Methods and compositions for treating prostate cancer
Inventors
Shemi, Amotz • ZORDE KHVALEVSKY, Elina • MALKA GABAI, Rachel
Assignees
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Publication Number
US-9006199-B2
Publication Date
2015-04-14
Expiration Date
Abstract
Treatment of prostate cancer by regional and prolonged release of one or more nucleotide-based RNAi agents is provided.
Core Innovation
The invention relates to a millimeter-scale drug delivery device (DDD) that is biodegradable and includes an RNA interference (RNAi) agent incorporated within a biodegradable polymeric matrix. The biodegradable polymeric matrix comprises a mixture of polylactic acid (PLA) and polyglycolic acid (PGA), with a PLA:PGA ratio of 50:50 or between 65:35 and 95:5 inclusive.
The disclosed RNAi-based DDDs are directed to regional, prolonged release of nucleotide-based RNAi agents for prostate carcinoma. The RNAi agents target prostate-cancer-associated genes, including androgen receptor and other listed genes, by using sense and antisense strand designs.
The DDD is positioned for implanting in the prostate as part of the treatment concept. The document further characterizes the DDDs by describing controlled release profiles and prolonged release behavior from the biodegradable polymeric matrix, including sustained release over a prolonged period and delayed release characteristics.
Claims Coverage
Only one independent claim is provided, and the coverage focuses on a millimeter-scale biodegradable polymeric matrix DDD with PLA/PGA ratio constraints and an incorporated RNAi agent with sense/antisense strands targeting specified gene sequences; multiple dependent claims refine this core with additional formulation, RNAi modification, delivery, and release-related constraints.
Millimeter-scale biodegradable polymeric matrix DDD with PLA/PGA ratio constraints
A millimeter-scale drug delivery device (DDD) comprising a biodegradable polymeric matrix comprising a mixture of polylactic acid (PLA) and polyglycolic acid (PGA), wherein the PLA:PGA ratio is 50:50, or between 65:35 and 95:5, inclusive.
Incorporated RNAi agent with sense and antisense targeting specified gene sequences
An RNAi agent incorporated within the biodegradable polymeric matrix, wherein the RNAi agent comprises a sense strand and an antisense strand, and wherein the sequences of the sense strand and the antisense strand target a gene sequence selected from the group consisting of SEQ ID NO: 14 (NETO2), SEQ ID NO: 20 (PTPRA), and SEQ ID NO: 31 (Brd4).
The claim coverage anchors protection around a millimeter-scale biodegradable PLA/PGA DDD that contains an RNAi agent with sense and antisense strands targeting NETO2, PTPRA, or Brd4. Dependent refinements further constrain release kinetics and allow specific RNAi chemical modification and siRNA conjugation/complexation options.
Stated Advantages
Regional, prolonged release of nucleotide-based RNAi agents for prostate carcinoma.
Controlled release profiles and prolonged release behavior from the biodegradable polymeric matrix.
Sustained release over a prolonged period and delayed release characteristics.
In vitro target downregulation and associated biological effects.
Documented Applications
Treatment of prostate carcinoma using millimeter-scale biodegradable drug delivery device(s) implanted in the prostate to provide regional, prolonged release of RNAi agents.
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