DETAILED ACTION
This action is in reply to papers filed 4/1/2026. Claims 32-44 are pending and examined herein.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20230226153A1, Published 7/20/2023.
Withdrawn Claim Rejections
The 112(b) rejection of claims 43 and 44 are withdrawn in view of amendments made to independent claim 32.
Maintained Claim Rejections
The 103 (a) rejection of claims 32-44 as being unpatentable over Engelhardt et al. (PgPub US20080249050A1, Published 10/9/2008) in view of Shabbir et al. (Transplantation 87(9):p 1275-1282, May 15, 2009.) and Bostick et al. (Hum Gene Ther . 2008 Aug;19(8):851-6 .) is maintained. Applicant’s arguments will be addressed following maintained rejection.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 32-44 remain rejected under 35 U.S.C. 103 as being unpatentable over Engelhardt et al. (PgPub US20080249050A1, Published 10/9/2008) in view of Shabbir et al. (Transplantation 87(9):p 1275-1282, May 15, 2009.) and Bostick et al. (Hum Gene Ther . 2008 Aug;19(8):851-6.). The rejection is maintained for the reasons advanced in the previous office action and will not be reiterated herein.
Applicant’s Arguments/Response to Arguments
Applicant argues: Engelhardt is directed to methods and compositions for enhancing AAV transduction particularly in polarized epithelial tissues such as are present in the airway. Engelhardt teaches that post-entry intracellular processing steps, rather than viral binding or second-strand DNA synthesis alone, are key rate-limiting barriers to effective rAAV transduction. Based on that insight, the application discloses methods, agents, and compositions capable of enhancing rAAV transduction by modulating intracellular trafficking, processing, and degradation pathways.
To the extent that Engelhardt makes any mention of an immune response at all, it is to
indicate that (1) rAAV lacks "undesirable cellular immune responses since all viral genes can be deleted from the vector" (Paragraph [0003) and (2) agents that enhance viral transduction are useful in vaccines that employ rAAV to induce an immune response (Paragraph [0021]).
There is certainly no teaching or suggestion in Engelhardt to downregulate an immune response as an approach to "enhancing AAV transduction".
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. Examiner disagrees with Applicant’s narrow characterization of Engelhardt. Independent claim 33 of Engelhardt is copied below:
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Dependent claim 42 recites the following:
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The pertinence of the teachings of Engelhardt is directly related to the claimed method for treating DMD, as secondary reference Bostick et al. taught dystrophin deficiency leads to Duchenne muscular dystrophy (DMD) (Pg. 851). Applicant’s arguments regarding an immune response, as related to Engelhard, are unclear as the Examiner never cited Engelhardt for teaching such.
Applicant argues: Applicant submits that it is exceedingly unconventional to combine cell therapies and gene therapies for the same condition.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. The art is replete with ex vivo cell therapy in combination with gene therapy, for example CAR-T cells. Also Shabbir teaches genetic engineering of MSCs.
Applicant argues: Applicant’s arguments from Pg. 6 is copied below:
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Examiner Response: Applicant’s arguments have been fully considered, but are not found persuasive. However, the second paragraph quoted by Applicant is not complete. Notably, the term “gene product” is missing. Pg. 6, para. 2 of Shabbir is copied below, in full:
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Moreover, Examiner is unpersuaded by Applicant’s argument regarding Shabbir’s focus for a DMD therapy that was non-autologous. Shabbir, on several occasions, teaches the limitations of their studies. For example, Shabbir teaches that it remained unclear whether the immunosuppressive effect of intramuscularly injected MSCs can be sustained as the current study only involved a one-month time period. In addition, Shabbir teaches another limitation of the current therapeutic approach is the rapid loss of the injected MSCs after implantation. (Pg. 6, last paragraph). Therefore, it is clear that Shabbir did not convey their teachings as a singular treatment for DMD.
Applicant argues: Applicant argues that Shabbir is squarely focused on identifying a non-autologous cell type that is useful in treatment of muscular dystrophy (by local administration) while at the same time, not triggering an immune response against the cells, a problem, which Shabbir recognizes has been a vexing issue for cell therapy. Nowhere in Shabbir is there a teaching or suggestion that hMSCs, particularly intramuscular administration of hMSCs, should be used as a generic method to suppress the immune system in combination with other forms of therapy for muscular dystrophy.
In Response: Applicant’s arguments have been fully considered, but are not found persuasive. At the outset, the Courts have consistently held that the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. >See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.");< In re Linter, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991) (discussed below). Although Ex parte Levengood, 28 USPQ2d 1300, 1302 (Bd. Pat. App. & Inter. 1993) states that obviousness cannot be established by combining references "without also providing evidence of the motivating force which would impel one skilled in the art to do what the patent applicant has done" (emphasis added), reading the quotation in context it is clear that while there must be motivation to make the claimed invention, there is no requirement that the prior art provide the same reason as the applicant to make the claimed invention.
Shabbir makes clear that although both gene and cell therapies have been attempted to treat muscular dystrophy, host immune reactions against the expressed gene product and transplanted cells limit the efficacy of these therapeutic approaches and more efficient immunosuppression is often deemed necessary(Examiner’s emphasis). Under ‘Discussion’, Shabbir teaches little data on potential host immune responses following stem cell administration are available in the literature. Given the recognition that host immune responses can compromise the efficacy of stem cell therapeutics, Shabbir teaches they focused their attention on the hamster immune responses after the transplantation of human and porcine MSCs. Consistent with the general notion that MSCs are immune privileged cells, neither human nor porcine MSCs triggered adverse immune reactions based on their analyses of blood cells, serum inflammatory markers, tissue oxidative stress, and expression of immune cytokines, CD45, and NF-κB in muscle (Examiner’s emphasis).
Examiner emphasizes Shabbir teaches the therapeutic efficacy of both gene therapy and stem cell therapy for DMD are limited by adverse host immune responses and that an adverse host immune response was not observed after MSCs were transplanted. On the contrary, Shabbir teaches post-MSC transplantation, down-regulated immune cytokines, myeloperoxidase, and NF-κB were observed. However, nothing in Shabbir teaches or suggest MSC transplantation as a singular treatment for DMD. In
Therefore, when all of Shabbir’s teachings are taken as a whole and for the same benefit of preventing an adverse host immune response against an exogenous therapeutic, one of ordinary skill would have found it prima facie obvious to administer the immunomodulatory MSCs of Shabbir prior to the AAV mediated dystrophin DMD treatment of Engelhardt in view of Bostic.
Lastly, Examiner disagrees with Applicant’s statement that Shabbir does not suggest hMSCs could be used with other forms of therapy. In fact, Shabbir teaches they and others have shown that MSCs are capable of producing a broad spectrum of trophic factors, and this capacity can be further boosted by genetic engineering of MSCs. Shabbir adds that MSC engineering aimed at promoting trophic factor outputs may represent an effective therapeutic module.
Applicant argues: On the other hand, as noted above, Engelhardt, far from noting that rAAV induces a problematic immune response teaches that rAAV does not induce an undesirable cellular immune response.
In Response: As noted in Shabbir, an adverse host response is raised against the gene product.
Applicant argues: With respect to claim 35, Applicant submits that the claimed subject matter is nonobvious over the cited combination for the additional reason that claim 35 requires systemic administration of hMSCs, which stands in contrast to the intramuscular administration of hMSCs taught and suggested in Shabbir for the treatment of muscular dystrophy.
In Response: As noted in the previous office action, Engelhardt teaches a systemic administration. It would have been prima facie obvious to administer the cells in the same manner as the gene therapy vector.
Because Applicant’s arguments were not found persuasive, the rejection is maintained.
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 extension fee 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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/TITILAYO MOLOYE/ Primary Examiner, Art Unit 1632
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