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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 45-49, drawn to a method of treating a subject in recognized need of treatment for a disease or disorder responsive to NMDA modulation, and major depressive disorder as the elected disease or disorder responsive to NMDA modulation are maintained.
Claims 1-11, 13, 43-44 and 50 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim.
Claims 54-59, drawn to a method of treating a subject in recognized need of treatment for Alzheimer’s disease, remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species of disease or disorder responsive to NMDA modulation, there being no allowable generic or linking claim.
Status of Claims
Acknowledgement is made of the receipt and entry of the amendment to claims filed on February 20, 2026, wherein claims 1-11, 13, 43-44, 50 and 54-59 are unchanged; claims 12, 14-42, 45-47 and 53 are cancelled; and claims 48-49 and 51-52 are amended.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-11, 13, 43-44, 48-52 and 54-59 are pending.
Claims 1-11, 13, 43-44, 50 and 54-59 are withdrawn.
Claims 48-49 and 51-52 are under examination.
Priority
The instant application 17/621,907 filed on December 22, 2021 is a 371 of PCT/US2020/039163 filed on June 23, 2020, which claims priority to, and the benefits of U.S. Provisional Application No.
62/865,826 filed on June 24, 2019.
Action Summary
Applicant’s amendment to the claims overcome each and every objection previously sets forth in the Final Office Action mailed on December 29, 2025.
Claims 45 and 55 rejected under 35 U.S.C. 103 as being unpatentable over Lowe, III et al. (WO 2014/120783 A1) in view of Khan et al. (WO 2017/201283 A1) are withdrawn in light of the claim amendments.
Claim Interpretation
The limitation of “a subject in recognized need of treatment for major depressive disorder” is reasonably construed under its broadest reasonable interpretation to include each and every subject with major depressive disorder, such as those with comorbidities (e.g., major depressive disorder with other conditions, disorder or disease); and each and every subject at risk of major depressive disorder (e.g., those with a familial history of major depressive disorder that is at risk of developing major depressive disorder).
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 49 and 52 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 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 49 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having 3, 4 or 5 peaks (2θ) chosen from those having the following values: 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, 15.7, 16.8, 17.3, 18.5, and 19.9 each of the diffraction angles being ± 0.2 degrees (2θ) in a powder X-ray diffraction pattern”.
Instant claim 52 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having 3, 4 or 5 peaks (2θ) chosen from those having the following values: 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, 16.0, 20.0, 20.4, 21.3 and 23.3 each of the diffraction angles being ± 0.2 degrees (2θ) in a powder X-ray diffraction pattern”.
In the present case, the specification discloses only two solid crystalline species of compound A, which are Crystalline Form I of compound A and Crystalline Form II of compound A. The specification does not disclose any other solid crystalline form species of Compound A as broadly encompassed by the claim(s); and also, does not disclose any other species of pharmaceutical composition comprising other solid crystalline form species of compound A.
Regarding the requirement for adequate written description of chemical entities, Applicant's attention is directed to the MPEP §2163. In particular, Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 1568 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), holds that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, "not a mere wish or plain for obtaining the claimed chemical invention." Eli Lilly, 119 F.3d at 1566. The Federal Circuit has adopted the standard set forth in the Patent and Trademark Office ("PTO") Guidelines for Examination of Patent Applications under the 35 U.S.C. 112.I "Written Description" Requirement ("Guidelines"), 66 Fed. Reg. 1099 (Jan. 5,2001), which state that the written description requirement can be met by "showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics," including, inter alia, "functional characteristics when coupled with a known or disclosed correlation between function and structure ..." Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 316, 1324-25 (Fed. Cir. 2002) (quoting Guidelines, 66 Fed. Reg. at 1106 (emphasis added)). Moreover, although Eli Lilly and Enzo were decided within the factual context of DNA sequences, this does not preclude extending the reasoning of those cases to chemical structures in general. Univ. of Rochester v G.D. Searle & Co., 249 Supp. 2d 216, 225 (W.D.N.Y. 2003).
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing, identifying characteristics of the claimed genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the present case, the specification only described two solid crystalline species of Compound A. Specifically, the specification describes a crystalline form I of compound A in Example 1 with a X-ray powder diffraction pattern shown in Fig. 1, and orthorhombic crystal system (P212121 space group, and the following unit cell dimensions: a= 5.85088 (9) Å, b = 11.57133 (12) Å, and c = 25.8340 (3) Å, [Symbol font/0x61] = [Symbol font/0x62] = γ = 90°, V = 1749.02 (4) Å3, Z=4 (see e.g., [00165])); the specification further specification describes a crystalline form II of compound A in Example 2 with a X-ray powder diffraction pattern shown in Fig. 3, and orthorhombic crystal system (P212121 space group, and the following unit cell dimensions: a= 8.9035 (2) Å, b = 10.5404 (2) Å, and c = 21.3018 (5)
Å, [Symbol font/0x61] = [Symbol font/0x62] = γ = 90°, V = 1999.10 (8) Å3, Z=4 (see e.g., [00171])). In other words, each of these solid crystalline forms is characterized by a specific X-ray powder diffraction pattern and orthorhombic crystal system to identify said form. However, the instant claims pertain to the full scope of pharmaceutical composition comprises a pharmaceutically acceptable carrier and each and every solid crystalline Form of compound A having 3, 4 or 5 peaks (2θ) chosen from the list of values instantly claimed.
To the extent that said crystalline form has 3 claimed characteristics peaks in the X-ray powder diffraction pattern, it is insufficient to identify a specific crystalline species. A complete pattern containing at least four strongest reflections (major peaks) is often required to reveal the crystal's unique fingerprint. Weak reflections (minor peaks) cannot be used for crystalline phase or polymorphism identification, as they are often indistinguishable from background noise. Therefore, in order to sufficiently identify a specific crystalline form species of compound A, at least four major peak positions in a X-ray powder diffraction pattern are required to determine arrangements of all atoms within its unit cell, including lattice parameters, crystal system, and space group.
In the absence of sufficient recitation of a representative number of species for the claimed genus, while applicant is in possession of a solid crystalline form I of compound A described in Example 1 with a X-ray powder diffraction pattern in Fig. 1 and an orthorhombic crystal system described in paragraph [00165], and a solid crystalline form II of the compound A described in Example 2 with an X-ray powder diffraction pattern as shown in Fig. 3 and an orthorhombic crystal system described in paragraph [00171], it is not apparent that Applicant was actually in possession of the full scope of solid crystalline form of compound A having at least 3 claimed characteristics peaks in the X-ray powder diffraction pattern based on the limited disclosure at the time the application was filed.
Claims 48-49 and 51-52 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 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claim 48 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having a crystal form with an orthorhombic crystal system, P212121 space group, and the following unit cell dimensions: a= 5.85088 (9) Å, b = 11.57133 (12) Å, and c = 25.8340 (3) Å, [Symbol font/0x61] = [Symbol font/0x62] = γ = 90°, V = 1749.02 (4) Å3, Z=4”; instant claim 49 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having 3, 4 or 5 peaks (2θ) chosen from those having the following values: 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, 15.7, 16.8, 17.3, 18.5, and 19.9 each of the diffraction angles being ± 0.2 degrees (2θ) in a powder X-ray diffraction pattern”; instant claim 51 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form II of compound A having a crystal form with an orthorhombic crystal system, P212121 space group, and the following unit cell dimensions: a= 8.9035 (2) Å, b = 10.5404 (2) Å, and c = 21.3018 (5) Å, [Symbol font/0x61] = [Symbol font/0x62] = γ = 90°, V = 1999.10 (8) Å3, Z=4”; and instant claim 52 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having 3, 4 or 5 peaks (2θ) chosen from those having the following values: 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, 16.0, 20.0, 20.4, 21.3 and 23.3 each of the diffraction angles being ± 0.2 degrees (2θ) in a powder X-ray diffraction pattern”. There is insufficient written basis for “a therapeutically effective amount”, “a subject”, and “administering” in the specification. There is also lack of representative number of method species for treating the full scope of subject in recognized need of treatment for major depressive disorder.
The Written Description Guidelines for examination of patent applications indicates, “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, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical characteristics and/or other 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 applicant was in possession of the claimed genus.” (Federal register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see especially page 1106 column 3) and (see MPEP §2164). 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 gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Thus, the specification fails to describe these DNA sequences. The Court further elaborated that generic statements are not adequate written description of the genus because it does not distinguish the claimed genus from others, except by function.
In the present case, applicant only describe the term "therapeutically effective amount," in paragraph [0095] of the specification shown below:
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, such that it includes any amount of a compound that can prevents, alleviates, abates, or reduce the severity of a symptoms of a disease or disorder responsive to NMDA modulation. Applicant does not describe how the pharmaceutical composition is being administered (e.g., route of administration) to the subject; and also fails to describe what “subject in recognized need of treatment for major depressive disorder” is receiving the pharmaceutical composition. There is also no representative number of method species describing the claimed genus. The only factor present in the claims is a recitation that any therapeutically effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the claimed solid form of compound A can be used for treating the full scope of subject in recognized need of treatment for major depressive disorder. Thus, in the absence of sufficient representative number of method species, applicant has not provided sufficient written description that would reasonably convey to one skilled in the relevant art that the applicant was actually in the possession of the entire scope of administering any therapeutically effective amount of the pharmaceutical composition through any route of administration to each and every subject species for preventing, alleviating, abating, or reducing the severity of a symptoms of a disease or disorder responsive to NMDA modulation, including major depressive disorder.
Claims 48-49 and 51-52 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 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.
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. All of the Wand’s factors have been considered and discussed below:
(1, 5) The breadth of the claims and the Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
Instant claim 48 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having a crystal form with an orthorhombic crystal system, P212121 space group, and the following unit cell dimensions: a= 5.85088 (9) Å, b = 11.57133 (12) Å, and c = 25.8340 (3) Å, [Symbol font/0x61] = [Symbol font/0x62] = γ = 90°, V = 1749.02 (4) Å3, Z=4”.
Instant claim 49 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having 3, 4 or 5 peaks (2θ) chosen from those having the following values: 6.9, 8.4, 10.3, 12.8, 13.7, 15.3, 15.7, 16.8, 17.3, 18.5, and 19.9 each of the diffraction angles being ± 0.2 degrees (2θ) in a powder X-ray diffraction pattern”.
Instant claim 51 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form II of compound A having a crystal form with an orthorhombic crystal system, P212121 space group, and the following unit cell dimensions: a= 8.9035 (2) Å, b = 10.5404 (2) Å, and c = 21.3018 (5) Å, [Symbol font/0x61] = [Symbol font/0x62] = γ = 90°, V = 1999.10 (8) Å3, Z=4”.
Instant claim 52 recites “[a] method of treating a subject in recognized need of treatment for major depressive disorder, comprising administering to said subject in need thereof a therapeutically effective amount of a pharmaceutical composition, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier and a solid form of compound A:
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, wherein the solid form of compound A is a solid crystalline Form I of compound A having 3, 4 or 5 peaks (2θ) chosen from those having the following values: 9.4, 10.8, 11.9, 13.0, 13.7, 15.5, 16.0, 20.0, 20.4, 21.3 and 23.3 each of the diffraction angles being ± 0.2 degrees (2θ) in a powder X-ray diffraction pattern”.
The claimed term "therapeutically effective amount", when reasonably construed in light of the special definition sets forth in paragraph [0095] of the specification, to includes any amount of the compound sufficient to show benefit to the individual or subject, including preventing, alleviating, abating, and reducing the severity of a symptom of a disease or disorder.
The limitation of “a subject in recognized need of treatment for major depressive disorder” recites in the preamble is reasonably construed under its broadest reasonable interpretation to include each and every subject with major depressive disorder, such as those with comorbidities (e.g., major depressive disorder with other conditions, disorder or disease); and each and every subject at risk of major depressive disorder (e.g., those with a familial history of major depressive disorder that is at risk of developing major depressive disorder).
Therefore, the breath of these claims pertains to administering any therapeutically effective amount of pharmaceutical composition comprising a pharmaceutically acceptable carrier and each and every species of solid form of compound A having at least 3 of the claimed peaks in the X-ray diffraction pattern and the claimed orthorhombic crystal system for treating the full scope of subject with major depressive disorder and the full scope of subject at risk of major depressive disorder, such that it includes preventing.
(2, 3, 4) The state of the prior art, the level of skill in the art, and the predictability or lack
thereof in the art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the
art would have known, at the time the application was filed, about the subject matter to which the
claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art
refers to the skill of those in the art in relation to the subject matter to which the claimed invention
pertains at the time the application was filed.”
At the time the application was filed, one skilled in the art would have known tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro [3.4]octane-5-carboxylate having the structure of:
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is a white solid, and obtained as an intermediate during the synthesis of compound B having the structure of:
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that is NMDA modulator according to Khan et al. (WO 2017/201283 A1; cited in the Office Action mailed on February 20, 2025) (see e.g., p. 34, “Example 2 - Synthesis of Compound B and Compound B Maleic Acid Salt”; p. 38, line 18 to p. 39, line 4; p. 3, line 4-10). Please note tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro [3.4] octane-5-carboxylate of Khan et al. is referred to as compound “B4” in the cited reference whereas the instant application referred to as “compound A". It is noted that Khan et al. does not discloses the utility and the biological or pharmaceutical activity of said intermediate; and Khan et al. does not disclose a solid crystalline form species of said intermediate. In other words, one skilled in the art would have known tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro [3.4] octane-5-carboxylate is an intermediate and a temporary species formed during a chemical reaction.
At the time the application was filed, one skilled in the art would have known compound 2S-FNL-2, tert-butyl 2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro[3.4]octane-5-carboxylate, having the structure of
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is an exemplary compound represent by formula I that are NMDA modulators (e.g., partial agonists of NMDA) according to Lowe, III et al. (WO 2014/120783 A1; cited in the IDS filed on March 22, 2022) (see e.g., [008]; [0091]; p. 29, Table 1, “2S-FNL-2”; p. 74). While 2S-FNL-2 of Lowe, III et al. shares the structural similarity, one skilled would have known the compound 2S-FNL-2 of Lowe, III et al. is not tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro [3.4] octane-5-carboxylate because it contains 2 chiral centers rather than 3 chiral centers.
One of ordinary skill in the art would have known intermediates serve as building blocks in early stage of production, undergoing various chemical transformations to eventually produce the active pharmaceutical ingredients (APIs). Intermediate are temporary, transitional compounds used to create APIs, but do not have therapeutic properties on their own; and they often require specific storage as they may have shorter lifespans according to SimSon Pharma Limited (“What Are Intermediates in Pharma|APIs vs Intermediates” [Online]. Published on November 18, 2024) (see e.g., p. 1; p. 3, “function and purpose”). In other words, the relative skill of those in the art using an intermediate as an active pharmaceutical ingredient would have been low, because there is lack of predictability as to whether an intermediate can possess therapeutic properties without any further testing.
One of ordinary skill in the art would have also known a difference in a single stereocenter can have dramatic effects on biological activity for natural products and FDA-approved drugs, for example, 1,4-dihydropyrans are ligands of L-type calcium channel that exhibit stereoselectivity for the type of activity; and the S-enantiomer is an activator of the channel and the R-enantiomer is an inhibitor of the channel, according to Scott et al. (Current Research in Chemical Biology, 2022. Vol. 2: 100028). Therefore, the cited reference demonstrates there is lack of predictability that tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro [3.4] octane-5-carboxylate, which contains additional stereocenter compared to 2S-FNL-2 of Lowe, III et al., would successfully modulate NMDR.
According to FirstWord Pharma (“Top Story Allergan's rapastinel fails to meet primary endpoints in Phase III depression studies” [Online]. Published on March 6, 2019), the results from the Phase III RAP-MD-01, RAP-MD-02 and RAP-MD-03 studies of the major depressive disorder drug candidate rapastinel, a modest and selective positive NMDA receptor modulator, saying treatment arms did not differentiate from placebo on the primary and key secondary endpoints; and an interim analysis of rapastinel in the RAP-MD-04 relapse prevention study suggests the primary and key secondary endpoints will not be met either (see e.g., page 1). The cited reference demonstrates there is lack of predictability in the art for treating or preventing major depressive disorder.
According to Carnegie Mellon University (“A cure for Alzheimer’s is taking longer than expected; here’s why” [Online]. Published on January 20, 2022), age is the most significant factor in whether a person shows symptoms of Alzheimer’s, and although diagnostic information to confirm the disease is improving, there are still no cures or treatments to slow down or stop the progression of the disease (see e.g., 2nd paragraph). Therefore, the cited reference demonstrates there is lack of predictability surrounding the treatment of Alzheimer’s disease to the extent that the subject in recognized need of treatment for major depressive disorder includes subject with comorbidities, such as Alzheimer’s disease.
Therefore, based upon the cited references, it is uncertain whether any therapeutic effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and each and every solid form of compound A with the claimed orthorhombic crystal system or with the claimed powder X-ray diffraction pattern can successfully treat the entire scope of subject in recognized need for treatment for major depressive disorder.
(6, 7, 8) The amount of guidance given, the presence of working example and the quantitation
of experimentation required:
In view of all of the foregoing, at the time the application was filed, it would have required undue experimentation to practice the entire scope of the claimed invention. The specification only describe the method of preparing the solid crystalline form I of compound A and solid crystalline form II of compound A; and does not disclose their biological activities nor exemplify the administration of said solid crystalline form in the working examples. Based on the limited disclosure, the relative skill of those in the art could not reasonably predict whether the solid crystalline form of tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro [3.4]octane-5-carboxylate, which is known to be an intermediate for synthesizing the active pharmaceutical ingredient, could successfully treat the entire scope of subject in recognized need of major depressive disorder without confirming their biological or pharmaceutical activity. Therefore, it would require undue experimentations as it is highly unpredictable that the administration any therapeutic effective amount of a pharmaceutical composition comprising a pharmaceutically acceptable carrier and the claimed solid crystalline form of tert-butyl (S)-2-((2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl)-1-oxo-2,5-diazaspiro [3.4]octane-5-carboxylate would, in fact, be usable across the entire scope of subject in recognized need of treatment for major depressive disorder, including prevention.
Accordingly, the method of treating the full scope of subject in recognized need of treatment for major depressive disorder, comprising administering to said subject any therapeutically effective amount of each and every pharmaceutical composition comprising a pharmaceutical acceptable carrier and any solid crystalline form of compound A with the powder X-ray diffraction pattern or orthorhombic crystal system instantly claimed are not enabled by the specification.
This is a full enablement rejection.
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 48-49 and 51-52 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 48-49 and 51-52,
the phrase of “in recognized need” in the recitation of “[a] method of treating a subject in recognized need of treatment for major depressive disorder” renders the claim indefinite, because the term “recognized” is a relative term. The term “recognized” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In the present case, it is not clear what is considered recognized versus not recognized as this depends on the context and the knowledge of the person using it. The fact a person of ordinary skill in that cannot tell from the specification what criteria defines "recognition" in a consistent way, the claim lacks clarity. Therefore, the metes and bounds of the claimed subject matter cannot be determined.
With respect to the phrase “said subject in need thereof”, the claim is circular. That means the definition of "a subject in recognized need of treatment for major depressive disorder" loops back onto itself by reciting "said subject in need thereof". For instance, the claim highlights "a subject in recognized need of treatment" and then later just "subject in need thereof", but never give objective criteria for what "in need" means beyond needing treatment, it is like defining a word with a word. Without an external, clear standard, the claim becomes circular. In another word, the claim leaves the reader unsure of what the boundaries of that "need" are.
Conclusion
No claims are allowed.
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/CHIHYI LEE/Examiner, Art Unit 1628 /JEAN P CORNET/Primary Examiner, Art Unit 1628
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