Abstract: Techniques are described for linked blockchains that allow computing devices to access information from an acceptance blockchain about acceptance reports stored in an enterprise delivery blockchain that are also linked to a product blockchain that stores information of the products of the acceptance reports. An acceptance report is indicative of operability of a product in a service provided by a service provider. A processor is configured to access the block in the enterprise delivery blockchain, retrieve the acceptance report from the block in the enterprise delivery blockchain, determine an identifier, identified in the block in the enterprise delivery blockchain, to a block in an acceptance blockchain, access the block in the acceptance blockchain via the determined identifier, retrieve from the block in the acceptance blockchain contextual information of the acceptance report, and output the acceptance report and contextual information of the acceptance report.

Abstract: An isolated nucleic acid that contains a nucleotide sequence that encodes the polypeptide of SEQ ID NO: 3. The polypeptide of SEQ ID NO: 3 specifically binds to stage-specific embryonic antigen 4 (SSEA4). Also disclosed is a recombinant cell comprising the isolated nucleic acid described above, a viral vector containing the above isolated nucleic acid, and an isolated polypeptide including the sequence of SEQ ID NO: 3. Provided as well is a chimeric antigen receptor (CAR) that includes a single chain Fv having the sequence of SEQ ID NO: 3 and specifically binding to SSEA4. Moreover, a method is disclosed for treating a tumor by transducing in vitro the T cells of a subject having a tumor expressing SSEA4 with a vector that encodes the CAR, expanding the transduced T cells, and infusing the expanded transduced T cells into the subject, whereby an anti-tumor T cell response is raised.

Abstract: A nucleic acid construct that encodes a monoclonal antibody or antigen-binding fragment that specifically binds to stage-specific embryonic antigen 4. The monoclonal antibody or antigen-binding fragment includes a heavy-chain CDR1 having the sequence of SEQ ID NO: 33 or SEQ ID NO: 40, a heavy-chain CDR2 having the sequence of SEQ ID NO: 34 or SEQ ID NO: 39, a heavy-chain CDR3 having the sequence of SEQ ID NO: 35 or SEQ ID NO: 41, a light-chain CDR1 having the sequence of SEQ ID NO: 36 or SEQ ID NO: 42, a light-chain CDR2 having the sequence of SEQ ID NO: 37 or SEQ ID NO: 43, and a light-chain CDR3 having the sequence of SEQ ID NO: 38 or SEQ ID NO: 44. Also disclosed are recombinant cells containing the nucleic acid construct.

Abstract: An isolated nucleic acid that contains a nucleotide sequence that encodes the polypeptide of SEQ ID NO: 3. The polypeptide of SEQ ID NO: 3 specifically binds to stage-specific embryonic antigen 4 (SSEA4). Also disclosed is a recombinant cell comprising the isolated nucleic acid described above, a viral vector containing the above isolated nucleic acid, and an isolated polypeptide including the sequence of SEQ ID NO: 3. Provided as well is a chimeric antigen receptor (CAR) that includes a single chain Fv having the sequence of SEQ ID NO: 3 and specifically binding to SSEA4. Moreover, a method is disclosed for treating a tumor by transducing in vitro the T cells of a subject having a tumor expressing SSEA4 with a vector that encodes the CAR, expanding the transduced T cells, and infusing the expanded transduced T cells into the subject, whereby an anti-tumor T cell response is raised.

Abstract: A nucleic acid construct that encodes a monoclonal antibody or antigen-binding fragment that specifically binds to stage-specific embryonic antigen 4. The monoclonal antibody or antigen-binding fragment includes a heavy-chain CDR1 having the sequence of SEQ ID NO: 33 or SEQ ID NO: 40, a heavy-chain CDR2 having the sequence of SEQ ID NO: 34 or SEQ ID NO: 39, a heavy-chain CDR3 having the sequence of SEQ ID NO: 35 or SEQ ID NO: 41, a light-chain CDR1 having the sequence of SEQ ID NO: 36 or SEQ ID NO: 42, a light-chain CDR2 having the sequence of SEQ ID NO: 37 or SEQ ID NO: 43, and a light-chain CDR3 having the sequence of SEQ ID NO: 38 or SEQ ID NO: 44. Also disclosed are recombinant cells containing the nucleic acid construct.

Abstract: An isolated nucleic acid that contains a nucleotide sequence that encodes the polypeptide of SEQ ID NO: 3. The polypeptide of SEQ ID NO: 3 specifically binds to stage-specific embryonic antigen 4 (SSEA4). Also disclosed is a recombinant cell comprising the isolated nucleic acid described above, a viral vector containing the above isolated nucleic acid, and an isolated polypeptide including the sequence of SEQ ID NO: 3. Provided as well is a chimeric antigen receptor (CAR) that includes a single chain Fv having the sequence of SEQ ID NO: 3 and specifically binding to SSEA4. Moreover, a method is disclosed for treating a tumor by transducing in vitro the T cells of a subject having a tumor expressing SSEA4 with a vector that encodes the CAR, expanding the transduced T cells, and infusing the expanded transduced T cells into the subject, whereby an anti-tumor T cell response is raised.

Abstract: An isolated monoclonal antibody or antigen-binding fragment that specifically binds to stage-specific embryonic antigen 4. The monoclonal antibody or antigen-binding fragment includes a heavy-chain CDR1 having the sequence of SEQ ID NO: 33 or SEQ ID NO: 40, a heavy-chain CDR2 having the sequence of SEQ ID NO: 34 or SEQ ID NO: 39, a heavy-chain CDR3 having the sequence of SEQ ID NO: 35 or SEQ ID NO: 41, a light-chain CDR1 having the sequence of SEQ ID NO: 36 or SEQ ID NO: 42, a light-chain CDR2 having the sequence of SEQ ID NO: 37 or SEQ ID NO: 43, and a light-chain CDR3 having the sequence of SEQ ID NO: 38 or SEQ ID NO: 44. Also disclosed is an anti-tumor method carried out by administering the above monoclonal antibody or antigen-binding fragment to a subject having a tumor that expresses stage-specific embryonic antigen 4. Further provided are nucleic acids encoding the above sequences and recombinant cells containing the nucleic acids.

Abstract: Disclosed is a controlled-release formulation for treating disturbed sleep or insomnia in a subject. The formulation is formulated to release diphenhydramine HCl and a sleep aid in sequence at two stages.

Abstract: An isolated monoclonal antibody or antigen-binding fragment that specifically binds to stage-specific embryonic antigen 4. The monoclonal antibody or antigen-binding fragment includes a heavy-chain CDR1 having the sequence of SEQ ID NO: 33 or SEQ ID NO: 40, a heavy-chain CDR2 having the sequence of SEQ ID NO: 34 or SEQ ID NO: 39, a heavy-chain CDR3 having the sequence of SEQ ID NO: 35 or SEQ ID NO: 41, a light-chain CDR1 having the sequence of SEQ ID NO: 36 or SEQ ID NO: 42, a light-chain CDR2 having the sequence of SEQ ID NO: 37 or SEQ ID NO: 43, and a light-chain CDR3 having the sequence of SEQ ID NO: 38 or SEQ ID NO: 44. Also disclosed is an anti-tumor method carried out by administering the above monoclonal antibody or antigen-binding fragment to a subject having a tumor that expresses stage-specific embryonic antigen 4. Further provided are nucleic acids encoding the above sequences and recombinant cells containing the nucleic acids.

Abstract: An isolated nucleic acid that contains a nucleotide sequence that encodes the polypeptide of SEQ ID NO: 3. The polypeptide of SEQ ID NO: 3 specifically binds to stage-specific embryonic antigen 4 (SSEA4). Also disclosed is a recombinant cell comprising the isolated nucleic acid described above, a viral vector containing the above isolated nucleic acid, and an isolated polypeptide including the sequence of SEQ ID NO: 3. Provided as well is a chimeric antigen receptor (CAR) that includes a single chain Fv having the sequence of SEQ ID NO: 3 and specifically binding to SSEA4. Moreover, a method is disclosed for treating a tumor by transducing in vitro the T cells of a subject having a tumor expressing SSEA4 with a vector that encodes the CAR, expanding the transduced T cells, and infusing the expanded transduced T cells into the subject, whereby an anti-tumor T cell response is raised.

Abstract: A method for treating a tumor in a subject by administering at least three of the following treatment modalities: (i) an antibody, (ii) T cells bearing a first chimeric antigen receptor (CAR), (iii) NK cells bearing a second CAR, and (iv) NKT cells bearing a third CAR. The antibody binds specifically to stage-specific embryonic antigen 4 and each CAR contains a scFv that also binds specifically to SSEA4.

Abstract: A method for treating a tumor includes administering (i) a vaccine that contains stage-specific embryonic antigen 4 conjugated to a carrier, (ii) an antibody that binds specifically to SSEA-4, and (iii) immune cells expressing a chimeric antigen receptor that specifically binds to SSEA-4. The tumor, which expresses SSEA-4, can be a breast, colon, gastrointestinal, kidney, lung, liver, ovarian, pancreatic, rectal, stomach, testicular, thymic, cervical, prostate, bladder, skin, nasopharyngeal, esophageal, oral, head and neck, bone, cartilage, muscle, lymph node, bone marrow, or brain tumor.

Abstract: A method for treating a tumor by administering an antibody or antibody fragment that binds specifically to stage-specific embryonic antigen 4, and an agent that enhances T cell anti-tumor responses. Also provided is a pharmaceutical composition for treating a tumor. The pharmaceutical composition contains an anti-SSEA4 antibody or antibody fragment, an agent that enhances T cell responses, and a pharmaceutically acceptable excipient.

Abstract: A chimeric antigen receptor containing (i) a single chain Fv that specifically binds to stage-specific embryonic antigen 4 and (ii) an endodomain from CD3? or Fc?RI?. Also provided is a nucleic acid encoding the chimeric antigen receptor and an expression vector that contains the nucleic acid operably linked to a promoter that is active in T cells. Furthermore, two similar methods for treating a tumor are disclosed. The first method includes (i) obtaining T cells from a subject, (ii) transducing the T cells in vitro with an expression vector encoding a chimeric antigen receptor that contains an scFv specifically recognizing stage-specific embryonic antigen 4, (iii) expanding the transduced T cells in vitro, and (iv) infusing the expanded transduced T cells into the subject.

Abstract: Two methods for treating a tumor are disclosed. The first method includes (i) obtaining NK cells or NKT cells from a subject, (ii) transducing the NK cells or NKT cells in vitro with an expression vector encoding a chimeric antigen receptor that contains an scFv specifically recognizing stage-specific embryonic antigen 4, (iii) expanding the transduced NK cells or NKT cells in vitro, and (iv) infusing the expanded transduced NK cells or NKT cells into the subject. The second method includes, in place of step (ii) above, transducing the NK cells or NKT cells in vitro with an expression vector encoding a chimeric antigen receptor that is specific for a tumor antigen other than stage-specific embryonic antigen 4, and further requires a step of administering an antibody against stage-specific embryonic antigen 4.

Abstract: An immunogenic composition that includes a glycoconjugate containing a fusion protein composed of an immunoglobulin gamma Fc domain fused to a tumor-associated antigen, the fusion protein being cross-linked to an azido-modified stage-specific embryonic antigen 4 conjugated to diphtheria toxoid cross-reactive material 197; and ?-galactosylceramide C34 or ?-glucosylceramide C34. Also provided are methods for treating cancer by administering the immunogenic composition to a patient.

Abstract: A method for treating a tumor with at least two bifunctional agents. The bifunctional agents each include a binding domain that specifically binds to stage-specific embryonic antigen 4 (SSEA4) or an SSEA4 analog, and an effector domain selected from a cytokine, a cytotoxic agent, an immunoglobulin Fc domain, anti-CD3, and anti-CD16.

Abstract: Described is a controlled-release formulation for treating disturbed sleep or insomnia in a subject. The formulation is formulated to release a compound or combination of compounds in sequence at multiple stages.

Abstract: Described is a controlled-release formulation for treating disturbed sleep or insomnia in a subject. The formulation is formulated to release a compound or combination of compounds in sequence at multiple stages.

Abstract: Described is a controlled-release formulation for treating disturbed sleep or insomnia in a subject. The formulation is formulated to release a compound or combination of compounds in sequence at multiple stages.