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 II and the species of TM6SF1 and TMEM130 in the reply filed on 12/10/2025 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)).
Claim 5 was inadvertently added to Group II however should have been placed in Group I. It is noted that the MPEP 814 states “ While every claim should be accounted for, the omission to group a claim, or placing a claim in the wrong group will not affect the propriety of a final requirement where the requirement is otherwise proper and the correct disposition of the omitted or erroneously grouped claim is clear”. As such claim 5 will be moved to Group I as claim 5 does not require any steps that are dependent on the limitations of Group II of “methods for detecting predisposition or presence of colorectal cancer:”
Claims 1-5, 8-11, 13-17, 19-24 are pending. Claims 6-7, 12, 18, 25-26 have been cancelled.
Claims 1-3, 5, 8-11, 13-17, 19-24 are withdrawn as being drawn to nonelected claims.
An action on the merits for claim 4 is set forth below.
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.
Claim 4 is 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.
Claim 4 is indefinite over “in a sample according to the method of claim 1”. This phrase is unclear as it appears that “a sample” encompasses a larger number of potential samples than the “a sample containing colorectal tumor or colorectal cancer nucleic acid” in claim 1 and as such it appears that Claim 4 is drawn to measurement in any sample “according to the method of claim 1”. This phrase is further unclear as it is not clear if the claim is intending to performed the assay of claim 1 or if the claim intends some other relationship with claim 1 (e.g. according to”). It is noted that therefore Claim 4 is unclear with regard to steps encompassed. The claims should be complete in themselves, however, it is not clear the limitations required by claim 4.
The term “alternations in expression” in claim 4 is a relative term which renders the claim indefinite. The term “alternations in expression” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In particular as there is no comparison step it is not clear which expression would be considered “alternative”.
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.
Claim 4 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim is drawn to detecting alterations in expression status in TM6SF1 and TMEM130 in a sample being indicative of predisposition to or presence or colorectal cancer. The claim therefore encompasses any difference of expression in these genes in any sample from any species.
Therefore the claim encompass an extremely huge genus of any expression level in any sample from any subject; however, the instant specification does not provide guidance as to the critical structures needed to determine which of these species would functionally provide predisposition to or presence of colorectal cancer.
The specification provides an example of methylation expression of a pattern of genes that is particularly associated in human patients, however, this specific example does not provide description for the genus of any expression included mRNA expression. Further the specification does not provide the alterations of expression that would functionally determine predisposition to or presence of colorectal cancer using the two genes claims.
The examples provided in the specification are not sufficient to provide description for the critical structure needed to determine functionality as the specification does not provide associations in any expression of any sample in any species and the functionality. Based upon the description in the specification the critical structural elements needed for the recited gene expression to function to identify a subject for acne 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.
The art of Cobb et al (Crit Care Med 2002 Vol. 30 p. 2711) teaches the unpredictability in analysis of gene expression in spleen and liver sample from septic mice. Notably, the reference teaches that, when compared to a non-septic sample, the relevant expression profiles of the septic mouse spleen and the septic mouse liver contain different nucleic acids at different levels (Table 1; p.2714, middle col., lns.2-8). As such the art teaches that expression levels of the same nucleic acids in different tissue samples differ. Therefore the art indicates that an association of expression level to a disease in one sample would not be functionally correlative to an association to any other sample type.
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 Improper Markush - 35 USC § 112
Claim 4 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 706.03(y).
The Markush groupings of genes listed in the tables are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
It is first noted that MPEP 706.03(y) states that “A Markush claim may be rejected under judicially approved “improper Markush grouping” principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an “improper Markush grouping” if either: (1) the members of the Markush group do not share a “single structural similarity” or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)). “ Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class (prong 1) and the members of a Markush group share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent (prong 2).
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved” (see MPEP 706.03(y)IIA).
Herein, the recited alternative species do not share a single structural similarity, as each gene in the listing has a different chemical structure in that it consists of a different nucleotide sequence. The only structural similarity present is that all of the chromosomal regions comprise unmethylated and methylated regions. The fact that the genes comprise nucleotide sites per se does not support a conclusion that they have a common single structural similarity because the structure of comprising nucleotides alone is not essential to the asserted common activity of the genes being correlated colorectal.
Further, the recited genes do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that genes behave in the same manner and can be substituted for one another with the same intended result achieved. There is no evidence of record to establish that it is clear from their very nature that the recited sequences possess the common property of being associated with treatment. There is no evidence of record to establish that it is clear from their very nature that the recited control markers possess the common property of being having a relationship of determination of origin.
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.
Claim 4 is rejected under 35 U.S.C. 101 because the claimed invention is directed to correlation of colorectal cancer and expression of TM6SF1 and TMEM130 without significantly more. The claim(s) recite(s) a judicial exception of a natural correlation based upon this recitation. This judicial exception is not integrated into a practical application because the steps recited are considered a routine and general recitation of determination of expression levels. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims apply know expression analysis to detect a natural correlation.
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, natural phenomena.
The claims are directed to correlation of expression levels to colorectal cancer without significantly more. This is a natural correlation. The steps do not further integrate the judicial exception and the steps as discussed below are routine methods of expression analysis.
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 of the claims are routine and conventional.
Step 2B. Does the claim recite additional elements that are significantly more than the judicial exceptions? No
Spinella et al. (US Patent Application Publication 20150197813 July 16, 2015) teaches detecting of alterations in expression TM6SF1 and TMEM130 as compared to a reference (para 34, table 15). Further the art teaches using well known conventional assays for detection (p. 15). Therefore the claims are rejected under 35 USC 101.
Claim Rejections - 35 USC § 102/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 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.
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 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Spinella et al. (US Patent Application Publication 20150197813 July 16, 2015).
With regard to claim 4, the term “a sample” is not limited to any particular sample. Spinella et al teaches detecting of alterations in expression TM6SF1 and TMEM130 as compared to a reference (para 34, table 15). The wherein clause is the intended result of the detection and as such Spinella et al. teaches the detection expression step required.
With regard to claim 4, Spinella et al teaches detecting of alterations in expression TM6SF1 and TMEM130 as compared to a reference (para 34, table 15). The wherein clause is the intended result of the detection and as such Spinella et al. teaches the detection expression step required. However, Spinella et al. does not teaches that the sample contains colorectal tumor or colorectal cancer nucleic acid. Spinella et al. suggests that samples that are being treated with treatments associated with colorectal cancer can be sampled (para 7). As such it would be prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to modify Spinella et al. to use the suggested samples from patients with colorectal cancer. It would be obvious to one of ordinary skill in the art to screen known samples that have expressions changes in a patient population with the intended results of detecting expression.
Conclusion
No claim is 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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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