DETAILED ACTION
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 .
Status of the Claims
Claims 1-4, 6, and 28-31 are pending.
Claims 1, 28, and 30 are newly amended.
Claims 1-4, 6, and 28-31 have been examined on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
In reconsideration of the claims, the previous rejection under 35 USC 112(a) have been withdrawn. New grounds of rejection under 35 USC 103 are made as discussed below. Additionally, a new ground of rejection under 35 USC 112(a) is made to address subject matter not described in the specification as newly amended in the claims.
Response to Arguments - persuasive
In regards to the limitation of “the concentration of the anti-CD3 antibody and the anti-CD28 antibody in the nanomatrix is sufficient to increase T cell expansion in a culture containing the nanomatrix 100-fold above a control T cell culture that does not contain the nanomatrix”, Applicant points to an exact description of an exemplary anti-CD3/CD28 nanomatrix and references the publication US2014/0087462 (now U.S. Patent 10,513,687), as enablement and disclosure of this limitation (Remarks, p7-8).
Applicant further points to Fig. 3 which demonstrates that all nanomatrices falling within the scope of amended claim 1 induce a 100-fold increase in cell count while cells without the nanomatrix either do not expand or decrease in number (Remarks, p7-8).
Applicant’s arguments, see p7-8, filed 01/21/2026, with respect to the rejection under 35 USC 112(a) have been fully considered and are persuasive. The rejection of the claims under 35 USC 112(a) have been withdrawn. However, it is noted that Fig. 3 while showing a fold expansion in all groups, does not show results for cells not cultured in the nanomatrix.
Response to Arguments – not persuasive
In regards to the limitation of a “volume of a starting human cell population between 3000 and 5000 mL”, Applicant points to paragraph [0162] and argues that this volume is inherent in the term “donor blood” (see Remarks, p5, Status of the Claims).
Applicant’s arguments filed 01/21/2026 have been fully considered but are not found persuasive. As discussed below, a generic disclosure of “donor blood” is not a volume of starting human cell populations, but rather only describes a source from which cells may be found, and therefore does not necessarily imply (nor is it inherent to) the range of a volume of a starting human cell population as claimed.
In the remarks on 10/08/2025 Applicant argues that the claims recite that the resulting cells are CAR-T cells with the CAR-T cell population having an improved measurement of one or more of the total number of cells, the number of CD45RA+ cells, the number of CD45RA+/CD5+ cells (reflecting the number of Tscm), the number of CAR+ cells and the number of TCRaß- cells than a CAR-T cell population made according to the prior art method (Remarks 10/08/2025, p6-7).
Applicant arguments filed 10/08/2025 have been fully considered but upon reconsideration are not found persuasive.
In regards to a step of genetically modifying a T cell to express a CAR, as discussed above, in regards to step d), Scheffold teaches that the resulting T cell population can be genetically transduced and used for immunotherapy (paragraph [0090], but is silent as to expressing a CAR. However, Kaiser teaches that T cells expanded in TransAct can be modified to express a CAR, or any other accessory molecule on their surfaces (paragraph [0037]).
A person of ordinary skill in the art would have been motivated to express a CAR in order to use these cells in immunotherapies. Furthermore, because Kaiser teaches that T cells cultured in TransAct can be engineered to express CARs, it could have been done with predictable results and a reasonable expectation of success.
In regards to other cell types, the claims do not require these cells, but only states that the they can be measured (measuring none would satisfy the claim). Additionally, as discussed above, Rasaiyaah teaches, at least, a number of CAR T cells (Fig. 1, p3).
In the remarks on 10/08/2025 Applicant argues that while the Applicant agrees that it was generally known (e.g., from the art cited herein) that a greater volume of the CD3/CD28 antibody matrix relative to the volume of cells would result in more cell activation, there is no teaching on the relationship between the volumetric ratio and the numbers of Tscm, or the volumetric ratio and successful genome modification of cells including a gene insertion and a gene knockout, or the volumetric ratio and the combination of the parameters measured according to the amended claim 1, the parameters being critical for the CAR- T cell survival and potency (Remarks 10/08/2025, p7).
Applicant arguments filed 10/08/2025 have been fully considered but upon reconsideration are not found persuasive.
As Applicant admits it was known in the art that a greater volume of the CD3/CD28 antibody matrix relative to the volume of cells would result in more cell activation. Therefore, a greater number of stem memory T cells would have been the expected results of culturing T cells in a higher volumetric ratio of TransAct.
In regards to successfully genetically modifying T cells, this is explicitly taught in the prior art. As discussed above, Scheffold teaches that the resulting T cell population can be genetically transduced and used for immunotherapy (paragraph [0090] and Kaiser teaches that T cells expanded in TransAct can be modified to express a CAR, or any other accessory molecule on their surfaces (paragraph [0037]).
In the remarks on 10/08/2025 Applicant argues that there are unexpected results (Remarks 10/08/2025, p7). In particular, Applicant argues that it was unexpected and non-obvious to have found that the claimed volumetric ratio of cells to the CD3/CD28 antibody matrix produces the combined phenomena of the maximum cell yield together with the maximum number of Tscm together with the maximum number of CAR-expressing cells together with the maximum number of TCR-negative cells (Remarks 10/08/2025, p7). Applicant argues that this is supported in Figures 1-5, 10A, 11A and 12 (Remarks 10/08/2025, p7). Applicant argues that whole the increase in a parameter is not dramatic, the practical significance is contained in the combination of increases yielding an improved CAR-T cell population having a greater therapeutic potential than the CAR-T cell population prepared according to the method existing in the art (Remarks 10/08/2025, p7). Lastly, with respect to commensurate scope, the scope of the amended, Applicant argues that claim 1 is commensurate with the experimental data (Figures 1-5, 10A, 11A and 12) (Remarks 10/08/2025, p7).
Applicant arguments filed 10/08/2025 have been fully considered but upon reconsideration are not found persuasive.
As noted by Applicant, the provided data only demonstrates non-dramatic increases in cell number. However, there is no indicated that these results were greater than expected. According to MPEP 716.02(a), Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (Evidence showing greater than additive sweetness resulting from the claimed mixture of saccharin and L-aspartyl-L-phenylalanine was not sufficient to outweigh the evidence of obviousness because the teachings of the prior art lead to a general expectation of greater than additive sweetening effects when using mixtures of synthetic sweeteners.).
However, the provided data only demonstrates a linearly greater amount of cell expansion with higher volumetric ratios. However, as discussed above, and as admitted by Applicant, it was known in the art that a greater volume of the CD3/CD28 antibody matrix relative to the volume of cells would result in more cell activation. Therefore, a greater number of stem memory T cells would have been the expected results of culturing T cells in a higher volumetric ratio of TransAct.
Additionally, according to the disclosure, the claimed volumetric ratios do not even show greater fold expansion until after specific expansion with a G-Rex (see Fig. 4, there is no difference, whether significant or not in expansion until after being cultured in a G-Rex). This feature is not required by the claims, and therefore, even if there were differences, the data is not commensurate in scope with the claims (see MPEP 716.02(d), whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the “objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support.” In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)).
Furthermore, Fig. 12 at least, comparing the percentages of cells, the differences are only within low percentages, and in fact, hTransAct 1:20 centrifugation demonstrates a 3% greater number of CAR+/TCRAB- cells compared to hTransAct 1:10 diluted.
Claim Rejections - 35 USC § 112(a)
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.
Claims 1-4, 6, and 28-31 are 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.
Specifically, claim 1 as newly amended recites the limitation, “with a volume of a starting human cell population between 300 and 5000 mL.” For justification for this limitation, Applicant points to paragraph [0162] and argues that this volume is inherent in the term “donor blood” (see Remarks, p5, Status of the Claims).
However, a generic disclosure of “donor blood” is not a volume of starting human cell populations, but rather only describes a source from which cells may be found, and therefore does not necessarily imply (nor is it inherent to) the range of a volume of a starting human cell population as claimed.
Additionally, even if the generic disclosure of “donor blood” implied a broad genus of volumes of starting human cell populations, an adequate description of a genus may not support claims to a subgenus or species within the genus (see MPEP 2163(I)(B), In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972); see also n re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) (subgenus range was not supported by generic disclosure and specific example within the subgenus range)).
In the instant case, even if the generic disclosure of “donor blood” was a genus that could suggest a volume of starting human cell populations, the specification provides no indication that this generic disclosure suggests a starting human cell population between 300 and 5000 mL, and the specification does not convey with reasonable clarity to those skilled in the art that, as of the filing date sought, the inventor was in possession of the invention as now claimed (See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117).
Claims 2-4, 6, and 28-31 are rejected under 35 USC 112(a) for their dependence on claim 1.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4, 6, and 28-31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Applicant is directed to the subject matter eligibility test for products processes (MPEP 2106; specifically, MPEP 2106(III) flowchart).
Briefly summarized here, the new guidance cites a two part test: is the claimed invention directed to a statutory category of invention (Step 1), if so, then is the claimed invention as a whole directed to a law of nature, natural phenomena, or an abstract idea (i.e. set forth or described in the claim) (Step 2A, Prong One), if so, then is the claimed invention recite additional elements that integrate the judicial exception into a practical application (Step 2A, Prong Two), and if not, then does the claim as a whole amount to significantly more than the judicial exception (Step 2B).
In regard to Step 1, claims 1-4, 6, and 28-31 are drawn to a process, “a method”, which is a statutory category (thus, Step 1, YES).
In regard to Step 2A, Prong One, this part of the eligibility analysis evaluates whether the claim recites a judicial exception.
Claim 1 recites “A method for increasing a percentage of stem memory T cells in a human CAR-T cell population comprising . . . f) obtaining in a resulting human CAR-T cell population a measurement of one or more of i) a total number of cells, etc.”
Similarly, claim 31 recites, “The method of claim 1, wherein the step f) comprises obtaining . . . a measurement of the total number of cells, etc.”
A step of obtaining a measurement “can be performed in the human mind, or by a human using a pen and paper” (CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011)) and is therefore a mental process (a judicial exception). As discussed in MPEP 2106.04(a)(2)(III), “[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work” (Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012), quoting Benson, 409 U.S. at 67, 175 USPQ at 675)) (thus, Step 2A, Prong One, YES).
In regards to Step 2A, Prong Two, this part of the eligibility analysis evaluates whether the claim as a whole integrates the recited judicial exception into a practical application of the exception.
With respect to Step 2A, prong two, limitations that may be enough to qualify as additional elements that integrate the judicial exception into a practical application include:
Improvements to another technology or technical field.
Improvements to the functioning of the computer itself.
Applying the judicial exception with, or by use of, a particular machine.
Effecting a transformation or reduction of a particular article to a different state or thing
Adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application.
Other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
With respect to Step 2A, prong two, limitations that were found not to be enough to qualify as additional elements that integrate the judicial exception into a practical application include:
Adding the words ‘‘apply it’’ (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well understood, routine and conventional activities previously known to the industry
Adding insignificant extra-solution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea
Generally linking the use of the judicial exception to a particular technological environment or field of use.
In the instant claim 1, although the claims recite steps of contacting T cells with anti-CD3/CD28 nanomatrix and then genetically modifying those cells to establish a CAR-T cell population (steps a) through e)), these steps all built up to the final step of measuring, and therefore, are all insignificant extra-solution activity and amount to mere gathering for the mental process (the judicial exception). See MPEP 2106.05(g), determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)). Therefore, the claim does not additional elements that integrate the judicial exception as a whole into a practical application (thus, Step 2A, Prong Two, NO).
In regard to Step 2B, this part of the eligibility analysis evaluates whether the claim as a whole amount to significantly more than the judicial exception.
As discussed above, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception, but rather, are all mere data gathering steps for a final step of the mental process of measuring.
Furthermore, the additional elements of contacting stem memory T cells with anti-CD3/CD28 nanomatrix and then modifying those T cells to express a CAR were all routine in the art in the art before the effective filing date.
Specifically, as evidenced by Scheffold et al. (US20140087462, on IDS 12/04/2020; cited by Applicant in the Response on 01/21/2026) (see claim 1; paragraphs [0019, 0026]); Kaiser et al. (US 20170037370 A1, 2017, previously cited)(claim 2, paragraphs [0035-0036]); Mockel-Tenbrinck et al. (Mol Ther, 2017, previously cited) (see Table 1), it was known in the art that T cells could be contacting with varying concentrations of anti-CD3/anti-CD28 nanomatrix. While as evidenced by Rasaiyaah et al. (JCI Insight, 2018)(see Methods, p9-10), it was known that CAR T cells with a disrupted TCR gene could be engineered.
As a result, the additional elements individually or in combination with the judicial exception were routine in the art, and therefore, do not provide an inventive concept, and therefore, the claim as a whole does not amount to significantly more than the judicial exception (thus, Step 2B: NO).
Regarding dependent claims 2-4, 6, and 28-31, the claims neither add additional elements that are sufficient to amount to significantly more than the judicial exception (e.g., the claims are directed to routine or conventional sources of cells, cell markers, and methods for engineering CAR T cells).
Additionally, claim 31 itself, repeats the measuring step of step f).
Therefore, the claims are not considered to recite something significantly different than a judicial exception and thereby are not directed to patent eligible subject matter.
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 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.
Claims 1-4, 6, and 28-30 are rejected under 35 U.S.C. 103 as being unpatentable over Scheffold et al. (US20140087462, on IDS 12/04/2020; cited by Applicant in the Response on 01/21/2026) in view of Kaiser et al. (US 20170037370 A1, 2017, previously cited), Mockel-Tenbrinck et al. (Mol Ther, 2017, previously cited), Casati et al. (Cancer Immunol Immunother, 2013, on IDS 12/04/2020, previously cited) and Rasaiyaah et al. (JCI Insight, 2018).
In regards to claims 1, 3, and 30, Scheffold teaches methods for stimulating human T cells, including at least memory T cells (claim 1; paragraphs [0019, 0026]).
In regards to step a), Scheffold teaches that the method comprises contacting T cells with a nanomatrix attached (conjugated) to anti-CD3 and anti-CD28 antibodies (claims 1, 3-4, and 6-7).
It is noted that Scheffold is the patent application for the commercial product TransAct (Miltenyi), which the instant specification indicates is a suitable nanomatrix (see paragraph [0103]).
In regards to whether the nanomatrix being sufficient to increase T cell expansion 100-fold above a control culture that does not contain the nanomatrix, it is noted that as argued by Applicant (see Remarks 01/21/2026, p5, “Status of the Claims”), justification for disclosure of this limitation is explicitly premised on incorporation of Scheffold (see instant specification paragraph [0103]). Thus, the method of Scheffold would naturally also produce a 100-fold increase in T cell expansion.
In regards to “a starting human cell population between 300 and 5000 mL”, and also in regards to substep 1), it is noted that as cells are not liquids, they cannot be measured by volume (rather they must be measured by mass). However, in as much as the claim intends to mean cells in a starting volume, and while Scheffold is silent as to the density of the starting human population, culturing cells in TransAct at densities that overlapped with the claimed ranges and in volume that were at least close to the claimed ranges where known in the art before the effective filing date.
In particular, Kaiser teaches methods for culturing T cells with TransAct comprising culturing T cells at densities between 0.5 x 106 cells/mL to 4 x 106 cells/mL (claim 2, paragraphs [0035-0036]), which lies within the range of about 0.2 x 106 cells/mL to 5.8 x 106 cells/mL (and which also overlaps with the densities in claims 7-12). Kaiser also teaches initial starting volumes of 200 mL (paragraph [0063]), which is at least close to a volume range of 300 and 5000 mL (1 (see MPEP 2144.05(I), a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)).
A person of ordinary skill in the art would have been motivated to culture cells at this density because Kaiser teaches that it is suitable for culturing T cells in TransAct and in particular and because Kaiser teaches that with TransAct, T cells can be cultured at high densities (greater than 3e6 T cells/mL) (paragraph [0035-36]). Furthermore, because Kaiser explicitly teaches that T cells can be cultured at densities that overlap with the claims and because both Scheffold and Kaiser are the same applicant (Milenyi) using the same TransAct nanomatrix, it could have been done with predictable results and a reasonable expectation of success.
Additionally, a person of ordinary skill in the art could have used a starting volume of 300 to 5000 mL by routine optimization, and the disclosure does not point to a criticality in this amount. See a MPEP 2144.05(II), generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). In the instant case, because Kaiser teaches a range of initial volume (paragraph [0063]) and cellular densities that overlap with the claimed range (which would require larger volumes), it could have been done with predictable results and a reasonable expectation of success.
In regards to substep ii), Scheffold teaches the ratio of CD3/CD28 nanomatrix to cells can be large, and can be least 100:1 to 1000:1 (paragraph [0020]), which is magnitudes higher than the claimed range of 1:5 to 1:10).
However, it was known in the art before the effective filing date that lower matrix to cell ratios could also be utilized.
Indeed, as taught Mockel-Tenbrinck the recommended initial dilution of TransAct is 1:17.5 (Table 1), which is lower, but close to the claimed range of 1:5 to 1:10 as in claim.
Thus, a broad range of ratios that are both greater and smaller than the claimed ratios was taught by the prior art.
Therefore, a person of ordinary skill in the art could also have arrived at a concentration of 1:5 to 1:10 as in claim 1 by routine optimization, and the disclosure does not point to a criticality in this amount.
Moreover, a person of ordinary skill in the art would have been motivated to use a higher ratio of matrix to cell because as indicated by Mockel-Tenbrinck, higher concentrations (less diluted TransAct) result in higher percentage of activated cells (Fig. 1, percentage of CD69+ cells). A person of ordinary skill in the art would have recognized that more nanomatrix has more CD3/CD28 antibody, and therefore, would be more potent. Furthermore, because Mockel-Tenbrinck teaches that increases in concentration of TransAct results linearly in increases in T cell activation and because Scheffold teaches that cells can be cultured with much higher concentrations of TransAct, it could have been done with predictable results and a reasonable expectation of success.
Moreover, that concentrations of TransAct can be optimized is agreed upon by Casati who teaches methods for stimulating T cells utilizing a TransAct CD3/28 nanomatrix system (p1565), and teaches that anti-CD3 and anti-CD28 TransAct reagents can also be used when conjugated on separate matrices and mixed in variable ratios and concentrations to achieve optimal T cell activation (Flexible nanomatrix for T cell stimulation (TransAct), p1565).
In regards to step b), as above, Kaiser teaches methods for culturing T cells with TransAct comprising culturing T cells at densities between 0.5 x 106 cells/mL to 4 x 106 cells/mL (claim 2, paragraphs [0035-0036]), which overlaps with the range as in step b).
In regards to step c), Scheffold teaches that TransAct may be removed before subsequent applications of the stimulated T cells (paragraph [0053]).
In regards to step d), Scheffold teaches that the resulting T cell population can be genetically transduced and used for immunotherapy (paragraph [0090], but is silent as to expressing a CAR. However, Kaiser teaches that T cells expanded in TransAct can be modified to express a CAR, or any other accessory molecule on their surfaces (paragraph [0037]).
A person of ordinary skill in the art would have been motivated to express a CAR in order to use these cells in immunotherapies. Furthermore, because Kaiser teaches that T cells cultured in TransAct can be engineered to express CARs, it could have been done with predictable results and a reasonable expectation of success.
In regards to steps e), again, as above, Scheffold teaches that the resulting T cell population can be genetically transduced and used for immunotherapy (paragraph [0090]), but is silent as to editing cells to disrupt a TCR specifically.
However, Rasaiyaah teaches that TCRαβ/CD3 disruption enables CD3-specific antileukemic T cell immunotherapy (Title, Abstract, p1), and therefore, a person of ordinary skill in the art would have been motivated to engineer a T cell population with a disrupted TCR in order to use them in specific immunotherapies. Furthermore, because Rasaiyaah teaches that T cells can be engineered to disrupt the TCR locus (Methods, p9-10, by using TALEN), and indeed that engineered T cells were first activated with TransAct (Methods, p9-10), and because as above, Kaiser teaches that T cells expanded in TransAct can be modified to express any other accessory molecule on their surfaces (paragraph [0037]), it could have been done with predictable results and a reasonable expectation of success.
In regards to step f), in regards to a resulting human CAR-T cell population, it is noted that there is no conjunction between substeps i) through v). Therefore, giving this clause its broadest reasonable interpretation, it has been interpreted for allowing for the measuring of a single subset (thus, implying the conjunction “or”) in order to satisfy the claim. To this end, Rasaiyaah teaches, at least, a number of CAR T cells (Fig. 1, p3).
In regards to wherein the measurements of one or more resulting human CAR T cells is increased relative to a second human CAR-T cell in a population wherein the second starting human contacted with the nanomatrix wherein the cell to matrix ratio is 1:17.5 or more as in claim 1, Applicant should note that this is a property or natural consequence of culturing cells in a higher volume of matrix to cells. As discussed above, as demonstrated by higher concentrations of TransAct result in higher percentage of activated cells (Fig. 1, percentage of CD69+ cells). Therefore, the method of Scheffold, as modified, as discussed above, would have this same property absent evidence to the contrary.
In regards to claim 2, Scheffold teaches that the T cell may be derived from blood (peripheral blood) (paragraph [0094]).
In regards to claim 4, Scheffold teaches that the cells may be peripheral blood mononuclear cells (paragraph [0094]).
In regards to claim 6, Scheffold teaches that the cells may be purified CD4+ T cells (paragraph [0094]).
In regards to claims 28 and 29, Scheffold teaches that in an embodiment, T cells are genetically manipulated to induce antigen receptors and are transduced using a retroviral vector to induce expression (paragraph [0111]). A person of ordinary skill in the art would have recognized that this implies transducing cells with a nucleic acid.
As above, a person of ordinary skill in the art would have been motivated to express a CAR in order to use these cells in immunotherapies. Furthermore, because Kaiser teaches that T cells cultured in TransAct can be engineered to express CARs, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Scheffold, Kaiser, Mockel-Tenbrinck, Casati, and Rasaiyaah renders the invention unpatentable as claimed.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Scheffold et al. (US20140087462, on IDS 12/04/2020; cited by Applicant in the Response on 01/21/2026) in view of Kaiser et al. (US 20170037370 A1, 2017, previously cited), Mockel-Tenbrinck et al. (Mol Ther, 2017, previously cited), Casati et al. (Cancer Immunol Immunother, 2013, on IDS 12/04/2020, previously cited) and Rasaiyaah et al. (JCI Insight, 2018) as applied to claim 1 above, and further in view of Jamin et al. (Clin Exp Immunol, 1993).
In regards to claim 31, it is noted that the claim does not require any number of CD45RA+ cells, CD45RA+/CD5+ cells, or TCRαβ-, as there are no method steps that produce these specific cells.
As above, Rasaiyaah teaches that numbers of cells (including CAR T cells, including TRAC-KO (TCRαβ- cells) can be counted (Figure 1, p3). While Rasaiyaah is silent as to counting the other specific cell types, a person of ordinary skill in the art would have been motivated to count these in order to have a base-line as to the total number of cells in the population, or the numbers of cells with specific phenotypes. Indeed, Scheffold teaches that CD45RA+ cells are a subset of naïve T cells (paragraph [0111]). Additionally, as taught by Jamin, virtually all T cells express CD5 (Summary, p245) (and is therefore, a well-known T cell marker). Furthermore, because counting cells is well-established in the art, because Rasaiyaah teaches that chimeric T cells can be counted, and because these are all known markers, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Scheffold, Kaiser, Mockel-Tenbrinck, Casati, Rasaiyaah, and Jamin renders the invention unpatentable as claimed.
Conclusion
No claims are allowed.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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