DETAILED ACTION
Claims 1, 3, 5-9 and 16-28, submitted 22 May 2026, are pending in the application and subject to examination in the instant Office 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 .
Election/Restrictions
The Applicant has traversed the Restriction Requirement mailed on 26 March 2026. Upon reconsideration, the Examiner has agreed that the restriction requirement between Groups I and II was improper, therefore the requirement for restriction has been withdrawn in whole.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3, 5-9, 18-21 and 25-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “A compound of formula I, or an optical isomer thereof, or a racemate thereof, or a pharmaceutically acceptable salt thereof, or a prodrug thereof…”, for which the specification does not provide adequate written description to convey that the inventors were in possession of the full scope of the claimed invention.
The Applicant has provided adequate written description for certain aspects of the instantly claimed invention. For example, the Applicant has provided guidance with respect to the synthesis of the compounds of formula I, found in Examples 1-17 found on pages 35-67 of the instant specification. Written description was also provided in Example 18 regarding the inhibitory activity of the compounds with respect to TRPA1, found on pages 67-69 of the specification. Finally, the Applicant provided adequate written description pertaining to the treatment of models of ulcerative colitis in Wistar rats, which mimic Crohn’s disease, inflammatory colitis in C57BL/6 mice, which mimics ulcerative colitis, and the acetic acid writhing pain, which is used for evaluating visceral pain and acute inflammatory pain, all of which are detailed in Examples 19-21 on pages 69-78 of the specification.
The instant specification fails to adequately describe wherein the compound of formula I is a prodrug thereof. It’s known in the art that the design and synthesis of prodrugs is complex and presents many challenges. For example, the prior art, Rautio et al. ("The expanding role of prodrugs in contemporary drug design and development." Nature reviews drug discovery 17.8 (2018): 559-587.), teaches the challenges associated with prodrug design and development. Rautio states “Though great progress has been made to characterize prodrugs, the limitations of the different approaches should be carefully considered with respect to the uncertainty in translation to humans. The development of prodrugs is, in general, much more complex and less predictable in the clinic than that of other drugs” (pg. 578, Section “Prodrug challenges and considerations”, Right Col., 1st paragraph). As claim 1 currently reads, the Examiner cannot conclude that the Applicant was in possession of the full scope of the claimed invention.
Claims 3, 5-9, 18-21 and 25-28 are rejected as they are dependent upon a rejected independent claim.
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 16 and 22-24 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 inhibiting transient receptor potential channel protein A (TRPA1) and treating models of, Crohn’s disease, ulcerative colitis and acute inflammatory pain, does not reasonably provide enablement for the inhibition of all transient receptor potential channel proteins or the prevention of all diseases associated with TRPA1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Breadth of the Claims
Claim 16 recites “A method for inhibiting transient receptor potential channel protein, or preventing and/or treating disease related to transient receptor potential channel protein TRPA1…”. The first method of claim 16 is not drawn to any particular transient receptor potential channel protein and thus is interpreted to encompass all TRP channel proteins.
Additionally, claim 16 recites prevention of disease related to TRPA1. Prevention is defined in the instant specification on page 21, which states, “…the term “prevent” refers to a method of preventing the onset of a disease and/or its accompanying symptoms or protecting the protected subject from acquiring the disease…”.
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to the inhibition of transient receptor potential channel protein or preventing and/or treating disease related to TRPA1 in a subject in need thereof.
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 those in the art at the time the application was filed. See MPEP 2164.05(b). See Pac. Bioscience 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 enabled requirement. The state of the prior art is also related to the need for working examples in the specification. See MPEP 2165.05(a).
Moran ("TRP channels as potential drug targets." Annual review of pharmacology and toxicology 58 (2018): 309-330.) states that “The diversity of TRP channel function is accompanied by a corresponding diversity in structure. The TRP superfamily contains six groups: ankyrin (TRPA), canonical (TRPC), melastatin (TRPM), mucolipin (TRPML), polycystin (TRPP), and vanilloid (TRPV).”. This statement is followed by Moran teaching that while the TRP channels are likely composed of four subunits, either homo- or heterotetramers, there is low sequence homology between the family and the structures an diverge significantly (pg. 310, Section “Introduction”, 2nd paragraph). In view of Moran, one skilled in the art would acknowledge that there would be great unpredictability in the inhibition of all TRP channels with a single compound.
To add to the unpredictability, Kanju et al. ("Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain." Scientific reports 6.1 (2016): 26894.) teaches a TRPV4 inhibitor which, through unexpected results, also inhibits TRPA1 (Abstract). Kanju states “In heterologously transfected permanent N2a cells, we did not observe inhibitory potency of compounds 16-8 or 16-19 toward TRPV1, TRPV2 and TRPV3 (Fig. 5A). However, we made the unexpected discovery of sub-micromolar inhibitory potency vs TRPA1 for compounds 16-8 and 16-19…” (pg. 4, Section “Novel TRPV4 inhibitors are selective…”, 1st paragraph). In view of the Moran and Kanju references, it can be concluded that while dual inhibition of TRP channel proteins is possible, these results are considered to be unpredictable and require more research which would lead the practitioner to discover that which the Applicant has failed to disclose.
With regards to the prevention of all diseases related to TRPA1, Karas (Orlando Health “Tips to Prevent Irritable Bowel Syndrome”) teaches that “IBS is a multifactorial condition, meaning there’s not one single thing we can point out as a cause. That also means there’s not one single thing we can point out as a cure or as a preventive measure.” (pg. 2, Section “Treating or Preventing IBS”, Subsection “Take medication for IBS as prescribed”, 2nd paragraph). It is also relevant that Karas states that “While there is no known cause for IBS, theories include a motility disorder of the muscles in the gastrointestinal tract, bowel gut hypersensitivity, an alteration in the quantity or quality of microbiomes that live in the colon, or a sensitivity to dairy. Genetics do not appear to be a cause, and it’s possible that several factors play a part in the condition.” (pg. 1, Section “Introduction”, 3rd paragraph), indicating that there is still much uncertainty in preventing the onset of the condition or preventing a subject from acquiring the disease.
If a publication demonstrates that those of ordinary skill in the art would find that
a particular invention was not enabled years after the filing date, the publication would
be evidence that the claimed invention was not possible at the time of filing. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513-14 (Fed. Cir. 1993). See MPEP 2164.05(a). In view of the MPEP, it is appropriate to use post filed art as evidence to limit the scope of the instantly claimed invention based on what is known in the art. Ananthakrishnan (Mass General Brigham “Can You Prevent Inflammatory Bowel Disease?”) states that “There’s no known way to prevent IBD. But there may be things you can do to help reduce your risk.” (pg. 3, Section “IBD prevention and risk factors”, 1st paragraph). Again, this leads to unpredictability in the ability of the compounds of the invention to prevent a disease which the post-filed art states cannot be prevented.
Level of Skill in the Art
The person of ordinary skill in the art is a 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 medical or pharmaceutical arts. One of ordinary skill would be trained in pharmacology, biochemistry, medicine, or a related art field with a Ph. D or other advanced degree in these or other related fields.
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 of 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 in 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 art, 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. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). See MPEP 2164.03. The applicant would need to provide more objective evidence to support the enablement of the aforementioned claims to contrast the unpredictability of the subject matter art.
There is unpredictability in the field of endeavor regarding the currently claimed method of inhibiting all transient receptor potential channel protein, or preventing and/or treating all diseases related to TRPA1 with a singular compound. Unpredictability stems from the lack of prior art which would suggest that the compounds of the claimed invention can be administered to prevent and/or treat the above-mentioned diseases or conditions.
Amount of Direction Provided by the Inventor
The amount of direction provided by the inventor is correlated by the nature of the unpredictability of the art. Given the context and scope of the claims mentioned above, the inventor failed to provide the necessary amount of direction for one skilled in the art to adequately use the invention across all suggested utility in the broadly stated disease and disorders disclosed above. (See: Section (A) Breadth of the Claims).
The Applicant provided guidance for certain aspects of the instantly claimed invention. Guidance was provided pertaining to the synthesis of the compounds of the invention. Additionally, the Applicant provided data for the inhibitory activity of the compounds with regards to TRPA1, found in Example 18. Additionally, the Applicant provided guidance pertaining to the treatment of models of ulcerative colitis in Wistar rats, which mimic Crohn’s disease, inflammatory colitis in C57BL/6 mice, which mimics ulcerative colitis, and the acetic acid writhing pain, which is used for evaluating visceral pain and acute inflammatory pain, all of which are detailed in Examples 19-21 on pages 69-78 of the specification.
Existence of Working Examples
The provided working examples focused on the compounds ability to inhibit TRPA1 using automated patch clamp detection. Additionally, the provided working examples focused on the treating of diseases or conditions, detailed in Section (F). However, the specification does not provide working examples for the inhibition of other known TRP channel protein, nor does it provide working examples for the prevention of the known diseases related to TRPA1. Thus, one skilled in the art would be unable to adequately use the invention without unduly experimentation, which would require the practitioner to discover that which the Applicant has failed to disclose.
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
As previously stated, the amount of experimentation depends on the art, the predictability of the art, and the direction provided by the inventor. For one skilled in the art to practice the invention as disclosed, the artisan trying to practice Applicant’s claimed invention would be required to undertake unduly burdensome activities including:
Experimentation to demonstrate the inhibitory activity of the compounds of the instantly claimed invention against all transient receptor potential channel protein.
Experimentation to demonstrate the prevention of all diseases related to TRPA1.
Allowable Subject Matter
Claim 17 is allowed.
The following is a statement of reasons for the indication of allowable subject matter: the intermediate compounds of instant claim 17 are not disclosed or fairly suggested in the prior art and therefore, are considered novel and unobvious over the prior art.
Conclusion
Claim 17 is allowed. Claims 1, 3, 5-9, 16, and 18-28 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
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JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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