Anti-HER2 glycoantibodies and uses thereof

• US 10,005,847 B2
• Filed: 05/27/2015
• Issued: 06/26/2018
• 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
• Primary Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US14/723,181
• Publication Number:
  US 20150344587A1
• Time in Patent Office: 1,126 Days
• Field of Search: 4241331, 4241581, 5303891
• CPC Class Codes: A61K 31/517 ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/283 against Fc-receptors, e.g. CD16, CD32, CD64 CD23 C07K16/2851
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 16/40 against enzymes
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/40 characterized by post-translational modification
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• 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 a novel class of anti-HER2 monoclonal antibodies comprising a homogeneous population of anti-HER2 IgG molecules having the same N-glycan on each of Fc. The antibodies of the invention can be produced from anti-HER2 monoclonal antibodies by Fc glycoengineering. Importantly, the antibodies of the invention have improved therapeutic values with increased ADCC activity and increased Fc receptor binding affinity compared to the corresponding monoclonal antibodies that have not been glycoengineered.

Claims

1. A composition of anti-HER2 glycoantibodies or antigen binding fragments comprising a homogeneous population of glycoengineered anti-HER2 IgG antibodies having the same N-glycan at the Asn-297 position in the Fc region of each anti-HER2 lgG antibody, wherein the N-glycan is selected from the group consisting of

Sia₂(α

2-6)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia₂(α

2-6)Gal₂GlcNAc₃Man₃GlcNAc₂, Sia₂(α

2-3)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia₂(α

2-3)Gal₂GlcNAc₃Man₃GlcNAc₂, Sia₂(α

2-3/α

2-6)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia₂(α

2-6/α

2-3)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia₂(α

2-3/α

2-6)Gal₂GlcNAc₃Man₃GlcNAc₂, Sia₂(α

2-6/α

2-3)Gal₂GlcNAc₃Man₃GlcNAc₂, Sia(α

2-6)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia(α

2-3)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia(α

2-6)Gal₂GlcNAc₃Man₃GlcNAc₂, Sia(α

2-3)Gal₂GlcNAc₃Man₃GlcNAc₂, Sia(α

2-6)GalGlcNAc₂Man₃GlcNAc₂, Sia(α

2-3)GalGlcNAc₂Man₃GlcNAc₂, Sia(α

2-6)GalGlcNAc₃Man₃GlcNAc₂, Sia(α

2-3)GalGlcNAc₃Man₃GlcNAc₂, Gal₂GlcNAc₂Man₃GlcNAc₂, Gal₂GlcNAc₃Man₃GlcNAc₂, GalGlcNAc₂Man₃GlcNAc₂, GalGlcNAc₃Man₃GlcNAc₂, GlcNAc₃Man₃GlcNAc₂, GlcNAc₂, Man3GlcNAc₂, GlcNAcMan₃GlcNAc₂ and Man₃GlcNAc₂.

2. The composition of claim 1, wherein the glycoengineered anti-HER2 IgG antibody comprises a heavy chain having the amino acid sequence set forth in SEQ ID NO:

1, and a light chain having the amino acid sequence set forth in SEQ ID NO;

2.

3. The composition of claim 1, wherein the glycoengineered anti-HER2 IgG antibody comprises a light chain sequence and a heavy chain sequence of Trastuzumab (Herceptin).

4. The composition of claim 1, wherein the N-glycan is selected from the group consisting of Sia₂(α

2-6)Gal₂GlcNAc₂Man₃GlcNAc₂, Gal₂GlcNAc₂Man₃GlcNAc₂, GalGlcNAc₂Man₃GlcNAc₂, GlcN-Ac₃Man₃GlcNAc₂, GlcNAc₂Man₃GlcNAc₂, and Man₃GlcNAc₂, and wherein the anti-HER2 glycoantibodies have improved ADCC over Trastuzumab.

5. The composition of claim 1, wherein the N-glycan is selected from the group consisting of Sia₂(α

2-6)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia₂(α

2-3)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia(α

2-6)GalGlcNAc₂Man₃GlcNAc₂, Gal₂GlcNAc₂Man₃GlcNAc₂, GalGlcNAc₂Man₃GlcNAc₂, GalGlcNAcMan₃GlcNAc₂, GlcNAc₃Man₃GlcNAc₂, GlcNAc₂Man₃GlcNAc₂, GlcNAcMan₃GlcNAc₂ and Man₃GlcNAc₂, and wherein the anti-HER2 glycoantibodies have improved binding to Fcγ

RIIIA over Trastuzumab.

6. The composition of claim 1, wherein the N-glycan is free of fucose.

7. The composition of claim 1, wherein the N-glycan is selected from the group consisting of Sia₂(α

2-6)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia₂(α

2-3)Gal₂GlcNAc₂Man₃GlcNAc₂, Sia(α

2-6)GalGlcNAc₂Man₃GlcNAc₂, Gal₂GlcNAc₂Man₃GlcNAc₂, GalGlcNAc₂Man₃GlcNAc₂, GlcNAc₃Man₃GlcNAc₂, GlcNAc₂Man₃GlcNAc₂, GlcNAcMan₃GlcNAc₂ and Man₃GlcNAc₂.

8. The composition of claim 1, wherein the N-glycan is selected from the group consisting of Sia₂(α

2-3)Gal₂GlcNAc₂Man₃GlcNAc₂, Gal₂GlcNAc₂Man₃GlcNAc₂, GlcNAc₃Man₃GlcNAc₂, GlcNAcMan₃GlcNAc₂, Man₃GlcNAc₂, and GalGlcNAc₂Man₃GlcNAc₂.

9. The composition of claim 1, wherein the glycoengineered anti-HER2 IgG antibody has the N-glycan GlcNAcMan₃GlcNAc₂ having the glycan structure shown for GAb 109 depicted in Table 2:

10. The composition of claim 1, wherein the glycoengineered anti-HER2 IgG molecule antibody has the N-glycan GlcNAcMan₃GlcNAc₂ having the glycan structure shown for GAb 110 depicted in Table 2:

11. A pharmaceutical formulation comprising a composition of anti-HER2 glycoantibodies or antigen binding fragments according to claim 1 and a pharmaceutically acceptable carrier.