DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of claims / Response to Amendment
This office action is in response to an amendment filed February 17, 2026.
Claims 1-20 were previously pending. Applicant amended claims 1-2, 13-20; cancelled claim 12.
Claims 1-11 and 13-20 are currently pending, with claims 5-11 and 14-20 withdrawn.
Claims 1-4 and 13 are under consideration.
Applicant's submission of the specification amendment obviated the previously presented objection.
Terminal Disclaimer: Applicant filed a terminal disclaimer on 02/17/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 9631239, and the expiration date any patent granted on pending reference Application 18/905,647, has been reviewed and approved by the office. Therefore the following double patenting rejections have been overcome:
Rejection of Claims 1-4 and 13 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 8 of U.S. Patent No. 9631239B2 ('239 Patent);
Provisional rejection of Claims 1-4, 12 and 13 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 10, 13 and 17 of copending Application No. 18/905,647 ('647 Application).
Applicant's claim amendments overcame the following rejections:
Rejections of Claims 1-4 and 12-13 under 35 U.S.C. 112 (pre-AIA ), second paragraph;
Rejection of Claim 12 under 35 U.S.C. 112 (pre-AIA ), first paragraph;
Rejections of Claims 1-4 and 12-13 under 35 U.S.C. 101;
Rejections of Claims 1-4 and 13 under 35 U.S.C. 102(a)(1) as being anticipated by Hu , as evidenced by Agilent 1AV2 Microarray and Trevino;
Rejection of Claim 12 under 35 U.S.C. 103 as being unpatentable over Hu, in view of Fuchs.
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection necessitated by amendment.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 contains more than one periods in lines 14 and 18. See MPEP 608.01(m): "Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. "
Priority -- Updated
The priority date of the instant claims 1-4 and 13 is May 30, 2008, filling date of the US provisional application NO. 61/057,508.
New Grounds of Rejections - 35 USC § 112, 2nd Paragraph
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 1-4 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.
Regarding claim 1, it has been amended to recite "said plurality of genes expression profile comprises expression levels corresponding to a plurality of genes consisting of comprise…" which is indefinite.
Specifically, the recitation "a plurality of genes consisting of comprise" makes it unclear whether the claimed "plurality of genes" excludes additional genes other than the specifically listed genes in the claim. The back-to-back use of closed language ("consisting of") followed by open language ("comprising") creates ambiguity regarding the metes and bounds of the claimed "plurality of genes." It is unclear whether the claim requires at least 40 of the listed 50 genes in the claim, while allowing additional genes beyond the listed genes; or whether the claim is limited to a range of 40 to 50 genes, with 50 being the maximum.
Accordingly, the scope of the claim cannot be determined with reasonable certainty.
Claims 2-4 and 13 are rejected for depending from claim 1 and not remedying the indefiniteness.
Claim 13 recites "plurality of genes comprise at least 41 genes," which raises further indefiniteness issue regarding the scope of "plurality of genes" in view of claim 1.
For the purpose of compact prosecution and applying prior art under 35 USC§ 102 and 103, "plurality of genes" is interpreted as consisting of a range of 40-50 genes, selected from a gene list of 50 specific genes in the claim (i.e. any genes not listed in the claim are excluded).
New Grounds of 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 1-4 and 13 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Independent claim 1 has been amended to recite:
A method, comprising
(a) providing a biological sample of a human subject, and
(b) assaying said biological sample for expression products of a plurality of genes of said biological sample to generate an expression profile,
wherein said plurality of genes expression profile comprises expression levels corresponding to a plurality of genes consisting of comprise
(i) at least 40 genes to 50 genes selected from ACTR3B,ANLN,BAG1,BCL2,BIRC5,BLVRA,CCNB1,CCNE1,CDC20,CDC6,CDCA1, CDH3,CENPF,CEP55,CXXC5,EGFR,ERBB2,ESR1,EXO1,FGFR4,FOXA1,FOXC1, GPR160, GRB7,HSPC150(UBE2T), KIF2C,KNTC2,KRT14, KRT17,KRT5,MAPT,MDM2, MELK,MIA,MKI67,MLPH,MMP11,MYBL2,MYC,NAT1,ORC6L,PGR,PHGDH,PTTG1, RRM2, SFRP1, SLC39A6, TMEM45B, TYMS, and UBE2C and
(ii) one or more housekeeping genes, and
wherein said assaying comprises use of probes having sequences complementary to said expression products of said plurality of genes.
(c) comparing said gene expression profile to one or more references, wherein said one or more references correspond to a plurality of breast cancer subtypes; and
(d) assigning said biological sample to a breast cancer subtype of said plurality of breast cancer subtype based at least in part on the comparing of (c).
Therefore, the claims are directed to steps to assay for expression values of genes from a subject, and identify corresponding disease phenotypes based on the gene expression values.
Following the analysis below the claims are not patent eligible under 35 U.S.C. 101.
Step 1 - Whether the Claim is to a Statutory Category : YES. The claims are drawn to a method, therefore to one of the of statutory categories.
Step 2A Prong 1 - Whether the Claim Recite an Abstract idea, Law of Nature, or Natural Phenomenon: Yes. The claim recites a natural correlative relationship between the gene expression levels in the subject when compared to expression profiles for a specific condition, and the subject having the condition.
As stated in MPEP 2106.04(b)(I), laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
The differential gene expression levels/profile, and the presence of cancer in a subject is classified as naturally occurring principles/relations because the correlation between a disease biomarker and the disease is a natural correlation.
In conclusion, the claims recite laws of nature and natural phenomena.
Step 2A Prong 2 - Whether the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application: No. The claim as a whole do not integrates the exception into a practical application of that exception.
For a claim reciting a judicial exception to be eligible, the additional elements (if any) in the claim must “transform the nature of the claim” into a patent-eligible application of the judicial exception, Alice Corp., 573 U.S. at 217, 110 USPQ2d at 1981.
The additional elements in the claim do not transform the claimed natural correlation to something that are markedly different than their naturally occurring counterparts in their natural state, nor does it integrate the recited judicial exception into a practical application of the exception.
Here, considering the claim as a whole, the claim describes a generic way to observe the judicial exception.
While the claim includes a step of "assaying" to determine expression level of naturally occurring genes using probes, this merely applies the judicial exception using conventional techniques (e.g. probe hybridization) without any additional elements that impose a meaningful limit on the judicial exception. See MPEP §2106.04(d). The steps are recited at a high level of generality and reflect extra-solution activities for data gathering.
The further recited “comparing” and “assigning steps”, which are also recited at high level of generality, merely observe the judicial exception of a natural correlation between gene expression and a disease condition. Accordingly, these steps do not integrate the judicial exception into a practical application.
Therefore, the steps recited in the claim merely applies the judicial exception in the field of molecular diagnostics for purpose of identifying a disease subtype, therefore these language merely indicate a field of use or technological environment in which to apply a judicial exception. See MPEP 2106.05(h) and 2106.04(d).
Integration into a practical application is assessed by looking at whether the claim applies, relies on, or uses the judicial exception in a manner that imposes meaningful limits beyond generally linking use to a technological environment. See MPEP 2106.04(d)(2)
In the present claim, the recited steps are directed to broad data-gathering steps and mental analysis steps, which themselves fall within judicial exceptions. The claim does not recite any meaningful additional step based on the information gathered or the breast cancer subtype assignment, such as specific treatment step or other active step that applies the judicial exception in a way that is not routine and conventional.
Accordingly, the claim as a whole does not integrate the judicial exception into a practical application.
Step 2B - Whether a Claim Amounts to Significantly More: No.
According to MPEP§ 2106.05, The second part of the Alice/Mayo test is often referred to as a search for an inventive concept. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217, 110 USPQ2d 1976, 1981 (2014) (citing Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 71-72, 101 USPQ2d 1961, 1966 (2012)). An “inventive concept” is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Alice Corp., 573 U.S. at 27-18, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 72-73, 101 USPQ2d at 1966).
In this instant case, the claims, when considered as a whole, do not recite any inventive concept with additional elements that amount to significantly more than the judicial exception.
Methods for detecting gene expression using probes are well known and conventional in the field of biology, as indicated by Applicant’s own disclosure in para.[0039], citing both PCR based methods and array-based methods ꟷ both utilize probes in analyzing gene expression ꟷ are known in the art. The claims do not appear to add markedly different characteristics that significantly modify or use the naturally occurring correlation in a manner that is not naturally occurring.
The comparing and assigning steps do not provide an inventive concept (significantly more than the judicial exception) because they are classified as an abstract mental process, which is also a judicial exception. Moreover, the steps of “assigning” and “comparing,” recited at a high level of generality, are merely observing the law of nature. Thus, these steps are insignificant extra-solution activities and do not qualify as “significantly more.” (see MPEP § 2106.05(g))
The dependent claims do not recite additional elements that amount to significantly more than the judicial exception, as they represent mere general linkage of the judicial exception to the additional elements in the claims (MPEP § 2106.05(h)).
In conclusion, the claims are not patent eligible under 35 U.S.C. 101.
Conclusion
No claims are 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 TIAN NMN YU whose telephone number is (703)756-4694. The examiner can normally be reached Monday - Friday 8:30 am - 5:30 pm.
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, Gary Benzion can be reached at (571) 272-0782. 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.
/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681