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 .
A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. Since this application is eligible for continued examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on 9/23/2025 has been entered.
This application has been reassigned within Bioinformatics, 1686. Please see the name and information at the end of this Office Action.
Claims 1, 4, 6 and 8-13 are pending in this application. Claims 2, 3, 5, 7 and 14-17 have been canceled.
Newly amended claim 1 (and all dependent claims) is now directed to a separate and distinct invention, lacking all of the previously examined computer-implemented assistance, and algorithmic processes, and is now wholly directed to a treatment of a patient with no analytical steps. As per MPEP 819, while the Office does not generally permit a shift in invention, a review of the application indicates an intent to simplify the issues, and the Examiner accepts this shift. No further shift in invention will be permitted in this application.
This application claims priority as a CON of 14/668518, filed 3/25/2015, which claims priority to US provisional application 61/970,054, filed 3/25/2014. The examiner has reviewed the prosecution history. The US Provisional application does not provide support for the amended claims, with respect to providing a treatment to a patient, which is a treatment that “targets at least one gene selected from…” The provisional application does not provide any elements which target any of the listed genes, nor does it clearly recite these particular genes. Therefor, the effective filing date for the claims amended 9/23/2025 is 3/25/2015.
The IDS filed 10/24/2025 has been entered and considered as the appropriate statements and fees were paid.
Claim Rejections - 35 USC § 112
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, 4, 6, 8-13 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.
Claim 1 has been re-written, and are now directed to:
“1. (Currently amended) A method of treating a patient having a tumor, comprising:
administering to the patient a treatment that targets at least one gene selected from the group consisting of CDKN2A, ARID1A, FAT1, TP53, PTEN, AHNAK, SRRM2, RASA1, PIK3R1, and MRPL32, and
wherein the tumor tissue of the patient upregulates the at least one gene compared to a normal tissue of the patient.”
The specification, as filed, does not provide any specific treatments which “target” at least one gene, as listed. The claim, as amended, encompasses the use of any possible “treatment” from radiation / surgical treatments to small molecules, antisense polynucleotides, genetic modification, use of polypeptides or antibodies, complex chemotherapy, or combinations thereof, as long as one of the listed genes is “targeted.” The term “targeted” is not equal in scope to “inhibiting” with respect to moderation of the behavior of a gene. “Targeted” suggests that the treatment selectively acts on that gene, however no activities of any gene are provided to be targeted, and “selectively acts” does not imply whether the activity of the gene is to be increased, decreased, removed, etc.
MPEP 2163 sets forth the guidelines for written description:
“To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116...”
“An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it"). "Compliance with the written description requirement is essentially a fact-based inquiry that will ‘necessarily vary depending on the nature of the invention claimed.’" Enzo Biochem, 323 F.3d at 963, 63 USPQ2d at 1612.”
As directed by MPEP 2163, the Examiner has reviewed the application for sufficient written description of the claimed invention. The Background of the Invention discusses types of ‘omics data, and the need for sophisticated data analysis to properly examine the large amounts of data being generated. The Summary of the Invention, beginning at [0007] discloses the invention to be systems and methods of integrating RNomics information with genomics analysis and analytic systems, to identify biomarkers for neoplastic diseases and does not speak to treatments. The remainder of the Summary is directed to disclosing computer processing steps, databases, data gathered, and “differential sequence objects.” A computer ‘omics record system is disclosed at [0011]. Elements of updating computer records with mutation information for a list of “cancer -associated genes”, is disclosed. The method may “confirm a diagnosis (e.g. of a neoplastic disease) or suggest a therapeutic option (e.g. for the neoplastic disease).” This statement about suggestion of a therapeutic option is not borne out by the remainder of the disclosure. [0013]. Figures 1-14 are briefly discussed, and are largely directed to sequence mutation information, gene expression levels, and the analysis of nonsense mutations for certain genes. The Disclosure describes “various method of processing omics data and omics record computer systems” beginning at [0030], describing the computer systems, programming, datasets and databases. Data file formats are discussed at [0033], where the need for matched sequence information for healthy and diseased tissue is disclosed, and the use of multiple sequence alignments. Transcriptomic data is disclosed at [0034], including RNA data for both diseased and healthy tissue. Combined datasets are disclosed at [0035]. Simultaneous analysis of tumor and matched RNA is disclosed, to identify “pathway relevant data”. Other ‘omics information can be incorporated such as proteomics, other patient data, or patient health records. [0037] sets forth that at least two distinct tissues are employed in the generation of the genomic and transcriptomic data sets. [0038] discusses certain analytic or algorithmic steps for aligning and comparing ‘omics data. [0039] discusses mutation identification algorithmic modules, and types of mutations to be identified. [0040] sets forth a programmed module to correlate position information for the mutation within the transcript. [0041] discusses updating omics computer records for the patient based on the data analysis steps. [0042] sets forth that the application “will readily provide a new avenue for identification of potential molecular markers for treatment and diagnostics for cancers based on genomic and transcriptomic information.” [0043] discusses types of cancer within the TCGA database, that have matched DNA/ RNA data pairs. [0044] discusses the types of mutations identified in the TCGA data. [0046] discusses the Major or Minor allele fraction for DNA vs RNA datasets. [0047] discusses the cancer-associated genes of Table 3, and the cancers with which they are associated, and the possibility of developing diagnostic signatures for certain cancers.
The application, as filed, fails to provide any particular treatment for a tumor which “targets” any of the listed genes. No information is provided about any of the listed genes, other than by name, cancer type, and certain mutations identified. No cellular or biological activity for any product of the identified genes is provided such that one of skill might be able to identify a treatment that would “target” any particular gene. The specification does not provide any type of treatment that may target any type of differently expressed gene, RNA or protein.
The application does not provide words, structures, figures, diagrams or formulae of any specific treatment that targets any of the listed genes in claim 1, whether mutated, or unmutated. (Lockwood v. Amer. Airlines) No reduction to practice of any specific treatment is provided. No distinguishing or identifying characteristics of any particular or specific treatment that targets one of the listed genes are provided by the disclosure. (Pfaff v. Wells Elecs., Inc) The application lacks “disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that inventor was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” (Enzo Biochem,)
As further set forth in MPEP 2163: “describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)).”
Claim 1 recites the genus of treatments only by referring to a function- “targeting” one or more of the listed genes.
MPEP 2163 continues: “An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described.")”
MPEP 2163 points out “What is conventional or well known to one of ordinary skill in the art need not be disclosed in detail. See Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d at 1384, 231 USPQ at 94. See also Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1085 (Fed. Cir. 2005) ("The ‘written description’ requirement must be applied in the context of the particular invention and the state of the knowledge…. As each field evolves, the balance also evolves between what is known and what is added by each inventive contribution.").”
The Examiner reviewed the state of the art around the time of filing, to assess what was known in the prior art about “treatments that target” one or more of the particular listed genes in claim 1.
Around the time of filing, treatments that “target” any of the listed genes were not all conventional, or well known in the art. For example, with respect to CDKN2A2, the role of the “cyclin dependent kinase inhibitor 2A2” was not settled in all human cancer types. This gene is silenced by methylation processes within the cell in some cancers, while the gene is deleted altogether in others, such as certain melanomas, astrocytomas, and some cutaneous sarcomas. In other cancers for which CDKN2A2 is a biomarker, such as squamous cell carcinoma of the larynx, the treatment for the carcinoma (surgery and/or radiation) does not directly target the CDKN2A2 gene itself (Chernock et al. 2013). Huang et al. (2015) studied a particular inhibitor, CDK4/6 inhibitor PD-0332991, and found it was an effective treatment for gastric cancer cells harboring a particular mutation of CDKN2A2. This is not a disclosure of a treatment that “targets” CDKN2A2 in an unmutated state, or any different mutational state. The specification fails to provide any specific treatments targeting CDKN2A2 for any or all tumors, and particularly for cancers in which this gene has been deleted outright.
A different example is ARID1A: in a study of certain ovarian carcinomas, Bitler et al disclosed a study of treating cancer cells harboring ARID1A mutations using a small molecule that inhibits not ARID1A, but EZH2 histone methyltransferase.
“ARID1A is a subunit of the Switch/ Sucrose NonFermentable (SWI/SNF) chromatin-remodeling complex that regulates gene expression by controlling gene accessibility. ARID1A shows one of the highest mutation rates across different human cancer types. For example, ARID1A is mutated in ~50% of ovarian clear cell carcinoma (OCCC). There is considerable interest in developing cancer therapeutics that correlate with ARID1A mutational status. A recent study demonstrated a synthetic lethality by targeting EZH2 histone methyltransferase activity in ARID1A-mutated OCCC using a clinically applicable small molecule inhibitor…” that selectively promotes apoptosis in ARID1A mutated OCCC cells.
Bitler points out that cancers with ARID1A mutations “may also be subjected to therapeutic intervention by targeting residual SWI/SNF activity, the PI3K/AKT pathway, the DNA damage response, the tumor immunological microenvironment and stabilizing wild-type p53. In summary, we propose EZH2 inhibitor-based combinatorial strategies for targeting ARID1A-mutated cancers.”
This is not a disclosure of treatments that target AID1A in its unmutated or mutated state. The specification is silent with respect to any particular treatment that targets ARID1A.
With respect to FAT1, in 2016 Pileri et al. identified a monoclonal antibody that binds FAT1 in colorectal cancer cells, described FAT1 as an “atypical cadherin” and FAT1’s role in invasiveness of colon cancer cells, but not apoptosis. The role of FAT1 in cells were not well settled, nor were its particular biologic activities. “The role of FAT1 is highly debated, being reported as a tumour suppressor … or a tumour promoter... FAT1 has been reported to undergo an aberrant processing in melanoma and pancreatic cancer” (p41, references removed for brevity). The identification of a monoclonal antibody which bound FAT1 was not an identification of an actual treatment targeting and inhibiting FAT1 for the treatment of a colorectal cancer or tumor, but an indication that possibly, monoclonal antibodies bearing a treatment modality could, in the future, be applied. The specification is silent with respect to any particular treatment that targets FAT1.
With respect to TP53 (p53), around the time of filing, it was characterized as “the most frequently mutated gene in cancer… In most, if not all, cancers lacking mutation, wild-type (WT) p53 is inactivated by interaction with cellular (MDM2/MDM4) or viral proteins, leading to its degradation. Because of its near universal alteration in cancer, p53 is an attractive target for the development of new targeted therapies for this disease. However, until recently, p53 was widely regarded as ‘‘undruggable’’. This situation has now changed, as several compounds have become available that can restore wild-type properties to mutant p53 (e.g., PRIMA-1 and PRIMA-1MET). Other compounds are available that prevent the binding of MDM2/MDM4 to WT p53, thereby blocking its degradation (e.g., nutlins).” (Duffy et al. 2014) Duffy points out that p53 exists in at least 12 isoforms generated by alternative splicing, differing initiation sites of translation, and the use of alternative promoters. The specification is silent with respect to any of these particular isoforms or any particular treatments.
With respect to the PTEN gene, around the time of filing, Spinelli et al. (2015) discuss small molecule inhibitors for use in treatment of diseases such as nerve injury. Spinelli noted that: “Efforts to develop inhibitors against the lipid phosphatase and tumour suppressor, PTEN, was for some time limited by concerns that their use as therapy could result in increased risk of cancer. However, the accumulation of evidence that short term PTEN inhibition may be valuable in conditions such as nerve injury has raised interest.” (abstract). Spinelli reviews the state of the knowledge about PTEN and cancer, noting:
“PTEN activity has potent effects in many cell lineages on cell proliferation, growth, survival and associated changes in metabolism and in a more lineage-specific manner, can control cell polarization and movement... Many of these effects are mediated through PTEN-mediated metabolism of the lipid PtdInsP3, but evidence for the importance of PIP3/PI3K independent functions of PTEN has been presented … and alternate mechanisms of action have been proposed … although their significance is currently hard to judge. In transgenic mouse models, tissue specific Pten deletion promotes tumorigenesis in many tissues (eg mammary gland, prostate, keratinocytes, B-cells, T-cells) but can also affect other processes such as oocyte maturation through mechanisms that are unclear ... PTEN activity appears to be regulated in physiology at several levels, through regulation of PTEN expression and post-translational control of PTEN activity…” (p103, references removed).
The specification is silent with respect to any modulator of PTEN activity or using a treatment that targets PTEN activity for patients with tumors. In fact, it would appear that targeting/inhibiting PTEN may increase the incidence of tumorigenesis.
With respect to the AHNAK gene, Davis et al (2014) describe it as a “jack of all trades” as well as “an unusual and somewhat mysterious scaffolding protein…” The art at the time was not well versed in inhibitors or treatments that targeted AHNAK.
“Several aspects of this protein remain uncertain, including its exact molecular function and regulation on both the gene and protein levels. Various studies have attempted to annotate AHNAK and, notably, protein interaction and expression analyses have contributed greatly to our current understanding of the protein. The implicated biological processes are, however, very diverse, ranging from a role in the formation of the blood–brain barrier, cell architecture and migration, to the regulation of cardiac calcium channels and muscle membrane repair. In addition, recent evidence suggests that AHNAK might be yet another accomplice in the development of tumour metastasis…” (abstract).
Davis discusses the possible functions in detail, reviewing a large number of studies of metastasis, however, “Studies specifically investigating the role of AHNAK in cancer are especially limited.” (p2959.) Studies indicating AHNAK as a tumor promoter and others indicating AHNAK as a tumor suppressor were reviewed. See Fig 2.
“These results are indeed intriguing; AHNAK seems to be important in preventing cancer proliferation in response to TGFβ, while it also seems to be important in the progression of cancer to a metastatic state which can be in response to TGFβ. The specific direction of AHNAK activity is thus regulated in the context of cancer, and this might be mediated by TGFβ. TGFβ is known to have contrasting roles in cancer and has been described as both a tumour suppressor, based on its ability to induce growth arrest and apoptosis, and a tumour promoter, based on its ability to induce angiogenesis and EMT.” (p2959)
The specification fails to provide any treatments that specifically target AHNAK for the treatment of patients with tumors.
With respect to the SRRM2 gene, around the time of filing, there do not appear to be known targeting inhibitors, nor was it clearly associated with cancer. SRRM2 an acronym for: Serine arginine repetitive matrix 2. Horvath, (2015) studies this protein in neurodegenerative diseases, and the response of those diseases to Serotonin treatment. Horvath identified SRRM2 as a splicing coactivator protein, with potentially damaging missense mutations in the analysis of a family with a genetic degenerative disorder. The treatment with serotonin improved patient function, but it is unclear if serotonin was acting directly on SRRM2 (Fig 5). “Genome-wide transcription analysis in Parkinson’s disease revealed that the pre-mRNA splicing gene SRRM2 (serine-arginine repetitive matrix 2) was the only gene differentially upregulated in PD patients compared to controls 144. The authors argued that this gene might have some role as a biomarker in PD.” (p28). SRRM2 forms a complex with SRRM1, which is a co-activator of pre-mRNA splicing. Horvath notes that the sequence of SRRM1/2 suggest they are capable of interacting with many splicing co-factors, as well as binding to the nuclear matrix in the nucleus of the cell (Fig 10). Horvath studied the in-silico modeling of protein-protein interactions for SRRM2, and found a large number of interactions (Fig 11). Orthologs of SRRM2 were also studied. Knockout and knockdown studies are reviewed. Horvath performed a study of SRRM2 structure in silico, including for certain known mutated forms (Fig 34). While some treatments for the overall neurodegenerative diseases have been identified (Serotonin, GABA) no specific treatments specifically targeting SRRM2 are provided, nor does the specification identify any.
RASA1 is part of the RAS signalling pathway, and is also known as RAS p21 GTPase-activating protein 1. Sun et al (2015) associated RASA1 with human colorectal cancer, and attempted to inhibit RASA1 with miRNA (miR-223). “Upregulation of miR-223 was detected in CRC tissues (P<0.01) and was involved in downregulation of RASA1 in CRC tissues. Furthermore, the direct inhibition of RASA1 translation by miR-223 and the activation of miR-223 by CCAAT/enhancer binding protein-β (C/EBP-β) were evaluated in CRC cells. An in vivo xenograft model of CRC suggested that the upregulation of miR-223 could promote tumour growth and that the inhibition of miR-223 might prevent solid tumour growth.” The disclosure fails to identify any inhibitors such as miR-223, nor does it suggest the use of miRNA in the inhibition of RASA1, or the treatment of a tumor.
Wang et al. (2015) reviews the state of the art in treatment of cancer with PI3K inhibitors. The PIK3R1 gene a member of a family of lipid kinases (PI3K) which are divided into three classes.
“Class IA PI3Ks are heterodimers of one p110 catalytic subunit encoded by PIK3CA (p110α), PIK3CB (p110β) or PIK3CD (p110δ) and one p85 regulatory subunit encoded by PIK3R1 (p85α), PIK3R2 (p85β) or PIK3R3 (p85γ) … In quiescent settings, class I PI3Ks possess little kinase activity due to the self-inhibition of p85 regulatory subunits and/or localization in the cytosol, where no substrates are available. Upon activation via binding of receptor tyrosine kinase (RTK), G protein-coupled receptor (GPCR), Ras or other adaptor proteins, class I PI3Ks are recruited to the cell membrane proximity, where they switch to an active conformation and utilize PtdIns(4,5)P2 to generate PIP3.”
Wang reviews knowledge in the prior art of PI3K class 1 in cancer:
“Aberrant PI3K activities are frequently observed in many types of cancers through different mechanisms including (but not limited to) hyperactivated RTKs, mutant Ras, functional loss of PTEN and activating mutations and/or overexpression of PI3K isoforms. PIK3CA is mutated across different tumors with a frequency of approximately one-third in endometrial, breast, ovarian and colorectal cancer specimens.”
Table 1 of Wang sets forth the wide variety of compounds being tested for a variety of anti-tumor, anti-platelet, or anti-leukemic effects. However, these compounds target the entire PI3K complex, and not PIK3R1 (p85α) itself. The specification does not identify any PI3K inhibitors, nor any PIK3R1 inhibitors, or any treatments that target PIK3R1.
In a study of mitochondrial matrix proteases as possible targets in cancer treatments, Goard et al. (2014) discuss the interaction of the m-AAA protease with a precursor of MRPL32, beginning at page 2695. “the yeast m-AAA protease initiates N-terminal degradation of the soluble mitochondrial large ribosome subunit mitochondrial ribosomal protein L32 (MrpL32), but this is terminated proximal to a tightly folded domain, protecting this substrate from complete degradation and releasing mature MrpL32.” (see fig 3). Goard identifies mAAA protease as a good target for anticancer treatment development. Goard does not identify any specific inhibitors of MRPL32, nor does the specification.
Overall, with respect to the genes listed in claim 1, one of skill in the art would not have been readily apprised of “treatments that target” the genes, nor their use in the treatment of tumors. The specification does not provide any such treatments, and the prior art indicates that at the time, knowledge of treatments that target any one gene was limited, and the results of targeting any of the genes were unpredictable.
MPEP 2163 discusses new or amended claims, and the written description requirement.
“Thus, the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed. New or amended claims which introduce elements or limitations that are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971)...
PNG
media_image1.png
18
19
media_image1.png
Greyscale
While there is no in haec verba requirement, newly added claims or claim limitations must be supported in the specification through express, implicit, or inherent disclosure.”
The newly amended claims introduce the genus of “treatments” that were not adequately described in the application.
“With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4, 83 USPQ2d 1373, 1376, n.4 (Fed. Cir. 2007) …”
The rejected claims attempt to encompass any possible “treatment” that “targets” one or more of a list of genes, however no particular treatments that target any of the genes are disclosed within the application as filed. The genes can harbor unlisted mutations, as set forth in the dependent claims. The “treatment” is not limited to a particular type of treatment, nor type of structure. It encompasses any possible treatment from radiation or surgical treatments, to small molecules, polynucleotide treatment, polypeptides, complex chemotherapy or antibodies. The elements of the genus of “treatments” do not share any structural features, or particular activity. The list of genes all encode differing proteins, having differing activities or biological effects. The claims do not recite any particular mutations of any particular gene which may be targeted for a specific treatment. As shown above, treatments for cancers with any one gene (mutated or wild type) are not expected to be the same as treatments for cancers with mutations in any other of the listed genes. No chemical structures, structural drawings, or other words describing specific treatments targeting one or more of the listed genes are present in the application as filed. No partial or complete chemical structures, or other physical/ chemical properties of any treatment are disclosed. No connection is made in the specification between any particular gene, transcript, or protein, and any enzymatic or biological activity to be targeted.
MPEP 2163: “For some biomolecules, examples of identifying characteristics include a sequence, structure, binding affinity, binding specificity, molecular weight, and length. Although structural formulas provide a convenient method of demonstrating possession of specific molecules, other identifying characteristics or combinations of characteristics may demonstrate the requisite possession. As explained by the Federal Circuit, "(1) examples are not necessary to support the adequacy of a written description; (2) the written description standard may be met … even where actual reduction to practice of an invention is absent; and (3) there is no per se rule that an adequate written description of an invention that involves a biological macromolecule must contain a recitation of known structure." Falkner v. Inglis, 448 F.3d 1357, 1366, 79 USPQ2d 1001, 1007 (Fed. Cir. 2006); ... However, the claimed invention itself must be adequately described in the written disclosure and/or the drawings. For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties)”
“For example, in the biotech art, if a strong correlation has been established between structure and function, one skilled in the art would be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Thus, the written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate").
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4, 6 and 8-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The metes and bounds of claim 1 are unclear. Claim 1 fails to particularly point out and distinctly claim what treatment is to be applied to the patient with the unspecified tumor. The treatment is claimed in terms of “targeting” a gene, from a list. The claim fails to point out any specific treatments, nor does the specification provide a definition of any possible treatment which may target one of the listed genes. It is unclear if the treatment is intended to inhibit, or promote any of the activities of any of the listed genes. It is unclear if in the tumor of the patient, the gene is in a mutated or unmutated state. As the claim is worded, it does not appear to matter, as the treatment occurs without any analysis of the tumor of the patient. Claim 1 fails to particularly point out and distinctly claim the actual genes being targeted by SEQ ID NO or characteristics which spell out the mutational status of the genes in the tumor. Recitation of a name, whether it is a laboratory designation or an accepted name in the field is not a recitation of the specific sequence to be targeted. It does not describe any mutations of that encompassed gene. Further in claim 1 the final “wherein” clause is quite confusing. The patient is not tested to determine whether any one of the genes is upregulated, and is treated no matter what the gene expression levels may, or may not be. This limitation appears to be an inherent property of the tumor of the patient, and does not limit or describe the treatment itself. This limitation should be deleted from the claim.
Claim 4 recites the limitation "the diseased tissue" in reference to claim 1. There is insufficient antecedent basis for this limitation in the claim. Claim 1 does not recite “diseased tissue” but does recite “a tumor.”
The metes and bounds of claim 6 are entirely unclear with respect to the method of treatment of claim 1. Claim 1 does not obtain samples of the tumor. Claim 1 does not determine whether any upregulation of any gene has occurred. Claim 1 does not generate any transcriptomic data, from cDNA or polyA+- RNA. No determinations of upregulations are carried out, nor does the presence of any upregulation change how the patient is treated, thus how claim 6 is intended to modify claim 1 is entirely unclear.
With respect to claims 8-13, the claims fail to particularly point out and distinctly claim the steps required to identify a position of a mutation in any tumor-associated gene, or number of cancers, as claim 1 does not obtain a sample of the tumor from the patient. Without such a sample, no mutation analysis can be performed. Further, the claims lack any particular wild type sequence of any gene, such that any mutation could be identified in comparison. The claims directing the mutation identification do not affect any part of the treatment of the patient with the tumor. Whether or not a mutation exists, the patient is treated. As such, the metes and bounds of these claims are undeterminable.
Further with respect to claims 11-12, the patient has a single tumor, not multiple distinct cancers as recited. As such it is entirely unclear what is to be tested for mutation in these claims. The identification of a mutation meeting these limitations has no effect on the actual treatment of the patient.
Claim 13 is a duplicate claim, as it merely repeats the same genes listed in claim 1, which are the same genes allegedly studied in claim 8.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 4, 6, 8-13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 4 describes the tumor tissue of the patient as “a cancerous tissue.” The patient is already determined to have a tumor, which by definition is cancerous. This fails to further limit claim 1.
None of the steps of claims 6, and 8-13 materially change the treatment of the patient, and as such are not further limiting of claim 1.
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.
Claim(s) 1, 4, 6, 8-13 are is/are rejected under 35 U.S.C. 102a1 as being anticipated by Duffy (2014).
As set forth above, the effective filing date for the amended claims is 3/25/2015.
Duffy, M. J. et al. (2014) p53 as a target for the treatment of cancer. Cancer Treatment Reviews, vol 40, p1153-1160.
Claim 1 has been re-written, and are now directed to:
“1. (Currently amended) A method of treating a patient having a tumor, comprising:
administering to the patient a treatment that targets at least one gene selected from the group consisting of CDKN2A, ARID1A, FAT1, TP53, PTEN, AHNAK, SRRM2, RASA1, PIK3R1, and MRPL32, and
wherein the tumor tissue of the patient upregulates the at least one gene compared to a normal tissue of the patient.”
Duffy et al. is directed to targeting TP53 (also known as p53) in human cancers (meeting claims 1 and 13, reciting TP53). Duffy discloses treating cancer cells with compounds that restore wild-type properties to mutant p53, which are PRIMA-1 and PRIMA-1MET. Duffy also discloses treatments which prevent an activity related to p53, the binding of a MDM2/MDM4 complex to wild type p53. Duffy notes the first set of compounds are most useful in cancers with a high prevalence of p53 mutations, meeting the limitations of claims 6 and 8-10. Duffy notes that p53 mutations are present in a multitude of differing cancers, meeting the limitations of claim 11-12. Duffy addresses expression levels, and treatments at pages 1154-1157, meeting the requirements for claims 6 and 8. The cancers of Duffy meet the requirements for claim 4.
Claim(s) 1, 4 are is/are rejected under 35 U.S.C. 102a1 as being anticipated by Spinelli (January, 2015).
As set forth above, the effective filing date for the amended claims is 3/25/2015.
Spinelli et al. (January, 2015) PTEN inhibitors: an evaluation of current compounds. Advances in Biological Regulation, vol 57, p102-111.
Spinelli is directed to an analysis of the use of PTEN inhibitors in the treatment of some human diseases. Spinelli discloses 4 available PTEN inhibitors, and their use in the inhibition of PTEN, in comparison to the inhibition of related enzymes. Spinelli notes that PTEN may be involved in tumorigenesis (p103). The compounds are disclosed beginning at page 104. In vitro inhibition of phosphatase activity is carried out for each.
Claim(s) 1, 4, 6, 8-13 are is/are rejected under 35 U.S.C. 102a1 as being anticipated by Chen (2010).
As set forth above, the effective filing date for the amended claims is 3/25/2015.
Chen, M. et al. (2010) Enhanced growth inhibition by combined DNA methylation/ HDAC inhibitors in lung tumor cells with silenced CDKN2A. Int. J. Oncology, vol 37, p963-971.
Chen is directed to the treatment of non-small cell lung cancer cell lines with zebularine or zebularine plus depsipeptide. “… zebularine treatment resulted in inhibition of cell growth in 11 out of 12 lung cancer cell lines with silenced CDKN2A, but no cell growth inhibition was detected in the 7 lung cancer cell lines tested with deleted CDKN2A (p>0.001). In addition, we found that the combination of 30 μM zebularine and 6 or 7 nM depsipeptide resulted in a synergistic inhibition of cell growth in tumor cells with silenced CDKN2A (p<0.001, CI=0.70 and 0.57, respectively) but not in tumor cells with deleted CDKN2A.” (abstract). As such, this meets at least claims 1, 4 and 13.
Changes in gene expression levels of CDKN2A are discussed throughout, with respect to whether the gene is silenced, expressed, or absent, meeting claim 6. With respect to whether the tumor comprises mutations (claims 8-10), Chen states:
“Aberrant hypermethylation at regulatory CpG sites in cancer genes is associated with both gene silencing and tumorigenesis (1,2). In addition, the observation that CDKN2A hypermethylation is mutually exclusive with somatic retinoblastoma (RB) or CDKN2A mutations in tumor samples suggests that hypermethylation is functionally comparable to somatic point mutations for cancer gene pathway inactivation (3). In contrast to acquired gene mutation, silenced genes may also serve as targets for reversible reactivation by DNA methylation inhibitors that efficiently re-induce mRNA and protein expression.”
With respect to multiple cancers, and claims 11-12, Chen notes that CDKN2A may be involved in lung cancer. Leukemia, myelodysplastic diseases and solid tumors (p963.)
Claim(s) 1, 4, 6, 8-13 are is/are rejected under 35 U.S.C. 102a1 as being anticipated by Anderson (2010).
As set forth above, the effective filing date for the amended claims is 3/25/2015.
Anderson, J. N. et al. (2010) Pathway based identification of biomarkers for targeted therapeutics: personalized oncology with PI3K pathway inhibitors. Science Translational Medicine vol 2 issue 43, e43ra55, 14 pages.
Anderson is directed to identifying inhibitors of P13K pathways, in tumors or cancers. Anderson identifies biomarkers that predict responsiveness to certain inhibitors, particularly those targeting AKT, PDK1 and mTOR. Each of these acts at some point on genes present in tumors including PTEN, AHNAK, a TP53binding protein, et al (table 1). Anderson applies Compound 2 (AKTi), compound 17 (PDKi), or PI-103 to determine their effect on the phosphorylation of the genes in the various pathways. (Fig 2). Anderson applies the inhibitors to breast cancer samples, cell lines, and certain mouse models. Anderson notes that PTEN is often mutated in certain cancers, but that other pathways may rescue the pathway. As such, Anderson meets at least claims 1, 4, 6 and 8-13.
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, 4, 6, 8-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-20 of copending Application No. 17/740,040 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘040 application is drawn to cancer therapeutics which target certain cancer driver neoepitopes, including: CDKN2A, PTEN, TP53. It would have been prima facie obvious to treat a patient with a tumor, with the composition of the ‘040 application, as they are therapeutics which target at least one of the genes listed in claim 1. (The ‘040 has published as US 2022/0270709 A1)
This is a provisional nonstatutory double patenting reject