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 .
Non-Final Rejection
The Status of Claims:
Claims 1-2, 4-5, 8, 10-11, 13, 15, 18-29 and 33 are pending.
Claims 1-2, 4-5, 8, 10-11, 13, 15, 18, 20-25, and 27-29 are rejected.
Claims 19 and 26 are objected.
Claim 33 is allowable.
DETAILED ACTION
1. Claims 1-2, 4-5, 8, 10-11, 13, 15, 18-29 and 33 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/EP2022/067376 06/24/2022 ,which has a priority of 63215054 06/25/2021.
Drawings
3. None.
IDS
4. The IDS filed on 9/24/2024 are reviewed by the examiner.
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 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.
Claim Objections
Claims 19 and 26 are objected to because of the following informalities: the boxes surrounding the compounds can be improper. The examiner recommends to remove them from the compounds. Appropriate correction is required.
Claim Rejections - 35 USC § 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.
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 1-2, 4-5, 8, 10-11, 13, 15, 18-25, and 27-29 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 pre-AIA the applicant regards as the invention.
Claims 1-2, 4-5, 8, 10-11, 13, 15, 18-25, and 27-29 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 Parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush 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 members of the improper Markush grouping do not share a substantial feature and /or a common use that flows from the substantial structural feature for the following reasons :
Claim 1 contains the followings:
1 (Original) A compound of Formula (I):
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(I)or a pharmaceutically acceptable salt thereof,
wherein A is a heteroaryl; L1 is -O-, -CR5R6- or a bond; L2 is - CR5R6 ;R1 is alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, or -NR7R8, or R1 and R2 together with the atom to which they are attached form a heterocycle; R2, R3, R4 are independently hydrogen, alkyl, cycloalkyl, heterocyclyl, or halogen, or R2 and R3 together with the atom to which they are attached to form a carbocycle or heterocycle, or R2 and R4 together with the atom to which they are attached to form a carbocycle or heterocycle; R5 and R6 are each independently hydrogen, alkyl, cycloalkyl, heterocyclyl,alkoxy, -O-cycloalkyl, -O-heterocyclyl, or halogen, or R5 and R6 together with the atom to which they are attached to form a carbocycle or heterocycle; R7 and R8 are independently hydrogen, alkyl, cycloalkyl, or heterocyclyl, or R7 and R8 together with the atom to which they are attached form a heterocycle; Y is cycloalkyl, heterocyclyl, heteroaryl or aryl; and Z is absent, heteroaryl or aryl, wherein if L1 is a bond or CR5R6 then Z is heteroaryl or aryl; and with the proviso that the compound is not: Ph -Me
The variables of A, Y and Z in the Formula (I) are described in the specification in the followings:
A is a heteroaryl (a number of species: 78); Y is cycloalkyl(a number of species: 7), heterocyclyl (a number of species: 28), heteroaryl (a number of species: 78) or aryl (a number of species: 19); Z is absent, heteroaryl (a number of species: 78) or aryl (a number of species: 19).
Aryl" refers to aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, fluoranthene, fluorene, as-indacene, s-indacene, indane, indene, naphthalene, phenalene, phenanthrene, pleiadene, pyrene, and triphenylene.
Cycloalkyls include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Polycyclic cycloalkyls include, for example, adamantyl, norbornyl, decalinyl, 7,7-dimethyl-bicyclo[2.2.1]heptanyl.
Heterocyclyl includes dioxolanyl, thienyl[1,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, and 1,1 -dioxo-thiomorpholiny.
"Heteroaryl" includes azepinyl, acridinyl, benzimidazolyl, benzothiazolyl, benzindolyl, benzodioxolyl, benzofuranyl, benzooxazolyl, benzothiazolyl, benzothiadiazolyl, benzo[b] [1,4]dioxepinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl (benzothiophenyl), benzotriazolyl,
benzo[4,6]imidazo[1,2-a]pyridinyl, carbazolyl, cinnolinyl, dibenzofuranyl, dibenzothiophenyl, furanyl, furanonyl, isothiazolyl, imidazolyl, indazolyl, indolyl, indazolyl, isoindolyl, indolinyl, isoindolinyl, isoquinolyl, indolizinyl, isoxazolyl, naphthyridinyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 1-oxidopyridinyl, 1-oxidopyrimidinyl, 1-oxidopyrazinyl, 1-oxidopyridazinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, quinazolinyl, quinoxalinyl, quinolinyl, quinuclidinyl, isoquinolinyl, tetrahydroquinolinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and thiophenyl (i.e. thienyl).
From the above, it is estimated that each of the A , Y, and Z rings contains at least from 7 different compounds to 78 different compounds in combination with the variables R1, R2, R3 ,R4, R5 ,R6, R7 , R8 which contain numerous substituents containing cycloalkyl, heterocycloalkyl, aryl or heteroaryl groups; the claim 1 does read on an extremely high number of possible species due to all the permutations and combinations in terms of mathematically speaking. There is no substantial structural feature (for example a common core) shared by all species; furthermore, there is no indication that the species share a specific common on utility.
In response to this rejection, Applicant should either amend the claims to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims in a fact share a substantial structural feature as well as a common use that flows from the substantial structural feature.
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.
Claim 28 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claim is not directed to the treatment of the specific diseases, but the method of treating a disease or disorder that is treatable by administration of an Orexin agonist, the method comprising administering a therapeutically effective amount of the compound of claim 1
The specification falls short because data essential for treating numerous diseases treatable by administration of an Orexin agonist is not described in the specification. In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. § 112, first paragraph, have been described. They are:
1. the nature of the invention,
2. the state of the prior art,
3. the predictability or lack thereof in the art,
4. the amount of direction or guidance present,
5. the presence or absence of working examples,
6. the breadth of the claims,
7. the quantity of experimentation needed, and
8. the level of the skill in the art.
The Nature of the Invention
The current claim 28 is recited in the followings:
28. A method of treating a disease or disorder that is treatable by administration of an Orexin agonist, the method comprising administering a therapeutically effective amount of the compound of claim 1
The state of the prior art are in the followings:
DE Brabander et al (WO 2019191327) discloses a method of treating one of the diseases known as narcolepsy in a subject in need thereof, comprising administering to the subject an effective amount of compounds of
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or a pharmaceutically acceptable salt thereof.
Bogen et al (WO 2020167706 A1) discloses 5-alkyl pyrrolidine compounds which are agonists of orexin receptors in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved.
Bogen et al (WO 2020167701 A1) discloses substituted Pyrrolidine compounds are Orexin-1 receptor agonists used to treat sleep disorder, excessive daytime sleepiness In narcolepsy, repeatability hypersomnia, Alzheimer's Disease, cognitive Impairment and Parkinson's disease
However, there are no conclusive data which allow the approval for treating all kinds of diseases or conditions by using any orexin agonist in the art for any individuals.
The amount of direction or guidance present
The direction present in the current specification is that the claimed compounds can be used to treat various diseases or conditions by Orexin agonist. These diseases include
narcolepsy, narcolepsy syndrome accompanied by narcolepsy-like symptoms, cataplexy in narcolepsy, excessive daytime sleepiness (EDS) in narcolepsy, hypersomnia, idiopathic hypersomnia, repeatability hypersomnia, intrinsic hypersomnia, hypersomnia accompanied by daytime hypersomnia, interrupted sleep, sleep apnea, hypersomnia associated with sleep apnea, nocturnal myoclonus, disturbances of consciousness, such as coma, REM sleep interruptions, jet-lag, excessive daytime sleepiness, shift workers' sleep disturbances, dyssomnias, sleep disorders, sleep disturbances, hypersomnia associated with depression, emotional/mood disorders, drug use, Alzheimer's disease or cognitive impairment, Parkinson's disease, Guillain-Barre syndrome, Kleine Levin syndrome, and sleep disorders which accompany aging, muscular dystrophies, immune-mediated diseases; Alzheimer's sundowning; conditions associated with circadian rhythmicity as well as mental and physical disorders associated with travel across time zones and with rotating shift-work schedules; fibromyalgia; cardiac failure; diseases related to bone loss; sepsis; syndromes which are manifested by non-restorative sleep and muscle pain or sleep apnea which is associated with respiratory disturbances during sleep; conditions which result from a diminished quality of sleep; and other diseases related to general orexin system dysfunction.
However, the specification is silent and fails to provide guidance as to whether all those diseases require the mechanistic nature of modulating an orexin receptor by orexin agonists in the patient with the claimed compounds, i.e. the specification fails to provide a correlation between all those diseases and the activity of orexin agonist in the patient. Also, there is no direction and guidance for how all those diseases would be cured by using the claimed compounds of orexin agonists in the claims.
The presence or absence of working examples
There are no examples of treatments of various diseases
except for IP-1 accumulation assay and a section for methods of treatment without any actual data for treating the various diseases mentioned in the above. Thus, the specification fails to provide sufficient working examples as to how those diseases can be treated by using orexin agonists in the patient, i.e. again, there is no direct correlation between the diseases and the claimed compounds directly.
The breadth of the claims
The breadth of the claim is that the claimed compounds can be used to treat all the known diseases benefited by the modulation of an orexin receptor by orexin agonists, without regards as to the side-effect of the claimed compounds on the stated diseases.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to determine which kinds of those disorders would be benefited by the effect of the claimed orexin agonist compounds and would furthermore then have to determine whether or not the claimed orexin agonist compounds would provide treatment of all the known diseases listed in the above.
The level of the skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which orexin agonist compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the claimed orexin agonist compounds for all kinds of diseases-treatment. As a result, necessitating one of skill to perform an exhaustive search for which all the known diseases can be treated by all kinds of the claimed orexin agonist compounds in order to practice the claimed invention.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001 (3/13/1997), states that “ a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated by the claimed Akt3 inhibitor compound encompassed in the instant claims, with no assurance of success.
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)(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.
Claim(s) 1, 4-5, 10, 15, 18, and 27-29 are rejected under 35 U.S.C. 102(a)(2) as being anticipated clearly by DE Brabander et al (WO 2019191327)
DE Brabander et al discloses compounds and their pharmaceutical composition in the following:
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(see page 89, a paragraph#0632)
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(see page 91 , a paragraph#0646)
Aslo, it teaches that a method of treating one of the diseases known as narcolepsy in a subject in need thereof, comprising administering to the subject an effective amount of those compounds (see page 267, claim 84). These are identical with the claims.
Conclusion
Claims 1-2, 4-5, 8, 10-11, 13, 15, 18, 20-25, and 27-29 are rejected.
Claims 19 and 26 are objected.
Claim 33 is allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625
2/20/2026