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 .
DETAILED ACTION
Claim status
Claims 1-20 are pending
Claims 11-20 are withdrawn
Claims 1-10 are under examination
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 11/05/2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-10, drawn to methods of using nucleic acids to modify a cell.
Claims 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 9/16/2022, 1/27/2023, 5/01/2024, 8/11/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification 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.
Objection to Specification
The Specification does not conform to sequence rules, requiring the use of “SEQ ID NO:” (37 CFR 1.821-1.825).
Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by “SEQ ID NO:” in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. 37 CFR 1.821 (d). In instant case, Applicant’s specification recites nucleic acid sequences greater than 10 nucleotides without an accompanying SEQ ID NO on p. 38, line 28, p. 39, line 25 and line 39
The applicant is reminded that claims and specification must be amended in order to comply with regulations cited above. All references to sequences in claims and specification should be referred to as “SEQ ID NO:1”, for example. To avoid all doubts of the examiner and to ensure correct interpretation of the claims and specification, the identification of sequences with proper sequence identifiers is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 10 is 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 pre-AIA the applicant regards as the invention.
Claim 10 recites the limitation "Introduced into the cell" in regard to the introducing step c of Claim 1. There is insufficient antecedent basis for this limitation in the claim because Claim 1, step c is directed to “one or more cell(s)”, thereby rendering Claim 10 indefinite as to the scope of the cell.
Furthermore, Claim 10 recites the limitation the introducing step of the fuNA is into “composition comprising the target NA" in regard to the introducing step c of Claim 1. There is insufficient antecedent basis for this limitation in the claim because Claim 1, step c is directed to introducing the fuNA into “one or more cell(s) comprising the target NA”, thereby rendering Claim 10 indefinite as to the scope of the composition.
Appropriate correction is required.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-10 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Cotta-Ramusino et al. (WO 2017/180711, published October 18, 2017 and having priority to April 13, 2016 based on US Provisional document 62/322,099, see IDS filed 9/16/2022).
Cotta-Ramusino et al. teach methods for modification of a target nucleic acid in a cell comprising
providing a Cas9 molecule and at least one single guide RNA fusion, comprising a sgRNA covalently linked to a donor template nucleic acid,
contacting the cell with the sgRNA fusion(s) and Cas9 such that they are introduced into the cell,
[AltContent: textbox ([img-media_image1.png])]wherein the cell is incubated such that at least one break in the target nucleic acid is repaired by homologous recombination with the donor template (p. 6, last 2 para., Claims 49-50, see also labeled excerpt from Fig. 3 of priority document adjacent).
In regard to the donor template comprising two homology arms being directly adjacent to each other, Cotta-Ramusino teaches an embodiment, wherein the target site is a single nucleotide polymorphism in the HBB gene that causes an E6V mutations (p. 22, last para., p. 127, 2nd para., p. 185, 4th & 5th para. of priority document). Since, the only “replacement sequence” is with a wildtype sequence with no intervening nucleotides, the homology arms are directly adjacent to each other. Note that instant claims allow as low as 60% complementary sequence in the homology arms with the target NA molecule.
In regard to claim 2, Cotta-Ramusino claims the cells after homologous recombination are in a pharmaceutical composition (claims 58-59 of priority document), and teaches that after the cells are treated ex vivo, they are returned to the subject as cell therapy (p. 180, 3rd para. to p. 181, last para. of priority document). Note that Applicant’s specification defines “isolated” as being removed by the hand of man and exists apart from its original, native environment.
In regard to claims 3 and 4, Cotta-Ramusino teaches the sgRNA is RNA and the donor repair template is RNA (p. 30, last para., p 49, Section (C), to p. 50 see Figs 1 & 3 of priority document).
In regard to claims 5 and 6, Cotta-Ramusino teaches the homology arms are at least 50 nucleotides (p. 155, last 2 para. of priority document), wherein each homology arm would have comprised at least 15 consecutive bases that are 100% identical to the target nucleic acid.
In regard to claim 7, Cotta-Ramusino teaches the sgRNA comprises a 20 nucleotide spacer region that is 100% complementary to the same number of consecutive bases of the target nucleic acid (p. 53, Section III, to p. 58, 2nd para. of priority document), and demonstrates that the sgRNA comprises a tracr/crRNA scaffold with at least one hairpin (see Fig 3 of priority document).
In regard to claim 8, Cotta-Ramusino the target cell is a human cell (p. 7, lines 13-14, see Claim 57 of priority document).
In regard to claim 9, Cotta-Ramusino teaches the Cas9 is a double-stranded cutter or single-stranded nickase (p. 6, last 2 para., see Claims 49 or 50 of priority document).
In regard to claim 10, as stated supra, Cotta-Ramusino teaches the gRNA and repair donor template are RNA, and are introduced into the cells as an RNA molecule (see also p. 226, last para., of Example 9, Table 6, last row, see Fig. 3 of priority document).
Accordingly, Cotta-Ramusino anticipates instant claims.
Double Patenting
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1-10 are rejected on the grounds of nonstatutory double patenting over claims 1-20 of U.S. Patent No. 11,608,499 (Neuteboom et al., Patented 3/21/2023), in view of Li et al. (Metabolic Eng, 2015, 31:13-21).
The subject matter claimed in the instant application is disclosed in the referenced patent as follows: the method for modification of a target nucleic acid in a cell comprising a guide nucleic acid covalently linked to donor nucleic acid makes obvious the method of instant application. It is clear that elements of the cited patent claims are to be found in instant claims. The difference between the cited patent claims and the instant claims lies in the fact that the instant claims are more specific with respect to the donor nucleic acid comprising homology arms that are directly adjacent.
[AltContent: textbox ([img-media_image2.png])]Nevertheless, Li teaches that homology arms are to be directly adjacent in the donor template when deleting a target sequence during genome editing using CRISPR-Cas9 based system (see Fig.1 excerpt, adjacent).
Accordingly it would have been obvious to claim the method comprising a donor nucleic acid of cited patent and to claim a donor with left and right homology arms directly adjacent for the purposes of deleting a genomic sequence as taught by Li with a reasonable expectation of success. One of ordinary skill would have been motivated to do so because targeted deletions from the taught donor would have been immediately envisioned as one from a limited number of options for gene modification.
Since the instant application claims are obvious over cited patent claims in view of Li, said claims are not patentably distinct.
Claims 1-10 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 17/933,003. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the method for modification of a target nucleic acid in a cell comprising a guide nucleic acid covalently linked to donor nucleic acid anticipates the method of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are more specific with respect to the step of introducing a single composition. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
Claims 1, 3-10 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 17/933,015. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the method for modification of a target nucleic acid in a subject comprising a guide nucleic acid covalently linked to donor nucleic acid anticipates the method of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are more specific with respect to the method being in vivo. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
Claims 1, 3-10 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No. 17/933,023. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the method for modification of a target nucleic acid in a subject comprising a guide nucleic acid covalently linked to donor nucleic acid anticipates the method of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the cited application claims are more specific with respect to the method being in vivo. Thus the invention of said claims of the cited application are in effect “species” of the “generic” invention of the instant claim. It has been held that the generic invention is “anticipated” by the “species”. See In re Goodman, 29 USPQ2d 2010 (Fed. Cir. 1993).
Since the instant application claims are anticipated by cited application claims, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631