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 CLAIMS
This action is in response to papers filed on July 22, 2026. Claims 1-12, and 14-19 are currently pending. As of the amendments filed July 22, 2026, claims 1, 3-8, 10-12, and 14 have been amended, claim 13 has been canceled, and claim 19 is newly added.
Therefore, claims 1-12 and 14-19 are under examination to which the following grounds of rejection are applicable.
Priority
The instant application claims benefit under 35 U.S.C. 119(e) of prior-filed provisional application 63/459,735 filed April 17, 2023.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d).
The translated certified copy has been filed in Canadian Application No. 3230173, filed on February 26, 2024.
Thus, the earliest possible priority for in the instant application is February 26, 2023.
Response to Arguments
Withdrawn Arguments in view of the Amendments filed July 22, 2026
Claim Rejections - 35 USC § 103
In view of the Amendments filed July 22, 2026, the rejection of claims 1, 10 and 11 under USC § 103 as being unpatentable over Wang, Kondo and Beckman has been withdrawn.
Any pertaining arguments are moot in reference to the withdrawn rejection. A response to any argument pertaining to a new or maintained rejection can be found below.
Maintained Rejections in Response to Applicants’ Arguments or Amendments
Claim objections
Regarding claim 15 line 2, is objected to because of the acronyms “HSA” and “PBS” are recited but not defined in the claim. An acronym should be defined the first time it appears in an independent claim or in the group of claims under an independent claim. For the purposes of examination, “HSA” will be interpreted as Human Serum Albumin and PBS will be interpreted as Phosphate-Buffered Saline.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-12 and 14-18 remain rejected and claim 19 is newly 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.
Claim 1 has been amended to recite: “by Antibody-Dependent Cellular Cytotoxicity (ADCC),” Claim 1 is incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. While all of the technical details of a method need not to be recited, the claims should include enough information to clearly and accurately describe the invention and how it is to be practice. The only required steps in claim 1 are defined by steps (i) (iii), (iv) (v) and (vi) . None of these steps requires addition of any antibody, let alone any ADCC. It is not apparent as to under what structural or functional parameters the culturing, adding zoledronate, adding IL-2 and removing up to half of the basal medium is indicative or correlative to the preamble of the claims.
Claims 2-12 and 14-19 are indefinite insofar as they depend from claim 1.
Claim 3 is indefinite in its recitation of “the zoledronate is added to the medium
basal medium in step (iv) on day 0”. Claim 3 which depends on claim 1 requires that “day 0 of culturing begins when the MNCs are cultured in step (iii)”. Thus, it is unclear how the zoledronate can be simultaneously added on day 0 of culturing which begins in step (III) and in step (iv) on day 0. As such the metes and bounds of the claim are indefinite.
Claim 5 is indefinite in its recitation of “the IL-2 is added to the medium basal in step (v) on day 2 of culturing” because it is unclear if day 2 of culturing corresponds to step (v) or a different step after step (iii).
Claim 14 is indefinite because it is unclear if “a mixture of zoledronate and IL-2 is
added to the basal medium in steps (iv) and (v).” in addition to adding zoledronate in step (i) and adding IL-2 in step (v), respectively. As such the metes and bounds of the claim are indefinite.
Claim 19 is indefinite because it is unclear after which step a subpopulation of Vy 9V 8 2 T cells is selected. As such the metes and bounds of the claim are indefinite.
In relation to step (ii) in claim 1 and the recitation of “optionally”, for the purposes of examination, the claim is interpreted as excluding the step of “isolating said MNCs by centrifugation”.
Claim Rejections - 35 USC § 101
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 17 and 18 remain rejected under U.S.C 101 because the claimed invention is directed to a naturally occurring product without significantly more. The claims recite gamma delta T cells obtained by the method of claim 1, and gamma delta T cells in combination with one or more monoclonal antibodies for immunotherapy. Although the cells are recited as being obtained from donor peripheral blood mononuclear cells, gamma delta T cells are a naturally occurring subset of T lymphocytes present in human blood in vivo.
The judicial exception is not integrated into a practical application because the recited gamma delta T cells, even though recited as being obtained or optionally isolated (Claim 1 step [ii]), is not markedly different than their naturally occurring counterpart. Furthermore, although the Specification (paragraph [0005-0008]) indicates that “patients’ own Gamma Delta T cells is often limited (especially in cancer patients)” and that the claimed methods expand the cells (e.g. using zoledronate, Interleukin-5 or Interleukin-2) to increase their activity, such expansion or stimulation merely restores the natural function of these Gamma Delta T cells, rather than employing markedly different characteristics. Therefore, the resulting cells remain the same type of naturally occurring Gamma Delta T cells.
The Supreme Court in Funk Bros. Seed Co. v. Kalo Inoculant Co. 333 U.S. 127, 131 (1948) held that even though the combination of bacteria did not occur in nature, the combination [of bacteria] did not provide a different structural or functional characteristic than each bacterium possessed on its own.
“It is no more than the discovery of some of the handiwork of nature and hence is not patentable. The aggregation of select strain of the several species into one product is an application of that newly-discovered natural principle…Each species has the same effect it always had. The bacteria perform in their natural way.” Id. The instant situation if “bacteria” was replaced with “Gamma Delta T cells” the same reasoning applies. The claims and Specification do not indicate that the cells are genetically modified, engineered or altered to display properties distinct from those found in nature. Instead, the claimed cells appear to be the same as already existing Gamma Delta T cells that exist in nature, just merely enriched from their natural state.
The claims also do not include additional elements that are sufficient to amount to significantly more than the judicial exception. Any additional steps, such as isolating or enriching the Gamma Delta T cells from donors and cultivating them with monoclonal antibodies are routine in the art and do not transform the nature of the claim do be something distinct from their naturally occurring counterpart. The monoclonal antibody represents a therapeutic agent, and its combination with Gamma Delta T cells constitutes merely an aggregation of components, each performing their own expected functions.
Therefore, claims 17-18 are directed to a judicial exception without significantly more and does not have a eligible subject matter under 35 U.S.C. §101.
Response to Arguments as they pertain to the rejection of claims 17 and 18 over USC § 101
Beginning on claim 5 of the remarks filed July 22, 2026, Applicants essentially argue the following:
"Gamma Delta T cells" of claim 17 and the claimed "Gamma Delta T cells in combination with one or more monoclonal antibodies" of claim 18, are in fact different from their natural counterparts. As shown in Figures 2B, and described in paragraphs [0030] to [0034], the gamma delta T cells made by the method of the present invention have superior anti-tumor activity and cytotoxicity. This makes them functionally more effective in cellular immunotherapy applications than their natural counterparts. As such, the applicant submits the judicial exception does not apply.
In response, Applicants’ arguments have been persuasive but found not persuasive for the following reasons:
Regarding 1), while the Specification may describe embodiments in which culturing the gamma-delta T cells (para 0030-0034) results in increased proliferation and anti-tumor efficiency, as described in Figures 1 and 2B, these claims as presently drafted do not require the cells to possess such increased therapeutic efficacy, nor do the claims recite structural, phenotypic, functional or other characteristics that distinguishes the claimed cells from naturally occurring gamma-delta T cells. The markedly different characteristics analysis is based on the characteristics applied to the full scope of the claimed nature-based product (i.e. gamma-delta T cells). Here, the claimed gamma-delta T cells encompass the same characteristics as their natural counterpart isolated from donors. Although Applicants disclosed certain culturing conditions that display an increased therapeutic effect, the claims do not require the cells to have this functional characteristic. However, no such limitation exists in the claims as written. Hence the argument is not persuasive as they argue limitations that are not present in the claims.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1-9, 12 and 14-18 remain rejected and claim 19 is newly rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Published: 2019. Cited in IDS filed: April 5, 2024, Cite No. 11. Mol Med Rep., vol. 19(3), pp. 1471-1480), in view of Kondo et al. (Published: 2011. J Vis Exp. 2011 Sep 9;(55):3182), as evidenced by Gay et al. (Published: 2022. Front Immunol. 2022 Jul 18;13:928441) This is a modified rejection necessitated by the Amendments filed July 22, 2026.
Regarding claim 1, 17 and 18, Wang teaches a cultivation method for gamma delta T cells for immunotherapy (pp. 147, col 2, "Therefore, Vγ9δ2 T cells have been considered a promising candidate for immunotherapeutic drug development and represent a novel therapeutic tool") comprising obtaining peripheral blood mononuclear cells (MNCs) from a donor, (pp. 1472, col 2, “Briefly, PBMCs were isolated from whole blood of healthy donors and the proportion of Vγ9δ2 T cells was detected using flow cytometry.”; pp. 1471 col 2, "To yield abundant γδ T cells with high vitality, most researchers preferred to expand γδ T cells from PBMCs instead of purifying them prior to in vitro culture."), culturing said MNCs in a basal medium containing a basal media (pp.1472, col 2, "PBMCs were stimulated with different doses of IPP and recombinant human IL-2 in RPMI 1640 medium supplemented with 10% FBS at 37˚C with 5% CO2”), adding zoledronate to the medium (pp. 1471, col 2, "Multiple common antigens have been used to stimulate...zoledronate (Zometa)") and adding interleukin 2 (IL-2) to the medium (pp.1472, col 2, "PBMCs were stimulated with different doses of IPP and recombinant human IL-2 in RPMI 1640 medium supplemented with 10% FBS at 37˚C with 5% CO2”).
It is noted that Vγ9δ2 are capable of antibody dependent cell-mediated cytotoxicity (ADCC), as evidenced by Gay et al. (pp. 3, right col, para 3). Gay teaches that gamma-delta T cells have been shown to be able of antibody dependent cell-mediated cytotoxicity under stimulation by pAgs, and express CD16 (pp. 3, right col, para 3).
However, Wang does not expressly teach the basal medium to comprise human plasma and albumin as required in step (iii) of claim 1 and removing and replacing up to half of the basal medium with a fresh basal medium for cultivation of gamma delta T cells as required in step (vi) of claim 1.
Kondo teaches a method gamma delta T cells by obtaining PBMCs from a donor, centrifuging them and culturing the PBMCs in autologous human plasma and albumin (pp. 2, top of page, “Add autologous plasma (section 1.3), pooled human AB sera, or FCS so that it is approximately 10% of the volume of the culture (100 μl for each well of a 24-well plate). Place the plates in a humidified 37°C, 5% CO2 incubator for 24-48 hr.”). Moreover, Kondo teaches that the culture medium is replaced with fresh medium (pp. 2, top of page, “Add fresh medium containing human IL-2 (1000 IU/ml) only (without Zometa) every 2-3 days, and transfer cultured cells into new wells or flasks as necessary, according to the degree of cell proliferation”).
It would have been obvious for one with ordinary skill in the art to incorporate human plasma and albumin into the basal medium with the motivation of culturing gamma delta T cells. This practice of expanding gamma delta T cells is known and routine in the art at the time of the instant invention, therefore it would be obvious to incorporate said autologous human plasma and albumin for gamma delta T cell proliferation. Moreover, it would be obvious to replace up to half of the basal medium with a fresh medium every few days as it promotes cellular proliferation and replenishes used culture medium, as Kondo acknowledges that the replacement of adding fresh medium can be changed as necessary, according to the degree of cell proliferation. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
Regarding claim 2, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Wang teaches that the donors are less than 40 years old (pp. 1472, col 1-2, "A total of 5 healthy volunteer donors without a history of autoimmune or other diseases were recruited from Nanfang Hospital between January 2016 and April 2018; their age ranged from 20–28 years old, and 3 of them were female and 2 male.").
Regarding claim 3, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Kondo teaches that the zoledronate is added to the medium on day 0 of cultivating or after medium (pp. 1, bottom of page, “Prepare culture medium (CM) by adding human IL-2 (IL-2) and zoledronate (Zometa) to final concentrations of 1000 IU/ml and 5 μM, respectively. ALyS203 (Cell Science & Technology Institute) or OpTmizer (Invitrogen) media support good expansion of γδ T cells (more information in references 6 and 9). Zometa is provided in liquid form (4 mg/5-ml vial). To prepare a 5 μM solution, add 50 μl of Zometa to 30 ml of culture medium”).
Regarding claim 4, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Kondo teaches adding zoledronate (Zometa) to the medium (pp. 1, bottom of page, “Prepare culture medium (CM) by adding human IL-2 (IL-2) and zoledronate (Zometa) to final concentrations of 1000 IU/ml and 5 μM, respectively. ALyS203 (Cell Science & Technology Institute) or OpTmizer (Invitrogen) media support good expansion of γδ T cells (more information in references 6 and 9). Zometa is provided in liquid form (4 mg/5-ml vial). To prepare a 5 μM solution, add 50 μl of Zometa to 30 ml of culture medium”).
It would have been obvious to optimize aspects of the cultivation method for gamma delta T cells based on influential such as increasing zoledronate concentration, adjusting the IL-2 concentration, or changing the basal medium. Compound dosages in a composition are clearly a result of effective parameter that a person of ordinary skill in the art would optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); 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 2).
Regarding claim 5, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Kondo teaches that the IL-2 is added to the medium on Day 2 of cultivating or after (pp. 2, top of page, “Add fresh medium containing human IL-2 (1000 IU/ml) only (without Zometa) every 2-3 days, and transfer cultured cells into new wells or flasks as necessary, according to the degree of cell proliferation”).
Regarding claim 6, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Kondo teaches that a concentration of 1000U/ml IL-2 is added to the medium (pp. 1, bottom of page, “Prepare culture medium (CM) by adding human IL-2 (IL-2) and zoledronate (Zometa) to final concentrations of 1000 IU/ml and 5 μM”).
Regarding claim 7 and 8, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Kondo teaches that the medium was added on days 4, 7, 9, 10 and 11 “Add fresh medium containing human IL-2 (1000 IU/ml) only (without Zometa) every 2-3 days, and transfer cultured cells into new wells or flasks as necessary, according to the degree of cell proliferation”).
It would have been obvious to optimize aspects of the cultivation method for gamma delta T cells based on influential such as changing different days of when fresh medium is added to the existing culture medium, whether half of the existing culture medium is removed from the culture flask, and/or the number of cells seeded in a flask or well plate. Moreover, Kondo teaches that transferring cultured cells and the frequency of which they are transferred is necessitated according to the degree of cell proliferation, implying that the days which fresh medium is replaced is a result effective variable.
The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature 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). (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421.
MPEP § 2144 sets forth Applicant' s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount.
Regarding claim 9, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Wang teaches a concentration of 1000 U/mL, but does not expressly teach that the final concentration to be 1000 U/mL (pp. 1, bottom of page, “Prepare culture medium (CM) by adding human IL-2 (IL-2) and zoledronate (Zometa) to final concentrations of 1000 IU/ml and 5 μM, respectively. ALyS203 (Cell Science & Technology Institute) or OpTmizer (Invitrogen) media support good expansion of γδ T cells (more information in references 6 and 9). Zometa is provided in liquid form (4 mg/5-ml vial). To prepare a 5 μM solution, add 50 μl of Zometa to 30 ml of culture medium”). It would further be obvious to continuously add 1000U/mL of IL-2 to achieve a final concentration of 1000U/mL, as it is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ.
It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); 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 2).
Regarding claim 12, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Wang teaches several protocols that utilized IL-2 and IL-15 for cultivating gamma delta T cells (Table I, see below).
PNG
media_image1.png
602
734
media_image1.png
Greyscale
Regarding claim 14, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Wang teaches that a mixture of zoledronate (Zometa) and IL-2 are added to the medium (pp. 1471, col 2, "Multiple common antigens have been used to stimulate...zoledronate (Zometa)"; "In addition, interleukin 2 (IL-2) is an essential cytokine for maintaining T cell expansion and has been widely used in culture of γδ T cells").
Regarding claim 15, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Kondo teaches wherein the mixture of zoledronate and IL-2 is prepared by diluting zoledronate and IL-2 in PBS/5%HSA, mixing and incubating at about 37 °C and about 5% CO2 (pp. 2, top of page, “Add autologous plasma (section 1.3), pooled human AB sera, or FCS so that it is approximately 10% of the volume of the culture (100 μl for each well of a 24-well plate). Wang teaches that cells were incubated at 37°C with 5% CO2 (p. 1472, col. 2, para 3).
However, regarding the limitation wherein the mixture of zoledronate and IL-2 is prepared by diluting zoledronate and IL-2 in PBS/5%HSA, mixing and incubating at about 37 °C and about 5% CO2, it is noted Wang teaches that cultivating gamma delta T cells can be done with utilizing zoledronate and IL-2, therefore the cultivated gamma delta T cells of Wang and Kondo wherein the mixture of zoledronate and IL-2 have the same structural limitations of the claimed product obtained by the process of cultivation method of claim 15, absent any evidence to the contrary. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient as needed to achieve the desired results.
Regarding claim 16, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Wang teaches that the cultivating is performed over 10 days (pp. 1472, col 2, "During the 16 day culture period, the proportion of Vγ9δ2 T cells was monitored using flow cytometry and cell growth was observed under a fluorescence microscope (Nikon Corporation, Tokyo, Japan).").
Regarding claim 19, the combined teachings of Wang, Kondo and Gay render obvious the claimed methodology. Moreover, Wang teaches Vγ9δ2 T cells have been identified by researchers and are perceived as a promising candidate for immunotherapeutic development (pp. 1471, right col para 1). Further, Wang teaches that Vγ9δ2 T cells were selected using flow cytometry (ppp. 1472, right col para 2).
Response to Arguments
Beginning on page 7 of the remarks, Applicants’ essentially argue the following:
Applicants argue that the claimed invention causes: Generation of high Gamma Delta T cell numbers; High cellular purity to minimize adverse effects from contaminating cells; Appropriate stimulation enabling effective cytotoxic activity (in the present case via monoclonal antibodies, i.e., ADCC); and A GMP-compliant, serum-free process to prevent the transmission of infectious agents.
However, the use of plasma or serum components in Kondo significantly increases the risk associated with clinical application.
In Wang, Isopentenyl pyrophosphate (IPP) is used instead of zoledronate.
Applicant's arguments have been fully considered but they are not persuasive for the following reason(s):
Regarding 1), although the Applicant notes that the instant invention achieves high levels of purity, cellular proliferation, these characteristics are not described in the claims. The discussed characteristics is based on the characteristics applied to the full scope of the claimed method, which is silent on increased proliferation, purity, etc. Moreover, the asserted improvements in proliferation, efficacy, and purity do not distinguish over the claimed method from the combined teachings of Wang and Kondo, as Wang discloses various methods of cultivating gamma-delta T cells through the addition of zoledronate, and IL-2, and Kondo further teaches the addition of human plasma. Therefore, such properties of the T cell culture would represent inherent results of the method rendered obvious by Kondo and Wand, rather than a patentable distinguishing limitation. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). The claims do not recite generation of high Gamma Delta T cell numbers, high cellular purity to minimize adverse effects from contaminating cells, or appropriate stimulation enabling effective cytotoxic activity (in the present case via monoclonal antibodies, i.e., ADCC), for example, taught in the specification.
Regarding 2), while Applicants assert that the use of plasma or serum increases certain risks, the presently claimed method recites the use of plasma. Moreover, the identification of a potential disadvantage associated with a prior art method does not, by itself, constitute a teaching away, especially as Kondo is silent on these proclaimed risks and applies the culture method in phase 1 clinical trials (pp. 5, under “Discussion”). Applicants have not identified a disclosure in Kondo that teaches or discourages the use of plasma for cultivation. Furthermore, toxicity is a safety issue and not relevant to the enablement of the presently claimed invention.
Regarding 3), although it is noted that Wang does not teach the use of zoledronate in their actual experiment, Wang discloses a table of known embodiments in the art that comprise zoledronate and IL-2 (Table 1). Moreover, Kondo alleviates these deficiencies; Kondo teaches culturing the cells initially in IL-2, and then followed with treatment if Zometa (pp. 2). It would have been obvious for one with ordinary skill in the art to incorporate human plasma and albumin into the basal medium with the motivation of culturing gamma delta T cells. This practice of expanding gamma delta T cells is known and routine in the art at the time of the instant invention, therefore it would be obvious to incorporate zoledronate and IL-2 for gamma delta T cell expansion.
New Rejections Necessitated by the Amendments
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 10 and 11 are newly rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Published: 2019. Cited in IDS filed: April 5, 2024, Cite No. 11. Mol Med Rep., vol. 19(3), pp. 1471-1480), in view of Kondo et al. (Published: 2011. J Vis Exp. 2011 Sep 9;(55):3182) as evidenced by Gay et al. (Published: 2022. Front Immunol. 2022 Jul 18;13:928441), and in further view of Jakobovits et al. (Published: 2019. US 20190119634 A1). This is a new rejection necessitated by the amendments filed on July 22, 2026.
With regard to claim 1, the combined teachings Wang, Kondo and Gay render obvious the claimed methodology, as iterated above in the 103 rejection the content of which is incorporated in.
However, Kondo, Wang and Gay do not expressly teach that the MNCs are shaken after day 4 of culturing, as required by claim 10.
Jakobovits teaches a method for the selective expansion of gamma-delta T-cell populations (Abstract). Jakobovits teaches that the peripheral blood mononuclear cells (PBMCs) were cultured under static conditions for 3-7 days, after which the activated cells were harvested and used for subsequent expansion (para 0557). Jakobovits then teaches that after 5 days, PBMCs were transferred to shake flasks and expanded accordingly (para 0567). Jakobovits also teaches that in a shake flask, it ensures sufficient mixing and aeration (para 0559).
It would have been prima facie obvious to one of ordinary skill in the art to combine the method of cultivating gamma-delta T cells as taught by Wang, Kondo and Gay with an additional step of shaking the PBMCs after day 4 of culturing, as taught by Jakobovits, since Jakobovits demonstrates that expansion of gamma-delta T cells occurred after placing the cells under shaking conditions. A skilled artisan would have been motivated to apply the shaking conditions of Jakobovits to provide sufficient mixing and aeration during gamma-delta T cell expansion with a reasonable expectation of success expanding such cells. There would have been reasonable expectations of success in combining these teachings as one of ordinary skill in the art would recognize to combine known elements in the art to give predictable results.
However, Jakobovits does not explicitly teach that the MNCs are shaken at 250 rpm, as required by claim 11.
It would have been obvious to optimize aspects of the culture method of mononuclear cells based on influential such as the duration of which the cells are shaken and the revolutions per minute (RPM) that the cells are shaken at for the sake of improving cellular proliferation. Moreover, optimizing the revolutions per minute used in cell culture is a result-effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal rotational speed needed to achieve the desired results.
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Katriel B Kasayan whose telephone number is (571)272-1402. The examiner can normally be reached 10-4p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria G Leavitt can be reached at (571) 272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KATRIEL BARCELLANO KASAYAN/Examiner, Art Unit 1634
/MARIA G LEAVITT/Supervisory Patent Examiner, Art Unit 1634
