A molecule comprising a lipid, a peptide and a linker to bind the lipid to the peptide which have specific amino acid sequence to bind to Epidermal Growth Factor Receptor (EGFR) of tumor cells, and a liposomal composition which is targeted by the molecule, and method for preparing thereof is disclosed.

Variant factor H binding proteins that can elicit antibodies that are bactericidal for at least one strain of Neisseria meningitidis, compositions comprising such proteins, and methods of use of such proteins, are provided.

The disclosure provides methods and compositions for suppressing retroviruses, including novel methods for treating a retroviral infection in a human in need of such treatment, comprising delivering a functional meiosis arrest female protein 1 (MARF1) to cells containing a retroviral provirus, together with novel expression constructs comprising a coding sequence encoding a functional MARF1 operatively linked to a promoter, vectors comprising such constructs, and packaging cell lines for use in making such vectors.

This disclosure relates to combination therapies comprising anti-Pseudomonas Psl and PcrV bispecific binding molecules and related compositions, for use in prevention and treatment of Pseudomonas infection.

The present invention relates to methods and compositions for treating, preventing, and diagnosing Alzheimer's Disease or other tauopathies in a subject by administering an immunogenic tau peptide or an antibody recognizing the immunogenic tau epitope under conditions effective to treat, prevent, or diagnose Alzheimer's Disease or other tauopathies. Also disclosed are methods of promoting clearance of aggregates from the brain of the subject and of slowing progression of tau-pathology related behavioral phenotype in a subject.

This document provided methods and materials involved in treating medical conditions. For example, methods and materials for using anti-Interleukin 4, anti-Interleukin 5, and/or anti-Interleukin 13 antibodies to treat asthma in a mammal identified as having a Th2 immune response using a whole blood cell-based cytokine whole blood cell-based cytokine assay are provided.

Agents that specifically bind to an opioid receptor in a conformationally specific way can be used to induce a conformational change in the receptor. Such agents have therapeutic applications and can be used in X-ray crystallography studies of the receptor. Such agents can also be used to improve drug discovery via compound screening and/or structure-based drug design.

The present invention relates to compositions and methods for characterizing, diagnosing, and treating cancer. In particular the invention provides the means and methods for the diagnosis, characterization, prognosis and treatment of cancer and specifically targeting cancer stem cells. The present invention provides an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor and inhibits tumor growth. The present invention further provides a method of treating cancer, the method comprising administering a therapeutically effective amount of an antibody that specifically binds to a non-ligand binding membrane proximal region of the extracellular domain of a human Notch receptor protein and inhibits tumor growth.

The present invention relates to VEGF-binding agents, DLL4-binding agents, VEGF/DLL4 bispecific binding agents, and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human VEGF, antibodies that specifically bind human DLL4, and bispecific antibodies that specifically bind human VEGF and/or human DLL4. The present invention further provides methods of using the agents to inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

Provided are methods of generating chimeric antigen receptors (CAR). In some embodiments, library screening of CAR is performed by generating a vector encoding the CAR from random attachment of vectors from libraries of vectors encoding antigen-binding domains (e.g., scFv regions), hinge regions, and endodomains. In some embodiments, the vectors contain a transposon.

Provided in some embodiments are antibodies comprising a heavy chain having no native interchain cysteine amino acids, a light chain having no native interchain cysteine amino acids, and having no native interchain disulphide linkages between the heavy chain and the light chain. Also provided in certain embodiments are antibodies comprising a heavy chain having no native interchain cysteine amino acids, a light chain having no native interchain cysteine amino acids, and having no native interchain disulphide linkages between the heavy chain and the light chain where the native interchain cysteine amino acids have been replaced by amino acids having no thiol moiety.

The present invention concerns modified recombinant J-chain polypeptides, binding molecules, such as antibodies, comprising the same, and their uses.

The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing B-Klotho, and or FGF21-like mediated signaling. In embodiments, the antigen binding proteins specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a CD123 monoclonal antibody, conferring specific immunity against CD123 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia.

Cysteine engineered antibodies useful for the site-specific conjugation to a variety of agents are provided. Methods for the design, preparation, screening, selection and use of such antibodies are also provided.

The invention provides compositions and methods for treating leukemia, for example, acute myeloid leukemia (AML) and B-cell acute lymphoid leukemia (B-ALL). The invention also relates to at least one chimeric antigen receptor (CAR) specific to CD123, vectors comprising the same, and recombinant T cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises a CD123 binding domain. The invention also includes methods of bone marrow ablation for use in treatments necessitating bone marrow reconditioning or transplant.

Described herein are doppel-targeting molecules useful for inhibiting pathological angiogenesis and treating diseases and conditions associated with pathological angiogenesis, such as tumors, cancers, atherosclerosis, tuberculosis, asthma, pulmonary arterial hypertension (PAH), neoplasms and neoplasm-related conditions, and for detecting doppel expression in a subject. Related compositions and methods also are described.

The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a BCMA monoclonal antibody, conferring specific immunity against BCMA positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas, multiple myeloma and leukemia.

The present disclosure provides compositions and methods of use involving binding proteins, e.g., antibodies and antigen-binding fragments thereof, that bind to the matrix metalloproteinase-9 (MMP9) protein (MMP9 is also known as gelatinase-B), such as where the binding proteins comprise an immunoglobulin (Ig) heavy chain (or functional fragment thereof) and an Ig light chain (or functional fragment thereof).

Provided herein are methods of treatment to regenerate, restore or rejuvenate a tissue. Methods include making adult somatic and germ cells pluripotent for administration to a patient. Alternatively, created pluripotent cells may be differentiated to the desired tissue type and administered to a patient to repair or enhance the target tissue.

A recombinant vector comprises simian adenovirus 36, simian adenovirus 42.1, simian adenovirus 42.2 and/or simian adenovirus 44 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses one or more simian adenovirus-36, -42.1, -42.2 or -44 gene(s) is also described. Methods of using the vectors and cell lines are provided.

Materials and methods for treating and preventing American Foulbrood disease in honeybees, such as materials and methods for using phage lysin enzymes to lyse Paenibacillus larvae, are provided herein.

The present invention relates to the use of the miRNA expression profile, particularly of miR-199a-5p, and the target genes regulated thereby for the diagnosis, prognosis and use of miR-199a-5p inhibitors for treating fibroproliferative disorders.

The invention relates to polynucleotide agents targeting the complement component C5 gene, and methods of using such polynucleotide agents to inhibit expression of C5 and to treat subjects having a complement component C5-associated disease, e.g., paroxysmal nocturnal hemoglobinuria.

In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobic ally modified oligonucleotide cargo, and uses thereof, are also provided.

Provided herein are compositions and methods for modifying a predetermined nucleic acid sequence. A programmable nucleoprotein molecular complex containing a polypeptide moiety and a specificity conferring nucleic acid (SCNA) which assembles in-vivo, in a target cell, and is capable of interacting with the predetermined target nucleic acid sequence is provided. The programmable nucleoprotein molecular complex is capable of specifically modifying and/or editing a target site within the target nucleic acid sequence and/or modifying the function of the target nucleic acid sequence.

The invention provides diagnostic and therapeutic targets for pulmonary disease, in particular, fibrotic lung disease. The inventors have found that a genetic variant MUC5B gene is associated with increased expression of the gene, increased risk of developing a pulmonary disease, and an improved prognosis and survival among those developing the pulmonary disease.

By a genome-wide gene analysis of expression profiles of known or putative gene sequences in peripheral blood and biopsy samples, the present inventors have identified a consensus set of gene expression-based molecular biomarkers for distinguishing liver transplantation patients who have Acute Rejection (AR), Hepatitis C Virus Recurrence (HCV-R), both AR/HCV-R, or Acute Dysfunction No Rejection (ADNR). These molecular biomarkers are useful for diagnosis, prognosis and monitoring of liver transplantation patients.

Provided herein are methods for the prognosis of prostate cancer progression in a patient by analyzing the gene expression in a tumor sample obtained from the patient the prognosis of prostate cancer progression in a patient by analyzing the gene expression in a tumor sample obtained from the patient. In particular, gene expression levels of GCOM1, MEX3D, TRPM4, ATPAF1, PTRF, GLYATL1, FLNA, OBSCN, STRA13, WHSCl, ARFGAP3, KDM2A, FAM83H, CLDN7, CNOT6, and B3GNT9 are measured. Kits containing means for the measurement of gene expression as described herein and methods for treatment of prostate cancer are also provided.

The present invention concerns cancer biomarkers. In particular, the invention concerns HGF as a biomarker for patient selection and patient prognosis in cancer, as well as methods of therapeutic treatment, articles of manufacture and methods for making them, diagnostic kits, methods of detection and methods of advertising related thereto.

This disclosure relates to methods, computer products, computer-implemented methods, and systems for predicting the probability or risk of prostate cancer recurrence and tumor aggressiveness in a patient. The method is based, in part, on the patient's risk profile that includes the presence/degree of specific copy number variations and predictive clinical factors. The methods and systems can be used to aid in treatment selection.

Fibrous structures that exhibit a novel combination of properties and to methods for making such fibrous structures are provided.

The invention provides for a proteomic approach for identification of specific bacterial protein profiles that may be used in the development of methods for the diagnosis of bacterial chronic sinusitis. The invention provides for methods for determining the presence of pathogenic bacteria in the upper respiratory tract of a subject using protein profiles of the pathogenic bacteria. The invention also provides for methods of diagnosing a bacterial infection of the upper respiratory tract of a subject using protein profiles of a pathogenic bacteria. In addition, the invention provides for devices, immunoassays and kits for identifying pathogenic bacteria in the upper respiratory tract.

This invention relates to novel monoclonal antibodies that specifically bind to the alpha-folate receptor. In some embodiments, the antibodies inhibit a biological activity of folate receptor-α (FR-α). The antibodies are useful in the treatment of certain cancers, particularly cancers that have increased cell surface expression of the alpha-folate receptor (“FR-α”), such as ovarian, breast, renal, colorectal, lung, endometrial, or brain cancer. The invention also relates to cells expressing the monoclonal antibodies, antibody derivatives, such as chimeric and humanized monoclonal antibodies, antibody fragments, and methods of detecting and treating cancer using the antibodies, derivatives, and fragments.

Described herein are methods and compositions for treatment of immune-related diseases or disorders by modulating DD1α activity, alone or in combination with modulation of PD-1 activity. In some embodiments, the methods and compositions described herein are directed to treatment of cancer and/or infections (e.g., bacterial infection, and/or fungal infection). In some embodiments, the methods and compositions described herein are directed to treatment of autoimmune diseases and/or inflammation. In some embodiments, the methods and compositions described herein are directed to treatment of asthma, and allergy. Methods for identifying patients who are more likely to be responsive to and benefit from an immunotherapy that targets DD1α and/or PD-1 activity or expression are also described herein.

The present invention provides methods for assessing whether a subject is at risk of developing a neurological disorder, diagnosing or confirming whether a subject is afflicted with a neurological disorder, assessing whether PD has progressed in a subject afflicted with PD, assessing whether a neurological disorder is developing in a subject who has been identified as being at risk of developing the neurological disorder, assessing whether a subject afflicted with a neurological disorder is likely to benefit from a therapy, assessing whether a subject afflicted with a neurological disorder has benefited from a therapy, treating a subject afflicted with a neurological disorder, and prophylactically treating a subject who has been identified as being at risk of developing a neurological disorder. The present invention also provides epitopes, compounds and compositions relating to these methods.

A cold rolling mill is described wherein the unstressed shape of metal sheet is continuously sensed during rolling by a plurality of negligible displacement force sensors perpendicularly disposed relative to the pass line at a mill location producing a tensile stress above 4,000 p.s.i. in the metal sheet being rolled. The output signals from those sensors underlying opposite edges of the metal sheet are compared to equalize reduction at the sheet edges while the difference between the force measured by a centrally situated sensor and the average force measured by the sensors underlying opposite edges of the sheet provide a signal indicative of the roll bending force required to produce flat sheet.

A button and pin assembly machine for producing badges and the like comprising buttons having rearwardly extending rims adapted to receive and retain respective pin structures therein, in which the buttons are sequentially supplied to a pin-forming head and supported thereat with the button rim encircling the end of such head, straight pin blanks being sequentially supplied to said head, with a portion of a pin blank being inserted into the head and rotated thereby with respect to a stationary abutment to curl an end of such blank sufficiently to enable its insertion in the rim of a button disposed thereat, said head having means for forming a bend in the portion of the pin blank inserted in such head to resiliently bias the pointed end of the pin blank toward the button.

Portions of a pin-on button are cut and assembled as a result of a plurality of operations in a machine having a vertical press. Cutter and work deforming tools are displaced by a single press ram to cut blanks and deform the blanks onto a button top placed in one of two die assemblies positioned in alignment below the work deforming tool on the lower end of the ram.

Device for forming buttons from a pin-on back plate, a front plate, and a cover over the front plate, with the device having a pair of button-forming dies alternately shiftable into operation alignment with a forming punch which on descent with the successively aligned dies cooperates with the latter to assemble the separate button parts into a button, and a cover-blanking punch and die set above the forming punch, of which the blanking die is topmost and has a die aperture open at the top and bottom and a cutting edge at the bottom of the aperture, with the blanking die being by the forming punch raised into blanking cooperation with the blanking die, and the forming punch being moved upwardly and downwardly by manually operable means.