# US 2016/0250352 A1 · Shielded biologic therapeutic

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- Number: US 2016/0250352 A1
- Document ID: US20160250352A1
- Status: Published application
- Kind: A1
- Application number: 15/031,182
- Filed: 2014-10-21
- Published: 2016-09-01
- Earliest claimed: 2013-10-22
- Assignees: Isis Innovation Limited
- Applicants: Isis Innovation Limited
- Inventors: STEVEN MO; ROBERT CRISPIN CARLISLE; LEONARD W. SEYMOUR; CONSTANTIN-CASSIOS COUSSIOS
- Web page: https://patentgrep.com/patent/US20160250352A1

## CPC

- A61K 41/0047: {Sonopheresis, i.e. ultrasonically-enhanced transdermal delivery, electroporation of a pharmacologically active agent}
- A61K 35/76: Viruses; Subviral particles; Bacteriophages
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 47/6923: {the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb}
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61K 49/221: {characterised by the targeting agent or modifying agent linked to the acoustically-active agent}
- A61P 35/00: Antineoplastic agents
- A61K 2039/525: {Virus}
- A61K 2039/60: {characteristics by the carrier linked to the antigen}
- A61K 2039/627: {characterised by the linker}
- A61K 2039/64: {characterised by the architecture of the carrier-antigen complex, e.g. repetition of carrier-antigen units}
- 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

## Abstract

The present invention provides a shielded biologic therapeutic comprising a biologic therapeutic which is covalently and cleavably bound to one or more nanoparticle, with a plurality of polymer chains bound to the or each nanoparticle.

## Claims

### Claim 1

A shielded biologic therapeutic comprising a biologic therapeutic which is covalently and cleavably bound to one or more nanoparticles, with a plurality of polymer chains bound to the or each nanoparticle.

### Claim 2 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the biologic therapeutic is covalently and cleavably bound to a plurality of nanoparticles, each nanoparticle having a plurality of polymer chains bound thereto.

### Claim 3 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the or each nanoparticle is from 1 to 100 nm in size, preferably from 1 to 10 nm in size.

### Claim 4 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the or each nanoparticle is a gold nanoparticle.

### Claim 5 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein at least 50% of the surface of the or each nanoparticle is modified by attachment to a polymer chain.

### Claim 6 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the polymer chains bound to the or each nanoparticle are PEG polymer chains.

### Claim 7 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the polymer chains bound to the or each nanoparticle comprise a plurality of polymer chains each having a molecular weight MW1 and one or more polymer chains having a molecular weight MW2, wherein MW2 is greater than MW1 and the number of polymer chains having molecular weight MW1 is greater than the number of chains having MW2.

### Claim 8 (depends on 7)

A shielded biologic therapeutic according to claim 7, wherein MW1 is from 1 to 3 kD and MW2 is from 4 to 6 kD.

### Claim 9 (depends on 7)

A shielded biologic therapeutic according to claim 7, wherein 95% to 99.5% of the polymer chains are of MW1 and 5% to 0.5% are of MW2.

### Claim 10 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the biologic therapeutic is covalently bound to the or each nanoparticle via a polymer chain, the or each polymer chain optionally comprising one or more cleavable moieties.

### Claim 11 (depends on 10)

A shielded biologic therapeutic according to claim 10, wherein the biologic therapeutic is covalently bound to the or each nanoparticle via a polymer chain, the or each polymer chain comprising one or more cleavable moieties, the cleavable moieties being cleavable under reducing conditions, oxidising conditions, basic conditions, acidic conditions, or conditions with raised endopeptidase levels

### Claim 12 (depends on 11)

A shielded biologic therapeutic according to claim 11, wherein the one or more cleavable moieties comprise N-succinimidyl-3-(2-pyridyldithio)propionate (SPDP).

### Claim 13 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the biologic therapeutic is a virus.

### Claim 14 (depends on 13)

A shielded biologic therapeutic according to claim 13, comprising 50 to 200 nanoparticles with a plurality of polymer chains bound thereto.

### Claim 15 (depends on 1)

A shielded biologic therapeutic according to claim 1, wherein the biologic therapeutic is an antibody.

### Claim 16 (depends on 15)

A shielded biologic therapeutic according to claim 15, comprising 1 to 5 nanoparticles with a plurality of polymer chains bound thereto.

### Claim at position 17

17-19. (canceled)

### Claim 20 (depends on 8)

A shielded biologic therapeutic according to claim 8, wherein 95% to 99.5% of the polymer chains are of MW1 and 5% to 0.5% are of MW2.

### Claim 21

A method of treatment or diagnosis of a human or animal subject in need thereof, which method comprises administering to said subject an effective amount of a shielded biologic therapeutic comprising a biologic therapeutic which is covalently and cleavably bound to one or more nanoparticles, with a plurality of polymer chains bound to the or each nanoparticle.

### Claim 22 (depends on 21)

A method according to claim 21, wherein the method further comprises exposing the subject to ultrasound induced cavitation.

### Claim 23 (depends on 21)

A method according to claim 21, wherein the method is for the diagnosis or treatment of tumor.
