The polymer conjugate of interferon beta with enhanced biological availability

The polymer conjugate of interferon beta with enhanced biological availability

  • CN 102,319,437 B
  • Filed: 12/23/2003
  • Issued: 10/13/2017
  • Est. Priority Date: 12/26/2002
  • Status: Active Grant
First Claim
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1. a kind of method for the vitro bioefficacy for increasing Non-glycosylated interferon β

  • , included in there is lauryl sodium sulfate(SDS) a kind of PEG (PEG) is optionally coupled under to the amino terminal amino acid of the interferon beta, to obtain warpThe interferon beta of modification,Wherein the amino-terminal amino acid is located at the distal end in acceptor-binding function domain of the interferon beta,The molecular weight that wherein PEG has be 10kDa-30kDa, wherein the increased vitro bioefficacy be in response toThe increased antiproliferative effect measured in the cell culture assays of interferon beta, andWherein described coupling includes(a) (i) mixes the interferon beta and the PEG aldehyde derivatives to form schiff bases, and (ii) is used under certain conditionGentle reducing agent, reduces the schiff bases, so that secondary amine key is formed, wherein the external biological of the interferon-beta through modificationEffect is 2.5 times -6 times of the vitro bioefficacy of the interferon-beta before the coupling, and wherein described selectivity couplingThe PEG for obtaining 90% is conjugated in amino-terminal amino acid;

    Or(b) (i) has the bar of minimum oxidation reaction at least one required methionine residues to the interferon-betaUnder part, with periodate by the N- terminal filaments propylhomoserin or threonine residues oxidation Decomposition of the interferon-beta into aldehydes, and (ii) willThe carbazic acid ester derivant of the aldehyde and the PEG is coupled, wherein the vitro bioefficacy of the interferon-beta through modificationIt is 6-10 times of the vitro bioefficacy of the interferon-beta before the coupling.

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