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 .
This action is in response to papers filed 1/19/2026.
Applicant’s election of Group II and NOTCH1 and GENEID4851 in the reply filed on 8/8/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
CLiams 1-20 are pending. Claims 1-12 are withdrawn as being drawn to a nonelected invention.
The following rejections are modified or newly applied as necessitated by amendment. Response to arguetmsn follows.
This action is FINAL.
Withdrawn Objections and Rejections
The objection to the specification made in the previous office action is withdrawn based upon amendments to the claims.
The 35 USC 112b, 35 USC 103 rejection made in the previous office action is withdrawn based on amendments to the claims.
Modified Claim Rejections - 35 USC § 112
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 13-20 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.
The claims are drawn to a method for predicting sensitive to an immune checkpoint inhibitor therapy in any subject with a solid tumor based upon performing bioinformatic analysis of gDNA sequencing data to obtain information about the NOTCH1.
The claims are drawn to a very large genus of immune checkpoint inhibitor therapy in any subject with a solid tumor based upon any bioinformatics analysis.
The claims are drawn to any subject and analysis of prediction of sensitivity to immune checkpoint inhibitor therapy based upon sequencing and performed bioinformatic analysis of gDNA of NOTCH1. The specification describes human patients with solid cancer and detection of NOTCH 1. The specification has not provided any written description of any bioinformatics of NOTCH1 and the functionality of sensitivity of immune checkpoint inhibitor. The specifical describes NOTCH1, but does not describe the functionality of any bioinformatics analysis and the determination of sensitivity.
In analysis of the claims for compliance with the written description requirement of 35 U.S.C. 112, first paragraph, the written description guidelines note regarding genus/species situations that "Satisfactory disclosure of a ``representative number'' depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features of the elements possessed by the members of the genus in view of the species disclosed." (See: 'Written Description" Requirement, Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001.) In the instant case, the specification fails to teach the necessary common attributes or features of the variants/mutations in view of the species disclosed. As such, one of skill in the art would not recognize that applicant was in possession of the genus encompassed by the broadly claimed invention.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the claims have been amended such that the solid tumor is selected from particular tumors and that the immune checkpoint limits to a particular inhibitor therapy (p. 7). These arguments have been reviewed but have not been found persuasive. Although the claims are limited based upon the amendments the claims, the newly amended claims do not address the functionality issues with regard to “any subject”. The specification describes human patients with solid cancer and detection of NOTCH 1. The specification has not provided any written description of any bioinformatics of NOTCH1 and the functionality of sensitivity of immune checkpoint inhibitor. The specifical describes NOTCH1, but does not describe the functionality of any bioinformatics analysis and the determination of sensitivity.
Newly Applied Claim Rejections - 35 USC § 112
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 13-20 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 13-20 are indefinite over step f in claim 13. In particular the step is drawn to “counting number of mutant NOTCH genes”. This is unclear as the steps do not require determining “number of mutant NOTCH genes”, but rather measures NOTCH gene variations in at least one of the group of NOTCH1, NOTCH2, NOTCH3, and NOTCH4. Therefore the metes and bounds are unclear with regard to performing step f in claim 13.
Claims 13-20 are indefinite over the phrase “a greater number of mutant NOTCH genes” in claim 13 step f. Further the phrase “more suitable for receiving” in claim 13 step f. These terms are relative terms which renders the claim indefinite. The terms “a greater number of mutant NOTCH genes” and “more suitable for receiving” are 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. In particular it is not clear which mutant number would be considered “greater” as there is not a comparison step. The term “more suitable” is not clear as it is not clear the comparison to the receiving the therapy.
Maintained 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 13-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claim(s) recite(s) a judicial exception of classifying based upon expression or methylation. This judicial exception is not integrated into a practical application because the claims require steps of detecting expression does not provide a step to integrate the judicial exception.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not integrate the judicial exception to steps that are not considered routine and conventional steps. In particular a step of obtaining and measuring are positive active steps that are routine steps of gDNA library hybridization and bioinformatics.
These judicial exceptions are not integrated into a practical application because the claims only recite the natural correlation, wherein the step of obtaining and measuring does not integrate the judicial expectation. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps are considered general and routine knowledge in the prior art as exemplified by the art (as discussed below).
According to the 2019 Patent Eligibility Guidance an initial two step analysis is required for determining statutory eligibility.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? In the instant case the Step 1 requirement is satisfied as the claims are directed towards a process.
Step 2A Prong one. Does the claim recite a law of nature, a natural phenomenon or an abstract idea? Yes, a natural phenomenon as discussed above.
Step 2A prong two. Does the claim recite additional elements that integrate the judicial exception into a practical application? The answer is no as the steps require only routine and convention steps and does not integrate the judicial exception to a practical application.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No as the claims do not require any elements that integrate the judicial exception.
The steps that are not considered judicial expectations are the steps of obtaining and measuring using known and conventional assays. Jensen et al (US Patent Application Publication 2019/0390265 December 26, 2019) teaches extracting DNA from a patient with a solid tumor and preparing a gDNA library (para 382 and 605). Jensen et al. teaches hybridizing to a NOTCH1 probe (table 2). Jensen et al. teaches sequencing the data and performing bioinformatic analysis (para 605). The claims do not require an integration of the judicial exception, for example, treating with immunotherapy based upon the integration to the bioinformatic analysis. Therefore the steps are general and routine hybridization methods.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the recitation of “counting of mutant NOTCH genes” requires complex qualitative biological information to be transformed into an objective numerical parameter (p. 8). The reply asserts that the classification is directly corresponded to a positive or negative responders (p. 8). The reply asserts that it address a technical solution for a specific practical problem and as such integrates the methods (p. 8).
This argument has been reviewed but have not been found persuasive.
First step f does not require detecting mutations but rather “mutant NOTCH genes”. As such the step would not encompass individual mutations within a NOTCH gene, but rather an assessment of “mutant NOTCH”. Further, there is not requirement for detection of these in an assay but “counting number”. As such step f can be interpreted as an abstract step which can be performed mentally. The step does not require complex information, but rather it can be interpreted as mentally looking a data and counting the number of mutants. This abstract step would be considered a judicial exception and therefore is not used to integrate a judicial exception. The rejection is maintained.
Newly Applied 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.
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) 13, 15-16, 18-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jensen et al (US Patent Application Publication 2019/0390265 December 26, 2019 previously cited) in view of Campbell et al. (US Patent Application Publication 2019/0209573 July 11, 2019).
With regard to claim 13, Jensen et al teaches extracting DNA from a patient with a solid tumor and preparing a gDNA library (para 382 and 605). Jensen et al. teaches hybridizing to a NOTCH1 probe (table 2). Jensen et al. teaches sequencing the data and performing bioinformatic analysis (para 605).
However, Jensen et al. does not teach that NOTCH1 analysis was associated with prediction of sensitivity to an immune checkpoint inhibitor.
With regard to claim 15, Jensen et al. teaches fragmenting the extracted DNA (para 42, 133, 394).
With regard to claim 16, Jensen et al. teaches construction of the library suing the steps of end repair, a-tailing, adapter ligation, and clean up (para 394).
With regard to claim 13 and 18, Campbell et al. teaches a method of determining sensitivity of PD-1 or PD-L1 inhibitors based upon mutations in NOTCH1 (para 116). As Campbell et al. teaches targeting somatic mutations of NOTCH1, Campbell would encompass “counting” as Campbell et al. teaches having numbers would be associated with treatment of checkpoint inhibitors including PD-L1 and PD-1.
With regard to claim 19, Campbell et al teaches that the PD-L1 inhibitor is pembrolizumab (para 169).
With regard to claim 20, Campbell et al. teaches atezolizumab (para 167).
Therefore it would be prima facie obvious to the ordinary artisan at the time of the effective filing date to modify the method of Jensen et al. to use the methodology and bioinformatic analysis to determine sensitivity of PD-1 and PDL-1 based upon the presence of a mutation (counting) of NOTCH1. The ordinary artisan would have a motivation to use the method of analysis of Jensen in order to determine sensitivity as Campbell et al. teaches that data from mutations of NOTCH1 provides sensitivity analysis.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jensen et al (US Patent Application Publication 2019/0390265 December 26, 2019 previously cited) and of Campbell et al. (US Patent Application Publication 2019/0209573 July 11, 2019) as applied to Claims 13, 15-16, 18-20 in view of White et al. (US Patent Application Publication 2018/0126354 May 10, 2018 previously cited).
Jensen et al teaches extracting DNA from a patient with a solid tumor and preparing a gDNA library (para 382 and 605). Jensen et al. teaches hybridizing to a NOTCH1 probe (table 2). Jensen et al. teaches sequencing the data and performing bioinformatic analysis (para 605). However, Jensen et al. and Campbell et al. does not teach that the DNA extracted to create the library of Jensen is between 50 to 500ng.
With regard to claim 14, White et al. teaches designing library of genomic DNA with 250 ng of DNA from the sample (para 77).
Therefore it would be prima facie obvious to the ordinary artisan at the time of the effective filing date to use known amounts of genomic DNA as taught by White to produce a gDNA library. The ordinary artisan would have a reasonable expectation of success to modify the amount of gDNA as the amount taught by White et al. is a routine amount of gDNA that can be used to produce libraries.
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 KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Cheng (Winston) Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682