# US 10,307,487 B2 · Microvessel endothelial cell surface markers and uses thereof

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- Number: US 10,307,487 B2
- Document ID: US10307487B2
- Status: Granted
- Kind: B2
- Application number: 14/903,964
- Filed: 2014-07-09
- Published: 2016-11-24
- Granted: 2019-06-04
- Earliest claimed: 2013-07-09
- Assignees: President and Fellows of Harvard College; The Brigham and Women's Hospital, Inc.
- Applicants: President and Fellows of Harvard College; The Brigham and Women's Hospital Inc.
- Inventors: Ulrich H. von Andrian; Aude Thiriot; Omid Farokhzad; Jinjun Shi
- Web page: https://patentgrep.com/patent/US10307487B2

## CPC

- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 31/00: Medicinal preparations containing organic active ingredients
- A61K 49/00: Preparations for testing in vivo
- A61K 49/0058: {Antibodies}
- G01N 33/5064: {Endothelial cells}
- G01N 2333/705: Assays involving receptors, cell surface antigens or cell surface determinants
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Disclosed herein are microvessel endothelial cell surface markers and methods, compositions, agents, and kits relating to those surface markers.

## Claims

### Claim 1

A method of delivering a targeting agent to a microvessel endothelial cell in adipose tissue or skin in a subject, comprising administering to the subject a microvessel endothelial cell targeting agent which binds to a protein encoded by Il6st expressed on the surface of a microvessel endothelial cell in adipose tissue or skin, wherein the microvessel endothelial cell targeting agent is delivered specifically to a microvessel endothelial cell in adipose tissue or skin expressing the protein encoded by Il6st, and causes an effect in the microvessel endothelial cell, or a microvessel, tissue or organ adjacent to the microvessel endothelial cell.

### Claim 2 (depends on 1)

A method according to claim 1, wherein the microvessel endothelial cell targeting agent is internalized into or transported across the endothelial cells lining the microvessel.

### Claim 3 (depends on 1)

A method according to claim 1, wherein the microvessel endothelial cell targeting agent is selected from the group consisting of antibodies; small organic or inorganic molecules; saccharides; oligosaccharides; polysaccharides; a biological macromolecule selected from the group consisting of peptides, proteins, peptide analogs and derivatives; peptidomimetics; nucleic acids selected from the group consisting of siRNAs, shRNAs, antisense RNAs, ribozymes, dendrimers and aptamers; an extract made from biological materials selected from the group consisting of bacteria, plants, fungi, animal cells, and animal tissues; naturally occurring or synthetic compositions; and any combination thereof.

### Claim 4 (depends on 1)

A method according to claim 1, wherein the microvessel endothelial cell targeting agent is selected from a therapeutic agent, an anti-inflammatory agent, a diagnostic agent, an imaging agent, a multi-purpose agent, and combinations thereof.

### Claim 5 (depends on 1)

A method according to claim 1, wherein delivering a targeting agent to microvessel endothelial cells in adipose tissue or skin of the subject treats, prevents, or ameliorates a symptom of, a disease of adipose tissue or skin in the subject.

### Claim 6 (depends on 5)

A method according to claim 5, wherein the disease is an inflammatory disease of adipose tissue or skin.

### Claim 7 (depends on 6)

A method according to claim 6, wherein the inflammatory disease is selected from the group consisting of cancer, obesity-related insulin resistance, diabetes, polycystic ovary syndrome, metabolic syndrome, hypertension, cerebrovascular accident, myocardial infarction, congestive heart failure, cholecystitis, gout, osteoarthritis, Pickwickian syndrome, ischaemic heart disease, peptic, gastric, and duodenal ulcers, CVHD, fibrosis, lipodystrophy, herpes infection, candidiasis, burns, dermatitis, dermatomyositis, sunburn, urticaria, warts, wheals, acne, eczema, oily skin, rosacea, cutaneous lymphoma, and Behcets's syndrome.

### Claim 8 (depends on 5)

A method according to claim 5, wherein the disease is a disease of the microvasculature of adipose tissue or skin selected from the group consisting of a venular disorder and a non-venular disorder.

### Claim 9

A method of treating a microvessel endothelial cell-associated disorder of adipose tissue or skin in a subject in need thereof, comprising administering to the subject an effective amount of a microvessel endothelial cell targeting agent which binds to a protein encoded by Il6st expressed on the surface of a microvessel endothelial cell in adipose tissue and skin, wherein the microvessel endothelial cell targeting agent is delivered specifically to a microvessel endothelial cell in adipose tissue and skin expressing the protein encoded by Il6st; and the microvessel endothelial cell targeting agent is a therapeutic agent for treating the microvessel endothelial cell-associated disorder.

### Claim 10 (depends on 9)

A method according to claim 9, wherein the microvessel endothelial cell targeting agent is internalized into or transported across the endothelial cells lining the microvessel.

### Claim 11 (depends on 9)

A method according to claim 9, wherein the microvessel endothelial cell-associated disorder of adipose tissue or skin is selected from the group consisting of a venular disorder and a non-venular disorder.

### Claim 12

A method of delivering a targeting agent to a microvessel endothelial cell in adipose tissue or skin, comprising administering a microvessel endothelial cell targeting agent which binds to a protein encoded by Il6st expressed on the surface of a microvessel endothelial cell in adipose tissue or skin, wherein the microvessel endothelial cell targeting agent is delivered specifically to a microvessel endothelial cell in adipose tissue or skin expressing the protein encoded by Il6st and causes an effect in the microvessel endothelial cell, or a microvessel, tissue or organ adjacent to the microvessel endothelial cell.
