Abstract: A strategy for site specific covalent modification of antibodies using a specialized targeting covalent heterobivalent ligand (cHBL), and corresponding design for a covalent heterobivalent inhibitor (cHBI) that can be used to prevent Immunoglobulin E (IgE) mediated allergic reactions triggered by drug molecules, according to one embodiment. These molecules contain four important components: (1) an IgE antigen binding site (ABS) ligand that can be a mimotope for the allergen protein, a small molecule, or a peptidomimetic, (2) an appropriate linker, which can be any flexible or rigid chemical linker, providing spacing between the ABS binder and the other moieties, (3) a nucleotide binding site (NBS) ligand, and (4) a reactive moiety to form a covalent link with an amino acid side chain of target IgE antibodies.

Abstract: The invention provides a strategy for site specific covalent modification of antibodies using a specialized targeting covalent heterobivalent ligand (cHBL), and corresponding design for a covalent heterobivalent inhibitor (cHBI) that can be used to prevent Immunoglobulin E (IgE) mediated allergic reactions triggered by drug molecules, according to one embodiment. These molecules contain four important components: (1) an IgE antigen binding site (ABS) ligand that can be a mimotope for the allergen protein, a small molecule, or a peptidomimetic, (2) an appropriate linker, which can be any flexible or rigid chemical linker, providing spacing between the ABS binder and the other moieties, (3) a nucleotide binding site (NBS) ligand, and (4) a reactive moiety to form a covalent link with an amino acid side chain of target IgE antibodies.

Abstract: Embodiments of the present disclosure provide a nanoparticle based platform, and nanoallergens for identifying, evaluating and studying allergen mimotopes as multiple copies of a single mimotope or various combinations on the same particle. The nanoparticle is extremely versatile and allows multivalent binding to IgEs specific to a variety of mimotopes, simulating allergen proteins. Nanoparticles can include various molecular ratios of components. For example, the nanoallergens can include about 0.1-40% mimotope-lipid conjugate and about 60-99.9% lipid. The mimotope-lipid conjugate includes a mimotope, a first linker, and lipid molecule. Nanoallergens can be used in in vitro and in vivo applications to identify a specific patient's sensitivity to a set of epitopes and predict a symptomatic clinical response, identify allergen epitopes through blind screening peptide sequences from allergen protein, and in a clinical application similar to a scratch test.

Abstract: A method of crosslinking a hetero-bifunctional photo crosslinking compound to an immunoglobulin having at least one heterocyclic photo reactive group and at least one non-photo reactive group where the non-photo reactive group is coupled to an effector molecule and the photo reactive group is coupled to the nucleotide binding site of an immunoglobulin. Alternatively, the photo crosslinker contains an orthogonal reactive group such as a thiol, which can be coupled to an effector molecule or functionalized ligand.

Abstract: A method of crosslinking a hetero-bifunctional photo crosslinking compound to an immunoglobulin having at least one heterocyclic photo reactive group and at least one non-photo reactive group where the non-photo reactive group is coupled to an effector molecule and the photo reactive group is coupled to the nucleotide binding site of an immunoglobulin. Alternatively, the photo crosslinker contains an orthogonal reactive group such as a thiol, which can be coupled to an effector molecule or functionalized ligand.

Abstract: Embodiments of the present disclosure provide a nanoparticle based platform, and nanoallergens for identifying, evaluating and studying allergen mimotopes as multiple copies of a single mimotope or various combinations on the same particle. The nanoparticle is extremely versatile and allows multivalent binding to IgEs specific to a variety of mimotopes, simulating allergen proteins. Nanoparticles can include various molecular ratios of components. For example, the nanoallergens can include about 0.1-40% mimotope-lipid conjugate and about 60-99.9% lipid. The mimotope-lipid conjugate includes a mimotope, a first linker, and lipid molecule. Nanoallergens can be used in in vitro and in vivo applications to identify a specific patient's sensitivity to a set of epitopes and predict a symptomatic clinical response, identify allergen epitopes through blind screening peptide sequences from allergen protein, and in a clinical application similar to a scratch test.

Abstract: The invention provides a strategy for site specific covalent modification of antibodies using a specialized targeting covalent heterobivalent ligand (cHBL), and corresponding design for a covalent heterobivalent inhibitor (cHBI) that can be used to prevent Immunoglobulin E (IgE) mediated allergic reactions triggered by drug molecules, according to one embodiment. These molecules contain four important components: (1) an IgE antigen binding site (ABS) ligand that can be a mimotope for the allergen protein, a small molecule, or a peptidomimetic, (2) an appropriate linker, which can be any flexible or rigid chemical linker, providing spacing between the ABS binder and the other moieties, (3) a nucleotide binding site (NBS) ligand, and (4) a reactive moiety to form a covalent link with an amino acid side chain of target IgE antibodies.

Abstract: The invention provides a strategy for site specific covalent modification of antibodies using a specialized targeting covalent heterobivalent ligand (cHBL), and corresponding design for a covalent heterobivalent inhibitor (cHBI) that can be used to prevent Immunoglobulin E (IgE) mediated allergic reactions triggered by drug molecules, according to one embodiment. These molecules contain four important components: (1) an IgE antigen binding site (ABS) ligand that can be a mimotope for the allergen protein, a small molecule, or a peptidomimetic, (2) an appropriate linker, which can be any flexible or rigid chemical linker, providing spacing between the ABS binder and the other moieties, (3) a nucleotide binding site (NBS) ligand, and (4) a reactive moiety to form a covalent link with an amino acid side chain of target IgE antibodies.

Abstract: Embodiments of the present disclosure provide a nanoparticle based platform, and nanoallergens for identifying, evaluating and studying allergen mimotopes as multiple copies of a single mimotope or various combinations on the same particle. The nanoparticle is extremely versatile and allows multivalent binding to IgEs specific to a variety of mimotopes, simulating allergen proteins. Nanoparticles can include various molecular ratios of components. For example, the nanoallergens can include about 0.1-40% mimotope-lipid conjugate and about 60-99.9% lipid. The mimotope-lipid conjugate includes a mimotope, a first linker, and lipid molecule. Nanoallergens can be used in in vitro and in vivo applications to identify a specific patient's sensitivity to a set of epitopes and predict a symptomatic clinical response, identify allergen epitopes through blind screening peptide sequences from allergen protein, and in a clinical application similar to a scratch test.

Abstract: The invention provides a strategy for site specific covalent modification of antibodies using a specialized targeting covalent heterobivalent ligand (cHBL), and corresponding design for a covalent heterobivalent inhibitor (cHBI) that can be used to prevent Immunoglobulin E (IgE) mediated allergic reactions triggered by drug molecules, according to one embodiment. These molecules contain four important components: (1) an IgE antigen binding site (ABS) ligand that can be a mimotope for the allergen protein, a small molecule, or a peptidomimetic, (2) an appropriate linker, which can be any flexible or rigid chemical linker, providing spacing between the ABS binder and the other moieties, (3) a nucleotide binding site (NBS) ligand, and (4) a reactive moiety to form a covalent link with an amino acid side chain of target IgE antibodies.

Abstract: A method of crosslinking a hetero-bifunctional photo crosslinking compound to an immunoglobulin having at least one heterocyclic photo reactive group and at least one non-photo reactive group where the non-photo reactive group is coupled to an effector molecule and the photo reactive group is coupled to the nucleotide binding site of an immunoglobulin. Alternatively, the photo crosslinker contains an orthogonal reactive group such as a thiol, which can be coupled to an effector molecule or functionalized ligand.

Abstract: The invention provides pharmaceutical compositions and method of using the compositions, wherein the compositions comprise liposomes or micelles that contain one or more targeting peptides and/or anticancer drugs. In various embodiments, the components of the liposomes can include a) a phospholipid and optionally a lipid that is not a phospholipid; b) a pegylated lipid; c) a peptide-ethylene glycol (EG)-lipid conjugate wherein the peptide is a targeting ligand, and d) one or more drug-conjugated lipid, encapsulated drugs, or a combination thereof. The peptide-EG-lipid conjugate can be, for example, a compound of Formula (I) or Formula (II). The ethylene glycol (EG) segments of the peptide-EG-lipid conjugate can be, for example, EG6 to about EG36; and the EG segment can be conjugated to one or more lysine moieties.

Abstract: Embodiments of the present disclosure provide a nanoparticle based platform, and nanoallergens for identifying, evaluating and studying allergen mimotopes as multiple copies of a single mimotope or various combinations on the same particle. The nanoparticle is extremely versatile and allows multivalent binding to IgEs specific to a variety of mimotopes, simulating allergen proteins. Nanoparticles can include various molecular ratios of components. For example, the nanoallergens can include about 0.1-40% mimotope-lipid conjugate and about 60-99.9% lipid. The mimotope-lipid conjugate includes a mimotope, a first linker, and lipid molecule. Nanoallergens can be used in in vitro and in vivo applications to identify a specific patient's sensitivity to a set of epitopes and predict a symptomatic clinical response, identify allergen epitopes through blind screening peptide sequences from allergen protein, and in a clinical application similar to a scratch test.

Abstract: The disclosure provides pharmaceutical compositions and method of using the compositions, wherein the compositions comprise liposomes that contain two or more anticancer drugs. In various embodiments the components of the liposomes can include a) a phospholipid, b) a pegylated lipid, c) an aqueous core, and d) at least one covalently-linked drug-conjugated lipid, an encapsulated drug, or a combination thereof, wherein the drug of the lipid-drug conjugate, encapsulated drug, or both, are anticancer drugs.

Abstract: Embodiments provide systems, methods, and compositions for nanoparticle-based drug delivery to target cells or tissues. A drug delivery system may include a nanoparticle with a targeting component and a therapeutic component. The nanoparticle may have a predetermined number or valence of targeting molecules for multivalent interaction with a target cell or tissue. Binding of the targeting molecules to the target cell may result in receptor-mediated uptake of the nanoparticle by the target cell. The therapeutic component may be subsequently released within an endocytic vesicle of the target cell. Nanoparticle-based drug delivery systems as described herein may provide improved efficacy and/or reduced toxicity.

Abstract: Embodiments provide systems, methods, and compositions for nanoparticle-based drug delivery to target cells or tissues. A drug delivery system may include a nanoparticle with a targeting component and a therapeutic component. The nanoparticle may have a predetermined number or valence of targeting molecules for multivalent interaction with a target cell or tissue. Binding of the targeting molecules to the target cell may result in receptor-mediated uptake of the nanoparticle by the target cell. The therapeutic component may be subsequently released within an endocytic vesicle of the target cell. Nanoparticle-based drug delivery systems as described herein may provide improved efficacy and/or reduced toxicity.

Abstract: Embodiments herein provide methods of purifying monoclonal and polyclonal anti-bodies (e.g., immunoglobulins) from biological fluids, such as cell lysates, cell supernatant and ascites fluids, using small molecule affinity chromatography. Various embodiments disclose a class of small molecules that selectively bind a nucleotide binding site that is inherent to all immunoglobulins, and in various embodiments, methods are disclosed that use one of these small molecules as a capture molecule in small molecule affinity chromatography. In some embodiments, the small molecule may be an indole, and in particular embodiments, the small molecule may be indole-3-butyric acid.

Abstract: Embodiments herein provide methods of purifying monoclonal and polyclonal antibodies (e.g., immunoglobulins) from biological fluids, such as cell lysates, cell supernatant and ascites fluids, using small molecule affinity chromatography. Various embodiments disclose a class of small molecules that selectively bind a nucleotide binding site that is inherent to all immunoglobulins, and in various embodiments, methods are disclosed that use one of these small molecules as a capture molecule in small molecule affinity chromatography. In some embodiments, the small molecule may be an indole, and in particular embodiments, the small molecule may be indole-3-butyric acid.

Abstract: The invention provides pharmaceutical compositions and method of using the compositions, wherein the compositions comprise liposomes or micelles that contain one or more targeting peptides and/or anticancer drugs. In various embodiments, the components of the liposomes can include a) a phospholipid and optionally a lipid that is not a phospholipid; b) a pegylated lipid; c) a peptide-ethylene glycol (EG)-lipid conjugate wherein the peptide is a targeting ligand, and d) one or more drug-conjugated lipid, encapsulated drugs, or a combination thereof. The peptide-EG-lipid conjugate can be, for example, a compound of Formula (I) or Formula (II). The ethylene glycol (EG) segments of the peptide-EG-lipid conjugate can be, for example, EG6 to about EG36; and the EG segment can be conjugated to one or more lysine moieties.

Abstract: The invention provides for a method of crosslinking a hetero-bifunctional photo crosslinking compound to an immunoglobulin having at least one heterocyclic photo reactive group and at least one non-photo reactive group where the non-photo reactive group is coupled to an effector molecule and the photo reactive group is coupled to the nucleotide binding site of an immunoglobulin. Alternatively, the photo crosslinker contains an orthogonal reactive group such as a thiol, which can be coupled to an effector molecule or functionalized ligand.