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. Impor
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.
대표청구항▼
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
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(α2-6)Gal2GlcNAc2Man3GlcNAc2, Sia2(α2-6)Gal2GlcNAc3Man3GlcNAc2, Sia2(α2-3)Gal2GlcNAc2Man3GlcNAc2, Sia2(α2-3)Gal2GlcNAc3Man3GlcNAc2, Sia2(α2-3/α2-6)Gal2GlcNAc2Man3GlcNAc2, Sia2(α2-6/α2-3)Gal2GlcNAc2Man3GlcNAc2, Sia2(α2-3/α2-6)Gal2GlcNAc3Man3GlcNAc2, Sia2(α2-6/α2-3)Gal2GlcNAc3Man3GlcNAc2, Sia(α2-6)Gal2GlcNAc2Man3GlcNAc2, Sia(α2-3)Gal2GlcNAc2Man3GlcNAc2, Sia(α2-6)Gal2GlcNAc3Man3GlcNAc2, Sia(α2-3)Gal2GlcNAc3Man3GlcNAc2, Sia(α2-6)GalGlcNAc2Man3GlcNAc2, Sia(α2-3)GalGlcNAc2Man3GlcNAc2, Sia(α2-6)GalGlcNAc3Man3GlcNAc2, Sia(α2-3)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(α2-6)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(α2-6)Gal2GlcNAc2Man3GlcNAc2, Sia2(α2-3)Gal2GlcNAc2Man3GlcNAc2, Sia(α2-6)GalGlcNAc2Man3GlcNAc2, Gal2GlcNAc2Man3GlcNAc2, GalGlcNAc2Man3GlcNAc2, GalGlcNAcMan3GlcNAc2, GlcNAc3Man3GlcNAc2, GlcNAc2Man3GlcNAc2, GlcNAcMan3GlcNAc2 and Man3GlcNAc2, and wherein the anti-HER2 glycoantibodies have improved binding to FcγRIIIA 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(α2-6)Gal2GlcNAc2Man3GlcNAc2, Sia2(α2-3)Gal2GlcNAc2Man3GlcNAc2, Sia(α2-6)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(α2-3)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: wherein ▪ is an N-acetylglucosamine (GlcNAc) and ● is a mannose (Man). 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: wherein ▪ is an N-acetylglucosamine (GlcNAc) and ● is a mannose (Man). 11. A pharmaceutical formulation comprising a composition of anti-HER2 glycoantibodies or antigen binding fragments according to claim 1 and a pharmaceutically acceptable carrier.
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