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US 2014/0193453 A1Published application
Immunomodulatory agent-polymeric compounds
AssigneeSelecta Biosciences, Inc.
InventorsCHARLES ZEPP, GRAYSON B. LIPFORD, YUN GAO, LLOYD JOHNSTON, FEN-NI FU, MARK J. KEEGAN, SAM BALDWIN
Life of this patent
Estimating the term…
Abstract
This invention relates to compositions, and related compounds and methods, of conjugates of immunomodulatory agents and polymers or unit(s) thereof. The conjugates may be contained within synthetic nanocarriers, and the immunomodulatory agents may be released from the synthetic nanocarriers in a pH sensitive manner.
Claims29
A compound that comprises a structure as in formula (I):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- and
- R8 is a biodegradable polymer or unit thereof.
6 more elements
2-3. (canceled)
A compound that comprises a structure as in formula (II):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- R5 is a polymer or unit thereof;
- X═C, N, O, or S;
- R6 and R7 are each independently absent, H, or substituted;
- and
- R9, R10, R11, and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino.
9 more elements
5-18. (canceled)
(canceled)
22-24. (canceled)
(canceled)
(canceled)
A method for making a conjugate that comprises a structure as in formula (I):
- comprising:
- 1) activating a biodegradable polymer or unit thereof, and exposing the activated biodegradable polymer or unit thereof and a compound comprising a structure as in formula (III) to a base and/or solvent:
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- and
- R8 is a biodegradable polymer or unit thereof or
- 2) exposing a composition comprising a polymer or unit thereof and a compound comprising a structure as in formula (III) to a coupling agent and base and/or solvent:
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- and
- R8 is a polymer or unit thereof.
18 more elements
35-37. (canceled)
A method for making a conjugate that comprises a structure as in formula (II):
- comprising:
- 1) combining an alcohol, a catalyst, and a compound comprising a structure as in formula (IV):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- R5 is a polymer or unit thereof;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11, and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino;
- and
- heating the alcohol, catalyst, and compound;
- or
- 2) combining an alcohol and a compound comprising a structure as in formula (IV):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- R5 is a polymer or unit thereof;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11 and R12 are each independently H, a halogen, OH, thio, NH7, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino;
- heating the alcohol and compound;
- and
- adding a catalyst;
- or
- 3) combining an alcohol, a catalyst, and a compound comprising a structure as in formula (IV):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- R5 is a polymer or unit thereof;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11 and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino.
44 more elements
39-57. (canceled)
A compound that comprises a structure as in formula (IV):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11, and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino.
8 more elements
59-67. (canceled)
A method for making a compound that comprises a structure as in formula (IV):
- comprising:
- combining, in the presence of a solvent and/or heat, a compound that comprises a structure as in formula (III):
- and
- a compound comprising a structure as in formula (V):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11, and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino.
12 more elements
69-76. (canceled)
A method for making a conjugate that comprises a structure as in formula (VI):
- comprising:
- 1) combining a catalyst, a diol having the formula (VII):
- HO-polymer-OH (VII),
- and a compound comprising a structure as in formula (IV):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11, and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino;
- and
- heating the alcohol, catalyst, and compound;
- or
- 2) combining a diol having the formula (VII):
- HO-polymer-OHμ(VII),
- and a compound comprising a structure as in formula (IV):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11 and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino;
- heating the alcohol and compound;
- and
- adding a catalyst;
- or
- 3) combining a catalyst, a diol having the formula (VII):
- HO-polymer-OH (VII),
- and a compound comprising a structure as in formula (IV):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11 and R12 are each independently H, a halogen, OH, thio, NH7, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino.
47 more elements
78-94. (canceled)
A compound that comprises a structure as in formula (VI):
- wherein R1═H, OH, SH, NH2, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino;
- R2═H, alkyl, or substituted alkyl;
- Y═N or C;
- R3 is absent if Y═N;
- or is H, alkyl, substituted alkyl, or combined with R4 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected if Y═C;
- R4 is H, or substituted or unsubstituted alkyl, alkoxy, alkylthio, or alkylamino when not combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- or is combined with R3 to form a carbocycle or heterocycle with the carbon atoms of the pyridine ring to which they are connected;
- X is C, N, O, or S;
- R6 and R7 are each independently H or substituted;
- and
- R9, R10, R11, and R12 are each independently H, a halogen, OH, thio, NH2, or substituted or unsubstituted alkyl, aryl, heterocyclic, alkoxy, aryloxy, alkylthio, arylthio, alkylamino, or arylamino.
8 more elements
96-122. (canceled)
Dependencies are inferred from the claim text.