DETAILED ACTION
This action is in reply to papers filed 12/8/2025.
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.
Election/Restrictions
Applicant’s election without traverse of Group II, claims 32-40, in the reply filed on 12/8/2025 acknowledged. Group I, as set forth in claims 12-20, has been cancelled. Claims 41-44 are newly added. Claims 32-44 are pending and examined herein.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 43 and 44 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 43 and 44 both recite the limitation "the initial administration” in line 2. There is insufficient antecedent basis for this limitation in the claim or in any of the claims these claims depend from. Note that independent claim 32 only recites “….comprising administering”. There is no recitation of an initial administration.
Appropriate correction is requested.
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 are 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.).
Regarding claim 32,in-part, Engelhard teaches a method of treating a condition associated with aberrant expression of the endogenous dystrophin gene, comprising: contacting a human subject (as in claim 40) (Pg. 2, para. 14; Pg. 8-9, para. 64) having the condition, with an effective amount of at least one agent that enhances AAV transduction and an effective amount at least one rAAV comprising a transgene encoding at least a portion of the functional gene product, the expression of which in the mammal treats at least one symptom of the condition (Pg. 6,para. 40). Engelhard teaches the agent(s) and/or virus may each be administered once, or in repeated dosing, so as to achieve the desired effect, i.e., to enhance rAAV transduction (as in claim 34, in-part, and as in claim 42) (Pg. 4, para. 27). Engelhard teaches the agent and/or virus is administered locally or systemically (as in claim 35), such as intravenously (as in claim 37and as in claim 38, in-part) or intramuscularly (as in claim 36 and as in claim 38, in-part) (Pg. 18,para. 153; Pg. 15, para. 133; Pg. 18,para. 156).
However, Engelhard fails to teach the condition is Duchenne muscular dystrophy (as further in claim 32).
Before the effective filing date of the claimed invention, Bostick et al. taught dystrophin deficiency leads to Duchenne muscular dystrophy (DMD) (Pg. 851). Bostick teaches dystrophin is a 427-kDa subsarcolemmal protein. Continuing, Bostick teaches the large size of the full-length dystrophin coding sequence has been a longstanding challenge for DMD gene therapy. This is because it exceeds the packaging capacity of many viral vectors. To overcome this obstacle, investigators have developed highly truncated but partially functional minigenes and microgenes. In their report, Bostick and colleagues tested cardiac AAV-9 (as in claim 39) micro dystrophin (as in claim 33) transduction in neonatal mdx mice (Abstract). Bostick teaches their results suggest that a single intravenous injection in the absence of additional pharmacological agents can lead to robust microdystrophin expression throughout the entire heart of newborn mdx mice. Bostick adds that four months after AAV-9 therapy, heart rate and PR and QT intervals were all normalized in treated mdx mice. These results are consistent with previous reports and together they suggest that microdystrophin gene therapy holds great promise in ameliorating both skeletal and cardiac muscle diseases in DMD (Pg. 852, Col. 1).
However, neither Engelhard nor Bostick et al. teach administering to a the subject a human mesenchymal stem cell (as further in claim 32).
Before the effective filing date of the claimed invention, Shabbir et al. taught 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 (Pg. 1276, Col. 1, para. 1). In this aspect, Shabbir reasons that the immunomodulatory property of MSCs may be particularly well suited for tackling the inflammatory nature of dystrophic muscle (as in claim 41, claim 43 and claim 44). Towards this end, Shabbir explored the immunomodulatory property of human and porcine MSCs (as further in claim 32) for the treatment of δ-sarcoglycan-deficient dystrophic hamster muscle without immunosuppression. Shabbir teaches circulating levels of immunoglobulin A, vascular cell adhesion molecule-1, myeloperoxidase, and major cytokines involved in inflammatory response were not elevated by MSCs, nor were expression of the leukocyte common antigen CD45 and the cytokine transcriptional activator NF-κB in the injected muscle (Abstract). In fact, treated muscles exhibited increased cell-cycle activity and attenuated oxidative stress. Shabbir concludes that intramuscular injection of nonautologous MSCs can be safely used for the treatment of dystrophic muscle in immunocompetent hosts without inflaming the host immune system (Pg. 1281, Col. 2, para. 1).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Engelhard et al., wherein Engelhard teaches a method of treating a condition associated with aberrant expression the endogenous dystrophin gene, wherein said method comprises administering to a human subject having the condition at least one agent that enhances AAV transduction and an effective amount at least one rAAV comprising a transgene encoding at least a portion of the functional gene product, with the teachings of Shabbir et al., wherein Shabbir teaches the immunomodulatory property of MSCs may be particularly well suited for tackling the inflammatory nature of dystrophic muscle, with a reasonable expectation of arriving at the claimed invention. That is, one of ordinary skill in the art would have found it prima facie obvious to first prime the in vivo environment of the human subject having DMD by first administering MSCs such that said administering results in immunomodulation of the inflammatory dystrophic muscle. The skilled artisan would have found it prima facie obvious to do so because Shabbir teaches that although gene therapies have been attempted to treat muscular dystrophy, host immune reactions against the expressed gene product limit the efficacy of these therapeutic approaches. Thus, for the purposes of enhancing rAAV transduction in vivo by reducing a host immune response, the combination would have been prima facie obvious.
Moreover, one of ordinary skill in the art would have found it prima facie obvious to substitute the generic rAAV vector in Engelhard for the rAAV-9 vector in Bostick because Bostick observed success when a microdystrophin gene was delivered via an rAAV-9 vector into a Duchenne muscular dystrophy model mice.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious.
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.
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/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632