# US 2021/0277077 A1 · Recombinant transmembrane domain-deficient sting as biomimetic protein carrier for cgamp enhanced cancer immunotherapy

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- Number: US 2021/0277077 A1
- Document ID: US20210277077A1
- Status: Published application
- Kind: A1
- Application number: 17/181,884
- Filed: 2021-02-22
- Published: 2021-09-09
- Earliest claimed: 2020-02-21
- Assignees: Northeastern University
- Applicants: Northeastern University
- Inventors: Jiahe Li
- Web page: https://patentgrep.com/patent/US20210277077A1

## CPC

- C07K 14/4702: {Regulators; Modulating activity}
- A61K 31/7084: Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
- A61K 38/19: Cytokines; Lymphokines; Interferons
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07K 14/4705: {stimulating, promoting or activating activity}
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- 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)
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2319/10: containing a tag for extracellular membrane crossing, e.g. TAT or VP22
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- 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

Disclosed are compositions comprising a fusion protein and a STING agonist, wherein the fusion protein comprises STINGΔTM protein fused to a cell-penetrating domain or a nanobody to deliver STING agonists. Also disclosed are methods of treating cancer, which is achieved by a administering said compositions.

## Claims

### Claim 1

A composition, comprising a fusion protein and a STING agonist, wherein the fusion protein comprises STINGΔTM protein fused to a cell-penetrating domain or a nanobody.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the STINGΔTM comprises an amino acid sequence with at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% homology to the amino acid sequence selected from SEQ ID NOs: 3-6.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the cell-penetrating domain or the nanobody is fused to the N-terminus of the STINGΔTM.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the cell-penetrating domain comprises an amino acid sequence selected from SEQ ID NOs: 7-42.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the nanobody is capable of binding to a cancer cell.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the nanobody is capable of binding to CTLA4, PD-1, PD-L1, PD-L2, A2AR, B7-H3, B7-H4, BTLA, KIR, LAG3, TIM-3 or VISTA.

### Claim 7 (depends on 1)

The composition of claim 1, wherein the STING agonist is a cytosolic cyclic dinucleotide (CDN).

### Claim 8 (depends on 7)

The composition of claim 7, wherein the CDN is c-di-GMP, 3′,3′cGAMP, 2′,3′cGAMP, c-di-AMP, cAIMP, cAIMP Difluor, cAIM(PS)2 Difluor (Rp,Sp), 2′2′-cGAMP, 2′3′-cGAM(PS)2 (Rp,Sp), 3′3′-cGAMP Fluorinated, c-di-AMP Fluorinated, 2′3′-c-di-AMP, 2′3′-c-di-AM(PS)2 (Rp,RP), 2′3′-c-di-AM(PS)2, c-di-GMP Fluorinated, 2′3′-c-di-GMP, or c-di-IMP.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the STING agonist is a non-nucleotidyl small molecule.

### Claim 10 (depends on 9)

The composition of claim 9, wherein the non-nucleotidyl small molecule is 5,6-dimethylxanthenone-4-acetic acid 7 (DMXAA), flavone-8-acetic acid, 2,7-bis(2-diethylamino ethoxy)fluoren-9-one, 10-carboxymethyl-9-acridanone, 2,7,2″,2″-dispiro[indene-1″,3″-dione]-tetrahydro dithiazolo[3,2-a:3′,2′-d]pyrazine-5,10(5aH,10aH)-dione, 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-yl methyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide, 6-Bromo-N-(naphthalen-1-yl)benzo[d][1,3]dioxole-5-carboxamide, 3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide, 2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine-7-carboxamide, 2-oxo-1,2,3,4-tetrahydroquinoline-7-carboxamide, or 2-Oxo-1,2,3,4-tetrahydroquinazoline-7-carboxamides.

### Claim 11

A fusion protein, comprising STINGΔTM protein fused to a cell-penetrating domain or a nanobody.

### Claim 12 (depends on 11)

The fusion protein of claim 11, wherein the STINGΔTM comprises an amino acid sequence with at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% homology to the amino acid sequence selected from SEQ ID NOs: 3-6.

### Claim 13 (depends on 11)

The fusion protein of claim 11, wherein the cell-penetrating domain or the nanobody is fused to the N-terminus of the STINGΔTM.

### Claim 14 (depends on 11)

The fusion protein of claim 11, wherein the cell-penetrating domain comprises an amino acid sequence selected from SEQ ID NOs: 7-42.

### Claim 15 (depends on 11)

The fusion protein of claim 11, wherein the nanobody is capable of binding to a cancer cell.

### Claim 16 (depends on 15)

The fusion protein of claim 15, wherein the nanobody is capable of binding to CTLA4, PD-1, PD-L1, PD-L2, A2AR, B7-H3, B7-H4, BTLA, KIR, LAG3, TIM-3 or VISTA.

### Claim 17 (depends on 11)

A nucleic acid molecule that hybridizes, under stringent conditions, with the complement of a nucleic acid encoding the fusion protein of claim 11.

### Claim 18 (depends on 17)

A vector comprising the nucleic acid of claim 17.

### Claim 19

A method of treating cancer or an infectious disease, comprising administering to a patient in need thereof an effective amount of a composition comprising a fusion protein and a STING agonist, wherein the fusion protein comprises STINGΔTM protein fused to a cell-penetrating domain or a nanobody.

### Claim 20 (depends on 19)

The method of claim 19, wherein the STINGΔTM comprises an amino acid sequence with at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% homology to the amino acid sequence selected from SEQ ID NOs: 3-6.

### Claim at position 21

-37. (canceled)