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 .
This action is in response to applicants correspondence mailed 12/1/2025. The amendment to the claims mailed 12/1/2025 has been entered.
Election/Restrictions
Applicant’s election without traverse of group II, claims 11-15 and 17-20 and species CMS1 and ITGAE in the reply filed on 12/1/2025 is acknowledged.
Claims 1-10, 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/1/2025. As indicated in the response on page 10, group I should be claims 1-10 and 16.
Claims 11-15 and 17-20 are under examination. Claim 13 is under examination with respect to ITGAE. Claim 14 and 18 are under examination with regard to CMS1.
Drawings
The drawings are acceptable.
Claim Objections
Claims 11, 14-15 and 17-20 are objected to because of the following informalities: each of the claims recite PSI. PSI should be written in its full term followed by abbreviation in parenthesis upon first mention in the claims. For example, claim 11 and claim 17 should recite percent spliced in (PSI). 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 11-15 and 17-20 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.
Claim 11 and 17 recites the limitation "the disease outcome" in step c of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 15 and 18 recites “the disease” . It is unclear if the disease outcome is the outcome of a subject suffering from colorectal cancer or a subject having cancer, as recited in step a. Step a does not require or relate back to the preamble of the colorectal cancer and encompasses any type of cancer. The preamble recites predicting outcome for a subject suffering from colorectal cancer whereas step c recites the disease outcome. It is unclear what disease is “the disease”, is the disease colorectal cancer or cancer. For these reasons the claims are indefinite.
Claims 12-15 and 18-20 depend from claim 11 and claim 17 are indefinite for the reasons applied to claim 11 and claim 17.
Improper Markush Rejection
Claim 13 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 § 2117.
The Markush grouping of ITGAE, CCNDBP1, CPT1B, CDC16, PTPN6, ACCS, EXOSC9, ZNF611, MRRF, NUP153, WARS, D2HGDH, LUC7L, EPB41, DGUOK, MDM4, PTP4A2, MKNK2, CCDC112, FRYL, CEP78, FNBP1, ECT2, ANKRD26, ZMIZ2, C6orf48, USPL1, RBM39, MIS12, AFMID, MACROD1, FN1, WBP1, XPO1, PTPN18, ARHGAP27, C16orfl3, FCGRT, DOCK6, EXOC7, BPTF, PXN, EXOC1, PLOD2, CD47, ARHGEF 11, PBRM1, MAGI1, MBNL1, TNC, ENAH, BAZ2B, RAI14, FNIP1, MAP3K7, ERBIN, SULF2, SORBS1, SRSF6, WASH3P, OPAl, GOLGB1, APLP2, CPNE1, WIPF1, ATG9A, NUBP2, ANO1, AURKA, EPB41L3, KALRN, ADAM15, KRAS, SLC39A14, MYO9A, TPM1, MYO6, KIAA1217, GIT2, MYL6, MYH1l, NUMB, TEAD1, SPAG9, FAT1, TNS1, ESYT2, SLMAP, AKAP9, RUBCN, ATP2B4, LRRFIP2, TBC1D23, EHBP1, SLK, WDFY3, SMARCC2, KIF13A, MPRIP, LRRFIP1, NIN, RPS24, ACTN1, CTNND1, CD44, APBB2, SEC31A, SYTL2, MYOF, NAV2, GAB1, PLEKHM2, CLSTN1, GOLGA4, PBX1 and FKBP14 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use.
The Markush groupings of the claimed genes is improper because the because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use.
The members of the improper Markush grouping do not share a substantial feature and/or common use that flows from the substantial structural feature because each member of the claimed genes are structurally unique relative to one another. There is no disclosed common substantial structural feature and the genes do not share a single structural similarity, as each gene represents a different gene that has no substantial common nucleotide sequence. The only structurally similarity present is that each gene comprises nucleic acid molecules. The fact that the genes comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated to classifying a sample. Accordingly while the different genes are asserted to have the property of one exon skipping event that is indicative of colorectal cancer it is not clear from their very nature or from the prior art that all of them possess this property. The nature of different genes is that they are differently expressed with different alternative splicing events in different disorders. Following this analysis, the claims are rejected as containing an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 11-15 and 17-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and law of nature without significantly more.
Claims 11 and 17 recite determining PSI values and converting PSI values to determine disease outcome indication. This step encompasses a data analysis process which can be practiced in the mind. The claims additionally set forth identifying disease outcome
Claims 11, 14, 17 and 18 recite a law of nature/natural phenomenon and an abstract idea. Claim 11 and 17 recites an abstract idea that is a mental process and includes mathematical concepts. The recitation of converting PSI values to determine disease outcome indication is a mental process. The recitation of determining PSI values is a mathematical concept that can encompass a mathematical calculation. Neither the claims nor the specification set forth limiting definitions for determining and the claims do not set forth how determining PSI is accomplished. The broadest reasonably interpretation of determining is a step that can be accomplished mentally by evaluating data and critical thinking process wherein one mentally reads information in a database or report regarding PSI levels. Additionally PSI values can include a step that encompasses mathematical calculations using splicing events and this encompasses an abstract idea.
Claim 11, 14, 17 and 18 recites a law of nature/natural phenomenon. Claim 11 and 17 recite PSI values to determine the disease outcome. PSI values as based on the occurrence of at least one alternative splicing event. Claims 14 and 18 add an additional judicial exception, an abstract idea, as the claim recites the conversion of PSI values to determine disease outcome indication classifies the tumors as CMS1, CMS2, CMS3 or CMS4. These recited relationships are a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of a natural process.
This judicial exception is not integrated into a practical application because the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps in addition to the judicial exception are data gathering steps recited at a high level of generality employing techniques that were well-established, routine and conventional at the time of the invention. For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
While claim 11 and claim 17 recite determining PSI values, the claims generically recites PSI values with no additional elements for determining PSI. Additionally PSI values were well known routine and conventional in the art taught by Xiong (EBioMedicine, 2018, 26:183-195).
Claims 12-13 recite the alternative splicing event is skipping exons and the gene is ITGAE. These claims only limit the judicial exceptions. However, it was routine in the art to determine PSI and identifying exon skipping in ITGAE, as taught by Xiong (EBioMedicine, 2018, 26:183-195) (see supplemental table 2).
Claims 15-16 further limit the PSI conversion to decide treatment or surveillance, which is an additional judicial exception since deciding treatment or surveillance is a mental process. There is no step of administering a treatment. It is noted that treating a subject with active surveillance would encompass a mental process.
Claim 19-20 limit the subject, thus is a field of use limitation which does not amount to significantly more.
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.
Claims 11-14 and 17-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Xiong (EBioMedicine, 2018, 26:183-195).
Xiong teaches alternative splicing in colorectal cancer. Xiong teaches obtaining CRC tissue from a human subject and determining PSI values (see materials and methods, 2.2) (claim 19-20). Xiong teaches CRC patients were divided into groups based on PSI values to determine hazard ratios, overall survival and disease free survival (see fig 1). Xiong teaches the alternative splicing events are disclosed in supplementary table S2. Table S2 discloses exon skipping for ITGAE (claim 12-13). Xiong discloses the prognostic value of differential expression alternative splicing events in CRC (see 3.5). Xiong teaches clustering of different CMS, TNM stage, and survival status in CRC samples between clusters from PSI values aligned (see figure 8 and 3.6) (conversion of PSI values classifies CMS1) (claim 14 and 18). Xiong teaches determining PSI values and conversion of PSI values to determine disease outcome.
With regard to claims 17, 18 and 20, the preamble of claim 17 recites a method for treating a subject suffering from colorectal cancer using PSI values however the only active process steps of the claims are collecting a sample, determining PSI values and conversion of PSI values to determine disease outcome. The recitation in the preamble of “treating a subject” in the context of the present claim does not result in a manipulative difference, none of the process steps require treating a subject. Accordingly the process steps are able to stand alone and the preamble limitation in not accorded patentable weight. Xiong teach of the active steps of claim 17.
Claims 11-12, 15, 17, 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Epstein (WO2021101452A2)
Epstein teaches a method of identifying splicing alternations in colorectal cancer. Epstein teaches determining PSI values for each sample. Epstein teaches PSI values can be used for treatment of CRC patient (see fig 21 and pg. 16) (claim 17). Epstein teaches alternative splicing by increased exon skipping compared to normal samples (see fig 22 and pg17). Epstein teaches the method characterizing a medical condition and characterizing a cancer. Epstein teaches the subject or patient includes humans (see pg. 73)
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699