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 the Claims
Claims 1-8, 10-11, and 13-22 are pending (claim set as filed on 09/02/2022).
Priority
This application is a 371 of PCT/EP2021/055694 filed on 03/05/2021, which has a foreign application to EP 20161220.7 filed on 03/05/2020.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 09/02/2022 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the Examiner.
Drawings
The drawings filed on 09/02/2022 have been accepted.
Specification
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the Applicant’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM.
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825). A “Sequence Listing” is required on paper if the application discloses a nucleotide or amino acid sequence as defined in 37 CFR 1.821(a) and if the required “Sequence Listing” is not submitted as an electronic document either on read-only optical disc or as a text file via the patent electronic system.
Claim Rejections - 35 USC §112(b), Indefinite
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.
Claims 20-22 are 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.
Regarding claims 20 and 22, 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)).
Moreover, claim 20’s recitation of the phrase “behavioral deficit is selected from the group consisting of: impaired learning, impaired memory such as impaired working memory, deficits in reading, writing and/or mathematics such as deficits in grammatical and/or mathematical reasoning, difficulties creating connections with other people, problems with friendships or romantic relationships, reduced social competence, lack of social awareness, unfocused thinking, reduced social engagement, lack of motivation, and reduced attention” is considered indefinite as being subjective terminology. The MPEP 2173.05(b) states that “When a subjective term is used in the claim, the examiner should determine whether the specification supplies some objective standard for measuring the scope of the term. Some objective standard must be provided in order to allow the public to determine the scope of the claim. A claim term that requires the exercise of subjective judgment without restriction may render the claim indefinite. Claim scope cannot depend solely on the unrestrained, subjective opinion of a particular individual purported to be practicing the invention”. Accordingly, such conditions may be experienced or extrapolated to the general population and thus, the scope of the claims are unclear and difficult to objectively ascertain as they may be natural conditions of the aging process, temporarily experienced, and/or personality traits of an individual. For the purposes of compact prosecution and prior art examination, the patient population of claim 20 will be interpreted as the same as in claim 1.
Claim 21 is rejected because it is a dependent claim that does not overcome the deficiencies of the rejected claim from which it depends.
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.
Claims 1-6 and 13-21 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
The claims recite extremely broad genus term “a modulator of gamma-aminobutyric acid (GABA)” or “a modulator of Aralar” which attempts to functionally describe a feature "by what it does rather than by what it is" (MPEP 2173.05(g)). However, the claimed term of “a modulator” is a generic and vague term (similar to describing it as “a molecule”, “a compound”, “a substance”, etc.) such that the structure cannot be immediately envisage by one ordinary skill in the art. The pharmacophore (i.e., the chemical structure or chemical group responsible its effect) of a drug dictates its mechanism of action. Thus, the genus does not have sufficient description in the specification, nor are a representative number of compounds described within this genus to demonstrate that Applicant was in possession at the time of filing of any one of these genus terms.
The level of skill and knowledge in the art is high, generally that of a biochemist. The MPEP 2163 states that written description for a genus can be achieved by a representative number of species within a broad generic claim. It is unquestionable that the claims are broad and generic, with respect to all possible drugs or compounds encompassed by the claims. The possible structural variations are limitless to any compound. Although the claims may recite some functional characteristics, the claims lack written description because there is no disclosure of a correlation between function and structure of the molecule and its ability to module GABA/aralar beyond those compounds specifically disclosed in the examples in the specification. Moreover, the specification lacks sufficient variety of species to reflect this variance in the genus.
Claim Rejections - 35 USC §102, Anticipation
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, 7, 13-20, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stefansson (US 2011/0111419 A1).
Stefansson’s general disclosure relates to methods and kits for risk management of schizophrenia in a human individual, by assessing such copy number variations in the genome of individuals (see abstract, ¶ [0011]).
Regarding claims 1 and 13-20 pertaining to the patient population with a neurological disorder, Stefansson discloses that schizophrenia is an illness is characterized by a variety of positive and negative signs and symptoms, as well as cognitive dysfunction that typically commence in early adulthood and often continue throughout life (see ¶ [0003], [0062], [0011]). Stefansson teaches “markers and CNVs described herein can be combined with other risk factors for schizophrenia” (see ¶ [0023]) and further teaches copy number variation (CNV) at 15q11.2 (see ¶ [0029]-[0033], [0065]-[0067]). Stefansson teaches “gene deletions in the 15q11.2 region are most likely to be responsible for both the autistic and obsessive-compulsive features observed in AS and PWS with class one deletions, and the schizophrenia phenotype in this study is CYFIP1 (FIG. 1C). CYFIP1 interacts with fragile X mental retardation protein (FMRP) as well as with the Rho GTPase Rael, which is involved in regulating axonal and dendritic outgrowth and the development and maintenance of neuronal structures” (thereby affecting GABA neurotransmitter in the neurons) (see ¶ [0236], [0286], [0289], & Example 1).
Regarding claims 7 and 22 pertaining to the pharmaceutical agent for treatment, Stefansson teaches “treatment options for schizophrenia include (i) medication, (ii) psychological and social Intervention and (iii) other therapies. Medication: The most common medication is antipsychotic medication, which mainly serves to reduce positive symptoms of the disease. Antipsychotic medications include … Aripiprazole (Abilify)” (see ¶ [0181]-[0182]).
Claim Rejections - 35 USC §103, Obviousness
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claims 2, 5, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Stefansson as applied to claims 1, 7, 13-20, and 22 above, and in view of Friesen (US 2010/0197635 A1).
Stefansson’s teachings are discussed above as it pertains to a method of treating a neurological condition.
However, Stefansson does not teach: wherein said modulator is a modulator of Aralar (claims 2, 5, and 21).
Friesen’s general disclosure relates to the treatment of tardive dyskinesia through the administration of pyridoxal 5’-phosphate (see abstract & ¶ [0002]). Friesen discloses that tardive dyskinesia occurs in schizophrenic patients as a result neuroleptic treatments (see ¶ [0016]). Friesen discloses “the mechanism of action of pyridoxine is not clear since plasma P5P levels do not display a linear relationship with perfect positive correlation. It is believed that the role of
P5P in decarboxylation of dopa resulting in the production of dopamine as well as formation of other neurotransmitters (gamma-amino butyric acid (GABA), serotonin and melatonin) may be involved in the symptoms of tardive dyskinesia” (see ¶ [0007]-[0008]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ a modulator of Aralar (e.g., pyridoxal 5’-phosphate as per the instant pre-grant specification at ¶ [0151]-[0152]) such as taught in Friesen in the method of Stefansson for the treatment of a neurological disorder. The ordinary artisan would have been motivated to do so is because Friesen suggests pyridoxal 5’-phosphate can be used in the therapy of patients with schizophrenia. Thus, it is prima facie obvious to combine known elements in the art to arrive at the claimed invention. The ordinary artisan would have had a reasonable expectation of success is because both of the cited references are in the same field of endeavor directed to treatment of neurological conditions.
Claims 3-4, 6-8, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Stefansson as applied to claims 1, 7, 13-20, and 22 above, and in view of Tyers (US 2009/0076019 A1).
Stefansson’s teachings are discussed above as it pertains to a method of treating a neurological condition.
However, Stefansson does not teach: wherein said modulator comprises diazepam, GABA, valproic acid, diaminobutyric acid, acetohexamide, chlorpropamide, melatonin, trimetazidine dihydrochloride, ciprofibrate (claims 7 and 11).
Tyers’ general disclosure relates to “compositions comprising the identified modulators and methods of using the modulators and compositions, in particular to treat neurological disorders or damage are also disclosed” (see abstract & ¶ [0001]).
Regarding claims 17 and 20 pertaining to the neurological disorder or behavioral condition, Tyer further teaches “the condition or disease is a neurological disorder including without limitation a presenile dementia (early onset Alzheimer’s disease), senile dementia (dementia of the Alzheimer’s type), Parkinsonism including Parkinson’s disease, Huntington’s chorea, tardive dyskinesia, hyperkinesias, mania, attention deficit disorder, attention deficit hyperactivity disorder, sleep-wake disorder, chronic-fatigue syndrome, tremor, epilepsy, neuropathic pain, addiction (e.g., nicotine addiction), anxiety, dyslexia, schizophrenia, obsessive-compulsive disorder, and Tourette’s syndrome” (see ¶ [0083]).
Regarding claims 3-4 and 6, pertaining to a modulator of GABA levels, Tyers teaches the “modulating agents in the composition are one or more agents that modulate neuro-transmission in the dopamine, serotonin, opioid, glutamate, and/or vanilloid pathways” (see ¶ [0012]). Thus, these agents whether directly or indirect, affect GABA levels, for example, glutamate is a precursor molecule of GABA:
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Regarding claims 7 and 11 pertaining to the modulator, Tyers perform assay to screen and identify modulating agents that could be used for neurological treatment and identified compounds such as GABA, valproic acid, acetohexamide, melatonin, ciprofibrate, et al. (see Table 3 and Table 10). Tyers also teaches aripiprazole (see ¶ [0065]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to employ the drugs such as taught by Tyers in the method of Stefansson in the treatment of a neurological disorder. The ordinary artisan would have been motivated to do so is because Tyers suggests these agents may be used to treat a neurological condition such as schizophrenia which is also a condition taught by Stefansson. Thus, the MPEP 2141 provides “examples of rationales that may support a conclusion of obviousness include: (a) combining prior art elements according to known methods to yield predictable results; (b) simple substitution of one known element for another to obtain predictable results; (e) obvious to try - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success.
Claims 8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Stefansson and in view of Tyers as applied to claims 1, 3-4, 6-7, 11, 13-20, and 22 above, and in further view of Kuo (US 2016/0038495 A1).
Stefansson’s teachings are discussed above as it pertains to a method of treating a neurological condition. Tyers teaches brain tumors in schizophrenic patients (see Tyers at ¶ [0130]).
However, modified-Stefansson-Tyers do not teach: wherein said inhibitor is ML309 (claims 8 and 10).
Kuo teaches an anti-cancer agent that inhibits isocitrate dehydrogenase 1 (IDH1) comprising ML309 (see ¶ [0004], [0077]).
It would have been obvious to one of ordinary skill in the art to use an inhibitor of IDH1 such as ML309 as taught by Kuo in the method of modified-Stefansson-Tyers which discloses a schizophrenic patient having brain tumor. The ordinary artisan would have been motivated to add the administration of ML309 is because it can treat the cancer as a co-morbidity in modified-Stefansson-Tyers.
Conclusion
No claims were allowed.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653