DETAILED ACTION
Applicant’s amendment and response received on 12/1/25 has been entered. Claims 5-6, 8, 12-13, and 16 have been canceled and new claim 19 has been added. Claims 1-4, 7, 9-11, 14-15, and 17-19 are currently pending and under examination. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . An action on the merits follows.
Claim Rejections - 35 USC § 101
The rejection of claims 12-14 under 35 U.S.C. 101 because the claimed invention is both in one aspect directed to non-statutory subject matter, and in another aspect is directed to a product of nature, is withdrawn in view of the cancelation of claims 12-13 and the amendment to claim 14 which now depends on the method of claim 4.
Claim Rejections - 35 USC § 112
The rejection of claims 4-16, and 18 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the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention, is withdrawn over canceled claims 5-6, 8, 12-13, and 16, and further withdrawn over pending claims 4, 7, 9-11, 14-15, and 18 in view of applicant’s amendments to the claims.
Claim Rejections - 35 USC § 102
The rejection of claims 12-16 under 35 U.S.C. 102(a)(1) as being anticipated by Guilinger et al. (2014) Nat. Biotech., Vol. 32(6), 577-583, published online April 25, 2014, is withdrawn in view of the cancellation of claim 12-13 and 16 and the amendments to claims 14-15 which now recite a method, not a product.
The rejection of claims 12-16 under 35 U.S.C. 102(a)(1) as being anticipated by U.S. Patent Application Publication 2014/0068797 (March 6, 2014), hereafter referred to as Doudna et al., is withdrawn in view of the cancellation of claim 12-13 and 16 and the amendments to claims 14-15 which now recite a method, not a product.
Claim Rejections - 35 USC § 103
The rejection of claims 1-18 under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2014/0068797 (March 6, 2014), hereafter referred to as Doudna et al. , in view of Guilinger et al. (2014) Nat. Biotech., Vol. 32(6), 577-583, published online April 25, 2014, and U.S. Patent No. 9,410,134 (August, 2016), hereafter referred to as Kuhn, with an effective filing date of June 7, 2011, is withdrawn over canceled claims 5-6, 8, 12-13, and 16, and further withdrawn over claims 1-4, 7, 9-11, 14-15, and 17-18 in view of applicant’s amendments to the claims, arguments, and the Declaration under 37 CFR 1.132 by Dr. Blair Madison filed on 12/1/25, hereafter referred to as the Madison Declaration. Applicant’s arguments the supporting evidence provided by the Madison Declaration demonstrate that a composition comprising a gRNA as a DNA localization component, and a fusion protein comprising dCas9 or inactivated nuclease domain thereof and Clo051 or nuclease domain thereof exhibits unexpected functionality in terms of target cutting efficiency. Specifically, the applicant argues that the actual data in Figure 8A of Kuhn shows that the TAL-FokI construct was more active than the TAL-Clo051 construct. The applicant also points to the Madison Declaration which provides as Exhibit A a publication by Jung et al. which shows that dCas9-FokI, a construct similar to that described by Tsai, performed poorly and exhibited decreased target cutting efficiency compared to Cas9, whereas applicant’s data, provided as Exhibit B, shows that Cas-Clover (dCas9-Clo51) had substantially higher cutting efficiency-more than double- in comparison to Cas9. The Madison Declaration also provided in Exhibit B data showing that Cas-Clover exhibited substantially increased HDR for gene knock-in compared to Cas9. As such, applicant’s arguments and the Madison Declaration provide evidence of unexpected results when using the claims Cas-Clover fusion protein in gRNA mediated modification of the genome of a cell which would not have been reasonably expected by the cited prior art.
Double Patenting
The rejection of claims 1-18 on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,473,082, hereafter referred to as the ‘082 patent in view of U.S. Patent Application Publication 2014/0068797 (March 6, 2014), hereafter referred to as Doudna et al., is maintained over amended and new claims 1-4, 7, 9-11, 14-15, and 17-19. Applicant’s amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed below.
The applicant argues that claims 1-4, 7, 9-11, 14-15, and 17-18 as amended are now all method claims and that nonstatutory double patenting between the instant method claims and the ‘082 patent claims, which are product claims, should not be applied because the product and a process of use may be distinct if the process for using the product as claimed can be practiced with another materially different product or if the product as claimed can be used in a materially different process of using that product, citing MPEP 806.05(h).
In response, applicant’s argument does not apply to new claim 19 which is itself a product claim. Claim 1 of the ‘082 patent recites a species of instant claim 19 which only differs from instant claim by further including a linker sequence between dCas9 and Clo051. It is well established that a species of a claimed invention renders the genus obvious. In re Schaumann , 572 F.2d 312, 197 USPQ 5 (CCPA 1978). As such the ‘082 patent claims render obvious instant claim 19.
In regards to the nonstatutory double patenting between a product claim and a method claim, the section of the MPEP cited by applicant, MPEP 806.05 is directed to restriction practice and the burden placed on the examiner for restricting between related inventions such as a product and a method of using the product. However, no restriction has been made in this application, and no statements have been made suggesting that the product claims and method claims are patentably distinct. Further, the section cited by applicant refers to potential distinctness between a product and a method of using the product, however, the ‘082 patent claims are drawn to not only the composition comprising the gRNA and the dCas9-Clo051 fusion protein, but also to a cell or organism comprising the composition, which would be a relationship between a method of making the cell and the cell made. Either way, a more relevant section of the MPEP in regards to nonstatutory double patenting is MPEP 804, which was cited in the rejection of record. The rejection of record stated that based on the process recited in the instant claims, the genomic sequence in a cell/cell of an organism is modified by the presence of the gRNA and dCas9-Clo051 fusion protein. The ‘082 patent claims, particularly ‘082 patent claims 7-28, recite products which are cells comprising the exact gRNA and dCas9-Clo051 fusion protein as claimed or a multicellular organism comprising the dCas9-Clo051 fusion protein. While not specifically recited in the ‘082 patent claims, the presence of the gRNA and the dCas9-Clo051 fusion protein in the cell generates a modified genome. The specification of the ‘082 patent, which is identical to the specification of the instant application, clearly discloses the gene editing activity of the gRNA and the dCas9-Clo051 fusion protein in a cell, where the presence of the gRNA and the dCas9-Clo051 fusion protein in the cell modifies a target sequence specific to the gRNA in the genome of the cell. MPEP 804(II)(2)(a) sets forth instances where it is acceptable to utilize the disclosure of a U.S. patent document in conjunction with its claims for obvious-type double patenting rejections. In particular, the MPEP notes that the portion of the specification that supports the patent claims may be considered. See In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). The court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Pfizer, Inc. v. Teva Pharm. USA, Inc., 518 F.3d 1353, 86 USPQ2d 1001 (Fed. Cir. 2008); Geneva Pharmaceuticals Inc. v. GlaxoSmithKline PLC, 349 F3d 1373, 1385-86, 68 USPQ2d 1865, 1875 (Fed. Cir. 2003). In particular, those portions of the specification which provide support for the reference claims may be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application (as distinguished from an obvious variation of the subject matter disclosed in the reference patent or application). In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970). The court in Vogel recognized “that it is most difficult, if not meaningless, to try to say what is or is not an obvious variation of a claim,” but that one can judge whether or not the invention claimed in an application is an obvious variation of an embodiment disclosed in the patent or application which provides support for the claim. According to the court, one must first “determine how much of the patent disclosure pertains to the invention claimed in the patent” because only “[t]his portion of the specification supports the patent claims and may be considered.” The court pointed out that “this use of the disclosure is not in contravention of the cases forbidding its use as prior art, nor is it applying the patent as a reference under 35 U.S.C. 103, since only the disclosure of the invention claimed in the patent may be examined.” In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014). Thus, looking only at the portions of the specification that support the claimed products, and the disclosed utility of those products, it has been determined that the disclosed use for the composition recited in the ‘082 patent claims for modifying a target genome in a cell is an obvious variant of the ‘082 patent product claims, and that likewise the disclosed method of making the cells and organisms claimed in the ’082 patent claims is an obvious variation of the cells and organisms made.
Further, the gene editing effects of providing gRNA and a Cas9 or dCas9 fusion protein to a cell’s genome were known at the time of filing. Doudna et al. teaches a method of modifying a target nucleotide sequence comprising contacting the sequence with a DNA targeting RNA comprising a sequence complementary to a target sequence and a sequence that interacts with a site-directed modifying polypeptide, also known as a guide RNA (gRNA), and a site-directed modifying polypeptide comprising an RNA binding portion that interacts with the DNA targeting RNA and an effector portion that exhibits site-directed enzymatic activity (Doudna et al., paragraphs 1-11, 130). More specifically, Doudna et al. discloses a CRISPR/Cas system where co-expression of guide RNA and Cas9 nucleic acids, or vectors encoding the nucleic acids, or provision of guide RNA and Cas9 protein to a cell generates double-strand DNA breaks at the target locus in the cell genome, and wherein the cells include both human cells and non-human cells such as mouse, rat, or cow cells (Doudna et al., claims, and paragraphs 272-273, 284-285, and 361-369). Doudna et al. also teaches methods of generating non-human transgenic organisms with genetically modified genomes comprising providing Cas9 and gRNA to cells in the organism, wherein the genetic modification can include the insertion of a donor heterologous nucleic acid at the target site (Doudna et al., paragraphs 359-369). In addition, Doudna et al. teaches that two DNA-targeting RNA targeting the same gene can be used (Doudna et al., paragraph 271). Finally, Doudna et al. teaches variants of Cas9, including dCas9 and dCas9 fusion proteins with a heterologous polypeptide (Doudna et al., paragraphs 261, 420, and 456).
Thus, based on the teachings of Doudna et al. for generating a cell or multi-cellular organism comprising a gRNA and a dCas9 fusion protein by providing these components to a cell such as non-human cell, and the further teachings of Doudna et al. that the presence of these components in a cell modifies a target genomic sequence present in the cell, including deletions an insertions, it would have been obvious to the skilled artisan at the time of filing that that the presence of the gRNA and a dCas9 fusion protein in the cell(s) and multi-cellular organisms of the ‘082 patent claims would generate a modified genomic sequence in the genome of the cell(s). As such, it is maintained that the ‘082 patent claims in view of Doudna et al. render obvious the instant method of making cells or organisms comprising a modified genomic sequence by providing a gRNA and a dCas9 fusion protein to a cell.
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.
Any inquiry concerning this communication from the examiner should be directed to
Anne Marie S. Wehbé, Ph.D., whose telephone number is (571) 272-0737. If the examiner is not available, the examiner’s supervisor, Maria Leavitt, can be reached at (571) 272-1085. For all official communications, the technology center fax number is (571) 273-8300. Please note that all official communications and responses sent by fax must be directed to the technology center fax number. For informal, non-official communications only, the examiner’s direct fax number is (571) 273-0737. For any inquiry of a general nature, please call (571) 272-0547.
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Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634