# US 2022/0031633 A1 · Poly(amine-co-ester) polymeric particles for selective pulmonary delivery

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- Number: US 2022/0031633 A1
- Document ID: US20220031633A1
- Status: Published application
- Kind: A1
- Application number: 17/332,175
- Filed: 2021-05-27
- Published: 2022-02-03
- Earliest claimed: 2020-07-28
- Assignees: Yale University
- Applicants: Yale University
- Inventors: W. Mark Saltzman; Daniel Greif; Aglaia Ntokou; Amy Kauffman
- Web page: https://patentgrep.com/patent/US20220031633A1

## CPC

- A61K 9/5146: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides}
- A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 9/007: {Pulmonary tract; Aromatherapy}
- A61K 35/15: Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00)
- A61K 45/00: Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- B82Y 30/00: Nanotechnology for materials or surface science, e.g. nanocomposites
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

Poly(amine-co-ester) polymers, methods of forming active agent-load polyplexes and particles therefrom, and methods of using them for delivery of nucleic acid agents with optimal uptake have been developed. Examples demonstrate critical molecular weights in combination with exposed carboxylic and/or hydroxyl groups, and methods of making. Typically, the compositions are less toxic, more efficient at drug delivery, or a combination thereof compared to a control other transfection reagents. In some embodiments, the compositions are suitable for in vivo delivery, and can be administered systemically to a subject to treat a disease or condition.

## Claims

### Claim 1

A delivery formulation for selective delivery to pulmonary immune cells such as macrophages and monocytes comprising nanoparticles between 100 and 500 nm average diameter, preferably between 200 and 400 nm, and comprising a polymer having the formula
wherein n is an integer from 1-30, m, o, and p are independently integers from 1-20, x, y, and q are independently integers from 1-1000, Rx is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, or substituted or unsubstituted alkoxy, Z and Z′ are independently O or NR′, wherein R′ is hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted aryl,
wherein R1 and R2 are chemical entities containing a hydroxyl group, a primary amine group, a secondary amine group, a tertiary amine group, or combinations thereof.

### Claim 2 (depends on 1)

The formulation of claim 1, wherein R1 and/or R2 are not

### Claim 3 (depends on 1)

The formulation of claim 1 wherein the polymer is in the form of polyplexes or particles thereof containing nucleic acid.

### Claim 4 (depends on 3)

The formulation of claim 3, wherein R1 and/or R2 consist of

### Claim 5 (depends on 1)

The formulation of claim 1, wherein the polymer has a structure of Formula II:
wherein J1 and J2 are independently linking moieties or absent,
R3 and R4 are substituted alkyl containing a hydroxyl group, a primary amine group, a secondary amine group, a tertiary amine group, or combinations thereof.

### Claim 6 (depends on 1)

The formulation of claim 1, wherein the polymer has a structure of Formula III:

### Claim 7 (depends on 1)

The formulation of claim 1 wherein the polymer has a weight average molecular weight, as measured by gel permeation chromatography using narrow polydispersity polystyrene standards, is between about 2,000 Daltons and 20,000 Daltons, preferably between about 2,000 Daltons and about 10,000 Daltons, most preferably between about 2000 Daltons and about 7,000 Daltons.

### Claim 8 (depends on 1)

The formulation of claim 1 wherein the nanoparticles comprise therapeutic, prophylactic or diagnostic agent.

### Claim 9 (depends on 8)

The formulation of claim 8 wherein the agent is for treatment, prevention or diagnosis of a pulmonary disorder or disease.

### Claim 10 (depends on 8)

The formulation of claim 8 wherein the agent is an inhibitor of PDGF-β.

### Claim 11 (depends on 8)

The formulation of claim 8 wherein the agent is a protein or peptide, sugar or carbohydrate, lipid, lipoprotein, or lipopolysaccharide, nucleic acid molecule, or small molecule having a molecular weight of less than 2000 Daltons.

### Claim 12 (depends on 8)

The formulation of claim 8 wherein the formulation is formulated for administration as an aerosol, for instillation, in a nebulizer, in an inhaler, in a ventilator or breathing mask, or as a dry powder.

### Claim 13 (depends on 8)

The formulation of claim 8 wherein the agent is in an amount for local delivery of the agent to the pulmonary system, not systemically.

### Claim 14 (depends on 8)

A method for treating an individual in need thereof comprising administering an effective amount of the formulation of claim 8.

### Claim 15 (depends on 13)

The method of claim 13 wherein an inhibitor of PDGF-β is administered to an individual with pulmonary hypertension.

### Claim 16 (depends on 14)

The method of claim 14 wherein the individual has congestive heart failure.

### Claim 17 (depends on 14)

The method of claim 14 wherein the individual has lung fibrosis.

### Claim 18 (depends on 14)

The method of claim 14 wherein the individual has lung cancer.

### Claim 19 (depends on 14)

The method of claim 14 wherein the individual has or is at risk of developing acute respiratory distress syndrome.

### Claim 20 (depends on 14)

The method of claim 14 wherein the individual has a viral disease such as COVID-19.