Abstract: Variants of FVII or FVIIa comprising at least one amino acid modification in position 196, 237 or 341 relative to hFVII or hFVIIa. The variants exhibit an increased clotting activity, i.e. reduced clotting time, compared to rhFVIIa.

Abstract: The present invention clearly demonstrates that vWF-collagen interaction, via the A3 domain of vWF, plays an important role in acute platelet-dependent arterial thrombus formation and that blocking the A3 domain in a vWF-collagen interaction can induce complete abolition of thrombus formation in the injured and stenosed baboon femoral arteries. Accordingly, an antibody or an antigen recognizing fragment thereof binding specifically to the A3 domain of vWF or an epitope thereof can be used for the prevention of acute arterial thrombotic syndromes or to manufacture medicines to for the prevention of acute arterial thrombotic syndromes.

Abstract: The present invention provides monoclonal antibodies for human TrkB. In certain embodiments the inventive antibodies bind and activate human TrkB. In certain embodiments the inventive antibodies are selective for human TrkB in that they do not bind (or activate) human TrkA or human TrkC. In some embodiments the inventive monoclonal antibodies cross-react with murine TrkB. Humanized or veneered versions of the inventive antibodies are also encompassed. Pharmaceutical compositions that comprise inventive antibodies are provided as are methods for preparing the inventive antibodies and methods of using these for treatment, detection or purification purposes.

Abstract: Disclosed herein are methods for treating a pregnancy related hypertensive disorder, such as pre-eclampsia and eclampsia, using combinations of compounds that alter soluble endoglin and sFlt-1 expression levels or biological activity. Also disclosed are methods for treating a pregnancy related hypertensive disorder, such as pre-eclampsia and eclampsia, using compounds that increase endothelial nitric oxide synthase levels or biological activity.

Abstract: The invention includes compositions, kits and methods comprising a monoclonal antibody which shares key functional properties with the polyclonal antibodies which participate in the pathogenesis of heparin induced thrombocytopenia/thrombosis (HIT/HITT) in a mammal. The monoclonal antibody of the invention preferentially binds with a PF4/heparin complex relative to the binding of the antibody with PF4 or heparin alone. The monoclonal antibody of the invention also binds specifically with PF4 in a complex with other glycosaminoglycans besides heparin, and also activates platelets. The monoclonal antibody of the invention is useful in methods for diagnosing and treating HIT/HITT in a mammal. A humanized version of the monoclonal antibody of the invention is also included, along with a process for humanizing the monoclonal antibody of the invention.

Abstract: The present application concerns concentrated protein formulations with reduced viscosity, which are particularly suitable for subcutaneous administration. The application further concerns a method for reducing the viscosity of concentrated protein formulations.

Abstract: The invention relates to antibodies, including monoclonal and polyclonal, or fragments thereof, which discriminate between the histidine and tyrosine isoforms of Complement Factor H and to their use in diagnostic methods and therapeutic treatments relating to Complement Factor H mediated diseases.

Abstract: The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of A? in the brain of a patient. Preferred agents include antibodies, e.g., humanized antibodies.

Abstract: The invention relates to antibodies which are directed against the FSAP Marburg I variant and to their preparation and use, in particular in therapy and diagnosis. The antibodies are characterized by the fact that they bind specifically to the FSAP MR I variant but not to the FSAP wild-type protein or other mutant variants which are characterized by amino acid substitutions at other positions in the FSAP protein.

Abstract: A method for conveniently detecting binding between the von Willebrand factor and glycoprotein Ib and a means to be used therein. The von Willebrand factor fixed in a reactor immobilized in a reaction vessel in the presence of bottrocetin is bound to a chimeric protein constructed by fusing the carboxyl terminal of a partial protein containing the von Willebrand factor-binding site of glycoprotein Ib with the amino terminal of the Fc region of an immunoglobulin molecule. Then the Fc region of the above immunoglobulin molecule is detected to thereby detect the binding between the von Willebrand factor and the glycoprotein Ib or inhibition of this binding.

Abstract: Disclosed are binding molecules which are recombinant polypeptides containing: (i) a binding domain capable of binding a target molecule, and (ii) an effector domain having an amino acid sequence substantially homologous to all or part of a constant domain of a human immunoglobulin heavy chain; characterized in that the binding molecule is capable of binding the target molecule without triggering significant complement dependent lysis, or cell mediated destruction of the target, and more preferably wherein the effector domain is capable of specifically binding FcRn and/or Fc?RIIb. These are generally based on chimeric domains which are derived from two or more human immunoglobulin heavy chain CH2 domains domains. In preferred embodiments the regions 233-236, and 327-331, are modified, as are further residues to render the molecule null allotypic. Also disclosed are nucleic acids, host cells, production processes and materials, and uses. Pharmaceutical preparations are also disclosed.

Abstract: The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

Abstract: The present invention discloses anti-idiotypic antibodies and fragments thereof against inhibitory Factor VIII anti-bodies, said inhibitory antibodies having an affinity for the C2 domain of Factor VIII. The anti-idiotypic antibodies of the present invention are able to completely neutralise in vitro and in an in vivo mouse model the inhibitory activity of FVIII inhibitors. The anti idiotypic antibodies of the present invention can be applied for the prevention, treatment or reduction of bleeding disorders of hemophilia patients with inhibitory antibody against the C2 domain of Factor VIII.

Abstract: This invention relates to novel antibodies that bind with greater affinity to the factor VIIa/tissue factor (FVIIa/TF) complex than to tissue factor (TF) alone, do not compete for binding to TF with FVII and FX, an inhibit FX activation. The antibodies bind at the site of injury and prevent the initiation of thrombosis. The antibodies can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

Abstract: Lipoprotein Lipase like polypeptides, nucleic acids encoding said polypeptides, antisense sequences, and antibodies to said polypeptides are disclosed. Also disclosed are methods for the preparation of said polypeptides in a recombinant system and for the use of said polypeptides to screen for agonists and or antagonists of said polypeptides. Also disclosed are methods and compositions for the treatment of disorders of lipid metabolism.

Abstract: The present invention encompasses isolated antibodies, or fragments thereof, that are humanized variants of murine antibody 266 which employ complementarity determining regions derived from murine antibody 266. The variant antibodies are useful for treatment or prevention of conditions and diseases associated with A?, including Alzheimer's disease, Down's syndrome, cerebral amyloid angiopathy, mild cognitive impairment, and the like.

Abstract: It is intended to provide an antibody showing immunoreactivity selectively to ADAMTS-13 and applications of this antibody in epitope analysis or diagnosis of an ADAMTS-13 autoantibody-positive patient. Alternatively, it is intended to provide a process for producing and use of a modified ADAMTS-13 molecule partially deleted aiming at the application in pharmaceutical products. An antibody specific for ADAMTS-13 which can be obtained from a warm-blooded animal immunized and sensitized with a polypeptide containing a part or the whole of ADAMTS-13 amino acid sequence; a process for producing an antibody comprising a step of immunizing and sensitizing a warm-blooded animal with a polypeptide containing a part or the whole of ADAMTS-13 amino acid sequence; use of the above-described antibody including a method of detecting and purifying ADAMTS-13; and a modified ADAMTS-13 molecule partially deleted are provided.

Abstract: The present invention relates to methods and compositions for modulating platelet activity, and methods and compositions for treating a disease or disorder associated with platelet activity in a subject, comprising administering a single chain anti-TREM-like transcript-1 (TLT-1) antibody or a functional fragment or variant thereof in an amount effective to modulate platelet activity.

Abstract: The vascular endothelial growth factor (VEGF) activity in a patient's bloodstream or other biological sample can serve as a diagnostic and prognostic index for cancer, diabetes, heart conditions, and other pathologies. Antibody-sandwich ELISA method and kits for VEGF as an antigen were developed to detect VEGF levels in biological samples from animal models and human patients and are used as a diagnostic/prognostic index.

Abstract: The present invention relates to monoclonal antibodies binding to the N-terminal procollagen (III) propeptide (PIIINP) molecule which is a proteolytic fragment emanating from the specific cleavage of procollagen (III) by N-proteinase after exocytosis and to an assay using these antibodies.

Abstract: In the serum, PSP94 occurs as a free form or is associated with a carrier protein. PSP94 in its bound form has been quantified in the blood of prostate cancer patients and these measurements have shown utility as evaluation or prognosis of prostate cancer. Diagnostic assays, methods, and kits for detecting a free form of PSP94, and reagents such as antibodies able to bind to a free form of PSP94 are disclosed herein.

Abstract: The invention relates to high affinity human monoclonal antibodies, particularly those directed against isotypic determinants of immunoglobulin E (IgE), as well as direct equivalents and derivatives of these antibodies. These antibodies bind to their respective target with an affinity at least 100 fold greater than the original parent antibody. These antibodies are useful for diagnostics, prophylaxis and treatment of disease.

Abstract: The present invention provides anti-aPC antibodies that suppress the inactivation of activated protein C (aPC), and uses thereof. The present inventors screened anti-aPC antibodies, and succeeded in isolating anti-aPC antibodies comprising the activity of suppressing aPC inactivation in blood. The antibodies of the present invention can be used to maintain aPC activity by suppressing aPC inactivation, and can thus be used to sustain aPC bioactivities, such as the activity of suppressing activation of the blood coagulation system, and anti-inflammatory activity. In addition, the present invention provides uses of the antibodies of the present invention in aPC therapy for diseases such as thrombosis and sepsis. The therapeutic effect of aPC can be prolonged in treatment that uses aPC administration by allowing an antibody of the present invention to bind with aPC. The antibodies of the present invention can be used in the treatment and prevention of diseases such as thrombosis and sepsis.

Abstract: The present invention relates generally to immunointeractive molecules and more particularly antibodies which bind to vascular endothelial growth factor-B (VEGF-B) or its functional or structural equivalent and inhibit the biological activity of VEGF-B. In particular, the present invention relates to deimmunized such as humanized or human antibodies that bind to VEGF-B and inhibit the biological activity of VEGF-B. These antibodies have uses in the treatment or prevention of diseases associated with perturbations in normal vasculogenesis or angiogenesis or vascular remodelling. The present invention further contemplates a method of modulating diseases associated with perturbations in normal vasculogenesis or angiogenesis or vascular remodelling by the administration of the subject antibodies. The present invention further provides an assay system useful for identifying antibodies which bind to VEGF-B and block the biological activity of VEGF-B.

Abstract: A tissue factor antibody which binds to non-human tissue factor and is useful as a surrogate in preclinical testing where the human therapeutic tissue factor candidate antibody does not interact with the homolog target protein in a manner that would provide meaningful information about treatment efficacy or safety.

Abstract: The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of ?-amyloid proteins.

Abstract: The present invention provides compositions and methods for regulating the alternative complement pathway.

Abstract: The present invention is based on the finding that plasma cell disorders such as Multiple Myeloma and Monoclonal Gammopathy of Unknown Significance are characterized by an increase in the expression of JAG2. Accordingly, the present invention provides a method for diagnosis of plasma cell disorders by detecting the expression or overexpression of JAG2. The expression or overexpression of JAG2 may be detected as increased mRNA transcripts or increased protein.

Abstract: For the effective treatment of diseases such as cancer in which hIGF participates, there have been desired to be developed antibodies which strongly bind to both factors hIGF-I and hIGF-II and inhibit their functions and fragments of these antibodies. The present invention provides antibodies which have the ability to specifically bind to human IGF-I and IGF-II to thereby inhibit the functions of human IGF-I and IGF-II and have binding activity with a binding constant of 5×109 M?1 or more measured with a biosensor BIACORE. In addition, the present invention provides diagnostics, preventives and remedies for an hIGF-mediated disease and a disease showing pathological progressing due to abnormally promoted hIGF production, which use said antibodies.

Abstract: The invention concerns anti-tissue factor (anti-TF) antibodies with enhanced anticoagulant potency, and methods and means for identifying, producing and using such antibodies. The anti-TF antibodies of the present invention are designed to comprise a region binding to an epitope in the C-terminal macromolecular substrate binding region of TF.

Abstract: The invention relates to inhibitors that bind to C5 and C5a, but which do not prevent the activation of C5 and do not prevent formation of or inhibit the activity of C5b. One example of such an inhibitor molecule is the monoclonal antibody designated MAb137-26, which binds to a shared epitope of human C5 and C5a. These inhibitors may be used to inhibit the activity of C5a in treating diseases and conditions mediated by excessive or uncontrolled production of C5a. The inhibitor molecules are also useful for diagnostic detection of the presence/absence or amount of C5 or C5a.

Abstract: The present invention is related to antibodies directed to the antigen properdin and uses of such antibodies. In particular, in accordance with the present invention, there are provided fully human monoclonal antibodies directed to the antigen properdin. Nucleotide sequences encoding, and polypeptides comprising, heavy and light chain immunoglobulin molecules, particularly sequences corresponding to contiguous heavy and light chain sequences spanning the framework regions and/or complementarity determining regions (CDR's), specifically from FR1 through FR4 or CDR1 through CDR3, are provided. Hybridomas or other cell lines expressing such immunoglobulin molecules and monoclonal antibodies are also provided.

Abstract: The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Abstract: There are provided uses of an antibody directed to CX3CR1 and fractalkine. Killer lymphocytes can be readily identified, eliminated and separated by using an anti-CX3CR1 antibody. Further, there can be provided an antibody drug for suppressing chemotaxis and cytotoxic activity of killer lymphocytes by suppressing an interaction between CX3CR1 and fractalkine.

Abstract: The present invention is directed to recombinant human antibodies specific for Cn2 toxin from C. noxius scorpion venom. The antibodies are able to recognize the toxin and preferably neutralize it as well as the whole venom of C. noxius scorpion. This invention is also directed to a human non-immune phage display library. One clone that specifically binds the Cn2 toxin was affinity matured by directed evolution. Three cycles of maturation were performed and several scFv clones were isolated which specifically recognize toxin Cn2 with increased Kd of 446 fold. All variants were monomeric and only variants 6009F, 6105F and 6103E showed to be capable of neutralizing toxin Cn2 and the whole venom. Variant 6009F recognizes a different epitope than that of BCF2, a murine monoclonal antibody raised against scorpion toxin Cn2 which is also capable of neutralizing both Cn2 toxin and the whole venom when tested in mice, as well as that of commercially available polyclonal antibody fragments antivenom from horse.

Abstract: A polynucleotide, comprising a contiguous nucleotide sequence coding for a human antibody with factor VIII specificity, or complementary to a nucleotide sequence coding for a human antibody for factor VIII specificity, or capable of selectively hybridizing under stringent conditions to such nucleotide sequence. Such polynucleotide may be used as a probe or primer for detection of factor VIII inhibitors, or be used for producing a recombinant polypeptide. A polypeptide, comprising a contiguous amino acid sequence corresponding to or mimicking a fragment or derivative of a human antibody with factor VIII specificity capable of specific binding to factor VIII. An antibody, comprising a recombinant human antibody with factor VIII specificity or an anti-idiotypic antibody directed against a human antibody with factor VIII specificity. Pharmaceutical compositions which contain such polypeptide or antibody.

Abstract: The invention provides for the isolation, identification, synthesis, expression and purification of antibodies reactive with factor IX (FIX)/factor IXa (IXa). In particular aspects, the invention provides human antibodies reactive with the human FIX Gla domain. The invention further provides compositions especially pharmaceutical compositions, articles of manufacture, and methods of inhibiting the activation of FIX and inhibiting FIX/IXa dependent coagulation.

Abstract: The invention relates to a monoclonal antibody or antigen binding fragment thereof having binding specificity for ouabain, wherein the antibody or antigen binding fragment does not crossreact with digoxin. Preferably the anti-ouabain monoclonal antibody can bind ouabain with an affinity of at least about 10?7M, preferably 10?8M, and more preferably 10?9M. The invention also relates to diagnostic and therapeutic uses of the monoclonal antibodies described herein.

Abstract: It is intended to provide an antibody efficacious in diagnosing, preventing or treating Alzheimer's disease, DNA encoding the antibody, a method of screening a drug and drugs. The amino acid sequence and the gene sequence of the variable region of an antibody, which specifically recognizes a GM1 ganglioside-bound amyloid ?-protein occurring in the early stage of ?-amyloid fibril formation, are determined. Based on the data of the amino acid sequence and the gene sequence thus obtained, an antibody is designed.

Abstract: The invention provides a grafted antibody, or functional fragment thereof, comprising one or more complementarity determining regions (CDRs) having at least one amino acid substitution in one or more CDRs of a heavy chain CDR, where the grafted antibody or functional fragment thereof has specific binding activity for a cryptic collagen epitope. The invention also provides methods of using an antibody having specific binding activity for a cryptic collagen epitope, including methods of inhibiting angiogenesis, tumor growth, and metastasis.

Abstract: The invention features hK1 binding polypeptides as well as compositions comprising such polypeptides and methods of making and using such polypeptides.

Abstract: Anti-thrombotic agents containing humanized antibodies which bind to von Willebrand factor.

Abstract: Ligands such as antibodies that can bind factor IX/factor IXa and increase the procoagulant activity of factor IXa (FIXa), pharmaceutical compositions containing such ligands, methods for treating patients afflicted with blood coagulation with such ligands, and a nucleic acid that encodes, or a cell that expresses such ligands, are provided.

Abstract: A method of inhibiting microvascular bleeding is provided. Antibody to protein C administered to a patient in a pharmaceutically acceptable carrier prevents anticoagulation by greater than 90% of activated protein C in human plasma.

Abstract: The use of compounds that block complement component C5 or its active fragments C5a and/or C5b (such compounds collectively referred to as “C5 blockers”) to treat established joint inflammation (arthritis) is disclosed. Administration of such C5 blockers has been found to: 1) arrest and/or reduce inflammation in joints which are already inflamed, and 2) inhibit the spread of inflammation to unaffected joints.

Abstract: An antibody or antibody derivative against factor IX/activated factor IX (FIXa) which increases the procoagulant activity of FIXa.

Abstract: The invention relates to methods and products for regulating lectin complement pathway associated complement activation. The methods include both in vitro and in vivo methods for inhibiting lectin complement pathway associated complement activation. The methods are accomplished by contacting a mammalian cell having surface exposed MBL ligand with an effective amount of a mannan binding lectin inhibitor to inhibit lectin complement pathway associated complement activation. The mannan binding lectin inhibitor may be administered to a subject to prevent cellular injury mediated by lectin complement pathway associated complement activation. The products of the invention include compositions of a mannan binding lectin inhibitor. The mannan binding lectin inhibitor is an isolated mannan binding lectin binding peptide that selectively binds to a human mannan binding lectin epitope and that inhibits lectin complement pathway associated complement activation.

Abstract: The present invention relates to antibodies which, in agueous solution, selectively bind to a transferrin-homologous carbohydrate deficient transferrin (CDT) without the latter needing to be bound to a solid phase. CDT is characterized by at least one of the two oligosaccharide chains which are normally bound to Asn 413 and/or Asn 611 of transferrin being entirely or substantially entirely lacking.

Abstract: This invention relates to novel fusion proteins which are comprised of a targeting protein that binds tissue factor (TF), which is operably linked to the thrombomodulin (TM) EGF456 domain alone or in combination with at least one other TM domain selected from the group consisting of the N-terminal hydrophobic region domain, the EGF123 domain, the interdomain loop between EGF3 and EGF4, and the O-glycosylated Ser/Thr-rich domain, or analogs, fragments, derivatives or variants thereof. The fusion protein binds at the site of injury and prevents the initiation of thrombosis. The fusion protein can be used to treat a variety of thrombotic conditions including but not limited to deep vein thrombosis, disseminated intravascular coagulation, and acute coronary syndrome.

Abstract: The present invention relates to identification of polypeptides useful for generating antibodies specific for non-human IgE, particularly equine IgE. The invention, therefore, also relates to antibodies that specifically bind to IgE and methods to detect IgE using the antibodies. The invention also provides a kit for detection of IgE.