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 action is in response to the papers filed September 10, 2026.
Election/Restrictions
Applicant’s reply filed 09/10/2026 to the Requirement for Restriction/Election mailed 06/11/2026 is acknowledged.
Applicant elected without traverse the invention of Group 1, drawn to a polynucleotide, a vector comprising thereof, a rAAV comprising thereof, a virion comprising thereof, a transformed cell comprising thereof, a pharmaceutical composition comprising thereof, and an effective amount thereof.
Claim Amendments
Applicant’s amendment to the claims filed 09/10/2026 is acknowledged.
Claims 31-41 have been cancelled.
Claims 1-30 and 42-53 are pending and under examination.
Priority
The instant application 18832458 was filed on 07/23/2024. This application is a national stage of international application PCT/GB2023/050207 filed 01/31/2023, claiming priority based on U.K. Patent Application GB2201242.1 filed 01/31/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Effective filing dates: Sufficient written support for SEQ ID NO: 25 is not found in Applicant’s priority document, GB2201242.1 filed 01/31/2022. Therefore, claims 19 and 49-53 have an effective filing date of 01/31/2023 based on international application PCT/GB2023/050207.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/23/2024, 09/22/2025, 10/09/2025, 04/07/2026 and 09/10/2026 have been considered.
The listing of references in the specification 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, or by applicant in an information disclosure statement (IDS), they have not been considered.
Allowable Subject Matter
Claims 51-53 are allowed.
The following is a statement of reasons for the indication of allowable subject matter:
The prior art does not teach or fairly suggest a polynucleotide comprising the nucleic acid sequence of SEQ ID NO: 25.
Claim Objections
Claims 4-5, 7, 13 and 19 are objected to because of the following informalities:
In claim 4, the phrase “comprises SEQ ID NO: 4” should be “comprises the sequence of SEQ ID NO: 4” instead.
In claim 5, the phrase “a nucleotide sequence having at least 90% identity to SEQ ID NO:7, at least 95% identity, at least 97% identity, at least 99% identity to SEQ ID NO: 7 or 100% identity to SEQ ID NO: 7” should be “a nucleotide sequence having at least 90% identity to SEQ ID NO:7, at least 95% identity to SEQ ID NO:7, at least 97% identity to SEQ ID NO:7, at least 99% identity to SEQ ID NO: 7 or 100% identity to SEQ ID NO: 7” instead.
In claim 7, the phrase “comprising SEQ ID NO: 13” should be “comprising the sequence of SEQ ID NO: 13” instead.
In claim 13, the phrase “comprise SEQ ID NO: 8” should be “comprise the sequence of SEQ ID NO: 8” instead.
In claim 19, the phrase “comprises SEQ ID NO: 25” should be “comprises the sequence of SEQ ID NO: 25” instead.
Appropriate action is required.
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 1-30 and 42-50 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.
The limitation “a protein translation initiation site (Kozak sequence)” in claim 1, lines 4 and 14, and claim 2, lines 4 and 12, renders the claims indefinite because it is unclear whether the limitations in the parenthetical are part of the claimed invention or merely exemplary. In particular, it is unclear if the protein translation initiation site must be a Kozak sequence. See, MPEP 2173.05(d).
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Claim 5 is 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.
The limitation “the human MECP2 coding sequence or codon optimized coding sequence” in claim 5 lacks sufficient antecedent basis. In particular, the claims do not previously recite a “codon optimized coding sequence.”
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 8 is 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 8 recites “a CBM or CBM promoter as set forth in SEQ ID NO: 21 or 22.” The phrase “as set forth in” renders the scope of the limitation indefinite. In this case, it is unclear if the promoter sequence must comprise the complete sequence according to SEQ ID NO: 21 or 22, or if the promoter sequence may merely be a subsequence within SEQ ID NO: 21 or 22. To the extent that the promoter sequences lie within SEQ ID NOs: 21-22, but does not include the entire sequence according to SEQ ID NOs: 21-22, then it is unclear what fragment of SEQ ID NO: 21 or 22 provides the claimed promoter sequence.
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 8-9 and 17-18 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.
The claims recite “CBM” and “CBE” promoter sequences (claims 8-10, 17-18). Paragraph 112 of the specification defines a CBE promoter as “cytomegalovirus early enhancer element and the promoter of chicken beta-actin, and the first exon, first intron, and second exon of human
elongation factor I alpha),” and a CBM promoter is defined as “cytomegalovirus early enhancer element and the promoter of chicken beta-actin, and the first exon, first intron, and second exon of MINIX.” The limitation of a “CBM promoter” is indefinite because, in its definition, it is unclear what gene “MINIX” refers to. Based on the evidence of record, “MINIX” is not a term of art, and there does not appear to be a gene known in the art using the symbol “MINIX,” as described in the present application. Accordingly, lacking of a clear definition, the term “CBM promoter” is indefinite, absent evidence to the contrary. For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claims 17-18 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.
The claims recite a polynucleotide comprising “an optimized Kozak sequence” (claim 17, lines 3, and claim 18, line 3). The term “optimized” is a relative term which renders the claim indefinite. The term “optimized” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the limitation. In this case, it is unclear what particular Kozak sequence is optimized and how, e.g., improved translation initiation. There is no standard Kozak sequence recited by the claims by which may serve as a benchmark in determining an “optimized Kozak sequence,” as claimed.
For these reasons, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
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, 3-5, 7-17, 19-30 and 42-50 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.
In the amendment filed 09/10/2026, Applicant amended claim 1 to further recite an alternative arrangement of the claimed invention. In particular, claim 1 was amended to recite a polynucleotide comprising, from 5’ to 3’, (i) a promoter, (ii) at least one miRNA expressed within an intron, (iii) a protein translation initiation site, (iv) a human MECP2 coding sequence, (v) at least three miRNA binding sites for the miRNA, (vi) at least on 3’ stability element and (vii) a polyadenylation signal. However, the specification as originally filed discloses the arrangement, from 5’ to 3’, of (i) a promoter, (ii) at least one miRNA expressed within an intron, (iii) a protein translation initiation site, (iv) a human MECP2 coding sequence, (v) at least on 3’ stability element, (vi) at least three miRNA binding sites for the miRNA and (vii) a polyadenylation signal. Accordingly, Applicant’s amendment filed 09/10/2026 introduced an alternative arrangement of the claimed polynucleotide, wherein the positions of “3’ stability element” and the “at least three miRNA binding sites” are swapped. The specification as originally filed is not found to disclose this new arrangement, as claimed.
In remarks filed 09/10/2026, Applicant states that support for the new and amended claims can be found in the specification and claims as originally filed, citing paragraphs 7, 31, 40 and 107 of the specification as filed. However, paragraphs 7, 31, 40 and 107 of the specification as filed do not disclose the alternative arrangement introduced by Applicant’s amendment to claim 1. For these reasons, Applicant’s remarks are not found to identity written support for the amendment.
For these reasons, absent evidence to the contrary, the amendment to claim 1 introduces new matter not described in the specification as originally filed. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Claims 1-30 and 42-50 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 recite a polynucleotide comprising “at least one 3’ stability element” (claim 1, lines 7 and 18, and claim 2, lines 6 and 14). The specification as filed provides no definition of a “3’ stability element,” as claimed. Under the broadest reasonable interpretation, the term “3’ stability element” broadly includes any nucleic acid sequence that provides stability to a polynucleotide molecule, such as an mRNA transcript. Therefore, the claims are directed to a structurally-undisclosed genus of 3’ nucleic acid sequences functionally-defined as conferring stability to a polynucleotide.
An adequate written description of a genus of nucleic acid sequences that confer stability to a polynucleotide requires more than a mere statement that it is part of the invention. What is required is either (1) a description of a common core structure shared among the members (species) of the functionally described genus or (2) a disclosure of a representative number of species of the functionally described genus. It is not sufficient to define a genus of nucleic acid sequences solely by its desired biological property, i.e., conferring stability to a polynucleotide, because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any nucleic acid sequence that is capable of conferring stability to a polynucleotide. Also, naming a type of material generically known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Thus, claiming all nucleic acid sequences that confer stability to a polynucleotide, without defining what means will do or without disclosing a representative number of species, is not in compliance with the written description requirement.
The specification as filed describes only a single example of a “3’ stability element,” i.e., woodchuck hepatitis virus post-transcriptional regulatory element (WPRE). Besides WPRE itself, the specification describes no other species of “3’ stability element,” as instantly claimed.
Accordingly, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that the applicant is in possession of the broad genus of stability-conferring nucleic acid sequences at the time the application was filed. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
Claims 1, 3-5, 7-17, 19-30 and 42-50 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 recite a human MECP2 coding sequence according to SEQ ID NO: 7 or “a functionally active fragment thereof” (claim 1, lines 6 and 16, and claim 5). The specification as filed provides no definition of a “functionally active fragment,” as claimed. Under the broadest reasonable interpretation, the term “functionally active fragment” broadly includes any fragment of human MECP2, of any size, that retains at least one functional activity of wild-type human MECP2. Therefore, the claims are directed to a structurally-undisclosed genus of fragments of human MECP2 that possess at least one functional activity of wild-type human MECP2.
An adequate written description of a genus of functionally-active fragments of human MECP2 requires more than a mere statement that it is part of the invention. What is required is either (1) a description of a common core structure shared among the members (species) of the functionally described genus or (2) a disclosure of a representative number of species of the functionally described genus. It is not sufficient to define a genus of human MECP2 fragments, of any size, by its desired biological property, i.e., any activity of wild-type human MECP2, because disclosure of no more than that, as in the instant case, is simply a wish to know the identity of any fragment of human MECP2 that retains one or more activities of wild-type human MECP2. Also, naming a type of material generically known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material. Thus, claiming all functionally-active fragments of human MECP2, without defining what means will do or without disclosing a representative number of species, is not in compliance with the written description requirement.
The specification as filed describes only provides the coding sequence of SEQ ID NO: 7 for human MECP2. The specification does not describe any fragment of human MECP2. The specification does not describe a common core structure of human MECP2 shared among all functionally-active fragments.
Accordingly, absent evidence to the contrary, this limited information is not deemed sufficient to reasonably convey to one skilled in the art that the applicant is in possession of the broad genus of functionally-active fragments of human MECP2, of any size, at the time the application was filed. Dependent claims are included in the basis of the rejection because they do not correct the deficiencies of the claim upon which they depend.
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.
Claims 2, 6 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/219766 A1 to Wilson et al.; Strovas et al. (2014) “MicroRNA-based single-gene circuits buffer protein synthesis rates against perturbations” ACS synthetic biology, 3(5), 324-331; and Lillacci et al. (2018) “Synthetic control systems for high performance gene expression in mammalian cells” Nucleic acids research, 46(18), 9855-9863.
Wilson discloses a recombinant adeno-associated virus (rAAV) having an AAV capsid and a vector genome which comprises a nucleic acid sequence encoding human MECP2 (hMECP2). See, Abstract.
The AAV genome comprises, from 5’ to 3’, a promoter sequence, a Kozak sequence, a coding sequence for human MECP2, and a SV40 polyadenylation signal, flanked by ITR sequences. The AAV genome further contains a WPRE sequence for stabilizing the cytoplasmic mRNA transcript, which is placed upstream of the polyadenylation signal and downstream of the coding sequence. See, Figure 1. See also, page 4, lines 5-17; pages 13-16; and page 24, lines 15-21.
The coding sequence for MECP2 is the wild-type sequence or codon optimized sequence according to SEQ ID NO: 3. See, page 8, lines 19-21; page 24, lines 15-21; page 52, line 22; and page 54, line 12.
The AAV genome may further comprise an intron upstream of the hMECP2 coding sequence and downstream of the promoter sequence (pg. 21, ll. 8; pg. 23, ll. 16-18; pg. 24, ll. 15-21).
The AAV genome may further encode, in addition to the hMECP2 coding sequence, another non-AAV coding sequence, e.g., a functional RNA molecule, e.g., a miRNA. The AAV genome may also further comprise up to four miRNA binding sites upstream of the polyadenylation signal and downstream of the hMECP2 coding sequence, wherein the miRNA binding sites are designed to be specifically targeted by endogenous miRNA in cells in which repression of hMECP2 transgene expression is desired. See, pages 16-17; page 24, lines 15-21; and Figure 2A.
The instantly pending claims require that the polynucleotide comprises (i) an miRNA expressed within an intron and (ii) at least three miRNA binding sites for the intronic miRNA. Although Wilson describes the AAV genome may further comprise an intron, an miRNA coding sequence and at least three miRNA binding sites, as outlined above, Wilson does not teach or fairly suggest that (i) the encoded miRNA is intronic and (ii) the said miRNA targets the miRNA binding sites downstream of the hMECP2 coding sequence.
However, regulatory circuits for transgene expression, comprising (i) an intronically-encoded miRNA and (ii) at least three miRNA binding sites for said intronically-encoded miRNA, was known in the art prior to the effective filing date of the instantly claimed invention, as found in Strovas and Lillacci. This regulatory circuit design is known in the art as an “incoherent feed-forward loop” and comprises an intronic miRNA that targets its own transcript, resulting in buffered protein production and reduced transcriptional noise, and enabling tunability of transgene expression, which unregulated expression may be otherwise poorly tolerated by transformed host cells. See, Strovas: Abstract, and Figure 1. See, Lillacci: Abstract, and Figure 1.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the AAV genome of Wilson to comprise an incoherent feed-forward loop comprising an intronic miRNA that targets its own transcript, as found in Strovas and Lillacci, with a reasonable expectation of success because such a regulatory circuit buffers protein production, reduces transcriptional noise, and enables tunability of transgene expression, which unregulated expression may be otherwise poorly tolerated by transformed host cells. As discussed above, the incoherent feed-forward loop comprises (i) an intronically-encoded miRNA and (ii) at least three miRNA binding sites for said intronically-encoded miRNA, as instantly claimed.
For these reasons, the polynucleotide according to claims 2 and 6, including the particular arrangement of parts (i.e., the claimed 5’ to 3’ order of sequences), would have been prima facie obvious over the prior art. Absent evidence to the contrary, dependent claim 18 is also included in the basis of this rejection in light of the indefinite scope of a “CBM promoter” as provided under 35 U.S.C. 112(b). For example, Wilson describes various promoter sequences may be used, including a chicken beta actin promoter with a cytomegalovirus enhancer element or a human elongation initiation factor 1 alpha (EF1a) promoter. See, page 14, ll. 3-20.
Claims 1, 3, 5, 7, 11-12, 14-17, 20-30, 42-48 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson, Strovas and Lillacci, as applied to the claims above; in further view of US 2020/0179467 A1 to Kaspar et al.
The teachings of Wilson, Strovas and Lillacci, combined, have been provided above and hereby incorporated by reference.
Wilson does not teach the human MECP2 coding sequence comprises the sequence according to SEQ ID NO: 7, as instantly claimed.
Kaspar is relevant prior art for teaching a recombinant adeno-associated virus 9 (rAAV9) encoding human MECP2 according to SEQ ID NO: 3. See, Abstract and paragraph 50. SEQ ID NO: 3 of Kaspar is identical to SEQ ID NO: 7 of the instant application. See, Alignments.
Therefore, prior to the effective filing date of the instantly claimed invention, one of ordinary skill in the art would have recognized that either (i) the hMECP2 coding sequence in Wilson or (ii) the hMECP coding sequence in Kaspar, i.e., the sequence according to SEQ ID NO: 7 of the instant application, were suitable coding sequences for rAAV gene therapy. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to substitute the hMECP2 coding sequence in Wilson with the hMECP2 coding sequence according to SEQ ID NO: 7 of the instant application, as found in Kaspar, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding dependent claim 7, Wilson’s vector in SEQ ID NO: 1 comprises the Kozak sequence according to SEQ ID NO: 13 of the instant application. See, Alignments.
Regarding dependent claim 14, Strovas teaches the miRNA binding site comprises at least one mismatch to the intronic miRNA, which inhibits catalytic cleavage but still provides very strong interactions between miRNA and mRNA transcript. See, Figure 4, and page 328.
Regarding dependent claim 16, Wilson’s vector in SEQ ID NO: 1 comprises a SV40 polyadenylation signal sequence that is 99.2% identical to SEQ ID NO: 12 of the instant application. See, Alignments. Wilson does not teach a SV40 polyadenylation signal comprising the nucleotide sequence of SEQ ID NO: 12 of the instant application, as claimed in claim 16. However, the sequence of SEQ ID NO: 12 was a known SV40 polyadenylation signal sequence prior to the effective filing date of the instantly claimed invention. Official Notice taken, if necessary. Therefore, it would have been prima facie obvious to one of ordinary skill in the art to substitute the SV40 polyadenylation signal sequence in Wilson with the SV40 polyadenylation signal sequence according to SEQ ID NO: 12, as previously known in the art, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding dependent claim 25, Wilson teaches the AAV is AAV9. See, page 3, line 10. Kaspar also teaches AAV9. See, Abstract.
Regarding dependent claim 29, Wilson teaches a transformed cell. See, pages 13-14.
Regarding dependent claim 30, Wilson teaches a pharmaceutical compositions comprising the rAAV and a pharmaceutically acceptable carrier. See, page 35.
For these reasons, and those outlined above, claims 1, 3, 5, 7, 11-12, 14-17, 20-30, 42-48 would have been prima facie obvious over the prior art.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Wilson, Strovas, Lillacci and Kaspar, as applied to the claims above; in further view of US 2017/0130244 A1 to Yang et al.
The teachings of Wilson, Strovas, Lillacci and Kaspar, combined, have been provided above and hereby incorporated by reference.
Wilson does not teach a CBE promoter comprising a nucleotide sequence having at least 90% identity to SEQ ID NO: 22, as claimed in claim 10.
Yang is relevant prior art for teaching chimeric gene regulatory units capable of driving strong and sustained heterologous gene expression. See, Abstract. Yang further teaches a promoter sequence according to SEQ ID NO: 48 (Table 2), which is 97.2% identical to SEQ ID NO: 22 of the instant application. See, Alignments.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to substitute the promoter sequence in Wilson with Yang’s promoter sequence of SEQ ID NO: 48 with a reasonable expectation of success because Yang’s promoters provide strong and sustained heterologous gene expression, and the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. As shown above, Yang’s promoter sequence of SEQ ID NO: 48 reads on a promoter sequence comprising a nucleotide sequence having at least 90% identity to SEQ ID NO: 22 of the instant application.
For these reasons, the polynucleotide according to claim 10 would have been prima facie obvious over the prior art. Absent evidence to the contrary, dependent claim 8 is also included in the basis of this rejection in light of the indefinite scope of the phrase “as set forth in” as provided under 35 U.S.C. 112(b).
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 1-8, 10-18, 20-30 and 42-48 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending U.S. Application No. 18/003,021 (reference to claim listing filed 04/07/2026); in view of Wilson, Strovas, Lillacci, Kaspar and Yang. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been prima facie obvious over the reference claims.
The reference claims recite a construct comprising a promoter, at least one miRNA comprising the nucleic acid sequence of SEQ ID NO: 9, a transgene, at least one miRNA binding site(s) complementary to the miRNA, and a polyadenylation signal. See, claim 1.
The reference claims further recite that the miRNA binding site(s) are provided within the 3’ untranslated region (claim 2); the miRNA is expressed in an intron (claim 6); there are at least three miRNA binding sites (claim 8); the miRNA binding site is SEQ ID NO: 34 or 40 (claim 13); a stability element is located in the 3’ untranslated region (claim 18); the stability element is SEQ ID NO: 74 or 75, which are WPRE sequences (claim 19); the construct comprises a Kozak sequence according to SEQ ID NO: 73 (claim 20); the miRNA binding site has been designed to partially reduce miRNA binding (claim 21); an AAV vector comprising the construct (claim 23), and the transgene is MECP2 (claim 30).
SEQ ID NO: 9 of the reference claims is identical to SEQ ID NO: 4 of the instant application. See, Alignments.
SEQ ID NO: 34 and 40 of the reference claims are identical to SEQ ID NO: 8 of the instant application. See, Alignments.
SEQ ID NO: 73 of the reference claims are identical to SEQ ID NO: 13 of the instant application. See, Alignments.
The reference claims do not recite that the MECP2 coding sequence is a codon optimized or wildtype human MECP2 coding sequence, as instantly claimed.
The teachings of Wilson has been provided above and hereby incorporated by reference.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to substitute a MECP2 coding sequence, as in the reference claims, with a codon optimized or wildtype human MECP2 coding sequence, as found in Wilson, with a reasonable expectation of success because the human MECP2 coding sequence is suitable for administration to humans, and the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
The reference claims do not recite that the MECP2 coding sequence comprises the sequence according to SEQ ID NO: 7, as instantly claimed.
The teachings of Kaspar has been provided above and hereby incorporated by reference.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to substitute the hMECP2 coding sequence in Wilson with the hMECP2 coding sequence according to SEQ ID NO: 7 of the instant application, as found in Kaspar, with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
The reference claims do not recite the miRNA binding site comprises at least one mismatch for the intronic miRNA, as instantly claimed.
The teachings of Strovas and Lillacci have been provided above and hereby incorporated by reference.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the miRNA binding site(s) to comprise at least one mismatch for the intronic miRNA, in view of Strovas and Lillacci, with a reasonable expectation of success the mismatch inhibits catalytic cleavage but still provides strong interaction between miRNA and mRNA transcript.
The reference claims do not recite a CBE promoter comprising a nucleotide sequence having at least 90% identity to SEQ ID NO: 22, as instantly claimed.
The teachings of Yang has been provided above and hereby incorporated by reference.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to substitute the promoter sequence in the reference claims with Yang’s promoter sequence of SEQ ID NO: 48 with a reasonable expectation of success because Yang’s promoters provide strong and sustained heterologous gene expression, and the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. As shown above, Yang’s promoter sequence of SEQ ID NO: 48 reads on a promoter sequence comprising a nucleotide sequence having at least 90% identity to SEQ ID NO: 22 of the instant application.
For these reasons, and those set forth above, instantly pending claims 1-8, 10-18, 20-30 and 42-48 would have been prima facie obvious over the reference claims and secondary references.
Alignments
Alignment between SEQ ID NO: 7 of the instant application (Qy) and SEQ ID NO: 3 of Kaspar (Db).
PNG
media_image1.png
878
639
media_image1.png
Greyscale
PNG
media_image2.png
876
648
media_image2.png
Greyscale
Alignment between SEQ ID NO: 13 of the instant application (Qy) and SEQ ID NO: 1 of Wilson (Db).
PNG
media_image3.png
153
628
media_image3.png
Greyscale
Alignment between SEQ ID NO: 12 of the instant application (Qy) and SEQ ID NO: 1 of Wilson (Db).
PNG
media_image4.png
303
623
media_image4.png
Greyscale
Alignment between SEQ ID NO: 22 of the instant application (Qy) and SEQ ID NO: 48 of Yang (Db).
PNG
media_image5.png
937
646
media_image5.png
Greyscale
PNG
media_image6.png
1007
637
media_image6.png
Greyscale
Alignment between SEQ ID NO: 4 of the instant application and SEQ ID NO: 9 of copending U.S. Application No. 18/003,021.
PNG
media_image7.png
543
619
media_image7.png
Greyscale
Alignment between SEQ ID NO: 8 of the instant application and SEQ ID NO: 34 or 40 of copending U.S. Application No. 18/003,021.
PNG
media_image8.png
225
622
media_image8.png
Greyscale
Alignment between SEQ ID NO: 13 of the instant application and SEQ ID NO: 73 of copending U.S. Application No. 18/003,021.
PNG
media_image9.png
151
614
media_image9.png
Greyscale
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
