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 .
Election/Restrictions
1. Applicant’s election without traverse of the invention of Group II, drawn to a
(+)ss RNA vector comprising an exogenous imperfect hairpin insert), in the reply filed on 02/09/2026 is acknowledged.
The applicant also elected with traverse of the species of APE. The traversal is on the ground(s) that claims 26, 30, 31, and 34 are dependent on claim 22 or recite an APE range specified in claim 22. This is found persuasive and the species election requirement regarding claims 26, 30, 31, and 34 is withdrawn. Upon further considerations, the species election requirement regarding claims 23 and 27-29 is also withdrawn.
In view of the above noted withdrawal of the restriction requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1-20 and 40-49 have been cancelled. Claims 21, 26, 30, 31, 33, 34, 36, and 39 have been amended. Claims 50-52 are new.
Claim 24 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 21-23, 25, 26, 27-39, and 50-52 are under examination.
Claim Objections
2. Claim 25 is objected to because of the recitation “in a non-base-paired region” in line 2 and second to last line, respectively. Correction to “in one or more of the non-base paired regions” is required.
3. Claim 27 is objected to because of the recitations “a range of” and “length of the insert (# of nt)”. Correction to “the range of” and “length of the insert in nt” is required.
4. Claim 31 is objected to because of the recitation “or both” in the last line. There is only one maximum value (i.e., either 2.0 or 1.5). Correction to delete this recitation from the claim is required.
5. Claim 33 is objected to because of the recitation “a sequence” in line 4 and last line. Correction to “the sequence” is required.
6. Claim 34 is objected to because of the recitation “no more that” in line 5. Correction to “no more than” is required.
7. Claim 36 is objected to because of the recitation “a wild type” in lines 6. Correction to “the wild type” is required.
8. Claim 36 is objected to because of the recitation “within (or within 50% of the limits of) a range of the parameter” in lines 5-6. Correction to “within or within 50% of the limits of the range of the one or more parameters” is required.
9. Claim 52 is objected to because of the recitation “a stack” in lines 6. Correction to “the stack” is required.
Double Patenting
10. 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.
11. Claims 21-23, 25-38, and 50-52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 39, 42, 43, 51-53, 55-57, and 59-62 of copending Application No. 18/311,495 (reference application). 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 (+)ssRNA viral vector comprising the same exogenous imperfect RNA hairpin.
Thus, the instant claims and the application claims are obvious variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112(a) – written description
12. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
13. Claim 27 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC1993). The Guidelines for the Examination of Patent Application Under the 35 U.S.C.112, 1"Written Description Requirement" makes it clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species disclosures of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see especially page 1106 3rd column).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail such that the Artisan can reasonably conclude the inventors had possession of the claimed invention. Such possession may be demonstrated by describing the claimed invention with all its limitations using such descriptive means as words, structures, figures, diagrams, and/or formulae that fully set forth the claimed invention. Possession may be shown by an actual reduction to practice, showing that the invention was "ready for patenting", or by describing distinguishing identifying characteristics sufficient to show that the Applicants were in possession of the claimed invention (January 5, 2001, Fed. Reg., Vol. 66, No. 4, pp.1099-11).
Claim 27 recites a genus of hairpin-like inserts of any length having a minimum free energy ([Symbol font/0x44]G) within the range of -5 to +15 of the [Symbol font/0x44]G obtained by using the equation: [Symbol font/0x44]G = -0.44 x (length in nt) - 1.89. As recited, this equation is supposed to predict [Symbol font/0x44]G (and thus, stability) for inserts regardless of their length.
The specification discloses that the equation represents the line of best fit for the data set generated with just four hairpin inserts; the specification also discloses that the equation could be used to provide [Symbol font/0x44]G for inserts similar in length with the four hairpins used to generate the data (see [0358]). Thus, the equation is only reliable for predicting [Symbol font/0x44]G within the length range of the original four hairpins.
However, claim 27 is broader than this because it is not limited by the hairpin length. The claimed equation cannot predict [Symbol font/0x44]G/stability (a feature deemed essential for the invention) for lengths outside the range of the four hairpins, as the claim encompasses (see the attached IB Math Notes and Statistics from A to Z). In conclusion, the limited information provided by the specification is not sufficient to reasonably convey to one of skill in the art that the applicant was in possession of what is claimed.
Claim Rejections - 35 USC § 112(b)
14. 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.
15. Claims 25, 27, 32, 35-39, 51, and 52 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.
Regarding claim 25, the recitation “a non-base pared region” renders the claim unclear because the parent claim 21 recites “one or non-base pared regions”, and thus, the recitation “a non-base pared region” in the dependent claim 25 makes it uncertain which of the non-base paired regions is intended.
Claim 27 recites that the exogenous segment (i.e., the insert) has a minimum free energy ([Symbol font/0x44]G) “in a range of -5 to +15 of the [Symbol font/0x44]G determined by the equation: -0.44 multiplied by the length of the insert (# of nt) - 1.89”. Multiplication “by the length of the insert” would result in the [Symbol font/0x44]G for the insert itself; it is not clear how the insert could have a [Symbol font/0x44]G in the range of -5 to +15 of its own [Symbol font/0x44]G.
Regarding claims 32, 35, and 38, the phrase "for example" renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 36, the recitations “a base-paired region” and “a non-base pared region” (lines 9 and 11) renders the claim unclear because the claim recites “two or more base paired regions” and “one or more non-base paired regions” in lines 2-3, and thus, the later recitations“a base-paired region” and “a non-base pared region” in lines 9 and 11 makes it uncertain which of the base-paired region and non-base paired region is intended.
Regarding claim 36, the recitation “the parameter” (line 6) renders the claim unclear because the claim recites “one or more parameters” in line 5, and thus, the later recitation “the parameter” in line 6 makes it uncertain which of the one or more parameters is intended.
Regarding claims 37 and 39, the terms “other” and “another” render the claims indefinite because the claim includes elements not actually disclosed (those encompassed by “other” and “another”), thereby rendering the scope of the claims unascertainable. See MPEP § 2173.05(d).
Regarding claim 52, the recitation “a region including two loops” in line 1 is reasonably interpreted as pertaining to the exogenous RNA segment (which is consistent with the specification, see [0406]-[0407]). There is insufficient antecedent basis for this limitation in the claim.
Claim 51 is rejected for being dependent on the rejected claim 36 and also for failing to further clarify the basis of the rejection.
Claim Rejections - 35 USC § 102
16. 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.
17. Claim 33 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Westerhout et al. (NAR, 2007, 35: 4322-4330).
Westerhout et al. teach the exogenous hairpin-like shRNAs T5, T6, and T7, each comprising first and second strands and an apical loop connecting the first and second strands, where the first stand comprises a noncoding sequence targeted at a pathogen and where the second strand is 79%, 70%, and 66% complementary to the first strand, respectively (see p. 4324, Fig. 1; p. 4325, column 1, second full paragraph). Thus, Westerhout et al. teach all claim limitations and anticipate the claimed invention.
Claim Rejections - 35 USC § 103
18. 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.
19. Claims 21-23, 25, 26, 28-38, and 50-52 are rejected under 35 U.S.C. 103 as being unpatentable over Simon et al. (WO 20/102210, published on 05/22/2020; cited on the IDS filed on 04/15/2023), in view of both Westerhout et al. (NAR, 2007, 35: 4322-4330) and Secondary Science 4 All (2014).
Simon et al. teach a plus-sense single stranded RNA (+ssRNA) viral vector such as CYVaV (i.e., a ulaRNA; see the specification, Fig. 2) comprising an exogenous hairpin generating an siRNA targeting a plant pathogen; the hairpin could have a length of 50 nucleotides (claims 21, 28m 29, 32, 35, 37, and 38) (see [0019]; [0034]; [0036]; [0071]; [0079]; [0112]-[0113]; [0124]; [0129]; [0132]; [0143]; [0148]-[0149]; [0152]; [0159]; [0164]; Fig. 9).
Simon et al. do not specifically teach an imperfect hairpin (claims 21 and 33). Westerhout et al. teach that destabilizing shRNAs (i.e., hairpin generating an siRNA) within a specific negative thermodynamic stability ([Symbol font/0x44]G) range, by creating an imperfect hairpin via introducing non-base-paired regions, increases their target binding efficiency and silencing activity (see p. 4324, Fig. 1; p. 4325; paragraph bridging p. 4325 and 4326). Based on these teachings, one of skill in the art would have found obvious to use routine experimentation and modify the hairpin of Simon et al. by introducing non-base-paired regions as taught by Westerhout et al., with the reasonable expectation that doing so would identify the optimal negative [Symbol font/0x44]G range resulting in increased silencing efficiency. By doing so, one of skill in the art would have obtained an ss(+)RNA vector comprising an imperfect hairpin having at least two base-paired regions, at least one non-paired base region between the base-paired regions, and an apical loop at one end of the base-paired regions (claims 21 and 33).
With respect to claims 22, 26, 30, 31, 34, 36, 50, and 51, it was common knowledge in the art that [Symbol font/0x44]G and positional entropy are correlated (see Secondary Science 4 All). By using routine experimentation to determine the optimal [Symbol font/0x44]G range for the imperfect hairpin, one of skill in the art would have also determined the optimal average positional entropy (APE) for each of the base-paired regions, optimal range of APE for the imperfect hairpin, the APE standard deviation, and the PE range for each base that would result in the optimal APE. By doing so, one of skill in the art would have also identified the optimal percent of complementarity within the stem of the hairpin (claims 23, 25, 33, 34, and 36). Routine optimization is not considered inventive, and no evidence has been presented that the selection of the claimed ranges was other than routine or that the results should be considered unexpected in any way as compared to the closest prior art (see MPEP 2144.05 II).
With respect to claim 52, it was common knowledge in the prior art that a negative [Symbol font/0x44]G is associated with spontaneous (feasible) reaction, while a positive [Symbol font/0x44]G is not (see Secondary Science 4 All). Furthermore, Westerhout et al. teach that the [Symbol font/0x44]G optimal for increased silencing activity lies within a negative range. Thus, one of skill in the art would have found obvious to use routine experimentation and maintain negative [Symbol font/0x44]G throughout each of the imperfect hairpin regions which would result in the identified optima [Symbol font/0x44]G optimal range.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
20. Claims 21-23, 25-39, and 50-52 are rejected under 35 U.S.C. 103 as being unpatentable over Simon et al. taken with both Westerhout et al. and Secondary Science 4 All, in further view of Zhang et al. (J. Chem. Phys., 2008, 128: 1-10)
The teachings of Simon et al., Westerhout et al. and Secondary Science 4 All are applied as above for claims 21-23, 25, 26, 28-38, and 50-52. Simon et al., Westerhout et al. and Secondary Science 4 All do not teach an APE as recited in claims 27 and 39. Zhang et al. teach that entropy is correlated with RNA stability (see Abstract). Thus, one of skill in the art would have found obvious to adjust hairpin APE such as to not disturb the stability of the +ssRNA viral vector.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
21. No claim is allowed. No claim is free of prior art.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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