Compositions and methods relating to universal glycoforms for enhanced antibody efficacy

• US 10,118,969 B2
• Filed: 01/30/2016
• Issued: 11/06/2018
• Est. Priority Date: 05/27/2014
• Status: Active Grant

• Current Assignee: Academia Sinica (Government of The Republic of China)
• Original Assignee: Academia Sinica (Government of The Republic of China)
• Inventors: Wong, Chi-Huey, Wu, Chung-Yi, Ma, Che, Wu, Han-Chung
• Primary Examiner(s): Bristol, Lynn A
• Application Number:
  US15/011,544
• Publication Number:
  US 20160280794A1
• Time in Patent Office: 1,011 Days
• Field of Search: 1 1, 4241331, 4241731
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07K 16/1018 Orthomyxoviridae, e.g. influenza virus
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/241 Tumor Necrosis Factors
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C12N 9/24 acting on glycosyl compounds (3.2)
• CPC Class Codes: C12P 21/005 Glycopeptides, glycoproteins
• CPC Class Codes: C12Y 302/01 Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
• CPC Class Codes: C12Y 302/01051 Alpha-L-fucosidase (3.2.1.51)

Abstract

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

Claims

1. An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα

2→

3Galβ

1→

3GalNAcβ

1→

3Galα

1→

4Galβ

1→

4Glcβ

1, 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( α

2-6)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).

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

3. 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.

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

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

6. 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.

7. 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).

8. An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα

2→

3Galβ

1→

3GalNAcβ

1→

3Galα

1→

4Galβ

1→

4Glcβ

1, 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(α

2-6)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.

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

10. 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.

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

12. An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα

2→

3Galβ

1→

3GalNAcβ

1→

3Galα

1→

4Galβ

1→

4Glcβ

1, 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(α

2-6)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.

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

14. 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.

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

16. An isolated monoclonal antibody or antigen-binding fragment thereof that binds to Neu5Acα

2→

3Galβ

1→

3GalNAcβ

1→

3Galα

l→

4Galβ

1→

4Glcβ

1, 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(α

2-6)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.

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

18. 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.

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