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 election without traverse of species I, drawn to claim 11, in the reply filed on 1/20/2026 is acknowledged. The claims examined include 1-11 and 17-20.
Claims 12-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species 2-6 there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/20/2026.
Claim Interpretation
Claim 19 uses the term “trivalent gene construct” and claim 20 uses the term “polyvalent gene construct”. Upon review of the specification the examiner found no definition, and, no guidance on how to interpret these terms. They are not well known in the field. Therefore, the examiner has interpreted the meaning of “trivalent gene construct” as a genetic sequence that codes for protein(s) that have 3 antigen binding sites, or, 3 epitopes capable of being bound, or, possess 3 ligands that are functionally enabled to bind anything. By extension “polyvalent gene construct” has been interpreted as a genetic sequence that codes for protein(s) that have more than 1 antigen binding site, or, more than 1 epitope capable of being bound, or, possess more than 1 ligand that is functionally enabled to bind anything. Under the broadest reasonable interpretation, the event of binding will be defined as the stable interaction between anything and the protein encoded by the genetic sequence.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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.
Claim 17 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the method claimed in claim 1, does not reasonably provide enablement for performing the method of claim 17. Claim 17 claims the method of claim 1, however stipulates xenofree media be used throughout the process. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
When examining the predictability of the art it becomes clear the process of dedifferentiation into iPSCs and then inducing stem cells to take a specific developmental pathway is highly unpredictable for the following reasons. Cell fate during differentiation is significantly influenced and control many distinct factors. Cytokine concentration gradients, cell densities, substrate interactions, the timing, length and concentration of growth factor exposure, residual epigenetic memory that is not wiped during the dedifferentiation process, notch ligand presentation mechanics (which is particularly relevant in the instant case). All these individual factors, and their combined interactions, can have significant effects on the differentiation process and outcome. Therefore, a person of ordinary skill in the art would be required to explore a large number of combination conditions. Additionally, federal courts have consistently recognized biotechnology as an unpredictable field. (See: Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010), Eli Lilly & Co. v. Bd. of Regents of the Univ. of Wa., 334 F.3d 1264, 1269-70, 67 USPQ2d 1161, 1164-65 (Fed. Cir. 2003), and re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)).
When one considers the number of working examples provided by the applicant it is clear that there is little/no guidance provided on what values or range of values should be assigned to each of the aforementioned variables. Additionally, there is no guidance on how to develop the method from scratch. Explicitly, there are no working examples provided for the method of clam 1 or for how to perform the method as detailed by claim 17 (xenofree conditions).
When one considers the amount of direction provided by the inventor, they find there is no formal defined/disclosed media composition for any of the steps of the protocol under xenofree conditions. Additionally, the inventors do not take the time to provide any suggestions or direction on how/what to supplement the xenofree media with to replace all of the animal products. It is clear that each component (animal or not) of the composition serves a significant role. How/what do you replace all the removed animal products with so that their roles/effects/ functions are restored?
When one considers the state of the prior art, it becomes clear that there is no disclosed or established protocol and corresponding composition/media identities that can efficiently and reproducibility differentiate iSPCs into T-cells under completely xenofree conditions. There are several discreate steps of the complete protocol that have established xenofree media conditions. However, the differentiation step that turns hematopoietic progenitors in to T-cell lineage commitment has proven especially difficult. During this step the differentiating cells need strong and spatially organized Notch ligand/signaling which is very difficult to produce with soluble notch ligands alone. A mouse cell line has been engineered to express the Notch ligand strong enough on its surface and therefore these cells are cocultured with the differentiating hematopoietic progenitors and promote t-cell differentiation, but these conditions are not xenofree. Some people have used plate-bound notch ligand instead of expressing the ligand in mouse cells, but results are vague, severely inefficient, and highly unreproducible. Developing a truly xenofree protocol for the HSC -[Wingdings font/0xE0]T-cell progenitor step is an active area of research and development. (Trotman-Grant, C. A. et al. 2021) (Netsrithong, R et al. 2024) (Zhu, E, et al. 2026).
The differentiation of induced pluripotent stem cells into regenerative T cells is a highly context-dependent and biologically complex process involving temporally coordinated cytokine exposure, spatially organized Notch signaling, and multi-stage lineage commitment. Federal Circuit precedent recognizes biotechnology as an unpredictable art. In the absence of working examples, defined media formulations, or guidance for eliminating xenogeneic components at the Notch commitment stage, a person of ordinary skill would be required to engage in extensive iterative optimization. This is a case where the specification requires the skilled artisan to discover how to perform the invention rather than teaching how to perform it. Such experimentation exceeds routine substitution and constitutes undue experimentation under In re Wands. Additionally, this is not a case where a skilled artisan could simply substitute animal-free reagents, this is the reconstruction of a multi-signal developmental microenvironment.
Claim 17 is 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. Applicant claims performing the method of claim 1, with the added limitation of using xenofree media. However, the applicant provided no explicit definition and no explanation of the limits and requirement of media to be “xenofree”. For instance, are human recombinant proteins produced in animal cells xenofree? Do tracer stabilizers disqualify the media? Does residual feeder-derived matrix contamination disqualify the media? Does the use of animal trypsin for cell passaging render them irreversibly contaminated? This leaves the metes and bounds of the claim unclear.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lei, F et al 2009.
Lei, F et al 2009 discloses, “…we assessed expression of CD3 and TCRβ on iPS cell-derived cells. After 12-day co-culture with OP9-DL1 cells, iPS cells lost CD117 expression and retained CD4− CD8−, but expressed CD44 and CD25 on the surface of thymocyte-like populations (DN1 and DN3. Fig. 2A). From day 18, cells expressed both CD4 and CD8, including CD4+ CD8+, and CD4− CD8+ populations (Day 22. Fig. 2B), and expressed CD3 and TCRβ (Day 22. Fig. 2C). By gating CD45+ population on day 18 (Fig. 2D), we found the cells were CD4+ CD8+ (DP), CD4− CD8− (DN), and CD4− CD8+ (SP) (Fig. 2E). The majority of CD3+ cells were located in CD4− CD8+ population, however, approximately 5% of CD4+ CD8+ population also expressed CD3 (Fig. 2F), suggesting CD3+ TCRβ+ cells were generated from CD4+ CD8+ population. These CD4+ CD8+ cells are thymocyte progenitors, which have a large nucleus with dense heterochromatin and a thin rim of cytoplasm.” (3.2. iPS cells differentiated to T lymphocytes section paragraph 1). Importantly, OP9-DL1 cells are stable bone marrow-derived stromal cell line (aka mesenchymal stem cells). (Sigma Data Sheet OP9-DL1 2023). Additionally, it is known that CD4- CD8- DN T-cells are regenerative and repair-oriented, carrying out regulatory functions that aid in tissue regeneration, supported by Young, K et al. 2002. Separation of the different populations of T-cells was performed by flow cytometry (see Figure 2). Therefore, Lei, F et al 2009 disclose a method of culturing pluripotent stems cells and differentiated iPSCs into T-cells that have regenerative capabilities. Importantly, during differentiation the cells are in coculture/contact with mesenchymal stem cells (OP9-DL1 cells). This anticipates claim 1 (A method for production of T cells possessing ability to regenerate injured tissue comprising the steps of: a) obtaining [[a]] pluripotent stem cells; b) differentiating said pluripotent stem cells into [[a]] T cells; c) contacting said pluripotent stem cells at one or more time points during the differentiation process with mesenchymal stem cells (MSCs)or products derived thereof, and d) isolating T cells possessing regenerative activity).
It also anticipates claim 2 (The method of claim 1, wherein said pluripotent stem cells are selected from one or more sources from the group consisting of: a) inducible pluripotent stem cells…) because the stem cells used are induced pluripotent stem cells (iPSCs).
Furthermore, Lei, F et al 2009 discloses, “iPS cells were washed once in OP9-DL1 medium before plating onto subconfluent OP9-DL1 monolayers for T lineage differentiation in the presence of murine recombinant Flt-3 ligand and 1 ng/ml murine IL-7.” (2. Materials and methods section paragraph titled 2.3. Cell culture). This detailed disclosure of culture conditions during iPSC to T-cell differentiation outlines the use of cytokines in the process, and as disclosed above, the iPSC cells went through the standard process of hemopoiesis (aka iPS cells lost CD117 expression and retained CD4− CD8−, then became CD4+ CD8+, then became single positive.). These disclosures anticipate clam 3 (The method of claim 1, wherein said pluripotent stem cells are differentiated into T cells by sequential culture in cytokines and conditions replicating thymopoiesis). Importantly, they say, “In addition, patient-specific iPS cells would be useful in the terms of drug discovery and regenerative medicine” (Introduction).
Finally, Lei, F et al 2009 discloses, “After 12-day co-culture with OP9-DL1 cells, iPS cells lost CD117 expression and retained CD4- CD8-, but expressed CD44 and CD25 on the surface” (paragraph 1 of section “3.2. iPS cells differentiated to T lymphocytes”). Furthermore, they say, “On Day 22, 3 *106 iPS cell-derived CD3+ cells were injected i.v. into 4-week Rag1-deficient mice. After 4 weeks, single-cell suspensions from lymph nodes and spleen were analyzed for expression of CD4, CD8, CD3 and TCRb using flow cytometry.” (paragraph titled: 2.5. Adoptive cell transfer). The doubling time of undifferentiated iPSC cells is around 16 hours, and lengthens to 20 hours after differentiation as supported by Chatterjee, I et al. 2016. The methods outline that the cells were maintained for 22 days in-vitro and then 4 weeks in vitro. With a doubling time of 20 hours, this means the iPSC cells went through at least 60 doublings. Note: they were still able to be extracted, labeled, and analyzed by flow cytometry. Furthermore, the fact that the iPSC derived T-cells exhibited normal morphology, protein expression patterns (see figure 4), and were properly localized in the RAG-1 deficient mice after 60 doublings supports the idea that very few, if any, developed aneuploidy. Upon aneuploidy, cells began their transformation into malignancies, which results in changes to their size, shape, bio-distribution, and protein expression patterns. Therefore, these disclosures anticipate claim 6 (The method of claim 2, wherein said inducible pluripotent stempossess[[es]] one or more markers selected from the group consisting of: CD10, CD13, CD44, CD73, CD90, PDGFr-alpha, PD-L2, and HLA-A, -B, -C and possesses ability to undergo at least 40 doublings in culture, while maintaining a normal karyotype upon passaging up to 50 times.)
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 4 is rejected under 35 U.S.C. 103 as being unpatentable over Lei, F et al 2009 and further in view of US 20250230411 A1.
Lei, F et al 2009 anticipates the method of claim 1, 2 and 3 as outlined above. Lei, F et al 2009 does not disclose the following additional steps outlined in claim 4.
US 2025230411 A1 discloses, “iPSC was expanded by culture on iMatrix-511 of StemFit AK02N for 6 to 7 days and dissociated into single cells with 0.5×TryPLE select (Thermo Fisher Scientific).” (paragraph 0264). The method continues, “T cell differentiation was induced on a rhDL4-coated plate prepared the day before iHPC seeding.” (paragraph 0266). Furthermore, “For seeding iHPC… 2000 CD34+ /CD43+ cells were directly FACS-sorted into wells of a DL4-coated plate containing a T cell differentiation medium consisting of…50 ng/mL rhIL-7…The differentiated cells were transferred to a new DL4-coated plate on day 7…” (paragraph 0267). The following section is titled: “Maturation of Progenitor T Cells into CD8 Single-Positive T Cells” (paragraph 268). Importantly, “DL4 cells on day 21 were stimulated with 500 ng/mL anti-CD3 monoclonal antibody (clone: OKT3, eBioscience) in a maturation medium consisting of…10 ng/mL rhIL-7, 10 ng/mL rhIL-2…After 3 days, the cells were recovered, washed, resuspended in an OKT3-free maturation medium…” (paragraph 0269). Importantly, CD8+ CD4- negative cells are capable of tissue regeneration, and in fact, are essential in the regeneration of damaged muscle tissue. (Zhang, J. et al. 2014).
Integrating the specific culture conditions and incubation times detailed in the protocol disclosed in US 2025230411 A1 into the method of Lei, F et al 2009, which is used to differentiate iPSCs into regenerative T cells, would be obvious to a person of ordinary skill in the art, before the effective filing date and therefore renders claim 4 obvious. The motivation/rationale to do so is the following: 1) The detailed methodology is well known in the field and it is a trusted and proven method because the same detailed methodology has been disclosed elsewhere indicating others have used it with successes. Additionally, it is also well known that inducing differentiation of pluripotent stems cells in a controlled and directed manner requires very idiosyncratic conditions that are defined by specific mixtures of chemicals/media and modes of cell stimulation. Therefore, it would be obvious to use the methodology already developed and proven to work. Importantly, US 2025230411 A1 details changing the concentration of IL2 during different culture conditions, indicating that cytokine concentration is an optimizable parameter which changes based on the particulars of the method, stage of differentiation, cellular heritage, and the intended differentiation pathway (see paragraph 0144 for details). They also outline the optimization of time in culture in terms of the number of days cells are maintained in each step of the differentiation process. Thus, they are routine optimizable parameters that depend on the seeding density, growth kinetics of the individual cell types and their heritage, as well as culture conditions.
Claims 5, and 8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Lei, F et al 2009 and further in view of US 2023014637 A1 as supported by Gang, E et al. 2006, A.D. Ho, et al 2008, Bakhshi T. et al. 2008, Vilotić, A et al. 2022, and Jang, K, Y et al. 2006.
Lei, F et al 2009 anticipates the method of claim 1, 2 and 3 as outlined above. Lei, F et al 2009 does not disclose the claim limitations of 5, and 8-11.
US 2023014637 A1 discloses, “Preferred methods include embodiments wherein said embryonic stem cells express stage-specific embryonic antigens (SSEA) 4.” (paragraph 590, instant claim 5). Additionally, they disclose, “Preferred methods include embodiments wherein said mesenchymal stem cells are derived from a group selected of: …c) umbilical cord blood; …” (paragraph 0684, instant claim 8). Furthermore, they disclose, “Preferred methods include embodiments wherein said umbilical cord derived mesenchymal cell expresses CD90.” (paragraph 0228, instant claim 9). Additionally, “Preferred methods include embodiments wherein agent capable of increasing anti-inflammatory activity in said regenerative cell is an activator of a pattern recognition receptor.” (paragraph 0682). Furthermore, “Preferred methods include embodiments wherein said activator of said pattern recognition receptor is a toll like receptor agonist.” (paragraph 0683, instant claim 10). “Preferred methods include embodiments wherein said TLR-1 is activated by Pam3CSK4.” (paragraph 0866, instant claim 11).
Therefore, US 2023014637 A1 provides a teaching that makes it obvious to one of ordinary skill in the art, before the effective filing date, to use embryonic stems cells expressing SSEA 4 as the pluripotent stem cells in the method of Lei et al. 2009. One would do this because expressing SSEA 4 indicates cells are very early in the development process and contain self-renewal and pluripotency potential, and therefore continually produce new stem cells during mitosis. The embryonic stem cells expressing SSEA-4 also have a naïve epigenetic environment that renders them superior to iPSCs, which still contain epigenetic hallmarks of the cell they were derived from (and therefore detracts from their ability to be truly reprogramed). (supported by Gang, E et al. 2006). This renders claim 5 obvious.
US 2023014637 A1 also provides a teaching/suggestion that makes it obvious to one of ordinary skill in the art, before the effective filing date, to use umbilical-derived mesenchymal stem cells (UC-MSC) as the feeder layer in the method of Lei, F et al 2009. One would do this because UC-MSCs offer a more robust, consistent feeder layer that can be expanded rapidly and for a longer period in vitro without premature senescence, which often limits the use of adult BM-MSCs., as supported by Jang, K, Y et al. 2006. This renders claim 8 obvious.
Furthermore, US 2023014637 A1 provides a teaching/suggestion that makes it obvious to one of ordinary skill in the art, before the effective filing date, to use only UC-MSCs expressing the pluripotent marker CD90 in the feeder layer when carrying out the method of Lei, F et al 2009. One would do this because CD90 is a marker for identifying undifferentiated MSCs, and therefore aids in their separation from other cell types after umbilical cord harvest Additionally, it’s a key surface protein that can enhance osteogenic differentiation and influence the fate of stem cells, making it crucial for a stable, high-quality microenvironment, as supported by A.D. Ho, et al 2008 and Bakhshi T. et al. 2008. This renders claim 9 obvious.
Additionally, US 2023014637 A1 provides a teaching/suggestion that makes it obvious to one of ordinary skill in the art, before the effective filing date, to activate the mesenchymal stem cell feeder layer used in the method of Lei, F et al 2009 via TLR1 binding, and specifically using the Pam3CSK4 ligand. One would do this because activating a mesenchymal stem cell (MSC) feeder layer using Pam3CSK4, a TLR1 agonist, results in changes in cytokine expression, particularly upregulation of IL-6, which influences t-cell differentiation towards the regenerative phenotype, as supported by Vilotić, A et al. 2022. This renders claim 10 and 11 obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Lei, F et al 2009 as applied to claim 2 above, and further in view of Hwang W, S, et al.2004 as supported by Matoba, S. et al. 2018.
Lei, F et al 2009 anticipates the method of claim 1 in its entirety. It also anticipates claim 2, which is dependent on claim 1, by using iPSCs. However, Lei, F et al 2009 does not disclose the use of somatic cell nuclear transfer derived stem cells, and it does not disclose that they possess a phenotype negative for SSEA-1 and positive for SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, and alkaline phosphatase.
Hwang W, S, et al.2004 discloses, “Autologous SCNT was performed; that is, the donor’s own cumulus cell, isolated from the cumulus-oocyte complex (COC), was transferred back into the donor’s own enucleated oocyte.”(Middle of paragraph 2). Furthermore, “A total of 30 SCNT-derived blastocysts were cultured, 20 ICMs were isolated by immunosurgical removal of the trophoblast, and one ES cell line (SCNT-hES-1) was derived.” (top of paragraph 5). Additionally, they disclose, “Furthermore, the SCNT-hES-1 cells expressed ES cell markers such as alkaline phosphatase, SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, and Oct-4, but not SSEA-1 (Fig. 2).”(middle of paragraph 5).
Hwang W, S, et al.2004 has provided a teaching on how to generate SCNT-hES-1 cells. Therefore, other researchers have the ability to generate somatic cell nuclear transfer derived stem cells using their detailed methodology. Therefore, it is obvious to a person of ordinary skill in the art, before the effective filing date, to use SCNT-hES-1 as the pluripotent cells in the method of Lei, F et al 2009. The rationale for substituting SCNT-hES-1 cells in place of iPSCs cells for the generation of regenerative T-cells is as follows: 1) SCNT derived ES cells experience a much more complete epigenetic reprograming which more closely resembles natural ESCs compared to iPSCs. 2) iPSCs retain a larger “epigenetic memory” compared to SCNT derived ES cells. This memory is biased toward the cell type that was reprogramed to become the iPSC. These epigenetic markers will hinder the development of iPSCs into cells types that don’t match the original cell type. 3) the generation of iPSCs requires significantly longer time in culture than SCNT derived ECs. Therefore, IPSCs face a much greater risk of acquiring DNA mutations that affect the safety and efficacy of iPSCs compared to SCNT derived ECs. (Matoba, S. et al. 2018).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Lei, F et al 2009 as applied to claim 1 above, and further in view of US 2023014637 A1.
US 2023014637 A1 discloses, “The term “subject” or “individual” as used herein refers to an animal having an immune system, preferably a mammal (e.g., rodent such as mouse). In particular, the term refers to human.” (paragraph 1043). Furthermore, “the therapeutically reprogrammed cells…of the present invention are administered systemically, such as intravenously, and migrate to the site of the freshly traumatized tissue…another embodiment of the present invention, the therapeutically reprogrammed cells…can be administered locally to a treatment site in need or repair or regeneration.” (paragraph 1075).
Therefore, US 2023014637 A1 has provided a suggestion/teaching, making it obvious to a person of ordinary skill in the art, before the effective filing date, to administer the regenerative t-cells created from the method of Lei, F et al 2009, as a treatment for a person suffering from damaged tissue. The motivation to administer the regenerative t cells to a patient could be either monetary, or could simply be to fulfill the desire to test and improve one’s invention. This renders claim 18 obvious.
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Lei, F et al 2009 as applied to claim 1 above, and further in view of US 2025230411 A1.
US 2025230411 A1 discloses, “FIG. 10 shows a structure of a CAR molecule used in Example 4.” (paragraph 0075). (see the annotations in figure 10). Furthermore, they disclose, “In these experiments, as iPS cells, non-T cell-derived iPS cell strain FFI01s04 not having a reconstituted TCR gene was used…antigen specificity was imparted by gene transduction of a chimeric antigen receptor (CAR). CAR has a chimeric structure in which a single-chain antibody (scFv) composes a variable light chain (VL) and a variable heavy chain (HL) of a monoclonal antibody to an antigen molecule. are bound in series is used as an extracellular domain, and a costimulatory molecule and a CD3z chain are used as an intracellular domain. This time, HA-A2 was employed as an antigen, and CD28 was employed as a costimulatory molecule (see FIG. 10 ). By expressing this molecule by gene transduction, T cells (CAR-T cells) expressing this molecule can directly recognize an antigen on the cell surface, here, HA-A2, in an HLA non-restricted manner.” (paragraph 0236). Additionally, “… CAR-expressing cells were labeled using a PE-conjugated antibody (Cell Signaling Technology, clone: 9B11) with respect to myc tag, and concentrated by the MACS method…” (paragraph 0237).
Therefore, they have provided a teaching/suggestion, making it obvious to a person of ordinary skill in the art, to incorporate a polyvalent/ trivalent gene construct that codes for a protein having 3 individual binding pockets (vL and vH regions both binding HA-A2 individually, and the CD28 domain) into the regenerative T-cells created from the method of Lei, F et al 2009. Importantly, when bound, the CAR receptor is activated and results in T-cell activation. The rationale to combine this trivalent gene construct with the regenerative T-cells derived from the method of Lei, F et al 2009 is that it gives the doctor/scientist/patient the ability to control regenerative t-cell activation in space and time. This renders claim 19 and 20 obvious.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Adam M Smith whose telephone number is (571)272-7517. The examiner can normally be reached Monday- Friday 10:30AM-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at (571) 272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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