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. Priority The instant application, filed 11/17/2023 , is a national stage entry of PCT/EP2022/063422 , filed 05/18/2022 , which claims foreign priority to FR2105217 , filed 05/19/2021 . Receipt is acknowledged of certified copies of papers required by 37 CFR § 1.55 . Amendments and Claim Status The preliminary amendment filed on 11/17/2023 is acknowledged and entered. Claims 3-10, 12, and 13 are amended; Claims 1-15 are pending . Information Disclosure Statement The Information Disclosure Statement filed on 11/17/2023 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered. Specification The disclosure is objected to becau se of the following informalities: Throughout the disclosure, several low resolution images of the two-dimensional chemical structures disclosed are included (see pages 3-7). Applicant is kindly requested to include images of better resolution and clearer images to describe the compounds. Drawings The drawings filed on 11/17/2023 are objected to under 37 CFR § 1.83(a) for the following reasons: The residue numbers are indistinguishable in Figure 5A. The original figure relies on color-coding of the data, a feature not available in the black and white drawings. Specifically, the shading of data points 7506 and 7605 is very close and hard to distinguish. The figures must be remade with direct labels of the data, shapes or line-types , used to more clearly describe the different data points. The residue numbers are indistinguishable in Figures 11B and 11C due to the low resolution of the images used. The figures must be remade with clear images which reflect the residue numbers. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). 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 Claims 2, 3, 5, 6, and 8 are objected to for the use of low resolution images of the two-dimensional chemical structures disclosed. Furthermore, the images used to describe the chemical structures is not consistent with the rest of the claim set. Applicant is kindly requested to include images of higher resolution and clearer images to describe the chemical structures . Claim Interpretation Claim 10 is subject to the following interpretation: Claim 10 recites, “wherein L 2 and L(E3 ligase) are as defined according to claim 1 . ” Although L(E3 Ligase) is defined by claim 1, L 2 is not. That is, the limitation of L 2 is not recited in claim. As such, the limitation L 2 is interpreted as being drawn to L 2 as defined by claim 7. Claim Rejections - 35 U.S.C. § 112 (a) 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 1-7, 9, 10, 12-15 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. Claims 1-7, 9, 10, 12-15 of the instant application are drawn to compounds having the following substituents: X’ is —C(O)— or —CH 2 —; Y represents H or a C1-C6 alkyl group; Linker represents a C1-C20 alkylene group, optionally interrupted or optionally terminating at either and/or both ends, by one of the groups —O—, —S—, —N(R′)—, —C(O)—, —C(O)O—, —OC(O)—, —OC(O)O—, —C(NOR′)—, —C(O)N(R′)—, —C(O)N(R′)C(O)—, —C(O)N(R′)C(O)N(R′)—, —N(R′)C(O)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —OC(O)N(R′)—, —C(NR′)—, —N(R′)C(NR′)—, —C(NR′)N(R′)—, —N(R′)C(NR′)N(R′)—, —S(O) 2 —, —OS(O)—, —S(O)O—, —S(O)—, —OS(O) 2 —, —N(R′)S(O) 2 —, —S(O) 2 N(R′)—, —N(R′)S—, —S(O)N(R′)—, —N(R′)S(O) 2 N(R′)—, —N(R′)S(O)N(R′)—, C 3 -C 12 carbocyclene , 3-to-12-membered heterocyclene comprising 1, 2 or 3 heteroatoms selected from N, O, S, 5-to-12-membered heteroarylene comprising 1, 2 or 3 heteroatoms selected from N, O, S, or any combination thereof ; R′ represents H or a C 1 -C 6 alkyl group ; Z represents H or a C1-C6 alkyl group; L 1 and L 2 represent an alkylene group of 1 to 12 carbon atoms optionally interrupted or terminating by a 3-to-12-membered heterocyclene comprising 1, 2 or 3 heteroatoms selected from N, O, S; 35 U.S.C. § 112(a) and the first paragraph of pre-AIA 35 U.S.C. § 112 require that the "specification shall contain a written description of the invention ...." This requirement is separate and distinct from the enablement requirement. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1340, 94 USPQ2d 1161, 1167 (Fed. Cir. 2010) ( en banc); Vas-Cath, Inc. v. Mahurkar , 935 F.2d 1555, 1560, 19 USPQ2d 1111,1114 (Fed. Cir. 1991); see also Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920-23, 69 USPQ2d 1886, 1890-93 (Fed. Cir. 2004) (discussing the history and purpose of the written description requirement); In re Curtis, 354 F.3d 1347, 1357, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004) ("conclusive evidence of a claim’s enablement is not equally conclusive of that claim’s satisfactory written description"). The written description requirement has several policy objectives. "[T]he ‘essential goal’ of the description of the invention requirement is to clearly convey the information that an applicant has invented the subject matter which is claimed." In re Barker, 559 F.2d 588, 592 n.4, 194 USPQ 470, 473 n.4 (CCPA 1977). Another objective is to convey to the public what the applicant claims as the invention. See Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997), cert, denied, 523 U.S. 1089 (1998). "The ‘written description’ requirement implements the principle that a patent must describe the technology that is sought to be patented; the requirement serves both to satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed." Capon v. Eshhar , 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1084 (Fed. Cir. 2005). Further, the written description requirement promotes the progress of the useful arts by ensuring that patentees adequately describe their inventions in their patent specifications in exchange for the right to exclude others from practicing the invention for the duration of the patent’s term. 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 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 applicant was in possession of the claimed invention. See, e.g., Pfaffv . Wells Bees., Inc., 525 U.S. 55, 68, 119 S.Ct . 304, 312, 48 USPQ2d 1641, 1647 (1998); EliLilly , 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). An application specification may show actual reduction to practice by describing testing of the claimed invention. In the present case, the important factors leading to a conclusion of inadequate written description is the absence of any working example of the invention as claimed, and the lack of predictability in the art. In the instant specification, there is no disclosure of compounds having the following claimed substituents: X ’ as —CH 2 —; Y as a C1-C6 alkyl group; Linker as a C1-C7 or C16-C20 alkylene group optionally interrupted or optionally terminating at either and/or both ends, by one of the groups —O—, —S—, —N(R′)—, , —C(O)O—, —OC(O)—, —OC(O)O—, —C(NOR′)—, —C(O)N(R′)—, —C(O)N(R′)C(O)—, —C(O)N(R′)C(O)N(R′)—, —N(R′)C(O)N(R′)—, —N(R′)C(O)O—, —OC(O)N(R′)—, —C(NR′)—, —N(R′)C(NR′)—, —C(NR′)N(R′)—, —N(R′)C(NR′)N(R′)—, —S(O) 2 —, —OS(O)—, —S(O)O—, —S(O)—, —OS(O) 2 —, —N(R′)S(O) 2 —, —S(O) 2 N(R′)—, —N(R′)S—, —S(O)N(R′)—, — N(R′)S(O) 2 N(R′)—, —N(R′)S(O)N(R′)—, C 3 -C 12 carbocyclene , 3-to -5 or 7 - to- 12-membered heterocyclene comprising 1, 2 or 3 heteroatoms selected from N, O, S, 5-to-12-membered heteroarylene comprising 1, 2 or 3 heteroatoms selected from N, O, S, or any combination thereof; R′ as a C 1 -C 6 alkyl group; Z as a C1-C6 alkyl group; L 1 as an alkylene group of 8 to 12 carbon atoms optionally interrupted or terminating by a 3- to-12-membered heterocyclene comprising 1, 2 or 3 heteroatoms selected from N, O, S; L 2 as an alkylene group of 8 to 12 carbon atoms optionally interrupted or terminating by a 3-to-12-membered heterocyclene comprising 1, 2 or 3 heteroatoms selected from N, O, S; The instant specification (pages 12-15 and 24-42 ) teaches compounds which are characterized as having only the following substituents: X’ is —C(O)— ; Y is H ; R′ is H ; Z is H ; L 1 is an alkylene group of 1 to 7 carbon atoms ; L 2 is an alkylene group of 1 to 7 carbon atoms optionally interrupted or terminating by a 6-membered heterocyclene comprising 1or 2 N heteroatoms ; Therefore, the compounds described in the instant specification detail only a limited number of the total substituents claimed (see substituents 1- 6 , above). All working examples presented in the instant specification are related to the compounds containing a fraction of the total claimed substituents (see substituents 1 4 -1 9 , above). Regarding claims 1, 2, 9, 10 and 12-15, the claims are inclusive of essentially any linker and any ligand capable of binding to PXR and not to the specific ligands , linkers, or bifunctional compounds disclosed in the specification or claims. Thus, Applicant claims subject matter for which possession has not been shown. For example, the L(PXR) may be a compound other than that of Formula (II) , w hich is , at present, unsupported by the instant specification . The same is true for L(E3 ligase) and the Linker. Therefore, the subject matter of the specific instant claims remains unsupported by the specification, as no evidence of possession has been provided for that which is claimed. There are no working examples in the instant specification for the wide range of linkers, ligands , and substituents claimed, but for which evidence of possession has not been provided (see substituents 7-13 , above ). Thus the instant specification does not provide any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application. Vas-Cath Inc. Mahurkar , 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed" ( s ee page 1117) . The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" ( s ee Vas-Cath at page 1116). Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F. 3d 1565, 1572, 41 USPQ2d 1961, 1966(1997); In re Gosteli , 872 F.2d 1008, 1012,10 USPQ2d 1614, 1618 (Fed Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.") Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966. It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For example, disclosure of only a method of making the invention and the function may not be sufficient to support a product claim other than a product-by-process claim. See, e.g., Fiers v. Revel, 984 F.2d at 1169, 25 USPQ2d at 1605; Amgen, 927 F.2d at 1206, 18 USPQ2d at 1021. Thus, since Applicant has not described in adequate detail methods to synthesize compounds containing the claimed substituents, or provided evidence that said compounds have been characterized, or that they exist, an ordinary skilled artisan could not completely envisage Applicants’ invention. Moreover, it is clear that the written description requirement has not been met since Applicant has not provided any evidence that Applicant was in possession of the claimed invention prior to the effective filing of the instant application. Thus, claims 3-7 of the instant application are not supported by the instant specification and thus a rejection under 35 U.S.C. § 112 (a) for failing to comply with the written description requirement is proper . Claim s 13 -15 are rejected under 35 U.S.C. § 112 (a), or 35 U.S.C. § 112 (pre-AIA) first paragraph, because the specification, while being enabling a bifunctional compound of formula (I) for the degradation of PXR, it does not reasonably provide enablement for a bifunctional compound of formula (I) for use in the prevention of cancer overexpressing PXR nuclear receptor. The specification does not provide sufficient information to support the claim as recited. The instant specification fails to provide information that would allow the skilled artisan to fully practice the instant invention without undue experimentation . Attention is directed to In re Wands , 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman , 230 USPQ 546 ( BdApls 1986) at 547 the court recited eight factors, which are considered in determining whether undue experimentation is required to practice the invention: (1) Nature of the invention; (2) Breadth of the claims; (3) State of prior art; (4) Level of ordinary skill in the art; (5) Level of predictability in the art; (6) Amount of direction provided; (7) Presence of working examples; and (8) Quantity of experimentation required to make or use the invention. In re Wands , 858 F.2d 731, 737 (Fed. Cir. 1988). All of the Wands factors have been considered with regard to the instant claim, with the most relevant factors discussed below. Nature of the invention : Claim 13 of the instant application is drawn to a compound useful in the treatment and/or prevention of cancer overexpressing PXR nuclear receptor. Breadth of the claims : The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims are extremely broad. Applicant claims that the claimed compounds can be used to treat a subject having, suspected of having, or at risk of developing cancer overexpressing PXR nuclear receptor. Thus the cited claims are deemed very broad since these claims read on essentially preventing any cancer related to the overexpression of PXR nuclear receptor comprising the administration of a compound of Formula (I), which includes subjects at risk of developing a broad range of cancers. State of the Prior Art: While the state of the art with regard to the treatment of cancer is relatively high, the state of the art with regard to the prevention of cancer is underdeveloped. This is because there would be no way to determine that cancer would have predictably occurred without treatment. Regarding prevention of cancer, the American Cancer Society maintains that “ There's no sure way to prevent cancer , but you can help reduce your risk by making healthy choices like eating right, staying active, and not smoking” ( American Cancer Society. Cancer Risk and Prevention. https://www.cancer.org/cancer/risk-prevention.html ). Predictability/Unpredictability in the Art : It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity in preventing diseases. In re Fisher , 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that the recitation encompasses the prevention of cancer and other disorders and treating subjects and risk of developing and those subjects suspected having of cancer overexpressing PXR nuclear receptor. Thus, the skilled artisan would view that the prevention of all disorders/diseases encompassed by the claims, by administering a compound of Formula (I), is highly unpredictable. Guidance of the Specification/Working Examples : Applicant has only provided working examples suggesting that compounds of Formula (I) may degrade PXR in vivo and that PROTACs may be used in chemoresistant colic cancer stem cells. Thus, the specification fails to provide sufficient evidence in support of prevention or treatment of those suspected of having or at risk of developing cancer overexpressing PXR nuclear receptor as recited in the instant claims. Additionally, the examples provided do not demonstrate the prevention of any cancer . T he disclosure does not discuss, or demonstrate through working examples, a method that could be used to determine that recurrence of diseases/disorders was prevented using the claimed agents as there is no disclosed method to determine that recurrence of cancer or any of the aforementioned diseases would have predictably occurred without treatment . The Quantitation of Experimentation Required : In order to practice Applicants invention, it would be necessary for one to design and conduct an exhaustive amount of complex experiments to demonstrate that the claimed compounds could be administered to a subject at risk of developing cancer overexpressing PXR nuclear receptor . The population of subjects could include any subject, and thus the quantitation of experimentation is unreasonably large. Therefore, in order to practice the claimed invention, the amount of experimentation required would be considered undue and burdensome. In conclusion, Genentech , 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p] atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. A compound of Formula (I) for use in t he prevention of cancer overexpressing PXR nuclear receptor is not enabled by the instant specification . Claim s 1 3-15 are rejected under 35 U.S.C. § 112 (a), or 35 U.S.C. § 112 (pre-AIA) first paragraph, because the specification, while being enabling for a bifunctional compound of formula (I) for use in the degradation of PXR, it does not reasonably provide enablement for a bifunctional compound of formula (I) for use in the treatment of any cancer overexpressing PXR nuclear receptor. The specification does not provide sufficient information to support the claim as recited. The instant specification fails to provide information that would allow the skilled artisan to fully practice the instant invention without undue experimentation . Attention is directed to In re Wands , 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman , 230 USPQ 546 ( BdApls 1986) at 547 the court recited eight factors, which are considered in determining whether undue experimentation is required to practice the invention: (1) Nature of the invention; (2) Breadth of the claims; (3) State of prior art; (4) Level of ordinary skill in the art; (5) Level of predictability in the art; (6) Amount of direction provided; (7) Presence of working examples; and (8) Quantity of experimentation required to make or use the invention. In re Wands , 858 F.2d 731, 737 (Fed. Cir. 1988). All of the Wands factors have been considered with regard to the instant claim, with the most relevant factors discussed below. Nature of the invention : Claim s 13 -15 of the instant application are drawn to a compound useful in the treatment and/or prevention of cancer overexpressing PXR nuclear receptor. Breadth of the claims : The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The rejected claims are extremely broad. Applicant claims that the claimed compounds can be used to treat any cancer overexpressing PXR nuclear receptor. Thus the cited claims are deemed very broad since these claims read on the use of a broad range of compounds in treating or preventing all cancers overexpressing PXR nuclear receptor, which includes numerous cancers. State of the Prior Art: There are no art recognized methods that could be used to establish that the instantly claimed diseases can be commonly addressed using the claimed compounds . Additionally, the disclosure does not discuss, or demonstrate through working examples, using the claimed agents to prevent or treat any disease . Additionally, there are no art recognized methods that could be used to identify subjects who would have predictably developed the broad spectrum of the cancers claimed in order to determine that the cancers were treated using the claimed compounds . With regard to the compounds instantly claimed, according to Bansard et al ( Oncogenisis , Volume 14, Issue 43, published August 30, 2025), hereinafter Bansard , the state of the art demonstrates that the instantly claimed bifunctional compound is capable of degrading PXR in selected cancer cell lines—colon adenocarcinoma, hepatoma, and metastatic pancreatic adenocarcinoma cells (pages 4-11) . It is proposed as a therapeutic strategy for chemo resistant cancers, especially in the context of colon adenocarcinoma, hepatoma, and metastatic pancreatic adenocarcinoma cancer types. The disclosure therefore supports relationship between the PROTAC and treatment of certain PXR-associated chemo resistant cancers, but it does not establish that the PROTAC is a universal cancer treatment for any and all cancers overexpressing PXR nuclear receptors. That is, the disclosure demonstrates that the instantly claimed compounds may be capable of successful treatment of colon adenocarcinoma, hepatoma, and metastatic pancreatic adenocarcinoma which overexpress PXR nuclear receptors and not all cancers overexpressing PXR nuclear receptors, in general. In support of the argument of limited efficacy of the compounds, Bansard reports that JMV7048, a PXR-targeted PROTAC is not capable of degrading PXR in human hepatocytes (Figure 4 and page 6). As such, the state of the prior art demonstrates that the instantly claimed compounds may treat a limited number of cancers overexpressing PXR nuclear receptors, and not all cancers overexpressing PXR nuclear receptors, as instantly claimed. Regarding common disease mechanisms and biomarkers in cancer, McKean et al. (Biomarkers in precision cancer immunotherapy: Promise and challenges. American Society of Clinical Oncology – Educational Book (2020), 40, p.e275-e291), hereinafter McKean , teaches that although ongoing studies and trials investigate the use of multiple biomarkers predictive of patient response or harm, none of these are comprehensive in predicting potential benefit (of treatment). This unmet need for validated biomarkers is largely secondary to a prohibitive complexity within tumor parenchyma and tumor microenvironment, dynamic clonal and proteomic changes to therapy, heterogenous host immune defects, and varied standardization among sample preparation and reporting (Abstract). McKean also teaches that treatment failures occur even in ICI patient cohorts, despite respective prescreening with biomarkers such as PD-L1 tumor proportion scores (p.e275). Regarding gene expression profiles specifically, McKean teaches that an important concept within gene expression profiles is that the predictive utility of such algorithms may be dependent on individual therapy plans. Data suggest that signaling and transcriptomic patterns may correlate only with response to therapy of directly related targets (p.e280). Unrelated immune pathways may require separate and individualized gene expression assays for different therapies (p.e280). Therefore, the selection of a particular therapy for any specific type of cancer is unpredictable , and requires individualized assays that are fully described to achieve correlation. Predictability/Unpredictability in the Art : The pharmaceutical arts, particularly the treatment of cancer, are well-recognized as highly unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher , 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. The courts have upheld that in unpredictable arts, a greater degree of specificity is required to satisfy the enablement requirement. Cancer comprises a heterogeneous group diseases the distinct molecular drivers, signaling pathways, and therapeutic responses. As such, a person of ordinary skill in the art would recognize the inhibition of cancer- implicated enzymes in vitro, do not reliably predict therapeutic efficacy across different cancers, cancer subtypes, or patient populations. The translation of enzyme inhibition or cell line activity into effective cancer treatment depends on numerous factors, including tumor biology, compensatory signaling mechanisms, tissue specific effects, toxicity, and therapeutic window, none of which are addressed in a comprehensive or predictive manner in the instant specification. Moreover, one of skill in the art would recognize that it is highly unpredictable in regard to therapeutic effects, side effects and toxicity generated by administering a singular class of compounds for used in treating/preventing all the diseases and cancers encompassed by the claims. Guidance of the Specification/Working Examples : Applicant has only provided working examples suggesting that compounds of claim 1 may treat chemoresistan t colic cancer stem cells (page 48). Thus, the specification fails to provide sufficient evidence in support of the broad treatment of all cance rs overexpressing PXR nuclear receptor as recited in the instant claims . The Quantitation of Experimentation Required : In order to practice Applicants invention, it would be necessary for one to design and conduct an exhaustive amount of complex experiments to demonstrate that the large range of cancers overexpressing PXR nuclear receptors can be treated by the administration of the compounds claimed. Therefore, in order to practice the claimed invention, the amount of experimentation required would be considered undue and burdensome. Such experimentation would necessarily include cancer specific validation of therapeutic efficacy, optimization of dosing regimens, assessment of toxicity and side effect profiles, and identification of responsive versus nonresponsive cancer subtypes. The specification provides only limited in vitro data demonstrating activity in to the numerous additional cancers recited in the claims. Accordingly, determining which cancers may be effectively treated would require extensive, individualized experimentation, amounting to undue burden. In conclusion, Genentech , 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p] atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. A compound of Formula (I) for use in the treatment and/or prevention of cancers overexpressing PXR nuclear receptors is not enabled by the instant specification. Claim Rejections - 35 U.S.C. § 112 ( b ) The following is a quotation of 35 U.S.C. § 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. § 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the appl icant regards as his invention. Claim 10 is 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. Claim 10 recites, “wherein L 2 and L(E3 ligase) are as defined according to claim 1 . ” Although L(E3 Ligase) is defined by claim 1, L 2 is not. That is, the limitation of L 2 is not recited in claim 1 whatsoever . Therefore, there is insufficient antecedent basis for th e limitation (L 2 ) in the claim. Claim Rejections - 35 U.S.C. § 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 1 and 13 is rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Chai et al ( Med Res Rev , Volume 40 , pages 1061–1083 ), hereinafter Chai . The instant claim is drawn to a bifunctional compound of Formula (I), made up of a ligand capable of binding to the PXR nuclear receptor, a ligand of the E3-ubiquitin ligase, and group which makes it possible to link the two ligands to each other. 2644140 799465 0 0 2446020 210185 Figure 1 . Bifunctional compound: PXR-targeting linked to machinery for degradation by E3 Ligase by PROTACs as taught by Chai 0 0 Figure 1 . Bifunctional compound: PXR-targeting linked to machinery for degradation by E3 Ligase by PROTACs as taught by Chai 2583180 2915285 Fig 1 . a) A bifunctional compound targeting PXR, linked to recruiting machinery E3 ubiquitin ligase by PROTACs (see Figure 5D and caption, page 1076 of Chai) 0 0 Fig 1 . a) A bifunctional compound targeting PXR, linked to recruiting machinery E3 ubiquitin ligase by PROTACs (see Figure 5D and caption, page 1076 of Chai) Chai surveys the development of P regnane X receptor (PXR) antagonists, and discusses the principal challenges and proposed development approaches (Title, Abstract ). One of the development strategies discussed by Chai is the use of PROTACs to c oupl e PXR ligand s to recruit machinery for degradation, such as the recruitment of E3 ubiquitin ligase (Figure 5D, page 1076). Within the Figure, the PXR ligand is linked to a protein for degradation using a linker (see Figure 5D reproduced herein ). Regarding claim 13, wherein the compound of claim is for use in the treatment and/or prevention of cancer over expressing the PXR nuclear receptor , this is merely recitations of intended use of the compound . According to MPEP § 2112.01 (I), where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. The courts have stated , In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not. “See In re Spada "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty."). Therefore, if the prior art structure is capable of performing the intended use, the prior art is capable of performing the claimed use, and thus , meets the claims. Claim Rejections - 35 U.S.C. § 103 The following is a quotation of pre-AIA 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. Claim s 2, 14, and 15 are rejected under 35 U.S.C. § 103 as being unpatentable over Chai (see earlier citation) as applied to claim 1, above, in view of Benod et al. ( Bioorg Med Chem, Volume 16, pages 3537-3549 , published February 13, 2008, cited on Applicant IDS dated 11/17/2023 ), hereinafter Benod . 3642360 228600 0 4465955 954161 0 0 The instant claim is drawn to a bifunctional compound having the general Formula (I) , where in the ligand L(PXR) capable of binding to the PXR nuclear receptor, wherein the compound is of Formula ( I I) : The teachings of Chai are as set forth above. In relation to the instant claims, Chai further teaches that PXR is implicated in cancer drug resistance because PX R activation induces resistance to c hemotherapeutic agents used to treat cancer (page) and enhances the drug metabolizing pathway to reduce the sensitivity of tumor cells to chemotherapeutic agents (page 1062 ). Chai teaches that PX art antagonists may be co - administered with other drugs activate PXR, highlighting that such antagonists are being developed as co-drugs to prevent or overcome cancer drug resistance (page 1075). Chai fails to teach wherein the specific ligand capable of binding to PXR in a bifunctional PROTAC is that of Formula ( I I) . The deficiencies of Chai are remedied by Benod , who teaches N-1H-Benzimidazol-5-ylbenzenesulfonamide derivatives as potent hPXR agonists (Title). Specifically, Benod teaches CAS Registry Number: RN 1026754-80-2 . [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 1026754-80-2 , Entered STN: 09 Jun 2008 ] (Table 3, compound 6 m ). Benod reported a sharp increase in potency through the introduction of three methyl groups on the phenyl ring of R 5 , with a resulting EC 50 of 1.5 nM. The compound 6m was shown to be one of the most highly active (see section 3.3, page 3544). The disclosure identified N-1H-benzimidazol-5ylbenzenesulfonamide scaffold that allows for the design of potent PXR agonist ligands (page 3545). Prior to the filing of the instant application, a person having ordinary skill in the art following the teachings of Chai would have found it prima facie obvious to use a known highly - active compound known to bind to PXR taught by Benod into a dual PROTAC compound in an order to develop an effective PXR-targeted compound in order to degrade the well-known disease target. Regarding claim s 14, and 15, Chai teaches that PROTACs targeting the degradation of PXR may be useful in the treatment of cancer. Furthermore, Chai explicitly teaches that the administration of PXR-directed therapy with an anticancer agent might be useless therapeutics that can be co-administered with other drugs that activate PXR (page 1076), specifically identifying paclitaxel as a relevant PXR-targeting therapy (1065), in order to reduce PXR-mediated drug resistant and toxicity . Thus, the reference explicitly teaches that inhibition of PXR is useful in combination with anticancer therapy to address cancer drug resistance. Further regarding claim 14, a ccording to MPEP 2144.06 (I), combining equivalents known for the same purpose is rendered obvious. The courts have said, It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980 ) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). According to the teachings of Chai as set forth above, a PXR-targeting PROTAC and an anticancer drug are equivalents that would be used for the same objective—cancer treatment and mediating drug resistance. Therefore, a person of ordinary skill in the art prior to the filing of the instant application would have found it obvious to combine a PROTAC and degrades or otherwise inhibits PXR with an anticancer drug, as both are found to be used for a common purpose, i.e., treating cancer and preventing or overcoming PXR-mediated cancer drug resistance. Statement of Allowable Subject Matter Claim 11 is allowed . The following is a statement of reasons for the indication of allowable subject matter: The instant claim is drawn to a compound of Formula ( A ) , also known as CAS Registry Number: RN 2871774-93-3. [Database Registry Chemical Abstracts Service, Columbus, Ohio, Accession No. RN 2871774-93-3, Entered STN: 19 Dec 2022]. In searches of the prior art, the disclosure of Benod (IDS reference, see earlier citation) was identified as the closest prior art, disclosing compounds which contain the N-1H-Benzimidazol-5-ylbenzenesulfonamide scaffold found in the instantly claimed Formula ( A ) . However, the disclosed compounds lack the long-chain hydrocarbon terminating with an unsubstituted amino substituent as instantly claimed. This reference does not encompass the scope of the instantly claimed compound with the long hydrocarbon amino substituent on the core of the molecule. This is considered a non- obvious feature, as nothing within the prior art would suggest or drive a person of ordinary skill in the art to substitute the unique long-chain hydrocarbon amino substituent in the compounds disclosed by Benod . Correspondence Claims 2, 3, 5, 6 , and 8 are objected to . Claims 1-10 and 12-15 are rejected. Claim 11 is allowed . Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Sophia P. Hirakis whose telephone number is +1 FILLIN "Phone number" \* MERGEFORMAT (571) 272-0118 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT within the hours of 5:00 am to 5:00pm EST, Monday through Friday . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached on +1 (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is +1 (571) 273-8300. 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