# US 2026/0144871 A1 · Human Placental Derived Natural Killer Cells with High Affinity and Cleavage Resistant CD16 and Secreted IL-15, and uses thereof

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- Number: US 2026/0144871 A1
- Document ID: US20260144871A1
- Status: Published application
- Kind: A1
- Application number: 18/921,811
- Filed: 2024-10-21
- Published: 2026-05-28
- Earliest claimed: 2023-10-20
- Assignees: Celularity Inc.
- Applicants: Celularity Inc.
- Inventors: Lin KANG; Marina GERGUES; Yuechao ZHAO; Irene RAITMAN KHUTORSKOY; Shengchen Lin; Valentina ROUSSEVA; Shuyang HE; Adrian KILCOYNE; Robert J. HARIRI
- Web page: https://patentgrep.com/patent/US20260144871A1

## CPC

- A61K 40/15: Natural-killer [NK] cells; Natural-killer T [NKT] cells
- C07K 16/32: against translation products of oncogenes
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 40/30: characterised by the recombinant expression of specific molecules in the cells of the immune system
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/42: Cancer antigens
- A61P 35/00: Antineoplastic agents
- C07K 16/2887: {against CD20}
- C12N 5/0646: {Natural killers cells [NK], NKT cells}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- A61K 2239/31: characterized by the route of administration
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/59: Reproductive system, e.g. uterus, ovaries, cervix or testes
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- 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)
- 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)
- 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

Provided herein are new and useful placental derived natural killer (NK) Cell or population thereof, or one or more cells within the population that express a cleavage resistant CD 16 polypeptide and a secreted IL-15 polypeptide, as well as uses thereof.

## Claims

### Claim 1

A placental derived natural killer (NK) cell or population thereof wherein the placental derived NK cell comprises, or one or more cells within the population of the placental derived NK Cell comprises:
(a) a first polynucleotide encoding a cleavage resistant CD 16 polypeptide and a second polynucleotide encoding a secreted IL-15 polypeptide; or
(b) a polynucleotide that encodes the cleavage resistant CD16 polypeptide and the secreted IL-15 polypeptide.

### Claim 2 (depends on 1)

The cell or population of claim 1, wherein the polynucleotide construct further comprises a polynucleotide that encodes a self-cleaving peptide.

### Claim 3 (depends on 2)

The cell population of claim 2, wherein the self-cleaving protein is a T2A peptide.

### Claim 4 (depends on 2)

The cell or population of cells of claim 2, wherein the polynucleotide construct encodes a polypeptide comprising the amino acid sequences of the cleavage resistant CD16, the T2A protein, and the secreted IL-15, wherein the cleavage resistant CD16 variant comprises a Valine residue at position 176 relative to the wild-type CD 16 polypeptide.

### Claim 5 (depends on 4)

The cell or population of cells of claim 4, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:7.

### Claim 6 (depends on 1)

The cell or population of cells of claim 1, wherein the CD 16 is selected from the group consisting of a CD 16a isoform and a CD 16b isoform.

### Claim 7 (depends on 6)

The cell or population of cells of claim 6, wherein the CD16b isoform is selected from the group consisting of an NA1 allelic variant and an NA2 allelic variant.

### Claim 8 (depends on 1)

The cell or population of cells of claim 1, wherein the cleavage resistant CD 16 variant comprises a residue other than serine or proline at position 197 relative to the wild-type CD 16 polypeptide.

### Claim 9 (depends on 1)

The cell or population of cells of claim 1, wherein the cleavage resistant CD 16 variant comprises an amino acid sequence comprising:
(a)
[SEQ ID NO: 1]
TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACD
or
at least 15 consecutive residues of [SEQ ID NO: 1];
(b)
[SEQ ID NO: 2]
IEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKP,
or
at least 15 consecutive residues of [SEQ ID NO: 2];
(c)
[SEQ ID NO: 3]
PELELQVLGLQLPTPVWFH,
or
at least 15 consecutive amino acids of the sequence
PELELQVLGLQLPTPVWFH [SEQ ID NO: 3].

### Claim 10 (depends on 1)

The cell or population of cells of claim 1, wherein the cleavage resistant CD 16 variant comprises an amino acid selected from the group consisting of:
[SEQ ID NO: 4]
MWQLLLPTALLLLVSAGMRTEDLPKAVVFLEPQWYRVLEKDSVTLKCQG
AYSPEDNSTQWFHNESLISSQASSYFIDAATVDDSGEYRCQTNLSTLSD
PVQLEVHIGWLLLQAPRWVFKEEDPIHLRCHSWKNTALHKVTYLQNGKG
RKYFHHNSDFYIPKATLKDSGSYFCRGLVGSKNVSSETVNITITQGLAV
CTISSFFPPGYQVSFCLVMVLLFAVDTGLYFS VKTNIRS
STRDWKDHKFKWRKDPQDK.

### Claim 11 (depends on 1)

The placental derived NK Cell or population of claim 1, wherein the placental derived NK T-cells are placental CD34+ cell-derived (NK) cells.

### Claim 12 (depends on 5)

The placental derived NK Cell or population thereof of claim 5, wherein the polynucleotide construct encodes the amino acid sequence of SEQ ID NO:7.

### Claim 13 (depends on 12)

The placental derived NK cell or population thereof of claim 12, wherein the polynucleotide construct comprises the nucleotide sequence of:
[SEQ ID NO: 8]
ATGTGGCAGCTGCTCCTCCCAACTGCTCTGCTACTTCTAGTTTCAGCTG
GCATGCGGACCGAGGACCTGCCCAAGGCCGTGGTGTTCCTGGAGCCCCA
GTGGTACCGGGTGCTGGAGAAGGACAGCGTGACCCTGAAGTGCCAGGGC
GCCTACAGCCCCGAGGACAACAGCACCCAGTGGTTCCACAACGAGAGCC
TGATCAGCAGCCAGGCCAGCAGCTACTTCATCGACGCCGCCACCGTGGA
CGACAGCGGCGAGTACCGGTGCCAGACCAACCTGAGCACCCTGAGCGAC
CCCGTGCAGCTGGAGGTGCACATCGGCTGGCTGCTGCTGCAGGCCCCCC
GGTGGGTGTTCAAGGAGGAGGACCCCATCCACCTGCGGTGCCACAGCTG
GAAGAACACCGCCCTGCACAAGGTGACCTACCTGCAGAACGGCAAGGGC
CGGAAGTACTTCCACCACAACAGCGACTTCTACATCCCCAAGGCCACCC
TGAAGGACAGCGGCAGCTACTTCTGCCGGGGCCTGGTGGGCAGCAAGAA
CGTGAGCAGCGAGACCGTGAACATCACCATCACCCAGGGCGTGATCACC
GCCCTGAGCAGCAGCTTCTTCCCCCCCGGCTACCAGGTGAGCTTCTGCC
TGGTGATGGTGCTGCTGTTCGCCGTGGACACCGGCCTGTACTTCAGCGT
GAAGACCAACATCCGGAGCAGCACCCGGGACTGGAAGGACCACAAGTTC
AAGTGGCGGAAGGACCCCCAGGACAAGGGAAGTGGTGAAGGACGGGGAT
CACTGCTCACTTGCGGGGACGTCGAAGAGAACCCAGGCCCAATGCGAAT
TTCTAAGCCTCACCTCCGAAGTATTAGCATACAGTGCTATCTGTGTCTT
TTGCTGAACTCTCACTTTCTGACCGAAGCGGGAATCCATGTATTCATCC
TCGGGTGTTTTTCAGCGGGCCTCCCAAAGACAGAGGCGAACTGGGTCAA
CGTCATATCTGACCTCAAGAAAATTGAGGATTTGATACAATCAATGCAT
ATTGATGCGACACTCTACACTGAGAGCGATGTTCACCCAAGCTGTAAGG
TAACGGCTATGAAATGTTTTCTCTTGGAGCTCCAGGTTATTTCATTGGA
GTCAGGGGACGCAAGTATACACGACACTGTGGAAAATCTTATAATCCTG
GCTAATAACTCCCTCAGTTCTAATGGAAATGTCACTGAGTCTGGATGCA
AAGAGTGCGAAGAGTTGGAAGAGAAGAATATCAAAGAGTTTCTTCAGTC
CTTCGTGCATATAGTCCAAATGTTTATCAACACCTCCTGATAA;
or
(ii) a degenerate variant thereof.

### Claim 14

A vector comprising:
(a) a first polynucleotide encoding a cleavage resistant CD 16 polypeptide operatively associated with a promoter;
(b) a second polynucleotide encoding a secreted IL-15 polypeptide operatively associated with a promoter; or
(c) a polynucleotide construct that ecodes a polypeptide comprising:
(i) the amino acid sequence of a cleavage resistant CD16,
(ii) the amino acid sequence of a T2A polypeptide, and
(iii) the amino acid sequence of a secreted IL-15 polypeptide.

### Claim 15 (depends on 14)

The vector of claim 14, wherein the vector is a lentivirus vector.

### Claim 16 (depends on 14)

The vector of claim 14, comprising the polynucleotide construct of SEQ ID NO:7 operatively associated with a promoter.

### Claim 17 (depends on 16)

A placental derived natural killer (NK) Cell or population thereof wherein the placental derived NK cell comprises, or one or more cells within the population of the placental derived are transformed or transfected with the vector of claim 16.

### Claim 18 (depends on 17)

A method of suppressing the proliferation of tumor cells comprising contacting the tumor cells with
(i) a placental derived natural killer (NK) cell or one or more cells of population thereof of claim 17; and
(ii) a cancer specific antigen antibody.

### Claim 19 (depends on 18)

The method of claim 18, the cancer specific antigen antibody comprises:
(a) a human cancer specific antigen antibody;
(b) a humanized cancer specific antigen antibody;
(c) a chimeric cancer specific antigen antibody;
(d) a monoclonal cancer specific antigen antibody;
(e) a polyclonal cancer specific antigen antibody; or
(f) any combination of (a)-(e).

### Claim 20 (depends on 19)

The method of claim 19, wherein the cancer specific antigen antibody comprises trastuzumab ([HERCEPTIN]), or rituximab ([RITUXAN]).

### Claim 21 (depends on 18)

The method of claim 18, wherein the tumor cells are CD20+ lymphoma tumor cells.