Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/30/2025 has been entered.
Applicant' s amendment and response filed on 09/30/2025 has been received and entered into the case.
Amendments
In the reply filed 09/30/2025, Applicant has amended claim 1 and has newly canceled claim 12.
Claim Status
Claims 1-11, 13-24 and 26-28 are pending.
Claims 16-24 and 26-27 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/14/2023.
Claims 1-11, 13-15 and 28 are considered on the merits.
Withdrawn Claim Rejections - 35 USC § 112(b)
The prior rejection of claims 1-11, 13-15 and 28 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for lack of antecedent basis has been withdrawn in light of Applicant’s amendment to claim 1.
New Claim Rejections - 35 USC § 112(b)
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 4 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.
Claim 4 (a) recites the term “appropriately”, which renders the claim indefinite because it is a subjective term. A claim that requires the exercise of subjective judgment without restriction may render the claim indefinite. See MPEP § 2173.05(b).
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claims 1-11, 13-15 and 28 under 35 U.S.C. 102 (a)(1) set forth in the prior Office action mailed on 06/30/2025 is withdrawn in light of Applicant’s amendment to claim 1 to recite new limitation “at least 80% of the conjugates comprise a ratio of 1:1 live iNKT cells to live DC” that is not addressed in the prior rejection.
New Claim Rejections - 35 USC § 103
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 1-2, 4, 6-8 and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Cellular & Molecular Immunology. 2020; 17:496-506. Published online June 2019. Prior art of record) in view of Xu et al., (Cell Reports. 2016; 16: 3273-3285. Prior art of record).
With respect to claim 1, Wang teaches iNKT cells are cocultured with dendritic cells (DCs) to form iNKT cell-DC crosstalk (equivalent to the claimed in vitro-derived iNKT cell-DC conjugate) (see e.g., p. 504, right col, para “Cell culture”, and see e.g., Figs 3-7, specifically see Fig 3e for IL4 secretion by iNKT cells in the conjugates after 10 hours), thus teaches an in vitro-derived multicell conjugate between an iNKT cell and a DC that remains conjugated after at least 10 hours of culture.
In regard to the limitation that the iNKT cell and DC remain conjugated after pipetting in a calcium and magnesium-free PBS containing a chelating agent, Wang teaches a cytokine secretion assay to detect the secretory site of IL4 in iNKT cells, in which the iNKT-DC conjugates are labeled with an IL4 capture reagent on ice for 5 min, transferred to a warm medium, incubated at 37°C for 45 min, washed in buffer and stained with an IL4 detection antibody (see p. 504, right col, para “Cell culture and a cytokine secretion assay”). It is noted that at least the transfer step and the wash step require pipetting the conjugates in a medium or a buffer. Thus, Wang teaches the iNKT cells and DCs in the conjugates remain conjugated after pipetting in a medium or buffer. Regarding a specific phosphate buffered saline buffer (PBS), prior art Xu teaches that iNKT cell-DC conjugates, that have formed in a culture well by co-culturing iNKT cells and DCs, are pelleted by centrifugation, resuspended in PBS and injected subcutaneously into a mouse footpad model (p. 3283, left col, para “Induction of tissue inflammation”, note that at least the step of injection requires pipetting the conjugates in PBS into a syringe and pipetting/injecting the conjugates from the syringe to the mouse). Thus, Xu teaches that the iNKT cell and DC in the conjugates remain conjugated after pipetting in PBS.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have immediately expected that the iNKT cell and DC in Wang’s conjugates would likely remain conjugated after pipetting in a calcium and magnesium-free PBS containing a chelating agent as suggested by Wang and Xu with a reasonable expectation of success, because both Wang and Xu teach co-culturing iNKT and DC to form a conjugate and the iNKT cell and DC remain conjugated after pipetting in a medium or a buffer such as PBS (see above).
Furthermore, Applicant is reminded that the courts have stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” See In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004). In the instant case, since the material (i.e., an in vitro-derived multicell conjugate between an iNKT cell and a DC) is known as taught by prior art Wang and Xu, the discovery of the claimed property, the iNKT cell and DC remaining conjugated after pipetting in a specific buffer, does not make the claimed material novel.
Additionally, Applicant is also reminded that MPEP 2112.01(II) recites that "products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable." Applicant’s specification discloses that the claimed conjugate with the claimed property is formed simply by co-incubation of iNKT cells and DCs in the same manner as being done by Wang et al. Thus, the conjugate of Wang would exhibit the properties of Applicant’s claimed conjugate because they are the same compositions.
Since the Patent Office does not have the facilities for examining and comparing applicants' conjugates with the conjugates of the prior art, the burden is upon applicants to show a distinction between the material structural and functional characteristics of the claimed conjugates and the conjugates of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
In regard to the limitation that at least 80% of the conjugates comprise a ratio of 1:1 live iNKT cells to live DCs, this is examined as a composition comprising multiple multicell conjugates between iNKT cells and DCs wherein at least 80% of the conjugates in the composition comprise a ratio of 1:1 live iNKT cells to live DCs. As stated supra, Wang aims to study polarized IL4 spatial distribution in iNKT cell-DC crosstalk (see e.g., title, abstract and Fig 3). Wang teaches a cytokine secretion assay to detect the secretory site of IL4 in iNKT cells, in which the iNKT-DC conjugates are labeled with an IL4 capture reagent on ice for 5 min, transferred to a warm medium, incubated at 37°C for 45 min, washed in buffer and stained with an IL4 detection antibody (see p. 504, right col, para “Cell culture and a cytokine secretion assay”. It is noted that there is no fixation in this assay thus the cells are alive). Thus, Wang teaches an IL4 secretion assay in a composition comprising iNKT-DC conjugates comprising live iNKT cells and live DCs.
However, Wang is silent on the composition in which at least 80% of the conjugates comprise a ratio of 1:1 iNKT cell to DC.
Nevertheless, Wang illustrates the method to quantify the polarized secretion of IL4 in Fig. 3a in which there is one DC (APC) and one iNKT cell (the iNKT cell is divided into 4 areas paralleled from the interface with the DC), and shows the IL4 secretion assay in Figs. 3b, 3c, 4f, 5b, 7b in which there are one DC and one iNKT cell (evidenced by polarized IL4 secretion in fluorescent images) and the data are representative of three independent experiments and more than 70 cells per group are assayed (see e.g., Fig 3b, 3c legend).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition comprising iNKT-DC conjugates comprising live iNKT cells and live DCs for polarized IL4 secretion assay taught by Wang and Xu, by choosing conjugates comprising one iNKT cell and one DC as suggested by Wang so as to obtain a composition comprising iNKT-DC conjugates in which at least 80% of the conjugates comprise a ratio of 1:1 iNKT cell to DC with a reasonable expectation of success. Since one ordinary skill in the art would have known that a conjugate comprising one iNKT cell and one DC is the simplest model to study polarized secretion of IL4 as it only comprises one interface between the iNKT cell and DC (as illustrated in Wang’s Fig 3a), and since Wang teaches conjugates having one iNKT cell and one DC in multiple figures showing representative data (see Figs. 3b, 3c, 4f, 5b, 7b and legend), one of ordinary skill in the art would have had a reason to choose conjugates comprising one iNKT cell and one DC so as to obtain a composition in which at least 80% of the conjugates comprise a ratio of 1:1 iNKT cell to DC in order to assay the polarized distribution of IL4 secretion without disturbance from multiple interfaces.
With respect to claim 2 directed to the conjugate being maintained in culture for at least 30 minutes, as stated supra, Wang disclosed in cytokine secretion assay that the iNKT-DC conjugate is maintained in culture for at least 10 hours (see Fig 3e).
With respect to claim 4, directed to the iNKT cell within the conjugate expressing an rearranged TCR and CD4, Wang teaches the iNKT cells are isolated with anti-CD4 microbeads (p. 504, right col, para “Cell culture”), indicating the iNKT cell expresses CD4. Furthermore, Wang teaches the inhibitors, such as nocodazole, are added 2 hours after T cell receptor (TCR) engagement to exclude their influence on cell activation (p. 500, right col, para 1), indicating the iNKT cell within the conjugate expresses an rearranged TCR that involves in engagement and cell activation.
With respect to claim 6, directed to the DC expressing MHC molecules I or II, Wang teaches an intratumoral MHC II+ CD24+ F4/80− CD11c+ DCs (see Fig 7d). It is known that MHC class I molecules are expressed on the cell surface of all nucleated cells, thus the DC expresses MHC molecules I and II.
With respect to claim 7, directed to the DC being allogenic to the iNKT cell, Wang teaches the DC is isolated from wildtype or tumor bearing mice (p. 504, right col, para 1) and iNKT cells are isolated from Va14 transgenic mice (p. 504, right col, para “Cell culture”), thus teaches the DC is allogenic to the iNKT cell.
With respect to claim 8, directed to the multicell conjugate secreting IL-12p70 and IFN-γ into a culture medium, Wang teaches the IL12p70 and IFNγ are detected in supernatant (see Fig 2b and 2c, and legend).
With respect to claim 13 directed to the DC loaded with an antigen and claim 14 directed to the antigen being a pathogenic antigen, Wang teaches the DCs are pulsed with lipid antigens such as α-galactosylceramide (αGC) (see e.g. Fig 3), or are stimulated with lipopolysaccharide (LPS) (p. 497, left col, last para and p. 501, 1st para). It is noted that LPS is also known as endotoxin which is a potent pathogenic antigen.
With respect to claim 15 directed to a composition comprising the conjugate and a pharmaceutically acceptable carrier, Wang teaches the iNKT cell-DC conjugate is cultured in a culture medium (p. 504, right col, para “Cell culture”), which is a sterile diluent, thus teaches a composition comprising the conjugate and a pharmaceutically acceptable carrier.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Cellular & Molecular Immunology. 2020; 17:496-506. Published online June 2019. Prior art of record) in view of Xu et al., (Cell Reports. 2016; 16: 3273-3285. Prior art of record), as applied to claim 1 above, and further in view of Shimizuhira et al (Journal of Investigative Dermatology. 2014; 134: 2709-2718. Prior art of record) and Hongo et al (Blood. 2017; 129(12): 1718-1728. Prior art of record).
With respect to claim 3 directed to the conjugate being maintained in culture for at least 24 hours, and claim 5 directed to the conjugate being maintained in culture for at least 96 hours, although Wang does not disclose the claimed lifetimes of the conjugates, these limitations are merely a natural property of the conjugates taught by prior art. First, since Wang teaches the same cell types (iNKT cell and DC) as claimed in the same ratio (one iNKT cell and one DC) as claimed that is conjugated by the same method (co-culturing iNKT cell and DC) as claimed, the claimed functional characteristics of the conjugate would be the same as that of Wang. MPEP 2112.01(II) recites that products of identical composition cannot have mutually exclusive properties. A composition and its properties are inseparable.
Second, prior art Shimizuhira teaches that the DCs are cocultured with iNKT cells for 48 hours and have markedly increased expression levels of co-stimulatory molecules (p. 2714, left col, para 1, last sentence, also see Fig 6c). Prior art Hongo teaches that sorted iNKT cells and DCs are cultured for 4 days (i.e., 96 hours, p. 1719, right col, para 2) and coculture of DCs with NKT cells markedly increased IL-4 secretion (p. 1724, left col, para 3, line 5, see Fig 5E and legend for coculture for 5 days), thus teaches that the conjugate can be maintained in culture for at least 96 hours.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have immediately expected that Wang’s conjugates would have been capable of being maintained in culture for at least 24 hours or at least 96 hours as suggested by Shimizuhira and Hongo with a reasonable expectation of success, because all the cited prior art teach co-culturing iNKT and DC to form a conjugate and the conjugate can be maintained in culture for at least 96 hours (see e.g. Hongo above).
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Claims 9-11 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al (Cellular & Molecular Immunology. 2020; 17:496-506. Published online June 2019. Prior art of record) in view of Xu et al., (Cell Reports. 2016; 16: 3273-3285. Prior art of record), as applied to claim 1 above, and further in view of Shimizuhira et al (Journal of Investigative Dermatology. 2014; 134: 2709-2718. Prior art of record), Van de Ven et al. (Immunotherapy. 2015; 7(6): 655-667. Prior art of record), and O’Neill et al (Journal of Immunology. 2017; 199: 3700-3710. Prior art of record).
With respect to claim 9 directed to the DC expressing one or more molecules such as CD80 and CD86, claim 10 directed to the DC expressing co-stimulatory molecules for at least 24 hours in vitro, and part of claim 28 directed the conjugated DC expressing increased CD137L, CD134L and CD215 as compared to unconjugated DC, Wang teaches activated DCs express increased CD86 (see Fig 1d). Shimizuhira teaches that the expression levels of co-stimulatory molecules including CD40, CD80, and CD86 on DCs (BMDCs) 48 hours after cocultivation with a-GalCer-activated NKT cells are markedly increased (p. 2714, left col, para 1, last sentence, also see Fig 6c), thus teaches the DC within the conjugate expresses one or more co-stimulatory molecules such as CD80 and CD86 on its surface for at least 24 hours in vitro.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have immediately expected that the conjugated DC in Wang’s iNKT-DC conjugate would have expressed one or more co-stimulatory molecules such as CD80 and CD86 for at least 24 hours in vitro and would likely have expressed increased CD137L, CD134L and CD215 as compared to unconjugated DC as suggested by Wang and Shimizuhira with a reasonable expectation of success, because both Wang and Shimizuhira teach co-culturing iNKT and DC to form a conjugate and the conjugated DC expresses co-stimulatory molecules such as CD80 and CD86 for at least 24 hours in vitro at an increased level as compared to unconjugated DC (see e.g., Shimizuhira Fig 6c).
Furthermore, Applicant is reminded that the courts have stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” See In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004). In the instant case, since the material (i.e., an in vitro-derived multicell conjugate between an iNKT cell and a DC) is known as taught by prior art Wang and Shimizuhira, the discovery of the claimed property, the conjugated DC expresses increased CD137L, CD134L and CD215 as compared to unconjugated DC, does not make the claimed material novel.
Additionally, Applicant is also reminded that MPEP 2112.01(II) recites that "products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable." Applicant’s specification discloses that the claimed conjugate with the claimed property is formed simply by co-incubation of iNKT cells and DCs in the same manner as being done by Wang et al. Thus, the conjugate of Wang would exhibit the properties of Applicant’s claimed conjugate because they are the same compositions.
Since the Patent Office does not have the facilities for examining and comparing applicants' conjugates with the conjugates of the prior art, the burden is upon applicants to show a distinction between the material structural and functional characteristics of the claimed conjugates and the conjugates of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
With respect to claim 11 and part of claim 28, directed to the iNKT cell expressing CD70 on the surface after conjugation and the conjugated iNKT cell expressing increased CD70 as compared to unconjugated iNKT cells, firstly, Wang teaches DC-iNKT cell interaction subsequently leads to iNKT cell activation and expression of IL-12 and IFN-γ (see Fig 2b,c). Furthermore, prior art Van de Ven et al. (2015) teaches that CD70 is expressed on a variety of immune cells, including T cells and natural killer cell types after activation and is tuned by cytokines such as IL-12 (“Executive summary” in p. 663, also see p. 658, left col, para 2. It is noted that iNKT cell is one type of T cell). Prior art O’Neill teaches that CD70 is expressed on T cells after activation (p. 3700, right col, last para, line 1) and “IFN-γ treatment significantly upregulates CD70 on T cells” (p. 3703, right col, last para, line 10, see Fig 5A-5B).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have immediately expected that the conjugated iNKT cell in Wang’s iNKT-DC conjugate would likely have expressed CD70 on the surface after conjugation and expressed increased CD70 as compared to unconjugated iNKT cells as suggested by Van de Ven and O’Neill with a reasonable expectation of success, because Wang teaches co-culturing iNKT and DC to form a conjugate in which the conjugated iNKT cell is activated and expresses IL-12 and IFN-γ (see Fig 2b,c), and both Van de Ven and O’Neill teach that CD70 is expressed on activated T cells and is upregulated by IL-12 and IFN-γ (Van de Ven, “Executive summary”, and O’Neill, p. 3703, right col, last para, line 10).
Furthermore, Applicant is reminded that the courts have stated that “just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel.” See In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004). In the instant case, since the material (i.e., an in vitro-derived multicell conjugate between an iNKT cell and a DC) is known as taught by prior art Wang, the discovery of the claimed property, the conjugated iNKT cell expresses CD70 on the surface and expresses increased CD70 as compared to unconjugated iNKT cells, does not make the claimed material novel.
Additionally, Applicant is also reminded that MPEP 2112.01(II) recites that "products of identical chemical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable." Applicant’s specification discloses that the claimed conjugate with the claimed property is formed simply by co-incubation of iNKT cells and DCs in the same manner as being done by Wang et al. Thus, the conjugate of Wang would exhibit the properties of Applicant’s claimed conjugate because they are the same compositions.
Since the Patent Office does not have the facilities for examining and comparing applicants' conjugates with the conjugates of the prior art, the burden is upon applicants to show a distinction between the material structural and functional characteristics of the claimed conjugates and the conjugates of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 09/30/2025 are acknowledged.
As a first matter, Applicant argues that the Examiner relies on a total of six references to support the anticipation rejection (Remarks, p. 7, para 3). This becomes moot because the new ground of rejection in this Office action is under 35 U.S.C. 103.
Furthermore, regarding the claimed features, Applicant initially argues that cell surface expression of proteins is a structural feature of a cell or conjugate and is not an inherent feature and thus carries patentable weight (Remarks, p. 7, last para.). This becomes moot because the new ground of 103 rejection does not rely on inherent feature or not carrying patentable weight specifically challenged in the argument.
Applicant secondly argues that (1) the images in Figures 3-6 of Wang are selected to demonstrate polarized secretion of cytokines, not cellular conjugation. (2) Simply counting the cells visible in the selected microscopy images is not an appropriate means of quantifying the cellular interactions in a cell culture. Additionally, by counting the number of images in Wang, it is not clear if the images are in fact the same cells at different time points, or before or after treatment. (3) Wang describes the iNKT cells and DC as "clusters" and “it was difficult to count the absolute numbers”, thus, it is reasonable to assume that the microscopy images selected by Wang for publication were selected for their ability to show cytokine polarization, and not representative of how the cells actually interacted (Remarks, p. 8, para 2-3).
Applicant’s arguments have been fully considered but they are not persuasive.
Firstly, Wang clearly teaches an in vitro-derived multicell conjugate comprising an iNKT cell and a DC. The fact that Wang uses the conjugates for assaying polarized secretion of cytokines, does not negate Wang’s teaching of the iNKT cell-DC conjugate.
Secondly, it is noted that the instant claim 1 recites “an in vitro-derived multicell conjugate… wherein… at least 80% of the conjugates…”, thus the claim can be broadly reasonably interpreted as multiple separate conjugates that do not need to be in the same composition. In other words, the claim encompasses separate conjugates from multiple experimental groups in different experiments as taught in the multiple figure panels in Wang, that do not require the conjugates in the panels to be the same cells. However, for the sake of compact prosecution, the claim is currently examined as a composition comprising multiple multicell conjugates between iNKT cells and DCs wherein at least 80% of the conjugates in the composition comprise a ratio of 1:1 live iNKT cells to live DCs, as discussed above.
Thirdly, Applicant’s quotation of Wang (page 497, second paragraph) refers to in vivo experiment (“We investigated the interactions between iNKT cells and APCs in vivo”, see page 497, second paragraph, before Applicant’s quotation). Thus, it does not apply to the in vitro experiments on cytokine secretory assay recited in the prior and instant Office action. In fact, that is the reason why the prior 101 rejection is withdrawn because the instantly claimed ratio of the iNKT cells to DCs in the conjugate seems to be markedly different from its naturally occurring in vivo counterpart demonstrated in Wang (see page 4 in prior Office action mailed on 06/30/2025).
Applicant thirdly argues it is not possible to determine if fluorescent images contain one iNKT cell and one DC without corresponding brightfield images (Remarks, p. 8, last para – p. 9, first para). This is not persuasive because Wang teaches when the iNKT cell and DC form a conjugate, the iNKT cell is activated and secrete IL4 in a polarized manner, near the interface between the iNKT cell and DC (e.g., Fig 3). Thus, the fluorescent images of IL4 secretion assay faithfully reflect the interaction of iNKT cell and DC, and thus do not require, and are even more accurate than, brightfield images.
Applicant fourthly argues Wang's conjugate requires a lipid antigen while no addition of a lipid antigen is recited in the current claims (Remarks, p. 9, para 2). This is not persuasive. The antigen in Wang’s conjugate does not negate Wang’s teaching of an iNKT-DC conjugate that makes obvious the instantly-claimed iNKT-DC conjugate. Applicant is further reminded that the feature of no addition of a lipid antigen that Applicant relies on is not recited in the instant claim 1.
Applicant fifthly argues Xu shows clusters of cells, iNKT cells are motile and make dynamic contacts with the DC and when they are centrifuged some DCs are not in contact with iNKT cells (Remarks, p. 9, para 3). This is not persuasive. Applicant is reminded that a 35 U.S.C. § 103 based test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case, primary reference Wang has demonstrated the iNKT-DC conjugate remains conjugated after multiple steps of transfer/pipetting in different media/buffer. Xu is cited to teach that the iNKT-DC conjugate (identical to that in Wang and instant claims) remains conjugated after pipetting in PBS (see above).
Applicant sixthly argues Shimizuhira, Hongo, Van de Ven and O'Neil do not cure the deficiency of Wang and Xu (Remarks, p. 9, last para – p. 10, first para). This is not persuasive. The arguments regarding Wang and Xu have been discussed above.
Conclusion
No claims are allowed.
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/JIANJIAN ZHU/Examiner, Art Unit 1631