DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 4, 6, 8-9, 12-16, 18, 20-21, 24-24, and 27-30 are pending as amended 7/7/23, and are considered herein.
Formalities:
The drawings of 4/10/23 are accepted.
The specification as amended 4/10/23 is accepted.
The IDS filings of 7/10/23 (two filings) and 11/25/24 have been considered, along with the references cited. The IDSs are signed off by the Examiner herewith.
Claim Objections
Applicant is advised that should claim 1 be found allowable, claim 8 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 1 requires the at least one miRNA binding site to be miR-652-5p binding site, and although the same may contain other miRNA binding sites, they are optional, according to the claim. Claim 8, which depends from Claim 1, requires the miRNA binding site to be miR-652-5p binding site, and optionally encoded by SEQ ID NO: 39. Optionally here, also indicates a non-requirement of the claim. Thus, these claims, despite having a slight difference in wording, have the same substantial scope.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 6, 9, 16, 18 and 21 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.
Claim 1 recites an AAV comprising a promoter linked to an RNA transcript comprising an miRNA binding site, the miRNA binding site being “a miR-652-5pBS, alone or in combination with one or more of the following miRNA binding sites: a miR-33-5pBS, a miR-223BS, or a miR142BS.” However, Claim 6 recites “further comprising a binding site for one of the following miRNAs: [a large list of miRs, including miR-652-5p, miR-33-5p, miR-223, miR-142, and a list of other miR binding sites]”. Given this dependency, it is not clear what is meant by “alone or in combination with …” in Claim 1. I.e., Claim 6 states that it contain a further miR, which may be chosen from miRs that are not present in Claim 1. If it is, for example, miR-652-5p and miR-106, this would not meet the “alone” or “in combination with”, as alone means alone, while the “in combination with” would seem to indicate that one 33-5, 223, or 142 is also required. Thus, it is not clear what applicant intends to claim. For purposes of compact prosecution, it will be assumed that one of the 33-5, 226, or 142 sites is required, along with 652-5, to have an miRNA that is not one of these.
Claim 6 recites the miRNA binding site may comprise miR-652-3p or miR-652-5p, in an alternative fashion. How these differ is not clear. To wit, 652-3p is also known as 652-5p, and is encoded by the MIR652 gene, as shown in “MIR652 Gene - GeneCards | MIR652 RNA Gene, Author Unknown, downloaded 12/8/2025, published by LifeMap Sciences, entitled MIR652 Gene – MicroRNA 652, 15 pages long, page 1.
Claim 6 also recites “miR-9-3p, miR-9-5p”. Similar to the above problem with the 652 recitations, the Art recognizes these terms as aliases for the same gene encoded miR. Thus it is not clear what is being claimed, with these separate terms as alternatives. Applicant may look to “MIR9-3 Gene - GeneCards | MIR9-3 RNA Gene”, Author Unknown, downloaded 12/8/2025, published by LifeMap Sciences, entitled MIR9-3 Gene – MicroRNA 9-3, 15 pages, page 1.
Claim 9 recites “the at least one binding site is a combination of miR-142BS and miR-652BS”. It is not clear what is being claim. I.e., Claim 1 requires “miR-652-5pBS”, The mismatch here again leads to a lack of clarity, as to what is meant. I.e., the Art, as shown by the other rejections above, they are the same, yet Applicant has claimed them in a manner that indicates distinctions between them. Thus, the Artisan would not know the scope of what is claimed.
Claim 16 recites an AAV comprising a promoter linked to an RNA transcript comprising an miRNA binding site, the miRNA binding site being “a miR-652-5pBS, alone or in combination with one or more of the following miRNA binding sites: a miR-33-5pBS, a miR-223BS, or a miR142BS.” However, Claim 18 recites “further comprising a binding site for one of the following miRNAs: [a large list of miRs, including miR-652-5p, miR-33-5p, miR-223, miR-142, and a list of other miR binding sites]”. Given this dependency, it is not clear what is meant by “alone or in combination with …” in Claim 16. I.e., Claim 18 states that it contain a further miR, which may be chosen from miRs that are not present in Claim 16. If it is, for example, miR-652-5p and miR-106, this would not meet the “alone” or “in combination with”, as alone means alone, while the “in combination with” would seem to indicate that one 33-5, 223, or 142 is also required. Thus, it is not clear what applicant intends to claim. For purposes of compact prosecution, it will be assumed that one of the 33-5, 226, or 142 sites is required, along with 652-5, to have an miRNA that is not one of these.
Claim 18 recites the miRNA binding site may comprise miR-652-3p or miR-652-5p, in an alternative fashion. How these differ is not clear. To wit, 652-3p is also known as 652-5p, and is encoded by the MIR652 gene, as shown in “MIR652 Gene - GeneCards | MIR652 RNA Gene, Author Unknown, downloaded 12/8/2025, published by LifeMap Sciences, entitled MIR652 Gene – MicroRNA 652, 15 pages long, page 1.
Claim 18 also recites “miR-9-3p, miR-9-5p”. Similar to the above problem with the 652 recitations, the Art recognizes these terms as aliases for the same gene encoded miR. Thus it is not clear what is being claimed, with these separate terms as alternatives. Applicant may look to “MIR9-3 Gene - GeneCards | MIR9-3 RNA Gene”, Author Unknown, downloaded 12/8/2025, published by LifeMap Sciences, entitled MIR9-3 Gene – MicroRNA 9-3, 15 pages, page 1.
Claim 21 recites “the at least one biding site is a combination of miR-142BS and miR-652BS”. It is not clear what is being claim. I.e., Claim 16 requires “miR-652-5pBS”, The mismatch here again leads to a lack of clarity, as to what is meant. I.e., the Art, as shown by the other rejections above, they are the same, yet Applicant has claimed them in a manner that indicates distinctions between them. Thus, the Artisan would not know the scope of what is claimed.
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.
Claims 1, 4, 6, 8-9, 12-16, 18, 20-21, 24-24, and 27-30 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.
The claims are generic for a recombinant AAV that does or does not contain flanking ITRs. This is evidenced by Claim 28, which states the AAV is flanked by ITRs, indicating the generically claimed AAVs do not require ITRs flanking the nucleic acid of the AAV. Additionally, the ITRs are generic, as they do not require AAV ITRs, even in Claim 28.
The specification states, in open ended fashion, that the transgene may be flanked by ITRs (p. 6). Further, it is stated in open ended fashion that the AAV vectors contain 5’ and 3’ ITRs (p. 24). It is taught that ITRs are about 145 bp in length, and the ITRs are 5’ and 3’, for AAV, utilizing AAV ITRs (pp. 25-26).
The art recognizes that the defining characteristic of AAV is the presence of the ITRs, the ITRs being AAV ITRs. Such allows for the packaging of the nucleic acid into the AAV capsid. Thus, not only would it appear that the ITRs are needed, but specifically AAV ITRs, otherwise it would not be able to be packed in a AAV capsid. See Naso, et al. (2017) “Adeno-Associated Virus (AAV) as a Vector for Gene Therapy”, BioDrugs, 31: 317-34, e.g., pp. 318-319.
Thus, given the non-requirement of ITRs, and/or ITRs of AAV, at the 3’ and 5’ locations of the nucleic acid, the Artisan would not have understood Applicant to have been in possession of the invention as generically claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 6, 8-9, 12-16, 18, 20-21, 24-24, 27-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,655,483 to Gao, et al. Although the claims at issue are not identical, they are not patentably distinct from each other because
Claim 1: The patent teaches delivery of a transgene to target cells of a subject, comprising administering an AAV comprising a transgene, the transgene comprising a promoter linked to a sequence encoding an RNA transcript comprising at least one miRNA binding site (BS), the AAV infecting the target cells, thereby delivering the transgene, the miRNABSs comprising a miR-652-5pBS and a miR142BS.
Claim 4: Claim 2 teaches the same same cells expressing the miRNA.
Claim 6: Claim 3 is drawn to the same further provided miRBS Markush. It is noted that the sequence identifiers are the essential written description for these sequences are the same in the present case as the Patent.
Claim 8: Claim 4 teaches the same miR-652-5p BS encoded by SEQ ID NO: 39.
Claim 9: Claim 1 provides for the combination of miR BSs, and Claim 5 provides for SEQ ID NO: 40 encoding.
Claim 12: Claim 6 teaches the 3’ location of at least one miR BS.
Claim 13: Claim 7 teaches the therapeutic protein.
Claim 14: Claim 8 teaches IM administration.
Claim 15: Claim 9 teaches human.
Claim 16: Claim 10 recites an AAV comprising a transgene encoding a transcription that contains miR-652-5pBS and miR-142BS.
Claim 18: Claim 11 is drawn to the same further provided miRBS Markush. It is noted that the sequence identifiers are the essential written description for these sequences are the same in the present case as the Patent.
Claim 20: Claim 12 requires the same SEQ ID NO: 43.
Claim 21: Claim 13 requires the same SEQ ID NO: 44.
Claim 24: Claim 14 requires the presence of an miR BS iun the 3’ UTR.
Claim 25: Claim 15 recites the same therapeutic protein, or a Markush of inhibitory RNAs.
Claim 27: Claim 16 requires the same Markush of capsids.
Claim 28: Claim 17 requires the ITRs.
Claim 29: Claim 18 is to the same host cell.
Claim 30: Claim 19 requires the host cell to be mammalian.
Thus, in light of the patent, the invention is obvious. The Artisan would make the invention, and expect it to work, as it is claimed subject matter.
For clarity, U.S. Patent No. 10,975,391 was considered for NSDP purposes. However, the patent does not require an miR-652 binding site. Thus, it was deemed not eligible, even in light of the art.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/ Primary Examiner, Art Unit 1638