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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on July 21, 2025 has been entered.
This action is in response to the papers filed on July 21, 2025. Pursuant to amendment filed on July 21, 2025, claims 1-19 have been amended and claim 20 is newly added.
Therefore, claims 1-20 are currently under examination.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2019/048311 filed on August, 27, 2019. Applicants' claim for the benefit of a prior-filed application parent provisional applications 62/820,636 filed on March 19, 2019 and 62/723,105 filed on August 27, 2018 under 35 U.S.C. l 19(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
The disclosures of the prior-filed provisional application 62/723,105 fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Specifically, 62/723,105 does not support the claimed subject matter of the newly amended claim 20, such as expression of CD117, CD105, etc. CD117, CD105, and expression of the rhodamine 123 efflux activity is not mentioned or taught in the specification of 62/723,105.
Thus, the earliest possible priority for claims 1-19 is March 19, 2019.
Withdrawn Claim Objections
In view of Applicants’ amendment to claim 2-19, reciting “the fibroblast cell,” the objections to improper form are moot and have been withdrawn.
In view of Applicants’ amendment to claim 5, reciting “the intracellular domain of TLR4,” the objection to improper form is moot and have been withdrawn.
In view of Applicants’ amendment to claim 18, reciting “the fibroblast cell is a human fibroblast,” the objection to improper form is moot and have been withdrawn.
In view of Applicants’ amendment to claim 19, reciting “of the fibroblast cells from claim 1,” the objection to improper form is moot and have been withdrawn.
Withdrawn Claim Rejections - 35 USC§ 112(b)
In view of Applicants’ amendment to claim 1, no longer reciting “expression of the rhodamine efflux activity,” the rejection of claim 1 under 35 U.S.C. 112(b) is moot and has been withdrawn.
Withdrawn Claim Rejections - 35 USC § 103
In view of Applicants amendment to the instant claims, requiring the expression of CD34, the rejection under 35 U.S.C. 103 to claims 1-19 as being unpatentable over Wagner et al (US 2016/0237407 A1, hereinafter 'Wagner'), in view of Denu et al (Acta Haematol. 2016; 136(2): 85-97.), and further in view of Kang (CN108795877A) has been withdrawn. A response to Applicant’s arguments with regard to a withdrawn rejection is moot. A response to Applicant’s arguments pertinent to a new or remaining rejection can be found below.
Specification Objection
The disclosure is objected to because of the following informalities: The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See instant specification [0077]. Appropriate correction is required.
Claim interpretation
New claim 20 recites the fibroblast cell of claim 1, further comprising cell-surface marker expression of:
(a) CD117, CD105, and rhodamine 123;
(b) a cell-surface marker selected from the group consisting of Oct-4, KLF-4, Nanog, Sox-2, Rex-I, GDF-3, Stella, and GDF-11; and/or
(c) a cell surface marker selected from the group consisting of c-Kit, Nanog, Sox-2, Hey1, SMA, Vimentin, Cyclin D2, Snail, E-cadherin, Nkx2.5, GATA4, CD105, CD90, CD29, CD73, Wt1, and CD45
Hence, the ordinary artisan would interpret the fibroblast cell of claim 20 to be limited by requiring the expression of a CAR, CD34, and alternatively either markers CD117, CD105, and rhodamine 124, or a single marker selected from the group of (b) or (c). This interpretation has already been communicated in response to Argument 1 of the last action, and during interview April 10, 2025 with Joel Levin (Examiner), Christopher Babic (Supervisory Patent Examiner). If applicant intended to define or further limit the fibroblast cell as requiring markers from (a), (b), and (c), applicant is invited to amend the claim language to delete the recitation of “or”.
New Claim Rejections - 35 USC§ 102
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kang (CN108795877A, published Nov. 13, 2018), evidenced by Cords et al. (Nat Commun. 2023 Jul 18;14:4294.) and Schulze et al. (Thorac Cancer. 2020 Jan;11(1):120-129.).
Regarding claims 1-2, Kang discloses an engineered fibroblast expressing CAR, or CAR-F cell (Abstract; claim 1). Kang additionally discloses the antigen-specific targeting region, transmembrane domain, intracellular signaling domain, and scFV (pg. 2, para. 3-4 and last para.)
Kang discloses the fibroblast cell expressing the CAR for treatment of tumor diseases (Abstract; pg. 2, para. 3). Where the fibroblast is a species which is administered to, or exists in, a physiological inflammatory or cancer state/environment, the fibroblast can naturally or inherently express CD34, as evidenced by Cords et al. and Schulze. These fibroblasts are commonly termed inflammatory associated fibroblasts (iCAFs) or cancer-associated fibroblasts (CAFs). The disclosure of Cords evidence that a fibroblast cell inherently expresses the cell-surface marker CD34, along with other cell surface markers selected from conventional fibroblast markers, such as vimentin (pg. 2-3, bridging para.; Fig. 4; Table 1). Likewise, the disclosure of Schulze evidence markers including CD34 and SMA are inherently expressed by fibroblasts (Abstract; pg. 126-127, bridging para.). Thus, fibroblast cell subtypes inherently express markers such as CD34, as well as conventional fibroblast markers such as vimentin.
Modified & Maintained Claim Rejections - 35 USC § 102
Claims 1-3, 7, and 16-19 remain rejected, and claim 20 is newly rejected, under 35 102(a)(1)(2) as being anticipated by Shiku et al. (US 2014/0242701 A1, patented Aug. 28, 2014), evidenced by Cords et al. (Nat Commun. 2023 Jul 18;14:4294.) and Schulze et al. (Thorac Cancer. 2020 Jan;11(1):120-129.). Applicants’ arguments filed on July 21, 2025 have been fully considered but they are not persuasive. This is a modified rejection necessitated by Applicants’ amendments to the claims in the response filed on July 21, 2025.
Regarding claims 1 and 20, Shiku discloses a fibroblast, where said fibroblast expresses a chimeric antigen receptor (CAR), and wherein the chimeric antigen receptor comprises at least one antigen-specific targeting region, at least one transmembrane domain, and at least one intracellular signaling domain ([0011]; [0014]; [0083]).
Shiku discloses the cell expressing the CAR for administration or use as a therapeutic agent for diseases including inflammatory disease and cancer ([0091]). Where the fibroblast is a species which is administered to, or exists in, a physiological inflammatory or cancer state/environment, the fibroblast can naturally or inherently express CD34, as evidenced by Cords et al. and Schulze. These fibroblasts are commonly termed inflammatory associated fibroblasts (iCAFs) or cancer-associated fibroblasts (CAFs). The disclosure of Cords evidence that a fibroblast cell inherently expresses the cell-surface marker CD34, along with other cell surface markers selected from conventional fibroblast markers, such as vimentin (pg. 2-3, bridging para.; Fig. 4; Table 1). Likewise, the disclosure of Schulze evidence markers including CD34 and SMA are inherently expressed by fibroblasts (Abstract; pg. 126-127, bridging para.). Thus, fibroblast cell subtypes inherently express markers such as CD34, as well as conventional fibroblast markers such as vimentin.
Regarding claim 2, dependent on claim 1, Shiku discloses a chimeric antigen receptor comprising an extracellular domain capable of binding to an antigen, a transmembrane domain,
and at least one intracellular domain ([0014]).
Regarding claim 3, dependent on claim 1-2, Shiku discloses the antigen-specific targeting region is an scFv, stating that a domain capable of binding to an antigen or a ligand can be used, preferably a scFv (Fig. 1-2, [0004], [0029-0030], [0052], and [0055]).
Regarding claim 7, dependent on claim 1, Shiku discloses that the cell expressing a chimeric antigen receptor, which are useful in the field of adoptive immunity gene therapy for tumors and an effect of the invention is adoptive immunity gene therapy targeting an antigen such as a tumor antigen ([0001]; [0028]).
Regarding claim 16-18, dependent on claim 1, Shiku discloses that the cell is a human cell collected, isolated, purified or induced from a body fluid, a tissue or an organ such as blood (peripheral blood, umbilical cord blood etc.) or bone marrow ([0083]).
Regarding claim 19, dependent on claim 1, Shiku discloses cells, in the plural ([0031-0047]).
New Claim Rejections - 35 USC§ 103
Claims 1-20 are newly rejected, under 35 U.S.C. 103 as being unpatentable over Wagner et al. (US 2016/0237407 A1, patented Aug. 18, 2016), in view of Denu et al. (Acta Haematol. 2016; 136(2): 85-97.), Ichim et al. (J Transl Med (2018) 16:212), and Kang (CN108795877A, published Nov. 13, 2018), as evidenced by Cords et al. (Nat Commun. 2023 Jul 18;14:4294.) and Schulze et al. (Thorac Cancer. 2020 Jan;11(1):120-129. Epub 2019 Nov 24.). This is a new rejection necessitated by Applicants’ amendments to the claims in the response filed on July 21, 2025.
Regarding claims 1 and 20, Wagner teaches universal donor chimeric allogeneic cells useful for the treatment of cancer, including mesenchymal stem cells which are transfected with CAR (CAR-MSC) to enhance migration into tumors and induce tumor death, reduction of inflammation, or immune sensitization, (Abstract and claims 18-36). Furthermore, Wagner teaches where the mesenchymal stem cell expressing CAR (claim 18) with antigen binding domains for Wt1 (claim 19).
Additionally, where the fibroblast is a species which is administered to, or exists in, a physiological inflammatory or cancer state/environment, the fibroblast can naturally or inherently express CD34, as evidenced by Cords et al. and Schulze. These fibroblasts are commonly termed inflammatory associated fibroblasts (iCAFs) or cancer-associated fibroblasts (CAFs). The disclosure of Cords evidence that a fibroblast cell inherently expresses the cell-surface marker CD34, along with other cell surface markers selected from conventional fibroblast markers, such as vimentin (pg. 2-3, bridging para.; Fig. 4; Table 1). Likewise, the disclosure of Schulze evidence markers including CD34 and SMA are inherently expressed by fibroblasts (Abstract; pg. 126-127, bridging para.). Thus, fibroblast cell subtypes inherently express markers such as CD34, as well as conventional fibroblast markers such as vimentin.
While Wagner teaches a CAR-MSC, or mesenchymal stem cells expressing CAR, Wagner never explicitly teaches a fibroblast cell expressing a chimeric antigen receptor (CAR).
However, in view of Denu and Ichim, which teach fibroblast as a practical and interchangeable alternative to MSCs, including for therapeutic use, a person of ordinary skill in the art would have found it obvious to employ fibroblasts, rather than mesenchymal stem cells, as taught by Wagner, as the CAR-expressing cellular platform or substitute fibroblast in place of mesenchymal stem cells as the CAR-expressing cell type.
Denu teaches that fibroblasts and mesenchymal stromal/stem cells are phenotypically indistinguishable. Moreover, Denu teaches that human mesenchymal stromal/stem cells (MSCs), derived from many different tissues, are characterized by a fibroblast-like morphology, possess ability to differentiate into adipocytes, chondrocytes, osteoblasts, express certain cell surface markers like CD105, and produce of vimentin, a canonical fibroblast marker (abstract; pg. 6, para. 1; pg. 8, para. 3). Denu states that fibroblast, as well as MSCs express vimentin,
“Prior studies have also presented evidence that MSCs exhibit properties typically thought to characterize fibroblasts. One study showed that bone marrow MSCs express the same types of collagens as skin fibroblasts. Another study demonstrated that adipose tissue-derived MSCs make collagen type I, fibronectin, vimentin, and nestin matrices similar to those of dermal fibroblasts, and another report demonstrated these same findings in bone marrow MSCs compared to adult bronchial and fetal lung fibroblasts.”
Likewise, Ichim teaches fibroblast as a practical and effective therapeutic substitute for mesenchymal stem cells, recognizing their similar immunophenotypic properties and efficacy in cell therapy. Ichim explicitly states,
“While the most commonly used MSC source, the bone marrow provides relatively little starting material for cellular expansion, and requires invasive extraction means, fibroblasts are easily harvested in large numbers from various biological wastes. Additionally, in vitro expansion of fibroblasts is significantly easier given the robustness of these cells in tissue culture and shorter doubling time compared to typical MSC. In this paper we put forward the concept that in some cases, fibroblasts may be utilized as a more practical, and potentially more effective cell therapy than mesenchymal stem cells (abstract).”
“Accordingly, tissue sources, such as fibroblasts, in which larger numbers of cells may be originally extracted, may serve as an attractive alternative to MSC (pg. 2, column 1, para 3).”
“Based on currently accepted definitions for cultured human MSCs and fibroblasts, the investigators could not find any immunophenotypic property that could make a characteristic distinction between MSCs and fibroblasts (pg. 5, column 1, para. 2).”
Furthermore, the teachings of Kang demonstrate that the prior art already taught and recognized the utility of engineered fibroblast CAR cells, or fibroblasts as the CAR-expressing cellular platform. Kang teaches a chimeric antigen receptor fibroblast and establishing method and application thereof for treating tumor diseases (abstract; claim 1).
Hence, prior to the effective filing date of the instant application, one of ordinary skill in the art, would have found it obvious to simply substitute the fibroblasts, rather than mesenchymal stem cells, as taught by Wagner, as the CAR-expressing cellular platform, motivated by the teachings of Denu and Ichim, to achieve the predictable result of obtaining a CAR-Fibroblast cellular composition suitable to treat cancer. This substitution would have obtained the predictable result of producing a fibroblast cell expressing a chimeric antigen receptor (CAR), with a reasonable expectation of success, further in view of Kang.
Regarding claim 2, the combined teachings of Wagner, Denu, Ichim and Kang render claim 1 obvious. Wagner additionally teaches the expression of an antigen binding domain, a transmembrane domain, and an intracellular signaling domain (claim 1).
Regarding claim 3, the combined teachings of Wagner, Denu, Ichim and Kang render claims 1 and 2 obvious. Wagner additionally teaches CARs are usually generated by joining a single chain antibody (scFv) to an intracellular signaling domain, and the antigen binding affinity of scFv is typically much higher than the binding moiety of most TCRs ([0006-0007]).
Regarding claim 4, the combined teachings of Wagner, Denu, Ichim and Kang render claims 1 and 2 obvious. Wagner additionally teaches antigen binding domain binds antigens selected from the group comprising of TEM-1, TEM-2, TEM-3, TEM-4, TEM-5, TEM-6, TEM-7, TEM-S, ROBO-4, VEGFR2, CD109, survivin, and CD93 (claim 32).
Regarding claim 5, the combined teachings of Wagner, Denu, Ichim and Kang render claims 1 and 2 obvious. Notably, Wagner additionally teaches the engineered cell, where said intracellular signaling domain of the TLR-4 protein is linked to an activator of molecular pathways. This activator, the functional portion of the TLR-4 protein, triggers TLR4 signaling transduction, thereby endowing the cell with an MSC-1 phenotype (claims 20 and 33-36).
An MSC-1 phenotype is characterized by an enhanced ability to stimulate a mixed lymphocyte reaction, which correlates with improved anti-cancer activity (claims 20-24). The prior art’s disclosure of CAR-fibroblasts is significant because fibroblasts, as disclosed by Denu and Kang, offer unique advantages: they are readily isolated and modified, can persist in the tumor microenvironment, and may influence tissue architecture in ways that further support anti-cancer responses. Therefore, integrating the intracellular TLR4 domain into CAR-fibroblasts is desirable. It is reasonable to expect that such modification would enhance the anti-cancer ability of these cells by combining the robust immune-stimulatory effects of TLR4 signaling with the advantageous properties of fibroblasts as a therapeutic cell type.
Thus, it would have been obvious to further modify the CAR-fibroblasts by incorporating the intracellular TLR4 domain, with the expectation that this modification would enhance their anti-cancer capabilities.
Regarding claim 6, the combined teachings of Wagner, Denu, Ichim and Kang render claims 1 and 2 obvious. intracellular domain containing CD3 zeta chain and at least one shRNA domain encoding a transcript which generates at least one siRNA capable of inhibiting expression of HLA I and/or HLA II (abstract).
Regarding claim 7, the combined teachings of Wagner, Denu, Ichim and Kang render claim 1 obvious. Wagner additionally teaches that CARs are capable of endowing the cells with ability to trigger a T cell mediated immune response ([0031]).
Regarding claim 8, the combined teachings of Wagner, Denu, Ichim and Kang render claim 1 and 7 obvious. Wagner additionally teaches CAR is utilized to activate T cells to endow cytokine production or to stimulate cytotoxicity against tumors ([0009-0010]). Moreover, Wagner teaches an appropriate amount of soluble agent to be added will vary with the specific agent, but can be determined by assaying different amounts of the soluble agent in T cell cultures and measuring the extent of co-stimulation by proliferation assays or production of cytokines ([0029]).
Regarding claim 9, the combined teachings of Wagner, Denu, Ichim and Kang render claim 1, 7, and 8 obvious. Wagner additionally teaches the utilization of IL-12 and IL-21 as tumor targeting agents delivered by the cells ([0011]).
Regarding claim 10 and 11, the combined teachings of Wagner, Denu, Ichim and Kang render claims 1 and 5 obvious. Wagner additionally teaches the enhanced ability of the cells expressing the TLR4 intracellular domain to stimulate NK cells as compared to a naive cell, wherein the NK cells are CD94+ and/or CDI 17 + and/or CD 161- and/or NKG2D+ and/or NKp46+ and/or CD226+ and/or CD57+ (claims 23-31).
Regarding claim 12-15, the combined teachings of Wagner, Denu, Ichim and Kang render claim 1 obvious. Wagner additionally taches the CAR cells are transfected with anti-apoptotic proteins to enhance in vivo longevity, and a method of using CAR-MSC that have been cultured under conditions to express increased amounts of at least one anti-apoptotic protein as a therapy to inhibit or prevent apoptosis. Furthermore, Wagner teaches the CAR cells have been contacted with an apoptotic cell secrete high levels of at least one anti-apoptotic protein, including but not limited to, STC-1, BCL-2, XIAP, Survivin, and Bcl-2XL ([0035] and claims 19 and 32).
Regarding claim 16-18, the combined teachings of Wagner, Denu, Ichim and Kang render claim 1 obvious. Kang teaches that fibroblasts are the most common cells in connective tissues (p. 1). Isolating fibroblasts from any connective tissue, including human placental connective tissue would have been obvious.
Regarding claim 19, the combined teachings of Wagner, Denu, Ichim and Kang render claim 1 obvious. Wagner additionally teaches that the cell can be expanded to obtain a plurality of cells ([0021] and [0026]).
***
Claims 12-15 remain additionally rejected under 35 U.S.C. 103 as being unpatentable over Shiku et al. (US 2014/0242701 A1), evidenced by Cords et al. and Schulze et al. as applied to claims 1-3, 7, and 16-20 above, in view of Wagner et al. (US 2016/0237407 A1). Applicants’ arguments filed on July 21, 2025 have been fully considered but they are not persuasive. This is a modified rejection necessitated by Applicants’ amendments to the claims in the response filed on July 21, 2025.
Regarding claim 12-15, dependent on claim 1, Shiku discloses claim 1, as clarified above, and that the cell is capable of binding to a tumor antigen such as survivin ([0060]). Shiku further discloses that a "tumor antigen" means a biological molecule having antigenicity, expression of which comes to be newly recognized in association with canceration of a cell. The tumor antigen in the present invention includes a tumor specific antigen (an antigen which is present only in tumor cells and is not found in other normal cells), and a tumor-associated antigen (an antigen which is also present in other organs and tissues or heterogeneous and allogeneic normal cells, or an antigen which is expressed on the way of development and differentiation) ([0050]).
Shiku does not teach anti-apoptotic proteins or that survivin is an anti-apoptotic protein.
However, Wagner taches the CAR cells are transfected with anti-apoptotic proteins to enhance in vivo longevity, and a method of using CAR-MSC that have been cultured under conditions to express increased amounts of at least one anti-apoptotic protein as a therapy to inhibit or prevent apoptosis. Furthermore, Wagner teaches the CAR cells have been contacted with an apoptotic cell secrete high levels of at least one anti-apoptotic protein, including but not limited to, STC-1, BCL-2, XIAP, Survivin, and Bcl-2XL ([0035]).
Thus, prior to the effective filing date, one of ordinary skill in the art would have found it obvious to apply the known anti-apoptotic function of survivin and other anti-apoptotic proteins, as taught by Wagner, to improve the similar method of utilizing tumor antigenecity of the cell, as taught by Shiku, ready for improvement. This would have yielded the predicable result of exposing, expressing, the known anti-apoptotic proteins with the CAR-fibroblast, with a reasonable expectation of success.
Response to Applicants’ arguments as they apply to the rejection of Claims 1 -20 under 35 USC § 102 & 103
Applicant's arguments filed July 21, 2025, have been fully considered but they are
not persuasive.
At pages 6-10 of the remarks filed on July 21, 2025, Applicants essentially argue
the following:
Applicant argues Shiku does not disclose a step of selecting a cell, and points to the instant specification for methods of selection, such as flow cytometry, ELISA, or magnetic beads. Additionally, applicant states “Shiku never teaches or suggests selecting a cell based on expression of a gene or cell-surface marker.”
This argument is not persuasive because the pending claims are directed to a fibroblast cell product, or a composition, not to a method of selection. Since, they are claims to a fibroblast cell product, methods of selection are immaterial to the patentability of the cell product, where no structural limitation is recited. Here, the alternatively recited expression of the markers is the structural or phenotypic limitation of the fibroblast cell product. The references of record evidence that fibroblast cell subtypes inherently express markers such as CD34, as well as conventional fibroblast markers such as vimentin.
Applicant further argues that Denu teaches away because fibroblasts and mesenchymal stem cells are described as CD34 negative, and that Wagner, Kang, and Shiku cannot remedy this alleged deficiency because they are silent as to CD34 expression.
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This argument is not persuasive because the cited art does not teach away from the claimed fibroblast cell. As set forth in MPEP § 2112(II), an inherent feature need not be disclosed or recognized in the prior art so long as the feature is necessarily present in the disclosed subject matter. While Denu reports found low CD34 expression, under certain conditions, this does not preclude the fact that subsets of fibroblast are inherently capable and do express CD34. In fact, pointing to Denu, Fig. 2, it is noted that, while low in the specific cells assayed understand culture conditions, CD34 expression was not entirely absent. The cells did in fact express CD34, be it a low levels.
Here, the fibroblast cells in the context of an inflammatory, cancerous, or tumor environment would express higher levels of CD34. The cited references collectively disclose fibroblast cells, including CAR expressing fibroblasts, see Shiku, and substantial evidence demonstrates that fibroblasts inherently include subpopulations that express CD34 depending on physiological state, as evidenced by Cords and Schulze. Hence, the evidence supports the fact that fibroblasts naturally express CD34.
Finally, applicant repeats the argument previously responded to pertaining to Ichim et al. (J Transl Med (2018) 16:212). This argument has been previously responded to and the previous response is maintained and repeated below.
While the references cited by applicant have been considered, the totality of the record does not lead to the conclusion that one of skill in the art would be taught away from employing fibroblast, rather than mesenchymal stem cells, as the CAR-expressing cellular platform, in view of the combined teachings of Wagner, Denu, Ichim and Kang. The prior art clearly taught CAR fibroblasts, for example, see Kang which expressly teaches CAR Fibroblast cells. Furthermore, the prior art does recognize fibroblasts as a practical alternative to mesenchymal stem cells, in view of Ichim. Ichim clearly teaches that indeed fibroblast are viewed in the art as a practical alternative to mesenchymal stem cells (MSCs).
The disclosure of Ichim states:
“While the most commonly used MSC source, the bone marrow provides relatively little starting material for cellular expansion, and requires invasive extraction means, fibroblasts are easily harvested in large numbers from various biological wastes. Additionally, in vitro expansion of fibroblasts is significantly easier given the robustness of these cells in tissue culture and shorter doubling time compared to typical MSC. In this paper we put forward the concept that in some cases, fibroblasts may be utilized as a more practical, and potentially more effective cell therapy than mesenchymal stem cells (abstract).”
“Accordingly, tissue sources, such as fibroblasts, in which larger numbers of cells may be originally extracted, may serve as an attractive alternative to MSC (pg. 2, column 1, para 3).”
“Based on currently accepted definitions for cultured human MSCs and fibroblasts, the investigators could not find any immunophenotypic property that could make a characteristic distinction between MSCs and fibroblasts (pg. 5, column 1, para. 2).”
Hence, there is strong evidence of an express recognition of fibroblasts as a practical, interchangeable, and in some cases preferable alternative to mesenchymal stem cells, and the prior art further explicitly teaches the utility of fibroblasts as CAR-expressing platforms, CAR-engineered fibroblast cells, or CAR-F cells. Therefore, a person of ordinary skill in the art would have found it obvious and been motivated to substitute fibroblasts for MSCs with as reasonable expectation of success.
Conclusion
Claims 1-20 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOEL D LEVIN whose telephone number is (571)270-0616. The examiner can normally be reached Fulltime Teleworker.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.D.L./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633