Patent classifications
C07K17/06
Multivalent antibody complexes targeting IGF-1R show potent toxicity against solid tumors
The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK (DNL) (complex produced by binding interaction between anchor domain moiety of A-kinase anchoring protein and dimerization and docking domain moiety of protein kinase A regulatory subunit) complex. Preferably, the DNL (complex produced by binding interaction between anchor domain moiety of A-kinase anchoring protein and dimerization and docking domain moiety of protein kinase A regulatory subunit) complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.
Enhanced targeting platform
A platform technology provides particle and nucleic acid conjugates, and compositions thereof, with enhanced targeting to cells, tissues, organs. The particles and nucleic acids and other deliverables contain a synthetic binding protein such as a polypeptide monobody covalently conjugated to the surface of the particle or the nucleic acid, for linking a targeting agent to the particle's surface or the nucleic acid. The particles and nucleic acids and other deliverables optionally contain an antibody non-covalently conjugated to the binding protein, via an Fc domain of the antibody. The particles can include therapeutic agents, diagnostic agents, prophylactic agents, or a combination thereof, to be delivered to desired cells, tissues, and/or organs. The particles and nucleic acids and other deliverables can be used in a wide array of applications including, but not limited to, ex vivo perfusion of mammalian organs and in vivo disease treatment.
Photochemical activation of surfaces for attaching biomaterial
A water-soluble photo-activatable polymer including: a photo-activatable group adapted to be activated by an irradiation source and to form a covalent bond between the water-soluble photo-activatable polymer and a matrix having at least one carbon; a reactive group adapted to covalently react with a biomaterial for subsequent delivery of the biomaterial to a cell; a hydrophilic group; and a polymer precursor. A composition including a monomolecular layer of the water-soluble photo-activatable polymer and a matrix having at least one carbon, wherein the monomolecular layer is covalently attached to the matrix by a covalent bond between the photo-activatable group and the at least one carbon. The composition further includes a biomaterial having a plurality of active groups, wherein the biomaterial is covalently attached to the monomolecular layer by covalent bonding between the active groups and reactive groups. Also provided is a method for delivery of a biomaterial to a cell.
Photochemical activation of surfaces for attaching biomaterial
A water-soluble photo-activatable polymer including: a photo-activatable group adapted to be activated by an irradiation source and to form a covalent bond between the water-soluble photo-activatable polymer and a matrix having at least one carbon; a reactive group adapted to covalently react with a biomaterial for subsequent delivery of the biomaterial to a cell; a hydrophilic group; and a polymer precursor. A composition including a monomolecular layer of the water-soluble photo-activatable polymer and a matrix having at least one carbon, wherein the monomolecular layer is covalently attached to the matrix by a covalent bond between the photo-activatable group and the at least one carbon. The composition further includes a biomaterial having a plurality of active groups, wherein the biomaterial is covalently attached to the monomolecular layer by covalent bonding between the active groups and reactive groups. Also provided is a method for delivery of a biomaterial to a cell.
Affinity tag system
The present invention pertains to an affinity tag system for the immobilization and/or purification of molecules such as biological or organic molecules. The invention provides EF-hand subdomains of calcium binding proteins, such as calbindin D9k, as affinity tags and affinity ligands for immobilizing, detecting and/or for purifying molecules, particularly proteins. Also provided are methods utilizing the affinity tag system of the invention, affinity matrices comprising EF-hand subdomain affinity ligands and fusion proteins comprising EF-hand subdomain affinity tags.
Affinity tag system
The present invention pertains to an affinity tag system for the immobilization and/or purification of molecules such as biological or organic molecules. The invention provides EF-hand subdomains of calcium binding proteins, such as calbindin D9k, as affinity tags and affinity ligands for immobilizing, detecting and/or for purifying molecules, particularly proteins. Also provided are methods utilizing the affinity tag system of the invention, affinity matrices comprising EF-hand subdomain affinity ligands and fusion proteins comprising EF-hand subdomain affinity tags.
LIGANDS AND METHODS OF MAKING LIGANDS FOR AFFINITY CAPTURE ON A SURFACE OF MRNA IN A SOLUTION
Separation constructs such as membranes, porous beads, etc. are modified with a plurality of oligomeric ligands. The ligands are bound to the surface of the separation substrates via linker constructs such as acrylate groups or azide groups, e.g., via Single-Electron Transfer-Living Radical Polymerization (SET-LRP). A plurality of spacer constructs, such as polyethyleneglycol (PEG) groups and hydrocarbyl groups, separate the linker constructs from oligomer constructs. The oligomer constructs can include between 5% and about 10% guanine and about 90% to about 95% thymine, and can further include between about 20 and about 60 nucleotides including at least 15 thymines and at least 1 guanine. The oligomer constructs exhibit improved binding of mRNA with oligo-dA.sub.n tails, e.g., for purification of mRNA production and commercialization, enabling fast, efficient, and continuous production of mRNA vaccines such as those against coronaviruses, e.g., SARS-CoV-2.
LIGANDS AND METHODS OF MAKING LIGANDS FOR AFFINITY CAPTURE ON A SURFACE OF MRNA IN A SOLUTION
Separation constructs such as membranes, porous beads, etc. are modified with a plurality of oligomeric ligands. The ligands are bound to the surface of the separation substrates via linker constructs such as acrylate groups or azide groups, e.g., via Single-Electron Transfer-Living Radical Polymerization (SET-LRP). A plurality of spacer constructs, such as polyethyleneglycol (PEG) groups and hydrocarbyl groups, separate the linker constructs from oligomer constructs. The oligomer constructs can include between 5% and about 10% guanine and about 90% to about 95% thymine, and can further include between about 20 and about 60 nucleotides including at least 15 thymines and at least 1 guanine. The oligomer constructs exhibit improved binding of mRNA with oligo-dA.sub.n tails, e.g., for purification of mRNA production and commercialization, enabling fast, efficient, and continuous production of mRNA vaccines such as those against coronaviruses, e.g., SARS-CoV-2.
Composition for long-acting peptide analogs
The invention describes compositions of peptide analogs that are active in blood or cleavable in blood to release an active peptide. The peptide analogs have a general formula: A-(Cm).sub.x-Peptide (SEQ ID NO: 76), wherein A is hydrophobic moiety or a metal binding moiety, e.g., a chemical group or moiety containing 1) an alkyl group having 6 to 36 carbon units, 2) a nitrilotriacetic acid group, 3) an imidiodacetic acid group, or 4) a moiety of formula (Z.sub.yHis.sub.w).sub.p (SEQ ID NO: 50), wherein Z is any amino acid residue other than histidine, His is histidine, y is an integer from 0-6; w is an integer from 1-6; and p is an integer from 1-6; wherein if A has alkyl group with 6 to 36 carbon units x is greater than 0; and Cm is a cleavable moiety consisting of glycine or alanine or lysine or arginine or N-Arginine or N-lysine, wherein x is an integer between 0-6 and N may be any amino acid or none. The peptide analogs are complexed with polymeric carrier to provide enhanced half-life.
PROTEIN ENRICHED MICROVESICLES AND METHODS OF MAKING AND USING THE SAME
Protein enriched micro-vesicles and methods of making and using the same are provided. Aspects of the methods include maintaining a cell having a membrane-associated protein comprising a first dimerization domain and a target protein having a second dimerization domain under conditions sufficient to produce a micro-vesicle from the cell, wherein the micro-vesicle includes the target protein. Also provided are cells, reagents and kits that find use in making the micro-vesicles, as well as methods of using the micro-vesicles, e.g., in research and therapeutic applications.