Abstract: The invention provides a fusion protein comprising (a) a first protein comprising a polypeptide which specifically binds to Annexin A1 and (b) a second protein comprising a polypeptide which induces a cytotoxic activity of a cytotoxic lymphocyte, pharmaceutical compositions comprising the fusion protein, and methods of treating or preventing cancer by administering the pharmaceutical compositions.

Abstract: 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 are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CA6 glycotope. The present invention is also directed to humanized or resurfaced versions of DS6, an anti-CA6 murine monoclonal antibody, and epitope-binding fragments thereof.

Abstract: Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology uses.

Abstract: Ligand Drug Conjugates are provided having a DRS binding moiety attached via linking groups andor spacers to a therapeutic agent that are effective in treatment of various cancers. In some embodiments, the Ligand Drug Conjugate has the formula: L-(LU-D)p, where L is a Ligand unit, LU is a Linker unit and D is a Drug unit (or cytotoxic agent). The subscript p is an integer of from 1 to 20. Accordingly, the Ligand Drug Conjugates comprise a Ligand unit covalently linked to at least one Drug unit. The Drug units can be covalently linked directly or via a Linker unit (-LU-). The Ligand unit is a DR5 binding agent, such as an anti-DRS antibody.

Abstract: Subject matter of the invention are antibody-cytokine fusion proteins having proapoptotic and immune modulating properties, but wherein the cytokine moiety a priori has a bioactivity which is very low or restricted to certain receptor subtypes. These reagent exert their full biological activity via the corresponding cytokine receptor(s) only after antibody-mediated binding of the fusion protein to a specific cell membrane-expressed target molecule. By suitable choice of the antibody specificity, the cytokine activity is directed to the tissue, e.g. tumor tissue, to be treated, and a therapeutic agent can be produced being specifically designed/optimized for the respective indication/tumor entity.

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: Provided herein are modified anti-EGFR antibodies and nucleic acid molecules encoding modified anti-EGFR antibodies. Also provided are methods of treatment and uses using modified anti-EGFR antibodies.

Abstract: The present invention relates to Fc variants with optimized Fc ligand binding properties, methods for their generation, Fc polypeptides comprising Fc variants with optimized Fc ligand binding properties, and methods for using same.

Abstract: New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the ?-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

Abstract: Disclosed is a conjugate in which a c-Met targeting compound and a bioactive material are chemically conjugated with each other, and methods of use thereof.

Abstract: The present invention relates to a pharmaceutical composition for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD), including a conjugate prepared by covalently linking an insulinotropic peptide, a non-peptidyl polymer and an immunoglobulin Fc region. The composition of the present invention maintains the in-vivo activity of the peptide at a relatively high level, and remarkably increases the blood half-life, thereby preventing triglyceride accumulation which is a typical feature of non-alcoholic fatty liver disease. Ultimately, it can be desirably employed for the prevention and treatment of non-alcoholic fatty liver disease.

Abstract: The present invention provides antibodies that bind to prolactin receptor (PRLR) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human PRLR with high affinity. In certain embodiments, the invention includes antibodies that bind PRLR and block prolactin-mediated cell signaling. In other embodiments, the invention includes antibodies that bind PRLR but do not block prolactin-mediated cell signaling. According to certain embodiments, the invention includes antibodies that bind to the first fibronectin-like type III domain of the extracellular domain of PRLR. The antibodies of the invention may be fully human antibodies. The invention includes anti-PRLR antibodies conjugated to a cytotoxic agent, radionuclide, or other moiety detrimental to cell growth or proliferation. The antibodies of the invention are useful for the treatment of various cancers as well as other PRLR-related disorders.

Abstract: The present invention relates to conjugates of therapeutically useful anthracyclines with carriers such as polyclonal and monoclonal antibodies, proteins or peptides of natural or synthetic origin; methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors.

Abstract: Provided are bispecific antibodies having a full-size antibody portion with two light chains and two heavy chains, wherein the two heavy chains each is fused to a single-chain variable fragment (scFv) portion. In certain embodiments, the full-size antibody has specificity to EGFR and the scFv has specificity to VEGF.

Abstract: The present invention provides antibodies and related molecules that bind to chemokine receptor 4 (CXCR4). The invention further provides antibody-drug conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and anti-CXCR4 antibody-drug conjugates for the treatment of a disorder associated with CXCR4 function or expression (e.g., cancer), such as colon, RCC, esophageal, gastric, head and neck, lung, ovarian, pancreatic cancer or hematological cancers.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: The present invention relates to a linker for forming conjugates of a protein or peptide with a therapeutically active agent and which comprise a thiomaleamic acid moiety that is susceptible to cleavage under the pH conditions prevalent in the lysosome.

Abstract: The present invention relates to a conjugate of acetylated biocompatible polysaccharide and phthalocyanine-based compound for photodynamic diagnosis or therapy in which biocompatible polysaccharide is acetylated and a phthalocyanine-based compound is bound to the acetylated polysaccharide. The conjugate for photodynamic diagnosis or therapy according to the present invention is characterized in that the polysaccharide is acetylated to improve solubility in a solvent and thus enable various chemical modifications, and the conjugate may specifically target tumor cells, has superior cancer cell selecting and accumulating capacity, and has excellent effects of killing cancer cells when near infrared ray is irradiated. The conjugate of the present invention may not show cytotoxicity for cells other than cancer cells even when near infrared ray is irradiated, and thus exhibits superior in vivo stability, and therefore, may be valuably used in disease diagnosis or therapy using photodynamics.

Abstract: The present application relates to new binder-drug conjugates (ADCs) of N,N-dialkylauristatins that are directed against the target C4.4a, to active metabolites of these ADCs, to processes for preparing these ADCs, to the use of these ADCs for treating and/or preventing illnesses, and also to the use of these ADCs for producing medicaments for treating and/or preventing illnesses, more particularly hyperproliferative and/or angiogenic diseases such as, for example, cancer diseases. Such treatments may be practised as a monotherapy or else in combination with other medicaments or further therapeutic measures.

Abstract: Disclosed herein are methods and compositions dock and lock (DNL) complexes comprising an AD moiety selected from an AKAP protein and a DDD moiety selected from a protein kinase A regulatory subunit. Also disclosed are fusion proteins comprising an AD moiety or DDD moiety attached to an effector moiety. The DDD moieties form dimers that bind to the AD moiety to form the DNL complexes. The effector moieties may be selected from a wide range of known effector moieties that produce one or more physiological effects, including but not limited to cell death. The DNL complexes may further comprise one or more diagnostic and/or therapeutic agents. The DNL complexes are of use for treating and/or diagnosing a variety of diseases or conditions.

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract: The present application relates to new antibody drug conjugates (ADCs) of N,N dialkylauristatins directed against the target FGFR2, drug metabolites of said ADCs, a method for producing said ADCs, the use of said ADCs for the treatment and/or prevention of illnesses as well as the use of said ADCs for producing pharmaceuticals for the treatment and/or prevention of illnesses, particularly of hyperproliferative and/or angiogenic diseases such as carcinosis. Such treatments can be carried out as monotherapy or in combination with other pharmaceuticals or additional therapeutic measures.

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: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

Abstract: The invention provides novel chemical entities based on sugar alcohols. These new chemical entities are biocompatible and biodegradable. The molecules can be made in a single and pure form. The molecular weights of these molecules range from small (<1000 Da) to large (1000-120,000 Da). The sugar alcohol-based molecules can have functional groups throughout the molecule for crosslinking compounds, such as the preparation of antibody-drug conjugates, or to facilitate the delivery of therapeutic proteins, peptides, siRNA, and chemotherapeutic drugs. Also provided are new conjugate entities prepared through sugar alcohol molecules. Methods of synthesizing sugar alcohol-based molecules and conjugates are also within the scope of the invention.

Abstract: The invention relates generally to compositions and methods for conjugating antibodies and activatable antibodies, and methods of partially reducing antibodies and/or activatable antibodies prior to conjugation, e.g., thiol-based conjugation, with an agent, e.g., a therapeutic and/or diagnostic agent.

Abstract: Drug compositions, fusions and conjugates are provided. The drug fusions and conjugates contain a therapeutic or diagnostic agent that is fused or conjugated to an antigen-binding fragment of an antibody that binds serum albumin. The drug compositions, fusions and conjugates have a longer in vivo half-life in comparison with the unconjugated or unfused therapeutic or diagnostic agent.

Abstract: The present invention relates to a glucagon-like peptide-2 (GLP-2) conjugate comprising native GLP-2 or its derivative and an immunoglobulin Fc fragment being covalently linked via a non-peptidyl polymer, wherein the native GLP-2 or its derivative has a thiol group introduced at its C-terminal end, and one end of the non-peptidyl polymer is linked to an amino acid residue of the GLP-2 other than the N-terminal amino group thereof; a method for preparing the GLP-2 conjugate; a pharmaceutical composition comprising the same; and a method for treating or preventing intestinal disease, intestinal injury, or gastrosia by using the same. Since the GLP-2 conjugate of the present invention has a remarkably increased binding affinity to a GLP-2 receptor, it shows a prolonged in vivo half-life and an improved in vivo durability and stability.

Abstract: An immunoconjugate in which a phosphate-prodrugged DNA minor groove binding agent of formula (I), where X is a nucleophilically displaceable leaving group, is conjugated to an antibody or an antigen binding fragment of an antibody, and compounds that can be used for making such immunoconjugates, and uses of such immunoconjugates.

Abstract: 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.

Abstract: Novel modulators, including antibodies and derivatives thereof, and methods of using such modulators to treat proliferative disorders are provided.

Abstract: The present invention relates to a prodrug or a pharmaceutically acceptable salt thereof comprising a drug linker conjugate D-L, wherein -D is an amine containing biologically active moiety; and -L is a non-biologically active linker moiety -L1 represented by formula (I), wherein the dashed line indicates the attachment to the amine of the biologically active moiety and wherein R1, R1a, R2, R2a, R3, R3a, X, X1, X2, X3 have the meaning as indicated in the description and the claims and wherein L1 is substituted with one to four groups L2-Z and optionally further substituted, provided that the hydrogen marked with the asterisk in formula (I) is not replaced by a substituent; wherein L2 is a single chemical bond or a spacer; and Z is a carrier group. The invention also relates to A-L, wherein A is a leaving group, pharmaceutical composition comprising said prodrugs and their use as medicaments.

Abstract: The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Abstract: The present invention relates to immunoglobulin Fc variants having an increased binding affinity for FcRn, which is characterized by including one or more amino acid modifications selected from the group consisting of 307S, 308F, 380S, 380A, 428L, 429K, 430S, 433K and 434S (this numbering is according to the EU index) in the constant region of a native immunoglobulin Fc fragment. Owing to the high binding affinity for FcRn, the immunoglobulin Fc variants according to the present invention show more prolonged in vivo half-life, and thus can be used for the preparation of a long-acting formulation of protein drugs.

Abstract: The present application relates to methods for the functionalization of immunoglobulins, in particular with drugs. Also disclosed herein are linking reagents, functionalized antibodies, pharmaceutical compositions, and method of treating disease and/or conditions.

Abstract: The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

Abstract: Peptides that specifically bind erythrocytes are described. These are provided as peptidic ligands having sequences that specifically bind, or as antibodies or fragments thereof that provide specific binding, to erythrocytes. The peptides may be prepared as molecular fusions with therapeutic agents, tolerizing antigens, or targeting peptides. Immunotolerance may be created by use of the fusions and choice of an antigen on a substance for which tolerance is desired.

Abstract: The invention provides anti-wall teichoic acid antibodies and antibiotic conjugates thereof, and methods of using the same.

Abstract: The present invention is directed to the combination therapy of an afucosylated anti-CD20 antibody with a CD79b antibody-drug conjugate for the treatment of cancer, especially to the combination therapy of CD20 expressing cancers with an afucosylated humanized B-Ly1 antibody and a CD79b antibody-drug conjugate.

Abstract: The present invention relates to conjugates of therapeutically useful anthracyclines with carriers such as polyclonal and monoclonal antibodies, proteins or peptides of natural or synthetic origin; methods for their preparation, pharmaceutical composition containing them and use thereof in treating certain mammalian tumors.

Abstract: Compositions of and methods for making and using alpha-1 antitrypsin (AAT) fusion molecules or peptide derivatives thereof are disclosed. The compositions and methods relate to generating an AAT fusion molecule of use in pharmaceutically acceptable compositions to treat a subject in need of AAT therapy or treatment. Compositions and methods disclosed herein concern linking AAT or derivative thereof to an immune fragment.

Abstract: The present invention relates to multivalent polypeptides comprising at least two fibronectin scaffold domains connected via a polypeptide linker. The invention also relates to multivalent polypeptides for use in diagnostic, research and therapeutic applications. The invention further relates to cells comprising such proteins, polynucleotide encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the innovative proteins.

Abstract: The present invention concerns methods and compositions for delivery of therapeutic agents to target cells, tissues or organisms. In preferred embodiments, the therapeutic agents are delivered in the form of therapeutic-loaded polymers that may comprise many copies of one or more therapeutic agents. In more preferred embodiments, the polymer may be conjugated to a peptide moiety that contains one or more haptens, such as HSG. The agent-polymer-peptide complex may be delivered to target cells by, for example, a pre-targeting technique utilizing bispecific or multispecific antibodies or fragments, having at least one binding arm that recognizes the hapten and at least a second binding arm that binds specifically to a disease or pathogen associated antigen, such as a tumor associated antigen. Methods for synthesizing and using such therapeutic-loaded polymers and their conjugates are provided.

Abstract: The present invention concerns methods and compositions comprising an anti-IGF-1R antibody or fragment thereof for treatment of cancer or autoimmune disease. Preferably, the cancer is renal cell carcinoma, breast cancer or pancreatic cancer. The anti-IGF-1R antibody or fragment may be part of a complex, such as a DOCK-AND-LOCK™ (DNL™) complex. Preferably, the DNL™ complex also comprises a second antibody, a second antibody fragment, an affibody or a cytokine. More preferably, the cytokine is interferon-?2b. Most preferably, the second antibody, second fragment or affibody binds to IGF-1R, TROP2 or CEACAM6. The anti-IGF-1R antibody or complex may be administered alone or in combination with a therapeutic agent, such as an mTOR inhibitor.

Abstract: The invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a camptothecin as a therapeutic moiety, and further relates to processes for making and using the said conjugates.

Abstract: The invention provides anti-B7-H4 antibodies and immunoconjugates and methods of using the same.

Abstract: The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Abstract: The present invention relates to pharmaceutical and medical technologies, and more particularly to novel nanobodies against pulmonary surfactant protein A (SP-A) and their preparation methods. The nanobodies of the present invention comprises an amino acid sequence having certain formula. The present invention also relates to nucleic acid sequences encoding the nanobodies, their preparation method and their applications. Immunohistochemistry and in vivo imaging show that the nanobodies of the present inventions have high lung-targeting specificity.

Abstract: The present invention relates to anti-FGFR2 antibodies, antibody fragments, antibody drug conjugates, and their uses for the treatment of cancer.

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