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
This application filed on 09/15/2023 is a U.S. National Stage filing under 35 U.S.C. Q 371 of International Application No. PCT/US2022/020364, filed on 03/15/2022, which claims the benefit of priority to U.S. Provisional Applications No. 63/161,129, filed on 03/15/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 05/12/2025, complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits, except where noted.
Status of claims
The preliminary amendment filed on 04/03/2026, that cancelled claims 1-25, is acknowledged. Claims 26-45 are pending.
Election/Restriction
Applicant’s response filed on 04/03/2026 to Restriction/Election Requirement filed on 02/03/2026, is acknowledged. Applicant elected without traverse Group I drawn to a compound of formula I, II, Ia, Ib, Ic, Id, Iaa, Iaaa1, Iaaa2, Iaaa3, Iaaa4, Iaaa5, Iba, Ibaa1, Ibaa2, Ibaa3, Ibaa4, or Ibaa5. Claims 26-34 read on the elected Group. Claims 35-45 of Group II are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Pursuant to the Election of Species Requirement, Applicant respectively elected without traverse, (1S,4S)-N-(tert-butyl)-5-(5-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl) pyridin-2-yl)-2,5- diazabicyclo [2.2.1] heptane-2-carboxamide depicted below for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable:
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Claims 26-34 read on the elected species. Applicant’s elected species was searched, and determined to be free of the art of record. Pursuant to MPEP § 803.02, the search and examination was extended to the non-elected species discussed below, which new search species falls within the scope of instant claims 26-34 (i.e., claims to proper Markush groupings that include both the new search species as well as the originally elected species. MPEP § 803.02(III)(C)(2)). The new search species underlies rejections of these claims pursuant to 35 U.S.C. § 102. As such, the election of species requirement is maintained as provisional, and claims 35-45 are provisionally withdrawn from consideration pursuant to 37 CFR 1.142(b). See, MPEP § 803.02.
Thus, claims 26-45 are pending with claims 35-45 are withdrawn from further consideration, and claims 26-34 are under consideration.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation for diamines or spirocyclic diamines
Claim 2 recites “… wherein L is bicyclic diamines or spirocyclic diamines”.
As provided in MPEP 211.01 III, [T]he ordinary and customary meaning of a claim term is the meaning that the term would have to a person of ordinary skill in the art in question at the time of the invention, i.e., as of the effective filing date of the patent application." Phillips v. AWH Corp.,415 F.3d 1303, 1313, 75 USPQ2d 1321, 1326 (Fed. Cir. 2005) (en banc); Sunrace Roots Enter. Co. v. SRAM Corp., 336 F.3d 1298, 1302, 67 USPQ2d 1438, 1441 (Fed. Cir. 2003); Brookhill-Wilk 1, LLC v. Intuitive Surgical, Inc., 334 F.3d 1294, 1298, 67 USPQ2d 1132, 1136 (Fed. Cir. 2003) ("In the absence of an express intent to impart a novel meaning to the claim terms, the words are presumed to take on the ordinary and customary meanings attributed to them by those of ordinary skill in the art."). Where neither the claims, nor the specification, nor the prosecution history offer sufficient clarity on claim scope, extrinsic evidence may become a necessary part of claim interpretation. Moreover, MPEP 2111.01 stated that it is improper to “read limitations into a claim from the preferred embodiment described in the specification, even if it is the only embodiment described, absent clear disclaimer in the specification."
The instant specification does not provide clear definition to the term “diamines or spirocyclic diamines”. The instant specification recites “in some embodiment” and “such embodiment are not limited to a particular chemical moiety”:
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A preferred embodiment is not a definition and, therefore, the diamines or spirocyclic diamines are given its plain meaning as defined by F. Kelleher et al. Tetrahedron, Volume 63, Issue 37, 10 September 2007, Pages 9235-9242, cited in the PTO-892), and O. Grygorenko et al. Chemical Reviews, 2011, VL 111, IS 9, SP 5506-5568, cited in the PTO-892). In view of Kelleher et al. and Grygorenko et al. the definition of diamines or spirocyclic diamines is not limited on the preferred embodiment above. The diamines or spirocyclic diamines is interpreted as defines by Kelleher et al. and Grygorenko et al.
Abstract
The Abstract of the disclosure is objected to because the Abstract recites “the present disclosure relates to …”. Applicant is reminded of the proper language and format for an abstract of the disclosure. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. 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).
Claims Objection
Claim 26 is objected to for the following informalities:
Claim 26 recites in part:
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The underlined “aryl” is repeated. The repeated word should be removed.
Appropriate correction is required.
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.
Claims 29 and 34 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.
Pursuant to 35 U.S.C. 112(b), the claim must apprise one of ordinary skill in the art of its scope so as to provide clear warning to others as to what constitutes infringement. MPEP 2173.02(II); Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000).
Claim 34 recites “wherein R10 is selected from hydrogen, halogen (e.g., chlorine). As provided in MEMP 2173.05(d), “Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made. The examiner should analyze whether the metes and bounds of the claim are clearly set forth. The examples or preferences have been recited throughout unexamined claims.
Claim 29 recites “the compound of claim 26, wherein the compound is recited in Tables I, II, III, or IV”. Referencing to the structure of Tables I, II, III, or IV without reciting the structures in the claims render the claim indefinite. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). Reference characters corresponding to elements recited in the detailed description and the drawings may be used in conjunction with the recitation of the same element or group of elements in the claims.
Claim Rejections - 35 USC § 112(a)- Written Description
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 26-34 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.
The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the art that the inventors, at the time the application was filed, had possession of the claimed invention. See MPEP 2143. The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filling date of the application, of the specific subject matter claimed. Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. MPEP § 2163(II)(A)(3)(a)(ii). A "representative number of species" means that the species which are adequately described are representative of the entire genus. MPEP § 2163(II)(A)(3)(a)(ii). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. MPEP § 2163(II)(A)(3)(a)(ii) (citing AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Claim 26 recites Formula (II), “wherein R7, R8, R9, and R10 independently include any chemical moiety that permits the resulting compound to inhibit HDAC6 activity”:
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Thus, claim 26 is drawn to millions of compounds structurally different, and the structure-activity-relationship to HDAC6 does not describe by the claims or the specification. The disclosure should contain representative examples which provide reasonable assurance to one skilled in the art that ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter claimed. The applicants have broadly claimed a compound of formula (II). MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that claims 26-34 are broad and generic, with respect to all possible compounds encompassed by claim 26. There is a very large number of structural variations encompassed by formulas (II). The claims lack in written description because the specification lacks sufficient variety of species to reflect this variance in the genus, especially with respect to any compound with the core of formula (II). The specification provides guidance to a limited number of compounds, specifically 123 compounds, see Table I-IV. The instant specification does not provide a representative number of examples that show substituents that would have this function of inhibiting HDAC6. The instant specification does not draw the connection between formula (II) and HDAC6 inhibition. The specification does not provide sufficient descriptive support for the myriad of compounds embraced by the claims. There are millions of combinations of elements of any substituent as in the instant claim 26, embraced by formula (II). Considering the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of claim 26.
What is conventional or well known to one of ordinary skill in the art need not be disclosed in detail. MPEP § (II)(A)(3)(a). Thus, the state of and predictability in the art is a relevant consideration in determining compliance with § 112(a), written description. MPEP § (II)(A)(3)(a) (citing Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1085 (Fed. Cir. 2005) ("The ‘written description’ requirement must be applied in the context of the particular invention and the state of the knowledge…. As each field evolves, the balance also evolves between what is known and what is added by each inventive contribution”). However, in the instant case, neither the instant specification not the state of the prior art described all the compounds encompasses by formula (II) that would function as HDAC6 inhibitors.
When there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. MPEP § 2163(II)(A)(3)(a)(ii) (citing AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). However, neither the art nor the specification teaches the representative of formula II such that one of skill can recognize which species of formula II have the claimed function of inhibiting HDAC6. Indeed, one of skill cannot glean from the disclosure or the art of record which other substances (aside from the disclosed substances) are even HDAC6 inhibitor in the first place.
Claim breath is relevant to the instant § 112(a) written description rejection. The written description must lead a person of ordinary skill in the art to understand that the inventor possessed the entire scope of the claimed invention. MPEP § 2163(II)(A)(3)(a)(ii) (citing Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021)). Applicant is not in possession of the full claim scope because neither the specification nor the art of record provides sufficient guidance (representative species or a structure-function relationship) allowing one of skill to correctly predict these species, aside from those disclosed. A "representative number of species" means that the species which are adequately described are representative of the entire genus. MPEP § 2163(II)(A)(3)(a)(ii); see also, Idenix Pharms. LLC v. Gilead Scis. Inc., 941 F.3d 1149, 1164 (Fed. Cir. 2019) (“[a]s a result, a POSA is deprived of any meaningful guidance into what compounds beyond the examples and formulas, if any, would provide the same result”).
§ 112(a)- Written Description for claims 26-34- Prodrug
The instant claim 26 is directed to “an article of manufacture comprising a compound of formula (I)- (Ibaa5), that is claimed to have a biological activity as a HDAC6 inhibitors”. The recitation of prodrug of compounds of formula (I)- (Ibaa5) is not adequately defined in the instant specification.
The MPEP states that for a generic claim can be adequately described if the disclosure presents a sufficient number of representative species in examples that encompass the genus. (MPEP § 2163). A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole cover, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing. Each of these factors has been considered, with the most relevant factors discussed below. For each claim drawn to a genus, each of these factors is to be considered to determine whether there is disclosure of a representative number of species that would lead one skilled in the art to conclude that applicant was in possession of the claimed invention.
With respect to the scope of the claims, the full scope includes “an article of manufacture comprising a compound of Formula (I)- (Ibaa5), or a pharmaceutically acceptable salt, solvates, and/or prodrug thereof.”
J. Zawilska et al. (Prodrugs: a challenge for the drug development. Pharmacol Rep. 2013; 65(1):1-14), teaches that “Prodrugs, which have no or poor biological activity, are chemically modified versions of a pharmacologically active agent, which must undergo transformation in vivo to release the active drug.” [Abstract]. Zawilska teaches that “the rationale behind the use of prodrugs is to optimize the absorption, distribution, metabolism, excretion, and unwanted toxicity of the parent drug.” [Pg. 2, col. 1]. Zawilska teaches that there are two main classes of prodrugs, carrier-linked prodrugs (the drug is temporary linked to a carrier that undergoes biotransformation, releasing the parent drug and the carrier), and bio precursor prodrugs (result from a molecular modification of the drug and transformed metabolically or chemically by hydration or reduction. [Pg. 2, col. 2]. Zawilska teaches the major groups of prodrugs:
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Zawilska teaches that “some esters are not suitable substrates for endogenous esterases, sulfatases or phosphatases, which, in turn, impose unfavorable, too slow kinetics of the prodrug hydrolysis.” [Pg. 4, col. 1, 1st para.]. Zawilska teaches that the prodrug should be easily dissolved in water, and marginally taken up by cells, the drug should be efficiently and rapidly transported, the enzyme should have high intrinsic activity, and enzyme cannot be inactivated by a prodrug or drug. Zawilska teaches that “Despite the remarkable progress made in the field of prodrug design, more studies are clearly needed, especially at early stages of the drug discovery, for prodrugs to achieve the desired state of art and take their place in modern pharmacotherapy.” Pg. 11, col. 21st para.].
The instant claims directed to compound of formula (I)- (Ibaa5), wherein the substituents of (I)- (Ibaa5) includes COOH, C=O, NH, OH, SO2, etc. As discussed above by Zawilska, these functional group leads to multiples prodrugs. Additionally, compound of formula (I)- (Ibaa5) includes multiple sites to which a prodrug moiety could bind. The description does not provide adequate description on the binding moiety, the type of prodrugs (carrier linked prodrugs or bio precursor prodrugs), kinetics of the prodrug hydrolysis, or the enzyme-prodrug interaction. See Zawilska above. The specification does not provide answer to question regarding prodrug of compound of formula (I)-(Ibaa5), for example, does the metabolism of compound of formula (I)- (Ibaa5) are well understood, does the prodrug will be active, does the prodrug will introduce any unfavorable interaction, etc. Zawilska teaches that “more studies are clearly needed, especially at early stages of the drug discovery, for prodrugs to achieve the desired state of art”
The description does not include a definition of the prodrug that satisfies the functional definition of the genus. "The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention."). Problems satisfying the written description requirement for original claims often occur when claim language is generic or functional, or both. Ariad, 593 F.3d at 1349, 94 USPQ2d at 1171 ("The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus."
Comparison of the scope of the claims and the scope of the specification reveals that the scope of the claims is broader than that supported by the specification. There is no guidance in the specification regarding prodrugs.
The instant specification does not define or describe the prodrugs for compound of formula (I)- (Ibaa5), because compound of formula I encompass hundreds/thousands of species each of which encompasses multiple sites for prodrug binding. The instant specification provides no example for any prodrug of any compound of formula (I)- (Ibaa5), let alone, its activity, metabolism, enzymatic interaction, toxicity, etc. BOC Sciences (https://www.bocsci.com/blog/prodrug-activation-strategies-in-drug-discovery/?srsltid=AfmBOor0dyaRkHg4KY8ggdEj09mix1fTx8ZGgnvoIJzT5gtvjX5jYSHE, 2023), teaches that “the design of prodrugs must ensure their ability to degrade and release the parent drug at the appropriate time and site. This requires that the designed prodrugs have suitable chemical stability and enzymatic stability. They should neither degrade before reaching the target site nor remain undegraded for an extended period after entering the target site, as this would hinder their pharmacological effect. Additionally, prodrugs often have distinct chemical structures from the parent drug, which may introduce new toxicities. On one hand, this could result from unexpected metabolism of the prodrug, leading to the formation of unforeseen metabolites. On the other hand, it may occur because inert carriers generated from prodrug cleavage can transform into toxic metabolites, such as formaldehyde and acetaldehyde. Therefore, the comprehensive evaluation of prodrugs should include their physicochemical properties, pharmacological effects, pharmacokinetic properties, and potential toxic reactions.” [Pg. 8]. Thus, in view of BOC Science, claiming prodrug of compound of formula I required more than what provided by instant specification. One skilled in the art cannot, as one can do with a fully described prodrugs, visualize or recognize the identity of the prodrugs of the genus of formula (I)- (Ibaa5).
Having analyzed the claims with regard to the written description guidelines, the specification does not disclose a representative number of prodrugs or relate the functional language of “a prodrug that provides HDAC6 inhibition activity” to sufficiently to describe said prodrugs. Thus, one of ordinary skill in the art would be led to conclude that applicants were not in possession of the invention commensurate with the scope of the claims, at the time the application was filed.
Claim Rejections — Improper Markush Group
Claims 26-34 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex Hozumi,3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int.1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature.
The rejection is on the grounds that the members of the following claim 26 Markush grouping:
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or a pharmaceutically acceptable salt, solvates and/or prodrugs, wherein X and X' are N when Y is O, or X and Y are N when X' is O; wherein A1 and A2 are independently CH or N, or A1 and A2 are independently CH, or A1 and A2 taken together as S; wherein R1 is CF3 or CF2H; wherein L is bicyclic diamines or spirocyclic diamines; wherein R2 is hydrogen, -COR3, -CO2R3, -(CH2)nNR3R4, -CONR3 R4, -(CH2)nR3R4, and - SO2R3, wherein n = 1 or 2 optionally substituted with a CH3 group; wherein R3 is hydrogen, C1-C6alkyl or C1-C6branchedalkylalkyl or C1-C6cycloalkyl, aryl, cycloalkylalkyl, heterocyclyl, heteroaryl, arylalkyl, arylaryl, or aryl, each of which is optionally mono-, di-, or tri-substituted independently with C1-C6alkyl, halogen, cycloalkyl, and aryl; wherein R4 is C1-C6alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, heteroaryl, arylalkyl, or aryl, each of which is optionally mono-, di-, or tri-substituted independently with C1-C6alkyl, halogen, cycloalkyl, and aryl; and wherein R5 is hydrogen or CH3, wherein R is Fluorine or Hydrogen, wherein R7, R8, R9 and R10 independently include any chemical moiety that permits the resulting compound to inhibit HDAC6 activity,
do not share a "single structural similarity", nor do dependent claims 27-34 sufficiently narrow the claim 26 Markush genus to a “single structural similarity”.
“A Markush grouping is proper if the members of a group share a single structural similarity and a common use”. MPEP § 2117(I). A Markush claim may be rejected under judicially approved "improper Markush grouping" principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an "improper Markush grouping" if either: (1) the members of the Markush group do not share a "single structural similarity" or (2) the members do not share a common use. MPEP § 2117(II) (citing 76 Federal Register 7162-7175 (2011); In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)).
Members of a Markush group share a "single structural similarity" when they belong to the same recognized physical or chemical class or to the same art-recognized class. MPEP § 2117(II)(A). A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. MPEP § 2117(II)(A).
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a "single structural similarity" and common use when the alternatively usable compounds share a “substantial structural feature” that is essential to a common use. MPEP § 2117(II)(B).
In the instant case, the claimed Markush group alternatives are disclosed to share the common use in the inhibition of HDAC6. [Instant Specification, page 1]. see MPEP § 2117(II) (“the alternatives . . . share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent in the context of the claimed invention”). However, the instantly claimed Markush members do not share a "single structural similarity" and as discussed below, the alternatives appear to not share a common use.
The Claimed Alternatives Are Not Members of a Physical, Chemical, or Art-Recognized Class and do not Share a “Single Structural Similarity”
All the variables within the claim 26 Markush grouping of1:
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are defined generically. The alternatives are not members of a recognized physical or chemical class or members of an art-recognized class. There is no art of record (or other evidence of knowledge in the art in the Application’s file) providing an expectation from the knowledge in the art that all the members of the recited genera of the claim 26 Markush grouping will behave in the same way in the context of the claimed invention. MPEP § 2117(II)(A). The only structure similarity of the Markush grouping is the N in an aromatic ring. The N-aromatic ring moiety encompasses multiple different rings resulted in at least 6 different aromatic ring including pyridine ring, pyridazine ring, pyrimidine ring, pyrazine ring, 1,2,4-triazine, or thiazole ring, wherein the n-aromatic ring connected to a 5-membered heterocyclic ring that also encompasses multiple different rings. L as broadly interpreted as defines by Kelleher et al. and Grygorenko et al. encompass large numbers of bicyclic rings (see claim interpretation above). R2-5 are selected from multiple substituents optionally substituted with alkyl, halogens, cycloalkyl, aryl group, etc. In sum, the claim 26 alternatives are not members of a recognized physical or chemical class or members of an art-recognized class. Having two different aromatic rings connected by a bond does not put compounds having these rings in a recognizable physical or chemical class. While most of the species recited in the specification in Table I-IV share substantial structure similarity by having same rings, same L, the claim 26 does not limited to the compounds recited in Table I-IV. Claim 26 is drawn to millions of compounds structurally different, and each moiety having different structural core, and L encompasses large genus of nitrogen bicyclic rings.
Where the alternatives do not belong to a recognized class as above, the members of the Markush grouping may still be considered to be proper where the alternatives share a “substantial structural feature that is essential to a common use”. MPEP § 2117(II)(B). However, in view of the specification, the member of claim 26 formula (I)-(Ibaa5) does not appear to be the “substantial structural feature that is essential to a common use” or function. There is no evidence by instant specification that all members of formula (I)-(Ibaa5) are HDAC6 inhibitors. In fact, the specification does not include any study, testing, in vitro testing, or binding assays connecting the claimed species of formula (I)-(Ibaa5) to HDAC6. The specification does not provide structure-activity relationship of formula (I)-(Ibaa5) and HDAC6 inhibition. Thus, the members of formula (I)-(Ibaa5) does not share structure similarity, and there is no evidence that the members of formula (I)-(Ibaa5) share common use. There is no evidence in the specification or the art that the common structural feature permits the HDAC6 inhibition. Therefore, the claimed compounds do not belong to a recognized class or share a “substantial structural feature that is essential to a common use”.
Dependent claims 27-34 do not sufficiently narrow the claim 26 Markush genus to a “single structural similarity”.
In view of the foregoing, claimed compound alternatives falling within the scope of instant claims 26-34 do not: (1) share a "single structural similarity" because they do not belong to the same recognized physical or chemical class or to the same art-recognized class; or (2) share a “substantial structural feature” that is essential to a common use because the claimed generic formulae do not comprise a “substantial structural feature”. As such, these claims are directed to an improper Markush grouping.
This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C.\134 and 37 CFR 41.31(a)(1) (emphasis provided).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
§ 102 Rejection over Ghosh
Claims 26, 30, 32, and 33 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by S. Ghosh, et al. (WO2013/066831A1, 05/10/2013 "Ghosh" cited in the IDS dated 05/12/2025).
Ghosh discloses compounds for the treatment of diseases or conditions ameliorated by inhibition of HDAC, i.e., HDAC6, activity and pharmaceutical compositions comprising these compounds [Pg. 1, In. 5-8, 18]. Ghosh discloses, for example, compound of Example 25 [Pg. 64, In. 23]:
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112
314
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Ghosh's compound of Ex. 25 above anticipates instant claimed compound of Formula (II), wherein:
R7 is N; R8 is CH; R9 is
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70
98
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; and R10 is
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100
148
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. Thus, Ghosh anticipates claims 26 and 33.
Claims 30 and 32 are met because R7 is N; R8 is CH.
§ 102 Rejection over Walji
Claims 26, 30, 32, and 33 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by A. Walji et al. (WO 2017/222951A1, 12/28/2017, "Walji" cited in the IDS dated 05/12/2025).
Walji discloses HDAC6 inhibitors of formula (I) [Abstract]. Walji discloses species of formula (I), for example, compound 158 [Pg. 135, comp. 158]:
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322
546
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Compound 158 above anticipates instant claim 26, for example formula (Iaaa4) wherein: L is bicyclic diamines (see claim interpretation above),
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115
152
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; R3 and R5 are H.
Walji’s compound 158 also anticipates formula (II) because compound 158 is a HDAC6 inhibitor. Thus, claims 30 and 32 are met because R7 is N; R8 is CH. Claim 33 is met because R9 is
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70
98
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.
Conclusion
Claims 26-34 are rejected. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MANAHIL MIRGHANI ALI ABDALHAMEED whose telephone number is (571)272-1242. The examiner can normally be reached M-F 7:30 am - 5:00 pm.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
1 Please refer to the above Written Description rejection with respect to Formula (II).
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