381 results about "Phage display" patented technology

The present invention relates to the identification of macaque antibodies to human B7.1 and B7.2 by screening of phage display libraries or monkey heterohybridomas obtained using B lymphocytes from B7.1 and/or B7.2 immunized monkeys. More specifically, the invention provides four monkey monoclonal antibodies 7B6, 16C10, 7C10 and 20C9 which inhibit the B7:CD28 pathway and thereby function as effective immunosuppressants. The invention further provides the complete DNA and amino acid sequences of the light and heavy chain of three primatized antibodies derived from those monkey monoclonal antibodies which bind B7.1 and possibly B7.2, primatized 7C10, primatized 7B6 and primatized 16C10. These primatized and monkey antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.

The present invention relates to the design of trimeric polypeptides using polypeptide structural elements derived from the tetranectin protein family, and their use in rational de novo design and production of multi-functional molecules including the application of the multi-functional molecules in protein library technology, such as phage display technology, diagnostic and therapeutic systems, such as human gene therapy and imaging. The trimeric polypeptides being constructed as a monomer polypeptide construct comprising at least one tetranectin trimerising structural element (TTSE) which is covalently linked to at least one heterologous moiety, said TTSE being capable of forming a stable complex with two other TTSEs; or as an oligomer which is comprised of two monomer polypeptide constructs as mentioned above, and which comprises three TTSEs or a multiplum of three TTSEs, or which is comprised of three monomer polypeptide constructs.

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.

Abstract of the Disclosure The present invention relates to methods for selecting repertoires of polypeptides using generic and target ligands. In particular, the invention relates to a library comprising a repertoire of polypeptides of the immunoglobulin superfamily, wherein the members of the repertoire have a known main chain conformation.

A pharmaceutical composition for treating allergy is described. The composition comprises as an active ingredient a recombinant polyclonal antibody or a mixture of different monoclonal antibodies capable of reacting with or binding to an allergen together with one or more pharmaceutically acceptable excipients. The composition may be used topically as a solution, dispersion, powder, or in the form of microspheres. The polyclonal antibody is preferably a recombinant polyclonal antibody produced by phage display technology. The pairing of specific immunoglobulin variable region light chain and heavy chain maintained from the original polyclonal immune response or selected by panning using the allergen in question is preferably maintained by bulk transfer of the pairs into an expression vector.

The invention relates to posttranslational modification of phage-displayed polypeptides. These displayed polypeptides comprise at least one unnatural amino acid, e.g., an aryl-azide amino acid such as p-azido-L-phenylalanine, or an alkynyl-amino acid such as para-propargyloxyphenylalanine, which are incorporated into the phage-displayed fusion polypeptide at a selected position by using an in vivo orthogonal translation system comprising a suitable orthogonal aminoacyl-tRNA synthetase and a suitable orthogonal tRNA species. These unnatural amino acids advantageously provide targets for posttranslational modifications such as azide-alkyne [3+2] cycloaddition reactions and Staudinger modifications.

Described and claimed herein are combinatorial synthetic Fab libraries displayed on a phage pIX protein. The libraries were built on scaffolds representing the most frequently used genes in human antibodies, which were diversified to mirror the variability of natural antibodies. After selection using a diverse panel of proteins, numerous specific and high-affinity Fabs were isolated. By a process called in-line maturation the affinity of some antibodies was improved up to one hundred-fold yielding low pM binders suitable for in vivo use. This work thus demonstrates the feasibility of displaying complex Fab libraries as pIX-fusion proteins for antibody discovery and lays the foundations for studies on the structure-function relationship of antibodies.

The invention is directed to novel CDRs and immunoglobulin products that bind to A33 antigens and methods for their use. The invention also involves a method for making humanized antibodies, using a rabbit as a host animal, and phage display library methodologies, and the antibodies themselves. The methodology is useful, for example, in generating humanized antibodies against molecules associated with cancer, such as A33, which is associated with colon cancer.

The invention provides a novel human Mab Fab, cloned by phage display, and its use in diagnostic and therapeutic methods. In particular the invention provides a method for analyzing the OxLDL components of atherosclerotic plaques in vivo and a means to determine their relative pathology. As the method is based on a human Fab rather than a mouse Mab, the progress or regression of the disease may be monitored over time. The antibody may also be used for the analysis of surgical or serum samples ex vivo for the presence of OxLDL. The antibody may also be used to target therapeutic agents to the site of atherosclerotic plaques or may have use as a therapeutic agent itself.

The invention relates to a compositions and methods for generating and using pIX phage display libraries for producing non-antibody peptide or protein proteins or peptides using engineered hybrid phage vectors derived from pIX of M 13 phage.

The invention overcomes the deficiencies of the prior art by providing a rapid approach for isolating binding proteins capable of binding small molecules and peptides. In the technique, libraries of candidate binding proteins, such as antibody sequences, may be expressed in the periplasm of gram negative bacteria with at least one target ligand. In clones expressing recombinant polypeptides with affinity for the ligand, the ligand becomes bound and retained by the cell even after removal of the outer membrane, allowing the cell to be isolated from cells not expressing a binding polypeptide with affinity for the target ligand. The target ligand may be detected in numerous ways, including use of direct fluorescence or secondary antibodies that are fluorescently labeled, allowing use of efficient screening techniques such as fluorescence activated cell sorting (FACS). The approach is more rapid and robust than prior art methods and avoids problems associated with the outer surface-expression of ligand fusion proteins employed with phage display.

The present invention concerns methods and compositions for in vivo and in vitro targeting. A large number of targeting peptides directed towards human organs, tissues or cell types are disclosed. The peptides are of use for targeted delivery of therapeutic agents, including but not limited to gene therapy vectors. A novel class of gene therapy vectors is disclosed. Certain of the disclosed peptides have therapeutic use for inhibiting angiogenesis, inhibiting tumor growth, inducing apoptosis, inhibiting pregnancy or inducing weight loss. Methods of identifying novel targeting peptides in humans, as well as identifying endogenous receptor-ligand pairs are disclosed. Methods of identifying novel infectious agents that are causal for human disease states are also disclosed. A novel mechanism for inducing apoptosis is further disclosed.

Methods and compositions for identifying and characterizing one or more ligands of a peptide are provided. In particular, the invention provides a phage ligand sensor device (PLSD) comprising a sensor coupled to a binding element of interest. Binding elements of interest comprise phage displaying at least one foreign peptide. The PLSD and assays find particular use in identifying and characterizing ligand-peptide interactions.

A method is provided for identifying and isolating peptides capable of binding of inorganic materials such as silica, silver, germanium, cobalt, iron, or oxides thereof, or other materials on a nanometric scale such as carbon nanotubes, using a combinatorial phage display peptide library and a polymerase-chain reaction (PCR) step to obtain specific amino acids sequences. In the method of the invention, a combinatorial phage display library is used to isolate and select the desired binding peptides by a series of steps of target binding of phage with the nanometric material of interest, elution and purification of the bound phages, and amplification using PCR to determine the sequences of phages producing the desired binding peptides. The binding peptides of the invention are particularly advantageous in that they may be used as templates to guide the development of useful structures on a nanometric scale.

Transdermal delivery peptides for the treatment of skin diseases and/or facilitation or enhancement of transdermal delivery of pharmaceutically active agents are provided. Compositions comprising the transdermal delivery peptides and methods of therapeutic use, including the improvement of transdermal delivery of drugs or other pharmaceutically active agents, are also disclosed. Nucleic acids, expression vectors, and methods of their use, which encode the transdermal delivery peptides are disclosed. Methods are also provided for in vivo phage display for identifying further peptides with enhanced transdermal delivery capability.

Peptides having general and specific binding affinities for the Src homology region 3 (SH3) domains of proteins are disclosed in the present invention. In particular, SH3 binding peptides have been isolated from phage-displayed random peptide libraries which had been screened for isolates that bind to bacterial fusion proteins having an SH3 domain and glutathione S-transferase (GST). Preferred peptides are disclosed which comprise a core 7-mer sequence (preferably, a consensus motif) and two or more, preferably at least six, additional amino acid residues flanking the core sequence, for a total length of 9, preferably at least 13, amino acid residues and no more than about 45 amino acid residues. Such peptides manifest preferential binding affinities for certain SH3 domains. The preferred peptides exhibit specific binding affinities for the Src-family of proteins. In vitro and in vivo results are presented which demonstrate the biochemical activity of such peptides.

Glycan arrays that can detect and distinguish between various sub-types and strains of influenza virus are provided. Methods for using the glycan arrays with assays using nanoparticle amplification technique are disclosed. Sandwich assays using gold nanoparticles conjugated to phage particles comprising influenza virus-specific antibodies for detecting multiple serotypes using a single reaction are provided. Plurality of glycans directed to specific target HA of influenza virus comprises the array. Detector molecules comprising noble metals conjugated to (a) phage display particles expressing antibodies against hemagglutinin and (b) neuraminidase binding agents are disclosed.

The invention belongs to the technical field of protein polypeptides, relates to a polypeptide with a brain targeted medicine delivery characteristic, and provides a molecular structure of the polypeptide, and application of the polypeptide to brain targeted medicine delivery. A phage monoclonal antibody which has the function of penetrating a blood brain barrier and can be enriched in a brain is obtained through repeated in-vivo Sprague Dawley (SD) outbred stock rat screening by a phage display technology; deoxyribonucleic acid (DNA) sequencing proves that the phase display polypeptides comprise a consensus sequence; meanwhile, an immunohistochemical method and in-vivo recovery rate comparison prove that the obtained polypeptide has the brain targeted medicine delivery characteristic. The polypeptide and derivative peptides thereof can be used for modifying medicine-carrying nanoparticles, liposomes, vesicles or micelles to construct a brain targeted medicine delivery system; and the delivery of medicines in the brain can be improved, the treatment effect on brain diseases is enhanced and systemic toxic and side effects are reduced.