# US 12,760,113 B2 · Anti-transferrin receptor antibodies and uses thereof

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- Number: US 12,760,113 B2
- Document ID: US12760113B2
- Status: Granted
- Kind: B2
- Application number: 18/489,583
- Filed: 2023-10-18
- Published: 2024-04-25
- Granted: 2026-10-13
- Earliest claimed: 2018-12-21
- Assignees: Atrium Therapeutics, Inc.
- Applicants: Atrium Therapeutics, Inc.
- Inventors: Beatrice Diana Darimont; Venkata Ramana Doppalapudi; Rachel Johns
- Web page: https://patentgrep.com/patent/US12760113B2

## CPC

- C07K 16/2881: {against CD71}
- A61K 47/6811: {the drug being a protein or peptide, e.g. transferrin or bleomycin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/51: Complete heavy chain or Fd fragment, i.e. VH + CH1
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- 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)
- 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)

## Abstract

Disclosed herein, in certain embodiments, are anti-transferrin receptor antibodies, anti-transferrin receptor antibody conjugates, and pharmaceutical compositions which comprise the anti-transferrin receptor antibodies or conjugates. In some embodiments, also disclosed herein are methods of delivering a payload utilizing an anti-transferrin receptor antibody described herein, and methods of treatment with use of an anti-transferrin receptor antibody described herein.

## Claims

### Claim 1

A method of treating muscular dystrophy in a subject in need thereof, comprising:
administering to the subject an anti-transferrin receptor antibody conjugate comprising i) anti-transferrin receptor antibody comprising a variable heavy chain (VH) region and a variable light chain (VL) region, wherein the VH region comprises HCDR1 sequence comprising SEQ ID NO: 1; HCDR2 sequence EINPIX1GRSNYAX2KFQG (SEQ ID NO: 88), wherein X1 is selected from N or Q and X2 is selected from Q or E; and HCDR3 sequence comprising SEQ ID NO: 3, wherein the VL region comprises LCDR1 sequence RTSENIYX3NLA (SEQ ID NO: 89), LCDR2 sequence AX4TNLAX5 (SEQ ID NO: 90), and LCDR3 sequence QHFWGTPLTX6 (SEQ ID NO: 91), wherein X3 is selected from N or S, X4 is selected from A or G, X5 is selected from D or E, and X6 is present or absent, and if present, is F, and ii) a payload, wherein the payload hybridizes to a target region of an mRNA that causes muscular dystrophy, thereby treating muscular dystrophy in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the payload comprises a small molecule, a peptide, a protein, or a polynucleic acid molecule.

### Claim 3 (depends on 2)

The method of claim 2, wherein the polynucleic acid molecule is a single stranded polynucleotide.

### Claim 4 (depends on 3)

The method of claim 3, wherein the single stranded polynucleotide is a phosphorodiamidate morpholino oligonucleotide (PMO).

### Claim 5 (depends on 1)

The method of claim 1, wherein the muscular dystrophy is Duchenne Muscular Dystrophy (DMD), Becker muscular dystrophy, facioscapulohumeral muscular dystrophy (FSHD), or congenital muscular dystrophy.

### Claim 6 (depends on 1)

The method of claim 1, wherein the muscular dystrophy is Duchenne Muscular Dystrophy (DMD).

### Claim 7 (depends on 1)

The method of claim 1, wherein reticulocyte levels in the subject are not reduced following the administration of the anti-transferrin receptor antibody.

### Claim 8 (depends on 1)

The method of claim 1, wherein the administration of the anti-transferrin receptor antibody conjugate delivers the payload to the target region of the mRNA.

### Claim 9 (depends on 6)

The method of claim 6, wherein the payload is a polynucleic acid molecule that hybridizes to a target region of an mRNA of the DMD gene.

### Claim 10 (depends on 9)

The method of claim 9, wherein the target region of the mRNA has an incorrectly spliced mRNA transcript.

### Claim 11 (depends on 10)

The method of claim 10, wherein the polynucleic acid molecule induces exon skipping or exon inclusion of the incorrectly spliced mRNA transcript in the subject.

### Claim 12 (depends on 11)

The method of claim 11, wherein the exon skipping or exon inclusion is in muscle.

### Claim 13 (depends on 12)

The method of claim 12, wherein the muscle is skeletal muscle.

### Claim 14 (depends on 12)

The method of claim 12, wherein the muscle is cardiac muscle.

### Claim 15 (depends on 9)

The method of claim 9, wherein the target region of the mRNA has at least one mutated exon in the DMD gene.

### Claim 16 (depends on 15)

The method of claim 15, wherein the at least one mutated exon of the DMD gene is an exon selected from the group consisting of exon 3, 4, 5, 6, 7, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, and 63.

### Claim 17 (depends on 15)

The method of claim 15, wherein the at least one mutated exon of the DMD gene is an exon selected from the group consisting of exon 8, 23, 35, 43, 44, 45, 50, 51, 52, 53, and 55.

### Claim 18 (depends on 15)

The method of claim 15, wherein the at least one mutated exon of the DMD gene is an exon selected from the group consisting of exon 44, 45, 50, 51, and 52.

### Claim 19 (depends on 1)

The method of claim 1, wherein the anti-transferrin receptor antibody comprises a humanized antibody or antigen binding fragment thereof, a chimeric antibody or antigen binding fragment thereof, or a multi-specific antibody or antigen binding fragment thereof.

### Claim 20 (depends on 1)

The method of claim 1, wherein the anti-transferrin receptor antibody comprises an IgG-scFv, nanobody, BiTE, diabody, DART, TandAb, scDiabody, scDiabody-CH3, triple body, mini-antibody, minibody, TriBi minibody, scFv-CH3 KIH, Fab-scFv-Fc KIH, Fab-scFv, scFv-CH-CL-scFv, Fab′, F(ab′)2, F(ab′)3, F(ab′)2-scFv2, scFv, scFv-KIH, Fab-scFv-Fc, tetravalent HCAb, scDiabody-Fc, diabody-Fc, tandem scFv-Fc, or intrabody.

### Claim 21 (depends on 1)

The method of claim 1, wherein the anti-transferrin receptor antibody further comprises at least one mutation in the Fc region, and the at least one mutation is at residue position D265, N297, K322, L328, or P329, wherein the residue position is in reference to IgG1.

### Claim 22 (depends on 1)

The method of claim 1, wherein the anti-transferrin receptor antibody further comprises at least one mutation in the Fc region at L233 and L234, and wherein the residues correspond to position 233 and 234 of SEQ ID NO: 23.