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US 11,959,118 B2Granted
Fc-containing polypeptides having improved properties and comprising mutations at positions 243 and 264 of the Fc-region
AssigneeMerck Sharp & Dohme Corp.
InventorsTerrance A. Stadheim, Dongxin Zha, Liming Liu
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Abstract
The present invention is directed to methods and compositions for the production of Fc-containing polypeptides having improved properties and comprising mutations at positions 243 and 264 of the Fc region.
Claims13
A method for increasing the bioavailability of an Fc-containing polypeptide when administered subcutaneously, comprising:
- introducing mutations at amino acid positions 243 and 264 of the Fc region of an Fc-containing polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 18, wherein the mutation at position 243 is selected from the group consisting of:
- F243A, F243 G, F243 S, F243 T, F243V, F243L, F243I, F243D, F243Y, F243E, F243R, F243W, and F243K and the mutation at position 264 is selected from the group consisting of:
- V264A, V264G, V264S, V264T, V264D, V264E, V264K, V264W, V264H, V264P, V264N, V264Q and V264L,
- wherein the numbering is according to the EU index as in Kabat;
- and
- wherein the bioavailability of the Fc-containing polypeptide comprising the mutations is increased when the Fc-containing polypeptide is administered subcutaneously compared to subcutaneous administration of an Fc-containing polypeptide without said mutations.
4 more elements
A method for producing an Fc-containing polypeptide having increased bioavailability when administered subcutaneously, comprising:
- (a) providing a host cell comprising a nucleic acid molecule encoding an Fc-containing polypeptide comprising the amino acid sequence set forth in SEQ ID NO:
- 18 and having alanine at positions 243 and 264 of the Fc, wherein the host cell has been genetically engineered to produce glycoproteins having sialylated N-glycans in which the sialic acid residues in the sialylated N-glycans are attached via α-2,6 linkages, and wherein the Fc numbering is according to the EU index as in Kabat;
- (b) culturing the transformed host cell under conditions that induce expression of the nucleic acid molecule encoding the Fc-containing polypeptide to produce an Fc-containing polypeptide comprising sialylated N-glycans in which the sialic acid residues in the sialylated N-glycans are attached via α-2,6 linkages;
- and
- (c) isolating the Fc-containing polypeptide comprising the sialylated N-glycans in which the sialic acid residues in the sialylated N-glycans are attached via α-2,6 linkages from the transformed host cell to produce the Fc-containing polypeptide having increased bioavailability when administered subcutaneously compared to subcutaneous administration of an Fc-containing polypeptide without said mutations.
2 more elements
Dependencies are inferred from the claim text.