Claims for Patent: 10,005,847

Summary for Patent: 10,005,847

Title:	Anti-HER2 glycoantibodies and uses thereof
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.
Inventor(s):	Wong; Chi-Huey (Rancho Santa Fe, CA), Wu; Chung-Yi (New Taipei, TW)
Assignee:	ACADEMIA SINICA (Taipei, TW)
Application Number:	14/723,181
Patent 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 Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, Sia.sub.2(.alpha.2-3)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia.sub.2(.alpha.2-3)Gal.sub.2GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, Sia.sub.2(.alpha.2-3/.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.- 2, Sia.sub.2(.alpha.2-6/.alpha.2-3)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.su- b.2, Sia.sub.2(.alpha.2-3/.alpha.2-6)Gal.sub.2GlcNAc.sub.3Man.sub.3GlcNAc.- sub.2, Sia.sub.2(.alpha.2-6/.alpha.2-3)Gal.sub.2GlcNAc.sub.3Man.sub.3GlcNA- c.sub.2, Sia(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-3)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-6)Gal.sub.2GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-3)Gal.sub.2GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-6)GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-3)GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-6)GalGlcNAc.sub.3Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-3)GalGlcNAc.sub.3Man.sub.3GlcNAc.sub.2, Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Gal.sub.2GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GalGlcNAc.sub.3Man.sub.3GlcNAc.sub.2, GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, GlcNAc.sub.2, Man3GlcNAc.sub.2, GlcNAcMan.sub.3GlcNAc.sub.2 and Man.sub.3GlcNAc.sub.2. 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 Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GlcN-Ac.sub.3Man.sub.3GlcNAc.sub.2, GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, and Man.sub.3GlcNAc.sub.2, 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 Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia.sub.2(.alpha.2-3)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-6)GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GalGlcNAcMan.sub.3GlcNAc.sub.2, GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GlcNAcMan.sub.3GlcNAc.sub.2 and Man.sub.3GlcNAc.sub.2, and wherein the anti-HER2 glycoantibodies have improved binding to Fc.gamma.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 Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia.sub.2(.alpha.2-3)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Sia(.alpha.2-6)GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GlcNAcMan.sub.3GlcNAc.sub.2 and Man.sub.3GlcNAc.sub.2. 8. The composition of claim 1, wherein the N-glycan is selected from the group consisting of Sia.sub.2(.alpha.2-3)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2, GlcNAc.sub.3Man.sub.3GlcNAc.sub.2, GlcNAcMan.sub.3GlcNAc.sub.2, Man.sub.3GlcNAc.sub.2, and GalGlcNAc.sub.2Man.sub.3GlcNAc.sub.2. 9. The composition of claim 1, wherein the glycoengineered anti-HER2 IgG antibody has the N-glycan GlcNAcMan.sub.3GlcNAc.sub.2 having the glycan structure shown for GAb 109 depicted in Table 2: ##STR00042## wherein .box-solid. is an N-acetylglucosamine (GlcNAc) and .circle-solid. is a mannose (Man). 10. The composition of claim 1, wherein the glycoengineered anti-HER2 IgG molecule antibody has the N-glycan GlcNAcMan.sub.3GlcNAc.sub.2 having the glycan structure shown for GAb 110 depicted in Table 2: ##STR00043## wherein .box-solid. is an N-acetylglucosamine (GlcNAc) and .circle-solid. 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.

Details for Patent 10,005,847

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2034-05-27
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2034-05-27
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2034-05-27