FINAL ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is responsive to the Amendments and Response filed 06 July 2026. Claims 1-2, 8, 10, and 14 have been amended and claims 3-5 and 9 have been canceled. All prior rejections of claims 3-5 and 9 are moot in view of the cancelation of those claims. Claims 6-7 and 11-20 remain withdrawn, and claims 1-2, 8, and 10 remain under consideration herein. Applicant’s amendments and arguments have been thoroughly reviewed, and have overcome the following objections/rejections set forth in the prior Office action:
The objections to claims 8 and 10, in view of Applicant’s amendments correcting typographical errors;
Several rejections under 35 USC 112(b), in view of Applicant’s clarifying amendments; and
The rejection of claims under 35 USC 102(a)(1) as being anticipated by To et al, in view of the amendment of independent claim 1 to require LEPRE1.
Claims 1-2, 8, and 10 remain rejected for the reasons given below, which include new grounds of rejection necessitated by Applicant’s amendment. Any rejections and/or objections not reiterated in this action have been withdrawn. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicant’s election without traverse of Group I, and the species of LEPRE1, in the reply filed on 05 November 2025 is acknowledged. Claims 1-2, 8, and 10 continued to read on the elected invention.
Claims 11-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05 November 2025.
Claim 6-7 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05 November 2025.
Claim Interpretation
Independent claim 1 (from which claims 2, 8, and 10 depend) has been amended to recite the preamble limitation “of determining sensitivity or resistance of a cancer cell line to Pelitinib”, and (following a step/activity of “measuring an expression level of LEPRE1 in a cancer cell line, wherein the expression level is an RNA expression level or a protein expression level”), the steps/activities of (with emphasis added):
comparing the measured expression level of LEPRE1 with a reference LEPRE1 expression level for a corresponding control cancer cell line;
identifying the cancer cell line as sensitive to Pelitinib when the measured expression level of LEPRE1 is greater than the reference LEPRE1 expression level, and identifying the cancer cell line as resistant to Pelitinib when the measured expression level of LEPRE1 is less than the reference LEPRE1 expression level; and
contacted the cancer cell identified as sensitive to Pelitinib with Pelitinib, wherein the cancer cell line is A549, THP-1, or KG-1.
The “comparing” and “identifying” as recited in the claim may be accomplished by thought/mental activity, simply be comparing the results of the active “measuring” with another expression level, and forming a conclusion regarding the “identification” of the cells. Such a “comparing” and “identifying” also constitute instructional limitations added to a method known in the art, i.e., nonfunctional descriptive material that need not be given patentable weight when comparing a claimed invention to the prior art (see MPEP 2111.05). Additionally, the “identifying” as written sets forth conditional/ contingent steps (given the use of the language “when….the level” meets a recited criterion), and also fails to specify what type of “identifying” occurs in instances when there is no difference in expression levels between cell types. The “contacting” of the claim also clearly only occurs with respect to a cancer cell line “identified as sensitive” (which is also clearly not a required outcome of the “identifying”). MPEP 2111.04(II) states that: “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met”. Thus, in the instant situation, the only activities necessarily required by the claims are the “measuring” and the (mental) “comparing”. Finally, with regard to the preamble recitation of “determining sensitivity or resistance of a cancer cell line to Pelitinib”, based on the recited steps of the claim, this “determining” results from the “identifying” of the claim (i.e., by observing the results of the “measuring” and “comparing” those results, with the language of the preamble requiring no further concrete actions/limitations on what is claimed). Thus, the preamble language constitutes a statement of an intended use (see MPEP 2111.02).
Claim Rejections - 35 USC § 112(b)/second paragraph
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claim 10 is 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 10 is indefinite over the recitation of the limitation “wherein the expression level of the LEPRE1 gene is measured by detecting Chromosome 1, 4, or 20 having a substitution at locations 205849911, 205849976, 68337362, 182680440, 182680513, or 32983679 with T, A, or C”, because it is unclear what is required by this claim language, and how it further limits claim 1, from which it depends. First, it is noted that independent claim 1 refers to “measuring an expression level of LEPRE1”, further stating “wherein the expression level is an RNA expression level or a protein expression level”. The wording of amended claim 10 does not make sufficiently clear how requiring that “the expression level of the LEPR1 gene is measured by detecting” the recited chromosome substitutions actually relates to the “measuring” of claim 1. Clear antecedent basis is lacking for the recitation of “the LEPRE1 gene”, and it is not clear whether claim 10 is reciting a further/additional activity to be performed with regard to the status of “the LEPRE1 gene”, or whether the activity of claim 10 is intended to achieve the “measuring” of claim 1 (but without making clear how this is to be accomplished). Second, the recitation “Chromosome 1, 4, or 20 having a substitution at locations 205849911, 205849976, 68337362, 182680440, 182680513, or 32983679 with T, A, or C” does not make sufficiently clear what substitutions are being referenced. The claim relies on a chromosomal position numbering system for which no frame of reference is provided in the application, and the information corresponding to database entries for such numbering systems change over time, rendering them fluid rather than fixed. Thus, the present claim language does not provide sufficient clarity with regard to what must actually be detected in order for the conditions specified in the claim to be met.
Claim Rejections - 35 USC § 112(a)/first paragraph
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.
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claim 10 is 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. This is a new matter rejection.
Claim 10 as amended recites “wherein the expression level of the LEPRE1 gene is measured by detecting Chromosome 1, 4, or 20 having a substitution at locations 205849911, 205849976, 68337362, 182680440, 182680513, or 32983679 with T, A, or C”. While this language is indefinite for the reasons given above, the claim as written encompasses any of the recited locations in any of the recited chromosomes, as well as a substitution of any of T, A, or C at each location. In contrast, the specification discloses two alterations on chromosome 1, three on chromosome 4, and one on chromosome 20 (see, e.g., Table 1), with each of those limited to substitution of a specific nucleotide (not any of the recited alternatives). Accordingly, while the application as filed refers to a subset of the substitutions now recited in claim 10, basis is lacking for those not originally disclosed. Applicant’s amendment of 06 July 2026 thus adds new matter to the claims.
Claim Rejections - 35 USC § 102
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claim(s) 1-2, 8, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al (Cellular Physiology and Biochemistry 45:917-934 [08 Feb 2018]; previously cited), as evidenced by Li et al-2 (Experimental Cell Research 363:121-128 [2018; online 27 Dec 2017]; previously cited).
Li et al disclose methods in which the effects of the anticancer medical herb triptolide (TP) on protein expression in A549 lung adenocarcinoma cells – i.e., a preferred cell type meeting the requirements set forth in Applicant’s claims – were studied (see entire reference, particularly the Abstract). Li et al disclose growing A549 cells and exposing the cells to different concentrations of TP (page 918 bridging to page 919, “Cell culture and treatment”), and subsequently identifying and quantifying expressed proteins, and comparing TP treated cells to untreated control cells (which also encompasses comparing control cells to treated cells) (page 919-920). Li et al report analysis of several thousand of proteins, of which 141 were found to be upregulated and 171 downregulated in association with TP treatment (page 921 bridging to 922, “Comparative proteomics”); all of these results correspond to “measuring an expression level….in a cancer cell line” as recited in independent claim 1, with protein being measured, and with two different types/categories of cells (treated and untreated) being compared with one another. Among the proteins taught by Li et al as being upregulated in TP-treated A549 cells as compared to untreated cells - which also corresponds to lower expression in the untreated cells relative to the treated cells - is P3H1; see page 921-922 discussion of “Comparative proteomics”, and Table 2 on page 923, 14th listed gene). As evidenced by the teachings of Li et al-2, P3H1 is another known name for LEPRE1; i.e., the teachings of Li et al-2 establish that it is an inherent property of the gene identified by Li et al as P3H1 that is meets the requirement of being “LEPRE1” (see in particular Li et al-2 at page 125, right column, stating “P3H1 (also called Lepre1 or GROS1)”, as well as page 122, top of left column, and page 127, left column, each referencing “P3H1 (Lepre1)”).
Li et al thus anticipate independent claim 1. As set forth above, Li et al disclose measuring expression of LEPRE1 in two types of A549 cells, one treated and one untreated; just as the untreated cells serve as a “control”/”reference” for the effects of treatment in the treated cells, the treated cells inherently functional as a control/reference for the untreated cells. The untreated cells of Li et al meet the condition “when the measured expression level of LEPRE1 is less than the reference level….”, corresponding to the claim alternative of “identifying the cancer cell as resistant when….”, such that the subsequently recited conditional “contacting” of the claims does not apply to this embodiment disclosed by Li et al. (As noted above under “Claim Interpretation”, these claims recite an “identifying….when” that is a conditional instructional step, and which does not necessarily result in any further action being taken). Regarding the preamble language “determining sensitivity or resistance of a cancer cell line to Pelitinib”, it is reiterated that the claims as written do not require use of pelitinib (other than in the situation when a particular result of the conditional/contingent “identifying” occurs); thus, the preamble language constitutes a statement of an intended use that does not result in a manipulative difference between the claimed invention and the teachings of Li et al.
Regarding dependent claims 2 and 8, the limitations of a lung cancer cell line and the preferred such cell line A549 are address above.
With further regard to claim 10, the measurement of LEPRE1 protein discussed above meets the limitation of measuring expression of “the LEPRE1 gene” (based on the production of a gene product), and the claim is otherwise indefinite (as there is no clear indication in the claim itself as to what further activities are required/sufficient to achieve the “by detecting…” of the claim). Accordingly, the claim is anticipated for the reasons indicated above (and it is also noted that to the extent that the claim may be directed to detecting a chromosomal alteration that is causative of altered protein expression, the measurement of the corresponding protein, as is taught by Li et al, meets the requirements of the claim).
Accordingly, claims 1-2, 8 and 10 are anticipated by Li et al.
The reply of 06 July 2026 traverses the prior rejection of claims based on Li et al as evidenced by Li et al-2 on the following grounds. Applicant urges that claim as amended “requires determining Pelitinib sensitivity or resistance based on LEPRE1 expression”, while Li et al “does not disclose using LEPRE1 expression to classify Pelitinib sensitivity or resistance” (Reply page 9). This argument has been thoroughly considered, but is not persuasive because Li et al discloses an embodiment of the claimed invention, as discussed above. It is particularly noted that the claims as written embrace embodiments that do not require any use of pelitinib (again, as is set forth in the rejection of the amended claims, above).
Claim Rejections - 35 USC § 101
THE FOLLOWING INCLUDES NEW GROUNDS OF REJECTION NECESSITATED BY APPLICANT’S AMENDMENTS:
Claims 1-2, 8, and 10 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Amended independent claim 1 (from which claims 2, 8, and 10 depend) recite(s) a method “of determining sensitivity or resistance of a cancer cell line to Pelitinib”, and also recites the limitations “comparing the measured expression level of LEPRE1 with a reference LEPRE1 expression level for a corresponding control cancer cell line”, and “identifying the cancer cell line as sensitive to Pelitinib when the measured expression level of LEPRE1 is greater than the reference LEPRE1 expression level, and identifying the cancer cell line as resistant to Pelitinib when the measured expression level of LEPRE1 is less than the reference LEPRE1 expression level”. The activities of “comparing” measured expression levels, as well as “determining”/ “identifying” sensitivity/resistance, may be performed entirely in the human mind, and the claims are thus directed to an abstract idea (i.e., a type of judicial exception [JE]).
This judicial exception is not integrated into a practical application because the only active/wet step required by the claims, of “measuring an expression level”, is a data gathering step that does not add a meaningful limitation to the method as it constitutes insignificant extra-solution activity. While the claims do include a final recitation of “contacted the cancer cell line identified as sensitive….”, as noted above this is clearly a conditional/contingent activity, rather than a required action/step. As discussed in MPEP 2106.03(II), “A claim whose BRI covers both statutory and non-statutory embodiments embraces subject matter that is not eligible for patent protection and therefore is directed to non-statutory subject matter”.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because such a “measuring” constituted well-understood, routine, and conventional activity as of Applicant’s effective filing date; see, e.g., Li et al (Cellular Physiology and Biochemistry 45:917-934 [08 Feb 2018]; cited herein and also discussed above). Accordingly, claim 1 is not directed to patent eligible subject matter.
Regarding dependent claims 2 and 8, these claims recite more particular types of cells in which gene expression is measured; again, the claims relate to the gathering of data (i.e., insignificant extrasolution activity) rather than any type of application/ implementation of a JE, and also set forth the gathering of such data in a manner that was routine and conventional as of Applicant’s effective filing date, using well-known types/categories of cancer cell lines (such that nothing “significantly more” is added by the claims). Regarding dependent claim 10, this claim (while indefinite) appears to simply require measurement of LEPRE1 expression, i.e., data gathering (rather than an application/implementation of a JE), and was also well-known as of Applicant’s effective filing date, such that nothing “significantly more” is added. It is also noted that expression levels of a gene, including LEPRE1, in a cancer cell are natural phenomena, rather than something “more” than a JE (and an inventive concept cannot be furnished by a judicial exception [i.e., a law of nature/natural phenomenon/abstract idea] itself [see MPEP 2106.05(I)]). Accordingly, none of claims 1-2, 8, and 10 is directed to patent eligible subject matter.
The Reply of 06 July 2026 traverses the prior rejection of claims under 35 USC 101 on the following grounds. Applicant notes the language of amended independent claim 1, argues that the claims “are not merely a mental determination because it requires laboratory measurement of LEPRE1 expression, comparison to a defined reference, classification of Pelitinib sensitivity or resistance, and contacted the identified sensitive cancer cell line with Pelitinib”, and further urges that the data provided in the application support “the practical biomarker relationship recited in the amended claims” (Reply page 10).
These arguments have been thoroughly considered but are not persuasive. As discussed above in the rejection of the amended claims, the claims are not limited to the methods referenced in Applicant’s arguments; rather, the claims clearly - particularly given the recitation of the conditional/contingent activities of “identifying…when” -embrace embodiments in which the only active method step is the “measuring an expression level”. Again, a claim whose BRI covers both statutory and non-statutory embodiments “embraces subject matter that is not eligible for patent protection and therefore is directed to non-statutory subject matter” (MPEP 2106.03(II)). Applicant’s arguments rely on a claim limitation that is not in fact a requirement of the claims, and thus these arguments cannot be found persuasive. 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).
Conclusion
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 DIANA B JOHANNSEN whose telephone number is (571)272-0744. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm EST.
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682
