Ionizable compounds and compositions and uses thereof
AssigneeNitto Denko Corporation
InventorsRoger Adami, Hao Bai, John Gaudette, Bharat Majeti, Seiji Nukui, Kwok Yin Tsang, Hai Wang, Haiqing Ying, Wenbin Ying
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Abstract
This invention includes ionizable compounds, and compositions and methods of use thereof. The ionizable compounds can be used for making nanoparticle compositions for use in biopharmaceuticals and therapeutics. More particularly, this invention relates to compounds, compositions and methods for providing nanoparticles to encapsulate active agents, such as nucleic acid agents, and to deliver and distribute the active agents to cells, tissues, organs, and subjects.
Claims40
A compound comprising the structure shown in Formula I
- wherein R1 and R2 are
- R1=CH2(CH2)nOC(═O)R4
- R2=CH2(CH2)mOC(═O)R5
- wherein n and m are each independently from 1 to 2;
- and R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is selected from
- wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, and aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R8 may form a ring;
- q is from zero to four;
- Q is O or NR7;
- p is from 1 to 4.
A compound comprising the structure shown in Formula II
- wherein R1 and R2 are
- R1=CH2(CH2)nOC(═O)R4
- R2=CH2(CH2)mOC(═O)R5
- wherein n and m are each independently from 1 to 2;
- and R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is a C(12-20) alkyl group or a C(12-20) alkenyl group that is substituted with a carboxylic acid or ester group.
A compound comprising the structure shown in Formula III
- wherein R1 and R2 are
- R1=CH2(CH2)nOC(═O)R4
- R2=CH2(CH2)mOC(═O)R5
- wherein n and m are each independently from 1 to 2;
- and R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is selected from alkyl, hydroxyalkyl, alkoxyalkoxy, and carboxyalkyl;
- wherein R6 is selected from NR72, N+HR72 and N+R73;
- wherein R7 is selected from H, alkyl, hydroxyalkyl, and aminoalkyl.
A compound comprising the structure shown in Formula IV
- wherein R1 and R2 are
- R1=C(═O)OR4
- R2=C(═O)OR5
- wherein R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is selected from
- wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R8 may form a ring;
- q is from zero to four;
- Q is O or NR7;
- p is from 1 to 4.
A compound comprising the structure shown in Formula IV-B
- wherein R1 and R2 are
- R1=C(═O)OR4
- R2=C(═O)OR5
- wherein R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein Z is S or 0;
- wherein R3 is selected from
- wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- p is from 1 to 4.
A compound comprising the structure shown in Formula V
- wherein R1 and R2 are
- R1=NHC(═O)R4
- R2=C(═O)OR5
- wherein R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein p is from 1 to 4;
- wherein R3 is selected from
- wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R8 may form a ring;
- q is from zero to four;
- Q is O or NR7.
A compound comprising the structure shown in Formula VI
- wherein R1 is
- R1=OC(═O)R4
- wherein R2 and R4 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is selected from aminoalkyl, quaternary aminoalkyl.
A compound comprising the structure shown in Formula VII
- wherein R1 and R2 are
- R1=OC(═O)R4
- R2=OC(═O)R5
- wherein n and m are each independently from 1 to 2;
- and R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is selected from H, alkyl, aminoalkyl, quaternary aminoalkyl, hydroxyalkyl, alkoxyalkyl, alkoxyalkoxyalkyl.
A compound comprising the structure shown in Formula VIII
- wherein R1 and R2 are
- R1=OC(═O)R4
- R2=C(═O)ZR5
- wherein Z is NH or 0,
- wherein R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is selected from
- amino;
- quaternary amino;
- aminoalkyl;
- quaternary aminoalkyl;
- NHC(═O)(CH2)pR10;
- NHC(═O)SR9;
- wherein R10 is selected from
- carboxyalkyl;
- aminoalkyl;
- wherein R9 is selected from
- alkyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- and wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R8 may form a ring;
- q is from zero to four;
- Q is O or NR7.
A compound comprising the structure shown in Formula VIII-B
- wherein R1 and R2 are
- R1=CH2(CH2)nOC(═O)R4
- R2=CH2(CH2)mOC(═O)R5
- wherein n and m are each independently from 1 to 2;
- R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein Z is N, O;
- wherein R3 is selected from
- alkyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- p is from 1 to 4.
A compound comprising the structure shown in Formula IX
- wherein R1 and R2 are
- R1=C(═O)OR4
- R2=NHC(═O)R5
- wherein R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein p is from 1 to 4;
- wherein R3 is selected from
- wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R8 may form a ring;
- q is from zero to four;
- Q is O or NR7.
A compound comprising the structure shown in Formula X
- wherein R1 and R2 are
- R1=C(═O)OR4
- R2=NHC(═O)R5
- wherein R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein R3 is selected from
- amino;
- quaternary amino;
- aminoalkyl;
- quaternary aminoalkyl;
- hydroxyalkylamino.
A compound comprising the structure shown in Formula XI
- wherein R1 and R2 are
- R1=C(═O)R4
- R2=C(═O)OR5
- wherein R4 and R5 are independently for each occurrence a C(12-20) alkyl group, or a C(12-20) alkenyl group;
- wherein Z is O or NH;
- wherein p is from 1 to 4;
- wherein R3 is selected from
- wherein
- each R6 is independently selected from H, alkyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkoxy, aminoalkyl;
- each R7 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl;
- each R8 is independently selected from H, alkyl, hydroxyalkyl, and aminoalkyl, and any two R8 may form a ring;
- q is from zero to four;
- Q is O or NR7.
A composition comprising an ionizable compound and a pharmaceutically acceptable carrier.
A pharmaceutical composition comprising an ionizable compound, an active agent, and a pharmaceutically acceptable carrier.
A composition for use in distributing an active agent for treating a condition or disease in a subject, the composition comprising an ionizable compound, a structural lipid, a stabilizer lipid, and a lipid for reducing immunogenicity of the composition.
Dependencies are inferred from the claim text.