Methods and compositions for enhancing immune response

A method of enhancing a subject's immune response, the method comprising:

• depositing within a localized tissue region of the subject an immune response modifier (IRM) depot preparation that provides an extended residence time within the localized tissue region, wherein the IRM is a TLR agonist of at least one of TLR 7 or TLR 8, and wherein the IRM is a compound of compound of following Formula I:
• wherein:
• R1 has the formula alkylene-L-R1-1, alkenylene-L-R1-1, or alkynylene-L-R1-1, wherein:
• the alkylene, alkenylene, and alkynylene groups are optionally interrupted with
• one or more —O— groups;
• L is a bond or a functional linking group selected from the group consisting of
• —NH—S(O)2—, —NH—C(O)—, —NH—C(S)—, —NH—S(O)2—NR3—, —NH—C(O)—NR3—,
• —NH—C(S)—NR3—, —NH—C(O)—O—, —O—, —S—, and —S(O)2—;
• and
• R1-1 is a linear or branched aliphatic group having at least 11 carbon atoms, optionally including one or more unsaturated carbon-carbon bonds;
• R″ is selected from the group consisting of:
• hydrogen;
• alkyl;
• alkenyl;
• aryl;
• heteroaryl;
• heterocyclyl;
• alkylene-Y-alkyl;
• alkylene-Y-alkenyl;
• alkylene-Y-aryl;
• and
• alkyl or alkenyl substituted by one or more substituents selected from the group consisting of:
• —OH;
• halogen;
• —N(R4)2;
• —C(O)—C1-10alkyl;
• —C(O)—O—C1-10alkyl;
• —N3;
• aryl;
• heteroaryl;
• heterocyclyl;
• —C(O)-aryl;
• and
• —C(O)-heteroaryl;
• wherein aryl is phenyl, naphthyl, biphenyl, fluorenyl or indenyl;
• heteroaryl is furyl, thienyl, pyridyl, quinolinyl, isoquinolinyl, indolyl, isoindolyl, triazolyl, pyrrolyl, tetrazolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, benzofuranyl, benzothiophenyl, carbazolyl, benzoxazolyl, pyrimidinyl, benzimidazolyl, quinoxalinyl, benzothiazolyl, naphthyridinyl, isoxazolyl, isothiazolyl, purinyl, quinazolinyl, pyrazinyl, or 1-oxidopyridyl;
• and heterocyclyl is the fully saturated or partially unsaturated derivative of any one of the above heteroaryl groups, pyrrolidinyl, tetrahydrofuranyl, morpholinyl, thiomorpholinyl, piperidinyl, piperazinyl, thiazolidinyl, imidazolidinyl, isothiazolidinyl, tetrahydropyranyl, quinuclidinyl, or homopiperidinyl;
• wherein:
• Y is —O— or —S(O)0-2—;
• and each R4 is independently selected from the group consisting of hydrogen, C1-10alkyl, and C2-10alkenyl;
• RA and RB are taken together to form a fused benzene ring or a fused 5- to 7-membered saturated ring not containing a heteroatom, and unsubstituted or substituted by one or more R groups;
• each R is independently selected from the group consisting of halogen,
• hydroxy,
• alkyl,
• alkenyl,
• haloalkyl,
• alkoxy,
• alkylthio, and
• —N(R3)2;
• and
• each R3 is independently selected from the group consisting of hydrogen and alkyl;
• with the proviso that when L is —NH—S(O)2— and RA and RB join to form an unsubstituted benzene ring, R1-1 is a linear or branched aliphatic group having greater than 16 carbon atoms, optionally including one or more unsaturated carbon-carbon bonds;
• or a pharmaceutically acceptable salt thereof.