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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/26/2025 has been entered.
DETAILED ACTION
Claims 11, 12, 15, and 20 have been cancelled. Claims 21-24 are newly added. Claims 1-10, 13, 14, 16-19, and 21-24 are pending and under examination.
Claim Objections
Claims 1are objected to because of the following informalities: the claims contain grammatical errors and redundant recitations.
Claim 1 may be amended to recite:
A method for treating : selecting a subject afflicted with depression, and administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of a eukaryotic elongation factor 2 kinase (eEF2K)-inhibiting compound.
Claim 19 may be amended to recite:
A method for treating depression in a subject in need thereof, comprising: administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of an eEF2K-inhibing compound.
Appropriate correction is required.
Response to Arguments
Applicant’s arguments, with respect to the rejection of claims 1-10 under 35 USC 102, and claims 13, 14, and 16-18 under 35 USC 103, have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 112(b)
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.
Claim 5 is 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.
Claim 5 contains a Markush group, i.e., a closed group of alternatives, but recites “or” instead of “and” at the end of the list. Therefore, the list is open-ended and it is unclear what other alternatives are intended to be encompassed by the group. Claim 5 also recites “other…inorganic compounds”. However, the claim does not recite any inorganic compounds. Therefore, it is unclear what is meant by “other”.
To obviate the rejection, claim 5 may be amended to recite: The method of claim 1, wherein said eEF2K-inhibiting compound is selected from the group consisting of: nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids, organic compounds, and inorganic compounds.
Claim Rejections - 35 USC § 112(a)
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, 19, 21, and 22 are 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
Applicant is referred to MPEP 2163(II)(A)(3)(a)(i and ii), which states that the written description requirement for a claimed genus may be satisfied 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. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure indicates that the patentee has invented species sufficient to constitute 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.
Claims 1-10, 19, 21 and 22 are drawn to a method for treating depression comprising administering to a subject a pharmaceutical composition comprising a therapeutically effective amount of an eEF2K-inhibiting compound. Claim 5 recites that the eEF2K inhibitory compound is selected from the group consisting of: nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic compounds. The specification does not disclose all species that are representative of the entire genus of eEF2K inhibitory compounds as claimed.
The specification reduces to practice one species of the claimed genus of eEF2K-ihibitory compounds, namely ketamine (Figures 7I-7L; para. [0133]), which is an organic compound. The specification does not disclose any eEF2K inhibitory compounds that are nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids, or other organic or inorganic compounds. Therefore, the disclosed species is not representative of the entire genus of eEF2K inhibitory compounds as claimed.
The instant specification does not disclose what structural properties the claimed compounds must possess to inhibit eEF2K and to treat depression as claimed. Autry et al., (NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. 7 July 2011. Vol 475. NATURE) teaches that ketamine, which is an ionotropic glutamatergic NMDAR antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder (Abstract). Autry teaches that ketamine-mediated blockade of NMDAR at rest deactivates eEF2K (Abstract), and teaches that ketamine-treated neurons showed decreased eEF2 phosphorylation compared to controls (Page 94, Column 1, Paragraph 1). However, Autry does not teach any other eEF2K-inhibitory compounds that treat depression, nor does Autry teach whether or not the eFF2K-inhibiting activity of ketamine is responsible for the alleviation of depression symptoms.
In summary, neither the specification, nor the prior art, disclose a structure-function relationship between eEF2K-inhibitory compounds and their ability to treat depression. One of ordinary skill in the art cannot reasonably predict every compound that inhibits eEF2K and meets the functional requirement as claimed.
Based on the above analysis, one of ordinary skill in the art would not conclude that Applicant was in possession of the entire genus of eEF2K-inhibitory compounds that are able to treat depression.
Claim Rejections - 35 USC § 112(d)
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.
Claim 9 is 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.
Claim 9 depends from claim 2, which depends from claim 1. Claim 1 is drawn to a method of treating a subject afflicted with depression. Claim 2 recites wherein treating comprises inducing neuron proliferation. Claim 9 is drawn to the method of claim 2 wherein said neuron is of a subject afflicted with a neurological disease. A neurological disease is broader than depression, which is a specific neurological disease. Therefore, claim 9 fails to further limit the subject matter of the claim from which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 1-10, 19, 21, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Autry et al., (NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. NATURE 7 July 2011. Vol 475, pp.91-95) as evidenced by PubChem (National Center for Biotechnology Information (2025). PubChem Compound Summary for CID 3821, Ketamine. Retrieved September 17, 2025) and Clarke et al., (Ketamine modulates hippocampal neurogenesis and pro-inflammatory cytokines but not stressor induced neurochemical changes. Neuropharmacology 112 (2017) 210-220)
Regarding claims 1 and 19, Autry teaches that the administration of ketamine, an ionotropic glutamatergic NMDAR antagonist, produces fast-acting antidepressant responses in patients suffering from major depressive disorder (Abstract). It is interpreted that subjects suffering from depression were selected and were administered ketamine to treat said depression. Autry also teaches the administration of ketamine to mice, and teaches that said administration resulted in antidepressant-like behavioral effects (Figure 1). Based on the instant specification, the term “subject” refers to an animal, including mice (para. [073]). Autry teaches that mice were subjected to chronic mild stress, which is an animal model of depression (Page 91, Column 1, Paragraph 2). Therefore, the mice of Autry are considered subjects afflicted with depression. Autry teaches that the ketamine-mediated blockade of NMDAR at rest deactivates eukaryotic elongation factor 2 kinase (eEF2K) (Abstract). Therefore, ketamine is considered an eEF2K inhibitor.
Regarding claims 2, 9, and 21, Autry teaches administration of ketamine, an eEF2K inhibitor, to mice subjected to chronic stress, which are considered subjects afflicted with depression (Abstract). Ketamine induces neurogenesis in mice subjected to stress, as evidenced by Clarke (Abstract; Figure 5). Therefore, it is interpreted that the method of Autry inherently results in proliferation of neurons in mice afflicted with depression, i.e., a neurological disease.
Regarding claim 3, Autry teaches that NMDAR activity causes sustained activation of eEF2 kinase, whereas acute NMDAR blockade at rest attenuates eEF2 phosphorylation (Page 93, Column 1, Paragraph 3). Autry teaches that ketamine-mediated blockade of NMDAR at rest deactivates eEF2K (Abstract), and teaches that ketamine-treated neurons showed decreased eEF2 phosphorylation compared to controls (Page 94, Column 1, Paragraph 1). Therefore, it is interpreted that administration of ketamine inhibits eEF2K kinase activity.
Regarding claim 4, Autry teaches that ketamine-treated neurons showed decreased eEF2 phosphorylation compared to controls (Page 94, Column 1, Paragraph 1) and that ketamine administration led to rapid decrease in the level of phosphorylated eEF2 in the hippocampus (Page 94, Column 2, Paragraph 1). Therefore, it is interpreted that the method of Autry reduced the number of phosphorylated eEF2 molecules.
Regarding claim 5, ketamine is an organic molecule as it contains carbon and hydrogen, as evidenced by PubChem (National Center for Biotechnology Information (2025). PubChem Compound Summary for CID 3821, Ketamine. Retrieved September 17, 2025).
Regarding claim 6, Autry teaches administration of ketamine, an eEF2K inhibitor, to a subject afflicted with depression (Abstract). Ketamine administration increases adult hippocampal neurogenesis in mice, as evidenced by Clarke (Abstract). Therefore, it is interpreted that the method of Autry inherently results in neurogenesis in the hippocampus.
Regarding claim 7, Autry teaches administration of ketamine, an eEF2K inhibitor, to a subject afflicted with depression (Abstract). Ketamine induces neurogenesis in the dentate gyrus, as evidenced by Clarke (Page 218, Column 2, Paragraphs 2 and 3).
Regarding claim 8, Autry teaches administration of ketamine, an eEF2K inhibitor, to a subject afflicted with depression (Abstract). Ketamine increases the proportion of functionally mature neurons (Page 218, Column 2, Paragraph 2). A mature neuron is interpreted to be synonymous with a mature excitatory neuron.
Regarding claims 10 and 22, according to the instant specification “old” encompasses a subject past the embryonic neurodevelopmental period, such as neonatal, baby, child, adolescent, mature, or aged (para. 053). Autry teaches the administration of ketamine, an eEF2K inhibitor, to 6- to 8-week-old mice (Methods, Paragraph 1, Mice), i.e., mice that are past the embryonic neurodevelopmental period. Therefore, is interpreted that the mice of Autry are considered old subjects. Ketamine induces neurogenesis in mice that are 8 to 10 weeks of age, as evidenced by Clarke (Page 211, Column 1, Experimental Procedures, 2.1). Therefore, it is interpreted that the method of Autry inherently induces neurogenesis the brains of old mice.
Claims 13, 14, 16-18, 23 and 24 are drawn to a method for screening for a compound suitable for treating depression, however, the only active steps required by the claims are: contacting a neuron with a compound, and immunostaining said neuron with Bromodeoxyuridine (BrdU) or Doublecortin (DCX). The steps of determining eEF2K activity and determining neuron proliferation are considered mental processes, i.e., steps that can be performed in the mind, are therefore not given patentable weight.
See MPEP 2106.04(a)(2)III, which states: The courts consider a mental process (thinking) that “can be performed in the human mind, or by a human using a pen and paper” to be an abstract idea. CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). As the Federal Circuit explained, “methods which can be performed mentally, or which are the equivalent of human mental work, are unpatentable abstract ideas the ‘basic tools of scientific and technological work’ that are open to all.’” 654 F.3d at 1371, 99 USPQ2d at 1694 (citing Gottschalk v. Benson, 409 U.S. 63, 175 USPQ 673 (1972)). See also Mayo Collaborative Servs. v. Prometheus Labs. Inc., 566 U.S. 66, 71, 101 USPQ2d 1961, 1965 (2012) (“‘[M]ental processes[] and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work’” (quoting Benson, 409 U.S. at 67, 175 USPQ at 675)); Parker v. Flook, 437 U.S. 584, 589, 198 USPQ 193, 197 (1978) (same). Accordingly, the “mental processes” abstract idea grouping is defined as concepts performed in the human mind, and examples of mental processes include observations, evaluations, judgments, and opinions
Thus, it is interpreted that any reference that teaches contacting a neuron with a compound and staining said neuron with BrdU or DCX meets the limitations of instant claims 13-18 and 24.
Claims 13, 14, 16-18, 23 and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clarke et al., (Ketamine modulates hippocampal neurogenesis and pro-inflammatory cytokines but not stressor induced neurochemical changes. Neuropharmacology 112 (2017) 210-220) as evidenced by Jewett and Thapa. (Physiology, NMDA Receptor. 2022 Dec 11. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 30137779.)
Regarding claims 13, 14, 16-18, 23 and 24, Clarke teaches administration of ketamine to mice (Abstract). Ketamine is an NMDA receptor antagonist, i.e., ketamine binds to the NMDA receptor. NMDA receptors are neuronal receptors, as evidenced by Jewett and Thapa (Page 2, Organ Systems Involved) therefore, because ketamine binds to neuronal receptors, it is interpreted that administration of ketamine to mice meets the limitation of “contacting a neuron with a compound”. Clarke teaches that ketamine treatment increased neurogenesis in the middle portions of the hippocampal dentate gyrus, as indicated by DCX staining (Figure 5 legend). Therefore, it is interpreted that hippocampal neurons contacted with ketamine, i.e., a compound, were stained with DCX.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHEL EMILY MARTIN whose telephone number is (703)756-1416. The examiner can normally be reached M-Th 8:30-16:00, F 8:30-10:00 EST.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/RACHEL EMILY MARTIN/Examiner, Art Unit 1657