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 .
Applicant’s remarks, filed 2/2/2026, are acknowledged and entered into the record. Applicants amended claims 1-2, 5-6, 20 and 23; canceled claims 3, 7-19, 21-22 and 24; and added new claims 25-26, in the remarks of 2/2/2026.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(a)-(d) and (f) or under 35 U.S.C. 120, 121, 365(a) or (b), or 386(a) is acknowledged. The present application is drawn from PCT/CN2021/091341, filed 4/30/2021; and claims benefit under 35 U.S.C. (119(a)-(d) to foreign application CN202010366867.4, filed 4/30/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Receipt of an English translation of CN202010366867.4, filed 2/2/2026, is acknowledged. The priority date for the instant claims is 4/30/2020.
Status of Claims
Claims 1-2, 4-6, 20, 23 and 25-26 are pending and are being examined on the merits.
Claim Rejections - Withdrawn
Claim Rejections - 35 USC § 112
The rejection of claim 23 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, is withdrawn. Applicants amended claim 23 to remove the indefinite language.
Claim Rejections - 35 USC § 102
The rejection of claims 1-6 and 11-24 under 35 U.S.C. 102(a)(1) as being anticipated by Zhu et al., (from IDS, Cite No. 8; Scientific Reports, 10(1), 2020), is withdrawn. Specifically, applicants submitted an English translation of the priority document, therefore setting the priority date at 4/30/2020, see above. Thus, Zhu et al. does not qualify as prior art.
The rejections of claims 1-2, 4-6, 19-20 and 23-24 under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Miller et al., (from IDS, Cite No. 4; WO 2019/221991; published 11/21/2019), is withdrawn. Applicants amended the claims to be drawn to CD8+ T cells; Miller does not anticipate CD8+ T cells.
The rejection of claims 1-6 and 11-19 under 35 U.S.C. 102(a)(1) as being anticipated by Lin et al., (Electromagnetic Biology and Medicine, 38(2), 3/19/2019) as evidenced by Zhu et al., (from IDS, Cite No. 8; Scientific Reports, 10(1), 2020), is withdrawn. Applicants amended the claims to be drawn to CD8+ T cells; Lin does not teach CD8+ T cells.
Claim Rejections - 35 USC § 103
The rejection of claims 20-24 under 35 U.S.C. 103 as being unpatentable over Lin et al., (Electromagnetic Biology and Medicine, 38(2), 3/19/2019) as evidenced by Zhu et al., (from IDS, Cite No. 8; Scientific Reports, 10(1), 2020), is withdrawn. Lin does not teach wherein the immune cells are CD8+ T cells, as recited in the amended claims.
Claim Rejections – New, necessitated by amendment
Claim Rejections - 35 USC § 112
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.
Claims 1-2, 4, 20, 23 and 25-26 are 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 recites the limitation "the magnetic field" in line , and recites the limitation “the treatment” in line 4. There is insufficient antecedent basis for this limitation in the claim. Claim 1 is drawn to a product, i.e. “an activated immune cell”. Thus it is unclear what “the magnetic field” is referring to, or what “the treatment” is referring to. Further, it is unclear from the language of claim 1 whether the claim is intended to be drawn to a product or a method of making a product. Thus, as the limitations to a product are patentably distinct from limitations (i.e. “active steps”) of a method, it is unclear what the limitations of the claim are. Thus, as the metes and bounds of the claim are unclear, claim 1 is rejected for indefiniteness and lack of antecedent basis. As claims 2 and 4 depend from claim 1, but do not correct the indefiniteness issues of claim 1, claims 2 and 4 are also rejected.
Claim 20 recites “a method for treating cancer comprising administering to a subject in need an immune cell according to claim 1, or treating a subject with a magnetic field,” but then goes on to recite, “wherein the immune cell is a CD8+ T cell, the magnetic field is a static magnetic field with a strength of 0.3 T – 0.6 T, and the treatment is subjecting the cell to the magnetic field for 48 h – 72 h.” Thus the claim is reciting a method of treating cancer comprising administering an immune cell or treating the subject with a magnetic field, but also recites the “treatment is subjecting the cell to the magnetic field”. Thus it is unclear if the methods are for treating cancer in a subject, or for treating a cell with a magnetic field. As the metes and bounds of the method of the claim are unclear, claim 20 is rejected indefiniteness. As claims 23 and 25-26 depend from claim 20, but fail to rectify the indefiniteness of the method of claim 20, claims 23 and 25-26 are also rejected.
Claim Interpretation
In view of the indefinite language of claim 1, whereby it is unclear whether the claim is drawn to activated immune cells (i.e. a product) or a method of activating immune cells (i.e. a method), as described above; claim 1 is being interpreted as a product claim. Claims 2 and 4 depend from claim 1 and also recite products, thus supporting that claim 1 is a product claim. Reference to “the magnetic field” and “the treatment” lack antecedent basis, as described above, and therefore are not considered limitations of the product. Thus, claim 1 is interpreted as an activated immune cell, characterized by upregulated Uqcrb and/or Ndufs6, wherein the immune cell is a CD8+ T cell.
Claim Rejections – new, necessitated by amendment
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.
Claims 1-2, 4-6, 20, 23 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Miller et al., (from IDS, Cite No. 4; WO 2019/221991; published 11/21/2019).
Miller et al. teaches manipulating ARID5B expression in immune cells to promote metabolism, survival and function (title). Miller teaches the immune cells may be NK cells, T cells and progenitors; and that the modified immune cells are genetically modified to increase ARID5B expression and thus improve persistence and increase anti-tumor efficacy (abstract). Miller teaches that ARID5B directly regulates UQCRB (protein) expression and uqcrb (gene) mRNA expression (pg. 7, para. 0019; Figs. 7A-B); whereby, for example, knockdown of UQCRB leads to a decrease in mitochondrial membrane potential, oxidative mitochondrial metabolism, and IFN-γ production (pg. 8, para. 0020; pg. 30, paras. 0096-0097 and 0099). Miller teaches that lentiviral transduction of NK-92 cells to over-express ARID5B led to an increase in mitochondrial membrane potential, higher maximal respiration, and higher frequencies of IFN-γ production in response to IL-12 and IL-18 stimulation (pg. 30, para. 0095). Thus, Miller claims an isolated population of modified immune cells having increased expression of ARID5B relative to wild-type immune cells, resulting in increased persistence, an increased level of glycolysis and increased mitochondrial oxidative metabolism (pg. 43, claim 1); whereby the immune cells comprises T cells, NK cells or NKT cells (claim 2); a pharmaceutical composition comprising the modified immune cells (pg. 44, claim 16); and a method of treating a tumor, cancer or a subject in need of an adoptive cell therapy (pg. 44, claims 17-19); and wherein the cancer is breast cancer (pg. 45, claim 20).
While Miller suggests that T cells may be modified in the same manner as demonstrated with NK cells, Miller does not explicitly demonstrate an embodiment with CD8+ T cells.
It would have been obvious to one of skill in the art to apply the methods of isolating or genetically engineering a population of modified immune cells characterized by upregulated Uqcrb to be CD8+ T cells. One would have been motivated to do so given that upregulating Uqcrb results in promoting mitochondrial respiration and/or increases the IFN-γ mediated killing capacity of the immune cells, as taught by Miller et al. There would have been a reasonable expectation for success given that Miller transduces immune cells to over-express ARID5B, teaches that ARID5B directly regulates UQCRB, results in cells with increased mitochondrial respiration and increased IFN-γ production, and that the methods of engineering cells to over-express ARID5B can be applied to T cells as well as NK cells and NKT cells. Thus the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claims 1-2 and 4; as Miller demonstrates that ARID5B directly regulates Uqcrb mRNA and protein expression, the modified immune cells having increased expression of ARID5B, of Miller, encompass immune cells with upregulated expression or activity of the mitochondrial respiratory chain related gene Uqcrb. Miller teaches the modified immune cells may be T cells (pg. 12, para. 0032; pg. 43, claims 1-2). Therefore, Miller makes obvious the modified immune cells, whereby the immune cells are CD8+ T cells, of instant claim 1. Miller demonstrates that ARID5B over-expression increases IFN-γ production and thus makes obvious the increased expression of cytokines, of instant claim 2. Miller teaches a pharmaceutical composition comprising the modified immune cells (pg. 44, claim 16) and thus makes obvious instant claim 4.
Regarding claims 5-6; Miller teaches a method of increasing ARID5B in NK-92 cells via lentiviral transduction, resulting in increased mitochondrial membrane potential, higher maximal respiration and higher frequencies of IFN-γ production (pg. 30, para. 0095, Figure 6). Thus, the methods of Miller, wherein the immune cells are CD8+ T cells, make obvious the method of promoting mitochondrial respiration of a cell and increasing expression or secretion of cytokines of an immune cell comprising upregulating expression of mitochondrial respiratory chain related genes of the cell, of instant claim 5; and whereby the cytokine is IFN, of instant claim 6. Note that as claim 5 step (3) does not require a magnetic field, the limitations of the last “wherein” clause of claim 5 (last 3 lines) is interpreted to only apply to the alternatives of claim 5 step (1) or step (2).
Regarding claims 20, 23 and 25-26; Miller teaches a method for treating cancer comprising administering the modified immune cells (pg. 44, claims 17-20), and thus makes obvious instant claim 20; whereby the cancer is a hematological malignancy (pg. 44, claim 19) of instant claim 23; whereby the cancer is breast cancer (pg. 45, claim 20) of instant claim 25, or whereby the hematological malignancy is acute lymphoid leukemia (pg. 21, para. 0060), of instant claim 26.
Response to Arguments
Applicant's arguments filed 2/2/2026 have been fully considered but they are not persuasive. First, the rejections over Zhu and Lin, or the combination of Lin and Zhu have been withdrawn in view of applicant’s amendments to the claims. Regarding Miller, applicants contend that Miller discloses “modified” NK cells, whereby Miller generates cells by modifying genetic information. Conversely, the present application does not relate to the modification of CD8+ T cells, instead, it subjects CD8+ T cells to magnetic field treatment, which is non-genetic and non-invasive. Thus, applicants contend that the claims possess novelty over Miller (remarks, pg. 6, bullet point (2)). Applicants also recite that the present application establishes a complete causal chain of molecular mechanisms: magnetic field [Wingdings font/0xE0] mitochondrial gene upregulation [Wingdings font/0xE0] enhanced mitochondrial respiration [Wingdings font/0xE0] improved CD8+ T cell function; and that Lin does not disclose this specific pathway, and it would not have been obvious to those skilled in the art (remarks, pg. 7, para. 2). Applicants also state that the magnetic field effects were technically meaningful, as CD25 was specifically upregulated (an indication of immune cell activation) in CD8+ T cells with no comparable effect observed on other immune cells such as CD4+ T cells; thus, the selective activation represents a non-obvious technical feature.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., treatment with a magnetic field, or the molecular pathway associated with such a treatment leading to activated immune cells) are not recited in the rejected claims. 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, 26 USPQ2d 1057 (Fed. Cir. 1993). Specifically, instant claim 1 is drawn to a product, which is an activated immune cell characterized by upregulated expression or activity of the mitochondrial respiratory chain genes. While amended claim 1 seems to attempt to introduce methods steps to generating the activated immune cells, the claim is drawn to a product. Even if the claim were interpreted as being a product-by-process claim, which it is not (see claim interpretation, above), MPEP section 2113 states that product-by-process claims are not limited to the manipulation of the recited steps, only the structure implied by the steps. That is, the patentability of a product does not depend on its method of production; the product may be anticipated or made obvious by the prior art, even if the prior art product is made by different processes. Thus, the genetic manipulations of immune cells by Miller, resulting in upregulated Uqcrb mitochondrial genes, and an activated immune cell, make obvious the activated immune cells of instant claim 1, even though Miller does not contemplate using magnetic field stimulation in the process of engineering the activated immune cells. Similarly, instant claim 5, which does claim a method for preparing immune cells, recites that the methods comprises one or more steps selected from (1)-(3). Steps (1) and (2) require treating the cell with a magnetic field; however step (3) only requires upregulating the expression of mitochondrial respiratory chain related genes of the cell, whereby no magnetic field stimulation is required. Thus, the genetically engineered cells of Miller meet the limitation of claim 5. Therefore, if the applicants are relying on the use of a magnetic field stimulation for the production of the activated immune cells, the claims should be narrowed in a manner which requires such limitations.
Similarly, regarding applicant’s contention that a chain of molecular mechanisms is presented, which is non-obvious for CD8+ T cells, the chain begins with magnetic field stimulation, which is not required in the claims as written. Further, invoking molecular pathways in cell function are often inherent properties of the cell, which are not a point of novelty, whether they were known or unknown at the time of the invention (see MPEP section 2112). That is, something which is old does not become patentable upon the discovery of a new property. For example, in the Office Action of 10/31/2025, the examiner made a rejection over Lin, as evidenced by Zhu. Applicant’s arguments contend that Zhu does not qualify as prior art, and thus cannot be used to assess the novelty and inventiveness of the present application (remarks, pg. 7, para. 1). However, the examiner was using Zhu to demonstrate that the methods of Lin would inherently result in the upregulation of Uqcrb gene regulation, as taught by Zhu. Therefore, in this example, Zhu is not relied on for prior art, but rather to evidence that the methods of Lin result in the property of upregulated Uqcrb gene regulation, even though Lin was silent on Uqcrb gene regulation. Thus, the molecular pathway described by the applicants, if deemed to be inherent properties of the methods of modifying immune cells, would not be a point of patentability, and would not require prior art to provide evidence of such properties. In this case, the rejection over Lin, as evidenced by Zhu, was withdrawn due to aspects of non-obviousness of Lin with regard to the amended claims, and not because the inherent properties evidenced by Zhu did not qualify as prior art, it doesn’t need to. Thus, the identification of the molecular pathway induced by magnetic field stimulation is not a limitation of the product of the claims, and does not provide patentability. Regarding applicant’s assertion that the magnetic field stimulation provided unexpected results by way of being specific for CD8+ T cells versus CD4+ T cells, the examiner contends that unexpected effects must be relative to the closest alternative in the art. Miller teaches the genetic manipulation of NK cells, and also describes that such manipulation may be extended to T cells and NKT cells. It is known in the art that both NK cells and CD8+ T cells are effector cells, whereas CD4+ T cells are regulatory cells. Miller teaches methods of enhancing mitochondrial respiration, and increasing cytokine release in order to generate immune cells with enhanced anti-tumor properties. Miller is focused on effector function of the immune cells. Miller repeatedly references CD8+ T cells for comparison; see for example pg. 26, para. 0085 and pg. 32, paras. 00102-00103. Miller is presenting context for enhanced IFN-γ production in the effector immune cells. Thus, an argument for unexpected effects of, for example magnetic field stimulation, having specificity for CD8+ T cells, the results should be compared to alternative effector cells, such as NK cells, rather than phenotypically and functionally divergent CD4+ T cells. Without such an example, it is obvious for a skilled artisan, with a reasonable expectation for success, to take the teachings and guidance from Miller, and perform the same methods in CD8+ T cells rather than NK cells. In total, applicant’s arguments are not found persuasive, and the rejections are maintained.
Conclusion
No claims are 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 JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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