Methods and compositions for RNAi-based cancer treatment
Inventors
Shemi, Amotz • Khvalevsky, Elina Zorde
Assignees
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Publication Number
US-9080173-B2
Publication Date
2015-07-14
Expiration Date
Abstract
The present invention generally concerns methods and compositions for treating mutated K-ras expressing cancers.
Core Innovation
An RNAi (RNA interference) agent is provided for treating a patient having a solid tumor expressing a mutated K-ras protein. The RNAi agent comprises a sense strand and an antisense strand having sequences set forth in A, B, or C, with SEQ ID No: 37 and SEQ ID No: 38, or SEQ ID No: 39 and SEQ ID No: 40, or SEQ ID No: 55 and SEQ ID No: 56. A preceding “o” denotes a 2′-O-Methyl modification of the residue.
A millimeter-scale drug delivery device is provided for delivering an RNAi agent. The device comprises a biodegradable polymeric matrix and an RNAi agent incorporated within the biodegradable polymeric matrix. The RNAi agent comprises a sense strand selected from SEQ ID Nos: 37, 39, and 55 and an antisense strand selected from SEQ ID Nos: 38, 40, and 56 as set forth in A, B, or C.
In one refinement, the RNAi agent is further modified with 2′-F. In the device, the biodegradable polymeric matrix is specified as a polymeric matrix including PLA and PGA with a PLA:PGA ratio of at least 75:25 or at most 25:75, and additional device refinements describe optional excipients, including additives that modulate pH and sugars for formulation support, as well as constraints on device geometry and RNAi agent loading.
Claims Coverage
The provided patent excerpt includes two independent claims. Together, the claims cover specific RNAi agents using defined sense/antisense sequence sets with 2′-O-Methyl residue modifications, and a millimeter-scale drug delivery device incorporating such an RNAi agent in a biodegradable polymeric matrix.
RNA interference agent for solid tumors expressing mutated K-ras with defined sense/antisense sequences
An RNAi agent for treating a patient having a solid tumor expressing a mutated K-ras protein, comprising a sense strand and an antisense strand having sequences set forth in A, B, or C (SEQ ID Nos: 37/38, 39/40, or 55/56), wherein “o” preceding a residue denotes a 2′-O-Methyl modification of the residue.
Millimeter-scale drug delivery device incorporating defined RNAi agent in biodegradable polymeric matrix
A millimeter-scale drug delivery device comprising a biodegradable polymeric matrix and an RNAi agent incorporated within the biodegradable polymeric matrix, where the RNAi agent comprises a sense strand selected from SEQ ID Nos: 37, 39, and 55 and an antisense strand selected from SEQ ID Nos: 38, 40, and 56 as set forth in A, B, or C, wherein “o” preceding a residue denotes a 2′-O-Methyl modification of the residue.
The excerpted independent claims define specific RNAi agents with 2′-O-Methyl residue modification for treating solid tumors expressing mutated K-ras, and a millimeter-scale drug delivery device that incorporates those RNAi agents within a biodegradable polymeric matrix.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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