# US 9,750,709 B2 · Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists, and formulations thereof

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- Number: US 9,750,709 B2
- Document ID: US9750709B2
- Status: Granted
- Kind: B2
- Application number: 14/185,010
- Filed: 2014-02-20
- Published: 2014-10-23
- Granted: 2017-09-05
- Earliest claimed: 2003-09-15
- Assignees: Nanopharmaceuticals LLC
- Applicants: NanoPharmaceuticals LLC
- Inventors: Shaker A. Mousa; Faith B. Davis; Paul J. Davis
- Web page: https://patentgrep.com/patent/US9750709B2

## CPC

- A61K 31/198: Alpha-amino acids, e.g. alanine or edetic acid [EDTA] (betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00)
- A61K 9/0048: {Eye, e.g. artificial tears}
- A61K 9/5153: {Polyesters, e.g. poly(lactide-co-glycolide)}
- A61K 31/192: having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid {(cannabinoids A61K31/658)}
- A61K 31/195: having an amino group
- A61K 31/4365: the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
- A61K 31/60: Salicylic acid; Derivatives thereof
- A61K 31/65: Tetracyclines
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61K 31/727: Heparin; Heparan
- A61K 39/44: Antibodies bound to carriers
- A61K 47/58: obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61K 47/593: {Polyesters, e.g. PLGA or polylactide-co-glycolide}
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof
- 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 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K 47/6801: {Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent}
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61K 47/6937: {the polymer being PLGA, PLA or polyglycolic acid}
- A61K 47/6939: {the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin}
- A61K 49/0008: {Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure}
- A61K 49/085: {conjugated systems}
- A61K 49/10: Organic compounds
- A61K 49/12: Macromolecular compounds
- A61K 51/0402: {carboxylic acid carriers, fatty acids (amino acids A61K51/0406)}
- A61K 51/0497: {conjugates with a carrier being an organic compounds}
- A61K 51/065: {conjugates with carriers being macromolecules}
- C07K 16/2848: {against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- Y10T 428/2982: Particulate matter [e.g., sphere, flake, etc.]
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- Y10T: TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION

## Abstract

Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric Nanoparticle form of thyroid hormone agonist, partial agonist or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.

## Claims

### Claim 1

An imaging compound comprising:
a thyroid hormone analog, wherein the thyroid hormone analog is covalently bonded to a linker selected from the group consisting of diaminopropane, ether, sulfhydryl, ester and anhydride linkages, and the linker is covalently bonded to a radio-labelled tracer selected from the group consisting of iodine-123 (123I), iodine-124 (124I), iodine-125 (125I), iodine-131 (131I), fluorine-18 (18F), technetium-99m (99mTc), indium-111 (111In), carbon-11 (11C) and astatine-210 (210At), wherein the imaging compound is a nanoparticle.

### Claim 2 (depends on 1)

The imaging compound of claim 1, wherein the thyroid hormone analog is tetrac, triac or a combination thereof.

### Claim 3 (depends on 1)

The imaging compound of claim 1, wherein the nanoparticle has a diameter between 1 nm and less than 1000 nm.

### Claim 4 (depends on 1)

The imaging compound of claim 1, wherein the thyroid hormone analog is covalently bonded to a diaminopropane linker and the diamino propane linker is covalently bonded to indium-111.

### Claim 5 (depends on 1)

A method for imaging tumor tissues and neovascularization using the imaging compound of claim 1 comprising the steps of:
administering the imaging compound of claim 1 to a patient, wherein the imaging compound binds to a plurality of αvβ3 integrin receptors;
generating an image representing a distribution of the imaging agent binding to the αvβ3 integrin receptors.

### Claim 6 (depends on 5)

The method of claim 5, wherein the step of generating the image is performed by an imaging technique selected from the group consisting of positron emission topography (PET) and single photon emission (SPECT).

### Claim 7 (depends on 1, 5)

The method of claim 5, wherein the imaging compound of claim 1 includes a thyroid hormone analog selected from the group consisting of tetrac, triac or a combination thereof.

### Claim 8 (depends on 1)

A method for diagnosing a degenerative disease comprising the steps of:
administering the imaging compound of claim 1 to a patient, wherein the imaging compound binds to a plurality of transthyretin; and
generating an image representing a distribution of the imaging compound binding to the plurality of the transthyretin.

### Claim 9 (depends on 1, 8)

The method of claim 8, wherein the thyroid hormone analog of the imaging compound of claim 1 is triac or tetrac covalently bound to a the diaminopropane linker.

### Claim 10 (depends on 8)

The method of claim 8, wherein the neurodegenerative disease is Alzheimer's disease.

### Claim 11 (depends on 1, 8)

The method of claim 8, further comprising the step of inhibiting the formation of amyloid fibrils with the imaging compound of claim 1.

### Claim 12 (depends on 8)

The method of claim 8, wherein the step of generating the image is performed by positron emission topography (PET) or single photon emission (SPECT).

### Claim 13 (depends on 8)

The imaging method of claim 8, wherein the image representing a distribution of the imaging compound is at least one portion of the brain.