# US 8,771,664 B2 · Compositions comprising apolipoprotein A polypeptide and interleukin 15, and methods of treatment using the same

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,771,664 B2
- Document ID: US8771664B2
- Status: Granted
- Kind: B2
- Application number: 13/514,855
- Filed: 2010-12-10
- Published: 2012-09-27
- Granted: 2014-07-08
- Earliest claimed: 2009-12-11
- Assignees: FundacióN Para La InvestigacióN MéDica Aplicada; Research Center Borstel
- Applicants: Pedro Berraondo Lopez; Jessica Fioravanti; Jose Medina Echeverz; Ignacio Javier Melero Bermejo; Maria del Carmen Ochoa Nieto; Francisco de Asis Palazon Garcia; Silvia Bulfone-Paus; Erwin Hans Duitmann
- Inventors: Pedro Berraondo Lopez; Jessica Fioravanti; Jose Medina Echeverz; Ignacio Javier Melero Bermejo; Maria del Carmen Ochoa Nieto; Francisco de Asis Palazon Garcia; Silvia Bulfone-Paus; Erwin Hans Duitmann
- Web page: https://patentgrep.com/patent/US8771664B2

## CPC

- C07K 14/5443: {IL-15}
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/04: Immunostimulants
- C07K 14/7155: {for interleukins [IL]}
- C07K 14/775: Apolipopeptides
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- 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
- 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)

## Abstract

The present invention relates to compositions capable of promoting both the innate immune response as well as the adaptive immune response in a subject based on the jointly use of ApoA, interleukin 15 and the Sushi domain of the IL15 receptor alpha chain, as well as to the use of these compositions for the stimulation of the immune response in a patient and to therapeutic methods for the treatment of infectious and neoplastic diseases.

## Claims

### Claim 1

A composition comprising, separately or in the form of a single fusion molecule,
(i) a first component selected from the group of
(a) a polypeptide comprising an Apolipoprotein A “Apo A” polypeptide and
(b) a polynucleotide encoding an Apo A polypeptide and
(ii) a second component selected from the group of
(a) Interleukin 15 “IL15” and
(b) a polynucleotide encoding IL15 and
(iii) a third component selected from the group of
(a) the Sushi domain of the IL15 receptor alpha chain and
(b) a polynucleotide encoding the Sushi domain of the IL15 receptor alpha chain.

### Claim 2 (depends on 1)

A composition according to claim 1, wherein the first and second component form part of a single molecule and wherein
a. if the first and second components are polypeptides, said single molecule is a fusion protein comprising an Apo A polypeptide and IL15 and
b. if the first and second components are polynucleotides, said single molecule is a polynucleotide encoding a fusion protein comprising a polypeptide comprising an Apo A polypeptide and IL15.

### Claim 3 (depends on 2)

A composition according to claim 2, wherein the arrangement of the first and second component of said single molecule is selected from the group consisting of
c. the first component is located in the N terminal or 5′ position in relation to the second component and
d. the first component is located in the C terminal or 3′ position in relation to the second component.

### Claim 4 (depends on 1)

A composition according to claim 1, wherein
the Apo A polypeptide is of human origin or of murine origin,
the IL15 polypeptide is of human origin or of murine origin and/or
the Sushi domain of the IL15 receptor alpha chain is of human origin or of murine origin.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising a composition according to claim 1 and a pharmaceutically acceptable vehicle.

### Claim 6 (depends on 1)

An In vitro method for promoting the expansion of antigen-specific T lymphocytes comprising contacting a population of lymphocytes previously exposed in vivo to said antigen with a composition according to claim 1.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the lymphocytes are previously subjected to an in vitro activation by contacting the lymphocytes with the antigen to which the aforesaid T-lymphocytes have been exposed, wherein said activation is carried out prior to said contacting step.

### Claim 8 (depends on 1)

A method for increasing the proliferation of CD8 T lymphocytes and/or natural killer (NK) cells in a subject, comprising the administration to said subject of a composition according to claim 1.

### Claim 9 (depends on 1)

A composition according to claim 1 comprising, separately or in the form of a single fusion molecule,
(i) a first component selected from the group of
(a) a polypeptide comprising an Apo A polypeptide comprising the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2 or SEQ ID NO: 3;
(b) a polynucleotide encoding an Apo A polypeptide wherein the polynucleotide comprises the nucleotide sequence set forth in SEQ ID NO: 4, SEQ ID NO: 5 or SEQ ID NO: 6; and
(ii) a second component selected from the group of
(a) IL15 comprising the amino acid sequence set forth in SEQ ID NO: 7, SEQ ID NO:8 or SEQ ID NO: 9;
(b) a polynucleotide encoding IL15 wherein the polynucleotide comprises the nucleotide sequence set forth in SEQ ID NO: 12, SEQ ID NO: 13 or SEQ ID NO: 14; and
(iii) a third component selected from the group of
(a) the Sushi domain of the IL15 receptor alpha chain comprising the amino acid sequence set forth in SEQ ID NO: 17 or SEQ ID NO: 18 and
(b) a polynucleotide encoding the Sushi domain of the IL15 receptor alpha chain wherein the polynucleotide comprises the nucleotide sequence set forth in SEQ ID NO: 19 or SEQ ID NO: 20.

### Claim 10

A fusion protein comprising
(i) a region A formed by an Apo A polypeptide,
(ii) a region B formed by IL15 and
(iii) a region C formed by the Sushi domain of the IL15 receptor alpha chain.

### Claim 11 (depends on 10)

A fusion protein according to claim 10, wherein the arrangement of regions A, B and C in the direction N-to C-terminal in said fusion protein is selected from the group consisting of A-B-C, A-C-B, B-A-C, B-C-A, C-A-B and C-B-A.

### Claim 12 (depends on 11)

A fusion protein according to claim 11, wherein at least one of the bonds between regions A, B and C is established by a peptide linker.

### Claim 13 (depends on 10)

A fusion protein according to claim 10, further comprising a peptide linker connecting at least one of the regions A, B and C to at least one neighboring region.

### Claim 14 (depends on 10)

A polynucleotide encoding a fusion protein according to claim 10.

### Claim 15 (depends on 14)

A vector or a gene construct comprising a polynucleotide according to claim 14.

### Claim 16 (depends on 10)

A host cell comprising a fusion protein according to claim 10.

### Claim 17 (depends on 10)

A fusion protein according to claim 10, wherein
a. the Apo A polypeptide is of human origin or of murine origin,
b. the IL15 polypeptide is of human origin or of murine origin and/or
c. the Sushi domain of the IL15 receptor alpha chain is of human origin or of murine origin.

### Claim 18 (depends on 10)

A pharmaceutical composition comprising a fusion protein according to claim 10 and a pharmaceutically acceptable vehicle.

### Claim 19 (depends on 10)

An in vitro method for promoting the expansion of antigen-specific T lymphocytes comprising contacting a population of lymphocytes previously exposed in vivo to said antigen with a fusion protein according to claim 10.

### Claim 20 (depends on 19)

The method according to claim 19, wherein the lymphocytes are previously subjected to an in vitro activation by contacting the lymphocytes with the antigen to which the aforesaid T-lymphocytes have been exposed, wherein said activation is carried out prior to said contacting step.

### Claim 21 (depends on 10)

A method of increasing survival of a subject suffering from adenocarcinoma, comprising the administration to said subject of a fusion protein according to claim 10.

### Claim 22 (depends on 10)

A fusion protein according to claim 10 which comprises the sequence set forth in SEQ ID NO: 42 or SEQ ID NO: 43.