1736 results about "Covalent modifier" patented technology

A codrug composition of at least two drug compounds covalently linked to one another via a labile bond to form a single codrug composition, or ionically linked to one another to form a single workings composition, and methods of use of the codrug for the treatment of various medical conditions. The codrug may be administered by itself or in the form of a bioerodible or nonbioerodible substance.

This invention relates to novel pharmaceutically useful compositions that bind to a biological molecule, having improved circulatory half-life, increased avidity, increased affinity, or multifunctionality, and methods of use thereof. The present invention provides a pseudo-antibody comprising an organic moiety covalenty coupled to at least two target-binding moieties, wherein the target-binding moieties are selected from the group consisting of a protein, a peptide, a peptidomimetic, and a non-peptide molecule that binds to a specific targeted biological molecule. The pseudo-antibody of the present invention may affect a specific ligand in vitro, in situ and/or in vivo. The pseudo-antibodies of the present invention can be used to measure or effect in an cell, tissue, organ or animal (including humans), to diagnose, monitor, modulate, treat, alleviate, help prevent the incidence of, or reduce the symptoms of, at least one condition.

This invention provides methods for covalently affixing a biomolecule to either a second molecule or a solid surface using 1,3-dipolar cycloaddition chemistry. This invention also provides related methods and compositions.

The invention provides a process for preparing a conjugate comprising a cell binding agent chemically coupled to a drug. The process comprises covalently attaching a linker to a cell binding agent, which then is conjugated to a drug, as well as purification and holding steps, and optionally a tangential flow filtration (TFF) step.

This invention relates to polymeric nanoparticles useful for drug delivery with target molecules bonded to the surface of the particles and having sizes of up to 1000 nm, preferably 1 nm to 400 nm, more preferably 1 nm to 200 nm, that are dispersed homogeneously in aqueous solution. The target drug/target substance is covalently bonded to the novel polymeric nanoparticles to secure them from outer intervention in vivo or cell culture in vitro until they are exposed at the target site within the cell. This invention also relates to microemulsion polymerization techniques useful for preparing the novel nanoparticles.

The invention relates to antibody drug conjugate (ADC) compounds represented by Formula I:

Ab-(L-D)_p  I

where one or more 1,8 bis-naphthalimide drug moieties (D) having Formulas IIa and IIb are covalently linked by a linker (L) to an antibody (Ab). The invention also relates to pharmaceutical compositions comprising an effective amount of a Formula I ADC for treatment of hyperproliferative disorders and other disorders. The invention also relates to methods for killing or inhibiting the multiplication of a tumor cell or cancer cell including administering to a patient an effective amount of a Formula I ADC.

Asymmetric bifunctional silyl (ABS) monomers comprising covalently linked pharmaceutical, chemical and biological agents are described. These agents can also be covalently bound via the silyl group to delivery vehicles for delivering the agents to desired targets or areas. Also described are delivery vehicles which contain ABS monomers comprising covalently linked agents and to vehicles that are covalently linked to the ABS monomers. The silyl modifications described herein can modify properties of the agents and vehicles, thereby providing desired solubility, stability, hydrophobicity and targeting.

The present invention provides polypeptide conjugates wherein a modifying group such as a water-soluble polymer, a therapeutic agent or a biomolecule is covalently linked to the polypeptide through a glycosyl linking group. In one embodiment, the polypeptide includes a glycosylation consensus sequence, wherein glycosylation occurs at an aromatic amino acid residue, such as the C-2 or the N-1 position of a tryptophan side chain. Exemplary polypeptides of the invention are those in which the glycosylation consensus sequence has been introduced into the amino acid sequence of the polypeptide by mutation. In another aspect the invention provides polypeptide conjugates wherein the modifying group is covalently linked to the polypeptide via a glycosyl mimetic linking group. Also provided are methods of making and using as well as pharmaceutical compositions containing the polypeptide conjugates of the invention. Further provided are methods of treating, ameliorating or preventing diseases in mammals by administering an amount of a polypeptide conjugate of the invention sufficient to achieve the desired response.

A composition and an associated method for hepatic targeted delivery of thyroid receptor beta1 (TRβ1) agonist to a liver of a subject. The composition includes hydrophobic nanoparticles, a liver targeting moiety exterior to each nanoparticle and covalently bonded to each nanoparticle, and at least one TRβ1 agonist encapsulated within each nanoparticle. The nanoparticles include chitosan hybrid nanoparticles, amine-modified PLGA nanoparticles, solid lipid nanoparticles, and combinations thereof. The liver targeting moiety includes Glycyrrhetinic acid (GA), Lactobionic acid (LA), or combinations thereof.

The invention provides processes for preparing a cell-binding agent chemically coupled to a drug. A first process comprises covalently attaching a linker to a cell-binding agent, an optional purification step, conjugating a drug to the cell-binding agent, a subsequent purification step, and optional holding steps. A second process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent, a subsequent purification step, holding steps, and optionally a tangential flow filtration (TFF) step.

The invention provides processes for manufacturing cell-binding agent-cytotoxic agent conjugates of improved homogeneity comprising performing the modification reaction at a lower temperature. The inventive processes comprise contacting a cell-binding agent with a bifunctional crosslinking reagent at a temperature of about 15° C. or less to covalently attach a linker to the cell-binding agent and thereby prepare a mixture comprising cell-binding agents having linkers bound thereto.

Coupling reactions, suitable for use in organic or aqueous media, are performed by contacting a 1,2,4,5-tetrazine with a dienophile. The dienophile may be covalently bonded to a protein, and the coupling reaction may be performed in biological media such as those containing cells or cell lysates. The reactions may be performed in the presence of primary amines, thiols, acetylenes, azides, phosphines, and products of Staudinger and/or Sharpless-Huisgen reactions Novel 3-substituted cyclopropene compounds and trans-cyclooctenes are exemplary dienophiles for these reactions.

The invention relates to nucleic acids covalently coupled to electrodes via conductive oligomers. More particularly, the invention is directed to the site-selective modification of nucleic acids with electron transfer moieties and electrodes to produce a new class of biomaterials, and to methods of making and using them.

The invention provides a process for preparing a cell-binding agent chemically coupled to a drug. The process comprises covalently attaching a linker to a cell-binding agent, a purification step, conjugating a drug to the cell-binding agent and a subsequent purification step.

An organometallic complex having formula (I)

• • wherein M is a transition metal; each A¹ and A² is independently a monodentate ligand, or A¹ and A² are covalently joined together to form a bidentate ligand; R¹ is H, C_1-18 alkyl, C_1-18 alkoxy, C_3-18 heteroalkyl, C_3-20 aryl, C_3-20 heteroaryl, or C_3-20 cycloalkyl; R² is the same or different and is H, C_1-18 alkyl, C_1-18 alkoxy, C_3-18 heteroalkyl, C_3-20 aryl, C_3-20 heteroaryl, or C_3-20 cycloalkyl, or two R² groups link together with the carbon atoms to which they are attached to form a 4- to 12-member aromatic or heteroaromatic ring; R³ is the same or different and is H, CN, tricyanovinyl, halogen, CX₃, C_1-18 alkyl, C_1-18 alkoxy, C_3-18 heteroalkyl, C_3-20 aryl, C_3-20 heteroaryl, or C_3-20 cycloalkyl, wherein X is halogen; m is the charge of M; n is 1, 2, or 3.

Novel site-specific mono-conjugates of Granulocyte Colony Stimulating Factor (G-CSF) are hereby described, with analogues and derivatives thereof, which stimulate proliferation and differentiation of progenitor cells to mature neutrophiles. These conjugates have been obtained using transglutaminase to covalently and site-specifically bind a hydrophilic, non-immunogenic polymer to a single glutamine residue of the human G-CSF native sequence and analogues thereof. These novel site-specific mono-conjugated derivatives are recommended for therapeutic use since they are stable in solution and exhibit significant biological activity in vitro and a longer bloodstream half-life, as compared to the non-conjugated protein, with a consequent prolonged pharmacological activity.

The present invention provides labeling reagents and methods for labeling primary antibodies and for detecting a target in a sample using an immuno-labeled complex that comprises a target-binding antibody and one or more labeling reagents. The labeling reagents comprise monovalent antibody fragments or non-antibody monomeric proteins whereby the labeling proteins have affinity for a specific region of the target-binding antibody and are covalently attached to a label. Typically, the labeling reagent is an anti-Fc Fab or Fab′ fragment that was generated by immunizing a goat or rabbit with the Fc fragment of an antibody. The present invention provides for discrete subsets of labeling reagent and immuno-labeled complexes that facilitate the simultaneous detection of multiple targets in a sample wherein the immuno-labeled complexes are distinguished by i) a ratio of label to labeling reagent, or ii) a physical property of said label, or iii) a ratio of labeling reagent to said target-binding antibody, or iv) by said target-binding antibody. This is particularly useful for fluorophore labels that can be attached to labeling reagents and subsequently immuno-labeled complexes in ratios for the detection of multiple targets.

Abstract of Disclosure The invention relates to compounds for topically influencing the activity of dipeptidyl peptidase of the general formula wherein A is an amino acid having at least one functional group in the side chain;B is a chemical compound covalently bound to a functional group of the side chain of A, chosen from the group consisting of (a) oligopeptides having a chain length of up to 20 amino acids, (b) homopolymers of glycine consisting of up to 6 glycine monomers, and (c) polyethylene glycols having molar masses of up to 20 000 g/mol; and C is a group amide-bonded to A chosen from the group consisting of thiazolidine, pyrrolidine, cyanopyrrolidine, hydroxyproline, dehydroproline or piperidine. The invention further relates to the use of said compounds for targeted intervention in local immunological processes (chemotaxis, inflammatory processes, autoimmune diseases), as well as effective and targeted treatment of pathophysiological and physiological processes related thereto (psoriasis, periodontitis, arthritis, allergies, inflammation), inter alia.

The present invention provides compositions, methods, and kits for covalently linking nucleic acid molecules. The methods include a strand invasion step, and the compositions and kits are useful for performing such methods. For example, a method of covalently linking double stranded (ds) nucleic acid molecules can include contacting a first ds nucleic acid molecule, which has a topoisomerase linked to a 3' terminus of one end and has a single stranded 5' overhang at the same end, with a second ds nucleic acid molecule having a blunt end, such that the 5' overhang can hybridize to a complementary sequence of the blunt end of the second nucleic acid molecule, and the topoisomerase can covalently link the ds nucleic acid molecules. The methods are simpler and more efficient than previous methods for covalently linking nucleic acid sequences, and the compositions and kits facilitate practicing the methods, including methods of directionally linking two or more ds nucleic acid molecules.