The present invention is directed to a composition and method which to treat diseases and to enhance a regulated immune response. More particularly, the present invention is drawn to compositions that are based on dendritic cells modified to express an inducible form of a co-stimulatory polypeptide.

Emerging evidence indicates that diminished activity of the vasoprotective axis of the renin-angiotensin system, constituting angiotensin converting enzyme2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to pulmonary hypertension (PH). However, clinical success for long-term delivery of ACE2 or Ang-(1-7) would require stability and ease of administration to increase patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect from acids and gastric enzymes; fusion to a transmucosal carrier facilitates effective systemic absorption. Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) attenuated monocrotaline (MCT)-induced increase in right ventricular systolic pressure, decreased pulmonary vessel wall thickness and improved right heart function in both prevention and reversal protocols. Furthermore, combination of ACE2 and Ang-(1-7) augmented the beneficial effects against cardio-pulmonary pathophysiology induced by MCT administration.

Experiments have also been performed which indicate that this approach is also suitable for the treatment or inhibition of experimental uveitis and autoimmune uveoretinitis These studies provide proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary and ocular disease therapeutics.

The present invention relates to methods of cleaving the N-terminal amino acid from a polypeptide, which may be in free form or conjugated to a carrier or surface, such as a bead. It provides methods to activate the N-terminal amine of a polypeptide to promote formation of a cyclic adduct of the N-terminal amino acid, resulting in cleavage of the N-terminal amino acid from the polypeptide. The method can be used to sequence and/or analyze a polypeptide. For example, the methods can be combined with methods described herein for sequencing and/or analysis that employ barcoding and nucleic acid encoding of molecular recognition events, and/or detectable labels. The invention also provides compounds and kits useful for practicing these methods.

Provided herein are methods and compositions for treatment of Batten disease. Such compositions include a recombinant adeno-associated virus (rAAV), said rAAV comprising an AAV capsid, and a vector genome packaged therein, said vector genome comprising (a) an AAV 5′ inverted terminal repeat (ITR) sequence; (b) a promoter; (c) a CLN2 coding sequence encoding a human TPP1; (d) an AAV 3′ ITR. Also provided herein are methods of treating Batten disease comprising administering to a subject in need thereof the rAAV described herein via more than one route. Also provide herein are pharmaceutical compositions comprising the rAAV described herein and related methods of treating Batten disease.

The invention relates to a composition comprising at least one first aminopeptidase and at least one second aminopeptidase, the first aminopeptidase representing up to 40% by weight relative to the total weight of the composition.

Disclosed are protease inhibitors capable of inhibiting the protease activity of a S1 or a S8 protease at ambient pH, but where the inhibitor further has a pH dependent binding to the S1 or the S8 inhibitor meaning that a complex of a S1 and a S8 protease and the inhibitor dissociates when pH is lowered to a pH below 6.0, e.g. to a pH value in the range of 4.0 to 6.0; e.g. in the range of 4.5 to 6.0; e.g. in the range of 4.5 to 5.5; whereby the protease activity is released.

Disclosed are protease inhibitors capable of inhibiting the protease activity of a S1 or a S8 protease at ambient pH, but where the inhibitor further has a pH dependent binding to the S1 or the S8 inhibitor meaning that a complex of a S1 and a S8 protease and the inhibitor dissociates when pH is lowered to a pH below 6.0, e.g. to a pH value in the range of 4.0 to 6.0; e.g. in the range of 4.5 to 6.0; e.g. in the range of 4.5 to 5.5; whereby the protease activity is released.

Provided are compositions and methods for prophylaxis and/or therapy of ErbB2-positive cancer. The compositions include pharmaceutical preparations that contain isolated or recombinant or modified peptidase D (PEPD) proteins. The methods include prophylaxis and/or therapy of ErbB2-positive cancer by administering a PEPD to an individual who has or is at risk for developing ErbB2-positive cancer.

The present disclosure provides various insights relating to treatment of viral infection with soluble ACE2 variants, specifically including soluble human ACE2 (hACE2) variants. For example, the present disclosure teaches that decoy activity, which may intercept virus-receptor interactions, and ACE2 enzymatic activity can provide separate contributions to therapeutic efficacy; among other things, the present disclosure provides particular therapeutic regimens (e.g., relating to treatment of particular patient populations and/or to dosing regimens, combination therapies, etc.) for certain soluble ACE2 variants. Still further, the present disclosure provides certain particular ACE2 variants and methods of making and/or using them, including in accordance with particular therapeutic regimens.

The present disclosure provides various insights relating to treatment of viral infection with soluble ACE2 variants, specifically including soluble human ACE2 (hACE2) variants. For example, the present disclosure teaches that decoy activity, which may intercept virus-receptor interactions, and ACE2 enzymatic activity can provide separate contributions to therapeutic efficacy; among other things, the present disclosure provides particular therapeutic regimens (e.g., relating to treatment of particular patient populations and/or to dosing regimens, combination therapies, etc.) for certain soluble ACE2 variants. Still further, the present disclosure provides certain particular ACE2 variants and methods of making and/or using them, including in accordance with particular therapeutic regimens.