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 .
Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 4/9/2026 has been entered.
Claim Status
Applicant’s amendments to the claims submitted on 4/9/2026 are acknowledged. Claims 1, 6-14, and 16-21 are pending. Claims 6-14 and 16-20 are withdrawn (consonant with the Election/Restriction of 10/30/2024, and upheld in the Office Action of 3/7/2025).
Claims 1 and 21 are being examined on the merits.
Claim Objections
The objection to claim 1 is withdrawn in light of Applicant’s amendment to the claim.
Claim Rejections - 35 USC § 112b – Indefiniteness
The rejection of claims 1, 15, and 21-22 under 35 U.S.C. 112(b) described in the Office Action of 1/15/2026 is withdrawn in light of Applicant’s amendment to claim 1 to remove the trade name/mark CellTitre Glo® and cancellation of claims 15 and 22.
Claims 1 and 21 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 contains the trademark/trade name “taxol”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the cell-toxic substance and, accordingly, the identification/description is indefinite. Taxol is a brand name of the generic “paclitaxel”. Therefore, the claim can be amended to read “(i) a cell-toxic substance, wherein the cell-toxic substance is [[taxol]]paclitaxel” to overcome this rejection. “Paclitaxel” has support throughout the specification (paragraphs [0027, 0083-0085] and Figure 2).
Claim 21 depends from claim 1, inherits this deficiency, and is rejected on the same basis.
Claim Rejections - 35 USC § 103
Withdrawn:
The rejections of claims 15 and 22 under 35 U.S.C. 103 as detailed in the Office Action of 1/15/2026 is withdrawn in light of Applicant’s cancellation of said claims. The rejection that has been maintained below has been amended in light of this cancellation and new claim amendments.
Maintained:
Claims 1 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over McCaw (April 1, 2016; cited on IDS submitted on 1/12/2022) in view of Hernlund et al. (International Journal of Cancer, 2008; cited on IDS submitted on 1/12/2022), Rosenbaum et al. (Journal of Medicinal Chemistry, 2010; cited on PTO-892 of 3/7/2025), dos Santos et al. (Lipids in Health and Disease, 2014; cited on IDS submitted on 1/12/2022), and Priyadarshini and Keerthi (Medicinal Chemistry, 2012; cited on PTO-892 of 3/7/2025).
McCaw teaches a method of applying an inhibitor of acid lipase (lalistat) to chronic
lymphocytic leukemia cells (CLL; cancer cells of a cancer cell line) and ascertaining a property
of the cancer cells (page 29). McCaw teaches determining the effect of the acid lipase inhibitor
on the CLL cancer cells by comparing the same property of the cancer cells incubated without
the acid lipase inhibitor under the same conditions as those incubated with the acid lipase
inhibitor (Figure 4 and Figure 7). In McCaw, one of the properties ascertained was the “% cell
viability”, which reads on survivability (relevant to claim 1, see paragraph [0050] of the instant specification; Figure 4 of McCaw). McCaw assessed survivability of the cells on the basis of a color reaction (Trypan Blue, Figure 4).
McCaw does not teach combining the acid lipase inhibitor in an adjuvant treatment to the
cancer cells. However, combining metabolic inhibitors with cell-toxic substances to potentiate
the effect of the inhibitor on cancer cells is known in the art, as taught by Hernlund et al.
Hernlund et al. teach a method for assessing the synergistic effect of an adjuvant
treatment of two different metabolic inhibitors (2-deoxyglucose and etomoxir) in combination
with known cell-toxic substances (such as cisplatin, see Table 1). Hernlund et al. compare
survivability (in the form of measuring apoptosis) in colon cancer cells when treated with a cell-
toxic substance alone, and when treated with the same cell toxic substance in combination with
the metabolic inhibitor (Figure 2b).
It would have been prima facie obvious to one having ordinary skill in the art, as of the
effective filing date of the instant application, to have modified the method of McCaw (which
teaches application of an acid lipase inhibitor to cancer cells) to ascertain the effect of the
metabolic inhibitor when combined with a cell-toxic substance, as taught by Hernlund et al. One
would have been motivated to combine a cell-toxic substance with a metabolic inhibitor such as
an acid lipase inhibitor in order to potentiate the killing of cancer cells and thus increase the
benefits of any developed treatment, as demonstrated by Hernlund et al. (Figure 2 and Table
IIA). One would have a reasonable expectation of successful combination give that application
of acid lipase inhibitors to cancer cells was successfully demonstrated in McCaw and a
combinatory application of an inhibitor and cell-toxic substances was successfully performed by
Hernlund et al.
McCaw in view of Hernlund et al. does not teach screening multiple compounds for
selection of an acid lipase inhibitor based on their inhibition of acid lipase enzymatic activity.
However, screening methods for testing multiple compounds to assess their ability to inhibit the
enzymatic activity of acid lipase were known in the art, as taught by Rosenbaum et al.
Rosenbaum et al. teach screening of multiple different compounds in an in vitro assay to
determine relative abilities to inhibit the enzymatic activity of lysosomal acid lipase (Figure 3;
Experimental Section – LAL Activity Assay).
It would have been prima facie obvious to one having ordinary skill in the art, as of the
effective filing date of the instant application, to have modified the method of McCaw in view of
Hernlund et al. (which teaches application of an acid lipase inhibitor to cancer cells in
combination with a cell-toxic substance) to perform a screen for potent inhibitors of acid lipase
enzymatic activity, as taught by Rosenbaum et al. One would be motivated to perform the screen
of test substances in order to determine the most potent inhibitors for validation and use in more
costly cellular experiments (as taught by Rosenbaum et al.). Performing a screen of test
substances to determine a test substance with the greatest inhibitory effect on acid lipase, as
taught by Rosenbaum et al., would yield the predictable result of providing a substance that
could then be applied to cancer cell lines, as taught by McCaw, to assess survivability.
McCaw in view of Hernlund et al. and Rosenbaum et al. does not teach finding acid lipase inhibitors suitable for adjuvant treatment of triple-negative breast cancer (TNBC). However, association of lipid metabolism with triple-negative breast cancer cell proliferation is known in the art, as taught by dos Santos et al.
Dos Santos et al. teaches that LDL-cholesterol promotes the proliferation of breast cancer cells, in particular TNBC cells (MDA MB 231 cells; Abstract and Fig 1A).
It would have been prima facie obvious to one having ordinary skill in the art, as of the
effective filing date of the instant application, to apply acid lipase inhibitors as taught by McCaw in view of Hernlund et al. and Rosenbaum et al., to TNBC cells. One would be motivated to do this given the assertion by dos Santos et al. that high LDL-cholesterol stimulates growth of TNBC cells (Fig 1A) and given the teaching by McCaw that lysosomal acid lipase is responsible for breaking down LDL components (cholesteryl esters and triglycerides; pg 3, 1.2.1.3 Low-density lipoproteins (LDL) and Lalistat). One would have a reasonable expectation of successful application to breast cancer cells of an inhibitor of lysosomal acid lipase given that McCaw successfully applies lalistat (an inhibitor of lysosomal acid lipase) to CLL cells and there is no evidence presented to indicate that this inhibitor could not also be successfully applied to TNBC cells.
McCaw in view of Hernlund et al., Rosenbaum et al., and dos Santos et al. does not teach specifically using taxol (also known as paclitaxel) as the cell-toxic substance combined with an acid lipase inhibitor. However, use of taxol to treat cancers, particularly in adjuvant therapies to increase effectiveness of treatment, is known in the art, as taught by Priyadarshini and Keerthi.
Priyadarshini and Keerthi review the extensive use of taxol as a cell-toxic substance
commonly used to treat cancers such as “lung, breast, ovarian, leukopenia and liver cancer” (pg.
2, column 1, paragraph 4). Priyadarshini and Keerthi list numerous studies indicating the
synergistic effect of taxol when used in combination with inhibitors (pg. 2, column 1, paragraphs
2-3).
It would have been prima facie obvious to one having ordinary skill in the art, as of the
effective filing date of the instant application, to have modified the method of McCaw in view of
Hernlund et al., Rosenbaum et al., and dos Santos et al. (testing of an adjuvant therapy combining a metabolic inhibitor with a cell-toxic substance and ascertaining effect on cancer cell growth) to use taxol as the adjuvant therapy combined with the inhibitor, as taught by Priyadarshini and Keerthi. One would be motivated to employ taxol given its use in treatment of diseases such as breast cancer. Dos Santo et al. teach that there is a link between LDL-cholesterol signaling and breast cancer (Abstract), and McCaw teaches that an acid lipase inhibitor (Lalistat) can reduce the stimulatory effect of LDLs on cancer growth (in CLL cells). Therefore, one would be motived to employ taxol to test the effect of adjuvant therapy combining a known cancer drug (taxol) with an acid lipase inhibitor (one of which has been shown to decrease the stimulatory effects of LDLs on cancer growth). One would have a reasonable expectation of successfully testing this combination, as application of inhibitors and taxol, together and alone, has successfully been applied to cancer cell lines (as taught by McCaw and Priyadarshini and Keerthi).
Response to Remarks
Applicants have traversed the rejections of claims 1, 15, 21, and 22 under 35 USC 103 (pages 7-10 of Remarks of 4/9/2026). Applicant’s arguments have been carefully considered but are not deemed persuasive for the following reasons.
Applicant asserts that McCaw observes an antitumor effect of Lalilstat in CLL cell culture models and then states “In contrast, there is little to no effect on cell viability in triple-negative breast cancer” (pg 8 of Remarks). No evidence is cited to support this claim, and indeed it is unclear if this is referring to data the Applicant gathered or if it is meant to assert that McCaw does not show evidence of Lalistat acting on TNBC cells. Therefore, the argument is unpersuasive. Furthermore, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant argues that Hernlund, Rosenbaum, dos Santos, and Priyadarshini, alone or in combination, do not cure this defect. However, as noted above in the 103 rejection, dos Santos teaches that high levels of LDL-cholesterol stimulates the growth of TNBC cells. McCaw teaches that lysosomal acid lipase is responsible for breaking down LDL components (cholesteryl esters and triglycerides; pg 3, 1.2.1.3 Low-density lipoproteins (LDL) and Lalistat). One would have a reasonable expectation of successful application to breast cancer cells of an inhibitor of lysosomal acid lipase given that McCaw successfully applies lalistat (an inhibitor of lysosomal acid lipase) to CLL cells and there is no evidence presented to indicate that this inhibitor could not also be successfully applied to TNBC cells. Applicant further provides no evidence that Lalistat alone does not have an inhibitory affect on TNBC cells.
Applicant goes on to summarize the advantages of adjuvant treatment between an acid lipase inhibitor and taxol (pg 9-10 of Remarks), however these advantages of combination therapies of metabolic inhibitors with taxol is taught by the prior art, as noted above in the 103 rejection.
Applicant then asserts that there is no evidence that “improved recognition of cytotoxic T cells through inhibition of TNBC-LIPA leads to reduced viability of tumor cells due to their destruction by the T cells” (pg 10 of Remarks). However, this is a species that is withdrawn from examination and thus has not been examined on the merits, given Applicant’s election with traverse of a single disclosed adjuvant treatment species “(i) a cell-toxic substance” and specifically, “paclitaxel (taxol)” in the Response to Election/Restriction filed on 10/30/2024. The Election/Restriction was deemed proper and FINAL in the Office Action of 3/7/2025. Therefore, the species of “(iii) immune cells directed against cancer cells” has not been examined and thus the statement of lack of evidence that this has been described cannot be addressed.
For the reasons presented above, the rejection of claims 1 and 21 under 35 USC 103 is maintained. The rejection of claims 15 and 22 were withdrawn given Applicant’s cancellation of said claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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