DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a continuation in part of PCT/KR2021/007706, filed 18 June 2021, claiming foreign priority to Korean application 10-2020-0075057, filed 19 June 2020. As an English translation of PCT/KR2021/007706 has not been filed (and was also not present/available via other tools available to the examiner, such as Global Dossier), an English translation of the corresponding publication WO20210256907A1 was reviewed (however it is suggested that applicant provide a certified translation of the PCT application). It is also noted that a certified translation of Korean application 10-2020-0075057 has not been provided.
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. Applicant has identified claims 1-5 and 8-10 as reading on the elected Group and species, and claims 1-5 and 8-10 are now under consideration.
Claims 11-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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Claim 6-7 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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.
Information Disclosure Statement
With regard to the two forms PTO/SB/08a filed 12/19/2022 and 12/20/2022, it is noted that these forms pertain to the same group of cited references, with the 12/20/2022 version correcting a typographical error (duplicate citation) on the earlier (12/19/2022) form. Thus, only the second (12/20/2022) is marked as considered (however, all cited references were reviewed/considered).
Drawings
The drawings are objected to because Figures 7-9 each include at least some text that is blurry/not plainly legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 8 is objected to because of the following informalities: the claim fails to end in a period. Appropriate correction is required.
Claim 10 is objected to because of the following informalities: the claim recites the “method of claims 1” rather than the “method of claim 1”. Appropriate correction is required.
Claim Interpretation
With regard to claim 1 and claims dependent therefrom, it is noted that while the claim is drawn to a method “to determine a sensitivity or resistance to a drug”, and recites “determine the sensitivity is high based on overexpression of the gene, and the resistance is high based on underexpression of the gene” (which is indefinite language as discussed below), there is only a single recited active method step set forth in the claim – “measuring an expression level of a gene in a cancer cell line” – and there is nothing in the claim indicating any requirement that any drug actually be employed as part of the claimed method, or that the practice of the “measuring” recited in the claim actually result in either over or under expression of a gene (rather, the claims embrace method in which gene “overexpression” or “underexpression” is relied upon to determine sensitivity/resistance, without any requirement that a drug be employed in the claimed method, or that over or under expression occur/be established as having occurred, etc.). Accordingly, claim 1 and claims dependent therefrom embrace both methods in which drugs may potentially be employed (as such methods are broadly encompassed by the claims, although no use of drugs is referenced/recited in the claims), as well as methods in which no use of a drug is required; further, the claims embrace methods in which the “measuring” may or may not result in “an expression level” indicative of overexpression or underexpression (the nature of which is also entirely unclear based on the present claim language, as discussed below). With particular regard to the embodiments of dependent claims 2-3, it is noted that while these claims specify a more particular drug/category of drugs, the methods claimed do not require use of these drugs (rather, the claims relate to a determination of “a sensitivity or resistance” that is based on gene expression level).
Claim Rejections - 35 USC § 112(b)/second paragraph
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 1-5 and 8-10 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.
Claims 1-5 and 8-10 are indefinite over the recitation in independent claim 1 of the limitation “determine the sensitivity is high based on overexpression of the gene, and the resistance is high based on underexpression of the gene”. First, the term “high” is a relative term that renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Additionally, while the claim states that a determination of “high” sensitivity is to be “based on overexpression of the gene”, and of “high” resistance to be ‘based on underexpression of the gene”, the terms “overexpression” and “underexpression” are themselves relative terms, and the claim language gives no indication as to what point of comparison might be employed to establish that either “overexpression” or “underexpression” is present. Thus, the recitations in the claim regarding over and under expression are themselves indefinite for failing to provide clear boundaries on what is claimed, and this lack of clarity also contributes to the lack of clarity with regard to what would be considered “high” sensitivity or resistance. Clarification is therefore required.
Claim 4 is indefinite over the recitation of the limitation “wherein the drug has multi-target efficacy as shown in Table 4 or an efficacy profile similar thereto”. First, it is noted that (as stated in MPEP 2173.05(s)):
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
In the instant case, the reliance on Table 4 to define what is claim renders the claim indefinite, as it is not clear what elements of Table 4 might be sufficient (and insufficient) to meet the requirements of the claim. Further, the language “an efficacy profile similar thereto” is also indefinite, given the indefiniteness of the already noted reliance on Table 4, as well as the fact that the language “efficacy profile similar thereto” is vague, and does not reasonably apprise one of skill in the art as to what characteristics/properties would meet the requirements of the claim (particularly with regard to what would be considered “similar”/not similar). Further clarification is therefore needed.
Claim 10 is indefinite over the recitation of the limitation “the expression level of the LEPRE1 gene is measured by detecting at least one alteration selected from Table 1”. Again, MPEP 2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
In this case, the reliance on Table 1 does not make sufficiently clear what would/would not be required to achieve what is required by the claim, such that the boundaries of what is claimed are not clear. The claim should be amended to simply specify what is required thereby.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-5 and 8-10 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]; cited herein), as evidenced by Li et al-2 (Experimental Cell Research 363:121-128 [2018; online 27 Dec 2017]; cited herein).
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 dependent claims 8-9 – 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 (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 of a gene in a cancer cell line” as recited in independent claim 1 (as it is noted that the claims embrace any “measuring an expression level of a gene”, without specifying that expression is to be based on any particular type of gene expression product). Additionally, among the proteins taught by Li et al as being upregulated in TP-treated A549 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 (the preferred gene set forth in dependent claims 5 and 10); 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 gene” (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 also disclose that TP treatment induced apoptosis and cell cycle arrest in A549 cells (page 920 bridging to page 921), and thus their method accomplishes the preamble objective set forth in independent claim 1 of determining “a sensitivity or resistance to a drug”.
Li et al thus anticipate claim 1. As set forth above, Li et al disclose a variety of embodiments embraced by the present claims, as they measure expression of numerous genes in a cancer cell line and achieve the objective of determining drug sensitivity or resistance. With further regard to the recitation in claim 1 of the limitation “determine the sensitivity is high based on overexpression of the gene, and the resistance is high based on underexpression of the gene”, it is noted that: a) this language is indefinite, and does not clearly further limit what is required by the claims (as discussed above); b) Li et al clearly teach measurement of gene expression levels as required by the claims, with some genes (including P3H1/LEPRE1) exhibiting altered expression in association with drug sensitivity; given the indefiniteness of the claims, such embodiments appears to meet the requirements of “determine the sensitivity” as set forth in claim 1; c) Li et al (again) clearly teach measurement of gene expression levels as required by the claims, with many genes exhibiting unchanged expression upon TP treatment; given that the claim language states “determine the” sensitivity/resistance “based on” over or under expression, such embodiments are also embraced by the claims (as the “determine” language of the claim does not limit/relate to genes without over or under expression); and d) the recitation “determining the sensitivity is high based on overexpression….determine the resistance is high based on underexpression” also constitutes an instructional limitation added to a method known in the art, i.e., nonfunctional descriptive material that need not be given patentable weight (see MPEP 2111.05).
With further regard to dependent claims 2-3, while Li et al do not discuss EGFR inhibitors including Pelitinib, these claim limitations are only further limiting of what is indicated by an outcome of the active step “measuring an expression level of a gene”, which activity is clearly taught by Li et al. The claims require no manipulative difference(s) as compared to the methods set forth by Li et al, and thus Li et al anticipate claims 2-3. While the fact that some gene expression levels (such as those for the preferred gene LEPRE1/P3H1, which is clearly among the genes measured by Li et al both in control and treated cells) may be associated with sensitivity or resistance to EGFR inhibitors/Pelitinib is not disclosed by Li et al, this is an inherent feature of the method of Li et al, and something which is old/known does not become patentable upon the discovery of a new property (see MPEP 2112).
Regarding dependent claim 4, this claim is indefinite as noted above, and is not clearly further limiting of what is claimed in any way; thus, the claim is anticipated for the reasons given above with regard to claim 1.
Regarding claims 5 and 10, the LEPRE1 gene is addressed above. With further regard to claim 10, this claim is otherwise indefinite (i.e., beyond the requirement for LEPRE1, as discussed above), and thus is also anticipated for the reasons given above.
Regarding claims 8-9, the limitations of a lung cancer cell line and the preferred such cell line A549 are address above.
Accordingly, all of claims 1-5 and 8-10 are anticipated by Li et al.
Claim(s) 1-4 and 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by To et al (British Journal of Pharmacology 172:4089-4106 [2015]; cited herein).
To et al teach methods in which the EGFR TK inhibitor Pelitinib (i.e., a preferred drug as set forth in dependent claims 2-3) was studied in regards to its ability to target cancer cells with upregulated ABCB1/ABCG2 after hyperthermia (see entire reference, particularly the Abstract). With particular regard to the instant claims, To et al disclose methods in which the human non-small cell lung cancer cell line A549 (i.e., a preferred cell line meeting the requirements of dependent claims 8-9) was grown in the presence (and absence) of Pelitinib, with measurement of resulting expression of ABCB1 and ABCG2 at both the mRNA and protein level (see entire reference, particularly page 4091, left column, top paragraph; page 4098, left column “Pelitinib did not alter the expression of ABCB1 and ABCG2 at both mRNA and protein levels”, and Figure 2B and the description thereof). To et al thus anticipate claim 1. To et al clearly disclose a “measuring an expression level of a gene in a cancer cell line”, which method includes use of a preferred cell line (A549), and relates to a preferred drug (Pelitinib). As To et al report no differences in expression levels, the conditions specified in the “determine” step are not met, which is an embodiment embraced by the claim to the extent that it is presently understood. Further, a failure to determine either sensitivity or resistance achieves the intended use of “to determine a sensitivity or resistance to a drug”. With further regard to claims 2-3, it is reiterated that To et al disclose use of the EGFR inhibitor Pelitinib, which is an embodiment clearly embraced by the claims. Regarding dependent claim 4, this claim is indefinite as noted above, and is not clearly further limiting of what is claimed in any way; thus, the claim is anticipated for the reasons given above with regard to claim 1. Regarding claims 8-9, the limitations of a lung cancer cell line and the preferred such cell line A549 are address above.
Accordingly, each of claims 1-4 and 8-9 is anticipated by To et al.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-5 and 8-10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Independent claim 1 (from which claims 2-5 and 8-10 depend) recite(s) a method “to determine a sensitivity or resistance to a drug” concluding with the recitation “determine the sensitivity is high based on overexpression of the gene, and the resistance is high based on underexpression of the gene”. While this language is indefinite (as discussed above), it appears to indicating forming a conclusion regarding drug sensitivity or resistance based on expression level(s) determined via a prior (wet) method step of “measuring an expression level of a gene in a cancer cell line”; such an activity of “determining” may be performed entirely in the human mind (such as by thinking about the implications of measured expression levels with regard to drug sensitivity/resistance), 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 of a gene in a cancer cell line”, is a data gathering step that does not add a meaningful limitation to the method as it constitutes insignificant extra-solution activity. 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) and To et al (British Journal of Pharmacology 172:4089-4106 [2015]; cited herein and also discussed above), as well as Kaul et al (Oncogene 19:3576-3583 [2000]; cited herein), particularly at page 3578, right column and 3581-3582 (disclosing measurement of expression of Gros1/LEPRE1 in A549 cells, i.e., the preferred gene and a preferred cell type set forth in Applicant’s dependent claims). Accordingly, claim 1 is not directed to patent eligible subject matter. Regarding dependent claims 2-3, these claims recite a more particular category/type of drug, but limit only what is indicated by test results (as the claims make no reference to any actual use of such drugs); the claims are thus further limiting of the abstract idea of the claims, rather than any something “more” than a JE, or requiring any type of application of a JE. Claim 4 similarly recites a property that applies to a JE, rather than something more than a JE, or a practical application of a JE. Claims 5 and 10 each require measurement of the LEPRE1 gene; however, such measurement is a more particular type of 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)]). Regarding claims 8-9, 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). Accordingly, none of claims 1-5 and 8-10 is directed to patent eligible subject matter.
Conclusion
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