# US 2021/0277083 A1 · GM-CSF and IL-4 Conjugates, Compositions, and Methods Related Thereto

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- Number: US 2021/0277083 A1
- Document ID: US20210277083A1
- Status: Published application
- Kind: A1
- Application number: 17/324,030
- Filed: 2021-05-18
- Published: 2021-09-09
- Earliest claimed: 2012-10-23
- Assignees: Emory University; Children's Healthcare of Atlanta, Inc.
- Applicants: Emory University; Children's Healthcare of Atlanta, Inc.
- Inventors: Jacques Galipeau; Jiusheng Deng
- Web page: https://patentgrep.com/patent/US20210277083A1

## CPC

- C07K 14/5406: {IL-4}
- A61K 35/14: Blood; Artificial blood (perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42)
- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 38/2026: {IL-4}
- A61K 39/0011: {Cancer antigens}
- A61K 39/39: characterised by the immunostimulating additives, e.g. chemical adjuvants
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/13: B-cells
- A61K 40/24: Antigen-presenting cells [APC]
- A61K 40/4271: {Melanoma antigens}
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 37/04: Immunostimulants
- C07K 14/535: Granulocyte CSF; Granulocyte-macrophage CSF
- C12N 5/06: {Animal cells or tissues; Human cells or tissues (preservation of excised living parts A01N1/10)}
- C12N 15/09: Recombinant DNA-technology
- C12N 15/1024: {In vivo mutagenesis using high mutation rate "mutator" host strains by inserting genetic material, e.g. encoding an error prone polymerase, disrupting a gene for mismatch repair}
- C12N 15/1027: {by DNA shuffling, e.g. RSR, STEP, RPR}
- C12N 15/1062: {mRNA-Display, e.g. polypeptide and encoding template are connected covalently}
- 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)
- A61K 2039/5152: {Tumor cells}
- A61K 2039/55522: {Cytokines; Lymphokines; Interferons}
- A61K 2039/55527: {Interleukins}
- 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 2239/57: Skin; melanoma
- C07K 2319/00: Fusion polypeptide
- 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

In certain embodiments, this disclosure relates to conjugates comprising GM-CSF and IL-4 and uses related thereto, e.g., enhancing the immune system. Typically, the GM-CSF and IL-4 are connected by a linker. In certain embodiments, the disclosure relates to isolated nucleic acids encoding these polypeptide conjugates, vectors comprising nucleic acid encoding polypeptide conjugates, and protein expression systems comprising these vectors such as infectious viral particles and host cells comprising such a nucleic acid.

## Claims

### Claim 1

A method of treating cancer comprising administering an effective amount of a conjugate comprising a granulocyte macrophage colony stimulating factor (GM-CSF) polypeptide and an interleukin 4 (IL-4) polypeptide, wherein said GM-CSF polypeptide and said IL-4 polypeptide are connected by a peptide linker consisting of amino acids selected from glycine, serine, threonine, asparagine, alanine and proline, wherein the conjugate is at least 70% identical to SEQ ID NO: 8, wherein said conjugate induces proliferation of B-cells, to a subject in need thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer is a hematological malignancy.

### Claim 3 (depends on 2)

The method of claim 2, wherein the hematological malignancy is selected from leukemia, lymphoma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), chronic myelogenous leukemia, acute monocytic leukemia (AMOL), Hodgkin's lymphomas, and non-Hodgkin's lymphomas such as Burkitt lymphoma, B-cell lymphoma and multiple myeloma.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer is melanoma.

### Claim 5 (depends on 1)

The method of claim 1, wherein said GM-CSF polypeptide is located closer to the N-terminus of said conjugate relative to said IL-4 polypeptide.

### Claim 6 (depends on 1)

The method of claim 1, wherein said GM-CSF polypeptide comprises the amino acid sequence of SEQ ID NO: 6 and said IL-4 polypeptide comprises the amino acid sequence of SEQ ID NO: 3.

### Claim 7 (depends on 1)

The method of claim 1, wherein said GM-CSF polypeptide and said IL-4 polypeptide are connected by a peptide linker consisting of amino acids selected from glycine and serine.

### Claim 8 (depends on 1)

The method of claim 1, wherein the linker comprises repeats of serine or repeats of glycine.

### Claim 9 (depends on 1)

The method of claim 1, wherein the linker is 1 to 5 amino acids.

### Claim 10 (depends on 1)

The method of claim 1, wherein the linker comprises GGGGS (SEQ ID NO:5).

### Claim 11

A method of treating cancer comprising administering an effective amount of a nucleic acid encoding a conjugate comprising a granulocyte macrophage colony stimulating factor (GM-CSF) polypeptide and an interleukin 4 (IL-4) polypeptide, wherein said GM-CSF polypeptide and said IL-4 polypeptide are connected by a peptide linker consisting of amino acids selected from glycine, serine, threonine, asparagine, alanine and proline, wherein the conjugate is at least 70% identical to SEQ ID NO: 8, to a subject in need thereof.

### Claim 12 (depends on 12)

The method of claim 12, wherein the nucleic acid is a recombinant vector comprising the nucleic acid.

### Claim 13 (depends on 11)

The method of claim 11, wherein the cancer is a hematological malignancy.

### Claim 14 (depends on 13)

The method of claim 13, wherein the hematological malignancy is selected from leukemia, lymphoma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), chronic myelogenous leukemia, acute monocytic leukemia (AMOL), Hodgkin's lymphomas, and non-Hodgkin's lymphomas such as Burkitt lymphoma, B-cell lymphoma and multiple myeloma.

### Claim 15 (depends on 11)

The method of claim 11, wherein the cancer is melanoma.

### Claim 16 (depends on 11)

The method of claim 11, wherein said GM-CSF polypeptide comprises the amino acid sequence of SEQ ID NO: 6 and said IL-4 polypeptide comprises the amino acid sequence of SEQ ID NO: 3.

### Claim 17 (depends on 11)

The method of claim 11, wherein said GM-CSF polypeptide and said IL-4 polypeptide are connected by a peptide linker consisting of amino acids selected from glycine and serine.

### Claim 18 (depends on 11)

The method of claim 11, wherein the linker comprises repeats of serine or repeats of glycine.

### Claim 19 (depends on 11)

The method of claim 11, wherein the linker is 1 to 5 amino acids.

### Claim 20 (depends on 1)

The method of claim 1, wherein the linker comprises GGGGS (SEQ ID NO:5).