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
Priority
This application is a national stage entry under 35 USC 371 of PCT/JP2022/036403 (filed on 09/29/2022), which claims priority to JAPAN 2021-161312 (filed on 09/30/2021).
Claim Status
Claims 1-14 are pending and have been examined on the merits.
Drawings
The drawings filed on 03/27/2024 are objected to because they contain color images, with no granted petition.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 5, 6, 10 and 11 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 5, 6, 10 and 11 are drawn to “kits”, but it is unclear what is required as part of the kit. The claims being with "…in a cell”, and then go on to recite language from the method claims 1 and 7, respectively. It is unclear if the kits require the unedited cell, per se, the combination of nickases, used in the method of claims 1 and 7, the final, edited cell that results from the methods of claims 1 and 7, respectively, or a combination thereof. Therefore, the metes and bounds of the claims cannot be determined.
For compact prosecution, claims 5, 6, 10 and 11 are being interpreted as kit(s) that comprises a cell having different bases between homologous chromosomes at a specific site of the homologous chromosomes. This is effectively ‘the starting cell’ used in the methods of claims 1 and 7. The scope of claims 5 and10 are treated as identical. Claim 6 is interpreted as kits that comprise a cell having different bases between homologous chromosomes, wherein the cell has a suppressed function of a FANC gene. Claim 11 is interpreted as kits that comprise a cell having different bases between homologous chromosomes at a mutation site.
Appropriate action is required.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-7 and 9-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Osborn et al (Stem cells and development, 2016).
Regarding claim 1, Osborn et al teaches the use of Cas9 nickase to gene correct mutations in cells (See, Abstract). Osborn et al teaches the use of Cas9 nuclease (a nickase) with 5 guide RNAs (gRNAs) that cleave one strand of DNA. The Cas9 plasmid and gRNAs were introduced to cells and analyzed for functionality (See, p1594 col 2 paragraph 2, Figure 1C). This reads on, a method for producing a cell having deletion specific to chromosome A of homologous chromosomes….
Osborn et al teaches that the FANC1 gene targeted in the cells acquired from a male patient had two FANC1 heterozygous mutations, that likely caused splicing abnormalities that prevented the production of functional protein (See, p 1594 col 2 paragraph 1)…this reads on a cell having different bases between homologous chromosomes at a specific site of the homologous chromosomes…
Figure 1 of Osborn et al teaches the gRNAs, Cas9 nuclease, and the HNH/RuvC nuclease, unwind the DNA, and cleave the strands at specific regions. This reads on …introducing into [said cell]... a combination of site specific nickases each of which causes a single strand break at a DNA region proximal to the specific site and on chromosome B, the combination either cause a single stranded break at one of the sites corresponding to the sites single strand broken on chromosome A,…
Regarding claim 2, following the discussion above, Osborn et al teaches that the FANC1 gene targeted in the cells acquired from a male patient had two FANC1 heterozygous mutations, that likely caused splicing abnormalities that prevented the production of functional protein (See, p 1594 col 2 paragraph 1). This reads on, wherein the cell having…is a cell with suppressed function of a FANC gene.
Regarding claims 3 and 11, following the discussion above, the heterozygous mutations of the FANC1 gene, reads on wherein the bases different between homologous chromosomes are bases at a mutation site.
Regarding claims 4 and 12-13, following the discussion above, Figure 1 of Osborn et al teaches the gRNAs, Cas9 nuclease, and the HNH/RuvC nuclease, unwind the DNA, and cleave the strands at specific regions. This reads on, wherein each of the site specific nickases is a CRISPR-Cas system.
Regarding claims 5, 6, 10 and 11, following the discussion above, the metes and bounds of claim 5 are unclear as set forth above. For the purpose of compact prosecution, claims 5 is being interpreted as a ‘kit comprising cell having different bases between homologous chromosomes at a specific site of the homologous chromosomes’. The two cells obtained from the patient having two FANC1 heterozygous mutations, having suppressed function of a FANC gene, reads on this cell.
Regarding claim 7, following the discussion above, Osborn et al has taught method of introducing into a cell a combination of site-specific nickases to cause single strand break at a DNA region proximal to specific site.
Osborn et al further teaches the efficacy is then tested with surveyor nuclease to determine nonhomologous end-joining repair and a representative gel shows where the changes were in the cells (See, Figure 1 p 1595). This reads on, detecting chromosome A-specific DNA deletion generated.
Figure 1 legend details that unmodified alleles or chromosome strands have a green box, nuclease modification have a lightning bolt, that results in nonhomologous end-joining repair with small unmodified sequences that are cleaved into fragments (See, p1595). This reads on, combination of site specific nickases causes single strand breaks at multiple sites in the DNA region proximal to the specific site on chromosome A, and the single strand breaks are single stranded breaks of both DNA strands or single DNA strand…and the homologous recombination function in a cell is evaluated as suppressed when a frequency of chromosome A-specific DNA deletion occurring is high than control, as evidenced in the gel in figure 1 of Osborn et al.
Regarding claim 9, following the discussion above, the use of Cas9 nuclease/nickase and other components, reads on wherein each of the site specific nickases is a CRISPR-Cas system.
Therefore, claims 1-7 and 9-13 are anticipated by Osborn et al.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 8 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Osborn et al (Stem cells and development, 2016) as applied to claims 1-7 and 9-13 above, and further in view of Errazquin et al (Genes, 2021).
The teachings of Osborn et al are set forth above.
Regarding claim 8, Osborn et al does not teach the method of evaluating homologous recombination function in a cancer cell.
Errazquin et al teaches that patients with Fanconi anemia have chromosome instability and exacerbated risk of head and neck squamous cell carcinoma (HNSCC) (See, Abstract and p. 1). Errazquin et al use CRISPR/Cas9 editing tools to interrupt the human FANCA gene by generation insertion and deletions in exon 4 in two cancer cell lines (See, Abstract).
It would have been prima facie obvious to a person having ordinary skill in the art to substitute the cells of Osborn et al with the cancer cell lines of Errazquin et al. Both Osborn et al and Errazquin et al teach the use of CRISPR/Cas9 systems to edit FANC genes in cells for furthering understanding of Fanconi Anemia. The use of cancer cells would have a predictable result of success evidenced by Errazquin et al editing the cell lines in a similar method. This rationale aligns with the principle of KSR for simple substitution of one known element for another to obtain predictable results (See, MPEP 2143).
Regarding claim 14, following the discussions above, Figure 1 of Osborn et al teaches the gRNAs, Cas9 nuclease, and the HNH/RuvC nuclease, unwind the DNA, and cleave the strands at specific regions. This reads on, wherein each of the site specific nickases is a CRISPR-Cas system.
Therefore, claims 8 and 14 are rendered obvious by Osborn et al in view of Errazquin et al.
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 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.
Claims 1,3,4,5,6,10,11, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,2, 3, and 4 of U.S. Patent No. 12365923.
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons:
Regarding claim 1, reference patent claim 1 recites a method for producing a genome-edited cell, comprising:, this reads on a method for producing a cell having a DNA deletion specific to chromosome A of homologous chromosomes… as a DNA deletion is genome editing.
…introducing, into a cell having homologous chromosomes, said homologous chromosomes comprising a donor homologous chromosome having a first base at a target site and a recipient homologous chromosome having a second base at a target site corresponding to the target site of the donor homologous chromosome, wherein the second base of the recipient homologous chromosome differs from the first base of the donor homologous chromosome, this reads on introducing into a cell having different bases between homologous chromosomes….
wherein the combination of site-specific nickases cleaves a single strand in a neighboring DNA region of the target site of the donor homologous chromosome and a single strand in a neighboring DNA region of the target site of the recipient homologous chromosome, this reads on the combination of site specific nickases cause single strand breaks at multiple sites in the DNA region proximal to the specific site on chromosome A.
Regarding claim 3, reference patent claim 2 recites, wherein the second base of the recipient homologous chromosome is a mutant base and the first base of the donor homologous chromosome is a normal base, this reads on wherein the bases different between homologous chromosomes are bases at a mutation site.
Regarding claims 4 and 13, reference patent claim 3 recites, wherein the site-specific nickases are a CRISPR-Cas system, this reads on wherein each of the site specific nickases is a CRISPR-Cas system.
Regarding claims 5-6 and 10-11, reference patent claim 1 recites a method starts with a cell and ends with an edited cell. The cell at the beginning of the method anticipates the cell in claims 5, 6, 10 and 11. The cell at the beginning of the method can be a cell with suppressed function of a FANC gene, which reads on ‘at a mutation site’.
Therefore claims 1,3,4,5,6,10,11, and 13 are anticipated by U.S. Patent No. 12365923.
Claims 2,7,9, and 12 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12365923 in view of Osborn et al (Stem cells and development, 2016).
The teachings of U.S. Patent No. 12365923 and Osborn et al are set forth above.
Regarding claim 2 and 12, US12365923 (reference patent) does not teach the targeting of FANC gene.
Osborn et al teaches the use of Cas9 nuclease (a nickase) with 5 guide RNAs (gRNAs) that cleave one strand of DNA. The Cas9 plasmid and gRNAs were introduced to cells and analyzed for functionality (See, p1594 col 2 paragraph 2, Figure 1C).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method disclosed in the reference patent to target FANC gene as taught by Osborn et al. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification because it would be advantageous to target dysfunctional FANC gene to treat Fanconi anemia, as taught in Osborn et al. One would have had a reasonable expectation of success due to the success of the method in referenced patent and taught by Osborn et al.
Regarding claims 7 and 9, US12365923 does not disclose a method for evaluating homologous recombination in a cell.
Osborn et al has taught method of introducing into a cell a combination of site-specific nickases to cause single strand break at a DNA region proximal to specific site.
Osborn et al further teaches the efficacy is then tested with surveyor nuclease to determine nonhomologous end-joining repair and a representative gel shows where the changes were in the cells (See, Figure 1 p 1595). This reads on, detecting chromosome A-specific DNA deletion generated.
Figure 1 legend details that unmodified alleles or chromosome strands have a green box, nuclease modification have a lightning bolt, that results in nonhomologous end-joining repair with small unmodified sequences that are cleaved into fragments (See, p1595). This reads on, combination of site specific nickases causes single strand breaks at multiple sites in the DNA region proximal to the specific site on chromosome A, and the single strand breaks are single stranded breaks of both DNA strands or single DNA strand…and the homologous recombination function in a cell is evaluated as suppressed when a frequency of chromosome A-specific DNA deletion occurring is high than control, as evidenced in the gel in figure 1 of Osborn et al.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method disclosed in the reference patent to further comprise a method for evaluating homologous recombination function in a cell as taught by Osborn et al. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification because it would be advantageous to evaluate and understand the efficacy of the gene editing method in a cell, as taught in Osborn et al. One would have had a reasonable expectation of success due to the success of the method taught by Osborn et al.
Therefore, claims 2,7,9, and 12 are rendered obvious non-statutory double patenting over US 12365923 in view of Osborn et al.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. 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.
/CAROLINE M LARA/ Examiner, Art Unit 1633
/ALLISON M FOX/ Primary Examiner, Art Unit 1633
Prosecution Insights