DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-5, 7-12, 21, & 29, in the reply filed on 03/27/2026 is acknowledged. Group II, claim 34, Group III, claim 41, and Group IV, claim 48, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
A first office action on the merits of claims 1-5, 7-12, 21, & 29 is set forth herein and claims 34, 41, & 48 are withdrawn from consideration.
Information Disclosure Statement
The listing of references in the specification, in pg. 90-100, is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5, 7-12, 21, & 29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1, the recitation of “wherein the modulating of condensate dependent transcription of the gene treats, prevents or reduces the likelihood of a disease or condition” in lines 3-4 of the claim if prevents or reduces is part of the same effect of modulating the condensate dependent transcription or if this is the result of a typographical error and should read “wherein the modulating of condensate dependent transcription of the gene treats, prevents, or reduces the likelihood of a disease or condition”.
Regarding claim 29, the recitation of “A method of treating, preventing or reducing the likelihood of a disease or condition” in lines 1-2 of the claim if prevents or reduces is part of the same group of methods or if this is the result of a typographical error and should read “A method of treating, preventing, or reducing the likelihood of a disease or condition”.
Claims 2-5, 7-12, & 21 are rejected due to their dependence on claim 1.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5, 7-12, 21, & 29 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Young (WO 2019/183552 A2, September 2019), as cited on the IDS dated 05/25/2023.
Regarding claim 1, Young teaches a method of modulating transcriptional condensates to use the condensates as a tool that reflects intracellular gene expression for discovering therapeutics comprising modulating transcription by enhancing or decreasing transcriptional condensate formation, composition, maintenance, dissolution, and regulation (modulating an amount, effective charge, structure, or behavior of nucleic acid incorporated in the condensate) and further treating diseases and conditions by administering an agent that modulates condensate formation, composition, maintenance, dissolution, activity, or regulation (the modulating of condensate dependent transcription of the gene treats, prevents or reduces the likelihood of a disease or condition in the subject) comprising modulating a level or activity of ncRNA, comprising enhancer RNA (eRNA) (a regulatory RNA (regRNA)), associated with the condensate to treat or reduce the likelihood of a disease caused by, or dependent on, condensate formation (the disease or condition is associated with a regulatory RNA variant) (paragraph [0014] lines 1-9; paragraph [0015] lines 1-16; paragraph [0016] lines 1-5; paragraph [0017] lines 1-15; paragraph [0041] 1-7; paragraph [0042] lines 1-7).
Regarding claim 2, Young teaches that the agent that modulates condensate formation, composition, maintenance, dissolution, activity, or regulation increases the level of transcription by 1.5 fold (transcription of the gene is increased by at least 1.1 fold) (paragraph [0025] lines 1-13; paragraph [0050] lines 1-9; paragraph [0173] lines 1-10).
Regarding claim 3, Young teaches the agent that modulates the condensate can reduce or eliminate transcription of a target gene comprising reduction of transcription of the target genes by at least 5% (transcription of the gene is reduced by at least 5%) (paragraph [0332] lines 1-6).
Regarding claim 4, Young teaches the transcriptional condensate is modulated by modulating a level or activity of ncRNA associated with the condensate, comprising eRNA (a regRNA), (condensate dependent transcription of the gene occurs in the presence of one or more species of regRNA in the condensate) (paragraph [0041] lines 1-7).
Regarding claim 5, Young teaches the transcriptional condensate is modulated by modulating a level or activity of ncRNA associated with the condensate, comprising eRNA (a regRNA) in which the method of treating or reducing the likelihood of a disease by administering an agent that modulates condensate comprises treatment of transcription factors that are not expressed in normal tissue (one or more species of regRNA is a tissue specific regRNA) (paragraph [0041] 1-7; paragraph [0042] lines 1-7).
Regarding claim 7, Young teaches the transcriptional condensate is modulated by modulating a level or activity of ncRNA associated with the condensate, comprising eRNA (a regRNA), (nucleic acid comprises one or more species of regRNA) (paragraph [0041] lines 1-7).
Regarding claim 8, Young teaches the transcriptional condensate is modulated by modulating a level or activity of ncRNA associated with the condensate, comprising eRNA (a regRNA), comprising modulating transcription by enhancing or decreasing condensate formation, composition, maintenance, dissolution, and regulation (the amount of one or more species of regRNA in the condensate is modulated by modulating transcription of the one or more species of regRNA) (paragraph [0017] lines 1-15; paragraph [0041] lines 1-7).
Regarding claims 9-11, Young teaches the level of activity of the ncRNA, comprising eRNA (regRNA), is modulated by contacting the ncRNA with an anti-sense oligonucleotide that binds the ncRNA (condensate dependent transcription of the gene is modulated by contacting one or more species of regRNA with an agent capable of binding and comprises a nucleic acid having a sequence complementary to the one or more species of regRNA wherein the nucleic acid in an antisense oligonucleotide) (paragraph [0041] lines 1-7).
Regarding claim 12, Young teaches the transcriptional condensate is modulated by modulating a level or activity of ncRNA associated with the condensate, comprising eRNA (a regRNA), (the one or more species of regRNA comprises eRNA) (paragraph [0041] lines 1-7).
Regarding claim 21, Young teaches the transcriptional condensate is modulated by modulating a level or activity of ncRNA associated with the condensate, comprising eRNA (a regRNA), comprising treating or reducing the likelihood of a disease of cancer in which the cancer is associated with a mutation in a condensate component (the one or more species of regRNA variant comprises eRNA variant) (paragraph [0041] lines 1-7; paragraph [0042] lines 1-7).
Regarding claim 29, Young teaches a method of modulating transcriptional condensates to use the condensates as a tool that reflects intracellular gene expression for discovering therapeutics comprising modulating transcription by enhancing or decreasing transcriptional condensate formation, composition, maintenance, dissolution, and regulation (modulating an amount, effective charge, structure, or behavior of nucleic acid incorporated in the condensate) and further treating diseases and conditions by administering an agent that modulates condensate formation, composition, maintenance, dissolution, activity, or regulation (administering to the subject an agent that modulates of condensate dependent transcription of the gene treats, prevents or reduces the likelihood of a disease or condition in the subject) comprising modulating a level or activity of ncRNA, comprising enhancer RNA (eRNA) (a regulatory RNA (regRNA)), associated with the condensate to treat or reduce the likelihood of a disease caused by, or dependent on, condensate formation (the disease or condition is associated with a regulatory RNA variant) (paragraph [0014] lines 1-9; paragraph [0015] lines 1-16; paragraph [0016] lines 1-5; paragraph [0017] lines 1-15; paragraph [0041] 1-7; paragraph [0042] lines 1-7).
Claim(s) 1, 4, 5, 7, 8, 12, 21, & 29 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arnold (Arnold, Wells, & Li; Frontiers in Cell and Developmental Biology, Vol. 7, pages 1-14, January 2020), as cited on the IDS dated 05/25/2023.
Regarding claim 1, Arnold teaches that enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising increase in expression of mRNA target transcription (modulating condensate dependent transcription of a gene comprises modulating an amount, structure, or behavior of a nucleic acid incorporated in the condensate) in which eRNAs may be utilized to map specific disease states and show the ability to identify disease-specific variants in a broad range of disease for treatment in these diseases associated with eRNAs (modulating the condensate dependent transcription of the gene treats, prevents or reduces the likelihood of a disease or condition in the subject wherein the disease or condition is associated with a regRNA variant) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Regarding claim 4, Arnold teaches enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising increase in expression of mRNA target transcription (the condensate dependent transcription of the gene occurs in the presence of one or more species of regRNA) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Regarding claim 5, Arnold teaches that eRNA (a regRNA) expression profiles are highly tissue specific (the one or more species of regRNA is a tissue specific regRNA) (pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-19).
Regarding claim 7, Arnold teaches enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising increase in expression of mRNA target transcription (the nucleic acid comprises one or more species of regRNA) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Regarding claim 8, Arnold teaches enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising increase in expression of mRNA target transcription (the amount of the one or more species of regRNA in the condensate is modulated by modulating transcription of the one or more species of regRNA) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Regarding claim 12, Arnold teaches enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising increase in expression of mRNA target transcription (the one or more species of regRNA comprises eRNA) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Regarding claim 21, Arnold teaches enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation in which eRNAs may be utilized to map specific disease states and show the ability to identify disease-specific variants in a broad range of disease for treatment in these diseases associated with eRNAs (the regRNA variant is an eRNA variant) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Regarding claim 29, Arnold teaches that enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising increase in expression of mRNA target transcription (modulating condensate dependent transcription of a gene comprises modulating an amount, structure, or behavior of a nucleic acid incorporated in the condensate) in which eRNAs may be utilized to map specific disease states and show the ability to identify disease-specific variants in a broad range of disease for treatment in these diseases associated with eRNAs (treating by modulating the condensate dependent transcription of the gene treats, prevents or reduces the likelihood of a disease or condition in the subject wherein the disease or condition is associated with a regRNA variant) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arnold (Arnold, Wells, & Li; Frontiers in Cell and Developmental Biology, Vol. 7, pages 1-14, January 2020), as cited on the IDS dated 05/25/2023, in view of Wei (Wei et al.; Nature Cell Biology Letters, Vol. 22, pages 1187-1205, October 2020).
The teachings of Arnold with respect to claim 1 are discussed above and incorporated herein.
Regarding claim 2, Arnold teaches that enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising increase in expression of mRNA target transcription (transcription of the gene is increased) (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Arnold does not teach the transcription of the gene is increased by at least 1.1 fold.
Wei teaches that transcriptional condensates have can locally promote biomolecular interactions underlying gene expression condensates amplified expression in a target gene by nearly two fold (transcription of the gene is increased by at least 1.1 fold) (abstract lines 1-23; pg. 1191 column 2 2nd full paragraph lines 13-15). In addition, Wei teaches that this method highlights important structure and functional relationships at the heart of transcription to better understand transcriptional regulation (pg. 1194 paragraph bridging column 1 & 2 lines 1-19).
Arnold and Wei are considered to be analogous to the claimed invention because they are all in the same field of analysis of gene expression in transcriptional condensates. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the use of eRNA playing a role in transcription regulation comprising increase in expression of mRNA target transcription in Arnold to incorporate the transcription of a target gene being increased by 2 fold in transcriptional condensates as taught in Wei because Wei teaches that doing so would provide a method to determine the structure and function relationship of transcription to better understand transcriptional regulation.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arnold (Arnold, Wells, & Li; Frontiers in Cell and Developmental Biology, Vol. 7, pages 1-14, January 2020), as cited on the IDS dated 05/25/2023, in view of Sabari (Sabari et al.; Science, Vol. 361, pages 1-11, June 2018).
The teachings of Arnold with respect to claim 1 are discussed above and incorporated herein.
Regarding claim 3, Arnold teaches that enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising alteration in expression of mRNA target transcription (pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Arnold does not teach the transcription of the gene is reduced by at least 5%.
Sabari teaches that transcriptional condensates are formed at super enhancers and has multiple roles in transcription in which expression of target genes were reduced by 44% and 80% in transcriptional condensates formed at super enhancers (transcription of the gene is reduced by at least 5%) (abstract rationale lines 1-25; pg. 5 paragraph bridging column 1 & 2 lines 1-20). Sabari also teaches that this method show that condensates are formed at super enhancers and that the super enhancer condensates compartmentalize and concentrate the transcription at key cell-identity genes therefore displaying the mechanisms involved in the control of genes in healthy and diseased cell states (abstract conclusion lines 1-19).
Arnold and Sabari are considered to be analogous to the claimed invention because they are all in the same field of analysis of gene expression in transcriptional condensates. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the use of eRNA playing a role in transcription regulation comprising alteration in expression of mRNA target transcription in Arnold to incorporate the transcription of a target gene being reduced by at least 5% in transcriptional condensates formed at super enhancers as taught in Sabari because Sabari teaches that doing so would provide a method to analyze condensates are formed at super enhancers and their compartmentalization and concentration of the transcription at key cell-identity genes therefore displaying the mechanisms involved in the control of genes in healthy and diseased cell states.
Claim(s) 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Arnold (Arnold, Wells, & Li; Frontiers in Cell and Developmental Biology, Vol. 7, pages 1-14, January 2020), as cited on the IDS dated 05/25/2023, in view of Avitabile (Avitabile, Cimmino, & Romanelli; Journal of Medicinal Chemistry, Vol. 57, pages 10220-10240, October 2014).
The teachings of Arnold with respect to claims 1 & 7 are discussed above and incorporated herein.
Regarding claims 9-11, Arnold teaches that enhancer RNA (eRNA) (a regulatory RNA (regRNA)) play an important role in the formation, regulation, maintenance, dissolution of super enhancers a biomolecular condensates in which eRNA plays a role in transcription regulation comprising alteration in expression of mRNA target transcription and further that antisense transcription of enhancers may play a role in attenuating and fine-tuning gene transcription by interfering with or pausing the sense mRNA transcription (pg. 4 column 2 3rd full paragraph lines 7-12; pg. 4-5 paragraph bridging pg. 4 & 5 lines 1-24; pg. 5 column 1 1st full paragraph lines 1-30; pg. 9-10 paragraph bridging pg. 9 & 10 lines 13-29; pg. 10 paragraph bridging column 1 & 2 lines 1-14; pg. 10-11 paragraph bridging pg. 10 & 11 lines 1-47).
Arnold does not teach that the condensate dependent transcription of the gene is modulated by contacting the one or more species of regRNA with an agent capable of binding and having a nucleic acid sequence complementary, that is an antisense oligonucleotide, to the one or more species of regRNA (see claims 9-11).
Avitabile teaches the use of antisense oligonucleotides to regulate expression of ncRNAs (regRNAs) comprising lncRNAs (regRNAs) that show eRNA activity (contacting the one or more species of regRNA with an agent capable of binding and having a nucleic acid sequence complementary that is an antisense oligonucleotide) (pg. 10223 paragraph bridging column 1 & 2 lines 13-19; pg. 10225-10226 paragraph bridging pg. 10225 & 10226 lines 1-8). In addition, Avitabile teaches that the use of antisense oligonucleotide to target ncRNAs (regRNAs) overcome the stability and specificity drawbacks of standard oligonucleotides (pg. 10225-10226 paragraph bridging pg. 10225 & 10226 lines 1-8).
Arnold and Avitabile are considered to be analogous to the claimed invention because they are all in the same field of analysis of gene expression in transcriptional condensates. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of the use of eRNA playing a role in transcription regulation comprising alteration in expression of mRNA target transcription in Arnold to incorporate the use of an antisense oligonucleotide to regulate expression of lncRNAs (regRNAs) that show eRNA activity as taught in Avitabile because Avitabile teaches that doing so would provide a method to target ncRNAs (regRNAs) without the drawbacks in stability and specificity of standard oligonucleotides.
Conclusion
Claims 1-5, 7-12, 21, & 29 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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