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.

Disclosed are variants of ACE2, pharmaceutical compositions comprising the variants of ACE2, and treatment methods for reducing Angiotensin II (1-8) plasma levels and/or increasing Angiotensin (1-7) plasma levels in a subject in need thereof. The disclosed variants of ACE2 may include polypeptide fragments of ACE2 having ACE2 activity for converting AngII(1-8) to Ang(1-7). Suitable subjects suitable for the disclosed methods of treatment may include subjects having or at risk for developing diabetic and non-diabetic chronic kidney disease, acute renal failure and its prevention, chronic kidney disease, severe hypertension, scleroderma and its skin, pulmonary, kidney and hypertensive complications, malignant hypertension, renovascular hypertension secondary to renal artery stenosis, idiopathic pulmonary fibrosis, liver fibrosis such as in liver cirrhosis patients, an aortic aneurysm, cardiac fibrosis and remodeling, left ventricular hypertrophy, and an acute stroke.

Provided are compositions and methods for prophylaxis and/or therapy of ErbB1-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 ErbB1-positive cancer by administering a PEPD to an individual who has or is at risk for developing ErbB1-positive cancer.

A method for making an acellular human amnion-derived composition configured for therapeutic use is disclosed and generally includes the steps: obtaining amniotic membrane tissue; testing the amniotic membrane tissue for pathogens; washing the amniotic membrane tissue; manually removing blood-containing chorion tissue from the amniotic membrane tissue decellularizing the amniotic membrane tissue with xeno-free enzymes; collecting amniotic cells from the decellularized amniotic membrane tissue; seeding the amniotic cells for culture into xeno-free media formulated for mesenchymal stem cells; growing the amniotic cells to a specified confluency; collecting conditioned media; and freezing the collected conditioned media; wherein the method further includes irradiating the conditioned media.

The present invention relates to modified angiotensin converting enzyme 2 (ACE2) polypeptides and pharmaceutical and analytical uses thereof. In particular, the present invention relates to Zn.sup.2+ depleted-, Zn.sup.2+ free-, mixed metal- and metal ion substituted-ACE2 as well as methods for the manufacture of these variants and uses thereof, such as therapeutic and analytic uses of these ACE2 variants.

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.

This disclosure is directed to inhibitory oligonucleotides, inhibitory peptides, compositions and methods for preventing or treating Coronavirus disease 2019 (COVID-19). In one aspect, the disclosure is directed to compositions that comprise inhibitory oligonucleotides against one or more SARS-CoV-2 virus genes. In another aspect, the disclosure is directed to compositions that comprise inhibitory peptides that inhibit SARS-COV-2 entry into cells. Another aspect of the disclosure is directed to gene therapy methods for treating COVID-19, and vectors for carrying out the same. Finally, the disclosure provides nutritional supplements to support human immunity and prevent or inhibit viral infections.

It is disclosed a therapeutic composition for use in the treatment of COVID-19 and other cytokine storm associated disorders, wherein the therapeutic composition comprises at least one active agent being selected from the following active agent groups a) to e): a) complement factor 3-targeting inhibitor of complement activation cascade b) carboxypeptidase B enzyme c) complement factor 5a receptor-targeting inhibitor of complement activation cascade d) endothelin A receptor-targeting inhibitor of extravasation e) bone morphogenic protein.

It is further disclosed a method of treating COVID-19 and other cytokine storm associated disorders, wherein said method comprises administering an effective amount of at least one active agent being selected from the above mentioned active agent groups a) to e).

Disclosed herein are compositions and methods useful for treating diseases and conditions of the cornea in a subject in need thereof, comprising administering a therapeutically effective amount of an angiotensin converting enzyme 2 (ACE2) and/or variants of ACE2 to the subject. The disclosed variants of ACE2 may include fragments of ACE2 having ACE2 biological activity for converting AngII (1-8) to Ang (1-7).

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.