# US 11,028,179 B2 · Anti-transferrin receptor antibodies and uses thereof

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- Number: US 11,028,179 B2
- Document ID: US11028179B2
- Status: Granted
- Kind: B2
- Application number: 17/133,413
- Filed: 2020-12-23
- Published: 2021-05-06
- Granted: 2021-06-08
- Earliest claimed: 2018-12-21
- Assignees: Avidity Biosciences, Inc.
- Applicants: Avidity Biosciences, Inc.
- Inventors: Beatrice Diana Darimont; Venkata Ramana Doppalapudi; Rachel Johns
- Web page: https://patentgrep.com/patent/US11028179B2

## CPC

- C07K 16/2881: {against CD71}
- A61K 47/6807: {the drug or compound being a sugar, nucleoside, nucleotide, nucleic acid, e.g. RNA antisense}
- 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}
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- 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 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- C12N 2310/14: interfering nucleic acids [NA]
- C12N 2310/3513: Protein; Peptide
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## 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

An antibody or antigen-binding fragment thereof that binds to transferrin receptor, wherein the antibody or antigen-binding fragment comprises i) a variable heavy chain (VH) region comprising a sequence selected from SEQ ID NOs: 13-16, and ii) a variable light chain (VL) region comprising a sequence selected from SEQ ID NOs: 18-21.

### Claim 2 (depends on 1)

The antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof comprises a humanized antibody or binding fragment thereof or a chimeric antibody or binding fragment thereof.

### Claim 3 (depends on 1)

The antibody or antigen-binding fragment of claim 1, wherein the antigen-binding fragment is selected from 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, and intrabody.

### Claim 4 (depends on 3)

The antibody or antigen-binding fragment of claim 3, wherein the antigen-binding fragment is selected from a nanobody, BiTE, diabody, DART, TandAb, scDiabody, scDiabody-CH3, triple body, 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, and scFv-KIH.

### Claim 5 (depends on 1)

The antibody or antigen-binding fragment of claim 1, wherein the antibody comprises a heavy chain (HC) sequence selected from SEQ ID NOs: 23-46 and a light chain (LC) sequence selected from SEQ ID NOs: 47-50.

### Claim 6 (depends on 1)

A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable excipient.

### Claim 7

An anti-transferrin receptor antibody conjugate, comprising Formula (I):
A-(X1—B)n Formula (I)
wherein A comprises an anti-transferrin receptor antibody or antigen-binding fragment thereof, wherein the anti-transferrin receptor antibody or antigen-binding fragment thereof comprises a variable heavy chain (VH) region comprising a sequence selected from SEQ ID NOs: 13-16, and a variable light chain (VL) region comprising a sequence selected from SEQ ID NOs: 18-21;
B comprises a polynucleic acid molecule;
X1 consists of a bond or linker; and
n is an averaged value selected from 1-12.

### Claim 8 (depends on 7)

The anti-transferrin receptor antibody conjugate of claim 7, wherein the antigen-binding fragment is selected from 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, and intrabody.

### Claim 9 (depends on 7)

The anti-transferrin receptor antibody conjugate of claim 7, wherein the polynucleic acid molecule is selected from a short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), short hairpin RNA (shRNA), antisense oligonucleotide (ASO), a phosphorodiamidate morpholino oligo (PMO), and mRNA.

### Claim 10 (depends on 7)

The anti-transferrin receptor antibody conjugate of claim 7, wherein the polynucleic acid molecule is a double-stranded RNA (dsRNA).

### Claim 11 (depends on 7)

The anti-transferrin receptor antibody conjugate of claim 7, wherein the polynucleic acid molecule is a single stranded antisense oligonucleotide (ASO).

### Claim 12 (depends on 7)

The anti-transferrin receptor antibody conjugate of claim 7, wherein the polynucleic acid molecule comprises a passenger strand and a guide strand.

### Claim 13 (depends on 12)

The anti-transferrin receptor antibody conjugate of claim 12, wherein the guide strand comprises at least one modified internucleotide linkage, at least one inverted abasic moiety, at least one 5′-vinylphosphonate modified non-natural nucleotide, or a combination thereof.

### Claim 14 (depends on 12)

The anti-transferrin receptor antibody conjugate of claim 12, wherein the polynucleic acid molecule further comprises a modification of a sugar moiety at the 2′ position, and wherein the modification at the 2′-position is selected from 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O—N-methylacetamido (2′-O-NMA) modified nucleotide.

### Claim 15 (depends on 12)

The anti-transferrin receptor antibody conjugate of claim 12, wherein the passenger strand comprises at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more phosphorodiamidate morpholino oligomer-modified non-natural nucleotides.

### Claim 16 (depends on 12)

The anti-transferrin receptor antibody conjugate of claim 12, wherein A-X1 is conjugated to the 5′ end of the passenger strand or 3′ end of the passenger strand.

### Claim 17 (depends on 7)

The anti-transferrin receptor antibody conjugate of claim 7, wherein the polynucleic acid molecule hybridizes to a target sequence of a gene, and wherein the polynucleic acid molecule mediates RNA interference against the gene.

### Claim 18 (depends on 17)

The anti-transferrin receptor antibody conjugate of claim 17, the gene comprises an unregulated gene within the IGF1-Akt-FoxO pathway, the glucocorticoids-GR pathway, the PGC1α-FoxO pathway, the TNFα-NFκB pathway, or the myostatin-ActRIIb-Smad2/3 pathway, E3 ligase, Forkhead box transcription factor, atrogin-1 gene (FBXO32), MuRF1 gene (TRIM63), FOXO1, FOXO3, MSTN, DMD, or DMPK.

### Claim 19 (depends on 17)

The anti-transferrin receptor antibody conjugate of claim 17, wherein the RNA interference is preferentially mediated in a muscle when the anti-transferrin receptor antibody conjugate is administered to a subject.

### Claim 20 (depends on 7)

A pharmaceutical composition comprising the anti-transferrin receptor antibody conjugate of claim 7 and a pharmaceutically acceptable excipient.