175 results about "Cell binding" patented technology

The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.

Disclosed is a method of making conjugates of cell binding agents and small molecule drugs comprising reacting a cell binding agent with a bifunctional cross-linking moiety to thereby provide the cell binding agent with a reactive disulfide group and then reacting the modified cell binding agent with a small molecule drug comprising a free thiol group. Bifunctional cross-linking moieties are also disclosed.

Charged or pro-charged cross-linking moieties and conjugates of cell binding agents and drugs comprising the charged or pro-charged cross-linking moieties and method of making the same.

The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

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.

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.

Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5, and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.

This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues

The present invention involves the fabrication and use of biocompatible polymers that are injected percutaneously into the inner portion of a defective region of a spinal disc and swell or expand or subsequently cure in situ to form a disc nucleus prosthesis. The polymers may be synthetic or natural (e.g., collagen), and may be provided in forms including, but not limited to hydrogels, compressible foams, cords, balloons, etc. Subsequent to injection into a target space or void within the disc, one or more cell binding agents, growth factors, and / or drugs on or within the cured polymer then interact with the remaining portion of the disc to support tissue ingrowth and to achieve a higher probability of biological mimicking.

Methods and compositions for the development of effective cancer therapies using mitotic inhibitors which have limited general toxicity to normal, non-cancerous cells and tissues are provided. The methods and compositions utilize cytotoxic compounds comprised of a cell-binding agent (e.g., antibodies) conjugated to an anti-mitotic compound (e.g., maytansinoids). The invention further provides antibodies which are substantially incapable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC) and / or complement dependent cytotoxicity (CDC), thereby ensuring that the therapeutic effect is mediated primarily by the anti-mitotic component of the cytotoxic compound, rather than by indirect cell killing via ADCC and / or CDC. The antibodies of the invention further are capable of differentiating between polypeptide antigens which are more highly expressed on proliferating cancer cells as compared to proliferating non-cancer cells.

The present invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising contacting a cell population or tissue suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate, wherein one or more maytansinoids is covalently linked to the cell-binding agent via a non-cleavable linker and the cell-binding agent binds to cells of the selected cell population.

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.

Implantable materials having defined patterns of affinity regions for binding endothelial cells and providing for directed endothelial cell migration across the surface of the material. The affinity regions include photochemically altered regions of a material surface and physical members patterned on the material surface that exhibit a greater affinity for endothelial cell binding and migration than the remaining regions of the material surface.

A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

The invention concerns a cell support comprising an RGD-enriched gelatine that has a more even distribution of RGD sequences than occurring in a natural gelatine and with a minimum level of RGD sequences. More precise the percentage of RGD sequences related to the total number of amino acids is at least 0.4 and if the RGD-enriched gelatine comprises 350 amino acids or more, each stretch of 350 amino acids contains at least one RGD motif. Preferably the RGD-enriched gelatines are prepared by recombinant technology, and have a sequence that is derived from a human gelatine or collagen amino acid sequence. The invention also relates to RGD-enriched gelatines that are used for attachment to integrins. In particular The RGD-enriched gelatines of the invention are suitable for coating a cell culture support for growing anchordependant cell types. Further, the RGD-enriched gelatines of the invention may find use in medical applications, in particular as a coating on implant or transplant material or as a component of drug delivery systems.

The present invention relates to the compositions, methods, and applications of a new approach to pattern recognition based targeting by which an exponential amplification of effector response can be specifically obtained at a targeted cells. The purpose of this invention is to enable the selective delivery of large quantities of an array of effector molecules to target cells for diagnostic or therapeutic purposes. The invention is comprised of two components designated as “Compound 1” and “Compound 2”: Compound 1 is comprised of a cell binding agent and a masked female adaptor. Compound 2 is comprised of a male ligand, an effector agent, and two or more masked female receptors. The male ligand is selected to bind with high affinity to the female adaptor. Compound 1 can bind with high affinity to the target cell and the female receptor can then be unmasked by an enzyme enriched at the tumor cell. The male ligand of Compound 2 can then bind to the unmasked female adaptor bound to the target cell. The masked female adaptor on the bound Compound 2 can then be specifically unmasked. One receptor has in effect become two. Two new molecules of Compound 2 can bind to the unmasked adaptors receptors. After unmasking two receptors in effect become four. The process can continue in an explosive exponential like fashion resulting in enormous amplification of the number of effector molecules specifically deposited at the target cell.

The present application relates to compositions of modified diphtheria toxin and fusion proteins containing modified diphtheria toxin that reduce binding to vascular endothelium or vascular endothelial cells, and therefore, reduce the incidence of Vascular Leak Syndrome, as well as methods of making the compositions. The present application also relates to a polypeptide toxophore from a modified diphtheria toxin, where the modification is at least one amino acid residue at the amino acid residues 6-8, 28-30 or 289-291 of an unmodified native diphtheria toxin. Also described are fusion proteins which contain a modified diphtheria toxin and a non-diphtheria toxin fragment which contains a cell binding portion. The modified diphtheria toxins described can be used for the treatment of a malignant disease or a non-malignant disease.

The present invention relates to chimeric chemical compounds which are used to recruit antibodies to cancer cells, in particular, prostate cancer cells or metastasized prostate cancer cells. The compounds according to the present invention comprise an antibody binding terminus (ABT) moiety covalently bonded to a cell binding terminus (CBT) through a linker and optionally, a connector molecule.

The invention relates to novel cytotoxic agents comprising taxanes and their therapeutic use as a result of delivering the taxanes to a specific cell population in a targeted fashion by chemically linking the taxane to a cell binding agent.

A method is described for treating a specimen of semen containing sperm cells to increase the relative number of sperm cells of a desired sex type in a treated specimen to increase the potential for conceiving an offspring of the desired sex. A specimen of semen is treated after a predetermined time to increase the relative ability of a at least a portion of the semen to conceive an offspring of the desired sex. The treatment preferably comprises contacting the sperm cells with an agent that preferentially effects sperm cells of a selected sex type. In some preferred embodiments, the semen is separated into two components. A first component has a higher number of sperm of the desired sex type than sperm of a non desired sex type and a second component has a higher number of sperm of the non desired sex type relative to sperm of the desired sex type. In one embodiment, the separating step is performed after a predetermined percent of the sperm cells exhibit a punctate pattern, which is capable of determination by labeling the sperm cells with Koo antibody and determining the percent of cells labeled. In another embodiment, the separating step is performed after waiting for a time determined by locating a maximum in the curve obtained by plotting percent female cells determined by FISH against percent Koo positive cells, determining the time at which the maximum percent female cells occurs, and beginning the following step no earlier than about one hour before the time of the maximum percent female cells. In yet another embodiment, the separating step is performed after waiting for a period of time between about 2 hours and about 24 hours after collection of the ejaculate. Preferably, in the separating step, the sperm is contacted with a cell binding agent, permitting the sperm of the non desired sex type to preferentially bind to the cell binding agent, and the cell binding agent with preferentially bound sperm of the non desired sex type is separated from non bound sperm.

This invention provides method of making and using of a porous 3 dimensional cyclic RGD peptide-modified alginate scaffold that can be loaded with different cell types and / or growth factors for implantation at sites of tissue damage to promote tissue regeneration. The cyclic RGD peptide promotes vascular formation of the host tissue, cell binding and survival of seeded cells. Scaffolds with growth factors but without cells can also be implanted to create a vascular bed in which cells are transplanted at a later time point.

Antibodies, humanized antibodies, resurfaced antibodies, antibody fragments, derivatized antibodies, and conjugates of same with cytotoxic agents, which specifically bind to CD38, are capable of killing CD38+ cells by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and / or complement-dependent cytotoxicity (CDC). Said antibodies and fragments thereof may be used in the treatment of tumors that express CD38 protein, such as multiple myeloma, chronic lymphocytic leukemia, chronic myelogenous leukemia, acute myelogenous leukemia, or acute lymphocytic leukemia, or the treatment of autoimmune and inflammatory diseases such as systemic lupus, rheumatoid arthritis, multiple sclerosis, erythematosus, and asthma. Said derivatized antibodies may be used in the diagnosis and imaging of tumors that express elevated levels of CD38. Also provided are cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CD38 protein.

The invention discloses a method for targeting maytansinoids to a selected cell population, the method comprising: contacting a cell population suspected of containing the selected cell population with a cell-binding agent maytansinoid conjugate or tissue, wherein one or more maytansinoids are covalently linked to the cell-binding agent through a non-cleavable linker, and the cell-binding agent binds cells in a selected cell population.

Bioerodable devices such as stents containing one or more endothelial cell binding agents are provided.

A method is disclosed for increasing the efficiency of retroviral mediated gene transfer into viable target cells, which comprises transducing the target cells by infecting the target cells with a replication defective recombinant retrovirus that infects the target cells in an aqueous medium in the presence of(a) a mixture of an effective amount of a first functional material having a retrovirus binding domain that binds said retrovirus, and an effective amount of a second functional material having a target cell binding domain that binds said target cell, or(b) an effective amount of a bifunctional material having both a retroviral binding domain which does not contain the heparin binding domain derived from human fibronectin, and a target cell binding domain, wherein the bifunctional material has a retrovirus binding domain that binds to said retrovirus and a target cell binding domain that binds to the target cell.

The invention provides processes for manufacturing cell-binding agent-cytotoxic agent conjugates of improved stability comprising performing the modification reaction at a high pH. The inventive processes comprise contacting a cell-binding agent with a bifunctional crosslinking reagent in a solution having a pH of 7.1 to 9 to covalently attach a linker to the cell-binding agent and thereby prepare a mixture comprising cell-binding agents having linkers bound thereto.

Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.

The present invention is related to novel cytotoxic agents, pyrrolo[2,1-c][1,4]benzodiazepine (PBD) derivatives, their conjugates with a cell-binding agent, the preparation and the therapeutic uses in the targeted treatment of cancers, autoimmune disorders, and infectious diseases.