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 .
Claim Status
Claims 2, 5-6, 9-12, 15-16, 18-32, 35-36, 40, and 43-51 are cancelled.
Claims 1, 3-4, 7-8, 13-14, 17, 33-34, 37-39, 41-42, and 52-56 are currently pending and under exam herein.
Priority
Applicant’s claim for the benefit of prior-filed application 371 National Phase of International Application No. PCT/US22/11264, filed on January 5, 2022, which claims priority to U.S. Provisional Application No. 63/227,930, filed on July 30, 2021, is acknowledged. At this point in examination, the effective filing date of claims 1, 3-4, 7-8, 13-14, 17, 33-34, 37-39, 41-42, and 52-56 is July 30, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on January 26, 2024 and August 2, 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings are objected to because the quality of the drawings is poor and Figure 1 is illegible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 14 is objected to because of the following informalities: The word ‘the’ is missing between ‘wherein subject’ in line 1 and the word features in line 2 should be ‘feature.’ 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 1, 3-4, 7-8, 13-14, 17, 33-34, 37-39, 41-42, and 52-56 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 (and its’ dependent claims 3-4, 7-8, 13-14, and 17):
The claim 1 limitation of “(a statin)” in line 6 renders the claim indefinite because it is unclear whether limitation is limiting the HMGCR inhibitor to be a statin or if a statin is an example of such an inhibitor. Therefore, the metes and bounds of the claim cannot be established and it is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. Claims 3-4, 7-8, 13-14, and 17 are also rejected because they depend from claim 1 and do not resolve the issue of indefiniteness present in claim 1. For the purpose of examination, it will be interpreted as the HMGCR inhibitor is a statin.
Regarding claims 3 and 7:
Referring to Table 5 in claim 3 renders the claim indefinite because the claim is incomplete so as to not set forth the boundaries of the invention. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or 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, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (See MPEP 2173.05s). Other claims (e.g., claim 7 which depends on claim 3) list all the genes of Table 5 in their recited limitations, so this is not an exceptional circumstance.
Therefore, claim 3 is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112,
second paragraph. Dependent claim 7 is also rejected because although it recites all the genes in Table 5, it only resolves the issue of indefiniteness present in claim 3 for the change of expression of any gene in Table 5 and not for a mutation in any gene in Table 5. For the purpose of examination, the listed Table 5 genes will be used.
Regarding claim 33 (and its’ dependent claims 34, 37-39, and 41-42):
Claim 33 recites the limitation “when the gene expression profile indicates that expression levels of at least one gene is altered in a predictive manner as compared to the gene expression profile of the reference training set” in lines 28-30 which renders the claim indefinite because it’s not possible to discern the metes and bounds of the phrase ‘predictive manner.’ Although the specification provides a definition in paragraph 0064, it merely restates that changes in expression predict metastatic risk. The claim does not recite which changes (i.e., upregulated or downregulated) for each gene in the genetic expression profile would predict metastatic risk for all the possible combinations of genes recited in claim 33.
Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112,
second paragraph. Claims 34, 37-39, and 41-42 are also rejected because they depend from claim 33 and do not resolve the issue of indefiniteness present in claim 33. For the purpose of examination, any change that predicts metastatic risk taught in the prior art of the genes listed will be used.
Regarding claim 52 (and its’ dependent claims 53-56):
The claim is rendered indefinite for the same reason as claim 1 above where claim 52 recites the limitation ‘(a statin)’ in line 4.
Therefore, the claim is indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112,
second paragraph. Claims 53-56 are also rejected because they depend from claim 52 and do not resolve the issue of indefiniteness present in claim 52. For the purpose of examination, it will be interpreted as the HMGCR inhibitor is a statin.
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.
Claims 1, 3-4, 7-8, 13-14, 17, 33-34, 37-39, 41-42, and 52, and 55-56 are 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 1 (and its’ dependent claims 3-4, 7-8, 13-14, and 17):
The instant specification provides sufficient support for the possession of reducing the risk of future melanoma metastasis and/or progression in a subject with high-risk primary melanoma by administering a composition comprising a statin (paragraph 0271, 0275). However, the instant specification is insufficient to establish possession of the full scope of a genus of 3-Hydroxy-3-Methylglutaryl-CoA Reductase inhibitors to reduce the risk of future melanoma metastasis recited in claim 1. For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus (Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997)). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
MPEP § 2163 instructs that the "written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice reduction to drawings or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus..." See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG V. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
In consideration of whether the disclosed statins could be representative of the entire scope of the claimed genus, the following art applies:
Lin et al. (Drug Design, Development and Therapy, June 2015, p. 3313) teach identifying various candidate molecules as potential HMGCR inhibitors (p. 3315, Selection of candidate compounds after ADMET predictions, paragraph 1; Figure 3) and validated predictions with experimental assays to identify docosanol, curcumin, and salvianolic acid C as effective inhibitors of HMGCR (p. 3317, Inhibitory effects of the selected compounds on hHMGR activities and their potential cellular toxicities, paragraph 2). These teachings demonstrate HMGCR inhibitors contain molecules other than statins. Even though they share the same inhibitory property it does not necessarily follow that those non-statin molecules will also be effective at reducing the risk of future melanoma metastasis, therefore, a person having ordinary skill in the art would not recognize that applicant reasonably had possession of the full scope of HMGCR inhibitors reducing the risk of future melanoma metastasis. Claims 3-4, 7-8, 13-14, and 17 are also rejected for lack of written description because they depend from claim 1.
Regarding claims 3 and 7:
The instant application provides support for identifying high-risk melanoma with genes listed in Table 5 when the change in expression of the genes is in the direction listed in the table, however, the scope of claim 3 and claim 7 encompasses identifying high-risk melanoma by any change in expression of the recited genes. Additionally, the specification does not provide any support in identifying high-risk melanoma by detecting mutations in genes and the scope of claim 3 encompasses being able differentiate high-risk melanoma from low-risk melanoma by any mutation in the genes listed in Table 5. The instant specification does not provide any data or examples demonstrating such diagnostic ability.
Regarding claims 4, 8, and 13:
As explained in the previous paragraph above, the scope of claims 8 and 13 encompass identifying high-risk melanoma by a change in expression of the listed genes in either direction (e.g., whether ANGPT2 is upregulated or downregulated, it still predicts high-risk melanoma). However, Table 5 of the instant specification shows that ANGPT2 needs to be increased in high-risk melanoma. Additionally, the scope of claim 4 is broader and doesn’t require a change in methylation, but only measuring the methylation level of any one of the listed genes to identify high-risk melanoma. However, the specification of the instant application doesn’t provide support for detecting high-risk melanoma by measuring methylation levels of the listed genes. Rather, methylation levels are used as a proxy to indirectly measure changes in gene expression (paragraphs 0047, 0113-0114).
Regarding claim 33 (and its’ dependent claims 34, 37-39, and 41-42):
As explained for claim 1 above, the scope of claim 33 encompasses treatment of melanoma with any molecule that is a HMGCR enzyme inhibitor, but the specification only provides support for treating patients with statins. Additionally, as explained above for claims 3-4, 7-8, and 13, the scope of claim 33 encompasses predicting high-risk melanoma by any change in expression of the recited genes which is not supported by the specification. Claim 34 and 42 partially resolves the issue of the written description requirement by narrowing the HMGCR inhibitor to be a statin, but does not resolve the issue of diagnosing high-risk melanoma by any change in differential gene expression. Claims 34, 37-39, and 41-42 are also rejected because they depend on claim 33.
Regarding claim 52 (and its’ dependent claims 55-56):
As outlined above, the scope of claim 52 encompasses treating a melanoma patient with any HMGCR enzyme inhibitor which is not supported by the specification. Claims 55-56 are also rejected because they depend from claim 52.
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 33-34, 37-39, and 41-42 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Step 1:
The first part of the eligibility analysis evaluates whether a claim falls withing any statutory
category (See MPEP 2106.03). The claims recite steps taken to identify a subject afflicted with melanoma for treatment with a HMGCR inhibitor by obtaining a sample, measuring gene expression, and analyzing the data collected to form a conclusion. The claims are directed to a method and fall within one of the statutory categories of invention (Step 1: YES).
Step 2A, prong 1:
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES)
are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of
nature, or natural phenomenon (Step 2A, prong 1). In the instant application, the claims recite the
following limitations that equate to an abstract idea:
Claim 33 recites a method of selecting a subject afflicted with melanoma for treatment with a molecule inhibiting activity of HMGCR enzyme, producing a gene expression profile comprising the gene expression levels of the at least two genes; comparing the gene expression profile to a gene expression profile of a reference training set gene expression profile, which training set gene expression profile comprises the same at least two genes; and generating an indication that the primary cutaneous melanoma tumor is low-risk or high- risk of metastasis when the gene expression profile indicates that expression levels of at least one gene is altered in a predictive manner as compared to the gene expression profile of the reference training set.
Claim 34 recites wherein the subject afflicted with primary melanoma is selected for treatment with a statin in order to reduce likelihood of a future metastasis of the melanoma.
Claim 39 recites wherein the gene expression profile: consists essentially of the genes BAP1, MGP, SPP1, CXCL14, CLCA2, S100A8, BTG1, SAP130, ARG1, KRT6B, GJA1, ID2, EIF1B, S100A9, CRABP2, KRT14, ROBO1, RBM23, TACSTD2, DSC1, SPRR1 B, TRIM29, AQP3, TYRP1, PPL, LTA4H, and CST6; consists essentially of the genes CXCL8, ITGB3, LAMB1, PLAT, and TP53; consists essentially of the genes ANGPT1, ANGPT2, BMP2, FGF2, S1PR1, TGFB1, VEGFA, VEGFC, VEGFD, and IFNG; or consists essentially of the genes GDF15, MLANA, PLAT, CXCL8 /IL8, ITGB3, LOXL4, PRKCB, SERPINE2, ADAM12, LGALSI, and TGFBRI.
Claim 42 recites wherein the HMGCR enzyme inhibitor is fluvastatin, pitavastatin, atorvastatin, simvastatin, lovastatin, rosuvastatin, or pravastatin.
The preamble of claim 33 directs the entire claim to a mental process of evaluating subjects. The limitations in claim 33 of producing a gene expression profile, comparing the gene expression profile, and generating an indication recites mental processes of choosing what genes to include in a profile to analyze against a reference set and form a conclusion about the risk of the primary melanoma. These steps can be accomplished by a human mind by observation, evaluation, and judgment. Additionally, comparing the gene expression profile and generating an indication encompass performing mathematical calculations in statistical analysis that can be performed in the human mind with the aid of pen and paper or through use of a generic computer.
The limitation in claim 34 only positively recites selecting the patient for treatment which is a mental process. Claim 39 only further limits the mental process of choosing specific genes to include when producing a gene expression profile and claim 42 only provides specific examples of molecules that may be used in the mental process of selecting a patient for treatment.
Therefore, these limitations fall under the “Mathematical concepts” and “Mental processes” groupings of abstract ideas (Step 2A, prong 1: YES).
Step 2A, prong 2:
Claims found to recite a judicial exception under Step 2A, prong 1 are then further analyzed to
determine if the claims as a whole integrate the recited judicial exception into a practical application
(Step 2A, prong 2). The claims recite the following additional elements:
Claim 33 recites obtaining a sample from a primary cutaneous melanoma tumor in the subject; and measuring a gene expression level of each of at least two of several specific genes in the sample.
Claim 37 recites wherein measuring gene expression levels comprises measurement of a level of fluorescence by a sequence detection system following RT-PCR.
Claim 38 recites treating the selected subject with a statin or other HMGCR inhibitor when the primary cutaneous melanoma is determined to be at high-risk for metastasis.
Claim 41 recites wherein the primary cutaneous melanoma tumor is a Stage 3 (regional) or Stage 4 (metastatic) melanoma.
The additional elements of obtaining a sample, measuring gene expression, and specifically measuring by detecting fluorescence with a sequence detection system don’t impose significant limits on the judicial exception because they are only tangentially related to the invention. Particularly, the additional elements amount to necessary data gathering and all uses of the recited judicial exception require such data gathering steps. These additional elements are considered insignificant extra-solution activity (See MPEP 2106.05g). The additional element of treating a subject with a statin or other HMGCR inhibitor is an insignificant application that’s tangential to the judicial exception because the treatment is recited at a high-level of generality; this is also considered insignificant extra-solution activity. Additionally, since the additional element of treating the selected subject is a contingent limitation (i.e., it only happens when the primary cutaneous melanoma is determined to be high-risk), the broadest reasonable interpretation of the claim 38 limitation encompasses situations when this treatment step is not performed. Lastly, the additional element of claim 41 only describes the disease state of the patients being treated.
Therefore, the judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies/uses the recited judicial exception in some other meaningful way and the claims are directed to the judicial exception (Step 2A, prong 2: NO).
Step 2B:
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). The additional elements recited in the claims amount to well-understood, routine and conventional (WURC) activity because they fall into laboratory techniques that the courts have ruled are WURC such as: Using polymerase chain reaction to amplify and detect DNA, Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015); and Detecting DNA or enzymes in a sample, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017).
As such, the combination of additional elements recited in the claims is well-understood,
routine and conventional. The additional elements do not comprise an inventive concept when
considered individually or as an ordered combination that transform the claimed judicial exception into
a patent-eligible application of the judicial exception. Therefore, the claims do not amount to
significantly more than the judicial exception itself (Step 2B: NO) and claims 33-34, 37-39, and 41-42 are not patent eligible.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yu et al. (Journal of Investigative Dermatology, vol. 141, no. 7, January 2021, pp. 1802-09; IDS document 8/2/2024).
The claim 1 limitation of selecting a subject with high-risk primary melanoma based on genetic features reads on the Yu et al. teaching that melanomas at high risk of metastasis can be identified by there gene expression signature (p. 1802, Introduction, paragraph 2). The limitations of reducing risk of future melanoma metastasis by administering a statin to a subject read on the Yu et al. teaching that there is consistent evidence that statins could prevent melanoma metastasis (p. 1803, Introduction, paragraph 5).
Claims 52-56 are rejected under 35 U.S.C. 102(a)(1) & (a)(2) as being anticipated by Shi et al. (US20160271106A1, September 2016; IDS document 1/26/2024), as evidenced by Bustos et al. (Oncotarget, vol. 9, no. 18, March 2018, pp. 14567-79), Kainthla et al. (Small Molecules in Oncology, edited by Uwe M. Martens, vol. 201, Springer Berlin Heidelberg, 2014, pp. 227-40), and Kane et al. (Clinical Cancer Research, vol. 12, no. 24, December 2006, pp. 7271-78).
Regarding claims 52 and 53, Shi et al. teach methods of treating cancers in a subject by administering a therapeutically effective amount of a statin (paragraph 0023) and that statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors (paragraph 0151). In some embodiments, the cancer is melanoma (Paragraph0083). The claim 52 limitation of treating primary melanoma by administering a stain read on these teachings. Shi et al. teach, in another embodiment, the statin is administered in conjunction with at least one additional cancer therapy to achieve a combination cancer therapy (paragraph 0042) and the additional cancer therapy can be immunotherapy (paragraph 0047). The claim 52 limitation of administering an immunotherapy to a patient and the claim 53 limitation of concurrent administration read on these teachings.
Regarding claims 52 and 55, Shi et al. teach in some embodiments, the at least one additional cancer therapy can be Vemurafenib, Tafinlar®, Nexavar® (paragraph 0188). The claim 52 limitation of administering a BRAF inhibitor to the patient and the claim 55 limitations of the BRAF inhibitor being Vemurafenib, dabrafenib, PLX 4032, or Sorafenib Tosylate read on this teaching. The teaching of Shi et al. discloses PLX 4032 because that is a synonym for Vemurafenib as evidenced by Bustos et al. (Title; Abstract). The teaching discloses dabrafenib because Tafinlar® is the brand name for dabrafenib as evidenced by Kainthla et al. (2 Mechanism of Action, paragraph 1; Figure 2). The teaching also discloses Sorafenib Tosylate because Nexavar® is the brand name for the drug as evidenced by Kane et al. (Clinical Cancer Research, vol. 12, no. 24, December 2006, pp. 7271-78) (Introduction, paragraph 1).
Regarding claims 54 and 56, the previous teachings of Shi et al. include embodiments of treating melanoma without administering a ROR-gamma inhibitor, thus teaching the claim 56 limitation of not treating the patient with such an inhibitor. Shi et al. teach the statin used in their method can be fluvastatin, atorvastatin, simvastatin, lovastatin, rosuvastatin, or pravastatin (paragraph 0033). The claim 54 limitations reciting such statins read on the teaching. Although, the teaching doesn’t disclose using pitavastatin, the recited group of statins would allow one of ordinary skill in the art to at once envisage that pitavastatin can also be applied as a treatment (MPEP 2131.02(III)).
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.
Claims 1, 3, 7, 14, 17, 33-34, 37-39, and 41-42 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (US20160271106A1, September 2016; IDS document 1/26/2024) as applied to claims 52-56 above, and further in view of Cook et al. (US20200362419A1, November 2020; IDS document 8/2/2024).
The limitations of claims 52-56 have been taught by Shi et al.
Regarding claims 1, 17, 38, and 42, Shi et al. teach methods of treating cancers in a subject by administering a therapeutically effective amount of a statin (paragraph 0023) and that statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors (paragraph 0151). In some embodiments, the cancer is melanoma (Paragraph0083). The limitations of claims 1 and 38 of administering a statin/HMGCR inhibitor to a patient with melanoma read on these teachings. Although, Shi et al. didn’t identify the primary melanoma as high-risk as recited in claim 38, that is a contingent limitation that does not need to occur, and the claimed method encompasses an embodiment of not performing any treatment in which case the claim limitation is not required to be performed (MPEP 2111.04(II)). Shi et al. teach the statin can be administered in conjunction with at least one additional cancer therapy to achieve a combination cancer therapy (paragraph 0042) and the additional cancer therapy can be immunotherapy or chemotherapy (paragraph 0047). These teachings disclose the claim 17 limitations of treating the subject with immunotherapy or chemotherapy. The limitations of claim 42 read on the teaching of Shi et al. where the statin used in their method can be fluvastatin, atorvastatin, simvastatin, lovastatin, rosuvastatin, or pravastatin (paragraph 0033). Although, the teaching doesn’t disclose using pitavastatin, the use of statins to treat cancer and the recited group of statins would make it obvious to one of ordinary skill in the art to try using pitavastatin as a treatment.
Regarding claims 14, 34, and 41, The limitations of claim 34 read on the teaching of Shi et al. that subjects can be selected by screening by several diagnostic methods such as additional biomarkers, tissue biopsy, and histopathological examination (Paragraph 0192). The limitations of claim 14 of selecting the subject based on at least one high risk clinicopathologic feature also reads on this teaching. Although Shi et al. does not disclose specific methods, they teach a skilled oncologist or physician will be able to differentially diagnose cancer using medical methods known in the art (Id.) Shi et al. define the examples of cancer treated in their method include melanoma and the cancer can be in the form of a metastatic tumor (Paragraphs 0083-0084) which discloses the limitations of claim 41.
Shi et al. are silent to the claim 1 limitation of selecting a subject with high-risk primary melanoma, wherein primary melanoma is determined to be high-risk based on one or more genetic features and the limitations of claims 3, 7, the specific clinicopathologic features recited in claim 14, the limitations of claims 33, 37, and 39. However, these limitations were known in the art at the effective filing date of the invention as taught by Cook et al.
Regarding claims 1, 3, 7, 33, 37, and 39, Cook et al. teach a method of predicting risk of metastasis of a primary cutaneous melanoma comprising measuring gene expression levels of at least eight genes in a sample taken from the primary cutaneous melanoma tumor, wherein measuring gene-expression levels of the at least eight genes comprises measurement of a level of fluorescence by a sequence detection system following RT-PCR (Paragraph 0021). The teachings discloses the claim 1 limitation of selecting a subject with high-risk melanoma based on one or more genetic features, the limitations of claim 3 and 7 where the genetic feature is a change in expression of any gene in Table 5, the limitations of claim 33 and 37, and the limitations of claim 39 of where the gene expression profile is the genes BAP1, MGP, SSP1, CXCL14, CLCA2, S100A8, BTG1, SAP130, ARG1, KRT6B, GJA1, ID2, EIF1B, S100A9, CRABP2, KRT14, ROBO1, RBM23, TACSTD2, DSC1, SPRR1B, TRIM29, AQP3, TYRP1, PPL, LTA4H, and CST6.
Lastly, regarding claim 14, Cook et al. disclose several histological factors used to identify the stage of cutaneous melanoma and are associated with prognosis (paragraph 0003). The claim 14 limitations of the clinicopathologic features being Breslow depth, mitotic rate, ulceration, and sentinel lymph node status read on this teaching.
An invention would have been prima facie obvious to one of ordinary skill in the art at the
effective filing date of the invention if some motivation in the prior art would have led that person to
combine the prior art teachings to arrive at the claimed invention. Cook et al. teach that some patients with stage I melanoma go on to develop metastatic disease and inaccurate prognosis has profound effects on patient treatment and there is a need for methods to predict tumors with aggressive metastatic activity to increase survival rates (Paragraphs 0003, 0005, 0008). Shi et al. teach that many types of cancers remain common and there is an unmet desire for more anti-cancer agents to complement or replace existing treatments (Paragraphs 0005-0006). One of ordinary skill in the art would be motivated to combine the gene expression profiling methods taught by Cook et al. with the statin cancer treatment method taught by Shi et al. because it would increase cancer patient survival and positive response to treatment. Furthermore, one or ordinary skill in the art would expect a reasonable chance of success because Shi et al. teach that statins were shown to reduce incidence of new melanomas (paragraph 0282) and Cook et al. teach that survival is likely if cutaneous melanoma is detected early and treated appropriately (paragraph 0003). The invention is therefore prima facie obvious.
Claims 4, 8, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (US20160271106A1, September 2016; IDS document 1/26/2024) and Cook et al. (US20200362419A1, November 2020; IDS document 8/2/2024) as applied to claims 1, 3, 7, 14, 17, 33-34, 37-39, and 41-42 above, and further in view of Okino et al. (US10683551B2, June 2020).
The limitations of claims 1, 3, 7, 14, 17, 33-34, 37-39, and 41-42 have been taught by Shi et al. and Cook et al.
Regarding claims 4, 8, and 13, the limitations of the claims read on the teaching of Cook et al. of measuring gene expression changes to determine high-risk melanoma in the same manner as the limitations of claims 3, 7, and 39 (Paragraph 0021).
Shi et al. and Cook et al. are silent to the claim 4 limitation of wherein the genetic features comprise methylation level of genes. However, this limitation was known in the art at the effective filing date of the invention as taught by Okino et al.
Regarding claim 4, Okino et al. teach methods of determining the biological, pathological, genetic, epigenetic or disease status in a biological sample by determining the methylation status of a subpopulation of genomic DNA in a sample (Abstract). Particularly, Okino et al. teach that “The invention provides methods of detecting the presence of cancer in a biological sample. In some embodiments, the methods comprise: a) dividing a biological sample comprising gDNA, wherein the biological sample comprises cells suspected of being cancerous, into at least a first portion and a second portion; b) enriching a subpopulation of gDNA in the first portion; and c) determining the DNA methylation status at one or more gDNA regions in the first portion and in the second portion, wherein a difference in the extent of DNA methylation in the enriched gDNA in the first portion relative to the extent of DNA methylation in the gDNA in the second portion at the one or more gDNA regions indicates or is correlated with the presence of cancer in the biological sample.” (p. 11, column 1, line 43 – column 2, line 7). The claim 4 limitation of the genetic features comprising a methylation level reads on this teaching.
An invention would have been prima facie obvious to one of ordinary skill in the art at the
effective filing date of the invention if some motivation in the prior art would have led that person to
combine the prior art teachings to arrive at the claimed invention. Cook et al. teach that some patients with stage I melanoma go on to develop metastatic disease and inaccurate prognosis has profound effects on patient treatment and there is a need for methods to predict tumors with aggressive metastatic activity to increase survival rates (Paragraphs 0003, 0005, 0008). Okino et al. teach “The present methods find use as a diagnostic and/or prognostic tool. Once a diagnosis or prognosis is established using the present methods, a regimen of treatment can be established or an existing regimen of treatment can be altered in view of the diagnosis or prognosis” (p. 26, column 31, lines 57-63). One of ordinary skill in the art would be motivated to combine the gene expression profiling methods to determine and treat high-risk melanoma taught by the combined teachings of Shi et al. and Cook et al. with the methods of measuring methylation taught by Okino et al. because it would help accurately identify the cancer status in a patient and increase cancer patient survival. Furthermore, one or ordinary skill in the art would expect a reasonable chance of success because both references are used to diagnose or prognose cancer. The invention is therefore prima facie obvious.
Conclusion
Claims 1, 3-4, 7-8, 13-14, 17, 33-34, 37-39, 41-42, and 52-56 are rejected.
Claim 14 is objected to.
Claims 1, 3-4, 7-9, 13-14, 17, and 52-56 are not rejected under 35 U.S.C. 101 because the independent claims 1 and 52 do not recite a judicial exception and the additional elements recite a particular treatment.
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/T.Y.O./Examiner, Art Unit 1685
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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