# US 10,118,969 B2 · Compositions and methods relating to universal glycoforms for enhanced antibody efficacy

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

- Number: US 10,118,969 B2
- Document ID: US10118969B2
- Status: Granted
- Kind: B2
- Application number: 15/011,544
- Filed: 2016-01-30
- Published: 2016-09-29
- Granted: 2018-11-06
- Earliest claimed: 2014-05-27
- Assignees: Academia Sinica
- Applicants: Academia Sinica
- Inventors: Chi-Huey Wong; Chung-Yi Wu; Che Ma; Han-Chung Wu
- Web page: https://patentgrep.com/patent/US10118969B2

## CPC

- C07K 16/30: from tumour cells
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07K 16/108: Orthomyxoviridae (F), e.g. influenza virus
- C07K 16/18: against material from animals or humans
- C07K 16/241: {Tumor Necrosis Factors}
- C07K 16/2887: {against CD20}
- C07K 16/32: against translation products of oncogenes
- C12P 21/005: {Glycopeptides, glycoproteins}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/734: Complement-dependent cytotoxicity [CDC]
- C07K 2319/00: Fusion polypeptide
- C12N 9/24: acting on glycosyl compounds (3.2)
- C12Y 302/01: Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
- C12Y 302/01051: Alpha-L-fucosidase (3.2.1.51)
- 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)
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- 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

The present disclosure relates to compositions and methods of use comprising antibodies or binding fragments thereof further comprising universal Fc glycoforms.

## Claims

### Claim 1

An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα2→3Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glcβ1, wherein the antibody or antigen-binding fragment thereof comprises a glycan attached to Asn-297 of the Fc region, wherein the glycan has the formula:
Sia2( α2-6)Gal2GlcNAc2Man3GlcNAc2, as in the structure shown in FIG. 1, and wherein the antibody or antigen-binding fragment thereof comprises an H-CDR1, an H-CDR2, an H-CDR3, an L-CDR1, an L-CDR2, and an L-CDR3, wherein:
(i) the H-CDR1 comprises the sequence of SEQ ID NO:152 (GFSLTSYG);
(ii) the H-CDR2 comprises the sequence of SEQ ID NO:153 (IWGEGST);
(iii) the H-CDR3 comprises the sequence of SEQ ID NO:154 (AMTGTAY);
(iv) the L-CDR1 comprises the sequence of SEQ ID NO:149 (SSVSY);
(v) the L-CDR2 comprises the sequence of SEQ ID NO:150 (DTS); and
(vi) the L-CDR3 comprises the sequence of SEQ ID NO:151(HQWSSSPHT).

### Claim 2 (depends on 1)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1, wherein the antibody is an IgG1.

### Claim 3 (depends on 2)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 2 wherein the antibody comprises a VH having SEQ ID NO:147 and a VL having SEQ ID No:148.

### Claim 4 (depends on 1)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 wherein the antibody is a humanized antibody.

### Claim 5 (depends on 1)

A pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 2)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 2, wherein the antibody comprises a VH having SEQ ID NO:137 and a VL having SEQ ID NO:138.

### Claim 7 (depends on 1)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 1, wherein the antibody or antigen-binding fragment thereof further comprises an H-FR1, an H-FR2, an H-FR3, an HFR4, an L-FR1, an L-FR2, an L-FR3, and an L-FR4, wherein:
(i) the H-FR1 comprises the sequence of SEQ ID NO: 159 (QVQLKESGPGLVAPSQSLSITCTVS);
(ii) the H-FR2 comprises the sequence of SEQ ID NO:160 (VSWIRQPPGKGLEWIGV);
(iii) the H-FR3 comprises the sequence of SEQ ID NO:161 (NYHSVLISRLTISKDNSKSQVFLKLNSLQTDDTATYYC);
(iv) the H-FR4 comprises the sequence of SEQ ID NO:162 (WGQGTLVTVSS);
(v) the L-FR1 comprises the sequence of SEQ ID NO:155 (QIVLTQSPAIMSASPGEKVTMTCSAS);
(vi) the L-FR2 comprises the sequence of SEQ ID NO 156 (MHWYQQKSGTSPKRWIY);
(vii) the L-FR3 comprises the sequence of SEQ ID NO:157 (KLSSGVPGRFSGSGSGTSYSLTISRLEAEDAATYYC); and
(viii) the L-FR4 comprises the sequence of SEQ ID NO:158 (FGGGTKVEIKR).

### Claim 8

An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα2→3Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glcβ1, wherein the antibody or antigen-binding fragment thereof comprises a glycan attached to Asn-297 of the Fc region, wherein the glycan has the formula:
Sia2(α2-6)Gal2GlcNAc2Man3GlcNAc2, as in the structure shown in FIG. 1, and wherein the antibody or antigen-binding fragment thereof comprises an H-CDR1, an H-CDR2, an H-CDR3, an L-CDR1, an L-CDR2, and an L-CDR3, wherein:
(i) the H-CDR1 comprises the sequence of SEQ ID NO:207;
(ii) the H-CDR2 comprises the sequence of SEQ ID NO:208;
(iii) the H-CDR3 comprises the sequence of SEQ ID NO:209;
(iv) the L-CDR1 comprises the sequence of SEQ ID NO:204;
(v) the L-CDR2 comprises the sequence of SEQ ID NO:205; and
(vi) the L-CDR3 comprises the sequence of SEQ ID NO:206.

### Claim 9 (depends on 8)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 8, wherein the antibody is a humanized antibody.

### Claim 10 (depends on 8)

The isolated monoclonal antibody of claim 8, wherein the monoclonal antibody or antigen-binding fragment thereof comprises a VH having SEQ ID NO:202 and a VL having SEQ ID No:203.

### Claim 11 (depends on 8)

A pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment thereof of claim 8 and a pharmaceutically acceptable carrier.

### Claim 12

An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα2→3Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glcβ1, wherein the antibody or antigen-binding fragment thereof comprises a glycan attached to Asn-297 of the Fc region, wherein the glycan has the formula:
Sia2(α2-6)Gal2GlcNAc2Man3GlcNAc2, as in the structure shown in FIG. 1, and wherein the antibody or antigen-binding fragment thereof comprises an H-CDR1, an H-CDR2, an H-CDR3, an L-CDR1, an L-CDR2, and an L-CDR3, wherein:
(i) the H-CDR1 comprises the sequence of SEQ ID NO:217;
(ii) the H-CDR2 comprises the sequence of SEQ ID NO:218;
(iii) the H-CDR3 comprises the sequence of SEQ ID NO:219;
(iv) the L-CDR1 comprises the sequence of SEQ ID NO:214;
(v) the L-CDR2 comprises the sequence of SEQ ID NO:215; and
(vi) the L-CDR3 comprises the sequence of SEQ ID NO:216.

### Claim 13 (depends on 12)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 12, wherein the antibody is a humanized antibody.

### Claim 14 (depends on 12)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 12, wherein the antibody comprises a VH having SEQ ID NO:212 and a VL having SEQ ID NO:213.

### Claim 15 (depends on 12)

A pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment thereof of claim 12 and a pharmaceutically acceptable carrier.

### Claim 16

An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα2→3Galβ1→3GalNAcβ1→3Galαl→4Galβ1→4Glcβ1, wherein the antibody or the antigen-binding fragment thereof comprises a glycan attached to Asn-297 of the Fc region, wherein the glycan has the formula:
Sia2(α2-6)Gal2GlcNAc2Man3GlcNAc2, as in the structure shown in FIG. 1, and wherein the antibody or antigen-binding fragment thereof comprises an H-CDR1, an H-CDR2, an H-CDR3, an L-CDR1, an L-CDR2, and an L-CDR3, wherein:
(i) the H-CDR1 comprises the sequence of SEQ ID NO:227;
(ii) the H-CDR2 comprises the sequence of SEQ ID NO:228;
(iii) the H-CDR3 comprises the sequence of SEQ ID NO:229;
(iv) the L-CDR1 comprises the sequence of SEQ ID NO:224;
(v) the L-CDR2 comprises the sequence of SEQ ID NO:225; and
(vi) the L-CDR3 comprises the sequence of SEQ ID NO:226.

### Claim 17 (depends on 16)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 16, wherein the antibody is a humanized antibody.

### Claim 18 (depends on 16)

The isolated monoclonal antibody or antigen-binding fragment thereof of claim 16, wherein the antibody comprises a VH having SEQ ID NO:222 and a VL having SEQ ID NO:223.

### Claim 19 (depends on 16)

A pharmaceutical composition comprising the isolated monoclonal antibody or antigen-binding fragment thereof of claim 16 and a pharmaceutically acceptable carrier.