The present invention relates to Tri-Specific Binding Molecules, which are multi-chain polypeptide molecules that possess three Binding Domains and are thus capable of mediating coordinated binding to three epitopes. The Tri-Specific Binding Molecule is preferably characterized in possessing binding domains that permit it to immunospecifically bind to: (1) an epitope of a first Cancer Antigen, (2) an epitope of a second Cancer Antigen, and (3) an epitope of a molecule that is expressed on the surface of an immune system effector cell, and are thus capable of localizing an immune system effector cell to a cell that expresses a Cancer Antigen, so as to thereby facilitate the killing of such cancer cell.

(Objective) An objective of the present invention is to provide therapeutic agents that, in association with stimulation of PDGFRα-positive cells such as bone marrow mesenchymal stem cells, promote their mobilization into blood and accumulation in a damaged tissue, and induce tissue regeneration in a living body.

(Means for solution) Multiple peptides were synthesized, and the migration-promoting activity of each peptide was evaluated. As a result, the present inventors successfully identified multiple peptides that have migration-promoting activity on a PDGFRα-positive bone marrow mesenchymal stem cell line (MSC-1). Further, the present inventors confirmed that the identified peptides also have migration-promoting activity on skin fibroblasts, which are PDGFRα-positive cells.

In one aspect, the invention relates to compounds having the formula: ##STR00001##
where R.sup.1-R.sup.6, a, b, and Z are as defined in the specification, or a pharmaceutically acceptable salt thereof. These compounds have neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and processes and intermediates for preparing such compounds.

Method for treating a disease, condition, or syndrome in a subject comprising administering, to a subject in need thereof, a solid or liquid pharmaceutical composition comprising: (a) a high purity botulinum neurotoxin or a complex comprising botulinum neurotoxin, wherein the botulinum neurotoxin is of type A, B, C, D, E, F or G; and (b) a surfactant;
wherein the composition does not comprise albumin or a polysaccharide.

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

The subject matter described herein is directed to ferroportin inhibitor compounds of Formula I or I′ and pharmaceutical salts thereof, methods of preparing the compounds, pharmaceutical compositions comprising the compounds, and methods of administering the compounds for prophylaxis and/or treatment of diseases caused by a lack of hepcidin or iron metabolism disorders, particularly iron overload states, such as thalassemia, sickle cell disease and hemochromatosis, and also kidney injuries.

Compounds within the scope of the present invention have a Formula 1 ##STR00001##
or a salt or produg thereof, where ring A is selected from cycloaliphatic; ring B is aryl; R.sup.1 is selected from (C1-C10)alkyl, (C3-C10)cycloalkyl, halo, aryl, and heteroaryl; and R.sup.2 and R.sup.3 are independently selected from hydrogen and (C1-C6)alkyl. Disclosed compounds may have an IRAK4 IC.sub.50 of from 0.003 μM to 3.7 μM; a TAK1 IC.sub.50 of from 0.008 μM to 132 μM; and/or an IRAK4/TAK1 selectivity of from 1 to 450. Particular compounds may have an IRAK4/TAK1 selectivity of from 100 to 500. Disclosed compositions may be formulated as pharmaceutical compositions. A method for using the compounds and/or compositions also are disclosed. The method may comprise administering to a subject an effective amount of a compound within the scope of the present invention, particularly to selectively inhibit IRAK 1 and/or IRAK4 over TAK1.

Provided are formulations and methods for treating one or more genitourinary conditions. The formulations may include a therapeutic agent that includes a calcium channel blocker, a rho kinase inhibitor, or a combination thereof. The methods may include locally administering a therapeutic agent into a ureter. Systems for delivering a therapeutic agent also are provided.

The present invention provides, in part, compounds of Formula I: or an N-oxide thereof, or a pharmaceutically acceptable salt of the compound or the N-oxide, wherein: X.sup.1, X.sup.2, R.sup.1, R.sup.2, m and n are as described herein; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds, N-oxides, or salts, and their uses for treating M4-mediated (or M4-associated) disorders including, e.g., Alzheimer's Disease, Parkinson's Disease, schizophrenia (e.g., its cognitive and negative symptoms), pain, addiction, and a sleep disorder. ##STR00001##

The present invention describes novel nanoparticle compositions, and systems and methods utilizing them for treating disorders and/or conditions. Methods generally involve administering nanoparticle compositions (e.g., nanoparticle compositions comprising at least one known therapeutic agent and/or independently active biologically active agent; and/or empty nanoparticle compositions) to a subject in need thereof.