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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. GB2106872.1, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. A claim by claim analysis indicated that claims 22-24 contained several compounds not supported in application GB2106872.1 (e.g. the last compounds of claim 22). Thus these claims were given a priority date of 05/13/2022. The rest of the claims were given a priority date of 05/13/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 11/20/2023, 02/15/2024, 08/14/2024, 08/28/2024 are being considered by the examiner.
Claim Interpretation
Claims 34-36 are composition claims and thus do not depend on the use of the composition.
Claim Objections
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Claim 22 is objected to because of the following informalities: poor compound resolution (e.g. shown below). 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 26-33 and 37-38 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while possibly being enabling for treatment of specific central nervous system disorders, an otic diseases or disorders or a pain disorders related to mGlu7 allosteric modulator, does not reasonably provide enablement for treatment of any condition in a mammal or any disorder or disease modulated by the effect of a mGlu7 allosteric modulator or the prevention of any central nervous system disorders, otic diseases or disorders or pain 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 use the invention commensurate in scope with these claims.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The specification does not provide sufficient information that all conditions are treatable or preventable with pharmaceutical composition comprising compound of Formula I described in the method claims.
The instant specification fails to provide information that would allow the skilled artisan to practice the instant invention without undue experimentation. Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
(1). The Nature of the Invention:
AII of the rejected claims are drawn to an invention which pertains to a method of treatment or prevention of a disease by administering a pharmaceutical composition comprising compound of Formula I. The nature of the invention is complex in that it encompasses the treatment of all conditions whether or not mediated by mGlu7 allosteric modulator comprising administering a pharmaceutical composition comprising a compound of Formula I
(2). Breadth of the Claims:
The claims are very broad. The claims would reasonably encompass any condition in a mammal by administering a pharmaceutical composition comprising compound of Formula I. The claims would reasonably encompass any disease mediated by hypofunction of the mGlu7 system which could be the treatment of unknown diseases by administering a pharmaceutical composition comprising compound of Formula I. The coverage of diseases in the claim is immense. The breadth of the claims includes hundreds of diseases such as PTSD, degenerative neurological disorders, inflammatory, cancers or immunomodulatory or asthma or osteoperosis, etc.
The treatment of acquired PTSD or a degenerative neurological disorder is extremely quite broad, since it reads on all diseases and conditions that involve any degenerative neurological disorder as well as PTSD and brain injuries. The term "neurodegenerative disorder" covers an immense array of largely unrelated disorders that have different modes of action and different origins. The term covers such diverse disorders as Alzheimer's Disease; Parkinson's Disease; ALS and variants such as forms of ALS-PDC; dementia of the frontal lobe type (DFT) and DFT with motor neuron disease (DFT-MND); Diffuse Lewy Body Disease; Cortical Lewy body disease; Hallervordon-Spatz disease; Senile dementia of the neurofibrillary tangle type (“tangle-only dementia”); progressive familiar myoclonic epilepsy; Corticodentatonigral degeneration; more than a dozen dementias collectively called "frontotemporal dementia” (FTD); Tourette's syndrome; multiple systems atrophy (MSA; once called Shy-Drager syndrome), which exists in two forms: MSA-P type or MSA-C type; Neurological syphilis; Neurosarcoidosis; Pure autonomic failure (Bradbury-Eggleston syndrome); Friedreich ataxia and other spinocerebellar degenerations; Olivopontocerebellar atrophy (OPCA); spasmotic torticollis; Striatonigral degeneration; various types of torsion dystonia; certain spinal muscular atrophies, such as Werdnig-Hoffmann and Wohlfart-Kugelberg-Welander; Hereditary spastic paraplegia, Primary lateral sclerosis; peroneal muscular atrophy (Charcot-Marie-Tooth); Hypertrophic interstitial polyneuropathy (Dejerine-Sottas); ophthalmic disorders such as primary open-angle glaucoma (POAG) and retinitis pigmentosa; Leber's Disease; Wallerian degeneration, and Hypertrophic interstitial polyneuropathy. Neurodegeneration can also arise from stroke, and from certain types of spinal cord injuries.
(3). Guidance of the Specification /(4). Working Examples:
The guidance given by the specification as to how one would administer the claimed compounds to a subject in order to treat any disease is Iimited. All of the guidance given by the specification is the inhibitory properties of the compounds for mGlu7, and stress test, hearing tests, and pain test in rats given compounds of formula (I). See pages 118-124 of specification.
There are no working examples for the treatment or prevention of a disease using pharmaceutical compositions comprising compounds of Formula (I). There are no working examples for treatment of any condition in a mammal or any disorder or disease modulated by the effect of a mGlu7 allosteric modulator or the prevention of any central nervous system disorders, otic diseases or disorders or pain disorders.
(5). State of the Art:
While the state of the art is relatively high with regard to treating specific disease, the state of the art with regard to treating or preventing any disease is underdeveloped. In particular, there is no known compound which is effective against all diseases. For example, there are compounds that treat a range of diseases, but no one has ever been able to figure out how to get a compound to be effective against any disease generally. Thus, the existence of such a ''silver bullet'' is contrary to our present understanding in pharmaceutical art. This is true in part because diseases arise from a wide variety of sources, such as viruses (e.g. EBV, HHV-8, and HTLV-I), exposure to chemicals such as tobacco tars, genetic disorders, ionizing radiation, and a wide variety of failures of the body's cell growth regulatory mechanisms.
Additionally, one skilled in the art knowns many sources of pain are not preventable for instance one can’t prevent all injuries and all levels of pain because many occur unexpectedly and without prior warning and bring unknown levels of pain.
The state of the replete in terms of use of certain mGlu7 modulators for use with conditions such as PTSD has been show as a potential treatment. They may have potential therapeutic affects showing neuroprotective effects and improving cognitive function in animal models. However, the state of the art recognizes that these conditions are not preventable.
Sullivan’s “Pharmacotherapy of PTSD: Current Status and Controversies” discloses that “In summary, there are currently no pharmacotherapy treatments that can be recommended clinically for the prevention of PTSD development posttrauma”.
The NIH indicates that only noise induced hearing loss is completely preventable “NIHL is the only type of hearing loss that is completely preventable”(page 7).
One skilled in the art would not reasonably expect that one agent or group of related agents would be effective in preventing all acquired brain injuries, PTSD, or a degenerative neurological disorder.
(6) The predictability or unpredictability of the art:
The invention is directed to treatment of any disease in general and the prevention of specific diseases and well as unknown diseases. It is well established that ''the scope of enablement various 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 (1970).
In the instant case the unpredictability of the art is very high because there are thousands of diseases which have fundamentally different mechanism and different causes. The method of diagnosing or treating one disease or condition does not necessitate the treatment or diagnosis of another disease or condition since diseases and conditions have unique chemical pathways by which they are expressed. Additionally, a single disease or condition can be diagnosed via multiple biochemical pathways and treated via multiple biochemical pathways. Thus, the treatment and diagnosis of diseases and conditions is highly unpredictable. For example all conditions encompasses various type of cancers and yet applicant failed to provide enablement for various cancers utilizing the various compounds of formula (I). Further, the predictability of treating cancer is relatively low given that the various types of cancers have different causative agents, involve different cellular mechanisms, and consequently, differ in treatment protocol. It is known (see Jin et al., Nature Reviews Drug Discovery | Volume 22 | March 2023 | 213–234) in the current art that the challenge of cancer treatment has been to target specific therapies to pathogenetically distinct tumor types, to maximize efficacy and minimize toxicity.
(7). The Quantity of Experimentation Necessary:
In order to practice the claimed invention, one of skill in the art would have to first envision a combination of a compound of Formula I with an appropriate pharmaceutical carrier, a dosage for each, the duration of treatment, route of treatment, etc. and, in the case of human treatment, an appropriate animal model system for one of the claimed compounds. One would then need to test the combination in the model system to determine whether or not the combination is effective. If unsuccessful, one of skill in the art would have to then need to envision a modification of the combination of the compound with an appropriate pharmaceutical carrier, compound dosage, duration of treatment, route of administration, etc. and appropriate animal model system, or envision an entirely new combination of the above and test the system again. In order to practice Applicant's invention, it would be necessary for one to conduct the preceding experimentation for each type of disease because there is no known drug effective for treating all types of diseases. Therefore, it would require undue, unpredictable experimentation to practice the claimed invention to treat or prevent any disease in a mammal by administration of a pharmaceutical composition of Formula I.
(8) The quantity of experimentation necessary:
Since every disease and disorder has its unique chemical pathway of expression, diagnosis and treatment of individual diseases and condition cannot be predicted a priori but must be determined from case to case by painstaking experimental study and when the above factors are weighed together, one of ordinary skill in the art would be burdened with undue ''painstaking experimentation study'' to determine which compounds of Formula I treats which diseases/conditions. For example, chemical modification of biomolecules may alter the biological property that is important in the use of that particular, and also other properties such as solubilities in aqueous media, binding affinities etc. Thus variety of compounds encompassed by structure (I) will have different biological properties. Considering variety of compounds covered by Formula I and the multitude of different diseases to be treated, this is a very large degree of experimentation.
Genetech, 108 F.3d at 1366 states that “a patent is not a hunting Iicense. 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, a method for treating or preventing any disease in general or those mediated by mGLU7 by administering a pharmaceutical composition of Formula I of the claims is not considered to be enabled by the instant specification.
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 1-38 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.
Regarding claims 27, 31, 35, 37, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 37-38 provide for the use of a compound of claim 1, but, since the claims do not set forth any steps involved in the method/process, it is unclear what method/process Applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Claims 1-38 are rejected because the scope of the claims is unclear due to the term “N-oxide form” it is unclear where on the structure the “N-oxide form” would modify. For example can the N-oxide form replace P or Q or does it modify the C=O or is it on another group entirely? Can it change formula (I)? It is unclear what structures are included in the “N-oxide form”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 34-36 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 34-36 are composition claims and thus do not depend on the use of the composition and so do not further claim 1 from which they dependent. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 37-38 are rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Non-Relevant Close Art
The closet art was provided in the IDS and was the document WO2015189433. This reference teaches compounds of a similar structure and gives options that could be combine to give the instant compounds but requires that if R1 is an aryl than R2 is not and vice versa(shown below) Since R1-R2 cannot both be an aryl at the same time it is not obvious to get a compound of the instant invention.
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Conclusion
Claims 1-38 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR SALAMATIAN whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.A.S./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627