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 03/26/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 12/31/2025 are hereby withdrawn.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 03/26/2026, claims 195-197, 199, 200, 202-215, 217 and 219-247 are pending in the application. Claims 228-247 are new claims that are in the scope of the elected claims and will be examined. Claims 215, 217 and 219-227 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 195-197, 199, 200, 202-214 and 228-247.
The 103 rejection is withdrawn as the claims have been canceled.
Withdrawn Rejections
Any rejection not reiterated in this Office Action is hereby withdrawn.
New Claim Rejections
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.
Written Description
Claims 228-247 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 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.
Claim 228 depends from claim 199 and 195 and is drawn to a genus of guide sequences, passenger sequences, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors having 85% or more sequence identity to the claimed sequences with the function of targeting Grik2 and reducing expression in cells and in mice. Claims 229-247 are drawn to a polynucleotide comprising 85% sequence identity which comprises miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors all with 85% sequence identity to their respective SEQ ID Nos.
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 Fig. 8D-F as showing schematic diagrams of AAV9 dual-miRNA expression constructs and none of these describes miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors with the function of targeting Grik2 and reducing expression in cells and in mice. Each structure appears to have the full sequences of miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences and expression cassettes. These examples do not encompass the vast number of different polynucleotides having 85% sequence identity to SEQ ID No. 811 because there is no description of what nucleotides in the polynucleotide can be excluded and still be considered a functional polynucleotide having guide sequences, passenger sequences, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors.
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 is a decrease in Grik2 expression using a polynucleotide having the full sequence of miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences and expression cassettes. The disclosure has not described any polynucleotide with at least 85% identity to SEQ ID No. 812 with the claimed function or for claim 228, describe a complete structure of the large genus of different sequences having the claimed function. For example, promotors having 85% sequence identity to SEQ ID No. 685 can encompass a vast number of different promoter sequences that may not have the activity of a promoter and the specification has not described a common structure or required nucleotides that are required to be a functional promoter. 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.
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 sequences of guide sequences, passenger sequences, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors with the function of targeting Grik2 and reducing expression in cells and in mice, 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 size of polynucleotides comprising 85% of SEQ ID No. 812 with the function of reducing expression go Grick2. 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.
Maintained Rejections
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.
Written Description
The rejection of claims 195-197, 199, 200 and 202-214 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 is maintained for the reasons of record.
Applicant’s argument is acknowledged but not found persuasive. Applicant argues the specification as filed teaches that SEQ ID NO: 77 and SEQ ID NO: 80 lead to 83% and 79% knockdown of Grik2 mRNA levels, respectively (see, e.g., Table 2). Additionally, SEQ ID NO: 78 and SEQ ID NO: 79, both of which share 76% sequence identity with SEQ ID NO: 77, are also capable of reducing Grik2 mRNA levels by 43% and 51%, respectively (see, e.g., Table 2). Further, SEQ ID NO: 3, which shares 85.7% sequence identity with SEQ ID NO: 80, reduces Grik2 mRNA levels by 72% (see, e.g., Table 2). Thus, a skilled person in the art would recognize that guide sequences that share at least 85% sequence identity with SEQ ID NO: 77 or SEQ ID NO: 80 would still be effective at inhibiting Grik2 expression. Moreover, the specification demonstrates that dual siRNA expression constructs, which contain both SEQ ID NO: 77 and SEQ ID NO: 80 effectively reduce Grik2 mRNA and/or Gluk2 protein levels (see, e.g., FIGs. 8D-8F; see also, e.g., DMTPV4-6 and DMSPV1 in FIGs. 12, 19, and 28).
In response, while Applicant does provide written description for guide RNAs having at least 85% sequence identity to SEQ ID Nos. 77 and 80 and siRNA constructs that reduce Grik2 mRNA expression, the specification does not provide adequate written description for miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors having 85% or more sequence identity to the claimed sequences with the function of targeting Grik2 and reducing expression in cells and in mice. Demonstrating a reduction in Grik2 using guide sequences having at least 85% sequence identity to SEQ ID Nos. 77 and 80 does not provide any description for the remaining sequences.
The genus of the expression vectors comprising 85% or more sequence identity to each of passenger sequences, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes encompasses a vast number of different sequences assembled in differently sized expression vectors. The specification does not describe a complete structure of the large genus of different sequences having the claimed function. For example, promotors having 85% sequence identity to SEQ ID No. 685 can encompass a vast number of different promoter sequences that may not have the activity of a promoter and the specification has not described a common structure or required nucleotides that are required to be a functional promoter.
Applicant points to Fig. 8D-F, DMTPV4-6 and DMSPVI in Figs 12, 19 and 28. The specification describes Fig. 8D-F as showing schematic diagrams of AAV9 dual-miRNA expression constructs and none of these describes miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors with the function of targeting Grik2 and reducing expression in cells and in mice. Each structure appears to have the full sequences of miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences and expression cassettes.
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 comprising a vast number of sizes of the sequences in the vector, 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). A skilled artisan cannot visualize or recognize miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors having 85% or more sequence identity to the claimed sequences with the function of targeting Grik2 and reducing expression in cells and in mice.
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).
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every size of miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors. 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.").
Closest prior art
A search of the sequence data base did not reveal a polynucleotide having sequences with at least 85% or more identity to SEQ ID Nos. 77, 80, 759, 746, 761, 767, 760, 766, 685, 789, 792, 798, 799, 811 or 812 comprising a 5’-inverted repeat sequence, a guide and passenger sequence, a promoter, a polyA sequence, a stuffer, a mRNA loop sequence and a 3’ inverted terminal repeat sequence.
Davidson et al. (of record cited on 892 mailed 12/31/2025) teach making miRNA shuttle vectors that express a therapeutic RNA molecule wherein the shuttle has 5’ and 3’ flanking regions, a guide strand, a passenger strand and a miRNA loop having SEQ ID No. 184 that is identical to claimed SEQ ID No. 761. (see col. 2-3). Davidson et al. does not teach or make obvious the claimed polynucleotide compositions comprising a guide strand and passenger strand as claimed along with 5’-inverted repeat sequence, a promote, a polyA sequence, a stuffer and a 3’ inverted terminal repeat sequence.
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]
PNG
media_image1.png
18
19
media_image1.png
Greyscale
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.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public. For more information about the PAIR system, see http://pair-direct.uspto.gov.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
Prosecution Insights