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 .
Applicant’s amendments and arguments of February 26, 2026, are entered.
Claims 1-2, 7-8, 10-12, and 13 have been amended.
Claims 3-6, 9, and 14-15 have been canceled.
No new claims have been added.
Claim Objections
Objections to claims 1, 2, 12, and 13 are withdrawn. Applicant’s amendments overcome the objections to those claims. Claims 3, 4, 5, 14, and 15 are also withdrawn due to Applicant canceling these claims.
Double Patenting
Applicant’s cancellation of claims 3, 4, 6, and 9 render the double patent warnings under 35 U.S.C. §101 as moot. Therefore, the double patent warnings to these claims are withdrawn.
Applicant’s amendment to claims 10 and 11 overcome the double patent warning under 35 U.S.C. §101. Therefore, the double patent warning for claim 11 if claim 10 is found allowable is withdrawn.
Claim Rejections - 35 USC § 112
In light of the amendments, the rejections to Claims 1 and 12 being 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35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention, are withdrawn.
Claims 4, 5, and 14 were canceled making the §112(a) written description rejection moot.
Claim Rejections - 35 USC § 112
In light of the amendments, the rejections to claims 1-2, 7-8, and 10-13 as being 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention are withdrawn.
Claims 3-6, 9, and 14-15 were canceled making the §112(b) indefinite rejection moot.
Claim Rejections - 35 USC § 103
In light of the amendments, Claims 1-5 and 12-15 are rejected under 35 U.S.C. § 103 as being unpatentable over Gao et al. [Human SLE bone marrow mesenchymal stem cells (BMSCs) have a senescence-associated phenotype (SASP) mediated by MAVS-IFNβ feedback loop, Arthritis Rheumatol., 2018], in view of Stem Cells for Cancer & Genetic Disease Treatment (Hereinafter Stem Cells) [Chapter: Mesenchymal Stem Cells as Vectors for Cancer Therapy, pp. 13-27, Springer Nature, 2018], in view of Sneed [Mail order CRISPR kits allow absolutely anyone to hack DNA, Scientific American, 2017], is withdrawn.
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
Claims 1-2, 7-8, 10-13 are newly rejected under 35 U.S.C. 103 as being unpatentable over Gao et al. [Human SLE bone marrow mesenchymal stem cells (BMSCs) have a senescence-associated phenotype (SASP) mediated by MAVS-IFNβ feedback loop, Arthritis Rheumatol., 2018], in view of Stem Cells for Cancer & Genetic Disease Treatment (Hereinafter Stem Cells) [Chapter: Mesenchymal Stem Cells as Vectors for Cancer Therapy, pp. 13-27, Springer Nature, 2018], in view of Sneed [Mail order CRISPR kits allow absolutely anyone to hack DNA, Scientific American, 2017], in view of Kerrigan et al. [Mesenchymal stem cells for the delivery of oncolytic viruses in gliomas, Cytotherapy, 2017], in view of Draganov and Szalay (Hereinafter Draganov) [WO 2019 236633 A2].
Regarding claim 1 where a composition contains mesenchymal stem cells with a silenced MAVS gene and an oncolytic virus, Gao et al. discloses bone marrow derived mesenchymal stem cells with the MAVS gene silenced in both SLE bone derived mesenchymal stem cells and healthy mesenchymal stem cells [Results and Silencing MAVS blocks IFN-Beta expression, reduces SASP related cytokine production and improves immunomodulatory factor expression in SLE BMSCs ¶ 1]. However, Gao et al. does not teach the use of mesenchymal stem cells as a carrier for oncolytic viruses. Additionally, Draganov teaches the use of mesenchymal stem cells that are derived from bone marrow, adipose tissue, etc. for delivery of oncolytic viruses, i.e. ICOVIR-5, where the MAVS gene has been inhibited [Para starting with “Provided herein are carrier cells”, Summary ¶ 1, Para starting with “MSCs have served as carriers of oncolytic adenovirus for the treatment of pancreatic cancer”, Para starting with IFNGR1/IFNGR2 signaling”].
For claim 1’s limitation that where mesenchymal stem cells are used as carriers for oncolytic viruses, both Stem Cell and Kerrigan et al. disclose the use of mesenchymal stem cells being used as carrier molecules for transporting oncolytic viruses [2.5 Clinical applications of engineered mesenchymal stem cells for cancer therapy, Kerrigan et al., Abstract].
For claim 2 where the MSCs are derived from any one of known tissues or fluids that contain MSCs, Gao et al. teaches that MSCs can be derived from bone marrow [Abstract]. Given this, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the teachings of Gao et al. where it is taught that mesenchymal stem cells derived from bone marrow can have the MAVS gene silenced with the additional teachings of both Stem Cell and Kerrigan et al. where both discuss mesenchymal stem cells being used as carrier molecules for oncolytic viruses for the purposes of treating solid tumors. Furthermore, Kerrigan et al. states “[t]he therapeutic prospect of MSCs lies primarily in their inherent capacity to home to injured or inflamed tissue, their ability to secrete anti-inflammatory, tissue-rejuvenating factors, and the ease with which they can be modified or engineered to serve as delivery vehicles of exogenous biological agents” [Introduction ¶ 1]. Based on this, a person of ordinary skill in the art would have a reasonable expectation of success to combine mesenchymal stem cells where the MAVS gene has been silenced that displays the same structure and function and combining it with the teachings of both Stem Cell and Kerrigan et al. to create a carrier molecule for oncolytic viruses where particular genes could either be enhanced or silenced based on need.
For claim 7 where the oncolytic virus is ICOVIR-5, Stem Cell discloses that mesenchymal stem cells were infected with ICOVIR-5 as the oncolytic virus [2.5 Clinical applications of engineered mesenchymal stem cells for cancer therapy]. it would have been prima facie obvious to a person of ordinary skill in the art to prior to the filing of the claimed invention to modify the systems and methods of Gao et al. where researchers were able to create bone derived MSCs with an inhibited MAVS gene with the teachings of Stem Cell that teaches the use of MSCs as a vector capable of carrying a ICOVIR-5, an oncolytic virus. Because of this, there is a reasonable expectation of success to combine the teachings of Gao et al. and Stem Cell to develop a substantially pure, i.e. isolated, MSC where the MAVS gene has been silenced to be used as a vector capable of carrying an oncolytic virus, more specifically the ICOVIR-5.
For claim 8 where the composition of claim 1 is combined with a pharmaceutically acceptable vehicles, adjuvants, and/or excipients, Although not specifically referenced in the listed prior art, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the mesenchymal stem cell composition with a pharmaceutically acceptable vehicle, adjuvant, and/or excipient given such components are routinely used in clinical and pharmaceutical practice to facilitate administration, stability, delivery, and biocompatibility of therapeutic agents and represent well understood, conventional techniques and would have been obvious as a matter of routine optimization.
For claim 10 where the composition of claim 1 or the pharmaceutical composition of claim 8 are used for treating solid tumors, Kerrigan et al. discloses that mesenchymal stem cells “avidly” home to solid tumors [Introduction ¶ 1].
For claim 11 where the solid tumor is brain cancer, lung cancer, renal cancer, ovarian cancer, and/or liver cancer, Kerrigan et al. discloses that engineered mesenchymal stem cells carrying anti-tumor agents, e.g. oncolytic viruses, have been used in various cancers, including glioblastoma, the most common and deadly malignant brain tumor in adults [Introduction ¶ 1].
For claim 12 where the substantially pure population of MSCs are isolated, cultured, and the MAVS gene is inhibited, Gao et al. teaches bone derived MSCs were isolated, cultured, and the MAVS gene silenced [Abstract, Human BMSC isolation and culture, Nucleic acid sensing protein MAVS and its target IFNβare activated in SLE BMSCs ¶ 1]. Additionally, both Stem Cell and Kerrigan et al. disclose infecting mesenchymal stem cells with oncolytic viruses for the use in treating solid tumors. Given this, there is a reasonable expectation of success that the mesenchymal stem cells where the MAVS gene is silenced could be used as a carrier molecule for oncolytic viruses given that Kerrigan et al. discloses that mesenchymal stem cells have an affinity towards certain solid tumors [Introduction ¶ 1].
For claim 13 where the oncolytic virus is ICOVIR-5, the same analysis for claim 7 is applied here.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Argument
Applicant argues that a person of ordinary skill in the art would not have motivation to combine the teachings of Gao et al. with the additional teachings of Stem Cell given that Gao et al. is focused on MAVS was silenced in SLE bone marrow mesenchymal stem cells to explore the role of MAVS in senescence -associated secretory phenotype and that Gao et al. was silent with respect to oncolytic viruses or treating cancer. Applicant further argues that in combination with Stem Cell, that although Stem Cell discloses the use of ICOVIR-5 as the oncolytic virus carried by mesenchymal stem cells, Stem Cell was silent as to the MAVS gene being inhibited.
The examiner does not find this argument persuasive.
With respect to Gao et al., Gao et al. expressly teaches both SLE and healthy mesenchymal stem cells where the MAVS gene has been inhibited thereby providing the exact cellular modification that is recited in claim 1. Although Gao et al. discloses this modification in the context of studying disease mechanisms associated with SLE. Gao et al. still demonstrates that mesenchymal stem cells can be successfully engineered to inhibit MAVS expression while remaining viable and functional. Additionally, Gao et al. teaches that MAVS is a central adaptor in innate immune signaling pathways, linking cytoplasmic nucleic acid sensors, e.g. RIG-1 and MDA5, to downstream activation of IFN-Beta production, NFkB signaling, and cellular senescence pathways that include p53 and p16. Furthermore, MAVS or mitochondrial antiviral-signaling protein is essential for antiviral innate immunity. In other words, MAVS is responsible for connecting viral sensing to interferon-driven antiviral immunity and downstream inflammatory and senescence programs that triggers the antiviral innate immunity of the cell, e.g. mesenchymal stem cell. A person of ordinary skill would also understand this to mean that mesenchymal stem cells carrying an oncolytic virus would be more therapeutic since inhibiting MAVS is effectively taking away the cell’s response to the presence of a virus. Based on this, Gao et al. provides a sort-of a map how mesenchymal stem cell’s built-in defense system, i.e. MAVS, detects viruses. This would lead a person of ordinary skill in the art to conclude that inhibiting MAVS in mesenchymal stem cells would make mesenchymal stem cells more therapeutically effective for the purpose of acting as a carrier molecule for oncolytic viruses. Based on this, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Gao et al. with the additional teachings of both Stem Cell and Kerrigan et al. since both articles discuss the use of mesenchymal stem cells as delivery vehicles for oncolytic viruses with Stem Cell specifically citing the use of ICOVIR-5 as the oncolytic virus to be used. Based on this analysis, Claims 1-2, 7-8, and 10-13 are newly rejected.
Conclusion
No claims 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN DAVID MOORE whose telephone number is (703)756-1887. The examiner can normally be reached M-F 8-5.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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