DETAILED ACTION
Status of the Application
Claims 1, 5, and 7-21 are pending. Claims 8-18 are withdrawn.
Claims 1, 5, 7, and 19-21 are under examination.
The following Office Action is in response to Applicant's communication dated 01/02/2026.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/02/2026 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . Please note that the new examiner of record is Khai Q Pham.
Withdrawn Claim Rejection(s) and/or Objection(s)
Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. This withdrawal does not constitute a determination that the claims are allowable.
The prior rejections of claims 1, 5, 7, and 19- 21 under 35 U.S.C. 101 are here by withdrawn. The Office no longer considers the claimed subject matter to be directed to a naturally occurring products of nature for purposes of eligibility analysis. The claims recite non-native libraries and engineered constructs associates with vectors, which are not naturally occurring compositions.
The prior rejections of claims 1, 5, 7, and 19- 21 under 35 U.S.C. 103 are also withdrawn. Those rejections were premised on the same interpretation of the claims that underlay the prior 35 U.S.C. 101 rejection. In view of the Office’s revised understanding of the claimed subject matter and the unresolved issues of the claim scope and clarity discuss below, the prior art previously applied under 35 U.S.C. 103 is no longer relied upon.
Claim Interpretation
For purposes of examination, the claims are interpreted according to their plain language as would be understood by one of ordinary skill in the art. Where the claim language is internally inconsistent or unclear, the Office does not infer unstated limitations or supply missing relationships. The interpretations set forth below are adopted solely to permit examination and do not resolve ambiguities in the claim language.
Claim 1 is directed to “a non-native pri-miRNA library” comprising a plurality of pri-miRNA molecules, claim 1 further recites that each pri-miRNA is “in a vector comprising promoter”. Although claim 1 does not recite DNA or an encoding relationship, vector and promoters are typically associate with DNA constructs that encode RNA.
For purposes of examination only, claim 1 is provisionally interpreted as being directed to library of DNA constructs encoding pri-miRNA sequences that are cloned into vectors comprising promoters, rather than RNA molecules themselves. This interpretation is adopted solely to permit examination and does not resolve the internal inconsistencies in the claim langue.
Claim 19 also recites a “non-native pri-miRNA library”, but expressly describes the library as being constructed from engineered DNA sequences that are cloned into a vector comprising a promoter. Although claim 19 further recites “solid-phase synthesis and/or automated synthesis” as part of how DNA sequences generate, this langue describes a process of manufacture rather than structural limitation of the claimed library. Claim 19 therefore constitutes a product-by-process claim, for which patentability and claim scope are determined only by the structure of the end nucleic acid constructs, not the method by which they are made.
For purposes of examination only, claim 1 and 19 are provisionally interpreted as being directed to the same general invention, namely library of DNA constructs encoding pri-miRNA sequences in vectors, albeit recited using materially different and inconsistent terminologies. This interpretation is adopted solely to permit examination and does not resolve whether the claims have the same scope, different scope, or overlapping scope
Claim 20 recites “a pair of intermediate DNA libraries”. However, the claim does not define the term “intermediate”, does not explain what stage the libraries are intermediate to, and does not consistently distinguish between the two libraries throughout the claim. Further, the claim initially introduces a pair of libraries, later portions of the claim refer to as “said library” without specifying which library is being referenced. As written, the claim does not identify whether the claimed subject matter is directed to two distinct libraries, a single library formed from the pair, or a product derived from processing the pair of libraries. Claim 20 further recites multiple process steps, including polymerization, nicking, annealing, amplification, and cloning, but does not clearly identify the structure of the nucleic acid product purportedly produced by these steps due to the unclear identity of the claimed libraries.
For purposes of examination only, claim 20 cannot be interpreted to have a definitive structural interpretation of due to the nature of the claim and the internal inconsistencies regarding the identity of the claimed library or libraries. Furthermore, claim 20 contains product-by-process language, in which the claim scope is determined by the structure of the resulting product. Accordingly, claim 20 is not examined any further, as the claim language does not to define the claimed library or libraries with sufficient clarity to permit meaningful patentability analysis.
Claim 21 depends on claim 1 and recites preparations of the claimed library using process steps similar to those recited in claim 20. Hence, claim 21 interpreted as a product-by-process claim, for which patentability is based on the structure of the resulting product rather than the recited process steps.
Claim Rejections - 35 USC § 112(a)
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.
Claim 20 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. Specially, the specification fails to provide description support for the recited “pair of intermediate DNA libraries” in claim 20. The specification does not describe or define “pair” of libraries, does not disclose any library characterized as “intermediate”, and does not describe any stage of library generation to which such libraries are intermediates. Nor does the specification disclose structural, functional, or exemplified embodiments distinguishing an intermediate library from the final library product. Accordingly, the specification does not reasonably convey to ne of ordinary skill in the art that the inventor had possession, at the time of filing, of the claimed invention comprising a pair of intermediate libraries.
Applicant is advised that amendment to introduce support for the recited “pair of intermediate libraries” would require written description support in the originally filed disclosure. Absent such disclosure, such amendment may raise issue under 35 U.S.C. 132(a).
Claim Rejections - 35 USC § 112(b)
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, 5, 7, and 20 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 1 is directed to a “non-native pri-miRNA library” comprising pri-miRNA molecules, while further reciting that each pri-miRNA is “in a vector comprising a promoter”. A pri-miRNA is an RNA molecule. However, vectors and promoters are components that operate on DNA, not RNA, and are typically associate with DNA constructs that encode RNA. Claim 1 does not expressively recite DNA, an encoding relationship, transcription, or expression. As a result, it is unclear whether the claim library is directed to (i) RNA molecules themselves, (ii) DNA constructs encoding pri-miRNA, or (iii) vectors comprising such DNA constructs. Because these distinct types of subject matter with different structural characteristics, one cannot determine the identity of the claimed product from the claim langue. Accordingly, because the claimed product cannot be identified with reasonable certainty from the claim langue itself, the scope of claim 1 is indefinite.
Claim 19 also recites a “non-native pri-miRNA library”, but expressly describes the library as being constructed from engineered DNA sequences that are cloned into a vector comprising a promoter. At the same time, claim 19 continues to characterize the claimed subject matter as a pri-miRNA library. As written, it is unclear whether claim 19 is directed to RNA molecules, DNA constructs encoding pri-miRNA, or vectors comprising such constructs. Additionally, when reading in view of claim 1, it is unclear whether claim 19 is intended to have the same scope as claim 1, a different scope, or an overlapping scope, as the two independent claims describe similar subject matter using materially different terminology. Accordingly, because the claimed product cannot be identified with reasonable certainty from the claim langue itself, the scope of claim 19 is indefinite.
Claim 20 recites “a pair of intermediate DNA libraries”. The claim does not define the term “intermediate”, does not explain what stage the libraries are intermediate to, and does not specify any structural characteristics that distinguish the intermediates libraries from a final product.
Further, although claim 20 introduces a pair of libraries, the claim does not maintain a distinction between the two libraries throughout. Later portions of the claim refer to “said library” without specifying which of the two libraries is being referenced. Because two libraries are recited, and the claim does not clarify which library is being processed at each step, this claim drafting langue create a substantive ambiguity regarding which structure is being act upon.
Finally, claim 20 further recites multiple process steps, including polymerization, nicking, annealing, amplification, and cloning in to a vector. However, it is unclear whether these steps are applied to each intermediate library separately, to the pair of libraries together, or to a product derived from combining the libraries. As a result, the claim does not clearly identify what product exists at the conclusion of the recited steps.
Because the identity and structure of the claimed product cannot be determined with reasonable certainty from the claim langue itself, the scope of claim 20 is indefinite.
Claim 21 depends from claim 1 and recites preparation of the claimed library using process steps. Claim 21 is therefore a product-by-process claim, for which patentability depends only on the final product’s structures. Because the nature of the library recites in claim 1 is unclear, the identity and structure of the product in claim 21 cannot be determined with reasonable certainty from the claim langue itself, the scope of claim 21 is indefinite.
Claims 5 and 7 depend from independent claims 1 and 20 and recite additional limitation directed to a library complexity. Claim 1 and 20 recite a library complexity on the order of 42 to 49, whereas claim 5 recites a library complexity on the order of 410 to 412, and claim 7 recites a library complexity on the order of 413 to 415.
Because claims 5 and 7 depends from claim 1 and 20, whose scope is already unclear, and further recite complexity ranges that extend beyond, rather than narrow, the complexity ranges recite in the independent claims. It is unclear whether claim 5 and 7 are intended to narrow the scope of claim 1 and 20 or to recite subject matter inconsistent with the independent claims. Because the scope of claims 5 and 7 cannot be determined with reasonable certainty from the claim langue itself, the scope of claims 5 and 7 are indefinite.
By way of illustrate, a dependent claim further limits the subject matter of the claim from which it depends. For example, if an independent claim recites a library complexity of 42 to 49, a dependent claim would typically recite a subset within that range (such as 45 to 47) in order to narrow the scope. In contrast, claims 5 and 7 recite complexity ranges that exceed the upper limit recited in the independent claims, hence create ambiguity as to the intended scope of the dependent claims.
Claim Rejections - 35 USC § 112(d)
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.
Claims 5 and 7 are 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.
As mentioned above, , claims 5 and 7 are rejected , as they are not further limiting of claim 1 or 20. 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
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.
Claim(s) 1, 19, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US20110020816A1, disclosed in the IDS).
Regarding claim 1, Chen discloses a non-native pri-miRNA library, comprising: 1. a plurality of non-native pri-miRNAs (e.g. Libraries of modifications, e.g. random modifications, of precursor RNAs can be prepared to a target mRNA [paragraph 0064]), each of the plurality of non-native pri-miRNAs comprising:
5' and 3' flanking regions (e.g. one can select flanking regions attached to the 5′- and 3′-end of the precursor miRNA because flanking regions are known to provide increased transcription, enhanced stability [paragraph 0062]) of at least 20 unpaired and base-paired nucleotides (e.g. in one embodiment, the flanking region is approximately 250 nucleotides sequence [paragraph 0157]),
a terminal loop of less than 35 unpaired and base-paired nucleotides (Fig. 2B and Fig. 3A show terminal loops of around 13-15 nucleotides),
a stem of at least 30 base-paired nucleotides; a palindromic sequence for facilitating pri-miRNA hairpin formation (e.g. the precursors comprise stem-loop structure of about 65 ±10 nucleotides, including a stem region and a loop (hairpin) region, wherein the hairpin comprises of at least about 8 nucleotides [paragraph 0059]. Although claim 1 recites a “palindromic” sequence, under broadest reasonable interpretation this limitation reasonably encompasses self-complimentary nucleotide sequences that allow intramolecular base pairing between opposing regions to form a double-stranded stem. In the context of pri-miRNA structures, a person of ordinary skill in the art would recognize that complimentary between opposing sequences is sufficient to form a stem-loop hairpin satisfying the palindromes limitation.);
a Drosha/DGCR8 binding sequence (e.g. a sequence configured to be recognized and processed by Drosha/DGCR8 microprocessor complex [Fig. 6]);
each of the plurality of non-native pri-miRNAs is in a vector comprising a promoter (e.g. The transcriptional construct comprises promoter region [paragraph 0074]);
a miRNA sequence of 19 to 23 nucleotides comprising a non-native miRNA seed sequence of 6 nucleotides and a non-native adjacent sequence, wherein said miRNA seed sequence and/or said adjacent sequence is fully-randomized or partially-randomized (e.g. at the level of primary nucleotide sequences, the mature ~22-nt (include the 6-8 nt seeds), loop nucleotides, and even the complementary strand of mature miRNA all contribute to target recognition and interaction. [paragraph 0011]. Precursor RNAs may be selected from a library of precursor RNA molecules with randomized loop sequences through in vitro and in vivo screening assays [paragraph 0015]).
However, Chen does not disclose said library has a complexity of from 4² to 49.
Chen further discloses generation and screening of libraries comprising numerous sequence variants produced by randomization of defined regions [paragraph 0098 and 0064], wherein such randomization produces combinatorial libraries having exponential complexity, as each randomized nucleotide position independently contributes four nucleotide identities (A, C, G, and T). A person of ordinary skill in the art would therefore have understood that randomization of even a small number of nucleotide positions, as disclosed by Chen, necessarily yields libraries having complexities on the order of 4n, where n is the number of randomized positions. For example, randomization of two to ten nucleotide positions would give libraries having complexities on the order of 4² to 410. Hence, selecting or employing a library having a complexity from 4² to 49 , as recited in the claim, represent a routine and obvious design choice within the scope of the combinatorial libraries disclosed by Chen. This reasoning is consistent with KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, E).
Claim 19 is directed to a Product-by-Process Claim. Although claim 19 recites various process steps for generating the claimed library, Product-by-Process claims are not limited by the recited steps but instead are defined but the structure of the final product. See MPEP § 2113; In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). As discussed in the claim interpretation section above, since the process steps in claim 19 do not impart additional structural limitations to the claimed non-native pri-miRNA library beyond those recited in independent claim 1, claim 19 is directed to the same library as claim 1 and has the same scope for purpose of patentability. Therefore, for the same reasons set forth with respect to claim 1, claim 19 is rejected as being unpatentable over Chen et al.
Claim 21 depends on claim 1 and recites a method for preparing the claimed non-native pri-miRNA library. As a dependent claim, claim 21 further limits only the mater in which the library of claim 1 is prepared and does not recite additional structural limitations that distinguish the claimed library from that of claim 1. As discussed above, the patentability of product claims is determined by the structure of the claimed product, not by the process by which it is made. See MPEP § 2113; In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). The preparation steps do not impart a structurally distinct non-native pri-miRNA library relative to claim 1. Therefore, claim 21 is rejected for the same reasons as claim 1.
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Khai Quynh Tien Pham whose telephone number is (571)272-6998. The examiner can normally be reached M-T, 9-4 ET.
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, Heather Calamita can be reached at (571) 272-2876. 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.
/KHAI QUYNH TIEN PHAM/ Examiner, Art Unit 1684
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684