DEAILED 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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/09/2026 has been entered.
In the submission, claim 1 is amended. Accordingly, claims 1-10 are pending and under current examination.
Priority
The instant application is a national stage entry of PCT application PCT/KR2020/016994, filed 11/26/2020. Acknowledgment is made of applicant's claim for foreign priority based on an application KR10-2019-0166845 filed in Republic of Korea on 12/13/2019.
Status of Prior Rejection/Response to Arguments
The rejection of claims 1-3, 5 and 8-10 under 35 U.S.C. §103 over Szechtman et al. in view of Simmler et al. is withdrawn:
The rejection of claims 1-10 under 35 U.S.C. §103 over Szechtman et al. in view of Simmler et al., and further in view of Viasov et al. is withdrawn:
Applicant amends claim 1, and asserts instant application having unexpected results that the activation of the neural circuit connecting from basolateral amygdala to dorsomedial striatum causes the animal to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior (Remarks, p5-6). Specifically, Applicant alleges that the comprehensive OCD phenotype achieved by the present claims, particularly the prominent hoarding behavior, was completely unexpected and represents a significant contribution to the field that cannot be derived from the cited references (see Remarks, p6). The cited references do not teach or suggest that activation of the BLA-DMS circuit would induce OCD, but only teach that "disconnection" of the BLA-DMS circuit (Remarks, p6-7). Applicant further cites several references to demonstrate that the brain circuits which involved in OCD is comprehensive and unpredictable in different species, different experiment conditions, as well as different cell population in the same brain region (Remarks, p9-10, summary).
Applicant’s argument is found persuasive. Specifically, it is acknowledged that the neural circuits related to OCD is comprehensive, which involved in different brain regions and connection between these brain regions. Different species, different brain structures and/or different cell populations may lead to distinct behavior outcomes. Given that Szechtman et al. in view of Simmler et al. do not directly demonstrate activating the neural circuit connecting from basolateral amygdala to dorsomedial striatum, there would have been no reasonable expectation that the activation of the neural circuit would cause the animal to exhibit ALL of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior, as recited in instant claims. Therefore Applicant’s amendment and argument overcomes the obviousness rejection on record. The rejection is withdrawn.
New grounds of rejection are made upon re-consideration of the scope of instant claims.
New 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 1-10 are newly 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.
From M.P.E.P. § 2163, the analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated possession of the claimed invention from the standpoint of one of skill in the art at the time the application was filed. For inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession. For claims drawn to a genus, possession may be shown (for example) 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 applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus, and is an inverse function of the skill and knowledge in the art. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to
reflect the variation within the genus. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly. If a representative number of adequately described species are not disclosed for a genus, the claim to that genus must be rejected as lacking adequate written description under 35 U.S.C. 112, para. 1.
Instant claims are directed to a method for constructing an animal model of obsessive- compulsive disorder, the method comprising a step of activating a neural circuit connecting from basolateral amygdala to dorsomedial striatum in animals exclusive of humans. The claims recite animal models that include ANY animals exclusive of humans (non-human animal models), which cover a genus of animal species including ALL members of the animal kingdom except humans, including rodents (such as mice and rats), non-human primates, large animals (such as dogs, pigs and sheep), as well as simpler organisms such as zebrafish, fruit fly, worms and frogs. Therefore the scope of the claims is extremely broad. The issue at hand is whether or not Applicants have possession of the full scope of the genus of non-human animal models of obsessive- compulsive disorder, wherein the activation of a neural circuit connecting from basolateral amygdala to dorsomedial striatum in these animals causes the animals to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior, as recited in instant claims.
In the instant case, Applicants have failed to provide disclosure of species which are representative of the full scope of the genus of the animals exclusive of humans. The dependent claims have not further provided any species of the animals in the claimed method. The specification only discloses male (BL/6N) mice (see -17, line 30) as the animal model of obsessive- compulsive disorder (see i.e., p17, Examples). There is no other species disclosed in instant application regarding the animal model of obsessive- compulsive disorder.
Furthermore, Applicants have failed to provide disclosure of relevant, identifying characteristics, such as the phenotypic changes associated with the structure change (activated brain region and/or cell populations in the neural circuit of different species of animals). While Applicants have recited the phenotypes (e.g., causes the animal to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior), Applicants have failed to identify or show a known correlation exists between the phenotypic changes and the brain structures and/or the activation of the cell populations in the neural circuits in a representative species of animals. Given the genus of animals exclusive of humans cover such broad species which have structurally different brain regions and functionally distinctive neural circuits, one of ordinary skill in the art, in looking to the instant specification, would not be able to determine that Applicants were in possession of the invention, as claimed, at the time the invention was made.
Accordingly, the claims are considered to lack sufficient written description and are properly rejected under 35 USC 112(a).
Scope of Enablement
Claims 1-10 are newly 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 mouse model of obsessive- compulsive disorder, wherein the activation of a neural circuit connecting from basolateral amygdala to dorsomedial striatum of causes the mouse to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior, does not reasonably provide enablement for ANY animal exclusive of humans as an animal model of obsessive- compulsive disorder, to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior when the neural circuit connecting from basolateral amygdala to dorsomedial striatum is activated. 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.
In determining whether Applicant’s claims are enabled, it must be found that one of skill in the art at the time of invention by applicant would not have had to perform “undue experimentation” to make and/or use the invention claimed. Such a determination is not a simple factual consideration, but is a conclusion reached by weighing at least eight factors as set forth in In re Wands, 858 F.2d at 737, 8 USPQ 1400, 2d at 1404. Such factors are: (1) The breadth of the laims; (2) The nature of the invention; (3) The state of the art; (4) The level of one of ordinary skill in the art; (5) The level of predictability in the art; (6) The amount of direction and guidance provided by Applicant; (7) The existence of working examples; and (8) The quantity of experimentation needed to make and/or use the invention.
The office has analyzed the specification in direct accordance to the factors outlines in Jn re Wands. MPEP 2164.04 states: “[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection.” These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform “undue experimentation” to make and/or use the invention and therefore, applicant’s claims are not enabled.
Nature of the Invention:
The claims are directed to a method for constructing a non-human animal model of obsessive- compulsive disorder, wherein the activation of a neural circuit connecting from basolateral amygdala to dorsomedial striatum in the animal causes the animal to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior. The claims are further drawn to an animal model made by the method and a method of using the animal model for screening a candidate drug for the obsessive-compulsive disorder.
Breadth of the claims:
The claims broadly embrace a genus of animal models that includes ANY animals exclusive of humans, which cover a genus of animals including any member of the animal kingdom, including rodents (such as mice and rats), non-human primates, large animal models (such as dogs, pigs and sheep), as well as simpler organisms such as zebrafish, fruit fly, worms and frogs. Therefore the scope of the claims is extremely broad.
Guidance of the Specification and The Existence of Working Examples:
The specification of instant application discloses one species of animals: male (BL/6N) mice as the animal model of OCD in the working examples (see i.e., p17), wherein the mice were injected AAV virus and/or administered drugs, the neural circuits connecting from basolateral amygdala to dorsomedial striatum is activated by optogenetics stimulation and/or chemical administration, and their behaviors are tested and analyzed. All the behavior outcomes disclosed in the specification are obtained from these BL/6N mice. There are no other species of animals disclosed in the specification.
State of the Art and Predictability of the Art and the Amount of Experimentation Necessary:
The state of the art regarding animal models of obsessive- compulsive disorder at the time of the invention is summarized by references including Alonso et al. (Neuropsychiatr Dis Treat. 2015 Aug 4;11:1939-55), Albelda et al. (Neurosci Biobehav Rev. 2012 Jan;36(1):47-63) and Szechtman et al. (Neurosci Biobehav Rev. 2017 May;76(Pt B):254-279). Alonso et al. review strengths and limitations of the leading animal models of OCD including genetic, pharmacologically induced, behavioral manipulation-based, and neurodevelopmental models according to their face, construct, and predictive validity (Abstract). Alonso et al. teach genetic models of OCD (mice model) based on behavioral similarity such as 5-HT2c receptor knockout (KO) mice and dopamine transporter knockdown mice (p1943, left column), pharmacologically induced animal models of OCD (rats and/or mice model) such as 8-OHDPAT-induced decrease in spontaneous alternation (p1944, left column) and quinpirole-induced compulsive checking (p1945, left column), behavioral manipulation-based animal models of OCD (rats and/or mice model) such as marble burying (p1947, left column) and the signal attenuation model (p1948, left column), as well as neurodevelopmental animal models of OCD (rats model). Alonso et al. teach compulsivity of OCD can also be tested in animals including rodents, horses, pigs, cats, or dogs for locomotion change (p1940, right column). Albelda et al. evaluate each animal model’s face validity, derived from similarity between the behavior in the model and the specific symptoms of the human condition, predictive validity, derived from similarity in response to treatment (pharmacological or other), and construct validity, derived from similarity in the mechanism (physiological or psychological) that induces behavioral symptoms and in the neural systems involved (Abstract). Albelda et al. teach the way of evaluating the validity of animal models (see p49, left column), introduce leading animal models of OCD (p50, left column) including 8-OHDPAT induced decrease in spontaneous alternation in rats (p50, left column), quinpirole-induced compulsive checking in rats (p51, left column), marble burying in mice and rats (p52, right column), the signal attenuation model in rats (p55, left column) as well as spontaneous stereotypy in deer mice (p56, left column). Szechtman et al. review research with animal models of OCD, including different animals (mouse, deer mouse, rat), different research tools (optogenetic and/or chemogenetic tools) and different brain structures and neural circuits involved (i.e., cortico-basal ganglia-thalamo-cortical (CBGTC) circuits). Thus, the art of record clearly establishes that before the effective filing date of instant invention the mice and rats are widely used as animal models of OCD, other large animals, such as horses, pigs, cats, or dogs also can be used (i.e., when test the locomotion of the OCD behavior). None of the references teach that ANY AND ALL animals exclusive humans are suitable as an animal model of OCD, as well as the behavior outcomes of these animals include all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior. Therefore, in view of the state of the art for animal models of OCD at the time of filing, the lack of specific guidance in the specification for providing a representative species of animals as the test animals and the behavior outcomes, regarding the breadth of the claims, it would have required undue experimentation to make the breadth of non-human animals as claimed.
In conclusion, in view of breadth of the claims and absence of a strong showing by Applicant, in the way of specific guidance and direction, and/or working examples demonstrating the same, such invention as claimed by Applicant is not enabled commensurate with full scope. An artisan of skill would have required undue experimentation to practice the invention without reasonable expectation of success.
Related Prior Art
Instant claims are directed to a method for constructing an animal model of obsessive- compulsive disorder, the method comprising a step of activating a neural circuit connecting from basolateral amygdala to dorsomedial striatum in animals exclusive of humans, wherein the activation of the neural circuit causes the animal to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior. Szechtman et al. and Simmler et al. are considered as closet prior arts. Szechtman et al. teach animal models of OCD, the manipulation of neural circuits such as cortico-basal ganglia-thalamo-cortical (CBGTC) circuits with optogenetic and/or chemogenetic tools (i.e., activation of the neural circuits) leads to the phenotypes of OCD behaviors (p256-257). Szechtman et al. do not teach activating the neural circuit connecting from basolateral amygdala to dorsomedial striatum, as well as the behavior outcomes including all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior. Simmler et al. teach the neural circuit connecting from basolateral amygdala to dorsomedial striatum is related to goal-directed and habitual behavior, disconnection between the BLA and the DMA impairs goal-directed behavior (p5, left column). Neither Szechtman et al. or Simmler et al. teach or suggest activating the neural circuit connecting from basolateral amygdala to dorsomedial striatum , as well as the animals with the activated neural circuit will exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior. Given the complexity of the brain regions and/or neural circuits related to OCD, there would be no reasonable expectation of success of causing the animal (i.e., mice) to exhibit all of checking behavior, repetitive behavior, cleaning behavior, and hoarding behavior by activating the neural circuit connecting from basolateral amygdala to dorsomedial striatum, as recited in instant claims. Therefore the instant claims are considered novel and patentable.
Conclusion
No claims are allowed.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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