# US 12,180,263 B2 · Cells lacking B2M surface expression and methods for allogeneic administration of such cells

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- Number: US 12,180,263 B2
- Document ID: US12180263B2
- Status: Granted
- Kind: B2
- Application number: 15/524,968
- Filed: 2015-11-06
- Published: 2018-05-24
- Granted: 2024-12-31
- Earliest claimed: 2014-11-06
- Assignees: President and Fellows of Harvard College
- Applicants: President and Fellows of Harvard College
- Inventors: Chad A. Cowan; Leonardo M. R. Ferreira; Torsten B. Meissner; Jack L Strominger
- Web page: https://patentgrep.com/patent/US12180263B2

## CPC

- C07K 14/70539: {MHC-molecules, e.g. HLA-molecules}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61P 31/18: for HIV
- C12N 5/0647: {Haematopoietic stem cells; Uncommitted or multipotent progenitors}
- C12N 9/22: Ribonucleases {[RNase]; Deoxyribonucleases [DNase]}
- C12N 9/222: {Clustered regularly interspaced short palindromic repeats [CRISPR]-associated [CAS] enzymes}
- C12N 15/11: DNA or RNA fragments; Modified forms thereof (DNA or RNA not used in recombinant technology, C07H21/00); {Non-coding nucleic acids having a biological activity}
- C12N 15/1138: {against receptors or cell surface proteins}
- A61K 48/0066: {Manipulation of the nucleic acid to modify its expression pattern, e.g. enhance its duration of expression, achieved by the presence of particular introns in the delivered nucleic acid}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood cells}
- C12N 2310/10: Type of nucleic acid
- C12N 2310/20: involving clustered regularly interspaced short palindromic repeats [CRISPR]
- C12N 2510/00: Genetically modified cells
- 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
- 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 cells and populations of cells comprising a genome in which the B2M gene has been edited to eliminate surface expression of MHC Class I protein in the cells or population of cells, and methods for allogeneic administration of such cells to reduce the likelihood that the cells will trigger a host immune response when the cells are administered to a subject in need of such cells.

## Claims

### Claim 1

An isolated primary human cell or population of primary human cells comprising a genome in which the β2-microglobulin (B2M) gene on chromosome 15 has been edited to delete a contiguous stretch of genomic DNA consisting of the nucleotide sequence as set forth in SEQ ID NO: 1, wherein the contiguous stretch of genomic DNA is deleted between a first human B2M gene target site complementary to a nucleotide sequence consisting of SEQ ID NO: 16 and a second human B2M gene target site complementary to a nucleotide sequence consisting of SEQ ID NO: 21, wherein the isolated primary human cell or population of primary human cells are selected from the group consisting of a T cell and a CD34+ cell, thereby eliminating surface expression of MHC Class I molecules in the cell or population of cells.

### Claim 2 (depends on 1)

The cell or population of cells of claim 1, wherein the cell or population of cells is obtained from a subject suffering from, being treated for, diagnosed with, at risk of developing, or suspected of having, a disorder selected from the group consisting of a genetic disorder, an infection, and cancer.

### Claim 3 (depends on 2)

The cell or population of cells of claim 2, wherein the disorder HIV or AIDs.

### Claim 4 (depends on 1)

The cell or population of cells of claim 1, wherein the cell or population of cells are CD4+ T cells.

### Claim 5 (depends on 1)

The cell or population of cells of claim 1, wherein the cell or population of cells are CD34+ cells.

### Claim 6 (depends on 1)

The cell or population of cells of claim 1, wherein the cell or population of cells is obtained from a subject suffering from or diagnosed with cancer.

### Claim 7 (depends on 1)

The cell or population of cells of claim 1, wherein the cell or population of cells is obtained from a subject being treated for cancer.

### Claim 8 (depends on 1)

The cell or population of cells of claim 1, wherein the cell or population of cells is obtained from a healthy subject.