DETAILED ACTION
Applicant’s response, filed Jan 7 2026, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Status
Claims 79-80, 82, 84-86, 89, 94, 96, 99, 106, 110-111, 125-127, and 147 are pending.
Claims 1-78, 81, 83, 87-88, 90-93, 95, 97-98, 100-105, 107-109, 112-124, and 128-146 and 148 are canceled.
Claim 79 is objected to.
Claims 79-80, 82, 84-86, 89, 94, 96, 99, 106, 110-111, 125-127, and 147 are rejected.
Priority
The instant Application claims domestic benefit to US provisional application 62/622,655, filed 26 Jan 2018, 62/622,656, filed 26 Jan 2018, and 62/797/926, filed 28 Jan 2019.
Applicant's claim for the benefit of a prior-filed application, PCT/US2019/015484, filed 28 Jan 2019, is acknowledged.
Claims 79-80, 82, 84-86, 89, 94, 96, 99, 106, 110-111, 125-127, and 147 are therefore afforded the effective filing date of 28 Jan 2019.
Claim Objections
The outstanding objections to the claims are withdrawn in view of the amendments submitted herein.
The claims are objected to because of the following informalities. The instant objection is newly stated and is necessitated by claim amendment.
In claim 79, limitation 6, the semicolon after “complex disease” should be changed to a comma.
Claim Rejections- 35 USC § 112
The outstanding rejections to the claims are withdrawn in view of the amendments submitted herein.
35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 79-80, 82, 84-86, 89, 94, 96, 99, 106, 110-111, 125-127, and 147 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for correcting a variants in a small number of genes, does not reasonably provide enablement for performing mutagenesis on cells to correct any type of an unlimited number of variants in an unlimited number of genes, genome wide. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In In re Wands (8 USPQ2d 1400 (CAFC 1988)), the CAFC considered the issue of enablement in molecular biology. The CAFC summarized eight factors to be considered in a determination of "undue experimentation”. These factors include: (a) the quantity of experimentation necessary; (b) the amount of direction or guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the relative skill of those in the art; (g) the predictability of the art; and (h) the breadth of the claims.
In considering the factors for the instant claims:
(a) In order to practice the claimed invention, one of skill in the art must be able to perform mutagenesis on cells to correct any type of an unlimited number of variants in an unlimited number of genes, genome wide. For the reasons discussed below, there would be an unpredictable amount of experimentation required to practice the claimed invention.
(b) The specification as published provides guidance for a variant being a single nucleotide variant (SNV), a copy number variant (CNV), an insertion, or a deletion [0217]. The specification as published provides guidance for manipulating genetic material in order to analyze variants, including changing a rare variant into a common variant, especially when determining the effect of “correcting” a potential pathogenic variant [0275] The specification as published provides guidance for a cell line can be derived from an individual (e.g., from a biopsy) which would harbor the variants identified in that individual, and genetically manipulating the cell line from the individual to “correct” a set of pathogenic variants [0276].
(c) The specification does not provide a working example of performing mutagenesis on genomic DNA of one or more cells derived from the individual, wherein the mutagenesis corrects each variant of the set of pathogenic variants within the one or more cells.
(d) The invention is drawn to identifying a set of one or more pathogenic variants within the set of regulatory variants, wherein the set of regulatory variants is genome wide, and performing mutagenesis on genomic DNA of one or more cells derived from the individual, wherein the mutagenesis corrects each variant of the set of pathogenic variants within the one or more cells.
(e) The state of the art of performing mutagenesis on genomic DNA of one or more cells derived from the individual to correct each variant of the set of pathogenic variants within the one or more cells can be represented by Jehuda et al. (Stem Cell Reviews and Reports, 2018, 14:323-336; newly cited). The reference makes clear that technologies such as ZFNs, TALENs, an CRIPSR exist for genome editing of human derived cells (p 324, col. 1), which have been used to knockout, disrupt, or correct a single gene at a time (p. 325, col. 1, par. 2 through p. 331, col. 2, par. 2; Table 1). Jehuda makes clear that genome engineering can delete single mutated alleles, reduce the copy number of CGG repeats (p. 326, col. 1, par. 2), correct point mutations (p. 326, col. 2, par. 2 through p. 330, col. 2, par. 1), or perform biallelic editing (p. 330, col. 2, par. 2). There is no direction as to how to perform mutagenesis to correct a set of variants, when the set of variants contains any number of variants potentially greater than 2, or where the set of variants contains variants which require more complex correction, like larger regions of copy number changes.
(f) The skill of those in the art of molecular biology and bioinformatics is high.
(g) The art is unpredictable because the genome editing techniques, described by Jehuda, require extensive planning for each proposed change, have low correction efficiency for each change (~10%; p. 327, col. 1, par. 2), and produce off-target changes (p. 324, col. 2, par. 2).
(h) The claims are broad because they are drawn to performing mutagenesis on cells to correct any type of an unlimited number of variants which are genome wide. However, the instant specification does not provide specific guidance to practice these embodiments. As such, the skilled practitioner would turn to the prior art for such guidance. However, the prior art makes clear that genome editing to correct variants is far more limited. Finally, said practitioner would turn to trial and error experimentation to determine how to correct any number and type of variant, which represents undue experimentation.
Claim Rejections - 35 USC § 101
The outstanding rejections from the previous Office Action are withdrawn in view of the amendments submitted herein. Specifically, claim 79 now recites “performing mutagenesis on genomic DNA of one or more cells derived from the individual, wherein the mutagenesis corrects each variant of the set of pathogenic variants within the one or more cells”, which at the least recites a transformation (see MPEP 2106.05(c)) of the naturally derived cells from the individual into cells which were not previously naturally present, where the transformation relies on the results determined by the judicial exceptions in the claims.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANNA NICOLE SCHULTZHAUS whose telephone number is (571)272-0812. The examiner can normally be reached on Monday - Friday 8-4.
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/J.N.S./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685