# US 2021/0330712 A1 · Use of anti-aging glycoprotein for enhancing survival of neurosensory precursor cells

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- Number: US 2021/0330712 A1
- Document ID: US20210330712A1
- Status: Published application
- Kind: A1
- Application number: 17/369,075
- Filed: 2021-07-07
- Published: 2021-10-28
- Earliest claimed: 2016-01-27
- Assignees: Protokinetix Inc.
- Applicants: Protokinetix Inc.
- Inventors: Lachlan Grant Young
- Web page: https://patentgrep.com/patent/US20210330712A1

## CPC

- A61K 35/30: Nerves; Brain; Eyes; Corneal cells; Cerebrospinal fluid; Neuronal stem cells; Neuronal precursor cells; Glial cells; Oligodendrocytes; Schwann cells; Astroglia; Astrocytes; Choroid plexus; Spinal cord tissue
- A61K 31/16: Amides, e.g. hydroxamic acids
- A61K 31/164: of a carboxylic acid with an aminoalcohol, e.g. ceramides
- A61K 31/335: having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K 38/14: Peptides containing saccharide radicals; Derivatives thereof {, e.g. bleomycin, phleomycin, muramylpeptides or vancomycin}
- A61P 27/00: Drugs for disorders of the senses
- C07K 5/08: Tripeptides
- C07K 5/0827: {containing heteroatoms different from O, S, or N}
- C07K 9/001: {the peptide sequence having less than 12 amino acids and not being part of a ring structure}
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K 5/1027: {containing heteroatoms different from O, S, or N}
- 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
- 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)

## Abstract

The present disclosure relates to an in vitro method for enhancing engraftment of neurosensory precursor cell comprising the step of contacting an isolated neurosensory precursor cell prior to a transplantation in a subject in need thereof, with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate thereof:

## Claims

### Claim 1

A method for protecting isolated neurosensory precursor cells from prostaglandin E2 toxicity comprising the step of:
a) contacting an isolated neurosensory precursor cell with a gem-difluorinated C-glycopeptide compound of general formula I, or a pharmaceutically acceptable base, addition salt with an acid, hydrate or solvate thereof, and then washing the isolated neurosensory cells to remove the compound:
in which:
N is an integer between 1 and 5,
R4═H, AA1, or AA1-AA2,
R5═OH, AA1, or AA1-AA2,
AA1 and AA2 independently represent amino acids with a non-polar side chain and
R1, R2, R3 are independent groups in which two of R1, R2 and R3 are selected from H, CH3, CH2Ph, CH(CH3)2, CH2CH(CH3)2 or CH(CH3)CH2CH3 and the remaining R1, R2, R3 is
in which:
n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′═H, OR, N3, NR′R″, or SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl or acetate group,
R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl or C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is H, CH3, CH2OH, CH2-glycoside group or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′ or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R8 is a hydrogen atom H or a free or protected alcohol function, and
if R1═R2═H, CH3, CH2Ph, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3
then
in which: n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′═H, OR, N3, NR′R″, or SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is H, CH3, CH2OH, CH2-glycoside group, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R8 is a hydrogen atom H or a free or protected alcohol function,
if R1═R3═H, CH3, CH2Ph, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3
then
in which: n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′═H, OR, N3, NR′R″, or SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is H, CH3, CH2OH, CH2-glycoside group, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R8 is a hydrogen atom H or a free or protected alcohol function,
if R2═R3═H, CH3, CH(CH3)2, CH2CH(CH3)2, or CH(CH3)CH2CH3
then
in which: n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′H, OR, N3, NR′R″, or SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is H, CH3, CH2OH, CH2-glycoside group, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tertbutyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R8 is a hydrogen atom H or a free or protected alcohol function
b) transplanting the treated isolated neurosensory precursor cells of step a) in a subject in need thereof,
wherein said compound protects said isolated neurosensory precursor cell from prostaglandin E2 toxicity and wherein the method comprises no step where said isolated neurosensory precursor cells are cryopreserved.

### Claim 2 (depends on 1)

The method of claim 1, wherein the compound of formula I is a compound of formula II:
in which: N is an integer between 1 and 5, and
R1, R2, R3 are independent groups in which two of R1, R2 and R3 are selected from H, CH3 and the remaining R1, R2 and R3 is
in which: n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′═H, OR, N3, NR′R″ or SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is selected from H, CH3, CH2OH, CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′, NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl or acetate group,
R8 is a hydrogen atom H or a free or protected alcohol function, and
if R1═R2═H or CH3,
then
in which: n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′═H, OR, N3, NR′R″, or SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group,
C(═O)-alkyl, or
C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is selected from H, CH3, CH2OH, CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′, NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R8 is a hydrogen atom H or a free or protected alcohol function,
if R1═R3═H or CH3,
then
in which: n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′═H, OR, N3, NR′R″, SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R′, R″ independently=H, alkyl, allyl,
Bn, tosylate, C(═O)-alkyl, or C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is selected from H, CH3, CH2OH, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R8 is a hydrogen atom H or a free or protected alcohol function,
if R2═R3═H or CH3,
then
in which: n is an integer between 3 and 4,
Y, Y′ are independent groups
in which Y, Y′H, OR, N3, NR′R″, or SR′″,
where R═H, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R′, R″ independently=H, alkyl, allyl, benzyl, tosylate group, C(═O)-alkyl, or C(═O)-Bn,
R′″═H, alkyl, or acetate group,
R6 is selected from H, CH3, CH2OH, or CH2—OGP in which GP is a protector group selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R7═OH, OGP′, NH2, N3, NHGP′, or NGP′GP″ in which GP′ and GP″ are independently selected from alkyl, benzyl, trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, or acetate group,
R8 is a hydrogen atom or a free or protected alcohol function.

### Claim 3 (depends on 1)

The method of claim 1, wherein said compound of formula I is a compound of formula III:

### Claim 4 (depends on 1)

The method of claim 1, wherein the isolated neurosensory precursor cell is contacted with the compound for at least 1 hour.

### Claim 5 (depends on 1)

The method of claim 1, wherein concentration of the compound is from about 1 mg/ml to about 5 mg/ml.

### Claim 6 (depends on 5)

The method of claim 5, wherein concentration of said compound is from about 1 mg/ml to about 3 mg/ml, or from about 3 mg/ml to about 5 mg/ml.

### Claim 7 (depends on 1)

The method of claim 1, wherein said neurosensory precursor cell is a photoreceptor precursor cell.

### Claim 8 (depends on 1)

An isolated neurosensory precursor cell prepared according to the method of any one of claim 1.

### Claim 9 (depends on 1)

The method of claim 1, wherein said subject is receiving an immunosuppressant drug.

### Claim 10 (depends on 9)

The method of claim 9, wherein the immunosuppressant drug is daclizumab, sirolimus, tacrolimus, cyclosporine, or a combination thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein said subject is a human subject.

### Claim 12 (depends on 1)

The method of claim 1, wherein said method is for treating a retinal degenerative disease.

### Claim 13 (depends on 12)

The method of claim 12, where said retinal degenerative disease is age-related macular degeneration (AMD), retinitis pigmentosa (RP), retinal vasculitis, or sarcoidosis.