Abstract: A method of stimulating ventilatory and/or respiratory drive in a subject in need thereof includes administering to the subject a therapeutically effective amount of a composition comprising a cystine ester or a pharmaceutically acceptable salt thereof. Embodiments described herein relate to compositions and methods of stimulating ventilatory and/or respiratory drive in a subject in need thereof, and particularly relates to compositions and methods of treating breathing diseases and/or disorders associated with impaired ventilatory and/or respiratory drive.

Abstract: The present invention relates to therapeutic antibodies for the treatment of cancer, and more specifically, for the treatment of prostate, bladder, and/or pancreatic cancer. An embodiment of the present invention is an anti-glypican-1 (GPC 1) antibody, which may be conjugated to at least one cytotoxic agent that is toxic to a prostate, bladder, and/or pancreatic cancer cell.

Abstract: The present disclosure relates to a sensitive, multidimensional chromatography method for extraction, detection, and quantification of non-conjugated cytotoxic agents and associated linker molecules used in cysteine based antibody-drug-conjugate production.

Abstract: It is an object of the present invention to provide an anti-cadherin antibody having a high internalization capacity and provide an anti-cadherin antibody-drug conjugate that effectively kills cadherin-expressing cancer cells with the use of such antibody. The present invention provides an anti-cadherin antibody which recognizes a cadherin domain 1 (EC1) of cadherin and exhibits a high internalization capacity.

Abstract: The present invention relates to Cadherin-11 antagonists and compositions comprising Cadherin-11 antagonists. The invention also relates to methods for treating inflammatory joint disorders, such as rheumaotid arthritis, in a mammalian subject by administering a therapeutically effective amount of a Cadherin-11 antagonist.

Abstract: Provided herein are monovalent antibody constructs. In specific embodiments is a monovalent antibody construct comprising: an antigen-binding polypeptide construct which monovalently binds an antigen; and a dimeric Fc polypeptide construct comprising a CH3 domain, said construct comprising two monomeric Fc polypeptides, wherein one said monomeric Fc polypeptide is fused to at least one polypeptide from the antigen-binding polypeptide construct. These therapeutically novel molecules encompass monovalent constructs that display an increase in binding density and Bmax (maximum binding at a target to antibody ratio of 1:1) to a target cell displaying said antigen as compared to a corresponding monospecific bivalent antibody construct with two antigen binding regions. Provided herein are methods for creation of monovalent antibody constructs that shows superior effector efficacy as compared to the corresponding bivalent antibody construct at equimolar concentrations.

Abstract: This invention provides a method that allows selection of antibodies against cells (e.g., tumor cells) in situ using laser capture microdissection. By restricting antibody selection to binders of internalizing epitopes, a panel of phage antibodies was generated that targets clinically represented prostate cancer antigens.

Abstract: This disclosure relates to anti-Siglec-15 antibodies and uses thereof, in particular in the treatment of leukaemia, such as acute myeloid leukaemia.

Abstract: Methods of identifying antigen-specific antibody-secreting and antibody-forming cells, such as antigen-specific B cells, and methods for cloning the antigen-specific antibody sequences of the antibody produced by these cells are provided. In particular, the methods include enriching B cells for antigen-specific B cells, culturing the antigen-specific B cells to generate clonal B cell populations, detecting clonal B cells that produce a single antigen-specific antibody, optionally screening the clonal B cell populations for functional activity, staining and sorting the cells to isolate the antigen-specific B cells, sequencing the nucleic acids encoding the antigen-specific antibody sequences, expressing the sequences to produce an antibody, isolating the antibody and screening the antibody for antigen recognition. The methods provide improved enrichment and selection of antigen-specific antibody-secreting and antibody-forming cells, which enhances recovery of antigen-specific antibodies.

Abstract: Provided are antigenic determinants of human death receptor DR5. The antigenic determinants have the amino acid sequence of LITQQDLAPQQRA (SEQ ID No. 7), wherein the core polypeptide is QDLAP (SEQ ID No. 1). The polypeptides comprising said antigenic determinants can activate the signal pathway downstream of DR5 after binding to monoclonal antibody AD5-10, then result in apoptosis. The antigenic determinants can be used for screening and preparing anti-human DR5 agonistic antibody, small molecular compound binding to DR5 and DR5 vaccine.

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 present invention is related to the obtaining of modified antibodies by means of DNA recombinant technology from the murine monoclonal antibody P3 (MAb P3), produced by the hybridoma cell line deposited under Budapest Treaty with accession number ECACC 94113026, and from its anti-idiotype murine monoclonal antibody 1E10(MAbai 1E10), produced by the hybridoma cell line with deposit number ECACC 97112901, with the objective of achieving monoclonal antibodies which preserve the biological function of specifically binding the antigen of the original antibodies, but being at the same time less immunogenic.

Abstract: The present invention relates to a method of diagnosis and therapy of cancers expressing the HER2 receptor. The invention provides antibodies or fragments thereof that recognise an epitope of the HER2 receptor truncated form CTF-611, said epitope being defined by a sequence included in SEQ ID NO: 2, and that are capable of discriminating between CTF-611 and CTF-616 (represented by SEQ ID NO:7), preferably additionally capable of discriminating between CTF-611 and CTF-613 (represented by SEQ ID NO:6). The invention also provides a method of cancer diagnosis using the disclosed antibodies, which comprises the detection of the presence of the HER2 receptor truncated form consisting of the amino acid sequence SEQ ID NO: 1 in a patient sample.

Abstract: To provide a method for detecting cellular DNA damage by specifically recognizing molecules responsive to DNA strand breaks. A method for detecting DNA damage in cells, which comprises administering in vivo, to cells, an antibody against a cell membrane surface antigen that is expressed in cells undergoing DNA strand breaks to a greater extent than in cells not undergoing DNA strand breaks in an environment that causes DNA damage, and analyzing the expression status of the cell membrane surface antigen.

Abstract: Provided is a novel therapeutic agent specific for a malignant tumor expressing MHC class II. The present invention provides an antibody recognizing a protein constituting MHC class II expressed on a malignant tumor, the antibody comprising at least one selected from heavy chain CDR1 (amino acid sequence represented by positions 49 to 54 of SEQ ID NO: 54), heavy chain CDR2 (amino acid sequence represented by positions 69 to 84 of SEQ ID NO: 54), heavy chain CDR3 (amino acid sequence represented by positions 117 to 128 of SEQ ID NO: 54), light chain CDR1 (amino acid sequence represented by positions 46 to 55 of SEQ ID NO: 56), light chain CDR2 (amino acid sequence represented by positions 71 to 77 of SEQ ID NO: 56), and light chain CDR3 (amino acid sequence represented by positions 100 to 108 of SEQ ID NO: 56).

Abstract: Isolated human monoclonal antibodies which bind to and inhibit human CD20, and related antibody-based compositions and molecules, are disclosed. The human antibodies can be produced by a transfectoma or in a non-human transgenic animal, e.g., a transgenic mouse, capable of producing multiple isotypes of human monoclonal antibodies by undergoing V-D-J recombination and isotype switching. Also disclosed are pharmaceutical compositions comprising the human antibodies, non-human transgenic animals and hybridomas which produce the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.

Abstract: Novel anti-cancer agents, including, but not limited to, antibodies, that bind to human frizzled receptors are provided. Novel epitopes within the human frizzled receptors which are suitable as targets for anti-cancer agents are also identified. Methods of using the agents or antibodies, such as methods of using the agents or antibodies to inhibit Wnt signaling and/or inhibit tumor growth are further provided.

Abstract: Novel peptides that inhibit the release of microparticles from cells are disclosed. Also disclosed are polynucleotides encoding the peptides, expression vectors carrying the polynucleotides and methods for treating tumors using the novel peptides.

Abstract: It is an object of the present invention to provide an anti-cadherin antibody having high antibody-dependent cellular cytotoxicity. The present invention provides an anti-cadherin antibody, which recognizes any one of an upstream region of EC1, a cadherin domain 4 (EC4) and a cadherin domain 5 (EC5), wherein an antibody-dependent cellular cytotoxicity at an antibody concentration of 1 ?g/mL is 30% or more.

Abstract: The present invention provides a method for diagnosing and detecting diseases associated with colon. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in colon diseases (CCAT) and antibodies binds to CCAT. The present invention provides that CCAT is used as targets for screening agents that modulates the CCAT activities. Further the present invention provides methods for treating diseases associated with colon.

Abstract: The invention relates to antibodies against S100A4, methods for the preparation of these antibodies, pharmaceutical compositions comprising these antibodies, and therapeutic and diagnostic uses thereof.

Abstract: The present invention relates to reagents and methods for the detection of osteopontin fragments and distinguishing them from each other and from the full-length osteopontin protein. The present invention also relates to assays for the determination of the presence of osteopontin fragments in samples obtained from subjects and, further, the correlation of osteopontin fragment levels fragment levels with disease detection, progression and prognosis.

Abstract: Novel immuno-interactive fragments of the ?C portion of a mammalian inhibin ? subunit, together with their variants and derivatives, produce antigen-binding molecules that are interactive with the ?C portion, and which are chemically well defined and which can be produced in commercially significant quantities. The antigen-binding molecules of the invention can be used for the detection of a mammalian inhibin and for the treatment and/or prevention of conditions associated with aberrant levels of a mammalian inhibin.

Abstract: The present invention relates to the use of a milled homogenate and/or a suspension and/or a cell lysate, stemming from a tumor resistant to at least one anti-tumoral compound in order to immunize and generate in vitro an antibody, or one of its functional fragments, directed against a tumoral antigen specifically expressed at the surface of said resistant tumor and being possibly involved in the resistance of said resistant tumor. More particularly, the present invention is directed to such antibodies obtained by applying the method, such as the antibodies 1A6, 1A9, 2E11, 3C11 and 3G7, as well as to their use for treating cancer.

Abstract: Provided is a monoclonal antibody, or an antigen binding fragment thereof, which binds specifically to an epitope within the sequence KPGAKKDTKDSRPKL (Sequence ID No. 2) of AGR2. Such monoclonal antibodies are of prognostic and diagnostic utility in the investigation of cancer, particularly metastatic cancer. The antibodies described may also be used in prognosis or diagnosis of inflammatory diseases. Also provided are kits and solid supports comprising such antibodies, as well as the therapeutic use of antibodies of the invention.

Abstract: In a wide variety of human solid tumors, an aggressive, metastatic phenotype and poor clinical prognosis are associated with expression of the receptor tyrosine kinase Met. Disclosed herein are (a) a monoclonal antibody named Met4, which antibody is specific for Met, and (b) a hybridoma cell line that produces Met4. The Met4 antibody is particularly useful for detecting Met in formalin-fixed tissue. Methods of using the Met4 antibody for detection, diagnosis, prognosis, and evaluating therapeutic efficacy are provided.

Abstract: The present invention relates to an isolated antibody or antigen-binding fragment thereof that specifically binds with high affinity to at least a portion of a segment of human prostate-derived Ets transcription factor (PDEF). The anti-PDEF antibody of the present invention is effective in prognostic and diagnostic assays for detecting PDEF with immunohistochemistry. The present invention also relates to methods of making the anti-PDEF antibody disclosed herein. The present invention further relates to vaccines against cancers associated with positive expression of PDEF, as well as methods for treating those cancers. Vectors, diagnostic kits, and hybridomas are also disclosed.

Abstract: The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLD18, including tumor-related diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder.

Abstract: Pharmaceutical compositions and kits useful for the treatment of cancer include certain alkyl esters of cystine and certain alkyl-substituted cystamine derived esters, including, for example, cystine dimethyl ester and a di-alkyl peptidyl cystamine ester, among others. These compounds may be employed in methods of treating cancers or methods of determining sensitivity of certain cancer cells to apoptosis alone, or in combination with other chemotherapeutic, radiological or apoptotic agents.

Abstract: The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLD1 8, including tumor-related diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder.

Abstract: A method of sensitizing a mammal, especially a human, to another anticancer therapy by administering a sensitizing effective amount of a GST-activated anticancer compound. A method of ameliorating a side effect of another anticancer therapy in a mammal, especially a human, by administering an ameliorating effective amount of a GST-activated anticancer compound. Pharmaceutical compositions for the methods. The GST-activated anticancer compound is preferably a compound of U.S. Pat. No. 5,556,942, and more preferably canfosfamide, especially as the hydrochloride salt.

Abstract: It is an object of the present invention to provide an anti-cadherin antibody having high antibody-dependent cellular cytotoxicity. The present invention provides an anti-cadherin antibody, which recognizes any one of an upstream region of EC1, a cadherin domain 4 (EC4) and a cadherin domain 5 (EC5), wherein an antibody-dependent cellular cytotoxicity at an antibody concentration of 1 ?g/mL is 30% or more.

Abstract: This invention provides novel erbB2-binding internalizing antibodies. The antibodies, designated F5 and C1, specifically bind to c-erbB2 antigen and, upon binding, are readily internalized into the cell bearing the c-erbB2 marker. Chimeric molecules comprising the F5 and/or C1 antibodies attached to one or more effector molecules are also provided.

Abstract: The detection of endothelial cell antibodies has been proven clinically important for successful organ transplantation. Disclosed are methods of isolating Tie-2+ and CD34? precursor endothelial cells for use in donor-specific crossmatching.

Abstract: The present invention relates to the discovery of antibodies that bind to novel epitopes present on membrane-anchored IgE and which bind to these novel epitopes on the surface of B cells and plasma cells. In addition, the antibodies of the present invention can mediate ADCC and can be useful to deplete those B cells and plasma cells expressing the novel epitopes of the invention. The antibodies of the present invention can be useful for the treatment of IgE-mediated diseases. Accordingly the present invention also provides compositions and methods for the prevention, management, treatment or amelioration of IgE-mediated diseases.

Abstract: Anti-HEPSIN monoclonal antibodies, and methods for using the antibodies, are provided.

Abstract: A murine anti-CD20 monoclonal antibody having cell growth inhibitory activities is disclosed. Cell growth inhibitory activities include apoptosis against human CD20 antigen expressing cells in culture of the CD20 antigen expressing cells without effector cells. The anti-CD20 monoclonal antibody is incorporated into chimeric anti-CD20 monoclonal antibodies in which the amino acid sequences of the variable regions of the anti-CD20 monoclonal antibody and the amino acid sequences of the constant regions of human immunoglobulin are fused. Also a humanized anti-CD20 monoclonal antibody is described which includes all of the variable region CDRs of the H chain of the anti-CD20 monoclonal antibody and all of the variable region CDRs of the L chain of the anti-CD20 monoclonal antibody and an amino acid sequence of human immunoglobulin. A nucleotide sequence encoding the amino acid sequence of the chimeric or humanized anti-CD20 monoclonal antibody can be expressed in mammalian cells.

Abstract: The present invention relates to a method for providing molecules that are capable of inhibiting angiogenesis, comprising the steps of providing a range of molecules; testing whether these molecules can prevent interaction between JAM-B and JAM-C; testing the positive molecules for their ability to block angiogenesis in vivo; and selecting molecules that are positive in the angiogenesis test as angiogenesis inhibiting molecules. The method may further comprise the step of isolating or producing the angiogenesis inhibiting molecules. The invention further relates to the angiogenesis inhibiting molecules thus provided and produced, to their use in the treatment of cancer, to therapeutical compositions comprising them. In a particular embodiment the invention relates to monoclonal antibodies, in particular Mab H33, to soluble JAM-C and JAM-B and to small molecules.

Abstract: The present invention provides a monoclonal antibody recognizing modification after translation of p53 in a manner specific to a modification site, an antibody microarray comprising the antibody immobilized on a substrate, etc. Disclosed is a monoclonal antibody which reacts specifically with a peptide consisting of an amino acid sequence of at least 6 consecutive amino acids containing a predetermined amino acid residue of the amino acid sequence represented by SEQ ID NO: 1, wherein the amino acid residue is phosphorylated or acetylated, or with a peptide having one to several arbitrary amino acids added to the above peptide, but does not react with the above peptide which is not phosphorylated or acetylated.

Abstract: The present invention provides a method for diagnosing and detecting diseases associated with colon. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in colon diseases (CCAT) and antibodies binds to CCAT. The present invention provides that CCAT is used as targets for screening agents that modulates the CCAT activities. Further the present invention provides methods for treating diseases associated with colon.

Abstract: 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.

Abstract: The present invention is directed to compositions of matter useful for the diagnosis and treatment of tumor in mammals and to methods of using those compositions of matter for the same.

Abstract: The present invention relates to a method for diagnosing cancer and a detection reagent based on detection of Epstein-Barr virus nuclear antigen 2 (EBNA2) coactivator p100 contained in a specimen, and a method for treating cancer by controlling expression of EBNA2 coactivator p100 protein or a gene thereof.

Abstract: The present invention relates to antibodies against human CDCP1 binding to the same epitope as CUB4 (Deposition No. DSM ACC2551) for the treatment of cancer.

Abstract: In a wide variety of human solid tumors, an aggressive, metastatic phenotype and poor clinical prognosis are associated with expression of the receptor tyrosine kinase Met. Disclosed herein are (a) a monoclonal antibody named Met4, which antibody is specific for Met, and (b) a hybridoma cell line that produces Met4. The Met4 antibody is particularly useful for detecting Met in formalin-fixed tissue. Methods of using the Met4 antibody for detection, diagnosis, prognosis, and evaluating therapeutic efficacy are provided.

Abstract: The present invention concerns antibodies that neutralize at least one biological activity of pleiotrophin. The antibodies can inhibit cancer cell growth and angiogenesis in vitro or in vivo. The present invention provides for methods of inhibiting cancer cell growth or angiogenesis in a subject comprising administering to said subject an effective amount of the antibodies described herein. The present invention also provides for methods of making the neutralizing antibodies described herein.

Abstract: The present invention relates to reagents and methods for the detection of osteopontin fragments and distinguishing them from each other and from the full-length osteopontin protein. The present invention also relates to assays for the determination of the presence of osteopontin fragments in samples obtained from subjects and, further, the correlation of osteopontin fragment levels fragment levels with disease detection, progression and prognosis.

Abstract: Disclosed herein is the discovery of a soluble MN/CA IX (s-CA IX) found in body fluids, such as, urine and serum. Soluble CA IX comprises the extracellular domain of CA IX or portions thereof. The predominant s-CA IX species is the extracellular domain comprising a proteoglycan-like (PG) domain and carbonic anhydrase (CA) domain, and having a molecular weight of about 50/54 kilodaltons. Diagnostic/prognostic methods for precancer/cancer that detect or detect and quantitate s-CA IX in body fluids, are described. Also disclosed is the coexpression of CA IX and HER-2 that provides potentially synergistic diagnostic/prognostic and therapeutic strategies for precancer/cancer. Further disclosed are new MN/CA IX-specific antibodies generated from MN/CA IX-deficient mice, useful diagnostically/prognostically and therapeutically for cancer/precancer.

Abstract: The present invention relates to angiogenesis inhibiting molecules that are the monoclonal antibody H33 or fragments or derivatives thereof, to their use in the treatment of cancer, in particular the treatment of solid tumors and to therapeutic and diagnostic compositions comprising them. The invention relates in particular to humanized derivatives of H33 of human monoclonal antibodies having the specificity of H33.

Abstract: The present invention relates to methods and compositions designed for the treatment, management, or prevention of cancer, particularly, metastatic cancer. In one embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 and agonize EphA4. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that bind to EphA4 and inhibit cancer cell colony formation in soft agar or tubular network formation in three-dimensional basement membrane or extracellular matrix preparation. In another embodiment, the methods of the invention comprise the administration of an effective amount of one or more antibodies that preferentially binds to an EphA4 epitope that is exposed on cancer cells but not non-cancer cells.