DETAILED ACTION
Status of Claims
The amendment submitted August 6, 2025 has been entered.
Claims 1-12 are pending
Claims 13-41 are/were previously cancelled by Applicant.
Claims 1-12 are under consideration in the instant office action as explained below in the Election/Restriction section.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12, drawn to a method of treating cancer, comprising selecting a patient who is AHR nuclear positive, and administering to the patient a therapeutically effective amount of an AHR inhibitor in the reply filed on August 6, 2025 is acknowledged.
Applicant’s election without traverse of Compound A as the AHR inhibitor or antagonist (shown below) in the reply filed on August 6, 2025 is likewise acknowledged.
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The elected species reads on claims 1-12.
The remaining claims 25, 27-30, 33-34 and 38 were cancelled by Applicant.
Consequently, claims 1-12 are currently under examination and are the subject of this office action.
Information Disclosure Statement
One information disclosure statements (IDS) submitted on January 23, 2023 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
Abstract Objections
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is less than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 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 1-12 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. See MPEP § 2164.01 (a).
Upon consideration of the factors discussed below, the examiner concludes that one skilled in the art would be unable to practice the invention as disclosed without being burdened with undue experimentation based on the information provided by the applicant.
A discussion of these factors in relation to the pending claims follows.
The breadth of the claims and nature of invention
Claims 1-12 are directed towards methods “of treating cancer, comprising selecting a patient who is AHR nuclear positive, and administering to the patient a therapeutically effective amount of an AHR inhibitor.”
Page 7 paragraph [0033] defines “AHR inhibitor” as “As used herein, the term “an AHR inhibitor’ refers to a compound, or a pharmaceutically acceptable salt or ester thereof, which inhibits AHR activity in a biological sample or in a patient. An AHR inhibitor, also referred to herein as an AHR antagonist, can bind but does not activate the AHR polypeptide or polynucleotide encoding the AHR, and the binding disrupts the interaction, displaces an AHR agonist, and/or inhibits the function of an AHR agonist. An AHR inhibitor, or an AHR antagonist, can include small molecules (organic or inorganic), proteins, such as antagonistic anti-AHR antibodies, nucleic acids, amino acids, peptides, carbohydrates, or any other compound or composition which decreases the activity of AHR, either by reducing the amount of AHR present in a cell, or by decreasing the binding or signaling activity or biological activity of AHR, such as by, for example, blocking AHR from translocating from the cytoplasm to the nucleus in the presence of a ligand and/or blocking downstream signaling activities. Various AHR antagonists have been described previously, for example, in WO02017202816A1, WO02018085348A1, WO02018195397, WO02019101642A1, WO02019101643A1, WO02019101641A1, WO02019101647A1, WO02019036657A1,US10570138B2, US10689388B1, US10696650B2, WO2020051207A2, WO2020081636A1, and WO02020081840A1, the contents of each of which are incorporated herein by reference in their entireties, and others are described herein.”
Consequently, it is reasonable to conclude Applicant’s definition of AHR inhibitor is broad.
Page 11, paragraph [0044] defines “treating” as “As used herein, the terms “treatment,” “treat,” and “treating” refer to reversing, alleviating, delaying the onset of, or inhibiting the progress of a disease or disorder, or one or more symptoms thereof, as described herein. In some embodiments, treatment may be administered after one or more symptoms have developed. In other embodiments, treatment may be administered in the absence of symptoms. For example, treatment may be administered to a susceptible individual prior to the onset of symptoms (e.g., in light of a history of symptoms and/or in light of genetic or other susceptibility factors). Treatment may also be continued after symptoms have resolved, for example to prevent or delay their recurrence.”
Consequently, based on Applicant’s definition “treating” is inclusive of “preventing.”
Applicant’s claims are furthermore directed to cancer, which is not defined by Applicant in their specification; therefore, is defined based on the state of the art.
Cancer is a broad class of heterogenous diseases for which there exists no general treatment or prophylaxis. Hanahan explains that “there are more than 100 distinct types of cancer, and subtypes of tumors can be found within specific organs” (Hanahan, Douglas, and Robert A. Weinberg. "The Hallmarks of Cancer." Cell 100, no. 1 (2000): 57-70).
Consequently, it is reasonable to conclude Applicant’s claims are broad with respect to disease type, treatment, and AHR inhibitor.
The state of the prior art
The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). See Pac. Biosciences of Cal., Inc. v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021).
The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP § 2164.05 (a).
To the best knowledge of the examiner, there is no pharmacological agent known to generally treat or prevent cancer.
Most prevention is guided towards lifestyle modifications such as nutrition, diet, and exercise and prevention exposure to cancer-causing agents such as chemicals and radiation. To date, there are few examples of chemoprevention of cancer with most successes geared towards specific types of breast cancer (See page 839, column 2, paragraph 3 and also page 840, Table 1) (Umar, Asad, Barbara K. Dunn, and Peter Greenwald. "Future directions in cancer prevention." Nature Reviews Cancer 12, no. 12 (2012): 835-848).
Additionally, the role of AHR in cancer is conflicting in the art.
Narasimhan teaches that “We have postulated that the aryl hydrocarbon receptor (AHR) drives the later, more lethal stages of some cancers when chronically activated by endogenous ligands. However, other studies have suggested that, under some circumstances, the AHR can oppose tumor aggression. Resolving this apparent contradiction is critical to the design of AHR-targeted cancer therapeutics (Narasimhan, S., Stanford Zulick, E., Novikov, O., Parks, A.J., Schlezinger, J.J., Wang, Z., Laroche, F., Feng, H., Mulas, F., Monti, S. and Sherr, D.H., 2018. Towards resolving the pro-and anti-tumor effects of the aryl hydrocarbon receptor. International journal of molecular sciences, 19(5), p.1388).”
Consequently, AHR has both pro and anti-tumor effects.
Narasimhan teaches that “…an accumulating body of evidence indicates that the AHR is important in the progression of a variety of cancer types [3,4,5,6,7,8,9,10,11,12,13,14,15,16]. For example, the AHR is hyper-expressed and “constitutively” active (likely a reflection of the presence of endogenous AHR ligands [13,17,18]) in a diverse array of human cancers including glioblastomas [18], adult T cell leukemias, and oral cavity, lung, liver, prostate and Her2+ breast adenocarcinomas [6,17,18,19,20,21,22,23,24,25]. However, because AHR activity is highly context (tissue type, cell type, ligand)-specific [10,26], predicting how the “Janus-faced” AHR [27] will act in any given system can be problematic. For example, it is sometimes unclear if the AHR promotes or inhibits tumor aggression in any given tumor type. In support of the AHR driving tumor aggression, AHR knockdown in lung adenocarcinoma [28] or oral squamous cell carcinoma [17], or depletion of putative endogenous AHR ligands in glioblastoma [18] decreases anchorage-independent growth and/or invasion. Ectopic AHR expression increases tumor cell motility and invasion [25]. Knockdown of the AHR repressor (AHRR), a putative tumor suppressor, increases anchorage-independent growth and tumor formation in lung cancer xenografts [29]. In contrast, the AHR has been reported to exhibit anti-tumorigenic effects in prostate [30], stomach [31] liver [9] pancreatic [32], and breast [33] cancers. A direct comparison between outcomes in these system has been confounded by the use of a variety of readouts (e.g., tumor growth or migration assays), AHR modulators (inhibitors, agonists, molecular knockdowns) and tumor types.”
Narasimhan further teaches that “After several decades of scrutiny as a xenobiotic sensor, the AHR is now being evaluated as a novel target for cancer and immuno-therapy. However, apparently conflicting results and the unpredictability of what outcomes can be expected after AHR modulation in different tissues and with different ligands (reviewed in [10,100]) has raised concerns about whether the AHR should be inhibited or hyper-activated in any given disease context. “
Consequently, the art teaches that AHR’s role is not consistent for all types of cancer or all types of AHR ligands.
Therefore, it is reasonable to conclude that the current state of the art is highly unpredictable, indicating that more details, working examples and guidance would be required to practice the invention as disclosed for all types of cancer in all subjects as claimed.
The level of one of ordinary skill
The person of ordinary skill in the art is a hypothetical person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) "type of problems encountered in the art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are made;" (D) "sophistication of the technology; and" (E) "educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP § 2141.03 (I)
The invention described pertains to the biomedical and pharmaceutical arts. One of ordinary skill would be a person with considerable training in medicine, veterinary medicine, pharmacology, medicinal chemistry, biochemistry or a related technical discipline.
The level of predictability in the art
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The "amount of guidance or direction" refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling.
The scope of the required enablement varies inversely with the degree of predictability involved, but even in unpredictable arts, a disclosure of every operable species is not required. A single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ 122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA 1971). However, in applications directed to inventions in arts where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. See MPEP § 2164.03.
Consequently, technologies involving physiological activity as opposed to mechanical or electrical inventions are generally regarded as being unpredictable sciences.
As forementioned, cancer is a dynamic disease and additionally known to be highly unpredictable. Causes of cancer are equally unreliable and, in some cases, still unknown and can originate from diet, genetics, environment and a combination of factors which are not easily predicted. Additionally, cancer prevention encompasses various risk factors and there are few examples of chemoprevention in the arts.
In terms of targeting AHR, the role of AHR in cancer is not consistent for all types of cancer, nor are all inhibitors the same. Consequently, this field is also highly unpredictable.
In this context, based on assessing the fields of study, the predictability in the art is very low.
Consequently, the applicant would need to provide more details, working examples and guidance in order for the claimed invention to be enabling based on the scope and nature of the claimed invention.
The amount of direction provided by the inventor
As aforementioned, the amount of direction provided depends on the prior art and predictability of in the art. Based on the scope of protection sought by the applicant and the discussion aforementioned, the inventor has failed to provide sufficient direction for one ordinarily skilled in the art to practice the disclosed invention as claimed.
The existence of working examples
The applicants’ working examples are directed towards:
CTA scoring of AHR nuclear staining for bladder cancer, melanoma, ovarian cancer and HNSCC patients (page 42, paragraph [00143], Tables 1-10). Notably, only Compound A was tested as an AHR inhibitor.
However, Applicant has failed to provide support for the broad range of AHR inhibitors claimed across the broad range of cancers claimed.
Applicant additionally has provided no support for cancer prevention, and there are very few details on actually treating the cancers claimed.
Applicant has provided no experimental data using any specific AHR inhibitor for treating or preventing cancer including any of the cancers recited. Applicant has only provided data for identifying AHR in the nucleus of cells derived from bladder cancer, melanoma, ovarian cancer and HNSCC; however, there is no connection or integration with the method for actually treating or preventing cancer in patients. Consequently, Applicant has failed to exemplify the method of treatment as claimed or to provide sufficient guidance for a person of ordinary skill in the art to practice the claimed invention without undue experimentation.
Therefore, it is also not reasonable to suggest Applicant’s invention can be used to treat the diverse types of cancers claimed in all subjects using all AHR inhibitors.
On this basis and the prior discussion, the working examples are both not commensurate with the scope of protection sought and are not enabling. One ordinarily skilled in the art would unable to simply translate the evidence provided by the applicant without undue experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
As aforementioned, the quantity of experimentation depends on the prior art, the predictability of the art, and the direction provided by the inventor, which are factors that were already discussed.
In order for one ordinarily skilled in the art to practice the invention as disclosed, some attributes one would require, but are not limited to:
Studies encompassing the diverse and heterogenous cancer types claimed and encompassing the diverse class of AHR inhibitors claimed for actually treating cancer in combination with the AHR nuclear staining protocol.
How to determine if a subject will develop or not develop cancer based on using the claimed invention.
Long-term studies to confirm no recurrence, particularly based on the prevalence of dormancy in different cancers such as breast cancer, which can lead to recurrence after decades
Additional details on development of a treatment regime including how to determine effective dosage, timing, monitoring plan and administration method for the diverse class of cancers, AHR inhibitors, and integration of the biomarker.
Based on the preponderance of evidence and rationale put forth, the examiner concludes that one ordinarily skilled in the art would require undue experimentation in order to practice invention based on the limited details provided and scope of invention defined in Claims 1-12.
Consequently, Claims 1-12 are rejected for lacking enablement.
Claim Rejections - 35 USC § 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 applicant regards as his invention.
Claims 8-9 and 12 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 8 recites the broad recitation “tumor microenvironment”, and the claim also recites “or stroma region” which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claims 9 and 12, the phrase "(including 1+, 2+ and 3+ intensities)" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase “including” and within the parentheses are part of the claimed invention. See MPEP § 2173.05(d).
Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Platten et al. (USPN 9,593,062 B2) teach methods of treatment for cancer utilizing an AHR ligand involving measuring AHR activity. Sherr et al. (USPN 10,314,810 B2) teach methods of treatment for cancer utilizing AHR modifiers and involve measuring AHR activity.
Conclusion
Claims 1-12 are under consideration and are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622