58 results about "Transferrin receptor binding" patented technology

Provided herein are compounds and conjugates comprising transferrin receptor binding protein, pharmaceutical compositions comprising such conjugates, and methods of treating CNS diseases (e.g., neurodegenerative disease) using such conjugates.

Provided are complexes and methods for targeting cells of interest for delivery of a cargo such as an oligomeric compound or an oligomeric duplex. In particular, the complex may comprise a transferrin receptor binding moiety and a half-life extension moiety.

Disclosed are fusion proteins (and homodimers and heterodimers thereof). Fusion proteins can bind to a protein of interest and to an internalizing receptor (transferrin receptor) on a cell surface. Once bound, the protein of interest can be internalized and / or degraded inside a cell.

Provided herein are proteins comprising TfR binding protein, conjugates comprising such TfR binding proteins, e.g., TfR binding proteins-dsRNA conjugates, pharmaceutical compositions comprising TfR binding proteins or conjugates, and methods of treating CNS diseases (e.g., neurodegenerative disease) using TfR binding proteins or conjugates. Also included are methods of treating or reducing pain.

Provided herein are proteins comprising one monovalent human TfR binding domain ("human TfR binding proteins"), conjugates comprising such human TfR binding proteins, e.g., human TfR binding proteins-dsRNA conjugates, pharmaceutical compositions comprising human TfR binding proteins or conjugates, and methods of treating CNS diseases (e.g., neurodegenerative disease such as neurodegenerative synucleinopathy or tauopathy) using human TfR binding proteins or conjugates.

Disclosed are fusion proteins (homodimers and heterodimers thereof). Fusion proteins that can bind to a protein of interest that is a G Protein-Coupled Receptor (GPCR) and to an internalizing receptor on a cell surface (transferrin receptor). Once bound, the protein of interest can be internalized and / or degraded inside a cell.

Described herein are compositions and methods for selective depletion of target molecules using a recyclable CDP-receptor-binding mediated complex to elicit endocytosis and cellular degradation of the target. Exemplary compositions containing a peptide, such as a CDP peptide, that bind a transferrin receptor can be linked to a peptide that binds a target molecule. Such compositions can be used to selectively recruit the target molecule to endosomes via transferrin receptor-mediated endocytosis of the composition and the bound target molecule. Once inside the endosome, the acidic pH can lead to release of the target molecule from the composition due to pH-dependent binding of the composition for the target molecule, and the transferrin receptor portion is recycled back to the cell surface for “reloading”. The target molecule can then be trafficked into lysosomes wherein it is degraded.

The present disclosure relates to binding proteins comprising: a first transferrin receptor 1 binding moiety M1 comprising an immunoglobulin heavy chain variable region (VH) and an immunoglobulin light chain variable region (VL) and having the ability to selectively bind to an epitope located in the hTfR1 protease-like domain; and a second portion M2, the M2 comprising an antibody Fc domain. In the binding protein, M1 and M2 are linked to each other by at least one peptide linker between M1 and M2.

The present invention relates to variable domains (VHHs) of camelid heavy chain molecules that bind to TfR, conjugate compounds containing such VHH molecules, and their use for, for example, transporting molecules for pharmaceutical purposes to cells and organs in pathological conditions in the CNS or PNS, including cancer.

Aspects of the disclosure relate to antibodies that bind to transferrin receptor (e.g., transferrin receptor 1) and complexes comprising the antibody covalently linked to a molecular payload. Methods of making and using the antibodies are also provided.

Described herein are A [beta]-targeting proteins comprising an A [beta]-binding region; a transferrin receptor (TfR) binding region that specifically binds to the TfR with an affinity of from about 900 nM to about 10,000 nM; and an Fc [gamma] R binding region. Also described are methods of making the A [beta]-targeting proteins and methods of using the A [beta]-targeting proteins in the treatment of neurodegenerative disorders.

The invention discloses a Fe-based T7 peptide targeted glioma micromolecular magnetic resonance contrast agent and a synthesis method and application thereof.The micromolecular magnetic resonance contrast agent is characterized in that one part of the micromolecular magnetic resonance contrast agent is targeted peptide, the other part of the micromolecular magnetic resonance contrast agent is an iron-coordinated pyridine ring contrast agent, and the targeted peptide and the iron-coordinated pyridine ring contrast agent are connected through click reaction. The T7 peptide part in the micromolecule magnetic resonance contrast agent can be combined with a transferrin receptor and can be more efficiently conveyed to the brain for imaging. Compared with a traditional Gd-based contrast agent, the magnetic resonance contrast agent disclosed by the invention has higher specificity and lower toxicity, and meanwhile, the contrast agent has better stability and can be used for efficiently imaging in-situ brain glioma.

Novel peptides that bind to the human transferrin receptor (hTfR) are provided. The peptide is a peptide comprising an amino acid sequence described in Ala-Val-MePhe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-K(MePEG4c)-Arg-Phe-MeTyr-Cys (SEQ ID NO: 1), or the peptide comprising one or more predetermined substitutions in the amino acid sequence described in SEQ ID NO:1.

Provided are transferrin receptor binding VHH domains as well as delivery complexes and methods for targeting cells of interest for delivery of an active cargo such as an oligomeric agent. In particular, the delivery complex may comprise modified Fc domain and a transferrin receptor binding VHH domain.

Complexes and methods are provided for targeting cells of interest to deliver cargo such as oligomeric compounds or oligodimers. In particular, the complexes may comprise a transferrin receptor-binding moiety and a half-life-extending moiety.

The invention discloses a blood-brain barrier crossing nucleic acid drug delivery system based on glycosyl functional nucleic acid and a preparation method and application thereof, and belongs to the technical field of biomedicine. The core of the system is a glycosylated transferrin receptor aptamer (GTA), and the GTA is formed by covalently linking a glycosyl modification module and a transferrin receptor binding sequence and can be combined with therapeutic nucleic acid to form a compound. According to the invention, the blood-brain barrier crossing efficiency and brain targeting property of nucleic acid drugs are remarkably improved through a dual-channel synergistic mechanism formed by transferrin receptor mediated transfection and glucose transporter assisted uptake; the GTA can be automatically prepared through a DNA solid-phase synthesis platform, and is controllable in structure, stable in batch, high in biocompatibility and low in immunogenicity. The delivery system can be compatible with multiple nucleic acid drugs such as siRNA, ASO and CpG ODN, and has a wide application prospect in treatment of central nervous system diseases such as glioblastoma.

Provided herein are proteins comprising a monovalent human TfR binding domain ("human TfR binding proteins"), conjugates comprising such human TfR binding proteins, e.g., human TfR binding protein-dsRNA conjugates, pharmaceutical compositions comprising human TfR binding proteins or conjugates, and methods of using human TfR binding proteins or conjugates to treat CNS diseases, e.g., neurodegenerative diseases such as neurodegenerative synucleinopathies or tauopathies.

Compounds for the delivery of progranulin, a progranulin fragment, and / or at least one granulin protein subunit across the blood brain barrier. Compounds for the delivery of progranulin, a progranulin fragment, and / or at least one granulin protein subunit across the blood brain barrier, the compounds including a progranulin domain, a TfR1 binding domain, and optionally an albumin binding domain. Compounds for the delivery of wildtype or unmodified progranulin across the blood brain barrier.

The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to improved TfR-binding moieties capable of crossing the blood brain barrier (BBB) and capable of carrying and releasing cargo specifically targeted to the parenchymal tissue of the brain. The present invention relates to a transcytosis selection method to obtain VNARs against mammalian blood brain barrier (BBB) receptors using phage display libraries as well as against receptors found in other directional cell barrier systems like the gastrointestinal tract and other organs. The VNARs may be used alone or as components in compositions or as conjugates that target the particular receptor transport systems for delivery of therapeutics or diagnostics to the brain (in the case of BBB receptors) or other tissues.

Engineered transferrin receptor (TfR) binding peptides are disclosed that can be used to deliver a therapeutic agent into a cell, tissue, organ or system of an individual. Conjugates, fusions, delivery vehicles and pharmaceutical compositions including the same also are disclosed, as well as methods of using the same for treating central nervous system (CNS) diseases, disorders or conditions or for treating TfR-associated diseases, disorders or conditions.

The invention relates to compounds comprising advantageous novel aptamers and aptamer conjugates, as well as compositions comprising the same, and their use in therapy or diagnosis. In particular, disclosed herein are aptamers and aptamer conjugates that bind to the human transferrin receptor (1) (hTfRl) without competing with human transfenin (hTf) for binding to hTfRl.

The present disclosure includes engineering methods and polypeptide libraries that are useful for introducing non-native binding sites into polypeptides. Also provided herein are polypeptides that bind to a CD98hc or transferrin receptor (TfR) protein, methods of generating such polypeptides, and methods of using the polypeptides to target a composition across the blood-brain barrier or to a CD98hc-expressing or TfR-expressing cell.

The present invention relates to a transporter peptide capable of binding to a transferrin receptor. The transporter peptide can be covalently or non-covalently conjugated with an effector to form a transporter peptide conjugate, or the transporter peptide and an effector form a recombinant transporter peptide conjugate in a manner that represents a nucleic acid encoding the transporter peptide and the effector. The transporter peptide and the recombinant transporter peptide transport the effector to a target by binding to a transferrin receptor. Binding of the transporter peptide to a transferrin receptor on a cell of a tissue barrier induces transendocytosis of the cell to transport the transporter peptide conjugate through the tissue barrier. The transport peptide can be used as a drug delivery system and can be used for related treatment of central nervous system (CNS) diseases.

To provide a peptide or the like capable of passing through a blood-brain barrier (BBB) by binding to a human transferrin receptor (hTfR).SOLUTION: A peptide having the amino acid sequence set forth in SEQ ID NO: 1 (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Ser-Cys); or an amino acid sequence having a substitution, deletion, addition, and / or insertion of 1 or more and 10 or less amino acid residues in the amino acid sequence set forth in SEQ ID NO: 1.SELECTED DRAWING: Figure 2

[Problem] To provide a novel peptide that binds to human transferrin receptor (hTfR), and various uses of the novel peptide. [Solution] A peptide comprising an amino acid sequence represented by Ala-Val-MeF3C-Val-W7N-Asn-3Py6NH2-F4OMe-Ile-Ile-Arg-Arg-4Py-MeTyr-Cys (SEQ ID NO: 1), or a pharmaceutically acceptable salt thereof, a complex comprising the peptide or the pharmaceutically acceptable salt thereof and a substance that has bound to a linker, and a composition comprising the peptide or the complex, and a method for producing a pharmaceutical or diagnostic composition.

This invention discloses a Fe-based T7 peptide-targeting small-molecule magnetic resonance imaging (MRI) contrast agent for gliomas, its synthesis method, and its applications. The small-molecule MRI contrast agent comprises a targeting peptide and an iron-coordinated pyridine ring contrast agent, linked by a click reaction. The T7 peptide portion of this small-molecule MRI contrast agent can bind to transferrin receptors, allowing for more efficient delivery to the brain for imaging. Compared to traditional Gd-based contrast agents, the MRI contrast agent of this invention exhibits higher specificity and lower toxicity, while also demonstrating better stability, enabling efficient imaging of in situ gliomas.

Provided herein are Activin Receptor type 2A (ACVR2A) and Activin Receptor Type 2B (ACVR2B) RNAi agents. Also provided herein are compositions comprising the ACVR2A and / or the ACVR2B RNAi agents conjugated to human transferrin receptor (TfR) binding proteins via a linker or a direct bond. Also provided herein are methods of using ACVR2A RNAi agent(s) in separate, simultaneous, or sequential combination with ACVR2B RNAi agent(s) for treating metabolic disorders, including for example, obesity, overweight, Type 2 diabetes mellitus (T2DM), and metabolic associated steatohepatitis (MASH) in a patient

Compounds disclosed herein have been shown to bind to the transferrin receptor making them capable of crossing the blood-brain barrier (BBB) and useful for treating diseases or disorders of the brain, such as cancer, ischemic stroke, Alzheimer's disease, or Parkinson's disease.