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 .
Nucleotide and/or Amino Acid Sequence Disclosures1
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code; page 24, paragraph 0072. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 20, 28, 32, 33, 42, 43, 47, 54 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Regev (US 2021/0047694, IDS reference).
Regarding claims 1 and 54, Regev disclosed (Regev claim 8): “A method of treating colorectal cancer in a subject in need thereof, comprising: detecting expression of a gene program comprising expression of one or more genes selected from the group consisting of…SARDH… and if the subject expresses the gene program, administering a checkpoint blockade (CPB) therapy and/or an IDO1 inhibitor…”. SARDH is listed among the genes of Table 1 of the instant application.
Regarding claim 20, Regev disclosed (paragraph 0011): “In certain embodiments, a program is measured using immunohistochemistry…”. See also paragraph 0157: “In one embodiment, the signature genes, biomarkers, and/or cells may be detected or isolated by immunofluorescence, immunohistochemistry (IHC)... In one embodiment, tumor cells are stained for cell subtype specific signature genes. In one embodiment, the cells are fixed. In another embodiment, the cells are formalin fixed and paraffin embedded.”
Regarding claim 28, Regev disclosed (paragraph 0127): “The signatures of the present invention may be discovered by analysis of expression profiles of single-cells within a population of cells from isolated samples (e.g. tumor samples)…”.
Regarding claims 32, 33 and 47, Regev disclosed that values could be either increased or decreased relative to the range expressed by a given population (paragraphs 0153-0155), such as normal or healthy subjects (paragraph [0144]).
Regarding claim 42, Regev disclosed determining the amount of protein produced; see paragraph 0126.
Regarding claim 43, Regev disclosed determining the amount of mRNA produced; see paragraph 0165.
Claim(s) 1, 8, 25, 27, 28, 43, 54 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pogue-Geile (US 2019/0076391).
Pogue-Geile disclosed (claim 5):
A method for treating colon cancer in a patient with Stage II or Stage III colon cancer comprising: a) obtaining a colon cancer tumor tissue sample from a patient with Stage II or Stage III colon cancer, b) isolating RNA or producing a lysate from the colon cancer tumor tissue sample, c) contacting said RNA or said lysate with a plurality of sequence specific probes capable of determining the level of expression of a panel of 72 genes, wherein the panel of 72 genes are AKAP12, ANKRD44, BGN, BHLHE41, BMP7, C8orf84, CAB39L, CDKN2B, CKMT2, COL11A1, COMP, CPE, CSGALNACT1, CXCL10, CXCL11, CXCL13, CXCL2, CXCL9, CYP1B1, DAPK1, DCBLD2, DPEP1, EPB41L4B, ERAP2, F5, FAP, FGL2, FN1, FNDC1, GBP1, GBP4, GPX3, GRM8, GZMB, HGD, HOXA13, HSD17B2, ID4, IDO1, IL8, INHBA, MFAP5, MGP, MMP11, MMP28, NFIB, OAS2, PAPPA, PIGR, PLA2G12B, POU2AF1, PRAP1, PROM2, PSMB9, PTPRC, ROBO1, SDC2, SELL, SERPINE1, SFRP2, SGK2, SLC4A4, SPARC, SPP1, SSPN, STC1, TACSTD2, TGFBR3, TM4SF1, TYMS, VCAN, and VNN1, d) measuring the gene expression level of the panel of 72 genes and obtaining a gene expression signature for said colon cancer tumor tissue from the gene expression level of said genes in c), e) responsive to the gene expression signature, identifying said colon cancer tumor tissue as being a subtype responsive to oxaliplatin, and f) administering oxaliplatin to said patient with Stage II or Stage III colon cancer.
SPP1 is listed in at least instant Table 1.
Regarding claim 27, Pogue-Geile disclosed normalizing the expression data (paragraph 0044).
Regarding claim 28, “a colon cancer tumor tissue sample” (as recited in Pogue-Geile claim 5) is “a sample from a biopsy of colorectal tissues”.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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) 17 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Regev (US 2021/0047694, IDS reference) in view of Eremo (Scientific Reports 10:1451 (2020)).
The teachings of Regev have been discussed. Regev disclosed measuring the biomarkers by immunohistochemistry (IHC); see paragraph 0053, 0055, 0157: “For example, a tissue sample may be obtained and analyzed for specific cell markers (IHC) or specific transcripts (e.g., RNA-FISH).”
Regev did not disclose calculating an H-score, or that the value of the H-score was greater than 100.
Eremo taught how to calculate an H-score as a way to derive a numerical result from immunohistochemical analysis (page 4, “Immunohistochemical scoring”).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to use the H-score method of Eremo when assessing biomarker levels when practicing the method of Regev, since this represents a known technique for quantifying the results of IHC analysis. Regarding claim 21, there would be no way for one practicing the method (either the claimed method or the method of Regev as modified by the teachings of Eremo) to force the results of a particular patient sample to have an H-score of greater than 100, or to know what the score of a particular patient sample would be prior to actually analyzing it. However, it would have been obvious to calculate an H-score when performing IHC analysis on a cancer patient tissue sample regardless of what the ultimate score turned out to be.
Claim(s) 26, 49-51 and 155 is/are rejected under 35 U.S.C. 103 as being unpatentable over Regev (US 2021/0047694, IDS reference).
The teachings of Regev have been discussed.
Regarding claims 26 and 49-51, Regev disclosed (claim 8): “A method of treating colorectal cancer in a subject in need thereof, comprising: detecting expression of a gene program comprising expression of one or more genes selected from the group consisting of…SARDH… and if the subject expresses the gene program, administering a checkpoint blockade (CPB) therapy and/or an IDO1 inhibitor…”. SARDH is listed among the genes of Table 1 of the instant application.
Regev also disclosed (paragraph 0114):
Colorectal cancer (CRC) can be separated into two molecularly and immunologically distinct types: 15% of patients have mismatch repair deficient (MSI) tumors with high mutational burden and high immunotherapy response rate, and 85% of patients have mismatch repair proficient (MSS) tumors with low mutational burden and either weak or no response to immunotherapy. MSI tumors differ in MMR deficiency due to hypermethylation induced silencing of the MLH1 gene or germline mutations in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6 and PMS2) or deletion of the 3′ end of EPCAM. MSI tumors can be distinguished in that MSI tumors can have a CpG island methylator phenotype or a non-methylator phenotype (Lynch type).
Regev also disclosed (paragraph 0116):
Immunotherapy with checkpoint blockade (CPB) has improved survival and outcomes in melanoma and other tumor types, but still a majority of cancer patients do not respond. CRCs that are mismatch repair deficient (MSI) are responsive to CPB therapy in about 50% of the cases, while CRCs that are mismatch repair proficient (MSS) generally are non-responsive to CPB therapy. A small percentage of MSS tumors are hyper-responsive to immunotherapy (about 3%).
Given that Regev’s method of claim 8 was determining whether or not to provide a checkpoint blockade therapy, and given that Regev disclosed that CRC patients that are MMR deficient (MMR-d/MSI+) are responsive to such therapy in about 50% of cases, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application, when practicing Regev’s method of claim 8, to evaluate the MMR-d/MSI status of the patient as recited in claim 49, based on the level of expression of MLH1 as recited in claim 50, and perform the method on MMR deficient (MMR-d/MSI+) CRC as recited in claim 51.
Regarding claim 155, Regev disclosed (paragraph 0010): “…a method of detecting or monitoring colorectal cancer (CRC) comprising measuring in a sample obtained from a subject one or more gene programs selected from any of Tables 1-14.” Table 1 of Regev lists SPP1 among other genes, which is listed in at least Table 2 of the instant application. Regev also disclosed measuring SARDH (Regev claim 8), which is listed in at least Table 1 of the instant application.
Regev also disclosed (paragraph 0158): “The present invention also may comprise a kit with a detection reagent that binds to one or more biomarkers or can be used to detect one or more biomarkers.”
It would have been prima facie obvious one of ordinary skill in the art prior to the effective filing date of the application to include reagents in the kit disclosed by Regev that bind to the biomarkers Regev expressly suggested measuring, including SPP1 and SARDH. This follows naturally from the teachings of the reference.
Claim(s) 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Regev (US 2021/0047694, IDS reference) in view of Paiva (US 2020/0048709).
The teachings of Regev have been discussed. Regev did not discuss normalizing measured expression levels.
Paiva taught that normalizing “refers to a transformation of quantified gene expression levels to account for potential systematic bias and to permit accurate comparison of relevant differential expression levels” (paragraph 0057).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application when practicing the method of Regev to normalize the measured expression levels of the biomarkers in order to account for potential systematic bias and to permit accurate comparison of relevant differential expression levels.
Claim(s) 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pogue-Geile (US 2019/0076391).
Pogue-Geile disclosed (claim 5):
A method for treating colon cancer in a patient with Stage II or Stage III colon cancer comprising: a) obtaining a colon cancer tumor tissue sample from a patient with Stage II or Stage III colon cancer, b) isolating RNA or producing a lysate from the colon cancer tumor tissue sample, c) contacting said RNA or said lysate with a plurality of sequence specific probes capable of determining the level of expression of a panel of 72 genes, wherein the panel of 72 genes are AKAP12, ANKRD44, BGN, BHLHE41, BMP7, C8orf84, CAB39L, CDKN2B, CKMT2, COL11A1, COMP, CPE, CSGALNACT1, CXCL10, CXCL11, CXCL13, CXCL2, CXCL9, CYP1B1, DAPK1, DCBLD2, DPEP1, EPB41L4B, ERAP2, F5, FAP, FGL2, FN1, FNDC1, GBP1, GBP4, GPX3, GRM8, GZMB, HGD, HOXA13, HSD17B2, ID4, IDO1, IL8, INHBA, MFAP5, MGP, MMP11, MMP28, NFIB, OAS2, PAPPA, PIGR, PLA2G12B, POU2AF1, PRAP1, PROM2, PSMB9, PTPRC, ROBO1, SDC2, SELL, SERPINE1, SFRP2, SGK2, SLC4A4, SPARC, SPP1, SSPN, STC1, TACSTD2, TGFBR3, TM4SF1, TYMS, VCAN, and VNN1, d) measuring the gene expression level of the panel of 72 genes and obtaining a gene expression signature for said colon cancer tumor tissue from the gene expression level of said genes in c), e) responsive to the gene expression signature, identifying said colon cancer tumor tissue as being a subtype responsive to oxaliplatin, and f) administering oxaliplatin to said patient with Stage II or Stage III colon cancer.
SPP1 is listed in at least instant Table 1.
Pogue-Geile also disclosed (paragraph 0002, citations omitted):
“Clinical trials MOSAIC (Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin trial) and C-07 showed that oxaliplatin added to fluorouracil (FU) and leucovorin (LV) significantly improved disease free survival (DFS) and established oxaliplatin as part of the standard of care for the adjuvant treatment of early-stage colon cancer.”
Given that Pogue-Geile’s method (claim 5) was determining which colon cancer patients should receive oxaliplatin, and given that oxaliplatin had been established as part of the standard of care for adjuvant treatment of early-stage colon cancer, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to practice Pogue-Geile’s method for determining whether to give oxaliplatin in the context of adjuvant chemotherapy.
Claim(s) 155 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pogue-Geile (US 2019/0076391) in view of Polansky (US 2004/0023207).
Pogue-Geile disclosed a sequence specific probe for SPP1 (see Pogue-Geile claim 5). Pogue-Geile did not disclose a kit containing such probe.
Polansky taught (paragraph [0919]): “Well known advantages of commercial kits include convenience and reproducibility due to manufacturing standardization, quality control and validation procedures.”
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to put the probes disclosed by Pogue-Geile into a kit to obtain the advantages of kits disclosed by Polansky.
Conclusion
No claims are free of the prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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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.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681
1 Nucleotide sequences appear in Table S7, page 58 of the published International Application WO 2022/182661 serving as the as-filed specification.