# US 11,998,544 B2 · Methods of using splicing modulators

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- Number: US 11,998,544 B2
- Document ID: US11998544B2
- Status: Granted
- Kind: B2
- Application number: 17/059,876
- Filed: 2019-05-31
- Published: 2021-11-11
- Granted: 2024-06-04
- Earliest claimed: 2018-06-01
- Assignees: Eisai R&D Management Co., Ltd.
- Applicants: Eisai R&D Management Co., Ltd.
- Inventors: Ermira Pazolli; Silvia Buonamici; James Palacino; Michael Seiler; Ping Zhu; Evan Barry; Lihua Yu
- Web page: https://patentgrep.com/patent/US11998544B2

## CPC

- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 38/191: {Tumor necrosis factors [TNF], e.g. lymphotoxin [LT], i.e. TNF-beta}
- A61K 38/2013: {IL-2}
- A61K 38/2066: {IL-10}
- A61K 38/208: {IL-12}
- A61K 38/2086: {IL-13 to IL-16}
- A61K 38/217: {IFN-gamma}
- A61K 39/0011: {Cancer antigens}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/505: {comprising antibodies}
- A61K 2039/6031: {Proteins}
- A61K 2039/6037: {Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT]}
- A61K 2039/6056: {Antibodies}
- A61K 2039/6081: {Albumin; Keyhole limpet haemocyanin [KLH]}
- C07K 16/2818: {against CD28 or CD152}
- 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

This disclosure relates to methods for the treatment of neoplastic disorders by administering Compound 1, or a pharmaceutically acceptably salt thereof, on its own and/or as part of a conjugate or composition, and inducing production of at least one neoantigen.

## Claims

### Claim 1

A method of treating a subject having or suspected of having a neoplastic disorder, comprising administering to the subject a therapeutically effective amount of Compound 1
or a pharmaceutically acceptable salt thereof, and at least one additional therapy comprising a CTLA4 inhibitor, and wherein the neoplastic disorder is selected from myelodysplastic syndrome, chronic lymphocytic leukemia, acute lymphoblastic leukemia, chronic myelomonocytic leukemia, acute myeloid leukemia, and colon cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein administration of the Compound 1, or a pharmaceutically acceptable salt thereof, is initiated before, after, or concurrently with administration of the at least one additional therapy.

### Claim 3 (depends on 1)

The method of claim 1, wherein administration of the Compound 1, or a pharmaceutically acceptable salt thereof, and/or the at least one additional therapy is repeated at least once after initial administration.

### Claim 4 (depends on 1)

The method of claim 1,
wherein the CTLA4 inhibitor is an anti-CTLA4 antibody.

### Claim 5 (depends on 1)

The method of claim 1, wherein the at least one additional therapy comprises at least one, at least two, at least three, at least four, or at least five additional therapies.

### Claim 6 (depends on 1)

The method of claim 1, further comprising detecting one or more neoantigens and/or a T-cell response in the subject after administration of the Compound 1, or a pharmaceutically acceptable salt thereof.

### Claim 7 (depends on 6)

The method of claim 6, further comprising continuing administration of the Compound 1, or a pharmaceutically acceptable salt thereof, after one or more neoantigens and/or a T-cell response is detected.

### Claim 8 (depends on 6)

The method of claim 6, further comprising administering a neoantigen vaccine, wherein the neoantigen vaccine comprises one or more neoantigens detected in the subject after administration of the Compound 1, or a pharmaceutically acceptable salt thereof.

### Claim 9 (depends on 1)

The method of claim 1, wherein the subject has a non-synonymous mutational burden of about 150 mutations or less.

### Claim 10 (depends on 1)

The method of claim 1, wherein the neoplastic disorder is myelodysplastic syndrome.

### Claim 11 (depends on 1)

The method of claim 1, wherein the Compound 1, or a pharmaceutically acceptable salt thereof, is administered as part of a conjugate.

### Claim 12 (depends on 4)

The method of claim 4, wherein the anti-CTLA4 antibody is ipilimumab.