S1P MODULATING AGENTS (Fri, 08 Aug 2014)
Compounds of formula (I) can modulate the activity of one or more S 1P receptors. Sphingosine 1-phosphate (S IP) is a lysophospholipid mediator that evokes a variety of cellular responses by stimulation of five members of the endothelial cell differentiation gene (EDG) receptor family, namely S1P1, S1P2, S1P3, S1P4, and S1P5 (formerly EDG1, EDG5, EDG3, EDG6 and EDG8). The EDG receptors are G-protein coupled receptors (GPCRs) and on stimulation propagate second messenger signals via activation of heterotrimeric G-protein alpha (Ga.) subunits and beta-gamma (G()y) dimers.
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DEUTERIUM SUBSTITUTED FUMARATE DERIVATIVES (Fri, 27 Jun 2014)
Provided is a compound of formula (I), or a pharmaceutically acceptable salt thereof. Also provided is a method of treating, prophylaxis, or amelioration of a disease, comprising administering to a subject in need of treatment for the disease an effective amount of a compound of formula (I) described herein. In one embodiment, the method is a neurodegenerative disease, such as multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease, or Alzheimer's disease.
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ANTI-BLOOD DENDRITIC CELL ANTIGEN 2 ANTIBODIES AND USES THEREOF (Fri, 20 Jun 2014)
Antibodies and antibody fragments that bind to BDCA2 are disclosed. Also disclosed are methods of using the antibodies and antibody fragments to induce death of a plasmacytoid dendritic cell, inhibit production or secretion of inflammatory cytokines and chemokines, and treat or prevent immunological disorders such as inflammatory and autoimmune conditions.
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S1P AND/OR ATX MODULATING AGENTS (Sat, 31 May 2014)
Compounds of formula (I), and pharmaceutically acceptable salts thereof, can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).
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S1P AND/OR ATX MODULATING AGENTS (Sat, 31 May 2014)
Compounds of formula (I) wherein: X is -0-, -S(0)r-, -CH2-, or -NR-, wherein r is 0, 1, or 2; X 1, X2, and X5 are each independently CR7 or N; one of X3 or X4 is C and is attached by a single bond to -L-, and the other is CR7 or N, provided that no more than three of X1, X2, X3, X or X5 are N; Ring A is monocyclic C5-6scycloalkyl or a 5- to 6-membered monocyclic heterocyclyl comprising from 1 to 5 heteroatoms independently selected from N, S, or 0; wherein Ring A is further optionally substituted with from 1 to 3 R4; provided that Ring A is not morpholinyl, thiomorpholinyl or tetrahydro-2H-pyranyl; L is a bond, -0-, -NR-, -S(0)n-, -CH2-,or -C(O)-, wherein n is 0, 1, or 2; 1 2 L1 is an C1-8alkylene, C3-scycloalkylene, -CH2-L2 -, or a 3- to 8- membered heterocyclylene comprising 1 to 5; R1 is C6-20alkyl or a monocyclic C3-8cycloalkyl; wherein said C3-8cycloalkyl is substituted with at least one R6 and may be optionally substituted with from 1 to 5 additional R6 substituents, wherein R6 for each occurrence is independently selected; and R2 is -C(0)OR3, -C(0)N(R3)-S(0)2R3, -S(0)2OR3, -C(0)NHC(0) R3, -Si(0)OH, - B(OH)2, -N(R3)S(0)2R3, -S(0)2N(R3)2, -O-P(O) (OR3)2, or -P(0)(OR3)2, -CN, - S(0)2NHC(0)R3, -C(0)NHS(0)2R3, - C(0)NHOH, -C(0)NHCN, -CH(CF3)OH, -C(CF3)2OH, or a selected heteroaryl or heterocyclyl; and pharmaceutically acceptable salts thereof, can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).
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NOVEL COMPOUNDS FOR MODULATION OF ROR-GAMMA ACTIVITY (Fri, 21 Feb 2014)
The present invention relates to aryl sulfones and related compounds that are modulators of ROR-gamma receptors. The invention also provides pharmaceutical compositions comprising these modulators, and methods of modulating ROR-gamma receptors using them. Also provided are methods of using aryl sulfones and related compounds as modulators of ROR-gamma to treat ROR-gamma mediated diseases.
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COMPOUNDS THAT ARE S1P MODULATING AGENTS AND/OR ATX MODULATING AGENTS (Fri, 14 Feb 2014)
Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).
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COMPOUNDS THAT ARE S1P MODULATING AGENTS AND/OR ATX MODULATING AGENTS (Fri, 14 Feb 2014)
Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).
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ATX MODULATING AGENTS (Fri, 31 Jan 2014)
Disclosed are bicyclic aryl compounds of formula (I), that can modulate the activity of the autotaxin (ATX) enzyme. This invention further relates to compounds that are ATX inhibitors, and methods of making and using such compounds in the treatment of demyelination due to injury or disease, as well as for treating proliferative disorders such as cancer.
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ATX MODULATING AGENTS (Fri, 31 Jan 2014)
Compounds of formula (I) can modulate the activity of autotaxin (ATX).
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COMPOUNDS THAT ARE S1P MODULATING AGENTS AND/OR ATX MODULATING AGENTS (Fri, 31 Jan 2014)
Compounds of formula (I) can modulate the activity of one or more SIP receptors and/or the activity of autotaxin (ATX).
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FACTOR VIII COMPLEX WITH XTEN AND VON WILLEBRAND FACTOR PROTEIN, AND USES THEREOF (Fri, 17 Jan 2014)
The present invention includes a chimeric protein comprising a VWF protein with D' domain and D3 domain ofVWF, one or more XTEN sequence, and a FVIII protein, wherein the VWF fragment, the XTEN sequence, or the FVIII protein are linked to or associated with each other. The chimeric protein can further comprise one or more Ig constant region or a portion thereof (e.g., an Fc region). A polypeptide chain of a VWF fragment is associated with a FVIII polypeptide chain linked to an XTEN sequence. The VWF fragment polypeptide chain can prevent or inhibit binding of endogenous VWF toFVIII protein linked to the XTEN sequence. By preventing or inhibiting binding of endogenous VWF to FVIII protein, VWF fragment can extend half-life of chimeric protein comprising FVIII protein. The invention includes nucleotides, vectors, host cells, use of VWF fragment, or chimeric proteins.
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BIARYL-CONTAINING COMPOUNDS AS INVERSE AGONISTS OF ROR-GAMMA RECEPTORS (Fri, 10 Jan 2014)
The present invention relates to biaryl-containing inverse agonists of ROR-gamma receptors. The invention also provides pharmaceutical compositions comprising these biaryl- containing inverse agonists, and methods of modulating ROR-gamma receptors using these inverse agonists. Also provided are methods of using biaryl-containing inverse agonists to treat ROR-gamma mediated diseases.
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PYRIMIDINYL TYROSINE KINASE INHIBITORS (Fri, 13 Dec 2013)
The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.
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INHIBITORS OF BRUTON'S TYROSINE KINASE (Fri, 13 Dec 2013)
The present invention provides a compound, solid forms, and compositions thereof, which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same. The present invention also provides methods of making provided compound and solid forms.
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TRAPPING REAGENTS FOR REACTIVE METABOLITES SCREENING (Fri, 29 Nov 2013)
The present invention provides compounds of Formula (I) and (II): (I) (II) wherein R1, R2, R4, R5, R6, X and n are as defined herein, and wherein R3 is hydrogen or a sulfur protecting group. Compounds of Formula (I) and (II), wherein R is hydrogen, may be useful in methods for detecting a reactive metabolite in a sample, e.g., wherein the metabolite is generated from the metabolism of a test compound, and wherein the metabolite and the compound of Formula (I) or (II) react to form a detectable adduct, e.g., detectable by mass spectrometry.
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Pharmaceutical Compositions Containing Dimethyl Fumarate (Fri, 08 Nov 2013)
<p id="p-0001" num="0000">Provided herein are compositions containing compounds, or pharmaceutically acceptable salts, that metabolize to monomethyl fumarate with certain pharmacokinetic parameters and methods for treating, prophylaxis, or amelioration of neurodegenerative diseases including multiple sclerosis using such compositions in a subject, wherein if the compositions contain dimethyl fumarate, the total amount of dimethyl fumarate in the compositions ranges from about 43% w/w to about 95% w/w.</p>
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PHARMACEUTICAL COMPOSITIONS CONTAINING DIMETHYL FUMARATE (Fri, 16 Aug 2013)
Provided herein are compositions containing compounds, or pharmaceutically acceptable salts, that metabolize to monomethyl fumarate with certain pharmacokinetic parameters and methods for treating, prophylaxis, or amelioration of neurodegenerative diseases including multiple sclerosis using such compositions in a subject, wherein if the compositions contain dimethyl fumarate, the total amount of dimethyl fumarate in the compositions ranges from about 43% w/w to about 95% w/w.
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SILICON-CONTAINING FUMARIC ACID ESTERS (Fri, 21 Jun 2013)
The present invention is directed to silicon-containing fumaric acid esters of the Formulae I-IV. The silicon- containing fumaric acid esters of Formulae I-IV are useful in transplantation medicine and for the treatment of autoimmune diseases and autoimmune-related diseases. (I), (II), (III) & (IV)
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ANTI-TIM-1 ANTIBODIES AND USES THEREOF (Fri, 31 May 2013)
Antibodies and antibody fragments that bind to human TIM-1 on the BED face of the protein are disclosed. Also disclosed are methods of using the antibodies and antibody fragments to inhibit or reduce TIM-1 binding to phosphatidylserine, inhibit or reduce TIM-1 binding to dendritic cells, and treat or prevent immunological disorders such as inflammatory and autoimmune conditions.
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LIGHT TARGETING MOLECULES AND USES THEREOF (Fri, 26 Apr 2013)
<p id="p-0001" num="0000">LIGHT-targeting molecules (e.g., LIGHT fusion molecules), compositions, e.g., pharmaceutical compositions thereof, are disclosed. Methods of using these molecules to treat, prevent and/or diagnose hyperproliferative, e.g., neoplastic, diseases or conditions, including, but not limited to, cancer and metastasis are also provided.</p>
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TREATING NEUROLOGICAL DISORDERS (Fri, 19 Apr 2013)
<p id="p-0001" num="0000">Methods of treating neuronal disorders, such as mechanical neuronal traumas and neurodegenerative disorders, with TWEAK or a TWEAK receptor blocking agents are presented.</p>
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Bicyclic aryl sphingosine 1-phosphate analogs (Fri, 08 Mar 2013)
<p id="p-0001" num="0000">Compounds that have agonist activity at one or more of the SIP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SIP receptors.</p>
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USE OF NUCLEAR MAGNETIC RESONANCE AND NEAR INFRARED TO ANALYZE BIOLOGICAL SAMPLES (Fri, 08 Mar 2013)
In one aspect, the disclosure provides methods for using NMR and NIR to evaluate biological samples. In some embodiments, the methods include a step of performing a Nuclear Magnetic Resonance (NMR) analysis on a sample to obtain an NMR spectrum, a step of performing a Near Infrared Spectroscopy (NIR) analysis on the sample to obtain an NIR spectrum, and/or a step of performing a data fusion analysis to evaluate the NIR spectrum.
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Binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind CD154 and uses thereof (Fri, 22 Feb 2013)
<p id="p-0001" num="0000">This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.</p>
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Detection and quantitation of cyclodextrins (Fri, 04 Jan 2013)
<p id="p-0001" num="0000">The invention relates to the detection and quantitation of cyclodextrins and cyclodextrin derivatives in solutions comprising a protein. The invention further relates to methods of evaluating pharmaceutical preparations for the presence of residual cyclodextrins.</p>
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PROCESS FOR PREPARING HIGH PURITY AND CRYSTALLINE DIMETHYL FUMARATE (Fri, 14 Dec 2012)
The present invention describes a process for the preparation of dimethyl fumarate. The process involves the esterification of fumaric acid and methanol in the presence of sulfuric acid as an acid catalyst. The high purity dimethyl fumarate contains no more than trace amounts of dimethyl sulfate. The present invention also provides a process for the preparation of highly pure dimethyl fumarate with a particle size from 20 to 250 μπι.
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Treating neurological disorders (Thu, 06 Dec 2012)
Methods of treating neuronal disorders, such as mechanical neuronal traumas and neurodegenerative disorders, with TWEAK or a TWEAK receptor blocking agents are presented.
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Biomarkers for multiple sclerosis and methods of use thereof (Thu, 01 Nov 2012)
Biomarkers useful for identifying treatments for and monitoring treatment of patients with multiple sclerosis (MS) are provided, as well as methods for their identification, methods of diagnosing MS, relapse of MS patients and disease progression in MS patients.
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S1P MODULATING AGENTS (Fri, 17 Aug 2012)
Compounds of formula (I) or (II) can modulate the activity of SIP receptors.
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Bruton's tyrosine kinase inhibitors (Fri, 22 Jun 2012)
<p id="p-0001" num="0000">The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.</p>
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Anti alpha v beta 6 antibodies and uses thereof (Thu, 31 May 2012)
The present invention is in the fields of cell biology, immunology and oncology. Specifically, the invention relates to humanized antibodies that recognizes v 6 integrins which comprises a variable region of nonhuman origin and at least -a portion of an immunoglobulin of human origin. The invention also relates to processes for their preparation, to pharmaceutical compositions comprising them and to methods of treating various diseases by administering humanized anti- v 6 antibodies. The invention also relates to the identification of differential expression of the integrin avß6 on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin avß6.
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HETEROCYCLIC TYROSINE KINASE INHIBITORS (Fri, 04 May 2012)
The present invention provides compounds useful as inhibitors of Tec family kinases, compositions thereof, and methods of using the same. In certain embodiments, the present invention provides pharmaceutical formulations comprising provided compounds. In certain embodiments, the present invention provides a method of decreasing enzymatic activity of a Tec kinase family member. In some embodiments, such methods include contacting a Tec kinase family member with an effective amount of a Tec kinase family member inhibitor. In certain embodiments, the present invention provides a method of treating a disorder responsive to Tec kinase family inhibition in a subject in need thereof.
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Anti alpha v beta 6 antibodies and uses thereof (Thu, 03 May 2012)
The present invention is in the fields of cell biology, immunology and oncology. Specifically, the invention relates to humanized antibodies that recognizes v 6 integrins which comprises a variable region of nonhuman origin and at least -a portion of an immunoglobulin of human origin. The invention also relates to processes for their preparation, to pharmaceutical compositions comprising them and to methods of treating various diseases by administering humanized anti- v 6 antibodies. The invention also relates to the identification of differential expression of the integrin ±v²6 on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin ±v²6.
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Anti-CD154 antibodies (Thu, 29 Dec 2011)
The present invention provides peptides, and fragments thereof, and antibodies, or fragments thereof comprising the same, wherein the peptide comprises at least one amino acid substitution compared to wild type 5c8 antibody. The present invention also provides compositions and methods of treating CD154-related diseases or disorders in a subject.
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Anti-Alpha v Beta 6 Antibodies and Uses Thereof (Fri, 16 Dec 2011)
<p id="p-0001" num="0000">The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize α<sub>v</sub>β<sub>6 </sub>integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-α<sub>v</sub>β<sub>6 </sub>antibodies of the invention. The invention also relates to the identification of differential expression of the integrin α<sub>v</sub>β<sub>6 </sub>on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin α<sub>v</sub>β<sub>6</sub>.</p>
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Stabilized polypeptide compositions (Fri, 09 Dec 2011)
<p id="p-0001" num="0000">The invention is based, at least in part, on the development of stabilized binding molecules that consist of or comprise a stabilized scFv and methods for making such stabilized molecules.</p>
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Compositions and Methods for Inhibiting Growth of SMAD-4 Deficient Cancers (Fri, 02 Dec 2011)
<p id="p-0001" num="0000">The present invention is in the fields of cell biology, immunology and oncology. The invention relates to the discovery that there is a relationship between the expression levels of the tumor suppressor gene smad4 (also known as dpc4) and integrin α<sub>v</sub>β<sub>6</sub>, and the responsiveness of patient populations to α<sub>v</sub>β<sub>6</sub>-active compounds and compositions (e.g., antibodies and other ligands that bind α<sub>v</sub>β<sub>6</sub>), particularly in cancer cells from such patient populations, more particularly on carcinomas such as pancreatic carcinomas. The invention thus provides methods for determining the responsiveness of tumor cells (particularly those from pancreatic tumors) to such α<sub>v</sub>β<sub>6</sub>-active compounds and compositions by examining the expression of α<sub>v</sub>β<sub>6 </sub>and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and small molecule drugs, that bind to integrin α<sub>v</sub>β<sub>6 </sub>on the surfaces of tumor cells and/or that block one or more components of the TGF-β pathway, particularly in smad4-deficient tumor cells.</p>
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Neonatal Fc rReceptor (FcRn)- binding polypeptide variants, dimeric Fc binding proteins and methods related thereto (Thu, 10 Nov 2011)
The compositions and methods of the present invention are based, in part, on our discovery that an effector function mediated by an Fc-containing polypeptide can be altered by modifying one or more amino acid residues within the polypeptide (by, for example, electrostatic optimization). The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof.
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STABILIZED ANTI-TNF-ALPHA scFv MOLECULES OR ANTI-TWEAK scFv MOLECULES AND USES THEREOF (Fri, 15 Jul 2011)
The instant invention is based, at least in part on the finding that binding molecules which simultaneously bind to multiple epitopes within TNF-alpha result in improved TNFR-1 and/or TNFR-2 blocking capabilities when compared to binding molecules that bind to a single TNF-alpha epitope. The instant invention provides compositions that bind to multiple epitopes of TNF-alpha, for example, combinations of monospecific binding molecules or multispecific binding molecules (e.g., bispecific molecules). Methods of making the subject binding molecules and methods of using the binding molecules of the invention to antagonize TNF-alpha signaling are also provided.
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Indazole derivatives as modulators of interleukin-1 receptor-associated kinase (Fri, 24 Jun 2011)
<p id="p-0001" num="0000">The present invention relates to modulators of IRAK kinases of formula (I) and provides compositions comprising such modulators, as well as methods therewith for treating IRAK-mediated or IRAK-associated conditions or diseases.</p>
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Treating neurological disorders (Thu, 16 Jun 2011)
Methods of treating neuronal disorders, such as mechanical neuronal traumas and neurodegenerative disorders, with TWEAK or a TWEAK receptor blocking agents are presented.
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Poycyloalkylpurines as adenosine receptor antagonists (Thu, 07 Apr 2011)
The invention is based on the discovery that compounds of Formula (I) are unexpectedly highly potent and selective inhibitors of the adenosine A 1 receptor. Adenosine A 1 antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I).
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HETEROARYL BTK INHIBITORS (Fri, 11 Mar 2011)
The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.
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BRUTON'S TYROSINE KINASE INHIBITORS (Fri, 11 Mar 2011)
The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.
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BRUTON'S TYROSINE KINASE INHIBITORS (Fri, 11 Mar 2011)
The present invention provides compounds useful as inhibitors of Btk, compositions thereof, and methods of using the same.</p>
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BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS (Fri, 11 Feb 2011)
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
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BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS (Fri, 11 Feb 2011)
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.</p>
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MODULATORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 28 Jan 2011)
<p id="p-0001" num="0000">The present invention relates to modulators of IRAK kinase and provides compositions comprising such modulators, as well as methods therewith for treating conditions or diseases mediated by or associated with IRAK kinase.</p>
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CARBOXYLIC ACID-CONTAINING COMPOUNDS, DERIVATIVES THEREOF, AND RELATED METHODS OF USE (Fri, 03 Dec 2010)
Compounds that modulate gamma secretase (e.g., alter the cleavage pattern of gamma secretase) are described herein. Also disclosed are pharmaceutical compositions, methods of modulating the activity of gamma secretase, and methods of treating Alzheimer's Disease using the compounds described herein.
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Biomarkers of Multiple Sclerosis (Fri, 12 Nov 2010)
<p id="p-0001-en" num="0000">Biomarkers of multiple sclerosis (MS) and of anti-TWEAK/TWEAK-Receptor therapy for MS are described.</p>
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CERTAIN SUBSTITUTED PYRIMIDINES, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS FOR THEIR USE (Fri, 15 Oct 2010)
Provided are certain Hsp90 inhibitors, i.e., compounds of Formula I and pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods for their use and preparation.
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BICYCLIC SPHINGOSINE 1-PHOSPHATE ANALOGS (Fri, 24 Sep 2010)
<p id="p-0001-en" num="0000">Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.</p>
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FC GAMMA RECEPTOR-BINDING POLYPEPTIDE VARIANTS AND METHODS RELATED THERETO (Fri, 13 Aug 2010)
<p id="p-0001-en" num="0000">The compositions and methods of the present invention are based, in part, on our discovery that an effector function mediated by an Fc-containing polypeptide can be altered by modifying one or more amino acid residues within the polypeptide (by, for example, electrostatic optimization). The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof.</p>
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STABILIZED FC POLYPEPTIDES WITH REDUCED EFFECTOR FUNCTION AND METHODS OF USE (Fri, 30 Jul 2010)
A method of producing Fc-containing polypeptides, such as antibodies, having stabilized Fc regions is provided, together with stabilized Fc polypeptides produced according to these methods as well as methods of using such antibodies as therapeutics.
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STABILIZED FC POLYPEPTIDES WITH REDUCED EFFECTOR FUNCTION AND METHODS OF USE (Fri, 30 Jul 2010)
A method of producing Fc-containing polypeptides, such as antibodies, having stabilized Fc regions is provided, together with stabilized Fc polypeptides produced according to these methods as well as methods of using such antibodies as therapeutics. </p>
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ALTERED BR-3 BINDING POLYPEPTIDES (Fri, 02 Jul 2010)
<p id="p-0001-en" num="0000">The present invention relates to novel BR3 binding antibodies having altered Fc effector function and/or having a mature core carbohydrate structure in the Fc region which lacks fiicose. The present invention also relates to the use of those BR3 binding antibodies and polypeptides in, e.g., methods of treatment, screening methods, diagnostic methods, assays and protein purification methods.</p>
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Transforming Growth Factor Modulators (Fri, 02 Jul 2010)
<p id="p-0001-en" num="0000">The invention is related to compounds of formula (I) that can be used as antagonists of the TGFβ family type I receptors, Alk5 and/or Alk4, compositions and methods of use. The compounds of formula (I) can be employed in the prevention and/or treatment of diseases such as fibrosis (e.g., renal fibrosis, pulmonary fibrosis, and hepatic fibrosis), progressive cancers, or other diseases for which reduction of TGFβ family signaling activity is desirable.</p>
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Bicyclic aryl sphingosine 1-phosphate analogs (Fri, 25 Jun 2010)
<p id="p-0001" num="0000">Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors.</p>
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Heterobicyclic sphingosine 1-phosphate analogs (Fri, 25 Jun 2010)
<p id="p-0001" num="0000">Compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.52mm" wi="47.24mm" file="US08349849-20130108-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors. </p>
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Polymorphs and solvates of a pharmaceutical and method of making (Fri, 28 May 2010)
<p id="p-0001-en" num="0000">Polymorphic and solvated forms of solid 3-(4-amino-3-methylbenzyl)-7-(furan-2-yl)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine, and methods of making them, are described.</p>
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Light targeting molecules and uses thereof (Fri, 14 May 2010)
<p id="p-0001" num="0000">LIGHT-targeting molecules (e.g., LIGHT fusion molecules), anti-HER2 antibody molecules, compositions, e.g., pharmaceutical compositions thereof, are disclosed. Methods of using these molecules to treat, prevent and/or diagnose hyperproliferative, e.g., neoplastic, diseases or conditions, including, but not limited to, cancer and metastasis are also provided.</p>
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BICYCLIC ARYL SPHINGOSINE 1-PHOSPHATE ANALOGS (Fri, 07 May 2010)
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S lP receptors.
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HETEROBICYCLIC SPHINGOSINE 1-PHOSPHATE ANALOGS (Fri, 07 May 2010)
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors.
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LIGHT TARGETING MOLECULES AND USES THEREOF (Fri, 07 May 2010)
LIGHT-targeting molecules (e.g., LIGHT fusion molecules), anti-HER2 antibody molecules, compositions, e.g., pharmaceutical compositions thereof, are disclosed. Methods of using these molecules to treat, prevent and/or diagnose hyperproliferative, e.g., neoplastic, diseases or conditions, including, but not limited to, cancer and metastasis are also provided.
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LIGHT TARGETING MOLECULES AND USES THEREOF (Fri, 07 May 2010)
LIGHT-targeting molecules (e.g., LIGHT fusion molecules), anti-HER2 antibody molecules, compositions, e.g., pharmaceutical compositions thereof, are disclosed. Methods of using these molecules to treat, prevent and/or diagnose hyperproliferative, e.g., neoplastic, diseases or conditions, including, but not limited to, cancer and metastasis are also provided.</p>
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Binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind CD154 and uses thereof (Fri, 30 Apr 2010)
<p id="p-0001" num="0000">This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.</p>
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Furanone Compounds and Methods of Making and Using The Same (Fri, 30 Apr 2010)
<p id="p-0001-en" num="0000">The invention features compounds of the general Formula (I): (formula should be inserted here) Compounds of Formula (I) possess unexpectedly high affinity for Alk5 and/or Alk4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders.</p> <p id="p-0002-en" num="0000"/>
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Anti-IGR-1R antibodies and uses thereof (Fri, 23 Apr 2010)
<p id="p-0001" num="0000">The invention relates to antibodies which bind to insulin like growth factor receptor-1 (IGF-1R) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-1) and insulin like growth factor 2 (IGF-2) to bind to IGF-1R, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.</p>
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Anti-IGF-1R Antibodies and Uses Thereof (Fri, 23 Apr 2010)
<p id="p-0001-en" num="0000">The invention relates to antibodies which bind to insulin like growth factor receptor-1 (IGF-1R) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-1) and insulin like growth factor 2 (IGF-2) to bind to IGF-1R, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.</p>
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Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues (Fri, 16 Apr 2010)
<p id="p-0001" num="0000">The present invention is based, at least in part, on the discovery that strategic modifications of non-human donor antibody CDR residue(s) can be used to humanize antibodies. Such modifications modulate the 3D structural fit between donor antibody CDRs and human acceptor antibody framework regions that comprise the variable domains of a CDR-grafted antibody. Whereas prior art methods of humanization have relied on making framework substitutions (in which selected human framework residues are backmutated to the corresponding amino acid residue present in the non-human donor antibody), the instant invention is based, at least in part, on a method of humanizing antibodies in which selected CDR residues, and optionally adjacent FR residues, are changed in order to accommodate differences in FR amino acid sequences between donor and acceptor antibodies.</p>
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Biomarkers for Multiple Sclerosis and Methods of Use Thereof (Fri, 12 Mar 2010)
<p id="p-0001-en" num="0000">Biomarkers useful for identifying treatments for and monitoring treatment of patients with multiple sclerosis (MS) are provided, as well as methods for their identification, methods of diagnosing MS, relapse of MS patients and disease progression in MS patients.</p>
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Substituted Pyrazalones (Fri, 05 Mar 2010)
<p id="p-0001-en" num="0000">The invention is related to compounds of formula (I) as antagonists of the TGFβ family type I receptors, Alk5 and/or AIk 4, compositions and methods of use. The compounds of formula (I) can be employed in the prevention and/or treatment of diseases such as fibrosis (e.g., renal fibrosis, pulmonary fibrosis, and hepatic fibrosis), progressive cancers, or other diseases for which reduction of TGFβ family signaling activity is desirable.</p>
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Imidazolone Compounds and Methods of Making and Using the Same (Fri, 12 Feb 2010)
<p id="p-0001-en" num="0000">In one aspect, the invention features a compound of the general Formula (I). Compounds of Formula (I) possess high affinity for Alk 5 and/or AIk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="23.37mm" wi="49.61mm" file="us20100035918a1-20100211-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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ANTI-FN14 ANTIBODIES AND USES THEREOF (Fri, 01 Jan 2010)
<p id="p-0001-en" num="0000">Antibodies and antibody fragments that bind to the receptor Fn14 and induce or enhance cell killing of Fn14-expressing cancer cells are disclosed. Also disclosed are methods of using the antibodies and antibody fragments to induce death of a tumor cell and treat disorders and in a subject.</p>
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METHODS OF TREATING FIBROSIS (Fri, 11 Dec 2009)
<p id="p-0001-en" num="0000">Methods and compositions for treating fibrosis are disclosed.</p>
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THERAPEUTIC COMBINATIONS OF ANTI-IGF-1R ANTIBODIES AND OTHER COMPOUNDS (Fri, 27 Nov 2009)
<p id="p-0001-en" num="0000">The invention relates to methods of treatment using combination therapy wherein a variety of therapeutically useful compounds may be combined with antibodies which bind to insulin-like growth factor receptor-1 (IGF-1R). Specific human and murine monoclonal antibodies which inhibit IGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-1) and insulin like growth factor 2 (IGF-2) to bind to IGF-1R, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention particularly includes methods of treating cancer using combination therapies with IGF-1R antibodies.</p>
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ANTI-FN14 ANTIBODIES AND USES THEREOF (Fri, 20 Nov 2009)
Antibodies and antibody fragments that bind to the receptor Fn14 and induce or enhance cell killing of Fn14-expressing cancer cells are disclosed. Also disclosed are methods of using the antibodies and antibody fragments to induce death of a tumor cell and treat disorders and in a subject.
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ANTI-FN14 ANTIBODIES AND USES THEREOF (Fri, 20 Nov 2009)
Antibodies and antibody fragments that bind to the receptor Fn14 and induce or enhance cell killing of Fn14-expressing cancer cells are disclosed. Also disclosed are methods of using the antibodies and antibody fragments to induce death of a tumor cell and treat disorders and in a subject. </p>
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ANTIBODIES AGAINST FCRN AND USE THEREOF (Fri, 30 Oct 2009)
This disclosure provides, inter alia, proteins that bind to FcRn, e.g., immunoglobulins that inhibit FcRn with high affinity and selectivity. The FcRn-binding proteins can be used to treat a variety of disorders including autoimmune disorders.
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FC RECEPTOR BINDING PROTEINS (Fri, 30 Oct 2009)
This disclosure provides, inter alia, proteins that bind to FcRn, e.g., immunoglobulins that inhibit FcRn with high affinity and selectivity. The FcRn-binding proteins can be used to treat a variety of disorders including autoimmune disorders. </p>
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THERAPEUTIC COMBINATIONS OF ANTI-IGF-1R ANTIBODIES AND OTHER COMPOUNDS (Fri, 16 Oct 2009)
The invention relates to methods of treatment using combination therapy wherein a variety of therapeutically useful compounds may be combined with antibodies which bind to insulin-like growth factor receptor-1 (IGF-1R). Specific human and murine monoclonal antibodies which inhibit iGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-I) and insulin like growth factor 2 (IGF-2) to bind to IGF-1R, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention particularly includes methods of treating cancer using combination therapies with IGF-1R antibodies.
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RECOMBINANT ANTI-CD4 ANTIBODIES FOR HUMAN THERAPY (Fri, 11 Sep 2009)
<p id="p-0001-en" num="0000">Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability (in vivo half-life).</p>
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RON antibodies and uses thereof (Fri, 11 Sep 2009)
<p id="p-0001-en" num="0000">The invention relates to antibodies which bind to RON (receptor d'origine nantais, MST1R) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific antibodies which inhibit RON-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific antibodies which block the ability of the ligand, MSP to bind to RON, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.</p>
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Detection and quantitation of cyclodextrins (Fri, 11 Sep 2009)
<p id="p-0001" num="0000">The invention relates to the detection and quantitation of cyclodextrins and cyclodextrin derivatives in solutions comprising a protein. The invention further relates to methods of evaluating pharmaceutical preparations for the presence of residual cyclodextrins.</p>
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RECOMBINANT ANTI-CD4 ANTIBODIES FOR HUMAN THERAPY (Fri, 04 Sep 2009)
<p id="p-0001-en" num="0000">Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability (in vivo half-life).</p>
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ADENOSINE RECEPTOR ANTAGONISTS AND METHODS OF MAKING AND USING THE SAME (Fri, 04 Sep 2009)
<p id="p-0001-en" num="0000">The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A<sub>1 </sub>receptor. Adenosine A<sub>1 </sub>antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable.</p> <p id="p-0002-en" num="0000">In one embodiment, the invention features a compound of formula I:</p> <p id="p-0003-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="27.60mm" wi="58.67mm" file="us20090221821a1-20090903-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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RON ANTIBODIES AND USES THEREOF (Fri, 31 Jul 2009)
The invention relates to antibodies which bind to RON (receptor d'origine nantais, MSTlR) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific antibodies which inhibit RON-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific antibodies which block the ability of the ligand, MSP to bind to RON, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.
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RON ANTIBODIES AND USES THEREOF (Fri, 31 Jul 2009)
The invention relates to antibodies which bind to RON (receptor d'origine nantais, MST1R) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific antibodies which inhibit RON-mediated pro-survival and tumor pro-liferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific antibodies which block the ability of the ligand, MSP to bind to RON, as well as fragments, variants and derivatives of such antibodies. The inven-tion also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention. </p>
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CD23 BINDING MOLECULES AND METHODS OF USE THEREOF (Fri, 19 Jun 2009)
<p id="p-0001-en" num="0000">The invention is based, at least in part, on the development of multivalent and stabilized forms of CD23 binding molecules and methods of use thereof for the treatment of immune cell disorders, including leukemias or lymphomas such as CLL.</p>
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Polycycloalkylpurines as adenosine receptor antagonists (Thu, 18 Jun 2009)
The invention is based on the discovery that compounds of Formula (I) are unexpectedly highly potent and selective inhibitors of the adenosine A 1 receptor. Adenosine A 1 antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I).
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COMPOSITIONS THAT BIND MULTIPLE EPITOPES OF IGF-1R (Fri, 22 May 2009)
<p id="p-0001-en" num="0000">The instant invention is based, at least in part on the finding that binding molecules which bind to different epitopes within IGF-1R result in improved IGF-1 and/or IGF-2 blocking capabilities when compared to binding molecules that bind to a single IGF-1R epitope. The instant invention provides compositions that bind to multiple epitopes of IGF-1R, for example, combinations of monospecific binding molecules or multispecific binding molecules (e.g., bispecific molecules). Methods of making the subject binding molecules and methods of using the binding molecules of the invention to antagonize IGF-1R signaling are also provided.</p>
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Anti-IGF-1R Antibodies and Uses Thereof (Fri, 10 Apr 2009)
<p id="p-0001-en" num="0000">The invention relates to antibodies which bind to insulin like growth factor receptor-1 (IGF-1R) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies capable of synergistically inhibiting the ability of the ligands, insulin like growth factor 1 (IGF-1) and insulin like growth factor 2 (IGF-2), to bind to IGF-1R; as well as fragments, variants and derivatives of such antibodies. Antibodies of the invention produce such synergistic effects via allosteric and/or competitive inhibition of IGF-1R ligand binding.</p>
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CD23 BINDING MOLECULES AND METHODS OF USE THEREOF (Fri, 03 Apr 2009)
The invention is based, at least in part, on the development of multivalent and stabilized forms of CD23 binding molecules and methods of use thereof for the treatment of immune cell disorders, including leukemias or lymphomas such as CLL.
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TREATING STROKE (Fri, 13 Mar 2009)
<p id="p-0001-en" num="0000">Methods of treating stroke with blocking agents of TWEAK or TWEAK receptor are presented.</p>
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COMPOSITIONS THAT BIND MULTIPLE EPITOPES OF IGF-1R (Fri, 13 Mar 2009)
The instant invention is based, at least in part on the finding that binding molecules which bind to different epitopes within IGF-IR result in improved IGF-I and/or IGF-2 blocking capabilities when compared to binding molecules that bind to a single IGF-IR epitope. The instant invention provides compositions that bind to multiple epitopes of IGF-IR, for example, combinations of monospecific binding molecules or multispecific binding molecules (e.g., bispecific molecules). Methods of making the subject binding molecules and methods of using the binding molecules of the invention to antagonize IGF-IR signaling are also provided.
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ANTI-IGF-1R ANTIBODIES AND USES THEREOF (Fri, 13 Mar 2009)
The invention relates to antibodies which bind to insulin like growth factor receptor -1 (IGF-IR) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-lR-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies capable of synergistically inhibiting the ability of the ligands, insulin like growth factor 1 (IGF-I) and insulin like growth factor 2 (IGF-2), to bind to IGF-IR; as well as fragments, variants and derivatives of such antibodies. Antibodies of the invention produce such synergistic effects via allosteric and/or competitive inhibition of IGF-IR ligand binding.
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ANTI-IGF-1R ANTIBODIES AND USES THEREOF (Fri, 13 Mar 2009)
The invention relates to antibodies which bind to insulin like growth factor receptor -1 (IGF-IR) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies capable of synergistically inhibiting the ability of the ligands, insulin like growth factor 1(IGF-I) and insulin like growth factor 2 (IGF-2), to bind to IGF-IR; as well as fragments, variants and derivatives of such antibodies. Antibodies of the invention produce such synergistic effects via allosteric and/or competitive inhibition of IGF-IR ligand binding. </p>
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COMPOSITIONS THAT BIND MULTIPLE EPITOPES OF IGF-1R (Fri, 13 Mar 2009)
The instant invention is based, at least in part on the finding that binding molecules which bind to different epitopes within IGF-IR result in improved IGF-I and/or IGF-2 blocking capabilities when compared to binding molecules that bind to a single IGF-IR epitope. The instant invention provides compositions that bind to multiple epitopes of IGF-IR, for example, combinations of monospecific binding molecules or multispecific binding molecules (e.g., bispecific molecules). Methods of making the subject binding molecules and methods of using the binding molecules of the invention to antagonize IGF-IR signaling are also provided. </p>
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Stabilized polypeptide compositions (Fri, 20 Feb 2009)
<p id="p-0001" num="0000">The invention is based, at least in part, on the development of stabilized binding molecules that consist of or comprise a stabilized scFv and methods for making such stabilized molecules.</p>
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BICYCLIC SPHINGOSINE 1-PHOSPHATE ANALOGS (Fri, 20 Feb 2009)
Compounds that have agonist activity at one or more of the SlP receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at SlP receptors. Formula (I):
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BICYCLIC SPHINGOSINE 1-PHOSPHATE ANALOGS (Fri, 20 Feb 2009)
Compounds that have agonist activity at one or more of the S1P receptors are provided. The compounds are sphingosine analogs that, after phosphorylation, can behave as agonists at S1P receptors. Formula (I): </p>
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Antibodies to the Human Prolactin Receptor (Fri, 16 Jan 2009)
<p id="p-0001-en" num="0000">This invention provides antibodies to the prolactin receptor, particularly the human prolactin receptor. Preferred antibodies are capable of blocking prolactin binding to the prolactin receptor, inhibiting signaling through the prolactin receptor, and/or inhibiting proliferation of cancer cells induced by prolactin. Also provided are nucleic acids encoding the antibodies, vectors and host cells comprising the nucleic acids, and uses of the antibodies and nucleic acids.</p>
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SPIRO COMPOUNDS AS ANTAGONISTS OF TGF-BETA (Fri, 16 Jan 2009)
The invention is related to compounds of formula (I) These compounds can be used as antagonists of the TGF-beta family tyle I receptors, Alk5 or Alk4. The compounds of formula (I) can be employed in the prevention and/or treatment of diseases such as fibrosis (e. g. renal fibrosis, pulmonary fibrosis and hepatic fibrosis), progressive cancers or other diseases for which reduction of TGF-beta family signalling activity is desirable.
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HETEROCYCLIC COMPOUNDS USEFUL AS RAF KINASE INHIBITORS (Fri, 09 Jan 2009)
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases Formula (I) or a pharmaceutically acceptable salt thereof, wherein: Cy1 is an optionally substituted phenyl or an optionally substituted 5-6 membered saturated, partially unsaturated, or aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Cy2 is an optionally substituted 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, or sulfur; L1 is a direct bond of an optionally substituted, straight or branched C1-6 alkylene chain; L2 is a direct bond, or is an optionally substituted, straight or branched C1-6 alkylene chain wherein 1 or 2 methylene units of L2 are optionally and independently replaced by -O-, -S-, -N(R)-, -C(O)-, -C(O)N(R)-, -N(R)C(O)N(R)-, -N(R)C(O)-, -N(R)C(O)O-, -OC(O)N(R)-, -SO2-, -SO2N(R)-, -N(R)SO2-, -OC(O)-, -C(O)O-, or a 3-6 membered cycloalkylene; each R is independently hydrogen or an optionally substituted C1-6 aliphatic group;
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PYRIMIDINE DERIVATIVES USEFUL AS RAF KINASE INHIBITORS (Fri, 09 Jan 2009)
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.
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COMPOUNDS USEFUL AS RAF KINASE INHIBITORS (Fri, 09 Jan 2009)
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases. </p>
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HETEROCYCLIC COMPOUNDS USEFUL AS RAF KINASE INHIBITORS (Fri, 09 Jan 2009)
The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases Formula (I) or a pharmaceutically acceptable salt thereof, wherein: Cy1 is an optionally substituted phenyl or an optionally substituted 5-6 membered saturated, partially unsaturated, or aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Cy2 is an optionally substituted 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms, independently se-lected ted from nitrogen, oxygen, or sulfur; L1 is a direct bond of an optionally substituted, straight or branched C1-6 alkylene chain; L is a direct bond, or is an optionally substituted, straight or branched C1-6 alkylene chain wherein 1 or 2 methylene units of L2 are optionally and independently replaced by -O-, -S-, -N(R)-, -C(O)-, - C(O)N(R)-, -N(R)C(O)N(R)-, -N(R)C(O)-, -N(R)C(O)O-, -OC(O)N(R)-, -SO2-, -SO2N(R)-, -N(R)SO2-, -OC(O)-, -C(O)O-, or a 3-6 membered cycloalkylene; each R is independently hydro-gen or an optionally substituted C1-6 aliphatic group; The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases Formula (I) or a pharmaceutically acceptable salt thereof, wherein: Cy1 is an optionally substituted phenyl or an optionally substituted 5-6 membered saturated, partially unsaturated, or aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Cy2 is an optionally substituted 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms, independently se-lected from nitrogen, oxygen, or sulfur; L1 is a direct bond of an optionally substituted, straight or branched C1-6 alkylene chain; L2 is a direct bond, or is an optionally substituted, straight or branched C1- 6 alkylene chain wherein 1 or 2 methylene units of L2 are optionally and independently replaced by -O-, -S-, -N(R)-, -C(O)-, - C(O)N(R)-, -N(R)C(O)N(R)-, -N(R)C(O)-, -N(R)C(O)O-, -OC(O)N(R)-, -SO2-, -SO2N(R)-, -N(R)SO2-, -OC(O)-, -C(O)O-, or a 3-6 membered cycloalkylene; each R is independently hydro-gen or an optionally substituted C1-6 aliphatic group; </p>
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NON - PEPTIDE INHIBITORS OF LIGAND BINDING TO VLA - 4 (Tue, 30 Dec 2008)

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Compositions and methods for inhibiting growth of smad4-deficient cancers (Fri, 26 Dec 2008)
<p id="p-0001" num="0000">The present invention is in the fields of cell biology, immunology and oncology. The invention relates to the discovery that there is a relationship between the expression levels of the tumor suppressor gene smad4 (also known as dpc4) and integrin α<sub>v</sub>β<sub>6</sub>, and the responsiveness of patient populations to α<sub>v</sub>β<sub>6</sub>-active compounds and compositions (e.g., antibodies and other ligands that bind α<sub>v</sub>β<sub>6</sub>), particularly in cancer cells from such patient populations, more particularly on carcinomas such as pancreatic carcinomas. The invention thus provides methods for determining the responsiveness of tumor cells (particularly those from pancreatic tumors) to such α<sub>v</sub>β<sub>6</sub>-active compounds and compositions by examining the expression of α<sub>v</sub>β<sub>6 </sub>and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and small molecule drugs, that bind to integrin α<sub>v</sub>β<sub>6 </sub>on the surfaces of tumor cells and/or that block one or more components of the TGF-β pathway, particularly in smad4-deficient tumor cells.</p>
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Anti-CD154 antibodies (Fri, 12 Dec 2008)
<p id="p-0001" num="0000">The present invention provides peptides, and fragments thereof, and antibodies, or fragments thereof comprising the same, wherein the peptide comprises at least one amino acid substitution compared to wild type 5c8 antibody. The present invention also provides compositions and methods of treating CD154-related diseases or disorders in a subject.</p>
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Membrane Associated Molecules (Fri, 05 Dec 2008)
<p id="p-0001-en" num="0000">The present invention is directed to novel methods of treating, identifying or diagnosing a hyperproliferative disorder in a patient in need thereof. The methods of the invention include administering to a patient a composition comprising a binding molecule which binds to a cell surface expressed glycoprotein expressed predominantly in tumor or tumor-associated cells. In particular, the therapeutic and diagnostic methods of the present invention include the use of a binding molecule, for example an antibody or immunospecific fragment thereof, which specifically binds to a membrane associated molecule, variant polypeptide or fragment thereof. The present invention is based, at least in part, on the discovery of membrane associated proteins, i.e., nucleic acid molecules which encode membrane proteins and the use of these molecules to generate custom arrays to screen for markers associated with various diseases and disorders, e.g., cancer, e.g., lung, colon, pancreatic and ovarian cancer and autoimmune diseases or disorders. The invention further relates to various methods, reagents and kits for diagnosing, staging, prognosing, monitoring and treating hyperproliferative diseases or disorders such as cancer, e.g., lung, colon, pancreatic and ovarian cancer and autoimmune diseases or disorders.</p>
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Anti-α<sub>v</sub>β<sub>6 </sub>antibodies and uses thereof (Fri, 21 Nov 2008)
<p id="p-0001" num="0000">The present invention is in the fields of cell biology, immunology and oncology. The invention provides humanized antibodies that recognize α<sub>v</sub>β<sub>6 </sub>integrins, which antibodies comprise a variable region of nonhuman origin and at least a portion of an immunoglobulin of human origin. The invention also provides methods for preparation of such antibodies, pharmaceutical compositions comprising them, and methods of treating, diagnosing and/or preventing various diseases and disorders by administering the humanized anti-α<sub>v</sub>β<sub>6 </sub>antibodies of the invention. The invention also relates to the identification of differential expression of the integrin α<sub>v</sub>β<sub>6 </sub>on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin α<sub>v</sub>β<sub>6</sub>.</p>
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Recombinant anti-CD4 antibodies for human therapy (Wed, 19 Nov 2008)
<p id="p-0001-en" num="0000">Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability (in vivo half-life).</p>
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ANTI-ALPHA 6 BETA 4 INTEGRIN ANTIBODIES AND USES THEROF (Fri, 24 Oct 2008)
The invention relates to antibodies which bind to alpha6beta4 integrin(α6β4 integrin) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine antibodies which inhibit α6β4 integrin-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine antibodies which block the ability of the ligand, laminin to bind to α6β4 integrin, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.
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Tweak binding antibodies (Fri, 03 Oct 2008)
<p id="p-0001" num="0000">Anti-Tweak antibodies are described.</p>
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BINDING PROTEINS, INCLUDING ANTIBODIES, ANTIBODY DERIVATIVES AND ANTIBODY FRAGMENTS, THAT SPECIFICALLY BIND CD154 AND USES THEREOF (Fri, 03 Oct 2008)
This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.
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BINDING PROTEINS, INCLUDING ANTIBODIES, ANTIBODY DERIVATIVES AND ANTIBODY FRAGMENTS, THAT SPECIFICALLY BIND CD154 AND USES THEREOF (Fri, 03 Oct 2008)
This invention provides binding proteins, including antibodies, antibody derivatives and antibody fragments, that specifically bind a CD154 (CD40L) protein. This invention also provides a chimeric, humanized or fully human antibody, antibody derivative or antibody fragment that specifically binds to an epitope to which a humanized Fab fragment comprising a variable heavy chain sequence according to SEQ ID NO: 1 and comprising a variable light chain sequence according to SEQ ID NO: 2 specifically binds. CD154 binding proteins of this invention may elicit reduced effector function relative to a second anti-CD154 antibody. CD154 binding proteins of this invention are useful in diagnostic and therapeutic methods, such as in the treatment and prevention of diseases including those that involve undesirable immune responses that are mediated by CD154-CD40 interactions.</p>
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Arylphenylamino- and Arylphenylether-Sulfide Derivatives, Useful For the Treatment of Inflammatory and Immune Diseases, and Pharmaceutical Compositions Containing Them (Fri, 26 Sep 2008)
<p id="p-0001-en" num="0000">The present invention relates in part to compounds of formulas (I) and (III): and pharmaceutically-acceptable salts and prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject.</p> <p id="p-0002-en" num="0000"/>
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FURANONE COMPOUNDS AND METHODS OF MAKING AND USING THE SAME (Fri, 08 Aug 2008)
The invention features compounds of the general Formula (I). Compounds of Formula (I) possess unexpectedly high affinity for Alk5 and/or Alk4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders.
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IMIDAZOLONE COMPOUNDS AS TGF-BETA FAMILY TYPE I RECEPTORS, ALK5 AND/OR ALK4 ANTAGONISTS (Fri, 08 Aug 2008)
In one aspect, the invention features a compound of the general Formula: (I); wherein R2 is aryl or heteroaryl and R1 is heteroaryl Compounds of Formula (I) possess high affinity for Alk 5 and/or AIk 4, and can be useful as antagonists thereof for preventing and/or treating fibrotic disorders or progressive cancers.
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1-H-PYRAZOLO (3,4B) PYRIMIDINE DERIVATIVES AND THEIR USE AS MODULATORS OF MITOTIC KINASES (Fri, 08 Aug 2008)
The invention relates to compounds of Formula (I), a polymorph, an enantiomer, a stereoisomer, a solvate, an N-oxide derivative, or a pharmaceutically acceptable salt thereof: Formula (I), which have inhibitory effect on one or more protein kinases that are involved in cell mitosis.
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1-H-PYRAZOLO(3,4B)PYRIMIDINE DERIVATIVES AND THEIR USE AS MODULATORS OF MITOTIC KINASES (Fri, 08 Aug 2008)
The invention relates to compounds of Formula (I), a polymorph, an enantiomer a stereoisomer, a solvate, an N-oxide, or a pharmaceutically acceptable salt thereof; which have inhibitory effect on one or more protein kinases that are involved in cell mitosis.
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MODULATORS OF MITOTIC KINASES (Fri, 08 Aug 2008)
The invention relates to compounds of Formula (I), a polymorph, an enantiomer, a stereoisomer, a solvate, an N-oxide derivative, or a pharmaceutically acceptable salt thereof: Formula (I), which have inhibitory effect on one or more protein kinases that are involved in cell mitosis.</p>
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MODULATORS OF MITOTIC KINASES (Fri, 08 Aug 2008)
The invention relates to compounds of Formula (I), a polymorph, an enantiomer a stereoisomer, a solvate, an N-oxide, or a pharmaceutically acceptable salt thereof; which have inhibitory effect on one or more protein kinases that are involved in cell mitosis.</p>
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ARYLPHENYLAMINO-,ARYLPHENYLAMIDE-,AND ARYLPHENYLETHER-SULFIDE DERIVATIVES (Thu, 31 Jul 2008)
</p> <p>-prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject.
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PHARMACEUTICALS, COMPOSITIONS AND METHODS OF MAKING AND USING THE SAME (Fri, 25 Jul 2008)
Compounds that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.
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PHARMACEUTICALS, COMPOSITIONS AND METHODS OF MAKING AND USING THE SAME (Fri, 25 Jul 2008)
Compounds that are capable of acting as purine receptor antagonists, pharmaceutical compositions including the compounds, and methods of making the compounds, are disclosed. The compounds and compositions can be used in treating or preventing disorders related to purine receptor hyperfunctioning.</p>
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POLYMORPHS AND SOLVATES OF A PHARMACEUTICAL AND METHODS OF MAKING (Fri, 18 Jul 2008)
Polymorphic and solvated forms of solid 3-(4-amino-3-methylbenzyl)-7-(furan-2- yl)-3H-[l,2,3]triazolo[4,5-d]pyrimidin-5-amine, and methods of making them, are described.
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POLYMORPHS AND SOLVATES OF A PHARMACEUTICAL AND METHODS OF MAKING (Fri, 18 Jul 2008)
Polymorphic and solvated forms of solid 3-(4-amino-3-methylbenzyl)-7-(furan-2- yl)-3H-[l,2,3]triazolo[4,5-d]pyrimidin-5-amine, and methods of making them, are described.</p>
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BIOMARKERS FOR MULTIPLE SCLEROSIS AND METHODS OF USE THEREOF (Thu, 12 Jun 2008)
Biomarkers useful for identifying treatments for and monitoring treatment of patients with multiple sclerosis (MS) are provided, as well as methods for their identification, methods of diagnosing MS, relapse of MS patients and disease progression in MS patients.
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BIOMARKERS OF MULTIPLE SCLEROSIS (Fri, 25 Apr 2008)
Biomarkers of multiple sclerosis (MS) and of anti-TWEAK/TWEAK-Receptor therapy for MS are described.
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INDAZOLE DERIVATIVES AS MODULATORS OF INTERLEUKIN- 1 RECEPTOR-ASSOCIATED KINASE (Fri, 14 Mar 2008)
The present invention relates to modulators of IRAK kinases of formula (I) and provides compositions comprising such modulators, as well as methods therewith for treating IRAK- mediated or IRAK -associated conditions or diseases.
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IRAK MODULATORS FOR TREATING AN INFLAMMATORY CONDITION, CELL PROLIFERATIVE DISORDER, IMMUNE DISORDER (Fri, 14 Mar 2008)
The present invention relates to modulators of IRAK kinase and provides compositions comprising such modulators, as well as methods therewith for treating conditions or diseases mediated by or associated with IRAK kinase, such as rheumatoid arthitis, multiple sclerosis, sepsis, osteoarthrites, inflammatory bowel disease, osteoporosis, myasthenia gravis, stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, psoriasis, cardiac contractile dysfunction, type I diabetes, type II diabetes, familial cold autoinf lammatory syndrome, severe bacterial infections, allergic disease, cancer, psoriasis, asthma, or graft rejection.
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MODULATORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 14 Mar 2008)
The present invention relates to modulators of IRAK kinase and provides compositions comprising such modulators, as well as methods therewith for treating conditions or diseases mediated by or associated with IRAK kinase, such as rheumatoid arthitis, multiple sclerosis, sepsis, osteoarthrites, inflammatory bowel disease, osteoporosis, myasthenia gravis, stroke, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, psoriasis, cardiac contractile dysfunction, type I diabetes, type II diabetes, familial cold autoinf lammatory syndrome, severe bacterial infections, allergic disease, cancer, psoriasis, asthma, or graft rejection.</p>
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INDAZOLE DERIVATIVES AS MODULATORS OF INTERLEUKIN-1 RECEPTOR-ASSOCIATED KINASE (Fri, 14 Mar 2008)
The present invention relates to modulators of IRAK kinases of formula (I) and provides compositions comprising such modulators, as well as methods therewith for treating IRAK- mediated or IRAK -associated conditions or diseases.</p>
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Stabilized polypeptide compositions (Fri, 29 Feb 2008)
<p id="p-0001" num="0000">The invention is based, at least in part, on the development of stabilized binding molecules that consist of or comprise a stabilized scFv and methods for making such stabilized molecules.</p>
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ALTERED POLYPEPTIDES, IMMUNOCONJUGATES THEREOF, AND METHODS RELATED THERETO (Fri, 22 Feb 2008)
The present invention features inter alia altered binding polypeptides having engineered cysteine residues or analogs thereof at a predetermined site within, for example, a constant region domain or a portion thereof. The engineered cysteine residues or analogs thereof provide sites for conjugating effector moieties (e.g. diagnostic or therapeutic agents) that impart novel functionality to the binding polypeptide, preferably without interfering with a desirable property (e.g. an Fc- mediated effector function). The invention includes methods for the rational design of such altered polypeptides, as well as methods for modifying (ie. conjugating) the altered polypeptides with desirable effector moieties. Particular modified binding polypeptides (ie. immunoconjugates) of altered binding polypeptides and methods for utilizing such modified binding polypeptides as protein-based therapeutics are also provided.
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TWEAK BINDING ANTIBODIES (Thu, 21 Feb 2008)
Anti-Tweak antibodies are described.
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POLYCYCLOALKYLPURINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME (Mon, 11 Feb 2008)

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ALTERED BR3-BINDING POLYPEPTIDES (Fri, 18 Jan 2008)
The present invention relates to novel BR3 binding antibodies having altered Fc effector function and/or having a mature core carbohydrate structure in the Fc region which lacks fiicose. The present invention also relates to the use of those BR3 binding antibodies and polypeptides in, e.g., methods of treatment, screening methods, diagnostic methods, assays and protein purification methods.
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COMPOSITIONS AND METHODS FOR INHIBITING GROWTH OF SMAD4-DEFICIENT CANCERS (Fri, 18 Jan 2008)
The present invention is in the fields of cell biology, immunology and oncology. The invention relates to the discovery that there is a relationship between the expression levels of the tumor suppressor gene smad4 (also known as dpc4) and integrin αvβ6, and the responsiveness of patient populations to αvβ6-active compounds and compositions (e.g., antibodies and other ligands that bind αvβ6), particularly in cancer cells from such patient populations, more particularly on carcinomas such as pancreatic carcinomas. The invention thus provides methods for determining the responsiveness of tumor cells (particularly those from pancreatic tumors) to such αvβ6-active compounds and compositions by examining the expression of αvβ6 and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and small molecule drugs, that bind to integrin αvβ6 on the surfaces of tumor cells and/or that block one or more components of the TGF-β pathway, particularly in 5/«αrf4-deficient tumor cells.
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COMPOSITIONS AND METHODS FOR INHIBITING GROWTH OF SMAD4-DEFICIENT CANCERS (Fri, 18 Jan 2008)
The present invention is in the fields of cell biology, immunology and oncology. The invention relates to the discovery that there is a relationship between the expression levels of the tumor suppressor gene smad4 (also known as dpc4) and integrin .alpha.v.beta.6, and the responsiveness of patient populations to .alpha.v.beta.6-active compounds and compositions (e.g., antibodies and other ligands that bind .alpha.v.beta.6), particularly in cancer cells from such patient populations, more particularly on carcinomas such as pancreatic carcinomas. The invention thus provides methods for determining the responsiveness of tumor cells (particularly those from pancreatic tumors) to such .alpha.v.beta.6-active compounds and compositions by examining the expression of .alpha.v.beta.6 and smad4 by the tumor cells, as well as methods of diagnosis and treatment/prevention of tumor progression using ligands, including antibodies and small molecule drugs, that bind to integrin .alpha.v.beta.6 on the surfaces of tumor cells and/or that block one or more components of the TGF-.beta. pathway, particularly in 5/<=.alpha.rf4-deficient tumor cells.</p>
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PYRIDINONYL PDK1 INHIBITORS (Fri, 11 Jan 2008)
The present invention provides pyridinonyl PDKl inhibitors and methods of treating cancer using the same.
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ADENOSINE RECEPTOR ANTAGONISTS AND METHODS OF MAKING AND USING THE SAME (Fri, 04 Jan 2008)
<p id="p-0001-en" num="0000">The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A<sub>1 </sub>receptor. Adenosine A<sub>1 </sub>antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. <br/> In one embodiment, the invention features a compound of formula I: </p>
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METHODS OF TREATING FIBROSIS (Fri, 07 Dec 2007)
Methods and compositions for treating fibrosis are disclosed.
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Antibodies to the human prolactin receptor (Fri, 23 Nov 2007)
<p id="p-0001-en" num="0000">This invention provides antibodies to the prolactin receptor, particularly the human prolactin receptor. Preferred antibodies are capable of blocking prolactin binding to the prolactin receptor, inhibiting signaling through the prolactin receptor, and/or inhibiting proliferation of cancer cells induced by prolactin. Also provided are nucleic acids encoding the antibodies, vectors and host cells comprising the nucleic acids, and uses of the antibodies and nucleic acids.</p>
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Arylphenylamino-,Arylphenylamide-, and Arylphenylether-Sulfide Derivatives (Fri, 09 Nov 2007)
<p id="p-0001-en" num="0000"> The present invention relates in part to compounds of formulas I and III: <chemistry id="chem-us-00001-en" num="1"><img id="emi-c00001" he="61.55mm" wi="59.18mm" file="US20070259863A1-20071108-C00001.TIF" img-content="chem" img-format="tif"/></chemistry> and pharmaceutically-acceptable salts and prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject. </p>
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ANTI-IGF-IR ANTIBODIES AND USES THEREOF (Fri, 09 Nov 2007)
The invention relates to antibodies which bind to insulin like growth factor receptor -1 (IGF-IR) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-lR-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-I) and insulin like growth factor 2 (IGF-2) to bind to IGF-IR, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.
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ANTI-IGF-IR ANTIBODIES AND USES THEREOF (Fri, 09 Nov 2007)
The invention relates to antibodies which bind to insulin like growth factor receptor -1 (IGF-IR) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-lR-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-I) and insulin like growth factor 2 (IGF-2) to bind to IGF-IR, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.</p>
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Anti-IGF-1R antibodies and uses thereof (Fri, 19 Oct 2007)
<p id="p-0001-en" num="0000">The invention relates to antibodies which bind to insulin like growth factor receptor-1 (IGF-1R) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-1) and insulin like growth factor 2 (IGF-2) to bind to IGF-1R, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.</p>
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STABILIZED POLYPEPTIDE COMPOSITIONS (Fri, 28 Sep 2007)
The invention is based, at least in part, on the development of stabilized binding molecules that consist of or comprise a stabilized. scFv and methods for making such stabilized molecules.
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STABILIZED POLYPEPTIDE COMPOSITIONS (Fri, 28 Sep 2007)
The invention is based, at least in part, on the development of stabilized binding molecules that consist of or comprise a stabilized. scFv and methods for making such stabilized molecules.</p>
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DETECTION AND QUANTITATION OF CYCLODEXTRINS (Thu, 06 Sep 2007)
The invention relates to the detection and quantitation of cyclodextrins and cyclodextrin derivatives in solutions comprising a protein. The invention further relates to methods of evaluating pharmaceutical preparations for the presence of residual cyclodextrins.
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A<sub>2a </sub>adenosine receptor antagonists (Fri, 27 Jul 2007)
<p id="p-0001-en" num="0000">The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A<sub>2a </sub>adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I).</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="24.64mm" wi="66.29mm" file="US07834014-20101116-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TRICYCLIC SPIRO COMPOUNDS USEFUL AS TRANSFORMING GROWTH FACTOR MODULATORS (Fri, 06 Jul 2007)
The invention is related to compounds of formula (I) that can be used as antagonists of the TGFβ family type I receptors, Alk5 and/or Alk4, compositions and methods of use. The compounds of formula (I) can be employed in the prevention and/or treatment of diseases such as fibrosis (e.g., renal fibrosis, pulmonary fibrosis, and hepatic fibrosis), progressive cancers, or other diseases for which reduction of TGFβ family signaling activity is desirable.
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CONDENSED IMIDAZOLES OR PYRAZOLES AND THEIR USE AS TRANSFORMING GROWTH FACTOR MODULATORS (Fri, 06 Jul 2007)
The invention relates to compounds of formula I that are modulators of Transforming Growth Factor β (TGF β) and are useful for treating TGF β related diseases. In Formula (I) one of Rl or R2 is heteroaryl and the other is aryl or heteroaryl, one of Xl or X2 is C and the other is N.
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ANTIBODY OR FRAGMENT THEREOF AND COMPOSITIONS COMPRISING THEM FOR TREATING DISEASE ASSOCIATED WITH CD154 (Thu, 05 Jul 2007)

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Neonatal Fc receptor (FcRn)-binding polypeptide variants, dimeric Fc binding proteins and methods related thereto (Fri, 29 Jun 2007)
<p id="p-0001-en" num="0000">The compositions and methods of the present invention are based, in part, on our discovery that an effector function mediated by an Fc-containing polypeptide can be altered by modifying one or more amino acid residues within the polypeptide (by, for example, electrostatic optimization). The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof. </p>
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Altered antibodies having improved antigen-binding affinity (Fri, 15 Jun 2007)
<p id="p-0001-en" num="0000">The invention relates to methods of modulating the antigen-binding affinity of an antibody by determining, using data corresponding to the structure of a complex between the antibody and an antigen in a solvent, a representation of a charge distribution of the CDRs of the antibody which minimizes electrostatic contribution to binding free energy between the antibody and the antigen in a solvent. Guided by these determinations, the antibody is accordingly modified (altered) to improve upon, e.g., antibody/antigen binding by modifying at least one amino acid residue to decrease the binding free energy between the antibody and antigen when bound in a solvent. </p>
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SUBSTITUTED PYRAZALONES (Fri, 25 May 2007)
The invention is related to compounds of formula (I) as antagonists of the TGFβ family type I receptors, Alk5 and/or AIk 4, compositions and methods of use. The compounds of formula (I) can be employed in the prevention and/or treatment of diseases such as fibrosis (e.g., renal fibrosis, pulmonary fibrosis, and hepatic fibrosis), progressive cancers, or other diseases for which reduction of TGFβ family signaling activity is desirable.
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Detecting protein similarity (Fri, 20 Apr 2007)
<p id="p-0001-en" num="0000">The disulfide bridges in a protein sequence can be described by a disulfide signature that includes information about cysteine spacing and disulfide topology. Proteins with similar disulfide signatures can be structurally similar despite low overall sequence homology. A database of disulfide signatures can be compiled from publicly available sequence data. </p>
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Adenosine receptor antagonists and methods of making and using the same (Thu, 19 Apr 2007)
The invention is based on the discovery that compounds of Formula (I) are unexpectedly highly potent and selective inhibitors of the adenosine A 1 receptor. Adenosine A1 antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I).
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BIOMARKERS FOR MULTIPLE SCLEROSIS AND METHODS OF USE THEREOF (Fri, 13 Apr 2007)
Biomarkers useful for identifying treatments for and monitoring treatment of patients with multiple sclerosis (MS) are provided, as well as methods for their identification, methods of diagnosing MS, relapse of MS patients and disease progression in MS patients.
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GAPR-1 METHODS (Fri, 06 Apr 2007)
Methods of treatment, diagnosis and screening related to GAPR-1 are disclosed.
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ANTI-ALPHA V BETA 6 ANTIBODIES AND USES THEREOF (Fri, 19 Jan 2007)
The present invention is in the fields of cell biology, immunology and oncology. Specifically, the invention relates to humanized antibodies that recognizes v 6 integrins which comprises a variable region of nonhuman origin and at least -a portion of an immunoglobulin of human origin. The invention also relates to processes for their preparation, to pharmaceutical compositions comprising them and to methods of treating various diseases by administering humanized anti- v 6 antibodies. The invention also relates to the identification of differential expression of the integrin avß6 on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin avß6.
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ANTI-ALPHA V BETA 6 ANTIBODIES AND USES THEREOF (Fri, 19 Jan 2007)
The present invention is in the fields of cell biology, immunology and oncology. Specifically, the invention relates to humanized antibodies that recognizes v 6 integrins which comprises a variable region of nonhuman origin and at least -a portion of an immunoglobulin of human origin. The invention also relates to processes for their preparation, to pharmaceutical compositions comprising them and to methods of treating various diseases by administering humanized anti- v 6 antibodies. The invention also relates to the identification of differential expression of the integrin av~6 on the surfaces of tumor cells and tissues, the use of this differential expression in determining the metastatic potential of tumor cells, and methods of diagnosis and treatment/prevention of tumor metastasis and for elimination of residual metastatic tumor cells using ligands, particularly antibodies, that bind to integrin av~6. </p>
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Triazolopyrazines and methods of making and using the same (Fri, 12 Jan 2007)
<p id="p-0001-en" num="0000">The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula I (See formula on paper copy)</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="24.55mm" wi="69.09mm" file="US07674791-20100309-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Cell adhesion inhibitors (Thu, 11 Jan 2007)
A cell adhesion inhibitor of the general formula: R 3 -L-L'-R 1 is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same.
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Triazolotriazines and pyrazolotriazines and methods of making and using the same (Fri, 08 Dec 2006)
<p id="p-0001-en" num="0000">The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A<sub>2a </sub>adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula I: (I)</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="24.64mm" wi="66.63mm" file="US07285550-20071023-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Fcgamma receptor-binding polypeptide variants and methods related thereto (Fri, 08 Dec 2006)
<p id="p-0001-en" num="0000">The compositions and methods of the present invention are based, in part, on our discovery that an effector function mediated by an Fc-containing polypeptide can be altered by modifying one or more amino acid residues within the polypeptide (by, for example, electrostatic optimization). The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof. </p>
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TWEAK BINDING ANTIBODIES (Fri, 08 Dec 2006)
Anti-Tweak antibodies are described.
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TWEAK BINDING ANTIBODIES (Fri, 08 Dec 2006)
Anti-Tweak antibodies are described. </p>
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Pyrazoles and methods of making and using the same (Fri, 24 Nov 2006)
<p id="p-0001-en" num="0000">The invention is based on the discovery that compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I (I). <chemistry id="chem-us-00001-en" num="1"><img id="emi-c00001" he="34.63mm" wi="69.85mm" file="us20060264440a1-20061123-c00001.tif" alt="embedded image" img-content="chem" img-format="tif"/></chemistry></p>
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Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues (Fri, 17 Nov 2006)
<p id="p-0001-en" num="0000">The present invention is based, at least in part, on the discovery that strategic modifications of non-human donor antibody CDR residue(s) can be used to humanize antibodies. Such modifications modulate the 3D structural fit between donor antibody CDRs and human acceptor antibody framework regions that comprise the variable domains of a CDR-grafted antibody. Whereas prior art methods of humanization have relied on making framework substitutions (in which selected human framework residues are backmutated to the corresponding amino acid residue present in the non-human donor antibody), the instant invention is based, at least in part, on a method of humanizing antibodies in which selected CDR residues, and optionally adjacent FR residues, are changed in order to accommodate differences in FR amino acid sequences between donor and acceptor antibodies.</p>
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COMPOUNDS AND METHODS FOR PEPTIDE SYNTHESIS (Fri, 06 Oct 2006)
A backbone nitrogen modifying group can prevent aggregation of peptides during peptide synthesis. The modifying group can promote aqueous solubility of the peptides, and be compatible with solid phase peptide synthesis. Methods for making peptides are also described.
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Pyrido pyrimidinones, dihydro pyrimido pyrimidinones and pteridinones useful as RAF kinase inhibitors (Fri, 22 Sep 2006)
<p id="p-0001-en" num="0000">The present invention provides compounds having the formula:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="21.76mm" wi="55.80mm" file="US07767687-20100803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001-en" list-style="none"> <li> <ul id="ul0002-en" list-style="none"> <li>wherein A-B together represent one of the following structures:</li> </ul> </li> </ul> </p> <p id="p-0003-en" num="0000"> <chemistry id="chem-us-00002-en" num="00002"> <img id="emi-c00002" he="108.97mm" wi="43.94mm" file="US07767687-20100803-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0003-en" list-style="none"> <li> <ul id="ul0004-en" list-style="none"> <li>n, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, L<sup>1</sup>, L<sup>2</sup>, Y and Z are as defined in classes and subclasses herein, and pharmaceutical compositions thereof, as described generally and in subclasses herein, which compounds are useful as inhibitors of protein kinase (e.g., RAF), and thus are useful, for example, for the treatment of RAF mediated diseases.</li> </ul> </li> </ul> </p>
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Treatment of cancer using antibodies to polypeptides differentially expressed in human lung tumors (Fri, 15 Sep 2006)
<p id="p-0001-en" num="0000">The present invention is directed to novel methods of treating, indentifying or diagnosing a hyperproliferative disorder in a patient in need thereof. The methods of the invention include administering to a patient a composition comprising a binding molecule which binds to a cell surface expressed glycoprotein expressed predominantly in tumor or tumor-associated cells. In particular, the therapeutic and diagnostic methods of the present invention include the use of a binding molecule, for example an antibody or immunospecific fragment thereof, which specifically binds to a lung tumor-associated polypeptide, variant polypeptide or fragment thereof. </p>
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METHODS OF HUMANIZING IMMUNOGLOBULIN VARIABLE REGIONS THROUGH RATIONAL MODIFICATION OF COMPLEMENTARITY DETERMINING RESIDUES (Fri, 15 Sep 2006)
The present invention is based, at least in part, on the discovery that strategic modifications of non-human donor antibody CDR residue(s) can be used to humanize antibodies. Such modifications modulate the 3D structural fit between donor antibody CDRs and human acceptor antibody framework regions that comprise the variable domains of a CDR-grafted antibody. Whereas prior art methods of humanization have relied on making framework substitutions (in which selected human framework residues are backmutated to the corresponding amino acid residue present in the non-human donor antibody), the instant invention is based, at least in part, on a method of humanizing antibodies in which selected CDR residues, and optionally adjacent FR residues, are changed in order to accommodate differences in FR amino acid sequences between donor and acceptor antibodies.
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METHODS OF HUMANIZING IMMUNOGLOBULIN VARIABLE REGIONS THROUGH RATIONAL MODIFICATION OF COMPLEMENTARITY DETERMINING RESIDUES (Fri, 15 Sep 2006)
The present invention is based, at least in part, on the discovery that strategic modifications of non-human donor antibody CDR residue(s) can be used to humanize antibodies. Such modifications modulate the 3D structural fit between donor antibody CDRs and human acceptor antibody framework regions that comprise the variable domains of a CDR-grafted antibody. Whereas prior art methods of humanization have relied on making framework substitutions (in which selected human framework residues are backmutated to the corresponding amino acid residue present in the non-human donor antibody), the instant invention is based, at least in part, on a method of humanizing antibodies in which selected CDR residues, and optionally adjacent FR residues, are changed in order to accommodate differences in FR amino acid sequences between donor and acceptor antibodies. </p>
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Therapies for chronic renal failure using one or more integrin antagonists (Thu, 14 Sep 2006)
The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects in, or at risk of chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain integrin antagonists.
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TREATING STROKE (Fri, 25 Aug 2006)
Methods of treating stroke with blocking agents of TWEAK or TWEAK receptor are presented.
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TREATING NEUROLOGICAL DISORDERS (Fri, 25 Aug 2006)
Methods of treating neuronal disorders, such as mechanical neuronal traumas and neurodegenerative disorders, with TWEAK or a TWEAK receptor blocking agents are presented.
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TREATING NEUROLOGICAL DISORDERS (Fri, 25 Aug 2006)
Methods of treating neuronal disorders, such as mechanical neuronal traumas and neurodegenerative disorders, with TWEAK or a TWEAK receptor blocking agents are presented. </p>
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Cell adhesion inhibitors (Fri, 28 Jul 2006)
<p id="p-0001-en" num="0000">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases. </p>
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Cell adhesion inhibitors (Fri, 28 Jul 2006)
<p id="p-0001-en" num="0000">A cell adhesion inhibitor of the general formula: <br/>R<sup>3</sup>-L-L′-R<sup>1 </sup> is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same. </p>
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THERAPIES FOR RENAL FAILURE USING INTERFERON-B (Thu, 27 Jul 2006)
malian subjects having, or at risk of developing, glomerulonephritis or chronic renal failure. The methods involve the administration
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POLYPEPTIDES THAT BIND BR3 AND USES THEREOF (Fri, 14 Jul 2006)
The present invention relates to novel BR3 binding antibodies and polypeptides, including antagonist and agonist polypeptides. The present invention also relates to the use of the BR3 binding antibodies and polypeptides in, e.g., methods of treatment, screening methods, diagnostic methods, assays and protein purification methods.
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POLYPEPTIDES THAT BIND BR3 AND USES THEREOF (Fri, 14 Jul 2006)
The present invention relates to novel BR3 binding antibodies and polypeptides, including antagonist and agonist polypeptides. The present invention also relates to the use of the BR3 binding antibodies and polypeptides in, e.g., methods of treatment, screening methods, diagnostic methods, assays and protein purification methods. </p>
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DETECTION AND QUANTITATION OF CYCLODEXTRINS (Fri, 16 Jun 2006)
The invention relates to the detection and quantitation of cyclodextrins and cyclodextrin derivatives in solutions comprising a protein. The invention further relates to methods of evaluating pharmaceutical preparations for the presence of residual cyclodextrins.
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DETECTION AND QUANTITATION OF CYCLODEXTRINS (Fri, 16 Jun 2006)
The invention relates to the detection and quantitation of cyclodextrins and cyclodextrin derivatives in solutions comprising a protein. The invention further relates to methods of evaluating pharmaceutical preparations for the presence of residual cyclodextrins. </p>
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PYRAZOLES AND METHODS OF MAKING AND USING THE SAME (Thu, 01 Jun 2006)
ery that compounds of formula I possess unexpectedly <br> high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating <br> — R<sup>2</sup>— R<sup>3</sup>— R<sup>4</sup> numerous diseases, including fibrotic disorders. In one <br> embodiment, the invention features a compound of form mula I (0-cn <br>c <br> © <br>© <br>o
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Pyrazolopyridines and methods of making and using the same (Fri, 19 May 2006)
<p id="p-0001-en" num="0000">Compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I:</p> <p id="p-0002-en" num="0000"/>
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PYRAZOLOPYRIDINES AND METHODS OF MAKING AND USING THE SAME (Thu, 27 Apr 2006)
une pectedly high affinity for All 5 and/or Alk</p> <p>< 4. and can be useful as antagonists thereof lor <br> preventing and/or treating numerous diseases, in including finroiie disorders. In one embodiment, o the invention features a compound of formula I : 4 (I) <br>o <br> V(R )r <br>o
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ANTI-CD154 ANTIBODIES (Fri, 31 Mar 2006)
The present invention provides peptides, and fragments thereof, and antibodies, or fragments thereof comprising the same, wherein the peptide comprises at least one amino acid substitution compared to wild type 5c8 antibody. The present invention also provides compositions and methods of treating CD154-related diseases or disorders in a subject.
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ANTI-CD154 ANTIBODIES (Fri, 31 Mar 2006)
The present invention provides peptides, and fragments thereof, and antibodies, or fragments thereof comprising the same, wherein the peptide comprises at least one amino acid substitution compared to wild type 5c8 antibody. The present invention also provides compositions and methods of treating CD154-related diseases or disorders in a subject. </p>
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Tri-substituted heteroaryls and methods of making and using the same (Fri, 24 Mar 2006)
<p id="p-0001-en" num="0000">Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders.</p> <p id="p-0002-en" num="0000">In one embodiment, the invention features a compound of the general formula (I).</p> <p id="p-0003-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="29.21mm" wi="60.88mm" file="US07612094-20091103-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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A2A ADENOSINE RECEPTOR ANTAGONISTS (Thu, 16 Mar 2006)
The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A<sb>2a</sb> adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I).
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PYRIMIDINYLPYRAZOLES AS TGF-BETA INHIBITORS (Fri, 10 Mar 2006)
The invention is based on the discovery that compounds of formula (I) possess high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. The invention features a compound of formula (I) and uses thereof: formula (I).
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PYRIMIDINYLIMIDAZOLES AS TGF-BETA INHIBITORS (Fri, 10 Mar 2006)
Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. The invention features a compound of the general formula (I) and uses thereof.
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PYRIMIDINYLPYRAZOLES AS TGF-BETA INHIBITORS (Fri, 10 Mar 2006)
The invention is based on the discovery that compounds of formula (I) possess high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. The invention features a compound of formula (I) and uses thereof: formula (I). </p>
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PYRIMIDINYLIMIDAZOLES AS TGF-BETA INHIBITORS (Fri, 10 Mar 2006)
Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. The invention features a compound of the general formula (I) and uses thereof. </p>
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CELL ADHESION INHIBITORS (Fri, 24 Feb 2006)
Cell adhesion inhibitors can interact with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. An inhibitor including a polyethylene glycol moiety can have advantageous pharmaceutical properties.
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Cell adhesion inhibitors (Wed, 22 Feb 2006)
<p id="p-0001-en" num="0000">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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TRI-SUBSTITUTED HETEROARYLS AND METHODS OF MAKING AND USING THE SAME (Thu, 01 Dec 2005)
thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (Γ).
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IMIDAZOLOPYRIDINES AND METHODS OF MAKING AND USING THE SAME (Thu, 01 Dec 2005)
thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I:
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ß-ALANINE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME (Mon, 21 Nov 2005)

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MEMBRANE ASSOCIATED MOLECULES (Fri, 18 Nov 2005)
The present invention is directed to novel methods of treating, indentifying or diagnosing a hyperproliferative disorder in a patient in need thereof. The methods of the invention include administering to a patient a composition comprising a binding molecule which binds to a cell surface expressed glycoprotein expressed predominantly in tumor or tumor-associated cells. In particular, the therapeutic and diagnostic methods of the present invention include the use of a binding molecule, for example an antibody or immunospecific fragment thereof, which specifically binds to a membrane associated molecule, variant polypeptide or fragment thereof. The present invention is based, at least in part, on the discovery of membrane associated proteins, i.e., nucleic acid molecules which encode membrane proteins and the use of these molecules to generate custom arrays to screen for markers associated with various diseases and disorders, e.g., cancer, e.g., lung, colon, pancreatic and ovarian cancer and autoimmune diseases or disorders. The invention further relates to various methods, reagents and kits for diagnosing, staging, prognosing, monitoring and treating hyperproliferative diseases or disorders such as cancer, e.g., lung, colon, pancreatic and ovarian cancer and autoimmune diseases or disorders.
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ARYLPHENYLAMINO-AND ARYLPHENYLETHER-SULFIDE DERIVATIVES, USEFUL FOR THE TREATMENT OF INFLAMMATORY AND IMMUNE DISEASES, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM (Fri, 11 Nov 2005)
The present invention relates in part to compounds of formulas (I) and (III): and pharmaceutically-acceptable salts and prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject.
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ARYLPHENYLAMINO-, ARYLPHENYLAMIDE-, AND ARYLPHENYLETHER-SULFIDE DERIVATIVES (Fri, 11 Nov 2005)
The present invention relates in part to compounds of formulas I and III: and pharmaceutically-acceptable salts and prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject.
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ARYLPHENYLAMINO-, ARYLPHENYLAMIDE-, AND ARYLPHENYLETHER-SULFIDE DERIVATIVES (Fri, 11 Nov 2005)
The present invention relates in part to compounds of formulas I and III: and pharmaceutically-acceptable salts and prodrugs thereof. These compounds can be useful for treating diseases such as inflammatory and immune diseases. The present invention also relates to pharmaceutical compositions comprising these compounds, and to methods of inhibiting inflammation or suppressing immune response in a subject. </p>
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Treatment of cancer using antibodies to LRRC15 (Fri, 28 Oct 2005)
<p id="p-0001-en" num="0000">The present invention is directed to novel methods of treating or diagnosing a hyperproliferative disease or disorder in an patient, where the methods include administrating to the patient a binding molecule which binds to a cell surface-expressed glycoprotein expressed predominantly in tumor or tumor-associated cells. In particular, the therapeutic and diagnostic methods of the present invention include the use of a binding molecule, for example an antibody or immunospecific fragment thereof, which specifically binds to the human LRRC15 protein. The present invention further provides a method of isolating and identifying cell surface expressed glycoproteins expressed in tumor or tumor associated tissues, where the method includes isolating desired glycoproteins via their affinity for specific lectins. </p>
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CELL ADHESION INHIBITORS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME (Thu, 01 Sep 2005)

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FCϜ RECEPTOR-BINDING POLYPEPTIDE VARIANTS AND METHODS RELATED THERETO (Fri, 15 Jul 2005)
The compositions and methods of the present invention are based, in part, on our discovery that an effector function mediated by an Fc-containing polypeptide can be altered by modifying one or more amino acid residues within the polypeptide (by, for example, electrostatic optimization). The polypeptides that can be generated according to the methods of the invention are highly variable, and they can include antibodies and fusion proteins that contain an Fc region or a biologically active portion thereof.
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DETECTING PROTEIN SIMILARITY (Fri, 10 Jun 2005)
The disulfide bridges in a protein sequence can be described by a disulfide signature that includes information about cysteine spacing and disulfide topology. Proteins with similar disulfide signatures can be structurally similar despite low overall sequence homology. A database of disulfide signatures can be compiled from publicly available sequence data.
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NEONATAL Fc RECEPTOR (FcRn)-BINDING POLYPEPTIDE VARIANTS, DIMERIC Fc BINDING PROTEINS AND METHODS RELATED THERETO (Fri, 27 May 2005)

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NEONATAL FC RECEPTOR (FCRN)-BINDING POLYPEPTIDE VARIANTS, DIMERIC FC BINDING PROTEINS AND METHODS RELATED THERETO (Fri, 27 May 2005)
Published without an Abstract </p>
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TREATMENT OF CANCER USING ANTIBODIES TO LRRC15 (Fri, 29 Apr 2005)
The present invention is directed to novel methods of treating or diagnosing a hyperproliferative disease or disorder in an patient, where the methods include administrating to the patient a binding molecule which binds to a cell surface-expressed glycoprotein expressed predominantly in tumor or tumor-associated cells. In particular, the therapeutic and diagnostic methods of the present invention include the use of a binding molecule, for example an antibody or immunospecific fragment thereof, which specifically binds to the human LRRC15 protein. The present invention further provides a method of isolating and identifying cell surface expressed glycoproteins expressed in tumor or tumor associated tissues, where the method includes isolating desired glycoproteins via their affinity for specific lectins.
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Cell adhesion inhibitors (Wed, 06 Apr 2005)
<p id="p-00001-en" num="00001">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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ALTERED ANTIBODIES HAVING IMPROVED ANTIGEN-BINDING AFFINITY (Fri, 11 Feb 2005)
The invention relates to methods of modulating the antigen-binding affinity of an antibody by determining, using data corresponding to the structure of a complex between the antibody and an antigen in a solvent, a representation of a charge distribution of the CDRs of the antibody which minimizes electrostatic contribution to binding free energy between the antibody and the antigen in a solvent. Guided by these determinations, the antibody is accordingly modified (altered) to improve upon, e.g., antibody/antigen binding by modifying at least one amino acid residue to decrease the binding free energy between the antibody and antigen when bound in a solvent.
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ALTERED ANTIBODIES HAVING IMPROVED ANTIGEN-BINDING AFFINITY (Fri, 11 Feb 2005)
The invention relates to methods of modulating the antigen-binding affinity of an antibody by determining, using data corresponding to the structure of a complex between the antibody and an antigen in a solvent, a representation of a charge distribution of the CDRs of the antibody which minimizes electrostatic contribution to binding free energy between the antibody and the antigen in a solvent. Guided by these determinations, the antibody is accordingly modified (altered) to improve upon, e.g., antibody/antigen binding by modifying at least one amino acid residue to decrease the binding free energy between the antibody and antigen when bound in a solvent. </p>
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STRUCTURAL INTERACTION FINGERPRINT (SIFt) (Fri, 28 Jan 2005)
Disclosed is a method for representing and analyzing 3D target molecule-ligand intermolecular interactions. The method generates structural interaction fingerprints (SIFts) that convert three-dimensional structural interaction information into linear information strings that contains a plurality of information blocks; each of which in turn containing a plurality of information units. By assigning to each information unit a calculated value to represent the characteristic of a set of intermolecular interactions occurring at each selected position (i.e., a position on the target molecule at which intermolecular interaction occurs), a SIR of the target molecule-ligand complex is constructed.
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METHODS FOR TREATING OR PREVENTING SKIN DISORDERS USING CD2-BINDING AGENTS (Thu, 27 Jan 2005)
</p> <p>Abstract: Methods for treating or preventin an e idermal or dermal disorder, e. ., soriasis, usin a CD2-bindin a ent
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TRIAZOLO[1,5-C]PYRIMIDINES AND PYRAZOLO[1,5-C]PYRIMIDINES USEFUL AS A2A ADENOSIN E RECEPTOR ANTAGONISTS (Fri, 29 Oct 2004)
The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I) .
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A2A ADENOSINE RECEPTOR ANTAGONISTS (Fri, 29 Oct 2004)
The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I).
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TRIAZOLO[1,5-A]PYRIMIDINES AND PYRAZOLO[1,5-A]PYRIMIDINES USEFUL AS A2A ADENOSIN E RECEPTOR ANTAGONISTS (Fri, 29 Oct 2004)
The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula (I) .
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TRIAZOLOPYRAZINES AND METHODS OF MAKING AND USING THE SAME (Fri, 29 Oct 2004)
The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson's disease. In one embodiment, the invention features a compound of formula I (See formula on paper copy)
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TRIAZOLOTRIAZINES AND PYRAZOLOTRIAZINES USEFUL AS A2A ADENOSINE RECEPTOR ANTAGON ISTS (Fri, 29 Oct 2004)
The invention is based on the discovery that compounds of formula (I) possess unexpectedly high affinity for the A2a adenosine receptor, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including Parkinson’s disease. In one embodiment, the invention features a compound of formula I: (I)
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THIOL-MEDIATED DRUG ATTACHMENT TO TARGETING PEPTIDES (Fri, 24 Sep 2004)
Compositions and methods for thiol-specific attachment of therapeutic and diagnostic agents to somatostatin and other targeting peptides.
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PYRAZOLES AND METHODS OF MAKING AND USING THE SAME (Fri, 27 Aug 2004)
The invention is based on the discovery that compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I (I).
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PYRAZOLES AND METHODS OF MAKING AND USING THE SAME (Fri, 27 Aug 2004)
The invention is based on the discovery that compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I (I). </p>
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Cell adhesion inhibitors (Fri, 09 Jul 2004)
<p id="p-0001-en" num="0000">A cell adhesion inhibitor of the general formula: [in-line-formulae]R<sup>3</sup>-L-L′-R<sup>1</sup>[/in-line-formulae] is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same. </p>
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CD40:CD154 binding interrupter compounds and use thereof to treat immunological complications (Fri, 09 Apr 2004)
<p id="p-0001-en" num="0000">The present invention relates to novel CD40:CD154 binding interrupter compounds and use of these compounds and pharmaceutical compositions comprising them, to treat conditions associated with inappropriate CD154 activation in a subject. Specifically, this invention provides compounds which are identified by screening a library of small molecules for those that are capable of specifically binding CD154 and interrupting CD40:CD154 interaction.</p>
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Adenosine receptor antagonists and methods of making and using the same (Fri, 09 Apr 2004)
<p id="p-a-0001-en">The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A<sub>1 </sub>receptor. Adenosine A<sub>1 </sub>antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. </p> <p id="p-a-0002-en">In one embodiment, the invention features a compound of formula 1: <chemistry id="chem-us-00001-en" num="1"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001" file="US20040067966A1-20040408-C00001.TIF" img-content="chem"/></chemistry></p>
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Cell adhesion inhibitors (Fri, 19 Mar 2004)
<p id="p-0001-en" num="0000">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
>> read more

IMIDAZOLOPYRIDINES AND METHODS OF MAKING AND USING THE SAME (Fri, 19 Mar 2004)
Compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I:
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PYRAZOLOPYRIDINES AND METHODS OF MAKING AND USING THE SAME (Fri, 19 Mar 2004)
Compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I:
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PYRAZOLOPYRIDINES AND METHODS OF MAKING AND USING THE SAME (Fri, 19 Mar 2004)
Compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I: </p>
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IMIDAZOLOPYRIDINES AND METHODS OF MAKING AND USING THE SAME (Fri, 19 Mar 2004)
Compounds of formula I possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of formula I: </p>
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Cell adhesion inhibitors (Wed, 04 Feb 2004)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
>> read more

THERAPIES FOR RENAL FAILURE USING INTERFERON-β (Fri, 23 Jan 2004)
The present invention provides methods for the treatment, and pharmaceuticals for the use in the treatment, of mammalian subjects having, or at risk of developing, glomerulonephritis or chronic renal failure. The methods involve the administration of IFN-β therapeutics.
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THERAPIES FOR RENAL FAILURE USING INTERFERON-.BETA. (Fri, 23 Jan 2004)
The present invention provides methods for the treatment, and pharmaceuticals for the use in the treatment, of mammalian subjects having, or at risk of developing, glomerulonephritis or chronic renal failure. The methods involve the administration of IFN-.beta. therapeutics. </p>
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CELL ADHESION INHIBITORS (Thu, 11 Dec 2003)
A VLA-4 inhibitor of the formula A-B wherein A comprises a VLA-4 specificity determinant which does not impart significant IIb/IIIa activity, and B comprises an integrin scaffold derived from a compound having IIb/IIIa activity.
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Adenosine receptor antagonists and methods of making and using the same (Fri, 05 Dec 2003)
<p id="p-a-0001-en">The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A<sub>1 </sub>receptor. Adenosine A<sub>1 </sub>antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. </p> <p id="p-a-0002-en">In one embodiment, the invention features a compound of formula I: <chemistry id="chem-us-00001-en" num="1"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001" file="US20030225038A1-20031204-C00001.TIF" img-content="chem"/></chemistry></p>
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Adenosine receptor antagonists and methods of making and using the same (Wed, 19 Nov 2003)
<p id="p-00001-en">The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A<sub>1</sub>receptor. Adenosine A<sub>1</sub>antagonists can be usefull in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable.</p> <p id="p-00002-en">In one embodiment, the invention features a compound of formula I:<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06649600-20031118-C00001.TIF" img-content="chem" alt="embedded image"/></chemistry></p> <p id="p-00003-en">wherein:</p> <p id="p-00004-en">R<sub>3</sub>is an optionally substituted bicyclic, tricylic, or pentacyclic group selected from:<chemistry id="chem-us-00002-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00002-en" file="US06649600-20031118-C00002.TIF" img-content="chem" alt="embedded image"/></chemistry></p> <p id="p-00005-en"> and wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>6</sub>, X<sub>1</sub>, X<sub>2</sub>, and Z are as described in the specification.</p>
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TRI-SUBSTITUTED HETEROARYLS AND METHODS OF MAKING AND USING THE SAME (Fri, 24 Oct 2003)
Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (I).
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TRI-SUBSTITUTED HETEROARYLS AND METHODS OF MAKING AND USING THE SAME (Fri, 24 Oct 2003)
Compounds of formula (I) possess unexpectedly high affinity for Alk 5 and/or Alk 4, and can be useful as antagonists thereof for preventing and/or treating numerous diseases, including fibrotic disorders. In one embodiment, the invention features a compound of the general formula (I). </p>
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Cell adhesion inhibitors (Wed, 08 Oct 2003)
<p id="p-00001-en">A cell adhesion inhibitor of the general formula:</p> <p id="p-00002-en">R<sup>3</sup>—L—L′—R<sup>1</sup></p> <p id="p-00003-en">is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same.</p>
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ALPHA1BETA1 ANTAGONISTS FOR TREATMENT OF ATHEROSCLEROSIS (Fri, 22 Aug 2003)
Methods of treating atherosclerosis by inhibiting the function or expression of VLA-1. Also included are antagonists of VLA-1 that are useful in the methods.
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Adenosine receptor antagonists and methods of making and using the same (Wed, 13 Aug 2003)
<p id="p-00001-en">The invention is based on the discovery that compounds of Formula I are unexpectedly highly potent and selective inhibitors of the adenosine A<sub>1</sub>receptor. Adenosine A<sub>1</sub>antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable.</p> <p id="p-00002-en">In one embodiment, the invention features a compound of formula I:<chemistry id="chem-us-00001-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00001-en" file="US06605600-20030812-C00001.TIF" img-content="chem" alt="embedded image"/></chemistry></p> <p id="p-00003-en">R<sub>3</sub>is an optionally substituted group selected from:<chemistry id="chem-us-00002-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00002-en" file="US06605600-20030812-C00002.TIF" img-content="chem" alt="embedded image"/></chemistry><chemistry id="chem-us-00003-en"><img he="N/A" wi="N/A" img-format="tif" id="emi-c00003-en" file="US06605600-20030812-C00003.TIF" img-content="chem" alt="embedded image"/></chemistry></p> <p id="p-00004-en">and wherein X<sub>1</sub>, X<sub>2</sub>, Z, R<sub>1</sub>, R<sub>2</sub>, and R<sub>6</sub>are as described in the specification.</p>
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CELL ADHESION INHIBITORS (Thu, 31 Jul 2003)
</p> <p>(ϋ^ A hstract: Λ cell adhesion inhibitor of the general formula: '-L-L<sup>'</sup>-R<sup>1</sup> is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VI.A-4 dependent cell adhesion. A lso disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compusitioris containing the same.
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Cell adhesion inhibitors (Wed, 23 Jul 2003)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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Cell adhesion inhibitors (Fri, 02 May 2003)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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Recombinant anti-CD4 antibodies for human therapy (Fri, 25 Apr 2003)
<p id="p-0001-en" num="0000">Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability (in vivo half-life).</p>
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CRYSTAL STRUCTURE OF BAFF, AND USE THEREOF IN DRUG DESIGN (Fri, 21 Mar 2003)
The present invention relates to crystallizable compositions and crystals of BAFF. In addition, this invention relates to the high resolution structure of a BAFF polypeptide as obtained by X-Ray crystallography. This invention also relates to a computer (machine) comprising a machine-readable data storage medium comprising a data storage material enconded with machine-readable data comprising the structure coordinates provided by this invention. This invention also relates to methods of using the structure coordinates of BAFF to solve the structure of similar or homologous molecules or molecular complexes and methods of determining the homology model of a similar or homologous molecule, such as APRIL. This invention also provides a computer capable of producing a three-dimensional representation of APRIL based on the homology model structure coordinates. This invention also relates to methods using the structure coordinates of BAFF to design chemical entities or compounds, including agonists or antagonists, with improved properties (such as increased or decreased binding affinity for (BAFF). This invention also provides variants of BAFF. This invention also relates to compositions comprising said chemical entities, compounds, including agonists or antagonists of BAFF, or variants.
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CRYSTAL STRUCTURE OF BAFF, AND USE THEREOF IN DRUG DESIGN (Fri, 21 Mar 2003)
The present invention relates to crystallizable compositions and crystals of BAFF. In addition, this invention relates to the high resolution structure of a BAFF polypeptide as obtained by X-Ray crystallography. This invention also relates to a computer (machine) comprising a machine-readable data storage medium comprising a data storage material enconded with machine-readable data comprising the structure coordinates provided by this invention. This invention also relates to methods of using the structure coordinates of BAFF to solve the structure of similar or homologous molecules or molecular complexes and methods of determining the homology model of a similar or homologous molecule, such as APRIL. This invention also provides a computer capable of producing a three-dimensional representation of APRIL based on the homology model structure coordinates. This invention also relates to methods using the structure coordinates of BAFF to design chemical entities or compounds, including agonists or antagonists, with improved properties (such as increased or decreased binding affinity for (BAFF). This invention also provides variants of BAFF. This invention also relates to compositions comprising said chemical entities, compounds, including agonists or antagonists of BAFF, or variants. </p>
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METHODS FOR TREATING OR PREVENTING SCLEROTIC DISORDERS USING CD2-BINDING AGENTS (Fri, 07 Feb 2003)
Methods and compositions for treating or preventing fibrotic disorders, e.g., sclerotic disorders, for example scleroderma, using CD2-binding agents, e.g., LFA-3/IgG fusion polypeptides or LFA-3-binding agents, are provided.
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METHODS FOR TREATING OR PREVENTING SCLEROTIC DISORDERS USING CD2-BINDING AGENTS (Fri, 07 Feb 2003)
Methods and compositions for treating or preventing fibrotic disorders, e.g., sclerotic disorders, for example scleroderma, using CD2-binding agents, e.g., LFA-3/IgG fusion polypeptides or LFA-3-binding agents, are provided. </p>
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Cell adhesion inhibitors (Fri, 24 Jan 2003)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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CELL ADHESION INHIBITORS (Thu, 19 Dec 2002)
A cell adhesion inhibitor of the general formula: R?3¿-L-L'-R?1¿ is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same.
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VLA-4 inhibitor: oMePUPA-V (Wed, 18 Dec 2002)
<p id="p-00001-en">OMePUPA-V, (R)-N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-prolyl-3-methyl)-β-Alanine, a cell adhesion inhibitor, pharmaceutical compositions, and methods of treatment of cell-adhesion mediated pathologies.</p>
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CELL ADHESION INHIBITORY COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME (Mon, 11 Nov 2002)
Cell adhesion inhibitory compounds selected from compounds of the formula 3120 ה' בכסלו התשס" ג - November 10, 2002 and pharmaceutically acceptable derivatives thereof, wherein: X is selected from the group consisting of -CO2H, -PO3H, -SO2R5, -SO3H, -OPO3H, and -CO2R4; wherein R5 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, aryl- substituted alkyl, and aryl-substituted alkenyl or alkynyl; Y is selected from the group consisting of -CO-, -SO2-, CH2 and PO2; R1 is selected from the group consisting of alkenyl, alkynyl, cycloalkyl, aryl-fused cycloalkyl, cycloakenyl, aryl, aralkyl, aryl- substituted alkenyl or alkynyl, cycloalkyl- substituted alkyl, cycloalkenyl-substituted alkyl, biaryl, alkoxy, alkenoxy, alkynoxy, aralkoxy, aryl-subsituted alkenoxy or alkynoxy, alkylamino, alkenylamino or alkynylamino, aryl-substituted alkylamino, aryl-substituted alkenylamino or alkynylamino, aryloxy, arylamino, N-alkylurea-substituted alkyl, N-arylurea-substituted alkyl, aminocarbonyl-substituted alkyl, heterocyclyl, hetercyclyl-substituted alkyl, heterocyclyl-substituted amino, carboxylalkyl substituted aralkyl, oxocarbocylyl-fused aryl and heterocyclylalkyl; R2 is selected from the group consisting of hydrogen, aryl, alkyl, alkenyl or alkynyl, cycloalkyl, cycloalkenyl, aryl-substituted alkyl and, wherein R2 and R3 may be taken together with the atoms to which they are attached, to form a heterocycle; R3 is selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl-substituted alkenyl or alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl-substituted alkenyl or alkynyl, hydroxy-substituted alkyl, alkoxy-substituted alkyl, aralkoxy- 3121 ה' בכסלו התשס" ג - November 10, 2002 substituted alkyl, amino-substituted alkyl, (aryl-substituted alkyloxycarbonylamino) - substituted alkyl, thiol-substituted alkyl, alkylsulfonyl-substituted alkyl, (hydroxyl- substituted alkylthio)-substituted alkyl, thioalkoxy-substituted alkyl, acylamino- substituted alkyl, alkylsulfonylamino- substituted alkyl, arylsufonylamino- substituted alkyl, morpholino-alkyl, thiomorpholino-alkyl, morpholino carbonyl-substituted alkyl, thiomorpholinocarbonyl-substituted alkyl, [N-alkyl, alkenyl or alkynyl) - or N, N-[dialkyl, dialkenyl, dialkynyl or (alkyl, alkenyl) - amino] carbonyl-substituted alkyl, carboxyl-substituted alkyl, dialkylamino- substituted acylaminoalkyl and amino acid side chains selected from arginine, asparagine, glutamine, S-methyl cysteine, methionine and corresponding sulfoxide and sulfone derivatives thereof, glycine, leucine, isoluecine, allo-isoleucine, tert- leucine, norleucine, phenylalanine, tyrosine, trytophan, proline, alanine, ornithine, histidine, glutamine, valine, thereonine, serine, beta-cyanoalanine, and allothreonine; and wherein R2 and R3 may be taken together with the atoms to which they are attached, to form a heterocycle; R4 is selected from the group consisting of aryl, alkyl, cycloalkyl, alkenyl, aryl- substituted alkyl, hydrogen, heterocyclyl, heterocyclylcarbonyl, amido, mono- or dialkylaminocarbonyl, mono- or diarylaminocarbonyl, alkylarylaminocarbonyl, diarylaminocarbonyl, mono- or diacylaminocarbonyl, aromatic acyl, alkyl optionally substituted by substituents selected from the group consisting of amino, carboxy, hydroxy, mercapto, mono- or dialkylamino, mono- or diarylamino, alkylarylamino, diarylamino, mono- or diacylamino, alkoxy, alkenoxy, aryloxy, thioalkoxy, thioalkenoxy, thioalkynoxy, thioaryloxy and heterocyclyl; and n is 0, 1, or 2; (1) provided that R1 and Y taken together are not t-butoxycarbonyl, benzyloxycarbonyl, benzoyl, isovaleryl, a phenylacyl group meta substituted with a carboxy group 2, 2-dibenzylacetyl, 3-phenylpronanoyl, methyl- 3-phenylpropanoyl, or imidazolylacetyl; or (2) provided that when R1 is N-alkylurea- substituted alkyl or N-arylurea-substituted alkyl, and when Y is CO, R3 is not an un
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POYCYLOALKYLPURINES AS ADENOSINE RECEPTOR ANTAGONISTS (Thu, 15 Aug 2002)
The invention is based on the discovery that compounds of Formula (I) are unexpectedly highly potent and selective inhibitors of the adenosine A¿1? receptor. Adenosine A¿1? antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I).
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ADENOSINE RECEPTOR ANTAGONISTS AND METHODS OF MAKING AND USING THE SAME (Thu, 15 Aug 2002)
The invention is based on the discovery that compounds of Formula (I), are unexpectedly highly potent and selective inhibitors of the adenosine A¿1? receptor. Adenosine A¿1? antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I), wherein R¿3? is selected from particular bicycloheptyl, bicyclooctyl, tricycloheptyl and tricyclooctyl groups.
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METHODS FOR TREATING OR PREVENTING SKIN DISORDERS USING CD2-BINDING AGENTS (Fri, 09 Aug 2002)
Methods for treating or preventing an epidermal or dermal disorder, e.g., psoriasis, using a CD2-binding agent, e.g., an inhibitor of the CD2/LFA-3 interaction (e.g., an LFA-3/IgG fusion polypeptide), in combination with an auxiliary agent, e.g., UVB irradiation, are disclosed.
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METHODS FOR TREATING OR PREVENTING SKIN DISORDERS USING CD2-BINDING AGENTS (Fri, 09 Aug 2002)
Methods for treating or preventing an epidermal or dermal disorder, e.g., psoriasis, using a CD2-binding agent, e.g., an inhibitor of the CD2/LFA-3 interaction (e.g., an LFA-3/IgG fusion polypeptide), in combination with an auxiliary agent, e.g., UVB irradiation, are disclosed. </p>
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THERAPIES FOR CHRONIC RENAL FAILURE USING ONE OR MORE INTEGRIN ANTAGONISTS (Thu, 20 Jun 2002)
The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects in, or at risk of chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain integrin antagonists.
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NOVEL VLA 4 INHIBITOR oMePupa V (Thu, 25 Apr 2002)
e - , - - - -me yp enyamnocar ony m - - - -inhibitor, pharmaceutical compositions, and methods of treatment of cell-adhesion mediated pathologies.
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Cell adhesion inhibitors (Wed, 24 Apr 2002)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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CO-CRYSTAL STRUCTURE OF MONOCLONAL ANTIBODY 5C8 AND CD154, AND USE THEREOF IN DRUG DESIGN (Fri, 08 Mar 2002)
The present invention relates to compositions and crystals of CD154 (CD40L) in complex with an anti-CD154 antibody. In addition, this invention relates to the high resolution structure of a CD154/anti-CD154 antibody complex as obtained by X-ray crystallography. Specifically, this structure provides binding sites defined by the structure coordinates determined herein. This invention also relates to a computer (machine) comprising a machine-readable data storage medium comprising a data storage material encoded with machine-readable data comprising the structure coordinates provided by this invention. The computer has instructions to process said machine-readable data into a three-dimensional representation of a molecular complex of CD154/anti-CD154 antibody based on the structure coordinates provided by this invention. This invention also relates to methods using the structure coordinates of an CD154/anti-CD154 antibody complex to solve the structure of similar or homologous molecular complexes, as well as methods using the structure coordinates of an CD154/anti-CD154 antibody complexto design chemical entities or compounds, including agonists or antagonists of CD154, that specifically bind CD154 and function as CD40:CD154 binding interruptors, as well as to design variants of monoclonal antibody 5c8, or humanized monoclonal antibody 5c8, or antigen binding fragements thereof, having improved properties (such as increased or decreased binding affinity for CD154). This invention also relates to compositions comprising said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8. The invention further relates to uses of said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8 to treat a subject having one or more conditons associated with inappropriate or abnormal CD154 induced activation.
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PYRIDINE DERIVATIVES USEFUL AS CD40:CD154 BINDING INTERRUPTOR COMPOUNDS AND USE THEREOF TO TREAT IMMUNOLOGICAL COMPLICATIONS (Fri, 08 Mar 2002)
The present invention relates to novel CD40:CD154 binding interruptor compounds of the formula (I), and use of these compounds and pharmaceutical compositions comprising them, to treat conditions associated with inappropriate CD154 activation in a subject. Specifically, this invention provides compounds which are identified by screening a library of small molecules for those that are capable of specifically binding CD154 and interrupting CD40:CD154 interaction.
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NOVEL CD40:CD154 BINDING INTERRUPTOR COMPOUNDS AND USE THEREOF TO TREAT IMMUNOLOGICAL COMPLICATIONS (Fri, 08 Mar 2002)
The present invention relates to novel CD40:CD154 binding interruptor compounds and use of these compounds and pharmaceutical compositions comprising them, to treat conditions associated with inappropriate CD154 activation in a subject. Specifically, this invention provides compounds which are identified by screening a library of small molecules for those that are capable of specifically binding CD154 and interrupting CD40:CD154 interaction. </p>
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CO-CRYSTAL STRUCTURE OF MONOCLONAL ANTIBODY 5C8 AND CD154, AND USE THEREOF IN DRUG DESIGN (Fri, 08 Mar 2002)
The present invention relates to compositions and crystals of CD154 (CD40L) in complex with an anti-CD154 antibody. In addition, this invention relates to the high resolution structure of a CD154/anti-CD154 antibody complex as obtained by X-ray crystallography. Specifically, this structure provides binding sites defined by the structure coordinates determined herein. This invention also relates to a computer (machine) comprising a machine-readable data storage medium comprising a data storage material encoded with machine- readable data comprising the structure coordinates provided by this invention. The computer has instructions to process said machine-readable data into a three-dimensional representation of a molecular complex of CD154/anti-CD154 antibody based on the structure coordinates provided by this invention. This invention also relates to methods using the structure coordinates of an CD154/anti-CD154 antibody complex to solve the structure of similar or homologous molecular complexes, as well as methods using the structure coordinates of an CD154/anti-CD154 antibody complexto design chemical entities or compounds, including agonists or antagonists of CD154, that specifically bind CD154 and function as CD40:CD154 binding interruptors, as well as to design variants of monoclonal antibody 5c8, or humanized monoclonal antibody 5c8, or antigen binding fragements thereof, having improved properties (such as increased or decreased binding affinity for CD154). This invention also relates to compositions comprising said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8. The invention further relates to uses of said chemical entities, compounds or variants of monoclonal antibody 5c8 or humanized monoclonal antibody 5c8 to treat a subject having one or more conditons associated with inappropriate or abnormal CD154 induced activation. </p>
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Cell adhesion inhibitors (Wed, 24 Oct 2001)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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Cell adhesion inhibitors (Thu, 11 Oct 2001)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.
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Cell adhesion inhibitors (Wed, 20 Jun 2001)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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Cell adhesion inhibitors (Wed, 30 May 2001)
<p id="p-00001-en">The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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ADENOSINE RECEPTOR ANTAGONISTS AND METHODS OF MAKING AND USING THE SAME (Fri, 18 May 2001)
The invention is based on the discovery that compounds of Formula (I), are unexpectedly highly potent and selective inhibitors of the adenosine A1 receptor. Adenosine A1 antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I), wherein R3 is selected from particular bicycloheptyl, bicyclooctyl, tricycloheptyl and tricyclooctyl groups.
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POLYCYCLOALKYLPURINES AS ADENOSINE RECEPTOR ANTAGONISTS (Fri, 18 May 2001)
The invention is based on the discovery that compounds of Formula (I) are unexpectedly highly potent and selective inhibitors of the adenosine A1 receptor. Adenosine A1 antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I).
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POLYCYCLOALKYLPURINES AS ADENOSINE RECEPTOR ANTAGONISTS (Fri, 18 May 2001)
The invention is based on the discovery that compounds of Formula (I) are unexpectedly highly potent and selective inhibitors of the adenosine A1 receptor. Adenosine A1 antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I). </p>
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ADENOSINE RECEPTOR ANTAGONISTS AND METHODS OF MAKING AND USING THE SAME (Fri, 18 May 2001)
The invention is based on the discovery that compounds of Formula (I), are unexpectedly highly potent and selective inhibitors of the adenosine A, receptor. Adenosine A, antagonists can be useful in the prevention and/or treatment of numerous diseases, including cardiac and circulatory disorders, degenerative disorders of the central nervous system, respiratory disorders, and many diseases for which diuretic treatment is suitable. In one embodiment, the invention features a compound of formula (I), wherein R3 is selected from particular bicycloheptyl, bicyclooctyl, tricycloheptyl and tricyclooctyl groups. </p>
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THERAPIES FOR CHRONIC RENAL FAILURE USING ONE OR MORE INTEGRIN ANTAGONISTS (Fri, 23 Mar 2001)
The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects in, or at risk of chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain integrin antagonists.
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THERAPIES FOR CHRONIC RENAL FAILURE USING ONE OR MORE INTEGRIN ANTAGONISTS (Fri, 23 Mar 2001)
The present invention provides methods for the treatment, and pharmaceuticals for use in the treatment, of mammalian subjects in, or at risk of chronic renal failure, or at risk of a need for renal replacement therapy. The methods involve the administration of certain integrin antagonists. </p>
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CELL ADHESION INHIBITORS (Fri, 23 Feb 2001)
A cell adhesion inhibitor of the general formula: R?3-L-L'-R1¿ is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same.
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CELL ADHESION INHIBITORS (Fri, 23 Feb 2001)
A cell adhesion inhibitor of the general formula: R3-L-L'-R1 is disclosed. An inhibitor of the present invention interacts with VLA-4 molecules and inhibits VLA-4 dependent cell adhesion. Also disclosed are methods for preparing and using such a cell adhesion inhibitor, as well as pharmaceutical compositions containing the same. </p>
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A NOVEL VLA-4 INHIBITOR: oMePUPA-V (Fri, 03 Dec 1999)
OMePUPA-V, (R)-N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L-prolyl-3-methyl)-β-Alanine, a cell adhesion inhibitor, pharmaceutical compositions, and methods of treatment of cell-adhesion mediated pathologies.
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A NOVEL VLA-4 INHIBITOR: OMEPUPA-V (Fri, 03 Dec 1999)
OMePUPA-V, (R)-N-[[4-[[(2-methylphenylamino)carbonyl]amino]phenyl]acetyl]-L- prolyl-3-methyl)-.beta.-Alanine, a cell adhesion inhibitor, pharmaceutical compositions, and methods of treatment of cell- adhesion mediated pathologies. </p>
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CELL ADHESION INHIBITORS (Thu, 27 May 1999)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.
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RECOMBINANT ANTI-CD4 ANTIBODIES FOR HUMAN THERAPY (Thu, 30 Jul 1998)
Chimeric antibodies specific to human CD4 antigen, DNA encoding, pharmaceutical compositions containing the and use thereof as therapeutic agents are taught. These chimeric antibodies contain Old World monkey variable sequences and human constant domain sequences, preferably human gamma 1, gamma 4 or mutated forms thereof. These antibodies possess desirable therapeutic properties including low antigenicity, reduced (or absent) T cell depleting activity, good affinity to human CD4 and enhanced stability ($i(in vivo) half-life).
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CELL ADHESION INHIBITORS (Thu, 21 May 1998)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical composition of this inveniton can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.
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PRODUCTION OF RECOMBINANT PLASMA GELSOLIN CONTAINING A DISULFIDE BOND (Fri, 06 Feb 1998)
A method is provided for producing recombinant gelsolin containing a disulfide bond. The oxidized gelsolin may be produced by treating intracellular recombinant gelsolin with an oxidant, or by denaturing gelsolin and then refolding gelsolin.
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CELL ADHESION INHIBITORS (Fri, 06 Feb 1998)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.
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CELL ADHESION INHIBITORS (Fri, 06 Feb 1998)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases. In one aspect the invention provides a cell adhesion inhibitor having Formula (I) A-B (I) wherein A comprises a VLA-4 specificity determinant which does not impart significant IIb/IIIa activity, and B comprises an integrin scaffold derived from a compound having IIb/IIIa activity. </p>
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CELL ADHESION INHIBITORS (Fri, 31 Jan 1997)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical composition of this inveniton can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.
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CELL ADHESION INHIBITORS (Fri, 31 Jan 1997)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical composition of this inveniton can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases. </p>
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CELL ADHESION INHIBITORS (Fri, 02 Aug 1996)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.
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CELL ADHESION INHIBITORS (Fri, 02 Aug 1996)
The present invention relates to novel compounds that are useful for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. This invention also relates to pharmaceutical formulations comprising these compounds and methods of using them for inhibition and prevention of cell adhesion and cell adhesion-mediated pathologies. The compounds and pharmaceutical compositions of this invention can be used as therapeutic or prophylactic agents. They are particularly well-suited for treatment of many inflammatory and autoimmune diseases.</p>
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