HOMOGENOUS ANTIBODY DRUG CONJUGATES VIA ENZYMATIC METHODS
First Claim
1. An antibody drug conjugate comprising an antibody conjugated to a conjugation moiety via an endogenous acceptor glutamine residue on the antibody, wherein the antibody drug conjugate is glycosylated in the Fc region.
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Accused Products
Abstract
The present application in one aspect provide Fc-containing polypeptide conjugates comprising an Fc-containing polypeptide conjugated to a conjugate moiety, wherein the Fc-containing polypeptide comprises an N-glycosylated Fc region comprising an acceptor glutamine residue flanked by an N-glycosylation site and wherein the conjugate moiety is conjugated to the Fc-containing polypeptide via the acceptor glutamine residue. Also provided are methods of making such Fc-containing polypeptide conjugates by using a wildtype or engineered transglutaminases. Further provided are engineered transglutaminases specifically designed for carrying out such reactions.
4 Citations
28 Claims
- 1. An antibody drug conjugate comprising an antibody conjugated to a conjugation moiety via an endogenous acceptor glutamine residue on the antibody, wherein the antibody drug conjugate is glycosylated in the Fc region.
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3-5. -5. (canceled)
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7-10. -10. (canceled)
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13. A method of making an antibody drug conjugate comprising an antibody specifically conjugated to a conjugate moiety comprising:
- contacting an antibody composition with the conjugate moiety in the presence of a transglutaminase under a condition sufficient to generate the antibody drug conjugate, wherein at least about 50% of the antibody in the composition is glycosylated in the Fc-region, and wherein the conjugate moiety is conjugated to the endogenous acceptor glutamine residue on the antibody.
- View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25)
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26. An engineered transglutaminase capable of conjugating an Fc-containing polypeptide to a conjugate moiety,
wherein the Fc-containing polypeptide comprises an N-glycosylated Fc region, wherein the N-glycosylated Fc region comprises an acceptor glutamine residue flanked by an N-glycosylation site, wherein upon reaction the conjugate moiety is conjugated to the Fc-containing polypeptide via the acceptor glutamine residue, and wherein the conjugation is at least about 10% more active than a wildtype transglutaminase under the same reaction conditions.
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28-29. -29. (canceled)
Specification