T (en) * | 2005-12-21 | 2016-10-10 | Amgen Research (Munich) Gmbh | Pharmaceutical compositions with resistance to soluble cea |
JP2009531324A (en) | 2006-03-20 | 2009-09-03 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Engineered anti-prostatic stem cell antigen (PSCA) antibody for cancer targeting |
US8470323B2 (en) * | 2007-01-09 | 2013-06-25 | The Trustees Of The University Of Pennsylvania | Drug delivery to human tissues by single chain variable region antibody fragments cloned by phage display |
US9580719B2 (en) | 2007-04-27 | 2017-02-28 | Pfenex, Inc. | Method for rapidly screening microbial hosts to identify certain strains with improved yield and/or quality in the expression of heterologous proteins |
JP5444553B2 (en) | 2007-04-27 | 2014-03-19 | フェネックス インコーポレイテッド | Methods for rapidly screening microbial hosts to identify specific strains with improved yield and / or quality of heterologous protein expression |
WO2009032949A2 (en) | 2007-09-04 | 2009-03-12 | The Regents Of The University Of California | High affinity anti-prostate stem cell antigen (psca) antibodies for cancer targeting and detection |
ES2613844T3 (en) | 2008-04-21 | 2017-05-26 | Lawrence Livermore National Security, Llc | Selective high affinity polydentate ligands and methods to produce them |
RS54900B1 (en) * | 2008-10-01 | 2016-10-31 | Amgen Res (Munich) Gmbh | Cross-species-specific psmaxcd3 bispecific single chain antibody |
CN101957365B (en) * | 2009-07-21 | 2013-08-07 | 卫生部北京医院 | Kit for detecting cyclic citrullinated peptide (CCP) and immunoglobulin G (IgG) resistant bispecific antibody |
US9493578B2 (en) | 2009-09-02 | 2016-11-15 | Xencor, Inc. | Compositions and methods for simultaneous bivalent and monovalent co-engagement of antigens |
US9273283B2 (en) | 2009-10-29 | 2016-03-01 | The Trustees Of Dartmouth College | Method of producing T cell receptor-deficient T cells expressing a chimeric receptor |
US9181527B2 (en) | 2009-10-29 | 2015-11-10 | The Trustees Of Dartmouth College | T cell receptor-deficient T cell compositions |
KR20120123299A (en) | 2009-12-04 | 2012-11-08 | 제넨테크, 인크. | Multispecific antibodies, antibody analogs, compositions, and methods |
KR101820987B1 (en) | 2010-04-15 | 2018-01-22 | 프로제닉스 파머슈티컬스, 인코포레이티드 | Antibodies for the treatment of clostridium difficile-associated infection and disease |
MX342239B (en) | 2010-05-03 | 2016-09-21 | Genentech Inc * | Compositions and methods for the diagnosis and treatment of tumor. |
JP5953303B2 (en) | 2010-07-29 | 2016-07-20 | ゼンコア インコーポレイテッド | Antibodies with modified isoelectric points |
DE102010039018B4 (en) | 2010-08-06 | 2013-02-28 | Technische Universität Dresden | Anti-La antibodies and their use for immuno-targeting |
NZ604510A (en) | 2010-08-17 | 2013-10-25 | Csl Ltd | Dilutable biocidal compositions and methods of use |
US9249217B2 (en) | 2010-12-03 | 2016-02-02 | Secretary, DHHS | Bispecific EGFRvIII x CD3 antibody engaging molecules |
CA2829628A1 (en) * | 2011-03-11 | 2012-09-20 | Amgen Inc. | Method of correlated mutational analysis to improve therapeutic antibodies |
US9624294B2 (en) | 2011-03-14 | 2017-04-18 | Cellmid Limited | Antibody recognizing N-domain of midkine |
US9833476B2 (en) | 2011-08-31 | 2017-12-05 | The Trustees Of Dartmouth College | NKP30 receptor targeted therapeutics |
SG10201800158XA (en) | 2011-09-22 | 2018-02-27 | Amgen Inc | Cd27l antigen binding proteins |
JP2014530009A (en) | 2011-09-29 | 2014-11-17 | エーピーオー‐ティー ビー.ヴイ. | Multispecific binding molecules targeting abnormal cells |
US10851178B2 (en) | 2011-10-10 | 2020-12-01 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
WO2013059886A1 (en) | 2011-10-28 | 2013-05-02 | Patrys Limited | Pat-lm1 epitopes and methods for using same |
KR101963230B1 (en) | 2011-12-26 | 2019-03-29 | 삼성전자주식회사 | Protein complex comprising multi-specific monoclonal antibodies |
CA2860914A1 (en) | 2012-01-13 | 2013-07-18 | Apo-T B.V. | Aberrant cell-restricted immunoglobulins provided with a toxic moiety |
KR102494534B1 (en) | 2012-03-14 | 2023-02-06 | 리제너론 파마슈티칼스 인코포레이티드 | Multispecific antigen-binding molecules and uses thereof |
GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
JO3623B1 (en) | 2012-05-18 | 2020-08-27 | Amgen Inc | St2 antigen binding proteins |
EP2861619A4 (en) | 2012-06-07 | 2016-01-27 | Univ Duke | HUMAN BISPECIFIC EGFRvIII ANTIBODY ENGAGING MOLECULES |
US20140004121A1 (en) | 2012-06-27 | 2014-01-02 | Amgen Inc. | Anti-mesothelin binding proteins |
US9682143B2 (en) * | 2012-08-14 | 2017-06-20 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
CA2874864C (en) | 2012-08-14 | 2023-02-21 | Ibc Pharmaceuticals, Inc. | T-cell redirecting bispecific antibodies for treatment of disease |
US20150231241A1 (en) | 2012-08-14 | 2015-08-20 | Ibc Pharmaceuticals, Inc. | Combination therapy for inducing immune response to disease |
KR101911438B1 (en) | 2012-10-31 | 2018-10-24 | 삼성전자주식회사 | Bispecific antigen binding protein complex and preparation methods of bispecific antibodies |
CA3211863A1 (en) | 2013-01-14 | 2014-07-17 | Xencor, Inc. | Novel heterodimeric proteins |
US10968276B2 (en) | 2013-03-12 | 2021-04-06 | Xencor, Inc. | Optimized anti-CD3 variable regions |
US10131710B2 (en) | 2013-01-14 | 2018-11-20 | Xencor, Inc. | Optimized antibody variable regions |
US9605084B2 (en) | 2013-03-15 | 2017-03-28 | Xencor, Inc. | Heterodimeric proteins |
US11053316B2 (en) | 2013-01-14 | 2021-07-06 | Xencor, Inc. | Optimized antibody variable regions |
US9701759B2 (en) | 2013-01-14 | 2017-07-11 | Xencor, Inc. | Heterodimeric proteins |
US10487155B2 (en) | 2013-01-14 | 2019-11-26 | Xencor, Inc. | Heterodimeric proteins |
WO2014113510A1 (en) | 2013-01-15 | 2014-07-24 | Xencor, Inc. | Rapid clearance of antigen complexes using novel antibodies |
EP2762496A1 (en) | 2013-02-05 | 2014-08-06 | EngMab AG | Method for the selection of antibodies against BCMA |
JP6636803B2 (en) | 2013-02-05 | 2020-01-29 | エンクマフ エスアーエールエル | Method for selection of antibodies to BCMA |
JP6133444B2 (en) | 2013-02-26 | 2017-05-24 | ロシュ グリクアート アーゲー | Bispecific T cell activation antigen binding molecule |
US9487587B2 (en) | 2013-03-05 | 2016-11-08 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells of a companion animal that express an activating receptor and cells that express B7-H3 and uses thereof |
US10106624B2 (en) | 2013-03-15 | 2018-10-23 | Xencor, Inc. | Heterodimeric proteins |
US10519242B2 (en) | 2013-03-15 | 2019-12-31 | Xencor, Inc. | Targeting regulatory T cells with heterodimeric proteins |
CA3093606A1 (en) | 2013-03-15 | 2014-09-18 | Xencor, Inc. | Heterodimeric proteins for induction of t cells |
US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
EP2789630A1 (en) | 2013-04-09 | 2014-10-15 | EngMab AG | Bispecific antibodies against CD3e and ROR1 |
JP6473138B2 (en) * | 2013-05-03 | 2019-02-20 | イェール ユニバーシティーYale University | Synthetic antibody mimetic compounds (SyAM) targeting cancer, particularly prostate cancer |
WO2014188423A1 (en) | 2013-05-21 | 2014-11-27 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Treatment of mast cell related pathologies |
PL3004167T3 (en) | 2013-05-30 | 2019-01-31 | Kiniksa Pharmaceuticals, Ltd. | Oncostatin m receptor antigen binding proteins |
TR201904121T4 (en) * | 2013-07-09 | 2019-04-22 | The Government Of The United States As Represented By The Secretary Of The Dept Of Health And Human | Human bispecific egfrviii antibody fusing molecules. |
JP6502931B2 (en) | 2013-10-11 | 2019-04-17 | アメリカ合衆国 | TEM 8 antibody and use thereof |
WO2015103549A1 (en) | 2014-01-03 | 2015-07-09 | The United States Of America, As Represented By The Secretary Department Of Health And Human Services | Neutralizing antibodies to hiv-1 env and their use |
SG10202008629XA (en) | 2014-03-28 | 2020-10-29 | Xencor Inc | Bispecific antibodies that bind to cd38 and cd3 |
SG11201609707WA (en) | 2014-07-01 | 2017-01-27 | Pfizer | Bispecific heterodimeric diabodies and uses thereof |
ES2688035T3 (en) | 2014-08-29 | 2018-10-30 | Gemoab Monoclonals Gmbh | Universal antigen receptor that expresses immune cells for addressing multiple multiple antigens, procedure for manufacturing it and using it for the treatment of cancer, infections and autoimmune diseases |
CA2959775A1 (en) | 2014-09-08 | 2016-03-17 | Yeda Research And Development Co. Ltd. | Compositions and methods for treating cancer resistant to a tyrosine kinase inhibitor (tki) |
CA2963692A1 (en) | 2014-10-09 | 2016-04-14 | Engmab Ag | Bispecific antibodies against cd3epsilon and ror1 |
US10160795B2 (en) | 2014-11-14 | 2018-12-25 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to Ebola virus glycoprotein and their use |
US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
EA037065B1 (en) | 2014-11-26 | 2021-02-01 | Ксенкор, Инк. | Heterodimeric antibodies that bind cd3 and cd38 |
LT3223845T (en) | 2014-11-26 | 2021-08-25 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and cd20 |
US20170058043A1 (en) * | 2014-12-06 | 2017-03-02 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Bispecific antibody for cancer immunotherapy |
EP3237449A2 (en) | 2014-12-22 | 2017-11-01 | Xencor, Inc. | Trispecific antibodies |
CA3225013A1 (en) | 2015-02-24 | 2016-09-01 | Bioatla, Llc | Conditionally active proteins |
KR20170140180A (en) | 2015-02-24 | 2017-12-20 | 더 유나이티드 스테이츠 오브 어메리카, 애즈 리프리젠티드 바이 더 세크러테리, 디파트먼트 오브 헬쓰 앤드 휴먼 서비씨즈 | Middle east respiratory syndrome coronavirus immunogens, antibodies, and their use |
US10227411B2 (en) | 2015-03-05 | 2019-03-12 | Xencor, Inc. | Modulation of T cells with bispecific antibodies and FC fusions |
AU2016235541B2 (en) | 2015-03-20 | 2021-04-01 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to gp120 and their use |
CN114920848A (en) * | 2015-05-13 | 2022-08-19 | 埃博灵克斯股份有限公司 | T cell recruitment polypeptides based on CD3 responsiveness |
US11191844B2 (en) | 2015-07-06 | 2021-12-07 | Regeneran Pharmaceuticals, Inc. | Multispecific antigen-binding molecules and uses thereof |
CN108350073B (en) | 2015-08-03 | 2022-03-18 | 英格玛布有限责任公司 | Monoclonal antibodies against BCMA |
MA43025A (en) | 2015-10-02 | 2021-05-26 | Hoffmann La Roche | BISPECIFIC BISPECIFIC MOLECULES OF ANTIGEN ACTIVATING T-LYMPHOCYTES ANTI-CEAXCD3 |
US10392441B2 (en) | 2015-10-07 | 2019-08-27 | United States Of America, As Represented By The Secretary, Department Of Health And Human Services | IL-7R-alpha specific antibodies for treating acute lymphoblastic leukemia |
WO2017075537A1 (en) | 2015-10-30 | 2017-05-04 | Aleta Biotherapeutics Inc. | Compositions and methods for treatment of cancer |
CN108472365A (en) | 2015-10-30 | 2018-08-31 | 艾丽塔生物治疗剂公司 | Composition and method for tumour transduction |
EP4011911A1 (en) | 2015-11-03 | 2022-06-15 | The United States of America as represented by The Secretary Department of Health and Human Services | Neutralizing antibodies to hiv-1 gp41 and their use |
US20180327499A1 (en) * | 2015-11-13 | 2018-11-15 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti- nkg2d single domain antibodies and uses thereof |
EP3176183A1 (en) | 2015-12-02 | 2017-06-07 | Yeda Research and Development Co. Ltd | Compositions and methods for treating cancer not resistant to a tyrosine kinase inhibitor (tki) |
US11623957B2 (en) | 2015-12-07 | 2023-04-11 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and PSMA |
CR20180318A (en) | 2015-12-14 | 2018-09-19 | Macrogenics Inc | BISPECIFIC MOLECULES THAT HAVE IMMUNORREACTIVITY WITH PD-1 AND CTLA-4, AND METHODS OF USE OF THE SAME |
EP3448891A1 (en) | 2016-04-28 | 2019-03-06 | Regeneron Pharmaceuticals, Inc. | Methods of making multispecific antigen-binding molecules |
WO2017192589A1 (en) | 2016-05-02 | 2017-11-09 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to influenza ha and their use and identification |
US10787518B2 (en) | 2016-06-14 | 2020-09-29 | Xencor, Inc. | Bispecific checkpoint inhibitor antibodies |
CA3029328A1 (en) | 2016-06-28 | 2018-01-04 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
US11186634B2 (en) | 2016-07-29 | 2021-11-30 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Antibodies targeting tumor associated macrophages and uses thereof |
US10793632B2 (en) | 2016-08-30 | 2020-10-06 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
MX2019004327A (en) | 2016-10-14 | 2019-10-14 | Xencor Inc | Bispecific heterodimeric fusion proteins containing il-15/il-15ralpha fc-fusion proteins and pd-1 antibody fragments. |
BR112019008426A2 (en) | 2016-11-02 | 2019-09-03 | Engmab Sarl | bispecific antibody against bcma and cd3 and an immunological drug for combined use in the treatment of multiple myeloma |
JP2020506971A (en) | 2017-02-08 | 2020-03-05 | ドラゴンフライ セラピューティクス, インコーポレイテッド | Multispecific binding proteins for the activation of natural killer cells and their therapeutic use for treating cancer |
US11021535B2 (en) | 2017-02-10 | 2021-06-01 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to plasmodium falciparum circumsporozoite protein and their use |
WO2018152496A1 (en) | 2017-02-17 | 2018-08-23 | The Usa, As Represented By The Secretary, Dept. Of Health And Human Services | Compositions and methods for the diagnosis and treatment of zika virus infection |
CN110944661A (en) | 2017-02-20 | 2020-03-31 | 蜻蜓疗法股份有限公司 | HER2, NKG2D and CD16 binding proteins |
US11274160B2 (en) | 2017-03-02 | 2022-03-15 | INSERM (Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to Nectin-4 and uses thereof |
WO2018189403A1 (en) | 2017-04-14 | 2018-10-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of cancer |
EP4230649A3 (en) | 2017-04-25 | 2023-10-25 | The U.S.A. As Represented By The Secretary, Department Of Health And Human Services | Antibodies and methods for the diagnosis and treatment of epstein barr virus infection |
MA49517A (en) | 2017-06-30 | 2020-05-06 | Xencor Inc | TARGETED HETERODIMERIC FC FUSION PROTEINS CONTAINING IL-15 / IL-15RA AND AREAS OF ANTIGEN BINDING |
CN111094334A (en) | 2017-07-19 | 2020-05-01 | 美国卫生与公众服务部 | Antibodies and methods for diagnosis and treatment of hepatitis B virus infection |
WO2019094637A1 (en) | 2017-11-08 | 2019-05-16 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-pd-1 sequences |
US10981992B2 (en) | 2017-11-08 | 2021-04-20 | Xencor, Inc. | Bispecific immunomodulatory antibodies that bind costimulatory and checkpoint receptors |
WO2019106126A1 (en) | 2017-12-01 | 2019-06-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Mdm2 modulators for the diagnosis and treatment of liposarcoma |
SG11202005732XA (en) | 2017-12-19 | 2020-07-29 | Xencor Inc | Engineered il-2 fc fusion proteins |
WO2019136029A1 (en) | 2018-01-02 | 2019-07-11 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to ebola virus glycoprotein and their use |
JP2021512630A (en) | 2018-02-08 | 2021-05-20 | ドラゴンフライ セラピューティクス, インコーポレイテッド | Antibody variable domain targeting NKG2D receptor |
CN111787949A (en) | 2018-02-15 | 2020-10-16 | 宏观基因有限公司 | Variant CD 3-binding domains and their use in combination therapy for the treatment of disease |
WO2019165122A1 (en) | 2018-02-21 | 2019-08-29 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to hiv-1 env and their use |
WO2019195623A2 (en) | 2018-04-04 | 2019-10-10 | Xencor, Inc. | Heterodimeric antibodies that bind fibroblast activation protein |
EP3775908A1 (en) | 2018-04-13 | 2021-02-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting outcome and treatment of patients suffering from prostate cancer or breast cancer |
EP3781598A1 (en) | 2018-04-18 | 2021-02-24 | Xencor, Inc. | Tim-3 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and tim-3 antigen binding domains |
WO2019204665A1 (en) | 2018-04-18 | 2019-10-24 | Xencor, Inc. | Pd-1 targeted heterodimeric fusion proteins containing il-15/il-15ra fc-fusion proteins and pd-1 antigen binding domains and uses thereof |
US20210171610A1 (en) | 2018-05-02 | 2021-06-10 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Antibodies and methods for the diagnosis, prevention, and treatment of epstein barr virus infection |
CN112513081A (en) * | 2018-06-14 | 2021-03-16 | 生物蛋白有限公司 | Multispecific antibody constructs |
WO2019244973A1 (en) * | 2018-06-20 | 2019-12-26 | 中外製薬株式会社 | Method for activating immune response of target cell and composition therefor |
KR20210023982A (en) * | 2018-06-21 | 2021-03-04 | 리제너론 파아마슈티컬스, 인크. | Bispecific anti-PSMA X anti-CD28 antibodies and uses thereof |
CN113227359A (en) | 2018-08-24 | 2021-08-06 | 耶达研究及发展有限公司 | Methods of modulating polarization of M2 macrophages and uses thereof in therapy |
WO2020072821A2 (en) | 2018-10-03 | 2020-04-09 | Xencor, Inc. | Il-12 heterodimeric fc-fusion proteins |
US20220089694A1 (en) | 2018-12-20 | 2022-03-24 | The U.S.A., As Represented By The Secretary, Department Of Health And Human Services | Ebola virus glycoprotein-specific monoclonal antibodies and uses thereof |
KR20210134725A (en) | 2019-03-01 | 2021-11-10 | 젠코어 인코포레이티드 | Heterodimeric Antibodies that Bind to ENPP3 and CD3 |
JP2022526764A (en) * | 2019-03-22 | 2022-05-26 | 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 | EGFRxCD28 multispecific antibody |
EP3715374A1 (en) | 2019-03-23 | 2020-09-30 | Ablevia biotech GmbH | Compound for the sequestration of undesirable antibodies in a patient |
EP3715376A1 (en) | 2019-03-23 | 2020-09-30 | Ablevia biotech GmbH | Compound for the prevention or treatment of myasthenia gravis |
EP3715375A1 (en) | 2019-03-23 | 2020-09-30 | Ablevia biotech GmbH | Compound for the prevention or treatment of pre-eclampsia |
US20220227853A1 (en) | 2019-05-03 | 2022-07-21 | The United States Of America,As Represented By The Secretary,Department Of Health And Human Services | Neutralizing antibodies to plasmodium falciparum circumsporozoite protein and their use |
KR20230031981A (en) | 2019-05-14 | 2023-03-07 | 프로벤션 바이오, 인코포레이티드 | Methods and compositions for preventing type 1 diabetes |
US20230085439A1 (en) | 2019-05-21 | 2023-03-16 | University Of Georgia Research Foundation, Inc. | Antibodies that bind human metapneumovirus fusion protein and their use |
EA202290208A1 (en) | 2019-07-02 | 2022-03-25 | Дзе Юнайтед Стейтс Оф Эмерика, Эз Репрезентед Бай Дзе Секретэри, Дипартмент Оф Хелт Энд Хьюман Сервисиз | MONOCLONAL ANTIBODIES THAT BIND EGFRvIII AND THEIR APPLICATIONS |
EP4072682A1 (en) | 2019-12-09 | 2022-10-19 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Antibodies having specificity to her4 and uses thereof |
JP2023525053A (en) | 2020-05-12 | 2023-06-14 | インサーム(インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル) | A new method to treat cutaneous T-cell lymphoma and TFH-derived lymphoma |
WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
IL300666A (en) | 2020-08-19 | 2023-04-01 | Xencor Inc | Anti-cd28 compositions |
WO2022063879A1 (en) | 2020-09-23 | 2022-03-31 | Ablevia Biotech Gmbh | Compound for the sequestration of undesirable antibodies in a patient |
WO2022132904A1 (en) | 2020-12-17 | 2022-06-23 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies targeting sars-cov-2 |
CA3209136A1 (en) | 2021-02-09 | 2022-08-18 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Antibodies targeting the spike protein of coronaviruses |
EP4291306A1 (en) | 2021-02-09 | 2023-12-20 | University of Georgia Research Foundation, Inc. | Human monoclonal antibodies against pneumococcal antigens |
KR20230156079A (en) | 2021-03-09 | 2023-11-13 | 젠코어 인코포레이티드 | Heterodimeric antibody binding to CD3 and CLDN6 |
WO2022192586A1 (en) | 2021-03-10 | 2022-09-15 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and gpc3 |
CA3226947A1 (en) | 2021-08-03 | 2023-02-09 | Muhammad YASSIN | Engineered tcr complex and methods of using same |
EP4130028A1 (en) | 2021-08-03 | 2023-02-08 | Rhazes Therapeutics Ltd | Engineered tcr complex and methods of using same |
AU2022345251A1 (en) | 2021-09-17 | 2024-03-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Synthetic humanized llama nanobody library and use thereof to identify sars-cov-2 neutralizing antibodies |
WO2023154824A1 (en) | 2022-02-10 | 2023-08-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Human monoclonal antibodies that broadly target coronaviruses |
WO2023192881A1 (en) | 2022-03-28 | 2023-10-05 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to hiv-1 env and their use |
CN115109160B (en) * | 2022-06-07 | 2023-08-01 | 博际生物医药科技(杭州)有限公司 | anti-EPCAM antibodies and bispecific antibodies |
WO2024030829A1 (en) | 2022-08-01 | 2024-02-08 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Monoclonal antibodies that bind to the underside of influenza viral neuraminidase |
WO2024054822A1 (en) | 2022-09-07 | 2024-03-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Engineered sars-cov-2 antibodies with increased neutralization breadth |
WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
CN117736335A (en) * | 2022-09-20 | 2024-03-22 | 深圳先进技术研究院 | Double-targeting CAR-T cell targeting mesothelin and NKG2D ligand and application thereof |
WO2024064826A1 (en) | 2022-09-22 | 2024-03-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Neutralizing antibodies to plasmodium falciparum circumsporozoite protein and their use |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999054440A1 (en) * | 1998-04-21 | 1999-10-28 | Micromet Gesellschaft Für Biomedizinische Forschung Mbh | CD19xCD3 SPECIFIC POLYPEPTIDES AND USES THEREOF |
WO2004106383A1 (en) * | 2003-05-31 | 2004-12-09 | Micromet Ag | Pharmaceutical composition comprising a bispecific antibody for epcam |
Family Cites Families (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3856559T2 (en) | 1987-05-21 | 2004-04-29 | Micromet Ag | Multifunctional proteins with predetermined objectives |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
US5525491A (en) | 1991-02-27 | 1996-06-11 | Creative Biomolecules, Inc. | Serine-rich peptide linkers |
WO1992015682A1 (en) | 1991-02-27 | 1992-09-17 | Creative Biomolecules, Inc. | Serine-rich peptide linkers |
MX9204374A (en) * | 1991-07-25 | 1993-03-01 | Idec Pharma Corp | RECOMBINANT ANTIBODY AND METHOD FOR ITS PRODUCTION. |
US5489288A (en) * | 1992-10-09 | 1996-02-06 | Advanced Surgical, Inc. | Device and method for applying large-diameter ligating loop |
US5858682A (en) * | 1996-08-02 | 1999-01-12 | Pharmingen | E2A/pbx1 fusion protein specific monoclonal antibodies |
TR199902553T2 (en) * | 1997-04-14 | 2000-03-21 | Micromet Gesellschaft F�R Biomedizinische Forschung Mbh | New methods and uses for the production of antigen receptors against the human body. |
GB9928789D0 (en) | 1999-12-03 | 2000-02-02 | Medical Res Council | Naive screening method |
WO2001090190A2 (en) | 2000-05-26 | 2001-11-29 | National Research Council Of Canada | Single-domain antigen-binding antibody fragments derived from llama antibodies |
CN1294148C (en) * | 2001-04-11 | 2007-01-10 | 中国科学院遗传与发育生物学研究所 | Single-stranded cyctic trispecific antibody |
WO2003002609A2 (en) * | 2001-06-28 | 2003-01-09 | Domantis Limited | Dual-specific ligand and its use |
WO2004058821A2 (en) * | 2002-12-27 | 2004-07-15 | Domantis Limited | Dual specific single domain antibodies specific for a ligand and for the receptor of the ligand |
JP2005289809A (en) | 2001-10-24 | 2005-10-20 | Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) | Mutant heavy-chain antibody |
-
2003
- 2003-12-22 US US10/743,697 patent/US7235641B2/en active Active
-
2004
- 2004-12-22 ES ES04804237T patent/ES2350935T3/en active Active
- 2004-12-22 WO PCT/EP2004/014643 patent/WO2005061547A2/en not_active Application Discontinuation
- 2004-12-22 AU AU2004303510A patent/AU2004303510B2/en not_active Ceased
- 2004-12-22 DE DE602004028957T patent/DE602004028957D1/en active Active
- 2004-12-22 AT AT04804237T patent/ATE479710T1/en active
- 2004-12-22 DK DK04804237.8T patent/DK1697421T3/en active
- 2004-12-22 MX MXPA06005592A patent/MXPA06005592A/en active IP Right Grant
- 2004-12-22 EP EP04804237A patent/EP1697421B1/en active Active
- 2004-12-22 CA CA2544562A patent/CA2544562C/en not_active Expired - Fee Related
- 2004-12-22 JP JP2006546068A patent/JP5376759B2/en not_active Expired - Fee Related
- 2004-12-22 SI SI200431500T patent/SI1697421T1/en unknown
-
2007
- 2007-05-29 US US11/754,792 patent/US20080305105A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999054440A1 (en) * | 1998-04-21 | 1999-10-28 | Micromet Gesellschaft Für Biomedizinische Forschung Mbh | CD19xCD3 SPECIFIC POLYPEPTIDES AND USES THEREOF |
WO2004106383A1 (en) * | 2003-05-31 | 2004-12-09 | Micromet Ag | Pharmaceutical composition comprising a bispecific antibody for epcam |
Non-Patent Citations (3)
Title |
---|
BORREBAECK CA ET AL: "Kinetic analysis of recombinant antibody-antigne interactions: relation between structural domains and antigen binding" BIO/TECHNOLOGY, vol. 10, no. 6, 1992, pages 697-698, XP008051970 US * |
DAVIES J ET AL: "ANTIBODY VH DOMAINS AS SMALL RECOGNITION UNITS" May 1995 (1995-05), BIO/TECHNOLOGY, NATURE PUBLISHING CO. NEW YORK, US, PAGE(S) 475-479 , XP002011336 ISSN: 0733-222X the whole document * |
S. EWERT ET AL: "Biophysical properties of human antibody variable domains" J. MOL.BIOL., vol. 325, 2003, pages 531-553, XP002343836 * |
Cited By (261)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8951737B2 (en) | 1996-05-06 | 2015-02-10 | Cornell Research Foundation, Inc. | Treatment and diagnosis of cancer |
US8853366B2 (en) | 2001-01-17 | 2014-10-07 | Emergent Product Development Seattle, Llc | Binding domain-immunoglobulin fusion proteins |
US10143748B2 (en) | 2005-07-25 | 2018-12-04 | Aptevo Research And Development Llc | B-cell reduction using CD37-specific and CD20-specific binding molecules |
US10307481B2 (en) | 2005-07-25 | 2019-06-04 | Aptevo Research And Development Llc | CD37 immunotherapeutics and uses thereof |
EP3770174A1 (en) * | 2005-10-11 | 2021-01-27 | Amgen Research (Munich) GmbH | Compositions comprising cross-species-specific antibodies and uses thereof |
US8236308B2 (en) | 2005-10-11 | 2012-08-07 | Micromet Ag | Composition comprising cross-species-specific antibodies and uses thereof |
EP1940881A2 (en) * | 2005-10-11 | 2008-07-09 | Micromet AG | Compositions comprising cross-species-specific antibodies and uses thereof |
JP2009511521A (en) * | 2005-10-11 | 2009-03-19 | ミクロメット・アクチェンゲゼルシャフト | Compositions comprising cross-species-specific antibodies and uses of the compositions |
US11925684B2 (en) | 2005-10-11 | 2024-03-12 | Amgen Research (Munich) Gmbh | Compositions comprising cross-species-specific antibodies and uses thereof |
WO2007042261A3 (en) * | 2005-10-11 | 2007-12-21 | Micromet Ag | Compositions comprising cross-species-specific antibodies and uses thereof |
EP1940881B1 (en) | 2005-10-11 | 2016-11-30 | Amgen Research (Munich) GmbH | Compositions comprising cross-species-specific antibodies and uses thereof |
EP3178850A1 (en) * | 2005-10-11 | 2017-06-14 | Amgen Research (Munich) GmbH | Compositions comprising cross-species-specific antibodies and uses thereof |
WO2007048849A1 (en) * | 2005-10-28 | 2007-05-03 | Novo Nordisk A/S | Fusion proteins that bind effector lymphocytes and target cells |
US8409577B2 (en) | 2006-06-12 | 2013-04-02 | Emergent Product Development Seattle, Llc | Single chain multivalent binding proteins with effector function |
US8921350B2 (en) | 2006-12-28 | 2014-12-30 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US9925189B2 (en) | 2006-12-28 | 2018-03-27 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US8975258B2 (en) | 2006-12-28 | 2015-03-10 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US9737537B2 (en) | 2006-12-28 | 2017-08-22 | Cymabay Therapeutics, Inc. | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
JP2017012201A (en) * | 2007-04-03 | 2017-01-19 | アムゲン リサーチ (ミュンヘン) ゲーエムベーハー | Cross-species-specific binding domain |
WO2008119566A3 (en) * | 2007-04-03 | 2009-01-08 | Micromet Ag | Cross-species-specific bispecific binders |
EP2520590A3 (en) * | 2007-04-03 | 2013-04-17 | Amgen Research (Munich) GmbH | Cross-species-specific binding domain |
WO2008119565A2 (en) * | 2007-04-03 | 2008-10-09 | Micromet Ag | Cross-species-specific binding domain |
CN101687915B (en) * | 2007-04-03 | 2017-02-08 | 安进研发(慕尼黑)股份有限公司 | Cross-species-specific cd3-epsilon binding domain |
JP2014064568A (en) * | 2007-04-03 | 2014-04-17 | Amgen Research (Munich) Gmbh | Cross-species-specific bispecific binders |
CN103694350B (en) * | 2007-04-03 | 2018-04-24 | 安进研发(慕尼黑)股份有限公司 | Cross-species-specific cd 3-epsilon binding domain |
EP2155783B2 (en) † | 2007-04-03 | 2022-10-19 | Amgen Research (Munich) GmbH | Cross-species-specific cd3-epsilon binding domain |
JP2014087336A (en) * | 2007-04-03 | 2014-05-15 | Amgen Research (Munich) Gmbh | Cross-species-specific binding domain |
CN101687915B8 (en) * | 2007-04-03 | 2018-08-03 | 安进研发(慕尼黑)股份有限公司 | Cross-species-specific cd 3-epsilon binding domain |
CN109456410B (en) * | 2007-04-03 | 2022-01-28 | 安进研发(慕尼黑)股份有限公司 | Cross-species specific CD 3-epsilon binding domains |
JP2018197253A (en) * | 2007-04-03 | 2018-12-13 | アムゲン リサーチ (ミュンヘン) ゲーエムベーハー | Cross-species-specific binding domain |
CN109456410A (en) * | 2007-04-03 | 2019-03-12 | 安进研发(慕尼黑)股份有限公司 | Cross-species-specific cd 3-epsilon binding domain |
WO2008119565A3 (en) * | 2007-04-03 | 2009-01-08 | Micromet Ag | Cross-species-specific binding domain |
JP2021101715A (en) * | 2007-04-03 | 2021-07-15 | アムゲン リサーチ (ミュンヘン) ゲーエムベーハー | Cross-species-specific binding domain |
JP2010524851A (en) * | 2007-04-03 | 2010-07-22 | マイクロメット アーゲー | Species-specific binding domains |
JP2010524435A (en) * | 2007-04-03 | 2010-07-22 | マイクロメット アーゲー | Species-specific bispecific binder |
WO2008119567A3 (en) * | 2007-04-03 | 2009-01-08 | Micromet Ag | Cross-species-specific cd3-epsilon binding domain |
US8846675B2 (en) | 2007-07-19 | 2014-09-30 | Cymabay Therapeutics, Inc. | N-linked heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
US9695236B2 (en) | 2008-04-02 | 2017-07-04 | Macrogenics, Inc. | BCR-complex-specific antibodies and methods of using same |
US10479831B2 (en) | 2008-04-02 | 2019-11-19 | Macrogenics, Inc | BCR-complex-specific antibodies and methods of using same |
US9101609B2 (en) | 2008-04-11 | 2015-08-11 | Emergent Product Development Seattle, Llc | CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof |
US9029508B2 (en) | 2008-04-29 | 2015-05-12 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US9035027B2 (en) | 2008-06-03 | 2015-05-19 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US9109026B2 (en) | 2008-06-03 | 2015-08-18 | Abbvie, Inc. | Dual variable domain immunoglobulins and uses thereof |
EP2303859A4 (en) * | 2008-06-20 | 2012-08-22 | Metabolex Inc | Aryl gpr119 agonists and uses thereof |
EP2303859A2 (en) * | 2008-06-20 | 2011-04-06 | Metabolex Inc. | Aryl gpr119 agonists and uses thereof |
US8822645B2 (en) | 2008-07-08 | 2014-09-02 | Abbvie Inc. | Prostaglandin E2 dual variable domain immunoglobulins and uses thereof |
RU2547600C2 (en) * | 2008-10-01 | 2015-04-10 | Эмджен Рисерч (Мьюник) Гмбх | Pscaxcd3, cd19xcd3, c-metxcd3, endosialin xcd3, epcamxcd3, igf-1rxcd3 or fap-alpha xcd3 bispecific single-chain antibody with inter-species specificity |
US10517969B2 (en) | 2009-02-17 | 2019-12-31 | Cornell University | Methods and kits for diagnosis of cancer and prediction of therapeutic value |
EP2459729A4 (en) * | 2009-07-29 | 2013-04-24 | Abbott Lab | Dual variable domain immunoglobulins and uses thereof |
EP2459729A2 (en) * | 2009-07-29 | 2012-06-06 | Abbott Laboratories | Dual variable domain immunoglobulins and uses thereof |
US8410127B2 (en) | 2009-10-01 | 2013-04-02 | Metabolex, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
US9150567B2 (en) | 2009-10-01 | 2015-10-06 | Cymabay Therapeutics, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
US8815886B2 (en) | 2009-10-01 | 2014-08-26 | Cymabay Therapeutics, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
US8716450B2 (en) | 2009-10-15 | 2014-05-06 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US8722855B2 (en) | 2009-10-28 | 2014-05-13 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US8772459B2 (en) | 2009-12-02 | 2014-07-08 | Imaginab, Inc. | J591 minibodies and Cys-diabodies for targeting human prostate specific membrane antigen (PSMA) and methods for their use |
US11180570B2 (en) | 2009-12-02 | 2021-11-23 | Imaginab, Inc. | J591 minibodies and cys-diabodies for targeting human prostate specific membrane antigen (PSMA) and methods for their use |
WO2011079283A1 (en) * | 2009-12-23 | 2011-06-30 | Bioalliance C.V. | Anti-epcam antibodies that induce apoptosis of cancer cells and methods using same |
US8658765B2 (en) | 2009-12-31 | 2014-02-25 | Avidbiotics Corp. | Non-natural MIC proteins |
US8796420B2 (en) | 2009-12-31 | 2014-08-05 | Avidbiotics Corp. | Non-natural MIC proteins |
US9079969B2 (en) | 2009-12-31 | 2015-07-14 | Avidbiotics Corp. | Non-natural MIC proteins |
US9714295B2 (en) | 2010-03-04 | 2017-07-25 | Macrogenics, Inc. | Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof |
EP2982380A1 (en) | 2010-03-04 | 2016-02-10 | MacroGenics, Inc. | Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof |
US10730945B2 (en) | 2010-03-04 | 2020-08-04 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and users thereof |
US9714296B2 (en) | 2010-03-04 | 2017-07-25 | Macrogenics, Inc. | Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof |
US10683364B2 (en) | 2010-03-04 | 2020-06-16 | Macrogenics, Inc. | Antibodies reactive with B7-H3, immunologically active fragments thereof and uses thereof |
US9896508B2 (en) | 2010-03-04 | 2018-02-20 | Macrogenics, Inc. | Antibodies reactive with B7-H3 and uses thereof |
WO2011109400A2 (en) | 2010-03-04 | 2011-09-09 | Macrogenics,Inc. | Antibodies reactive with b7-h3, immunologically active fragments thereof and uses thereof |
US10098843B2 (en) | 2010-06-23 | 2018-10-16 | Cymabay Therapeutics, Inc. | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
US9241924B2 (en) | 2010-06-23 | 2016-01-26 | Cymabay Therapeutics, Inc. | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
US9493560B2 (en) | 2010-08-03 | 2016-11-15 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US9046513B2 (en) | 2010-08-26 | 2015-06-02 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
US9085622B2 (en) | 2010-09-03 | 2015-07-21 | Glaxosmithkline Intellectual Property Development Limited | Antigen binding proteins |
US11066483B2 (en) | 2010-11-30 | 2021-07-20 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
WO2012122528A1 (en) * | 2011-03-10 | 2012-09-13 | Hco Antibody, Inc. | Bispecific three-chain antibody-like molecules |
US9358282B2 (en) | 2011-03-17 | 2016-06-07 | The University Of Birmingham | Re-directed immunotherapy |
US9402916B2 (en) | 2011-03-17 | 2016-08-02 | The University Of Birmingham | Re-directed immunotherapy |
US10287321B2 (en) | 2011-03-17 | 2019-05-14 | The University Of Birmingham | Re-directed immunotherapy |
US11236131B2 (en) | 2011-03-17 | 2022-02-01 | The University Of Birmingham | Re-directed immunotherapy |
WO2012162067A2 (en) | 2011-05-21 | 2012-11-29 | Macrogenics, Inc. | Cd3-binding molecules capable of binding to human and non-human cd3 |
EP3492494A1 (en) | 2011-05-21 | 2019-06-05 | MacroGenics, Inc. | Cd3-binding molecules capable of binding to human and non-human cd3 |
CN107586340A (en) * | 2011-08-23 | 2018-01-16 | 罗切格利卡特公司 | To T cell activation antigen and the bispecific antibody and application method of specific for tumour antigen |
US11639397B2 (en) | 2011-08-23 | 2023-05-02 | Roche Glycart Ag | Bispecific antibodies specific for T-cell activating antigens and a tumor antigen and methods of use |
CN107586340B (en) * | 2011-08-23 | 2022-01-21 | 罗切格利卡特公司 | Bispecific antibodies specific for T cell activating antigens and tumor antigens and methods of use |
EP2780375B1 (en) | 2011-11-15 | 2019-09-11 | Amgen Research (Munich) GmbH | Binding molecules for bcma and cd3 |
US10766969B2 (en) | 2011-11-15 | 2020-09-08 | Amgen Inc. | Binding molecules for BCMA and CD3 |
EP2780374B1 (en) | 2011-11-15 | 2019-08-21 | Amgen Research (Munich) GmbH | Binding molecules for bcma and cd3 |
US9120870B2 (en) | 2011-12-30 | 2015-09-01 | Abbvie Inc. | Dual specific binding proteins directed against IL-13 and IL-17 |
US9650445B2 (en) | 2012-02-28 | 2017-05-16 | The University Of Birmingham | Immunotherapeutic molecules and uses |
US10106621B2 (en) | 2012-02-28 | 2018-10-23 | The University Of Birmingham | Immunotherapeutic molecules and uses |
US9822180B2 (en) | 2012-02-28 | 2017-11-21 | The University Of Birmingham | Immunotherapeutic molecules and uses |
EP3505537A1 (en) | 2012-05-07 | 2019-07-03 | Trustees of Dartmouth College | Anti-b7-h6 antibody, fusion proteins, and methods of using the same |
US9045551B2 (en) | 2012-11-01 | 2015-06-02 | Abbvie Inc. | Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof |
US9163093B2 (en) | 2012-11-01 | 2015-10-20 | Abbvie Inc. | Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof |
US9944720B2 (en) | 2012-11-01 | 2018-04-17 | Abbvie Inc. | Anti-DLL4/VEGF dual variable domain immunoglobulin and uses thereof |
US11421031B2 (en) | 2013-03-14 | 2022-08-23 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof |
US9908938B2 (en) | 2013-03-14 | 2018-03-06 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof |
WO2014159940A1 (en) | 2013-03-14 | 2014-10-02 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor |
US10730947B2 (en) | 2013-03-14 | 2020-08-04 | Macrogenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor and an antigen expressed by a cell infected by a virus and uses thereof |
EP3839044A1 (en) | 2013-03-14 | 2021-06-23 | MacroGenics, Inc. | Bispecific molecules that are immunoreactive with immune effector cells that express an activating receptor |
US8987418B2 (en) | 2013-03-15 | 2015-03-24 | Abbvie Inc. | Dual specific binding proteins directed against IL-1β and/or IL-17 |
US9062108B2 (en) | 2013-03-15 | 2015-06-23 | Abbvie Inc. | Dual specific binding proteins directed against IL-1 and/or IL-17 |
WO2015095418A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
EP3647324A1 (en) | 2013-12-17 | 2020-05-06 | F. Hoffmann-La Roche AG | Methods of treating cancers using pd-1 axis binding antagonists and taxanes |
WO2015095410A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Methods of treating cancer using pd-1 axis binding antagonists and an anti-cd20 antibody |
EP3680254A1 (en) | 2013-12-17 | 2020-07-15 | F. Hoffmann-La Roche AG | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
US10100115B2 (en) | 2014-02-14 | 2018-10-16 | Macrogenics, Inc. | Methods for the treatment of vascularizing cancers |
US11485790B2 (en) | 2014-04-07 | 2022-11-01 | Chugai Seiyaku Kabushiki Kaisha | Immunoactivating antigen-binding molecule |
US11505605B2 (en) | 2014-05-13 | 2022-11-22 | Chugai Seiyaku Kabushiki Kaisha | T cell-redirected antigen-binding molecule for cells having immunosuppression function |
EP3954703A2 (en) | 2014-05-29 | 2022-02-16 | MacroGenics, Inc. | Tri-specific binding molecules and methods of use thereof |
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 |
US10647768B2 (en) | 2014-05-29 | 2020-05-12 | Macrogenics, Inc. | Multi-chain polypeptide-containing tri-specific binding molecules |
US11820818B2 (en) | 2014-05-29 | 2023-11-21 | Macrogenics, Inc. | Multi-chain polypeptide-containing tri-specific binding molecules |
WO2015184203A1 (en) | 2014-05-29 | 2015-12-03 | Macrogenics, Inc. | Tri-specific binding molecules and methods of use thereof |
US11697684B2 (en) | 2014-05-29 | 2023-07-11 | Macrogenics, Inc. | Tri-specific binding molecules that specifically bind to multiple cancer antigens |
US11098119B2 (en) | 2014-06-26 | 2021-08-24 | Macrogenics, Inc. | Covalently bonded diabodies having immunoreactivity with PD-1 and LAG-3, and methods of use thereof |
US10160806B2 (en) | 2014-06-26 | 2018-12-25 | Macrogenics, Inc. | Covalently bonded diabodies having immunoreactivity with PD-1 and LAG-3, and methods of use thereof |
US10519234B2 (en) | 2014-06-27 | 2019-12-31 | Innate Pharma | NKp46 binding proteins |
US11208480B2 (en) | 2014-06-27 | 2021-12-28 | Innate Pharma | Multispecific antigen binding proteins |
US10633443B2 (en) | 2014-09-26 | 2020-04-28 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD19 and CD3, and uses thereof |
US11639386B2 (en) | 2014-09-26 | 2023-05-02 | Macrogenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD19 and CD3, and uses thereof |
US10717778B2 (en) | 2014-09-29 | 2020-07-21 | Duke University | Bispecific molecules comprising an HIV-1 envelope targeting arm |
US11091530B2 (en) | 2014-11-05 | 2021-08-17 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
US11299539B2 (en) | 2014-11-05 | 2022-04-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
EP3753948A1 (en) | 2014-11-05 | 2020-12-23 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
US10112994B2 (en) | 2014-11-05 | 2018-10-30 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
US10066002B2 (en) | 2014-11-05 | 2018-09-04 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
WO2016073791A1 (en) | 2014-11-05 | 2016-05-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
WO2016073794A1 (en) | 2014-11-05 | 2016-05-12 | Genentech, Inc. | Methods of producing two chain proteins in bacteria |
US10093733B2 (en) | 2014-12-11 | 2018-10-09 | Abbvie Inc. | LRP-8 binding dual variable domain immunoglobulin proteins |
US10441649B2 (en) | 2015-02-02 | 2019-10-15 | The University Of Birmingham | Targeting moiety peptide epitope complexes having a plurality of T-cell epitopes |
WO2016154585A1 (en) | 2015-03-26 | 2016-09-29 | Charles Sentman | Anti-mica antigen binding fragments, fusion molecules, cells which express and methods of using |
US11857571B2 (en) | 2015-03-26 | 2024-01-02 | The Trustees Of Dartmouth College | Anti-mica antigen binding fragments, fusion molecules, cells which express and methods of using |
US10744157B2 (en) | 2015-03-26 | 2020-08-18 | The Trustees Of Dartmouth College | Anti-MICA antigen binding fragments, fusion molecules, cells which express and methods of using |
EP3763827A1 (en) | 2015-05-29 | 2021-01-13 | F. Hoffmann-La Roche AG | Pd-l1 promoter methylation in cancer |
US11254987B2 (en) | 2015-05-29 | 2022-02-22 | Genentech, Inc. | PD-L1 promoter methylation in cancer |
WO2016196381A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Pd-l1 promoter methylation in cancer |
US9840554B2 (en) | 2015-06-15 | 2017-12-12 | Abbvie Inc. | Antibodies against platelet-derived growth factor (PDGF) |
WO2016205320A1 (en) | 2015-06-17 | 2016-12-22 | Genentech, Inc. | Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes |
US10113003B2 (en) | 2015-06-23 | 2018-10-30 | Innate Pharma | Multispecific NK engager proteins |
US11267897B2 (en) | 2015-06-23 | 2022-03-08 | Innate Pharma | Multispecific NK engager protein |
US11254744B2 (en) | 2015-08-07 | 2022-02-22 | Imaginab, Inc. | Antigen binding constructs to target molecules |
WO2017025033A1 (en) * | 2015-08-10 | 2017-02-16 | 中山大学 | Bispecific nano-antibody used for treating cea positive expression tumour |
US11352426B2 (en) | 2015-09-21 | 2022-06-07 | Aptevo Research And Development Llc | CD3 binding polypeptides |
US11286300B2 (en) | 2015-10-01 | 2022-03-29 | Hoffmann-La Roche Inc. | Humanized anti-human CD19 antibodies and methods of use |
US11660340B2 (en) | 2015-11-18 | 2023-05-30 | Chugai Seiyaku Kabushiki Kaisha | Combination therapy using T cell redirection antigen binding molecule against cell having immunosuppressing function |
US11649293B2 (en) | 2015-11-18 | 2023-05-16 | Chugai Seiyaku Kabushiki Kaisha | Method for enhancing humoral immune response |
US10035856B2 (en) | 2015-11-19 | 2018-07-31 | Revitope Limited | Functional antibody fragment complementation for a two-components system for redirected killing of unwanted cells |
EP3178848A1 (en) | 2015-12-09 | 2017-06-14 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody for reducing formation of anti-drug antibodies |
EP4026848A1 (en) | 2015-12-09 | 2022-07-13 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody for reducing the cytokine release syndrome |
EP3862365A1 (en) | 2016-01-08 | 2021-08-11 | F. Hoffmann-La Roche AG | Methods of treating cea-positive cancers using pd-1 axis binding antagonists and anti-cea/anti-cd3 bispecific antibodies |
WO2017127499A1 (en) | 2016-01-22 | 2017-07-27 | Janssen Biotech, Inc. | Anti-ror1 antibodies, ror1 x cd3 bispecific antibodies, and methods of using the same |
US11591400B2 (en) | 2016-04-15 | 2023-02-28 | Macrogenics, Inc. | B7-H3 directed antibody drug conjugates |
US10961311B2 (en) | 2016-04-15 | 2021-03-30 | Macrogenics, Inc. | B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof |
EP3252078A1 (en) | 2016-06-02 | 2017-12-06 | F. Hoffmann-La Roche AG | Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer |
US11613572B2 (en) | 2016-06-21 | 2023-03-28 | Teneobio, Inc. | CD3 binding antibodies |
WO2018011421A1 (en) | 2016-07-14 | 2018-01-18 | Genmab A/S | Multispecific antibodies against cd40 and cd137 |
US10292983B2 (en) | 2016-08-03 | 2019-05-21 | Cymabay Therapeutics, Inc. | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
WO2018027204A1 (en) | 2016-08-05 | 2018-02-08 | Genentech, Inc. | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
US11046776B2 (en) | 2016-08-05 | 2021-06-29 | Genentech, Inc. | Multivalent and multiepitopic antibodies having agonistic activity and methods of use |
WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
US11505606B2 (en) | 2016-09-14 | 2022-11-22 | Teneobio, Inc. | CD3 binding antibodies |
WO2018114754A1 (en) | 2016-12-19 | 2018-06-28 | F. Hoffmann-La Roche Ag | Combination therapy with targeted 4-1bb (cd137) agonists |
WO2018114748A1 (en) | 2016-12-20 | 2018-06-28 | F. Hoffmann-La Roche Ag | Combination therapy of anti-cd20/anti-cd3 bispecific antibodies and 4-1bb (cd137) agonists |
US11434299B2 (en) | 2016-12-21 | 2022-09-06 | Teneobio, Inc. | Anti-BCMA heavy chain-only antibodies |
US11266745B2 (en) | 2017-02-08 | 2022-03-08 | Imaginab, Inc. | Extension sequences for diabodies |
WO2018162749A1 (en) | 2017-03-09 | 2018-09-13 | Genmab A/S | Antibodies against pd-l1 |
US11180571B2 (en) | 2017-04-03 | 2021-11-23 | Hoffmann-La Roche Inc. | Antibodies binding to STEAP-1 |
WO2018184966A1 (en) | 2017-04-03 | 2018-10-11 | F. Hoffmann-La Roche Ag | Antibodies binding to steap-1 |
US11685790B2 (en) | 2017-04-03 | 2023-06-27 | Hoffmann-La Roche Inc. | Antibodies binding to STEAP-1 |
WO2018191502A2 (en) | 2017-04-13 | 2018-10-18 | Agenus Inc. | Anti-cd137 antibodies and methods of use thereof |
EP4275698A2 (en) | 2017-05-01 | 2023-11-15 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
WO2018204363A1 (en) | 2017-05-01 | 2018-11-08 | Agenus Inc. | Anti-tigit antibodies and methods of use thereof |
WO2018220099A1 (en) | 2017-06-02 | 2018-12-06 | F. Hoffmann-La Roche Ag | Type ii anti-cd20 antibody and anti-cd20/cd3 bispecific antibody for treatment of cancer |
WO2019025545A1 (en) | 2017-08-04 | 2019-02-07 | Genmab A/S | Binding agents binding to pd-l1 and cd137 and use thereof |
WO2019086497A2 (en) | 2017-11-01 | 2019-05-09 | F. Hoffmann-La Roche Ag | Combination therapy with targeted ox40 agonists |
US11192957B2 (en) | 2017-12-21 | 2021-12-07 | Hoffmann-La Roche Inc. | Antibodies binding to HLA-A2/WT1 |
WO2019122052A2 (en) | 2017-12-21 | 2019-06-27 | F. Hoffmann-La Roche Ag | Antibodies binding to hla-a2/wt1 |
WO2019126634A2 (en) | 2017-12-22 | 2019-06-27 | Genentech, Inc. | Targeted integration of nucleic acids |
WO2019149715A1 (en) | 2018-01-31 | 2019-08-08 | F. Hoffmann-La Roche Ag | Stabilized immunoglobulin domains |
WO2019149716A1 (en) | 2018-01-31 | 2019-08-08 | F. Hoffmann-La Roche Ag | Bispecific antibodies comprising an antigen-binding site binding to lag3 |
WO2019154890A1 (en) | 2018-02-09 | 2019-08-15 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
WO2019175125A1 (en) | 2018-03-13 | 2019-09-19 | F. Hoffmann-La Roche Ag | Combination therapy with targeted 4-1bb (cd137) agonists |
WO2019175071A1 (en) | 2018-03-13 | 2019-09-19 | F. Hoffmann-La Roche Ag | Therapeutic combination of 4-1 bb agonists with anti-cd20 antibodies |
WO2019191552A1 (en) | 2018-03-29 | 2019-10-03 | Genentech, Inc. | Modulating lactogenic activity in mammalian cells |
WO2019202041A1 (en) | 2018-04-18 | 2019-10-24 | F. Hoffmann-La Roche Ag | Multispecific antibodies and use thereof |
US11492409B2 (en) | 2018-06-01 | 2022-11-08 | Novartis Ag | Binding molecules against BCMA and uses thereof |
US11530274B2 (en) | 2018-07-02 | 2022-12-20 | Amgen Inc. | Anti-STEAP1 antigen-binding protein |
WO2020058297A1 (en) | 2018-09-18 | 2020-03-26 | F. Hoffmann-La Roche Ag | Use of a cathepsin s inhibitor against the formation of anti-drug antibodies |
EP4249917A2 (en) | 2018-09-21 | 2023-09-27 | F. Hoffmann-La Roche AG | Diagnostic methods for triple-negative breast cancer |
WO2020061349A1 (en) | 2018-09-21 | 2020-03-26 | Genentech, Inc. | Diagnostic methods for triple-negative breast cancer |
WO2020096959A1 (en) | 2018-11-05 | 2020-05-14 | Genentech, Inc. | Methods of producing two chain proteins in prokaryotic host cells |
WO2020094744A1 (en) | 2018-11-06 | 2020-05-14 | Genmab A/S | Antibody formulation |
WO2020127619A1 (en) | 2018-12-21 | 2020-06-25 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 |
WO2020132165A1 (en) | 2018-12-21 | 2020-06-25 | Genentech, Inc. | Targeted integration of nucleic acids |
WO2020154410A1 (en) | 2019-01-23 | 2020-07-30 | Genentech, Inc. | Methods of producing multimeric proteins in eukaryotic host cells |
US11905326B2 (en) | 2019-06-14 | 2024-02-20 | Teneobio, Inc. | Multispecific heavy chain antibodies binding to CD22 and CD3 |
WO2021018925A1 (en) | 2019-07-31 | 2021-02-04 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
WO2021018859A2 (en) | 2019-07-31 | 2021-02-04 | F. Hoffmann-La Roche Ag | Antibodies binding to gprc5d |
WO2021042019A1 (en) | 2019-08-30 | 2021-03-04 | Agenus Inc. | Anti-cd96 antibodies and methods of use thereof |
WO2021055577A2 (en) | 2019-09-18 | 2021-03-25 | Genentech, Inc. | Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use |
WO2021084104A1 (en) | 2019-10-30 | 2021-05-06 | Bioinvent International Ab | Tetravalent antibody molecules |
WO2021122875A1 (en) | 2019-12-18 | 2021-06-24 | F. Hoffmann-La Roche Ag | Antibodies binding to hla-a2/mage-a4 |
WO2021133723A2 (en) | 2019-12-23 | 2021-07-01 | Genentech, Inc. | Apolipoprotein l1-specific antibodies and methods of use |
WO2021155916A1 (en) | 2020-02-04 | 2021-08-12 | BioNTech SE | Treatment involving antigen vaccination and binding agents binding to pd-l1 and cd137 |
WO2021156258A1 (en) | 2020-02-04 | 2021-08-12 | BioNTech SE | Treatment involving antigen vaccination and binding agents binding to pd-l1 and cd137 |
WO2021178896A1 (en) | 2020-03-06 | 2021-09-10 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
US11261254B1 (en) | 2020-03-18 | 2022-03-01 | Genmab A/S | Antibodies |
WO2021185934A1 (en) | 2020-03-18 | 2021-09-23 | Genmab A/S | Antibodies binding to b7h4 |
WO2021195464A2 (en) | 2020-03-26 | 2021-09-30 | Genentech, Inc. | Modified mammalian cells |
WO2021214277A1 (en) | 2020-04-24 | 2021-10-28 | F. Hoffmann-La Roche Ag | Enzyme and pathway modulation with sulfhydryl compounds and their derivatives |
US11390681B2 (en) | 2020-04-29 | 2022-07-19 | TeneoTwo, Inc. | Multispecific heavy chain antibodies with modified heavy chain constant regions |
WO2021249990A2 (en) | 2020-06-08 | 2021-12-16 | Hoffmann-La Roche Inc. | Anti-hbv antibodies and methods of use |
WO2021257503A1 (en) | 2020-06-16 | 2021-12-23 | Genentech, Inc. | Methods and compositions for treating triple-negative breast cancer |
WO2021255146A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and cea |
WO2021255143A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and folr1 |
WO2021255155A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and cd19 |
WO2021255142A1 (en) | 2020-06-19 | 2021-12-23 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 |
WO2021262783A1 (en) | 2020-06-24 | 2021-12-30 | Genentech, Inc. | Apoptosis resistant cell lines |
WO2021262798A1 (en) | 2020-06-24 | 2021-12-30 | Genentech, Inc. | Targeted integration of nucleic acids |
WO2022016037A1 (en) | 2020-07-17 | 2022-01-20 | Genentech, Inc. | Anti-notch2 antibodies and methods of use |
WO2022029011A1 (en) | 2020-08-06 | 2022-02-10 | BioNTech SE | Binding agents for coronavirus s protein |
WO2022047222A2 (en) | 2020-08-28 | 2022-03-03 | Genentech, Inc. | Crispr/cas9 multiplex knockout of host cell proteins |
US11845805B2 (en) | 2020-09-10 | 2023-12-19 | Genmab A/S | Bispecific antibody against CD3 and CD20 in combination therapy for treating diffuse large B-cell lymphoma |
US11858995B2 (en) | 2020-09-10 | 2024-01-02 | Genmab A/S | Bispecific antibodies against CD3 and CD20 for treating chronic lymphocytic leukemia |
WO2022129120A1 (en) | 2020-12-17 | 2022-06-23 | F. Hoffmann-La Roche Ag | Anti-hla-g antibodies and use thereof |
WO2022169825A1 (en) | 2021-02-03 | 2022-08-11 | Mozart Therapeutics, Inc. | Binding agents and methods of using the same |
WO2022169872A1 (en) | 2021-02-03 | 2022-08-11 | Genentech, Inc. | Multispecific binding protein degrader platform and methods of use |
WO2022187591A1 (en) | 2021-03-05 | 2022-09-09 | Go Therapeutics, Inc. | Anti-glyco-cd44 antibodies and their uses |
WO2022192647A1 (en) | 2021-03-12 | 2022-09-15 | Genentech, Inc. | Anti-klk7 antibodies, anti-klk5 antibodies, multispecific anti-klk5/klk7 antibodies, and methods of use |
WO2022217022A1 (en) | 2021-04-10 | 2022-10-13 | Profoundbio Us Co. | Folr1 binding agents, conjugates thereof and methods of using the same |
WO2022225880A1 (en) | 2021-04-19 | 2022-10-27 | Genentech, Inc. | Modified mammalian cells |
WO2022226317A1 (en) | 2021-04-23 | 2022-10-27 | Profoundbio Us Co. | Anti-cd70 antibodies, conjugates thereof and methods of using the same |
WO2022228706A1 (en) | 2021-04-30 | 2022-11-03 | F. Hoffmann-La Roche Ag | Dosing for treatment with anti-cd20/anti-cd3 bispecific antibody |
WO2022228705A1 (en) | 2021-04-30 | 2022-11-03 | F. Hoffmann-La Roche Ag | Dosing for combination treatment with anti-cd20/anti-cd3 bispecific antibody and anti-cd79b antibody drug conjugate |
WO2022234146A1 (en) | 2021-05-07 | 2022-11-10 | Genmab A/S | PHARMACEUTICAL COMPOSITIONS COMPRISING BISPECIFIC ANTIBODIES BINDING TO B7H4 and CD3 |
WO2022242644A1 (en) | 2021-05-18 | 2022-11-24 | 赛斯尔擎生物技术(上海)有限公司 | Method for modifying cell |
WO2022246259A1 (en) | 2021-05-21 | 2022-11-24 | Genentech, Inc. | Modified cells for the production of a recombinant product of interest |
WO2022268740A1 (en) | 2021-06-21 | 2022-12-29 | Genmab A/S | Combination dosage regime of cd137 and pd-l1 binding agents |
WO2023280227A2 (en) | 2021-07-06 | 2023-01-12 | Profoundbio Us Co. | Linkers, drug linkers and conjugates thereof and methods of using the same |
WO2023287663A1 (en) | 2021-07-13 | 2023-01-19 | Genentech, Inc. | Multi-variate model for predicting cytokine release syndrome |
WO2023001884A1 (en) | 2021-07-22 | 2023-01-26 | F. Hoffmann-La Roche Ag | Heterodimeric fc domain antibodies |
WO2023012147A1 (en) | 2021-08-03 | 2023-02-09 | F. Hoffmann-La Roche Ag | Bispecific antibodies and methods of use |
WO2023014863A1 (en) | 2021-08-05 | 2023-02-09 | Go Therapeutics, Inc. | Anti-glyco-muc4 antibodies and their uses |
WO2023025208A1 (en) | 2021-08-24 | 2023-03-02 | 赛斯尔擎生物技术(上海)有限公司 | Method for modifying cell |
WO2023025207A1 (en) | 2021-08-24 | 2023-03-02 | 赛斯尔擎生物技术(上海)有限公司 | T cell product and use thereof |
WO2023034571A1 (en) | 2021-09-03 | 2023-03-09 | Go Therapeutics, Inc. | Anti-glyco-lamp1 antibodies and their uses |
WO2023034569A1 (en) | 2021-09-03 | 2023-03-09 | Go Therapeutics, Inc. | Anti-glyco-cmet antibodies and their uses |
WO2023057571A1 (en) | 2021-10-08 | 2023-04-13 | Genmab A/S | Antibodies binding to cd30 and cd3 |
WO2023076876A1 (en) | 2021-10-26 | 2023-05-04 | Mozart Therapeutics, Inc. | Modulation of immune responses to viral vectors |
WO2023104938A1 (en) | 2021-12-10 | 2023-06-15 | F. Hoffmann-La Roche Ag | Antibodies binding to cd3 and plap |
WO2023141445A1 (en) | 2022-01-19 | 2023-07-27 | Genentech, Inc. | Anti-notch2 antibodies and conjugates and methods of use |
WO2023174952A1 (en) | 2022-03-15 | 2023-09-21 | Genmab A/S | Binding agents binding to epcam and/or cd137 |
WO2023174521A1 (en) | 2022-03-15 | 2023-09-21 | Genmab A/S | Binding agents binding to epcam and cd137 |
WO2023180353A1 (en) | 2022-03-23 | 2023-09-28 | F. Hoffmann-La Roche Ag | Combination treatment of an anti-cd20/anti-cd3 bispecific antibody and chemotherapy |
WO2023198727A1 (en) | 2022-04-13 | 2023-10-19 | F. Hoffmann-La Roche Ag | Pharmaceutical compositions of anti-cd20/anti-cd3 bispecific antibodies and methods of use |
US11766479B1 (en) | 2022-06-08 | 2023-09-26 | Zhejiang Shimai Pharmaceutical Co., Ltd. | Therapeutic use of antibodies against ENPP3 |
US11578139B1 (en) | 2022-06-08 | 2023-02-14 | Zhejiang Shimai Pharmaceutical Co., Ltd. | Antibodies against ENPP3 and uses thereof |
WO2024020564A1 (en) | 2022-07-22 | 2024-01-25 | Genentech, Inc. | Anti-steap1 antigen-binding molecules and uses thereof |
WO2024030956A2 (en) | 2022-08-03 | 2024-02-08 | Mozart Therapeutics, Inc. | Cd39-specific binding agents and methods of using the same |
WO2024069165A1 (en) | 2022-09-27 | 2024-04-04 | Coding Bio Limited | Cll1 binding molecules |
Also Published As
Publication number | Publication date |
---|---|
CA2544562C (en) | 2013-10-15 |
US7235641B2 (en) | 2007-06-26 |
ES2350935T3 (en) | 2011-01-28 |
US20080305105A1 (en) | 2008-12-11 |
DK1697421T3 (en) | 2010-12-06 |
EP1697421A2 (en) | 2006-09-06 |
JP2008523783A (en) | 2008-07-10 |
AU2004303510B2 (en) | 2011-02-24 |
SI1697421T1 (en) | 2010-10-29 |
WO2005061547A3 (en) | 2005-11-24 |
ATE479710T1 (en) | 2010-09-15 |
US20050136050A1 (en) | 2005-06-23 |
CA2544562A1 (en) | 2005-07-07 |
JP5376759B2 (en) | 2013-12-25 |
DE602004028957D1 (en) | 2010-10-14 |
MXPA06005592A (en) | 2006-12-15 |
EP1697421B1 (en) | 2010-09-01 |
AU2004303510A1 (en) | 2005-07-07 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2004303510B2 (en) | Bispecific antibodies | |
US5837821A (en) | Antibody construct | |
EP3131928B2 (en) | Trifunctional antigen-binding molecule | |
JP6936497B2 (en) | Multivalent Fv antibody | |
Simmons et al. | Expression of full-length immunoglobulins in Escherichia coli: rapid and efficient production of aglycosylated antibodies | |
US20040220388A1 (en) | Novel heterodimeric fusion proteins | |
KR102629905B1 (en) | Anti-PD-L1/anti-PD-1 natural antibody structure-like heterodimeric bispecific antibody and preparation thereof | |
KR20180120245A (en) | Inducible binding proteins and methods of use | |
JP2020534811A (en) | Conditionally activated binding moiety containing the Fc region | |
ZA200506282B (en) | Trimeric polypeptide construct to induce an enduring T cell response | |
EP1456238B1 (en) | Production of f(ab')2 fragments in mammalian cells | |
TWI690539B (en) | A target cell-dependent t cell engaging and activation asymmetric heterodimeric fc-scfv fusion antibody format and uses thereof in cancer therapy | |
RU2785766C9 (en) | MULTIVALENT Fv-ANTIBODIES | |
CN115397833A (en) | Method for producing multimeric IgA antibody and multispecific multimeric IgA antibody |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BW BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE EG ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NA NI NO NZ OM PG PH PL PT RO RU SC SD SE SG SK SL SY TJ TM TN TR TT TZ UA UG US UZ VC VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): BW GH GM KE LS MW MZ NA SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LT LU MC NL PL PT RO SE SI SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2004303510 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2544562 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2006/005592 Country of ref document: MX |
|
ENP | Entry into the national phase |
Ref document number: 2004303510 Country of ref document: AU Date of ref document: 20041222 Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2004804237 Country of ref document: EP |
|
WWP | Wipo information: published in national office |
Ref document number: 2004303510 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2006546068 Country of ref document: JP |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
WWW | Wipo information: withdrawn in national office |
Country of ref document: DE |
|
WWP | Wipo information: published in national office |
Ref document number: 2004804237 Country of ref document: EP |