# US 12,110,324 B2 · Antigen binding molecules targeting thymic stromal lymphopoietin (TSLP)

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- Number: US 12,110,324 B2
- Document ID: US12110324B2
- Status: Granted
- Kind: B2
- Application number: 18/356,891
- Filed: 2023-07-21
- Published: 2024-02-01
- Granted: 2024-10-08
- Earliest claimed: 2022-07-22
- Assignees: Flagship Pioneering Innovations VI, LLC
- Applicants: Flagship Pioneering Innovations VI, LLC
- Inventors: Antonios O. Aliprantis; Zachary Kohl Costello; Anthony John Coyle; Kristen Park Hopson; Ryan Terrell Phennicie; Alexis Hiram Ramos; Adam Reid Root; Lana Dinic; Karin Alma Frieda Reif
- Web page: https://patentgrep.com/patent/US12110324B2

## CPC

- A61P 11/00: Drugs for disorders of the respiratory system
- C07K 16/244: {Interleukins [IL]}
- A61P 11/06: Antiasthmatics
- 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 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/70: characterized by effect upon binding to a cell or to an antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

The disclosure provides, in various embodiments, polypeptides (e.g., antibodies and antigen binding fragments thereof) that specifically bind to a thymic stromal lymphopoietin (TSLP) (e.g., a full-length human TSLP). The disclosure also provides, in various embodiments, fusion proteins comprising one or more of the polypeptides, polynucleotides encoding the polypeptides, vectors and host cells suitable for expressing the polypeptides, and methods for treating a TSLP-associated disease or condition.

## Claims

### Claim 1

An anti-thymic stromal lymphopoietin (TSLP) antibody or antigen-binding fragment thereof comprising:
a) a heavy chain variable domain (VH) that comprises a heavy chain complementarity-determining region (HCDR) 1 comprising the amino acid sequence of SEQ ID NO:31, a HCDR2 comprising the amino acid sequence of SEQ ID NO:35, and a HCDR3 comprising the amino acid sequence of SEQ ID NO:50; and
b) a light chain variable domain (VL) that comprises a light chain complementarity-determining region (LCDR) 1 comprising the amino acid sequence of SEQ ID NO:60, a LCDR2 comprising the amino acid sequence DDS, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:71.

### Claim 2

An anti-TSLP antibody or antigen-binding fragment thereof comprising:
a) a heavy chain variable domain (VH) that comprises a heavy chain complementarity-determining region (HCDR) 1 consisting of the amino acid sequence of SEQ ID NO:31, a HCDR2 consisting of the amino acid sequence of SEQ ID NO:35, and a HCDR3 consisting of the amino acid sequence of SEQ ID NO:50; and
b) a light chain variable domain (VL) that comprises a light chain complementarity-determining region (LCDR) 1 consisting of the amino acid sequence of SEQ ID NO:60, a LCDR2 consisting of the amino acid sequence DDS, and a LCDR3 consisting of the amino acid sequence of SEQ ID NO:71.

### Claim 3 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising a heavy chain variable domain (VH) that is humanized, contains human framework regions, or a combination thereof.

### Claim 4 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising a VH comprising the amino acid sequence of SEQ ID NO:5.

### Claim 5 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising a light chain variable domain (VL) that is humanized, contains human framework regions, or a combination thereof.

### Claim 6 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising a VL comprising the amino acid sequence of SEQ ID NO:21.

### Claim 7 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising a VH comprising the amino acid sequence of SEQ ID NO:5, and a VL comprising the amino acid sequence of SEQ ID NO:21.

### Claim 8 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, wherein the antigen-binding fragment comprises a single-chain fragment variable (scFv), a fragment antigen-binding (Fab), a Fab′ or a F(ab′)2.

### Claim 9 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising an antibody heavy chain constant domain, an antibody light chain constant domain, or both an antibody heavy chain constant domain and an antibody light chain constant domain.

### Claim 10 (depends on 9)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 9, wherein the antibody heavy chain constant domain is an IgG1, IgG2, IgG3 or IgG4 constant domain.

### Claim 11 (depends on 9)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 9, wherein the antibody heavy chain constant domain is an IgG1 or IgG2 constant domain.

### Claim 12 (depends on 10)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 10, wherein the antibody heavy chain constant domain comprises one or more mutations which increase serum half-life of the antibody or antigen-binding fragment thereof in humans.

### Claim 13 (depends on 10)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 10, wherein the antibody heavy chain constant domain comprises, relative to a wild-type human IgG constant domain, amino acid substitutions with tyrosine, threonine and glutamic acid at amino acid residues 252, 254 and 256, respectively, wherein the amino acid residues are numbered according to the EU index as in Kabat.

### Claim 14 (depends on 2)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 2, comprising an antibody heavy chain (HC) comprising the amino acid sequence of SEQ ID NO:106.

### Claim 15 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising an antibody heavy chain (HC) comprising the amino acid sequence of SEQ ID NO: 106.

### Claim 16 (depends on 1)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising an antibody light chain (LC) comprising the amino acid sequence of SEQ ID NO:120.

### Claim 17 (depends on 14)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 14, comprising an antibody light chain (LC) comprising the amino acid sequence of SEQ ID NO:120.

### Claim 18 (depends on 15)

The anti-TSLP antibody or antigen-binding fragment thereof of claim 15, comprising an antibody light chain (LC) consisting of the amino acid sequence of SEQ ID NO:120.

### Claim 19 (depends on 1)

A composition comprising the anti-TSLP antibody or antigen-binding fragment thereof of claim 1, and one or more pharmaceutical excipients, diluents, or carriers.

### Claim 20 (depends on 19)

The composition of claim 19, further comprising one or more additional therapeutic agents.

### Claim 21 (depends on 1)

A polynucleotide comprising a nucleotide sequence encoding the anti-TSLP antibody or antigen-binding fragment thereof of claim 1.

### Claim 22 (depends on 21)

A host cell comprising the polynucleotide of claim 21.

### Claim 23 (depends on 1)

A method of making the anti-TSLP antibody or antigen-binding fragment thereof of claim 1, comprising culturing a host cell comprising a nucleotide sequence encoding the anti-TSLP antibody or antigen-binding fragment thereof under conditions where the anti-TSLP antibody or antigen-binding fragment thereof is expressed in the host cell.