Abstract: Methods for the treatment or prevention of disease, such as fatty liver disease and obesity, are described including the modulation the amount of CTRP1 in a subject. Novel mouse strains are also described.

Abstract: The present invention provides a peptide of formula (I), or a pharmaceutically acceptable salt thereof, wherein the N-terminal group of the peptide is a monoradical of formula —NHR1; the C-terminal group of the peptide is a monoradical of formula —C(O)—R2; R1 is a monoradical selected from hydrogen and —C(O)—(C1-C20)alkyl; R2 is a monoradical selected from —OH and —NR3R4 radical; R3 and R4 are independently selected from hydrogen and (C1-C10)alkyl; “a” to “j” are integers from 0 to 1, provided that at least one of “a” to “j” is 1; and X1 represents any amino acid. The present invention also provides conjugates and compositions comprising the peptide of formula (I). The peptide can be used in the treatment or prevention of neoplastic diseases such as pancreatic cancer.

Abstract: The present invention relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has clotting activity in absence of its cofactor. The present invention furthermore relates to variants of factor IX (F.IX) or activated factor IX (F.IXa), wherein the variant is characterized in that it has increased F.IX clotting activity compared to wildtype. The present invention furthermore relates to the use of these variants for the treatment and/or prophylaxis of bleeding disorders, in particular hemophilia A and/or hemophilia B or hemophilia caused or complicated by inhibitory antibodies to F.VIII. The present invention also relates to further variants of factor IX (F.IX) which have desired properties and can, thus be tailored for respective specific therapeutic applications.

Abstract: The present disclosure features signal-regulatory protein ? (SIRP-?) polypeptides and constructs that are useful, e.g., to target a cell (e.g., a cancer cell or a cell of the immune system), to increase phagocytosis of the target cell, to eliminate immune cells such as regulatory T-cells, to kill cancer cells, to treat a disease (e.g., cancer) in a subject, or any combinations thereof. The SIRP-? constructs include a high affinity SIRP-? D1 domain or variant thereof that binds CD47 with higher affinity than a wild-type SIRP-?. The SIRP-? polypeptides or constructs include a SIRP-? D1 variant fused to an Fc domain monomer, a human serum albumin (HSA), an albumin-binding peptide, or a polyethylene glycol (PEG) polymer. Compositions provided herein include (i) a polypeptide including a signal-regulatory protein ? (SIRP-?) D1 variant and (ii) an antibody.

Abstract: Among other things, the present disclosure provides technologies for modulating functions of beta-catenin. In some embodiments, the present disclosure provides stapled peptides that interact with beta-catenin. In some embodiments, provided stapled peptides interact with beta-catenin at an Axin-binding site of beta-catenin. In some embodiments, the present disclosure provides compounds, compositions and methods for preventing and/or treating conditions, disorders and diseases that are associated with beta-catenin.

Abstract: The disclosure features non-irritating pharmaceutical compositions containing CD101 in pharmaceutical acceptable salt (e.g., CD101 acetate) or neutral form. The pharmaceutical compositions can be intravenously administered to a subject to treat fungal infections (e.g., candidiasis) in the subject.

Abstract: The present invention provides a pharmaceutical formulation comprising LL-37 or a pharmaceutically-acceptable salt thereof and one or more pharmaceutically-acceptable diluent or carrier system, for use in a method of treatment of a chronic ulcer wound (such as a hard-to-heal venous leg ulcer or a diabetic foot ulcer), which method comprises: (a) topical application of the formulation to the ulcer; followed by (b) application of a dressing, and wherein the application of the formulation provides for a dose of LL-37 at the wound site that is below about 80 ?g of LL-37 applied per cm2 of wound area, and/or below about 26.7 ?g of LL-37 applied per cm2 of wound area, per day of treatment.

Abstract: This invention features new compositions and methods that are useful in treating a host with a Gram-negative bacterial infection. Combination therapies comprising an aminocoumarin compound and a polymyxin compound are disclosed, including certain combinations that exhibit synergistic effects. Furthermore, aminocoumarin compounds are described having altered inhibition of DNA gyrase in Gram-negative bacteria and/or the ability to target the transport proteins responsible for assembling lipopolysaccharide in the outer membrane of Gram-negative bacteria.

Abstract: The present disclosure pertains to compositions comprising aflibercept and methods for producing such compositions in chemically defined media and using chromatography to reduce amounts of certain aflibercept variants.

Abstract: In fibrotic lung fibroblasts, basal levels of p53 protein (and miR-34a) are markedly suppressed, leading to reduced p53-mediated inhibition of uPA and uPAR, or concurrent induction of PAI-1. These changes contribute to excessive FL-fibroblast proliferation and production of extracellular matrix (ECM), and, therefore, pulmonary fibrosis. These processes are reversed by treating the cells, and treating subjects suffering from idiopathic pulmonary fibrosis (IPF) with the small organic molecule nutlin-3a (NTL) or with a peptide, CSP-4 (SEQ ID NO:1), or variants or derivatives or multimers of this peptide, which increase p53 levels by inhibiting MDM2-mediated degradation of p53 protein. Use of these compounds serves as a new approach to the treatment of IPF, as they restore p53 expression and p53-mediated changes in the uPA-fibrinolytic system in FL-fibroblasts and restrict production and deposition of ECM.

Abstract: This invention is generally related to small proteins, such as miniature proteins, including avian pancreatic polypeptide (aPP), modified so that the small proteins reach the cytosol. In some embodiments, the modified protein molecules deliver an associated cargo molecule to the cytosol. Other embodiments of the invention relate to modified protein fusion molecules that reach the cytosol.

Abstract: The present invention relates to a CNP prodrug or a pharmaceutically acceptable salt thereof comprising a CNP moiety -D; and a carrier moiety —Z that is conjugated through a moiety -L2- to a reversible prodrug linker moiety -L1-, which reversible prodrug linker moiety -L1- is covalently and reversibly conjugated to -D; wherein -L2- is a chemical bond or a spacer; and —Z is a polymer having a molecular weight of at least 10 kDa. It further relates to pharmaceutical compositions comprising the CNP prodrug or a pharmaceutically acceptable salt thereof, their use as a medicament and to methods of treatment.

Abstract: In one aspect, the invention relates to compositions comprising stapled peptides, methods of making same, pharmaceutical compositions comprising same, and methods of treating various diseases, including, but not limited to, metabolic disorders such as diabetes, and cancers. The disclosed compounds comprise stapled peptides, including, but not limited to, stapled glucagon, axin, and p53 peptide homologues, which are useful as therapeutic agents for a variety of diseases as disclosed herein. The disclosed methods are useful in the preparation of a variety of stapled peptides, including stapled peptide homologues of glucagon, axin, and p53. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The present invention is directed to the following: methods of treating or preventing stent thrombosis using pharmaceutical compositions comprising cangrelor and optionally bivalirudin; methods of reducing mortality in a subject undergoing stent implantation using pharmaceutical compositions comprising cangrelor and optionally bivalirudin; medicaments comprising cangrelor and optionally bivalirudin useful for treating or preventing stent thrombosis, or useful for reducing mortality in a subject undergoing stent implantation; pharmaceutical compositions comprising cangrelor and bivalirudin; and methods of preparing a medicament comprising cangrelor and optionally bivalirudin useful for treating or preventing stent thrombosis, or useful for reducing mortality in a subject undergoing stent implantation.

Abstract: Described herein are nanopore protein conjugates that can be used in DNA sequencing reactions. The nanopore protein conjugates includes a nanopore protein monomer that is joined to a DNA binding domain. The nanopore protein monomer is available to oligomerize with other nanopore protein monomers, while the DNA binding domain is available to bind to a template DNA strand. In certain examples, the nanopore protein monomer is an alpha-hemolysin monomer or variant thereof and the DNA binding domain is an Sso7d protein or variant thereof, such as an Sso7d-like protein. Also provided are nanopore protein assemblies incorporating the nanopore protein conjugates, along with methods of using the nanopore protein assemblies in sequencing reactions.

Abstract: The present invention relates to a conjugate or a pharmaceutically acceptable salt thereof comprising an GLP-1/Glucagon receptor agonist, a linker and a hyaluronic acid hydrogel bearing -L1-L2-L-L-Y—R20 groups, wherein Y represents an GLP-1/Glucagon receptor agonist moiety; and -L is a linker moiety—by formula (Ia), wherein the dashed line indicates the attachment to one of the amino groups of the GLP-1/Glucagon receptor agonist moiety by forming an amide bond. The invention further relates to pharmaceutical compositions comprising the conjugate or the pharmaceutically acceptable salt thereof as well as their use as a medicament for treating or preventing diseases or disorders which can be treated by GLP-1/Glucagon receptor agonist.

Abstract: The invention provides processes of purifying a peptide including a GCC agonist sequence selected from the group consisting of SEQ ID NOs: 1-251 described herein. The processes include a solvent exchange step before a freeze-drying (lyophilization) step.

Abstract: Methods are provided for treatment of cancer cells, in a regimen comprising contacting the cancer cells with an inhibitor on NGly1, optionally in combination with a direct proteasome inhibitor.

Abstract: Synthetic methods are described herein operable to efficiently produce a wide variety of molecular species through conjugate additions via decarboxylative mechanisms. For example, methods of functionalization of peptide residues are described, including selective functionalization of peptide C-terminal residues. In one aspect, a method of peptide functionalization comprises providing a reaction mixture including a Michael acceptor and a peptide and coupling the Michael acceptor with the peptide via a mechanism including decarboxylation of a peptide reside.

Abstract: The disclosure provides apolipoprotein C-II (apoC-II) mimetic peptides and methods for treating hypertriglyceridemia in a patient with an effective amount of an apoC-II mimetic peptide.