# US 12,760,103 B2 · Variant IgG Fc polypeptides and uses thereof

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- Number: US 12,760,103 B2
- Document ID: US12760103B2
- Status: Granted
- Kind: B2
- Application number: 18/614,199
- Filed: 2024-03-22
- Published: 2025-03-06
- Granted: 2026-10-13
- Earliest claimed: 2022-10-25
- Assignees: Seismic Therapeutic, Inc.
- Applicants: Seismic Therapeutic, Inc.
- Inventors: Yen-Lin Chen; Ryan Peckner; Nathan Higginson-Scott; Daniela Cipolletta; Yanfeng Zhou; Kevin Lewis Otipoby; Jyothsna Visweswaraiah
- Web page: https://patentgrep.com/patent/US12760103B2

## CPC

- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/71: Decreased effector function due to an Fc-modification
- C07K 2317/72: Increased effector function due to an Fc-modification
- C07K 2317/75: Agonist effect on antigen
- 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

Embodiments provided herein, provide for variant IgG Fc polypeptides, dimeric molecules, pharmaceutical compositions, and methods that can be used to target at cells to modulate the activity of the same to treat disorders, such as autoimmune disorders or cancers.

## Claims

### Claim 1

A fusion protein comprising an Fc polypeptide linked to a heterologous protein, wherein the Fc polypeptide comprises an amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 88, provided that the Fc polypeptide comprises:
a glutamic acid residue at position 237 and a glutamic acid residue at position 238, wherein the positions are according to EU numbering;
an aspartic acid residue at position 237, a glycine residue at position 238, an alanine residue at position 240, an aspartic acid residue at position 269, a glutamic acid residue at position 270, and an arginine residue at position 330, wherein the positions are according to EU numbering; or
a phenylalanine residue at position 234, a glutamic acid residue at position 235, an aspartic acid residue at position 268, a glycine residue at position 271, and an alanine residue at position 329, wherein the positions are according to EU numbering.

### Claim 2 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the glutamic acid residue at position 237 and the glutamic acid residue at position 238, wherein the positions are according to EU numbering.

### Claim 3 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the aspartic acid residue at position 237, the glycine residue at position 238, the alanine residue at position 240, the aspartic acid residue at position 269, the glutamic acid residue at position 270, and the arginine residue at position 330, wherein the positions are according to EU numbering.

### Claim 4 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the phenylalanine residue at position 234, the glutamic acid residue at position 235, the aspartic acid residue at position 268, the glycine residue at position 271, and the alanine residue at position 329, wherein the positions are according to EU numbering.

### Claim 5 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 40.

### Claim 6 (depends on 5)

The fusion protein of claim 5, wherein the Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 40.

### Claim 7 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 102.

### Claim 8 (depends on 7)

The fusion protein of claim 7, wherein the Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 102.

### Claim 9 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 86.

### Claim 10 (depends on 9)

The fusion protein of claim 9, wherein the Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 86.

### Claim 11 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 103.

### Claim 12 (depends on 11)

The fusion protein of claim 11, wherein the Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 103.

### Claim 13 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 77.

### Claim 14 (depends on 13)

The fusion protein of claim 13, wherein the Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 77.

### Claim 15 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide comprises the amino acid sequence having at least 95% identity to an amino acid sequence of SEQ ID NO: 104.

### Claim 16 (depends on 15)

The fusion protein of claim 15, wherein the Fc polypeptide comprises the amino acid sequence of SEQ ID NO: 104.

### Claim 17 (depends on 1)

The fusion protein of claim 1, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 18 (depends on 2)

The fusion protein of claim 2, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 19 (depends on 3)

The fusion protein of claim 3, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 20 (depends on 4)

The fusion protein of claim 4, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 21 (depends on 5)

The fusion protein of claim 5, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 22 (depends on 6)

The fusion protein of claim 6, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 23 (depends on 8)

The fusion protein of claim 8, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 24 (depends on 10)

The fusion protein of claim 10, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 25 (depends on 12)

The fusion protein of claim 12, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 26 (depends on 14)

The fusion protein of claim 14, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 27 (depends on 16)

The fusion protein of claim 16, wherein the heterologous protein is an antibody, or an antigen binding fragment thereof.

### Claim 28 (depends on 1)

A pharmaceutical composition comprising the fusion protein of claim 1 and a pharmaceutically acceptable excipient.

### Claim 29 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide is directly linked to the heterologous protein.

### Claim 30 (depends on 1)

The fusion protein of claim 1, wherein the Fc polypeptide is linked to the heterologous protein with a peptide linker.
