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 .
Detailed Action
Summary
This is a Final Office action based on the 18/012007 application response filed 01/20/2026.
Claims 1-4, 7-8, 10-12, 14-16 & 29-36 have been fully considered.
Claims 29-36 are newly added.
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 ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
The claimed invention of Claims 1-4, 7-8, 10-12, 14-16 & 29-36 are directed to non-statutory subject matter.
The invention of instant claims are drawn towards a method for “predicting,” therapeutic response to immunotherapy in a patient suffering from lung cancer.
Through 101, inquiry analysis:
Step 1, Is the claim directed to a statutory category of invention?
Yes, the independent claims 1 & 4 are drawn towards a statutory category method.
Step 2 A, Prong One: Do the claims involve a Judicial Exception?
Yes. The independent claims 1 & 4 involve the judicial exceptions of a natural correlation (natural amount of claimed biomarker or biomarker panels and their association/correlation with lung cancer or likelihood that an immunotherapy would work).
Further, “predicting,” as claimed in the preambles of both claims is a mental process and the claimed calculations and analyzing using the claimed machine-learning, are mathematical calculations which are also an abstract idea judicial exception.
Step 2 A, Prong Two: Has the Judicial Exception, which here is a law of nature/natural correlation or abstract idea been integrated into a particular practical application?
Claim 1 & 4 includes additional steps to the claimed judicial exceptions which are:
Determining expression levels at two timepoints---With respect to this, determining expression levels are just data pulls which are performed to accomplish the judicial exception and therefore insignificant extra-solution activity. See MPEP 2106.05 (g). Further- the claimed “determining,” as broadly claimed with the “predicting,” claims can be interpreted broadly in that the levels are determined by looking and pulling numbers from a chart which is a mental process, which is an abstract idea.
Possibly immune-therapy, though this is not even claimed as a positive step in Claim 1, so is not required. For Claim 4, the immunotherapy can be performed between steps a & b, and also is very generally claimed. So therefore- it is not being claimed in a way which practically applies the judicial exception.
Further, the claimed machine-learning is only claimed in Claim 1, not in 4, and is claimed at a level of generality that it is not found to be something more than performing a process that can be performed by a human mind of a computer. Though, it is also noted that no computer is claimed.
For Claim 4, what makes something a responder versus a non-responder is a material property and part of the claimed natural correlation judicial exception itself.
Therefore, nothing is claimed which makes the instant claims a practical application of the judicial exceptions.
Step 2B: Do the claims recite any elements which are significantly more than the natural correlation or abstract idea?
Claim 1 & 4 includes additional steps to the claimed judicial exceptions which are:
Determining expression levels at two timepoints---With respect to this, determining expression levels are well understood, routine and conventional in the art (WURC).
Possibly immune-therapy, though this is not even claimed as a positive step in Claim 1, so is not required. For Claim 4, the immunotherapy can be performed between steps a & b, and also is very generally claimed. At the level of generality claimed, immunotherapy for cancer is WURC.
Things that are WURC in the are not enough to make claims significantly more than judicial exceptions. See MPEP 2106.05(d) which deals with what is considered “Well-Understood, Routine and Conventional.”
Further, the claimed machine-learning is only claimed in Claim 1, not in 4, and is claimed at a level of generality that it is not found to be something more than performing a process that can be performed by a human mind of a computer. Though, it is also noted that no computer is claimed. Therefore again, at the level of generality claimed, the claimed calculations and machine learning is WURC.
For Claim 4, what makes something a responder versus a non-responder is a material property and part of the claimed natural correlation judicial exception itself.
Further- as claimed for Claims 1 & 4-- there is no technological improvement as claimed and the method steps claimed still read as mental processes which are abstract ideas and encompass a natural correlation judicial exception.
The dependent claims undergo a similar analysis. Nothing in any of the dependent claims change the matters above.
Claim 2, again is claiming a material property and part of the claimed natural correlation judicial exception itself, therefore does not change the matters above.
Claim 3 indicates timepoints for detection are before and after treatment. Timepoints like this are WURC, and also do nothing to practically apply so this does not change the matters above.
Claims 7,11 & 29-32 adds biomarkers/factors to the signatures or specify what the biomarkers or factors are. These are part of the claimed natural correlation judicial exception itself, therefore does not change the matters above. Claim 12 & 14-16 specifies more on the natural sample/natural correlation for which the same thing applies.
Claim 8, specifies what the immune therapy is, though it still does not make the therapy required by Claim 1. Therefore, this does not change the matters above.
Claim 10, specifies the cancer present. This is part of the claimed natural correlation judicial exception itself, therefore does not change the matters above.
Claims 33-34, specify what the immune therapy is used for responders and that it is administered to responders, but still leaves the claims open to the patient not being responders so no immune therapy being administered. Further- “immunotherapy,” is not particular and specific. Therefore, this does not change the matters above.
Claims 35-36, specify what the immune therapy is used for responders and that the immunotherapy is one of the claimed particular drugs and that it is administered to responders, but still leaves the claims open to the patient not being responders so no immune therapy being administered. Therefore, this does not change the matters above.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
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) 1-4, 7-8, 10-12, 14-16, 29-36 is/are rejected under pre-AIA 35 U.S.C. 103 as obvious over NAKAMURA in US 20060024692 in view of BILD in US 20210164054 and further in view of HONJO in EP 3906942.
With respect to Claims 1 & 4, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065). NAKAMURA teaches of comparison to a control (paragraph 0077), and of obtaining and testing samples at various timepoints (paragraph 0092, 0094). NAKAMURA teaches further of using this detection for development determination of responses to new drugs and immunotherapies (paragraph 0016, 0064, 0225, 0229, 0690).
NAKAMURA does not specifically teach of detection of the two timepoints, or of calculating a fold change and analysis using the fold change by the claimed machine-learning.
BILD is used to remedy this and more specifically teaches of methods and systems of determining immunotherapy response in subjects prior and during treatment for non-small cell lung cancer(abstract). BILD further teaches of using various immunotherapy regimens (paragraph 0003-0004), of detecting expression levels of various factors (paragraph 0006, Fig. 18 A, -18 C and other places), of detection over multiple time points (paragraph 0017, 0019, 0022, 0024), calculating a fold change in expression at the timepoints (paragraph 0018, 0063), and analyzing the fold change through a machine learning classifier to predict a therapeutic response (paragraph 0026, 0016, 0132, 0180-0183). BILD also teaches of training the random forest (machine learning algorithm) using responders and non-responders (paragraph 0015, 0025, 0026).
BILD further teaches of administering a treatment (paragraphs 0048-0049, 0057-0059, 0091).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to use a machine learning algorithm and fold change calculations over a period of time as is done in BILD in the method of and NAKAMURA due to the advantage machine learning has for comparing annotations (BILD, paragraph 0132), and to compare across timepoints as this offers advantage in giving a reference value for how the value changes (paragraph 0068), and it would have been obvious to detect fold changes since fold changes give advantage in showing how the level of expression activity is different in magnitude or fold om certain instances (BILD, paragraph 0063, 0065). BILD also teaches of predicting therapeutic response by these methods (paragraph 0004, 0020, 0162, 0171, 0195-0198).
NAKAMURA and BILD do not specifically teach of using the fold change specifically in the machine learning algorithm and training on data with fold changes.
HONJO is used to remedy this. HONJO teaches of monitoring efficacy of therapy with PD-1 (abstract), and more specifically teaches of analyzing responders and non-responders and discriminating between them and using machine learning to validate this (train them with this information/the same cohort) (paragraph 0124). It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the instant invention to train a machine learning algorithm with the responders and non responders as is done in HONJO in the method of NAKAMURA and BILD due to the advantage this would have in validating and predicting other measurements and responses (HONJO, paragraph 0124).
With respect to Claim 2, NAKAMURA teaches of the above, but does not teach specifically of comparison to a threshold score.
BILD is used to remedy this and teaches of comparing the gene expression value to a reference and of comparing the score for the signature to a reference score or threshold. It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to compare the scores to a threshold due to the advantage this offers in determining activity level (BILD, paragraph 0072).
With respect to Claim 3, NAKAMURA teaches of the above, but not of the timepoints. BILD is used to remedy this and teaches of the timepoints as shown above for Claim 1. BILD further teaches of analyzing the different treatment timepoints (paragraph 0019), and also of specific before treatment measurements (paragraph 0142, 0153, 0164-0165), and after treatment measurements (paragraph 0124). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to make the timepoints before and after treatment as is done BILD in the method of NAKAMURA, due to the advantage this offers is being able to determine the effect/response of a treatment/immunotherapy and the need in the art for this (BILD, abstract, paragraph 0004).
With respect to Claim 7, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065). NAKAMURA teaches of comparison to a control (paragraph 0077), and of obtaining and testing samples at various timepoints (paragraph 0092, 0094). NAKAMURA teaches further of using this detection for development determination of responses to new drugs and immunotherapies (paragraph 0016, 0064, 0225, 0229, 0690).
With respect to Claim 8, BILD teaches methods and systems of determining immunotherapy response in subjects prior and during treatment for non-small cell lung cancer when the therapy is anti-D-1 therapy(abstract).
With respect to Claim 10, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract).
With respect to Claim 11, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065). NAKAMURA teaches of comparison to a control (paragraph 0077), and of obtaining and testing samples at various timepoints (paragraph 0092, 0094). NAKAMURA teaches further of using this detection for development determination of responses to new drugs and immunotherapies (paragraph 0016, 0064, 0225, 0229, 0690).
NAAKMURA does not call out some of the other factors in the signature with the above molecules. BILD is used to remedy this and teaches of detection of PLAUR, IL6 (paragraph 0145, 0139). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect additional factors as is done in BILD in the method of NAKAMURA due to the advantage that monitoring an expression profile offers for identifying responders versus non-responders (paragraph 0136, 0149, 0194).
With respect to Claim 12, NAKAMURA teaches of determining protein expression (paragraph 0300, 0302).
With respect to Claim 14, NAKAMURA teaches of determining protein expression (paragraph 0300, 0302).
With respect to Claim 15, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065). NAKAMURA teaches of comparison to a control (paragraph 0077), and of obtaining and testing samples at various timepoints (paragraph 0092, 0094). NAKAMURA teaches further of using this detection for development determination of responses to new drugs and immunotherapies (paragraph 0016, 0064, 0225, 0229, 0690).
With respect to Claim 16, NAKAMURA teaches of comparison to a control to determine increase or decrease and by what threshold (paragraph 0016, 0017, 0096-0097, 0119).
With respect to Claim 29, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065).
With respect to Claim 30, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065).
With respect to Claim 31, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065).
With respect to Claim 32, NAKAMURA teaches of a method of detecting, diagnosing, and treating non-small cell lung cancer (abstract). This includes determining the expression of two different genes including CDH3 (paragraph 0067 & Table 2) and PRELP (paragraph 0065).
With respect to Claim 33, BILD teaches of methods and systems of determining immunotherapy response in subjects prior and during treatment for non-small cell lung cancer(abstract) and of determining responders versus non-responders (paragraph 0014, 0016) and of performing a series of administration in patients who are responding (paragraph 0049, 0052, 0058-0059, 0326).
With respect to Claim 34, BILD teaches of methods and systems of determining immunotherapy response in subjects prior and during treatment for non-small cell lung cancer(abstract) and of determining responders versus non-responders (paragraph 0014, 0016) and of performing a series of administration in patients who are not responding (paragraph 0049, 0052, 0058-0059, 0326).
With respect to Claim 35, BILD teaches of methods and systems of determining immunotherapy response in subjects prior and during treatment for non-small cell lung cancer(abstract) and of determining responders versus non-responders (paragraph 0014, 0016) and of performing a series of administration in patients who are not responding (paragraph 0049, 0052, 0058-0059, 0326). BILD teaches of administration of pembrolizumab, nivolumab, or cemiplimab (paragraph 0093).
With respect to Claim 36, BILD teaches of methods and systems of determining immunotherapy response in subjects prior and during treatment for non-small cell lung cancer(abstract) and of determining responders versus non-responders (paragraph 0014, 0016) and of performing a series of administration in patients who are not responding (paragraph 0049, 0052, 0058-0059, 0326). BILD teaches of administration of pembrolizumab, nivolumab, or cemiplimab (paragraph 0093).
Response to Arguments
The 101 rejection is maintained for the significantly amended claims. The reasons for this are shown in the above rejection.
Applicant argues that due to Ex parte Desjardins that a claimed invention “providing an improvement in the functioning of a computer, or an improvement to other technology or technical field,” should be evaluated for in the instant claims.
Applicant argues that the technological improvement must be evaluated in light of the specification. The examiner notes, that this has been done and reminds applicant that patentability determinations are still made based on what is actually claimed. As shown above, what is claimed is not determined to be a technological improvement.
Applicant also argues that the response signatures of Claim 11 and also evaluation of biomarkers at two timepoints and the 4 proteins recited in Claim 29 are technological improvements. The examiner disagrees, as these things are part of the claimed natural correlation judicial exception itself. Further, the examiner notes that if applicant thinks Claims 11 & 29 are technological improvements, then why have they not added these limitations to the independent claims? Further- though applicant argues that the response signatures in Claims 11, 29, & 30 are a technological improvement for therapy selection, it is noted that the same therapies seem to be used in Claims 33-36 whether the patient is a responder or non-responder. All the claimed therapies in Claims 35-36 are known for NSCLC, so—in fact, there does not seem to be any improvement, especially as instantly claimed.
Further- it is noted that all the biomarker/biomarker combinations recited in the claims applicant argues (Claims 11, 29-30 & the new claims 29-32) are taught clearly by the prior art.
Applicant argues that new claims 33-36 are patent eligible. The examiner disagrees with this, for the reasons shown in the rejection above.
All claims remain rejection under 101.
Applicant’s arguments with respect to claim(s) have been considered but are moot because the new ground of rejection does not rely on the combination of references applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Specifically, in claims amendments dated 01/20/2026, applicant has amended out biomarkers that the priorly used BROGDON reference taught. Due to these amendments, a new reference, NAKAMURA is used. NAKAMURA teaches of the claimed biomarker/biomarker combinations as shown above.
Further- the examiner notes that applicant repeatedly argues that Claim 29 recites “four factors,” required. The examiner notes that only one of the four factors in Claim 29 is required as instantly claimed.
Applicant does not make any other arguments about the prior art.
All claims remain rejected.
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 REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758