Abstract: Disclosed is an IgG Fc fragment useful as a drug carrier. Also, the present invention discloses a recombinant vector expressing the IgG Fc fragment, a transformant transformed with the recombinant vector, and a method of preparing an IgG Fc fragment, comprising culturing the transformant. When conjugated to a certain drug, the IgG Fc fragment improves the in vivo duration of action of the drug and minimizes the in vivo activity reduction of the drug.

Abstract: Disclosed are compositions that include anti-CD74 immunoconjugates and optionally a therapeutic and/or diagnostic agent. In preferred embodiments, the immunoconjugates comprise one or more anti-CD74 antibodies or antigen-binding fragments thereof, conjugated to a liposome or micelle. Also disclosed are methods for preparing the immunoconjugates and using the immunoconjugates in diagnostic and therapeutic procedures. In certain preferred embodiments, the therapeutic methods comprise administering to a subject with a CD74-expressing disease an anti-CD74 immunoconjugate and thereby inducing apoptosis of CD74-expressing cells. In more preferred embodiments, the CD74 immunoconjugate is capable of inducing cell death in the absence of any other therapeutic agent, although such agents may be optionally administered prior to, together with or subsequent to administration of the anti-CD74 immunoconjugate. The compositions may be part of a kit for administering the anti-CD74 immunoconjugates or compositions.

Abstract: The invention provides an immunogenic composition comprising at least one antigen in association with microparticles, wherein the microparticles are in the same size range as viruses. In addition the invention also provides vaccine compositions and methods of eliciting immune responses in a subject.

Abstract: Provided are monoclonal antibodies and antigen binding fragments thereof that specifically bind vascular endothelial growth factor (VEGF). The anti-VEGF monoclonal antibodies block VEGF binding to its receptors (e.g., VEGFR1 and/or VEGFR2) and prevent phosphorylation of VEGFR2 by VEGF. Also provided are methods of using the monoclonal anti-VEGF antibodies for treatment of disease, including cancer.

Abstract: The present disclosure relates to immunoglobulins and immunoglobulin conjugates with reduced oligomerization and efficient labeling and compositions, methods of generating such immunoglobulins and immunoglobulin conjugates and methods of using such immunoglobulin conjugates particularly in the treatment and prevention of disease.

Abstract: The invention relates to a method for producing monomeric or dimeric proteins or peptides containing internal or external disulfide bonds, comprising the following steps: a) a cell-free lysate, obtainable from eukaryotic cells, is provided, which contains functional microsomal vesicles, b) a nucleic acid coding the protein or peptide and additionally containing a signal sequence is added to the lysate, c) the lysate with the nucleic acid is held for a given time at a temperature in the range from 20 to 35° C., proteins or peptides formed with the nucleic acid being translocated into the microsomal vesicles, d) the microsomal vesicles are then dissolved, and the proteins or peptides obtained thereby are optionally separated from the lysate.

Abstract: The present invention is directed to cytotoxic pentapeptides, to antibody drug conjugates thereof, and to methods for using the same to treat cancer.

Abstract: A drug composition comprising a charged moiety coupled to a therapeutic compound is disclosed. The charged moiety is configured to interact with at least one type of component of opposite charge in a biological tissue to create an in situ depot for prolonged drug delivery. The biological tissue may be eye tissue or any tissue containing charged components.

Abstract: The invention provides compositions and methods for the targeted bacteriostatic and antibacterial agents and for treatment of sepsis caused by infectious diseases, such as bacterial and fungal diseases. In one aspect, the invention provides methods and compositions for decreasing the levels of LPS in the circulation of an individual, e.g., a human patient with sepsis, e.g., gram negative septic shock. In one aspect, the invention is directed to chimeric proteins comprising the MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. In one aspect, the invention is directed to chimeric proteins comprising fragments or altered form of MD-2 polypeptide and an opsinizing agent, e.g., antibody Fc domains, or equivalent. The invention also provides pharmaceutical compositions comprising the chimeric polypeptides of the invention, and methods of making and using them, including methods for ameliorating or preventing sepsis.

Abstract: The present invention relates generally to the field of generating fusion proteins to be used in cancer therapy, and more specifically, to nucleotide sequences encoding the fusion proteins, wherein the chimeric fusion proteins comprises at least one targeting moiety and at least one immunomodulatory moiety that counteracts the immune tolerance of cancer cells.

Abstract: The present invention relates to drug fusions and conjugates that have improved serum half lives. These fusions and conjugates comprise immunoglobulin (antibody) single variable domains and insulinotropic and/or incretin and/or gut peptide molecules. The invention further relates to uses, formulations, compositions and devices comprising such drug fusions and conjugates. The invention also relates to compositions which comprise more than one insulinotropic and/or incretin and/or gut peptide molecules present as part of a fusion or conjugate and to uses and formulations thereof.

Abstract: Tubulysin compounds of the formula (I) where R1, R2, R3a, R3b, R4, R5, W, and n are as defined herein, are anti-mitotic agents that can be used in the treatment of cancer, especially when conjugated to a targeting moiety.

Abstract: Monoclonal antibodies that specifically bind to an extracellular domain of human Jagged 1 and inhibit growth of a tumor comprising cancer stem cells are described. Also described is a method of treating cancer that comprises administering a therapeutically effective amount of a monoclonal anti-Jagged 1 antibody.

Abstract: A polypeptide is provided that comprises an actinohivin variant polypeptide having an amino acid sequence selected from SEQ ID NOS: 4-12. The polypeptide can be provided as part of a fusion protein that includes the actinohivin variant polypeptide and either a fragment crystallizable domain of an antibody (Fc), a fragment antigen-binding domain of an antibody (Fab), or a single chain variable fragment of an antibody (scFv). Isolated nucleic acid molecules encoding the polypeptides are also provided along with vectors and plant cells capable of expressing the polypeptides. Methods of treating an infection of a subject by an enveloped virus are further provided and include administering an effective amount of the polypeptides to a subject.

Abstract: The present invention relates to methods of treating ovarian cancer in a subject by administering to the subject an anti-activin-A compound, such as an anti-activin-A antibody or an activin-A-binding receptor. In some embodiments, at least two compounds are administered to the subject, where the first compound is an anti-activin A compound, and the second compound is a chemotherapeutic compound, for example capecitabine. The invention further relates to methods of identifying subjects for treatment by evaluating the subject's expression levels of specific biomarkers or angiogenic factors.

Abstract: Disclosed are methods, compositions and uses of conjugates of prodrug forms of 2-pyrrolinodoxorubicin (P2PDox) with antibodies or antigen-binding fragments thereof (ADCs), with targetable construct peptides or with other targeting molecules that are capable of delivering the P2PDox to a targeted cell, tissue or pathogen. Once delivered to the target cell, the ADC or peptide conjugate is internalized, a highly toxic 2-pyrrolinodoxorubicin (2-PDox) is released intracellularly. The P2PDox-peptide or ADC conjugates are of use to treat a wide variety of diseases, such as cancer, autoimmune disease or infectious disease.

Abstract: Novel anti-cancer agents, including, but not limited to, antibodies and immunoconjugates, that bind to EGFR are provided. Methods of using the agents, antibodies, or immunoconjugates, such as methods of inhibiting tumor growth are further provided.

Abstract: The invention is directed to antibody drug conjugate compositions of matter useful for the diagnosis and treatment of tumors in mammals and to methods of using those compositions of matter for the same.

Abstract: Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration, and angiomas. A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12 (IL-12), Interferon-? (IFN-?), Tumor Necrosis Factor ? (TNF?) or Tissue Factor protein (which may be truncated).

Abstract: 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.

Abstract: The invention provides a sustained release composition for intravitreal injection to the eye of a subject in need thereof. The sustained release composition contains an effective amount of a therapeutic agent in association with a nanosphere. The nanosphere contains a particle that comprises a particle-forming component capable of forming a vesicle, and an agent-carrying component capable of forming a complex with the therapeutic agent via electrostatic charge-charge interaction or hydrophobic-hydrophobic interaction. The particle-forming component has at least one head group moiety selected from a hydrophobic head group moiety, a polar head group moiety and a combination thereof. The agent-carrying component is a chemical entity that contains one or more negatively or positively charged groups.

Abstract: The invention relates to molecules for treatment and diagnosis of tumors and malignancies, comprising a tumor seeking biomolecule, which is coupled to an intercalating moiety, which is capable of complexing a metal, which metal is preferably a radioactive metal, to the use of these molecules and to therapeutic and diagnostic compositions containing them.

Abstract: The present invention relates to amino acid sequences that are directed against/and or that can specifically bind Interleukin-6 Receptor (IL-6R) with improved affinity and/or avidity, and/or that have an improved efficacy and/or potency, and which are capable of (partially, or preferably totally) blocking the IL-6/IL-6R interaction and/or inhibit signalization through IL-6, IL-6R and/or the IL-6/IL-6R complex. The invention further relates to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences.

Abstract: The invention provides compositions, methods, and kits for increasing transport of GDNF across the blood brain barrier while allowing its activity to remain substantially intact. The GDNF is transported across the blood brain barrier via one or more endogenous receptor-mediated transport systems.

Abstract: The present disclosure provides conjugate structures (e.g., polypeptide conjugates) and hydrazinyl-indole compounds used to produce these conjugates. The disclosure also provides methods of production of such conjugates, as well as methods of using the same.

Abstract: The present invention provides a FGF21 molecule covalently attached to the combining site of an antibody via a linker, wherein the linker is covalently attached to the side chain of a linking residue within FGF21. Various uses of the compounds are provided, including methods to prevent or treat diabetes or diabetes-related conditions.

Abstract: The present invention provides water-soluble, polymer derivatives having a thiol-selective terminus suitable for selective coupling to thiol groups, such as those contained in the cysteine residues of proteins, as well as methods for preparing the water-soluble, polymer derivatives having a thiol-selective terminus.

Abstract: The present invention relates to a composition for the prevention or treatment of diabetes comprising a long-acting insulin conjugate and a long-acting insulinotropic peptide conjugate, and a therapeutic method for the treatment of diabetes, and more particularly, concurrent administration of the long-acting insulin conjugate and the long-acting insulinotropic peptide conjugate inhibits weight gain caused by insulin treatment, and vomiting and nausea caused by insulinotropic peptide treatment, and reduces the required dose of insulin, thereby remarkably improving drug compliance. Moreover, each of the long-acting insulin conjugate and the long-acting insulinotropic peptide conjugate of the present invention is prepared by linking insulin or insulinotropic peptide with an immunoglobulin Fc region via a non-peptidyl linker, thereby showing improved in-vivo duration of efficacy and stability.

Abstract: The present invention provides variant target binding agents and methods relating to the use of such binding agents for the prophylaxis or treatment of cancers and immunological disorders. The variant target binding agent is conjugated to a therapeutic agent that exerts a cytotoxic, cytostatic, or immunomodulatory effect on target cells.

Abstract: The present invention concerns antigen binding proteins and fragments thereof which specifically bind B Cell Maturation Antigen (BCMA), particularly human BCMA (hBCMA) and which inhibit the binding of BAFF and APRIL to the BCMA receptor. Further disclosed are pharmaceutical compositions, screening and medical treatment methods.

Abstract: This disclosure features compounds that are useful as pro-drugs of epoxy ketone protease inhibitors.

Abstract: The present invention provides variant target binding agents and methods relating to the use of such binding agents for the prophylaxis or treatment of cancers and immunological disorders. The variant target binding agent is conjugated to a therapeutic agent that exerts a cytotoxic, cytostatic, or immunomodulatory effect on target cells.

Abstract: The present invention relates to a poly(lactic glycolic) acid (PLGA) nanoparticle associated with therapeutic agents for a variety of therapeutic applications.

Abstract: The present invention provides antibodies or antigen-binding fragments thereof that specifically bind the ENDO180 polypeptide and are internalized thereby, to conjugates comprising the molecules, to compositions comprising the antibodies and conjugates and to methods of using the same for delivery of therapeutic agents to cells that express the ENDO180 polypeptide on the surface of the cell for treating cell proliferative diseases or disorders and fibrosis, and for controlling (modulating) tumor progression.

Abstract: The present invention provides methods of site-specific labeling of antibodies, using proteins having 4?-phosphopantetheinyl transferase activity that catalyze post-translational modification of peptide sequences (“peptide tags”) incorporated into one or more specific sites of an antibody of interest. Enzymatic labeling enables quantitative and irreversible covalent modification of a specific serine residue within the peptide tags incorporated into the antibody, and thus creates desirable antibody conjugates.

Abstract: The present invention relates to a delivery system that comprises a conjugate that facilitates the delivery of a compound such as a biologically-active macromolecule, a nucleic acid or a peptide in particular, into a cell. The present invention also relates to said conjugate for delivery of a compound, such as a biologically-active macromolecule, a nucleic acid or a peptide, into a cell. The present invention further relates to a pharmaceutical composition comprising said conjugate and to its use. The present invention also relates to a method of delivering a compound to a cell or an organism, preferably a patient.

Abstract: 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.

Abstract: Combinations of the antibody-drug conjugate trastuzumab-MCC-DM1 and chemotherapeutic agents, including stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting tumor cell growth, and for treating disorders such as cancer mediated by HER2 and KDR (VEGFR receptor 1). Methods of using such combinations for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

Abstract: The present invention relates to melanocortin receptor binding conjugates and methods of making and using the foregoing.

Abstract: Drug Linker compounds and Drug Linker Ligand conjugates are provided that have auristatins linked via the C-terminus. The conjugates show efficacy without the need for a self-immolative group to release the drug.

Abstract: This document relates to conjugates of TNF inhibitors or derivatives thereof and functionalized (e.g., mono- or bi-functional) polymers (e.g., polyethylene glycol and related polymers) as well as methods and materials for making and using such conjugates.

Abstract: Antibody drug conjugates (ADC's) that bind to 191P4D12 protein and variants thereof are described herein. 191P4D12 exhibits tissue specific expression in normal adult tissue, and is aberrantly expressed in the cancers listed in Table I. Consequently, the ADC's of the invention provide a therapeutic composition for the treatment of cancer.

Abstract: The present invention relates to new auristatin compounds and prodrugs thereof, compositions comprising them and uses thereof.

Abstract: A terminally modified polymer is provided herein. At least one terminus of the polymer is —O—(CH2)2-LM or —O—CH2—CH(OH)—CH2—CR1?CR2R3. LM, R1, R2, and R3 are defined herein Also disclosed are terminal conjugates comprising the polymer and a pharmaceutically useful modifier, as well as compositions comprising the conjugates, methods of their preparation, and methods of treating various disorders with the conjugates or their compositions.

Abstract: The present invention relates to a radioimmunoconjugate that binds human CD37. Pharmaceutical compositions and uses thereof for the treatment of cancer—and in particular B-cell malignancies—are aspects of the present invention.

Abstract: 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.

Abstract: Treatment of lesions of pathological angiogenesis, especially tumors, rheumatoid arthritis, diabetic retinopathy, age-related muscular degeneration. and angiomas. A conjugate is used comprising a molecule that exerts a biocidal or cytotoxic effect on target cells in the lesions and an antibody directed against an extracellular matrix component which is present in such lesions. The antibody may be directed against fibronectin-2 (IL-2), doxorubicin, interleukin-12(IL-12), Interferon-? (IFN-?), Tumor Necrosis Factor ?(TNF?) or Tissue Factor protein (which may be truncated).

Abstract: Herein is reported a polypeptide-polynucleotide-complex as therapeutic agent and its use as tool for the targeted delivery of an effector moiety. The polynucleotide part of the complex is essentially resistant to proteolytic and enzymatic degradation in vivo. Additionally the polypeptide part specifically binds to a compound or structure such as a tissue or organ, a process or a disease. Thus, one aspect as reported herein is a polypeptide-polynucleotide-complex comprising a) a polypeptide specifically binding to a target and conjugated to a first member of a binding pair, b) a polynucleotide linker conjugated at its first terminus to the second member of the binding pair, and c) an effector moiety conjugated to a polynucleotide that is complementary to at least a part of the polynucleotide linker.

Abstract: The present invention relates to melanocortin receptor binding conjugates and methods of making and using the foregoing.

Abstract: The present invention is based on the discovery that the administration of at least one immunoconjugate and at least one chemotherapeutic agent provides an unexpectedly superior treatment for cancer. The present invention is directed to compositions comprising at least one immunoconjugate and at least one chemotherapeutic agent and to methods of treating cancer using at least one immunoconjugate and at least one chemotherapeutic agent. The present invention also provides methods of modulating the growth of selected cell populations, such as cancer cells, by administering a therapeutically effective amount of at least one chemotherapeutic agent and at least one immunoconjugate.