177 results about "Antigen binding site" patented technology

The present application describes engineered antibodies, with three or more functional antigen binding sites, and uses, such as therapeutic applications, for such engineered antibodies.

The invention provides for a polyvalent protein complex (PPC) comprising two polypeptide chains generally arranged laterally to one another. Each polypeptide chain typically comprises 3 or 4 “v-regions”, which comprise amino acid sequences capable of forming an antigen binding site when matched with a corresponding v-region on the opposite polypeptide chain. Up to about 6 “v-regions” can be used on each polypeptide chain. The v-regions of each polypeptide chain are connected linearly to one another and may be connected by interspersed linking regions. When arranged in the form of the PPC, the v-regions on each polypeptide chain form individual antigen binding sites.

The present inventors devised methods for efficiently purifying bispecific antibodies using a chromatography column based on the difference in isoelectric points between the H chains of two types of antibodies, wherein the difference is introduced by modifying the amino acids present on the surface of the antibody variable regions of two types of antibodies that constitute a bispecific antibody. Furthermore, the inventors devised methods for efficiently purifying bispecific antibodies using a chromatography column by linking respective antigen binding sites (heavy chain variable regions) to the antibody constant regions having different isoelectric points, and then coexpressing these antibodies.

The invention provides for a polyvalent protein complex (PPC) comprising two polypeptide chains generally arranged laterally to one another. Each polypeptide chain typically comprises 3 or 4 “v-regions”, which comprise amino acid sequences capable of forming an antigen binding site when matched with a corresponding v-region on the opposite polypeptide chain. Up to about 6 “v-regions” can be used on each polypeptide chain. The v-regions of each polypeptide chain are connected linearly to one another and may be connected by interspersed linking regions. When arranged in the form of the PPC, the v-regions on each polypeptide chain form individual antigen binding sites.

The present invention concerns methods and compositions for treatment of HIV infection in a subject. The compositions may comprise a targeting molecule against an HIV antigen, such as an anti-HIV antibody or antibody fragment. The anti-HIV antibody or fragment may be conjugated to a variety of cytotoxic agents, such as doxorubicin. In a preferred embodiment, the antibody or fragment is P4 / D10. Other embodiments may concern methods of imaging, detection or diagnosis of HIV infection in a subject using an anti-HIV antibody or fragment conjugated to a diagnostic agent. In alternative embodiments, a bispecific antibody with at least one binding site for an HIV antigen and at least one binding site for a carrier molecule may be administered, optionally followed by a clearing agent, followed by administration of a carrier molecule conjugated to a therapeutic agent.

Masking ligands for reversibly concealing the antigen-binding site of an antibody comprise epitopes of the antibody and a cleavable linker. Methods for making masking ligands comprise joining at least two copies of the epitope of an antibody to a cleavable polypeptide linker.

Disclosed herein are fusion antibodies created to provide both an antigen-binding site that targets the CD4 receptor and an antigen-binding site that targets the HIV envelope. The fusion antibodies disclosed herein provide improved potency and breadth against HIV as compared to monospecific antibodies, and additionally provide high barrier against viral resistance. Also disclosed are pharmaceutical formulations and therapeutic methods utilizing such fusion proteins.

The present invention relates to bispecific antibodies comprising a first antigen binding site specific for a death receptor and a second antigen binding site specific for a second antigen, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

A recombinant or synthetic antibody or fragment thereof, said antibody or fragment thereof including three complementarity determining regions (CDR1L or H, CDR2L or H and CDR3L or H) for forming an antigen binding site that is capable of binding to a non functional P2X7 receptor but not capable of binding to a functional P2X7 receptor.

A molecule comprising at least one antigen binding site, comprising in sequence the hypervariable regions CDR1, CDR2 and CDR3, said CDR1 having the amino acid sequence Asn-Tyr-Ile-Ile-His (NYIIH), said CDR2 having the amino acid sequence Tyr-Phe-Asn-Pro-Tyr-Asn-His-Gly-Thr-Lys-Tyr-Asn-Glu-Lys-Phe-Lys-Gly (YFNPYNHGTKYNEKFKG) and said CDR3 having the amino acid sequence Ser-Gly-Pro-Tyr-Ala-Trp-Phe-Asp-Thr (SGPYAWFDT); e.g. further comprising in sequence the hypervariable regions CDR1′, CDR2′ and CDR3′, CDR1′ having the amino acid sequence Arg-Ala-Ser-Gln-Asn-Ile-Gly-Thr-Ser-Ile-Gln (RASQNIGTSIQ), CDR2′ having the amino acid sequence Ser-Ser-Ser-Glu-Ser-Ile-Ser (SSSESIS) and CDR3′ having the amino acid sequence Gln-Gln-Ser-Asn-Thr-Trp-Pro-Phe-Thr (QQSNTWPFT), e.g. a chimeric or humanised antibody, useful as a pharmaceutical.

The present invention relates to binding molecules, such as amino acid sequences with multiple antigen binding sites. In particular, the binding molecules of the present invention have at least two antigen binding sites that partially or fully overlap with each other and that are directed against at least two different naturally occurring binding molecules. The invention further relates to uses of such binders, for example in methods for inhibiting and / or blocking of the interaction between said at least two naturally occurring binding molecules and a third naturally occurring binding molecule.

Humanized antibody molecules (HAMs) are described having specificity for human milk fat globule and having an antigen binding site wherein at least one of the complementarity determining regions (CDRs) of the variable domains is derived from the mouse monoclonal antibody CTMO1 and the remaining immunoglobulin-derived parts of the HAM are derived from a human immunoglobulin. The HAMs may be chimeric humanized antibodies or CDR-grafted humanized antibodies and are preferably produced by recombinant DNA techniques. The HAMs are useful for in vivo diagnosis and therapy.

The present invention relates to bispecific antibodies comprising a first antigen binding site specific for a death receptor and a second antigen binding site specific for a second antigen, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

The invention relates to bispecific antibodies comprising a first antigen-binding site that specifically binds to PD1 and a second antigen-binding site that specifically binds to TIM3, in particular to bispecific antibodies, wherein the bispecific antibody binds to TIM3 with a lower binding affinity when compared to the binding to PD1. The invention further relates to methods of producing these molecules and to methods of using the same.

The invention discloses immunoglobulin fusion proteins designed to bind both CD47 and a tumor cell antigen. The immunoglobulin fusion proteins include a SIRP afla moiety that binds CD47 and an antigen binding site for a tumor cell antigen.

Endothelialization of vascular surfaces. According to one aspect, the invention involves a technique for re-endothelializing an artery whose endothelial layer has been damaged by balloon angioplasty. The technique comprises, in one embodiment, introducing into the bloodstream of a patient, prior to performing the angioplasty, a quantity of a bispecific antibody, the bispecific antibody having a first antigen binding site directed against a surface marker common to both endothelial progenitor cells (EPCs) and endothelial cells (ECs) and having a second antigen binding site directed against a subendothelial epitope. The bispecific antibody is introduced in a quantity sufficient to bind a substantial percentage of circulating EPCs and circulating ECs. In this manner, once the angioplasty has been performed and the target epitopes on the subendothelium have been exposed, the bispecific antibodies that have already become bound to the circulating EPCs and ECs also then bind to the subendothelium. Thus seeded by the bound EPCs and ECs, the exposed subendothelium is covered after a short period of proliferation and differentiation.

The present invention provides a novel artificially-designed triabody comprising three polypeptide chains. A first polypeptide chain comprises a first heavy-chain variable domain, and a second polypeptide chain comprises a first light-chain variable domain, and the first heavy-chain variable domain pairs with the first light-chain variable domain to form a first antigen binding site; and a third polypeptide chain comprises a single-domain second antigen binding site and a single-domain third antigen binding site. The present invention also provides polynucleotide encoding the triabody, a vector comprising the polynucleotide, host cells comprising the polynucleotide or the vector, immunoconjugate comprising the triabody, a pharmaceutical composition comprising the triabody or the immunoconjugate, and applications of the triabody in immunotherapy, prevention and / or diagnosis of diseases.

A molecule comprising at least one antigen binding site, comprising in sequence the hypervariable regions CDR1, CDR2 and CDR3, said CDR1 having the amino acid sequence Asn-Tyr-Ile-Ile-His (NYIIH), said CDR2 having the amino acid sequence Tyr-Phe-Asn-Pro-Tyr-Asn-His-Gly-Thr-Lys-Tyr-Asn-Glu-Lys-Phe-Lys-Gly (YFNPYNHGTKYNEKFKG) and said CDR3 having the amino acid sequence Ser-Gly-Pro-Tyr-Ala-Trp-Phe-Asp-Thr (SGPYAWFDT); e.g. further comprising in sequence the hypervariable regions CDR1′, CDR2′ and CDR3′, CDR1′ having the amino acid sequence Arg-Ala-Ser-Gln-Asn-Ile-Gly-Thr-Ser-Ile-Gln (RASQNIGTSIQ), CDR2′ having the amino acid sequence Ser-Ser-Ser-Glu-Ser-Ile-Ser (SSSESIS) and CDR3′ having the amino acid sequence Gln-Gln-Ser-Asn-Thr-Trp-Pro-Phe-Thr (QQSNTWPFT), e.g. a chimeric or humanised antibody, useful as a pharmaceutical.

A protein complex comprising (i) a first fusion protein comprising (a) a first polypeptide that comprises a first antigen-binding site and (b) a first binding protein linked to a terminus of the first polypeptide; and (ii) a second fusion protein comprising (a) a second polypeptide that comprises a second antigen-binding site and (b) a second binding protein linked to a terminus of the second polypeptide, wherein the protein complex comprises an amino acid sequence that enables cleavage between the first polypeptide and the first binding protein, and / or between the second polypeptide and the second binding protein, as well as a method for preparing a bi-specific antibody and related methods and compositions.

The invention belongs to the technical field of biosensors, and specifically discloses a jettisonable one-step electro-deposition immune-biosensor for detecting histamine and a preparation method of the immune-biosensor. The immune-biosensor adopts an electrode coated with a prussian blue, chitosan and nanogold composite film, wherein histamine coating antigen is fixed on the electrode, the molar concentration ratio of nanogold to prussian blue in the composite film is 1:2000 to 1:20, and the massic volume content of chitosan is 0.01-0.05%. Furthermore, the composite film is formed on the surface of the electrode through a one-step electrode deposition manner, the deposition step is simpler than a preparation step of the conventional electrode modified by high-molecular polymer, and the antigen binding site can be easily exposed out. According to the electro-deposition immune-biosensor, competition immunoreaction and a biosensor are combined, and a series of property characteristics such as a histamine detection working curve can be obtained according to needs, and the jettisonable one-step electro-deposition immune-biosensor has the advantages of simplicity in operation, high sensitivity, rapidness, convenience and the like, and can be used for on-site rapid detection for histamine in a sample.

The invention provides a leukemia bacteriophage single-chain antibody library, which uses phasmid pCANTA-5E as a carrier, has storage capacity of 1.5*10<9>, and has excellent diversity in proving of DNA (deoxyribonucleic acid) sequencing. A leukemia cell specific completely humanized single-chain antibody can be obtained conveniently in multiple screenings by using a specific leukemia related antigen as a target through a bacteriophage representation technology from the completely humanized single-chain antibody library. The antibody library provided by the invention has high storage capacity and excellent diversity, and comprises a combination of complete humanized single-chain antibodies; and a single-chain antibody is formed by connection of a heavy chain variable region VH and a light chain variable region VL through a connecting peptide (GGGGS)3, and contains a complete antigen-binding site. The method has the advantages of strong operability and high storage capacity, and can be used for conveniently screening the leukemia cell specific completely humanized single-chain antibody; and the completely humanized single-chain antibody can be used for preparing a target medicament, which is used for treating leukemia.

A bispecific antigen binding protein complex comprising a first polypeptide comprising a first antigen binding site at an N terminus; a second polypeptide comprising a second antigen binding site at an N terminus; and a linker connecting the first polypeptide and the second polypeptide; wherein the linker comprises a tag at one terminus thereof, and wherein the tag is connected to a C-terminus of the first polypeptide or to an N-terminus of the second polypeptide, and comprises a cleavable amino acid sequence; as well as related compositions and methods.

The invention provides a quick test dipstick used for testing a specific antigen of Brucella, which comprises a reaction membrane and a binder release liner. The reaction membrane is provided with a testing strap coated with a bp26 monoclonal antibody or bp26 polyclonal antibody and a quality control strap coated with anti-IgG; the binder release liner is coated with the bp26 monoclonal antibody which is marked by colloidal gold to be different from an antigen binding site on the reaction membrane. A membrane chromatography double antibody sandwich method is applied for detecting the specific antigen of the Brucella in a specimen. As the dipstick is adopted for test, the operation is simple, convenient, quick and concise, requiring no special equipment and facilities as well as professional training. Furthermore, the dipstick has clear and easy-identity results, simple operation and easy popularization, is applicable to matrixes, field tests of emergency on a large scale and the study of epidemiology and can aid in the infection diagnostics of the Brucella.

The invention relates to an antigen binding site for binding to a P2X7 receptor, the antigen binding site being defined by general formula 1:FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4

The invention relates to purinergic receptors, to antibodies and related fragments thereof for binding to said receptors, to production of said antibodies and fragments and to use of said antibodies and fragments for cancer detection and therapy. In particular the antibodies described bind specifically to non-functional P2X7 receptors expressed by live cells.

The present invention provides a novel artificially designed antibody molecule, which comprises (i) a single domain antigen binding site; (ii) an antigen binding Fab fragment; wherein (i) is located at the N-terminus of a light chain variable domain (VL) of (ii) or the C-terminus of a light-chain constant region (CL), or the (i) is located at the N-terminus of a heavy chain variable domain (VH) ofthe (ii) or the C-terminus of an immunoglobulin CH1 domain, (i) and (ii) respectively bind the same or different antigens, and a linking peptide is existed or does not exist in between (i) and (ii),and an (iii) immunoglobulin Fc domain is positioned at the C-terminus of (i) and (ii). The invention also provides the use of the polynucleotide encoding the antibody molecule, a vector comprising thepolynucleotide, a host cell comprising the polynucleotide or the vector, an immunoconjugate comprising the antibody molecule, and a pharmaceutical composition, and the antibody molecule for immunotherapy, prevention and / or diagnosis of a disease.

The invention relates to APRIL-binding antibodies, which bind the same epitope of human APRIL as an antibody having an antigen binding site of hAPRIL.01A. The antibodies of the present invention comprise specific selections of framework sequences of the VH and VL domains and have unexpected features in comparison to hAPRIL.01A. The invention further relates to compositions comprising an antibody of the invention and to the medical and diagnostic uses of the antibodies and compositions.

The present invention relates to humanized bispecific anti-HER2 antibodies that comprise one antigen binding site containing variable regions of heavy and light chain of trastuzumab, and another antigen binding site containing variable regions of heavy and light chain of pertuzumab. The bispecific anti-HER2 antibodies is effective for treating cancer, such as breast cancer, gastric cancer, or ovarian cancer. Preferred bispecific anti-HER antibodies of the present invention are afucosylated antibodies. The present invention also relates to Chinese Hamster ovary (CHO) mutant cell line that has a dysfunctional Slc35C1 gene, which is the only dysfunctional gene in the mutant that affects glycan regulation.