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 .
Election/Restrictions
Applicant’s election of Group I and rs3960984 in the reply filed on 4/12/2026 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)).
Claims 4-10 and 12-13 are pending. Claims 1-3 and 11 have been cancelled.
Claim 7 and 12 is withdrawn as being drawn to a nonelected invention or species.
An action on the merits for Claims 4-6, 8-10 and 13 is set forth below.
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 4-6, 8-10 and 13 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 treating a cancer patient comprising determining the expression level of a mutation PIK3CA and a wildtype PIK3CA and based upon the expression fold administering an effective dose of a PIK3 inhibitor drug. The claims therefore are drawn to in any cancer patient determining any allele that would be considered a mutant or a wildtype and administering any PIK3 inhibitor drug that is an effective dose.
Therefore the claims encompass a large genus of measurements of any mutant PIK3CA allele and expression level of any wildtype PIK3CA allele in any cancer patient that would encompass any species and functionality provided a functionality of administering an effective does of any PIK3 inhibitor drug.
The specification asserts that the term wildtype PIK3CA allele refers to the nucleic sequence of the PIK3CA gene lacking mutations (ENSG0000121879) (see page 6). However, the limiting definition in the specification is not described in such a way that it is clear the wild type being referred to in the claims. First, because of the parenthesis the definition can be interpreted as “a nucleic acid sequence of the PIK3CA lacking mutations” or ENSG00000121879. Second the recitation of ENSG000000121879 appears to be improper incorporation by reference. There is no incorporation by refence of the term in the specification and as it appears to be attempting to enter subject matter which was not previously disclosed or properly incorporated by reference. See 37 CFR 1.57(b). Thirdly, with regard to as “a nucleic acid sequence of the PIK3CA lacking mutations” as populations differ with regard to the allele that is predominant in the population, it would not be clear which alleles would be consider “mutant”. Furthermore the claims not limited to a particular species and as such the specification has not described these sequences in any species.
It is noted that the claims are drawn to an allele from a wildtype, but does not require that allele be at an identical position as the variant allele. As such the specificaoin has not described guidance for predictable functionality of measurement of levels of any allele from a wildtype and comparison to a variant allele with functionality of treatment.
The specification asserts that the term PIK3CA relates to a variant or alteration of the sequence withing the transcribed PIK3CA gene locus (p. 6). The specification asserts that there are 10 known splice variants and 344 known mutant variants and that most are SNPs (p. 6). The claims are drawn to “allele” and as such for the mutant variants that are not SNPs it is not clear if the claims are intending to measure just one allele. For example, with regard to the splice variants, would these be a measurement of one allele of the entire splice? The specification has not described such measurements and functionality of treatment. Further, even with regard to SNPs, the specification has not described the critical guidance for determining the functionality of any possible allele variant that has or has not been discovered. In particular the specification has not provided critical guidance that even for the 344 known mutant variants that functionality to treatment is found in any cancer patients from any species.
The specification provides in the examples rs3960984 in huma breast cancer patients (para 29-32) however the specification does not provide functionality to any PIK3 inhibitor drugs. The claims are drawn to “an effective dose” however, the specification does not describe this effective dose with any measurement of any PIK3 wildtype or mutant allele in any type of cancer patient.
Based upon the description in the specification the critical structural elements needed for the recited gene expression to function to identify effective dose have not been described.
The art does not provide the critical structural elements for the asserted functionality. In particular Enard et al. (Science 2002 Vol 296 p. 340) teaches that even between closely related species gene expression patterns differ (abstract). Enard et al. teaches that mRNA expression levels are different between humans, chimpanzees, orangutans and rhesus marcques (p. 340 1st column last sentence-2nd column 1st paragraph). Enard et al. teaches that there are a large number of quantitative differences in gene expression in closely related mammals (p. 342 2nd column last paragraph). Therefore the art teaches that even between very closely related mammals there is a divergence of gene expression. As such Enard et al. teaches that merely being a biomarker in one species would not be sufficient to provide support for the structure in other species.
Accordingly, the specification has not provided the critical elements needed in the structure to predictive functionally. Therefore the specification lacks written description of any subject representative of the broadly claimed genus.
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.)
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 4-6, 8-10 and 13 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 4-6, 8-10 and 13 are indefinite over the phrase “particularly a breast cancer patient” in claim 4. The phrase “particularly" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 4-6, 8-10 and 13 are indefinite over the preamble of treating a cancer patient in claim 4. In particular step c is only applied “if” certain conditions exist and therefore the claim encompasses embodiments wherein the preamble of treating is not performed.
Claims 5-7, 10 are indefinite over the phrase “particularly” and “more particularly “The phrase “particularly" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 4-6, 8-10 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of an abstract idea of “evaluating” 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 recite the judicial exception of an abstract idea. The step of “evaluating” is interpreted as a mental step.
Thus, the claims recite and are directed to the patent-ineligible concepts of an abstract idea.
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.
The additional steps are a. determining in a tumor sample expression of naturally occurring alleles.
With regard to step c, this step is considered an optional step as the claims recites “if”. As such the broadest reasonable limitation of the claims is performing step a and step b (e.g. the judicial exception).
Herein, the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). Step a is considered steps are part of the data gathering process necessary to apply the judicial exception. As noted below these steps are considered routine steps.
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 additionally recited steps of obtaining a sample, and determining expression level is routine. This fact is evidenced by the teachings in the specification. See, for example, p 6-10 where is shown that the applicant uses naturally occurring samples and detects using known and conventional assays. Further the dependent claims further limit the population and samples, but these are routine conventional samples in the prior art and routine to measure expression levels in such populations.
Greene et al. (WO 2020/076432 April 16, 2020 cited on IDS) teaches determining a tumor sample the expression of mutations of PIK3CA (p. 13).
The present claims do not require performing any steps that are not routine and conventional. For example, the claims do not require using novel oligonucleotide probes to detect the level of expression. See Ariosa Diagnostics, Inc. v. Sequenom, Inc., F. Supp. 2d, 2013 WL 5863022, at *10 (N.D. Cal. Oct. 30, 2013) noting that "had the inventors of the [patent-in-suit] created an innovative method of performing DNA detection while searching for paternally inherited cffDNA, such as a new method of amplification or fractionation, those claims would be patentable.” Note that this decision was affirmed by the Federal Circuit (No. 2014-1139, -1144. June 2015) wherein it is stated that “Where claims of a method patent are directed to an application that starts and ends with a naturally occurring phenomenon, the patent fails to disclose patent eligible subject matter if the methods themselves are conventional, routine and well understood applications in the art.”
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.
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) 4,6,8-10,13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Greene et al. (WO 2020/076432 April 16, 2020 cited on IDS).
With regard to claim 4, Greene et al. teaches determining a tumor sample the expression of mutations of PIK3CA (p. 13). Although Greene et al does not teach the evaluating step, as Greene et al. teaches activating mutations these mutations would be considered to have greater fold expression of the mutant allele versus the wildtype. Greene et al. teaches treating with PIK3 inhibitors drugs when the patient has the mutation (p 13 and 23-24).
With regard to claim 6, Greene et al. teaches measurement of a SNP (p. 13). It is noted that the “particularly” appears to be an optional limitation.
With regard to claim 8, Greene et al teaches a breast cancer patient (p. 13).
With regard to claim 9, Greene et al. teaches that the patient is HER2- (p. 13).
With regard to claim 10 and 13, Greene et al. teaches that the treatment is aplelisib which would be considered a conventional clinical management (p. 24).
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Greene et al. (WO 2020/076432 April 16, 2020 cited on IDS) as applied to claims 4, 6, 8-10 and 13 and in view of Danenberg et al (US Patent Application 2020/0248267 August 6, 2020.
Greene et al. teaches determining a tumor sample the expression of mutations of PIK3CA (p. 13). Although Greene et al does not teach the evaluating step, as Greene et al. teaches activating mutations these mutations would be considered to have greater fold expression of the mutant allele versus the wildtype. Greene et al. teaches treating with PIK3 inhibitors drugs when the patient has the mutation (p 13 and 23-24). However, Greene et al. does not teach using quantitative allele specific methods.
With regard to claim 5, Danenberg et al teaches that mutations of PIK3CA can be detected using quantitative real time PCR (para 85).
Therefore it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify the method of Greene et al. to detect using a well known assay method of Danenberg et al. The ordinary artisan would be motivated to use one of the finite number of assays to detect the known mutations with a reasonable expectation of success of measuring the variant.
Conclusion
No claims are allowed.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KATHERINE D SALMON/ Primary Examiner, Art Unit 1682
Prosecution Insights