Abstract: The present invention is directed to sequence-optimized CD123×CD3 bi-specific monovalent diabodies that are capable of simultaneous binding to CD123 and CD3, and to the uses of such diabodies in the treatment of hematologic malignancies.

Abstract: The present invention is directed to bi-specific monovalent diabodies that comprise two polypeptide chains and which possess at least one binding site specific for an epitope of CD3 and one binding site specific for an epitope of gpA33 (i.e., a “gpA33×CD3 bi-specific monovalent diabody”). The present invention also is directed to bi-specific monovalent diabodies that comprise an immunoglobulin Fc Domain (“bi-specific monovalent Fc diabodies”) and are composed of three polypeptide chains and which possess at least one binding site specific for an epitope of gpA33 and one binding site specific for an epitope of CD3 (i.e., a “gpA33×CD3 bi-specific monovalent Fc diabody”). The bi-specific monovalent diabodies and bi-specific monovalent Fc diabodies of the present invention are capable of simultaneous binding to gpA33 and CD3. The invention is directed to pharmaceutical compositions that contain such bi-specific monovalent diabodies or such bi-specific monovalent Fc diabodies.

Abstract: Method for enabling zero sign-on (ZSO) through a standard web browser. The device running the browser is first enrolled with a web service using an installed enrollment agent on the device which authenticates a user of the device. After authentication, the enrollment agent stores a device profile that includes a user certificate for the user and an authority certificate issued by said web service. The device profile is stored at a device location accessible by each of the web browsers used by said device. The enrollment agent configures each of the web browsers on the device to respond correctly to ZSO certificate challenges from the web service. Once enrolled, the device's web browsers can respond correctly to a ZSO Uniform Resource Locator (URL) certificate challenge received from the web service. After a successful response to the challenge, the browser is granted a secure socket layer (SSL) connection.

Abstract: The present invention relates to antibodies that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

Abstract: Bispecific heterodimeric diabody molecules and uses thereof in the treatment of cancer. The bispecific heterodimeric diabody molecules comprise two polypeptide chains that associate to form two epitope binding sites recognizing the P-cadherin tumor cell associated antigen and the CD3 T cell antigen.

Abstract: The present invention is directed to multivalent DR5-Binding Molecules that comprise Binding Domain(s) of anti-DR5 antibodies, and particularly Binding Domain(s) of anti-human DR5 antibodies. The DR5-Binding Molecules of the present invention include bivalent and tetravalent molecules having two, three or four DR5-Binding Domains each capable of binding human DR5. In particular, the present invention is directed to multivalent DR5-Binding Molecules that comprise diabodies, and more particularly, diabodies that comprise a covalently bonded complex of two or more polypeptide chains. The invention particularly pertains to such multivalent DR5-Binding Molecules that comprise of the anti-DR5 antibodies DR5 mAb 1 and/or DR5 mAb 2, and/or humanized and chimeric versions of such antibodies.

Abstract: The present invention relates to antibodies and their fragments that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies and their immunoreactive fragments that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

Abstract: Methods and compositions for diagnosing and treating diseases, particularly cancer, associated with differential expression of cancer-associated targets (CAT) in disease cells compared to healthy cells are provided. Also provided are antagonists and agonists of CAT, and methods for screening agents that modulate CAT level or activity in vivo or in vitro.

Abstract: The present invention is directed to sequence-optimized CD 123×CD3 bi-specific monovalent diabodies that are capable of simultaneous binding to CD 123 and CD3, and to the uses of such diabodies in the treatment of hematologic malignancies.

Abstract: An electromagnetic rotor drive assembly for use with an internal combustion engine, the electromagnetic rotor drive assembly including a conductive coil capable of generating a magnetic field upon energization; a rotor rotatably mounted proximate the conductive coil; and a magnet coupled to the rotor, the magnet responsive to the magnetic field to angularly displace the rotor; whereby the rotor fixedly couples to a crankshaft rotated by at least one piston reciprocally disposed within a cylinder; and whereby the conductive coil is energized at a predetermined time point associated with a position of the piston within the cylinder.

Abstract: CD 19×CD3 bi-specific monovalent diabodies, and particularly, CD 19×CD3 bi-specific monovalent Fc diabodies, are capable of simultaneous binding to CD 19 and CD3, and are used in the treatment of hematologic malignancies.

Abstract: The present invention is directed to optimized ROR1-binding molecules having enhanced affinity and superior ability to mediate redirected cytotoxicity of tumor cells relative to prior ROR1-binding molecules. More specifically, the invention relates to optimized ROR1-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been optimized for binding to an epitope present on the human ROR1 polypeptide so as to exhibit enhanced binding affinity for human ROR1 and/or a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific ROR1-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such optimized ROR1-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell.

Abstract: The present invention relates to antibodies and their fragments that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies and their immunoreactive fragments that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

Abstract: The present invention relates to antibodies and their fragments that are immunoreactive to the mammalian, and more particularly, the human B7-H3 receptor and to uses thereof, particularly in the treatment of cancer and inflammation. The invention thus particularly concerns humanized B7-H3-reactive antibodies and their immunoreactive fragments that are capable of mediating, and more preferably enhancing the activation of the immune system against cancer cells that are associated with a variety of human cancers.

Abstract: The present invention relates to Tri-Specific Binding Molecules, which are multi-chain polypeptide molecules that possess three Binding Domains and are thus capable of mediating coordinated binding to three epitopes. The Tri-Specific Binding Molecule is preferably characterized in possessing binding domains that permit it to immunospecifically bind to: (1) an epitope of a first Cancer Antigen, (2) an epitope of a second Cancer Antigen, and (3) an epitope of a molecule that is expressed on the surface of an immune system effector cell, and are thus capable of localizing an immune system effector cell to a cell that expresses a Cancer Antigen, so as to thereby facilitate the killing of such cancer cell.

Abstract: The present invention is directed to bi-specific diabodies that comprise two or more polypeptide chains and which possess at least one Epitope-Binding Site that is immunospecific for an epitope of PD-1 and at least one Epitope-Binding Site that is immunospecific for an epitope of LAG-3 (i.e., a “PD-I×LAG-3 bi-specific diabody”). More preferably, the present invention is directed to bi-specific diabodies that comprise four polypeptide chains and which possess two Epitope-Binding Sites that are immunospecific for one (or two) epitope(s) of PD-1 and two Epitope-Binding Site that are immunospecific for one (or two) epitope(s) of LAG-3 (i.e., a “PD-1×LAG-3 bi-specific, tetra-valent diabody”).

Abstract: The present invention relates to Tri-Specific Binding Molecules, which are multichain polypeptide molecules that possess three Binding Domains and are thus capable of mediating coordinated binding to three epitopes. The Binding Domains may be selected such that the Tri-Specific Binding Molecules are capable of binding to any three different epitopes. Such epitopes may be epitopes of the same antigen or epitopes of two or three different antigens. In a preferred embodiment, one of such epitopes will be capable of binding to CD3, the second of such epitopes will be capable of binding to CD8, and the third of such epitopes will be capable of binding to an epitope of a Disease-Associated Antigen. The invention also provides a novel ROR1-binding antibody, as well as derivatives thereof and uses for such compositions.

Abstract: The present invention is directed to a combination therapy involving the administration of: (1) a bi-specific molecule capable of specifically binding to CD19 and to CD3 (i.e., a CD19×CD3 bi-specific molecule), and (2) a Bruton's Tyrosine Kinase (BTK) inhibitor for the treatment of disease, in particular treatment of a disease associated with or characterized by the expression of CD19. Preferably, such a CD19×CD3 bi-specific molecules are bi-specific monovalent diabodies. The invention is directed to pharmaceutical compositions that contain such a CD19×CD3 bi-specific molecule, a BTK inhibitor, or a combination of such agents. The invention is additionally directed to methods for the use of such pharmaceutical compositions in the treatment of disease, in particular, treatment of a cancer associated with or characterized by the expression of CD19.

Abstract: A heating and cooling system for a vehicle having an internal combustion engine is provided. The system comprises at least one exhaust pipe conveying exhaust gases away from the engine, and a reactor vessel located in the exhaust pipe and containing an absorbent salt and a refrigerant fluid. A condenser is in fluid communication with the reactor vessel, and receives refrigerant vapour from the reactor when exhaust gases heat the reactor vessel in the exhaust pipe. An evaporator is locatable in a cab of the vehicle and is in fluid communication with the condenser and the reactor vessel. The evaporator receives condensed refrigerant from the condenser so as to cool the air surrounding the evaporator, and returning refrigerant vapour to the reactor vessel. A method of cooling a driver environment of a vehicle having an internal combustion engine is also provided, as is a vehicle incorporating the heating and cooling system.

Abstract: An electromagnetic rotor drive assembly for use with an internal combustion engine, the electromagnetic rotor drive assembly including a conductive coil capable of generating a magnetic field upon energization; a rotor rotatably mounted proximate the conductive coil; and a magnet coupled to the rotor, the magnet responsive to the magnetic field to angularly displace the rotor; whereby the rotor fixedly couples to a crankshaft rotated by at least one piston reciprocally disposed within a cylinder; and whereby the conductive coil is energized at a predetermined time point associated with a position of the piston within the cylinder.