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 .
DETAILED ACTION
Applicant's preliminary amendment filed on May 11, 2026 is acknowledged. Claims 1-47 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-39) and the following species: SEQ ID NO: 11 (which encodes the protein of SEQ ID NO: 1) in the reply filed on May 11, 2026 is acknowledged.
Claims 40-47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 11, 2026.
Claims 1-39 are examined on the merits herein.
Priority
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Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 20, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings were received on March 20, 2023.
The drawings are objected to because the key for FIG. 3E reads “+Pseudozym” and should read “+Pseudozyma” (emphasis added). In addition, the 7th image of FIG. 5C reads “Vesicular Stomattis Virus” and should read “Vesicular Stomatitis Virus” (emphasis added). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because the abstract uses the phrase “This disclosure provides”. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities:
Page 8: the heading for FIG. 2 should include “2D” and “2E”.
Page 8: the heading for FIG. 3 should include “3E” and “3F”.
Page 9, line 28 reads "A/Texas/36/9 and should read "A/Texas/36/91" (emphasis added).
Page 9, line 29 reads in part "2006" and should read "3006" (emphasis added).
The heading of the far right column in Table 1 on page 16 reads “identify” and instead should read “identity” (emphasis added).
Page 26, line 1 reads “protein sequence identify” and should read “protein sequence identity” (emphasis added).
Page 55, line 23 reads “bone fide” and should read “bona fide” (emphasis added).
The table on pages 16 and 63 are both designated as Table 1.
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See pages 11 and 14.
Claim Objections
Claims 4-15, 19-30, and 34-39 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
Claims 1-3, 16, 18, and 33 are objected to because of the following informalities:
Claims 1-3, 16, 18, and 33 contain numerous spacing issues where spaces are not inserted between words. Applicant is advised to thoroughly review and amend the claims accordingly.
Claim 1 recites in part “L7A eprotein” and should recite “L7Ae protein”.
Claim 2 part (i) recites “ammo acid” and should recite “amino acid”.
Claim 33 part (g) recites “comprises” and should recite “comprise”.
Appropriate correction is required.
Claim Interpretation
The claim limitations after the recitation of “optionally” are interpreted by the Examiner as optional and thus are not required.
Claim Rejections - 35 USC § 112
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.
Written Description
Claims 1-3, 16-18, and 31-33 are 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.
Claims 1, 16, and 31 are drawn to the provision of a genus of nucleic acid molecules comprising a polynucleotide encoding an L7Ae protein or any fragment/variant of an L7Ae protein.
Claims 2, 18, and 33 are drawn to the provision of a genus of nucleic acid molecules wherein the L7Ae protein comprises an amino acid sequence having at least 75% identity to any one of SEQ ID NOS: 1-10 or comprises an amino acid sequence of SEQ ID NOS: 1-10; or the L7Ae protein comprises an amino acid sequence having at least 63% identity to the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 1 or comprises the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 1.
Claim 3 is drawn to the provision of a genus of nucleic acid molecules wherein the polynucleotide comprises a nucleotide sequence having at least 75% identity to any one of SEQ ID NOS: 11-15 or comprises a nucleotide sequence of SEQ ID NOS: 11-15.
Thus, the claims encompass a broad genus of nucleic acid molecules that must function to prevent or treat an influenza virus infection or influenza virus disease (claims 1-3), to reduce influenza virus replication (claims 16-18), or to inhibit splicing of one or more influenza virus mRNA segments (claims 31-33).
The specification envisions the following:
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[page 3, first paragraph]. The specification envisions that the L7Ae protein comprises an amino acid sequence that is at least about 63% identical to SEQ ID NO: 4 wherein the L7Ae protein comprises specific amino acid residues at specific positions relative to SEQ ID NO: 1. The specification also envisions that the L7Ae protein comprises an amino acid sequence that is at least about 63% identical to SEQ ID NO: 1 wherein the L7Ae protein comprises specific amino acid residues at specific positions relative to SEQ ID NO: 1. The specification also envisions that the L7Ae protein comprises an amino acid sequence having at least 63% identity to the amino acid sequence of SEQ ID NO: 4 or 1 or comprises the amino acid sequence of SEQ ID NO: 4 or 1 [page 3, second paragraph through page 5]. Further, the specification envisions the following:
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[page 5, first full paragraph]. The specification also envisions the following:
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[page 14, first full paragraph]. Further, the specification envisions that a variant of a L7Ae protein may include one or more conservative modifications and may retain the desired functional properties which can be tested using the functional assays known in the art [page 21, first paragraph].
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification discloses SEQ ID NOS: 1-15 as shown in Table 1 (reproduced below) [pages 16-18].
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The specification also discloses that L7Ae is a member of the L30 ribosomal protein and is a protein that engages kink-turns (k-turns) in duplex RNA and stabilizes the RNA in this secondary structure [page 56, last paragraph].
No description is provided of any other nucleic acid molecules comprising a polynucleotide encoding an L7Ae protein or any other fragment/variant of an L7Ae protein.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples (SEQ ID NOS: 1-10) are only representative of a limited number of nucleic acid molecules wherein the L7Ae protein comprises an amino acid sequence having a specified percent identity to the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 1. The results are not necessarily predictive of other nucleic acid molecules falling within the broadly claimed genus. Thus, it is impossible for one to extrapolate from the limited examples described herein those nucleic acid molecules that would necessarily meet the structural/functional characteristics of the rejected claims.
Huang et al. (RNA 2019) discloses that archaeal L7Ae binds to a putative k-turn structure in the 5’-leader of the mRNA of its structural gene to regulate translation. To function as a regulator, the RNA should be unstructured in the absence of protein, but it should adopt a k-turn-containing stem–loop on binding L7Ae. Sequence analysis of UTR sequences indicates that their k-turn elements will be unable to fold in the absence of L7Ae [abstract].
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of nucleic acid molecules comprising a polynucleotide encoding an L7Ae protein or any fragment/variant of an L7Ae protein that encode an L7Ae protein.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 1-3, 16-18, and 31-33.
Enablement
Claims 1-3, 16-18, and 31-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is
sufficient evidence to support a determination that a disclosure does not satisfy the
enablement requirement and whether any necessary experimentation is "undue".
These factors include, but are not limited to: (A) The breadth of the claims; (B) The
nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary
skill; (E) The level of predictability in the art; (F) The amount of direction provided by the
inventor; (G) The existence of working examples; and (H) The quantity of
experimentation needed to make or use the invention based on the content of the
disclosure. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims and nature of the invention:
Claims 1-3 are drawn to a method for preventing or treating an influenza virus infection or influenza virus disease in a subject, comprising administering to a subject in need thereof a nucleic acid molecule comprising a polynucleotide encoding an L7Ae protein or a fragment/variant thereof or administering to the subject in need thereof the L7Ae protein or fragment/variant thereof. The broadest reasonable interpretation of claim 1 is that the method encompasses not only treating any influenza virus infection or any influenza virus disease in a subject, but also preventing any influenza virus infection or any influenza virus disease in a subject.
Claims 16-18 are drawn to a method for reducing influenza virus replication in a subject or a biological sample thereof comprising (i) administering to the subject a nucleic acid molecule comprising a polynucleotide encoding an L7Ae protein or a fragment/variant thereof or administering to the subject the L7Ae protein or a fragment/variant thereof; or (ii) contacting the biological sample with the nucleic acid molecule or the L7Ae protein or fragment/variant thereof.
Claims 31-33 are drawn to a method for inhibiting splicing of one or more influenza virus mRNA segments in a subject or a biological sample thereof comprising (i) administering to the subject a nucleic acid molecule comprising a polynucleotide encoding an L7Ae protein or a fragment/variant thereof or administering to the subject the L7Ae protein or fragment/variant thereof; or (ii) contacting the biological sample with the nucleic acid molecule or the L7Ae protein or fragment/variant thereof.
Amount of direction provided by the inventor and existence of working
examples:
Working example 2 discloses that a library of RNA binding proteins from Archaea was screened to ascertain whether they showed any antiviral activity against Influenza A virus (IAV). 21 codon-optimized RNA binding proteins from a diverse array of archaea were synthesized. Segment 8 was examined because it undergoes canonical and non-canonical processes that ultimately control the viral replication cycle. The data demonstrated that RBP11, RBP14, and RBP16 all successfully reduced virus levels. RBP11 exhibited a distinct phenotype and appeared to preferentially block production of the two spliced products of IAV, M2, and NS2. RBP11 encodes for a member of the L30 ribosomal protein and is commonly referred to as L7Ae in archaea. The working example demonstrated that L7Ae interferes with the capacity of IAV to process alternatively spliced transcripts, the mutant L30 maintained the capacity to inhibit M2 and NS2 production, L7Ae engages segment 8 RNA to prevent the processing of NS2 independent of its 5’ splice site, and only L7Ae containing an NLS was capable of inhibiting IAV splicing. Lastly, to demonstrate in vivo efficacy, recombinant full-length L7Ae or BSA were administered to BL/6 female mice 4-6 weeks of age. On day 3, L7Ae-treated animals showed a ~1 log reduction in viral titer and by the end of the experiment the L7Ae-treated animals reached full recovery weights and showed minimal signs of weight loss overall.
State of the prior art, level of predictability in the art, and level of one of
ordinary skill:
A review of the prior art shows that the state of the art of preventing or treating an influenza virus infection or influenza virus disease comprising administering a nucleic acid molecule comprising a polynucleotide encoding an L7Ae protein or a fragment/variant thereof or administering the L7Ae protein or a fragment/variant thereof is immature and nascent. A review of the prior art also shows that the state of the art of reducing influenza virus replication and inhibiting splicing of one or more influenza virus mRNA segments comprising administering a nucleic acid molecule comprising a polynucleotide encoding an L7Ae protein or a fragment/variant thereof or administering the L7Ae protein or a fragment/variant thereof or contacting a biological sample with the nucleic acid molecule or the L7Ae protein or fragment/variant thereof is immature and nascent.
Although post-filing, Nguyen et al. (Viruses 2021) discloses that although understanding of influenza viruses has greatly increased in recent years, shortcomings remain. Additionally, the continuous mutation of influenza viruses through genetic reassortment and selection of variants that escape host immune responses can render current influenza vaccines ineffective at controlling seasonal epidemics and potential pandemics. Thus, there is a knowledge gap in the understanding of influenza viruses and a corresponding need to develop novel universal vaccines and therapeutic treatments. Investigation of viral pathogenesis, transmission mechanisms, and efficacy of influenza vaccine candidates requires animal models that can recapitulate the disease. Furthermore, the choice of animal model for each research question is crucial in order for researchers to acquire a better knowledge of influenza viruses [abstract]. Nguyen et al. also discloses that in spite of the significant advantages there are concerns over the use of mouse models for biomedical research which include the differences between murine and human immune systems, such as frequencies of lymphocytes and neutrophils in peripheral blood, and differences in toll-like receptors, defensins, and IgG classes. With the exception of high pathogenetic strains, such as pandemic H1N1 2009, H5N1, H7N7, and H7N9, mice are not naturally infected with influenza viruses. Therefore, viruses must be adapted through multiple lung passages to allow for infection and replication. Moreover, because influenza viruses do not transmit well among mice, more suitable animal models must be used to study this aspect. In addition, unlike humans, mice exhibit influenza A virus replication in the lower respiratory tract; thus, IAV virulence is not preserved between these species [page 4, first paragraph].
While the state of the art of preventing or treating an influenza virus infection or influenza virus disease, reducing influenza virus replication, and inhibiting splicing of one or more influenza virus mRNA segments comprising administering a nucleic acid molecule comprising a polynucleotide encoding an L7Ae protein or a fragment/variant thereof or administering the L7Ae protein or a fragment/variant thereof is immature and nascent, as evidenced by Nguyen et al., there are also challenges of translating results from mouse models to humans because there are differences between murine and human immune systems, influenza viruses do not transmit well among mice thus more suitable animal models must be used, and IAV virulence is not preserved between mice and humans. Thus one of ordinary skill in the art would not expect to prevent or treat an influenza virus infection or influenza virus disease, reduce influenza virus replication, or inhibit splicing of one or more influenza virus mRNA segments.
Quantity of experimentation:
In view of the breadth of the claims which embrace treating any influenza virus infection or any influenza virus disease, preventing any influenza virus infection or any influenza virus disease, reducing influenza virus replication, and inhibiting splicing of one or more influenza virus mRNA segments, the state and level of predictability in the art, the lack of working examples, and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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