# US 11,998,612 B2 · Method for conjugating antibody and physiologically active substance

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- Number: US 11,998,612 B2
- Document ID: US11998612B2
- Status: Granted
- Kind: B2
- Application number: 18/338,832
- Filed: 2023-06-21
- Published: 2024-01-18
- Granted: 2024-06-04
- Earliest claimed: 2017-11-29
- Assignees: Novelty Nobility Inc.
- Applicants: Novelty Nobility Inc.
- Inventors: Tae Hyeon Yoo; Jisoo Park; Yumi Lee
- Web page: https://patentgrep.com/patent/US11998612B2

## CPC

- A61K 47/68: the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K 47/6855: {the tumour determinant being from breast cancer cell}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61K 47/6815: {Enzymes}
- A61K 47/6829: {Bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment}
- C07K 1/13: Labelling of peptides
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/21: from Pseudomonadaceae (F)
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/30: from tumour cells
- C07K 16/32: against translation products of oncogenes
- C12N 9/86: acting on amide bonds in cyclic amides, e.g. penicillinase {(3.5.2)}
- C12Y 305/02006: Beta-lactamase (3.5.2.6)
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2319/21: containing a His-tag
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C07K 2319/60: containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
- 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)
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES

## Abstract

An antibody conjugating peptide including an amino acid having a photoreactive functional group, a physiologically active substance modified with the conjugating peptide, and an antibody conjugate having an antibody linked to the physiologically active substance are disclosed. When the physiologically active substance modified with the conjugating peptide is linked to the antibody, the conjugation efficiency between the antibody and the physiologically active substance is remarkably improved as compared to that of the conventional art, and thus, the drug may be firmly bound without impairing the specificity of the antibody, thereby making it possible to accelerate commercialization of the antibody conjugate.

## Claims

### Claim 1

A substance modified with an Fc site-specific conjugating peptide mutant, wherein the substance is linked to the Fc site-specific conjugating peptide mutant either directly or via a linker,
wherein the Fc site-specific conjugating peptide mutant comprises the amino acid sequence of SEQ ID NO: 1, wherein the amino acid sequence of the Fc site-specific conjugating peptide further comprises a valine to p-benzoyl phenylalanine substitution at position 10, and wherein the Fc site-specific conjugating peptide mutant comprising p-benzoyl phenylalanine substitution at position 10 shows higher binding efficiency to Fc site of an antibody than a mutant comprising p-benzoyl phenylalanine substitution at position 5 or 11.

### Claim 2 (depends on 1)

The substance according to claim 1, wherein the substance is a therapeutic agent or a diagnostic agent.

### Claim 3 (depends on 2)

The substance according to claim 2, wherein the therapeutic agent or the diagnostic agent is selected from the group consisting of an enzyme, a hormone, a cytokine, an antibody, an antibody fragment, an analgesic, an antipyretic, an anti-inflammatory agent, an antibiotic, an anti-viral agent, an antifungal drug, a cardiovascular drug, a drug that acts on the central nervous system, a drug that affects renal function and electrolyte metabolism, and a chemotherapeutic agent.

### Claim 4 (depends on 1)

The substance according to claim 1, wherein the linker comprises a reactive functional group, an amino acid, and a self-cleaving spacer.

### Claim 5 (depends on 1)

A method of producing an antibody conjugate, wherein the method comprising:
(a) mixing a substance modified with the conjugating peptide according to claim 1 with an Fc domain-containing antibody;
(b) irradiating the mixture with light to produce an antibody conjugate in which the p-benzoyl phenylalanine and the Fc domain-containing molecule are covalently linked; and
(c) obtaining the produced antibody conjugate.

### Claim 6 (depends on 5)

The method according to claim 5, wherein the light is in a range of 320 nm to 380 nm.

### Claim 7 (depends on 5)

The method according to claim 5, wherein the Fc domain-containing antibody is a targeted natural or non-natural antibody capable of specifically binding to a target molecule.

### Claim 8 (depends on 5)

The method according to claim 5, wherein the Fc domain-containing antibody is selected from the group consisting of IgG, IgA, IgD, IgE, IgM, combinations thereof, and Fc regions thereof.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the Fc domain-containing antibody is selected from the group consisting of IgG1-derived domain combinations and Fc regions thereof.

### Claim 10 (depends on 1)

An antibody conjugate in which an antibody is linked to a substance modified with the conjugating peptide according to claim 1.