MATERIALS AND METHODS FOR TREATMENT OF HEREDITARY HAEMOCHROMATOSIS

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 . 1. Claims 1-66 have been cancelled. Claims 67-86 are new. Claims 67-86 are pending and under examination. Claim Objections 2. Claim 78 is objected to because of the recitation “wherein the CRISPR/Cas9 system comprising”. Correction to “wherein the CRISPR/Cas9 system comprises” is required. 3. Claim 79 should be rewritten as follows: The composition of claim 78, wherein the one or more nucleic acids encoding the DNA endonuclease are mRNAs. 4. Claim 85 is objected to because of the recitations “a group” (line 1) and “or cell from the testes” (line 2). Correction to “the group” and “and cell from the testes” is required. Double Patenting 5. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 ( CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web- based eTerminal Disclaimer may be filled out completely online using web- screens. An eTerminal Disclaimer that meets all requirements is auto- processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying- online/eterminal-disclaimer. 6. Claims 67-86 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent No. 11,083,799 in view of both Angel et al. (WO 14/071219; cited on the IDS filed on 03/28/2025) and Zuris et al. (Nature Biotechnol., 2015, 33: 73-80). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same sgRNA for editing the HFE gene in a cell. The instant claim 86 defines that the cell is a cell from a patient with HHC. The patent specification discloses that: the HFE gene is located in the 6p21.3 region, the sgRNA is modified as recited in the instant claims 71-73; the sgRNA could be delivered by an AAV, as recited in the instant claim 83; and the cell could be a liver cell, as recited in the instant claim 85 (see column 1, lines 47-49; paragraph bridging columns 5 and 6; column 6, lines 58-63; column 7, lines 62-67; column 33, lines 3-20; column 59, lines 38-39). The patent claim 8 does not recite Cas9 (instant claims 68 and 75), using a Cas9-encoding mRNA (instant claim 78 and 79), lipid nanoparticles (instant claims 76 and 77), a single-stranded donor template (instant claims 81 and 82); or single-strand brakes (instant claim 84). However, the patent claim 8 recites that the sgRNA is suitable for editing the HFE gene in cells from patients affected by HHC. Angel et al. teach gene editing by using an editing protein capable of creating a single-strand break and a repair template; the repair template could be a ssDNA and the edited gene could be HFE gene (see Abstract; p. 11, lines 27-30; paragraph bridging p. 22 and 23; p. 27, lines 18-30; p. 44, lines 31-33; p. 45, lines 16-18 and Table 7). Zuris et al. teach that gene editing with sgRNA requires forming a complex between the sgRNA and a Cas9 (such as an S. Pyogenes Cas9 nickase); the sgRNA and the Cas9 nickase are either pre-complexed or could form the complex inside cells upon transfection with sgRNA and a plasmid encoding Cas9 nickase. Zuris et al. teach that transfection with cationic lipids mediates potent sgRNA/Cas9 delivery and that Cas9 could also be delivered via an mRNA (see Abstract; p. 73, column 2, last paragraph; p. 74; p. 76, Fig. 4; p. 77, column 2, second full paragraph; p. 78, column 1, first three paragraphs; p. 79; Methods). Modifying the patent claims by encapsulating the sgRNA and an mRNA encoding an S. Pyogenes Cas9 nickase (i.e., mediating single-stranded breaks) into the same or different cationic lipid nanoparticles, and further adding an expression vector encoding the ssDNA repair template (having homology arms homologous to the HFE gene location region) would have been obvious to one of skill in the art with the reasonable expectation that doing so would result in a composition suitable for HFE gene editing. Thus, the instant claims and the patent claims are obvious variants. 7. No claim is allowed. Claims 67-86 are free of the prior art of record because the prior art of record does not teach or render obvious the sgRNA spacers recited in claim 67. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILEANA POPA whose telephone number is (571)272-5546. The examiner can normally be reached 8:00 am to 4:30 pm. 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Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ILEANA POPA/ Primary Examiner, Art Unit 1633