DETAILED ACTION
Notice of AIA Status
The instant application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the Leahy-Smith America Invents Act (AIA ).
Status of the Claims
The listing of claims filed 23 August 2024 has been examined.
Claims 1–19 are pending.
Claims 1, 3, 5, 7, 8, and 10–18 are amended.
Claim 19 is new.
Priority
The instant application was filed 23 August 2024; is a national stage application of PCT/CN2023/075805, filed 17 February 2023, and claims priority to CN 2022 10178772.9, filed 25 September 2022. Applicant’s claim for foreign priority is acknowledged, and a copy of the priority document has been received.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 28 October 2024 and 6 September 2025 are acknowledged and have been considered.
Claim Rejections - 35 U.S.C. § 112
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.
Claim 15 is rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The term “associated” in the phrase “GABAA receptor-associated disease” is a relative term and a clear standard or interpretive frame of reference for the term is not provided in any of the claims or in the specification. Because no standard has been provided for the term, it is unclear whether a disease that is modulated by inhibition of GABAA is a “GABAA receptor-associated disease” if the disease is also modulated by inhibition of GABAB or another receptor. In other words, it is unclear if the scope of “GABAA receptor-associated disease” is limited to diseases that are treated only through direct GABAA receptor activity or if the scope includes diseases treated primarily through another biological target that also happens to be modulated by the GABAA receptor. The specification does not define the term “GABAA receptor-associated disease” or provide guidance as to the scope of diseases that would or would not be encompassed by the phrase “GABAA receptor-associated disease.” As such, one of ordinary skill in the art would not be reasonably certain as to what was meant by “GABAA receptor-associated disease” in this context. Furthermore, the public would not be informed of the boundaries of what constitutes infringement of a patent issued to the claim.
Appropriate correction is required.
Claim Rejections - 35 U.S.C. § 112
The following is a quotation 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.
Claim 15 is rejected under 35 U.S.C. § 112(a) 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 the claims.
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.
The Wands factors are analyzed with respect to the claimed invention in turn below.
The breadth of the claim is broad in scope, as it extends to treating any disease that may be considered a “GABAA receptor-associated disease.”
The nature of the invention generally relates to the pharmaceutical art and more specifically to a compound of formula (1) and methods of administering the compound to a subject. The compounds are alleged to have an affinity to a GABAA receptor. (Spec., Table 3). Thus, the nature of the invention is sophisticated.
The state of the prior art is discussed in the instant specification, which explains the GABA is an inhibitory neurotransmitter and substances that modulate the GABAA receptor are used to treat epilepsy, anxiety, and depression. (Spec, p.1). The specification also notes that recent evidence suggests the GABAA receptor may be involved in certain pain states. (Id.).
Generally, in order to treat a disease, one of skill in the art must identify a biological target for affecting the disease, demonstrate a first drug candidate some way modulates the normal processes of the biological target, and demonstrate that a subject would benefit from such modulation without detrimental side effects. Typically, the process includes in vitro laboratory screening, in vivo testing, and clinical testing. Once that process has been successfully completed by the first drug candidate, subsequent drug candidates can benefit from the established proof of concept if a substantial correlation can be established between the first drug candidate and the subsequent drug candidates.
Examiner is aware of drugs like ganaxolone, which are used to treat seizures via the GABAA receptor, but Examiner is not aware of drugs for the treatment of any disease associated with a GABAA receptor. Thus, the state of the prior art is developed for treating epilepsy but closer to an infancy stage for treating any disease that may be considered to be associated with the GABAA receptor.
The level of one of ordinary skill may be found by inquiring into: (i) the type of problems encountered in the art; (ii) prior art solutions to those problems; (iii) the rapidity with which innovations are made; (iv) the sophistication of the technology; and (v) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of the factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983). Based on the typically high education level of workers in the pharmaceutical art and the high degree of sophistication required to solve problems encountered in the art, Examiner finds a person having ordinary skill in the art would have at least a college degree in chemistry, biology, biochemistry, pharmacology, or a related field, and several years of experience.
The level of predictability in the art is generally unpredictable. The relevant art requires each potential drug candidate to be assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18, 24 (CCPA 1970). The more unpredictable an area is the more specific disclosure is necessary to satisfy the statutory requirement. MPEP § 2164.02(II) explains that a correlation between the claimed invention and the evidence provided in an application, along with a correlation between the evidence and the models recognized in the art, are required:
“Correlation” as used herein refers to the relationship between in vitro or in vivo animal model assays and a disclosed or a claimed method of use. An in vitro or in vivo animal model example in the specification, in effect, constitutes a “working example” if that example “correlates” with a disclosed or claimed method invention. If there is no correlation, then the examples do not constitute “working examples.” In this regard, the issue of “correlation” is also dependent on the state of the prior art. In other words, if the art is such that a particular model is recognized as correlating to a specific condition, then it should be accepted as correlating unless the examiner has evidence that the model does not correlate. Even with such evidence, the examiner must weigh the evidence for and against correlation and decide whether one skilled in the art would accept the model as reasonably correlating to the condition. In re Brana, 51 F.3d 1560, 1566, 34 USPQ2d 1436, 1441 (Fed. Cir. 1995) (reversing a USPTO decision based on finding that in vitro data did not support in vivo applications).
Further, treatments may be effective for some subjects and ineffective for other subjects. Thus, each candidate for pharmaceutical or veterinary medicine must be evaluated on its own even when a nexus to an existing drug or class of drugs has been established.
The amount of direction provided by the inventor is limited to a list of diseases that may be associated with the GABAA receptor, and recommended dosages or formulations for use in such a method. (Spec., pp.20, 31–32).
The existence of working examples include in vitro assay screening of certain compounds of formula (1) for affinity for a2-GABAA receptor, functional activity on subtypes of GABAA receptors, and genotoxicity studies in a micronucleus assay. (Id., 93–99). There are no examples demonstrating in vivo activity against the numerous and various diseases that may be considered within the scope of the claimed “GABAA receptor-associated disease.”
The quantity of experimentation needed to make or use the invention based on the content of the disclosure is extensive, as it includes in vitro and in vivo screening for each specific disease or disorder encompassed by the claims. As claimed, the scope of such diseases is essentially unbound, which means the quantity of experimentation needed in extensive.
Scope of Enablement Conclusion
In view of the Wands factors discussed above, the disclosure of the instant application does not reasonably enable a person having ordinary skill in the art to use the full scope of the claimed invention. The breadth of the claims is broad in scope; the nature of the invention is sophisticated; the state of the prior art is in its infancy for the scope of diseases recited in the claims; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided by the inventor is limited to a list of diseases that may be associated with the GABAA receptor and recommended dosages or formulations for use in such a method; there examples are limited to in vitro screening assays but there are no working examples demonstrating in vivo activity against various diseases within the scope of a “GABAA receptor-associated disease”; and the quantify of experimentation needed to practice the claimed invention is extensive. Thus, when the evidence is considered as a whole, undue experimentation would be required to practice the full scope of the claimed invention.
Examiner recommends amending claim 15 to include the specific diseases in claim 16, and then cancel claim 16 and make claims 17 and 18 dependent from claim 15.
Allowable Subject Matter
Claims 1–14 and 19 are allowed. Close prior art includes WO 2015/189744 [IDS], which discloses related compounds according to formula (II), shown below, that have the same structural core but a fused bicyclic ring substituent with one heterocycle, which is distinct from the corresponding variable R1 in Formula (1) of the instant application because the instant variable R1 requires two heterocyclic rings fused together.
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Claims 16–18 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jason Nolan at (571) 272-2480. The examiner can normally be reached Monday through Friday between 9:00–5:00.
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/J.M.N./Patent Examiner, Art Unit 1623
/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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