DETAILED CORRESPONDENCE
Application Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment to the claims filed on 05/26/2026 in response to the Non-Final Rejection mailed on 02/05/2026 is acknowledged. This listing of claims replaces all prior listings of claims in the application.
3. Claim 17 is cancelled.
4. Claims 1-16, 18-20 and 25 are pending.
5. Applicant’s remarks filed on 05/26/2026 in response to the Non-Final Rejection mailed on 02/05/2026 have been fully considered and are deemed persuasive to overcome at least one of the rejections and/or objections as previously applied.
The text of those sections of Title 35 U.S. Code not included in the instant action can be found in the prior Office Action.
Specification/Drawings
6. The objection to the specification/drawings under 37 CFR 1.821 is withdrawn in view of applicants’ amendment to the specification/drawings to incorporate appropriate sequence identifiers.
Claim Rejections - 35 USC § 112(b)
7. The rejection of claims 10-15 and 18-19 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the relative term “about” is withdrawn in view of applicants’ amendment to the claims to remove said term.
8. The rejection of claim 25 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for lack of antecedent basis is withdrawn in view of applicant’s amendment to the claims to recite “the bridge oligonucleotide”.
9. Claims 1-16, 18-20, and 25 are newly 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. This new grounds of rejection is necessitated by applicants’ amendment to the claims to recite “wherein the bridge oligonucleotide positions the first and second oligonucleotides in the complex in close proximity to facilitate ligation at the ligation site”.
Regarding claim 1 (claims 2-16, 18-20 and 25 dependent therefrom), the recitation of “close proximity to facilitate ligation at the ligation site” is indefinite because the term “close” is a relative term which renders the claim indefinite. The term "close" is a term of degree and the examiner has reviewed the specification and can find no examples or teachings that can be used for ascertaining the variance intended by the recited term of degree. Moreover, there is nothing in the specification or prior art of record to indicate that one of ordinary skill in the art could have ascertain the scope of the recited degree. It is suggested that applicant clarify the meaning of the claims. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7165.
Claim Rejections - 35 USC § 102
10. The rejection of claim 17 under 35 U.S.C. 102(a)(1) as being anticipated by Gersbach et al. (US Patent Application Publication 2020/0347105 A1, published on 11/5/2020 with priority to 06/11/2018; cited on PTO-892 mailed on 02/05/2026) is withdrawn in view of applicants’ amendment to the claims to cancel claim 17.
11. The rejection of claims 1-16, 20 and 25 under 35 U.S.C. 102(a)(1) as being anticipated by Gersbach et al. (US Patent Application Publication 2020/0347105 A1, published on 11/5/2020 with priority to 06/11/2018; cited on PTO-892 mailed on 02/05/2026) is maintained for the reasons of record and the reasons set forth below. The rejection has been modified in order to address applicants’ amendment to the claims.
12. As amended, claims 1-16, 20, and 25 are drawn to a method of generating a CRISPR array, the method comprising: providing a first oligonucleotide comprising a CRISPR repeat sequence or a portion thereof, and a first portion of a first space sequence at its 3’end; providing a second oligonucleotide comprising, from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and a first portion of a second spacer sequence; providing a bridge oligonucleotide comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the bridge oligonucleotide to form a complex; and ligating the first and second oligonucleotide at a ligation site present between the first oligonucleotide and the second oligonucleotide, wherein the bridge oligonucleotide positions the first and second oligonucleotides in the complex in close proximity to facilitate ligation at the ligation site.
13. With respect to claim 1, Gersbach et al. teach a method of generating a CRISPR array comprising providing a first oligonucleotide comprising CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end; providing a second oligonucleotide comprising from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and first portion of a second spacer sequence; providing a protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the protospacer sequence and ligating the first and second oligonucleotide [see Abstract; Figures 1 and 9; paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175].
With respect to claim 2, Gersbach et al. teach the method wherein the first oligonucleotide further comprises a flanking sequence at its 5’ end [see paragraph 0194].
With respect to claim 3, Gersbach et al. teach a method of generating a CRISPR array comprising providing a first oligonucleotide comprising CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end; providing a second oligonucleotide comprising from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and first portion of a second spacer sequence; providing a protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the protospacer sequence and ligating the first and second oligonucleotide [see Abstract; paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175].
With respect to claim 4, Gersbach et al. teach the method wherein the flanking sequence comprises a portion of a sequence of a vector [see paragraph 0209].
With respect to claim 5, Gersbach et al. teach the method wherein the first oligonucleotide further comprises at its 5’ end, a portion of a third spacer sequence [see paragraphs 0016, 0024, 0075, 0116, 0199].
With respect to claim 6, Gersbach et al. teach the method wherein the first oligonucleotide comprises a third spacer sequence, a CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end [see paragraphs 0007, 0016, 0024, 0059, 0075, 0111-0112, 0116, 0174-0175, 0199].
With respect to claim 7, Gersbach et al. teach wherein the protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to a portion of the CRISPR repeat sequence at its 5’ or 3’ end [see paragraphs 0187-0189].
With respect to claim 8, Gersbach et al. teach the method wherein the portion of the CRISPR repeat sequence comprises about 1 to about 10 nucleotides [see paragraph 0177].
With respect to claim 9, Gersbach et al. teach the method wherein the protospacer sequence (bridge oligonucleotide) comprises from 5’ to 3’ a sequence substantially to a first portion of the CRISPR repeat sequence, the sequence substantially complementary to the first spacer sequence, and a sequence substantially complementary to a second portion of the CRISPR repeat sequence [see paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175; 0187-0189].
With respect to claim 10, Gersbach et al. teach the method wherein the first and/or second portion of the repeat sequence comprises about 1 to about 10 nucleotides [see paragraph 0177].
With respect to claims 11 and 12, Gerbsach et al. teach the method wherein each of the first and second oligonucleotides comprises about 40 or more nucleotides (encompasses the claimed range as “or more” can be interpreted as any value over 40 nucleotides) [see paragraph 0177]
With respect to claim 13, Gersbach et al. teach the method wherein the CRISPR repeat sequence comprises about 15 to 36 nucleotides [see paragraph 0177].
With respect to claim 14, Gersbach et al. teach the method wherein the protospacer sequence comprises about 30 to 50 nucleotides [see paragraph 0116].
With respect to claim 15, Gersbach et al. teach the method wherein teach of the first portion of the first spacer sequence, the second portion of the first spacer sequence, and the first portion of the second spacer sequence comprising about 5 to about 20 nucleotides [see paragraph 0116].
With respect to claims 16 and 17, Gersbach et al. teach the method wherein the first spacer sequence comprises a first target site in a target gene, and the second spacer sequence comprises a second target site in the target gene [see paragraphs 0009-0013; 0116].
With respect to claim 20, Gersbach et al. teach the method wherein the first oligonucleotide, the second oligonucleotide and the bridge oligonucleotide are DNA oligonucleotides [see paragraph 0084].
With respect to claim 25, Gersbach et al. teach the method further comprising generating a strand complementary to the ligated first and second oligonucleotide, wherein the complementary strand comprises the bridge oligonucleotide, thereby generating a double-strand construct [see paragraphs 0007; 0024; 0059; 0075; 0100; 0111-0112; 0174-0175; 0187-0189].
RESPONSE TO REMARKS: Beginning on p. 10 of applicants’ remarks, applicants in summary contend that Gersbach does not teach each and every element of claim 1 in that the Gersbach does not disclose a bridge oligonucleotide that positions a first and a second oligonucleotide in close proximity to facilitate ligation at the ligation site between the two. Applicants further contend that the ligation step demonstrated by Gersbach ligates a double stranded product into a vector and does not ligate to form a long continuous single stranded product.
This argument is found to be not persuasive because MPEP 2111 states “[d]uring patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard: The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." In the instant case, it is the examiner’s position that the complex disclosed in Figures 1 and 9 of Gersbach reasonably read on the structure recited in the claims given the breadth of the terms ‘portion’ and ‘bridge’ as recited in the claims, and also in view of the indefiniteness of the term ‘proximity’. The target loci taught by Gersbach that permits the hybridization of the spacer-repeat pairs can reasonably read on the “bridge oligonucleotide” as claimed [see paragraph 0024 and Figures 1 and 9].
Regarding applicants’ remarks that the ligation step demonstrated by Gersbach ligates a double stranded product into a vector and does not ligate to form a long continuous single stranded product, this argument is found to be not persuasive because it is noted that the features upon which applicant relies (i.e., single stranded product) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Claim Rejections - 35 USC § 103
14. The rejection of claims 18 and 19 under 35 U.S.C. 103 as being unpatentable over Gersbach et al. (US Patent Application Publication 2020/0347105 A1, published on 11/5/2020 with priority to 06/11/2018; cited on PTO-892 mailed on 02/05/2026) is maintained for the reasons of record and the reasons set forth below.
15. The relevant teachings of Gersbach et al. as applied to claims 1-16, 20 and 25 are set forth in the 102 rejection above.
With respect to claims 18 and 19, Gersbach et al. teach a method of generating a CRISPR array comprising providing a first oligonucleotide comprising CRISPR repeat sequence or a portion thereof, and a first portion of a first spacer sequence at its 3’ end; providing a second oligonucleotide comprising from 5’ to 3’, a second portion of the first spacer sequence, the CRISPR repeat sequence, and first portion of a second spacer sequence; providing a protospacer sequence (bridge oligonucleotide) comprising a sequence substantially complementary to the first spacer sequence; allowing the first oligonucleotide and the second oligonucleotide to hybridize with the protospacer sequence and ligating the first and second oligonucleotide [see Abstract; paragraphs 0007; 0024; 0059; 0075; 0111-0112; 0174-0175].
Although Gersbach et al. does not specifically teach the method of claims 18 and 19 wherein the bridge oligonucleotide is used at a ratio of between about 2:1 and about 3:1 by molarity in relation to a mixture of the first and second oligonucleotides and wherein the amount of the first and second oligonucleotides in the mixture are about equal, MPEP 2144.05.II.A states “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”. In the instant case, it would have been obvious for one of ordinary skill in the art creating the CRISPR array of Gersbach et al. to optimize the ratios of oligonucleotides in order to maximize the efficiency and effectiveness of the array production. Therefore, the above invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
RESPONSE TO REMARKS: Beginning on p. 13 of applicants’ remarks, applicants in summary contend that contend that Gersbach does not teach or suggest the relative amounts (ratios) as result effective variables.
This argument is found to be not persuasive because it is the examiner’s position that in the field of molecular biology involving nucleotide sequences and ligation reactions, it is within the level of one of ordinary skill in the art to optimize concentration ratios of oligonucleotides in order to determine the amounts of each component that maximizes ligation efficiency.
Conclusion
16. Status of the claims:
Claims 1-16, 18-20 and 25 are pending.
Claims 1-16, 18-20 and 25 are rejected.
No claims are in condition for an allowance.
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 or earlier communications from the examiner should be directed to PAUL J HOLLAND whose telephone number is (571)270-3537. The examiner can normally be reached Monday to Friday from 8AM to 5PM.
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, Manjunath Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL J HOLLAND/Primary Examiner, Art Unit 1656
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