Abstract: Provided are p97 (melanotransferrin)-trastuzumab fusion proteins and related methods of use thereof, for instance, to facilitate delivery of trastuzumab across the blood-brain barrier (BBB) and/or improve tissue penetration of the antibody in CNS and peripheral tissues, and thereby treat and/or diagnose HER2-positive cancers, including those of the central nervous system (CNS).

Abstract: Disclosed are therapeutic payloads comprising p97 fragments coupled with active agents having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, to facilitate delivery of therapeutic or diagnostic agents across the BBB. The therapeutic payloads can be effective in the treatment of conditions which involve the lymphatic system of the subject, and may also present a disease state in the brain of the subject. Methods of treating diseases involving the lymphatic system and pharmaceutical compositions are also disclosed.

Abstract: Provided are compositions and methods related to the co-administration of an immunoglobulin Fc region-containing polypeptide and a central nervous system (CNS)-targeted antibody or Fc-fusion polypeptide conjugate, to improve pharmacokinetics and/or delivery of the conjugate across the blood-brain barrier (BBB). Also provided are methods of treatment of indications and diseases of the CNS and indications and diseases with a CNS component.

Abstract: Disclosed are therapeutic payloads comprising p97 fragments coupled with active agents having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, to facilitate delivery of therapeutic or diagnostic agents across the BBB. The therapeutic payloads can be effective in the treatment of frontotemportal dementia (FTD). Methods of treating frontotemporal dementia (FTD) and pharmaceutical compositions are also disclosed.

Abstract: Provided are substantially dephosphorylated forms of lysosomal storage disease (LSD) proteins, including dephosphorylated forms of iduronate-2-sulfatase (IDS, or 12D) and iduronidase (IDU), having increased ability to traverse or penetrate the blood brain barrier (BBB) relative to phosphorylated forms of the protein, and p97 conjugates thereof. Also provided are compositions comprising such dephosphorylated LSD proteins and p97 conjugates, and methods of use thereof, for instance, to treat any one or more lysosomal storage diseases, such as Hunter Syndrome (or MPS Type II).

Abstract: Provided are fusion proteins between p97 (melanotransferrin) and iduronate-2-sulfatase (IDS), and related compositions and methods of use thereof, for instance, to facilitate delivery of IDS across the blood-brain barrier (BBB) and/or improve its tissue penetration in CNS and/or peripheral tissues, and thereby treat and/or diagnose Hunter Syndrome (Mucopolysaccharidosis type II; MPS II) and related lysosomal storage disorders, including those having a central nervous system (CNS) component.

Abstract: Provided are substantially dephosphorylated forms of lysosomal storage disease (LSD) proteins, including dephosphorylated forms of iduronate-2-sulfatase (IDS, or I2D) and iduronidase (IDU), having increased ability to traverse or penetrate the blood brain barrier (BBB) relative to phosphorylated forms of the protein, and p97 conjugates thereof. Also provided are compositions comprising such dephosphorylated LSD proteins and p97 conjugates, and methods of use thereof, for instance, to treat any one or more lysosomal storage diseases, such as Hunter Syndrome (or MPS Type II).

Abstract: Disclosed are therapeutic payloads comprising p97 fragments coupled with active agents having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, to facilitate delivery of therapeutic or diagnostic agents across the BBB. The therapeutic payloads can be effective in the treatment of Gaucher disease. Methods of treating Gaucher disease and pharmaceutical compositions are also disclosed.

Abstract: Disclosed are therapeutic payloads comprising p97 fragments coupled with active agents having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, to facilitate delivery of therapeutic or diagnostic agents across the BBB. The therapeutic payloads have dual functionality that may permit treatment of diseases in a subject other than diseases that present in the brain, e.g., solid tumors in the body. Methods of treating various diseases and pharmaceutical compositions are also disclosed.

Abstract: Provided are fragments of human p97 (melanotransferrin) polypeptides having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, conjugates comprising the p97 fragments, and related methods of use thereof, for instance, to facilitate the delivery of therapeutic or diagnostic agents across the BBB and into the central nervous system.

Abstract: Provided are fragments of human p97 (melanotransferrin) polypeptides having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, conjugates comprising the p97 fragments, and related methods of use thereof, for instance, to facilitate delivery of therapeutic or diagnostic agents across the BBB.

Abstract: Provided are fusion proteins between p97 (melanotransferrin) and iduronate-2-sulfatase (IDS), and related compositions and methods of use thereof, for instance, to facilitate delivery of IDS across the blood-brain barrier (BBB) and/or improve its tissue penetration in CNS and/or peripheral tissues, and thereby treat and/or diagnose Hunter Syndrome (Mucopolysaccharidosis type II; MPS II) and related lysosomal storage disorders, including those having a central nervous system (CNS) component.

Abstract: Provided are conjugates between p97 (melanotransferrin) and polynucleotides such as small interfering RNA (siRNA) molecules, and related compositions and methods of use thereof, for instance, to facilitate delivery of polynucleotides such as siRNA molecules across the blood-brain barrier (BBB) and/or improve their tissue penetration in CNS and/or peripheral tissues, and thereby treat and/or diagnose various diseases, including those having a central nervous system (CNS) component.

Abstract: Provided are fragments of human p97 (melanotransferrin) polypeptides having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, conjugates comprising the p97 fragments, and related methods of use thereof, for instance, to facilitate delivery of therapeutic or diagnostic agents across the BBB.

Abstract: Provided are substantially dephosphorylated forms of lysosomal storage disease (LSD) proteins, including dephosphorylated forms of iduronate-2-sulfatase (IDS, or I2D) and iduronidase (IDU), having increased ability to traverse or penetrate the blood brain barrier (BBB) relative to phosphorylated forms of the protein, and p97 conjugates thereof. Also provided are compositions comprising such dephosphorylated LSD proteins and p97 conjugates, and methods of use thereof, for instance, to treat any one or more lysosomal storage diseases, such as Hunter Syndrome (or MPS Type II).

Abstract: The present invention provides p97-antibody conjugates and related compositions and methods, which may be used in any of a variety of therapeutic methods, including methods for the treatment of cancers such as Her2/neu-expressing and Her1/EGFR-expressing cancers.

Abstract: Provided are fragments of human p97 (melanotransferrin) polypeptides having blood-brain barrier (BBB) transport activity, including variants and combinations thereof, conjugates comprising the p97 fragments, and related methods of use thereof, for instance, to facilitate delivery of therapeutic or diagnostic agents across the BBB.

Abstract: The present invention provides p97-antibody conjugates and related compositions and methods, which may be used in any of a variety of therapeutic methods, including methods for the treatment of cancers such as Her2/neu-expressing and Her1/EGFR-expressing cancers.

Abstract: The present invention is related to fragments of human melanotransferrin (p97). In particular, this invention relates to treatment of diseases through the introduction of the melanotransferrin fragment conjugated to a therapeutic or diagnostic agent to a subject.

Abstract: The present invention provides p97-antibody conjugates and related compositions and methods, which may be used in any of a variety of therapeutic methods, including methods for the treatment of cancers such as Her2/neu-expressing and Her1/EGFR-expressing cancers.