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 .
Status of the Claims
The listing of claims filed 13 April 2026 has been examined.
Claims 18-19, 21-22, and 24-34 are pending.
Claims 21-22 and 24-25 are amended.
Claims 26-34 are newly added.
Claims 1-17, 20, and 23 are cancelled.
Information Disclosure Statement
The 5 Information Disclosure Statements (IDSs) filed on 18 January 2025 are acknowledged and have been considered. The 1 IDS filed 11 March 2026 is acknowledged and has been considered.
Priority
The instant application was received 26 April 2024; it is a national stage application of PCT/EP2022/080045, filed 27 October 2022, and claims foreign priority to PCT/EP2021/080016, filed 28 October 2021. Acknowledgment is made of Applicant’s claim for foreign priority and certified copies of the priority documents have been received.
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 24-25 and 32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because 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.
Claims 24-25 and 32 recite, “A method for the prevention or treatment of cancer; or an inflammatory/autoimmune disease, condition, or disorder…” These are broad genera and, according to their broadest reasonable interpretation, include any cancer and any inflammatory/autoimmune disease, condition, or disorder. While the specification, in view of the prior art, reasonably provides enablement for the treatment of CCR6-related cancers or inflammatory/autoimmune diseases, conditions, or disorders, it does not reasonably provide enablement for the prevention or treatment of all cancers or inflammatory/autoimmune diseases, conditions, or disorders encompassed by claims 24-25 and 32.
MPEP § 2164.01(a) explains how enablement for the claimed invention can be analyzed:
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is “reasonable” or 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.
In view of the Wands factors, which are discussed individually below, the specification fails to provide adequate enablement for the full scope of the claimed method and one skilled in the art could not practice the invention without undue experimentation.
The breadth of the claims and b) the nature of the invention. The claims are directed to a method for the prevention or treatment of cancer or an inflammatory/autoimmune disease, condition, or disorder, said method comprising administering to a subject in need of said prevention or treatment a pharmaceutically active amount of the compound according to claims 18, 19, or 30, or a pharmaceutically acceptable salt thereof.
The range of disorders that can be associated with the terms “cancer” and “inflammatory/autoimmune disease, condition, or disorder” are extensive and could, for example, include cancers and inflammatory/autoimmune diseases, conditions, or disorders which lack notable CCR6 or T cell and/or B cell involvement. As such, the scope of the claims is broad.
The state of the prior art. Bonelli (Bonelli et al., “CCR6 controls autoimmune but not innate immunity-driven experimental arthritis,” (2018), Journal of Cellular and Molecular Medicine, 22(11), p. 5278-5285.) discloses CCR6 is involved in adaptive immunity-driven arthritis, but not innate immunity-driven arthritis (p. 5278, Abstract), stating, “To our surprise, deficiency of CCR6 did not affect the severity of arthritis in two different arthritis models, which are independent of T or B cells, namely the TNF transgenic arthritis and the serum transfer arthritis model. In sharp contrast, CCR6-/- mice developed a less severe arthritis in the CIA [collagen-induced arthritis] mouse model, which is dependent on the adaptive immune system.” (p. 5283, Col. 1).
As previously stated, the range of instantly recited diseases which can be associated with the terms “cancer” and “inflammatory/autoimmune disease, condition, or disorder” are extensive and could, for example, include arthritis which has a disease pathology independent of T or B cells.
As per the Specification, “The meaning of the term “prevention” may also be understood as “prophylaxis”.” (p. 33, Line 28). Because the Specification provides no additional definition for the term “treatment”, it is given its plain meaning. Traumatic Brain Injury (TBI) is an injury-related condition associated with neuroinflammation. While treating TBI symptoms may be possible, prevention is not possible. Likewise, Crohn’s disease is an inflammatory condition, but its cause remains unclear. Thus, while treating Crohn’s disease symptoms may be possible, prevention is not possible.
Additionally, the term “subject” is not given an alternative definition in the Specification and, accordingly, is given its plain meaning. According to its broadest reasonable interpretation, “subject” could include all animals, including humans, at any life-cycle or developmental stage (i.e., infant, child, adolescent, or adult), which can impact the dosage and/or efficacy of the treatment method.
The level of one of ordinary skill. One of ordinary skill in the art is a person having advanced training or other significant relevant experience in medicine, pharmacology, chemistry, or another related technical discipline.
The level of predictability in the art. Pharmacology is quite unpredictable (See In re Marzocchi and Horton 169 USPQ at 367 CJ ¶3). Similarly, it is well established that [T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor {See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970)}.
The amount of direction provided by the inventor and g) the existence of working examples. The amount of guidance 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. The less predictable the nature of the invention, the more information needs to be explicitly stated in the specification. See MPEP 2164.03.
The Specification provides some direction related to possible pharmaceutical formulations, stating the claimed compounds may be administered enterally or parenterally (p. 25, Lines 17-19), working examples related to synthesis methods (p. 40, Line 6 – p. 54, Line 25), and IC50 values (p. 55). Furthermore, the Specification suggests CCR6 is involved in many disease states including autoimmune diseases, inflammation, psoriasis, multiple sclerosis, and cancer (p. 2, Lines 3-7). There are no working examples demonstrating the in vivo activity of the claimed compounds or their efficacy in treating and/or preventing cancer or an inflammatory/autoimmune disease, condition, or disorder in a subject.
There is no detail nor experimental results, either in the application itself or in any other evidence of record, to support the notion that the claimed compounds are useful for treating or preventing all of the extraordinarily large range of diseases or disorders within the scope of this claim. Specifically, there are no examples that in any way suggest the compounds are useful in preventing cancer or an inflammatory condition.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure. The prevention or treatment of cancer or an inflammatory/autoimmune disease, condition, or disorder would depend at the very least on the cause of said disease (e.g., chemical or physical) and the developmental stage of the subject (e.g., infant, adult, etc.). The prior art demonstrates that it is not possible for a single pharmaceutical product (and its analogs) to treat or prevent all cancers and/or inflammatory/autoimmune diseases, conditions, and disorders.
In order to practice the invention commensurate with the full scope of the claims, the skilled artisan would need to undertake experiments in order to determine (1) whether the compound is, in fact, clinically useful for the treatment or prevention of the claimed diseases; (2) the amount of compound that is to be administered; (3) the frequency of dosing and the manner in which the compound is to be administered; (4) the likely side effects and how they should be mitigated; and (5) the pharmaceutical formulation that is suitable for administration to a patient.
Scope of Enablement Conclusion
While the state of the art does agree CCR6-related treatments have been effective in a wide range of cancers and inflammatory/autoimmune diseases, conditions, or disorders, claims 24-25 and 32, as written, capture too broad a scope. Given the level of unpredictability in this technology area, and the relative lack of working examples or other specific guidance or teachings by Applicant, Examiner concludes that one skilled in the art would be burdened with undue experimentation when attempting to practice the full scope of the invention as claimed. Deleting the word “preventing” and limiting the diseases to any of those disclosed in claims 26-29 or 33-34 would overcome the rejection.
Allowable Subject Matter
Claims 18-19, 21-22, 26-31, and 33-34 are allowed. None of the prior art of record nor a search in the pertinent art area teaches the compound N-[4-(3-{5-[(1,3-Dimethyl-azetidin-3-yl)-hydroxy-(4-isopropyl-phenyl)-methyl]-pyridin-3-yl}-[1,2,4]oxadiazol-5-yl)-cyclohexyl]-acetamide, or its stereoisomers, or compositions containing the instantly compounds nor methods of using the instantly claimed compounds in treating cancer or inflammatory/autoimmune diseases, conditions, or disorders.
The following is a statement of reasons for the indication of allowable subject matter:
The claimed compound is N-[4-(3-{5-[(1,3-Dimethyl-azetidin-3-yl)-hydroxy-(4-isopropyl-phenyl)-methyl]-pyridin-3-yl}-[1,2,4]oxadiazol-5-yl)-cyclohexyl]-acetamide (Claim 30), as well as its cis and trans isomers cis-N-[4-(3-{5-[(R)-(1,3-Dimethyl-azetidin-3-yl)-hydroxy-(4-isopropyl-phenyl)-methyl]-pyridin-3-yl}- [1,2,4]oxadiazol-5-yl)-cyclohexyl]-acetamide and trans-N-[4-(3-{5-[(R)-(1,3-Dimethyl-azetidin-3-yl)-hydroxy-(4-isopropyl-phenyl)-methyl]-pyridin-3-yl}- [1,2,4]oxadiazol-5-yl)-cyclohexyl]-acetamide:
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539
597
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Figure 1. N-[4-(3-{5-[(1,3-Dimethyl-azetidin-3-yl)-hydroxy-(4-isopropyl-phenyl)-methyl]-pyridin-3-yl}-[1,2,4]oxadiazol-5-yl)-cyclohexyl]-acetamide, drawn by JChem.
The closest prior art is Barbay (WO 2015/057626 A1; IDS dated 18 January 2025, Cite No. 18) and Jackson (WO 2019/147862 A1; IDS dated 18 January 2025, Cite No. 24). Shown below are exemplary compounds disclosed by Barbay and Jackson, which share some structural similarities with the instantly claimed compounds:
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272
525
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Barbay (p. 295)
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227
313
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Jackson (p. 276, ¶ [0840]).
Figure 2. Exemplary compounds disclosed by Barbay and Jackson.
The instantly claimed compounds differ from Barbay and Jackson in the following respects:
In the instantly claimed compounds, the phenyl group is substituted with an isopropyl group. However, in Barbay’s compounds, which have the highest structural similarity to the instantly claimed compounds among the prior art, the phenyl group fused to a pyridine ring having multiple substitutions, including a halogen. Additionally, Barbay’s compounds include trifluoromethyl groups.
In the instantly claimed compounds, the azetidine only has only a methyl substitution. However, the compounds described by Jackson have much larger moieties at this position. Furthermore, Jackson’s compounds contain halogen atoms whereas the instantly claimed compounds do not contain any halogens.
Thus, while Barbay’s and Jackson’s compounds share some structural similarities with the instantly claimed compounds, a skilled artisan would not have been motivated to make the aforementioned changes as a whole to the structures which would have resulted in the instantly claimed compounds.
Conclusion
Claims 18-19, 21-22, 26-31, and 33-34 are allowed. Claims 24-25 and 32 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIANNA L BAUER whose telephone number is (571)272-5752. The examiner can normally be reached 8am-5pm.
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/B.L.B./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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