Abstract: Disclosed herein are therapeutic conjugates having an extended circulating serum half-life. The therapeutic conjugates comprise a therapeutic moiety linked to a half-life extension moiety via a fibroblast activation protein, alpha (FAP?)-cleavable linker. Methods of using the therapeutic conjugates are also provided.

Abstract: Disclosed herein are therapeutic conjugates having an extended circulating serum half-life. The therapeutic conjugates comprise a drug moiety linked to a half-life extension moiety via an enzyme-cleavable linker. Methods of using the therapeutic conjugates are also provided.

Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Abstract: Methods, compositions, and devices for stimulating the number and/or differentiation of hematopoietic cells in vitro are provided. The methods involve contacting the hematopoietic cells with an inhibitor of dipeptidyl peptidase (DPIV) in the absence of exogenously provided cytokines.

Abstract: The present invention provides methods and compositions for modification and regulation of glucose and lipid metabolism, generally to reduce insulin resistance, hyperglycemia, hyperinsulinemia, obesity, hyperlipidemia, hyperlipoprotein-emia (such as chylomicrons, VLDL and LDL), and to regulate body fat and more generally lipid stores, and, more generally, for the improvement of metabolism disorders, especially those associated with diabetes, obesity and/or atherosclerosis.

Abstract: The present invention provides methods and compositions for modification and regulation of glucose and lipid metabolism, generally to reduce insulin resistance, hyperglycemia, hyperinsulinemia, obesity, hyperlipidemia, hyperlipoproteinemia (such as chylomicrons, VLDL and LDL), and to regulate body fat and more generally lipid stores, and, more generally, for the improvement of metabolism disorders, especially those associated with diabetes, obesity and/or atherosclerosis. The compositions of the present invention include dipeptidylpeptidase inhibitors, which are able to inhibit the proteolysis of GLP-1 and accordingly increase the plasma half-life of that hormone. The subject inhibitors may be peptidyl, peptidomimetic (e.g. boronyl peptidomimetics), or non-peptidyl nitrogen containing heterocycles.

Abstract: The present invention relates to prodrugs of protease inhibitors, such as inhibitors of proteosome, DPOP IV, FAP? and the like. These “pro-inhibitors” are activated, i.e., cleaved by an “activated protease” to release an active inhibitor moiety in proximity to a “target protease”. The identity of activating protease and target protease can be the same (such pro-inhibitors being refered to as “Target-Activated Smart Protease Inhibitors” or “TASPI”) or different (e.g., “Target-Directed Smart Protease Inhibitors” or “TDSPI”). After activation of the pro-inhibitor, the active inhibitor moiety can self-inactive by, e.g., intramolecular-cyclization or cis-trans isomerization.

Abstract: The present invention provides peptidomimetics derived from Apolipoprotein A-I, which is useful for beneficially influencing lipid parameters and/or plasma cholesterol levels. The invention also provides pharmaceutical compositions and methods of treatment for elevated levels of plasma cholesterol.

Abstract: The present invention relates to inhibitors of post-proline cleaving enzymes, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. In particular, the inhibitors of the present invention are improved over those in the prior art by selection of particular classes of sidechains in the P1 and/or P2 position of the inhibitor that contain a carboxylic acid moiety. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

Abstract: Synthetic crosslinking homobivalent and heterobivalent compounds have been designed and developed. These compounds are low in molecular weight, have antagonistic or agonistic activity, and induce the association between two identical or similar natural receptors (homobivalent compounds) or induce the association between two different natural receptors (heterobivalent compounds).

Abstract: The invention generally relates to improved methods for treatment or prophylaxis in animal subjects (including humans) of autoimmune disorders including Type I diabetes, septic shock, multiple sclerosis, inflammatory bowel disease (IBD) and Crohn's disease.

Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Abstract: The present invention provides methods and compositions for modification and regulation of GLP 1 metabolism, glucose and lipid metabolism, generally to reduce insulin resistance, hyperglycemia, hyperinsulinemia, obesity, hyperlipidemia, hyperlipoproteinemia (such as chylomicrons, VLDL and LDL), and to regulate body fat and more generally lipid stores, and, more generally, for the improvement of metabolism disorders, especially those associated with diabetes, obesity and/or atherosclerosis. The compositions described herein are high-affinity boronyl and non-boronyl peptidomimetic inhibitors of DPIV.

Abstract: Methods, compositions, and devices for stimulating the number and/or differentiation of hematopoietic cells in vitro are provided. The methods involve contacting the hematopoietic cells with an inhibitor of dipeptidyl peptidase (DPIV) in the absence of exogenously provided cytokines.

Abstract: Methods for expanding antigen-specific T cells in vitro are provided. The methods involve contacting hematopoietic precursor or progenitor cells with a heteroconjugate containing an inhibitor of dipeptidyl peptidase (DPIV) attached to an antigenic peptide, optionally with a culture step to expand T cells with a DPIV inhibitor. The culture may be performed in the absence of exogenously provided cytokines.

Abstract: Methods, compositions, and devices for stimulating the number and/or differentiation of hematopoietic cells in vitro are provided. The methods involve contacting the hematopoietic cells with an inhibitor of dipeptidyl peptidase (DPIV) in the absence of exogenously provided cytokines.

Abstract: Methods, compositions, and devices for stimulating the number and/or differentiation of hematopoietic cells in vitro are provided. The methods involve contacting the hematopoietic cells with an inhibitor of dipeptidyl peptidase (DPIV) in the absence of exogenously provided cytokines.