# US 2020/0399335 A1 · Modified immunomodulatory peptide

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- Number: US 2020/0399335 A1
- Document ID: US20200399335A1
- Status: Published application
- Kind: A1
- Application number: 16/968,398
- Filed: 2019-02-07
- Published: 2020-12-24
- Earliest claimed: 2018-02-08
- Assignees: Aarhus Universitet
- Applicants: Aarhus Universitet
- Inventors: Martin Roelsgaard Jakobsen; Claus Elsborg Olesen
- Web page: https://patentgrep.com/patent/US20200399335A1

## CPC

- C07K 14/52: Cytokines; Lymphokines; Interferons
- A61K 38/1709: {from mammals}
- A61K 38/19: Cytokines; Lymphokines; Interferons
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- A61P 31/22: for herpes viruses
- A61P 35/02: specific for leukemia
- 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

Modified polypeptides derived from the pyrin-domain of IFI16 are provided as well as their uses in medicine. Specifically, the polypeptides are provided for use in the treatment of disorders associated with STING activity, including cancer and immunodeficient or auto-immune disorders.

## Claims

### Claim at position 1

1-33. (canceled)

### Claim 34

A polypeptide or polypeptide analog, wherein the polypeptide or polypeptide analog comprises an amino acid sequence of the general formula:
KKX3KNIVLLX10GLX13VINX17YHF (SEQ ID NO: 31)
wherein X is selected from any proteinogenic and non-proteinogenic amino acid residues, with the proviso that one or more of X3 is not tyrosine (Y), X10 is not lysine (K), X13 is not glutamic acid (E) and X17 is not aspartic acid (D).

### Claim 35 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, comprising the sequence KKX3KNIVLLKGLEVINDYHF (SEQ ID NO: 4), KKYKNIVLLX10GLEVINDYHF (SEQ ID NO: 5), KKYKNIVLLKGLX13VINDYHF (SEQ ID NO: 29), or KKYKNIVLLKGLEVINX17YHF (SEQ ID NO: 30), wherein X is selected from any proteinogenic and non-proteinogenic amino acid residues, with the proviso that X3 is not tyrosine (Y) and X10 is not lysine (K) and X13 is not glutamic acid (E) and X17 is not aspartic acid (D).

### Claim 36 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein X is an amino acid residue selected from the group consisting of A, R, N, D, B, C, E, Q, Z, G, H, I, L, K, M, F, P, S, T, W and V.

### Claim 37 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein one or more of the amino acid residues at one or more of the positions 2, 6, 7, 11, 15, 16, 19 and 20 (K2, I6, V7, G11, I15, N16, H19 and F20) remain unsubstituted and/or unmodified.

### Claim 38 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein one or more of the amino acid residues at positions 2, 6, 7, 11, 15, 16, 19 and 20 have been substituted with alanine.

### Claim 39 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is selected from the group consisting of:
(SEQ ID NO: 9)
i.
KKAKNIVLLKGLEVINDYHF (peptide A3)
(SEQ ID NO: 16)
ii.
KKYKNIVLLAGLEVINTDYHF (peptide A10)
(SEQ ID NO: 19)
iii.
KKYKNIVLLKGLAVINTDYHF (peptide A13)
(SEQ ID NO: 23)
iv.
KKYKNIVLLKGLEVINTAYHF (peptide A17)
and
(SEQ ID NO: 27)
v.
KKYKNIVLLKGLAVINDYAA
(peptide 107).

### Claim 40 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is capable of eliciting a cytokine response.

### Claim 41 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is capable of eliciting a type I interferon response.

### Claim 42 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is capable of eliciting an interferon response without eliciting a cytokine response.

### Claim 43 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is capable of eliciting an interferon response without eliciting an IL6 cytokine response but still a CXCL10 cytokine response.

### Claim 44 (depends on 43)

The polypeptide or polypeptide analog according to claim 43, wherein said polypeptide is peptide A10 (SEQ ID NO: 16), A13 (SEQ ID NO: 19), peptide 101 (SEQ ID NO. 6) and/or peptide 107 (SEQ ID NO. 27).

### Claim 45 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is linked to at least one conjugated moiety.

### Claim 46 (depends on 45)

The polypeptide or polypeptide analog according to claim 45, wherein said at least one conjugated moiety is a cell-penetrating peptide, wherein the cell-penetrating peptide is optionally HIV TAT.

### Claim 47 (depends on 34)

The polypeptide or polypeptide according to claim 34, wherein said polypeptide is capable of interacting with IFI16 and/or STING.

### Claim 48 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is capable of inducing phosphorylation of STING at Ser366.

### Claim 49 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is capable of increasing STING activity.

### Claim 50 (depends on 34)

The polypeptide or polypeptide analog according to claim 34, wherein said polypeptide is capable of inducing STING phosphorylation.

### Claim 51 (depends on 34)

A method of treating a disorder associated with STING activity or insufficient STING activity comprising administering polypeptide of claim 34 to an individual in need thereof.

### Claim 52 (depends on 51)

The method of claim 51, wherein said disorder is cancer.

### Claim 53 (depends on 51)

The method of claim 51, wherein said disorder is an infection with a DNA pathogen, optionally wherein the DNA pathogen is HIV, HSV-1, HSV-2, HVP, HBV, malaria or listeria.

### Claim 54 (depends on 51)

The method of claim 51 further comprising administering one or more additional active compounds to the individual in need thereof.

### Claim 55 (depends on 54)

The method of claim 54, wherein the additional active compound is an anti-cancer agent.

### Claim 56 (depends on 51)

The method of claim 51, wherein said disorder is associated with TBK1 and/or IRF3 and/or NF-kB activity.

### Claim 57 (depends on 51)

The method of claim 51, wherein said disorder is cancer, optionally wherein the cancer is induced by chronic inflammatory signalling.

### Claim 58 (depends on 57)

The method of claim 57, wherein the cancer is a cutaneous skin tumour, optionally wherein the cutaneous skin tumour is basal cell carcinoma (BCC) or squamous cell carcinoma (SCC).

### Claim 59 (depends on 34)

A polynucleotide encoding upon expression the polypeptide or polypeptide analog of claim 34, optionally wherein the polynucleotide is comprised within a vector.

### Claim 60 (depends on 59)

A cell comprising the polynucleotide of claim 59.