599 results about "High avidity" patented technology

Anti-VEGF antibodies and variants thereof, including those having high affinity for binding to VEGF, are disclosed. Also provided are methods of using phage display technology with naïve libraries to generate and select the anti-VEGF antibodies with desired binding and other biological activities. Further contemplated are uses of the antibodies in research, diagnostic and therapeutic applications.

Mesothelin is a differentiation antigen present on the surface of ovarian cancers, mesotheliomas and several other types of human cancers. Because among normal tissues, mesothelin is only present on mesothelial cells, it represents a good target for antibody mediated delivery of cytotoxic agents. The present invention is directed to anti-mesothelin antibodies, including Fv molecules with particularly high affinity for mesothelin, and immunoconjugates employing them. Also described are diagnostic and therapeutic methods using the antibodies. The anti-mesothelin antibodies are well-suited for the diagnosis and treatment of cancers of the ovary, stomach, squamous cells, mesotheliomas and other malignant cells expressing mesothelin.

The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

Specificity in immune responses is in part controlled by the selective interaction of T cell receptors with their cognate ligands, peptide / MHC molecules. The discriminating nature of this interaction makes these molecules, in soluble form, good candidates for selectively regulating immune responses. Attempts to exploit soluble analogs of these proteins has been hampered by the intrinsic low avidity of these molecules for their ligands. To increase the avidity of soluble analogs for their cognates to biologically relevant levels, divalent peptide / MHC complexes or T cell receptors (superdimers) were constructed. Using a recombinant DNA strategy, DNA encoding either the MHC class II / peptide or TCR heterodimers was ligated to DNA coding for murine Ig heavy and light chains. These constructs were subsequently expressed in a baculovirus expression system. Enzyme-linked immunosorbant assays (ELISA) specific for the Ig and polymorphic determinants of either the TCR or MHC fraction of the molecule indicated that infected insect cells secreted approximately 1 .mu.g / ml of soluble, conformnationally intact chimeric superdimers. SDS PAGE gel analysis of purified protein showed that expected molecular weight species. The results of flow cytometry demonstrated that the TCR and class II chimeras bound specifically with high avidity to cells bearing their cognate receptors. These superdimers will be useful for studying TCR / MHC interactions, lymphocyte tracking, identifying new antigens, and have possible uses as specific regulators of immune responses.

Anti-VEGF antibodies and variants thereof, including those having high affinity for binding to VEGF, are disclosed. Also provided are methods of using phage display technology with naïve libraries to generate and select the anti-VEGF antibodies with desired binding and other biological activities. Further contemplated are uses of the antibodies in research, diagnostic and therapeutic applications.

Engineered peptides that bind with high affinity (low equilibrium dissociation constant (Kd)) to the cell surface receptors of fibronectin (α5β1) or vitronectin (αvβ3 and αvβ5 integrins) are disclosed. These peptides are based on a molecular scaffold into which a subsequence containing the RGD integrin-binding motif has been inserted. The subsequence (RGD mimic) comprises about 9-13 amino acids, and the RGD contained within the subsequence can be flanked by a variety of amino acids, the sequence of which was determined by sequential rounds of selection (in vitro evolution). The molecular scaffold is preferably based on a knottin, e.g., EETI (Trypsin inhibitor 2 (Trypsin inhibitor II) (EETI-II) [Ecballium elaterium (Jumping cucumber)], AgRP (Agouti-related protein), and Agatoxin IVB, which peptides have a rigidly defined three-dimensional conformation. It is demonstrated that EETI tolerates mutations in other loops and that the present peptides may be used as imaging agents.

This invention provides polyvalent or polyspecific protein complexes, comprising three or more polypeptides which associate to form three or more functional target-binding regions (TBRs), and in which each individual polypeptide comprises two or more immunoglobulin-like domains which are covalently joined together, such that two Ig-like domains in a single polypeptide do not associate with each other to form a TBR. By using a linker peptide of fewer than three amino acid residues the immunoglobulin-like domains of the individual polypeptides are prevented from associating, so that complex formation between polypeptides is favoured. Preferably the polyvalent or polyspecific protein is a trimer or tetramer. The proteins of the invention have specificities which may be the same or different, and are suitable for use as therapeutic, diagnostic or imaging agents.

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides synthetic nanocarriers capable of eliciting an immune system response in the form of antibody production, wherein the nanocarriers lack any T cell antigens. In some embodiments, the invention provides nanocarriers that comprise an immunofeature surface, which provides high avidity binding of the nanocarriers to antigen presenting cells. The invention provides pharmaceutical compositions comprising inventive nanocarriers. The present invention provides methods of designing, manufacturing, and using inventive nanocarriers and pharmaceutical compositions thereof.

High affinity, chemically modified triplex-forming oligonucleotides (TFOs) and methods for use thereof are disclosed. TFOs are defined as triplex-forming oligonucleotides which bind as third strands to duplex DNA in a sequence specific manner. Triplex-forming oligonucleotides may be comprised of any possible combination of nucleotides and modified nucleotides. Modified nucleotides may contain chemical modifications of the heterocyclic base, sugar moiety or phosphate moiety. A high affinity oligonucleotide (Kd≦2×10−8) which forms a triple strand with a specific DNA segment of a target gene DNA is generated. It is preferable that the Kd for the high affinity oligonucleotide is below 2×10−10. The nucleotide binds or hybridizes to a target sequence within a target gene or target region of a chromosome, forming a triplex region. The binding of the oligonucleotide to the target region stimulates mutations within or adjacent to the target region using cellular DNA synthesis, recombination, and repair mechanisms. The mutation generated activates, inactivates, or alters the activity and function of the target gene.

Aspects of the invention provide systems and methods for high-throughput screening of fluidic samples. In some embodiments, two chromatography columns are utilized in series. The first chromatography column can have a high affinity for phosphorylated compounds while the second chromatography column has a high affinity for one or more analytes of interest.

The invention provides methods for identifying antibody preparations that can form a pair of antibodies that optimally detect a target antigen, for example, in a sandwich immunoassay. These methods provide high affinity and epitope-specific antibodies.

Human antibodies, preferably recombinant human antibodies, that specifically bind to human interleukin-12 (hIL-12) are disclosed. Preferred antibodies have high affinity for hIL-12 and neutralize hIL-12 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and for inhibiting hIL-12 activity, e.g., in a human subject suffering from a disorder in which hIL-12 activity is detrimental. Nucleic acids, vectors and host cells for expressing the recombinant human antibodies of the invention, and methods of synthesizing the recombinant human antibodies, are also encompassed by the invention.

The present invention provides methods for preventing, managing, treating and / or ameliorating a Respiratory Syncytial Virus (RSV) infection (e.g., acute RSV disease, or a RSV upper respiratory tract infection (URI) and / or lower respiratory tract infection (LRI)), otitis media (preferably, stemming from, caused by or associated with a RSV infection, such as a RSV URI and / or LRI), and / or a symptom or respiratory condition relating thereto (e.g., asthma, wheezing, and / or reactive airway disease (RAD)) in a subject, comprising administering to said human an effective amount of one or more antibodies that immunospecifically bind to one or more RSV antigens with a high affinity and / or high avidity. In some embodiments, one or more antibodies comprise a modified IgG constant domain, or FcRn-binding fragment thereof resulting in longer in vivo serum half-life. In particular embodiments the methods of the invention comprising administering to subject an effective amount of one or more modified antibodies that immunospecifically bind to one or more RSV antigens with an association rate (kon) of at least 2×105 M−1s−1 and a dissociation rate (koff) of less than 5×10−4 s−1.

Ultra high affinity antibodies with binding affinities in the range of 1010 M−1, and even 1011 M−1 are disclosed. Such antibodies include antibodies having novel high affinity complementarity determining regions (CDRs), especially those with framework and constant regions derived from either humans or mice. Methods of preparing and screening such antibodies, as well as methods of using them to prevent and / or treat disease, especially virus-induced diseases, are also disclosed.

An isolated human anti-TNF-α antibody, or antigen-binding portion thereof, containing at least one high-affinity VL or VH antibody chain that is effective, when substituted for the corresponding VL or VH chain of the anti-TNF-α scFv antibody having sequence SEQ ID NO: 1, to bind to human TNF-α with a Koff rate constant that is at least 1.5 fold lower than that of the antibody having SEQ ID NO: 1, when determined under identical conditions.

The present invention encompasses IL-12p40 binding proteins, particularly antibodies that bind human interleukin-12 (hIL-12) and / or human IL-23 (hIL-23). Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-12 and / or hIL-23 and neutralize h IL-12 and / or hIL-23 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and / or hIL-23 and for inhibiting hIL-12 and / or hIL-23 activity, e.g., in a human subject suffering from a disorder in which hIL-12 and / or hIL-23 activity is detrimental.

The present invention provides isolated monoclonal antibodies, particularly human monoclonal antibodies, that specifically bind to PD-1 with high affinity. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for detecting PD-1, as well as methods for treating various diseases, including cancer and infectious diseases, using anti-PD-1 antibodies. The present invention further provides methods for using a combination immunotherapy, such as the combination of anti-CTLA-4 and anti-PD-1 antibodies, to treat hyperproliferative disease, such as cancer. The invention also provides methods for altering adverse events related to treatment with such antibodies individually.

This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

This invention relates to the use of oligourea molecules to specifically inhibit protein-nucleic acid interactions. In particular, it provides an oligourea molecule that competes with the Tat molecule for the TAR RNA of HIV-1. Also provided is a method specifically inhibiting protein-nucleic and interactions, and kits.

The use of model T cell receptors (TCRs) as scaffolds for in vitro engineering of novel specificities is provided. TCRs with de novo binding to a specific peptide-major histocompatibility complex (MHC) product can be isolated by: 1) mutagenizing a T cell receptor protein coding sequence to generate a variegated population of mutants (a library), 2) selection of the library of TCR mutants with the specific peptide-MHC, using a process of directed evolution and a “display” methodology (e.g., yeast, phage, mammalian cell) and the peptide-MHC ligand. The process can be repeated to identify TCR variants with improved affinity for the selecting peptide-MHC ligand.

The invention relates to using a mouse able to generate human IgGl heavy chain- k light chain to prepare humanized monoclonal antibody and its application. The characteristic: respectively knocking in huma k-chain and gl-chain constant gene at the sites of gene in mouse k- light chain constant region and heavy chain gl constant region; the humanized monoclonal antibody: the constant region is fully the same as that of human antibody and the variable region is mouse sourece, and the preparing steps: obtaining mouse k-chain and gl-chain gene groups; constructing a knoncking-in carrier; making homologous recombination in ES cell; producing the mouse with light-heave conversion; further mating to obtain a mouse with complete chimeric gene; the application: taking spleen and marrow cells of an immunized chemeric mouse to make fusion and culture; screening hybridomas of humanized monoclonal antibody generating antigenic specificity; preparing the humanized monoclonal antibody with antigenic specificity. The advantages is easy to obtain high-affinity human-mouse chimeric antibody.

Antibodies that bind human interleukin-18 (hIL-18) are provided, in particular antibodies that bind epitope(s) of human IL-18. The antibodies can be, for example, entirely human antibodies, recombinant antibodies, or monoclonal antibodies. Preferred antibodies have high affinity for hIL-18 and neutralize hIL-18 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-18 and for inhibiting hIL-18 activity, e.g., in a human subject suffering from a disorder in which hIL-18 activity is detrimental.

Ultrasound-assisted particle agglutination assay methods and apparatuses are described based on first providing a standing wave ultrasound field at a resonance frequency of a test liquid in a resonator cell containing microparticles covered with a binding agent with high affinity to an analyte sought to be detected by the assay test. Formation of the specifically-bound and nonspecifically-bound aggregates of these microparticles is then followed by effective stirring of the liquid with swept-frequency sonication causing disintegration of nonspecifically-bound aggregates and leaving specifically-bound aggregates in place for further detection and measurement. The methods and devices of the invention allow significant improvement in the sensitivity and specificity of agglutination tests and are advantageously applicable to detecting various proteins, DNA, RNA and other biologically active substances. Specific examples are provided.

The present invention provides compositions and systems for delivery of nanocarriers to cells of the immune system. The invention provides synthetic nanocarriers capable of eliciting an immune system response in the form of antibody production, wherein the nanocarriers lack any T cell antigens. In some embodiments, the invention provides nanocarriers that comprise an immunofeature surface, which provides high avidity binding of the nanocarriers to antigen presenting cells. The invention provides pharmaceutical compositions comprising such nanocarriers. The present invention provides methods of designing, manufacturing maceutical compositions thereof.

The invention relates to an anti-human TIGIT monoclonal antibody which is particularly related to high-affinity anti-human TIGIT monoclonal antibody with blocking activity. A large-capacity fully-synthetic human phage antibody library is constructed, the specific anti-human TIGIT monoclonal antibody and the high-affinity anti-human TIGIT monoclonal antibody which is optimized after molecular evolution are screened from the human phage antibody library, and the monoclonal antibody comprises a full-human frame region and variable regions of a full-human light chain and a heavy chain.

Compositions comprising non-naturally occurring fibrinogen binding moieties are described, together with methods of use thereof, e.g., for detecting or isolating fibrinogen molecules in a solution, for blood circulation imaging, and for linking therapeutics or other molecules to fibrinogen. Preferred binding peptides having a high affinity for fibrinogen are particularly disclosed.

This invention provides for novel human antibodies that specifically bind to c-erbB-2. The antibodies may be used alone or as components of chimeric molecules that specifically target and deliver effector molecules to cells overexpressing c-erbB-2.

The invention discloses an aptamer-based Sandwich ELASA method for detecting nervous necrosis virus infection of groupers. The method comprises the following steps: fixing a biotin-labeled aptamer onto a pore plate pre-coated with streptavidin; capturing CP proteins in a to-be-detected sample by the fixed aptamer, and combining the CP proteins by the biotin-labeled aptamer; adding horse radish peroxidase-streptavidin for incubating and combining, developing by a horse radish peroxidase developing kit, and analyzing whether NNV virus infection exists according to light absorption value change. According to the invention, by utilizing the characteristics of high affinity and high specificity of the aptamer, a Sandwich ELASA detection method based on aptamer detection is established and can be used for detecting nervous necrosis viruses during grouper culture. Compared with the traditional ELISA and other detection methods, the method disclosed by the invention has the characteristics of high detection speed, high sensitivity and specificity, low cost and high simplicity in operation.

The present invention discloses a humanized monoclonal antibody and an application thereof, belonging to the technical field of medicine. In the invention, the humanized transformation is carried outon a rat monoclonal antibody 2A10G6, the rat monoclonal antibody 2A10G6 is expressed by baculovirus, and the humanized antibody h2A10G6 is obtained. The h2A10G6 antibody of the present invention has high affinity and neutralization activity against yellow fever virus, dengue fever and West Nile virus, and can be applied to clinical treatment and prevention of yellow fever virus, dengue virus and West Nile virus.