# US 11,299,554 B2 · Heterodimeric proteins

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- Number: US 11,299,554 B2
- Document ID: US11299554B2
- Status: Granted
- Kind: B2
- Application number: 16/364,093
- Filed: 2019-03-25
- Published: 2020-02-13
- Granted: 2022-04-12
- Earliest claimed: 2013-03-15
- Assignees: Xencor, Inc.
- Applicants: Xencor, Inc.
- Inventors: Gregory Moore; Rumana Rashid; John Desjarlais
- Web page: https://patentgrep.com/patent/US11299554B2

## CPC

- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- C07K 16/22: against growth factors {; against growth regulators}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/72: Increased effector function due to an Fc-modification
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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

The present invention describes novel immunoglobulin compositions that co-engage at least two antigens, e.g. a first and second antigen, or, as outlined herein, three or four antigens can be bound, in some of the scaffold formats described herein. First and second antigens of the invention are herein referred to as antigen-1 and antigen-2 respectively (or antigen-3 and antigen-4, if applicable. As outlined herein, a number of different formats can be used, with some scaffolds relying combinations of monovalent and bivalent bindings.

## Claims

### Claim 1

A composition comprising a heterodimeric protein comprising a heterodimeric Fc domain, said heterodimeric Fc domain comprising:
a) a first monomer comprising a first variant Fc domain comprising amino acid substitutions S239D, 332E, L368E, K370S; and
b) a second monomer comprising a second variant Fc domain comprising amino acid substitutions S239D, 332E, and S364K wherein numbering is according to the EU index as in Kabat and wherein said first variant Fc domain and said second variant Fc domain are variant human IgG Fc domains.

### Claim 2 (depends on 1)

A composition according to claim 1 wherein said first monomer further comprises a first fusion partner and said second monomer further comprises a second fusion partner.

### Claim 3 (depends on 2)

A composition according to claim 2, wherein said first monomer comprises a third fusion partner.

### Claim 4 (depends on 3)

A composition according to claim 3, wherein said second monomer comprises a fourth fusion partner.

### Claim 5 (depends on 2)

A composition according to claim 2, wherein said fusion partners are independently selected from the group consisting of an immunoglobulin component, a peptide, a cytokine, a chemokine, an immune receptor and a blood factor.

### Claim 6 (depends on 5)

A composition according to claim 5, wherein said immunoglobulin component is selected from the group consisting of Fab, VH, VL, scFv, scFv2, and dAb.

### Claim 7 (depends on 5)

A composition according to claim 5, wherein both fusion partners are immunoglobulin components.

### Claim 8 (depends on 1)

A nucleic acid composition comprising:
a) a first nucleic acid nucleic acid encoding a first monomer according to claim 1; and
b) a second nucleic acid encoding a second monomer according to claim 1.

### Claim 9 (depends on 8)

A host cell comprising the nucleic acid composition of claim 8.

### Claim 10 (depends on 1)

A method of making a composition according to claim 1 comprising culturing a host cell according to claim 1 under conditions whereby said composition is produced.