DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim(s) 1-20 are pending and under consideration.
Preliminary Amendments
Applicant’s preliminary amendment filed on 09/24/2024 is acknowledged. The claims were amended to remove multiple dependencies.
Priority
Acknowledgement is made that this application is a 371 of PCT/IT2023/050088 filed 03/23/2023 and claims priority based on foreign application filed as IT102022000005786 on 03/24/2022.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
Receipt of the information disclosure statement(s) on 09/24/2024 is acknowledged. The signed and initialed PTO-1449 form(s) has/have been mailed with this action.
Drawings
The drawings are objected to because Figure 5A recites “giorni” instead of “Days” on the injection timeline. 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.
Specification
Trademarks and/or tradenames
The use of the following term(s), which is/are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
IncuCyte (p. 10, line 12; p.14, line 19; p.20, line 17);
SuperFrost (p.11, line 8);
JetPEI (p.12, line 13);
Q5 (p.12, line 33);
GloMax (p.13, line 1);
TRIzol (p.13, line 26);
Nanodrop (p.13, line 29);
QuantStudio (p. 13, line 32); and
Countess (p. 14, line 21);
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Embedded hyperlink
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. 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.
See line 21 of page 11
See line 12 of page 13
Claim Objections
Claim 20 is objected to because of the following informalities: “of” should be between “amount” and “an” in line 8.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) - indefiniteness
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.
Claim(s) 4-5, 10-11, and 13-19 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(s) 4, 5, 10, 11, 13, 17 and 18, the phrase "such as/for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Accordingly, claim(s) 14, 15, 16, and 19 are rejected for being dependent upon claim 13.
Claim Rejections - 35 USC § 112(a) – Total lack of enablement
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.
Claim(s) 1-19 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention:
Claim(s) 1, 7, and 13 are drawn to methods of treating a tumor that overexpresses TRF2 in a patient comprising administering a therapeutically effective amount of – hsa-miR-182-3p to the patient (of claim 1) or a pharmaceutical composition comprising hsa-miR-182-3p, together with one or more excipients and/or adjuvants to said patient (of claim 7). Claim 13, dependent upon claim 7 further comprises administering one or more antitumor drugs (see claim for list) to said patient. The nature of the invention is complex in that hsa-miR-182-3p must be capable of treating a tumor in a patient, wherein that tumor overexpresses TRF2 (for claims 1 and 7). The nature of the invention is further complexified in that hsa-miR-182-3p and one or more of the listed antitumor drugs must be capable of treating a tumor in a patient, wherein that tumor overexpresses TRF2.
Claim 14 is drawn to the method of claim 13, wherein the hsa-miR-182-3p and one or more antitumor drugs are administered separately or sequentially. The nature of the invention is complex in that no matter if the one or more antitumor drugs is administered before, after, or together with hsa-miR-182-3p, the combination must be capable of treating a tumor in a patient, wherein that tumor overexpresses TRF2.
Claim(s) 2 and 8 are drawn to the methods of claims 1 and 7, respectively. Claim 15 is drawn to the methods of claim 14. Wherein the tumor overexpressing TRF2 is not osteosarcoma. The nature of the invention is complex in that hsa-miR-182-3p (and/or one or more antitumor drugs) must be capable of treating a tumor in a patient, wherein that tumor overexpresses TRF2, but that the tumor is not osteosarcoma (and/or no matter if the one or more antitumor drugs is administered before, after, or together with hsa-miR-182-3p).
Claim(s) 3 and 9 are drawn to the methods of claims 1 and 7, respectively. Claim 16 is drawn to the methods of claim 14. Wherein the tumor overexpressing TRF2 is not neuroblastoma. The nature of the invention is complex in that hsa-miR-182-3p (and/or one or more antitumor drugs) must be capable of treating a tumor in a patient, wherein that tumor overexpresses TRF2, but that the tumor is not neuroblastoma (and/or no matter if the one or more antitumor drugs is administered before, after, or together with hsa-miR-182-3p).
Claim(s) 4-5 and 10-11 are drawn to the methods of claims 1 and 7, respectively. Claim(s) 17-18 are drawn to the methods of claim 14. Wherein the tumor is selected from breast cancer, cervical cancer, colon cancer, primary brain tumors, such as, for example, glioblastoma, metastatic brain tumors, pancreatic cancer, head and neck cancer (claims 4, 10, and 17). More specifically, claim(s) 5, 11, and 18 recite wherein said breast cancer is triple negative breast cancer, for example a triple negative breast cancer mutated in BRAC1, optionally resistant to PARP inhibitors, or a HER2-positive breast cancer. The nature of the invention is complex in that hsa-miR-182-3p (and/or one or more antitumor drugs) must be capable of treating breast cancer, cervical cancer, colon cancer, primary brain tumors in a patient, wherein that tumor overexpresses TRF2, and wherein the breast cancer is triple negative breast cancer mutated in BRAC1 (and/or no matter if the one or more antitumor drugs is administered before, after, or together with hsa-miR-182-3p).
Claim(s) 6 and 12 are drawn to the methods of claims 1 and 7, respectively. Claim 19 is drawn to the method of claim 14. Wherein the hsa-182-3p is encapsulated in lipid nanoparticles. The nature of the invention is complex in that LNP-hsa-miR-182-3p (and/or one or more antitumor drugs) must be capable of treating a tumor in a patient, wherein that tumor overexpresses TRF2 (and/or no matter if the one or more antitumor drugs is administered before, after, or together with hsa-miR-182-3p).
Breadth of the claims:
The broadest reasonable interpretation of claim(s) 1 and 7 is that the claims are directed to treating any/all types of tumors that overexpress TRF2 in a patient comprising any/all routes of administration of a therapeutically effective amount of hsa-miR-182-3p. The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the specification and existence of working examples:
Looking to the specification for guidance on administration and tumor types, the specifications teaches:
Methods - The specification teaches immunohistochemical analysis of TRF2 was carried out on a series of 30 samples of primary triple negative breast cancer and the corresponding metastases, 55 samples of invasive breast cancer of different molecular subtypes (10 Luminal A, 10 Luminal B/HER2 negative, 10 Luminal B/HER2 positive, 9 HER2, 16 triple negative) and 50 samples of benign breast lesions with adjacent normal tissue (which may considered as 41 cases) . . . Two biologists assessed the samples and those in which the immunostaining of TRF2 showed to be present in at least 10% of the neoplastic cells analyzed were considered positive. (p. 11, lines 1-17).
Results – TRF2 expression progressively increases in normal tissue to benign lesions and becomes even higher in malignant tumors (p. 17).
“These results indicate that TRF2 plays a fundamental role in promoting the metastatic process in human patients with TNBC. . . it was found that patients with the highest TRF2 levels showed the worse clinical outcome.”
Methods - Applicant computationally analyzed miRNAs that could target TRF2’s 3’UTR. High-throughput screening with miRNAs was conducted in HeLa cells transfected with either the 3’-UTR-TRF2 reporter plasmid. Validation studies were down with the wildtype 3’UTR-TRF2 or one with a mutated sequence corresponding to the hsa-miR-182-3p binding site.
Results – In order to verify that the activity of the miRNAs was not dependent on the cellular context, miR-182-3p was ectopically expressed in different tumor lines (Hela, HCT116, MDA-MB-231, MDA-MB-436 and U2-OS). It was observed that overexpression of miR-182-3p markedly reduced TRF2 protein levels in all tested models (Fig. 2E).
Methods - Applicant used Hela (cervical cancer), HCT116 (colon cancer), U2-OS (osteosarcoma), Panc1 and AsPC-1 (pancreatic cancer), M059J (glioblastoma), CAL27 (mouth cancer), MDA-MB-231 and MDA-MB-436 (TNBC).
Results – Applicant ectopically expressed miR-182-3p in MDA-MB-436 and monitored cell proliferation. Overexpression inhibited cell growth by 50% when transfected twice.
Methods – Applicant looked at cell confluence of the miR-182-3p alone and/or Paclitaxel/Germcitabine/Docetaxel/Platinum Derivative.
Results – Figures 4D-G, applicant observed synergistic effects with the antitumor drugs with the miR-182-3p.
Methods - Applicant took patient-derived tumor xenografts, dissociated them, performed two transfection cycles with hsa-miR-182-3p, and measured inhibition of growth.
Results – Figure 6A and B. Ectopic expression of miR-182-3p reduces TRF2 and growth.
Methods - Applicant infected the MD-MB-436 (TNBC) cell line with a lentiviral vector to constitutively overexpress TRF2. Applicant inoculated female mice with MDA-MB-436 cells intramuscularly. Applicant inoculated the luminescent-overexpressing TRF2 MDA-MB-436 cells intracranially. Applicant inoculated subcutaneously a fragment of about 25-30mm3 of patient-derived TNBC. LNPs were administered IV 5x, with a three day interval between injections for a total of six treatments.
Results – LNPs-miR-182-3p in the intramuscular injected model exhibited a lack of tumor growth compared to the control and inhibitor (Fig 5a) and toxicity study revealed overexpression of miR-182-3p not only in the tumor but also in organs including the brain. Brain metastasis artificially generated by the luminescent MDA-MB-436 cells (the ones overexpressing TRF2) showed a reduction in TRF2 when treated with the lipid nanoparticles containing miR-182-3p. The model of subcutaneous PD TNBC showed 50% tumor reduction in mice treated with LNP-miR-182-3p compared to controls.
Predictability and state of the art:
First, when it comes to the predictability of treating any/all tumors in a patient, i.e., treating a form of cancer, Zhang et al (The Risks of miRNA Therapeutics: In a Drug Target Perspective, Drug Design, Development and Therapy, pages 721-733, published February 22nd, 2021) covers the risks and challenges of any microRNA in therapeutics:
More specifically, “Only 10 obtainable miRNA drugs have been in clinical trials with none undergoing phase III…”, (abstract). Zhang et al goes on to teach, “Inherently, miRNA is endogenously produced and siRNA is exogenously designed. Designers can exactly endow siRNA giving them the purpose of gene silencing, while endogenous miRNA seemed more complicated because nobody assigned them specific tasks.”, (see parge 722, column 2, paragraph 2). “As expected, Figure 2A showed a flexible complementary ratio of miRNA with target sequence (within the range 20–90%) and none with complete complementation…”, (see page 722, column 2, paragraph 2; and Figure 2A). “…All ten miRNA drugs had tens and hundreds of unapproved targets…”, (see Figure 3A, and page 727, column 1, paragraph 1).
Moreover, Zhang et al teaches, “TMTME (“too many targets for miRNA effect”) is a typical and inevitable property of miRNA molecules, which is caused by incomplete complementation with the target sequence. TMTME leads to that miRNA could bind to various sequences suitable for the interaction (including protein-coding genes, lncRNA, circRNA, etc), which is different from all approved drugs (including siRNA drugs) with only a few targets… Therefore, both introduction and removal of miRNA in humans can lead to changes of a wide series of pathways and some of them are unknown, even unpredictable, probably triggering disorders of physiological function or the occurrence of additional disease.”, (Page 729, column 1, paragraph 2 to column 2, paragraph 1).
Secondly, Wang et al (A Ten-MicroRNA Signature Identified from a Genome-Wide MicroRNA Expression Profiling in Human Epithelial Ovarian Cancer, PLoS ONE, vol 9, issue 5, pages 1-8, published May 9th, 2014), Effatpanah et al (Circulating miR-6165 and mir-182-3p as Non-Invasive biomarkers for Early Detection of Breast Cancer, Asain Pac J Cancer Prev, vol 26, issue 7, pages 2407-2411, published 2025), and Zheng et al (The roles of tumor suppressor parafibromin in cancer, Front Cell Dev Bio, vol 10, pages 1-7, published September 21st, 2022) teach that miR-182-3p is upregulated in cancer and involved in cancer development.
Wang et al teaches the role of miR-182-3p in ovarian cancer.
“Epithelial ovarian cancer (EOC) is the most common gynecologic malignancy. To identify the micro-ribonucleic acids (miRNAs) expression profile in EOC tissues that may serve as a novel diagnostic biomarker for EOC detection, the expression of 1722 miRNAs from 15 normal ovarian tissue samples and 48 ovarian cancer samples was profiled by using a quantitative real-time polymerase chain reaction (qRT-PCR) assay. A ten-microRNA signature (hsa-miR-1271-5p, hsa-miR-574-3p, hsa-miR-182-5p, hsa-miR-183-5p, hsa-miR-96-5p, hsa-miR-15b-5p, hsa-miR-182-3p, hsa-miR-141-5p, hsa-miR-130b-5p, and hsa-miR-135b-3p) was identified to be able to distinguish human ovarian cancer tissues from normal tissues with 97% sensitivity and 92% specificity. Two miRNA clusters of miR183-96-183 (miR-96-5p, and miR-182, miR183) and miR200 (miR-141-5p, miR200a, b, c and miR429) are significantly up-regulated in ovarian cancer tissue samples compared to those of normal tissue samples, suggesting theses miRNAs may be involved in ovarian cancer development.”, (abstract).
Effatpanah et al teaches the role of miR-182-3p in breast cancer.
“Similarly, miR-182-3p has been extensively studied for its roles in cancer biology, with evidence suggesting its involvement in promoting migration and invasion in breast cancer cells [9]. The ability of miR-182-3p to influence processes such as epithelial-mesenchymal transition (EMT) makes it a potential contributor to metastasis and poor clinical outcomes in breast cancer patients [10]. The dysregulation of miR-182-3p in breast cancer adds to the urgency of investigating its levels in the bloodstream as a biomarker for early detection and monitoring of disease progression.”, (p. 2408, col 1, para 3).
Zheng et al teaches the role miR-182-3p plays in downregulating parafibromin, which in turn is linked to head and neck, gastric, lung, colorectal, and ovarian cancers.
“In this review, we discuss parafibromin protein, which is encoded by CDC73. A mutation in this gene causes hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disease. CDC73 is transcriptionally downregulated by the Wilms’ tumor suppressor gene WT1 and translationally targeted by miR-182-3p and miR-155. . . . In addition, down-regulated parafibromin is closely linked to the tumorigenesis, subsequent progression, or poor prognosis of head and neck, gastric, lung, colorectal, and ovarian cancers, and its overexpression might reverse the aggressiveness of these cancer cells. Therefore, parafibromin might be useful as a biological marker of malignancies and a target for their gene therapy.
With regard to the teachings of Wang et al, i.e., “Two miRNA clusters of miR183-96-183 (miR-96-5p, and miR-182, miR183) and miR200 (miR-141-5p, miR200a, b, c and miR429) are significantly up-regulated in ovarian cancer tissue samples”, Li et al (MiR-183/-96/182 cluster is upregulated in most breast cancers and increases cell proliferation and migration, Breast Cancer Research, vol 16, issue 473, pages 1-17, published November 14th, 2014) teaches that “The miR-183/-96/-182 cluster was highly expressed in most breast cancers, and its transcription is disordered in breast cancer. The miR-183/-96/-182 cluster was transcribed in the same pri-miRNA and its transcription was regulated by ZEB1 and HSF2. It increased breast cell growth by promoting more rapid completion of mitosis, promoted cell migration and was essential for cell survival.”, (Results, p. 1).
This is also true for Triple negative breast cancer, where Liu et al (Expression and Regulatory function of miRNA-182 in triple-negative breast cancer cells through its targeting of profilin 1, Tumor Biol, vol 34, pages 1713-1722, published February 22nd, 2013) teaches, “In conclusion, miR-182 is upregulated in TNBC tissues and cells. It promotes the proliferation and invasion of MDA-MB-231 cells and could negatively regulate PFN1 protein expression. Treatment strategies utilizing inhibition of miR-182 expression or overexpression of the PFN1 gene might benefit patients with TNBC.”, (p. 1713, col 2, para 1 – bottom).
Accordingly, the art teaches that increased levels of miR-182-3p promotes rapid completion of mitosis, cell migration, and cancer cell survival. The art teaches that dysregulation of miR-182-3p indicates poor clinical outcomes. Further Zhang et al teaches that the microRNAs have tens to hundreds of targets. Salmeron-Barcenas et al (Identification of Mir-182-3p/FLI-1 Axis as a Key Signaling in Immune Response in Cervical Cancer: A Comprehensive Bioinformatic Analysis, Int J of Mol Sci, vol 24, issue 6032, pages 1-16, published March 23rd, 2023) teaches that there are at least 330 targets of miR-182-3p (p. 2, para 4). Applicant also stated in the specification and drawings that not only was there high levels of miR-182-3p in the tumor, but also in non-tumor organs for example the brain (p. 21, lines 17-20). Thus, administration of miR-182-3p, a known as a cancer diagnosis marker in the art, one that is linked to tumorigenesis, is not enabled.
Amount of experimentation necessary:
The quantity needed to carry out the scope of the invention is large. The art teaches microRNAs are not enabled for therapeutic treatment, especially, miR-182-3p, a microRNA known for promoting cancer cell survival. One would need to identify a model of cancer/tumor where miR-182-3p is not elevated, but TRF2 is overexpressed. Once that model has been identified, one would need to perform local intratumorally administration of miR-182-3p so that high circulation of miR-182-3p does not cause cancer to form in other parts of the body. This type of experimentation is not routine in the art and would require a large amount of inventive effort. Further considering that any positive results (e.g., successful treatment of any/all tumors with miR-182-3p) would amount to a significant advancement in the state of the art, additional experimentation required is considered undue.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 1-19 are not considered to be enabled by the instant disclosure.
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.
Claim 20 is rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature without significantly more.
Step 2A: Prong One.
The independent claim recites, “wherein an expression level of TRF2 greater than the expression level of TRF2 in a sample of healthy tissue and/or in a sample of non-metastatic primary breast cancer indicates a risk of developing metastasis;. . .”. This is a natural law of correlation.
Step 2A: Prong Two.
The judicial exception is not integrated into a practical application. The independent claim as a whole, looking at the additional elements individually and in combination does not integrate the judicial exception into a practical application.
The independent claim recites the additional limitation, “measuring the expression of TRF2 in a sample of primary breast cancer from said patient . . . (natural law of correlation); and administering a therapeutically effective amount an adjuvant therapy to said patient who is at risk of developing metastasis.” The step of measuring is insignificant extra-solution activity, i.e., determining the level of a biomarker. The administered treatment is a general treatment that does not rely upon the judicial exception in a meaningful way because the same treatment is applied regardless of TRF2 expression in patients with primary breast cancer.
Step 2B
The independent claim does not include additional elements that are sufficient to amount
to significantly more than the judicial exception. As mentioned in Step 2A: Prong Two above,
the independent claim recites the additional limitation of (1) “measuring the expression of TRF2 in a sample of primary breast cancer” and (2) “administering a therapeutically effective amount an adjuvant therapy to said patient who is at risk of developing metastasis.”
The measuring of the expression of TRF2 in a sample of primary breast cancer well-understood, routine, and a conventional activity in the art. Cherfils-Vicini et al (Cancer cells induce immune escape via glycocalyx changes controlled by the telomeric protein TRF2, The Embo Journal, vol 38, pages 1-20 and supplement pages EV1-EV10, published April 18th, 2019) teaches measuring TERF2 levels with both RT-qPCR (p. 18, col 1, para 4 to col 2 para 1) and RNA sequencing in breast cancer versus normal tissues in Figure EV5F (p. EV9, under figure legend for figure EV5F).
The administration of an adjuvant therapy is routinely used by those of ordinary skill in the art. Administering an adjuvant therapy for breast cancer metastasis is well-understood, routine, and a conventional activity in the art. Chew (Adjuvant therapy for breast cancer: who should get it? West J Med, Vol 174, Issue 4, pages 284-287, published April of 2001) teaches “Unfortunately, nearly 30% of women with cancer confined to the breast and 75% of women with nodal involvement will ultimately relapse.2 This observation affirms the presence of micrometastases, clinically occult tumor present after surgery with a potential to metastasize and confer both morbidity and mortality. Adjuvant treatment is the administration of additional therapy after primary surgery to kill or inhibit micrometastases. Primary surgery for breast cancer is accomplished by lumpectomy followed by whole-breast irradiation or by mastectomy. Adjuvant treatment may include local irradiation after mastectomy, systemic therapy with cytotoxic chemotherapy, or endocrine therapy. For the first time, a decrease was noted in breast cancer mortality in the United States and the United Kingdom, a welcome trend likely due to the use of adjuvant treatments.”, (p. 284, col 1).
Thus, the additional elements do not add significantly more. The claim as a whole does not amount to significantly more than a judicial exception.
Accordingly, claim 20 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more.
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 20 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cherfils-Vicini et al (supra).
Regarding claim 20, Cherfils-Vicini et al teaches measuring TERF2 expression of breast cancer compared with normal tissue in Figure EV5F. Cherfils-Vicini et al et al further teaches adjuvant treated (surgery or endocrine therapy) patients with breast cancer according to TRF2 expression level in Figure EV5B. Lastly, Cherfils-Vicini et al teaches, “TRF2-mediated regulation of MDSCs plays a central role in the TRF2-dependent increases in tumorigenicity and metastasis, shaping the tumor immune microenvironment.”, (see page 4, col 1, para 1).
Accordingly, claim 20 is anticipated by Cherfils-Vicini et al.
Conclusion
No claims allowed.
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/L.M.T./Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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