GLYCOSYLATION ENGINEERED ANTIBODY THERAPY
First Claim
1. A method of producing an antibody having a desired glycosylation state comprising the steps ofa) removing one or more sugars,b) chemically synthesizing a sugar, andc) enzymatically attaching the chemically synthesized sugar to (i) the antibody or (ii) a sugar attached to the antibody.
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Abstract
The instant invention is drawn to methods of generating a glycosylation-engineered antibody, and using the glycosylation-engineered antibody for treating a patient, particularly a cancer patient or a patient with an immune disease or disorder. The instant invention is also drawn to methods of generating a glycosylation-engineered antibody for use in the treatment of patients having a polymorphism that does not respond to conventional antibody therapy. The instant invention is also drawn to methods of improving the biological activity of an antibody by glycosylation engineering. The instant invention is also drawn to methods of modulating antibody-dependent cell-mediated cytoxicity (ADCC) using a glycosylation-engineered antibody.
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Citations
25 Claims
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1. A method of producing an antibody having a desired glycosylation state comprising the steps of
a) removing one or more sugars, b) chemically synthesizing a sugar, and c) enzymatically attaching the chemically synthesized sugar to (i) the antibody or (ii) a sugar attached to the antibody.
- 10. An antibody composition comprising antibodies having a substantially pure glycosylation state.
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14. A method of evaluating a biological activity of a glycopolypeptide comprising the steps of
a) producing a substantially pure population of glycopolypeptides having a selected glycosylation state, and b) measuring the biological activity of the glycopolypeptide.
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19. A method of improving the outcome of an antibody based therapy comprising the steps of
a) determining for a subject an Fcg Receptor allele present in a subject, and b) treating the subject with a monoclonal antibody comprising a substantially pure glycosylation state selected for (i) increased binding affinity to the Fcg Receptor allele present in the subject or (ii) increased antibody-dependent cell-mediated cytotoxicity.
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21. A method of selecting the glycosylation state for a monoclonal antibody comprising the steps of
a) determining a Fcg Receptor allele on an immune cell, and b) selecting a glycosylation state which modulates, relative to a source monoclonal antibody having a heterogeneous glycosylation state, i) Antibody Dependent Cell Cytotoxicity, ii) Complement Dependent Cytotoxicity, iii) an Fc g receptor binding affinity, or iv) a monoclonal antibody induced cell signaling event.
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23. A method of selecting for clinical development a glycoform of a monoclonal antibody for use in a population having an Fcg receptor allele comprising the steps of
a) testing a glycoform of a monoclonal antibody for biological activity against the Fcg Receptor alleles present in the population, and b) selecting for clinical development the monoclonal antibody glycoform capable of (i) increased binding affinity to the Fcg Receptor allele present in the population or (ii) increased antibody-dependent cell-mediated cytotoxicity.
Specification