# US 2025/0084147 A1 · Method of Redirecting T Cells to Treat HIV Infection

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- Number: US 2025/0084147 A1
- Document ID: US20250084147A1
- Status: Published application
- Kind: A1
- Application number: 18/885,127
- Filed: 2024-09-13
- Published: 2025-03-13
- Earliest claimed: 2015-09-22
- Assignees: The Trustees of the University of Pennsylvania
- Applicants: The Trustees of the University of Pennsylvania
- Inventors: James L. Riley; Rachel Leibman; Aimee S. Payne; Christoph T. Ellebrecht; Michael C. Milone
- Web page: https://patentgrep.com/patent/US20250084147A1

## CPC

- C07K 14/70514: {CD4}
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- A61K 38/1774: {Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)}
- A61K 39/42: viral
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/31: Chimeric antigen receptors [CAR]
- A61K 40/46: Viral antigens
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/18: for HIV
- C07K 14/7051: {T-cell receptor (TcR)-CD3 complex}
- C07K 14/70517: {CD8}
- C07K 14/70521: {CD28, CD152}
- C07K 14/70578: {NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95 (NGF-receptor C07K14/71, TNF-receptor C07K14/7151)}
- C07K 16/114: Lentivirus (G), e.g. human immunodeficiency virus [HIV], feline immunodeficiency virus [FIV] or simian immunodeficiency virus [SIV]
- C12N 5/0636: {T lymphocytes}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/5158: {Antigen-pulsed cells, e.g. T-cells}
- A61K 2039/572: {cytotoxic response}
- C07K 2317/21: from primates, e.g. man
- 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 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/00: Fusion polypeptide
- 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 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- 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

The present invention relates to compositions and methods for treating of a HIV infected mammal using a CD4 membrane-bound chimeric receptor or a HIV specific scFvs CARs. One aspect includes a modified T cell and pharmaceutical compositions comprising the modified cells for adoptive cell therapy and treating a disease or condition associated with HIV infection.

## Claims

### Claim 1

A nucleic acid comprising a sequence encoding a membrane-bound chimeric receptor comprising a CD4 extracellular domain, a transmembrane domain, and a signaling domain, wherein the CD4 extracellular domain is capable of recognizing and binding a HIV infected cell.

### Claim at position 2

2-10. (canceled)

### Claim 11

A membrane-bound chimeric receptor comprising a CD4 extracellular domain, a transmembrane domain, and a signaling domain, wherein the CD4 extracellular domain is capable of recognizing and binding a HIV infected cell.

### Claim at position 4

12-20.

### Claim 21

A nucleic acid comprising a sequence encoding a chimeric antigen receptor (CAR) comprising a HIV-specific binding domain, a transmembrane domain, a costimulatory signaling region, and a signaling domain, wherein the HIV binding domain comprises an anti-HIV antibody or a fragment thereof.

### Claim 22 (depends on 21)

The nucleic acid of claim 21, wherein the HIV-specific binding domain comprises a heavy and light chain.

### Claim 23 (depends on 21)

The nucleic acid of claim 21, wherein the HIV-specific binding domain is a human antibody, a humanized antibody, and a fragment thereof.

### Claim 24 (depends on 21)

The isolated nucleic acid sequence of claim 21, wherein the antibody or a fragment thereof is selected from the group consisting of a Fab fragment, a F(ab′)2 fragment, a Fv fragment, and a single chain Fv (scFv).

### Claim 25 (depends on 24)

The isolated nucleic acid sequence of claim 24, wherein the scFv comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 17, 21, 25, 29, 57-60 and 61.

### Claim 26 (depends on 24)

The isolated nucleic acid sequence of claim 24, wherein the scFv is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 12, 16, 20, 24, 28, 75-78 and 79.

### Claim 27 (depends on 21)

The isolated nucleic acid sequence of claim 21, wherein the HIV-specific binding domain specifically binds to the surface of HIV infected cells, or HIV virions.

### Claim 28 (depends on 21)

The isolated nucleic acid sequence of claim 21, wherein the costimulatory signaling region comprises an intracellular domain of a costimulatory molecule selected from the group consisting of TCR, CD3 zeta, CD3 gamma, CD3 delta, CD3 epsilon, CD86, common FcR gamma, FcR beta (Fc Epsilon R1b), CD79a, CD79b, Fcgamma RIIa, DAP10, DAP12, T cell receptor (TCR), CD8, CD27, CD28, 4-1BB (CD137), OX9, OX40, CD30, CD40, PD-1, ICOS, a KIR family protein, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, a ligand that specifically binds with CD83, CDS, ICAM-1, GITR, BAFFR, HVEM (LIGHTR), SLAMF7, NKp80 (KLRF1), CD127, CD160, CD19, CD4, CD8alpha, CD8beta, IL2R beta, IL2R gamma, IL7R alpha, ITGA4, VLA1, CD49a, ITGA4, IA4, CD49D, ITGA6, VLA-6, CD49f, ITGAD, CD11d, ITGAE, CD103, ITGAL, CD11a, LFA-1, ITGAM, CD11b, ITGAX, CD11c, ITGB1, CD29, ITGB2, CD18, LFA-1, ITGB7, TNFR2, TRANCE/RANKL, DNAM1 (CD226), SLAMF4 (CD244, 2B4), CD84, CD96 (Tactile), CEACAM1, CRTAM, Ly9 (CD229), CD160 (BY55), PSGL1, CD100 (SEMA4D), CD69, SLAMF6 (NTB-A, Ly108), SLAM (SLAMF1, CD150, IPO-3), BLAME (SLAMF8), SELPLG (CD162), LTBR, LAT, GADS, SLP-76, PAG/Cbp, NKp44, NKp30, NKp46, NKG2D, Toll-like receptor 1 (TLR1), TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, and any combination thereof.

### Claim 29 (depends on 21)

The isolated nucleic acid sequence of claim 21, wherein the signaling domain comprises a CD3zeta signaling domain encoded by nucleic acid sequence SEQ ID NO: 6 or 68.

### Claim 30 (depends on 21)

The isolated nucleic acid sequence of claim 21, wherein the CAR is encoded by a nucleic acid sequence selected from the group consisting of SEQ ID NOs: 10, 14, 18, 22, 26, 34, 70-73, and 74.

### Claim 31 (depends on 21)

The isolated nucleic acid sequence of claim 21, wherein the CAR has an amino acid sequence selected from the group consisting of SEQ ID NOs: 11, 15, 19, 23, 27, 35, 52-55, and 56.

### Claim 32 (depends on 21)

A modified cell comprising the nucleic acid of claim 21.

### Claim 33 (depends on 32)

The modified cell of claim 32, wherein the cell is selected from the group consisting of a T cell, a natural killer (NK) cell, a cytotoxic T lymphocyte (CTL), and a regulatory T cell.

### Claim at position 18

34-35. (canceled)

### Claim 36 (depends on 33)

A composition comprising the modified cell of claim 33.

### Claim 37

(canceled)

### Claim 38 (depends on 33)

A pharmaceutical composition comprising the modified cell of claim 33 and a pharmaceutically acceptable carrier.

### Claim 39 (depends on 33)

A method for stimulating a cellular immune response in a HIV infected mammal, the method comprising administering to the mammal an effective amount of the modified cell of claim 33.

### Claim 40 (depends on 33)

A method of treating a HIV infected mammal, the method comprising administering to the mammal the modified cell of claim 33.

### Claim 41 (depends on 40)

The method of claim 40, wherein the modified cell is autologous to the mammal.

### Claim at position 25

42-43. (canceled)