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
This action is in response to papers filed 12/22/2025.
Applicant’s election of Group II and the combination of GHSR and MAL in the reply filed on 7/25/2022 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)).
4. Claims 1-16, 18-20, 26-30 are pending. Claims 17, 21-25 have been cancelled.
5. Claims 1-8, 10-14, 16 are withdrawn as being based upon nonelected inventions or species.
6. The following rejections are maintained with response to arguetmsn following.
7. This action for claims 9,15, 18-20, 26-30 is final.
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 9,15, 18-20, 26-30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for determining increased risk, does not reasonably provide enablement for diagnosing a human as having bladder cancer or recurrent bladder cancer or being at risk of having bladder cancer or recurrent bladder cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
The claims are drawn to a method of diagnosing a subject as having bladder cancer or recurrent bladder cancer or being at risk of developing bladder cancer or recurrent bladder cancer based upon comprising the methylation of GHSR and MAL and determining based upon hypermethylation. Therefore the claims are drawn to determining risk or diagnosis of bladder cancer or recurrent bladder cancer based upon detection of hypermethylation.
The invention is in a class of invention which the CAFC has characterized as “the unpredictable arts such as chemistry and biology.” Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The specification teaches measuring methylation of patients with bladder cancer and patients with no history of urinary tract malignancy (p. 28-29). The specification teaches that methylation levels are hypermethylated in patients with bladder cancer compared to controls for MAL and GHSR (p. 31). The specification discloses that GHSR and MAL are higher in patients with recurrent cancer (p. 32). As such the specification provides support for increased risk, but does not provide support for diagnosis based upon hypermethylation. In particular the specification has not provided guidance that measuring increased methylation of GHSR and MAL would predictably diagnosis bladder cancer or recurrent cancer.
The unpredictability of the art and the state of the prior art
The state of the art does not provide a correlation of GHSR and MAL hypermethylation and diagnosis of bladder cancer or diagnosis of recurrent cancer.
Level of Skill in the Art
The level of skill in the art is deemed to be high.
The skilled artisan would need to perform undue experimentation to determine such an association as the specification has not provided guidance that these associations are predictable with regard to diagnosis of bladder cancer based upon hypermethylation. Therefore to use the invention as presented would require a large amount of inventive effort, with each of the many intervening steps, upon effective reduction to practice, not providing any guarantee of success in the succeeding steps.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The claims asserts that claims 27-29 are not to diagnosing but methods of treatment (p. 8). The reply asserts that there is data showing that individuals with existing or recurrent bladder cancer exhibit statistically signification hypermethylation and as such provides diagnostic of the disease conditions (p. 9). The reply asserts that there is no undue experimentation as the specification provides data for the correlations (p. 10). These arguments have been reviewed but have not been found persuasive. Although claims 27-29 do not require a preamble of diagnosis, the steps of the claims require such a correlation and as such is included in the rejection. The reply asserts that the specification provides data for the diagnosis. However, as noted above, the examiner asserts that the data provides for risk but not diagnosis. In particular the claims requires that hypermethylation of GHSR and MAL as compared to a healthy indicates the diagnosis of bladder cancer or recurrent bladder cancer or being at risk of developing bladder or recurrent bladder cancer. The specification has not provided guidance that hypermethylation can diagnosis bladder cancer and being at risk of developing bladder cancer. In particular the same hypermethylation in the claims are correlative to both diagnosis and risk of developing, the specification has not provided how to diagnosis and risk based upon the same detection of hypermethylation.
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 9,15, 18-20, 26, 30 are rejected under 35 U.S.C. 101 because the claimed invention is a directed to the judicial exception of natural phenomena of correlation of to bladder cancer and the abstract idea of comparing without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Note that the unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., No. 10-1150 (March 20, 2012).
The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, No. 08-964, 2010 WL 2555192 (June 28, 2010) and in Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014).
Applicant’s attention is directed to the USPTO January 7, 2019 Revised Patent Subject Matter Eligibility Guidance (i.e., “PEG”) available at URL:
<https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf>.
Regarding Step 1 of the PEG, the claims are directed to the statutory category of a process.
Regarding Step 2A, prong one, the claims are directed to and recite the natural phenomena of correlation of bladder cancer or recurrent bladder cancer and hypermethylation and the abstract step of comparing. It is noted that comparing could encompass an abstract step of looking at data on a print out.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the recited correlation by including a step to integrate rather the claims only requires a routine step (as described below) of evaluating methylation.
Regarding Step 2B, the next question is whether the remaining elements/steps – i.e., the non-patent-ineligible elements/steps - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The broadly recited method for methylation expression analysis are routine and conventional steps of hybridization or amplification assays (see specification pages 13-14).
In Mayo v. Prometheus, the Supreme Court stated: "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
This is similar to the present situation wherein the additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide the inventive concept necessary to render the claims patent eligible. See also Genetic Technologies Ltd. v. Merial L.L.C. 818 F.3d at 1377 1379 (Fed. Cir. 2016).
For the reasons set forth above, when the claims are considered as a whole, the claims are not considered to recite something significantly more than a judicial exception and thereby are not directed to patent eligible subject matter.
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 are not towards a correlation in the abstract but a specific, concrete and transformative process (p. 11). The reply asserts that the claims require specific molecular targets and define sample handling and analysis procedures and therefore concrete laboratory steps (p. 11-12). The reply asserts that further the combination requires selection of 2 non obvious biomarkers, methylation analysis of defined region and a dual locus comparative assay (p. 12). The reply asserts that the claims ae limited to a specific context of methylation analysis of defined gene regions in using samples (p. 11-12). The reply asserts that the claims are integrated into a practical workflow such that the correlation is to diagnose or predict bladder cancer is tangible and non-trivial (p. 13).
These arguments have been fully reviewed but have not been found persuasive.
The reply appears to be asserting that there is a transformative step, however, the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than routine and conventional activity and do not add something “significantly more” so as to render the claims patent-eligible. The broadly recited method for methylation expression analysis are routine and conventional steps of hybridization or amplification assays (see specification pages 13-14). In particular the steps are drawn to obtaining a naturally occurring sample type (urine) and comparing methylation of known genes. The reply appears to assert that the claims are dawn to specific regions, however, the claim steps are not drawn to hypermethylation within SEQ ID No. 31 an SEQ ID No. 32, but rather hypermethylation of the regions that comprises SEQ ID No. 31-32. In order to provide a step that would be more than routine and conventional activity it is suggested that a step of determining of hypermethylation within SEQ ID No. 31 and 32 be considered. The reply asserts that the diagnosis is non-trivial, however, the correlation is considered a judicial exception and cannot be used as significantly more.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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