PATENT CLAIM ANALYSIS

Application Number: 15976847
Application Type: Utility
Filing Date: 2018-05
Publication Date: 2018-11
Patent Classification: ["424", "490000"]

Abstract:
An improved microparticle or lyophilized or otherwise reconstitutable microparticle composition thereof for medical therapy, including ocular therapy.

Claim (Index 1):
A solid aggregating microparticle comprising a prodrug of a therapeutically active compound, encapsulated in at least one biodegradable polymer and at least one hydrophobic polymer covalently bound to a hydrophillic polymer, wherein the microparticle has a mean diameter between 10 \u03bcm and 60 \u03bcm and surface surfactant and that:\n (i) has a solid core with less than 10% porosity by ratio of void space to total volume; (ii) has a modified surface which has been treated under mild conditions at a temperature less than about 18\u00b0 C. to remove surface surfactant; (iii) is capable of aggregating in vivo to form at least one pellet of at least 500 \u03bcm in vivo capable of sustained drug delivery in vivo for at least three months; and (iv) wherein the prodrug is selected from the formula: or a pharmaceutically acceptable salt thereof wherein R 1 , R 2 , and R 3  are selected from \u2014C(O)R 4 , C(O)A, and hydrogen; R 4  is selected from: (i) \u2014C 10 -C 30 alkylR 5 , \u2014C 10 -C 30 alkenylR 5 , \u2014C 10 -C 30 alkynylR 5 , \u2014C 10 -C 30 alkenylalkynylR 5 , \u2014C 10 -C 30 alkyl, \u2014C 10 -C 30 alkenyl, \u2014C 10 -C 30 alkynyl, and \u2014C 10 -C 30 alkenylalkynyl; and (ii) an unsaturated fatty acid selected from \u2014(CH 2 ) 8 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 ), \u2014(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 ), \u2014(CH 2 ) 8 (CHCHCH 2 ) 3 CH 3 ), stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; R 5  is selected from halogen, hydroxyl, cyano, mercapto, amino, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, \u2014S(O) 2 alkyl, \u2014S(O)alkyl, \u2014P(O)(Oalkyl) 2 , B(OH) 2 , \u2014Si(CH 3 ) 3 , \u2014COOH, \u2014COOalkyl, and \u2014CONH 2 ; R 6  is selected from: (i) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, a polyester, and polyamide;\n (ii) \u2014C 10 -C 30 alkylR 5 , \u2014C 10 -C 30 alkenylR 5 , \u2014C 10 -C 30 alkynylR 5 , \u2014C 10 -C 30 alkenylalkynylR 5 , \u2014C 10 -C 30 alkyl, \u2014C 10 -C 30 alkenyl, \u2014C 10 -C 30 alkynyl, and \u2014C 10 -C 30 alkenylalkynyl; \n (iii) an unsaturated fatty acid residue selected from \u2014(CH 2 ) 8 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 ), \u2014(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 ), \u2014(CH 2 ) 8 (CHCHCH 2 ) 3 CH 3 ), stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; and \n (iv) alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, arylalkyl, and heteroarylalkyl; \n R 7  and R 8  are independently selected from \u2014C(O)R 4 , \u2014C(O)A, hydrogen, and R 50 ; \n R 10  is selected from: \n (i) N\u2550C 4 -C 30 alkenylR 5 , \u2014N\u2550C 4 -C 30 alkynylR 5 , \u2014N\u2550C 4 -C 30 alkenylalkynylR 5 , \u2014N\u2550C 1 -C 30 alkylR 5 , \u2014N\u2550C 4 -C 30 alkenyl, \u2014N\u2550C 4 -C 30 alkynyl, \u2014N\u2550C 4 -C 30 alkenylalkynyl, \u2014N\u2550C 1 -C 30 alkyl, \u2014N\u2550CH\u2014C 3 -C 30 alkenylR 5 , \u2014N\u2550CH\u2014C 3 -C 30 alkynylR 5 , \u2014N\u2550CH\u2014C 3 -C 30 alkenylalkynylR 5 , \u2014N\u2550C 1 -C 30 alkylR 5 , \u2014N\u2550CH\u2014C 3 -C 30 alkenyl, \u2014N\u2550CH\u2014C 3 -C 30 alkynyl, \u2014N\u2550CH\u2014C 3 -C 30 alkenylalkynyl, \u2014N\u2550C 1 -C 30 alkyl, \u2014NHC 3 -C 30 alkenylR 5 , \u2014NH\u2014C 3 -C 30 alkynylR 5 , \u2014NH\u2014C 5 -C 30 alkenylalkynylR 5 , \u2014NHC 0 -C 30 alkylR 5 , \u2014NHC 3 -C 30 alkenylR 16 , \u2014NH\u2014C 3 -C 30 alkynylR 16 , \u2014NH\u2014C 5 -C 30 alkenylalkynylR 16 , and \u2014NHC 0 -C 30 alkylR 16 ; \n (ii) an imine-, amine- or amide-linked unsaturated fatty acid selected from \u2014N\u2550CH(CH 2 ) 7 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 , \u2014NHCH 2 (CH 2 ) 7 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 , \u2014NHC(O)(CH 2 ) 7 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 , \u2014N\u2550CH(CH 2 ) 2 (CHCHCH 2 ) 6 CH 3 , \u2014NH(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 , \u2014NHC(O)(CH 2 ) 2 (CHCHCH 2 ) 6 CH 3 , \u2014N\u2550CH(CH 2 ) 3 (CHCHCH 2 ) 5 CH 3 , \u2014NH(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 , \u2014NHC(O)(CH 2 ) 3 (CHCHCH 2 ) 5 CH 3 ), \u2014N\u2550CH(CH 2 ) 7 (CHCHCH 2 ) 3 CH 3 , \u2014NH(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 , \u2014NHC(O)(CH 2 ) 3 (CHCHCH 2 ) 5 CH 3 , stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; \n (iii) an imine-, amine- or amide-linked polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), \n polyglycolic acid, polyester, and polyamide;\n (iv)-NHC(O)C 1-20 alkyl, \u2014NHC(O)C 1-20 alkenyl, \u2014NHC(O)C 1-20 alkynyl, \u2014NHC(O)(C 1-20 alkyl with at least one R 5  substituent on the alkyl chain, \u2014NHC(O)(C 1-20 alkenyl with at least one R 5  substituent on the alkenyl chain, \u2014NHC(O)(C 1-20 alkynyl with at least one R 5  substituent on the alkynyl chain, \u2014NH(lactic acid) 2-20 C(O)C 1-20 alkyl, \u2014NH(lactic acid) 2-10 C(O)C 1-20 alkyl, \u2014NH(lactic acid) 4-20 C(O)C 1-20 alkyl, \u2014NH(lactic acid) 2-20 C(O)C 1-10 alkyl, \u2014NH(lactic acid) 2-20 C(O)C 4-10 alkyl, \u2014NH(lactic acid) 2-20 C(O)OH, \u2014NH(lactic acid) 2-10 C(O)OH, \u2014NH(lactic acid) 4-20 C(O)OH, \u2014NH(lactic acid) 2-10 C(O)OH, \u2014NH(lactic acid) 4-10 C(O)OH, \u2014NH(lactide-co-glycolide) 2-10 C(O)C 1-20 alkyl, \u2014NH(lactide-co-glycolide) 4-10 C(O)C 1-20 alkyl, \u2014NH(lactide-co-glycolide) 2-10 C(O)C 1-10 alkyl, \u2014NH(lactide-co-glycolide) 2-10 C(O)C 4-20 alkyl, \u2014NH(glycolic acid) 2-10 C(O)C 1-10 alkyl, \u2014NH(glycolic acid) 4-10 C(O)C 1-10 alkyl, \u2014NH(lactic acid) 4-10 C(O)C 1-10 alkyl, \u2014NH(lactic acid) 2-10 C(O)C 1-10 alkyl, NH(lactic acid) 2-10 C(O)C 4-10 alkyl, \u2014NH(lactic acid) 2-10 C(O)C 4-10 alkyl, and \u2014NH(lactic acid) 2-10 C(O)C 4-10 alkyl; \n and\n (vi) NH 2  wherein R 15  is R 16 ; \n R 15  is selected from R 16  and R 17 ; \n R 16  is selected from: \n (i) \u2014C(O)C 3 -C 30 alkylR 5 , \u2014C(O)C 3 -C 30 alkenylR 5 , \u2014C(O)C 3 -C 30 alkynylR 5 , \u2014C(O)C 3 -C 30 alkenylalkynylR 5 , \u2014C(O)C 3 -C 30 alkyl, \u2014C(O)C 3 -C 30 alkenyl, \u2014C(O)C 3 -C 30 alkynyl, and \u2014C(O)C 3 -C 30 alkenylalkynyl; \n (ii) an unsaturated fatty acid residue selected from \u2014C(O)(CH 2 ) 7 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014C(O)(CH 2 ) 2 (CHCHCH 2 ) 6 CH 3 ), \u2014C(O)(CH 2 ) 3 (CHCHCH 2 ) 5 CH 3 ), \u2014C(O)(CH 2 ) 7 (CHCHCH 2 ) 3 CH 3 ), y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; and \n (iii) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), \n polyglycolic acid, polyester, and polyamide;\n R 17  is selected from H and \u2014C(O)A; \n R 23 , R 24 , and R 25  are independently selected from hydrogen, halogen, hydroxyl, cyano, mercapto, nitro, amino, aryl, alkyl, alkoxy, alkenyl, alkynyl cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, \u2014S(O) 2 alkyl, \u2014S(O)alkyl, \u2014P(O)(Oalkyl) 2 , B(OH) 2 , \u2014Si(CH 3 ) 3 , \u2014COOH, \u2014COOalkyl, \u2014CONH 2 , \n R 26  is selected from H, C(O)A, \u2014C 0 -C 10 alkylR 5 , \u2014C 2 -C 10 alkenylR 5 , \u2014C 2 -C 10 alkynylR 5 , \u2014C 2 -C 10 alkenyl, and \u2014C 2 -C 10 alkynyl; R 29  is selected from: R 30  is selected from:\n (i) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), a polyglycolic acid, a polyester, and a polyamide; \n R 31  is hydrogen, A, \u2014COOH, \u2014C(O)A, alkyl, alkoxy, alkenyl, alkynyl cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, hydroxy, or polyethylene glycol; and R 31a  is hydrogen, \u2014C(O)alkyl, aryl, alkyl, cycloalkyl, cycloalkylalkyl, helerocyclyl, heterocycloalkyl, arylalkyl, heteroaryl, heteroarylalkyl, polylactic acid, polygylcolic acid, polyethylene glycol, stearoyl, or R 31b  is hydrogen, aryl, alkyl, cycloalky, cycloalkyl, cycloalkylalkyl, helerocyclyl, heterocycloalkyl, arylalkyl, heteroaryl, hcteroarylalkyl, or polyethylene glycol; R 32  is selected from R 35 , R 121 , alkyl, alkyloxy, polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), a polyglycolic acid, a polyester, and a polyamide, wherein each R 32  other than R 35  and R 121  is substituted with at least one L 4 -R 121 ;\n R 33  is selected from:\n (i) carbonyl linked polyethylene glycol, carbonyl linked polypropylene glycol, carbonyl linked polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), a polyglycolic acid, a polyester, and a polyamide; \n \n (iii) \u2014C(O)C 17-30 alkyl, \u2014C(O)C 10-30 alkenyl, \u2014C(O)C 10-30 alkynyl, \u2014C(O)C 10-30 alkyl with at least one R 5  substituent on the alkyl chain, \u2014C(O)C 10-30 alkenyl with at least one R 5  substituent on the alkenyl chain, and \u2014C(O)C 10-30 alkynyl with at least one R 5  substituent on the alkynyl chain; (iv) -(lactic acid) 1-20 C(O)C 1-30 alkyl, -(lactic acid) 1-10 C(O)C 1-30 alkyl, -(lactic acid) 4-20 C(O)C 1-30 alkyl, -(lactic acid) 1-20 C(O)C 1-10 alkyl, -(lactic acid) 1-20 C(O)C 4-10 alkyl, -(lactic acid) 1-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-10 C(O)OH, -(lactide-co-glycolide) 1-10 C(O)C 1-22 alkyl, -(lactide-co-glycolide) 4-10 C(O)C 1-22 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 1-12 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 4-22 alkyl, -(glycolic acid) 1-10 C(O)C 1-10 alkyl, -(glycolic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, and -(lactic acid) 1-10 C(O)C 4-10 alkyl; (v) \u2014(C(O)CH 2 O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, (C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 2-10 (C(O)CH(CH 3 )O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-12 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 4-22 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 2-10 (C(O)CH 2 O) 2-10 C(O)C 1-3 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-12 alkyl, and \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 4-22 alkyl; and R 34  is selected from R 381 , carbonyl linked polyethylene glycol, carbonyl linked polypropylene glycol, carbonyl linked polypropylene oxide, polylactic acid, and poly(lactic-co-glycolic acid), a polyglycolic acid, a polyester, polyamide, wherein each R 34  other than R 381  is substituted with at least one L 4 -R 121 ;\n R 35  is selected from: \n R 37  is selected from R 121 , polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), a polyglycolic acid, a polyester, and a polyamide wherein each R 37  other than R 38  and R 121  is substituted with at least one L 6 -R 121 ; R 38  is selected from: R 50  is selected from carbonyl derivatives of polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, a polyester, and apolyamide;\n R 61  and R 62  are independently selected from hydrogen, \n R 100  is selected from: (i) C 1 -C 10 alkyl, \u2014C 0 -C 10 alkyl(C 3 -C 7 cycloalkyl), heterocycle, \u2014C 0 -C 10 alkyl(C 3 -C 7 heterocycloalkyl), -arylC 0 -C 10 alkyl, -heteroarylalkyl, \u2014C 0 -C 10 alkylC 2 -C 10 alkenyl, and C 2 -C 10 alkynyl; (ii) an unsaturated fatty acid residue selected from \u2014(CH 2 ) 8 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 ), \u2014(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 ), \u2014(CH 2 ) 8 (CHCHCH 2 ) 3 CH 3 ), stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; (iii) \u2014C 10 -C 30 alkylR 5 , \u2014C 10 -C 30 alkenylR 5 , \u2014C 10 -C 30 alkynylR 5 , \u2014C 10 -C 30 alkenylalkynylR 5 , \u2014C 10 -C 30 alkyl, \u2014C 10 -C 30 alkenyl, \u2014C 10 -C 30 alkynyl, \u2014C 10 -C 30 alkenylalkynyl; and (iv) R 50 ; R 103  is selected from H, alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; R 106  is selected from: (ii) \u2014C(O)C 10-30 alkyl, \u2014C(O)C 10-30 alkenyl, \u2014C(O)C 10-30 alkynyl, \u2014C(O)(C 10-30 alkyl with at least one R 5  substituent on the alkyl chain), \u2014C(O)(C 10-30 alkenyl with at least one R 5  substituent on the alkenyl chain) \u2014C(O)(C 10-30 alkynyl with at least one R 5  substituent on the alkynyl chain), -(lactic acid) 1-20 C(O)C 1-30 alkyl, -(lactic acid) 1-10 C(O)C 1-30 alkyl, -(lactic acid) 4-20 C(O)C 1-30 alkyl, -(lactic acid) 1-20 C(O)C 1-10 alkyl, -(lactic acid) 1-20 C(O) C4-10 alkyl, -(lactic acid) 1-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-10 C(O)OH, -(lactide-co-glycolide) 1-10 C(O) C1-22 alkyl, -(lactide-co-glycolide) 4-10 C(O) C1-22 alkyl, -(lactide-co-glycolide) 1-10 C(O) C1-12 alkyl, -(lactide-co-glycolide) 1-10 C(O) C4-22 alkyl, -(glycolic acid) 1-10 C(O) C1-10 alkyl, -(glycolic acid) 4-10 C(O) C1-10 alkyl, -(lactic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, and -(lactic acid) 1-10 C(O)C 4-10 alkyl; and (iii) \u2014(C(O)CH 2 O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, (C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 2-10 (C(O)CH(CH 3 )O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-12 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 4-22 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 2-10 (C(O)CH 2 O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-12 alkyl, and \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 4-22 alkyl; R 116  is selected from R 117 , alkyl, alkyloxy, acyl, polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), a polyglycolic acid, a polyester, a polyamide, wherein each R 116  other than R 17  is substituted with at least one L 4 -R 121 ; R 117  is selected from: R 118  is selected from: (i) \u2014C(O)C 5 -C 30 alkylR 5 , \u2014C(O)C 2 -C 30 alkenylR 5 , \u2014C(O)C 2 -C 30 alkynylR 5 , \u2014C(O)C 4 -C 30 alkenylalkynylR 5 , \u2014C(O)C 5 -C 30 alkyl, \u2014C(O)C 2 -C 30 alkenyl, \u2014C(O)C 2 -C 30 alkynyl, and \u2014C(O)C 4 -C 30 alkenylalkynyl; (ii) \u2014C(O)(C 1-30 alkyl with at least one R 5  substituent on the alkyl chain, \u2014C(O)C 1-30 alkenyl with at least one R 5  substituent on the alkenyl chain, \u2014C(O)C 1-30 alkynyl with at least one R 5  substituent on the alkynyl chain), -(lactic acid) 1-20 C(O)C 1-30 alkyl, -(lactic acid) 1-10 C(O)C 1-30 alkyl, -(lactic acid) 4-20 C(O)C 1-30 alkyl, -(lactic acid) 1-20 C(O)C 1-10 alkyl, -(lactic acid) 1-20 C(O)C 4-10 alkyl, -(lactic acid) 1-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-10 C(O)OH, -(lactide-co-glycolide) 1-10 C(O)C 1-30 alkyl, -(lactide-co-glycolide) 4-10 C(O)C 1-30 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 1-12 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 4-22 alkyl, -(glycolic acid) 1-10 C(O)C 1-10 alkyl, -(glycolic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, and -(lactic acid) 1-10 C(O)C 4-10 alkyl; (iii) an unsaturated fatty acid residue selected from \u2014(CH 2 ) 8 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 ), \u2014(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 ), \u2014(CH 2 ) 8 (CHCHCH 2 ) 3 CH 3 ), stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; (iv) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, polyester, and a polyamide; and\n (vi) \u2014(C(O)CH 2 O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, (C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 2-10 (C(O)CH(CH 3 )O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-12 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 4-22 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 2-10 (C(O)CH 2 O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-12 alkyl, and \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 4-22 alkyl; \n R 121  is selected from: \n R 123  is selected from: (i) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, polyester, a polyamide, (ii) \u2014C(O)C 17-30 alkyl, \u2014C(O)C 10-30 alkenyl, \u2014C(O)C 10-30 alkynyl, \u2014C(O)(C 10-30 alkyl with at least one R 5  substituent on the alkyl chain), \u2014C(O)(C 10-30 alkenyl with at least one R 5  substituent on the alkenyl chain) \u2014C(O)(C 10-30 alkynyl with at least one R 5  substituent on the alkynyl chain), -(lactic acid) 1-20 C(O)C 1-30 alkyl, -(lactic acid) 1-10 C(O)C 1-30 alkyl, -(lactic acid) 4-20 C(O)C 1-30 alkyl, -(lactic acid) 1-20 C(O)C 1-10 alkyl, -(lactic acid) 1-20 C(O)C 4-10 alkyl, -(lactic acid) 1-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-10 C(O)OH, -(lactide-co-glycolide) 1-10 C(O)C 1-22 alkyl, -(lactide-co-glycolide) 4-10 -C(O)C 1-22 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 1-12 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 4-22 alkyl, -(glycolic acid) 1-10 C(O)C 1-10 alkyl, -(glycolic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, and -(lactic acid) 1-10 C(O)C 4-10 alkyl; (iii) \u2014(C(O)CH 2 O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, (C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 2-10 (C(O)CH(CH 3 )O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-12 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 4-22 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 2-10 (C(O)CH 2 O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-12 alkyl, and \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 4-22 alkyl; and (v) hydrogen, \u2014C(O)A, aryl, alkyl, alkenyl, alkynyl cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; R 130 , R 131 , and R 133  are independently selected at each occurrence from H, C 1 -C 30 alkyl, \u2014C(O)C 1 -C 30 alkyl, C 1 -C 30 heteroalkyl, and R 136 ; R 132  is selected from R 136 , C 1 -C 30 alkyl, C 1 -C 30 cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and alkylaryl; R 134  and R 135  are independently selected from H, alkyl, \u2014SO 2 CH 3 , \u2014C(O)CH 3 , and \u2014C(O)NH 2 ; or R 134  and R 135  can together form a heterocycloalkyl; R 136  is selected from R 137 , acyl, alkyl, alkyloxy, polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, polyester, and a polyamide, wherein each R 136  other than R 137  is substituted with at least one L 4 -R 121 ; or R 136  is L 4 -R 121  or R 121 ; wherein at least one of R 130 , R 131 , and R 133  is R 136 ; R 137  is selected from: R 140  is selected from R 136 , hydrogen, alkyl, cycloalkyl, heterocycloalkyl, and aryl; R 141  is selected from hydrogen, \u2014C(O)NR 161 R 162 , \u2014C(O)R 161 , \u2014C(O)OR 161 , nitro, amino, \u2014NR 134 R 135 , alkyl, alkoxy, alkylalkoxy, alkoxyalkoxy, haloalkoxy, cycloalkyl, heterocycloalkyl, heteroaryl, aryl, and halogen; R 150  and R 151  are independently selected at each occurrence from H, C 1 -C 30 alkyl, \u2014C(O)C 1 -C 30 alkyl, C 1 -C 30 heteroalkyl, and R 156  wherein at least one of R 150  and R 151  is R 156 ; R 152  is selected from C 1 -C 30 alkyl, C 1 -C 30 cycloalkyl, heterocycloalkyl, aryl, heteroaryl, and alkylaryl; or R 151  and R 152  can together form a cycloalkyl or heterocycloalkyl; R 156  is selected from: (i) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid) polyglycolic acid, polyester, and a polyamide; and R 160  is selected from H, C 1 -C 30 alkyl, C 1 -C 30 cycloalkyl, heterocycloalkyl, and aryl; R 161  and R 162  are independently selected from hydrogen, aryl, alkyl, cycloalkyl, arylalkyl, heteroaryl, heteroarylalkyl, and heterocyclyl; R 175  is selected from: C(O)A, C(O)R 4 , and R 178 ; R 178  is selected from: (i) carbonyl linked polyethylene glycol, carbonyl linked polypropylene glycol, carbonyl linked polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, polyester, polyamide, (ii) -(lactic acid) 1-20 C(O)C 1-22 alkyl, -(lactic acid) 1-10 C(O)C 1-22 alkyl, -(lactic acid) 4-20 C(O)C 1-22 alkyl, -(lactic acid) 1-20 C(O)C 1-10 alkyl, -(lactic acid) 1-20 C(O) C4-10 alkyl, -(lactic acid) 1-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-20 C(O)OH, -(lactic acid) 1-10 C(O)OH, -(lactic acid) 4-10 C(O)OH, -(lactide-co-glycolide) 1-10 C(O)C 1-22 alkyl, -(lactide-co-glycolide) 4-10 C(O)C 1-22 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 1-12 alkyl, -(lactide-co-glycolide) 1-10 C(O)C 4-22 alkyl, -(glycolic acid) 1-10 C(O)C 1-10 alkyl, -(glycolic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 4-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 1-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, -(lactic acid) 1-10 C(O)C 4-10 alkyl, or -(lactic acid) 1-10 C(O)C 4-10 alkyl; (iii) \u2014(C(O)CH 2 O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 4-20 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-20 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 4-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 1-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, (C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 C(O)C 4-10 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 2-10 (C(O)CH(CH 3 )O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 1-12 alkyl, \u2014(C(O)CH 2 O) 1-10 (C(O)CH(CH 3 )O) 1-10 C(O)C 4-22 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 2-10 (C(O)CH 2 O) 2-10 C(O)C 1-30 alkyl, \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 1-12 alkyl, and \u2014(C(O)CH(CH 3 )O) 1-10 (C(O)CH 2 O) 1-10 C(O)C 4-22 alkyl; and R 180  is C 1 -C 6  alkyl, acyl, or hydrogen; R 191  is selected from: and R 195 ;\n R 192  is independently selected from alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, cyano, amino, hydroxyl, and acyl; \n R 193  is independently selected from alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, amino, hydroxyl, and acyl; \n or two R 193  groups with the carbon to which they are linked form a carbonyl group; \n or two R 193  groups with the carbon(s) to which they are linked form a fused or spirocyclic ring; \n R 194  is selected from alkyl, cycloalkyl, R 175 , and acyl; \n R 195  is selected from aryl, heteroaryl, cycloalkyl, and heterocycle; \n R 302  and R 333  are independently selected from H, C 1 -C 30 alkyl, \u2014C(O)C 1 -C 30 alkyl, C 1 -C 30 heteroalkyl, C 2 -C 30 alkenyl, and R 356  wherein at least one of R 302 , R 333  and R 350  is R 356 ; \n R 303 , R 304 , and R 344  are independently selected at each occurrence from H, C 1 -C 30 alkyl, \u2014C(O)C 1 -C 30 alkyl, C 2 -C 30 alkenyl, C 1 -C 30 heteroalkoaryl, and R 336  wherein at least one of R 303 , R 304 , and R 344  is R 336 ; \n R 311  is hydroxy, amino, A, alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, or polyethylene glycol; \n R 314  is an unsaturated fatty acid residue selected from \u2014(CH 2 ) 8 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 ), \u2014(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 ), \u2014(CH 2 ) 8 (CHCHCH 2 ) 3 CH 3 ), stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; \n R 316  is selected from \n R 323  is independently selected from polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, polyester, polyamide, R 336  is selected from: R 341a  and R 341b  are independently selected from hydrogen and alkyl; R 350  is selected from H, C 1 -C 30 alkyl, \u2014C(O)C 1 -C 30 alkyl, C 1 -C 30 heteroalkyl, C 2 -C 30 alkenyl, and R 356  wherein at least one of R 302 , R 333  and R 350  is R 356 ; R 356  is selected from (i) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid) polyglycolic acid, polyester, and a polyamide; R 360  is selected from R 364  is selected from: acyl, carbonyl linked polyethylene glycol, carbonyl linked polypropylene glycol, carbonyl linked polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, polyester, polyamide, R 366  is selected from R 381  is selected from: R 433  is selected from hydrogen, \u2014C(O)A, acyl, aryl, alkyl, alkenyl, alkynyl cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; R 611  is selected from: (i) \u2014C(O)OC 5 -C 30 alkylR 5 , \u2014C(O)OC 2 -C 30 alkenylR 5 , \u2014C(O)OC 2 -C 30 alkynylR 5 , \u2014C(O)OC 4 -C 30 alkenylalkynylR 5 , \u2014C(O)OC 5 -C 30 alkyl, \u2014C(O)OC 2 -C 30 alkenyl, \u2014C(O)OC 2 -C 30 alkynyl, and \u2014C(O)OC 4 -C 30 alkenylalkynyl; (ii) \u2014C(O)OC 1-30 alkyl with at least one R 5  substituent on the alkyl chain, \u2014C(O)OC 1-30 alkenyl, with at least one R 5  substituent on the alkenyl chain, and \u2014C(O)OC 1-30 alkynyl, with at least one R 5  substituent on the alkynyl chain; (iii) \u2014C(O)(OCH 2 C(O)) 1-20 OC 1-30 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-20 OC 1-30 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 OC 1-30 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 OC 1-30 alkyl, \u2014C(O)(OCH 2 C(O)) 4-20 OC 1-30 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 4-20 OC 1-30 alkyl, \u2014C(O)(OCH 2 C(O)) 1-20 OC 1-10 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-20 OC 1-10 alkyl, \u2014C(O)(OCH 2 C(O)) 1-20 OC 4-10 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-20 OC 4-10 alkyl, \u2014C(O)(OCH 2 C(O)) 1-20 OH, \u2014C(O)(OCH(CH 3 )C(O)) 1-20 OH, \u2014C(O)(OCH 2 C(O)) 1-10 OH, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 OH, \u2014C(O)(OCH 2 C(O)) 4-20 OH, \u2014C(O)(OCH(CH 3 )C(O)) 4-20 OH, \u2014C(O)(OCH 2 C(O)) 4-10 OH, \u2014C(O)(OCH(CH 3 )C(O)) 4-10 OH, \u2014C(O)(OCH(CH 3 )C(O)) 4-10 OC 1-10 alkyl, \u2014C(O)(OCH 2 C(O)) 4-10 OC 1-10 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 OC 1-10 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 OC 1-10 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 OC 4-10 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 OC 4-10 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 OC 4-10 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 OC 4-10 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 OC 4-10 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 OC 4-10 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 (OCH(CH 3 )C(O)) 1-10 OC 1-30 alkyl, \u2014C(O)(OCH 2 C(O)) 2-10 (OCH(CH 3 )C(O)) 2-10 OC 1-30 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 (OCH(CH 3 )C(O)) 1-10 OC 1-12 alkyl, \u2014C(O)(OCH 2 C(O)) 1-10 (OCH(CH 3 )C(O)) 1-10 OC 4-22 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 (OCH 2 C(O)) 1-10 OC 1-30 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 2-10 (OCH 2 C(O)) 2-10 OC 1-3 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 (OCH 2 C(O)) 1-10 C 1-12 alkyl, \u2014C(O)(OCH(CH 3 )C(O)) 1-10 (OCH 2 C(O)) 1-10 OC 4-22 alkyl; (iv) polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, polyester, polyamide; and R 613  is selected from: R 615  and R 616  are independently selected from \u2014C(O)R 618 , C(O)A, and hydrogen; R 617  is selected from: (i) polyethylene glycol, polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, a polyester, and a polyamide; (ii) \u2014C 10 -C 30 alkylR 5 , \u2014C 10 -C 30 alkenylR 5 , \u2014C 10 -C 30 alkynylR 5 , \u2014C 10 -C 30 alkenylalkynylR 5 , \u2014C 10 -C 30 alkyl, \u2014C 10 -C 30 alkenyl, \u2014C 10 -C 30 alkynyl, and \u2014C 10 -C 30 alkenylalkynyl; (iii) an unsaturated fatty acid residue selected from \u2014(CH 2 ) 8 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 ), \u2014(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 ), \u2014(CH 2 ) 8 (CHCHCH 2 ) 3 CH 3 ), stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; and (iv) alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, arylalkyl, and heteroarylalkyl; R 618  is selected from: (i) \u2014C 10 -C 30 alkylR 5 , \u2014C 10 -C 30 alkenylR 5 , \u2014C 10 -C 30 alkynylR 5 , \u2014C 10 -C 30 alkenylalkynylR 5 , \u2014C 10 -C 30 alkyl, \u2014C 10 -C 30 alkenyl, \u2014C 10 -C 30 alkynyl, and \u2014C 10 -C 30 alkenylalkynyl; and (ii) an unsaturated fatty acid residue selected from \u2014(CH 2 ) 8 (CH) 2 CH 2 (CH) 2 (CH 2 ) 4 CH 3 ), \u2014(CH 2 ) 3 (CHCHCH 2 ) 6 CH 3 ), \u2014(CH 2 ) 4 (CHCHCH 2 ) 5 CH 3 ), \u2014(CH 2 ) 8 (CHCHCH 2 ) 3 CH 3 ), stearidonic acid, y-linolenic acid, arachidonic acid, docosatetraenoic acid, palmitoleic acid, vaccenic acid, paullinic acid, oleic acid, elaidic acid, gondoic acid, euric acid, nervonic acid and mead acid; R 620  is selected at each instance from hydrogen, alkyl, alkenyl, alkynyl cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl; R 622  is hydrogen, hydroxy, amino, A, alkyl, alkoxy, alkenyl, alkynyl cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, or stearoyl; R 624  is R 636  is selected from C(O)A, R 637  is selected from hydrogen, \u2014C(O)A, \u2014C(O)alkyl, aryl, alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocycloalkyl, arylalkyl, heteroaryl, and heteroarylalkyl; R 70  is selected from: (i) \u2014OC 15 -C 30 alkylR 5 , \u2014OC 2 -C 30 alkenylR 5 , \u2014OC 2 -C 30 alkynylR 5 , \u2014OC 4 -C 30 alkenylalkynylR 5 , \u2014OC 15 -C 30 alkyl, \u2014OC 2 -C 30 alkenyl, \u2014OC 2 -C 30 alkynyl, and \u2014OC 4 -C 30 alkenylalkynyl; (ii) \u2014OC 15-30 alkyl with at least one R 5  substituent on the alkyl chain, \u2014OC 1-30 alkenyl with at least one R 5  substituent on the alkenyl chain, and \u2014OC 1-30 alkynyl with at least one R 5  substituent on the alkynyl chain; (iii) \u2014(OCH 2 C(O)) 1-20 OC 1-30 alkyl, \u2014(OCH(CH 3 )C(O)) 1-20 OC 1-30 alkyl, \u2014(OCH 2 C(O)) 1-10 OC 1-30 alkyl, \u2014(OCH(CH 3 )C(O)) 1-10 OC 1-30 alkyl, \u2014(OCH 2 C(O)) 4-20 OC 1-30 alkyl, \u2014(OCH(CH 3 )C(O)) 4-20 OC 1-30 alkyl, \u2014(OCH 2 C(O)) 1-20 OC 1-10 alkyl, \u2014(OCH(CH 3 )C(O)) 1-20 OC 1-10 alkyl, \u2014(OCH 2 C(O)) 1-20 OC 4-10 alkyl, \u2014(OCH(CH 3 )C(O)) 1-20 OC 4-10 alkyl, \u2014(OCH 2 C(O)) 1-20 OH, \u2014(OCH(CH 3 )C(O)) 1-20 OH, \u2014(OCH 2 C(O)) 1-10 OH, \u2014(OCH(CH 3 )C(O)) 1-10 OH, \u2014(OCH 2 C(O)) 4-20 OH, \u2014(OCH(CH 3 )C(O)) 4-20 OH, \u2014(OCH 2 C(O)) 4-10 OH, \u2014(OCH(CH 3 )C(O)) 4-10 OH, \u2014(OCH(CH 3 )C(O)) 4-10 OC 1-10 alkyl, \u2014(OCH 2 C(O)) 4-10 OC 1-10 alkyl, \u2014(OCH(CH 3 )C(O)) 1-10 OC 1-10 alkyl, \u2014(OCH 2 C(O)) 1-10 OC 1-10 alkyl, \u2014(OCH(CH 3 )C(O)) 1-10 OC 4-10 alkyl, \u2014(OCH 2 C(O)) 1-10 OC 4-10 alkyl, \u2014(OCH 2 C(O)) 1-10 OC 4-10 -alkyl, \u2014(OCH(CH 3 )C(O)) 1-10 OC 4-10 alkyl, \u2014(OCH 2 C(O)) 1-10 OC 4-10 alkyl, \u2014(OCH(CH 3 )C(O)) 1-10 OC 4-10 alkyl, \u2014(OCH 2 C(O)) 1-10 (OCH(CH 3 )C(O)) 1-10 OC 1-30 alkyl, \u2014(OCH 2 C(O)) 2-10 (OCH(CH 3 )C(O)) 2-10 C 1-30 alkyl, \u2014(OCH 2 C(O)) 1-10 (OCH(CH 3 )C(O)) 1-10 OC 1-12 alkyl, \u2014(OCH 2 C(O)) 1-10 (OCH(CH 3 )C(O)) 1-10 OC 4-22 alkyl, \u2014(OCH(CH 3 )C(O)) 1-10 (OCH 2 C(O)) 1-10 OC 1-30 alkyl, \u2014(OCH(CH 3 )C(O)) 2-10 (OCH 2 C(O)) 2-10 OC 1-3 alkyl, \u2014(OCH(CH 3 )C(O)) 1-10 (OCH 2 C(O)) 1-10 OC 1-12 alkyl, and \u2014(OCH(CH 3 )C(O)) 1-10 (OCH 2 C(O)) 1-10 OC 4-22 alkyl; (iv) polypropylene glycol, polypropylene oxide, polylactic acid, poly(lactic-co-glycolic acid), polyglycolic acid, a polyester, a polyamide, and (v) \u2014OH; wherein R 701  cannot be OH when R 751  and R 752  are both hydrogen; R 740  is selected from: (ii) \u2014OH wherein R 740  cannot be \u2014OH when R 61  and R 62  are both hydrogen; R 751  and R 752  are independently selected from hydrogen, L 1  is selected from: L 2  is selected from: L 4  is bond, alkyl, alkenyl, alkynyl, \u2014C(O)\u2014, \u2014C(S)\u2014, \u2014NH\u2014, \u2014N(alkyl)-, \u2014O\u2014, or alkyl-C(O)\u2014; L 5  is double bond, alkyl, or alkenyl; L 6  is selected from \u2014O\u2014, \u2014NH\u2014, \u2014N(alkyl) 1-4 -, \u2014C(O)O\u2014, \u2014S\u2014, \u2014C(O)\u2014 and \u2014OC(O)\u2014; L 10  is \u2014O\u2014, \u2014NH\u2014, or \u2014N(alkyl)-; L 33  is selected from: bond, \u2014OC 1 -C 30 alkyl-O\u2014, \u2014NHC 1 -C 30 alkyl-O\u2014, N(alkyl)C 1 -C 30 alkyl-O\u2014, \u2014NHC 1 -C 30 alkyl-NH\u2014, N(alkyl)C 1 -C 30 alkyl-NH\u2014, \u2014NHC 1 -C 30 alkyl-N(alkyl)-, \u2014N(alkyl)C 1 -C 30 alkyl-N-(alkyl)-, \u2014OC 1 -C 30 alkenyl-O\u2014, \u2014NHC 1 -C 30 alkenyl-O\u2014, N(alkyl)C 1 -C 30 alkenyl-O\u2014, \u2014NHC 1 -C 30 alkenyl-NH\u2014, N(alkyl)C 1 -C 30 alkenyl-NH\u2014, \u2014NHC 1 -C 30 alkenyl-N(alkyl)-, \u2014N(alkyl)C 1 -C 30 alkenyl-N-(alkyl)-, \u2014OC 1 -C 30 alkynyl-O\u2014, \u2014NHC 1 -C 30 alkynyl-O\u2014, N(alkyl)C 1 -C 30 alkynyl-O\u2014, \u2014NHC 1 -C 30 alkynyl-NH\u2014, N(alkyl)C 1 -C 30 alkynyl-NH\u2014, \u2014NHC 1 -C 30 alkynyl-N(alkyl)-, and \u2014N(alkyl)C 1 -C 30 alkynyl-N-(alkyl)-; A is selected from H, alkyl, cycloalkyl, cycloalkylalkyl, heterocycle, heterocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, aryloxy, and alkyloxy; Q is selected from: N, CH, and CR 23 ; Y is CR 150  or N; Z is CR 130  or N; t is independently selected from 0, 1, 2, 3, and 4; tt is selected from 4, 5, 6, 7, 8, 9, and 10; a, b, and c are independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 wherein a and c cannot both be 0; x and y are independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30; z is independently selected from 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; and zz is independently selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20.

Metadata:
- Claim Count in Document: 41.0
- Percentile: 93.0
- Lexical Diversity: 1.1875
- Patent Class: 424.0
- Transitional Phrase Type: open
- Component Type: 1
- Foreign Priority: False
- Related Applications: ['15349985', '15782755', '15273686', '13995727', '15782744']

Analysis Scores:
- 35 USC 101 Eligibility (BERT): 0.7338623383688786
- 35 USC 102 Novelty (BERT): 0.5423251222938824
- Combined Prediction Score: 0.714708616761379
- Mean Citation Score: 283.64715200000006
- Max Citation Score: 399.21332
- Similarity Product: 307.7209536980105

Labels:
- Claim Label 101: 1
- Claim Label 102: 1
- Claim Label 103: 0
- Claim Label 112: 0
- Combined Label: 1
- Label 101 Adjusted: 1

Dataset: test