# US 11,026,973 B2 · Engineered phagocytic receptor compositions and methods of use thereof

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- Number: US 11,026,973 B2
- Document ID: US11026973B2
- Status: Granted
- Kind: B2
- Application number: 16/827,381
- Filed: 2020-03-23
- Published: 2020-11-05
- Granted: 2021-06-08
- Earliest claimed: 2019-04-30
- Assignees: Myeloid Therapeutics, Inc.
- Applicants: Myeloid Therapeutics, Inc.
- Inventors: Daniel Getts; Yuxiao Wang
- Web page: https://patentgrep.com/patent/US11026973B2

## CPC

- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- A61K 40/17: Monocytes; Macrophages
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/4202: {Receptors, cell surface antigens or cell surface determinants}
- A61K 40/4254: {Adhesion molecules, e.g. NRCAM, EpCAM or cadherins}
- A61P 35/00: Antineoplastic agents
- C07K 14/705: Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 14/70575: {NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154 (NGF C07K14/48, TNF C07K14/525)}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- A61K 2239/22: Intracellular domain
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/53: Hinge
- C07K 2317/55: Fab or Fab'
- C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present disclosure provides compositions and methods for making and using engineered killer phagocytic cells for immunotherapy in cancer or infection by expressing a chimeric antigen receptor having an enhanced phagocytic activity, the chimeric receptor is encoded by a recombinant nucleic acid.

## Claims

### Claim 1

A pharmaceutical composition comprising:
(a) myeloid cells from a human subject comprising a recombinant polynucleic acid, wherein the myeloid cells are CD14+ and CD16−, and wherein the recombinant polynucleic acid comprises a sequence encoding a chimeric fusion protein (CFP), the CFP comprising:
(i) an extracellular domain comprising a CD5 binding domain, wherein the CD5 binding domain comprises an scFv comprising a variable heavy chain (VH) sequence with SEQ ID NO: 1 and a variable light chain (VL) sequence with SEQ ID NO: 2,
(ii) a CD8 transmembrane domain operatively linked to the extracellular domain; and
(iii) an intracellular domain comprising at least two intracellular signaling domains, wherein the at least two intracellular signaling domains comprise:
(A) a first intracellular signaling domain derived from FcγR or FcεR, and
(B) a second intracellular signaling domain comprising a PI3K recruitment domain; and
(b) a pharmaceutically acceptable carrier;
wherein the myeloid cells express the CFP and exhibit at least a 1.1 fold increase in phagocytosis of a target cell expressing CD5; and
wherein the pharmaceutical composition comprises an effective amount of the myeloid cells to inhibit growth of a solid tumor when administered to a human subject with the solid tumor.

### Claim 2 (depends on 1)

The pharmaceutical composition of claim 1, wherein the CD5 binding domain binds to CD5 with an affinity of 250 nM or less.

### Claim 3 (depends on 1)

The pharmaceutical composition of claim 1, wherein the intracellular domain further comprises one or more additional intracellular signaling domains.

### Claim 4 (depends on 3)

The pharmaceutical composition of claim 3, wherein the one or more additional intracellular signaling domains comprise an intracellular signaling domain derived from a receptor other than Megf10, MerTk, FcαR, and Bai1.

### Claim 5 (depends on 3)

The pharmaceutical composition of claim 3, wherein the one or more additional intracellular signaling domains comprises a proinflammatory signaling domain.

### Claim 6 (depends on 3)

The pharmaceutical composition of claim 3, wherein the one or more additional intracellular signaling domains comprise an intracellular signaling domain derived from an intracellular signaling domain of CD40.

### Claim 7 (depends on 6)

The pharmaceutical composition of claim 6, wherein the intracellular signaling domain derived from an intracellular signaling domain of CD40 comprises a sequence with at least 90% sequence identity to SEQ ID NO: 5.

### Claim 8 (depends on 1)

The pharmaceutical composition of claim 1, wherein the intracellular domain comprises an intracellular signaling domain with at least 90% sequence identity to SEQ ID NO: 3.

### Claim 9 (depends on 1)

The pharmaceutical composition of claim 1, wherein the PI3K recruitment domain comprises a sequence with at least 90% sequence identity to SEQ ID NO: 4.

### Claim 10 (depends on 1)

The pharmaceutical composition of claim 1, wherein the CD8 transmembrane domain comprises a sequence with at least 90% sequence identity to SEQ ID NO: 6.

### Claim 11 (depends on 1)

The pharmaceutical composition of claim 1, wherein the extracellular domain further comprises a hinge domain derived from CD8, wherein the hinge domain is operatively linked to the transmembrane domain and the CD5 binding domain.

### Claim 12 (depends on 11)

The pharmaceutical composition of claim 11, wherein the hinge domain derived from CD8 comprises a sequence with at least 90% sequence identity to SEQ ID NO: 7.

### Claim 13 (depends on 1)

The pharmaceutical composition of claim 1, wherein the recombinant polynucleic acid is an mRNA or circRNA.

### Claim 14 (depends on 1)

The pharmaceutical composition of claim 1, wherein the CFP comprises a sequence having at least 90% sequence identity to SEQ ID NO: 14.

### Claim 15 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises at least 6×106 of the myeloid cells.

### Claim 16 (depends on 1)

The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises an effective amount of the myeloid cells to inhibit growth of a solid tumor that is T cell lymphoma when administered to a human subject with the solid tumor that is T cell lymphoma.