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 .
The claims filed 3/17/2026 are under consideration.
The amendments and arguments presented in the papers filed 3/17/2026 ("Remarks”) have been thoroughly considered. The issues raised in the Office action dated 12/18/2025 listed below have been reconsidered as indicated.
a) The objections of claims 8 and 21 are withdrawn in view of the amendments to the claims.
b) The rejections of claims 1, 5, 7, 8, 9, 10, 18 and 21 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn in view of the amendments to the claims.
c) The rejections of: claim(s) 1, 5, 7, 18 and 21 under 35 U.S.C. 102(a)(1) as being anticipated by Smith (Lancet Oncol. 2011. 12(2):137-143 and Supplementary webappendix) as evidence by Genome Browser from UCSC (retrieved on 12/5/2025 from the internet: https://genome.ucsc.edu/cgi-bin/hgGateway); and claim(s) 1, 5, 7-10, 18 and 21 under 35 U.S.C. 102(a)(1) as being anticipated by Kato (Experimental and Therapeutic Medicine. 2011. 2:47-56) as evidenced by Genome Browser from UCSC (retrieved on 12/5/2025 from the internet: https://genome.ucsc.edu/cgi-bin/hgGateway), are withdrawn because the references do not teach determining an outcome based on the recited genes.
c) The provisional rejections of: claim 1, 5, 7, 8, 9, 10, 18 and 21 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/271,793 (reference application); claims 1, 5, 7, 8, 9, 10, 18 and 21 on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 18/023,598 (reference application); and claims 1, 5, 7, 8, 9, 10, 18 and 21 on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of copending Application No. 18/022,565 (reference application), are withdrawn because the copending applications do not focus on bladder cancer or kidney cancer.
The Examiner’s responses to the Remarks regarding issues not listed above are detailed below in this Office action.
New and modified grounds of rejection necessitated by amendment are detailed below and this action is made FINAL.
Election/Restrictions
Applicant elected with traverse Group I, claims 1-10 and 18, in the reply filed on 10/22/2025.
Claims 11, 12, 13, 14, 15, 16, 17, 19 and 20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 10/22/2025.
Applicant elected the species of IFI16 (immune defense response gene), PRKACA (T-Cell receptor signaling gene) and RAP1GAP2 (PDE4D7 correlated gene) in the reply filed on 10/22/2025. 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)).
Claims 2, 3, 4 and 6 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 10/22/2025.
The withdrawn claims require a combination of more than 3 genes, which is more specific than the combination of exactly 3 genes applicant elected.
It is noted that claim 6 may have been intended to depend from claims 5, rather than claim 4.
Priority
The present application is a 371 national stage entry application of PCT/EP2021/075086 (filed 9/13/2021) and claim foreign priority to EPO 20199659.2 (filed 10/1/2020).
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892 or on a submitted IDS, they have not been considered.
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, 7, 8, 9, 10, 18 and 21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exceptions without significantly more.
The following rejections have been modified in view of the amendments to the claims.
The claim(s) recite(s):
“determining a prediction of an outcome of the bladder cancer or kidney cancer subject based on the gene expression profiles of the three or more genes” (claim 1).
The step of “determining a prediction” broadly encompasses an abstract idea. The limited amount of data encompassed by the claim, e.g., the expression level of 3 genes, to be considered in making a determination may be fully considered by the human mind alone or with the aid of pen and paper. See MPEP 2106.04(a)(2).III.
The judicial exceptions are not integrated into a practical application because the claims do not involve:
improvements to the functioning of a computer or to any other technology or technical field;
applying or using the judicial exceptions to effect a particular treatment or prophylaxis for a disease or medical condition;
applying the judicial exception with, or by use of, a particular machine; or
effecting a transformation or reduction of a particular article to a different state or thing.
The claimed limitations add insignificant extra-solution activity to the judicial exceptions. Any additional elements relate to data gathering. See MPEP 2106.05(g).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional step of “determining” expression profiles of the claimed samples broadly encompasses the use of conventional assays well-known in the field, such as PCR (p. 55 of instant specification). These methods are also routine and conventional as recognized by the courts. MPEP 2105.05(d)(I).
Claim 5 further describes the elements considered in the step of “determining a prediction”. The claim further encompasses an abstract idea.
Claim 7 further describes the elements considered in the step of “determining a prediction”. The claim further encompasses an abstract idea.
Claims 8, 9 and 10 further describes the elements considered in the step of “determining a prediction”. The claim further encompasses an abstract idea.
Claim 18 further sets forth an abstract idea which is the organizing of human activity involving conveying information from one individual to another individual.
Response to the traversal of the 101 rejection
The Remarks summarize the rejection and the analysis under section 101 (p. 11-12).
The examiner’s position is detailed in the above rejections that is consistent with the guidance in the MPEP.
The Remarks argue the claims are directed to a specific improvement in determining a prediction of an outcome of a bladder cancer or kidney cancer subject based on the gene expression profiles of three or more genes via the claimed methods (p. 12).
The arguments have been considered but are not persuasive as no evidence of an improvement is provided by the Remarks.
The Remarks argue the claimed process cannot be performed in the human mind alone because as amended it require determining the gene expression profiles of three or more genes (p. 13).
The arguments have been fully considered but are not persuasive. The claim as a whole is not an abstract idea. The step of “determining a prediction” is an abstract idea and the step of “determining…gene expression profiles of three or more genes” is data gathering that encompasses the use of well-known and convention techniques as noted above in the rejection. The arguments do not address the routine and conventional nature of the additional data gathering step of “determining…gene expression profiles of three or more genes”.
The Remarks argue the claims are not directed to a judicial exception, and assert that the claims do indeed incorporate any judicial exception because the claims comprise an improvement to the analysis and treatment of bladder cancer or kidney cancer, including determining a prediction of an outcome of a bladder cancer or kidney cancer subject based on gene expression profiles of three or more genes. The Remarks argue this is an important improvement, a life-saving improvement, that provides a practical application of the alleged abstract idea. See p. 13-14.
The arguments have been fully considered but are not persuasive. The arguments provide no evidence of any improvement. The mere assertation of an improvement in the analysis and treatment of bladder or kidney cancer is not persuasive.
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 1, 5, 7, 8, 9, 10, 18 and 21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
The following rejections have been modified in view of the amendments to the claims.
The specification, while being enabling for using the method of claim 1 to predict an outcome of a bladder cancer subject or a kidney cancer subject using mRNA gene expression profiles, does not reasonably provide enablement for methods of claim 1 to predict any outcome in any context using any gene expression profiles. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The claims broadly encompass embodiments in which gene expression profiles from the bladder cancer or kidney cancer at the protein levels are used to make determinations regarding an outcome of bladder cancer or kidney cancer. It is known that levels of protein in a cell is not necessarily reflective of the mRNA levels of a cell. See Maier (FEBS Letter. 2009. 583:3966-3973; previously cited); Kendrick (A gene’s mRNA level does not usually predict its protein level. 9/25/2014; previously cited); Chan (G&P magazine. 2006. 6(3):20-26; previously cited); Chen (Molecular & Cellular Proteomics 1.4. 2002. 1:304-313; previously cited); Pascal (BMC Genomics. 2008. 9:246; previously cited) and Greenbaum (Genome Biology. 2003. 4:117; previously cited). It is unpredictable that the results of the specification regarding mRNA expression can be extrapolated to making a diagnosis or prognosis based on protein levels observed. It would require undue experimentation, with no reasonable expectation of success, to establish that the nucleic acid expression level observed in particular types of cancers, i.e., prostate, kidney and bladder, can be applied to all other types of tissues and at the protein levels.
Quantity of Experimentation:
In order for one of ordinary skill in the art to practice the claimed method as broadly claimed, undue experimentation would be required. A number of parameters would have to be studied to establish that the protein expression of the recited genes can be used to predict a bladder cancer or kidney cancer subject’s outcome..
Conclusions:
Thus, given the breadth of claims in an art whose nature is identified as unpredictable and the large quantity of research required to define these unpredictable variables is balanced only against the high skill level in the art, it is the position of the examiner that it would require undue experimentation for one of skill in the art to perform the method of the claim as broadly written.
Response to the traversal of the enablement rejections
The Remarks argue Applicant has amended claim 1 to recite "wherein the gene expression profiles of the three or more genes are determined via a biological sample obtained from the bladder cancer or kidney cancer of a bladder cancer or kidney cancer subject; and determining a prediction of [[the]]an outcome of the bladder cancer or kidney cancer subject based on the gene expression profiles of the three or more genes." and as acknowledged by the Patent Office, the specification is "enabling for using the method of claim 1 to predict an outcome of a bladder cancer subject or a kidney cancer subject using mRNA gene expression profiles from bladder cancer samples or kidney cancer samples." See p. 10-11.
The arguments have been fully considered and are not persuasive. The arguments are not commensurate in scope with the claimed subject matter as the claims are not limited to analyzing mRNA gene expression profiles.
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, 7, 8, 9 and 10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Davicioni (US 2016/0258026 A1).
The following are new rejections over an unelected species.
Regarding claim 1, Davicioni teaches determining the RNA expression levels of at least three genes, including LRRFIP1, MYD88, EZR and SLC39A11 (para. 364-372; and Table 16) in samples from patients that underwent radical cystectomy for muscle invasive bladder cancer (para. 312).
Davicioni teaches using the expression profiles to predict the recurrence of muscle invasive bladder cancer (para. 364-366).
Regarding claims 5 and 7, Davicioni further teaches the determining is based on the lymph node status of the patient’s cancer (para. 365-366). See also para. 196, 199.
Regarding claims 8, 9 and 10, Davicioni teaches an outcome regarding a surgery treatment (para. 364-372).
Conclusion
No claims 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 JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays Off.
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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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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682
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