# US 11,304,976 B2 · Combination immune therapy and cytokine control therapy for cancer treatment

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- Number: US 11,304,976 B2
- Document ID: US11304976B2
- Status: Granted
- Kind: B2
- Application number: 16/194,417
- Filed: 2018-11-19
- Published: 2019-03-21
- Granted: 2022-04-19
- Earliest claimed: 2015-02-18
- Assignees: Enlivex Therapeutics Ltd.
- Applicants: Enlivex Therapeutics Ltd.
- Inventors: Shai Novik; Dror Mevorach
- Web page: https://patentgrep.com/patent/US11304976B2

## CPC

- 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 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 40/4211: {CD19 or B4}
- A61K 40/4217: {Receptors for interleukins [IL]}
- A61P 31/04: Antibacterial agents
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- 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
- A61K 2239/59: Reproductive system, e.g. uterus, ovaries, cervix or testes
- 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

Compositions disclosed herein, and methods of use thereof included those for treating or preventing sepsis in a subject in need, including methods of extending of the survival of a subject suffering from sepsis, and reduction of organ dysfunction or failure due to sepsis. Methods of treating or preventing sepsis in a subject in need includes administering compositions comprising early apoptotic cells or early apoptotic cell supernatants. Compositions and methods of use thereof may reduce the negative proinflammatory effect accompanying sepsis. In certain instances, compositions may include additional agents.

## Claims

### Claim 1

A method of treating, preventing, inhibiting, reducing the incidence of, ameliorating, or alleviating sepsis, or any combination thereof, in a subject in need, comprising the step of administering a composition comprising an early apoptotic cell population to said subject, wherein said early apoptotic cell population comprises ≥40% AnnexinV+ and ≤15% propidium iodide+cells and said early apoptotic cells comprise peripheral blood mononuclear cells, and wherein said administering treats, prevents, inhibits, reduces the incidence of, ameliorates, or alleviates sepsis in said subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein sepsis comprises mild or severe sepsis.

### Claim 3 (depends on 1)

The method of claim 1, wherein said treating, preventing, inhibiting, reducing the incidence of, ameliorating, or alleviating increases the survival of said subject.

### Claim 4 (depends on 1)

The method of claim 1, wherein said treating, preventing, inhibiting, reducing the incidence of, ameliorating, or alleviating reduces the incidence of organ failure or organ dysfunction, or organ damage, or a combination thereof.

### Claim 5 (depends on 4)

The method of claim 4, wherein organ failure comprises acute multiple organ failure.

### Claim 6 (depends on 1)

The method of claim 1, wherein said early apoptotic cell population comprises
(a) an apoptotic population stable for greater than 24 hours; or
(b) a mononuclear apoptotic cell population comprising a decreased of non-quiescent non-apoptotic cells, a suppressed cellular activation of any living non-apoptotic cells, or a reduced proliferation of any living non-apoptotic cells, or any combination thereof;
any combination thereof.

### Claim 7 (depends on 1)

The method of claim 1, wherein said early apoptotic cell population comprises a pooled population of early apoptotic cells.

### Claim 8 (depends on 1)

The method of claim 1, wherein said subject is a human subject.

### Claim 9 (depends on 1)

The method of claim 1, wherein said administering comprises a single infusion of said early apoptotic cell population.

### Claim 10 (depends on 1)

The method of claim 1, wherein said administering comprises multiple infusions of said apoptotic cell population.

### Claim 11 (depends on 1)

The method of claim 1, wherein said administering comprises intra venal administration.

### Claim 12 (depends on 1)

The method of claim 1, further comprising administering an additional therapy.

### Claim 13 (depends on 12)

The method of claim 12, wherein said additional therapy is administered prior to, concurrent with, or following administration of said early apoptotic cells.

### Claim 14 (depends on 1)

The method of claim 1, wherein said method comprises a first-line therapy.

### Claim 15 (depends on 1)

The method of claim 1, wherein said method comprises an adjuvant therapy.