DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. Applicant’s amendments received 02/17/2026 are acknowledged.
Claims 7, 11, and 15 have been canceled.
Claims 1, and 12-14 have been amended.
Claims 1-6, 8-10, and 12-14 are pending in the instant application.
Claim Objections
3. Applicant’s amendment to typo of claim 1, filed 02/17/2026, has been considered and accepted. Examiner withdraws previous objection to claim 1.
The following new ground of objection is necessitated by the amendment submitted 02/17/2026.
Claims 13-14 are objected to because it refers to “the antigen-specific T cell manufactured by the method of claim 1” however, base claim 1 only referenced to ”induced an antigen-specific T cell”. Correction is required.
Claim 14 is objected to because of the following informalities: there is a typo in line 1. The amended claim now reads “A method for of manufacturing…”
Claim Rejections - 35 USC § 112
4. The following new ground of rejection is necessitated by the amendment submitted 02/17/2026.
Written Description
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.
5. Claims 13-14 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims encompass a broad genus of antigen-specific T cell in preventing or treating cancer or virus infection.
However, there does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of preventing or treating cancer or virus infection. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
There is no information regarding what structural features would likely be associated with such preventing or treating cancer or virus infection. Thus, the specification does not disclose a correlation between antigen-specific T cell for preventing or treating cancer or virus infection and the structure of a putative antigen-specific T cell.
The disclosure does not allow one of skill in the art to visualize or recognize the structure of any antigen-specific T cell required to practice the claimed methods. Accordingly, one of ordinary skill in the art would conclude that the applicant would not have been in possession of the claimed method of using an antigen-specific T cell that preventing or treating cancer or virus infection because an antigen specific T cell possessing the desired activity required to practice the methods is not adequately described and was not known in the art.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
Enablement
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.
5. Claims 13-14 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 enablement requirement. The claim(s) contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 13 encompasses a broad genus of methods for preventing or treating cancer or virus infection comprising administering a composition comprising a genus of induced antigen-specific T cell culture to the subject.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
In regard to the scope of the claim, claim 13 recites “a method for preventing or treating cancer or virus infection, the method comprising administering a composition comprising a therapeutically effective amount of the antigen-specific T cell manufactured by the method of claim 1 and a pharmaceutically acceptable carrier to a subject in need thereof.” The burden of enabling the prevention of a disease (i.e. the need for additional testing) would be greater than that of enabling a treatment due to the need to screen those mammals susceptible to such diseases and the difficulty of proof that the administration of the drug was the agent that acted to prevent the condition. Further, the specification does not provide guidance as to how one skilled in the art would go about screening those patients susceptible to any cancer of any virus within the scope of the presently claimed invention. Nor is sufficient guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed antigen-specific T cell in preventing a cancer or virus state. For example, the specification discloses in vitro data showing cell killing but the specification does not show any in vivo data, nor does it show any data indicating an ability to prevent either a cancer or a virus state. Therefore, the specification at most discloses a method of treating by administering an antigen-specific T cell but not preventing either disease state.
It is not clear on the basis of in vitro studies, how to reliably predict in vivo relevance of antigen-specific T cells. Results obtained under controlled conditions often differ from the clinical response obtained in patients. This applies in particular to strategies based on responses, including strategies drawn to cancer or virus infection. Concerning animal models, the response of animals to chemotherapy, radiation and surgery is generally predictive of their effect in human patients (Osband et al., Immunol. Today 11: 193-195, 1990). However, the induced antigen-specific T cell depend on several factors such as tumor growth kinetics, site of tumor and tumor vascularization, tumor size and tumor cell heterogeneity. Since in large tumors most of the cells are not proliferating they are less likely to be killed by the induced antigen-specific T cells. Tumor cell heterogeneity also results in cells that proliferate in low rate therefore will be less likely killed by the claimed antigen-specific T cell. Also, the response to the induced antigen-specific T cells is profoundly influenced by the patient’s overall health status. Effective cancer strategies should be design to deal effectively with the nature of each of these cases. Thus in the absence of detailed guidance in the specification, the uses of any pharmaceutical composition comprising an antigen-specific T cell are fraught with uncertainties.
There is insufficient evidence or nexus that would lead the skilled artisan to predict the ability antigen-specific T cells to treat cancers or virus infection. It is not clear that such cells would reflect the therapeutic barriers presented by neoplastic cells in a clinical setting.
There is insufficient guidance in the specification as to how to determine humans or animals in whom the cellular reduction is desired versus those in whom it is not desired.
Finally, it is not clear whether the claimed cytokine cocktails used for the antigen-specific T cell would induce each and every antigen-specific T-cell. Also, at issue with the T-Cells obtained from the PBMC would be compatible with the each and every patient treated.
In reference to claim 14, which recites “a method for of manufacturing a medicament for treating cancer or virus infection, the method comprising formulating the antigen-specific T cell manufactured by the method of claim 1 with a pharmaceutically acceptable carrier for manufacture to form the medicament.”, this is also not enabled by the specification. The scope of the claim is broad, as there would be high variability in manufacturing of medicaments depending on the disease of choice. There is also very little direction or guidance provided in the specification, with exceedingly few mentions of manufacture. As such, there are no working examples of scale-up in terms of manufacture shown in the examples, although the term “manufacture” is noted after one of the expansion methods is described (see last paragraph of page 14 in the specification). Taken together, it would require and undue amount of experimentation to “manufacture a medicament for treating cancer or virus infection” based on the methods described in the instant specification. For one of skill in the art to arrive at the instant invention, it would be unduly burdensome.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Claim Rejections - 35 USC § 101
6. Applicant’s amendments of claims 13 and 14, filed 02/17/2026, have been considered and accepted. Examiner withdraws the claim rejections under 35 U.S.C. § 101 from the previous Office Action.
Claim Rejections - 35 USC § 103
7. The following new ground of rejection is necessitated by the amendment submitted 02/17/2026.
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.
Claims 1-6, 8-10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al (US Application No. US 20210017495A1, published 1/21/21, “Zhou”) in view of Liang et al (US Application No. US20210163890A1, published 06/03/2021, “Liang”), further in view of Xu et al (In Vitro Cellular & Developmental Biology – Animal, 54:559-566 (2018), IDS NPL #3, filed 04/04/2024, “Xu”), further in view of Canestrari et al (J Immunol Research, Vol. 2019, pp 1-11 (2019), IDS NPL #4, filed 04/04/2024, “Canestrari”).
Zhou teaches a method for inducing an antigen-specific T cell, comprising culturing a peripheral blood mononuclear cell (PBMC) in a medium comprising an antigenic peptide, IL-2, and IL-15.
The claimed invention differs from the reference teachings by the recitation of sequential steps of culture, inclusion of IFN-alpha in the first and second culture media (claim 1). Additionally, the claimed invention differs from the reference teachings by recitation of AIM-V medium, Human Platelet Lysate (HPL), and 1-3 days culture for all three culture mediums (claim 1).
Liang teaches sequential steps of culturing which are repeated in order to increase the yield of the target population of cells generated by those one or more steps of culture (Liang paragraph 52), and further teaches culturing a first population of cells in a medium which includes IFN-alpha in culturing PBMCs to produce the first cell population (Liang paragraphs 6 and 10). Liang also teach a culturing step of 1-3 days (Liang paragraph 14).
In additional analogous art, Xu teaches AIM-V medium as a viable serum-free medium for culturing of T cells, particularly for expansion and proliferation of T cells (Xu figs 1 and 2 and pp 560-561), and Canestrari teaches HPL as a viable additive to medium for culturing of T cells, particularly for expansion of T cells (Canestrari fig 2 and p 4).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to combine the teachings of these references to use AIM-V medium, with the additives of IL-2, IL-15, and HPL as a culture medium for 1-3 days per sequential step of cell culture in order to enrich a population of antigen-specific T cells. IFN-alpha would be obvious to try in the first medium (with antigen) and second medium as a selection and enrichment pressure for the preferred T cell population.
One of ordinary skill in the art at the time the invention was made would have been motivated to so because the medium itself would be ideal for expansion and proliferation of T cells, while using specific antigen and selection pressure to help with initial activation.
Regarding claim 2, further limiting the antigenic peptide of claim 1 to a cancer or virus in a concentration of 1pg/mL to 1mg/mL, the rejection is maintained. Liang teaches viral antigen peptides at a concentration of 1µg/mL (Liang paragraph 11).
Regarding claim 3, further limiting the method of claim 2 to a specific cancer or set of cancers, Liang teaches a variety of cancers including squamous cell carcinoma (Liang paragraph 20).
Regarding claim 4, further limiting the method of claim 2 to an EBV-related cancer, Zhou teaches the cancer to be Epstein-Barr virus (EBV)-associated cancer (Zhou paragraphs 112 and 138).
Regarding claim 5, further limiting the method of claim 4 to specific EBV-positive cancers, Zhou teaches the EBV-associated cancer to be nasopharyngeal carcinoma (Zhou paragraph 138).
Regarding claim 6, further limiting the method of claim 4 to antigens of BMLF-1, CMV peptide pool, or EBV peptide pool, Zhou specifically teaches virus-specific antigen peptides derived from EBV antigens (Zhou paragraph 112).
Regarding claim 8, further limiting the medium of claim 1 to have an IL-2 concentration in the range of 1ng/mL to 500ng/mL, Zhou teaches a concentration range within the range of the instant application (Zhou paragraph 0089).
Regarding claim 9, further limiting the medium of claim 1 to have an IL-15 concentration in the range of 1ng/mL to 100ng/mL, Liang teaches a concentration within the range of the instant application. (Liang paragraphs 12 and 13).
Regarding claim 10, further limiting the medium of claim 1 to have an IFN-alpha concentration in the range of 1ng/mL to 100ng/mL, Liang indicates a concentration of IFN-alpha (Liang paragraph 58). Through routine optimization, one of ordinary skill in the art would find a concentration range of the instant application.
Regarding claim 12, which further limits the HPL of the medium of claim 1 to a range of 1- 10 wt%, Canestrari teaches a concentration of 5% (v/v).
Response to Arguments
8. Applicant's arguments filed 02/17/2026 have been fully considered but they are not persuasive. Zhou et al (US Application No. US 20210017495A1, “Zhou”) recites a culture medium comprising antigenic peptide, IL-2, and IL-15 for the induction of antigen-specific T cells. It was noted in the previous Office Action that Zhou did not teach sequential steps of culturing or the inclusion of IFN-alpha in the culture media. In analogous art, Liang et al (US Application No. 20210163890A1, “Liang”) does include IFN-alpha in their initial medium and teaches sequential steps of culturing to obtain an isolated population of activated T cells. In reference to the inclusion of IFN-alpha in the media, the purpose of using IFN-alpha is obvious as a source of selection pressure to obtain an enriched population of activated T cells. As noted in the previous Office Action, Liang showed that their induction of PBMCs yielded the highest HPV-specific (i.e., antigen-specific) T cell frequency (Liang figure 10 and paragraph [161]). In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, this would be the motivation to include IFN-alpha in the second medium as well. In order to obtain the most highly enriched population of antigen-specific T cells, it would be obvious to try IFN-alpha as an additive in the second medium based on the teachings of Liang. Thus, Zhou and Liang, in combination, do suggest the original recited second medium as recited in claim 1.
Art of Record but not Relied Upon
9. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lee et al., US20230131917A1, Modified T Cells, Pharmaceutical Composition, Manufacturing Method Thereof, and Method of Using the Same. Filed 10/22/2021, Published 04/27/2023.
Golding et al., Interferon-alpha Regulates the Dynamic Balance between Human Activated Regulatory and Effector T Cells: Implications for Antiviral and Autoimmune Responses., Immunology, 131(1): 107-117, Sep 2010.
Conclusion
10. No claim is allowed.
11. 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.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALAN ALFANO whose telephone number is (571)272-3092. The examiner can normally be reached M-F 8-5 EST.
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/ALAN ALFANO/Examiner, Art Unit 1641
/MAHER M HADDAD/Primary Examiner, Art Unit 1641