# US 2019/0314418 A1 · Compositions and methods for inhibition of lineage specific antigens

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- Number: US 2019/0314418 A1
- Document ID: US20190314418A1
- Status: Published application
- Kind: A1
- Application number: 16/451,906
- Filed: 2019-06-25
- Published: 2019-10-17
- Earliest claimed: 2015-10-16
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: The Trustees of Columbia University in the City of New York
- Inventors: Siddhartha Mukherjee; Florence Borot; Abdullah Mahmood Ali
- Web page: https://patentgrep.com/patent/US20190314418A1

## CPC

- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/421: {Immunoglobulin superfamily}
- A61K 40/4252: {Phosphatases}
- 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
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/30: from tumour cells
- C07K 16/3061: {Blood cells}
- C12N 5/0647: {Haematopoietic stem cells; Uncommitted or multipotent progenitors}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- A61K 2039/505: {comprising antibodies}
- A61K 2239/31: characterized by the route of administration
- 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 2317/622: Single chain antibody (scFv)
- C07K 2319/02: containing a signal sequence
- C07K 2319/03: containing a transmembrane segment
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C12N 2510/00: Genetically modified cells
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Disclosed herein are methods of administering an agent targeting a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

## Claims

### Claim 1

A genetically engineered human hematopoietic cell that is engineered such that it is deficient in a lineage-specific cell-surface antigen which is expressed by its naturally-occurring hematopoietic cell counterpart, wherein the lineage-specific cell-surface antigen is not required for survival of a human subject.

### Claim 2 (depends on 1)

The genetically engineered human hematopoietic cell of claim 1, wherein the naturally-occurring hematopoietic cell counterpart is required for survival of a human subject.

### Claim 3 (depends on 1)

The genetically engineered human hematopoietic cell of claim 1, wherein the naturally-occurring hematopoietic cell counterpart is not required for survival of a human subject.

### Claim 4 (depends on 1)

The genetically engineered human hematopoietic cell of claim 1, wherein the lineage-specific cell-surface antigen is present on cancer cells.

### Claim 5 (depends on 1)

The genetically engineered human hematopoietic cell of claim 1, wherein the lineage-specific cell-surface antigen is an antigen that is naturally associated with human leukocytes, a subpopulation of human leukocytes, human lymphoid cells, human plasma cells, or human myeloid cells.

### Claim 6 (depends on 1)

The genetically engineered human hematopoietic cell of claim 1, wherein the cell-surface lineage-specific antigen is a cluster of differentiation (CD) antigen.

### Claim 7 (depends on 6)

The genetically engineered human hematopoietic cell of claim 6, wherein the CD antigen is selected from the group consisting of CD13, CD19, CD20, CD22, CD38, CD123, CD33, CD45, CD70, CD312, CD191, CD85D, CD117, CD96, and CD269.

### Claim 8 (depends on 7)

The genetically engineered human hematopoietic cell of claim 7, wherein the CD antigen is CD33 or CD19.

### Claim 9 (depends on 1)

The genetically engineered human hematopoietic cell of claim 1, wherein an endogenous gene encoding the lineage-specific cell-surface antigen is engineered using genome editing.

### Claim 10 (depends on 9)

The genetically engineered human hematopoietic cell of claim 9, wherein the whole or a portion of the endogenous gene encoding the lineage-specific cell-surface antigen is deleted.

### Claim 11 (depends on 9)

The genetically engineered human hematopoietic cell of claim 9, wherein the level of the lineage-specific cell-surface antigen is reduced as compared with the level of the lineage-specific cell-surface antigen expressed by its naturally-occurring hematopoietic cell counterpart.

### Claim 12 (depends on 9)

The genetically engineered human hematopoietic cell of claim 9, wherein the genome editing is a CRISPR system.

### Claim 13 (depends on 12)

The genetically engineered human hematopoietic cell of claim 12, wherein the CRISPR system comprises a guide nucleic acid that hybridizes to a coding sequence of the endogenous gene encoding the lineage-specific cell-surface antigen.

### Claim 14 (depends on 12)

The genetically engineered human hematopoietic cell of claim 12, wherein the CRISPR system comprises a guide nucleic acid that hybridizes to a non-coding sequence of the endogenous gene encoding the lineage-specific cell-surface antigen.

### Claim 15 (depends on 12)

The genetically engineered human hematopoietic cell of claim 12, wherein the CRISPR system cleaves the endogenous gene encoding the lineage-specific cell-surface antigen in a coding region or a non-coding region of the gene.

### Claim 16 (depends on 15)

The genetically engineered human hematopoietic cell of claim 15, wherein the CRISPR system cleaves the endogenous gene encoding the lineage-specific cell-surface antigen in one or more exon(s) of the gene.

### Claim 17 (depends on 16)

The genetically engineered human hematopoietic cell of claim 16, wherein the lineage-specific cell-surface antigen is CD33 or CD19.

### Claim 18 (depends on 15)

The genetically engineered human hematopoietic cell of claim 15, wherein the CRISPR system cleaves the endogenous gene encoding the lineage-specific cell-surface antigen in one or more intron(s) or in a non-transcribed region of the gene.

### Claim 19 (depends on 18)

The genetically engineered human hematopoietic cell of claim 18, wherein the lineage-specific cell-surface antigen is CD33 or CD19.

### Claim 20 (depends on 12)

The genetically engineered human hematopoietic cell of claim 12, wherein the CRISPR system produces an insertion, deletion and/or substitution of one or more nucleotides in a coding region or a non-coding region of the endogenous gene encoding the lineage-specific cell-surface antigen.

### Claim 21 (depends on 20)

The genetically engineered human hematopoietic cell of claim 20, wherein the CRISPR system produces an insertion, deletion and/or substitution of one or more nucleotides in one or more exons of the endogenous gene encoding the lineage-specific cell-surface antigen.

### Claim 22 (depends on 21)

The genetically engineered human hematopoietic cell of claim 21, wherein the lineage-specific cell-surface antigen is CD33 or CD19.

### Claim 23 (depends on 20)

The genetically engineered human hematopoietic cell of claim 20, wherein the CRISPR system produces an insertion, deletion and/or substitution of one or more nucleotides in one or more introns of the endogenous gene encoding the lineage-specific cell-surface antigen.

### Claim 24 (depends on 23)

The genetically engineered human hematopoietic cell of claim 23, wherein the lineage-specific cell-surface antigen is CD33 or CD19.

### Claim 25 (depends on 1)

The genetically engineered human hematopoietic cell of claim 1, wherein the hematopoietic cell is selected from the group consisting of a hematopoietic stem cell, a progenitor cell, a myeloid progenitor cell, a lymphoid progenitor cell, a myeloid cell, and a lymphoid cell.

### Claim 26 (depends on 1)

A population of genetically engineered human hematopoietic cells comprising the hematopoietic cells of claim 1.

### Claim 27 (depends on 8)

A population of genetically engineered human hematopoietic cells comprising the hematopoietic cells of claim 8.

### Claim 28 (depends on 25)

A population of genetically engineered human hematopoietic cells comprising one or more of the hematopoietic cells of claim 25.

### Claim 29 (depends on 27)

A method for generating the population of genetically engineered human hematopoietic cells of claim 27, the method comprising introducing into human hematopoietic cells a CRISPR system comprising at least one guide nucleic acid that hybridizes to a coding or non-coding sequence of an endogenous gene encoding CD33 or CD19, wherein the CRISPR system cleaves said endogenous gene.

### Claim 30 (depends on 1, 27)

A method for generating the population of genetically engineered human hematopoietic cells of claim 27, the method comprising introducing into the human hematopoietic cells a CRISPR system comprising at least one guide nucleic acid that hybridizes to a coding or non-coding sequence of an endogenous gene encoding the lineage-specific cell-surface antigen of claim 1, wherein the CRISPR system produces an insertion, deletion and/or substitution of one or more nucleotides in said endogenous gene.