Provided is a method of potentiating immunity or preventing or treating an immune-related disease comprising administering an anti-Ang2 antibody or an antigen-binding fragment thereof to a subject in need thereof.

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.

Provided is a method of decreasing blood sugar level or preventing and/or treating a hyperglycemia-related disease, including administering an anti-Ang2 antibody or an antigen-biding fragment thereof to a subject in need thereof.

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.

The invention relates to a human Interleukin-2 (hIL-2) specific monoclonal antibody (mAb), or antigen binding fragment thereof, the binding of which to hIL-2 inhibits binding of hIL-2 to CD25 and the antibody is characterized by any of the parameters: the variable chain of the mAb comprises the amino acid sequence of SEQ ID NO 005 or SEQ ID NO 006; the binding to hIL-2 is characterized by a dissociation constant (KD)≦7.5 nmol/L; the binding to hIL-2 is characterized by an off-rate (Koff)≦1×10−4 s−1 and/or the antibody displays no measurable cross-reactivity to murine IL-2.

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.

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.

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 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).

A modular engineered tissue construct includes a plurality of fused self-assembled, scaffold-free, high-density cell aggregates. At least one cell aggregate includes a plurality of cells and a plurality of biocompatible and biodegradable nanoparticles and/or microparticles that are incorporated within the cell aggregates. The nanoparticles and/or microparticles acting as a bulking agent within the cell aggregate to increase the cell aggregate size and/or thickness and improve the mechanical properties of the cell aggregate as well as to deliver bioactive agents.

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.

Various aspects and embodiments of the invention are directed to high-throughput phage-engineering methods and recombinant bacteriophages with tunable host ranges for controlling phage specificity.

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.

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.

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.

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.

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 operative alignment with a forming punch which on descent into the successively aligned dies cooperates with the latter to assemble the separate button parts into a button, and a blanking punch and die set above the forming punch, of which the blanking punch is raised into cooperation with the blanking die for blanking a cover from a supply sheet, and a handlever operatively connected with the punches for simultaneously lowering the forming punch and raising the blanking punch.

Apparatus for the manufacture of a laminated button comprising a metallic backing plate having a transverse peripheral edge and an outwardly extending flange, an illustrated paper sheet and a protective acetate covering. The apparatus comprises a pneumatically operated press which receives the plate, illustrated sheet and covering, and, with a single downward movement, causes the sheet to conform to the plate and be crimped between the transverse edge and flange.

Apparatus for covering buttons operable in an automatic, semi-automatic or manual mode. The apparatus includes a rotatable table having alternately positioned shell and back receiving lower dies, means for automatically delivering the shells and backs to their respective lower dies, a reciprocating upper die synchronized for movement with the rotation of the rotatable table and engageable with the lower dies at a first station to transfer a shell and fabric covering from a shell receiving lower die to the upper die and press-fit a back from a back receiving lower die into the covered shell in the upper die to form an assembled covered button and having means permitting its use with a range of fabric cover thicknesses, and means for ejecting the assembled covered buttons.

A machine for the manufacture of buckles, buttons or the like which comprises an upper tool and a lower tool. The lower tool has an outer, spring-mounted frame and an inner core piece displaceable vertically with respect to the surrounding frame. The lower tool is adapted to support the assembled button after the opening stroke of the upper tool. A device is provided for lifting the core piece of the lower tool relative to the surrounding frame up to about the height of a transversely directed stream of blast air serving for discharging the product from the lower tool.

A button covering device having a platform with a central opening which forms a well to receive a button to be covered and the fabric for covering the button. A pair of sliding plates having contoured recesses are mounted on the platform whereby the contoured recesses may be positioned to overlap the opening to gather the fabric over the rear of the button.

Pigmented substantially crack-free casein plastic compositions containing a minor, luster-imparting quantity of coated mica platelets, wherein at least 75% of the pigment particles possess an average platelet size of below 10 μm., a thickness of about 0.1 to 0.7 μm. and a ratio of diameter to thickness of about 10 to 200.

A fabric covered button comprising a button head having a peripheral groove for receiving a locking ring. The fabric is secured to the button head and the marginal edge thereof is retained within the groove by the locking ring.

Apparatus for assembling covered buttons in which a first die assembly including a first punch carrying a first sleeve which sequentially receives a piece of covering material and the button shell with its flange extending toward the open end of the sleeve. A second assembly including a second sleeve having a bore one end of which is formed with a first cam surface extending axially inwardly of the above. The second sleeve is spring loaded to an extended position on a supporting post having a centrally located button back fastener receiving cavity in the end thereof with a second cam surface extending inwardly from the outer edge of the end to the bottom of a recess surrounding the cavity. An annular boss at the inner edge of the recess around the cavity is elevated to allow the material and the shell flange to curl inwardly under the button back. In the retracted position of the second sleeve on the post, the second cam surface forms a continuation of the first. In operation, when the first assembly carrying the covering piece and the shell moves toward the second assembly, the first sleeve stops against the spring loaded bottom sleeve and the punch continues forcing the material down so that the material is tucked inward by the beveled or curved surface of the second sleeve. Upon continued relative movement of the assemblies, the shell flange acts on the cam surface of the second sleeve to force the sleeve to its retracted position and the shell flange is moved inwardly of the back wall under the continued action of the first post, the extent of the inward movement of the shell flange being determined by the thickness of the material of the covering piece, as well as the height of the shell and the type of back used.

Applicant's invention relates to a process and apparatus for the high speed welding in large quantities of various geometric shaped jump rings to buttons, pendants and other jewelry by utilizing composite jump ring apparatus having first and second projections extending from the jump rings at different locations so that they may function in automatic welding machines.

An improved method of forming and assembling two-part merchandise display hooks, including new design features of the hook itself, enable two-part hooks to be manufactured and assembled at extremely low cost. Wire from a continuous length is gripped and bent to form the outer portion of the hook. The wire is then severed and bent in a single operation to form a hook-mounting portion. While the severed wire remains gripped by its shaped outer end, a preoriented and guided base member is applied over the just-formed mounting portion of the wire. A retractable bend-forming member is withdrawn when the base member is applied to the wire, to enable the bent portion to be fully received within the plastic base. Major manufacturing economies are realized.

A device is disclosed for pressing objects by lifting the objects into a waiting pressing shaft. The shaft includes a forming element at its lower end for forming the object, and the shaft is engaged by its upper end through a pivot member to an air cylinder in a manner which provides a force advantage to the air cylinder. Also, a system for pressing objects is disclosed, in which the press device is employed in conjunction with a turntable for sequential and continuous pressing operations.

A machine for automatically joining front and back parts of buttons employs a turntable with nests that are rotated through a series of stations at which the parts are placed in the nests in a desired orientation, joined, and checked for defects. Orientation of the parts is achieved by video imaging of a first part as it is randomly placed in a nest, and computer-controlled placement of the second part based on the ascertained position of the first part.

A method and apparatus for substantially automatically joining front and back parts of buttons employs a turntable with retaining means that are rotated through a series of stations at which the parts are placed in the retaining means in a desired orientation, joined, and checked for defects. A human operator places button front parts at a first station, and the remaining stations carry out the assembly and quality control steps automatically. Placement at the first station determines the alignment and orientation of the two buttons.

A universal assembly machine manufactures conventional buttons with formed backs. The machine comprises a rotatably indexable die table to which are mounted pickup and crimp dies. The die table indexes about a center column of the machine frame. A ram die is advancable and retractable in a pickup stroke and a crimp stroke by means of a handle. The ram die includes a ram outer ring that is rotatable by means of a shifter post joined to the die table. Indexing the die table causes the shifter post to rotate the ram outer ring into a pickup mode or a crimp mode to suit the ram pickup and crimp strokes, respectively. The universal assembly machine also manufactures buttons with flat backs by using a different crimp die pedestal than is used with the formed backs. An adapter on the crimp die pedestal used with formed backs allows that crimp die pedestal to also be used for manufacturing buttons with flat backs. The invention also embraces button medallions. A flat back button is loaded into the pickup die, and the die table is indexed. The ram die is advanced in a third press to form the shell frusto-conical wall of the flat back button inwardly to be flat and parallel to the flat back.

A universal assembly machine manufactures button medallions. The machine comprises a rotatably indexable die table to which are mounted pickup and crimp dies. The die table indexes about a center column of the machine frame. A ram die is advancable and retractable in a pickup stroke and a crimp stroke by means of a handle. The ram die includes a ram outer ring that is rotatable by means of a shifter post joined to the die table. Indexing the die table causes the shifter post to rotate the ram outer ring into a pickup mode or a crimp mode to suit the ram pickup and crimp strokes, respectively. The universal assembly machine also manufactures buttons with flat backs. To make a button medallion a flat back button is loaded into the pickup die. The ram die is advanced in a third press stroke to bend the shell frusto-conical wall of the flat back button inwardly to be flat and parallel to the flat back. The thin edge of the button medallion enables it to be used as an attractive embellishment on flat surfaces.

A universal assembly machine manufactures conventional buttons with formed backs. The machine comprises a rotatably indexable die table to which are mounted pickup and crimp dies. The die table indexes about a center column of the machine frame. A ram die is advancable and retractable in a pickup stroke and a crimp stroke by means of a handle. The ram die includes a ram outer ring that is rotatable by means of a shifter post joined to the die table. Indexing the die table causes the shifter post to rotate the ram outer ring into a pickup mode or a crimp mode to suit the ram pickup and crimp strokes, respectively. The universal assembly machine also manufactures buttons with flat backs by using a different crimp die pedestal than is used with the formed backs. An adapter on the crimp die pedestal used with formed backs allows that crimp die pedestal to also be used for manufacturing buttons with flat backs. The invention also embraces button medallions. A flat back button is loaded into the pickup die, and the die table is indexed. The ram die is advanced in a third press stroke to bend the shell frusto-conical wall of the flat back button inwardly to be flat and parallel to the flat back.