DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 93-94, 99, 101-103, 106, 110, 112, 114, 118-119, and 123 are pending.
Claims 93-94, 99, 101, 106, 110, 112, 114, 118-119, and 123 are newly amended.
Claims 93-94, 99, 101-103, 106, 110, 112, 114, 118-119, and 123 have been examined on their merits.
Withdrawn Objections & Rejections
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application. Any objections or rejections not specifically reiterated are hereby withdrawn.
The previous rejection of claims 89-103, 106-111, 113-114, and 118-123 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn due to amendment or cancellation of the claims.
The previous rejection of claims 89-103, 106-113, and 118-123 under 35 U.S.C. 103 as being unpatentable over Low et al. (WO2014100615A1, on IDS 12/18/2025, previously cited, hereafter “Low I”) in view of Low et al. (WO2020033129A1, published 02/13/2020, on IDS 09/06/2022, previously cited, hereafter “Low II”) as evidenced by Merriam-Webster (“rejuvenate” definition, retrieved from internet 07/14/2026) and Kogina et al. (Mol Cells, 2009) is withdrawn due to amendment or cancellation of the claims.
The previous identification of claim 112 as being allowable is withdrawn in reconsideration of the claim.
Response to Arguments
Applicant argues that claim 112 is allowable and that claims 94, 99, 101-103, 106, 110, 112, 114, 118-119, and 123 as amended depends from that claim (Remarks, p14).
Applicant’s argument filed 09/17/2026 has been fully considered but is not persuasive. As discussed above, upon further consideration (see rejection under 35 USC 112(a)) identification of claim 112 as being allowable has been withdrawn.
Applicant argues that the previous rejections under 35 USC 112(a), 35 USC 103, and the double patenting rejections should be withdrawn because the claims as amended depend on claim 112 (15-17).
Applicant’s arguments filed 09/17/2026 have been fully considered and are persuasive. Therefore, the prior rejections under 35 USC 112(a), 35 USC 103, and the double patenting rejections have been withdrawn
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 93-94, 99, 101-103, 106, 110, 112, 114, 118-119, and 123 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted that claim 112 is the independent claim.
Independent claim 112 is a method for treating cancer. The active method steps are (a) administering to a subject one or more adapter compounds that comprise a small molecule ligand linked to a first targeting moiety; (b) administering the rejuvenating compound in step (b); and (c) administering a CAR T cell wherein the CAR is directed to the first targeting moiety, the second targeting moiety, or both.
The adapter compound is unlimited and can be any molecule comprise a small molecule ligand linked to a first targeting moiety. The claim does not require that the adapter molecule target the CAR T cell. Furthermore, the claim is broadly drawn to treating any cancer.
Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
Actual Reduction to Practice
In regards to claims 93-94, 99, 101-103, 106, 110, 112, 114, 118-119, and 123, the specification does not identify a broad genus of any adapter compounds, methods wherein CAR T cells do not bind to adapter compounds, or methods for treating any cancers.
Regarding binding of the adapter compound, the specification states, “a small molecule ligand linked to a first targeting moiety (by a first linker or directly) is used as an adaptor compound (i.e., a bridge) between one or more cancer cells and CAR-T cells that, in use, directs the CAR-T cells to the cancer for treatment of the cancer” (paragraph [0009]).
Regarding reduction to practice, the specification only discloses a single embodiment wherein anti-FITC CAR-T cells and FITC targeting adaptor compound are contacted (paragraph [0290]; example 16; Fig. 2).
Therefore, the specification indicates that the method requires binding of the adapter compound to the CAR T cell.
Regarding the composition of the adapter compound itself, the specification states that the targeting moiety can be any of DNP, TNP, biotin, dogoxigenin, various fluorescein derivatives (FITC, etc.), etc. (paragraph [0010]).
Regarding the small molecule ligand, the specification states that this can be a folate, DUPA, etc. (paragraph [0009]).
Regarding reduction to practice, the specification reduces to practice specific adapter compounds including a FITC-folate, FITC-PEG-folates, FITC-DUPA, FITC-PEG12-DUPA, FITC-PEG-11-NK1, and FITC-PEG2-CA9 (paragraphs [0247-0275]).
As above, the specification only discloses a single embodiment wherein anti-FITC CAR-T cells and FITC targeting adaptor compound are contacted (paragraph [0290]; example 16; Fig. 2).
Thus, specification only discloses reduction to practice of a method wherein the CAR is specifically an anti-FITC CAR and wherein the adapter compound targeting moiety is FITC.
Regarding treating cancer, the specification identifies cancer for treatment including at least renal, ovarian, vulvar, and breast cancer, colon, pancreas, prostate, lung, kidney, T and B cell lymphomas, thyroid, lung, pancreas, brain, stomach, gastrointestinal stroma, melanomas, leukemias, etc. (paragraph [0070]). However, the specification does not reduce to practice the treatment of any of these specific cancers.
Instead, the specification only reduces to practice a single instance of a KB xenograft model (paragraph [0299]). In this model, anti-FITC CAR-T cells previously contacted with the above described adapter compound were contacted with the TLR7 agonist/FITC rejuvenating compound which resulted in decreased tumor size and decreased tumor exhaustion marker expression in the CAR T cells (paragraph [0299]).
Accordingly, Applicant has not demonstrated the full genus of treating any cancer with any adapter compounds, and does not demonstrate methods wherein adapter compounds are not directed to the CAR T cells.
State of the Art
According to Vaughan et al. (Cancer Research, 2017), the KB xenograft model is frequently misidentified in the art and specifically refers to HeLa or cervical adenocarcinoma cells (Abstract, p2784). However, as further evidenced by Master (Nature Review, 2002), HeLa cells are “as result of genetic drift and being subjected to different conditions in various laboratories, each strain might have genetic and phenotypic differences. There is no common stock of HeLa cells, and consequently every batch from each source will be slightly different. The differences between the various cell stocks labelled HeLa are probably as great as the differences between these various strains given different names. Within the last year, some of the false cell lines listed below were catalogued and sold by some cell banks under the false name and false description” (Box 1, p317; and including KB cells specifically).
Thus, the lack of homogeneity in HeLa cells points to an unpredictability in generalizing the results to any cancer type.
Regarding the adapter compound, while as evidenced by Leone et al. (Oncotarget, 2015, previously cited), it is known that a small molecule ligand receptors such as folate receptor may be overexpressed in breast cancer compared to non-cancerous tissue (Abstract, p30327; Introduction, p30327), this overexpression is not universal (“breast cancer patients, HFR (high affinity folate receptor) is overexpressed in 33% of primary tumors”, Introduction, p30327) and upregulation of folate can be different in different tissues (Fig. 1, p30328).
Therefore, the art points to an unpredictability in using any adapter compound as clamed.
Conclusion
In regards to 93-94, 99, 101-103, 106, 110, 112, 114, 118-119, and 123, the claim suggests that the method can broadly be used to treat the genus of cancer. However, the specification only reduces to practice testing the method on a single HeLA-based cell line, which as discussed above is known in the art to be mischaracterized with genetic and phenotypic differences. Additionally, as discussed above, cancers are variable regarding targeting ligands. Furthermore, the claims suggest that any adapter compound can be used. However, the specification only demonstrates the use of adapter compounds comprising FITC targeting moieties.
Therefore, the Examiner concludes that there is insufficient written description of the instantly claimed limitation of treating any cancer with any adapter compound comprising a small molecule ligand and first targeting moiety as claimed. Furthermore, there is insufficient written description of a method that does not require that an adapter molecule be directed to a CAR T cell.
Claims 94, 99, 101-103, 106, 110, 112, 114, 118-119, and 123 are rejected under 35 USC 112(a) for their dependence on claims 112.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
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