573 results about "Antibody molecule" patented technology

The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.

The present invention refers to synthetic antibody molecules which comprise domains from naturally occuring antibodies, e.g. domains derivable from IgG, preferably of human origin, in a novel arrangement. Single chain molecules are provided which are suitable for expression in micro-organisms in their active conformation, which single chain molecules generally comprise a VL domain, a CL domain, and a VH domain, a CH1 domain, linked by a linker arranged between VUCL and VH / CH1. Accordingly, these antibody molecules can be termed single chain Fabs (scFabs). These antibody molecules are single chain proteins, which can also be associated to dimers, including heteromeric antibodies, wherein at least two single chain antibody molecules are associated.

The present inventors discovered that antibodies having weaker antigen-binding activity at the early endosomal pH in comparison with that at the pH of plasma are capable of binding to multiple antigen molecules with a single antibody molecule, have long half-lives in plasma, and have improved durations of time in which they can bind to antigen.

In accordance with the present invention, there are provided methods for the extension of serum half-lives of proteinaceous molecules, particularly antibody molecules, and compositions of molecules modified in accordance with the methods of the invention. In accordance with a first aspect of the present invention, there is provided a method of modifying the half-life of an antibody through providing an antibody containing an FcRn binding domain or the genes encoding such antibody and physically linking the antibody or the antibody as encoded to a second FcRn binding domain. In accordance with a second aspect of the present invention, there is provided a molecule that contains at least two distinct FcRn binding moieties.

The present invention relates to a novel process for the preparation of biologically active antibody dimers in a pharmaceutically acceptable composition. The dimers can be composed of two antibody molecules having the same antigen binding specificity and linked through reducible, disulfide, or a non-reducible thioether, bond (homodimer). Alternatively, the dimers can be composed of two different antibody molecules having binding specificity for two distinct antigens (heterodimer). These dimers are useful for inducing hyper-cross-linking of membrane antigens. The present invention further relates to the use of biologically active antibody dimers for the preferential killing or inhibition of selected cell populations in the treatment of diseases such as cancer and autoimmune disorders.

The present invention relates to a recombinant antibody composition having higher complement-dependent cytotoxic activity than a human IgG1 antibody and a human IgG3 antibody, wherein a polypeptide comprising a CH2 domain in the Fc region of a human IgG1 antibody is replaced by a polypeptide comprising an amino acid sequence which corresponds to the same position of a human IgG3 antibody indicated by the EU index as in Kabat, et al.; a DNA encoding the antibody molecule or a heavy chain constant region of the antibody molecule contained in the recombinant antibody composition; a transformant obtainable by introducing the recombinant vector into a host cell; a process for producing the recombinant antibody composition using the transformant; and a medicament comprising the recombinant antibody composition as an active ingredient.

A method for enhancing a binding activity of an antibody composition to Fcgamma receptor IIIa, which comprises modifying a complex N-glycoside-linked sugar chain which is bound to the Fc region of an antibody molecule; a method for enhancing an antibody-dependent cell-mediated cytotoxic activity of an antibody composition; a process for producing an antibody composition having an enhanced binding activity to Fcgamma receptor IIIa; a method for detecting the ratio of a sugar chain in which fucose is not bound to N-acetylglucosamine in the reducing end in the sugar chain among total complex N-glycoside-linked sugar chains bound to the Fc region in an antibody composition; an Fc fusion protein composition produced by using a cell resistant to a lectin which recognizes a sugar chain in which 1-position of fucose is bound to 6-position of N-acetylglucosamine in the reducing end through alpha-bond in a complex N-glycoside-linked sugar chain; and a process for producing the same.

The present invention features improved in vitro RNA display libraries to allow reliable expression and selection of scFv antibody molecules from expression libraries. The scFv antibody libraries of the invention contain an optimized, shortened inter-domain linker that improves expression scFv antibody expression. The scFv antibody libraries also include short nucleic acid barcodes that allow for identification of individual library clones, libraries or subsets thereof. Primers for generating, amplifying and spectratyping the scFv antibody libraries of the invention are also provided.

The invention discloses an integral detecting reacting board and protein chip agent box of Carcinoembryonic antigen,CEA, 15-3 CA15-3(Carbohydrate Antigen 15-3,CA15-3), CA 125 (Cancer antigen 125,CA125), Squamous cell carcinoma antigen,SCC, Human papillomavirus antibody,HPVAb, beta-human chorionic gonadotropin, beta-HCG and alpha-fetoprotein,AFP, wherein the reacting hole board contains base and reacting hole on the base; the reacting hole contains 2-384 sample holes, 2-200 standard sample holes; the fixing phase carrier is set on the bottom of each reacting hole, which is covered by seven antigen or antibody molecule arrays with anti-CEA, anti-CA15-3,anti-CA125,anti-SCC,HPV,anti- beta-HCG,anti-AFP.

The present invention relates to human thymic stromal lymphopoietin (hTSLP) antibodies and especially those which neutralize hTSLP activity. It further relates to methods for using anti-hTSLP antibody molecules in diagnosis or treatment of hTSLP related disorders, such as asthma, atopic dermatitis, allergic rhinitis, fibrosis inflammatory bowel disease, and Hodgkin's lymphoma.

The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

The invention relates to a medicine of a bispecific monoclonal antibody, and especially to a medicine of a bispecific monoclonal antibody to human vascular endothelial growth factor (VEGF / VEGF-A) and platelet-derived growth factor receptor (PDGFR) for resistance to angiogenesis of tumor. The bispecific antibody to VEGF / PDGFR beta provided in the invention is characterized in that: a monoclonal antibody to VEGF is used as the base for the antibody and a single chain antibody to PDGFR beta is connected with the terminal of FC segment of the monoclonal antibody to VEGF to form the bispecific antibody to VEGF / PDGFR beta. The bispecific antibody related to in the invention is obtained by employing technical means like gene engineering and constructing antibody segments which identify VEGF and PDGFR beta in a same antibody molecule that can be specifically bound with the two antibody segments; the effect of the bispecific antibody on inhibiting angiogenesis of tumor issue is obviously superior to that of a single antibody to VEGF; and the bispecific antibody has good activity in resisting tumors.

Bispecific single chain antibody molecules are disclosed which may be used to advantage to treat various forms of cancer associated with the overexpression of members of the EGFR protein family.

Disclosed are novel polyclonal antibodies, which target respiratory syncyticilal virus (RSV), and novel high affinity antibody molecules reactive with RSV. The polyclonal antibodies may comprise antibody molecules which are reactive with both RSV protein F and RSV protein G, and preferably the polyclonal antibodies target a variety of epitopes on these proteins. The single antibody molecules of the invention are shown to exhibit affinities which provide for dissociation constants as low as in the picomolar range. Also disclosed are methods of producing the antibodies of the invention as well as methods of their use in treatment for RSV infection.

The present invention relates to a recombinant antibody composition having higher complement-dependent cytotoxic activity than a human IgG1 antibody and a human IgG3 antibody, wherein a polypeptide comprising a CH2 domain in the Fc region of a human IgG1 antibody is replaced by a polypeptide comprising an amino acid sequence which corresponds to the same position of a human IgG3 antibody indicated by the EU index as in Kabat, et al.; a DNA encoding the antibody molecule or a heavy chain constant region of the antibody molecule contained in the recombinant antibody composition; a transformant obtainable by introducing the recombinant vector into a host cell; a process for producing the recombinant antibody composition using the transformant; and a medicament comprising the recombinant antibody composition as an active ingredient.

An objective of the present invention is to provide methods for stabilizing proteins and methods for suppressing protein aggregation, which comprise the step of adding for suppressing protein aggregation, which comprise meglumine. Still another objective of the present invention is to provide pharmaceutical compositions comprising antibody molecules stabilized by meglumine, methods for producing the pharmaceutical compositions, and kits comprising the pharmaceutical compositions.To achieve the objectives described above, the present inventors assessed the antibody-stabilizing effect of meglumine, an amino sugar. As a result, the inventors discovered that meglumine was useful as a stabilizer for antibody molecules and also as an excipient for freeze-dried preparations.

Bispecific single chain antibody molecules are disclosed which may be used to advantage to treat various forms of cancer associated with the overexpression of members of the EGFR protein family.

The present invention relates to a cell for the production of an antibody molecule such as an antibody useful for various diseases having high antibody-dependent cell-mediated cytotoxic activity, a fragment of the antibody and a fusion protein having the Fc region of the antibody or the like, a method for producing an antibody composition using the cell, the antibody composition and use thereof.

A method to produce a cell expressing an antibody from a genomic sequence of the cell comprising a modified immunoglobulin locus using Cre-mediated site-specific recombination is disclosed. The method involves first transfecting an antibody-producing cell with a homology-targeting vector comprising a lox site and a targeting sequence homologous to a first DNA sequence adjacent to the region of the immunoglobulin loci of the genomic sequence which is to be converted to a modified region, so the first lox site is inserted into the genomic sequence via site-specific homologous recombination. Then the cell is transfected with a lox-targeting vector comprising a second lox site suitable for Cre-mediated recombination with the integrated lox site and a modifying sequence to convert the region of the immunoglobulin loci to the modified region. This conversion is performed by interacting the lox sites with Cre in vivo, so that the modifying sequence inserts into the genomic sequence via Cre-mediated site-specific recombination of the lox sites. Also disclosed are a form of the method used to produce a cell expressing a modified antibody molecule using Cre-mediated site-specific recombination, and antibody-producing cells obtainable by the disclosed methods. Class-switching modifications of human antibodies produced in murine hybridoma cells are exemplified.

The present invention relates to antibody molecules, in particular antibody molecules that bind Transforming Growth Factor beta (TGFβ), and uses thereof. More particularly, the invention relates to antibody molecules that bind and preferably neutralise TGFβ1, TGFβ2 and TGFβ3, so-called “pan-specific” antibody molecules, and uses of such antibody molecules. Preferred embodiments within the present invention are antibody molecules, whether whole antibody (e.g. IgG, such as IgG1 or IgG4) or antibody fragments (e.g. scFv, Fab, dAb).

Bispecific single chain antibody molecules are disclosed which may be used to advantage to treat various forms of cancer associated with the overexpression of members of the EGFR protein family.

The present invention provides a dendrimer-based biochip, wherein a flow channel through which a solution containing biopolymer molecules is flowed is formed in the substrate of the biochip, a plurality of dendrimer molecules one end of each of which is bound to the walls of the flow channel are formed thereon, and probe biopolymer or antibody molecules are bound to the tips of the dendrimer molecules so that, if the probe biopolymer molecules are bound, then target biopolymer molecules can be captured by means of a complementary combination and, if the antibody molecules are bound, then protein can be extracted by means of antigen-antibody reaction, whereby biopolymers can be retrieved in a highly efficient manner.

An apparatus and methods for binding an analyte of interest in a sample are provided. The apparatus comprises a substrate with an exposed surface with an compound, that is electrostatically charged or capable of forming hydrogen bonds, provided bound to the solid substrate. A recombinant single chain antibody (scFv) molecule specific for the analyte of interest, having one or more amino acids with charged or hydrogen-bond forming sidechains in a linker polypeptide portion, is bound to the layer on the solid substrate. When the analyte of interest is present in the sample the scFv binds the analyte to the solid substrate. The apparatus can be used with an immunoglobulin layer to detect Fc receptors, so as to detect microorganisms such as Staphylococcus aureus having protein A or protein G.

The present invention relates to diagnostics, particularly binding assays for detecting and / or measuring an analyte. The present invention relates to methods for determining the presence and / or amount of an analyte by means of association with one or more non-antibody molecules, in particular non-antibody molecules derived from a species different from that of the analyte. Further, the present invention relates to methods for diagnosing and staging diseases by detecting and / or measuring analytes associated with certain diseases.

The invention provides methods and compositions employing hybrid molecules of a synthetic molecule and antibody or antibody fragment comprising a selenocysteine residue, wherein the synthetic molecule is covalently linked to the antibody or antibody fragment at the selenocysteine residue. The invention also provides a composition comprising a hybrid molecule as described above and a pharmaceutically acceptable carrier. The invention further provides for methods of making the hybrid molecules, and methods of using the hybrid molecule described above to inhibit cell surface receptor binding.

The present invention features improved methods of in vitro RNA display to allow reliable expression and selection of scFv antibody molecules from expression libraries. The improved methods, in part, involve the use of mildly reducing conditions, which favor of scFv intra-chain disulphide bond and thus correct folding of the scFv antibody molecules. Although particularly suited to expression and selection of scFv antibody molecules, the methods of the invention are also expedient for in vitro RNA display of all classes of protein.

An objective of the present invention is to provide methods for facilitating antigen-binding molecule-mediated antigen uptake into cells, methods for facilitating the reduction of antigen concentration in plasma, methods for increasing the number of antigens to which a single antigen-binding molecule can bind, methods for improving pharmacokinetics of antigen-binding molecules, antigen-binding molecules improved for facilitated antigen uptake into cells, antigen-binding molecules capable of facilitating the reduction of antigen concentration in plasma, antigen-binding molecules capable of repeatedly binding to antigens, antigen-binding molecules with improved pharmacokinetics, pharmaceutical compositions comprising such an antigen-binding molecule, and methods for producing those described above. The present inventors discovered that antigen uptake into cells is facilitated by an antibody having human FcRn-binding activity at the plasma pH and a lower antigen-binding activity at the early endosomal pH than at the plasma pH; such antibodies can increase the number of antigens to which a single antibody molecule can bind; the reduction of antigen in plasma can be facilitated by administering such an antibody; and antibody pharmacokinetics can be improved by using such antibodies.