# US 12,213,984 B2 · Immunoregulatory agent

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- Number: US 12,213,984 B2
- Document ID: US12213984B2
- Status: Granted
- Kind: B2
- Application number: 17/521,335
- Filed: 2021-11-08
- Published: 2022-02-24
- Granted: 2025-02-04
- Earliest claimed: 2015-11-20
- Assignees: Kyushu University, National University Corporation
- Applicants: Kyushu University, National University Corporation
- Inventors: Yoshinori Fukui; Takehito Uruno; Yuki Sugiura
- Web page: https://patentgrep.com/patent/US12213984B2

## CPC

- A61K 31/575: substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 35/76: Viruses; Subviral particles; Bacteriophages
- 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 45/00: Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 48/00: Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- C07K 14/47: from mammals
- 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
- 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

An immunoregulatory agent containing a regulatory agent that regulates Dedicator of cytokinesis 2 (DOCK2)-mediated Rac activation as an active ingredient is provided.

## Claims

### Claim 1

A method for regulating Rac-activating activity of DOCK2, the method comprising at least one of:
(i) forming an immune-privileged site by administering to a patient in need of treatment an effective amount of cholesterol 3-sulfate, a pharmacologically acceptable salt thereof, or a solvate thereof, to regulate DOCK2-mediated Rac activation;
(ii) forming an immune-privileged site by administering to a patient in need of treatment an effective amount of a SULT2B1b protein, or an expression vector of the SULT2B1b protein; and
(iii) destroying an immune-privileged site by administering to a patient in need of treatment an effective amount of an expression inhibition substance of the SULT2B1b protein,
wherein:
the SULT2B1b protein is a protein which comprises the amino acid sequence of SEQ ID NO: 2, or a protein which comprises an amino acid sequence formed by the deletion, substitution, or addition of 1 to 3 amino acids in the amino acid sequence of SEQ ID NO: 2, and acts to add a sulfonic acid group to the carbon at position 3 of cholesterol and generate cholesterol 3-sulfate, and
the expression inhibition substance of the SULT2B1b protein is siRNA or shRNA.

### Claim 2 (depends on 1)

The method for regulating Rac-activating activity of DOCK2 according to claim 1, wherein:
forming the immune-privileged site includes inhibiting Rac-activating activity of DOCK2, and
infiltration of immune cells is suppressed in the immune-privileged site.

### Claim 3 (depends on 1)

The method for regulating Rac-activating activity of DOCK2 according to claim 1, wherein destroying the immune-privileged site includes accelerating Rac-activating activity of DOCK2.

### Claim 4 (depends on 1)

The method for regulating Rac-activating activity of DOCK2 according to claim 1, wherein the SULT2B1b protein is a protein which comprises the amino acid sequence of SEQ ID NO: 2.

### Claim 5 (depends on 1)

The method for regulating Rac-activating activity of DOCK2 according to claim 1, the method comprising:
forming an immune-privileged site by administering to the patient an effective amount of the cholesterol 3-sulfate, a pharmacologically acceptable salt thereof, or a solvate thereof, to regulate DOCK2-mediated Rac activation.

### Claim 6 (depends on 1)

The method for regulating Rac-activating activity of DOCK2 according to claim 1, the method comprising:
forming an immune-privileged site by administering to the patient an effective amount of the SULT2B1b protein, or an expression vector of the SULT2B1b protein.

### Claim 7 (depends on 1)

The method for regulating Rac-activating activity of DOCK2 according to claim 1, the method comprising:
destroying an immune-privileged site by administering to the patient an effective amount of the expression inhibition substance of the SULT2B1b protein.

### Claim 8 (depends on 7)

The method for regulating Rac-activating activity of DOCK2 according to claim 7, wherein the expression inhibition substance of the SULT2B1b protein is siRNA, and sense strand of the siRNA has a base sequence selected from the group consisting of SEQ ID NOS: 4 to 7.

### Claim 9 (depends on 7)

The method for regulating Rac-activating activity of DOCK2 according to claim 7, wherein the expression inhibition substance of the SULT2B1b protein is shRNA, and the shRNA has a base sequence selected from the group consisting of SEQ ID NOS: 8 to 10.
