AGONISTI ANTIBODIES AGAINST THE THROMBOPOIETINREZEPTOR AND THEIR THERAPEUTIC USES

USE OF POLYKLONALEN ANTI- HIV GOAT SERUMS AS THERAPEUTIC MEANS

MODULATION NEUROTROPHINAKTIVITÄT; SCREENINGSVERFAHREN

POLYPEPTIDE WITH AN ACTIVITY OF THE HUMAN BETA ANDRENERGI RECEPTOR, INCLUDED THEIR NUCLEUS NSA YOUR SEQUENCES INTO THE LIPOLYTI ANSWER.

POLYPEPTIDE WITH DOPAMINERGER RECEPTOR ACTIVITY, FOR IT CODING NUCLEIC ACIDS AND YOUR USE

PROTEIN G COUPLED GLOW AMINE ACID RECEPTORS

MHC class I epitope delivering polypeptides

The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD 8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin- derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. 5 The present invention provides cell-targeted, CDS+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capabl e of delivering one or more 10 heterologous T- cell epitopes to the MHC class I presentation pathway, including polypeptides which are I ) B- cell and/or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and/or 3) comprises toxin effectors which retain toxin functions ...

Anti-Sortilin antibodies and methods of use thereof

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, affinity-matured, humanized antibodies, antibody fragments, etc., that specifically bind a Sortilin protein, e.g., human Sortilin or mammalian Sortilin, and have improved and/or enhanced functional characteristics, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof. 11769710_1 (GHMaers) P112218.AU ...

FUNCTIONAL INTERACTIONS BETWEEN GLIAL S-100B AND CENTRAL NERVOUS SYSTEM SEROTONERGIC NEURONS

G PROTEIN-COUPLED GLUTAMATE RECEPTORS

MHC class I epitope delivering polypeptides

The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD 8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin- derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capabl e of delivering one or more heterologous T- cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1 ) B- cell and/or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and/or 3) comprises toxin effectors which retain toxin functions.

Novel dual-targeted protein specifically binding to DLL4 and VEGF, and use thereof

The present invention relates to a dual-targeted protein comprising: a novel protein specifically binding to delta like ligand 4 (DLL4); and an antibody specifically binding to a vascular endothelial cell growth factor (VEGF).

Binding agonists for treatment of neurological and other disorders

The present invention relates to TrkB binding agonists, and to the use of such agonists in the treatment of neurological disorders and other disorders. The present invention also relates to specific TrkB binding agonists comprising CDRs, variable regions, heavy and light chains, and variant sequences thereof.

METHOD OF DIAGNOSING A NEURODEGENERATIVE DISEASE

The present invention provides a method for diagnosing a neurodegenerativ e disease or for determining the predisposition of a subject to a neurodegen erative disease. In particular, the methods of the present invention compris e detecting a marker linked to map position 9p21, e.g., a marker within an o pioid receptor sigma 1 (OPRS1) gene or an expression produce thereof. The pr esent invention also provides a method for identifying new markers that are associated with a neurodegenerative disease. The present invention also prov ides mutant forms of an OPRS1 gene or an expression product thereof and reag ents for detecting those mutations.

GPCR HETEROMER INHIBITORS AND USES THEREOF

This invention relates to inhibitors of CXC receptor 4 (CXCR4)-G protein-coupled receptor (GPCR) heteromers (CXCR4-GPCR heteromers) associated with cancers, where CXCR4 forms a functional heteromer with other G protein-coupled receptors (GPCRx). More specifically, this invention relates to GPCRx that form heteromers with CXCR4, which upon co-stimulation with CXCR4 agonists and GPCRx agonists leads to enhanced signaling downstream of CXCR4. This invention also provides for the use of inhibitors of the interacting GPCR partner of the CXCR4-GPCRx heteromer or CXCR4-GPCRx heteromer-specific inhibitors including inhibitors of the formation of the CXCR4-GPCRx heteromer and CXCR4-GPCRx heteromer-specific antibodies, and in the diagnosis and/or therapy for cancer.

AGENTS, USES AND METHODS FOR TREATMENT

The present invention relates to monoclonal anti-Sortilin antibodies which have been found useful in correcting a deficient level of progranulin (PGRN). In particular, these antibodies can be used in the treatment of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders such as Alzheimers disease (AD).

PROTEINS COMPRISING AMINO-TERMINAL PROXIMAL SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS AND CELL-TARGETING IMMUNOGLOBULIN-TYPE BINDING REGIONS

The present invention provides proteins comprising immunoglobulin-type binding regions for cell-type specific targeting and Shiga toxin A Subunit effector regions for Shiga toxin effector functions (e.g. cellular internalization, directing subcellular routing, and/or cytotoxicity), wherein binding regions and Shiga toxin effector regions are combined such that the Shiga toxin effector regions are proximal to amino-terminals of the proteins. The presently disclosed proteins can comprise additional exogenous materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, and are capable of targeted delivery of these additional exogenous materials into interiors of target cells. The proteins of present invention have uses in methods such as, e.g., methods involving targeted killing of target cells, delivering exogenous materials into target cells, labeling subcellular compartments of target cells, and diagnosing and/or treating a variety of conditions including cancers ...

NOVEL DUAL-TARGETING PROTEIN BINDING SPECIFICALLY TO DLL4 AND VEGF AND USE THEREOF

The present invention relates to a dual-targeted protein comprising: a novel protein specifically binding to delta like ligand 4 (DLL4); and an antibody specifically binding to a vascular endothelial cell growth factor (VEGF).

DE-IMMUNIZED SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES FOR APPLICATIONS IN MAMMALS

The present invention relates to Shiga toxin effector polypeptides with reduced antigenic and/or immunogenic potential. Immunogenicity can be a limitation for the repeated administration to mammals of proteins and polypeptides derived from Shiga toxins. The Shiga toxin effector polypeptides of the present invention have uses as components of therapeutics, diagnostics, and immunization materials. The cytotoxic proteins of the present invention have uses for selective killing of specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, immune disorders, and microbial infections. The proteins of the present invention also have uses for detecting specific cell types, collecting diagnostic information, and monitoring the treatment of a variety of diseases, such as, e.g., cancers, immune disorders, and microbial infections.

GASTRIN RELEASING PEPTIDE RECEPTOR

... 2067766 9106647 PCTABS00005 The gastrin releasing peptide receptor is solubilized and purified in an active form. The amino acid sequence and DNA encoding the receptor are provided.

POLYPEPTIDES WITH A DOPAMINERGIC RECEPTOR ACTIVITY; NUCLEIC ACIDS CODING FOR THESE POLYPEPTIDES AND USE OF THE LATTER FOR SCREENING ACTIVE SUBSTANCES ON SAID POLYPEPTIDES

L'invention a pour objet de nouveaux polypeptides ayant une activité de récepteur dopaminergique contenant: la séquence de 446 acides aminés de la Figure 1, ou un fragment de cette séquence, ce fragment étant tel que, soit il en contient néanmoins les sites contenus dans cette séquence et dont la présence est nécessaire pour que, lorsque ce fragment est exposé à la surface d'une cellule, il soit capable de lier l a dopamine a ses agonistes ou antagonistes de que de manière spécifique et mesurable, par exemple au moyen d'un ligand radioactif, soit il est susceptible d'être reconnu par des anticorps qui reconnaissent également la susdite séquence de 446 acides aminés, mais n e reconnaissent ni le récepteur dopamineregique D-1, ni le récepteur dopaminergique D-2, soit il est susceptible de générer des anticorps reconnaissant la susdite séquence de 446 acides aminés mais ne reconnaissant ni le récepteur dopaminergique D-1, ni l e récepteur dopaminergique D-2.

ANTIBODIES AGAINST SORTILINA AND METHODS OF THEIR APPLICATION

MEANS, TRACK APPLICATION AND METHODS OF TREATMENT

THERAPEUTIC AGENT

proteìnas moduladoras de receptores de glutamato e moléculas de ácidos nucléicos e aplicações das mesmas

VANILLOID RECEPTOR-2 LIGANDS FOR TREATING ANXIETY OR DEPRESSION

The present invention relates to the use of a compound selected from: (a) a VR2 polypeptide; (b) a compound which modulates the activity of a VR2 polypeptide; (c) a polynucleotide encoding a VR2 polypeptide; or (d) an antisense polynucleotide to a polynucleotide encoding a VR2 polypeptide, for the manufacture of a medicament for treating anxiety and/or depression, circadian rhythm disorders, pre-term labor, erectile dysfunction, hypertension and/or schizophrenia.

TARGETING THE NEUROMUSCULAR JUNCTION FOR TREATMENT

Compositions and methods for targeting therapeutic agents to neuromuscular junctions are disclosed. Also disclosed are methods for treating diseases and conditions affecting the neuromuscular junction. Compositions include a neuromuscular junction targeting peptide coupled to a therapeutic agent. Compositions may further include a linker peptide. Methods for targeting therapeutic agents to neuromuscular junctions and treating diseases and conditions affecting the neuromuscular junction include administering a composition including a neuromuscular junction targeting peptide coupled to a therapeutic agent.

THERAPEUTIC AGENT

Anti-HLA and other antibodies are present in goat serum after injection of HIV antigenic material, and form the basis for a most surprisingly effective treatment of HIV, multiple sclerosis and other conditions.

DOPAMINE RECEPTORS AND GENES

A mammalian D2 dopamine receptor gene has been cloned. Thus, DNA sequences encoding all or a part of the dopamine receptor are provided, as well as the corresponding polypeptide sequences and methods for producing the same synthetically and via expression of a corresponding sequence from a host transformed with a suitable vector carrying the corresponding DNA sequence. The various structural information provided by this invention enables the preparation of labeled or unlabeled immunospecific species, particularly antibodies, as well as nucleic acid probes labeled in conventional fashion. Pharmaceutical compositions and methods of using various products of this invention are also provided.

VACCINES FOR PREVENTING MENINGOCOCCAL INFECTIONS

The present invention stems from the finding that the interaction between the β2 adrenoceptor (β2AP) and type IV pilus-associated proteins initiates a process leading to the opening of the blood brain barrier. The invention therefore pertains to a vaccine for preventing the spreading of meningococci into the meningeal space, wherein said vaccine allows the production of antibodies inhibiting the interaction between the type IV pilus-associated proteins and the β2AP.

Diagnosis and therapy of multiple sclerosis

The serotonin receptor 5HT2A (5HT2aR) and membrane NADPH oxidases (NOX enzymes) are found to be a target of autoantibodies present in Multiple Sclerosis patients. The present invention refers to peptides comprised in the extracellular regions of the human 5HT2aR and/or NOXs for diagnosis and therapy of Multiple Sclerosis.

Anti-sortilin antibodies and methods of use thereof

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, humanized antibodies, antibody fragments, etc., that specifically bind on or more epitopes within a Sortilin protein, e.g., human Sortilin or a mammalian Sortilin, and use of such compostions in preventing, reducing risk, or treating an individual in need thereof.

INTEGRAL MEMBRANE PROTEIN DISPLAY ON POXVIRUS EXTRACELLULAR ENVELOPED VIRIONS

This disclosure provides compositions and methods for expressing and displaying isolated integral membrane proteins (IMPs) or fragments thereof in a native conformation for use in the screening, selecting, and identifying of antibodies or antibody-like molecules that bind to a target IMP of interest.

METHOD

НОВЫЕ БЕЛКИ, СПЕЦИФИЧНО СВЯЗЫВАЮЩИЕСЯ С ДВУМЯ МИШЕНЯМИ -DLL4 И VEGF-, И ИХ ПРИМЕНЕНИЕ

Изобретение относится к области биохимии. Описана группа изобретений, включающая антитело, направленное на две мишени, которое специфически связывается с VEGF и DLL4, полинуклеотид, кодирующий вышеуказанное антитело, экспрессионный вектор, включающий полинуклеотид, трансформированную клетку СНО для экспрессии вышеуказанного антитела, способ получения вышеуказанного антитела, фармацевтическую композицию для лечения рака, содержащую терапевтическое эффективное количество антитела, композицию для диагностики рака, способ диагностирования рака и способ лечения рака, включающий этап введения вышеуказанного антитела. В одном из представлений антитело специфически связывается с конформационным эпитопом DLL4, содержащим аминокислотные остатки с 58-го по 65-й и со 110-го по 115-й аминокислотной последовательности белка DLL4, представленного в SEQ ID NO: 21, и антитело специфически связывается с VEGF. Изобретение расширяет арсенал антител, связывающихся с VEGF и DLL4. 9 н. и 8 з.п. ф-лы, 12 ил., ...

ВЕЩЕСТВА И СПОСОБЫ ДЛЯ ПРИМЕНЕНИЯ ПРИ ПРЕДУПРЕЖДЕНИИ И/ИЛИ ЛЕЧЕНИИ БОЛЕЗНИ ГЕНТИНГТОНА

Изобретение относится к области биотехнологии, конкретно к получению иммуногенных полипептидов HTT, и может быть использовано в медицине. Полученные иммуногенные полипептиды HTT могут быть использованы для создания вакцины против HTT и получения антител к HTT, используемых в эффективном лечении болезни Гентингтона или отсрочки начала ее клинических симптомов путем иммунизации. 9 н. и 11 з.п. ф-лы, 29 ил., 9 пр.

ДИСПЛЕЙ ИНТЕГРАЛЬНОГО МЕМБРАННОГО БЕЛКА НА ВНЕКЛЕТОЧНЫХ ОБОЛОЧЕЧНЫХ ВИРИОНАХ ПОКСВИРУСА

Настоящее изобретение относится к биотехнологии, в частности к композициям и способам экспрессии и получения выделенных интегральных мембранных белков (IMP) или их фрагментов в нативной конформации для применения в скрининге, селекции и идентификации антител или антителоподобных молекул, которые связываются с представляющей интерес IMP-мишенью. 6 н. и 28 з.п. ф-лы, 10 ил., 1 табл., 9 пр.

DNS, DIE FÜR MENSCHLICHE 5-HT 1D REZEPTOREN KODIERT, UND VERWENDUNGEN DAVON

POLYPEPTIDE MIT EINER AKTIVITÄT DES MENSCHLICHEN BETA-ANDRENERGISCHEN REZEPTORS, EINBEZOGEN IN DIE LIPOLYTISCHE ANTWORT, DEREN NUKLEINSÄURESEQUENZEN.

DOPAMINE RECEPTORS AND GENES

HUMAN METABOTROPI GLUTAMATREZEPTOR UNTERTYPE HMGLUR7 AND USED DNS CONNECTIONS

FOR the HUMAN SUBUNIT 5-HT3-C of the SEROTONINREZEPTORS 5-HT3 CODING DNA

Treating inflammatory disorders with antibodies to the alpha-7 nicotinic receptors

Lrp4/Corin dopamine-producing neuron precursor cell marker

Vip2 (vasoactive intestinal polypeptide) receptor

SOLUBILIZATION AND PURIFICATION OF THE GASTRIN RELEASING PEPTIDE RECEPTOR

DNA ENCODING HUMAN 5-HT 1D RECEPTORS AND USES THEREOF

Antibodies that bind to Sortilin and inhibit the binding of progranulin

The present invention relates to monoclonal anti-Sortilin antibodies which have been found useful in correcting a deficient level of progranulin (PGRN). In particular, these antibodies can be used in the treatment of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS).

Methods for detecting prostate cancer

The present disclosure relates to methods for detecting a prostate cancer. Certain embodiments of the present disclosure provide a method of detecting a prostate cancer in a subject, the method comprising detecting a marker selected from an endosomal associated marker and/or a lysosomal associated marker from the subject.

MUTATION ASSOCIATED WITH EPILEPSY

An isolated mammalian DNA molecule encoding a mutant .gamma.-aminobutyric acid (GABA) receptor subunit, wherein a mutation event selected from the group consisting of point mutations, deletions, insertions and rearrangements has occurred and said mutation event disrupts the functioning of an assembled GABA receptor, or an otherwise functional fragment or homologue thereof.

METABOTROPIC GLUTAMATE RECEPTOR 7(MGLUR7)-BINDING ANTIBODY

The present invention provides an antibody directed to an epitope of a G -protein coupled receptor, wherein the antibody binds to the extracellular N terminal region of the receptor and the binding of the antibody to the G - protein coupled receptor induces receptor internalization in cells, wherein the receptor is metabotropic glutamate receptor 7 (mGluR7) and wherein the antibody is produced by hybridoma cell line deposited with DSMZ as DSM ACC2855.

HEPATITIS C VIRUS INHIBITORS

The present invention aims to provide hepatitis C virus inhibitors capable of inhibiting viral replication in hepatitis C virus-infected cells. The replication of hepatitis C virus can be inhibited and hepatitis C virus-infected cells can be specifically injured by specifically inhibiting BGT-1 or AKR1C1 involved in the replication of hepatitis C virus. Thus, viral inhibitors comprising a substance inhibiting BGT-1 or AKR1C1 are effective for the treatment of hepatitis C.

HEPATITIS C VIRUS INHIBITORS

The present invention aims to provide hepatitis C virus inhibitors capable of inhibiting viral replication in hepatitis C virus-infected cells. The replication of hepatitis C virus can be inhibited and hepatitis C virus-infected cells can be specifically injured by specifically inhibiting BGT-1 or AKR1C1 involved in the replication of hepatitis C virus. Thus, viral inhibitors comprising a substance inhibiting BGT-1 or AKR1C1 are effective for the treatment of hepatitis C.

METHODS FOR THE PREVENTION AND/OR TREATMENT OF MEMORY IMPAIRMENT

The present invention relates to methods for the prevention and/or treatment of memory impairment and for improving memory and particularly to methods for the prevention and/or treatment of memory impairment and improving memory comprising administering an agent that decreases activity of a GABAA receptor. The present invention also relates the use of an agent that decreases activity of a GABAA receptor for preventing or treating a memory deficit and for improving memory.

METHODS FOR THE PREVENTION AND/OR TREATMENT OF MEMORY IMPAIRMENT

The present invention relates to methods for the prevention and/or treatment of memory impairment and for improving memory and particularly to methods for the prevention and/or treatment of memory impairment and improving memory comprising administering an agent that decreases activity of a GABAA receptor. The present invention also relates the use of an agent that decreases activity of a GABAA receptor for preventing or treating a memory deficit and for improving memory.

HUMAN METABOTROPIC GLUTAMATE RECEPTOR SUBTYPES (HMR4, HMR6, HMR7) AND RELATED DNA COMPOUNDS

The present invention relates to human metabotropic glutamate receptor (hmGluR) proteins, isolated nucleic acids coding therefor, host cells producing the proteins of the invention, methods for the preparation of such proteins, nucleic acids and host cells, and uses thereof. Furthermore, the invention provides antibodies directed against the hmGluR proteins.

AGONIST ANTIBODIES TO THE THROMBOPOIETIN RECEPTOR, AND THEIR THERAPEUTIC USES

Various forms of c-mpl agonist antibodies are shown to influence the replication, differentiation or maturation of blood cells, especially megakaryocytes and megakaryocyte progenitor cells. Accordingly, these compounds may be used for treatment of thrombocytopenia.

ПРИМЕНЕНИЕ КОЗЬЕЙ СЫВОРОТКИ, ПОЛУЧЕННОЙ ИММУНИЗАЦИЕЙ КОЗЫ ВИЧ, ДЛЯ ИЗГОТОВЛЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВ

Анти-HLA- и другие антитела, присутствующие в сыворотке козы после введения материала ВИЧ-антигена, и основа, входящая в состав для наиболее эффективного лечения ВИЧ, рассеянного склероза и других заболеваний.

ANTIBODIES AGAINST SORTILINA AND METHODS OF THEIR APPLICATION

ANTIBODIES, THAT BIND WITH SORTILINOM AND INHIBIT BINDING PROGRANULINA

BINDING AGONISTS FOR TREATMENT OF NEUROLOGICAL AND OTHER DISORDERS

SEQUENCES CODING FOR RECEIVER MURINE BETA 3-ADRENERGIQUE, LEURUTILISATION LIKE PROBES AND FOR the PEPTIDE VECTORS EXPRESSION, HOTESCELLULAIRES CONTAINING THE AFOREMENTIONED VECTOR, AND APPLICATIONS OF THE AFORESAID PEPTIDES

POLYPEPTIDES HAVING an ACTIVITY OF RECEIVER (BETA) - ADRENERGIQUE AT the MAN, IMPLY IN the LIPOLYTIC ANSWER, NUCLEIC ACIDS CODING FOR THESE POLYPEPTIDES AND USE OF THESE POLYPEPTIDES FOR the SIFTING OF ACTIVE SUBSTANCE ON THESE POLYPEPTIDES

AN ANTIBODY BOUND SYNTHETIC VESICLE CONTAINING ACTIVE AGENT MOLECULES

A process is provided of delivering at least one active agent cargo molecule into an neuronal cell whereby a cargo molecule is placed within a synthetic vesicle such as a liposome and a biotinylated protein such as an antibody is bound to the synthetic vesicle to form a protein bound synthetic vesicle whereby the protein recognizes a receptor expressed on the surface of a neuronal cell, and exposing the protein bound synthetic vesicle to the cell until the cargo molecule is delivered into the neuronal cell. Numerous cargo molecules are delivered by the inventive synthetic vesicle including a calpain inhibitor and a caspase inhibitor. The protein illustratively targets a cellular receptor for a ligand such as glutamate, glycine, dopamine, nicotine, muscarine, acetylcholine, or serotonin, and the like.

ANTIBODY DIRECTED TO G PROTEIN COUPLED RECEPTORS (GPCR)

The present invention provides an antibody directed to an epitope of a G - protein coupled receptor, wherein the antibody binds to the extracellular N - terminal region of the receptor and the binding of the antibody to the G - protein coupled receptor induces receptor internalization in cells.

DNA ENCODING A HUMAN SUBUNIT 5-HT3-C OF THE 5-HT3 SEROTONIN RECEPTOR

Un ADN codant la 5-HT3-C humaine a été cloné et caractérisé. La protéine recombinée est capable de former une protéine bioactive humaine de 5-HT3-C. L'ADNc a été exprimé dans des cellules hôtes recombinées produisant des protéines recombinées actives. De plus, les cellules hôtes recombinées sont utilisées pour établir une méthode d'identification de modulateurs de l'activité du récepteur, et des modulateurs du récepteur sont identifiés.

Method for identifying a G protein coupled glutamate receptor agonist and antagonist

Mammalian G protein coupled glutamate receptors are identified, isolated and purified. The receptors have been cloned, sequenced and expressed by recombinant means. The receptors and antibodies thereby may be used to identify agonists and antagonists of G protein coupled glutamate receptor mediated neuronal excitation, as well as in methods of diagnosis.

ANTIBODIES WHICH BIND TYPE I CANNABINOID RECEPTOR/ANGIOTENSIS II RECEPTOR HETEROMERS

Compounds and compositions useful for the treatment of liver diseases and methods of treating liver diseases are disclosed. The compounds of the invention specifically interact with heteromers of cannabinoid receptors as compared to monomers or homodimers. The invention also relates to methods of screening for compounds useful for the treatment of liver diseases and to methods of screening for diacylglycerol lipase inhibitors.

AGONIST ANTIBODIES TO THE THROMBOPOIETIN RECEPTOR, AND THEIR THERAPEUTIC USES

ВЕЩЕСТВА И СПОСОБЫ ДЛЯ ПРИМЕНЕНИЯ ПРИ ПРЕДУПРЕЖДЕНИИ И/ИЛИ ЛЕЧЕНИИ БОЛЕЗНИ ГЕНТИНГТОНА

SOLUBILISIERUNG UND REINIGUNG DES REZEPTORS FÜR DAS GASTRIN-FREISETZENDE PEPTID

Method

HUMAN, METABOTROPE GLUTAMATREZEPTORSUBTYPEN (HMR6) AND USED DNS CONNECTIONS

Treatment of MS with goat serum

Method for reducing allergen-induced airway hyperresponsiveness

Agonist antibodies to the thrombopoietin receptor, and their therapeutic uses

Novel monoclonal antibody inhibitors targeting potassium channel KCNK9

The presently disclosed subject matter relates to antibodies, antibody fragments or derivatives thereof, which specifically bind to and/or interact with at least one epitope of the extracellular domain of the mammalian KCNK9 potassium channel, and to nucleic acid molecules encoding the same, as well as to vectors comprising said nucleic acid molecules. The presently disclosed subject matter provides methods for the preparation of said antibodies, antibody fragments or derivatives thereof, as well as pharmaceutical compositions, diagnostic compositions, and kits comprising the same. Compositions, kits, methods, and uses of the antibodies, antibody fragments or derivatives thereof for assessing for the presence of KCNK9 expressing cells, inhibiting KCNK9 activity in cells, inhibiting the growth or survival of KCNK9 expressing cells (e.g., cancer cells), inhibiting the growth and/or metastases of tumors, stimulating complement-dependent cancer cell cytotoxicity, and the treatment of cancer ...

Novel chimeric polypeptides for screening and drug discovery purposes

The present invention relates to novel polypeptides and their use for screening and drug discovery. More specifically, the invention provides chimeric polypeptides comprising a membrane protein, in particular a GPCR, fused to a binding domain, wherein the binding domain is directed against and/or specifically binds to said membrane protein. In particular, the chimeric polypeptides of the invention are single proteins wherein, in an intramolecular reaction, the binding domain stabilizes the membrane protein in a conformation of interest. Also provided are nucleic acid sequences encoding such chimeric polypeptides, cells capable of expressing such chimeric polypeptides as well as cellular compositions derived thereof. Also envisaged are screening methods for compounds using the chimeric polypeptides of the invention.

USE OF POLYCLONAL ANTI-HIV GOAT SERUM AS A THERAPEUTIC AGENT

Anti-HLA and other antibodies are present in goat serum after injection of HIV antigenic material, and form the basis for a most surprisingly effective treatment of HIV, multiple sclerosis and other conditions.

IGF-1R MONOCLONAL ANTIBODIES AND USES THEREOF

The present invention relates to conjugates including a chelating moiety of a metal complex thereof and a therapeutic or targeting moiety, methods for their production, and uses thereof. The present invention is directed to monoclonal antibodies that target the insulin-like growth factor-1 receptor and the radioimmunoconjugates thereof that demonstrate increased potency and enhance the excretion of a chelating moiety, or a metal complex thereof, when conjugated to a therapeutic moiety, a targeting moiety, or a cross-linking group. In another aspect, the invention features a pharmaceutical composition comprising a compound of the invention; and a pharmaceutically acceptable excipient. In another aspect, the invention features a method of radiation treatment planning and/or radiation treatment, the method comprising administering to a subject in need thereof a compound or pharmaceutical composition of the invention.

ANTI-SORTILIN ANTIBODIES AND METHODS OF USE THEREOF

The present disclosure is generally directed to compositions that include antibodies, e.g., monoclonal, chimeric, affinity-matured, humanized antibodies, antibody fragments, etc., that specifically bind a Sortilin protein, e.g., human Sortilin or mammalian Sortilin, and have improved and/or enhanced functional characteristics, and use of such compositions in preventing, reducing risk, or treating an individual in need thereof.

PROTEASE-CLEAVAGE RESISTANT, SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES AND CELL-TARGETED MOLECULES COMPRISING THE SAME

The present invention provides protease-cleavage resistant molecules comprising Shiga toxin effector polypeptides capable of exhibiting potent, Shiga toxin functions (e.g. subcellular routing and cytotoxicity). The present invention also provides protease-cleavage resistant, cell-targeted molecules for targeting specific cell types, e.g., infected or malignant cells. Certain molecules of present invention are cytotoxic, and certain cell-targeted molecules of present invention may be used for the targeted killing of specific cell types and treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections. Certain cell-targeted molecules of the invention exhibit improved, in vivo tolerability as compared to related cell-targeted molecules comprising protease-cleavage sensitive, wild-type, Shiga toxin effector polypeptides. The cell-targeted molecules of the invention can deliver additional materials, ...

TREATING INFLAMMATORY DISORDERS WITH ANTIBODIES TO THE ALPHA-7 NICOTINIC RECEPTORS

An antibody or an antigen binding fragment thereof which binds to mammalian .alpha.7 subunit of a nicotinic acetylcholine receptor or its functional variant and which is an agonist of said receptor or variant. Pharmaceutical compositions comprising same. A method of treating a subject suffering from an inflammatory condition comprising administering to said subject an antibody or an antigen-binding fragment as described herein.

DNA ENCODING HUMAN 5-HT1D RECEPTORS AND USES THEREOF

This invention provides isolated nucleic acid molecules encoding human 5-HT 1D receptors, isolated proteins which are human 5-HT 1D receptors, vectors comprising isolated nucleic acid molecules encoding human 5-HT 1D receptors, mammal- ian cells comprising such vectors, antibodies directed to the human 5-HT 1D receptors, nucleic acid probes useful for detect- ing nucleic acid encoding human 5-HT 1D receptors, antisense oligonucleotide s complementary to any sequences of a nucleic acid molecule which encodes a human 5-HT 1D p receptor, pharmaceutical compounds related to human 5-HT 1D p receptors, and nonhuman transgenic animals which express DNA a normal or a mutant human 5- HT 1D receptor. This invention fur- ther provides methods for determining ligand binding, detecting expression, drug screening, and treatment involving the hu- man 5-HT 1D receptor.

POLYPEPTIDES HAVING RECEPTOR ACTIVITY (Β) - ADRENERGIC IN HUMANS, INVOLVED IN THE LIPOLYTIC RESPONSE, NUCLEIC ACIDS ENCODING THE SAME AND USES THEREOF FOR SCREENING SUBSTANCES WHICH ACT ON THESE POLYPEPTIDES

Sequences encoding the receptor <T 354>murine 3 adrenergic, and in which their use as probes' expression of peptides, vectors, host cells containing said vector, and applications thereof

Séquences nucléotidiques codant pour le récepteur beta3-adrénergique (RAbeta3) murin, utilisation desdites séquences comme sondes et pour l'expression de peptides et/ou de fragments de ceux-ci ayant une activité de RAbeta3 murin, vecteurs utiles pour ladite expression, ainsi que les hôtes cellulaires contenant ledit vecteur. Anticorps polyclonaux et monoclonaux dirigés contre lesdits peptides et utilisables, notamment pour la détection de récepteurs beta3-adrénergiques murins, ainsi qu'un procédé de criblage de substances, à action agoniste ou antagoniste vis-à-vis des peptides ayant une action de récepteur beta3-adrénergique et des trousses ou kits pour la détection du degré d'affinité de différentes substances pour lesdits peptides à activité de récepteur beta3-adrénergique. Souris transgéniques et recombinantes contenant ladite séquence nucléotidique.

Lrp4/CORIN DOPAMINE-PRODUCING NEURON PRECURSOR CELL MARKER

A polynucleotide probe and antibody for detecting an Lrp4/Corin dopamine-producing neuron precursor cell marker by which dopamine-producing neuron precursor cells can be efficiently separated; and a method of selecting precursor cells by using the same. By using the expression of the Lrp4 in cells, cells suitable for the transplantation therapy for neurodegenerative diseases including Parkinson's disease can be selected while taking safety, survival ratio and network formation ability into consideration. © KIPO & WIPO 2007 ...

Polypeptides having a dopaminergic receptor activity, nucleic acids coding for these polypeptides and use of these polypeptides for the screening of substances active on these polypeptides

The invention is directed to novel polypeptides having dopaminergic receptor activity and nucleic acid sequences encoding these novel polypeptides. The novel polypeptides are useful as drugs and/or to screen other drugs that affect dopaminergic receptors. The nucleic acid sequences are useful as diagnostic agents and to prepare transformed cells and vectors expressing the novel polypeptides.

Anti-mGluR2 conformational single domain antibodies and uses thereof

The present invention relates to anti-metabotropic glutamate receptor subtype 2 (mGluR2) conformational single domain antibodies and uses thereof in particular in the therapeutic and diagnostic field.

AGENTS INHIBITING GRANULIN FOR TREATMENT OF CANCER

The disclosure provides agents that inhibit granulin signalling for use as medicaments to reduce cancer stem cell activity in the treatment of cancer. The disclosure also provides agents that inhibit soluble granulin signalling for use in the treatment of cancer. The treatments of the disclosure may be of particular utility in breast cancer; prostate cancer; and melanoma, and are also of use in treatment of cancers associated with hypoxic tumours. Suitable agents may include those that inhibit granulin expression, inhibit granulin cleavage, or bind to and inhibit soluble granulin. Such agents may be used in combination with inhibitors of angiogenesis.

Dopamine receptors and genes

A mammalian D2 dopamine receptor gene has been cloned. Thus, DNA sequences encoding all or a part of the dopamine receptor are provided, as well as the corresponding polypeptide sequences and methods for producing the same both synthetically and via expression of a corresponding sequence from a host transformed with a suitable vector carrying the corresponding DNA sequence. The various structural information provided by this invention enables the preparation of labeled or unlabeled immunospecific species, particularly antibodies, as well as nucleic acid probes labeled in conventional fashion. Pharmaceutical compositions and methods of using various products of this invention are also provided.

VACCINES FOR PREVENTING MENINGOCOCCAL INFECTIONS

Mutation associated with epilepsy

The present invention concerns an isolated mammalian DNA molecule encoding a mutant ?-aminobutyric acid type A (GABAA) receptor subunit, wherein a mutation event has occurred and said mutation event disrupts the functioning of an assembled GABAA receptor, or an otherwise functional fragment or homologue thereof. The invention also concerns mutant ?-aminobutyric acid type A (GABAA) receptor subunits and antibodies against the same. Furthermore the invention concerns the use of such DNA molecules, subunits and antibodies in diagnostic and therapeutic applications.

ВЕЩЕСТВА И СПОСОБЫ ДЛЯ ПРИМЕНЕНИЯ ПРИ ПРЕДУПРЕЖДЕНИИ И/ИЛИ ЛЕЧЕНИИ БОЛЕЗНИ ГЕНТИНГТОНА

High affinity antibodies to human il-6 receptor

A human antibody or an antigen-binding fragment which binds human IL-6 receptor (hIL-6R) with a K D of about 500 pM or less and blocks IL-6 activity with an IC 50 of 200 pM or less, is provided. In preferred embodiments, the antibody the antibody or antigen-binding fragment binds hIL-6R with an affinity at least 2-fold higher relative to its binding monkey IL-6R.

Estrogen receptors and methods of use

The present invention provides isolated polypeptides having an amino acid sequence having at least 70% identity to SEQ ID NO:20, wherein the polypeptide has ER-α36 activity. The invention further provides methods for identifying agents that bind to such polypeptides, methods for detecting such polypeptides, and methods for altering the activity of such polypeptides. Also provided are antibodies that specifically bind to an amino acid sequence depicted at SEQ ID NO:1, or an immunogenic fragment thereof, and methods for making and using such antibodies.

Induction of p53 expression by neutralization of neuropilin-2 for the treatment of cancers

The present invention relates to the use of anti-human neuropilin-2 antibodies, or of ligands of human neuropilin-2 derived from these antibodies, for obtaining a medicament intended to increase p53 expression and to induce tumour cell apoptosis in the context of an anticancer treatment.

Compositions and methods for treating or preventing inflammatory bowel disease and colon cancer

The invention provides compositions and methods for useful for the diagnosis of inflammatory bowel disease, ETBF-induced colitis, colonic hyperplasia and/or colon carcinogenesis in a subject in biological samples (e.g., stool, urine, blood, serum, tissue). The invention further provides compositions and methods for the treatment or prevention of colitis, colon cancer, or inflammatory bowel disease (e.g., Crohn's disease).

Methods of treating secondary bone tumors with antibodies against pdgfr alpha

The invention provides methods of treating bone cancer, particularly metastatic bone cancer, by administering an IGF-IR antagonist and/or a PDGFRα antagonist. The invention also provides antibodies that bind to human PDGFRα and neutralize activation of the receptor. The invention further provides a methods for neutralizing activation of PDGFRα, and a methods of treating a mammal with a neoplastic disease using the antibodie alone or in combination with other agents.

Methods of Treating Neurological Disorders

The present invention provides methods of treating epilepsy and other neurological disorders. The methods generally involve administering to an individual in need thereof an effective amount of an agent that blocks a transforming growth factor-beta pathway.

Novel Target for Regulating Multiple Sclerosis

Methods are provided for decreasing demyelinating inflammatory disease in a subject by inhibiting the activity of chemokine-like receptor 1 (CMKLR1). Methods are also provided for screening for agents that find use in treating demyelinating inflammatory disease in a subject.

Dual targeting antibody of novel form, and use thereof

The present invention relates to: a dual targeting antibody of a novel form having a water-soluble ligand fused to the N-terminus of a heavy chain or light chain of an antibody; a DNA encoding the dual targeting antibody; a recombinant expression vector containing the DNA; a host cell which is transformed with the recombinant expression vector; a method for preparing the dual targeting antibody by culturing the host cell; and a pharmaceutical composition including the dual targeting antibody.

Soluble il-17ra/rc fusion proteins and related methods

Disclosed are antagonists of IL-17A and IL-17F. The antagonists are based on soluble IL-17RA and IL-17RC fusion proteins, including hybrid soluble receptors comprising portions of both IL-17RC and IL-17RA (“IL-17RC/IL-17RA”). Such antagonists serve to block, inhibit, reduce, antagonize or neutralize the activity of IL-17F, IL-17A, or both IL-17A and IL-17F. Also disclosed are methods of using such antagonists for treating disease, particularly inflammatory diseases mediated at least in part by IL-17A and/or IL-17F.

Anti-il12rbeta1 antibodies and their use in treating autoimmune and inflammatory disorders

The present invention relates to antibodies that specifically bind to IL12Rβ1, the non-signal transducing chain of both the heterodimeric IL12 and IL23 receptors. The invention more specifically relates to specific antibodies that are IL12 and IL23 receptor antagonists capable of inhibiting IL12/1L18 induced IFNγ production of blood cells and compositions and methods of use for said antibodies to treat pathological disorders that can be treated by inhibiting IFNγ production, IL12 and/IL23 signaling, such as rheumatoid arthritis, psoriasis or inflammatory bowel diseases or other autoimmune and inflammatory disorders.

Anti-vegf-d antibodies

The invention relates to an isolated antibody that specifically binds vascular endothelial growth factor-D (VEGF-D) and to a humanized antibody that specifically binds VEGF-D.

Anti-ferroportin 1 monoclonal antibodies and uses thereof

Provided are monoclonal antibodies and antigen-binding fragments thereof that bind to, and inhibit the activity of human FPN1, and which are effective in maintaining or increasing the transport of iron out of mammalian cells and/or maintaining or increasing the level of serum iron, reticulocyte count, red blood cell count, hemoglobin, and/or hematocrit in a subject in vivo.

Compositions and methods for biological remodeling with frozen particle compositions

Certain embodiments disclosed herein relate to compositions, methods, devices, systems, and products regarding frozen particles. In certain embodiments, the frozen particles include materials at low temperatures. In certain embodiments, the frozen particles provide vehicles for delivery of particular agents. In certain embodiments, the frozen particles are administered to at least one biological tissue.

Tslp promotes immune evasion and persistence of viruses

It relates to the treatment or prevention of a chronic viral infection with a Thymic Stromal Lymphopoietin (TSLP) antagonist thereby avoiding immune evasion and persistence of the virus. It also provides a method of prognosing the evolution of a cervical dysplasia by TSLP expression in a sample of said cervical dysplasia.

Ifn-alpha/beta-independent mechanism of antiviral protection through a novel ligand-receptor pair: ifn- ligands engage a novel receptor ifn-rn (crf2-12) and il-10r2 (crf2-4) for signaling andinduction of biological activities

A novel IFN-α/β independent ligand receptor system which upon engagement leads, among other things, to the establishment of an anti-viral state is disclosed. Further disclosed are three closely positioned genes on human chromosome 19 that encode distinct but highly homologous proteins, designated IFN-λ1, IFN-λ2, IFN-λ3, based, inter alia, in their ability to induce antiviral protection. Expression of these proteins is induced upon viral infection. A receptor complex utilized by all three IFN-λ proteins for signaling is also disclosed. The receptor complex is generally composed of two subunits, a novel receptor designated IFN-λR1 or CRF2-12, and a second subunit, IL-10R2 or CRF2-4, which is also a shared receptor component for the IL-10 and IL-22 receptor complexes. The gene encoding IFN-λR1 is generally widely expressed, including many different cell types and tissues. Expression of these proteins is induced by immune events, including, for example, upon viral infection. Apoptotosis may also be induced under effective conditions.

Compositions and methods for inhibiting viral and/or bacterial infections

We describe herein compositions and methods related to inferring with microbial infection. Generally, the compositions include an infection antagonist that inhibits formation of a heparin sulfonated proteoglycan (HSPG)-containing infection complex. Generally, the methods include administering to a subject an amount of a composition as described herein effective to inhibit infection by a microorganism that that infects a host through interactions that involve HSPG.

Human antibodies derived from immunized xenomice

Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof.

Treatment of oncostatin m receptor beta mediated heart failure

The present invention relates to an inhibitor of the oncostatin M receptor β or an inhibitor of an activator of the oncostatin M receptor β for use in the treatment and/or prevention of heart failure. The present invention also relates to a method of treating and/or preventing heart failure comprising administering a pharmaceutically effective amount of an inhibitor of the oncostatin M receptor β or an inhibitor of an activator of the oncostatin M receptor β to a subject in need thereof. Further, the present invention also relates to methods of identifying a compound suitable as a lead compound and/or as a medicament for the treatment and/or prevention of heart failure.

Fc VARIANTS THAT EXTEND ANTIBODY HALF-LIFE

The invention relates generally to compositions and methods for altering the serum half-life in vivo of an antibody.

Soluble lymphotoxin-beta receptors and anti-lymphotoxin receptor and ligand antibodies as therapeutic agents for the treatment of immunological diseases

Compositions and methods comprising “lymphotoxin-β receptor blocking agents” which block lymphotoxin-β receptor signalling and are useful for altering immunological diseases, and particularly antibody mediated immune responses.

Human cdr-grafted antibody and antibody fragment thereof

A human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of human CC chemokine receptor 4 (CCR4) but does not react with a human blood platelet; a human CDR-grafted antibody or the antibody fragment thereof which specifically reacts with the extracellular region of CCR4 and has a cytotoxic activity against a CCR4-expressing cell; and a medicament, a therapeutic agent or a diagnostic agent comprising at least one of the antibodies and the antibody fragments thereof as an active ingredient.

Human domain antibodies against components of the human insulin-like growth factor (igf) system

The invention provides antibodies or antibody fragments that bind to insulin-like growth factor (IGF) 1 receptor (IGF-1R) or IGF-2, as well as method of using the antibodies for inhibiting the IGF-mediated signaling pathway, inhibiting IGF-1R signaling, and treating cancer. The invention also provides a method of detecting the presence of IGF-1R or IGF-2 in a sample using the inventive antibodies and antibody fragments.

Half immunoglobulin binding proteins and uses thereof

The invention provides compositions, methods, and kits related to half-Ig binding proteins that include a functional antibody binding site and a CH3 domain wherein the CH3 domain includes at least one mutation to inhibit CH3-CH3 dimerization.

Anti-il-22ra antibodies and binding partners and methods of using in inflammation

The present invention relates to blocking, inhibiting, reducing, antagonizing or neutralizing the activity of IL-22, IL-20, or both IL-20 and IL-22 polypeptide molecules. IL-20 and IL-22 are cytokines that are involved in inflammatory processes and human disease. IL-22RA (zcytor11) is a common receptor for IL-20 and IL-22. The present invention includes anti-IL-22RA antibodies and binding partners, as well as methods for antagonizing IL-22 or both IL-20 and IL-22 using such antibodies and binding partners.

Prophylaxis Against Cancer Metastasis

This document provides prophylactic methods for reducing cancer metastasis by targeting LCN2, MMP9, and CX-CR4.

Anti-il-6 receptor antibodies and methods of use

The present invention provides anti-IL-6R monoclonal antibodies and related compositions, which may be used in any of a variety of therapeutic methods for the treatment of rheumatoid arthritis and other diseases.

Stable formulations of immunoglobulin single variable domains and uses thereof

The present invention relates to stable formulations of polypeptides, e.g. immunoglobulin single variable domains.

Antigen Binding Proteins

The present invention relates to antigen binding proteins comprising two Fc parts, methods for their production, pharmaceutical compositions containing said antigen binding proteins, and uses thereof.

Compositions and methods relating to anti-igf-1 receptor antibodies

The present invention provides compositions and methods relating to or derived from anti-IGF-1R antibodies. In particular embodiments, the invention provides fully human, humanized, or chimeric anti-IGF-1R antibodies that bind human IGF-1R, IGF-1R-binding fragments and derivatives of such antibodies, and IGF-1R-binding polypeptides comprising such fragments. Other embodiments provide nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having IGF-1R-related disorders or conditions.

Biomarkers for prognoses of pulmonary diseases

The present invention relates to biomarkers that may be used to evaluate the prognoses of patients suffering from pulmonary diseases and assist in the determination of appropriate therapeutic regimens. It is based, at least in part, on the discovery that a number of T-cell antigens are differentially expressed in chronic lung disease patients depending on the prognosis of the patient. Non-limiting examples of these antigens include CD28, CD4, CD25, CD45, CD27 and CCR7 and combinations thereof. Use of these biomarker antigens, optionally in conjunction with pulmonary function tests, provides an indication of which patients are likely to suffer a severely adverse outcome within the year and/or be refractory to treatment.

Method of treatment of philadelphia chromosome positive leukaemia

The invention provides a method for the treatment of Ph+ leukemia in a patient comprising administering to the patient (i) a BCR-ABL tyrosine kinase inhibitor, and (ii) an agent which selectively binds to a cell surface receptor expressed on Ph+ leukemic stem cells. The invention further provides for the use of (i) and (ii) in, or in the manufacture of a medicament for, the treatment of Ph+ leukemia in a patient; and a composition for the treatment of Ph+ leukemia in a patient comprising (i) and (ii); and kits comprising (i) and (ii). In some embodiments, the tyrosine kinase inhibitor is or is not imatinib; or is selected from the group consisting of dasatinib, nilotinib, bosutinib, axitinib, cediranib, crizotinib, damnacanthal, gefitinib, lapatinib, lestaurtinib, neratinib, semaxanib, sunitinib, toceranib, tyrphostins, vandetanib, vatalanib, INNO-406, AP24534, XL228, PHA-739358, MK-0457, SGX393 and DC2036; or is selected from the group consisting of dasatinib and nilotinib. In some embodiments, the agent binds to a receptor involved in signalling by at least one of IL-3, G-CSF and GM-CSF. In some embodiments, the agent is a mutein selected from the group consisting of IL-3 muteins, G-CSF muteins and GM-CSF muteins. In some embodiments, the mutein is an IL-3 mutein. In some embodiments, the agent is a soluble receptor which is capable of binding to IL-3.

Tusc2 therapies

A method for predicting a subject's response to a TUSC2 therapy is provided. In particular, a subject's response is predicted based on the proportion of cancers cells that are apoptotic. Also provided is a method of treating a subject previously predicted to have a favorable response with a TUSC2 therapy. Methods for treating cancer by administration of a TUSC2 therapeutic in conjunction with an EGFR inhibitor and/or a protein kinase inhibitor are also disclosed. Kits and reagents for use in TUSC2 therapy are provided.

Antibodies Directed to Angiopoietin-1 and Angiopoietin-2 and Uses Thereof

Disclosed are specific binding agents, such as fully human antibodies, that bind to angiopoietin 1 and/or angiopoietin-2. Also disclosed are heavy chain fragments, light chain fragments, and CDRs of the antibodies, as well as methods of making and using the antibodies.

Interleukin-21 receptor binding proteins

The present invention provides binding proteins and antigen-binding fragments thereof that specifically bind to the human interleukin-21 receptor (IL-21R). The binding proteins can act as, e.g., antagonists of IL-21R activity, thereby modulating immune responses in general, and those mediated by IL-21R in particular. The disclosed compositions and methods may be used, e.g., in diagnosing and/or treating IL-21R-associated disorders, e.g., inflammatory disorders, autoimmune diseases, allergies, transplant rejection, cancer, and other immune system disorders.

Therapeutic human anti-il-1r1 monoclonal antibody

Antibodies that interact with interleukin-1 receptor type 1 (IL-1R1) are described. Methods of treating IL-1 mediated diseases by administering a pharmaceutically effective amount of antibodies to IL-1R1 are described. Methods of detecting the amount of IL-1R1 in a sample using antibodies to IL-1R1 are described.

Binding Partners for the Thyrotropin Receptor and Uses Thereof

A binding partner for the TSH receptor, which binding partner comprises, or is derived from, a human monoclonal or recombinant antibody, or one or more fragments thereof, reactive with the TSH receptor, uses thereof, methods of diagnosis and therapy employing the same, and anti-idiotypic antibodies thereto.

Prognostic,. screening and treatment methods and agents for treatment of metastasis and inflammation using 5t4 oncofoetal glycoprotein

Methods and agents are disclosed based on the finding that 5T4 interacts with CXCR4 in the cell membrane to form a complex, and that the 5T4 transmembrane region is involved in the promotion of CXCR4 membrane expression and chemotactic response.

Combination of angiopoietin-2 antagonist and of vegf-a, kdr and/or flt1 antagonist for treating cancer

The invention relates to agents which possess anti-angiogenic activity and are accordingly useful in methods of treatment of disease states associated with angiogenesis in the animal or human body. More specifically the invention concerns a combination of an antagonist of the biological activity of Angiopoietin-2 and an antagonist of the biological activity of VEGF-A, and/or KDR, and/or Flt1, and uses of such antagonists.

Dac hyp compositions and methods

The present disclosure relates to compositions of daclizumab suitable for subcutaneous administration and methods of manufacturing thereof.

Neutralizing prolactin receptor antibodies and their therapeutic use

The present invention is directed to the neutralizing prolactin receptor antibody 002-H08, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

Crystal structures and methods using same

The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention concerns modulators of FGFR3 function, and the identification and uses of said modulators.

Antibodies to c-met

The present invention relates to antibodies including human antibodies and antigen-binding portions thereof that specifically bind to c-Met, preferably human c-Met, and that function to inhibit c-Met. The invention also relates to human anti-c-Met antibodies and antigen-binding portions thereof. The invention also relates to antibodies that are chimeric, bispecific, derivatized, single chain antibodies or portions of fusion proteins. The invention also relates to isolated heavy and light chain immunoglobulins derived from human anti-c-Met antibodies and nucleic acid molecules encoding such immunoglobulins. The present invention also relates to methods of making human anti-c-Met antibodies, compositions comprising these antibodies and methods of using the antibodies and compositions for diagnosis and treatment. The invention also provides gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-c-Met antibodies. The invention also relates to transgenic animals or plants comprising nucleic acid molecules of the present invention.

Adam6 Mice

Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

Crystal structures of neuropilin fragments and neuropilin-antibody complexes

The invention provides crystal structures of neuropilin 1 (Nrp1) and neuropilin 2 (Nrp2) fragments alone and in complex with anti-neuropilin antibodies, and method for their use. The invention further provides anti-Nrp antibodies and methods for their therapeutic applications.

Method and system to remove soluble tnfr1, tnfr2 and il2 in patients

A method, and system, to induce remission in diseases characterized by excess production of sTNR and interleukin 2 has been developed. In the most preferred embodiment, the system consists of antibodies to sTNFR1, sTNFR2 and sIL2R immobilized in a column containing a material such as SEPHAROSE™. The patient is connected to a pheresis machine which separates the blood into the plasma and red cells, and the plasma is circulated through the column until the desired reduction in levels of sTNFR1, sTNFR2, and IL2 is achieved, preferably to less than normal levels. In the preferred method, patients are treated three times a week for four weeks. This process can be repeated after a period of time. Clinical studies showed reduction in tumor burden in patients having failed conventional chemotherapy and radiation treatments.

Trispecific Therapeutics Against Acute Myeloid Leukaemia

The present invention relates to a molecule having binding specificities for (a) CD123; (b) CD16 and (c) CD33. The present invention further relates to the molecule of the invention, wherein the molecule comprises a first immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD123; a second immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD16; and a third immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD33. The present invention furthermore relates to a nucleic acid molecule encoding the molecule of the invention. In addition, the present invention relates to diagnostic and pharmaceutical compositions and the use of the molecule or the nucleic acid molecule of the invention in the treatment of acute myeloid leukaemia and/or myelodysplastic syndrome.

Methods and compositions for modulating the activity of the interleukin-35 receptor complex

The receptor for Interleukin 35 (IL-35) is provided. The Interleukin 35 Receptor (IL-35R) comprises a heterodimeric complex of the Interluekin12Rβ2 receptor and the gp130 receptor. Various compositions comprising the IL-35R complex, along with polynucleotides encoding the same and kits and methods for the detection of the same the same are provided. Methods of modulating the activity of IL-35R or modulating effector T cell functions are also provided. Such methods employ various IL-35R antagonists and agonists that modulate the activity of the IL-35R complex and, in some embodiments, modulate effector T cell function. Further provided are methods for screening for IL-35R binding agents and for IL-35R modulating agents. Various methods of treatment are further provided.

Multivalent fibronectin based scaffold domain proteins

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.

DEspR ANTAGONISTS AND AGONISTS AS THERAPEUTICS

Provided herein are novel compositions comprising DEspR-specific antagonists and agonists, and methods of their use in a variety of therapeutic applications. The compositions comprising the DEspR-specific anatgonists and agonists described herein are useful in therapeutic, diagnostic and imaging methods, such as DEspR-targeted molecular imaging of angiogenesis, and for companion diagnostic and/or in vivo-non invasive imaging and/or assessments.

Vascular endothelial cell growth factor antagonists

The present invention provides human vascular endothelial cell growth factor (hVEGF) antagonists, including monoclonal antibodies, hVEGF receptors, and hVEGF variants that are useful for the treatment of age-related macular degeneration, and other diseases and disorders characterized by undesirable or excessive neovascularization.

Antagonist anti-il-7 receptor antibodies and methods

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus.

Diagnostic marker for effect of anticancer agent

The present invention enables to realize a convenient determination of a therapeutic effect of an anticancer agent on a cancer. Specifically, the present invention provides a diagnostic marker for an effect of an anticancer agent on a cancer, comprising a substance having an affinity for a fragment of an extracellular domain of c-MET; a diagnostic reagent for an effect of an anticancer agent on a cancer, comprising a substance having an affinity for a fragment of an extracellular domain of c-MET and the fragment of the extracellular domain of c-MET; and a method of testing an effect of an anticancer agent on a cancer, comprising (a) measuring a concentration of a fragment of an extracellular domain of c-MET in a biological sample from a subject, and (b) comparing the measured concentration of the fragment of the extracellular domain of c-MET with an indicator which presents a relationship between a concentration of the fragment of the extracellular domain of c-MET and the effect of the anticancer agent on the cancer.

Novel maytansinoid derivatives with peptide linker and conjugates thereof

The invention relates to novel cell-binding agent-cytotoxic agent conjugate having a peptide linkers and more specifically to conjugates of formula (I). The invention also provides novel cytotoxic agents of formula (II), linker compounds represented by formula (III), and drug-linker compounds represented by formula (IV). The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

Il-18 receptor antigen binding proteins

Provided herein are IL-18 receptor antigen binding proteins and polynucleotides encoding the same. Expression vectors and host cells comprising the same for production of the antigen binding proteins are also provided. In addition, provided are compositions and methods for diagnosing and treating diseases mediated by IL-18 receptor.

Methods of treating hematological proliferative disorders by targeting epha3 expressed on aberrant vasculature in bone marrow

The invention provides diagnostic and therapeutic methods for the treatment of hematological proliferative disorders.

Specific binding proteins and uses thereof

The invention provides specific binding proteins and the uses thereof. Particularly, the present invention provides a monoclonal antibody which can effectively bind to epidermal growth factor receptor variant type III (EGFRvIII) or can partially bind to the epidermal growth factor receptor (EGFR) over-expressed in cells, but not bind to EGFR normally-expressed in cells. Furthermore, the present invention said antibody has obvious therapeutic effect on a tumor cell line expressing the EGFRvIII. The invention also provides a method for preparing said monoclonal antibody and a pharmaceutical composition comprising said monoclonal antibody.

SOLUBLE FMS-LIKE TYROSINE KINASE-1 (sFLT-1) ANTIBODY AND RELATED COMPOSITION, KIT, METHODS OF USING, AND MATERIALS AND METHOD FOR MAKING

An isolated antibody that specifically binds to sFlt-1 or a fragment thereof having (i) a variable heavy domain region comprising the amino acid sequence of SEQ ID NO: 2, (ii) a variable light domain region comprising the amino acid sequence of SEQ ID NO: 4, or (iii) both (i) and (ii), a pharmaceutical composition and a kit comprising such an antibody, a method of making such an antibody, a method of determining the presence, amount or concentration of sFlt-1 or a fragment thereof in a test sample, a method of treating a patient in therapeutic or prophylactic need of an antagonist of sFlt-1, an isolated nucleic acid comprising a nucleotide sequence encoding the amino acid sequence of (i) SEQ ID NO: 2, (ii) SEQ ID NO: 4, or (iii) both (i) and (ii), optionally as part of a vector, and a host cell comprising and expressing such a nucleic acid.

Anti-fgfr3 antibodies and methods using same

The invention provides FGFR3 antibodies, and compositions comprising and methods of using these antibodies.

Engineered anti-il-23r antibodies

Antibodies to human IL-23R are provided, as well as uses thereof, e.g. in treatment of inflammatory, autoimmune, and proliferative disorders.

HUMANIZED ANTI-CCR2 ANTIBODIES AND METHODS OF USE THEREFOR

The present invention relates to a humanized antibody or functional fragment thereof which binds to a mammalian (e.g., human) CC-chemokine receptor 2 (CCR2) or a portion of the receptor and blocks binding of a ligand to the receptor. The invention further relates to a method of inhibiting the interaction of a cell bearing mammalian CCR2 with a ligand thereof, and to use of the antibodies and fragments in therapeutic, prophylactic and diagnostic methods. 1. A humanized immunoglobulin or antigen-binding fragment thereof having binding specificity for CCR2 , said immunoglobulin or fragment comprising an antigen binding region of nonhuman origin and at least a portion of an immunoglobulin of human origin.28.-. (canceled)9. The humanized immunoglobulin or antigen-binding fragment thereof of comprising a heavy chain and a light chain claim 1 , wherein said light chain comprises at least one complementarity determining region derived from an antibody of nonhuman origin which binds CCR2 and a framework region derived from a light chain of human origin claim 1 , and wherein said heavy chain comprises at least one complementarity determining region derived from an antibody of nonhuman origin which binds CCR2 and a framework region derived from a heavy chain of human origin.1014.-. (canceled)15. A humanized immunoglobulin light chain or antigen-binding fragment thereof comprising CDR1 claim 1 , CDR2 and CDR3 of the light chain of murine 1D9 antibody and a human light chain framework region.1617.-. (canceled)18. An isolated nucleic acid molecule encoding the humanized immunoglobulin light chain or antigen-binding fragment thereof of .19. (canceled)20. A humanized immunoglobulin heavy chain or antigen-binding fragment thereof comprising CDR1 claim 15 , CDR2 and CDR3 of the heavy chain of murine 1D9 antibody and a human heavy chain framework region.2122.-. (canceled)23. An isolated nucleic acid molecule encoding the humanized immunoglobulin light chain or antigen-binding fragment ...

INHIBITORS OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) RECEPTORS AND METHODS OF USE THEREOF

The present invention provides moieties that bind to the most membrane-proximal Ig-like domain of the ectodomain (D7) of vascular endothelial growth factor (VEGF) receptors, wherein the moieties antagonize the activity of the VEGF receptor. 1. A moiety that binds to the ectodomain of a human vascular endothelial growth factor receptor (VEGF receptor) , wherein said moiety antagonizes the activity of the VEGF receptor.2. The moiety of claim 1 , wherein said moiety binds to an Ig-like domain of a human VEGF receptor.3. The moiety of claim 2 , wherein said Ig-like domain is not responsible for the binding of a ligand to the VEGF receptor.4. The moiety of claim 2 , wherein said Ig-like domain is responsible for the binding of a ligand to the VEGF receptor.5. The moiety of claim 1 , wherein said moiety a) does not block the interaction between the VEGF receptor and a ligand for the VEGF receptor.6. The moiety of claim 1 , wherein said moiety blocks the interaction between the VEGF receptor and a ligand for the VEGF receptor.7. The moiety of claim 1 , wherein said moiety does not prevent dimerization of the VEGF receptor.8. The moiety of claim 1 , wherein said moiety prevents dimerization of the VEGF receptor.9. The moiety of claim 1 , wherein said moiety prevents the interaction between a membrane proximal region of the ectodomain from each protomer of the VEGF receptor.10. The moiety of claim 9 , wherein said interaction is homotypic.11. The moiety of claim 9 , wherein said interaction is heterotypic.12. The moiety of claim 9 , wherein said membrane proximal region of the ectodomain is the 7Ig-like domain (D7) of a VEGF receptor.13. The moiety of claim 12 , wherein said moiety binds to the following consensus sequence for the D7 domain of a VEGF receptor:{'sub': 1', '2', '3', '4', '5', '1', '2', '3', '4 and', '5, 'L/I XR ΦXXXD/E XG (SEQ ID NO:158), wherein L is Leucine, I is Isoleucine, R is Arginine, Φ is a hydrophobic amino acid, D is Aspartic Acid, E is Glutamic Acid ...

HIGH AFFINITY HUMAN ANTIBODIES TO HUMAN IL-4 RECEPTOR

The present invention provides nucleic acid molecules that encode antibodies or antigen-binding fragments thereof, which specifically bind human interleukin-4 receptor (IL-4R). Also provided are expression vectors comprising nucleic acid molecule that encode anti-IL-4R antibodies, host cells comprising the expression vectors, and methods of producing anti-IL-4R antibodies or antigen-binding fragments thereof comprising growing the host cells under conditions permitting production of the antibody or fragment, and recovering the antibody or fragment so produced 1. An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a heavy chain immunoglobulin variable domain region (HCVR) that binds human interleukin-4 receptor , wherein the HCVR comprises a heavy chain CDR1 (HCDR1) comprising SEQ ID NO:148 , a heavy chain CDR2 (HCDR2) comprising SEQ ID NO:150 , and a heavy chain CDR3 (HCDR3) comprising SEQ ID NO:152.2. The nucleic acid molecule of claim 1 , wherein the HCVR comprises the amino acid sequence of SEQ ID NO:162.3. The nucleic acid molecule of claim 1 , wherein the HCVR comprises an HCDR1 encoded by the nucleotide sequence of SEQ ID NO:147 claim 1 , an HCDR2 encoded by the nucleotide sequence of SEQ ID NO:149 claim 1 , and an HCDR3 encoded by the nucleotide sequence of SEQ ID NO:151.4. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO:161 or a substantially identical sequence having at least 95% homology thereof.5. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises the nucleotide sequence of SEQ ID NO:161.6. An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a light chain immunoglobulin variable region (LCVR) that binds human interleukin-4 receptor claim 1 , wherein the LCVR comprises a light chain CDR1 (LCDR1) comprising SEQ ID NO:156 claim 1 , a light chain CDR2 (LCDR2) comprising SEQ ID NO:158 claim 1 , and a light ...

Binding members-513

This invention relates to binding members, especially antibody molecules, specific for interleukin 1 receptor 1 (IL-1R1). For example, isolated binding members specific for IL-1R1 which competes with IL-1 and IL-1Ra for binding to IL-1R1 and binds Il-1R1 with a K D of 10 pM or less when measured by Kinexa™. The binding members are useful for, inter alia, treatment of disorders mediated by IL-1R1 including rheumatoid arthritis, athma and chronic obstructive pulmonary disease (COPD).

IGF-1R SPECIFIC ANTIBODIES USEFUL IN THE DETECTION AND DIAGNOSIS OF CELLULAR PROLIFERATIVE DISORDERS

The present invention relates to mammalian antibodies, designated 12B1 and antigen-binding portions thereof that specifically bind to insulin-like growth factor I receptor (IGF-IR), preferably human IGF-IR. Also included are chimeric, bispecific, derivatized, single chain antibodies derived from the antibodies disclosed herein. Nucleic acid molecules encoding the mammalian antibodies as well as methods of use thereof are also disclosed. Also included are pharmaceutical compositions comprising these antibodies and methods of using the antibodies and compositions thereof for treatment and diagnosis of pathological hyperproliferative oncogenic disorders associated with expression of IGf-1R. 1. An antibody or an antigen-binding portion thereof that specifically binds insulin-like growth factor I receptor (IGF-IR) , comprising at least one light chain sequence and at least one heavy chain sequence , wherein said light chain comprises at least one complementarity determining region (CDR) selected from the group consisting of the amino acids sequences as set forth in SEQ ID NO. 1 , 2 , or 3 , or at least one CDR comprising an amino acid sequence having at least 80% identity with the sequence set forth in SEQ ID NO. 1 , 2 , or 3 , and wherein said heavy chain comprises at least one complementarity determining region (CDR) selected from the group consisting of the amino acids sequences as set forth in SEQ ID NO. 4 , 5 or 6 , or at least one CDR comprising an amino acid sequence having at least 80% identity after with the sequence set forth in SEQ ID NO. 4 , 5 or 6.2. The antigen-binding portion according to claim 1 , wherein said portion is selected from the group consisting of: a Fab fragment claim 1 , an F(ab′)fragment and an Fv fragment.3. The antibody according to claim 1 , wherein said light chain comprises the amino acid sequence as set forth in SEQ ID NO: 7 and said heavy chain comprises the amino acid sequence as set forth in SEQ ID NO:8.4. A monoclonal antibody that ...

COMPOSITIONS AND METHODS FOR TARGETING TYPE 1 INTERFERON PRODUCING CELLS

The present disclosure provides a method for treating lupus, Sjörgen's syndrome or scleroderma, the method comprising administering to the mammal an immunoglobulin which binds an interleukin 3 receptor α (IL-3Rα) chain and which depletes or at least partly eliminates plasmacytoid dendritic cells (p DCs) and basophils to which it binds. 1. A method of treating lupus in a mammal , the method comprising administering to the mammal an immunoglobulin which binds an interleukin 3 receptor a (IL-3Rα) chain and competitively inhibits the binding of monoclonal antibody 7G3 to IL-3Rα and which depletes or at least partly eliminates plasmacytoid dendritic cells (pDCs) and basophils to which it binds to thereby treat lupus in the mammal , wherein the immunoglobulin is not conjugated to a toxic compound that kills a cell to which the immunoglobulin binds.2. The method of claim 1 , wherein the lupus is systemic lupus erythematosus (SLE)3. The method of claim 1 , wherein the IL3Rα chain is expressed by a pDC that produces one or more type I interferons and/or by a basophil that produces one or more cytokines.4. (canceled)5. The method of claim 1 , wherein the immunoglobulin binds to the same epitope as monoclonal antibody 7G3 or an overlapping epitope.6. The method of claim 1 , wherein the immunoglobulin neutralizes IL-3 signaling.7. The method of claim 1 , wherein the immunoglobulin is an antibody or an antigen binding fragment thereof.8. The method of claim 7 , wherein the antibody is a chimeric antibody or a humanized antibody or a human antibody.9. (canceled)10. (canceled)11. The method of claim 7 , wherein the humanized antibody is a humanized antibody comprising complementarity determining regions derived from monoclonal antibody 7G3.12. The method of claim 11 , wherein the humanized antibody comprises a light chain variable region (V) comprising a sequence set forth in SEQ ID NO: 3 and a heavy chain variable region (V) comprising a sequence set forth in SEQ ID NO: 2.13. ( ...

Antibodies to Thymic Stromal Lymphopoietin (TSLP) Receptor Molecules and Uses Thereof

The present invention provides Thymic Stromal Lymphopoietin Receptor (TSLPR) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing TSLPR polypeptides. The invention further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with TSLPR polypeptides. 16-. (canceled)7. A method of blocking human TSLP receptor activity , said method comprising contacting a cell expressing human thymic stromal lymphopoietin receptor with an effective amount of an isolated selective binding agent that specifically binds the amino acid sequence set forth in SEQ ID NO:6 and blocks human thymic stromallymphopoietin (TSLP) binding to the amino acid sequence.8. The method of claim 7 , wherein the selective binding agent is an antibody.9. The method of claim 8 , wherein the antibody is a monoclonal antibody.10. The method of claim 8 , wherein the antibody is a humanized antibody.11. The method of claim 8 , wherein the antibody is a human antibody.12. The method of claim 7 , wherein the selective binding agent comprises a fragment of an antibody.13. The method of claim 7 , wherein the isolated selective binding agent is administered to a patient. This application is a continuation of U.S. patent application Ser. No. 09/895,943, filed on Jun. 28, 2001, now allowed, which claims the benefit of priority from U.S. Provisional Patent Application No. 60/214,866, filed on Jun. 28, 2000, the disclosure of which is explicitly incorporated by reference herein.The present application is being filed along with a Sequence Listing in electronic format. The Sequence Listing is provided as a file entitled A-713-US-CNT2_ST25.txt, created May 23, 2011, which is 46 KB in size. The information in the electronic format of the Sequence Listing is incorporated herein by reference in its entirety.The ...

Antibody specifically binding to epitope in sema domain of c-met

An antibody or antigen binding fragment thereof that specifically binds to an epitope in a SEMA domain of c-Met protein, and pharmaceutical compositions, methods, kits, nucleic acids, and cells related thereto.

BONE MORPHOGENETIC PROTEIN RECEPTOR BINDING AGENTS AND METHODS OF THEIR USE

The present invention provides bone morphogenetic protein receptor (BMPR) binding agents, such as antibodies, and compositions comprising said binding agents. The binding agents are useful to treat diseases such as cancer. 1106-. (canceled)107. An isolated monoclonal antibody that specifically binds an extracellular domain of at least one bone morphogenetic protein receptor (BMPR) selected from the group consisting of: BMPR1A , BMPR1B , BMPR2 , ACVR2A and ACVR2B , wherein the antibody is:(i) an agonist of the BMP pathway, or(ii) an antagonist of the BMP pathway.108. The antibody of claim 107 , which is a recombinant antibody claim 107 , a monoclonal antibody claim 107 , a chimeric antibody claim 107 , a bispecific antibody claim 107 , a humanized antibody claim 107 , a human antibody claim 107 , or an antibody fragment.109. The antibody of claim 107 , which:(i) modulates BMP pathway activity;(ii) stimulates BMP pathway activity,(iii) increases BMPR activation, and/or(iv) inhibits tumor growth.110. A pharmaceutical composition comprising the antibody of and a pharmaceutically acceptable carrier.111. A cell comprising or producing the antibody of .112. An isolated polynucleotide molecule comprising a polynucleotide that encodes the antibody of .113. A method of modulating BMP pathway signaling in a cell claim 107 , comprising contacting the cell with an effective amount of the antibody of .114. The method of claim 113 , wherein the modulation is a stimulation of BMP pathway signaling.115. A method of inhibiting tumor growth in a subject claim 107 , comprising administering to the subject a therapeutically effective amount of the antibody of .116. The method of claim 115 , wherein the tumor is a colorectal tumor claim 115 , a breast tumor claim 115 , a prostate tumor claim 115 , a pancreatic tumor claim 115 , a lung tumor claim 115 , a head and neck tumor claim 115 , a glioblastoma tumor or a melanoma tumor.117. The method of claim 115 , further comprising ...

Epitope regions of a thyrotrophin (tsh) receptor, uses thereof and antibodies thereto

The present invention is concerned with epitope regions of a thyrotrophin (TSH) receptor, uses thereof and antibodies thereto.

Artery- and vein-specific proteins and uses therefor

Arterial and venous endothelial cells are molecularly distinct from the earliest stages of angiogenesis. This distinction is revealed by expression on arterial cells of a transmembrane ligand, called EphrinB2 whose receptor EphB4 is expressed on venous cells. Targeted disruption of the EphrinB2 gene prevents the remodeling of veins from a capillary plexus into properly branched structures. Moreover, it also disrupts the remodeling of arteries, suggesting that reciprocal interactions between pre-specified arterial and venous endothelial cells are necessary for angiogenesis. This distinction can be used to advantage in methods to alter angiogenesis, methods to assess the effect of drugs on artery cells and vein cells, and methods to identify and isolate artery cells and vein cells, for example.

Tweak receptor

The present invention provides the TWEAK receptor and methods for identifying and using agonists and antagonists of the TWEAK receptor. In particular, the invention provides methods of screening for agonists and antagonists and for treating diseases or conditions mediated by angiogenesis, such as solid tumors and vascular deficiencies of cardiac or peripheral tissue.

BMP-ALK3 ANTAGONISTS AND USES FOR PROMOTING BONE GROWTH

In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density and strength. In certain embodiments, the present invention provides ALK3 polypeptides, including ALK3-Fc fusion proteins. 1. An isolated polynucleotide comprising a coding sequence for a polypeptide comprising the amino acid sequence of SEQ ID NO:7.2. The isolated polynucleotide of claim 1 , wherein the isolated polynucleotide comprises a sequence of SEQ ID NO: 12.3. A recombinant polynucleotide comprising a promoter sequence operably linked to a polynucleotide of .4. A cell transformed with a recombinant polynucleotide of .5. The cell of claim 4 , wherein the cell is a mammalian cell.6. The cell of claim 5 , wherein the cell is a CHO cell or a human cell.7. A method for promoting bone growth claim 5 , increasing bone density or increasing bone strength claim 5 , the method comprising administering to a subject an effective amount of a BMP or ALK3 antagonist selected from the group consisting of:a) a polypeptide comprising an amino acid sequence at least 90% identical to SEQ ID NO: 3;b) a polypeptide comprising at least 50 consecutive amino acids selected from SEQ ID NO: 3;c) an antibody that binds to BMP2 and inhibits the interaction between BMP2 and ALK3;d) an antibody that binds to BMP4 and inhibits the interaction between BMP4 and ALK3; ande) an antibody that binds to ALK3 and inhibits the interaction between ALK3 and one or more ligands of ALK3. This application is a divisional of U.S. application Ser. No. 12/750,604, filed Mar. 30, 2010, which claims the benefit of U.S. Provisional Application No. 61/211,557, filed on Mar. 30, 2009, 61/306,331, filed on Feb. 19, 2010, and 61/314,556, filed on Mar. 16, 2010. The specifications of each of the foregoing applications are incorporated herein by reference in their entirety.The instant application contains a Sequence Listing which has been submitted via EFS-Web and is hereby incorporated ...

NOVEL ANTIBODY FOR THE DIAGNOSIS AND/OR PROGNOSIS OF CANCER

The present invention relates to the field of prognosis and/or diagnosis of a proliferative disease in a patient. More particularly, the invention relates to novel antibodies capable of binding specifically to the human cMet receptor, as well as the amino acid and nucleic acid sequences coding for these antibodies. The invention likewise comprises the use of said antibodies, and corresponding process, for detecting and diagnosing pathological hyperproliferative oncogenic disorders associated with expression of cMet. In certain embodiments, the disorders are oncogenic disorders associated with increased expression of cMet polypeptide relative to normal or any other pathology connected with the over expression of c Met. The invention finally comprises products and/or compositions or kits comprising at least such antibodies for the prognosis or diagnostic of certain cancers. 2. A binding protein claim 1 , or a functional fragment or derivative thereof claim 1 , according to claim 1 , characterized in that it consists of an isolated antibody or a functional fragment or derivative thereof claim 1 , selected from the group consisting of: a light chain comprising the following three CDRs as defined according to IMGT, respectively CDR-L1 having the sequence SEQ ID No. 1, CDR-L2 having the sequence SEQ ID No. 2 and CDR-L3 having the sequence SEQ ID No. 3; and', 'a heavy chain comprising the following three CDRs as defined according to IMGT, respectively CDR-H1 having the sequence SEQ ID No. 4, CDR-H2 having the sequence SEQ ID No. 5 and CDR-H3 having the sequence SEQ ID No. 6, and, 'a) an antibody, or a functional fragment or derivative thereof, comprising a light chain comprising the following three CDRs as defined according to IMGT, respectively CDR-L1 having the sequence SEQ ID No. 9, CDR-L2 having the sequence SEQ ID No. 10 and CDR-L3 having the sequence SEQ ID No. 11; and', 'a heavy chain comprising the following three CDRs as defined according to IMGT, respectively CDR ...

Recombinantly Produced Antibodies Targeting ErbB Signaling Molecules and Methods of Use Thereof for the Diagnosis and Treatment of Disease

Compositions and methods useful for the diagnosis and treatment of cancer are provided. 1. An isolated , recombinantly produced antibody having binding affinity for an ErbB signaling receptor molecule , selected from the group consisting of at least one of EGFR , ErbB2 , ErbB3 and ErbB4.2. The antibody of claim 1 , selected from the group consisting of a monoclonal antibody claim 1 , a polyclonal antibody claim 1 , a single chain Fv antibody claim 1 , a diabody claim 1 , a tribody claim 1 , a tetrabody claim 1 , a bispecific antibody claim 1 , a single domain antibody claim 1 , a minibody claim 1 , an scFv-Fc molecule claim 1 , a Fab fragment claim 1 , a Fab′ fragment and a F(ab′)fragment.3. The antibody of claim 2 , which is monoclonal.4. The antibody of claim 2 , which is a single chain Fv antibody.5. A molecule comprising the single chain Fv antibody of claim 4 , said molecule being selected from the group consisting of a diabody claim 4 , a tetrabody claim 4 , an immunotoxin claim 4 , a recombinantly produced IgG claim 4 , Fab claim 4 , Fab′ claim 4 , F(ab′) claim 4 , F(v) claim 4 , scFv claim 4 , scFv claim 4 , scFv-Fc claim 4 , minibody claim 4 , a bispecific antibody claim 4 , an Affibody® claim 4 , and a peptabody.6. The single chain Fv antibody of having immunospecificity for HER3 or EGFR claim 4 , wherein said antibody comprises an amino acid sequence selected from the group consisting of at least one of SEQ ID NOs:1-19 and 23-41.7. The single chain Fv antibody of which is produced recombinantly.8. The antibody of claim 1 , wherein said antibody is conjugated to a radioisotope.9. The antibody of claim 12 , wherein said radioisotope is selected from the group consisting of F claim 12 , I claim 12 , Zr claim 12 , Y claim 12 , Lu claim 12 , I claim 12 , and Re.10. A composition comprising an antibody of and a pharmaceutically acceptable carrier.11. The composition as claimed in claim 10 , wherein said antibody is conjugated to at least one molecule selected ...

ANTI-GITR ANTIBODIES

The invention provides antibodies that specifically bind to human GITR (hGITR) with high affinity and antagonize the binding of hGITRL to hGITR. The invention also provides pharmaceutical compositions, as well as nucleic acids encoding anti-GITR antibodies, recombinant expression vectors and host cells for making such antibodies, or fragments thereof. Methods of using antibodies of the invention to detect hGITR or to modulate hGITR activity, either in vitro or in vivo, are also provided by the invention. 1) An isolated monoclonal antibody , or antigen binding portion thereof , that binds specifically to human GITR comprising an HCDR3 region amino acid sequence selected from the group consisting of SEQ ID NO: 1 , 18 , 29 , and 35 , or conservative amino acid substitutions thereof.2) The antibody claim 1 , or antigen binding portion thereof claim 1 , of claim 1 , further comprising an HCDR2 region amino acid sequence selected from the group consisting of SEQ ID NO: 2 claim 1 , 19 claim 1 , 30 claim 1 , 33 claim 1 , and 36 claim 1 , or conservative amino acid substitutions thereof.3) The antibody claim 2 , or antigen binding portion thereof claim 2 , of claim 2 , further comprising an HCDR1 region amino acid sequence selected from the group consisting of SEQ ID NO: 3 claim 2 , 20 claim 2 , 37 and 43 claim 2 , or conservative amino acid substitutions thereof.4) The antibody claim 2 , or antigen binding portion thereof claim 2 , of claim 2 , further comprising an LCDR3 region amino acid sequence selected from the group consisting of SEQ ID NO: 4 claim 2 , 21 claim 2 , 26 claim 2 , and 38 claim 2 , or conservative amino acid substitutions thereof.5) The antibody claim 2 , or antigen binding portion thereof claim 2 , of claim 2 , further comprising an LCDR2 region amino acid sequence selected from the group consisting of SEQ ID NO: 5 claim 2 , 22 claim 2 , and 38 claim 2 , or conservative amino acid substitutions thereof.6) The antibody claim 2 , or antigen binding portion ...

Actriib binding agents and uses thereof

The disclosure provides, among other aspects, neutralizing antibodies and portions thereof that bind to ActRIIB and uses for same.

Blockade of ccl18 signaling via ccr6 as a therapeutic option in fibrotic diseases and cancer

The present invention relates to an isolated soluble CCR6 receptor polypeptide capable of binding to CCL18 and/or CCL20 and to a method for quantifying the concentration of a soluble CCR6 receptor polypeptide in a liquid sample from a subject. The present invention also relates to a method for detecting and/or prognosticating an interstitial lung disease or a cancer in a subject by determining the level of a soluble CCR6 receptor polypeptide in a sample from said subject and further provides a pharmaceutical composition comprising a compound capable of inhibiting the activity and/or the expression of CCL18 or CCL20 for the treatment of said diseases. The present invention further relates to an isolated polypeptide capable of binding to and inhibiting the activity of the chemokine receptor CCR6 and to a method for identifying further inhibitors of CCR6 receptor activity. The present invention also relates to a method for detecting an interstitial lung disease or a cancer in a subject by determining the level of CCR6 gene expression in a sample from said subject and further provides pharmaceutical compositions comprising inhibitors of CCR6 receptor activity and/or expression for the treatment of said diseases.

Process for the modulation of the antagonistic activity of a monoclonal antibody

The present disclosure relates to the antibody engineering field and, more particularly, to a process for the screening of antibodies and/or the modulation of the agonistic/antagonistic activity of antibodies. More particularly, the disclosure concerns a process of improving the antagonistic activity of a monoclonal antibody directed against a specific target molecule, or a divalent functional fragment or derivative thereof, said antibody being capable of inhibiting one or more of the biological activities of said target molecule, wherein said process comprises a stage of reconfiguration of the image region consisting of a modification of the amino acid sequence of said hinge region by the deletion, the addition or the substitution of at least one amino aced. The disclosure also relates to polypeptides useful for such a modulation method and the obtained antibodies.

NEUROPILIN ANTAGONISTS

Novel anti-NRP1 antibodies and variants thereof having unique structural and functional characteristics are disclosed. Also provided are uses of the antibodies in research, diagnostic and therapeutic applications. 1. A method for treating a mammal suffering from a disorder associated with pathological angiogenesis comprising administering an anti-neuropilin-1 (NRP1) antibody capable of inhibiting at least one neuropilin (NRP) mediated biological activity , which comprises a light chain variable domain comprising the following CDR amino acid sequences: CDRL1 (RASQSISSYLA; SEQ ID NO:123) , CDRL2 (GASSRAS; SEQ ID NO:124) and CDRL3 (QQYMSVPIT; SEQ ID NO:125).2. The method of claim 1 , wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO: 3.3. The method of claim 1 , wherein the antibody comprises a heavy chain variable domain comprising the following CDR amino acid sequences: CDRH1 (GFSFSSEPIS; SEQ ID NO:126) claim 1 , CDRH2 (SSITGKNGYTYYADSVKG; SEQ ID NO:127) and CDRH3 (WGKKVYGMDV; SEQ ID NO:128).4. The method of claim 3 , wherein the antibody comprises a heavy chain variable domain sequence of SEQ ID NO: 4.5. The method of claim 1 , wherein the antibody comprises a light chain variable domain sequence of SEQ ID NO:3 and a heavy chain variable domain sequence of SEQ ID NO:4.6. The method of claim 1 , wherein the antibody is a bispecific antibody.7. The method of claim 6 , wherein the bispecific antibody also binds to hVEGF.8. The method of claim 7 , wherein the portion of the antibody that binds to hVEGF is capable of binding to the same VEGF epitope as the antibody A4.6.1.9. The method of claim 1 , wherein the disorder is a cancer.10. The method of claim 9 , wherein the cancer is selected from the group consisting of breast cancer claim 9 , colorectal cancer claim 9 , non-small cell lung cancer claim 9 , renal cancer claim 9 , prostate cancer claim 9 , liver cancer claim 9 , head and neck cancer claim 9 , melanoma claim 9 , ovarian cancer ...

REDUCER OF IMMUNOSUPPRESSION BY TUMOR CELL AND ANTITUMOR AGENT USING THE SAME

The invention features methods for inhibiting enhancement of expression of a FoxP3 gene in a cell, methods for inhibiting induction of differentiation of a cell into a regulatory T cell, methods for reducing immunosuppression, methods for stimulating tumor immunity, and methods for treating a patient with a tumor. The methods of the invention involve suppressing function of an FSTL1 protein in the cell. In the methods of the invention, function of an FSTL1 protein in the cell may be suppressed using an anti-FSTL1 antibody. 1. A method for inhibiting enhancement of expression of FoxP3 gene in a cell , comprising suppressing function of an FSTL1 protein in the cell.2. A method of claim 1 , wherein function of an FSTL1 protein is suppressed with an anti-FSTL1 antibody.3. A method for inhibiting induction of differentiation of a cell into a regulatory T cell claim 1 , comprising suppressing function of an FSTL1 protein in the cell.4. A method of claim 3 , wherein function of an FSTL1 protein is suppressed with an anti-FSTL1 antibody.5. A method for reducing immunosuppression claim 3 , comprising suppressing function of an FSTL1 protein in a cell being capable of differentiating into a regulatory T cell.6. A method of claim 5 , wherein function of an FSTL1 protein is suppressed with an anti-FSTL1 antibody.7. A method for stimulating tumor immunity claim 5 , comprising suppressing function of an FSTL1 protein in the tumor cell.8. A method of claim 7 , wherein function of an FSTL1 protein is suppressed with an anti-FSTL1 antibody.9. A method for treating a patient with a tumor claim 7 , comprising suppressing function of an FSTL1 protein in the tumor cell.10. A method of claim 9 , wherein function of an FSTL1 protein is suppressed with an anti-FSTL1 antibody. This application is a continuation of U.S. patent application Ser. No. 12/674,881, having a 371(c) Date of Apr. 20, 2010, which is the U.S. National Stage filing under 35 U.S.C. §371 of International Application No. ...

ANTI-NEUROPILIN ANTIBODIES AND METHODS OF USE

The invention provides anti-NRP1 antibodies and methods of using the same. 1. An isolated antibody that binds to neuropilin-1 (NRP1) , wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:3 , (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:4 , and (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:5.2. The antibody of claim 1 , further comprising (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO:8; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO:9; and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO:10.3. An isolated antibody that binds to neuropilin-1 (NRP1) claim 1 , wherein the antibody comprises (a) HVR-L1 comprising the amino acid sequence of SEQ ID NO:8; (b) HVR-L2 comprising the amino acid sequence of SEQ ID NO:9; and (c) HVR-L3 comprising the amino acid sequence of SEQ ID NO:10.4. An isolated antibody that binds to neuropilin-1 (NRP1) claim 1 , wherein the antibody comprises (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:2; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:7; or (c) a VH sequence as in (a) and a VL sequence as in (b).5. The antibody of claim 4 , comprising a VH sequence of SEQ ID NO:2.6. The antibody of claim 4 , comprising a VL sequence of SEQ ID NO:7.7. An isolated antibody that binds to neuropilin-1 (NRP1) claim 4 , wherein the antibody comprises a VH sequence of SEQ ID NO:2 and a VL sequence of SEQ ID NO:7.8. The antibody of claim 1 , which is an IgG1 antibody.9. The antibody of claim 1 , which is an antibody fragment that binds neuropilin.10. An isolated nucleic acid encoding the antibody of .11. A host cell comprising the nucleic acid of .12. A method of producing an antibody comprising culturing the host cell of so that the antibody is produced.13. An immunoconjugate comprising the antibody of .14. The antibody of for use in detecting the presence of NRP1 ...

Human Antibodies Derived from Immunized Xenomice

Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. Various subsequent manipulations can be performed to obtain either antibodies per se or analogs thereof. 1. An isolated fully human antibody that binds to epidermal growth factor receptor (EGFR) , wherein the antibody was raised in a mouse that comprises 1020 kb of the human heavy chain locus.2. A transgenic mouse comprising 1020 kb of the human heavy chain locus , wherein the mouse produces a fully human antibody that binds to epidermal growth factor receptor (EGFR).3. A method of producing a fully human antibody to epidermal growth factor receptor (EGFR) comprising administering EGFR or an immunogenic portion thereof to a transgenic mouse comprising 1020 kb of the human heavy chain locus.4. A hybridoma cell comprising 1020 kb of the human heavy chain locus , wherein the hybridoma cell produces a fully human antibody that binds to epidermal growth factor receptor (EGFR).5. A method of producing cDNA encoding a fully human antibody to epidermal growth factor receptor (EGFR) comprising isolating the cDNA from the hybridoma cell of .6. A cDNA encoding a fully human antibody to epidermal growth factor receptor claim 4 , wherein the cDNA has been isolated from the hybridoma cell of .7. A vector comprising the cDNA of . The present application is a divisional of U.S. application Ser. No. 12/837,454, filed Jul. 15, 2010, which is a continuation of U.S. application Ser. No. 11/891,292, filed Aug. 8, 2007, which is a continuation of U.S. application Ser. No. 10/978,297, filed Oct. 29, 2004, now abandoned, which is a continuation of U.S. application Ser. No. 10/658,521, filed Sep. 8, 2003, now abandoned, which is a continuation of U.S. application Ser. No. 09/614,092, filed Jul. 11, 2000, now U.S. Pat. No. 6,713,610, which is a ...

METHODS OF INHIBITING TUMOR GROWTH BY ANTAGONIZING IL-6 RECEPTOR

The present invention provides methods for inhibiting or attenuating tumor growth in a subject by administering an IL-6 antagonist to the subject. In certain embodiments, the methods of the invention are used to inhibit the growth of an anti-VEGF-resistant tumor in a subject. The IL-6 antagonist may be, e.g., an antibody that specifically binds IL-6R. The IL-6 antagonist may be administered in combination with a VEGF antagonist, and/or an EGFR antagonist. 1. A method for inhibiting or attenuating the growth of an anti-VEGF-resistant tumor in a subject , the method comprising administering to the subject an anti-IL-6R antibody or antigen-binding fragment thereof.2. The method of further comprising administering to the subject VEGF antagonist.3. The method of claim 1 , wherein the anti-IL-6R antibody or antigen-binding fragment thereof comprises a heavy chain variable region (HCVR) and a light chain variable region (LCVR) claim 1 , wherein the HCVR comprises the complementarity determining regions (CDRs) of SEQ ID NO:2 claim 1 , and wherein the LCVR comprises the CDRs of SEQ ID NO:3.4. The method of claim 3 , wherein the HCVR comprises CDRs having the amino acid sequences of SEQ ID NOs:4 claim 3 , 5 claim 3 , and 6; and wherein LCVR comprises CDRs having the amino acid sequences of SEQ ID NOs:7 claim 3 , 8 and 9.5. The method of claim 2 , wherein the VEGF antagonist is a fusion protein comprising Ig domain 2 of VEGFR1 claim 2 , Ig domain 3 of VEGFR2 claim 2 , and a multimerizing domain.6. The method of claim 5 , wherein the Ig domain 2 of VEGFR1 comprises amino acids 27 to 129 of SEQ ID NO:11 claim 5 , the Ig domain 3 of VEGFR2 comprises amino acids 130 to 231 of SEQ ID NO:11 claim 5 , and the multimerizing domain comprises amino acids 232 to 457 of SEQ ID NO:11.7. A method of cancer therapy comprising: (i) measuring the level of IL-61STAT3 signaling in a sample from a subject; and (ii) administering an anti-IL-6R antibody or antigen-binding fragment thereof to the ...

ANTI-FERROPORTIN 1 MONOCLONAL ANTIBODIES AND USES THEREOF

Provided are monoclonal antibodies and antigen-binding fragments thereof that bind to, and inhibit the activity of human FPN1, and which are effective in maintaining or increasing the transport of iron out of mammalian cells and/or maintaining or increasing the level of serum iron, reticulocyte count, red blood cell count, hemoglobin, and/or hematocrit in a subject in vivo. 115-. (canceled)16. A polynucleotide comprising a nucleotide sequence encoding the light chain polypeptide as shown in SEQ ID NO: 154 or the heavy chain polypeptide as shown in SEQ ID NO: 152.171. The polynucleotide according to claim comprising a nucleotide sequence encoding the light chain polypeptide as shown in SEQ ID NO: 154 and the heavy chain polypeptide as shown in SEQ ID NO: 152.18. A recombinant expression vector comprising the polynucleotide of .19. A host cell which has been transformed by the expression vector of .20. The host cell according to wherein said cell is a Chinese hamster ovary (CHO) claim 19 , NS0 myeloma claim 19 , COS claim 19 , or SP2/0 cell.21. A method of increasing serum iron levels claim 19 , reticulocyte count claim 19 , red blood cell count claim 19 , hemoglobin claim 19 , and/or hematocrit comprising administering to a subject an effective amount of a monoclonal antibody comprising:a. the light chain and the heavy chain as shown in SEQ ID NO: 154 and SEQ ID NO: 152, respectively;b. the light chain and the heavy chain as shown in SEQ ID NO: 181 and SEQ ID NO: 179, respectively; orc. the light chain and the heavy chain as shown in SEQ ID NO: 158 and SEQ ID NO: 156, respectively.22. A method of treating anemia claim 19 , anemia of cancer claim 19 , or anemia of cancer associated with elevated levels of hepcidin in a subject claim 19 , comprising administering to the subject an effective amount of a monoclonal antibody comprising:a. the light chain and the heavy chain as shown in SEQ ID NO: 154 and SEQ ID NO: 152, respectively;b. the light chain and the heavy chain ...

NOVEL ANTI-IGF-IR ANTIBODIES AND USES THEREOF

The present invention relates to novel antibodies capable of binding specifically to the human insulin-like growth factor I receptor (IGF-IR). The invention likewise comprises the use of these antibodies as a medicament for the prophylactic and/or therapeutic treatment of cancers overexpressing IGF-IR, stimulated either by IGF1 and/or IGF2, or any pathology connected with the overexpression of said receptor as well as in processes or kits for diagnosis of illnesses connected with the overexpression of the IGF-IR and/or the IGF-I/Insulin hybrid receptor. 110-. (canceled)11. An isolated antibody , or one of its functional fragments , characterized in that it comprises a heavy chain comprising the three CDRs of sequence SEQ ID Nos. 2 , 4 and 6 , or three CDRs of sequence respectively having at least 80% of identity after optimum alignment with the sequence SEQ ID Nos. 2 , 4 and 6 and in that it moreover comprises a light chain comprising the three CDRs of sequence SEQ ID Nos. 1 , 3 and 5 , or three CDRs of sequence respectively having at least 80% of identity after optimum alignment with the sequence SEQ ID Nos. 1 , 3 and 5.1222-. (canceled)23. An isolated nucleic acid , characterized in that it is chosen from the following nucleic acids:{'claim-ref': {'@idref': 'CLM-00011', 'claim 11'}, 'a) a nucleic acid, DNA or RNA, coding for an antibody, or one of its functional fragments, as claimed in ;'}b) a complementary nucleic acid of a nucleic acid such as defined in a);c) a nucleic acid comprising the three CDRs of sequence SEQ ID No. 9, 10 and 11, and/or the three CDRs of sequence SEQ ID No 12, 13 and 144;d) a nucleic acid comprising the light chain of nucleic acid sequence SEQ ID No. 15 and/or the heavy chain of nucleic acid sequence SEQ ED No. 16; ande) a nucleic acid comprising the light chain of nucleic acid sequence SEQ ID No. 19 and/or the heavy chain of nucleic acid sequence SEQ ID No. 20.24. A vector comprising a nucleic acid as claimed in .25. A host cell ...

Purification of anti-c-met antibodies

Provided herein are methods of purifying anti-c-met antibodies, compositions and pharmaceutical formulations comprising purified anti-c-met antibodies, and methods of using the same.

Heterodimer Binding Proteins and Uses Thereof

The present disclosure provides polypeptide heterodimers formed between two different single chain fusion polypeptides via natural heterodimerization of an immunoglobulin CH1 region and an immunoglobulin light chain constant region (CL). The polypeptide heterodimer comprises two or more binding domains that specifically bind one or more targets (e.g., a receptor). In addition, both chains of the heterodimer further comprise an Fc region portion. The present disclosure also provides nucleic acids, vectors, host cells and methods for making polypeptide heterodimers as well as methods for using such polypeptide heterodimers, such as in directing T cell activation, inhibiting solid malignancy growth, and treating autoimmune or inflammatory conditions.

NEUTRALIZING PROLACTIN RECEPTOR ANTIBODIES AND THEIR THERAPEUTIC USE

The present invention is directed to the neutralizing prolactin receptor antibody 005-C04, as well as maturated forms thereof, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling. 1. Antibody or antigen-binding fragment , whereby said antibody antagonizes prolactin receptor-mediated signaling.2. Antibody of which binds to epitopes of the extracellular domain of the prolactin receptor and human polymorphic variants thereof claim 1 , whereby the amino acid sequence of the extracellular domain of the prolactin receptor corresponds to SEQ ID NO: 70 claim 1 , and the nucleic acid sequence corresponds to SEQ ID NO: 71.32. Antibody or antigen-binding fragment according to and/or claim 1 , whereby the antibody or the antigen-binding fragment competes to the antibody 005-C04 or defined maturated variants thereof according to table 5.4. Antibody or antigen-binding fragment according to claim 3 ,a. whereby the amino acid sequences of the variable heavy and light regions are at least 60%, more preferred 70%, more preferred 80%, or 90%, or even more preferred 95% identical to SEQ ID NO: 39 for the variable heavy chain domain and, identical to SEQ ID NO: 45 for the variable light chain domain, orb. whereby for the maturated forms of antibody 005-C04 the amino acid sequences of the variable heavy chain and light chain domain are at least 60%, more preferred 70%, more preferred 80%, or 90%, or even more preferred 95% identical thereto, orc. whereby the amino acid sequences ...

BIOLOGICAL MATERIALS RELATED TO HER3

The present disclosure relates to amino acid sequences that are directed against (as defined herein) HER3, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more such amino acid sequences (also referred to herein as “amino acid sequences of the invention”, “compounds of the invention”, and “polypeptides of the invention”, respectively). The disclosure also relates to nucleic acids encoding such amino acid sequences and polypeptides (also referred to herein as “nucleic acids of the invention” or “nucleotide sequences of the invention”); to methods for 10 preparing such amino acid sequences and polypeptides; to host cells expressing or capable of expressing such amino acid sequences or polypeptides; to compositions, and in particular to pharmaceutical compositions, that comprise such amino acid sequences, polypeptides, nucleic acids and/or host cells; and to uses of such amino acid sequences or polypeptides, nucleic acids, host cells and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes, such as the prophylactic, therapeutic or diagnostic purposes mentioned herein. 132-. (canceled)33. A protein or polypeptide comprising at least two immunoglobulin single variable (ISV) domains that are each directed to and/or that can each specifically bind to human HER3 (SEQ ID NO: 1) , in which each such ISV domain is independently:(a) capable of inhibiting or blocking binding of HRG to HER-3; and/or(b) capable of inhibiting or blocking heterodimerization of HER-3; and/or(c) capable of binding to domain II of HER-3.34. The protein or polypeptide according to claim 33 , comprising:(a) at least one ISV domain capable of inhibiting or blocking heterodimerization of HER-3; and(b) at least one ISV domain capable of inhibiting or blocking the binding of HRG to HER-3.35. The protein or polypeptide according to claim 33 , comprising:(a) at least one ISV domain capable of ...

ANTIBODY MOLECULES TO ONCOGENIC ISOFORMS OF FIBROBLAST GROWTH FACTOR RECEPTOR-2 AND USES THEREOF

Antibody molecules that specifically bind to one or more isoforms expressed and/or associated with oncogenic phenotypes in a hyperproliferative cell (e.g., a cancerous or tumor cell) are disclosed. The isoform-binding antibody molecules can be used to treat, prevent and/or diagnose cancerous conditions and/or disorders. Methods of using the isoform-binding molecules to selectively detect oncogenic isoforms, to reduce the activity and/or induce the killing of a hyperproliferative cell expressing an oncogenic isoform in vitro, ex vivo or in vivo are also disclosed. Diagnostic and/or screening methods and kits for evaluating the function or expression of an oncogenic isoform are also disclosed. 1. An antibody molecule that binds to human fibroblast growth factor receptor 2 (FGFR2) isoform IIIc or a fragment thereof , and shows less than 10% , cross-reactivity with human FGFR2 isoform IIIb.2. The antibody molecule of claim 1 , which selectively binds to an amino acid sequence encoded by Exon III of FGFR2 corresponding to about amino acids 301 to 360 of FGFR2-IIIc (SEQ ID NO:2); about amino acids 314 to 324 of FGFR2-IIIc (AAGVNTTDKEI claim 1 , SEQ ID NO:4); about amino acids 328 to 337 of FGFR2-IIIc (YIRNVTFEDA claim 1 , SEQ ID NO:6); about amino acids 350 to 353 of FGFR2-IIIc (ISFH claim 1 , SEQ ID NO:8); about amino acid residues 314-353 of FGFR2 IIIc (AAGVNTTDKEIEVLYIRNVTFEDAGEYTCLAGNSIGISFH (SEQ ID NO:84)); or about amino acids 342 to 353 of FGFR2-IIIc (TCLAGNSIGISFH (SEQ ID NO:86).3. The antibody molecule of claim 2 , having one or more biological properties chosen from one claim 2 , two claim 2 , three claim 2 , four claim 2 , five claim 2 , six claim 2 , seven claim 2 , or more of:(i) the antibody molecule competes for binding with human monoclonal antibody Atto-HuMab-01, Atto-HuMab-06 or Atto-HuMab-08;(ii) the antibody molecule competes for binding with monoclonal antibody Atto-MuMab-01, Atto-MuMab-02, or Atto-MuMab-03;(iii) binds to at least one amino acid ...

Zcytor17 heterodimeric cytokine receptor polynucleotides

Novel polypeptide combinations, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed for zcytor17-containing multimeric or heterodimer cytokine receptors that may be used as novel cytokine antagonists, and within methods for detecting ligands that stimulate the proliferation and/or development of hematopoietic, lymphoid and myeloid cells in vitro and in vivo. The present invention also includes methods for producing the multimeric or heterodimeric cytokine receptor, uses therefor and antibodies thereto.

Anti-ephrinb2 antibodies and methods using same

The invention provides anti-EphrinB2 antibodies, and compositions comprising and methods of using these antibodies.

Delivery System for Cytotoxic Drugs by Bispecific Antibody Pretargeting

The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.

Compositions for the treatment of rheumatoid arthritis and methods of using same

The present invention provides compositions and methods of treating and improving the symptoms of rheumatoid arthritis using an antibody or antigen-binding fragment thereof that specifically binds human interleukin-6 receptor (hIL-6R).

ANTIBODIES AGAINST GLUCAGON RECEPTOR AND THEIR USE

Disclosed are immunological compositions and methods for reducing activity of glucagon signaling using antibodies against glucagon receptor. 1. An isolated antibody , or an antigen-binding portion or a derivative thereof , comprising:(a) a first CDR set, CDR1, CDR2 and CDR3, that sequentially together comprises the amino acid sequences of heavy chain CDRs, CDR1, CDR2 and CDR3, sequentially together, that are included in the amino acid sequence as set forth in any one of SEQ ID Nos. 2, 4, 6, 8, 10, 12, 14, and 16;(b) a second CDR set, CDR1, CDR2 and CDR3, that sequentially together comprises the amino acid sequences of light chain CDRs, CDR1, CDR2 and CDR3, sequentially together, that are included in the amino acid sequence as set forth in any one of SEQ ID Nos. 18, 20, 22, 24, 26, 28 and 30; or,(c) a combination of said first CDR set of (a) and said second CDR set of (b).2. The isolated antibody claim 1 , or an antigen-binding portion or a derivative thereof claim 1 , according to claim 1 , comprising a heavy chain or a light chain claim 1 , or both of them claim 1 , wherein said heavy chain comprises a heavy chain variable region having the amino acid sequence as set forth in any one of SEQ ID Nos. 2 claim 1 , 4 claim 1 , 6 claim 1 , 8 claim 1 , 10 claim 1 , 12 claim 1 , 14 claim 1 , and 16 claim 1 , or antigen-binding fragments thereof; and said light chain comprises a light chain variable region having the amino acid sequence as set forth in any one of SEQ ID Nos. 18 claim 1 , 20 claim 1 , 22 claim 1 , 24 claim 1 , 26 claim 1 , 28 claim 1 , and 30 claim 1 , or antigen-binding fragments thereof.3. The isolated antibody claim 2 , or an antigen-binding portion or a derivative thereof claim 2 , according to claim 2 , which is selected from the group consisting of:(a) an antibody comprising the amino acid sequences as set forth in SEQ ID No. 2 and SEQ ID No. 18;(b) an antibody comprising the amino acid sequences as set forth in SEQ ID NO. 4 and SEQ ID NO. 20;(c) an ...

DESIGN AND DEVELOPMENT OF MASKED THERAPEUTIC ANTIBODIES TO LIMIT OFF-TARGET EFFECTS; APPLICATION TO ANTI-EGFR ANTIBODIES

In one embodiment, a masked monoclonal antibody (mAb) is provided, the mAb, encoded by a nucleic acid sequence or an amino acid sequence molecule comprising a signal sequence, a masking epitope sequence, a linker sequence that is cleavable by a protease specific to a target tissue; and an antibody or a functional fragment thereof. In another embodiment, a cross-masked mAb heterodimer complex is provided, comprising a first masked mAb, comprising a first signal sequence, a first masking epitope sequence, a first linker that is cleavable by a protease specific to a target tissue, and a first antibody or fragment thereof; and a second masked mAb, comprising a second signal sequence, a second masking epitope sequence, a second linker that is cleavable by a protease specific to a target tissue, and a second antibody or fragment thereof. 1. A masked monoclonal antibody (mAb) , encoded by a nucleic acid sequence or an amino acid sequence molecule comprising:(a) a signal sequence;(b) a masking epitope sequence;(c) a linker sequence that is cleavable by a protease specific to a target tissue; and(d) an antibody or a functional fragment thereof.2. The masked mAb of claim 1 , wherein the masking epitope sequence encodes an epitope specific to an antigenic recognition site of the antibody or functional fragment thereof.3. The masked mAb of claim 2 , wherein the antigenic recognition site is one or more complementary determining regions (CDRs).4. The masked mAb of claim 1 , wherein the protease is matrix metalloproteinase-9 (MMP-9).5. The masked mAb of claim 1 , wherein the antibody or functional fragment thereof is specific to EGFR.6. The masked mAb of claim 1 , wherein the antibody or functional fragment thereof is an IgG sequence.7. The masked mAb of claim 1 , wherein the antibody or functional fragment thereof is an scFv sequence.8. The masked mAb of claim 1 , wherein the masked mAb is a nucleic acid sequence consisting of SEQ ID NO:1.9. The masked mAb of claim 1 , wherein ...

Mammalian Receptor Proteins; Related Reagents and Methods

Nucleic acids encoding mammalian, e.g., primate, receptors, purified receptor proteins and fragments thereof. Antibodies, both polyclonal and monoclonal, are also provided. Methods of using the compositions for both diagnostic and therapeutic utilities are described. 1. A method of treating a human subject experiencing a physiological disorder comprising administering an effective amount of an agonist or antagonist of DCRS5 (SEQ ID NOs:1 or 2) or of p19 (SEQ ID NOs:5 or 6) , wherein the disorder comprises:a) rheumatoid arthritis;b) asthma or allergy;c) chronic obstructive pulmonary disorder (COPD);d) an interstitial lung disorder;e) an inflammatory bowel disorder (IBD); orf) an inflammatory skin disorder.2. The method of claim 1 , wherein the skin disorder is:a) psoriasis; orb) atopic dermatitis.3. The method of claim 1 , wherein the IBD is:a) Crohn's disease; orb) ulcerative colitis.4. The method of claim 1 , wherein the interstitial lung disorder is:a) idiopathic pulmonary fibrosis;b) eosinophilic granuloma; orc) hypersensitivity pneumonitis.5. The method of claim 1 , wherein the antagonist comprises a binding composition derived from the antigen binding site of an antibody that specifically binds to:a) DCRS5 (SEQ ID NO:2); orb) p19 (SEQ ID NO:6).6. The method of claim 5 , wherein the binding composition comprises:a) a polyclonal antibody;b) a monoclonal antibody;c) a humanized antibody; or{'sub': '2', 'd) an Fab, Fv, or F(ab′)fragment.'}7. The method of claim 1 , wherein the agonist comprises:a) DCRS5 (SEQ ID NO:2); orb) p19 (SEQ ID NO:6).8. The method of claim 1 , wherein the agonist or antagonist comprises a nucleic acid.9. The method of claim 8 , wherein the antagonist comprises:a) an antisense nucleic acid; orb) an RNA interference nucleic acid.10. A method of diagnosing a physiological disorder comprising contacting a binding composition that specifically binds to DCRS5 (SEQ ID NOs:1 or 2) claim 8 , or to p19 (SEQ ID NOs:5 or 6) claim 8 , to a sample derived ...

Optimized Fc Variants and Methods For Their Generation

The present invention relates to optimized Fc variants, methods for their generation, and antibodies and Fc fusions comprising optimized Fc variants.

TREATMENT OF DRY AGE RELATED MACULAR DEGENERATION

A method of treating dry age related macular degeneration (“AMD”) comprising administration to the eye of an individual in need thereof of a therapeutically effective amount of an anti-endoglin agent. 1. A method of treating dry age related macular degeneration (“AMD”) comprising administration to the eye of an individual in need thereof of a therapeutically effective amount of an anti-endoglin agent.2. The method of claim 1 , wherein the anti-endoglin agent is an antibody or fragment thereof.3. The method of claim 1 , wherein the anti-endoglin agent is an anticalin.4. The method of claim 1 , wherein the anti-endoglin agent is an ankyrin repeat.5. The method of claim 1 , wherein the anti-endoglin agent is an avimer.6. The method of claim 1 , wherein the anti-endoglin agent is a nanobody.7. The method of claim 1 , wherein the anti-endoglin agent is a versabody. This non-provisional patent application claims priority to U.S. provisional patent application Ser. No. 61/560,118, filed on Nov. 15, 2011, which is hereby incorporated by reference in its entirety.The present invention relates the treatment of dry age related macular degeneration, specifically with molecules that target endoglinAge-related macular degeneration (AMD) is the leading cause of blindness in developed nations. AMD is a medical condition which usually affects older adults and results in a loss of vision in the center of the visual field (the macula) because of damage to the retina. It occurs in “dry” and “wet” forms. It is a major cause of blindness and visual impairment in older adults (>50 years). Macular degeneration can make it difficult or impossible to read or recognize faces, although enough peripheral vision remains to allow other activities of daily life.Neovascular or exudative AMD, the “wet” form of advanced AMD, causes vision loss due to abnormal blood vessel growth (choroidal neovascularization) in the choriocapillaris, through Bruch's membrane, ultimately leading to blood and protein ...

Bispecific Anti ErbB1 / Anti cMet Antibodies

The present invention relates to bispecific antibodies against human ErbB-1 and against human c-Met, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof. 1. A bispecific antibody that specifically binds to human ErbB-1 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-1 and a second antigen-binding site that specifically binds to human c-Met , wherein the bispecific antibody causes an increase in internalization of c-Met on OVCAR-8 cells of no more than 15% when measured after 2 hours of OVCAR-8 cell-antibody incubation as measured by a flow cytometry assay as compared to internalization of c-Met on OVCAR-8 cells in the absence of the bispecific antibody.2. The bispecific antibody according to wherein the antibody is a bivalent or trivalent bispecific antibody comprising one or two antigen-binding sites that specifically bind to human ErbB-1 and a third antigen-binding site that specifically binds to human c-Met.3. The antibody according to comprisinga) a full length antibody that specifically binds to ErbB-1 consisting of two antibody heavy chains and two antibody light chains; andb) one single chain Fab fragment that specifically binds to human c-Met,wherein the single chain Fab fragment under b) is fused to the full length antibody under a) via a peptide connector to the C- or N-terminus of the heavy or light chain of the full length antibody.4. A bispecific antibody that specifically binds to human ErbB-1 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-1 and a second antigen-binding site that specifically binds to human c-Met claim 2 , wherein 'the second antigen-binding site comprises in the heavy chain variable domain a CDR3H region with the amino acid sequence of SEQ ID NO: 30, a CDR2H region with the amino acid sequence of, SEQ ID NO: 31, and a CDR1H region with the amino acid sequence of SEQ ID NO: 32, and in the light ...