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Claims 16-17 and 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group II and Group III respectively, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/28/2025.
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.
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Claims 1-11, 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 9 of copending Application No. 18658741 in view of EP 3620521 A1. The instant application claims 1-4 disclose the use of CTCF sites in an AAV vector. This limitation is absent from reference claim 1, which claims an AAV vector. However, EP 3620521 A1 discloses the use of CTCF binding sites in AAV vectors as described in detail in the art rejections below, which renders them an obvious variation of AAV vectors Furthermore, US 11779655 B2, US 11718860 B2, and US 11001841 B2 render claims 5-11 additional obvious variations, as described in the art rejections below. Additionally, EP 3620521 A1renders the virus particle of the application’s claim 13 and the reference application’s claim 9 overlapping as well because they are defined to include the construct in claim 1.
This is a provisional nonstatutory double patenting rejection.
Claims 1-11, 12, 14, 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 18, 20, 21 of copending Application No. 18551110 in view of EP 3620521 A1. The application claims 1-4 disclose the use of CTCF sites in an AAV vector. This limitation is absent from the reference claim 1, which claims an AAV vector. However, EP 3620521 A1 discloses the use of CTCF binding sites in AAV vectors, as described in the art rejections below, which renders them an obvious variation of AAV vectors. Furthermore, US 11779655 B2, US 11718860 B2, and US 11001841 B2 render claims 5-11 additional obvious variations, as described in the art rejections below. Additionally claims 12, 14, 15 of the application and claims 18, 20, 21 of the reference application, respectively, are rendered obvious by the same discloser due to the fact they are dependent on the construct of claim 1 (of both applications) and they claim the same additional limitations (a cell with the construct of claim 1, and a packaging cell line using trans complementation).
This is a provisional nonstatutory double patenting rejection.
Claims 1-11, 15, 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 13 of copending Application No. 17911367 in view of EP 3620521 A1. The application claims 1-4 disclose the use of CTCF sites in an AAV vector. This limitation is absent from the reference claim 1, which claims an AAV vector. However, EP 3620521 A1 discloses the use of CTCF binding sites in AAV vectors, as detailed in the art rejection below, which renders them an obvious variation of AAV vectors. Furthermore, US 11779655 B2, US 11718860 B2, and US 11001841 B2 render claims 5-11 additional obvious variations, as described in the art rejections below. Additionally, claim 15 and reference application claim 13 both contain the construct of claim 1 (from both applications) and claim the same additional limitation (packaging cell line using trans complementation). The same applies for claim 13 and reference claim 13 (a viral particle with the construct of claim 1).
This is a provisional nonstatutory double patenting rejection.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015006743 A1, and further in view of EP 3620521 A1, and Wit, E et al 2015.
WO 2015006743 A1 discloses, “In more particular embodiments of the invention, a vector or vector sequence includes a first inverted terminal repeat (ITR) of an AAV; a promoter operable in mammalian cells; the reporter transgene; a polyadenylation signal; and optionally a second ITR of an AAV.” (paragraph 0020). Additionally, they disclose, “As used herein, a "vector" can refer to a viral particle, such as a parvovirus (e.g., AAV) that can be used to deliver nucleic acid (e.g., reporter transgene) into cells, and which vector includes nucleic acid (e.g., reporter transgene) packaged into virions or encapsidated by viral proteins (envelope proteins or capsid proteins, such as AAV capsid). (paragraph 0047). However, WO 2015006743 A1 does not disclose implementing CTCF binding sites in the vector and does not indicate in which orientation CTCF sites should be in with regard to one another. It does not specify that the CTCF sites should be from human or viruses, or how many consensus sites should be in each binding site. It also does not disclose a host cell containing the construct, a packaging cell line, or a packaging cell line designed for trans complementation.
EP 3620521 A1 discloses, “In certain embodiments, a presently disclosed expression cassette comprises at least one insulator comprising the CTCF binding site sequence.” (paragraph 0017) “In one embodiment, the expression cassette comprises two of the insulator…where one insulator is positioned at the 3' end and the other insulator is positioned at the 5' end of the expression cassette.” (paragraph 0017). Additionally, “Also provided are vectors comprising such expression cassettes, cells transduced with such expression cassettes or such vectors…” (paragraph 0016). Furthermore, “Other viral vectors that can be used include, for example, adenoviral, lentiviral, and adeno-associated viral vectors…” (paragraph 0149). Additionally, EP 3620521 A1 discloses, “Additionally, the presently disclosed subject matter provides cells transduced with the above-described expression cassettes, cells transduced with the above-described recombinant vectors…” (paragraph 0025). Furthermore, “The vector itself, which encodes the therapeutic transgene or cDNA, retains the minimal viral sequences needed to enable packaging in viral particles in a packaging cell line, reverse transcription, and integration. The packaging cell expresses the necessary structural proteins and enzymes that are required to assemble an infectious recombinant particle that contains the vector sequence and the machinery needed for its reverse transcription and integration in the transduced cell.” (paragraph 0143). Finally, “The presently disclosed subject matter contemplates that the vectors and other delivery systems (eg, nucleases or CRISPR-Cas systems), viral particles…”(paragraph 087).
Wit, E et al 2015 discloses, “As recently reported, our data also suggest that chromatin loops preferentially form between CTCF binding sites oriented in a convergent manner. To directly test this, we used CRISPR/Cas9 genome editing to delete core CTCF binding sites in three loci, including the CTCF site in the Sox2 super-enhancer. In all instances, CTCF and cohesin recruitment were lost, and chromatin loops with distal, convergent CTCF sites were disrupted or destabilized. Re-insertion of oppositely oriented CTCF recognition sequences restored CTCF and cohesin recruitment, but did not re-establish chromatin loops. We conclude that CTCF binding polarity plays a functional role in the formation of higher-order chromatin structure.” (summary paragraph).
It would have been obvious to one of ordinary skill in the art, before the effective filing date to include a CTCF site in an AAV vector, and in particular in an AAV vector with the format disclosed by WO 2015006743 A1 above (5’ITR, promoter, transgene, 3’ ITR) because it is well known in the art that these types of DNA sequences (CTCF binding sites) are used to control and regulate gene expression. This particular embodiment (CTCF site in an AAV vector) is also taught explicitly by EP 3620521 A1. This renders claim 1 obvious. Additionally, EP 3620521 A1 also provides and explicit suggestion/teaching to include two CTCF sites, one at the 5’ end of the expression cassette (aka promoter and transgene), and one at the 3’ end of the expression cassette (aka promoter and transgene). This renders claim 2 and claim 3 obvious. Furthermore, Wit, E et al 2015 provides a strong teaching to place CTCF binding sites in a convergent orientation based on their functional data. This renders claim 4 obvious. It is well known in the field of virology that virus particles are the infectious material and thus full particles are required to transfer vectors. It is also known that viruses require a host cell to generate progeny and replicate their genetic material. EP 3620521 A1 provides explicit disclosure of an AAV particle containing the disclosed construct (claim 13), a cell line transduced with the AAV vector (claim 12), and a cell line designed specifically for progeny generation using trans complementation (claim 14-15). This renders claims 12-15 obvious.
Claims 5-11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015006743 A1 and EP 3620521 A1 as applied to claim 1 above, and further in view of US 11779655 B2, US 11718860 B2, and US 11001841 B2.
Claim 1 is rendered obvious by WO 2015006743 A1 and EP 3620521 A1 as outlined above.
US 11779655 B2 discloses Seq ID NO: 710 which contains the entire Seq ID:3 of the present application. They go on to disclose, “The present invention provides improved adeno-associated virus (AAV) constructs.” (paragraph 0012). Furthermore, “In specific embodiments, when the Rep/Cap plasmid is an AAV2/9 plasmid, such as the plasmid referred to herein as “pAAV2/9”, the plasmid may comprise: an AAV2 p5 promoter (SEQ ID NO: 710).” (paragraph 0174). It does not disclose the use of Seq ID NO: 1 or Seq ID NO: 42 of the present application. It also does not disclose CTCF sequences with 5 CTCF binding sites.
US 11718860 B2 discloses Seq ID NO: 4742 which contains Seq ID NO: 42 of the present application in a 100% match. They go on to say, “Some aspects of the present disclosure provide synthetic promoters that have differential activities in different cell types and/or different cellular states.” (paragraph 0006). Furthermore, “Further provided herein are viruses, such as lentiviruses, adenoviruses, adeno-associated viruses, and/or oncolytic viruses comprising an engineered nucleic acid described herein.” (paragraph 0015). Importantly, Seq ID NO: 4742 contains 8 potential CTCF binding sties (see additional data providing Seq ID NO: 4742 and CTCF consensus sequence).
US 11001841 B2 discloses Seq ID NO: 71950 which contains the entire Seq ID NO: 1 of the current application. Importantly, US 11001841 B2 identifies sequences containing CCCTC-binding factor sites. They disclose, “As described herein, crosslinking immunoprecipitation (CLIP) coupled with high-throughput sequencing (CLIP-seq) analysis was used to define an RNA interactome for CTCF in mouse embryonic stem cells (mESC) and human HEK293 kidney cells; in parallel.” (Summary section paragraph 1).
Therefore, US 11779655 B2 provides a strong motivation to include Seq ID NO: 710 (present application Seq ID NO:3) in an AAV considering it as a natural genetic element occurring in AAV2 (aka the p5 promoter of AAV2). This renders claim 5-7, 11 obvious as the CTCF sequence is from a virus (claim 5) and in particular, and adeno-associated virus (claim 6). Also, it contains Seq ID NO: 3 of the present application and therefore it is from the selected set of disclosed sequences required by claim 7 (NO: 1-28) and claim 11 (Seq ID NO:3). Additionally, it would be obvious to one of skill in the art before the effectively filling date to include US 11718860 B2 Seq ID NO: 4742 (aka present application Seq ID NO: 42) as a genetic element in an AAV vector because Seq ID NO: 4742 is designed to control transcription of sequences. Importantly, this sequence has 8 potential CTCF binding sites (see additional documentation). Furthermore, US 11718860 B2 provides an explicit suggestion/motivation to include this (and other) promoters in an adeno-associated virus. This renders claim 9 and claim 10 obvious. US 11001841 B2 provides a suggestion/motivation to include Seq ID NO: 71950 (Seq ID NO: 1 of the current application) in a AAV vector for control of transcription because it is identified specifically as A CTCF binding site, and it is known that these sites regulate transcription. Thus, with the US 11718860 B2 disclosure outlined above, claim 8 is rendered obvious as it is simply the addition of known elements (Seq ID NO: 71950 aka Seq ID NO: 1 of the current application and Seq ID NO: 4742 aka present application Seq ID NO: 42) to achieve predictable results.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Adam M Smith whose telephone number is (571)272-7517. The examiner can normally be reached Monday- Friday 10:30AM-5PM.
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/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638