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 .
Response to Amendment
The amendments received 06/04/2026 have been entered. Claims 12-15 are examined herein. Claims 1-4, 7-11, and 16-17 are withdrawn. Any objection or rejection previously set forth in the Office Action mailed 02/20/2026 not maintained herein has been overcome by amendment and is withdrawn.
New grounds of rejection are set forth as necessitated by amendment.
Election/Restrictions
As a result of Applicant’s amendments to the claims, Examiner has expanded the search scope to encompass the full scope of a compound/a candidate drug generally. The election of species requirement set forth in the Office Action mailed 10/20/2025 is therefore withdrawn. The restriction requirement, however, is maintained, there being no allowable generic or linking claim.
Specification
The disclosure is objected to because of the following informalities: on page 33 (Specification filed 06/04/2026, clean copy), "(CUDC-101, GSK-LSD1 and BML-210" is missing a closed parenthesis ")".
Appropriate correction is required.
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.
Claims 14-15 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 14 recites “further comprising contacting the tumor organoids with a checkpoint inhibitor against programmed death ligand 1 (PD-L1), PD-1, and CTLA-4”. The definition of CTLA-4 (“cytotoxic T-lymphocyte associated protein 4”) is set forth in claim 15 rather than claim 14, and no definition is set forth for PD-1 in either claim 14 or claim 15. This inconsistency causes confusion. Correction is required.
Claim 14 recites “further comprising contacting the tumor organoids with a checkpoint inhibitor against programmed death ligand 1 (PD-L1), PD-1, and CTLA-4”. It is unclear whether the PD-L1, PD-1, and CTLA-4 checkpoint inhibitor may be alternatively selected from or whether the checkpoint inhibitor must be all three of PD-L1, PD-1, and CTLA-4 checkpoint inhibitors. Examiner suggests that Applicant amend the claims to recite “or CTLA-4” instead of “and CTLA-4” if the former is true. Claim 15 is similarly rejected for not clarifying the limitation at issue.
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 12-15 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.
Applicant has amended the claims to recite “identifying the candidate drug as the compound for enhancing the sensitivity of the breast tumor cell to T-cell toxicity by measuring cytotoxicity of tumor cells following treatment with the candidate drug”. Examiner notes that in the Remarks filed 06/04/2026, Applicant has not specifically pointed to the location in the instant disclosure that provides support for the aforementioned amendment. See MPEP 2163.06(I).
Moreover, in looking to the specification, there is no disclosure that either implicitly or explicitly supports the amendment at issue. The closest disclosure that falls within the scope of the amendment is that of the working examples, namely Example 4 and Example 5. However, disclosure of a species or a narrower limitation does not necessarily constitute disclosure of a broader limitation. See MPEP 2163.05(I) and In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004). Moreover, limitations such as “measuring cytotoxicity of tumor cells” appear to have no support whatsoever, as the instant invention is not directed toward enhancing the cytotoxicity of the tumor cells themselves, nor is any disclosure set forth that suggests such an effect would be expected of the instant invention. The limitation additionally suggests that the criteria for “identifying” the candidate drug merely requires measuring cytotoxicity but does not provide any description for what criteria would be fulfilled for a candidate drug to be considered capable of enhancing the sensitivity of a breast tumor cell to T-cell cytotoxicity. As such, one of ordinary skill in the art would not be apprised that Applicant had possession of the claimed invention at the time of filing.
Claims 12-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a tumor or cancer cell that is a breast cancer cell and a candidate drug selected from BML-210, CUDC-101, and GSK-LSD1, does not reasonably provide enablement for a candidate drug generally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, "The Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)" (emphasis added). The "make and use the full scope of the invention without undue experimentation" language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: "A lack of enablement for the full scope of a claim, however, is a legitimate rejection." The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc., 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444.
Identifying compounds for the treatment of cancer generally cannot possibly be considered enabled.
By way of background, four cases are of particular relevance to the question of enablement of a method of treating cancers broadly or even generally:
In In re Buting, 57 CCPA 777, 418 F.2d 540, 163 USPQ 689, the claim was drawn to "The method of treating a malignant condition selected from the group consisting of leukemias, sarcomas, adenocarcinomas, lymphosarcomas, melanomas, myelomas, and ascitic tumors" using a small genus of compounds. The Court decided that human testing "limited to one compound and two types of cancer" was not "commensurate with the broad scope of utility asserted and claimed".
In Ex parte Jovanovics, 211 USPQ 907 the claims were drawn to "the treatment of certain specified cancers in humans" by the use of a genus of exactly two compounds, the N-formyl or N-desmethyl derivative of leurosine. Applicants submitted "affidavits, publications and data" for one of the compounds, and a dependent claim drawn to the use of that species was allowed. For the other, no data was presented, applicants said only that the other derivative would be expected to be less effective; claims to the genus were refused.
In Ex parte Busse, et al., 1 USPQ2d 1908, claims were drawn to "A therapeutic method for reducing metastasis and neoplastic growth in a mammal" using a single species. The decision notes that such utility "is no longer considered to be "incredible", but that "the utility in question is sufficiently unusual to justify the examiner's requirement for substantiating evidence. Note also that there is also a dependent claim 5 which specified "wherein metastasis and neoplastic growth is adenocarcinoma, squamous cell carcinoma, melanoma, cell small lung or glioma." The decision notes that "even within the specific group recited in claim 5 some of the individual terms used actually encompass a relatively broad class of specific types of cancer, which specific types are known to respond quite differently to various modes of therapy."
In Ex parte Stevens, 16 USPQ2d 1379 a claim to "A method for therapeutic or prophylactic treatment of cancer in mammalian hosts" was refused because there was "no actual evidence of the effectiveness of the claimed composition and process in achieving that utility."
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. Some experimentation is not fatal; the issue is whether the amount of experimentation is "undue"; see In re Vaeck, 20 USPQ2d 1438, 1444.
The analysis is as follows:
1) Breadth of claims.
"Cancer" is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. To be able to simply stop cancer cells generally from being able to proliferate. Many of these approaches --- and there have been others as well --- have produced anti-cancer drugs. However, despite high hopes for success, and a plausible theory why these should work for cancers generally, none of these approaches have ever produced a drug which come remotely near such a goal.
Specifically, the prior art knows that there never has been a compound capable of treating cancers generally. "The cancer therapy art remains highly unpredictable, and no example exists for efficacy of a single product against tumors generally." (<http://www.uspto.gov/web/offices/pac/dapp/1pecba.htm#7> ENABLEMENT DECISION TREE, Example F, situation 1). A similar statement appears at In re Application of Hozumi et al., 226 USPQ 353: "In spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in treating all types of cancer. Cancer is not a simple disease, nor is it even a single disease, but a complex of a multitude of different entities, each behaving in a different way". There are compounds that treat a modest range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers.
The attempts to find compounds to treat the various cancers arguably constitute the single most massive enterprise in all of pharmacology. This has not resulted in finding any treatment for tumors generally. Indeed, the existence of such a "silver bullet" is contrary to our present understanding in oncology. This is because it is now understood that there is no "master switch" for cancers generally; cancers arise from a bewildering variety of differing mechanisms. Even the most broadly effective antitumor agents are only effective against a small fraction of the vast number of different cancers known. This is true in part because cancers arise from a wide variety of sources, primarily a wide variety of failures of the body's cell growth regulatory mechanisms, but also such external factors such as viruses (an estimated at least 20% are of viral origin e.g. Human papillomavirus, EBV, Hepatitis B and C, HHV-8, HTLV-1 and other retroviruses, and quite possibly Merkel cell polyomavirus, and there is some evidence that CMV is a causative agent in glioblastoma), exposure to chemicals such as tobacco tars, excess alcohol consumption (which causes hepatic cirrhosis, an important cause of HCC), ionizing radiation, and unknown environment factors.
Accordingly, there is substantive "reason for one skilled in the art to question the objective truth of the statement of utility or its scope" (In re Langer, 183 USPQ 288, 297), specifically, the scope of covering cancer generally.
Similarly, In re Novak, 134 USPQ 335, 337-338, says "unless one with ordinary skill in the art would accept those allegations as obviously valid and correct, it is proper for the examiner to ask for evidence which substantiates them." There is no such evidence in this case. Likewise, In re Cortright, 49 USPQ2d 1464, states: "Moreover, we have not been shown that one of ordinary skill would necessarily conclude from the information expressly disclosed by the written description that the active ingredient" does what the specification surmises that it does. That is exactly the case here. Moreover, even if applicants' assertion that cancer in general could be treated with these compounds were plausible --- which it is not ---, that "plausible" would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: "If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions" consisting of little more than respectable guesses as to the likelihood of their success."
Different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. The skill thus depends on the particular cancer involved. There are some cancers where the chemotherapy skill level is high and there are multiple successful chemotherapeutic treatments. The mechanism in these situations, however, is not necessarily the same as is alleged for these compounds.
One skilled in the art knows that chemotherapy of brain tumors is especially difficult. This is because 1) the blood-brain barrier, which is often intact in parts or all of a brain tumor, will block out many drugs, as it is the purpose of the blood-brain barrier to protect the brain from alien chemicals, and 2) CNS tumors are characterized by marked heterogeneity, which greatly decreases vulnerability to chemotherapy. As a result, many categories of CNS tumors simply have no chemotherapy available. These include, generally, hemangioblastomas, meningiomas, craniopharyngiomas, acoustic neuromas, pituitary adenomas, optic nerve gliomas, glomus jugulare tumors and chordomas, to name just some. With regard to gliomas, GBM is considered untreatable; no effective agents have emerged for the treatment of GBM, despite 20 years of enrolling patients in clinical trials. It is radiation and surgery which are used for low grade gliomas (e.g. pilocytic astrocytoma and diffuse astrocytomas), as no drug has been found effective. There is no drug treatment established as effective for optic nerve gliomas or gangliogliomas. Indeed, very few gliomas of any type are treated with pharmaceuticals; it is one of the categories of cancer that is the least responsive to drugs.
Lymphomas of the stomach are not commonly treated with anti-cancer agents per se, but instead, surgery or radiation and antibiotic therapy (e.g. amoxicillin, metronidazole, bismuth, and omeprazole) are the primary treatments.
Neuroendocrine tumors of the cervix generally do not respond to chemotherapy.
A number of sarcomas, including alveolar soft part sarcoma (ASPS), retroperitoneal sarcoma, most liposarcomas, and the assorted chondrosarcomas, are generally considered not to respond to chemotherapy; no chemotherapeutic agent has been established as effective.
It is important to note that tumors can need to be treated quite differently even though they are tumors of the same organ. For example, the drugs used most often to treat Wilms tumor, the most common malignant tumor of the kidneys in children, are actinomycin D and vincristine. Such drugs are never used with clear cell renal carcinoma, which is treated, although without much success, with immunotherapy using the cytokines interleukin-2 and interferon-alpha. However, such immunotherapy has never been established as effective in non-clear cell RCC forms such as papillary renal cell carcinoma. Despite strenuous efforts over a period of decades, no chemotherapeutic agent has ever been found effective against this cancer. Cancers of the stomach can be lymphomas, GISTs, carcinoid tumors, carcinomas, or soft tissue sarcomas, and for a single agent to be effective against all or even most of these categories would be contrary to what is known in oncology.
The scope of treating inflammation generally is extraordinarily broad. Inflammation is a process which can take place in virtually any part of the body. There is a vast range of forms that it can take, causes for the problem, and biochemical pathways that mediate the inflammatory reaction. It is one of the most pervasive of all body processes. Inflammation is a very general term which encompasses a huge variety of specific processes.
2) The nature of the invention and predictability in the art.
With specific reference to cancer, Ex parte Kranz, 19 USPQ2d 1216, 1219 notes the "general unpredictability of the field [of] …anti-cancer treatment." In re Application of Hozumi et al., 226 USPQ 353 notes the "fact that the art of cancer chemotherapy is highly unpredictable". More generally, the invention is directed toward medicine and is therefore physiological in nature. It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
3) State of the Prior Art. The claimed method is directed toward determining if a candidate drug (generally) enhances the sensitivity of a breast tumor cell to T-cell cytotoxicity. So far as the examiner is aware, such a broad scope of compounds has not been successfully used as broad range anticancer agents or T-cell cytotoxicity sensitizers.
4) Working Examples. Applicants have provided no working examples which are successfully used to predict the activity of a broad range anticancer agents. Applicants have, however, demonstrated the claimed method wherein BML-210, CUDC-101, and GSK-LSD1 were identified as sensitizing breast cancer cells to T-cell cytotoxicity (see Examples, specification).
5) Skill of those in the art. Many, many mechanisms have been proposed over the decades as methods of treating assorted cancers generally. Cytotoxic agents could be applied directly to the tumor cells, directly killing them. Immunotherapy involves stimulating the patient's immune system to attack cancer cells generally, either by immunization of the patient, in which case the patient's own immune system is trained to recognize tumor cells as targets, or by the administration of therapeutic antibodies as drugs, so the patient's immune system is recruited to destroy tumor cells by the therapeutic antibodies. Another approach would be to increase the amount or activity of the body's tumor suppressor genes, e.g. p53, PTEN, APC and CD95, which can for example activate DNA repair proteins, suppress the Akt/PKB signaling pathway, or initiate apoptosis of cancer cells. The angiogenesis inhibitor strategy was based on cutting off the blood supply that growing tumors need by shutting off the growth of new blood vessels by, for example, suppressing proliferation of endothelial cells or inducing apoptosis of endothelial cells. There is also the cancer stem cell paradigm, which hypothesizes that cancer could be treated generally, either by targeting the cancer stem cells themselves, or by targeting the epithelial-to-mesenchymal transition which supposedly generates the cancer stem cells. Yet another approach is to inhibit one or more of the assorted HSP90 proteins, which will supposedly disrupt the proper folding of signaling proteins that all cancers rely on. Inhibiting telomerase was said to be able to be able to simply stop cancer cells generally from being able to proliferate. Many of these approaches --- and there have been others as well --- have produced anti-cancer drugs. However, despite high hopes for success, and a plausible theory why these should work for cancers generally, none of these approaches have ever produced a drug which come remotely near such a goal.
Accordingly, there is substantive "reason for one skilled in the art to question the objective truth of the statement of utility or its scope" (In re Langer, 183 USPQ 288, 297), specifically, the scope of covering cancer generally. Moreover, even if applicants' assertion that cancer in general could be treated with these compounds were plausible --- which it is not ---, that "plausible" would not suffice, as was stated in Rasmusson v. SmithKline Beecham Corp., 75 USPQ2d 1297, 1301: "If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions" consisting of little more than respectable guesses as to the likelihood of their success."
6) Scope of the claims. The scope of the claims involves “candidate compounds”
and their identification as potential treatment to breast cancers, thus, the scope of claims is very broad.
7) The quantity of experimentation needed. Given the fact that, historically, the development of new cancers drugs has been difficult and time consuming, and especially in view of factors 1 and 4 and 6, the quantity of experimentation needed is expected to be great.
MPEP 2164.01(a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here.
Claims 14-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a checkpoint inhibitor selected from atezolizumab, ipilimumab, nivolumab and pembrolizumab, does not reasonably provide enablement for checkpoint inhibitors generally. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The instant claims are directed toward a method of determining if a candidate drug enhances the sensitivity of a tumor cell to T-cell cytotoxicity, further comprising contacting the tumor organoid of claim 12 with a checkpoint inhibitor such as a CTLA-4 or PD-L1 inhibitor. The specification does not define that which is intended in the use of checkpoint inhibitor. Moreover, in the working examples, the checkpoint inhibitor used is specific to mice (“anti-mouse PD-1”, Table 4, p. 27 of specification). As such one of ordinary skill in the art would not be able to predict which checkpoint inhibitors could be combined with the candidate drugs of the instantly claimed method. There are hundreds of checkpoint inhibitors known in the art, ranging from small molecule inhibitors to antibodies. It is well established that "the scope of enablement varies inversely with the degree of unpredictability of the factors involved" and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). Thus, the amount of experimentation required to use the full scope of the claimed invention would certainly be undue.
Claim Rejections - 35 USC § 103
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) 12-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zavros et al. (WO 2020/154579 A1; published 30 July 2020) as evidenced by Gray et al. (International Journal of Molecular Medicine; published 2012) and further in view of Kretzschmar et al. (WO 2019/122388 A1; 2019).
Zavros et al. discloses a method of identifying compounds for their use as treatment for pancreatic cancer and their effect on T cell proliferation, wherein the method comprises generating pancreatic cancer organoids derived from cancer cells (p. 19-20), co-culturing the organoids with activated CD8+ T cells from mice (p. 28), contacting the co-culture with a combination of nivolumab (PD-1 inhibitor), gemcitabine, and epothilone A (p. 28), which resulted in death of PD-L1 expressing cells and increased proliferation of CD8+ T cells (p. 28-29) as determined by flow cytometry of cells stained with antibodies for cellular receptors (p. 20-21) and a CFSE uptake assay (p. 29), respectively. Zavros et al. discloses that the organoids were treated with the drugs for 72 hours (which includes 48 hours) prior to flow cytometry analysis (p. 21). Zavros et al. additionally teaches that the organoids tested included those between 70 and 150 μm (see Fig. 3 G and I and size legend).
As evidenced by Gray et al., gemcitabine is an epigenetic inhibitor that inhibits DNA methyltransferase (Abstract).
Examiner notes that while Zavros et al. discloses co-culturing the organoids with activated CD8+ T cells prior to treating the organoids with a chemotherapeutic drug, the open language of the claimed invention (“said method comprising”) allows for additional steps. Moreover, one of ordinary skill in the art would be apprised that following treatment of the organoids with the chemotherapeutic drug, the co-cultured CD+ T cells would still be contacting the treated organoids.
Zavros et al. does not disclose a method of identifying a compound for enhancing sensitivity of a breast tumor cell to T-cell cytotoxicity. This is obvious over Kretzschmar et al.
Kretzschmar et al. discloses a method of identifying an agent suitable for treating a cancer, wherein the method comprises contacting an organoid co-culture comprising immune cells and at least one organoid with one or more candidate agents, detecting the presence or absence of one or more changes in the organoid co-culture that indicates therapeutic efficacy, and identifying a candidate agent if one of said changes is detected (p. 2-5). Kretzschmar et al. further discloses that organoids and tumoroids are preferably obtained from epithelial cells, including breast cells (p. 20). Kretzschmar et al. further exemplifies co-culturing tumor organoids with activated CD8+ T-cells (p. 39).
It would be prima facie obvious for one of ordinary skill in the art to apply the method of Zavros et al., in view of the method of Kretzschmar et al., to breast tumor cells. One would have been motivated to do so in order to further identify candidate compounds for the treatment of breast cancer. One would have had a reasonable expectation of success in view of Kretzschmar et al., who suggests that their invention is particularly applicable to breast and pancreatic cancers (p. 22).
Response to Arguments
Applicant's arguments filed 06/04/2026 have been fully considered but they are not persuasive.
Claims 12-15 under 35 U.S.C. 112(a) scope of enablement
Examiner notes that Applicant has not provided any arguments or amendments pertaining to lack of enablement for identifying a candidate drug generally, as Applicant’s current arguments and amendments only address the scope of the cancer. The response is considered bona fide, however, the portion of the rejection pertaining to the scope of a candidate drug generally is maintained.
Claims 14-15 under 35 U.S.C. 112(a) scope of enablement
In the Remarks filed 06/04/2026, Applicant argues that the checkpoint inhibitors atezolizumab, ipilimumab, nivolumab and pembrolizumab are checkpoint inhibitors of PD-L1, PD-1, and CTLA-4, and no undue experimentation would be required to exemplify checkpoint inhibitors generally against PD-L1, PD-1, and CTLA-4. This is not persuasive. The invention is not only directed toward checkpoint inhibitors, now amended from checkpoint inhibitors generally to checkpoint inhibitors against PD-L1, PD-1, and CTLA-4 generally, but their combination with a candidate drug in the method of claim 12. The combination of general agents, and even particular species of agents, is not considered predictable in view of the unpredictability of physiology and pharmaceutical development. Furthermore, little guidance is provided as to what this “candidate drug” may be, nor does Applicant describe any checkpoint inhibitors (other than those to which Examiner has indicated the invention is enabled for) that can be used in combination with the limited scope of candidate drugs tested in the working examples.
The applicants may only claim whatever he or she regards as his or her invention, i.e., the applicant may not claim subject matter that he or she does not regard as his or her invention. The use of “additional therapeutic agent” does not set forth that which the applicants regard as their invention, nor do the agents solely defined by their function as in claim 28. The applicants are not entitled to preempt the efforts of others in future discoveries, wherein the claims are directed toward agents that have yet to be discovered. The applicants are only entitled to those additional active ingredients, i.e., anti- cancer agents, contemplated at the time of filing.
Where the utility is unusual or difficult to treat or speculative, such as in the case of treating cancer, the examiner has authority to require evidence that tests relied upon are reasonably predictive of in vivo efficacy by those skilled in the art. See In re Ruskin, 148 USPQ 221; Ex parte Jovanovics, 211 USPQ 907; MPEP 2164.05(a). While Applicant argues that the instant invention has demonstrated efficacy in combination with tamoxifen, abemaciclib, or N-allyl noroxymorphone, this does not mean that Applicant has demonstrated that the instant invention would be effective against cancer in combination with any and all anti-cancer agents (or even “therapeutic agents” broadly). Moreover, combinations of pharmaceuticals can be antagonistic, even if they are known to have similar properties or indications.
Patent Protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. Tossing out the mere germ of an idea does not constitute enabling disclosure. Genentech Inc. v. Novo Nordisk 42 USPQ2d 1001.
As stated in the MPEP, 2164.08 "[t]he Federal Circuit has repeatedly held that the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
As such, the rejection is 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 MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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/M.E.B./Examiner, Art Unit 1624 06/12/2026
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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