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
Status of Application/Amendment/Claims
Applicant's response filed 05/17/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 01/28/2026 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 05/17/2026, claims 1, 3, 5, 7, 10, 12, 14-16, 19 and 27-35 are pending currently under examination.
The 102, 103 and 112(a) rejections are withdrawn in response to claim amendments and therefore no response is required for Applicant’s Arguments.
New Claim Rejections – necessitated by claim amendments
Claim Rejections - 35 USC § 112
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 3 and 5 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.
Claim 3 recites “the administering inhibits pathogenesis in the subject” and fails to further limit claim 1 which is drawn to a specific type of pathogenesis such as influenza virus pathogenesis.
Claim 5 recites “involved in pathogenesis of a virus”, “a viral propagation”, a pathogen” and “the pathogen” and fails to further limit claim 1 which is drawn to a specific virus and pathogen such as influenza virus pathogen.
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 § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 1, 3, 5, 7, 9, 10, 12, 14-16, and 32-34 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification,
while being enabling for methods of inhibiting infection of influenza virus in A549 cells in vitro using a siRNA targeted to the lncRNA DGCR5,
does not reasonably provide enablement for methods of inhibiting an influenza virus in a subject comprising administering any inhibitory oligonucleotide targeted to DGCR5 long non-coding RNA or administering to a subject infected with or at risk of infection with any pathogen as in claim 32.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims and the nature of the invention:
The broadest reasonable interpretation of the claimed methods is using any engineered nucleic acid encoding any inhibitory oligonucleotide targeted to DGCR5 with the function of inhibiting influenza virus and treating subject infected with are at risk of infection with any pathogen. The inhibitory oligonucleotides can encompass gRNA to an Cas protein for use in a CRISPR Cas system.
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The state of the prior art:
The prior art of Jiao, Hanwei, et al. "MicroRNA expression profiles from HEK293 cells expressing H5N1 avian influenza virus non-structural protein 1." Innate Immunity 25.2 (2019): 110-117 of record 892 01/28/2026) teach long non-coding RNAs (lncRNAs) play an important role in many cancers and tumor pathogenesis, e.g., lncRNA digeorge syndrome critical region gene 5 (DGCR5) inhibits expression of hsa-miR-22-3p, which promotes the development of lung adenocarcinoma (LUAD) (see discussion).
The prior art of Gao, Fan, et al. ("Reverse-genetics studies of lncRNAs—what we have learnt and paths forward." Genome biology 21.1 (2020)) teach knockdown of expression of DGCR5 using antisense or siRNA demonstrated involvement of this lncRNA in regulating schizophrenia-related genes (page 3 first para).
A review of the prior art does not provide evidence that any inhibitory oligonucleotide, such as gRNA in a CRISPR Cas system, can target DGCR5 and inhibit influenza in a subject and the prior art does not provide evidence that using any inhibitory oligonucleotide can be used to treat a subject infected with or at risk of infection with any pathogen as in claim 32.
The level of one of ordinary skill:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention.
Because the state of the prior art does not provide evidence of the degree of predictability that methods of inhibiting any respiratory virus in a subject can occur by administering to the subject any type of inhibitory oligonucleotide that inhibits any respiratory virus, one of ordinary skill in the art would look for guidance or direction in the instant specification.
The level of predictability in the art:
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03).
The amount of direction provided by the inventor:
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The existence of working examples:
The working embodiment in the instant application describes methods of inhibiting infection of influenza virus in A549 cells in vitro using a single siRNA targeted to the lncRNA DGCR5. The working embodiments do not describe using any type of inhibitory oligonucleotide that targets DGCR5 that would inhibit infection of influenza or treat a subject infected with or at risk of infection with any pathogen as in claim 32.
The standard of an enabling disclosure is not the ability to make and test if the invention works but one of the ability to make and use with a reasonable expectation of success. A patent is granted for a completed invention, not the general suggestion of an idea (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant invention suggests administration of any inhibitory oligonucleotide to a subject that target any lncRNA and inhibits expression of any respiratory virus without an enabling disclosure or guidance in the prior art.
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role any inhibitory oligonucleotide, such as gRNA in a CRISPR Cas system, would target and inhibit an influenza virus or any inhibitory oligonucleotide that treats a subject infected with or at risk of infection with any pathogen as in claim 32 and without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Written Description
Claims 1, 3, 5, 7, 9, 10, 12, 14-16, 19, and 27-35 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of engineered nucleic acid molecules wherein the engineered nucleic encoding or comprising an inhibitory oligonucleotide having the function of targeting a DGCR5 lncRNA and inhibiting expression of influenza virus in a subject in need .
When determining whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the specification describes inhibiting infection of influenza virus in A549 cells in vitro using a single siRNA sequence targeted to the lncRNA DGCR5. The specification does not describe the entire genus of inhibitory oligonucleotides which can encompass guide RNA, aptamers, miRNA and ribozymes, for example. The example of a siRNA does not encompass the vast number of different oligonucleotide inhibitors, particularly gRNA as in claims 14, 15, 19 and 27-35. The prior art does not appear to provide written description to support the broad genus. The prior art of Koonin et al. ("Diversity, classification and evolution of CRISPR-Cas systems." Current opinion in microbiology 37 (2017): 67-78) teach there are numerous different Cas proteins from numerous different organisms (see Figure 1). Koonin et al. illustrates each has different structures based on the different class systems (see Figure 1 and Figure 3). Koonin et al. do not describe these different Cas proteins as having a RuvC active site and an amino acid terminus as claimed. The prior art teaches that the PAM sequence recognized by a Cas protein, such as Cas9, must be determined experimentally for each protein variant (Karvelis et al. Methods, Vol. 121-122, pages 3-8, March 24, 2017; e.g., Abstract).
It is then determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genera. In the instant case, the only other identifying characteristics are inhibition of lncRNA DGCR5 using a siRNA. Such functional limitations cannot be identifying characteristics for the vast number of engineered oligonucleotides given siRNA and gRNA are different molecules with different functions. With respect to SEQ ID Nos. 1-16, identified as targeting Cas9 or Cas13, the specification does not describe these gRNA sequences as targeting the gene in any CRISPR system comprising any Cas protein.
Okekpa et al. ("Small Interfering RNA (siRNA) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR): Emerging Molecular Tools for Genetic Manipulation." Malaysian Journal of Medicine & Health Sciences 16.3 (2020): 300) teach siRNA tool designs require sequence details and complementary gene transcripts whilst CRISPR/ Cas designs need gene sequence details. siRNA processing is homologue dependent. Therefore, the sequences of gene-specific RNAi-targeting must be cautiously selected to evade cross-interference amongst homologous sequences (57,58). Targeting genes with CRISPR/Cas requires a customized sgRNA that comprises a targeting sequence known as a crRNA sequence plus a Cas9 nuclease sequence recruiter known as tracrRNA (see page 305 second col.).
Liu et al. ("Applications and challenges of CRISPR-Cas gene-editing to disease treatment in clinics." Precision clinical medicine 4.3 (2021): 179-191) teach the class 1 CRISPR-Cas system, which functions through a multi-Cas protein complex, includes types I, III, and IV, employing representative endonucleases of Cas3, Cas10, and DinG, respectively. The class 2 CRISPR-Cas system, which employs single Cas protein, includes types II, V, and VI, to cleave RNA-guided genetic codes with Cas9, Cas12–Cas14, and Cas13, respectively (Fig. 1). Types I, II, and V systems are shown to specifically target DNA, and type III targets both RNA and DNA; type VI can only edit RNA. The function and mechanisms of type IV system remain largely unknown (page 180 and Fig. 1).
A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination given, for example, the diversity in different Cas proteins targeted by a gRNA which requires customization to a specific targeting sequence.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant a vast number of different inhibitory oligonucleotides, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every engineered nucleic acid with the function claimed. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Conclusion
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).
706.07(a) Final Rejection, When Proper on Second Action [R-07.2015]
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Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY CHONG at 571-272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
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