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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/22/2025 has been entered.
Response to Amendment
The amendment filed 12/22/2025, amending claim(s) 1, 21, and 35 (claims 21 and 35 first amended in claims set filed 08/08/2025) and cancelling claim(s) 9 and 20 is acknowledged.
Claims 1, 13, 19, 21, 22, 24, 26, 31, 32, 35, 36, 40, 43-48, and 50-67 are pending.
Claims 46-48, 50, 51, 53-58, 60, 61, and 63-67 are withdrawn.
Claims 1, 13, 19, 21, 22, 24, 26, 31, 32, 35, 36, 40, 43-45, 52, 59, and 62 are pending and under examination.
Claim Interpretation
Claim 1 recites “a nucleic acid for expressing a functional frataxin (FXN) protein in the heart”. The examiner notes that the recitation of “for expressing a functional frataxin (FXN) protein in the heart” in the preamble is interpreted as an intended use of the claimed invention and not a limitation of the claimed invention. “For expressing a functional frataxin (FXN) protein in the heart” does not limit the structure of the claimed invention; therefore, it does not provide significance to the claim construction. See MPEP § 2111.02.II.
Claim Rejections - 35 USC § 103- Maintained, modified due to amendments
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.
Claim(s) 1, 13, 21, 26, 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager (US20180021364A1, published January 25th, 2018) and further in view of McLaughlin (US20170362608A1, published December 21st, 2017).
Regarding claim 1, Voyager teaches a nucleic acid, comprising from 5’ to 3’:
a 5’ inverted terminal repeat (ITR);
a promoter;
a transgene sequence encoding the frataxin (FXN) protein;
one or more polyadenylation signals; and
a 3’ ITR [0396].
Voyager teaches SEQ ID NO: 62, which shares 100% identity with instant SEQ ID NO: 19 (SEQ ID NO: 62 is an AAV construct comprising FXN) (claim 21)[0451].
Because Voyager teaches instant SEQ ID NO: 19, representing the nucleic acid sequence of the FXN transgene, Voyager also inherently teaches instant SEQ ID NO: 65, representing the amino acid sequence of the FXN protein (which the transgene sequence comprises).
Voyager does not teach 5’ ITR and 3’ ITRs comprising sequences at least 95% identical to SEQ ID NO: 1 or SEQ ID NO: 2 respectively.
An Artisan, interested in ITR sequences in engineered polynucleotides, would be aware of McLaughlin for teaching increasing the transduction efficiency and heterologous gene expression of viral particles by altering the Rep nicking sequence found in parvoviral (e.g., AAV) ITR sequences.
McLaughlin also teaches SEQ ID NOs: 67, 73, 70, and 76, which share 100% identity with instant SEQ ID NO: 1, representing a 5’ ITR sequence [0076].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the 5’ ITR sequence taught by McLaughlin for the 5’ ITR sequence in the nucleic acid construct taught by Voyager 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. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, an artisan would have a reasonable expectation for success because replacing one sequence with another has long been done in the molecular biology art and would be routine. One would be motivated to make this substitution because Voyager teaches that the engineered ITR sequences may result in altered Rep binding sequence regions and decreased binding with Rep protein. Voyager teaches that the decrease in Rep binding affects the Rep nicking activity in a manner that promotes the formation of a self-complementary viral genome during replication [0014].
Regarding claim 13, Voyager teaches EF-1 alpha, CMV, CBA, and PGK promoters [0062, 0396, 0406].
Regarding claim 26, Voyager teaches the one or more polyA signals being SV40, rabbit beta-globin, or bovine growth hormone (bGH) [0396].
Regarding claim 44, Voyager teaches a plasmid comprising the nucleic acid of claim 1 [0396].
Regarding claim 45, Voyager teaches a cell comprising the nucleic acids of claim 1 [0390].
Regarding claim 59, Voyager teaches the nucleic acid comprising two polyA signals (i.e., the payload construct of the viral genome comprises at least one element…the element being polyA signal sequences) [0061].
Claim(s) 1, 13, 19, 21, 26, 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of Venditti (WO2016164642A1, published October 13th, 2016).
As shown above, the base claims are obvious over the base art.
Regarding claim 19, Voyager and McLaughlin do not teach a promoter sequence at least 95% identical to SEQ ID NO: 9.
An Artisan, interested in different types of promoters, would be aware of Venditti for teaching EF-1 alpha as a promoter in a nucleic acid construct to express a transgene.
Venditti teaches SEQ ID NO: 8, which shares 100% identity with instant SEQ ID NO: 9, which represents an EF-1 alpha promoter, in a nucleic acid construct (i.e., AAV vector) [0063] (Fig. 11).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the EF-1 alpha promoter sequence taught by Venditti for the EF-1 alpha in the nucleic acid construct taught by Voyager 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. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, an artisan would have a reasonable expectation for success because replacing one sequence with another has long been done in the molecular biology art and would be routine. One would be motivated to make this substitution because as taught by Venditti, the EF-1 alpha promoter sequence is constitutive and can be used in an AAV vector [e.g., 0147].
Claim(s) 1, 13, 21, 22, 26, 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of Bauer (Bauer, Asli Petra et al. “The impact of intragenic CpG content on gene expression.” Nucleic acids research vol. 38,12 (2010): 3891-908.).
As shown above, the base claims are obvious over the base art.
Regarding claim 22, Voyager teaches the transgene being codon optimized, but does not teach the transgene being CpG optimized [0396].
An Artisan, interested in the impact of CpG content on gene expression, would be aware of Bauer for studying the contribution of intragenic CpG content to expression efficiency in transiently and stably transfected mammalian cells.
Bauer teaches a CpG-depleted variant of a humanized version of green fluorescent protein (GFP) by carefully modulating codon usage (Abstract). Bauer teaches that the altered intragenic CpG content influenced de novo transcriptional activity, thus implying a common transcription-based mechanism of gene regulation via CpGs. (Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to apply the teaching of Bauer that CpG content of a gene impacts gene regulation to the nucleic acid construct of Voyager with a reasonable expectation for success. An artisan would have a reasonable expectation for success because CpG optimization is a form of codon optimization, and the transgene of the nucleic acid construct of Voyager can be codon optimized. One would be motivated to apply the teachings of Bauer because as taught by Bauer, optimization of codon usage has therefore substantially encouraged the development of safe lentiviral vectors and highly efficient packaging cell lines for vaccine design (pg. 3892, “Introduction”, para 1).
Claim(s) 1, 13, 21, 24, 26, 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of Lundberg (WO2018002783A1, published January 4th, 2018).
As shown above, the base claims are obvious over the base art.
Regarding claim 24, Voyager teaches nucleic acid constructs comprising a full or partial Kozak sequence [0396]. Voyager and McLaughlin do not teach a Kozak sequence at least 95% identical to instant SEQ ID NO: 17.
An Artisan, interested in modulating translation of FXN such as through Kozak sequences, would be aware of Lundberg for teaching sequences used in the gene editing of the FXN gene, such as through Kozak sequences.
Lundberg teaches SEQ ID NO: 16094, representing a FXN gene editing single-molecule gRNA spacer targeting the upstream region of FXN and Exon 1 (Fxn upstream and Exon1_T59), which shares 100% identity with instant SEQ ID NO: 17 (pg. 126, Table 7).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the Kozak sequence taught by Lundberg for the Kozak sequence in the nucleic acid construct taught by Voyager 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. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, an artisan would have a reasonable expectation for success because replacing one sequence with another has long been done in the molecular biology art and would be routine. One would be motivated to make this substitution because as taught by Lundberg, modifications of polynucleotides, including modifications of 5’ UTRs (i.e., Kozak sequences), are well known in the art and are applied to increase translation or stability or to reduce the tendency of the nucleic acid to elicit an innate immune response [000187, 000191].
Claim(s) 1, 13, 21, 26, 31, 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of CalTech (US2017029848A1, published February 2nd, 2017).
As shown above, the base claims are obvious over the base art.
Regarding claims 26 and 31, Voyager and McLaughlin do not teach a human growth hormone (hGH) polyA signal or instant SEQ ID NO: 22, which represents a nucleic acid sequence of an hGH polyA signal.
An artisan, interested in inducible/activity dependent nucleic acid expression, would be aware of CalTech for teaching AAV vectors comprising nucleic acids encoding a polyadenylation site from sources such as human growth hormone.
CalTech teaches SEQ ID NO: 31, representing a human growth hormone polyadenylation site (hGHpA) (claim 26), which shares 100% identity with instant SEQ ID NO: 22 (claim 31) [0018, 0084].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the hGH polyA signal sequence taught by CalTech for the polyA signal sequence in the nucleic acid construct taught by Voyager 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. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, an artisan would have a reasonable expectation for success because replacing one sequence with another has long been done in the molecular biology art and would be routine. One would be motivated to make this substitution because as taught by CalTech, a hGH polyA signal (i.e., instant SEQ ID NO: 22) can be used in an AAV vector activity-dependent expression system [0018] (Fig. 9).
Claim(s) 1, 13, 21, 26, 32 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of Tremblay (WO2018098587A1, published June 7th, 2018).
As shown above, the base claims are obvious over the base art.
Regarding claim 32, instant SEQ ID NO: 5 represents a nucleic acid sequence for a CBA-MVM hybrid intron. Voyager teaches that the nucleic acid may comprising an enhancer, including a 5’UTR/intron that is composed of CBA-MVM (i.e., CBA - MVM 5' UTR intron) [0077]. However, Voyager is silent on the sequence of the CBA-MVM enhancer with at least 95% identity to SEQ ID NO: 5.
An Artisan, interested in enhancers used in gene editing systems, would be aware of Tremblay for teaching enhancers, such as a CBA hybrid intron, may be used in gene editing system to modify FXN in a cell.
Tremblay teaches SEQ ID NO: 169, representing a CBA hybrid intron (CBH) (a CBA promoter with a hybrid intron composed of a 5’ donor splice site from the CBA 5’ UTR and 3’ acceptor splice site from MVM, which shares 100% identity with instant SEQ ID NO: 5 (pg. 48).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the enhancer (i.e., CBA-MVM intron) sequence taught by Tremblay for the enhancer (i.e., CBA-MVM intron) in the nucleic acid construct taught by Voyager 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. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, an artisan would have a reasonable expectation for success because replacing one sequence with another has long been done in the molecular biology art and would be routine. One would be motivated to make this substitution because as taught by Tremblay, SEQ ID NO: 169 is used in nucleic acid constructs to effectively edit the FXN gene [0078] (Fig. 17).
Claim(s) 1, 13, 21, 26, 35, 36, 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of Kaczmarczyk (WO2002081632A2, published October 17th, 2002).
As shown above, the base claims are obvious over the base art.
Regarding claims 35 and 36, Voyager teaches the nucleic acid construct comprising chimeric introns [0077; 0080]. Voyager and McLaughlin do not teach the nucleic acid further comprising a chimeric intronic sequence at least 95% identical to instant SEQ ID NO: 15.
An Artisan, interested in intronic sequences, would be aware of Kaczmarczyk for teaching intronic sequences used in transgene expression.
Kaczmarczyk teaches SEQ ID NO: 19, representing a human beta-globin intron from cloning vector pCI (pg. 4; pg. 7-8, “Intron Sequence”, pg. 9 “Intron Sequence”). SEQ ID NO: 19 of Kaczmarczyk shares 100% identity with instant SEQ ID NO: 15. Additionally, Kaczmarczyk teaches that SEQ ID NO: 19 is a nucleic acid sequence for a chimeric intron sequence (Genbank Accession No. U47119) (pg. 4, lines 36-37).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to substitute the chimeric intron sequence taught by Kaczmarczyk for the chimeric intron in the nucleic acid construct taught by Voyager 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. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” “When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982).” M.P.E.P. §2144.06.
Further, an artisan would have a reasonable expectation for success because replacing one intron with another has long been done in the molecular biology art and would be routine. One would be motivated to make this substitution because as taught by Kaczmarczyk, the chimeric intron sequence can be used in nucleic acid constructs to express transgenes in eukaryotes (pg. 8, lines 34-38; pg. 41, lines 23- 32; Fig. 5).
Claim(s) 1, 13, 21, 26, 40, 44, 45, and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of Sah (US 20200263199 A1, priority date September 28th, 2018).
As shown above, the base claims are obvious over the base art.
Regarding claim 40, Voyager and McLaughlin do not teach a nucleic acid sequence comprising a stuffer sequence at least 95% identical to instant SEQ ID NO: 26 (representing a stuffer sequence derived from Alpha-1 Antitrypsin, or A1AT).
An Artisan, interested in stuffer sequences, would be aware of Sah for teaching stuffer sequences used in polynucleotides encoding FXN.
Sah teaches AAV particles comprising a polynucleotides sequence encoding FXN ( Sah claim 1). Although Sah does not teach instant SEQ ID NO: 26, Sah teaches that the viral genomes can contain a stuffer or filler sequence, including alpha-1 antitrypsin (A1AT) sequences, and that any known viral mammalian, or plant sequence may be manipulated for use as a stuffer sequence [0119].
It would have been obvious to one of ordinary skill in the art before the effective filing date of the current invention to add the stuff sequence taught by Sah to the nucleic acid construct taught by Voyager to arrive at the claimed invention. One of ordinary skill in the art would understand how to design a stuffer sequence merely using readily available references with which to identify the finite potential options, whereby the ordinary artisan could have pursued the known potential options with a reasonable expectation of success. One would have reasonable expectation for success because including stuffer sequences in vectors are well known in the art in order to maintain optimum vector size, particularly when nucleic acid constructs comprise shorter transgene sequences. It would be only routine experimentation to arrive at an optimal stuffer sequence (i.e., instant SEQ ID NO: 26) to include in a nucleic acid construct.
Claim(s) 1, 13, 21, 26, 43-45, 59, and 62 is/are rejected under 35 U.S.C. 103 as being unpatentable over Voyager and McLaughlin as applied to claims 1, 13, 21, 26, 44, 45, and 59 above, and further in view of Venditti, CalTech, Bauer, Lundberg, Tremblay, Kaczmarczyk, and Sah.
Regarding claims 43 and 62, none of the cited references teach instant SEQ ID NO: 32 (representing a recombinant AAV transfer cassette DNA comprising ITR, promoter, transgene sequence that encodes FXN protein, and polyA signal). However, as discussed above, Voyager teaches that nucleic acid constructs comprising the FXN transgene were well known in the art before the effective filing date of the current invention. Additionally, McLaughlin, Venditti, CalTech, Tremblay, Kaczmarczyk, and Sah teach that the sequences of components of nucleic acid constructs of the current invention, such as 5’ and 3’ ITRs, a Kozak sequence, and introns were well known in the art before the effective filing date of the current invention. Although no references teach a nucleic acid sequence at least 95% identical to instant SEQ ID NO: 32. Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to combine the teachings of Voyager, McLaughlin, Venditti, CalTech, Bauer, Lundberg, Tremblay, Kaczmarczyk, and Sah to arrive at the nucleic acid of the claimed invention (i.e., SEQ ID NO: 32) with a reasonable expectation of success because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipate success, it is likely that product not of innovation but of ordinary skill and common sense.” One of ordinary skill in the art would understand how to design nucleic acid sequences comprising previously known transgene, ITR, promoter, and polyA signal sequences, the artisan merely using readily available references with which to identify the finite potential options, whereby the ordinary artisan could have pursued the known potential options with a reasonable expectation of success. As evidenced by the sequence search results, it would be only routine experimentation to determine which specific ITR, enhancer, promoter, etc. sequences to include in the nucleic acid construct, as all these have been well-known and widely used in the prior art.
Response to Arguments
Applicant's arguments filed 08/08/2025 have been fully considered but they are not persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., AAV9 capsid, AAV serotypes) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Additionally, a recitation of the intended use of the claimed invention (i.e., for expressing a functional frataxin (FXN) protein in the heart) 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. Further, the sequence taught by McLaughlin shares 100% identity with instant SEQ ID NOs: 1 and 2 and therefore reads on the claim limitations.
In response to the Applicant’s argument that there is no expectation of success because the EF1alpha promoter of Venditti is used for treating cholesterol storage diseases, similar to the response above, a recitation of the intended use of the claimed invention (i.e., what disease/disorder is treated) 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. Further, the Applicant fails to provide evidence that the EF1alpha promoter of Venditti would not result in increased expression of FXN.
The Applicant argues that Bauer doesn't provide any guidance on CpG optimization of transgenes or how said optimization may affect expression of transgene, but rather that CpG depletion has clear correlation with decreased levels of newly synthesized mRNA transcripts, and therefore does not elucidate he effects of CpG optimization on transgene expression in nucleic acids. This argument is not convincing because the teachings of Bauer read on the claim language of “CpG optimized”. Bauer teaching that reduction in protein expression is associated with CpG depletion by creating a CpG-depleted variant of a humanized version of GFP (i.e., a transgene), transfecting the variant into CHO 293 cells, which then resulted in significantly decreased GFP reporter activity and detectable protein amounts (Abstracts) provides an artisan sufficient knowledge on how to modify the nucleic acid construct of Voyager to be “CpG optimized”.
The Applicant’s argument that the sequence taught by Lundberg cited as teaching instant SEQ ID NO: 17 has a completely different function and is a different type of molecule. Additionally, the Applicant states that Lundberg is silent on its role as a Kozak sequence. This argument is not convincing because Kozak sequences are typically found upstream of the start codon, which is often located within the first exon (exon 1) of a gene (and Lundberg teaches that SEQ ID NO: 16094 represents a gRNA targeting the upstream region of FXN and Exon 1). With this in mind, an artisan may come to the conclusion that the SEQ ID NO taught by Lundberg could successfully be substituted into Voyager.
The Applicant’s argument that there is no expectation of success because the positioning of the hGH sequence in the rAAV is questionable is not convincing. CalTech teaches that the hGH polyadenylation signal sequence may be at the 5’ end or optionally located at the 3’ end. The location of the hGH sequence is not a claimed limitation. Additionally, CalTech teaching the sequence being present at the 5’ or 3’ end does not render the teachings of CalTech irrelevant. Further, in response to applicant's argument that incorporating the hGH into Voyager would result in unexpected effects, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
The Applicant’s argument that although Tremblay teaches the same sequence, is does not teach its use in connection with FXN expression in cardiac tissue. This argument is not convincing because as stated above, FXN expression in cardiac tissue is not a recited limitations and instead is interpreted to be an intended use of the invention.
The argument that Sah's recitation of A1AT as a non-limiting example of a stuffer sequence amongst a myriad of stuffer sequences means an artisan would not be motivated to choose the A1AT stuffer sequence based on Sah’s disclosure is not convincing. The Applicant fails to distinctly point out why Sah teaching that A1AT can be used as a stuffer sequence in viral genomes is not sufficient. Additionally, the recitation of A1AT as a stuffer sequence is amongst one of two non-limiting examples provided, not a myriad of sequences.
The Applicant’s arguments that no references teach the unexpected effect of the increase in expression in cardiac tissue or the codon optimized SEQ ID NO: 32 is not convincing. As stated in the rejection, SEQ ID NO: 32 is taught by the summation of Voyager, McLaughlin, Venditti, CalTech, Tremblay, Kaczmarczyk, and Sah. Additionally, in response to applicant's argument the claimed invention demonstrates unexpected results, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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/ALLISON MARIE JOHNSON/Examiner, Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
Prosecution Insights