Abstract: Methods of detecting and assessing functionally active folate receptors on tumors and treatment associated with those tumors are described. Also described are methods of selecting ovarian and lung cancer patients for therapy with a folate-vinca conjugate by identifying functionally active folate receptors on the tumors of the patient. Also described are methods and compositions for treating folate receptor expressing epithelial tumors with a folate-vinca conjugate in combination with doxorubicin such as pegylated liposomal doxorubicin in which the tumors include ovarian, endometrial or non-small cell lung cancer tumors, including platinum-resistant ovarian tumors and platinum sensitive ovarian tumors. Also described are methods of treating platinum-resistant ovarian cancer using a folate-targeted drug, in the absence or presence of selecting the patient by identifying functionally active folate receptors on the tumors of the patient.

Abstract: Described are methods and compositions for treating epithelial tumors with a folate-vinca conjugate in combination with at least one other chemotherapeutic agent in which the tumors include ovarian, endometrial or non-small cell lung cancer tumors, including platinum-resistant ovarian tumors and platinum-sensitive ovarian tumors.

Abstract: The present invention relates to compounds, compositions, kits, and methods of use in targeting nucleotides, such as siRNA's, to cancer cells or to immune system cells involved in inflammation. More particularly, the invention is directed to receptor binding ligand-nucleotide delivery conjugates for use in specifically targeting the conjugates to cancer cells or to immune system cells, methods of treatment with these conjugates, methods of preparation of these conjugates, and methods of reducing the expression of a gene in vitro or in vivo with the conjugates described herein.

Abstract: Methods for purifying pteroic acid, analogs of pteroic acid, and derivatives of pteroic acid are described. Methods for synthesizing and purifying conjugates of vitamins, including FITC conjugates of folic acid, folic acid analogs, and derivatives of folic acid and folic acid analogs are also described. Purified forms of pteroic acid, derivatives and analogs of pteroic acid, and conjugates thereof are also described.

Abstract: Conjugates of antifolates, releasable linkers, and drugs, and pharmaceutical compositions containing them are described. The conjugates are useful for treating diseases arising from pathogenic cell populations. Methods for treating such diseases are also described.

Abstract: Described herein are compositions and methods for use in targeted drug delivery using cell receptor binding drug delivery conjugates containing hydrophilic spacer linkers for use in imaging, diagnosing, and/or treating diseases and disease states caused by pathogenic cell populations.

Abstract: The invention relates to a method of treating a host animal to eliminate pathogenic cells. The method comprises the steps of administering to the host animal a hapten-carrier conjugate, administering to the host animal a TH-I biasing adjuvant, and administering to said host animal a ligand conjugated to a hapten herein the ligand-hapten conjugate is administered during the first cycle of therapy with the hapten-carrier conjugate. The invention also relates to the same method wherein the ratio of the hapten-carrier conjugate to the TH-I biasing adjuvant on a weight to weight basis ranges from about 1:10 to about 1:1.

Abstract: Processes are described for the preparation of tubulysins. The processes are useful for preparing predetermined mixtures of tubulysins, preparing single tubulysins from mixtures of tubulysins, and for converting one tubulysin into a different tubulysin. The tubulysins described herein are useful in treating diseases and disease states that include pathogenic cell populations.

Abstract: The invention relates to a method for diagnosing a kidney disease state. The method comprises the steps of administering to a patient a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises a diagnostic marker, and diagnosing the kidney disease state. The invention also relates to a method for treating a kidney disease state. The method comprises the steps of administering to a patient suffering from the disease state an effective amount of a composition comprising a conjugate or complex of the general formula V-L-D where the group V comprises a vitamin receptor binding ligand that binds to kidney proximal tubule cells and the group D comprises an antigen, a cytotoxin, or a cell growth inhibitor, and eliminating the disease state.

Abstract: Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations. The compounds described herein include conjugates of tubulysins and vitamin receptor binding ligands. The conjugates also include a releasable bivalent linker.

Abstract: Bivalent linkers derived from compounds of formulae (V), (VI), and (VII), where X1 and X2 are leaving groups and the other variables are as defined in the claims, to be included in or for preparing vitamin, drug, diagnostic agent, and/or imaging agent conjugates are described.

Abstract: The invention relates to a method for determining a prognosis for a cancer by quantifying vitamin receptor expression on the cancer cells. The method comprises the steps of quantifying vitamin receptor expression on the cancer cells, and determining a prognosis for the cancer. The invention also relates to methods and kits for determining the presence of vitamin receptors on cancer cells to select patients that should be treated with a therapy that utilizes vitamin receptor targeting and to develop a treatment regimen for such patients. The invention further relates to kits for performing the methods.

Abstract: Described herein are compounds, pharmaceutical compositions and methods for treating pathogenic cell populations in a patient. The compounds described herein include conjugates of cytotoxic drugs and vitamin receptor binding ligands. The conjugates also include a linker that is formed from one or more spacer linkers, heteroatom linkers, and releasable linkers.

Abstract: Methods for purifying pteroic acid, analogs of pteroic acid, and derivatives of pteroic acid are described. Methods for synthesizing and purifying conjugates of vitamins, including FITC conjugates of folic acid, folic acid analogs, and derivatives of folic acid and folic acid analogs are also described. Purified forms of pteroic acid, derivatives and analogs of pteroic acid, and conjugates thereof are also described.

Abstract: Novel lipid compounds are provided that may be termed “pro-cationic” in that they are neutral or negatively charged until they are either brought into contact with cellular membranes or are internalized by cells. The lipids have a hydrophobic tail group and a hydrophilic head group, the head group incorporating both a positively and negatively charged region at physiological pH. The hydrophobic tail group is stably connected to the positive region of the head group which in turn is connected to the negative region by a disulfide bond that is susceptible to cleavage by membrane-bound and intracellular factors. Cleavage of the disulfide bond removes the negatively charged region from the head group resulting in a lipid that is cationic and therefor fusogenic with negatively charged cell membranes. Consequently, lipids of the invention are useful as components of liposomes that serve as vehicles for delivering pharmaceutical agents into cells with reduced toxicity.

Abstract: Novel lipid compounds are provided that may be termed “pro-cationic” in that they are neutral or negatively charged until they are either brought into contact with cellular membranes or are internalized by cells. The lipids have a hydrophobic tail group and a hydrophilic head group, the head group incorporating both a positively and negatively charged region at physiological pH. The hydrophobic tail group is stably connected to the positive region of the head group which in turn is connected to the negative region by a disulfide bond that is susceptible to cleavage by membrane-bound and intracellular factors. Cleavage of the disulfide bond removes the negatively charged region from the head group resulting in a lipid that is cationic and therefor fusogenic with negatively charged cell membranes. Consequently, lipids of the invention are useful as components of liposomes that serve as vehicles for delivering pharmaceutical agents into cells with reduced toxicity.

Abstract: Novel lipid compounds are provided that may be termed “pro-cationic” in that they are neutral or negatively charged until they are either brought into contact with cellular membranes or are internalized by cells. The lipids have a hydrophobic tail group and a hydrophilic head group, the head group incorporating both a positively and negatively charged region at physiological pH. The hydrophobic tail group is stably connected to the positive region of the head group which in turn is connected to the negative region by a disulfide bond that is susceptible to cleavage by membrane-bound and intracellular factors. Cleavage of the disulfide bond removes the negatively charged region from the head group resulting in a lipid that is cationic and therefor fusogenic with negatively charged cell membranes. Consequently, lipids of the invention are useful as components of liposomes that serve as vehicles for delivering pharmaceutical agents into cells with reduced toxicity.