# US 2025/0144153 A1 · Methods and compositions for treating dry eye, tear hyperosmolarity-induced pathological changes, and other ocular conditions

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- Number: US 2025/0144153 A1
- Document ID: US20250144153A1
- Status: Published application
- Kind: A1
- Application number: 18/770,542
- Filed: 2024-07-11
- Published: 2025-05-08
- Earliest claimed: 2023-07-13
- Assignees: MAM Holdings of West Florida, L.L.C.
- Applicants: MAM Holdings of West Florida, L.L.C.
- Inventors: Carl Randall Harrell
- Web page: https://patentgrep.com/patent/US20250144153A1

## CPC

- A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
- A61P 27/02: Ophthalmic agents
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 38/1709: {from mammals}
- A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 27/04: Artificial tears; Irrigation solutions
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure is directed to compositions, formulations, and methods for treating diseases of the eye and other disorders. Specifically, d-MAPPS compositions, which may include d-MAPPS solutions (e.g., in liquid form and/or administered as eye drops), in addition to macromolecular proteins, growth factors, mesenchymal stem cells (MSC), can be used for topical application to the eye and treatment of, for instance, tear hyperosmolarity (TH), dry eye, dry eye disease, dry eye discomfort, tear hyperosmolarity, and tear hyperosmolarity-induced pathological changes in the eyes of patients. The d-MAPPS solutions can contain mesenchymal stem cells (MSC), MSC-derived exosomes (MSC-Exos), one or more MSC-sourced growth factors, and/or immunoregulatory proteins. In some embodiments, the d-MAPPS solutions can include a sterile de-cellularized human amniotic fluid (D-HAF). In embodiments, the d-MAPPS solutions are amenable to long-term storage without the loss of biological potency.

## Claims

### Claim 1

A method of preventing and/or treating tear hyperosmolarity, the method comprising:
administering to the eye of a subject an effective amount of a topical solution, the topical solution comprising:
one or more types of mesenchymal stem cells (MSC), one or more types of MSC-derived exosomes, one or more MSC-sourced growth factors and/or immunoregulatory proteins, and/or sterile non-heated de-cellularized human amniotic fluid (D-HAF), thereby treating, alleviating, and/or preventing tear hyperosmolarity.

### Claim 2 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of activation of transient receptor potential vanilloid 1 (TRPV1) signaling pathway in one or more corneal epithelial cells of the subject.

### Claim 3 (depends on 2)

The method of claim 2, wherein the administering results in a reduction of activation of nuclear factor kappa B (NF-κB).

### Claim 4 (depends on 3)

The method of claim 3, wherein the administering results in a reduction of expression of one or more inflammatory cytokines, wherein the one or more inflammatory cytokines are selected from the group consisting of: interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ, IL-17, and combinations thereof.

### Claim 5 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of one or more selectins on one or more membranes of one or more endothelial cells in a subject, and wherein the one or more selectins are selected from the group consisting of: E selectins, P selectins, and combinations thereof.

### Claim 6 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of expression of one or more matrix metalloproteinases.

### Claim 7 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of release of one or more neuropeptides, wherein the one or more neuropeptides are selected from the group consisting of: substance P, calcitonin gene-related peptide (CGRP), and combinations thereof.

### Claim 8 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of unfolded protein response (UPR) activity in one or more eye cells of the subject.

### Claim 9 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of activity of DNA-damage-inducible transcript 3 protein (DDIT3).

### Claim 10 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of generation of one or more pro-inflammatory immune cells in the subject.

### Claim 11 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of one or more apoptotic pathways in one or more corneal epithelial cells of the subject.

### Claim 12 (depends on 1)

The method of claim 1, wherein the administering results in a reduction in neutrophil extracellular trap (NET) formation and/or NETosis.

### Claim 13 (depends on 1)

The method of claim 1, wherein the administering results in a reduction of stimulation of natural killer (NK) and natural killer T (NKT) cells.

### Claim 14 (depends on 1)

The method of claim 1, further comprising:
administering to the subject one or more additional agents in combination with the topical solution, wherein the one or more additional agents are selected from the group consisting of: an adjuvant, an antigen, an excipient, a vaccine, an allergen, an antibiotic, a gene therapy vector, a kinase inhibitor, a co-stimulatory molecule, a Toll-like receptor (TLR) agonist, a TLR antagonist, a therapeutic agent, a prophylactic agent, a diagnostic agent, an antimicrobial agent, an analgesic, a local anesthetic, an anti-inflammatory agent, an anti-oxidant agent, an immunosuppressant agent, an anti-allergenic agent, an enzyme cofactor, an essential nutrient, a growth factor, and combinations thereof.

### Claim 15 (depends on 1)

The method of claim 1, wherein the administering further comprises:
administering, with the topical solution, a pharmaceutically acceptable carrier.

### Claim 16 (depends on 1)

The method of claim 1, wherein the topical solution is administered prior to, in conjunction with, subsequent to, or alternating with, one or more therapeutic, prophylactic, and/or diagnostic agents.

### Claim 17 (depends on 16)

The method of claim 16, wherein the one or more therapeutic, prophylactic, and/or diagnostic agents is selected from the group consisting of: an anti-glaucoma agent, an anti-angiogenesis agent, an anti-infective agent, an anti-inflammatory agent, an analgesic agent, a local anesthetic, a growth factor, an immunosuppressive agent, an immunomodulatory agent, an anti-allergic agent, an anti-oxidant, a cytokine, and combinations thereof.

### Claim 18

A topical solution comprising:
one or more types of mesenchymal stem cells (MSC), one or more types of MSC-derived exosomes, one or more MSC-sourced growth factors and/or immunoregulatory proteins, and/or a sterile de-cellularized filtered human amniotic fluid (D-HAF); and
one or more pharmaceutically acceptable excipients,
wherein the topical solution is hypoosmotic relative to an osmolarity of an eye in a subject with tear hyperosmolarity.

### Claim 19 (depends on 18)

A kit comprising:
a container containing one or more single, sterile unit doses of the topical solution of claim 18.

### Claim 20 (depends on 19)

The kit of claim 19, wherein the one or more single, sterile unit doses is about 0.1 cubic centimeters (cc) to about 10.0 cc, and wherein the one or more single, sterile unit doses is in the form of a solution or equivalent in the form of a lyophilized powder.