Claims for Patent: 8,815,237

Summary for Patent: 8,815,237

Title:	Aglycosylated immunoglobulin mutants
Abstract:	The present invention is based, in part, on our discovery of immunoglobulins (e.g., immunoglobulin G (IgG)) polypeptides (e.g., murine or human IgG, such as human IgG1) that are aglycosylated yet retain the ability to bind to an Fc receptor, such as an activating Fc receptor (e.g., Fc.gamma.RIIA and/or Fc.gamma.RIIIA).
Inventor(s):	Wittrup; K. Dane (Chestnut Hill, MA), Ravetch; Jeffrey (New York, NY), Sazinsky; Stephen Lael (Brookline, MA)
Assignee:	Massachusetts Institute of Technology (Cambridge, MA) The Rockefeller University (New York, NY)
Application Number:	12/746,411
Patent Claims:	1. An IgG antibody comprising a first mutation in the C'/E loop of the CH2 domain of the Fc region that eliminates antibody glycosylation in the CH2 domain and a second mutation in the F/G loop of the CH2 domain, wherein the antibody exhibits at least 50% binding activity to activating receptor Fc.gamma.RIIA or Fc.gamma.RIIIA, relative to the corresponding wild type antibody, wherein the mutation in the F/G loop of the CH2 domain comprises K326I. 2. The antibody of claim 1, comprising the mutations (a) K326I, (b) A327Y or A327E, and (c) L328G or L328A. 3. The antibody of claim 1, wherein the antibody specifically binds a cancer antigen or is useful as a cancer therapeutic. 4. The antibody of claim 1, wherein the mutation in the F/G loop of the CH2 domain comprises K326I, A327Y, and L328G. 5. The antibody of claim 1, wherein the mutation in the F/G loop of the CH2 domain comprises K326I, A327E, and L328A. 6. The antibody of claim 1, wherein the mutation in the C'/E loop of the CH2 domain comprises N297H and S298A; T299A; N297D and S298T; or N297D and S298A. 7. The antibody of claim 4, wherein the mutation in the C'/E loop of the CH2 domain comprises N297H and S298A; T299A; N297D and S298T; or N297D and S298A. 8. The antibody of claim 5, wherein the mutation in the C'/E loop of the CH2 domain comprises N297H and S298A; T299A; N297D and S298T; or N297D and S298A. 9. The antibody of claim 1, wherein first mutation in the C'/E loop of the CH2 domain comprises N297H, S298A, T299A, N297D, S298G, or S298T. 10. The antibody of claim 1, wherein the first mutation in the C'/E loop comprises a mutation at position 298 and/or 299 of the CH2 domain. 11. The antibody of claim 1, comprising one or more of the following mutations: E269D, D270E, N297D, N297H, S298A, S298G, S298T, T299A, T299G, T299H, K326E, K326I, A327E, A327Y, L328A, and L328G. 12. A pharmaceutically acceptable composition comprising the antibody of claim 1. 13. A nucleic acid comprising a sequence encoding the antibody of claim 1. 14. An expression vector comprising the nucleic acid of claim 13. 15. The expression vector of claim 14, further comprising a leader sequence. 16. A host cell comprising the expression vector of claim 14. 17. An IgG antibody comprising a first mutation in the C'/E loop of the CH2 domain of the Fc region that eliminates antibody glycosylation in the CH2 domain and a second mutation in the F/G loop of the CH2 domain, wherein the antibody exhibits at least 50% binding activity to activating receptor Fc.gamma.RIIA or Fc.gamma.RIIIA, relative to the corresponding wild type antibody, wherein the mutation in the C'/E loop of the CH2 domain comprises N297H and S298A; T299A; N297D and S298T; or N297D and S298A, and further wherein the mutation in the F/G loop of the CH2 domain comprises K326I, A327Y, and L328G; or K326I, A327E, and L328A. 18. The IgG antibody of claim 17, wherein the antibody specifically binds a cancer antigen. 19. The IgG antibody of claim 17, wherein the cancer antigen is selected from carcinoembryonic antigen (CEA), RAGE, MART (melanoma antigen), MAGE (melanoma antigen) 1-4, 6 and 12; MUC (mucin)-1 or 2, tyrosinase, Pmel 17 (gp100), GnT-V intron V sequence (N-acetylglucoaminyltransferase V intron V sequence), Prostate cancer psm, PRAME (melanoma antigen), .beta.-catenin, MUM-1-B (melanoma ubiquitous mutated gene product), GAGE (melanoma antigen) 1, BAGE (melanoma antigen) 2-10, c-ERB2 (Her2/neu), EBNA (Epstein-Barr Virus nuclear antigen) 1-6, gp75, human papilloma virus (HPV) E6 and E7, p53, lung resistance protein (LRP) Bc1-2, prostate specific antigen (PSA), and Ki-67.

Details for Patent 8,815,237

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2027-12-05
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2027-12-05
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2027-12-05