# US 11,897,928 B2 · Conjugates for delivering an anti-cancer agent to nerve cells, methods of use and methods of making thereof

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- Number: US 11,897,928 B2
- Document ID: US11897928B2
- Status: Granted
- Kind: B2
- Application number: 17/259,127
- Filed: 2019-07-17
- Published: 2021-05-20
- Granted: 2024-02-13
- Earliest claimed: 2018-07-18
- Assignees: Manzanita Pharmaceuticals, Inc.
- Applicants: Manzanita Pharmaceuticals, Inc.
- Inventors: Stephen B. Kahl; Constance A. McKee
- Web page: https://patentgrep.com/patent/US11897928B2

## CPC

- A61K 47/642: {the peptide or protein in the drug conjugate being a cytokine, e.g. IL2, chemokine, growth factors or interferons being the inactive part of the conjugate}
- C07K 14/48: Nerve growth factor [NGF]
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07D 211/60: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 225/04: condensed with carbocyclic rings or ring systems
- C07D 235/04: Benzimidazoles; Hydrogenated benzimidazoles
- C07D 235/08: Radicals containing only hydrogen and carbon atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 265/30: not condensed with other rings
- C07D 498/18: Bridged systems
- C07K 14/70575: {NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525)}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Conjugates for delivering an anti-cancer agent to nerve cells are provided. Conjugate compounds of the present disclosure according to certain embodiments include a compound having a protein, peptide or pepetidomimetic that binds selectively to a neurotrophin receptor, an anti-cancer agent and a linker that covalently bonds the anti-cancer agent to the protein, peptide or pepetidomimetic binds selectively to the neurotrophin receptor. Compositions and methods for delivering an anti-cancer agent selectively into nerve cells (e.g., in the treatment of optic pathway glioma) as well as indications such as perineural invasion and skin cancers are also described. Also provided are methods of making the anti-cancer conjugate compounds.

## Claims

### Claim 1

A compound of selected from the group consisting of:
a. a compound of Formula IA1:
b. a compound of Formula IA2:
c. a compound of Formula IB1:
d. a compound of Formula IB2:
e. a BDNF-selumetinib conjugate of Formula BDNF-SE:
f. an NGF-selumetinib conjugate of Formula NGF-SE:

### Claim 2 (depends on 1)

The compound according to claim 1, wherein the compound is of Formula IA1:

### Claim 3 (depends on 1)

The compound according to claim 1, wherein the compound is of Formula IA2:

### Claim 4 (depends on 1)

The compound according to claim 1, wherein the compound is of Formula IB1:

### Claim 5 (depends on 1)

The compound according to claim 1, wherein the compound is of Formula IB2:

### Claim 6 (depends on 1)

The compound according to claim 1, wherein the anti-cancer agent is a compound for the treatment of a glioma, a skin cancer or perineural invasion.

### Claim 7 (depends on 1)

A composition comprising:
a compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim 8 (depends on 1)

A method for delivering an anti-cancer agent selectively into nerve cells, the method comprising administering to a subject a compound of claim 1.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein the compound is the BDNF-selumetinib conjugate:

### Claim 10 (depends on 1)

The compound according to claim 1, wherein the compound is the NGF-selumetinib conjugate: