Protein-carrier conjugates
First Claim
1. A conjugate of a therapeutic protein, the conjugate comprising:
- a therapeutic protein;
a carrier group including a non-antigenic hydrophilic polymer;
a linker disposed between the protein and the carrier group, said linker attached to the therapeutic protein via a carbamate bond and located directly adjacent to the carbamate bond, and said linker comprising a linear and saturated chain of between four and ten atoms of C and/or S.
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Abstract
The invention provides compositions and methods for covalent attachment of polymer and lipid carriers to therapeutic proteins to form carrier-protein conjugates having linkers between the carrier and protein portions of the conjugates. The linkers are selected to minimize steric effects. The linkers reduce the shielding effect of the carrier on the therapeutic protein and also allow better access for enzymatic or chemical cleavage of the carbamate bond. The linkers attach to the therapeutic protein via a carbamate bond and are either directly adjacent to the carbamate bond or are separated by a single carbon having a nitrogen side chain. Such linkers are solely comprised of carbon, sulfur and hydrogen and are between four and ten atoms (either C or S) in length.
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Citations
10 Claims
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1. A conjugate of a therapeutic protein, the conjugate comprising:
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a therapeutic protein; a carrier group including a non-antigenic hydrophilic polymer; a linker disposed between the protein and the carrier group, said linker attached to the therapeutic protein via a carbamate bond and located directly adjacent to the carbamate bond, and said linker comprising a linear and saturated chain of between four and ten atoms of C and/or S. - View Dependent Claims (2, 3, 4, 8, 10)
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- 5. A conjugate of a therapeutic protein, the conjugate represented by the formula:
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9. A method for preparing a conjugate of a therapeutic protein, the method comprising:
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(step
1) conjugating one or more carrier groups to a linker, where the carrier groups are selected from the group comprising a non-antigenic hydrophilic polymer, a lipid or a fatty acid, and where the linker is a linear and saturated chain of between four and ten atoms of C and/or S; and(step
2) conjugating the product of step 1 to a therapeutic protein or peptide via a carbamate bond.
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Specification