# US 11,897,937 B2 · SIRPalpha-41BBL fusion protein and methods of use thereof

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- Number: US 11,897,937 B2
- Document ID: US11897937B2
- Status: Granted
- Kind: B2
- Application number: 17/400,179
- Filed: 2021-08-12
- Published: 2021-12-02
- Granted: 2024-02-13
- Earliest claimed: 2017-01-05
- Assignees: KAHR Medical Ltd.
- Applicants: KAHR Medical Ltd.
- Inventors: Noam Shani; Yosi Gozlan; Michal Dranitzki Elhalel; Edwin Bremer; Ido Kaminsky
- Web page: https://patentgrep.com/patent/US11897937B2

## CPC

- A61P 35/00: Antineoplastic agents
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- A61K 40/10: characterised by the cell type used
- A61K 40/42: Cancer antigens
- A61K 40/4254: {Adhesion molecules, e.g. NRCAM, EpCAM or cadherins}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61P 35/02: specific for leukemia
- C07K 14/70575: {NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525)}
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/2887: {against CD20}
- C07K 16/2893: {against CD52}
- C12N 5/0638: {Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]}
- C12N 15/85: for animal cells
- 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 2319/00: Fusion polypeptide
- C07K 2319/21: containing a His-tag
- 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)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

SIRP1alpha-41BBL fusion proteins are provided. Accordingly, there is provided a SIRPalpha-41BBL fusion protein comprising a single amino acid linker between the SIRPalpha and the 41BBL. Also there is provided a SIRPalpha-41BBL fusion protein in a form of at least a homo-trimer. Also provided are polynucleotides and nucleic acid constructs encoding the SIRP1alpha-41BBL fusion protein, host-cells expressing the SIRP1alpha-41BBL fusion protein and methods of use thereof.

## Claims

### Claim 1

A method of treating cancer in a subject in need thereof, wherein cells of said cancer express CD47, the method comprising administering to the subject a therapeutically effective amount of a Signal regulatory protein α (SIRPα)-4-1BB ligand (41BBL) fusion protein, wherein said SIRPα-41BBL fusion protein is characterized by a single amino acid linker between said SIRPα and said 41BBL and being in a form of a homo-trimer, and wherein said SIRPα-41BBL fusion protein amino acid sequence is at least 90% identical to SEQ ID NO: 1, thereby treating the cancer in the subject.

### Claim 2

A method of treating cancer in a subject in need thereof, wherein cells of said cancer express CD47, the method comprising administering to the subject a therapeutically effective amount of a Signal regulatory protein α (SIRPα)-4-1BB ligand (41BBL) fusion protein, wherein said SIRPα-41BBL fusion protein is characterized by a single amino acid linker between said SIRPα and said 41BBL, and wherein said SIRPα-41BBL fusion protein amino acid sequence is at least 90% identical to SEQ ID NO: 1, thereby treating the cancer in the subject.

### Claim 3

A method of treating cancer in a subject in need thereof, wherein cells of said cancer express CD47, the method comprising administering to the subject a therapeutically effective amount of a Signal regulatory protein α (SIRPα)-4-1BB ligand (41BBL) fusion protein, wherein said SIRPα-41BBL fusion protein is in a form of a homo-trimer, and wherein said SIRPα-41BBL fusion protein amino acid sequence is at least 90% identical to SEQ ID NO: 1, thereby treating the cancer in the subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein said homo-trimer is at least 140 kD in molecular weight as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).

### Claim 5 (depends on 1)

The method of claim 1, wherein said linker is glycine.

### Claim 6 (depends on 1)

The method of claim 1, wherein said fusion protein is capable of:
(i) binding CD47 and 4-1BB;
(ii) activating 4-1BB signaling pathway in a cell expressing said 4-1BB;
(iii) co-stimulating immune cells expressing said 4-1BB; and
(iv) enhancing phagocytosis of pathologic cells expressing said CD47 by phagocytes compared to same in the absence of said SIRPα-41BBL fusion protein.

### Claim 7 (depends on 1)

The method of claim 1, wherein said SIRPα-4-1BBL fusion protein amino acid sequence comprises SEQ ID NO: 1.

### Claim 8 (depends on 1)

The method of claim 1, wherein said cancer is selected from the group consisting of lymphoma, leukemia, colon cancer, pancreatic cancer, ovarian cancer, lung cancer and squamous cell carcinoma.

### Claim 9 (depends on 1)

The method of claim 1, wherein said cancer is selected from the group consisting of colon cancer, leukemia, lung cancer and ovarian cancer.

### Claim 10 (depends on 2)

The method of claim 2, wherein said cancer is selected from the group consisting of colon cancer, leukemia, lung cancer and ovarian cancer.

### Claim 11 (depends on 3)

The method of claim 3, wherein said cancer is selected from the group consisting of colon cancer, leukemia, lung cancer and ovarian cancer.