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 .
Status of Application/Amendments/Claims
Applicant’s response filed on 4/14/2026 has been considered. Claims 12-25 have been canceled. Claims 1-11 and 26-34 are pending. Claim 34 is currently withdrawn without traverse from further consideration pursuant to 37 CFR 1.142 (b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-11 and 26-33 are the present Official action. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Priority
Applicant’s claim for the benefit of a prior-filed application PRO 63/103,471 and 371 of PCT/CN2021/111092 filed on 8/7/2020 and 8/6/2021, respectively, under 35 U.S.C 119(e) or under 35 U.S.C 120, 121 or 365(c) is acknowledged.
Accordingly, the effective priority date of the instant application is granted as 8/7/2020.
Withdrawn Claim Rejections
The 35 U.S.C. 102(a)(1) and 102(a)(2) rejection of claim 1-25 as being anticipated by Gundlach has been withdrawn in light of applicants claim amendments specifying SEQ ID Nos and the new claim interpretation provided.
The 35 U.S.C. 103 rejection of claims 1-33 over Gundlach in view of Schlake has been withdrawn in light of the new claim interpretation and amendments.
New Claim Rejections - 35 USC § 112b
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 1-6 and 26-33 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 pre-AIA the applicant regards as the invention. This rejection is newly applied to address applicants claim amendments filed on 4/14/2026.
Claim 1 describes an artificial poly(A) sequence “consisting” of “about” 40-100 adenines. “Consisting of” is strict closed-ended claim language under MPEP 2111.03. It means the claim covers only the recited elements. However, “about” is open ended claim language. Thus, one of ordinary skill in the art would not understand if the artificial poly(A) sequence is strictly limited to 40-100 adenines or is open to variation.
Furthermore, the term “about” is not defined by the claim and the specification does not provide a standard for ascertaining the requisite degree to which one of ordinary skill in the art could reasonably apprised of the scope of the invention. Please note that the language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds", see MPEP 2173.
Claim Interpretation
Claim 1 describes an artificial poly(A) sequence “consisting” of “about” 40-100 adenines. Taking the broadest reasonable interpretation, “consisting” is interpreted as applying to only the contiguous “about” 40-100 adenines and does not necessarily apply to the entire artificial poly(A) sequence.
Furthermore, “about” is interpreted as reading on +/- 1 adenine form the recited range.
New 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 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.
(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 1-5 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gundlach et al. US 2012/0055792, published 3/8/2012 (hereinafter Gundlach, reference of record). This rejection is newly applied to address applicants claim amendments filed on 4/14/2026.
Claim 1: Gundlach describes the use of bacterial nanopores for detecting nucleic acids and other analytes (Gundlach, abstract). In Example 8, Gundlach describes the use of an artificial poly-a sequence comprising 48 contiguous adenines, followed by 1 cytosine and a final adenine as shown in the sequence search results and sequence below. Notably, the cytosine Is located in the last 1/3 portion of the poly(a) sequence.
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Seq ID NO: 33 alignment with instant SEQ ID NO: 5
Full length Seq ID NO: 33 = aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaca
As stated in the claim interpretation section above, “consisting of” is interpreted as applying to only the contiguous “about” 40-100 adenines and does not necessarily apply to the entire artificial poly(A) sequence. Thus, Gundlach teaches an artificial pol(A) sequence that anticipates newly amended claim 1.
Claims 2-5: The poly-a sequence disclosed by Gundlach comprises 49 adenines and 1 cytosine in which the last nucleotide is not a cytosine. Notably, the cytosine is consecutively grouped (with itself) and locate a the second to last nucleotide of the poly-a sequence (Gundlach, example 8).
Response to Traversal
Although the rejection is newly applied, some of applicant’s arguments are relevant and are addressed below.
Applicant traverses the rejection by arguing that the poly(A) sequence is now amended to “consisting of about 40-100 adenines”. Applicant argues that no passage in Gundlach teaches this limitation.
These arguments have been fully considered, but were not found persuasive since the broadest reasonable interpretation of “consisting” is interpreted as applying to only the contiguous “about” 40-100 adenines and does not necessarily apply to the entire artificial poly(A) sequence. Thus, Gundlach teaches an artificial pol(A) sequence that anticipates newly amended claim 1. The full-length sequence of Seq ID NO: 33 = aaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaca.
New 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 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 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over Gundlach (supra) in view of Sakurai et al, WO2007058323, published 5/24/2007 (hereinafter Sakurai), Geipel et al, WO 2018137826, published 8/2/2018 (hereinafter Geipel), Itin et al, RU2542476, published 7/29/2013 (hereinafter Itin), Schlegel et al. US 2004/0259086, published 12/23/2004 (hereinafter Schlegel) and Balatsos et al. "Modulation of poly (A)-specific ribonuclease (PARN): current knowledge and perspectives." Current medicinal chemistry 19.28 (2012): 4838-4849 (hereinafter Balatsos). This rejection is newly applied to address applicants claim amendments filed on 4/14/2026.
A description of Gundlach can be found above. Gundlach does not describe a poly(A) sequence consisting of SEQ ID NO: 5, 7, 9 10 or 22. However, each of these poly(A) sequences have been reported in the prior art and it would be obvious to shorten each sequence via deadenylation to better regulate gene expression.
Claims 6 and 7: As described previously, in Example 8 Gundlach describes the use of an artificial poly-a sequence comprising 48 contiguous adenines, followed by 1 cytosine and a final adenine as shown in the sequence search results and sequence below and shares 100% local similarity with instant SEQ ID NO: 5.
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Seq ID NO: 33 alignment with instant SEQ ID NO: 5
Claims 6 and 8: Sakurai discloses an artificial poly-a sequence that shares 100% local similarity with instant SEQ ID NO: 7 as shown in the sequence search results and sequence below:
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Claims 6 and 9: Geipel discloses an artificial poly-a sequence that shares 100% local similarity with instant SEQ ID NO: 9 as shown in the sequence search results and sequence below:
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Claims 6 and 10: Itin discloses an artificial poly-a sequence that shares 100% local similarity with instant SEQ ID NO: 10 as shown in the sequence search results and sequence below:
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Claims 6 and 11: Schlegel discloses an artificial poly-a sequence that shares 100% local similarity with instant SEQ ID NO: 22 as shown in the sequence search results and sequence below:
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Claims 6-11: Furthermore, there exist predictable means to shorten a poly(A) sequence in order to improve mRNA stability and achieve optimal translation as described by Balatsos. In particular, Balatsos describes how deadenylation can improve mRNA stability and improve translation (Balatsos, abstract and epilogue).
It would have been prima facie obvious to one of ordinary skill in the art to use the deadenylation approaches described in Balatsos to shorten the artificial poly-a sequences disclosed by Gundlach, Sakurai, Geipel, Itin and Schlegel to arrive at a poly(A) sequence consisting of SEQ ID NO: 5, 7, 9 10 or 22. It would have been a matter of combining prior art elements according to known methods to yield predictable results since Balatsos shows predictable means to shorten and modulate poly(A) tails. One of ordinary skill would have been motivated to modulate and shorten the specific poly(A) sequences disclosed in Gundlach, Sakurai, Geipel, Itin and Schlegel in order to improve mRNA stability and translation. One would have a reasonable expectation of success given the predictable mechanisms that allow poly(a)-specific ribonucleases shorten poly(A) sequences in a substrate specific manner as described by Balatsos. Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered claims 1-11 to have been prima facie obvious to at the time the invention was made.
Response to Traversal
Although the rejection is newly applied, some of applicant’s arguments are relevant and are addressed below.
Applicant traverses the rejection by arguing that a person of skill in the art would not be motivated to experiment with the adenine and cytosine composition in a poly(A) tail with the intent to optimize mRNA stability and protein expression since the cited references provide a practically endless number of ways for this modification.
These arguments have been fully considered, but were not found persuasive since Balatsos shows predictable means to shorten and modulate poly(A) tails. Thus, one of ordinary skill would have been motivated to modulate and shorten the specific poly(A) sequences disclosed in Gundlach, Sakurai, Geipel, Itin and Schlegel in order to improve mRNA stability and translation. One would have a reasonable expectation of success given the predictable mechanisms that allow poly(a)-specific ribonucleases shorten poly(A) sequences in a substrate specific manner as described by Balatsos.
Claims 26-33 are rejected under 35 U.S.C. 103 as being unpatentable over Gundlach (supra), Gundlach (supra), Sakurai (supra), Geipel (supra), Itin (supra), Schlegel (supra)and Balatsos (supra) as applied to claims 1-11 above in further view of Schlake et al. US 2022/0233568, published 7/28/2022, priority date 10/19/2017 (hereinafter Schlake, reference of record). This rejection is newly applied to address applicants claim amendments filed on 4/14/2026.
A description of Gundlach, Sakurai, Geipel, Itin, Schlegel and Balatsos can be found above. The cited prior art does not describe an expression cassette, expression vector or host cell comprising the poly-a sequence.
Claims 26-30: Schlake provides various artificial RNA molecules and poly(A) tail embodiments for increased protein expression efficiencies of coding regions operably liked to modified UTR elements (Schlake, para 406-412). Schlake describes the incorporation of these poly-a tail elements into expression constructs comprising multiple cloning sites, promoters, transcription initiation and termination codons (Schlake, para 28, 32, 419-425).
Claims 31-33: Schlake describes expression in a host and RNA polynucleotides which express said cassette comprising the poly-a sequence (Schlake, para 27-28).
It would have been prima facie obvious to one of ordinary skill in the art to use an artificial poly-a sequence like Seq ID NO: 33 disclosed by Gundlach in the methods for improving protein expression described by Schlake. It would have been a matter of combining prior art elements according to known methods to yield predictable results since Schlake shows that incorporating artificial poly-a sequences can increase translation efficiency and mRNA stability (Schlake, para 406-412). Thus, one of ordinary skill would have been motivated to experiment with different adenosine and cytosine combinations in order to optimize for mRNA stability and protein translation since it is recognized that these are result-effective variables, see MPEP § 2144.05. One would have a reasonable expectation of success given that Schlake provides reliable methods for modifying the A/C composition of a given poly-a tail sequence (Schlake, para 406-412). Accordingly, in the absence of evidence to the contrary, one of ordinary skill in the art would have considered the claimed invention to have been prima facie obvious to at the time the invention was made.
Conclusion
No claims allowed.
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 extension fee 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.
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Alexander Nicol
Patent Examiner
Art Unit 1634
/ALEXANDER W NICOL/Examiner, Art Unit 1634
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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