# US 12,215,172 B2 · Bio-responsive adhesive antibody delivery platform for immunotherapy and preparation method thereof

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- Number: US 12,215,172 B2
- Document ID: US12215172B2
- Status: Granted
- Kind: B2
- Application number: 17/065,368
- Filed: 2020-10-07
- Published: 2021-05-13
- Granted: 2025-02-04
- Earliest claimed: 2019-10-14
- Assignees: Postech Academy-Industry Foundation
- Applicants: Postech Academy-Industry Foundation
- Inventors: Kye Il Joo; Hyung Joon Cha; Yeon Su Jeong
- Web page: https://patentgrep.com/patent/US12215172B2

## CPC

- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- A61K 45/00: Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61P 35/00: Antineoplastic agents
- C07K 14/43504: {from invertebrates}
- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- A61K 2039/505: {comprising antibodies}
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- C07K 2319/33: fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
- C07K 2319/50: containing protease site
- 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

## Abstract

Disclosed are a bio-responsive adhesive antibody delivery platform for immunotherapy, use thereof, and a preparation method thereof. The bio-responsive adhesive antibody delivery platform for immunotherapy according to the present disclosure may enhance a retention time of the antibody at a target site via adhesiveness of the delivery platform and may selectively release the antibody in response to specific enzymes to efficiently deliver the antibody.

## Claims

### Claim 1

A mussel adhesive protein (MAP)-antibody (MAP-Ab) conjugate comprising a MAP and an anti-cancer antibody,
wherein the MAP is conjugated to the N-terminus of a peptide;
wherein the anti-cancer antibody is conjugated to the C-terminus of the peptide;
wherein the peptide is cleavable by a matrix metalloproteinase-2 (MMP2);
wherein the peptide has the amino acid sequence set forth in SEQ ID NO: 12,
wherein the anti-cancer antibody inhibits a surface protein of a cancer cell;
wherein when the MAP-Ab conjugate is exposed to an MMP2, the anti-cancer antibody is released therefrom; and
wherein the amino acid sequence of the MAP is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEO ID NO: 4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11, and any combination thereof.

### Claim 2 (depends on 1)

The MAP-Ab conjugate of claim 1, wherein the antibody is directly coupled to, or is coupled by a linker to, a cysteine positioned at the N-terminus of the peptide.

### Claim 3 (depends on 1)

The MAP-Ab conjugate of claim 1, wherein the anti-cancer antibody is selected from the group consisting of:
i) an anti-PD-L1 antibody or an antigen-binding fragment thereof;
ii) an anti-CTLA4 antibody or an antigen-binding fragment thereof;
iii) an anti-LAG-3 antibody or an antigen-binding fragment thereof;
iv) an anti-OX40 antibody or an antigen-binding fragment thereof;
v) an anti-TIM3 antibody or an antigen-binding fragment thereof;
vi) an anti-PD-1 antibody or an antigen-binding fragment thereof; and
vii) any combination thereof.

### Claim 4 (depends on 1)

An immunotherapy composition comprising an antibody and the MAP-Ab conjugate of claim 1.

### Claim 5 (depends on 4)

The immunotherapy composition of claim 4, wherein the immunotherapy composition is disposed within a pharmaceutical composition.

### Claim 6 (depends on 5)

The pharmaceutical composition of claim 5, further comprising an indoleamine (2,3)-dioxygenase (IDO) inhibitor.

### Claim 7 (depends on 4)

The immunotherapy composition of claim 4, wherein the immunotherapy composition is disposed within an anticancer adjuvant.

### Claim 8 (depends on 4)

A method for treating a solid cancer in a subject comprising administering to the subject a pharmaceutical composition comprising the immunotherapy composition of claim 4 by intratumoral injection.

### Claim 9 (depends on 8)

The method of claim 8, wherein the cancer is selected from the group consisting of skin cancer, melanoma, gastric cancer, esophageal cancer, colon cancer, rectal colon cancer, pancreatic cancer, colorectal cancer, rectal cancer, bile duct cancer, liver cancer, brain tumor, sarcoma, bone cancer, breast cancer, thyroid cancer, lung adenocarcinoma, uterine cancer, cervical cancer, endometrial cancer, prostate cancer, head and neck cancer, bladder cancer, endocrine cancer, urethral cancer, ovarian cancer, testicular cancer, kidney cancer, and any combination thereof.

### Claim 10 (depends on 8)

The method of claim 8, wherein the pharmaceutical composition is administered in combination with an IDO (indoleamine (2,3)-dioxygenase) inhibitor.

### Claim 11 (depends on 3)

The MAP-Ab conjugate of claim 3, wherein the anti-cancer antibody comprises an anti-PD-L1 antibody or an antigen-binding fragment thereof.

### Claim 12 (depends on 10)

The method of claim 10, wherein the IDO inhibitor comprises 1-methyl-tryptophan or NLG919.
