# US 2010/0168024 A1 · Direct utilization of plasma proteins for the in vivo assembly of protein-drug/imaging agent conjugates, nanocarriers and coatings for biomaterials

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- Number: US 2010/0168024 A1
- Document ID: US20100168024A1
- Status: Published application
- Kind: A1
- Application number: 12/649,941
- Filed: 2009-12-30
- Published: 2010-07-01
- Earliest claimed: 2008-12-30
- Assignees: University of North Texas
- Inventors: Robby A. Petros
- Web page: https://patentgrep.com/patent/US20100168024A1

## CPC

- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- 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)

## Abstract

The present invention includes compositions and methods for making and using a drug conjugated to a peptide or protein that binds specifically to a ligand in vivo, wherein the conjugate binds to its ligand in vivo and increases the half-life of the drug.

## Claims

### Claim 1

A method for targeted drug delivery comprising:
identifying a patient in need of drug therapy;
attaching a drug to a molecular recognition element to form a drug-molecular recognition element conjugate that binds specifically to a target in vivo; and
treating the patient with the conjugate, wherein the conjugate binds its ligand in vivo and increases the half-life of the drug.

### Claim 2 (depends on 1)

The method of claim 1, wherein the ligand comprises a serum protein, a cell surface, a cancer, or a tissue.

### Claim 3 (depends on 1)

The method of claim 1, wherein the drug and the molecular recognition element are conjugated by a biodegradable linker.

### Claim 4 (depends on 1)

The method of claim 1, wherein the drug and the molecular recognition element are conjugated by a cleavable linker.

### Claim 5 (depends on 1)

The method of claim 1, wherein the drug and the molecular recognition element are conjugated by a stimuli-responsive cleavable linker.

### Claim 6 (depends on 1)

The method of claim 1, wherein the molecular recognition element binds to its ligand in vivo with an affinity greater than 100 nM.

### Claim 7 (depends on 1)

The method of claim 1, wherein the molecular recognition element is multimeric and generates plasma protein-based nanoparticles in vivo.

### Claim 8 (depends on 1)

The method of claim 1, wherein the molecular recognition element directs assembly of a protective protein coat to the surface of nanoparticles in vivo.

### Claim 9 (depends on 1)

The method of claim 1, wherein the molecular recognition element binds a biomaterial surface and directs protein opsonization to the biomaterials surface.

### Claim 10

A composition comprising a drug conjugated to a molecular recognition element that binds specifically to a ligand in vivo, wherein the conjugate binds to its ligand in vivo and increases the half-life of the drug.

### Claim 11 (depends on 10)

The composition of claim 10, wherein the ligand comprises a serum protein, a cell surface, a cancer, or a tissue.

### Claim 12 (depends on 10)

The composition of claim 10, wherein the drug and the binding peptide or protein are conjugated by a biodegradable linker.

### Claim 13 (depends on 10)

The composition of claim 10, wherein the drug and the binding peptide or protein are conjugated by a cleavable linker.

### Claim 14 (depends on 10)

The composition of claim 10, wherein the drug and the binding peptide or protein are conjugated by a stimuli-responsive cleavable linker.

### Claim 15 (depends on 10)

The composition of claim 10, wherein the binding peptide or protein binds to its ligand with an affinity greater than 100 nM.

### Claim 16 (depends on 10)

The composition of claim 10, wherein the binding peptide or protein is multimeric and generates plasma protein-based nanoparticles in vivo.

### Claim 17 (depends on 10)

The composition of claim 10, wherein the binding peptide or protein directs assembly of a protective protein coat to the surface of nanoparticles in vivo.

### Claim 18 (depends on 10)

The composition of claim 10, wherein the binding peptide or protein binds a biomaterial surface and directs protein opsonization to the biomaterials surface.

### Claim 19

A composition comprising a drug conjugated to a peptide or protein that binds specifically to a ligand in vivo, wherein the conjugate binds to its ligand in vivo and increases the half-life of the drug.

### Claim 20 (depends on 19)

The composition of claim 19, wherein the ligand comprises a serum protein, a cell surface, a cancer, or a tissue.

### Claim 21 (depends on 19)

The composition of claim 19, wherein the drug and the binding peptide or protein are conjugated by a biodegradable linker.

### Claim 22 (depends on 19)

The composition of claim 19, wherein the drug and the binding peptide or protein are conjugated by a cleavable linker.

### Claim 23 (depends on 19)

The composition of claim 19, wherein the drug and the binding peptide or protein are conjugated by a stimuli-responsive cleavable linker.

### Claim 24 (depends on 19)

The composition of claim 19, wherein the binding peptide or protein binds to its ligand with an affinity greater than 100 nM.

### Claim 25 (depends on 19)

The composition of claim 19, wherein the binding peptide or protein is multimeric and generates plasma protein-based nanoparticles in vivo.

### Claim 26 (depends on 19)

The composition of claim 19, wherein the binding peptide or protein directs assembly of a protective protein coat to the surface of nanoparticles in vivo.

### Claim 27 (depends on 19)

The composition of claim 19, wherein the binding peptide or protein binds a biomaterial surface and directs protein opsonization to the biomaterials surface.

### Claim 28

A method for targeted drug delivery comprising:
identifying a patient in need of drug therapy;
attaching a drug to a peptide or protein to form a drug-ligand binding peptide or protein conjugate that binds specifically to a ligand in vivo,
treating the patient with the conjugate, wherein the conjugate binds its ligand in vivo and increases the half-life of the drug.

### Claim 29 (depends on 28)

The method of claim 28, wherein the ligand comprises a serum protein, a cell surface, a cancer, or a tissue.

### Claim 30 (depends on 28)

The method of claim 28, wherein the drug and the binding peptide or protein are conjugated by a biodegradable linker.

### Claim 31 (depends on 28)

The method of claim 28, wherein the drug and the binding peptide or protein are conjugated by a cleavable linker.

### Claim 32 (depends on 28)

The method of claim 28, wherein the drug and the binding peptide or protein are conjugated by a stimuli-responsive cleavable linker.

### Claim 33 (depends on 28)

The method of claim 28, wherein the binding peptide or protein binds to its ligand in vivo with an affinity greater than 100 nM.

### Claim 34 (depends on 28)

The method of claim 28, wherein the binding peptide or protein is multimeric and generates plasma protein-based nanoparticles in vivo.

### Claim 35 (depends on 28)

The method of claim 28, wherein the binding peptide or protein directs assembly of a protective protein coat to the surface of nanoparticles in vivo.

### Claim 36 (depends on 28)

The method of claim 28, wherein the binding peptide or protein binds a biomaterial surface and directs protein opsonization to the biomaterials surface.

### Claim 37

A method of making the composition for targeting a ligand for delivery of a drug in vivo comprising: identifying a ligand, isolating a ligand-specific molecular recognition element specific for the ligand, wherein the molecular recognition element is capable of binding to the ligand in vivo, and attaching a drug to the molecular recognition element.

### Claim 38

A composition made by the method comprising: selecting a ligand for targeting the delivery of a drug in vivo comprising identifying a ligand, isolating a ligand-specific molecular recognition element specific for the ligand, wherein the molecular recognition element is capable of binding to the ligand in vivo, and attaching a drug to the molecular recognition element.