# US 12,180,302 B2 · Heterodimeric antibodies that bind fibroblast activation protein

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- Number: US 12,180,302 B2
- Document ID: US12180302B2
- Status: Granted
- Kind: B2
- Application number: 17/233,083
- Filed: 2021-04-16
- Published: 2021-08-19
- Granted: 2024-12-31
- Earliest claimed: 2018-04-04
- Assignees: Xencor, Inc.
- Applicants: Xencor, Inc.
- Inventors: John Desjarlais; Alex Nisthal; Seung Chu
- Web page: https://patentgrep.com/patent/US12180302B2

## CPC

- C07K 16/40: against enzymes
- A61P 35/00: Antineoplastic agents
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/30: from tumour cells
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/35: Valency
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/66: comprising a swap of domains, e.g. CH3-CH2, VH-CL or VL-CH1
- 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
- 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
- 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 relates to novel antigen binding domains and heterodimeric antibodies that bind Fibroblast Activation Protein (FAP).

## Claims

### Claim 1

A composition comprising a fibroblast activation protein (FAP) binding domain, the FAP binding domain comprising:
a) a variable heavy domain comprising a vhCDR1, vhCDR2, and vhCDR3; and
b) a variable light domain comprising a vlCDR1, vlCDR2, and vlCDR3;
wherein vhCDR1-3 and vlCDR1-3 are selected from the following:
i) a vhCDR1 having the amino acid sequence of SEQ ID NO: 158, a vhCDR2 having the amino acid sequence of SEQ ID NO: 159, a vhCDR3 having the amino acid sequence of SEQ ID NO: 160, a vlCDR1 having the amino acid sequence of SEQ ID NO: 162, a vlCDR2 having the amino acid sequence of SEQ ID NO: 163, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 164;
ii) a vhCDR1 having the amino acid sequence of SEQ ID NO: 166, a vhCDR2 having the amino acid sequence of SEQ ID NO: 167, a vhCDR3 having the amino acid sequence of SEQ ID NO: 168, a vlCDR1 having the amino acid sequence of SEQ ID NO: 170, a vlCDR2 having the amino acid sequence of SEQ ID NO: 171, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 172;
iii) a vhCDR1 having the amino acid sequence of SEQ ID NO: 182, a vhCDR2 having the amino acid sequence of SEQ ID NO: 183, a vhCDR3 having the amino acid sequence of SEQ ID NO: 184, a vlCDR1 having the amino acid sequence of SEQ ID NO: 186, a vlCDR2 having the amino acid sequence of SEQ ID NO: 187, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 188; and
iv) a vhCDR1 having the amino acid sequence of SEQ ID NO: 190, a vhCDR2 having the amino acid sequence of SEQ ID NO: 191, a vhCDR3 having the amino acid sequence of SEQ ID NO: 192, a vlCDR1 having the amino acid sequence of SEQ ID NO: 194, a vlCDR2 having the amino acid sequence of SEQ ID NO: 195, and a vlCDR3 having the amino acid sequence of SEQ ID NO: 196.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 157 and the variable light domain has the amino acid sequence of SEQ ID NO: 161.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 165 and the variable light domain has the amino acid sequence of SEQ ID NO: 169.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 181 and the variable light domain has the amino acid sequence of SEQ ID NO: 185.

### Claim 5 (depends on 1)

The composition of claim 1 wherein the variable heavy domain has the amino acid sequence of SEQ ID NO: 189 and the variable light domain has the amino acid sequence of SEQ ID NO: 193.

### Claim 6 (depends on 1)

A nucleic acid composition encoding the FAP binding domain of claim 1, comprising:
a) a first nucleic acid encoding the variable heavy domain; and
b) a second nucleic acid encoding the variable light domain.

### Claim 7 (depends on 1)

An expression vector composition encoding the FAP binding domain of claim 1, comprising:
a) a first expression vector comprising a nucleic acid encoding the variable heavy domain; and
b) a second expression vector comprising second nucleic acid encoding the variable light domain.

### Claim 8 (depends on 7)

A host cell comprising the expression vector composition of claim 7.

### Claim 9 (depends on 8)

A method of making a FAP binding domain comprising culturing the host cell of claim 8 under conditions wherein the FAP binding domain is expressed and recovering the FAP binding domain.

### Claim 10

A composition comprising a fibroblast activation protein (FAP) binding domain, wherein the FAP binding domain comprises a variable heavy domain and a variable light domain selected from the following:
i) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 157, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 161;
ii) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 165, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 169;
iii) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 181, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 185; and
iv) a variable heavy domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 189, and a variable light domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 193.