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 .
This Action is in response to the papers filed November 14, 2025.
Claims 1-3, 5-13, and 21-27 are currently pending in the application. Claims 1 and 3 are amended, claims 4 and 14-20 are cancelled, and claims 21-27 are newly added. Claims 1, 15 and 20 is independent.
Therefore, claims 1-3, 5-13, and 21-27 are examined on the merits.
Priority
The present application is a CIP of US Application 17/592,803 filed February 4, 2022 and US Application 16/272,956 filed February 11, 2019 (now ABN).
Applicant’s claim for the benefit of a prior-filed parent provisional applications 63/305,836 filed 02/02/2022, 63/188,652 filed 05/14/2021, 63/146,538 filed 02/05/2021, and 62/723,469 filed 08/27/2018 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is August 27, 2018.
Response to arguments
Withdrawn objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112(d)
The rejection of claims 3 and 18 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends is withdrawn.
Applicant’s arguments and amendments filed 11/14/2025 have been considered and are persuasive regarding the rejection as previously set forth. Particularly, Applicant has amended to broaden the scope of the independent claims to encompass the dependent claim, and canceled claim 18.
Maintained objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 112(b)
Claims 1-3, 5-13 remain rejected and new claims and 21-27 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.
Claim 1 has been amended to recite “collecting a lysate from the cell culture” . The practitioner in the art would readily understand that a lysate requires lysis of a cell content as a result of lytic enzymes. It is unclear how transfecting the viral vector into a cell culture as required in amended claim 1 results in a lysate that can be collected. As such the metes and bounds of the claim are indefinite.
Claim 1 recites the term “and/or” in line 4. It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only TERT, or all of the genes, or, “or” would imply that the gene types are in the alternative. Appropriate correction is requested.
Claim 21 recites the term “and/or” in line 2. It is unclear what the metes and bounds of this term, as “and” could be interpreted to include only a KL gene, or all of the genes, or, “or” would imply that the gene types are in the alternative. Appropriate correction is requested.
Claims 25 and 26 have “and/or” conjunctions. This renders the metes and bounds indefinite as it is unclear whether the options are in the alternative or both are required in the claims. For instance, in claim 26, would the same amount of vector administered result in both the telomerase and follistatin serum level or would only one be effected as claimed.
Appropriate correction is required.
Claims 1-3, 5-13, and 22-27 are also included in the rejection as they directly or indirectly depend on claim 1.
Claim Rejections - 35 USC § 112 (a)
Claims 1-3, 5-13 remain rejected and new claims and 21-27 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.
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/14/2025.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The claims are directed towards the vast genus of a human cytomegalovirus (CMV encoding for hTERT or FST at any dosage.
The specification only provides for a list of donor genes wherein two or three of the select donor genes are utilized within the vector (para. 0032, 0054, 00116). The Examples themselves are directed towards gene therapy with MCMV TERT and/or FS344/FST (Example 3, para. 00186).
The specification only discloses 1x105 CFU/mouse as a “therapeutic amount” (Example 3).
Tang (Sci Adv. 2020 May 8;6(19):eaaz7492) teaches that the FST gene therapy through tail vein administration of AAV vectors prevents obesity, metabolic disease, loss of muscle function and post-traumatic osteoarthritis (Abstract). 5 × 1012 to 1.5 × 1013 vector copies/ml. AAV was delivered at a final dose of 5 × 1011 vg per mouse by intravenous tail injection under red light illumination at 9 weeks of age. This dose was determined on the basis of our previous studies showing that AAV9-FST gene delivery by this route resulted in a doubling of muscle mass at a dose of 2.5 × 1011 vg in 4-week-old mice or at 5 × 1011 vg in 8-week-old mice (p. 9, 1st paragraph). This is not a list encompassing any and all age related diseases and showing efficacy at any dosage amount.
Post filing art by inventors Jaijyan (PNAS 2022 pp. 1-7; IDS Reference filed 11/21/2025) provides support for gene therapy within mice, by administrating an intranasal and injectable gene therapy of MCMV carrying exogenous TERT or FST to extend longevity in a mouse model (abstract). (MCMVTERT or MCMVFST) .
Thus, it is immediately apparent to the ordinary artisan that the instant claims are vastly broader in scope to Applicant’s actual invention of administering CMV vector comprising FST344 or hTERT at a dosage of 1 x 105 CFU/mouse via intraperitoneal or intranasal administration (para. 0145) for encompassing any dosage to achieve a therapeutic effect. The specification as filed does not provide any support for gene therapy using a human cytomegalovirus comprising one or more donor genes including FST344 or TERT for a genus of mammalian subjects including a human subject. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”).
Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004)
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Therefore, independent claims 1-3, 5-13, and 22-27 and their dependent claims are rejected as lacking adequate written description.
Response to Applicants’ Arguments as they apply to rejection of claims 1-3, 5-13, and 22-27 under 35 USC § 112 (a)
Applicants’ Arguments filed 11/14/2025 have been considered, however they are not persuasive.
Applicant points to the examples 4, 5, 8, 10, 11, 13, and 14 in order to demonstrate that . Applicant had full possession of the scope of the claims. Addtionally, regarding the dosage amount, it is argued that the MPEP states that "it is not necessary to specify the dosage or method of use if it is known to one skilled in the art that such information could be obtained without undue experimentation." (MPEP 2164.01(c)). “Here, it is well within the capabilities of the skilled person to determine a dose that provides one or more of the recited effects.”
“Moreover, the dependent claims recite additional dosage details such as a dosage of at least 1x105 PFU (claim 27; see Example 3 of the Application), according to fold increases in mRNA markers (claim 26; see Example 7 of the Application), or according to plasma concentrations of follistatin and/or telomerase (claim 25; see Example 9 of the Application). Carrying out tests such as determining plasma concentration is routine and well within the capabilities of the skilled person and the specification thus demonstrates that the inventors had possession of the dosage features of the claims.”
Examiner disagrees that the scope of independent claim 1 has adequate written description. First, all examples are for mouse models, not for human therapy which is encompassed by the broad genus of “mammalian subject.” This is additionally supported by Jaijyan above which demonstrates effective therapy within mice. Second, as Tang demonstrates, and the Examples show, certain dosage ranges are required to effectively carry out the claimed therapy. Although dependent claims recite additional dosage details, the independent claim still encompasses any amount.
Claim Rejections - 35 USC § 103
Claims 1-3, 7 and 11 remain rejected and claims 22 and 25-27 are newly rejected under 35 U.S.C. 103 as being unpatentable over Mendell (Molecular Therapy Vol. 25 No 4 April 2017) in view of Mendez (Medical Microbiology and Immunology (2019) 208:349–363; IDS Reference), Morabito (Mucosal Immunology volume 10, pages 545–554 (2017)) and Warden (Journal of Biomedicine and Biotechnology Volume 2011, Article ID 124595, 16 pages)
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/14/2025.
Regarding claim 1 and 3, Mendell teaches a method for treating sporadic inclusion body myositis which affects subjects most commonly after the age of 50 (i.e. age-related disease) (Abstract, p. 870, 1st column). Subjects 50 years of age or older at the time of disease onset were injected directly with a recombinant rAAV1 vector comprising human follistatin 344 (FS344) for gene transfer (p. 871, 1st column).
However Mendell does not teach administration of FS344 in a HCMV viral vector.
Mendez teaches that human cytomegalovirus (HCMV) has desirable qualities in developing vectors such as a large genome of CMVs allowing the insertion of multiple foreign genes, since more than 50 kb can be removed from human CMV (HCMV) without affecting virus replication (p. 350, 1st paragraph). Additionally, CMV vectors can persist lifelong within their host and are a safer alternative due to the oncogenic potential of lentiviruses (p. 350, 2nd paragraph).
Based on such teachings, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize a human recombinant CMV viral vector as taught by Mendez in order to express the FS344 and hTERT gene as well as other anti-aging genes in vivo with a reasonable expectation of success. Mendez teaches that human CMV viral vectors have desirable qualities such as allowing insertion of multiple foreign genes and are a safer alternative to other known viral vectors (p. 350, 1st-2nd paragraph). Therefore, the anti-aging genes would be expressed by the human recombinant CMV viral vector a when administered to a subject or cell.
The combined teachings of Mendell and Mendez do not teach intranasal administration of the viral vectors.
Morabito teaches administration of CMV viral vectors via both intranasal and intraperitoneal administration (Abstract).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to administer the HCMV vector encoding FS344 as taught by the combination of Mendell and Mendez, via an intranasal route as taught by Morabito with a reasonable expectation of success. As discussed above, Morabito demonstrates that CMV viral vectors are known in the art to be administered via both intranasal and intraperitoneal administration. Therefore, an artisan would be motivated to utilize intranasal administration of the HCMV vector encoding FS344.
Neither Mendell, Mendez or Morabito teach the limitations of how the CMV vector is made with FS344 via inserting the gene cassette into a cloning vector/plasmid and transfecting the cloning vector into a bacterial cell via a cell lysate.
Warden teaches that ever since the creation of the first herpesvirus bacterial artificial chromosome (BAC) mutant (for murine cytomegalovirus, MCMV) over a decade ago, mutagenesis using BAC technology has been proven to be an invaluable tool for studying herpesvirus pathogenesis (p. 1-2, bridging paragraph). BACs are especially useful for studying herpesviruses because the DNAs of these viruses are too large to be cloned in individual plasmids or cosmids (p. 2, 1st column). Moreover, large amounts of the BAC DNA can be produced in bacterial cells before transfection into mammalian cells. Since the large herpesvirus genome is difficult to transfect, the ability to produce large amounts and high quality of viral BAC DNA has been a very useful development that has significantly aided the study of herpesvirus pathogenesis (p. 3). The process is outlined in the context of the production of the HCMV BAC in Figure 1 (page 5).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to produce the CMV vector of Mendell, Mendez and Morabito via utilizing the process detailed by Warden wherein the gene cassette is inserted into a plasmid which is then transfected into a bacterial cell with a reasonable expectation of success. An artisan would have been motivated to do so as Warden teaches this method is known in the art, and that BAC technology is an invaluable tool for studying pathogenesis of herpes viruses (CMV) and that large amounts of BAC DNA can be produced in bacterial cells before transfection into mammalian cells. Regarding the limitation of a cell lysate, athough not explicitly stated, it would have been obvious to obtain the viral vectors from the cell culture solution which would be in cell lysate form.
Regarding the limitations of wherein the recombinant CMV viral vector provides the subject one or more of increased glucose tolerance, decreased glycosylated hemoglobin, increased telomere length, reduced age- related hair loss, increased resistance to loss in body weight, increased mitochondria in skeletal muscle, increased mitochondria in heart muscle, or an increase in markers of autophagy, as each and every method step and limitation is rendered obvious by the combination of Mendell, Mendez and Morabito and Warden, the same method steps would yield the same predictable results with a reasonable expectation of success.
Regarding claim 2, as discussed above, the combined teachings of Mendell, Mendez and Morabito, teach administering CMV vectors intranasally.
Regarding claim 7, Mendell teaches that the vector comprises huFS344 (i.e. hFS344) (p. 871, 1st column).
Regarding claims 11, Mendell teaches that FS344 is administered to humans (p. 872, 1st column).
Regarding claim 22, the combined teachings of Mendell, Mendez, Morabito, and Warden render obvious claim 1. Moreover, Mendell states that the intermediate early promoter/enhancer of CMV is utilized (p. 875, 1st paragraph). Therefore, it is interpreted that the IE1 gene is utilized and therefore the gene is fused to said native CMV gene.
Regarding claim 25 and 26, the combined teachings of Mendell, Mendez, Morabito, and Warden render obvious claim 1. As each and every method step and claimed dosage is taught by the combination, the same method steps would yield the same predictable results with a reasonable expectation of success. Thus, an artisan would expect the serum levels and mRNA increase to be the same.
Regarding claim 27 the combined teachings of Mendell, Mendez, Morabito, and Warden render obvious claim 1. Moreover, Morabito teaches administering 6 x 105 PFU M-CMV eitgher intranasally or intraperitoneally (Figure 1).
Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
In response to Applicant’s arguments and amendments regarding the 103 rejection over Mendell and Mendez,
Applicant’s arguments and amendments which provide new limitations such as dosage have necessitated a new grounds of rejection. The maintained rejection has been modified by Bongard to address the limitations.
In response to applicant's argument that Mendez contemplates vaccine vectors and not gene therapy vectors, 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). Examiner has previously stated that by Applicant’s own admission, the faults of the CMV vectors make them promising candidates for gene therapy (Remarks filed 11/14/2025, p. 8, 2nd paragraph), therefore an artisan would have been motivated to utilize such a vector for the inclusion of additional genes such as hTERT, hFST, KLOTHO, Dsup, PGC1α and others and this would not teach away from utilizing CMV vectors in gene therapy. Upon responding to this, Applicant argues impermissible hindsight in citing findings in arguments. Examiner merely is utilizing the arguments to underscore a point. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). The rejection is not merely based on Applicant’s disclosure. The rejection is based on the properties that would lead one of ordinary skill to modify Mendell with Mendez’s concept due to advantageous properties. While Applicant argues that their intended use is different, this does not teach away when considering their advantageous properties outlined in the rejection. In relation to Applicants’ arguments that “While a strong induction of cytotoxic T cells is beneficial in the context of a vaccine, cytotoxicity against transduced cells can significantly limit the effectiveness of gene therapy” (page 10 of Applicants’ remarks, last paragraph), it is noted that to be given substantial weight in the determination of obviousness or nonobviousness, evidence of secondary considerations must be relevant to the subject matter as claimed, and therefore the examiner must determine whether there is a nexus between the merits of the claimed invention and the evidence of secondary considerations. Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 305 n.42, 227 USPQ 657, 673-674 n. 42 (Fed. Cir. 1985). The term “nexus” designates a factually and legally sufficient connection between the objective evidence of nonobviousness and the claimed invention so that the evidence is of probative value in the determination of nonobviousness. Demaco Corp. v. F. Von Langsdorff Licensing Ltd., 851 F.2d 1387, 7 USPQ2d 1222 (Fed. Cir. 1988). See M.P.E.P. § 716.01(b).
Furthermore, Applicants’ opinion is unsupported by any specific or real evidence, while the options of the skill in the art are given respectful consideration, in the absence of any actual evidence of “unexpected results”, the opinions of the inventor do not overcome a case of prima facie obviousness. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration.
In this case, Examiner has provided post filing art of Tsaregorodtseva et al. (Int. J. Mol. Sci. 2025, 26, 5224) in the PTO-892 highlighting the unpredictability of gene therapy in relation to formation of nAbs against AAV vectors based on crossreactivity to different wild-type AAV serotypes (page 3, para 1), activation of immune responses to the gene themselves (“therapeutic genes themselves can trigger immune responses that significantly impact their efficacy and safety”) (page 7, para 3), induction of Abs based on prior exposure to a similar virus or gene (page 7, para 8; page 8, para. 5), initial response relative to repeated administration of viral vectors (page 2, para 2) among others. Thus, in contrast to Applicant’s remarks, the nature of raising neutralizing antibodies that could significantly limit the effectiveness of gene therapy of transduced cells is a complex process that would not teach away from Mendell's intended purpose of reduced fibrosis after follistatin gene therapy. Furthermore, Applicant’s argument that the “suggestion of prior art” would not have led someone to utilize the CMV vector in Mendell’s method and teaches away is not persuasive. Again, it is reiterated that there is a suggestion in CMV’s advantageous properties in gene therapy.
Claims 6, 9, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Mendell (supra) in view of Mendez (supra), Morabito (supra) and Warden (supra) as applied to claims 1 and 15 above and in further view of de Jesus (EMBO Mol Med. 2012 Aug; 4(8): 691–704; IDS Reference).
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/14/2025.
As discussed in the above 103 rejection, Mendell, Mendez, Morabito and Warden teach a method of treatment via direct injectable administration of CMV viral vectors comprising human FS344 as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
However, Mendell, Mendez, Morabito and Warden do not teach TERT is utilized within the CMV vector as recited by claims 6 and 9 in combination with hFS344.
De Jesus teaches an AAV vector encoding mTERT which resulted in delays in ageing in mice, increasing median and maximum longevity (p. 692, 2nd column, Figure 3).
Based on such teachings, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to express mTERT in addition to the anti-aging hFS344 gene within the vector of Mendell in vivo with a reasonable expectation of success. An artisan would have been motivated to not only utilize the vector to express mTERT in addition to hFS344 in Mendell, but also substitute mTERT for hFS344 in a method of inhibiting aging and treating age related conditions as TERT is known in the art to increase the median and maximum longevity in mice treated with an AAV-TERT vector (De Jesus; Figure 3).
Regarding claims 12 and 13, Mendell, Mendez, Morabito and Warden do not teach administering the gene therapy to a lab animal such as a mouse.
DeJesus teaches administering gene therapy with mTERT to mice (p. 692, 2nd column).
Based on such teachings, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to administer the vector as discussed above to a mouse as taught by De Jesus with a reasonable expectation of success. An artisan would have been motivated to administer the CMV vector to mice as mice are known alternative test subjects to receive gene therapy.
Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Claims 5 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Mendell (supra) in view of Mendez (supra), Morabito (supra), Warden (supra), de Jesus (supra) as applied to claim 1 and 9 above and in further view of Podlevsky (Nucleic Acids Research, 2008, Vol. 36, Database issue D339–D343; IDS Reference).
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/14/2025.
As discussed in the above 103 rejection, Mendell, Mendez, Morabito, Warden and De Jesus teach a method of treating age related diseases via intranasal administration of CMV viral vectors comprising hFS344 and mTERT (i.e. gene therapy) as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
However, regarding claims 5 and 10, these references do not teach that the TERT is human TERT (hTERT) with the hFS344.
Podlevsky teaches that amino acid sequences of TERT are relatively conserved across all eukaryotes and vertebrates (p. D341, Alignments, Figure 1).
Based on such teachings, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to express hTERT instead of mTERT in the vector with a reasonable expectation of success. As Podlevsky teaches that amino acid sequences of TERT are relatively conserved across vertebrates, an artisan would find substituting hTERT in place of mTERT to be substituting known alternative species of TERT. De Jesus additionally teaches that the accumulation of short/damaged telomeres with increasing age is considering on of the main sources of aging associated DNA damage in both humans and mice (p. 697, last paragraph). In light of this, an artisan would be motivated to utilize human TERT to model human disease via the same mouse means of de Jesus.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Mendell (supra) in view of Mendez (supra), Morabito (supra) and Warden (supra) as applied to claims 1 and 15 above and in further view of Rodino-Klapac (Muscle Nerve. 2009 Mar;39(3):283–296)
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/14/2025.
As discussed in the above 103 rejection, Mendell, Mendez, Morabito and Warden teach a method of treating age related diseases via direct injectable administration of CMV viral vectors comprising human FS344 as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
However, these references do not teach utilizing murine FS344/follistatin instead of the human follistatin.
Rodino-Klapac teaches follistatin is highly conserved with overall species homology of 83% and 95% in mammals. (p. 3, 4th paragraph).
Based on such teachings, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to express mFS334 instead of hFS334 in the vector with a reasonable expectation of success. As Rodino-Klapac teaches that homology of follistatin are highly conserved across species, an artisan would find substituting mFS334 in place of hFS334 to be substituting known alternative species of FS334.
Therefore, the invention would have been obvious to one of ordinary kill in the art at the time of the effective filing date
Double Patenting
Claims 1-3, 5-13 and 21-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14, 16-18, 21-30 and 32-36 as per claims filed on 10/24/2024 of copending Application No. 17/592,803 (reference application).
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/14/2025.
Although the claims at issue are not identical, they are not patentably distinct from each other.
Application ‘708 teaches a method for gene therapy via administering genetically modified viral vectors comprising one or more donor genes wherein the viral vector is a human cytomegalovirus (CMV) wherein the genes are TERT and FS344 and the administration route is intranasal or injection (Claim 14, 32, and 36).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
***
Claims 1-3, 5-13 and 21-27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11,266,721 in view of Mendez (Medical Microbiology and Immunology (2019) 208:349–363)
Although the claims at issue are not identical, they are not patentably distinct from each other.
This rejection has been modified as necessitated by Applicant’s arguments and amendments filed 11/14/2025.
Patent ‘721 teaches a method comprising administering a therapeutically effective amount of hTERT gene and Follistatin-344 gene via a viral vector (Claim 1, 3). Patent ‘721 teaches Follistatin-344 genes are administered in a nucleic acid selected from a plasmid, phage, bacterial artificial chromosome (BAC) or viral vectors (Claim 2-3)
However, Patent ‘721 does not teach that the vector is a hCMV vector.
Mendez teaches that human cytomegalovirus (HCMV) has desirable qualities in developing vectors such as a large genome of CMVs allowing the insertion of multiple foreign genes, since more than 50 kb can be removed from human CMV (HCMV) without affecting virus replication (p. 350, 1st paragraph). Additionally, CMV vectors can persist lifelong within their host and are a safer alternative due to the oncogenic potential of lentiviruses (p. 350, 2nd paragraph).
Based on such teachings, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to utilize a human recombinant CMV viral vector as taught by Mendez in place of the vector taught by Patent ‘721 with a reasonable expectation of success. Mendez teaches that human CMV viral vectors have desirable qualities such as allowing insertion of multiple foreign genes and are a safer alternative to other known viral vectors (p. 350, 1st-2nd paragraph). The limitations of Claim 36 reciting particular therapeutic outcomes are inherent to the viral vector itself and therefore does not add structure.
While the limitation of intranasal administration is not present in Patent ‘721, Patent ‘721’s general administration is a genus to the present application’s species and therefore intranasal administration would be encompassed by the claims.
Therefore, the invention is rejected on the grounds of double patenting.
In response to Applicant’s arguments and amendments regarding the double patenting rejections,
Applicant argues that the present claims recite features not provided for by the other reference applications and patents. Examiner states that the claims of the referenced patents and applications are open and therefore not every step need be described for nonstatutory double patenting as the subject matter overlaps. Additionally, the obviousness type double patenting rejection addresses limitations not found within the referenced patent. Many of the limitations described as being missing are steps in the method of making, however the inventions are directed towards methods of treatment and the treatment steps are not patentably distinct.
New grounds of objections/ Rejections in response to Applicants’ arguments or amendments
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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.
Claims 21 are newly rejected under 35 U.S.C. 103 as being unpatentable over Mendell (supra) in view of Mendez (supra), Morabito (supra) and Warden (supra) as applied to claim 1 above, and in further view of Brodie (WO2018211510A1; previously cited).
As discussed in the above 103 rejection, Mendell, Mendez, Morabito and Warden teach a method of treatment via direct injectable administration of CMV viral vectors comprising human FS344 as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
However, these references do not teach that additionally Klotho is introduced via the viral vector.
Brodie teaches vectors which can be a viral vector such as adenoviral vectors and herpes viral vectors encoding multiple anti-aging genes such as Klotho (KL), TIMP2, and GDF11 which are administered to cells so that they express the anti-aging factor in a method of treating conditions related to anti-ageing (para. 0086, 0091, 0096).
Based on such teachings, it would be obvious to one of ordinary skill in the art to additionally include Klotho as taught by Brodie in the viral vector comprising FS344 with a reasonable expectation of success. An artisan would be motivated to administer Klotho as well as FS344 as Klotho is known to be an anti-aging gene and utilized in viral vectors to treat conditions associated with aging which are administered to subjects (para. 0086, 0091, 0096).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
Claims 23 and 24 are newly rejected under 35 U.S.C. 103 as being unpatentable over Mendell (supra) in view of Mendez (supra), Morabito (supra) and Warden (supra) as applied to claim 1 above, and in further view of Liu (2017, Scientific Reports 7: 2193).
As discussed in the above 103 rejection, Mendell, Mendez, Morabito and Warden teach a method of treatment via direct injectable administration of CMV viral vectors comprising human FS344 as iterated above in the 103 rejection the content of which is incorporated herein, in its entirety.
However, these references do not teach wherein one or more genes are fused to a native CMV gene via a sequence coding for a 2A self-cleaving peptide such as P2A.
Liu teaches that self-cleaving peptides such as P2A have been shown in studies to have high efficiency when utilized in polycistronic vectors (p. 2, 1st paragraph).
Based on such teachings, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to fuse the genes of interest via a P2A self-cleaving peptide in the CMV viral vector with a reasonable expectation of success. As Liu teaches that self-cleaving peptides specifically ones such as P2A have been shown in studies to have high efficiency in vectors with more than one gene (p. 2, 1st paragraph).
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
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).
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/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634