# US 11,298,423 B2 · Protection and delivery of multiple therapeutic proteins

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- Number: US 11,298,423 B2
- Document ID: US11298423B2
- Status: Granted
- Kind: B2
- Application number: 16/080,812
- Filed: 2017-03-03
- Published: 2019-04-25
- Granted: 2022-04-12
- Earliest claimed: 2016-03-04
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Eric M. Jeffries; Noah R. Johnson; Daniel Long; Yadong Wang
- Web page: https://patentgrep.com/patent/US11298423B2

## CPC

- A61K 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/06: Ointments; Bases therefor; {Other semi-solid forms, e.g. creams, sticks, gels (composition of ointments, creams or gels A61K47/00)}
- A61K 35/16: Blood plasma; Blood serum (umbilical cord blood A61K35/51)
- A61K 35/19: Platelets; Megacaryocytes
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/18: Growth factors; Growth regulators
- A61K 38/1825: {Fibroblast growth factor [FGF]}
- A61K 38/195: {Chemokines, e.g. RANTES}
- A61K 47/34: Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence)
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61L 15/225: {Mixtures of macromolecular compounds}
- A61L 15/40: containing ingredients of undetermined constitution or reaction products thereof {, e.g. plant or animal extracts}
- A61L 15/44: Medicaments
- A61L 27/18: obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
- A61L 27/20: Polysaccharides
- A61L 27/225: {Fibrin; Fibrinogen}
- A61L 27/26: Mixtures of macromolecular compounds
- A61L 27/3616: {Blood, e.g. platelet-rich plasma}
- A61L 27/52: Hydrogels or hydrocolloids
- A61L 27/54: Biologically active materials, e.g. therapeutic substances {(A61L27/227 takes precedence)}
- A61L 27/56: Porous materials, {e.g. foams or sponges}
- A61L 31/041: {Mixtures of macromolecular compounds}
- A61L 31/042: {Polysaccharides}
- A61L 31/046: {Fibrin; Fibrinogen}
- A61L 31/145: {Hydrogels or hydrocolloids}
- A61L 31/16: Biologically active materials, e.g. therapeutic substances {(A61L31/047 takes precedence)}
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61L 2300/25: Peptides having up to 20 amino acids in a defined sequence
- A61L 2300/252: Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
- A61L 2300/414: Growth factors
- A61L 2300/418: Agents promoting blood coagulation, blood-clotting agents, embolising agents
- A61L 2400/04: Materials for stopping bleeding
- A61L 2430/20: for reconstruction of the heart, e.g. heart valves
- 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)
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compositions are provided herein comprising a coacervate of a polycationic polymer, a polyanionic polymer, and platelet-rich plasma and/or serum, or a fraction or concentrate thereof. The composition is useful in wound healing. Compositions also are provided that comprise a hydrogel comprising TIMP-3; and a complex of a polycationic polymer, a polyanionic polymer, FGF-2 and SDF-1α embedded in the hydrogel, which is useful in treating a myocardial infarction.

## Claims

### Claim 1

A composition comprising a coacervate of:
a polycationic polymer,
a polyanionic polymer, and
a fraction or concentrate of platelet-rich plasma wherein platelets of platelet-rich plasma are activated to produce a fibrin clot, and wherein:
the fraction or concentrate of platelet-rich plasma comprises pure platelet-rich fibrin;
the fraction or concentrate of platelet-rich plasma comprises leukocyte-rich platelet-rich fibrin; or
the fibrin clot is removed and the protein content of the platelet-rich plasma is concentrated.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the fibrin clot is removed and the protein content of the platelet-rich plasma is concentrated.

### Claim 3 (depends on 1)

The composition of claim 1, further comprising a mixture of proteins or growth factors prepared from a bodily fluid of an organism, a cell or tissue lysate, or conditioned media in which cells or a tissue is grown.

### Claim 4 (depends on 1)

The composition of claim 1, further comprising a mixture of proteins or growth factors prepared from a bodily fluid of an organism, a cell or tissue lysate, or conditioned media in which cells or a tissue is grown, wherein the cells,
tissues, or organism is genetically-modified.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the polyanionic polymer is a sulfated or sulfamated polysaccharide.

### Claim 6 (depends on 1)

The composition of claim 1, wherein the ratio of the polycationic polymer to the polyanionic polymer in the composition results in a neutral charge in the coacervate.

### Claim 7 (depends on 1)

A method of treating a wound in a patient, comprising administering a composition according to claim 1 at or adjacent to a wound in the patient, in an amount effective to treat a wound in a patient.

### Claim 8

A method of preparing a therapeutic composition for use in treating a wound in a patient, comprising:
a. mixing a polyanionic polymer with a fraction or concentrate of platelet-rich plasma, wherein platelets of platelet-rich plasma are activated to produce a fibrin clot, and wherein:
the fraction or concentrate of platelet-rich plasma comprises pure platelet-rich fibrin;
the fraction or concentrate of platelet-rich plasma comprises leukocyte-rich platelet-rich fibrin; or
the fibrin clot is removed and the protein content of the platelet-rich plasma is concentrated; and
b. mixing a polycationic polymer with the mixture of the polyanionic polymer and the fraction or concentrate of platelet-rich plasma.

### Claim 9 (depends on 8)

The method of claim 8, wherein the polyanionic polymer is a sulfated or sulfamated polysaccharide.

### Claim 10 (depends on 8)

The method of claim 8, wherein the ratio of the polycationic polymer to the polyanionic polymer in the composition results in a neutral charge in the coacervate.

### Claim 11 (depends on 1)

A medical device or wound dressing comprising a composition according to claim 1.

### Claim 12 (depends on 1)

The composition of claim 1, wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant arginine groups.

### Claim 13 (depends on 8)

The method of claim 8, wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant arginine groups.

### Claim 14 (depends on 1)

The composition of claim 1, wherein the polycationic polymer is a copolymer comprising a polyester backbone comprising a copolymer of ethylene glycol diglyceride and either aspartic acid or glutamic acid, and pendant lysine groups.

### Claim 15 (depends on 1)

The composition of claim 1, wherein the polycationic polymer is poly(ethylene arginylaspartate diglyceride).

### Claim 16 (depends on 1)

The composition of claim 1, wherein the polycationic polymer is poly(ethylene lysinlyaspartate diglyceride).

### Claim 17 (depends on 11)

The medical device or wound dressing of claim 11, wherein the medical device or wound dressing is a bandage, suture, surgical mesh, limb or joint prosthesis, or a non-woven material.

### Claim 18 (depends on 1)

The composition of claim 1, wherein the fraction or concentrate of platelet-rich plasma is pure platelet-rich fibrin.

### Claim 19 (depends on 1)

The composition of claim 1, wherein the fraction or concentrate of platelet-rich plasma is leukocyte-rich platelet-rich fibrin.

### Claim 20 (depends on 1)

The composition of claim 1, wherein the polyanionic polymer is heparin or heparin sulfate.