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 1-45, 47, and 48 have been cancelled. Claims 55, 58, 71-90, and 92 have been withdrawn. Claims 46, 49, and 91 have been amended.
Claims 46, 49-54, 56, 57, 59-70, and 91 are under examination.
2. All rejections pertaining to claims 47 and 48 are moot because the claims were cancelled with the reply filed on 08/03/2026.
The objection to claim 49 is withdrawn in response to the amendment filed on 08/03/2026.
The rejection of claim 49 under 35 U.S.C. 112(d) is withdrawn in response to the amendment to make the claim dependent upon claim 46 and to delete the recitation that the sequence of (3) contains the stop codon.
The obviousness-type rejections set forth in the non-final rejection mailed on 04/02/2026 are withdrawn in view of the argument/evidence that the mutated luciferase cDNA of Czochor et al. does not comprise a stop codon. New grounds of rejection are set forth below.
Specification
3. The claim listing is objected to because the cancelled claims 1-45 are not listed are no listed as “cancelled”.
Claim Objections
4. The following amendment to claims 46 and 91 is suggested:
“(2) a mutant gene sequence encoding a protein, wherein the mutant gene comprises a cleavage site in the protein coding region and a stop codon upstream of the cleavage site”.
5. The following amendment to lines 11-12 in claim 70 is suggested:
“wherein the protein encoded by the gene sequence is a protein whose intracellular expression is detectable”.
New Rejections
Double Patenting
6. 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.
7. Claims 46, 49-54, 56, 57, 59-70, and 91 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 15-17, 24, and 26 of copending Application No. 18/684,590 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are drawn to (1) the same linear nucleic acid construct; and (2) the same method of using the linear nucleic acid construct for measuring HR in cells.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112(d)
8. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
9. Claim 54 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
By reciting that the nucleic acid construct is circular, claim 54 broadens the subject matter of the parent claim 46, which is limited to a linearized nucleic acid construct.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
10. 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.
11. Claims 46, 49-51, 53, 54, 56, 57, 59, 61-70, and 91 are rejected under 35 U.S.C. 103 as being unpatentable over Pierce et al. (Genes & Development, 1999, 13: 2633-2638), in in view of Czochor et al. (Mol. Cancer Res., 2016, 14: 363-373), as evidenced by the attached NEB Data Sheet.
Pierce et al. teach a circular plasmid comprising a construct containing in 5’ to 3’ order: a promoter, operably linked to a GFP cDNA mutated to comprise (1) the I-SceI site within the GFP coding region and a stop codon upstream of the I-SceI site which inactivates GFP by terminating its translation; and (2) a donor template consisting of a promoterless continuous partial GFP sequence having a length of 812 bp and which overlaps with the I-SceI site. Pierce et al. teach using the construct in a method for measuring HR activity in test cells, the method comprising transiently introducing the circular plasmid together with a plasmid encoding the I-SceI restriction enzyme into the test and control cells, where I-SceI linearizes the plasmid inside the cells; determining HR activity by measuring and comparing the GFP levels in the test cells and HR-proficient control cells; a lower GFP expression in the test cells compared to the control cells indicates that the test cells have lower HR activity (claim 46, 50, 53, 54, 56, 57, 59, 61, 70, and 91) (see p. 2634-2635).
Pierce et al. disclose that the I-SceI site has the sequence:
PNG
media_image1.png
20
206
media_image1.png
Greyscale
, where the underlined nucleotides represent termination codons (see Fig. 1). As evidenced by the NEB Data Sheet, I-SceI cleaves at the sites indicated by the arrowheads:
PNG
media_image2.png
58
290
media_image2.png
Greyscale
(see p. 1). Thus, the mutated GFP cDNA taught by Pierce et al. comprises a stop codon upstream of the cleavage site.
Since the continuous 812 bp GFP cDNA sequence overlaps with the stop codon and the I-SceI site (see Fig. 1), one of skill in the art would have readily understood that it comprises upstream and downstream regions adjacent to the stop codon and the cleavage site, respectively (claim 49).
Pierce et al. do not teach linearizing the plasmid with I-SceI before its introduction into cells (claims 46, 70, and 91). Czochor et al. teach a plasmid comprising a similar construct for measuring HR activity. Czochor et al. teach linearizing the plasmid by cleaving it with I-SceI before introducing it into test and control cells to determine HR activity in the test cells (see p. 365, column 2, second full paragraph; p. 368, column 2, last paragraph; p. 369). One of skill in the art would have found obvious to modify the method of Pierce et al. by linearizing the plasmid before introducing it into cells, to achieve the predictable result of obtaining a composition suitable for measuring HR activity. By doing so, one of skill in the art would have obtained a linear nucleic acid as recited in claims 46, 70, and 91.
With respect to claim 51, the 182 bp fragment of the GFP cDNA necessarily has homologous sequences having a length of at least 20 nucleotides.
The limitations recited on claims 62-69 only represent an intended use which does not state any distinct limitation differentiating the claimed composition from the composition taught by the prior art. The intended use is of no significance to the composition structure and therefore, it is of no significance to claim construction.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
12. Claims 46, 49-54, 56, 57, 59, 61-70, and 91 are rejected under 35 U.S.C. 103 as being unpatentable over Pierce et al. taken with Czochor et al., as evidenced by the attached NEB Data Sheet, in further view of Klauer et al. (Wiley Interdiscip. Rev. RNA, 2012, 3: 1-16).
The teachings of Pierce et al. and Czochor et al. are applied as above for claims 46, 49-51, 53, 54, 56, 57, 59, 61-70, and 91. Pierce et al. and Czochor et al. do not specifically teach a polyA downstream of the mutated luciferase gene (claim 52). Klauer et al. teach that the absence of a polyA tail leads to mRNA degradation (see p. 2, first paragraph). Thus, including a polyA tail downstream of the mutated luciferase gene to achieve the predictable result of expressing the luciferase reconstituted upon HR.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
13. Claims 46, 49-51, 53, 54, 56, 57, 59, 60-70, and 91 are rejected under 35 U.S.C. 103 as being unpatentable over Pierce et al. taken with Czochor et al., as evidenced by the attached NEB Data Sheet, in further view of Ahren (The Scientist, 1995).
The teachings of Pierce et al. and Czochor et al. are applied as above for claims 46, 49-51, 53, 54, 56, 57, 59, 61-70, and 91. Pierce et al. and Czochor et al. do not teach a kit (claim 60). However, the limitation of a kit is not innovative over the prior art; kits containing nucleic acid constructs and instructions for introducing them into cells have been used before the invention was made. One of skill in the art would have been motivated to assemble a kit, i.e., put the reagents in a box containing instructions how to use the reagents, because they are convenient to use and save time (see Ahren, p. 20, the paragraph entitled “The Kit Concept”).
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
It is noted that none of the arguments pertains to the new rejections.
14. No claim is allowed. No claim is free of prior art.
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.
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.
/ILEANA POPA/Primary Examiner, Art Unit 1633
