# US 2024/0197784 A1 · Methods and compositions for treating glioblastoma

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- Number: US 2024/0197784 A1
- Document ID: US20240197784A1
- Status: Published application
- Kind: A1
- Application number: 18/556,473
- Filed: 2022-04-22
- Published: 2024-06-20
- Earliest claimed: 2021-04-22
- Assignees: NeoTX Therapeutics Ltd.
- Applicants: NeoTX Therapeutics Ltd.
- Inventors: Michal Shahar; Asher Nathan
- Web page: https://patentgrep.com/patent/US20240197784A1

## CPC

- 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 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 47/6829: {Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A}
- A61P 35/00: Antineoplastic agents
- C07K 16/1271: Micrococcaceae (F); Staphylococcaceae (F), e.g. Staphylococcus (G)
- C07K 16/2818: {against CD28 or CD152}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/30: from tumour cells
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- A61K 2239/13: Antibody-based
- A61K 2239/47: Brain; Nervous system
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- 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

The disclosure provides methods and compositions for treating glioblastoma (GBM) using a 5T4-targeting agent, e.g., a superantigen conjugate comprising an anti-5T4 antibody.

## Claims

### Claim 1

A method of reducing tumor volume in a subject with glioblastoma, the method comprising administering to the subject an effective amount of a 5T4-targeting agent.

### Claim 2

A method of killing tumor cells in a subject with glioblastoma, the method comprising administering to the subject an effective amount of a 5T4-targeting agent.

### Claim 3

A method of treating glioblastoma in a subject in need thereof, the method comprising administering to the subject an effective amount of a 5T4-targeting agent.

### Claim 4 (depends on 1, 2, 3)

The method of any one of claims 1-3, wherein at least 0.5%, 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, or 30% of (i) tumor cells in the subject, (ii) tumor cells in a tumor in the subject, and/or (iii) tumor cells in a tumor sample (e.g., a tumor tissue sample) from the subject, exhibit cell membrane expression of 5T4, as measured by immunohistochemistry.

### Claim 5 (depends on 1, 2, 3, 4)

The method of any one of claims 1-4, wherein 0.5% to 10% (e.g., 0.5% to 3%, 3% to 5%, or 5% to 10%) of (i) tumor cells in the subject, (ii) tumor cells in a tumor in the subject, and/or (iii) tumor cells in a tumor sample (e.g., a tumor tissue sample) from the subject, exhibit cell membrane expression of 5T4, as measured by immunohistochemistry.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The method of any one of claims 1-5, wherein the 5T4-targeting agent comprises an antibody, a bispecific T-cell engager (BiTE), an immune cell, or a vaccine.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The method of any one of claims 1-6, wherein the 5T4-targeting agent is a superantigen conjugate comprising a superantigen covalently linked to an anti-5T4 antibody.

### Claim 8 (depends on 7)

The method of claim 7, wherein the superantigen comprises Staphylococcal enterotoxin A or an immunologically variant and/or fragment thereof.

### Claim 9 (depends on 7, 8)

The method of claim 7 or 8, wherein the superantigen comprises the amino acid sequence of SEQ ID NO: 3, or an immunologically reactive variant and/or fragment thereof.

### Claim 10 (depends on 7, 8, 9)

The method of any one of claims 7-9, wherein the anti-5T4 antibody comprises a Fab fragment that binds a 5T4 cancer antigen.

### Claim 11 (depends on 7, 8, 9, 10)

The method of any one of claims 7-10, wherein the anti-5T4 antibody comprises a heavy chain comprising amino acid residues 1-222 of SEQ ID NO: 8 and a light chain comprising amino acid residues 1-214 of SEQ ID NO: 9.

### Claim 12 (depends on 7, 8, 9, 10, 11)

The method of any one of claims 7-11, wherein the superantigen conjugate comprises a first protein chain comprising SEQ ID NO: 8 and a second protein chain comprising SEQ ID NO: 9.

### Claim 13 (depends on 6)

The method of claim 6, wherein the 5T4-targeting agent is an immune cell.

### Claim 14 (depends on 13)

The method of claim 13, wherein the immune cell is a chimeric antigen receptor (CAR)-expressing immune cell.

### Claim 15 (depends on 13, 14)

The method of claim 13 or 14, wherein the immune cell is a T-cell or a Natural Killer (NK) cell.

### Claim 16 (depends on 15)

The method of claim 15, wherein the immune cell is a T-cell.

### Claim 17 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16)

The method of any one of claims 1-16, wherein the method further comprises administering to the subject an immunopotentiator.

### Claim 18 (depends on 17)

The method of claim 17, wherein the immunopotentiator is a CTLA-4- or a PD-1-based inhibitor.

### Claim 19 (depends on 18)

The method of claim 18, wherein the PD-1-based inhibitor is a PD-1 or PD-L1 inhibitor.

### Claim 20 (depends on 19)

The method of claim 19, wherein the PD-1 inhibitor is an anti-PD-1 antibody.

### Claim 21 (depends on 20)

The method of claim 20, wherein the anti-PD-1 antibody is selected from nivolumab pembrolizumab, cemiplimab, spartalizumab, MEDI0680, pidilizumab, dostarlimab, sintilimab, toripalimab, camrelizumab, pimivalimab, tislelizumab, and prolgolimab.

### Claim 22 (depends on 19)

The method of claim 19, wherein the PD-L1 inhibitor is an anti-PD-L1 antibody.

### Claim 23 (depends on 22)

The method of claim 22, wherein the anti-PD-L1 antibody is selected from atezolizumab, avelumab, durvalumab, CS1001, tagitanlimab, cosibelimab, TQB2450, envafolimab, SHR-1316, STI-A1014, BGB-A333, MSB2311, HLX-20, and BMS-936559.

### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23)

The method of any one of claims 1-23, wherein the subject is a human subject.