110 results about "Neo epitope" patented technology

The present invention provides recombinant antigen-binding regions and antibodies and functional fragments containing such antigen-binding regions that are specific for CD38, which plays an integral role in various disorders or conditions. These antibodies, accordingly, can be used to treat, for example, hematological malignancies such as multiple myeloma. Antibodies of the invention also can be used in the diagnostics field, as well as for investigating the role of CD38 in the progression of disorders associated with malignancies. The invention also provides nucleic acid sequences encoding the foregoing antibodies, vectors containing the same, pharmaceutical compositions and kits with instructions for use. The invention also provides isolated novel epitopes of CD38 and methods of use therefore

The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In particular, the disclosure relates to concatemeric mRNA cancer vaccines encoding several cancer epitopes on a single mRNA construct, i.e. poly-epitope mRNA constructs or poly-neo-epitope constructs. The disclosure further relates to p53 and KRAS mutations, as well as incorporation of immune enhancers such as STING, e.g. mRNA constructs further encoding an immune stimulator or adjuvant. The disclosure further relates to inclusion of universal T cell epitopes, such as tetanus or diphtheria toxins to elicit an enhanced immune response.

The invention describes the patterns of deamidation in gluten, and it is found that this is highly dependent on the spacing between the glutamine and proline residues. This knowledge can be used to predict novel T cell stimulatory gluten peptides. Several newly defined peptides and epitopes are provided. Also, the finding can explain the formation of neo-epitopes in autoimmune diseases such as RA (rheumatoid arthritis), MS (multiple sclerosis), SLE (systemic lupus erythomatosus), SS (Sjogren syndrome) and DB (diabetes). Several neo-epitopes and the peptides that are substrate for deamidation are provided. Further, the inventions provides for methods for detecting these peptides and epitopes and methods for making food more suitable for celiac disease patients.

Provided are novel specific binding molecules, particularly human antibodies as well as fragments, derivatives and variants thereof that recognize neoepitopes of disease-associated proteins which derive from native endogenous proteins but are prevalent in the body of a patient in a variant form and / or out of their normal physiological context. In addition, pharmaceutical compositions comprising such binding molecules, antibodies and mimics thereof and methods of screening for novel binding molecules, which may or may not be antibodies as well as targets in the treatment of neurological disorders such as Alzheimer's disease are described.

A novel treatment of Alzheimer's disease and other disorders involving protein misfolding or aggregation is provided by enhancing or sustaining an antibody response against predominantly directed against pathological protein aggregates or neo-epitopes present on pathogenic forms of said protein or protein complex. Furthermore, therapeutic methods are also described, wherein ex vivo stimulated antigen-selected peripheral blood lymphocytes are regrafted into the cognate donor.

Novel MUC-1 epitopes outside the VNTR region are identified. In addition, the first agonist epitope of MUC-1 is described. The employment of agonist epitopes in peptide, protein and vector-based vaccine may well aid in the development of effective vaccines for a range of human cancers.

The present invention relates to isolated protein sequences that correspond to cell binding peptides, fragments, neo-structures and / or neo-epitopes of a normally occurring serum protein present in human tissue, wherein the peptide, fragment, neo-structure and / or neo-epitope has an immunoregulatory activity and is the result of either an enhanced proteolytic activity and / or conformational changes in a tissue, or a malignant tumour. In the present patent application, a common structure of several of these peptides, fragments, neo-structures and / or neo-epitopes, having immunoregulatory activity by binding to receptors on immune cells, has been identified. The present invention further also relates to monoclonal and / or polyclonal antibodies directed to a cell binding fragment of a normally occurring serum protein present in human tissue, as described above.

The invention relates to the identification of a novel epitope on non-functional P2X7 receptors which are implicated in cancer. The epitope includes a region from two adjacent monomers within the three subunit receptor. Antibodies which bind to the epitope and peptides for generating the antibodies are described. The antibodies and peptides are useful in the diagnosis and treatment of cancer.

The present invention relates to novel antibodies, which combine high affinity with high potency, particularly novel antibodies against a novel epitope.

A biosensor for use in detecting the presence of diseases, the biosensor comprising a detector for detecting a presence of at least one marker indicative of a specific disease. A method of determining efficacy of a pharmaceutical for treating a disease or staging disease by administering a pharmaceutical to a sample containing markers for a disease, detecting the amount of at least one marker of the disease in the sample, and analyzing the amount of the marker in the sample, whereby the amount of marker correlates to pharmaceutical efficacy or disease stage. Markers for gynecological disease. An immuno-imaging agent comprising labeled antibodies, whereby the labeled antibodies are isolated and reactive to proteins overexpressed in vivo. Informatics software for analyzing the arrays, the software including analyzing means for analyzing the arrays.

This invention provides a system of providing and a process of creating personalized immunotherapeutic compositions for a subject having a disease or condition, including therapeutic vaccine delivery vectors comprising gene expression constructs expressing peptides associated with one or more neo-epitopes or peptides containing mutations that are specific to an subject's cancer or unhealthy tissue. The invention further provides a scalable fully enclosed single use cell growth system, wherein the entire process of manufacturing of personalized immunotherapeutic compositions, up to and including dispensing said composition into containers for patient delivery is carried out within a single enclosed fluid flow path.

The invention discloses HLA-A2 restrictive epitope polypeptide of an LMP2A protein source, which is polypeptide LMP2A264 and comprises 9 amino acids in the positions of 264 to 272; the sequence is QLSPLLGAV. Mycobacteria heat shock protein 70 (HSP70) is expressed, identified and purified; a transgene animal model for evaluating EBV relevant polypeptide vaccine in vivo tests is established; the immune research on inducing EBV specific CTL inside and outside healthy volunteers and transgene rats for the new EBV epitope polypeptide LMP2A264 is systemically researched and the tumor prevention andthe tumor treating test of the polypeptide LMP2A264 on LMP2A positive solid tumors are evaluated, thereby proving that the polypeptide LMP2A264 can induce LMP2A specific cell toxic T lymphocyte reaction. Therefore, the polypeptide LMP2A264 can be applied to prepare medicaments for treating or preventing LMP2A positive solid tumors.

The invention relates to the identification of a novel epitope on non-functional P2X7 receptors which are implicated in cancer. The epitope includes a region from two adjacent monomers within the three subunit receptor. Antibodies which bind to the epitope and peptides for generating the antibodies are described. The antibodies and peptides are useful in the diagnosis and treatment of cancer.

The invention provides a system of providing and creating personalized immunotherapeutic compositions for a subject having a disease or condition, including therapeutic immunotherapy delivery vectorsand methods of making the same comprising gene expression constructs expressing peptides associated with one or more neo-epitopes or peptides containing mutations that are specific to a subject's cancer or unhealthy tissue. A delivery vector of the invention includes bacterial vectors including Listeria bacterial vectors; or viral vectors, peptide immunotherapy vectors; or DNA immunotherapy vectors, comprising one or more fusion proteins comprising one or more peptides comprising one or more neo-epitopes present in disease-bearing biological samples obtained from the subject. This invention also provides methods of using the delivery vector for inducing an immune response against a disease or condition, including a tumor or cancer, or an infection, or an autoimmune disease or an organ transplant rejection in the subject.

Methods for personalized neoantigen or neoepitope selection for a patient having cancer, whereby the patient can be treated in a personalized manner using a patient-specific cocktail of suitable neoantigen or neoepitope peptides and a pharmaceutically acceptable excipient, wherein the selection of suitable neoantigens or neoepitopes is based on properties of the patient-specific neoantigens or neoepitopes which are predicted or evaluated based on information derived from databases which in turn are derived from prior measurements and observations, and wherein the method reduces the influence of any errors in the underlying databases by binning certain descriptors of neoantigen or neoepitope properties and by improved ranking of the neonantigens or neoepitopes according to the binning of the descriptors; and pharmaceutical preparations selected by said methods, and data carriers and kits for carrying out said methods.

This disclosure pertains to isolated antibodies or antigen binding fragments thereof that specifically bind to the 3ABC non-structural protein of Foot-and-Mouth Disease virus (FMDV), wherein the antibodies or antigen binding fragments thereof recognize the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 or SEQ ID NO: 12. Accordingly, this disclosure also pertains to polypeptides having an amino acid sequence selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5 or SEQ ID NO: 12. Monoclonal antibody Mab 40C8 is also provided. The current disclosure also pertains to methods of detecting FMDV infection in an animal (including assays differentiating infected animals from vaccinated animals (DIVA)) and kits for performing the detection methods. Competitive ELISA kits comprising the antibody or antigen binding fragment thereof and immunoassay plates coated with the polypeptide comprising the amino acid sequence selected from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6 and / or SEQ ID NO: 12 are also provided.

Contemplated compositions and methods are directed to cancer neoepitopes and uses of such neoepitopes, especially to generate synthetic antibodies against neoepitopes that may then be employed in themanufacture of a therapeutic agent. Preferred therapeutic agents will comprise a synthetic antibody against a neoepitope, and most preferably in combination with a cellular or non-cellular component for use as a diagnostic or therapeutic agent.

Contemplated cancer treatments comprise recursive analysis of patient-, cancer-, and location-specific neoepitopes from various biopsy sites of a patient after treatment or between successive rounds of immunotherapy and / or chemotherapy to inform further immunotherapy. Recursive analysis preferably includes various neoepitope attributes to so identify treatment relevant neoepitopes.

Novel anti-cancer agents, including, but not limited to, antibodies, that bind to human frizzled receptors are provided. Novel epitopes within the human frizzled receptors which are suitable as targets for anti-cancer agents are also identified. Methods of using the agents or antibodies, such as methods of using the agents or antibodies to inhibit Wnt signaling and / or inhibit tumor growth are further provided.

In certain embodiments, methods and compositions are provided for generating immune responses against tumor neo-antigens or neo-epitopes. In particular embodiments there may be provided methods for constructing and producing recombinant adenovirus-based vector vaccines containing nucleic acid sequences encoding tumor neo-antigens and neo-epitopes that allow for vaccinations in individuals with preexisting immunity to adenovirus. In additional embodiments, methods and compositions are provided for the treatment of cancer using immunotherapy based on recombinant adenovirus-based vectors combinedwith engineered natural killer cells. In some embodiments, the methods and compositions further comprises a nucleic acid encoding for an immunological fusion partner.

The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In particular, the disclosure relates to concatemeric mRNA cancer vaccines encoding several cancer epitopes on a single mRNA construct, i.e. poly-epitope mRNA constructs or poly-neo-epitope constructs. The disclosure further relates to p53 and KRAS mutations, as well as incorporation of immune enhancers such as STING, e.g. mRNA constructs further encoding an immune stimulator or adjuvant. The disclosure further relates to inclusion of universal Tcell epitopes, such as tetanus or diphtheria toxins to elicit an enhanced immune response.

The present invention relates to a method for determining a tissue degradation process by detection on COMP (Cartilage Oligomeric Matrix Protein) neoepitopes, where said COMP neoepitopes appear after cleavage of COMP at one or more site between position 530 and 660 of the amino acid sequence of COMP. Such as between position 550 (N550) And 551 (W551) or between position 625 (N625) and 626 (P626). Furthermore, the invention relates to antibodies against COMP neoepitopes and to fragments and peptides containing COMP neoepitopes for generation of such antibodies, which fragments or peptides comprise in or more COMP neoepitopes with at least partial identity to a selected group of COMP peptides derived from the sequence between amino acids 539-550, 551-562, or 626-637 of human COMP.

The present invention relates to isolated protein sequences that correspond to cell binding peptides, fragments, neo-structures and / or neo-epitopes of a normally occurring serum protein present in human tissue, wherein the peptide, fragment, neo-structure and / or neo-epitope has an immunoregulatory activity and is the result of either an enhanced proteolytic activity and / or conformational changes in a tissue, or a malignant tumour. In the present patent application, a common structure of several of these peptides, fragments, neo-structures and / or neo-epitopes, having immunoregulatory activity by binding to receptors on immune cells, has been identified. The present invention further also relates to monoclonal and / or polyclonal antibodies directed to a cell binding fragment of a normally occurring serum protein present in human tissue, as described above.

Provided herein are methods of diagnosis or of quantitation of fibrosis. An immunoassay is conducted to measure neo-epitope containing protein fragments of collagen type III, collagen type I, collagen type IV, collagen type V, or collagen type VI, elastin, biglycan, decorin, lumican, versican, perlecan, neurocan, brevican, fibromodulin, serglycin, syndecan, betaglycan, vimentin, or C-reactive protein naturally present in a biofluid sample obtained from a patient. An above normal elevation of the measured protein fragments in the patient is associated with the presence or extent of fibrosis.

Antibodies (Abs) play roles in protection against influenza. Neutralizing Abs either inhibit the binding of hemagglutinin (HA) to cellular receptors or prevent the conformational change of HA induced by low pH. The former Ab binds to the regions near the sialic acid-binding pocket on the globular head formed by HA1 and generally shows narrow strain specificity. The latter Ab binds to the stem region formed mainly by HA2 and shows broad strain specificity. We isolated a broadly neutralizing Ab against H3N2 viruses. X-ray analysis of the HA / Ab complex indicated that the Ab binds to the valley formed by two neighboring HA monomers at the side of the globular head. The Ab shows neutralizing activity by preventing the conformational change of HA induced at low pH.

Novel methods to determine matrix metalloproteinase (MMP) activity are described. In a typical embodiment of the invention, the biological fluid sample is from a patient, and the methods of the invention are useful to assess disease severity or progression, diagnose a particular disease, or develop a profile of MMP activity for inflammatory diseases such as arthritis, or cancer. A novel method of the invention involves the use of particular amino acid sequences in substrates that include but are not limited to fluorescence, colorimetric, radiometric and unlabeled substrates. A second method of the invention use neo-epitope antibodies that bind to the cleavage sites generated by collagenase 3 digestion of type IV collagen or biglycan or the peptide substrates disclosed. There is also provided a diagnostic kit for use in determining the amounts of MMP activities in biological samples comprising (a) one or more substrates with different specificities against the MMPs, (b) one or more reagents capable of inhibiting non-metalloproteinase activities, (c) one or more reagents capable of specifically inhibiting metalloproteinase activities, (d) one or more activators of metalloproteinase activities, (e) reagents capable of altering the selectivity ratios for the substrates such as gelatin or type II collagen, and (f) collagenase 3, stromelysin 1, gelatinase A, gelatinase B and / or collagenase 1 as calibration standards.

The present invention relates to methods for determining whether neoepitopes that are only expressed in or on diseased cells are suitable disease-specific targets, such that the diseased cell is less likely to be able to escape immune surveillance, and use of the neoepitopes in providing an immune response against diseased cells expressing the neoepitopes.