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 .
Priority
This application is a CON of Application No. 14907372 (01/25/2016) which is a 371 of PCT US2014/048887 (07/30/2014) which claims priority from US Application No. 61/859,959 (07/30/2013) as reflected in the filing receipt mailed on 12/15/2021. As detailed on the 12/15/2021 filing receipt, the application claims priority as early as 07/30/2013. The claims to the benefit of priority are acknowledged. Claims 4 and 16 recite chemotherapy comprising 5- fluorouracil (5-FU) therapy, not found in provisional application 61/859,959. Claims 7 and 17 recite normalized by quantile normalization, not found in provisional application 61/859,959. Claims 4, 7, and 16-17 are interpreted as being according the priority date of the 371 of PCT application US2014/048887 (07/30/2014). The effective filing date of claims 1-3, 5-6, 8-15, and 18-20 is 07/30/2013.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on Dec. 13, 2021 was considered by the examiner.
Claim Rejections - 35 USC § 112(b)
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 1-20 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.
Claims 1, 5-6, and 11-14 refer to information listed in a “TABLE”. This table is disclosed on pages 11-18 of the instant specification. Independent claims 1 and 11 do not recite the relevant content within the tables in its entirety, thus it is unclear which genes the claims are intended to include. MPEP § 2173.05(s) explains that, where possible, claims are to be complete in themselves. Incorporation by reference to a specific table is “permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience. Ex parte Fressola... (citations omitted)" (MPEP § 2173.05(s)). It is not clear that the instant claim recitation(s) constitute "exceptional circumstances." As one option to overcome this rejection, the referenced genes may be individually recited in the claims, for example as a text list. Alternatively, an entire table may be copied into the claim. Any effective citation to the specification, e.g. recitation of "TABLE" must be deleted. Regarding the recitation “TABLE”, dependent claims 2-10, and 12-20are consequently rejected as they depend from a rejected base claim and do not clarify the issues.
Claims 11, and 18-19 as currently written lack antecedent basis. Claim 18 recites “the CRC score” and claim 19 recites “the EMT score”. There is no previous recitation of a CRC score in claim 18 nor in claim 11, from which claim 18 depends. There is no previous recitation of a EMT score in claim 19 nor in claim 11, from which claim 19 depends. As one option to overcome this rejection, dependent claims 18-19 could be amended to depend from claim 12.
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 1-20 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of “calculating a score that predicts risk of colorectal cancer recurrence”.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to methods (claims 1-20), which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in instant claims 1-2, 7-9, 11-12, and 17-19 include the terms “calculate” (claims 1-2); “calculating” (claims 1, 8-9, 12, 18-19); “quantile normalization” (claim 7 and 17); and “algorithm to convert the normalized expression values” (claims 11-12). The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one having ordinary skill in the art. Thus, the recited terms “calculate”; “calculating”; “quantile normalization”; and “algorithm to convert the normalized expression values” correspond to verbal equivalents of mathematical concepts (MPEP 2106.04(a)(2)). A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula". In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). Dependent claims 5-6 and 13-14 further limit the mathematical concepts recited in claims 1 and 11 since the dependent claims define the mathematical relationship between the expression levels and the calculated scores.
Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas. In the interest of compact prosecution, it is valid to point out that there is a law of nature recited in the claims (i.e. the correlation between the expression levels of genes in the patient and the risk of colorectal cancer recurrence). Dependent claims 3 and 15 recite further details about “to determine adjuvant chemotherapy is needed to prevent colorectal cancer recurrence”; not reciting any additional non-abstract elements; being all directed to further aspects of the information being analyzed, the manner in which that analysis is performed. The instant claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Instant claims 1-2 and 11 recite additional elements that are not abstract ideas: “computer programmed to execute” (claims 2 and 11) and “displaying or outputting to a user” (claim 2). The recited limitations in these claims are interpreted to require the use of a computer. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions. The claims relate to computers or further aspects of the information being analyzed by computers, and do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. Claim 2 recites “displaying or outputting to a user”, which reads on receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321. Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)). Claims 1 and 11 recite “assaying cells … for the expression level of genes”, which reads on detecting DNA in a patient sample, being an insignificant extra-solution activity since this limitation merely serve to gather data that is utilized as input for the judicial exception. See MPEP 2106.05(g) and MPEP 2106.04(d). Claims 10 and 20 recite additional elements about assaying cells, specifying the classification of colorectal cancer, which constitutes merely field of use limitations that inform about the population of patients that the claimed method is being practiced upon. These limitations are merely an intended use of the claimed invention or a field of use limitation, which cannot integrate a judicial exception as mere data gathering activity, and merely define the type of cancer being detected rather than limiting the physical assay step itself. See MPEP 2106.05(g). Claims 3-4 and 15-16 are directed to “treating the human patient … if a high risk of colorectal cancer recurrence is determined”. As it appears in the claims, the particular treatments recited are contingent limitations (MPEP 2111.04.II) because the treatment takes place ‘if a high risk colorectal cancer recurrence is determined”. Thus, the claims do not require that the patient is actually determined to have a high risk of colorectal cancer recurrence. Therefore, that condition is not required to be met causing the treatment steps to be contingent. Since these are method claims, the broadest reasonable interpretation does not require that the treatment steps to be performed and since the treatment isn’t included in the broadest reasonable interpretation, the claims do not affirmatively recite an action that require the treatment to occur. Without that affirmative recitation, the particular treatment consideration does not apply (see MPEP 2106.04(d)(2)). Because the instant claims recite an abstract idea and do not integrate that abstract idea into a practical application, the claims are directed to the abstract idea of “calculating a score that predicts risk of colorectal cancer recurrence” and law of nature (i.e. the correlation between the expression levels of genes in the patient and the risk of colorectal cancer recurrence). [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of the 35 USC § 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Instant claim 2 is directed to a computer or computer functions and are interpreted as instructions to apply the abstract idea using a computer, which can be performed without the use of a computer; where the computer does not impose meaningful limitations on the judicial exceptions (MPEP 2106.04(d) § I and MPEP 2106.05(f)). Claims directed to “displaying or outputting to a user” read on electronically outputting data on a computer, which is a conventional computer function (Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 225, 110 USPQ2d 1984 (2014) MPEP 2106.05(d)). Claims directed to “assaying cells … for the expression level of genes” read conventional practices of detecting DNA or enzymes in a sample (Fittipaldi et. al. “Progress in understanding preferential detection of live cells using viability dyes in combination with DNA amplification” Journal of Microbiological Methods 91:276–289 (2012)). Additionally, the instant specification discloses “A number of suitable high throughput formats exist for evaluating expression patterns and profiles of the disclosed genes” which confirms the recited “assaying cells … for the expression level of genes” as a conventional practice (pg.8 lines 17-19 Specification). As discussed above regarding the treatment limitations, these limitations are contingent limitations that are not required to be performed and not part of the broadest reasonable interpretation of the claims. The conventionality is only evaluated for those additional elements that are part of the broadest reasonable interpretation of the claim. Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For these reasons, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Regarding instant claims 1-20, the claimed invention does not constitute significantly more than the abstract idea, so instant claims 1-20 are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 102(a)
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 1-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Loboda A. et. al. (Loboda A. et. al. “EMT is the dominant program in human colon cancer” BMC Medical Genomics 4:1-10 (2011) – provided in IDS dated 12/13/2021 and referred to in the action as Loboda).
Independent claim 1 recites “a method for predicting the recurrence of colorectal cancer in a human patient, comprising:(a) assaying colorectal cells obtained from the human patient for the expression level of ten (10) or more genes listed in TABLE 2A, or their corresponding expression products, and ten (10) or more genes listed in TABLE 2B, or their corresponding expression products, and using normalized values of the expression levels to calculate a colorectal cancer (CRC) score; (b) assaying colorectal cells obtained from the human patient for the expression levels of ten (10) or more genes listed in TABLE 1A, or their corresponding expression products, and ten (10) or more genes listed TABLE 1B, or their corresponding expression products, and using normalized values of the expression levels to calculate an Epithelial to Mesenchymal Transition (EMT) score; and (c) calculating the difference between the CRC score and the EMT score to arrive at a Recurrence Signature Score that predicts risk of colorectal cancer recurrence”. Independent claim 11 recites method for analyzing a colorectal cancer tissue sample to determine adjuvant chemotherapy is needed to prevent colorectal cancer recurrence in a human patient, the method comprising:(a) assaying colorectal cells obtained from the human patient for normalized expression values of ten (10) or more genes listed in TABLE 1A, ten (10) or more genes listed in TABLE 1B, ten (10) or more genes listed in TABLE 2A, and ten (10) or more genes listed in TABLE 2B; and (b) inputting the normalized expression values into a computer programmed to execute an algorithm to convert the normalized expression values to a Recurrence Signature Score indicative of a likelihood of the risk of colorectal cancer recurrence, wherein the algorithm gives reduced weight to the normalized expression values for genes that are listed in more than one of TABLE 1A, TABLE 1B, TABLE 1C, and TABLE 1D. It is interpreted that the terms PC1 score and CRC score are claimed to be used interchangeably (pg. 7 line 15 instant specification); as well as the terms Recurrence Signature Score and "∆PC1.EMT score" (pg. 3 lines 1-2 instant specification), where high score predicted poorer overall survival due to higher cancer recurrence (pg. 4 lines 27-29 Specification).
Dependent claim 2 limits claim 1, further comprising displaying or outputting to a user, user interface device, computer readable storage medium, or local or remote computer system the calculated risk of colorectal cancer recurrence. Dependent claim 3 and 15 recite further comprising treating the human patient with post-operative adjuvant chemotherapy if a high risk of colorectal cancer recurrence is determined. Dependent claims 5 and 13 recite wherein increased expression of the genes listed in TABLE 2A, or their corresponding expression products, increases the CRC score; and wherein increased expression of the genes listed in TABLE 2B, or their corresponding products, decreases the CRC score. Dependent claims 6 and 14 recite wherein increased expression of the genes listed in TABLE 1A, or their corresponding expression products, increases the EMT score; and wherein increased expression of the genes listed in TABLE 1B, or their corresponding products, decreases the EMT score. Dependent claims 7 and 17 recite wherein the expression levels are normalized by quantile normalization. Dependent claims 8 and 18 recite wherein the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the CRC score. Dependent claims 9 and 19 recite wherein the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the EMT score. Dependent claims 10 and 20 recite wherein the colorectal cancer comprises Dukes B (stage II) or Dukes C (stage III) colorectal cancer. Dependent claim 12 recite wherein the algorithm converts the normalized expression values for the genes listed in TABLE 2A and TABLE 2B to a colorectal cancer (CRC) score, wherein the algorithm converts the normalized expression values for the genes listed in TABLE 1A and TABLE 1B to an Epithelial to Mesenchymal Transition (EMT) score, wherein the Recurrence Signature Score is determined by calculating the difference between the CRC score and the EMT score.
Loboda teaches a method for prediction of recurrence for both stages II and III of colon cancer useful for discerning responsiveness to adjuvant chemotherapy (pg. 7) via the microarray analysis (i.e., reading on “assaying” and “analyzing” steps) to identify the first principal component (PC1) score (pg.2) of the top 5000 most variable genes on colon cell lines using standard functional analyses algorithms (pg.3); including at least ten genes from TABLE 1A (TGFbeta genes (i.e., TGFB2), CTGF, FGFR1, FLRT2, SRPX, TCF4, VIM, MRAS, SPARC, and CDH2); at least ten genes from TABLE 1B (MAL2, LCN2, S100P, KRT19, CD24, TMPRSS4, PRSS8, RBM35B, CLDN7, and CDH1); at least ten genes from TABLE 2A (GLIS2, RECK, MGP, ARMCX1, ZFPM2, DZIP1, MSN, ECM2, HTRA1, and SNAI1); and at least ten genes from TABLE 2B (SHH, CDX1, KIAA0152, BCAR3 and proliferation genes (including but not limited to: NOX1, CYP2J2, EPHB2, PKP2, MYB, and EPS8L3) (pg. 5, Fig. 2 and additional file 12 in SI). Additionally, Loboda teaches that PC1 and EMT scores were computed (i.e., outputted to the user via the use of a hard drive) from the microarray analysis using quantile normalization with subsequent application of log10 to obtained probe intensities for the microarray data (i.e., each assayed gene given equal normalized weight via quantile normalization followed by reduction via the log10 application) (pg. 3) to obtain averaged probe intensities of the entire gene expression data set of 326 CRC samples (pg. 3); and a high PC1/EMT score would predict recurrence of disease (pg. 5); where PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence (i.e., CRC score) (pg.2). It is interpreted that an algorithm that employs quantile normalization with subsequent application of log10 to the assayed data uses equal statistical distribution of each sample (i.e., equal weight given to each data point) while applying logarithmic scales to reduce wide-ranging quantities to smaller scopes. Therefore, the algorithm would be using reduced weight to the normalized values.
Regarding the limitations “wherein increased expression of the genes listed in TABLE 2A, or their corresponding expression products, increases the CRC score; and wherein increased expression of the genes listed in TABLE 2B, or their corresponding products, decreases the CRC score” and “wherein increased expression of the genes listed in TABLE 1A, or their corresponding expression products, increases the EMT score; and wherein increased expression of the genes listed in TABLE 1B, or their corresponding products, decreases the EMT score”. This instant application describes the genes listed in Tables 1A and 2A as up-regulated genes (pgs. 11 and 15 specification); and the genes listed in Tables 1B and 2B as down regulated genes (pgs. 13 and 17 specification). Therefore, the limitation recited is interpreted as requiring down regulated genes to be anti-correlated with the CRC and EMT scores (i.e., increased expression of down regulated genes decreases CRC and EMT scores; while decreased expression of down regulated genes increases CRC and EMT scores) and up regulated genes being positively correlated with CRC and EMT scores (i.e., increased expression of up regulated genes increases CRC and EMT scores; while decreased expression of up regulated genes decreases CRC and EMT scores). Loboda teaches that down-regulated genes are anti-correlated with the PC1/EMT (pg.8) and up regulated genes are positively correlated with PC1/EMT (pg. 4).
Regarding the limitation “(c) calculating the difference between the CRC score and the EMT score to arrive at a Recurrence Signature Score that predicts risk of colorectal cancer recurrence”, Loboda teaches a ratio between PC1 (i.e., CRC) and EMT score (i.e., PC1/EMT) to arrive at a score that predicts the recurrence of colorectal cancer (i.e., disease recurrence score) (pg. 5 and Fig. 4A). The ratio PC1/EMT taught by Loboda anticipates the Recurrence Score claimed in this instant invention. A ratio (i.e., PC1/EMT) is interpreted as a parameter that shows variation between two quantities. The same description can be applied to the description of Recurrence Score described in this instant specification involving delta ("∆PC1.EMT score" (pg. 3 lines 1-2 instant specification)). A high "∆PC1.EMT score" predicts the recurrence of colorectal cancer (pg. 4 lines 27-29 Specification) – same as the relationship between a high PC1/EMT score and the recurrence score taught by Loboda (pg. 5 and Fig. 4A).
Regarding the limitation directed to “treating the human patient … if a high risk of colorectal cancer recurrence is determined” (claims 3-4 and 15-16), the particular treatment recited is contingent because the treatment takes place ‘if a high risk colorectal cancer recurrence is determined” (MPEP 2111.04.II). Thus, the broadest reasonable interpretation does not require that the treatment steps to be performed and; since the treatment isn’t included in the broadest reasonable interpretation, the claims do not affirmatively recite an action that require the treatment to occur (MPEP 2106.04(d)(2)). In summary, all described teachings by Loboda anticipates claims 1-20.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-20 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-29 of US Patent No. 11,035,006 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by the claims of the reference patent, as set forth in the following table.
Instant application
US Patent No. 11,035,006 B2
Claim
Limitation
Claim
Limitation
1
a) assaying colorectal cells obtained from the human patient for the expression level of ten (10) or more genes listed in TABLE 2A, or their corresponding expression products, and ten (10) or more genes listed in TABLE 2B, or their corresponding expression products, and using normalized values of the expression levels to calculate a colorectal cancer (CRC) score;
1
a) assaying colorectal cells from the human patient for the expression level of ten (10) or more genes associated with SEQ ID NOS: 7, 13, 18, 19, 30, 38, 43, 45, 52, 59, 67, 69, 76, 94, 95, 97, 98, 100, 101, 103, 104, 106, 122, 123, 127, 134, 135, 139, 142, 148, and 311-404, or their corresponding expression products, and ten (10) or more genes associated with SEQ ID NOS: 160, 173, 177, 190, 192, 213, 223, 230, 241, 248, 276, 280, 289, 295, 310, and 405-508, or their corresponding expression products, and using normalized values of the expression levels to calculate a colorectal cancer (CRC) score;
1
b) assaying colorectal cells obtained from the human patient for the expression levels of ten (10) or more genes listed in TABLE 1A, or their corresponding expression products, and ten (10) or more genes listed TABLE 1B, or their corresponding expression products, and using normalized values of the expression levels to calculate an Epithelial to Mesenchymal Transition (EMT) score;
1
b) assaying colorectal cells from the human patient for the expression levels of ten (10) or more genes associated with SEQ ID NOS: 1-149, or their corresponding expression products, and ten (10) or more genes associated with SEQ ID NOS: 150-310, or their corresponding expression products, and using normalized values of the expression levels to calculate an Epithelial to Mesenchymal Transition (EMT) score;
1
c) calculating the difference between the CRC score and the EMT score to arrive at a Recurrence Signature Score that predicts risk of colorectal cancer recurrence.
1
c) calculating the difference between the CRC score and the EMT score to arrive at a Recurrence Signature Score that determines that the patient with Dukes B colorectal cancer has a high risk of recurrence of colorectal cancer and would benefit from adjuvant chemotherapy;
2
displaying or outputting to a user, user interface device, computer readable storage medium, or local or remote computer system the calculated risk of colorectal cancer recurrence.
2
displaying or outputting to a user, user interface device, computer readable storage medium, or local or remote computer system the calculated risk of colorectal cancer recurrence.
5 and 13
increased expression of the genes listed in TABLE 2A, or their corresponding expression products, increases the CRC score; and wherein increased expression of the genes listed in TABLE 2B, or their corresponding products, decreases the CRC score.
4 and 10
increased expression of the genes associated with SEQ ID NOS: 7, 13, 18, 19, 30, 38, 43, 45, 52, 59, 67, 69, 76, 94, 95, 97, 98, 100, 101, 103, 104, 106, 122, 123, 127, 134, 135, 139, 142, 148, and 311-404, or their corresponding expression products, increases the CRC score; and wherein increased expression of the genes associated with SEQ ID NOS: 160, 173, 177, 190, 192, 213, 223, 230, 241, 248, 276, 280, 289, 295, 310, and 405-508, or their corresponding products, decreases the CRC score.
6 and 14
increased expression of the genes listed in TABLE 1A, or their corresponding expression products, increases the EMT score; and wherein increased expression of the genes listed in TABLE 1B, or their corresponding products, decreases the EMT score.
5 and 11
wherein increased expression of the genes associated with SEQ ID NOS: 1-149, or their corresponding expression products, increases the EMT score; and wherein increased expression of SEQ ID NOS: 150-310, or their corresponding products, decreases the EMT score.
7 and 17
expression levels are normalized by quantile normalization.
6 and 13
the expression levels are normalized by quantile normalization.
8 and 18
normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the CRC score.
7 and 14
the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the CRC score.
9 and 19
the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the EMT score.
8 and 15
the normalized expression values of the expression levels for each assayed gene are given equal weight in calculating the EMT score.
10 and 20
the colorectal cancer comprises Dukes B (stage II) or Dukes C (stage III) colorectal cancer.
1 and 9
16 and 24
human patient with Dukes B colorectal cancer
human patient with Dukes C colorectal cancer
11
a) assaying colorectal cells obtained from the human patient for normalized expression values of ten (10) or more genes listed in TABLE 1A, ten (10) or more genes listed in TABLE 1B, ten (10) or more genes listed in TABLE 2A, and ten (10) or more genes listed in TABLE 2B;
24
a) assaying colorectal cells from the human patient for normalized expression values of ten (10) or more genes associated with SEQ ID NOS: 1-149, ten (10) or more genes associated with SEQ ID NOS: 150-310, ten (10) or more genes associated with SEQ ID NOS: 7, 13, 18, 19, 30 38, 43, 45, 52, 59, 67 69, 76, 94, 95, 97, 98, 100, 101, 103, 104, 106, 122, 123, 127, 134, 135, 139, 142, 148, and 311-404, and ten (10) or more genes associated with SEQ ID NOS: 160, 173, 177, 190, 192, 213, 223, 230, 241, 248, 276, 280, 289, 295, 310, and 405-508.
11
b) inputting the normalized expression values into a computer programmed to execute an algorithm to convert the normalized expression values to a Recurrence Signature Score indicative of a likelihood of the risk of colorectal cancer recurrence, wherein the algorithm gives reduced weight to the normalized expression values for genes that are listed in more than one of TABLE 1A, TABLE 1B, TABLE 1C, and TABLE 1D.
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b) inputting the normalized expression values into a computer programmed to execute an algorithm to convert the normalized expression values to a Recurrence Signature Score indicative that the subject would not benefit from adjuvant chemotherapy, wherein the algorithm gives reduced weight to the normalized expression values for genes that are listed more than once in step a);
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the algorithm converts the normalized expression values for the genes listed in TABLE 2A and TABLE 2B to a colorectal cancer (CRC) score, wherein the algorithm converts the normalized expression values for the genes listed in TABLE A and TABLE 1B to an Epithelial to Mesenchymal Transition (EMT) score, wherein the Recurrence Signature Score is determined by calculating the difference between the CRC score and the EMT score.
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b) … the algorithm converts the normalized expression values for the genes associated with SEQ ID NOS: 7, 13, 18, 19, 30, 38, 43, 45, 52, 59, 67,69, 76,94,95,97,98, 100,101,103,104,106,122, 123,127,134,135,139,142,148, and 311-404 and the genes associated with SEQ ID NOS: 160, 173, 177, 190, 192, 213, 223, 230, 241, 248, 276, 280, 289, 295, 310, and 405-508 to a colorectal cancer (CRC) score, wherein the algorithm converts the normalized express10n values for the genes associated with SEQ ID NOS: 1-310 to an Epithelial to Mesenchymal Transition (EMT) score, wherein the Recurrence Signature Score is determined by calculating the difference between the CRC score and the EMT score;
Regarding claims directed to “treating the human patient … if a high risk of colorectal cancer recurrence is determined” (claims 3-4 and 15-16), the particular treatment recited is contingent because the treatment takes place ‘if a high risk colorectal cancer recurrence is determined” (MPEP 2111.04.II). Thus, the broadest reasonable interpretation does not require that the treatment steps to be performed and; since the treatment isn’t included in the broadest reasonable interpretation, the claims do not affirmatively recite an action that require the treatment to occur (MPEP 2106.04(d)(2)).
Conclusion
No claims allowed.
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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685