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
This Office Action is a reply to Applicant’s Election (Response to Restriction Requirement) filed February 2, 2026.
Claims 1-36 are pending in the instant application.
Election/Restrictions
Applicant’s election (with traverse) of Group I (claims 1-20) in the reply filed on February 2, 2026 is acknowledged.
The traversal is on the grounds that Groups I and II as detailed in the previous Requirement for Restriction/Election mailed December 3, 2025 represent a combination of a product and a process of using that product. Applicants submit that according to 37 CFR 1.475(b), "An international or a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories: (1) A product and a process specially adapted for the manufacture of said product; or (2) A product and a process of use of said product.” Applicants submit that the requirement for unity of invention has been fulfilled.
Applicants also disagree that Groups I and II as detailed in the previous Requirement for Restriction/Election mailed December 3, 2025 do not share a single general inventive concept because Kleopa et al. discloses a nucleic acid construct comprising an Mpz promoter for expression of a reporter gene (EGFP). However, Applicants submit that Kleopa et al. does not disclose any of the regulatory elements of SEQ ID NOs: 1-6, as recited in claim 2 of the instant invention.
Regarding the election of species, Applicants argue that all species are shRNA sequences targeting PMP22 and the Office have not provided sound reasons or examples supporting a conclusion that the species are patentably distinct from each other.
Applicants argue that the restriction requirement is improper and should be withdrawn. Applicants also submit that the requirement for election of species is improper and should be withdrawn.
Applicant’s traversal has been fully considered by the Examiner, however it is not found persuasive because a national stage application lacks unity of invention (product and process) when the claims do not share a single general inventive concept, specifically when the product is known and the process is not specially adapted to produce it. A lack of unity arises when the special technical features linking the product and process do not make a contribution over the prior art. In the present case, the linking feature between the product and process is known and therefore lacks unity.
As detailed in the previous Requirement for Restriction/Election mailed December 3, 2025, Groups I and II do not avoid the prior art because a nucleic acid construct comprising a Schwann cell-specific regulatory element, wherein the regulatory element is operably linked with a gene selected from the group consisting of myelin protein zero (MPZ), myelin-associated glycoprotein (MAG), myelin basic protein (MBP), and apoptosis-associated tyrosine kinase (AATK) was taught and suggested in the prior art of WO 2020/245169 A1 (Kleopa et al.). Contrary to Applicant’s arguments, the nucleic acid constructs comprising the regulatory elements of SEQ ID NOs: 1-6 (claim 2) do not constitute the special technical feature linking Groups I and II. Instead, the nucleic acid constructs comprising the regulatory elements selected from the group consisting of myelin protein zero (MPZ), myelin-associated glycoprotein (MAG), myelin basic protein (MBP), and apoptosis-associated tyrosine kinase (AATK) (claim 1) constitutes the special technical feature linking Groups I and II, said special technical feature being taught and suggested by Kleopa et al. Unity of invention exists only when the shared same or corresponding technical feature is a contribution over the prior art. Given the teachings and suggestions above, the claims do not confer novelty or inventive step over Kleopa et al.
Regarding the election of species, Applicant’s arguments are not found to be persuasive since the shRNA sequences targeting PMP22 target different regions of the PMP22 gene. For example, exon 1A or 1B (target sites 1, 2 and 3); and 5’-UTR (nos. 1, 2 and 3). The species are independent or distinct because claims to the different species recite the mutually exclusive characteristics of such species. In addition, these species are not obvious variants of each other based on the current record.
For these reasons, claims 21-36 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.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 1-20 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed December 27, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
The listing of references in the specification at pages 24 and 25 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 filed on June 29, 2023 are acknowledged and have been accepted by the Examiner.
Claim Interpretation
Claims 2, 6 and 11 recites the phrase, “at least a portion of a sequence selected from the groups consisting of SEQ ID NO: 1-6”. The present Specification does not define, “at least a portion of”. The claims in this application are given their broadest reasonable interpretation (BRI) using the plain meaning of the claim language in light of the Specification as it would be understood by one of ordinary skill in the art. See MPEP 2111. Interpreted broadly, “at least a portion of a sequence selected from the groups consisting of SEQ ID NO: 1-6” is anticipated by any dinucleotide or larger oligonucleotide sequence of SEQ ID NO: 1-6. The Examiner will therefore interpret the phrase, “at least a portion of a sequence selected from the groups consisting of SEQ ID NO: 1-6” to be any dinucleotide or larger oligonucleotide sequence of SEQ ID NO: 1-6.
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 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, 8 and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2020/245169 A1 (Kleopa et al.) (submitted and made of record on the Information Disclosure Statement filed December 27, 2024).
The claims are drawn to a nucleic acid construct comprising a Schwann cell-specific regulatory element, wherein the regulatory element is operably linked with a gene selected from the group consisting of myelin protein zero (MPZ), myelin-associated glycoprotein (MAG), myelin basic protein (MBP), and apoptosis-associated tyrosine kinase (AATK). Applicant is reminded of the interpretation of the phrase, “at least a portion of a sequence selected from the groups consisting of SEQ ID NO: 1-6” as recited in claim 2. For further explanation, see section above titled, “Claim Interpretation”.
Kleopa et al. teach AAV vectors with myelin protein zero (Mpz) promoters. Specifically, Kleopa et al. teach an AAV9 vector comprising a nucleotide sequence which can be transcribed into a first polynucleotide under control of a Schwann cell specific promoter, optionally the full length Mpz promoter or the minimal Mpz promoter. See Kleopa et al., Figure 1 - AAV vector transfer plasmids generated for Schwann cell-targeted gene expression: pAAV-Mbz.GJB1 vector containing the human GJB1 open reading frame expressing Cx32 (Full) and pAAV-Mpz.EGFP expressing the reporter gene EGFP (Mock). Also, see Kleopa et al., Figure 9 - where the inventors PCR-amplified the 410 bp from the Mpz promoter upstream of the start codon, and then further cloned this miniMpz promoter into the AAV transfer plasmid along with downstream EGFP as a reporter gene and produced the AAV9-miniMpz.Egfp vector.
The promoter(s) of the Kleopa et al. invention are myelin specific promoters, including myelin protein 22 (PMP22), myelin associated glycoprotein (Mag) or Mpz.
Kleopa et al. also teach the AAV constructs of their invention were produced and packaged into the AAV9 serotype to achieve viral titers.
Therefore, claims 1, 2, 8 and 17-20 are anticipated by Kleopa et al.
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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, 2, 4, 6, 8, 9, 11, 13 and 15-20 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/245169 A1 (Kleopa et al.) (submitted and made of record on the Information Disclosure Statement filed December 27, 2024) in view of Gautier et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.01.29.924605, posted January 30, 2020).
The claims are as described above. Applicant is reminded of the interpretation of the phrase, “at least a portion of a sequence selected from the groups consisting of SEQ ID NO: 1-6” as recited in claims 2, 6 and 11.
Kleopa et al. is relied upon as described above.
The Examiner is relying on Kleopa et al. to further teach:
In some embodiments, the viral vectors described herein comprises a first nucleic acid sequence that encodes a first polypeptide or protein, and the vector can also comprise a second nucleic acid that is transcribed into a non-coding RNA.
A person of ordinary skill in the art would have been motivated to modify the teachings of Kleopa et al. to further comprise the use of another myelin specific promoter, such as the PMPP2 promoter to drive expression of the second nucleic acid.
Kleopa et al. teach in a further additional embodiment, the first nucleic acid is transcribed into a non-coding RNA, such as a short-hairpin RNA (shRNA).
Kleopa et al. do not teach the shRNA targets PMP22.
Gautier et al. teach long term AAV2/9-mediated silencing of PMP22 prevents Charcot-Marie-Tooth disease 1A (CMT1A) in rats and validates skin biomarkers as treatment outcome measure by targeting PMP22 using shRNA.
Regarding claim 16 of the present invention which recites, “wherein the construct drives expression of the target gene at an attenuated level in oligodendrocytes as compared to expression of the target gene in Schwann cells”, such is nothing more than an intended use. Applicant is reminded that the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the nucleic acid construct comprising a Schwann cell-specific regulatory element, wherein the regulatory element is operably linked with MPZ and wherein the regulatory element is operably linked to a target gene of Kleopa et al. is capable of driving the expression of the target gene at an attenuated level in oligodendrocytes as compared to expression of the target gene in Schwann cells and therefore meets the functionality reported in the present application, absent some evidence to the contrary.
Before the effective filing date of the claimed invention, a nucleic acid construct comprising a Schwann cell-specific regulatory element, wherein the regulatory element is operably linked with MPZ and wherein the regulatory element is operably linked to a target gene was known and taught in the prior art of Kleopa et al.
A person of ordinary skill in the art would have been motivated to modify the teachings of Kleopa et al. to further comprise the use of another myelin specific promoter, such as the PMPP2 promoter to drive expression of the second nucleic acid.
A person of ordinary skill in the art would have expected reasonable success to devise the nucleic acid constructs of the present invention using the teachings, suggestion and motivation of Kleopa et al. in view of Gautier et al.
Therefore, the subject matter of claims 1, 2, 4, 6, 8, 9, 11, 13 and 15-20 are obvious over Kleopa et al. in view of Gautier et al.
Markush Rejection
Claim 14 is rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to a multitude of shRNA that target PMP22 with no common searchable core. The nucleotide sequences (e.g. SEQ ID NOs: 9-17) have no common structure other than being nucleic acid sequences. The specific activity of each shRNA molecule is dependent upon the specific sequence of nucleotides.
Furthermore, the Markush groupings of the shRNA SEQ ID NOs listed in claim 14 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Each of the shRNA sequences targeting PMP22 target different regions of the PMP22 gene. For example, exon 1A or 1B (target sites 1, 2 and 3); and 5’-UTR (nos. 1, 2 and 3). Each sequence has its own structure based on its sequence, so while they share a common use, the alternatives do not share a common structure.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, activity of any specific shRNA molecule is dependent upon the specific sequence of nucleotides. There is no expectation that any one of the nucleotide sequences as claimed can be substituted for any of the other with a completely different sequence with the expectation of the same activity.
The Patent Office does not have the resources to search all the sequences present in the present application and perform the corresponding examination.
Conclusion
Claims 3, 5, 7, 10 and 12 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/ Primary Examiner, Art Unit 1635