DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Applicant should note that the examiner assigned to this case has changed.
Election/Restrictions
Applicant’s election without traverse of Group I, presently claims 26-40, in the reply filed on 7/20/2026 is acknowledged.
Applicant’s species election without traverse of claim 26 (a), claim 29 (a), claim 30 (a), reporter genes for claim 33, a JAK pathway inhibitor of claim 35, claim 36, and claim 40 (b) in the reply filed on 7/20/2026 is acknowledged.
Claims 37, 38, and 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/20/2026.
Claims 26-36, 39, and 40 are under consideration on the merits, and are examined to the extent they read on the elected species.
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 26-36, 39, and 40 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.
Claims 26(a) and 35 are in improper Markush form; a Markush group should be in the form “an agent selected from the group consisting of A, B, and C” or “wherein the agent is A, B, or C”. Currently, it is not clear which species are included in the Markush group and which are not for these claims. Correction is required.
Regarding the Tables 1-3 of claim 29, incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim; incorporation by reference is a necessity doctrine, not for applicant’s convenience. See M.P.E.P. § 2173.05(s). In this case, claim 29 must be held indefinite because the data proffered in Tables 1-3 can be reasonably added to the claim. Correction is required.
Separately, claim 29(b) recites the limitation "the at least one transcription factor" and referencing Tables 1-3 of the specification. There is insufficient antecedent basis for this limitation in the claim, because Tables 1-3 in the specification do not recite any list of transcription factors. Correction is required.
In so much that claims 27-36, 39, and 40 depend from claim 26 and do not resolve the point of confusion, these claims must be rejected with claim 26 as indefinite.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 26-29, 31-36, 39, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Dowdy et al. (WO 2013/177133A2; provided in the IDS dated 8/14/2024) in view of Gough et al. (WO 2018/232458A1; provided in the IDS dated 8/14/2024).
Other species were found during the search. This rejection addresses the embodiment of B18R for claims 35 and 36.
Dowdy teaches an in vitro method of generating induced pluripotent stem cells, the method comprising: 1) introducing into the foreskin fibroblasts (e.g. differentiated source cells) a Venezuelan Equine Encephalitis (VEE) self-replicating RNA comprising a sequence encoding Oct-4, Klf4, and Sox2 (i.e. “OKS”) that transdifferentiates the fibroblasts into induced pluripotent stem cells (e.g. iPS) ([00130]-[00135] and [00152]), reading in-part on claim 26 and reading on claims 29 and 32. In a separate embodiment, Dowdy envisions driving transdifferentiation from a source cell as an alternative to iPS cell generation (0005] and [00150]), reading on claim 26. In a separate embodiment, Dowdy teaches utilizing either one- or two transcription/reprogramming factors (RF) selected from the group consisting of Oct-4 (i.e. POU5F1), Klf4, Sox-2, c-Myc (i.e. MYC), Nanog, and Glis1 ([0033] and [0042]), reading on not more than one of these transcription factors for claims 26 and 27. Dowdy teaches generating human induced pluripotent stem cells as set forth above that are at least 30% to at least 99% free of contaminating cell types carrying markers associated with lineage dedication ([0076]-[0079]), reading on the at least 0.1% limitation of claim 27. Dowdy further teaches the self-replicating RNA comprises sequences encoding non-structural proteins capable of directing replication of the self-replicating RNA when delivered into a cell ([0030]); VEE encodes four non-structural replication complex proteins (nsP) as a single ORF in the 5' end of the RNA that is separated from the viral structural protein ORF in the 3' end (Fig. 1a and [00143]); and, a SP6 or T7 promoter that can direct expression of an exogenous sequence ([00131]), reading on claim 31. Dowdy teaches GFP as a reporter gene ([00131] and Fig. 1B), reading on claim 33. Dowdy teaches multicistrionic self-replicating RNA ([00131]), reading on claim 34. Dowdy teaches culturing the fibroblasts in B18R conditioned medium for at least two days (00135]), reading on the embodiment of B18R for claims 35 and 36. Dowdy teaches an expression cassette comprising a DNA sequence encoding the self-replicating RNA ([00131]), reading on claim 40.
Regarding claim 26(a), 27 and 39, Dowdy does not teach a particular transdifferentiated target cell and the embodiment of upregulate genes of the target cell therein. Regarding claim 28, Dowdy does not negatively exclude POU5F1, SOX2, KLF4, MYC, MYCL, LIN28, NANOG and GLIS1.
Gough teaches methods of reprogramming a source cell to a cardiomyocyte (Abstract). Gough teaches reprogramming a source cell by forward programming of multipotent cells or transdifferentiation of one somatic cell exhibiting at least one characteristic of another somatic cell type (page 12, lines 10-16), reading on claim 26(a) and 39. Gough teaches that one or combination of BMP10, TBX5, ANKRD1, HAND2, PPARGC1, NKX2-5 and GATA4 as transcription factors effectively transdifferentiates cardiac fibroblasts to cardiomyocytes by targeting about 93% of genes necessary to transdifferentiate cardiac fibroblasts to cardiomyocytes (page 17, line 29 through page 19, line 7), reading on claims 26(a), 27, 28, and 39. Gough teaches upregulation of cardiac genes in cardiac fibroblasts transdifferentiated into cardiomyocytes (Examples 4 and 5), reading on claims 26(a), 27, and 39.
Regarding claims 26(a), 27, 28, and 39, it would have been obvious to a person of ordinary skill in the art before the invention was filed to substitute the Oct-4, Klf4, and Sox2 transcription factors of Dowdy with one or combination of BMP10, TBX5, ANKRD1, HAND2, PPARGC1, NKX2-5 and GATA4 of Gough in Dowdy’s methods. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Dowdy and Gough are in-part directed towards cellular transdifferentiation methods. The skilled artisan would have been motivated to do so because Gough teaches that the substitution would be predictably advantageous to generate cardiomyocytes from a starting fibroblast population, thus improving the embodiment of transdifferentiation envisioned by Dowdy.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Dowdy and Gough as applied to claim 26 above, and further in view of Firas et al. (WO 2017/106932; Reference N).
The teachings of Dowdy and Gough are relied upon as set forth above.
Regarding claim 30, Dowdy and Gough do not teach the combination of ASCL1, POU3F2 (i.e. Oct7), NEUROD1, and MYT1L.
Firas teaches methods of transdifferentiation of a cell to a different cell type (Abstract). Firas predicts that ASCL1, MYT1L, NEUROD1, and POU3F2 as transcription factors would transdifferentiate fibroblasts to neurons based upon calculated changes in gene expression patterns (Fig. 1 for the Mogrify algorithm; Example 2, particularly Tables 5 and 6), reading on claim 30.
It would have been obvious to a person of ordinary skill in the art before the invention was filed to further substitute the one or combination of BMP10, TBX5, ANKRD1, HAND2, PPARGC1, NKX2-5 and GATA4 of Gough with the ASCL1, MYT1L, NEUROD1, and POU3F2 of Firas in Dowdy’s methods. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Dowdy, Gough, and Firas are all in-part directed towards cellular transdifferentiation methods. The skilled artisan would have been motivated to do so because Firas teaches that the substitution would be predictably advantageous to generate neurons from a starting fibroblast population, thus improving the embodiment of transdifferentiation envisioned by Dowdy.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 35 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Dowdy and Gough as applied to claim 26 above, and further in view of Dzau et al. (US 2014/0011281A1; Reference A)
This rejection addresses the elected species of B18R and Ruxolitinib.
The teachings of Dowdy and Gough are relied upon as set forth above.
Regarding claims 35 and 36, Dowdy and Gough do not teach Ruxolitinib.
Dzau teaches a method of transdifferentiating cardiac fibroblasts to cardiac myocytes, wherein the addition of a JAK1 inhibitor improves conversion to cardiac myocytes by 30-50% ([0065-0067]), reading on claims 35 and 36. Dzau teaches Ruxolitinib is a known JAK1 inhibitor ([0053]),reading on claims 35 and 36
It would have been obvious to a person of ordinary skill in the art before the invention was filed to add the Ruxolitinib of Dzau to Dowry’s methods in view of Gough. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Dowdy, Gough, and Dzau are all in-part directed towards cellular transdifferentiation methods. The skilled artisan would have been motivated to do so because Dzau teaches that the addition would be predictably advantageous to improve the efficiency of generating cardiac myocytes from a starting fibroblast population, thus improving the embodiment of transdifferentiation envisioned by Dowdy.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Conclusion
No claims are allowed. No claims are free of the art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN C BARRON whose telephone number is (571)270-5111. The examiner can normally be reached 7:30am-3:30pm EDT/EST (M-F).
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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