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 Claims
Claims 1-11, 17, 31-33 are pending in the instant application.
Claims 12-16 and 18-30 have been canceled.
Election/Restriction
This action is in response to an election from a restriction requirement filed on April 23rd, 2026. There are 15 claims pending and 13 claims under consideration. Claims 31-32 have been withdrawn as claims directed to a non-elected invention. This is the first action on the merits. The present invention relates to a compound of formula I as recited at instant Claim 1.
Applicant’s election with traverse of Group I, Claims 1-11, 17, and newly presented Claim 33 and species election of a single species of a compound of formula I as compound 60:
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in the reply filed June 22nd, 2026 is acknowledged.
The traversal, as stated at Page 28, third paragraph under “II. Elections” of the remarks filed June 22nd, 2026 is on the grounds that “unity of invention is present and, given the nature of the claims and the subject matter encompassed by the claims, there would not be a serious burden if all of the claims and species were searched and considered at the same time.”
This argument is not found to be persuasive. The claims lack unity of invention because the compounds of formula I do not possess a single structural element that is shared by all of the alternatives. The common structural feature shared by all of the alternatives of formula I is the core structure, and this core structure, as demonstrated in the restriction requirement mailed April 23rd, 2026, is old. The common structural feature of formula I is not a patentable advance over the prior art.
The special technical feature is defined as meaning those technical features that define the contribution which each claimed invention, considered as a whole, makes over the prior art. The feature is, thus, not special if it is known. What is common here is the core structure of formula I, which is known.
The requirement for restriction is still deemed proper and therefore made FINAL.
The elected species was found to be free of the prior art. Thus, examination was extended to all compounds of formula I.
Priority
Acknowledgement is made of Applicant’s claim for foreign priority based on the CN20111117969.3, CN202210197277.2, and CN202210197158.7 applications filed in the People’s Republic of China on September 18th, 2021, March 2nd, 2022, and March 2nd, 2022, respectively.
Information Disclosure Statement
The Information Disclosure Statements filed September 10th, 2024, September 12th, 2024, and October 14th, 2025 have been fully considered by the examiner, except where marked with a strikethrough.
Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any of the errors of which Applicant may become aware of in the specification.
Drawings
Acknowledgement is made of the drawings received March 15th, 2024. These drawings are acceptable.
Claim Objections
Claim 1 is objected to because of the following informalities:
Claim 1 includes, in the structural formula of a compound of formula I, a character:
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. This character is not addressed or referenced in the claim. For clarity, this character should be removed.
Claims 1-6 are objected to because though multiple RC1 groups may be present, the limitation “each RC1 is independently selected from one of…” lacks clarity as to whether multiple RC1 groups must be the same, or if they may be distinct. Per MPEP 2173.05(h), I., “A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196.” To overcome this objection, the Examiner suggests amending the limitation to read “each RC1 is independently selected from the group consisting of…”
Similarly, Claim 7 is objected to because the variables R1 and R2 are “each independently selected from one of…” As above, this lacks clarity as to whether these variables must be the same, or if they may be distinct. The Examiner suggests amending this limitation to read “… R1 and the R2 are each independently selected from the group consisting of…”
Similarly Claim 9 is objected for the recitation that the substituent of Ra is “at least one of…”. The Examiner suggests amending this claim to read “the substituent is selected from the group consisting of …”
Claims 2, 3, and 7 are objected to because the formatting of the definitions of the variables are inconsistent with Claim 1, from which they depend. Claim 1 uses subscripts in the definitions of each variable. For example, at the sixth line of Claim 1, “C1-3 alkyl” is recited. Claims 2, 3, and 7 are inconsistent with this format. For example, at the third line of Claim 2, “C1-3 alkyl” is presented, failing to use subscripts in the variable definition.
Claim 8 is objected to because Formula III presents the variable “R1”. In the body of the claim, “R1” is defined. For consistence, “R1” should be amended to “R1” such that it is consistent with how it is illustrated in Formula III.
Appropriate correction is required.
Claim Rejections – Improper Markush Grouping
Claims 1-11, 17, and 33 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of a compound shown in formula I is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
The Markush grouping is directed to compounds of formula I. Formula I is:
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In formula I, variables Ra, Rb, and Rc are optionally further substituted, and represent distinct cyclic and acyclic groups with distinct substitution patterns. Further R1a and R1b are defined by acyclic and cyclic groups with distinct substitution patterns.
The result is a group of compounds with a fused bicyclic core that can be substituted by monocyclic, bicyclic, polycyclic, fused, and spirocyclic ring systems that share no significant structural similarity. This grouping includes compounds that are not obvious variants of each other. To this end, a comparison of example compounds 1 and 113, as recited, for example, at instant Claim 11 illustrates two compounds of formula I that are not obvious variants of each other.
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To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 1-10, 17, and 33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a compound of formula I in which Rb is an unsubstituted 8-membered spiroheterocycle in which the heteroatom in the spiroheterocycle is O, a C9 bridge ring substituted with OH, a substituted amino substituted with two C1-3 alkyls,
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wherein the number of double bonds is 0 or 1, m is 0, 1, 2, or 3, n is 0, 1, 2, or 3 and the Q and T are each independently N, O, or C,
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wherein f is 3, h is 0 or 1, the number of Rb1 is 1, and Rb1 is hydroxy, C1-3 alkyl, C1-3 alkoxy, C1-3 alkyl substituted by hydroxy or SOR2b,
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wherein D is C, R2b is
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wherein g is 1, R1b is
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, C1-3 alkyl, phenyl substituted with halogen, C3-6 cycloalkyl, or C2-5 alkenyl does not reasonably provide enablement for compounds of formula I in which Rb is otherwise defined. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2) The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to compounds of formula I.
Breadth of the invention:
The scope of the claimed invention is very broad, as it is drawn to any compounds of the formula:
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allowing for any of the myriad compounds possible by defining each of the variables according to the definitions set forth, for example, at Claim 1.
State of the prior art and predictability in the art:
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the 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).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F. 2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F. 2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F. 2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Level of ordinary skill in the art:
An ordinary artisan in the area of drug development would have experience in synthesizing chemical compounds for particular activities. The synthesis of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can be employed, developing a therapeutic method, as claimed, prior to synthesizing and testing compounds is generally not well-known or routine, given the complexity of certain biological systems.
The amount of direction provided and working examples:
The compound core depicted with specific substituents represents a narrow subgenus for which applicant has provided sufficient guidance to make and use; however, this disclosure is not sufficient to allow extrapolation of the limited examples to enable the scope of the compounds instantly claimed. Applicant has provided no working examples of any compounds, compositions, or pharmaceutically acceptable salts where Rb was not defined as mentioned above in the instant application.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims.” Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula. See MPEP 608.01(p).
MPEP § 2164.01 (a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here that Applicant is not enabled for making these compounds.
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 1-6 and 11 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.
Claim 1 is rendered indefinite, as the structure of formula I shows the variable Rb as a divalent moiety. The groups that may define Rb, as recited in Claim 1, however, are not divalent groups. In other words, it is indefinite as to how these groups, when defined as Rb, are bonded to the rest of the compound of formula I.
Claim 1 recites the limitation "Rb1 is …
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" in option 5) for Rb. There is insufficient antecedent basis for this limitation in the claim, as the variable k is not defined.
Claims 1-6 are rendered indefinite, as each claim recites that Rc can be
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. Based on this recitation, it is unclear as to which carbon atom(s) are intended to be bonded to the core structure of the compound.
The term “reasonable valence bond” in claims 1-6 is a relative term which renders the claim indefinite. The term “reasonable valence bond” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Within the context as claimed, “reasonable valence bond” appears in defining Rb as
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, “wherein the position of the a is any position with a reasonable valence bond in the ring.” With varying definitions of m, n, Q, and T, a person having ordinary skill in the art would not reasonably be able to ascertain the meaning of “reasonable valence bond”. Appropriate clarification is required.
Further, the recitation of “the insufficient valence bonds are complemented by H” renders Claims 1-6 indefinite, as the phrases “insufficient valence bonds” and “complemented by H” are insufficiently defined within the claims or the specification such that a person having ordinary skill in the art would be able to reasonably ascertain the metes and bounds of these limitations.
Claim 4 is rendered indefinite as in option 5, R1b is defined, for example as ((CH3)2CH2. This moiety does not have an open valence position such that it is clear as to how this moiety is bound to the rest of the compound.
Claim 8 is rendered indefinite, as defining W as O does not allow the variable R6 to be present. As instantly recited, the variable R6 is required.
Claim 10 recites the limitation "R6 is selected from …
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…
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" . There is insufficient antecedent basis for this limitation in the claim, as these groups require R2b to be defined as C4 or C5 alkyl, respectively. Claim 1, from which Claim 10 depends, defines R2b as C1-3 alkyl.
Claim 11 recites the limitation "
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…
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…
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" as a compound according to claim 1. There is insufficient antecedent basis for this limitation in the claim, as compounds 65 and 66 require R2b to be defined as C4 alkyl and C5 alkyl, respectively. Claim 1, from which Claim 11 depends, defines R2b as C1-3 alkyl. Compound 89 defines Ra as pyridinyl. As recited at Claim 1, from which Claim 11 depends, Ra is a substituted or unsubstituted phenyl, or a substituted or unsubstituted
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.
Conclusion
Claims 1-11, 17, and 33 are rejected.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL JOHN BURKETT whose telephone number is (703)756-5390. The examiner can normally be reached Monday - Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Murray can be reached at (571) 272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.J.B./Examiner, Art Unit 1624
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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