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Generated: September 16, 2019

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Claims for Patent: 8,815,237

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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.

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PCT Information
PCT FiledDecember 05, 2008PCT Application Number:PCT/US2008/085757
PCT Publication Date:June 25, 2009PCT Publication Number:WO2009/079242

Details for Patent 8,815,237

Applicant Tradename Biologic Ingredient Dosage Form BLA Number Approval Date Patent No. Assignee Estimated Patent Expiration Status Orphan Source
Schering INTRON A interferon alfa-2b VIAL 103132 001 1986-06-04   Try a Free Trial Massachusetts Institute of Technology (Cambridge, MA) The Rockefeller University (New York, NY) 2027-12-05 RX search
Schering INTRON A interferon alfa-2b VIAL 103132 002 1986-06-04   Try a Free Trial Massachusetts Institute of Technology (Cambridge, MA) The Rockefeller University (New York, NY) 2027-12-05 RX search
Schering INTRON A interferon alfa-2b VIAL 103132 003 1986-06-04   Try a Free Trial Massachusetts Institute of Technology (Cambridge, MA) The Rockefeller University (New York, NY) 2027-12-05 RX search
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Number >Approval Date >Patent No. >Assignee >Estimated Patent Expiration >Status >Orphan >Source

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