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 Claims
Pursuant to the amendment, filed on May 29, 2025, claims 1-14 and 16-17 have been amended. Claim 18 is cancelled. Claim 19 is new.
Claims 1-17 and 19 are pending.
Priority
This application, filed on October 21, 2024, is a National Stage entry from International Application No. PCT/JP2023/015990, filed on April 21, 2023, which claims priority under 35 U.S.C. 119 or 365 to Japanese Application No. JP2022-070484, filed on April 22, 2022. The certified copy of the foreign application has been received.
Information Disclosure Statement
The information disclosure statement (IDS) filed on October 21, 2024 has been acknowledged and considered.
Specification Objections
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
The instant abstract recites “Novel compounds are provided…” The term novel purports the merits of the invention and implicitly compares the invention with the prior art.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts. Appropriate correction is required.
Claim Objections
Claims 2–14 are objected to for minor informalities.
Claims 2–14 depend from claim 1.
A claim introducing subject matter for the first time typically recites indefinite article “a” preceding the subject matter. The same claim or a subsequent claim referring back to that subject matter typically recites definite article “the” preceding the subject matter. Such formal claim drafting provides proper antecedent basis for the claimed subject matter and avoids ambiguity, therefore improving the clarity of the claims.
In this case, each of claims 2–14 recites “A compound . . . according to claim 1,” which can cause confusion as to whether a new compound is claimed or whether the claim is referring to and further defining the compound recited in the referenced claims.
Appropriate correction is required.
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 19 is 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 treating narcolepsy, idiopathic, hypersomnia, etc., is not enabling for prevention of the same disorders. 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.
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. The claim recites: “A method for prevention or therapeutic treatment of narcolepsy, idiopathic hypersomnia…” This method purports to prevent narcolepsy and other hypersomnia related disorders. The specification discloses that narcolepsy-like symptoms produced in transgenic mice lacking endogenous orexin by denaturing orexin-producing neurons were ameliorated by intracerebroventricular administration of orexin peptide (Spec., ¶[0005]). The Specification also discloses patients with narcolepsy type 1 have low orexin levels in cerebrospinal fluid (Id., ¶[0008]) and that targeting orexin type 2 receptor (OX2R) can be used as prophylactic or therapeutic agents for narcolepsy, idiopathic hypersomnia, etc. (Id., ¶[0010]). The claim therefore encompasses a method of preventing narcolepsy with a composition containing compounds represented by Formula (1).
The nature of the invention generally relates to the pharmaceutical art and more specifically to a method for preventing narcolepsy, idiopathic hypersomnia, etc., comprising administering a compound or pharmaceutically acceptable salt of compounds represented by Formula (I). The instant specification states: “In fact, it has been reported that compounds with OX2R agonist activity improve the symptoms of narcolepsy (Patent Literature 1 ). A known compound having OX2R agonist activity, TAK-925, has been clinically tested in healthy subjects and narcolepsy patients (via intravenous administration), and another known compound, TAK-994, has been reported to cause adverse reactions in clinical trials, but the details thereof are unknown.” (Spec., ¶[0011]). Thus, the nature of the invention is sophisticated.
The state of the prior art is discussed in a review article (Kornum et al., Nature Reviews Disease Primers, volume 3, Article number: 16100 (2017)) about narcolepsy, which states: “Several medications are available for the symptomatic treatment of narcolepsy, all of which have quite good efficacy and safety profiles. However, to date, no treatment hinders or slows disease development. Improved diagnostic tools and increased understanding of the pathogenesis of narcolepsy type 1 are needed and might lead to therapeutic or even preventative interventions.” (Kornum et al., Abstract, p. 1). “No immune alterations or defects have been found in patients with narcolepsy that could allow for the screen-ing of individuals who are at risk of narcolepsy, and no treatment or lifestyle changes can prevent this disease.” (Kornum et al., p. 9, Screening and Prevention). In view of the review article, the state of the prior art acknowledges there are currently no “treatments or lifestyle changes that can prevent this disease.”
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. Ent. 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 Brane, 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 includes background information about narcolepsy and current therapies that possess OX2R agonist activity as discussed in factor (A). The direction provided in the Specification is directed towards agonist activity of the compounds represented by Formula (I) towards orexin type 1 receptor (OX1R) and OX2R.
The existence of working examples relates to testing compounds represented by Formula (I) in Flp-In 293 cells that forcibly express OX1R and OX2R, by transfecting the cells with plasmid DNAs expressing OX1R and OX2R proteins. The agonistic activity of Examples 1-134 was measured (¶¶[0763]-[0764]). The present disclosure does not provide working examples that demonstrate prevention of narcolepsy, idiopathic hypersomnia, etc., as instantly claimed.
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 indefinite scope of such diseases is essentially unbound.
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 acknowledges there are currently no treatments or lifestyle changes that can prevent narcolepsy; the level of skill in the art is high; the pharmaceutical art is unpredictable; the direction provided in the Specification is directed towards agonist activity of the compounds represented by Formula (I) towards OX1R and OX2R; and does not demonstrate possession of a method for prevention of narcolepsy, idiopathic hypersomnia, etc. nor is it commensurate in scope of the claim “A method for prevention or therapeutic treatment of narcolepsy, idiopathic hypersomnia…”; 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 the claim to omit prevention from claim 19.
Claim Rejections - 35 USC § 102
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.
Claims 1-8, 10-11, and 16-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2009080533 (“Knust”).
Claim 1 recites a compound represented by Formula (I) as shown below:
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303
406
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, wherein R1 represents a hydrogen atom, C1-6 alkyl group, etc.; R2-4 each represent, independently of each other, a hydrogen atom, C1-6 alkyl group, etc.; R7 represents a hydrogen atom, halogen, etc.; Ra represents a hydrogen atom, C1-6 alkyl group; X represents -O-, or -CRbRc-; Y represents, -CH2- OR -CO-; n represents 1 or 2; m represents 0 or 1; L represents -O- or -NH-; Q represents a 2- to 10-membered heterocyclyl group, 5- to 12-membered heteroaryl group which may be substituted with 1 to 4 R13; and R13 represents a halogen, hydroxy group, etc.
Claim 2 recites R1 is a C1-6 alkyl group, C1-6 alkoxy group, etc. Claims 3 and 5 recite R2 and R4, respectively, is a hydrogen or a halogen. Claim 4 recites R3 is a hydrogen or C1-6 alkyl group, or a halogen. Claim 6 recites Ra is a hydrogen atom. Claim 7 and 8 recites n is 1 and m is 0, respectively. Claim 10 recites Y is -CO-. Claim 11 recites Q is a 5- to 12-membered bicyclic heteroaryl group which may be substituted with 1 to 4 R13. Claim 16 recites compounds represented by Formula (I) are orexin type 2 receptor agonists. Claim 17 recites a pharmaceutical composition comprising a compound represented by Formula (I).
Knust teaches compound 93 as shown:
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389
368
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, wherein R1 is a C1-6 alkoxy group, R2-4, R7, and Ra are hydrogens, X represents -O-, Y represents -CO-, n represents 1, m represents 0, L represents -NH-, and Q represents a 5- to 12-membered heteroaryl group substituted with 2 R13 substituents, in which R13 are halogens. Accordingly, claims 1-8, 10-11, and 17 are anticipated.
Regarding claim 16, the limitation “An orexin type 2 receptor agonist” is intended use language (MPEP §2112.02) and does not provide further structural limitations to the compounds represented by Formula (I). Therefore compound 93 of Knust, would necessarily possess orexin type 2 receptor agonist activity instantly recited, because members of the Markush Formula (1) would be expected to share similar properties.
Allowable Subject Matter
Claims 9 and 12-15 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.
Conclusion
Claims 1-8, 10-11, 16-17, and 19 are rejected.
Claims 9 and 12-15 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHIL CHANDER AGGARWAL whose telephone number is (571)272-7755. The examiner can normally be reached 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAHIL CHANDER AGGARWAL/Examiner, Art Unit 1623
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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