# US 2020/0399342 A1 · Tigit- and light-based chimeric proteins

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- Number: US 2020/0399342 A1
- Document ID: US20200399342A1
- Status: Published application
- Kind: A1
- Application number: 17/017,108
- Filed: 2020-09-10
- Published: 2020-12-24
- Earliest claimed: 2017-02-27
- Assignees: Shattuck Labs, Inc.
- Applicants: Shattuck Labs, Inc.
- Inventors: Taylor SCHREIBER; George FROMM; Suresh DE SILVA
- Web page: https://patentgrep.com/patent/US20200399342A1

## CPC

- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- A61K 38/177: {Receptors; Cell surface antigens; Cell surface determinants}
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 38/1793: {for cytokines; for lymphokines; for interferons}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61P 35/00: Antineoplastic agents
- C07K 14/525: Tumour necrosis factor [TNF]
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/585: {wherein the target is cancer}
- A61K 2039/82: {Colon}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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

## Abstract

The present invention relates, inter alia, to compositions and methods, including TIGIT- and/or LIGHT-based chimeric proteins that find use in the treatment of disease, such as cancer and an inflammatory disease.

## Claims

### Claim at position 1

-47. (canceled)

### Claim 48

A chimeric protein of a general structure of:
N terminus-(a)-(b)-(c)-C terminus,
wherein:
(a) is a first domain comprising an extracellular domain of TIGIT,
(b) is a linker comprising at least one cysteine residue capable of forming a disulfide bond, and
(c) is a second domain comprising an extracellular domain of LIGHT,
wherein the linker connects the first domain and the second domain.

### Claim 49 (depends on 48)

The chimeric protein of claim 48, wherein the first domain is capable of binding a TIGIT ligand selected from CD155/PVR, Nectin-2, Nectin-3, and Nectin-4.

### Claim 50 (depends on 48)

The chimeric protein of claim 48, wherein the second domain is capable of binding a LIGHT ligand selected from LTBR, HVEM, and DcR3.

### Claim 51 (depends on 48)

The chimeric protein of claim 48, wherein the linker is a polypeptide selected from a flexible amino acid sequence, an IgG hinge region, a hinge-CH2-CH3 Fc domain, or an antibody sequence.

### Claim 52 (depends on 48)

The chimeric protein of claim 48, wherein the linker comprises hinge-CH2-CH3 Fc domain derived from IgG1 or IgG4.

### Claim 53 (depends on 52)

The chimeric protein of claim 52, wherein the hinge-CH2-CH3 Fc domain is derived from human IgG1 or human IgG4.

### Claim 54 (depends on 51)

The chimeric protein of claim 51, wherein the linker comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47, or SEQ ID NO: 48.

### Claim 55 (depends on 48)

The chimeric protein of claim 48, wherein the linker comprises one or more joining linkers, such joining linkers being independently selected from SEQ ID NOs: 49-95.

### Claim 56 (depends on 51)

The chimeric protein of claim 51, wherein the linker further comprises two or more joining linkers each joining linker independently selected from SEQ ID NOs: 49-95; wherein one joining linker is N terminal to the hinge-CH2-CH3 Fc domain and another joining linker is C terminal to the hinge-CH2-CH3 Fc domain.

### Claim 57 (depends on 48)

The chimeric protein of claim 48, wherein the first domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 10.

### Claim 58 (depends on 48)

The chimeric protein of claim 48, wherein the second domain comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2.

### Claim 59 (depends on 48)

The chimeric protein of claim 48, wherein:
(a) the first domain comprises the amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 10,
(b) the second domain comprises the amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 2, and
(c) the linker comprises an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47, or SEQ ID NO: 48.

### Claim 60 (depends on 59)

The chimeric protein of claim 59, wherein the linker further comprises one or more joining linkers, such joining linkers being independently selected from SEQ ID NOs: 49-95.

### Claim 61 (depends on 48)

The chimeric protein of claim 48, wherein the chimeric protein has an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO: 11.

### Claim 62 (depends on 48)

The chimeric protein of claim 48, wherein the chimeric protein is capable of forming a stable synapse between cells.

### Claim 63 (depends on 48)

The chimeric protein of claim 48, wherein the stable synapse between cells provides spatial orientation that favors tumor reduction.

### Claim 64 (depends on 63)

The chimeric protein of claim 63, wherein the spatial orientation positions T cells to attack tumor cells and/or sterically prevents a tumor cell from delivering negative signals, including negative signals beyond those masked by the chimeric protein of the invention.

### Claim 65 (depends on 48)

The chimeric protein of claim 48, wherein binding of either or both of the extracellular domains to its respective binding partner occurs with slow off rates (Koff), which provides a long interaction of a receptor and its ligand.

### Claim 66 (depends on 48)

The chimeric protein of claim 48, wherein the long interaction provides sustained negative signal masking effect.

### Claim 67 (depends on 48)

The chimeric protein of claim 48, wherein the long interaction delivers a longer positive signal effect.

### Claim 68 (depends on 67)

The chimeric protein of claim 67, wherein the longer positive signal effect allows an effector cell to be adequately stimulated for an anti-tumor effect.

### Claim 69 (depends on 48)

The chimeric protein of claim 48, wherein the long interaction provides T cell proliferation and allows for anti-tumor attack.

### Claim 70 (depends on 48)

The chimeric protein of claim 48, wherein the long interaction allows sufficient signal transmission to provide release of stimulatory signals.

### Claim 71 (depends on 70)

The chimeric protein of claim 70, wherein the stimulatory signal is a cytokine.

### Claim 72 (depends on 48)

The chimeric protein of claim 48, wherein the subject's T cells are activated.

### Claim 73 (depends on 48)

A pharmaceutical composition comprising the chimeric protein of claim 48.