DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Application Status
Applicant’s remarks and amendments to the claims April 14, 2026 are acknowledged. Claims 4, 11, 21, 27, 31, 33-36 were amended, and claims 5-8 were cancelled. Claims 4, 9-12, 14, 21, 27-28, and 31-37 are pending.
Restriction/Election
Claims 10 and 14 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species. Claims 4, 9, 11-12, 21, 27-28, and 31-37 are under examination herein.
Priority
The claims under examination find support in provisional Application No. 62/567,631, filed October 3, 2017. The effective filing date of the claims under examination is October 3, 2017.
Withdrawn Rejections
Applicant’s amendments to claim 11 are sufficient to overcome the § 112(b) rejections over the same. Applicant’s amendments to claim 21 are sufficient to overcome the remaining § 112(b) rejections raised in the prior action. The § 112(b) rejections raised in the prior action are withdrawn.
Applicant’s remarks and amendments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow. Any rejection or objection not reiterated herein has been overcome by amendment.
Claim Objections
Claim 12 is objected to because of the following informalities:
Claim 12 recites that the “isolated exogenous nucleic acid is in a pharmaceutical composition.” It is reasonably clear that the claim intends to require that the subject be delivered a pharmaceutical composition. Based on claim 4, the isolated exogenous nucleic acid is in a lentiviral vector, which is delivered in spheroid, autologous hepatocytes. It would be preferable to amend the claim to recite that the “spheroids are in a pharmaceutical composition,” accordingly.
Appropriate correction is required.
Claim Rejections - 35 USC § 103 – Nyberg in view of Ozawa and Chandler
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 4, 21, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Nyberg (Hickey et al., October 2015, “2. Autologous hepatocyte transplantation after ex vivo gene therapy in a large animal model of metabolic liver disease,” Hepatology, Vol. 62, No. 1, pg. 208A; of record) in view of Ozawa (Ozawa et al., US 2005/0147592 A1, published 7 July 2005; of record) and Chandler (Chandler et al., 2015, The Journal of Clinical Investigation, 125(2), p. 870-880; of record). The rejections that follow are maintained and modified as necessitated by Applicant’s amendments to the claims.
Regarding claims 4, 21, and 27, Nyberg teaches a method of delivering autologous hepatocytes in spheroid form to the liver of a subject via portal vein injection, wherein the autologous hepatocytes comprise a lentiviral vector comprising an isolated exogenous nucleic acid coding for a functional fumarylacetoacetate hydrolase protein (“we tested the hypothesis that ex vivo gene therapy with a lentiviral vector (LV) encoding FAH and autologous hepatocyte transplantation can correct the metabolic disorder in FAH-/- pigs,” “Hepatocytes were transduced with a LV expressing the FAH cDNA under the control of the thyroxine-binding globulin promoter. Pigs received autologous transplants of hepatocytes by portal vein infusion… after 24 hours of LV transduction during 3-dimensional hepatocyte spheroid formation”). Nyberg teaches the method corrects a defective FAH gene in hepatocytes, which treats subjects with hereditary tyrosinemia (“we tested the hypothesis that ex vivo gene therapy with a lentiviral vector (LV) encoding FAH and autologous hepatocyte transplantation can correct the metabolic disorder in FAH-/- pigs,” “Two pigs… indicat[ed] complete amelioration of the HT1 phenotype… demonstrating complete correction of tyrosine metabolism”).
Nyberg teaches that the FAH cDNA in the lentiviral vector was “under the control of the thyroxine-binding globulin promoter,” but does not teach that the FAH cDNA is under control of a human alpha1-antityrpsin (hAAT) promoter operably linked to a hepatic control region enhancer.
Ozawa teaches a method of correcting a defective FAH gene associated with hereditary tyrosinemia type I, by delivering an isolated exogenous nucleic acid substantially identical to that described by Nyberg (“1. A method of delivering a protein to a mammalian subject having an aminoacidopathy, comprising: a) providing recombinant adeno-associated virus (rAAV)… compris[ing] a heterologous gene encoding a metabolic protein involved in amino acid metabolism; b) administering said rAAV virions… wherein said administering results in transduction of at least one cell…” “5... wherein said aminoacidpathy is hypertyrosinemia. 6… wherein said hypertyrosinemia is tyrosinemia type I.” “13… to the liver of said mammalian subject”, pg. 13; “Tyrosinemia type I is an inherited disorder of tyrosine metabolism associated with deficient activity of fumarylacetoacetate hydrolase”, [0050]; [0041]-[0044]; [0048]-[0057]). Ozawa teaches that expression from the nucleic acid is driven by a liver-specific promoter, which in an especially preferred embodiment is the human alpha1-antitrypsin (hAAT) promoter operably linked to a hepatic control region (“In an especially preferred embodiment, the HAAT promoter is operably linked to an apolipoprotein E hepatic control region”, [0027]). Ozawa teaches that the apolipoprotein E hepatic control region is “an enhancer element useful for increasing gene expression in the liver” ([0040]).
Chandler teaches that mice delivered viral vectors (“AAV vectors”) carrying a therapeutic gene expressed under control of the TBG promoter develop hepatocellular carcinoma (HCC)(Fig. 5A; “Our results (Figure 5A and Table 1) and those previously reported document HCCs in mice after receiving AAV vectors carrying the TBG… promoter”, pg. 874). Chandler teaches that the hAAT promoter, in contrast, is not associated with HCC, likely because the hAAT promoter did not lead to overexpression of genes local to the integration site (pg. 877, right col.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the regulatory element operably linked to the FAH cDNA of Nyberg, for a human AAT promoter and hepatic control region enhancer taught by Ozawa and Chandler. It would have amounted to a simple substitution of known liver-specific regulatory elements, by known means, to yield predictable results. A skilled artisan would have had a reasonable expectation of success in substituting the elements because Ozawa teaches a substantially identical method and isolated exogenous nucleic acid to that of Nyberg, in which the therapeutic metabolic gene, FAH, is most preferably expressed in the liver under control of an human AAT promoter and hepatic control region enhancer. Because Ozawa teaches that the hepatic control region is “an enhancer element useful for increasing gene expression in the liver,” and Chandler teaches that the hAAT promoter, in contrast to the TBG promoter used by Nyberg, is not associated with HCC, a skilled artisan would have been motivated to substitute the regulatory element operably linked to the FAH cDNA of Nyberg, for a human AAT promoter operably linked to a hepatic control region enhancer.
Claim Rejections - 35 USC § 103 – Nyberg, Ozawa, and Chandler, in further view of Hickey
Claims 12, 28, and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Nyberg (Hickey et al., October 2015, “2. Autologous hepatocyte transplantation after ex vivo gene therapy in a large animal model of metabolic liver disease,” Hepatology, Vol. 62, No. 1, pg. 208A; of record), Ozawa (Ozawa et al., US 2005/0147592 A1, published 7 July 2005; of record) and Chandler (Chandler et al., 2015, The Journal of Clinical Investigation, 125(2), p. 870-880; of record) as applied to claims 4, 21, and 27 above, in further view of Hickey (Hickey et al., 27 July 2016, Science Translational Medicine, 8(349), p. 1-10, and Supplementary Materials; of record). The rejections that follow are maintained and modified as necessitated by Applicant’s amendments to the claims.
The teachings of Nyberg, Ozawa, and Chandler are described above and applied as to claims 4, 21, and 27 therein.
Hickey teaches a substantially identical method to Nyberg, in which a defective FAH gene in hepatocytes of the liver of a subject are corrected in an effort to treat a patient with hereditary tyrosinemia (Abstract; Fig. 1A-B; Fig. 2A). Hickey’s method also involves delivering autologous hepatocytes comprising a lentiviral vector encoding a functional fumarylacetoacetate hydrolase via portal vein injection (Fig. 2A-B; “A total of four Fah-/- pigs underwent ex vivo gene therapy… Hepatocytes were transduced with… LV-Fah”, pg. 3, right col.; “the pig Fah cDNA was cloned into the TBG vector… to produce the LV-TBG-Fah expression construct”, Methods: LV production, Supplementary Materials; “After LV transduction, between 350 and 864 million live cells were injected through the portal vein or using ultrasound guidance to inject hepatocytes percutaneously,” pg. 3, right col.). Like Nyberg, Hickey teaches that FAH expression was restored in hepatocytes of recipient porcine subjects (“In contrast to the nontransplanted Fah-/- pig (L768), robust FAH expression was detected in Y707 and Y846,” pg. 4, right col.; Fig. 3B-C).
Regarding claims 12 and 31, Nyberg teaches the autologous hepatocyte spheroids were delivered via portal vein injection, but does not teach that the delivery form was in a pharmaceutical composition.
However, Hickey teaches means to deliver autologous hepatocytes via portal vein injection (“Hepatocyte isolation, transduction, and transplantation,” pg. 8, right col.). Hickey teaches the hepatocytes are suspended in saline prior to transplantation (“hepatocytes were resuspended in saline… and transplanted through portal vein infusion,” pg. 8, right col.).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have delivered the autologous hepatocyte spheroids in the method rendered obvious above in a pharmaceutical composition in view of Hickey. It would have amounted to delivering known hepatocyte spheroids in a known composition suitable for portal vein injection, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in delivering the autologous hepatocyte spheroids in saline as taught by Hickey because Nyberg’s and Hickey’s methods are substantially identical in design and function, and Hickey’s method successfully delivers hepatocytes via portal vein injection. The skilled artisan would have been motivated to deliver the autologous hepatocyte spheroids as taught by Hickey because Nyberg’s methodology is generic, and Hickey provides a detailed methodology to achieve transplantation of autologous hepatocytes in a substantially identical method to Nyberg’s.
Regarding claims 28 and 32, Nyberg’s description of the lentiviral vector is relatively generic, and does not teach the additional elements of the lentiviral vector or their orientation therein required of claims 28 and 32.
However, as stated above, Hickey teaches a substantially identical lentiviral vector to Nyberg’s, which is used for the same purpose. Hickey describes each element of the lentiviral vector and their orientation therein (Fig. 1A). Hickey’s lentiviral vector matches the elements and orientation required of claims 28 and 32.
It would have been obvious to one of ordinary skill in the art before the effective filing date to have prepared the lentiviral vector used in the method rendered obvious above with the additional elements and orientation of the lentiviral vector of Hickey. It would have amounted to preparing an obvious lentiviral vector with elements and orientation of a substantially identical vector for the same purpose, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in preparing the lentiviral vector rendered obvious above as taught by Hickey because Nyberg’s and Hickey’s methods are substantially identical in design and function, and both employ a lentiviral vector encoding a FAH cDNA. The skilled artisan would have been motivated to prepare the lentiviral vector rendered obvious above as taught by Hickey because Nyberg’s lentiviral vector is set forth generically, and Hickey provides a detailed description of the additional functional elements of a lentiviral vector encoding FAH cDNA used in a substantially identical method to Nyberg’s.
Claim Rejections - 35 USC § 103 – Nyberg, Ozawa, and Chandler, in further view of Hickey as evidenced by NIH
Claims 9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Nyberg (Hickey et al., October 2015, “2. Autologous hepatocyte transplantation after ex vivo gene therapy in a large animal model of metabolic liver disease,” Hepatology, Vol. 62, No. 1, pg. 208A; of record), Ozawa (Ozawa et al., US 2005/0147592 A1, published 7 July 2005; of record) and Chandler (Chandler et al., 2015, The Journal of Clinical Investigation, 125(2), p. 870-880; of record) as applied to claims 4, 21, and 27 above, in further view of Hickey (Hickey et al., 27 July 2016, Science Translational Medicine, 8(349), p. 1-10, and Supplementary Materials; of record) as evidenced by NIH (“Child,” NIH Grants & Funding Glossary, https://grants.nih.gov/grants/glossary.htm#C, accessed 24 May 2026). The rejections that follow are new and necessitated by Applicant’s amendments to the claims.
The teachings of Nyberg, Ozawa, and Chandler are described above and applied as to claims 4, 21, and 27 therein.
Regarding claims 9 and 11, Nyberg teaches that their model “closely resembles the human phenotype,” and their method demonstrates “the feasibility and efficacy of ex vivo gene therapy” for hereditary tyrosinemia type I.
Nyberg does not teach a method in a human subject which is “an infant or 1 year old to 18 years old,” which is interpreted as encompassing human subjects between birth to 18 years of age.
However, as described above, Hickey teaches a substantially identical method to Nyberg, in which a defective FAH gene in hepatocytes of the liver of a subject are corrected in an effort to treat a patient with hereditary tyrosinemia (Abstract; Fig. 1A-B; Fig. 2A). Hickey teaches use of the method for human “children” (“pediatric patients with inborn errors of metabolism in the liver are most likely to benefit from the significant advantages of ex vivo LV gene therapy”, “we believe that ex vivo hepatocyte gene therapy with LV will provide a lasting impact for the treatment of inborn errors of metabolism of the liver in children before their disease has a change to reach an advanced stage”, pg. 8, left col.).
Hickey does not teach the specific age range which applies to the term “children.” However, as evidenced by the NIH Glossary, the skilled artisan would understand the term “children” to refer to human subjects under 18 years of age, i.e., encompassing birth to 18 years of age (“For the purposes of the NIH Policy and Guidelines on the Inclusion of Individuals Across the Lifespan as Participants in Research Involving Human Subjects, a child is defined as an individual under the age of 18 years”).
It would have been obvious to one of ordinary skill in the art before the effective filing date to have substituted the porcine subject in the method rendered obvious above, for a human subject from birth to 18 years of age in view of Hickey as evidenced by NIH. It would have amounted to a simple substitution of two subjects amenable to the method based on the prior art, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in substituting the subjects based on the success of Nyberg’s and Hickey’s methods in mammalian subjects, and particularly because Nyberg teaches that their model “closely resembles the human phenotype.” The skilled artisan would have been motivated to substitute the subjects because Hickey teaches that human pediatric patients or children are the group “most likely to benefit from the significant advantages of ex vivo LV gene therapy,” because it has the potential to treat their disease before it reaches an advanced stage.
Claim Rejections - 35 USC § 103 – Nyberg, Ozawa, and Chandler, in further view of GenBank
Claims 33-37 are rejected under 35 U.S.C. 103 as being unpatentable over Nyberg (Hickey et al., October 2015, “2. Autologous hepatocyte transplantation after ex vivo gene therapy in a large animal model of metabolic liver disease,” Hepatology, Vol. 62, No. 1, pg. 208A; of record), Ozawa (Ozawa et al., US 2005/0147592 A1, published 7 July 2005; of record) and Chandler (Chandler et al., 2015, The Journal of Clinical Investigation, 125(2), p. 870-880; of record) as applied to claims 4, 21, and 27 above, in further view of GenBank (Homo sapiens cDNA, FLJ94596, Homo sapiens fumarylacetoacetate hydrolase (fumarylacetoacetase)(FAH), mRNA, GenBank: AK313951.1, available 24 May 2008; of record). The rejections that follow are maintained and modified as necessitated by Applicant’s amendments to the claims.
The teachings of Nyberg, Ozawa, and Chandler are described above and applied as to claims 4, 21, and 27 therein. Nyberg teaches that their method “closely resembles the human phenotype,” and demonstrates “the feasibility and efficacy of ex vivo gene therapy” for hereditary tyrosinemia type I.
None of Nyberg, Ozawa, or Chandler teach a human functional fumarylacetoacetate hydrolase protein (claim 33), that the nucleotide sequence encoding the protein comprises SEQ ID NO: 8 (claims 34-35), or that the encoded protein comprises SEQ ID NO: 9 (claims 36-37).
GenBank teaches a nucleotide sequence encoding a human functional fumarylacetoacetate hydrolase protein, which as shown in the alignments of record comprises 100% identity to SEQ ID NO: 8. In addition, GenBank teaches the protein sequence encoded by the nucleotide sequence (“/translation= “MSF…”). As shown in the alignment of record, the protein sequence disclosed by GenBank is 100% identical to SEQ ID NO: 9.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted the generic FAH cDNA of Nyberg for the human FAH cDNA of GenBank. It would have amounted to a simple substitution of a generic FAH cDNA for a known, human FAH cDNA, by known means to yield predictable results. The skilled artisan would have had a reasonable expectation of success in substituting the two FAH cDNAs because they encode the same protein, and therefore, the skilled artisan would expect that the sequence disclosed by GenBank, when encoded in the lentiviral vector, would have the same effect as the FAH cDNA of Nyberg. Because Nyberg teaches the method is feasible and efficacious for treatment of hereditary tyrosinemia type I, a disease in humans, the skilled artisan would have been motivated to substitute the two FAH cDNAs in an effort to further develop the therapy for use in human subjects.
Response to Remarks - 35 USC § 103
Applicant’s remarks regarding the prior art rejections raised in the prior action have been reviewed. First, Applicant asserts that the skilled artisan would not have been motivated to replace Nyberg’s TBG promoter with the recited promoter-enhancer combination, nor had a reasonable expectation of success, because Ozawa’s teaching is prophetic and “provides no evidence to support the [] claim” that a human AAT promoter and hepatic control region enhancer are “most preferabl[e],” and because Ozawa’s examples do not illustrate successful use of the claimed elements in combination (i.e., a lentiviral vector, FAH transgene, hAAT promoter, or spheroid culturing).
These remarks are not found convincing. There is no requirement for Ozawa to illustrate successful use of the claimed elements in combination in order to make a prima facie case of obviousness. Nyberg teaches each element of instant claims 4, 21, and 27, save the use of the specifically recited promoter/enhancer combination. Applicant also has not provided any evidence to support that there would be no reasonable expectation of success in substituting the regulatory elements in Nyberg’s lentiviral vector, with Ozawa’s regulatory elements. Ozawa teaches that a human AAT promoter and hepatic control region enhancer is an “especially preferred embodiment” for promoting transgene expression in the liver, in a method substantially identical to Nyberg’s. Applicant provides no evidence that the skilled artisan would have sought out “evidence” to support this statement of preference. Furthermore, as described in the previous response to remarks, the ordinarily skilled artisan at the time of filing would have had substantial understanding of viral vectors used for therapeutic purposes, and the elements necessary and/or advantageous for use in such vectors, e.g., liver-specific promoters and enhancers. This is clearly established by at least Ozawa, Chandler, and Hickey, each of which teach viral vectors comprising various regulatory elements, including the specific promoter and enhancer combination specifically claimed. Thus, the use of a hAAT promoter and hepatic control region enhancer in a viral vector was not new in the context of hereditary tyrosinemia, as evidenced by at least the cited art. The skilled artisan also would have been familiar with use of an hAAT promoter and hepatic control region enhancer for expressing a transgene from a lentiviral vector, e.g., as described by Nash (Nash et al., The Journal of Gene Medicine, 2004, 6: 974-983), which is cited herein solely to respond to Applicant’s arguments that the skilled artisan would have had no expectation of success in making the substitution (“The results presented demonstrate that the hAAT promoter/ApoE enhancer system is capable of directing gene expression in hepatocytes…,” pg. 978, right col.; Fig. 1). The skilled artisan would have understood that a TBG promoter and the recited promoter-enhancer combination have the same purpose, regardless of viral vector type (i.e., regulating expression of a desired transgene). The skilled artisan would have had sufficient skill to prepare a lentiviral vector with the recited promoter-enhancer combination as evidenced by the prior art. Beyond argument, Applicant does not present any evidence that teaches or suggests that the skilled artisan would not have predicted success in substituting a TBG promoter for the recited promoter-enhancer combination in a lentiviral vector.
Applicant also asserts that Chandler’s teachings relate to AAV vectors, not lentiviral vectors, which Applicant asserts “are not interchangeable and do not predict the success of each other.” In support of this argument, Applicant asserts that AAV vectors do not integrate into the host genome, whereas lentiviral vectors do integrate. Applicant appears to attempt to draw a contrast between AAV vectors, for which there is “promoter-dependent risk,” and lentiviral vectors, which Applicant asserts are “more influenced” by SIN LTR designs and “the relationship between the strength of the internal promoter and/or enhancer.” Applicant cites Cesana et al., as finding that “a stronger promoter/enhancer led to increased risk of activating oncogenes near integration sites, leading to higher genotoxicity” of lentiviral vectors. Applicant also asserts, without evidence, that “TBG and hAAT are considered to have comparable strength levels for use in liver-specific gene expression.” Applicant also cites various differences between lentiviral vectors and AAV vectors, e.g., their “payload size limits, immunogenicity, and target cell types,” and cites Vandendriessche et al., as finding that AAV and lentiviral vector-based gene therapy results in different magnitudes of therapeutic expression and immune consequences. Applicant also cites Nathanson et al., as describing “variations in the levels of expression and immunological outcomes… with respect to promoters and vector type usage.”
As described in the prior response to remarks, the skilled artisan, having substantial knowledge of viral vectors used for therapeutic purposes, would have understood that Chandler’s teachings were relevant to Nyberg’s lentiviral vectors, because lentiviral vectors and AAV vectors both integrate into the genome. Applicant’s assertions that AAV vectors do not integrate into the genome are directly contradicted by the teachings of Chandler and the prior art cited by Applicant (see, for example, Nathanson et al., pg. 2, left col.). Applicant’s attempts to draw a contrast between AAV vectors and lentiviral vectors are also not successful; Applicant’s remarks and citations clearly identify that, as Chandler teaches for AAV vectors, a lentiviral vector’s regulatory element(s) influences the risks of activating oncogenes near integration sites. Applicant’s arguments, in effect, support that the skilled artisan would have understood that the teachings of Chandler with respect to the use of regulatory elements in AAV vectors would have also applied to the use of regulatory elements in lentiviral vectors, because both vector types integrate into the genome, and may, therefore, cause genotoxic effects. Indeed, Hickey specifically references the work of Chandler in this context: “further work to test genotoxicity of LV in human hepatocytes is required before initiation of any clinical trials, particularly given the recent data on genotoxicity of other viral vectors, including AAV, in inducing hepatocellular carcinoma in rodent models (40),” wherein reference “40” corresponds to Chandler (pg. 8, left col.). Given that Chandler teaches that the hAAT promoter, in contrast to the TBG promoter used by Nyberg, is not associated with hepatocellular carcinoma (HCC), and Ozawa teaches a substantially identical method to Nyberg’s, in which the recited promoter-enhancer combination is an “especially preferred embodiment,” the skilled artisan would have had motivation to substitute Nyberg’s TBG promoter for the recited promoter-enhancer combination in a lentiviral vector.
Applicant’s remarks that AAV vectors and lentiviral vectors are not interchangeable, or have various art-recognized differences are also not found convincing. Nyberg teaches each element of instant claims 4, 21, and 27, save the use of the specifically recited promoter/enhancer combination. The rejections of record, which are maintained above, do not substitute one vector type, for another vector type, and therefore the remarks alluding to such a substitution are not persuasive. The rejections of record, which are maintained above, substitute one known regulatory element, for another known regulatory element. The content of Nathanson et al. has been reviewed, accordingly. Nathanson does not provide any guidance which is relevant to the specifically claimed regulatory elements; Nathanson pertains to the use of AAV vectors and lentiviral vectors in inhibitory neurons, with different regulatory elements from those claimed. As stated above, and in the prior response to remarks, the ordinarily skilled artisan would have had substantial understanding of viral vectors used for therapeutic purposes, and the elements necessary and/or advantageous for use in such vectors, e.g., liver-specific promoters and enhancers. The skilled artisan would have understood that a TBG promoter and the recited promoter-enhancer combination have the same purpose, regardless of viral vector type (i.e., regulating expression of a desired transgene). The skilled artisan would have had sufficient skill to prepare a lentiviral vector with the recited promoter-enhancer combination. Beyond argument, Applicant does not present any evidence that teaches or suggests that the skilled artisan would not have predicted success in substituting a TBG promoter for the recited promoter-enhancer combination in a lentiviral vector.
Taken together, Applicant’s remarks are not sufficient to overcome the rejections above.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/JENNA L PERSONS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
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