# US 2021/0275638 A1 · Polyhedrin-based slow release growth factor system for neuroprotection of retinal ganglion cell neurons

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- Number: US 2021/0275638 A1
- Document ID: US20210275638A1
- Status: Published application
- Kind: A1
- Application number: 17/192,328
- Filed: 2021-03-04
- Published: 2021-09-09
- Earliest claimed: 2020-03-04
- Assignees: The Schepens Eye Research Institute, Inc.; Cell Guidance Systems Limited
- Applicants: The Schepens Eye Research Institute, Inc.; Cell Guidance Systems Ltd
- Inventors: Julia Oswald Clifton; Christian Pernstich; Petr Baranov; Michael Jones
- Web page: https://patentgrep.com/patent/US20210275638A1

## CPC

- A61K 38/185: {Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3}
- A61P 27/06: Antiglaucoma agents or miotics
- 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

Described herein are polyhedrin-based slow release growth factor systems and methods of use thereof for neuroprotection of host and donor retinal ganglion cell neurons.

## Claims

### Claim 1

A method of treating an optic neuropathy associated with neurodegeneration in the eye and loss of retinal ganglion cells (RGCs), the method comprising administering to an affected eye of the subject a therapeutically effective amount of a composition comprising complexes of one or more growth factors attached to polyhedra comprising polyhedrin protein.

### Claim 2 (depends on 1)

The method of claim 1, wherein the growth factors comprise one, two, or all three of human Brain-derived neurotrophic factor (BDNF), Glial cell line-derived neurotrophic factor (GDNF), and/or Ciliary neurotrophic factor (CNTF).

### Claim 3 (depends on 1)

The method of claim 1, wherein the growth factors have an N-terminal tag that facilitates attachment to the polyhedrin.

### Claim 4 (depends on 3)

The method of claim 3, wherein the N terminal tag comprises an H1-tag that comprises an N-terminus H1 helix of a polyhedrin protein or a VP3 tag comprising a region of a capsid protein VP3 of cytoplasmic polyhedrosis virus.

### Claim 5 (depends on 3)

The method of claim 3, wherein the H1-tag comprises Met Ala Asp Val Ala Gly Thr Ser Asn Arg Asp Phe Arg Gly Arg Glu Gln Arg Asn Ser Glu Gln Tyr Asn Tyr Asn Ser Ser (SEQ ID NO:1).

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject has glaucoma, diabetic retinopathy/RGC loss in diabetes, Leber's hereditary optic neuropathy (LHON), toxic optic neuropathy, nonarteritic anterior ischaemic optic neuropathy (NAION), ischemic optic neuropathy, or retrograde degeneration associated with a pathology involving the Central Nervous System (CNS).

### Claim 7 (depends on 6)

The method of claim 6, wherein the subject has early-stage glaucoma, diabetic retinopathy/RGC loss in diabetes, LHON, toxic optic neuropathy, NAION, ischemic optic neuropathy, or retrograde degeneration associated with a pathology involving the CNS.

### Claim 8 (depends on 1)

The method of claim 1, wherein the subject retains at least 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the normal Retinal Nerve Fiber Layer (RNFL) thickness assessed by optical coherence tomography (OCT).

### Claim 9 (depends on 1)

The method of claim 1, wherein the subject has late stage glaucoma, diabetic retinopathy/RGC loss in diabetes, LHON, toxic optic neuropathy, NAION, ischemic optic neuropathy, or retrograde degeneration associated with a pathology involving the CNS.

### Claim 10 (depends on 1)

The method of claim 1, wherein the subject retains less than 10%, 20%, 30%, 40%, or 50%, of the normal Retinal Nerve Fiber Layer (RNFL) thickness assessed by optical coherence tomography (OCT).

### Claim 11 (depends on 10)

The method of claim 10, further comprising administering a population of donor RGCs to the subject.

### Claim 12 (depends on 11)

The method of claim 11, wherein the donor RGCs are derived from iPSC generated from cells from the subject or universal HLA-matched donor iPSC.

### Claim 13 (depends on 1)

The method of claim 1, wherein the composition is administered by intravitreal or subretinal injection.

### Claim 14 (depends on 6)

The method of claim 6, wherein the pathology of the CNS is Alzheimer's disease, Parkinson's disease, or demyelinating optic neuritis.

### Claim 15 (depends on 1)

The method of claim 1, wherein the subject is human.