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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/25/2025 has been entered.
Claim Status
Applicant’s amendments to the claims submitted on 7/25/2025 are acknowledged. Claims 1, 3-4, and 6-20 are pending. Claims 6-14 and 16-20 are withdrawn. Claims 1, 3, 4, and 15 are being examined on the merits.
Maintained Claim Rejections – 35 USC § 112b – Indefiniteness
Modified as Necessitated by Claim Amendments
Claims 1, 3-4 and 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 1 is directed to a “method for finding inhibitors of acid lipase that are suitable for
adjuvant treatment of a cancer”. However, there is no particular practical step that involves
determination of suitability. The last step of the method of claim 1 merely recites comparing
ascertained properties of cancer cells with and without application of an inhibitor of acid lipase
in conjunction with a cell-toxic substance. Therefore, it is unclear how the method of
ascertaining suitability for cancer treatment is accomplished in this claim and the scope is
indefinite.
Claims 3-4 and 15 depend from claim 1, inherit this deficiency, and are rejected on
the same basis.
Response to Remarks
Applicants have traversed the rejection of claims under 35 USC 112(b) as being indefinite. Applicants have amended claim 1 to specify that the property being ascertained is the “survivability” of the cells. Applicants have argued that “defining that the ascertained property of the cancer cells is the survivability thereof should clarify that the suitability of the inhibitors of acid lipase according to amended claim 1 essentially resides in reducing (or at least helping to reduce) the amount of cancer cells, thereby treating (or at least helping to treat) the cancer” (pg 10 of Remarks of 7/25/2025). Applicant further argues that “one skilled in the art, considering the claims, particularly in light of the specification, would understand what is encompassed by the claimed method” (pg 8 of Remarks of 7/25/2025).
These arguments have been carefully considered, but are not found persuasive. The amendment to claim 1 still does not contain a practical, active step of determining suitability. As demonstrated by the examples provided from the specification in the Remarks of 7/25/2025 pages 8-9, there are many methods known in the art for assessing survivability of cells that can be done subjectively or objectively/quantitatively. Therefore, even though the property that is being assessed is survivability, the claim still does not provide guidance for how survivability is assessed which therefore does not help to overcome the lack of an active step for determination of suitability.
Additionally, it is noted that the features upon which applicant relies (i.e., assessment of survivability with CellTitre-Glo®, on the basis of a color reaction, or measurement of cellular ATP concentration) are not recited in the rejected claim(s). 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).
Regarding Applicant’s arguments concerning what skilled artisans would or would not know, Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
New Claim Rejections - 35 USC § 112d – Failure to Further Limit
Necessitated by Amendments
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends. Claim 3 is directed to the method of claim 1, “wherein the property of the cancer cells that is ascertained is the survivability thereof”. However, claim 1 has been amended in the most recent version of the claims to read “ascertaining a property of the cancer cells which is the survivability thereof”. Therefore, claim 3 no longer further limits claim 1, from which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Withdrawn Claim Rejections – 35 USC § 103
The rejections of claims 1 and 3 under 35 U.S.C. 103 as being unpatentable over McCaw
(April 1, 2016; cited on IDS) in view of Hernlund et al. (International Journal of Cancer, 2008; cited on IDS) and Rosenbaum et al. (Journal of Medicinal Chemistry, 2010) are withdrawn in light of Applicant’s amendments to claim 1. The rejections of claims 4 and 15 under 35 U.S.C. 103 as being unpatentable over McCaw (April 1, 2016; cited on IDS) in view of Hernlund et al. (International Journal of Cancer, 2008; cited on IDS) and Rosenbaum et al. (Journal of Medicinal Chemistry, 2010) as applied to claims 1 and 3 above, and further in view of Priyadarshini and Keerthi (Medicinal Chemistry, 2012) and dos Santos et al. (Lipids in Health and Disease, 2014; cited on IDS) are withdrawn in light of Applicant’s amendments to claim 1.
New Claim Rejections – 35 USC § 103
Necessitated by Claim Amendments
Claims 1 and 3 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), and dos Santos et al. (Lipids in Health and Disease, 2014; cited on IDS submitted on 1/12/2022).
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 claims 1 and 3, see paragraph [0050] of the instant specification; Figure 4 of McCaw).
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.
Claims 4 and 15 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), and dos Santos et al. (Lipids in health and disease, 2014; cited on IDS submitted on 1/12/2022) as applied to claims 1 and 3 above, and further in view of Priyadarshini and Keerthi (Medicinal Chemistry, 2012; cited on PTO-892 of 3/7/2025).
The teachings of McCaw in view of Hernlund et al., Rosenbaum et al., and dos Santos et al. are detailed above. Relevant to the instantly rejected claims, McCaw in view of Hernlund et al., Rosenbaum et al., and dos Santos et al. teaches treating triple-negative breast cancer cells with an inhibitor of acid lipase in combination with cell-toxic substances and determining an effect on cell survivability.
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 rejection of claims under 35 USC 103. Applicant’s arguments beginning on pg 11 and ending on pg 20 with the experimental data have previously been considered and responded to in Office Actions dated 3/7/2025, 4/28/2025, and 7/3/2025. No new arguments have been presented other than an amendment to claim 1. The amendment of claim 1 to specify that the type of cancer is triple-negative breast cancer prompted the rearrangement of references used for rejection as detailed above. Applicant argues that “the Office admits that it may be surprising that an acid lipase inhibitor affects TNBC cells” which therefore puts the claims in condition for allowance (pg 20-21 of Remarks of 7/25/2025). However, the cited office action (Advisory Action of 7/3/2025) states “while it may be that it is surprising that an acid lipase inhibitor affects TNBC cells” (emphasis added). The presented experimental evidence at the time was not commensurate in scope with the claimed invention, in that the previously claimed invention did not claim that the cancer being assessed was triple-negative breast cancer. The examiner was merely pointing out that even if that were the case, it was not a claimed feature at the time. The amendment of claim 1 to specify that the cancer was triple-negative breast cancer changed the scope of the claim and thus prompted a reassessment of known references and a new scope of search, which resulted in the 103 rejections above.
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
/Robert T. Crow/Supervisory Patent Examiner Trainer, Art Unit 4100