329 results about "Drug conjugation" patented technology

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -LD-D, the protein based recognition-molecule being connected to the polymeric carrier by LP. Each occurrence of D is independently a therapeutic agent having a molecular weight≦5 kDa. LD and LP are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

Disclosed are anti-CD70 antibodies and derivatives thereof conjugated to cytotoxic, immunosuppressive, or other therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody- and antibody derivative-drug conjugates. Also disclosed are methods, for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the disclosed pharmaceutical compositions.

The present invention relates to methods and compositions for the treatment of CD20-expressing cancers and immune disorders involving CD20-expressing cells. The present methods comprise administering to a subject an anti CD20 antibody-drug conjugate that has a high potency and / or is capable of internalizing into CD20-expressing cells. The present invention further provides pharmaceutical compositions and kits comprising such conjugates. The present invention yet further provides methods of and compositions relating to combination therapy of cancer and immune disorders involving CD20-expressing cells using the anti-CD20 antibody-drug conjugates of the invention.

The invention provides a liquid composition and a lyophilized composition comprising a therapeutically effective amount of a conjugate comprising an antibody chemically coupled to a maytansinoid. The invention further provides a method for killing a cell in a human comprising administering to the human either of the compositions such that the antibody binds to the surface of the cell and the cytotoxicity of the maytansinoid is activated, whereby the cell is killed.

This invention discloses compositions of chloroquine-coupled active agents such as therapeutic antibodies or insulin, including methods for their preparation. The prior art has shown that chloroquines given as free drug in high enough concentration, enhances the release of various agents from cellular endosomes into the cytoplasm. The purpose of these compositions is to provide a controlled amount of chloroquine at the same site where the drug is delivered, thereby reducing the overall dosage needed. The compositions comprise a chloroquine substance coupled to a drug directly or through a variety of pharmaceutical carrier substances. The carrier substances include polysaccharides, synthetic polymers, proteins, micelles and other substances for carrying and releasing the chloroquine compositions in the body for therapeutic effect. The compositions can also include a biocleavable linkage for carrying and releasing the drug for therapeutic or other medical uses. The invention also discloses carrier compositions that are coupled to targeting molecules for targeting the delivery of chloroquine substances and antibody or insulin to their site of action.

Chimeric and humanized anti-5T4 antibodies and antibody / drug conjugates and methods for preparing and using the same.

Disclosed are anti-CD70 antibodies and derivatives thereof conjugated to cytotoxic, immunosuppressive, or other therapeutic agents, as well as pharmaceutical compositions and kits comprising the antibody- and antibody derivative-drug conjugates. Also disclosed are methods, for the treatment of CD70-expressing cancers and immunological disorders, comprising administering to a subject the disclosed pharmaceutical compositions.

Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

A polymeric scaffold useful for conjugating with a protein based recognition-molecule (PBRM) to form a PBRM-polymer-drug conjugate is described herein. The scaffold includes one or more terminal maleimido groups. Also disclosed is a PBRM-polymer-drug conjugate prepared from the scaffold. Compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions are also described.

A drug conjugate is provided herein. The conjugate comprises a protein based recognition-molecule (PBRM) and a polymeric carrier substituted with one or more -LD-D, the protein based recognition-molecule being connected to the polymeric carrier by LP. Each occurrence of D is independently a therapeutic agent having a molecular weight ≦5 kDa. LD and LP are linkers connecting the therapeutic agent and PBRM to the polymeric carrier respectively. Also disclosed are polymeric scaffolds useful for conjugating with a PBRM to form a polymer-drug-PBRM conjugate described herein, compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

The present invention provides Ligand-Drug Conjugates comprising a PEG Unit in a parallel orientation to the Drug Unit. The invention provides inter alia, Ligand-Drug Conjugates (LDCs), methods of preparing and using them, and intermediates thereof. The Ligand-Drug Conjugates are stable in circulation, yet capable of inflicting cell death on targeted cells or inhibiting proliferation of targeted cells once its drug cargo is released in the vicinity or within targeted cells. In principle embodiments, an LDC of the present invention is represented by the structure of Formula I.

The invention relates to conjugates that bind to targets, methods of using conjugates that bind to targets and methods of treating undesirable or aberrant cell proliferation or hyperproliferative disorders, such as tumors, cancers, neoplasia and malignancies that express a target.

The present invention is directed to antibodies, and antigen-binding portions thereof, engineered to introduce amino acids for site-specific conjugation. The invention relates to engineered antibody constant region (Fc, Cγ, Cκ, and Cλ) polypeptides, and portions thereof, and antibodies comprising the polypeptides. Further, the invention relates to Fc fusion proteins comprising an engineered Fc region. The invention also relates to methods and uses of the engineered antibodies and portions for, among other things, production of antibody-drug conjugate therapeutics.

The present invention provides Lig-and-Drug Conjugates and Drug-Linker Compounds comprising a methylene carbamate unit. The invention provides inter alia, Ligand-Drug Conjugates, wherein the Ligand-Drug Conjugate is comprised of a Self-immolative Assembly Unit having a methylene carbamate unit for conjugation of a drug to a targeting ligand, methods of preparing and using them, and intermediates thereof. The Ligand-Drug Conjugates of the present invention are stable in circulation, yet capable of inflicting cell death once free drug is released from a Conjugate in the vicinity or within tumor cells.

The present invention provides folate receptor binding ligand‐drug delivery conjugates having the formula (F) nL1L2D. The conjugates have high affinity to folate receptor‐positive tumor cells and low toxicity for normal cells. The present invention also relates to preparation methods for such conjugates, pharmaceutical compositions comprising such conjugates, and use of such conjugates for preparing anti‐tumor medicaments.

Antibody-cytotoxin antibody-drug conjugates and related compounds, such as linker-cytotoxin conjugates and the linkers used to make them, tubulysin analogs, and intermediates in their synthesis; compositions; and methods, including methods of treating cancers.

The present disclosure provides anti-CD73 binding molecules, e.g., antibodies and antigen binding fragments thereof. Also provided are pharmaceutical formulations comprising the disclosed compositions, and methods for the diagnosis and treatment of diseases associated with CD73-expression, e.g., cancer. Such diseases can be treated, e.g., by direct therapy with the anti-CD73 binding molecules disclosed herein (e.g., naked antibodies or antibody-drug conjugates that bind CD73), by adjuvant therapy with other antigen-binding anticancer agents such as immune checkpoint inhibitors (e.g., anti-CTLA-4 and anti-PD-1 monoclonal antibodies), and / or by combination therapies where the anti-CD73 molecules are administered before, after, or concurrently with chemotherapy.

The invention relates to a Prodrug activation method, for therapeutics, wherein use is made of abiotic reactive chemical groups that exhibit bio-orthogonal reactivity towards each other. The invention also relates to a Prodrug kit comprising at least one Prodrug and at least one Activator, wherein the Prodrug comprises a Drug and a first Bio-orthogonal Reactive Group (the Trigger), and wherein the Activator comprises a second Bio-orthogonal Reactive Group. The invention also relates to targeted therapeutics used in the above-mentioned method and kit. The invention particularly pertains to antibody-drug conjugates and to bi- and trispecific antibody derivatives.

The present invention relates to, inter alia, extracellular drug conjugates (EDC) in which an antibody or other targeting agent (e.g. a targeting moiety) is linked to a drug through a linker (e.g. a non-cleavable linker). These conjugates are useful in the treatment of disease and / or as a tool in the evaluation of biological systems.

The present invention relates to antibody-drug conjugate compounds of Formula I:Ab-(L-D)p  Iwhere one or more nemorubicin metabolite or analog drug moieties (D) are covalently attached by a linker (L) to an antibody (Ab) which binds to one or more tumor-associated antigens or cell-surface receptors. These compounds may be useful in methods of diagnosis or treatment of cancer, and other diseases and disorders.

Among other aspects, provided herein is a mixed-acid salt of a water-soluble polymer-drug conjugate, along with related methods of making and using the same. The mixed-salt acid salt is stably formed, and appears to be more resistant to hydrolytic degradation than the corresponding predominantly pure acid salt or free base forms of the polymer-drug conjugate. The mixed acid salt is reproducibly prepared and recovered, and provides surprising advantages over non-mixed acid salt forms of the water-soluble polymer drug conjugate.

The invention relates to a biological nanometer magnetic target anti-cancer drug, which is formed by coupled biological nanometer magnetic smalls and anti-cancer chemical drug. Wherein, the biological nanometer magnetic small is nanometer magnetic particle formed in magnetic bacterial cell, at 35-120nm diameter, while its main component is Fe3O4 or Fe3S4; single magnetic particle is packed by film; and the coupled anti-cancer chemical drug comprises chemotherapy drug, nucleic acid drug, radioactive nuclide or antibody drug. The invention also provides relative production that using physical adsorption couple or based on the active function group contained by smalls and anti-cancer drug, to select right coupler via chemical reaction to couple them. And the smalls has better bioavailability, less side effect, therefore, the anti-cancer drug can be accurately transmitted to ill part via external magnetic field, to reduce the contact between drug and normal organism., to realize target positioning treatment.

The present invention relates to the use of about 2 to about 8 drug molecules, for example, maytansinoid, per cell binding agent, such as an antibody, and maximal efficacy as compared to a drug load of lesser or higher number of drugs linked to such a cell binding agent.

Linkers for binding drugs to cell binding agents are modified to hydrophilic linkers by incorporating a polyethylene glycol spacer. The potency or the efficacy of the cell-binding agent-drug conjugates is surprisingly enhanced several folds in a variety of cancer cell types, including those expressing a low number of antigens on the cell surface or cancer cells that are resistant to treatment. A method for preparing maytansinoids bearing a thioether moiety and a reactive group which allows the maytansinoid to be linked to a cell-binding agent in essentially a single step is also provided.

The present invention concerns compositions and methods of use of a humanized Class III anti-CEA antibody, comprising the heavy and light amino acid sequences SEQ ID NO:1 and SEQ ID NO:2. The antibody is effective to treat CEACAM5-expressing tumors, either alone or in combination with one or more therapeutic agents. Drug conjugated Class III anti-CEA antibodies, such as SN-38 or P2PDox immunoconjugates, are particularly efficacious. Surprisingly, the antibody-drug conjugates (ADCs) exhibit high anti-cancer efficacy, while exhibiting low levels of systemic toxicity that are readily treated with standard amelioration techniques. Antibodies and / or immunoconjugates comprising the amino acid sequences SEQ ID NO:1 and SEQ ID NO:2 are surprisingly efficacious for therapy of solid tumors, even when the tumor has proven resistant to standard anti-cancer therapies.

The invention discloses a poloxamer-carboxylic acid drug conjugate and a preparation method and application thereof. The conjugate is formed by directly linking the carboxyl of the carboxylic acid drug with the carboxyl of the poloxamer by the ester bond in the presence of a catalyst. The conjugate is the compound in the general formula (i) or (ii). Compared with the original carboxylic acid drugs, the conjugate has greatly improved drug solubility, enhanced pharmacological effects, reduced adverse reaction and higher safety. By utilizing the hydrophobic carboxylic acid drug, the conjugate can enhance the hydrophobicity of the poloxamer and greatly improve the amphipathy of the poloxamer, thus being capable of forming stable micellar structure under waterborne environment. As the drug carrier, the conjugate can complete further encapsulation of the drugs and can meet different release requirements by controlling the chemical grafted amount and the physical encapsulation amount or realize combined therapy of the drugs by physically embedding other pharmaceutically active drugs. The invention has simple preparation method, mature process and high yield and is suitable for industrialproduction.

Sulfonamide-containing linkage systems for release of payload compounds from an attached targeting moiety in drug conjugates. The conjugates have the formula of [(P)-(L)]m-(T), wherein (P) is a payload compound, (L) is a linker, (T) is a targeting moiety and m is an integer from 1- to 10. Also provided are pharmaceutical compositions comprising such conjugates and there use in treating cancer.

The invention discloses a multi-branch-chain drug conjugate with the following structural formula (I) as shown in description or a pharmacologically acceptable salt thereof, wherein R is an organic center, POLY is polymer, L is a multivalent joint, T is a targeted molecule, D is an activator, q is any integer from 3 to 8, L is as shown in the description, * is a connecting point for the multivalent joint L and the targeted molecule T, # is a connecting point for the multivalent joint L and the activator D, % is a connecting point for the multivalent joint L and POLY, l is any integer from 2 to20, m and n are any integer from 0 to 10, T is iRGD, cRGD, tLyp-1, Lyp-1 or RPARPAR, and D is a camptothecin drug. Compared with a small-molecule anti-cancer compound, the conjugate has stronger inhibiting ability in tumors, and is suitable for solid tumor types which comprise colon cancer, breast cancer, ovarian cancer, pancreatic cancer, gastric cancer, glioma as well as sarcoma, cancers and lymphoma of breasts, ovaries, colons, kidneys, bile ducts, lungs and brains.

The present invention describes small molecule ligand-drug conjugates and methods of using the small molecule ligand-drug conjugates for targeted treatment of cancer in a patient in need thereof. Further described are methods of sterilizing circulating tumor cells and determining drug concentration in cancer tissue.

The present invention discloses an antibody drug conjugate of a CLDN 18.2-resistant antibody. The structure of the antibody drug conjugate (ADC) is shown as Ab-[(L2)n-L1-D]y in a formula I, wherein Dis a small-molecule cytotoxic drug, L1 and L2 are connected to the drug and the antibody separately, and n is 0 or 1; y represents the average number of D which is coupled to Ab, 0 < y <= 10, and Ab is an antibody which can be specifically bound to human CLDN 18.2, and includes a light-chain variable region (VL) and / or a heavy-chain variable region (VH); and the CLDN 18.2-resistant antibody correspondingly contains at least one specific complementary determining region (CDR) sequence or a mutant sequence of the specific complementary determining region (CDR) sequence in the light-chain variable region (VL) and / or a heavy-chain variable region (VH), and binding of the antibody to CLDN 18.2 is maintained or improved through the mutation. The invention also discloses a ADC-containing pharmaceutical composition and a preparation method and application of ADC. The antibody drug conjugate of the antibody has a large security window and low toxic and side effects, and provides more specific,more effective and better treatment option for tumor patients.