Claims for Patent: 10,023,892

Summary for Patent: 10,023,892

Title:	Compositions and methods relating to universal glycoforms for enhanced antibody efficacy
Abstract:	The present disclosure relates to glycoproteins, particularly monoclonal antibodies, comprising a glycoengineered Fc region, wherein said Fc region comprises an optimized N-glycan having the structure of Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2. The glycoengineered Fc region binds Fc.gamma.RIIA or Fc.gamma.RIIIA with a greater affinity, relative to comparable monoclonal antibodies comprising the wild-type Fc region. The monoclonal antibodies of the invention are particularly useful in preventing, treating, or ameliorating one or more symptoms associated with a disease, disorder, or infection where an enhanced efficacy of effector cell function (e.g., ADCC) mediated by Fc.gamma.R is desired, e.g., cancer, autoimmune, infectious disease, and in enhancing the therapeutic efficacy of therapeutic antibodies the effect of which is mediated by ADCC.
Inventor(s):	Wong; Chi-Huey (Rancho Santa Fe, CA), Wu; Chung-Yi (New Taipei, TW), Ma; Che (Taipei, TW)
Assignee:	ACADEMIA SINICA (Taipei, TW)
Application Number:	14/723,297
Patent Claims:	1. A composition comprising an essentially homogeneous population of glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments thereof, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments thereof have a Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2 at each Asn-297 position in the Fc region, and wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments comprising the essentially homogeneous population have less than about 2% of precursor N-glycan. 2. The composition of claim 1, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments thereof exhibit an increased binding affinity for Fc.gamma.RIIA or Fc.gamma.RIIIA relative to a heterogeneously glycosylated population of the corresponding monoclonal IgG1 or IgG3 glycoantibodies. 3. The composition of claim 1, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments thereof exhibit an increased antibody-dependent cell mediated cytotoxicity (ADCC) activity relative to a heterogeneously glycosylated population of the corresponding monoclonal IgG1 or IgG3 glycoantibodies. 4. The composition of claim 1, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies bind to at least an antigen associated with cancers, autoimmune or inflammatory diseases, or infectious diseases. 5. The composition of claim 1, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies bind to an antigen associated with cancers. 6. The composition of claim 5, wherein the antigen is selected from the group consisting of GD2, GD3, GM2, Globo-H, SSEA-3, SSEA-4, CD16A, CD30, CD32B, CD33, CD52, EpCAM, CEA, gpA33, HER2/neu, A33, CD5, CD11c, CD19, CD20, CD22, CD23, CD27, CD40, CD45, CD79a, CD79b, CD103, CTLA4, ErbB1, ErbB3, ErbB4, VEGF receptor, TNF-.alpha. receptor, TNF-.beta. receptor, or TNF-.gamma. receptor, gpA33, Mucins, TAG-72, CAIX, PSMA, Folate-binding protein, VEGF, VEGFR, Integrin .alpha.V.beta.3, Integrin .alpha.5.beta.1, EGFR, ERBB2, ERBB3, MET, IGF1R, EPHA3, TRAILR1, TRAILR2, RANKL, FAP and Tenascin. 7. The composition of claim 1, wherein the composition is produced in vitro. 8. A pharmaceutical formulation comprising a composition according to claim 1 and a pharmaceutically acceptable carrier. 9. The composition of claim 1, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies comprise a light chain sequence and a heavy chain sequence of Rituximab (Rituxan.RTM.). 10. The composition of claim 1, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies comprise a light chain sequence and a heavy chain sequence of Trastuzumab (Herceptin.RTM.). 11. A composition comprising an essentially homogeneous population of glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments thereof, wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments thereof have a Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2 at each Asn-297 position in the Fc region, and wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments comprising the essentially homogeneous population have less than about 2% of precursor N-glycan and wherein the glycoengineered monoclonal IgG1 or IgG3 glycoantibodies or antigen binding fragments thereof exhibit an increased binding affinity for Fc.gamma.RIIA or Fc.gamma.RIIIA or an increased antibody-dependent cell mediated cytotoxicity (ADCC) activity, or a combination thereof, relative to a heterogeneously glycosylated population of the corresponding monoclonal IgG1 or IgG3 glycoantibodies. 12. A composition comprising an essentially pure population of glycoengineered monoclonal IgG1 or IgG3 antibodies or antigen binding fragments thereof, wherein at least about 90% by weight of the glycoengineered monoclonal IgG1 or IgG3 antibodies or antigen binding fragments thereof have a Sia.sub.2(.alpha.2-6)Gal.sub.2GlcNAc.sub.2Man.sub.3GlcNAc.sub.2 at each Asn 297 position in the Fc region.

Details for Patent 10,023,892

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2034-05-27
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.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2034-05-27