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 for the specific combination of the pathway of “a combination of retrograde neurotrophins signaling, loss of NLP from mitotic centrosomes, RNA polymerase III transcription initiation from Type 2 promoter, EIF2 pathway, and valine, leucine and isoleucine biosynthesis” and the combination of genes of “AP2S1, CDC, GTFC3, EIFA2AK3, and LARS” in the reply filed on 10/30/2025 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)).
Claims 1-5, 7-9, 11, 13-15, 17-19, 21-25 are pending. Claims 6,10,12, 16, 20 have been cancelled.
An action on the merits is set forth below.
Claim Objections
Claim14 is objected to because of the following informalities: The phrase “thereby treating” is duplicated. Appropriate correction is required.
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 1-5, 7-9, 11, 13-15, 17-19, 21-25 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 1, 4-5, 7-9, 11, 13, 15, 17, 19, 21-23 are indefinite over step ii of claim 1. In particular the claims are drawn to measuring expression and administering based upon increased or decreased relative to a control. However, it is not clear if the expression of the molecules in step I is combined or if the molecules are measured in individual pathways without a combination step. Therefore it would not be clear if some of the pathways are increased and some decreased which treatment to be administered.
Claims 2, 14 and 18 are indefinite over the steps of claim 2. In particular the claims are drawn to measuring expression and administering based upon increased or decreased relative to a control. However, it is not clear if the expression of the molecules is combined or if the molecules are measured in individual pathways without a combination step. Therefore it would not be clear if some of the pathways are increased and some decreased which treatment to be administered.
Claims 3, 24-25 are indefinite over the steps of claim 2. In particular the claims are drawn to measuring expression and administering based upon increased or decreased relative to a control. However, it is not clear if the expression of the molecules is combined or if the molecules are measured in individual pathways without a combination step. Therefore it would not be clear if some of the pathways are increased and some decreased which treatment to be administered.
Claims 17-18 and 25 are indefinite over the “p values of at least 0.01 or at least 0.02)”. This phrase is unclear as first the claim indication that treatment only occurs with these values, however, Claim 1 (or Claim 3) requires treatment based on increased or decreased. Therefore this limitation is unclear as to how to limit the treatment. Furthermore it is not clear what the value is referring to in the analysis. Is it expression of a pathway, combination of pathways or some other analysis.
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, 7-9, 11, 13-15, 17-19, 21-25 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.
Claims 1-5, 7-9, 11, 13-15, 17-19, 21-25 are drawn based upon the species election to a method of treating a subject with ER positive breast cancer , comprising:(i) measuring expression of molecules from a combination of retrograde neurotrophins signaling, loss of NLP from mitotic centrosomes, RNA polymerase III transcription initiation from Type 2 promoter, EIF2 pathway, and valine, leucine and isoleucine biosynthesis and administering tamoxifen when the expression is decreased and administering a non-tamoxifen therapy wherein expression is increased.
Further, the claims are drawn to particular molecules of AP2S1, CDC, GTFC3, EIFA2AK3, and LARS,
Therefore the claims are drawn to a genus of the measurement of expression of any of the genes within the recited pathways. Further the claims are limited to a particular combination of genes within the recited pathways.
The specification has not provided any guidance that the same functionality is determined in any of these encompassed breast cancer related molecules and treatment in sample type. Furhtermore, as noted below, such functionality is effected by sample type.
The specification provides listings of genes from the various pathways (p. 4-7, 9-14, 38-45). However the specification does not provide critical guidance as to which are estrogen positive related molecules similar to any control is functionally associated with treatment. These pathways have not been described in the specification as to which genes would be encompassed by these pathways and has not described the pathway in such a way that the skilled artisan would be able to determine which genes are encompassed by the pathways.
The table starting on page 6 lists some of the gernes associated with these pathways, however, this list does not provide the structural necessary to determine which other genes would be encompassed.
As such these expression correlations are dependent on the populations studied and the controls used, however, the specification has not provided guidance as to the critical structures required for any of the pathways, in any samples.
The specification provides candidate molecular pathways for a treatment response in figures 5-6. The figures do not provide any of the genes that would be considered to functionally provide tamoxifen response or non-response.
Further with regard to the specific combination of genes, the specification has not provided that expression to a control would functionally provide in any of the encompassed samples.
As shown below, the art teaches that this is a very large genus wherein merely being expressed in one sample is not sufficient to describe the critical features in any other sample.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. However, as discussed above, the specification provides on particular species and does not provide critical structures for the breadth of the claims.
Further, the art, as recited below, teaches that expression of biomarkers differ in different species. However, the specification has not provided identifying characteristics or functional attributes that would distinguish different members of the claimed genus. Rather, the art teaches that changes in the structure of nucleic acids between species can have an effect on expression. 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).
In the instant case the specification does not provide the skilled artisan with an adequate written description of particular nucleic acids suitable for performing the claimed method as generically encompassed in the claims.
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 biomarkers across species and samples and functionally determining breast cancer associated disease state 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.
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 2,3,18 and 25 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 correlation of expression with resistance to tamoxifen. 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.
These judicial exceptions are not integrated into a practical application because the claims only recite the natural correlation and routine and convention steps, wherein the routine and convention steps 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 prior (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
The correlation of methaytlion CpG data and diagnosis is considered a natural correlation. The step of providing determining the expression of the recited pathways in the sample are considered a routine and conventional step as detailed below.
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. In particular the steps only require expression analysis using a routine and conventional assay type of naturally occurring genes. M. et al. (US Patent Application Publication 2013/0012409 Jan 10, 2013) M. et al. teaches a method of measuring expression of ER breast cancer related molecules (para 14- and Table VI and Figures 15-18). M. et al. teaches measuring Affymetrix U133A, U33B and U133 for these samples.
These methods are considered generic recitations of general methods of methylation determination that do not overcome the rejection.
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) 1-3,7-8,13-14,19,21,24 is/are rejected under 35 U.S.C. 103 as being unpatentable over M. et al. (US Patent Application Publication 2013/0012409 Jan 10, 2013).
With regard to claims 1-2, 14, M. et al. teaches a method of measuring expression of ER breast cancer related molecules (para 14- and Table VI and Figures 15-18). M. et al. teaches measuring Affymetrix U133A, U33B and U133 for these samples. Although M. et al.does not explicitly teaches the recited pathways, as it is not clear which genes are encompassed by the pathway recitations and M. et al. teaches screening these genes for ER breast cancer analysis, this step is broadly encompassed by M. et al.. M. et al. teaches increased expression is associated with providing tamoxifen treatment (para 126-149). Therefore although M. et al does not explicitly state the measurement of the pathways, M. et al suggests such an analysis by measuring genes associated with ER breast cancer on the Affymetrix microarrays in view of the indefiniteness of these terms.
With regard to claims 3, 24 M. et al. teaches a method of measuring expression of ER breast cancer related molecules (para 14- and Table VI and Figures 15-18). M. et al. teaches measuring Affymetrix U133A, U33B and U133 for these samples. Although M. et al.does not explicitly teaches the recited pathways, as it is not clear which genes are encompassed by the pathway recitations and M. et al. teaches screening these genes for ER breast cancer analysis, this step is broadly encompassed by M. et al.. M. et al. teaches increased expression is associated with providing tamoxifen treatment and that the sample is not resistant to tamoxifen (para 126-149). Therefore although M. et al does not explicitly state the measurement of the pathways, M. et al suggests such an analysis by measuring genes associated with ER breast cancer on the Affymetrix microarrays in view of the indefiniteness of these terms.
With regard to claims 7-8, M et al. teaches that the samples can be Luminal A or luminal B (para 143).
With regard to claim 13, M. et al. teaches measuring mRNA expression (para 149).
With regard to claims 19, M. et al. teaches a method of measuring expression of ER breast cancer related molecules (para 14- and Table VI and Figures 15-18).
With regard to claim 21, M. et al. teaches subject that have ER breast cancer surgically removed but did not receive tamoxifen yet (para 126).
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.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682