# US 12,178,803 B2 · CD47 blockade with PARP inhibition for disease treatment

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- Number: US 12,178,803 B2
- Document ID: US12178803B2
- Status: Granted
- Kind: B2
- Application number: 17/272,413
- Filed: 2019-08-29
- Published: 2021-10-14
- Granted: 2024-12-31
- Earliest claimed: 2018-09-04
- Assignees: Pfizer Inc.
- Applicants: Trillium Therapeutics Ulc
- Inventors: Lisa Danae Schultz Johnson; Lei Cui
- Web page: https://patentgrep.com/patent/US12178803B2

## CPC

- A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
- A61K 31/5025: ortho- or peri-condensed with heterocyclic ring systems
- A61K 31/55: having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K 38/1709: {from mammals}
- A61K 41/0038: {Radiosensitizing, i.e. administration of pharmaceutical agents that enhance the effect of radiotherapy (radiotherapy per se A61N5/10)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- C07K 14/70503: {Immunoglobulin superfamily}
- 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

CD47+ disease cells such as cancer cells are treated using a combination of CD47 blocking agent and poly-(ADP-ribose) polymerase (PARP) inhibitor. The CD47 blocking agent can be SIRPαFc and the PARP inhibitor niraparib. The anti-cancer effect of niraparib is enhanced in the presence of SIRPαFc. Specific combinations include SIRPαFc forms that comprise an Fc that is either IgG1 or preferably IgG4 isotype. These combinations are useful particularly to treat solid tumours and blood cancers including lymphomas, leukemias and myelomas.

## Claims

### Claim 1

A method for treating a subject presenting with CD47+ disease cells, comprising administering to the subject a PARP inhibitor and a CD47 blocking agent in combination with radiation therapy, wherein the CD47 blocking agent is a CD47-binding SIRPα polypeptide and wherein the CD47-binding SIRPα polypeptide is an Fc fusion protein comprising a CD47-binding region of soluble human SIRPα.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the PARP inhibitor is an inhibitor of PARP-1.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the PARP inhibitor is talazoparib, veliparib, niraparib, olaparib, rucaparib, or iniparib.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the Fc fusion protein comprises SEQ ID NO: 8.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the Fc fusion protein comprises SEQ ID NO: 9.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the Fc fusion protein comprises soluble SIRPα having one or more activity-enhancing amino acid substitutions selected from L4V/I, V6I/L, A21V, V27|/L, I31T/S/F, E47V/L, K53R, E54Q, H56P/R, S66T/G, K68R, V92I, F94V/L, V63I, and F103V.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the radiation therapy is external beam radiation therapy.

### Claim 8 (depends on 1)

The method according to claim 1, wherein the CD47+ disease cells are CD47+ cancer cells.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the CD47+ cancer cells are blood cancers or solid tumours.

### Claim 10 (depends on 8)

The method according to claim 8, wherein the cancer cells are cells of a cancer type selected from acute lymphocytic leukemia (ALL); acute myeloid leukemia (AML); chronic lymphocytic leukemia (CLL); chronic myelogenous leukemia (CML); myeloproliferative disorder/neoplasm (MPDS); and myelodysplastic syndrome.

### Claim 11 (depends on 8)

The method according to claim 8 wherein the cancer is a lymphoma selected from a non-Hodgkin's lymphoma, both indolent and aggressive non-Hodgkin's lymphoma, T cell lymphoma, CD20+ lymphoma, Burkitt's lymphoma, and small cell follicular lymphoma, and large cell follicular lymphoma.

### Claim 12 (depends on 8)

The method according to claim 8, wherein the cancer is a myeloma selected from multiple myeloma (MM), giant cell myeloma, heavy-chain myeloma, and light chain or Bence-Jones myeloma.

### Claim 13 (depends on 8)

The method according to claim 8, wherein the cancer is melanoma, ovarian cancer, CTCL, mycosis fungoides, breast cancer, or glioblastoma.