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 with traverse of Group I (i.e., claims 1-10) in the reply filed on 6/24/2026 is acknowledged. The traversal is on the ground(s) that Group I and Group II include the same special technical feature drawn to a method of treating a neurological disorder in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising 15-deoxy-A12, 14-prostaglandin J2, 9-nitro-9E-octadecenoic acid, 10-nitro-9E- octadecenoic acid, a derivative thereof, or a combination thereof and that this special technical feature makes a contribution to the prior art in view of US 2010/0137270 A1 (Wulfert) and US 2019/0388433 A1 to University of South Florida (hereinafter "USF").
This is found unpersuasive because the claims of group I and group II are distinct inventions and they lack unity of invention based on the teachings of Wulfert and USF and their teaching of the same common technical feature i.e. treating a neurological disorder comprising administering to the subject a therapeutically effective amount of a composition comprising 15-deoxy-A12,14-prostaglandin J2,, 9-nitro-9E-octadecenoic acid, 10-nitro-9E- octadecenoic acid, a derivative thereof, or a combination thereof. Wulfert teaches (instant claim 1) a method of treating a neurological disorder in a subject (para [0036], use of an agent which enhances the production of 15-deoxy-prostaglandin J2 for the manufacture of a medicament to promote neurite outgrowth or to treat peripheral neuropathy; [0042], the compounds of the present invention may be used in the treatment and prophylaxis of chronic neurodegenerative diseases. Consequently, the applicant’s arguments are generic and do not actually address the finding that these common technical features fail to make contributions to the prior art as it is obvious to use these compounds to treat the neurological disorder.
In addition to the rationale outlined in the restriction requirement, the examiner notes that group I is clearly directed towards a method of treating a neurological disorder in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising 15-deoxy-A12,14-prostaglandin J2, 9-nitro-9E-octadecenoic acid, 10-nitro-9E- octadecenoic acid, a derivative thereof, or a combination thereof. Group II, on the other hand, is directed towards determining whether a biological sample obtained from the subject has an increased level of FKBP51 as compared to a control and additionally a method of treating a neurological disorder. Although the groups may share some common features, the examiner maintains that the inventions lack unity. The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: the use of 15-deoxy-delta 14-prostaglandin J2 as a therapeutic agent to a subject for the treatment of neurological disorder is known in the art as taught by Wulfert, US 2010/0137270 A1 ([0036], [0042] and [0029]), given that administering 15-deoxy-delta12,14-prostaglandin J2 has been practiced by USF, US 2019/0388433 A1 [0036].
Furthermore, applicant’s election of species as the single disclosed species of a
neurological disorder, “depression” with traverse is acknowledged. The traversal is on the ground(s) that the present genus of 4 claimed neurological disorders represents a finite number of species and thus the applicants should not be required in the present application to elect a species when applicants have not claimed an unreasonable number of species. This is found unpersuasive as well because the independent claims are not so limited. The examiner notes that the independent claims 1 and 11 are not amended to limit the neurological disorders to the four disorders claimed in dependent claims 5 and 16. Therefore, the species election is appropriate.
The requirement is still deemed proper and is therefore made FINAL.
Applicants’ amendment of claims 5-7, 9-10, and 13-19 is acknowledged. There are no new or cancelled claims.
Since, the applicant elected Group I, therefore, based on that election, claims 11-19, are withdrawn as being drawn to a non-elected group.
Claims 1-10 are under consideration in this office action and will be examined on the merits.
Status of Claims
Claims 1-19 are pending. Applicant amended claims 5-7, 9-10, and 13-19. There are no new or cancelled claims.
Claims 1-10 are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS/s) submitted on 4/4/2024 and 7/31/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling a method of treating a neurological disorder in a subject, comprising administering to the subject a therapeutically effective amount of a composition, does not reasonably provide enablement for “the full scope of neurological disorder” in a subject, “comprising administering to the subject a therapeutically effective amount of a composition comprising 15-deoxy-A12,14-prostaglandin J2, 9-nitro-9E-octadecenoic acid, 10-nitro-9E- octadecenoic acid, a derivative thereof, or a combination thereof.” across all routes, and the number of diseases listed in claim 5 as well as the specific recitation of “depression”.
Additionally, the specification does not reasonably provide enablement for particular administration routes, and pharmacokinetic properties. 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.
Claim 1 recites broadly “a method of treating a neurological disorder in a subject” using compositions comprising 15-deoxy-A12,14-prostaglandin J2, 9-nitro-9E-octadecenoic acid, 10-nitro-9E- octadecenoic acid, a derivative thereof, or a combination thereof.
Claim 5 expressly specifies that “the neurological disorder is selected from the group consisting of depression, post-traumatic stress disorder (PTSD), anxiety, and Alzheimer's disease”, thereby encompassing distinct neuropsychiatric and neurodegenerative diseases with differing etiologies, pathophysiologies, and treatment paradigms.
The specification provides enabling in vitro data showing modulation of FKBP51 expression and GRE-luciferase reporter activity in cultured H4 neuroglioma, Ht-22 hippocampal, and HeLa cells after exposure to the three fatty acids, particularly in dexamethasone-treated conditions.
Accordingly, the claims are far broader than what is actually taught and reasonably predictable, particularly the full scope of neurological disorders across all claimed routes, and disease types.
The instant specification fails to provide information that would allow the skilled artisan to practice the instant invention without imposing an undue burden on the skilled artisan. 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.
Nature of the Invention:
The instant invention relates to systemic therapeutic treatment of complex neurological and neuropsychiatric disorders via pharmacological modulation of FKBP51 using specific fatty acid derivatives and their synthetic medications.
The nature of these disorders-depression, PTSD, anxiety, Alzheimer’s disease-involves multifactorial pathophysiology, heterogeneous patient populations, and complicated clinical endpoints, making them a highly unpredictable field of drug development (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
The current art characterizes FKBP51 as a central chaperone and signaling hub in stress-related and neurodegenerative pathways, with context-dependent roles that can be beneficial or harmful depending on timing, cell type, and disease stage (Peng, Haokun et al. “Role of FK506 binding protein 51 in central nervous system diseases.” Frontiers in molecular neuroscience vol. 18 1725945. 12 Jan. 2026).
Thus, the invention lies in an unpredictable therapeutic area where small changes in dosing, patient selection, or disease stage can drastically alter efficacy and safety, increasing the need for detailed enabling disclosure (Peng, Haokun et al. “Role of FK506 binding protein 51 in central nervous system diseases.” Frontiers in molecular neuroscience vol. 18 1725945. 12 Jan. 2026).
The review “FKBP51 functions in the regulation of circadian rhythm and Alzheimer’s disease” describes FKBP51 as an important regulator of GR activity and epichaperone networks, emphasizing the complexity and dynamism of FKBP51’s role in AD pathogenesis (Johnson, Jill L. “FKBP51 functions in the regulation of circadian rhythm and Alzheimer's disease.” Cell stress & chaperones vol. 30,2 (2025): 81-83).
In such a complex and somewhat unpredictable nature and biological context, broad therapeutic claims to treating all neurological disorders-including depression and AD-require far more detailed, disorder-specific disclosure than is provided here to by enabled.
The State of the Prior Art:
As of the effective filing date, the prior art reflects that:
FKBP51 / FKBP5 have been identified as a promising target for a subset of neuropsychiatric disorders and stress-related phenotypes, with strong evidence linking FKBP5 polymorphisms and FKBP51 expression to susceptibility to depression, PTSD, and anxiety, and elevated FKBP51 to AD pathology (Peng, Haokun et al. “Role of FK506 binding protein 51 in central nervous system diseases.” Frontiers in molecular neuroscience vol. 18 1725945. 12 Jan. 2026).
Despite this, FKBP51-targeted therapies remained largely experimental, with ongoing efforts to characterize disease-specific FKBP51signaling, biomarker strategies, and pharmacological modulators and no established, clinically approved FKBP5-directed therapies for depression, PTSD, anxiety or AD (Peng, Haokun et al. “Role of FK506 binding protein 51 in central nervous system diseases.” Frontiers in molecular neuroscience vol. 18 1725945. 12 Jan. 2026).
While the prior art supports the plausibility that FKBP51modulation could be therapeutically relevant, it also shows that the field was still developing foundational knowledge on how, when and in whom FKBP51 should be modulated for safe and effective treatment (Matosin et al. "Brain expressed FKBP5 delineates a therapeutic subtype of severe mental illness" 8 Feb. 2020).
In this context, the present specification’s limited in vitro data and broad, generic therapeutic claims are not supported by established therapeutic paradigms in the art; instead, they extend substantially beyond what the art had demonstrated, amplifying the enabling burden on the specification.
Li et al. and related reviews on FKBP51-mediated signaling in neuropsychiatric disease collectively conclude that FKBP51 is a promising but incompletely understood therapeutic target, with further research needed to define biomarkers, treatment windows, and drug design strategies (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
Accordingly, the state of the art does not fill the gaps in this specification; rather, it confirms that significant further work is required to realize FKBP51-based therapies for the claimed neurological disorders.
The Relative Skill of those in the Art:
The level of skill in the art is a neuro-oncologist or clinician with a Ph.D., and/or an M.D.
The Predictability or Lack thereof in the Art:
The relationship between FKBP51 modulation, GR/HPA-axis signaling, and clinical outcomes in depression, PTSD, anxiety and AD is highly context-dependent and unpredictable.
For example, FKBP51 effects can vary with age, brain region, cell type, and stress history and many differentially influence synaptic transmission in early adulthood versus neuroinflammation and neurodegeneration later in life (Peng, Haokun et al. “Role of FK506 binding protein 51 in central nervous system diseases.” Frontiers in molecular neuroscience vol. 18 1725945. 12 Jan. 2026).
In depression, HPA-axis hyperactivity and altered GR feedback can contribute to pathogenesis; however, simply reducing FKBP51 in vitro does not reliably predict antidepressant efficacy in vivo, especially across diverse patient subgroups (O'Leary, John C 3rd et al. “A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51.” PloS one vol. 6,9 (2011): e24840).
Similarly, in AD, FKBP51 participates in chaperone networks and amyloid-related pathology, but the precise timing and extent of FKBP51 modulation needed to achieve cognitive benefit without adverse effects remain uncertain (Johnson, Jill L. “FKBP51 functions in the regulation of circadian rhythm and Alzheimer's disease.” Cell stress & chaperones vol. 30,2 (2025): 81-83.).
Given this unpredictability, broad claims to “treating a neurological disorder” (claim 1) and specifically “depression” (claim 5) using generic generic “therapeutically effective” dosing ranges and routes, with no disease-specific regimens or outcome data, are not commensurate with what one can reasonably infer from the in vitro examples (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
This unpredictability weighs strongly against enablement of the full claimed scope. Recent reviews on FKBP51 roles in neuropsychiatric diseases explicitly note that FKBP51 signaling is intricate and non-linear, and that therapeutic strategies must consider biphasic stress-response models and context-dependent effects (Peng, Haokun et al. “Role of FK506 binding protein 51 in central nervous system diseases.” Frontiers in molecular neuroscience vol. 18 1725945. 12 Jan. 2026).
This confirms that extrapolating from cell-line FKBP51, modulation to effective treatment of multiple neurological disorders, including depression, is scientifically unpredictable, supporting the scope of enablement rejection.
The Breadth of the Claims:
Claims 1 covers treating any “neurological disorder” in a subject using a composition comprising one or more of the three fatty acids or derivatives.
The specification defines “neurological disorder” broadly to include CNS diseases and the explicitly lists depression, PTSD, anxiety, and AD as examples, but does not limit the term to these four, thereby encompassing a much broader class of CNS disorders.
Claim 5 narrows the neurological disorder to a group of depression, PTSD, anxiety, and AD, yet these four conditions themselves represent distinct disease categories with different pathophysiological mechanisms, clinical features, and therapeutic requirements (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
The claims also encompass:
Multiple active compounds (15-deoxy-A12,14-prostaglandin J2, 9-nitro-9E-octadecenoic acid, 10-nitro-9E- octadecenoic acid), any “derivative thereof”, and any combination thereof, vastly expanding chemical space beyond the three disclosed structures.
Broad dosing and administration regimens across numerous routes (oral route, intracranially, or intravenously) and frequencies, with no disorder-specific constraints:
By contrast, the working examples disclose only three unmodified compounds in limited cell-culture settings under dexamethasone stress, with no demonstration that the same or any derivatives are effective in vivo for any neurological disorder.
This mismatch between narrow experimental support and broad therapeutic claims creates a significant enablement gap; the specification does not teach how to use all claimed compounds and derivatives to treat each claimed disorder without undue experimentation (Johnson, Jill L. “FKBP51 functions in the regulation of circadian rhythm and Alzheimer's disease.” Cell stress & chaperones vol. 30,2 (2025): 81-83).
The prior art literature on FKBP51 as a drug target indicates that drug design must be tailored to specific disease contexts and molecular interactions (e.g., FKBP51/GR/Hsp90 complex). And that not all FKBP51 modulators will have uniform or predictable effects across diseases (Jonathan J. Sabbagh et al. “Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD.” ACS Chemical Biology 2018 13 (8), 2288-2299.).
This supports the conclusion that the breadth of chemical and therapeutic scope in claims 1 and 5 is not enabled by the limited, specific cell-based examples (Peng, Haokun et al. “Role of FK506 binding protein 51 in central nervous system diseases.” Frontiers in molecular neuroscience vol. 18 1725945. 12 Jan. 2026).
Accordingly, the breadth of the claims is not commensurate with the scope of the enabling disclosure. The breadth of these claims far exceeds the limited examples and data actually provided.
As such, the breadth of the claims is great.
The Amount of Direction or Guidance Presented:
The specification provides general descriptions of what constitutes “neurological disorder” and high-level clinical symptom lists for depression, PTSD, anxiety, and Alzheimer's disease, but does not offer enabling guidance linking the cell-based FKBP51 results to actual therapeutic regimens for each condition.
Dosing ranges are presented in a very broad generic intervals (e.g., 0.01 mg/kg to 100 mg/kg, with numerous single-point examples) frequencies from once every year to every 10 minutes, without disease-specific rationale, titration strategies, or criteria for selecting doses or schedules for each neurological disorder.
In particular:
No disclosure explains how to select responsive patient subpopulation(s), beyond generic statements that patients “with elevated FKBP51”, including those with SNPs in FKBP5, “can benefit”, without teaching how to identify such SNPs or stratify by genotype or phenotype for each claimed disorder (Matosin et al. "Brain expressed FKBP5 delineates a therapeutic subtype of severe mental illness" 8 Feb. 2020).
No protocols are given for measuring FKBP51 in clinical samples in a way that would guide dosing, timing or assessment of treatment success across depression, PTSD, anxiety, and Alzheimer's disease (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
The discussion of potential synthetic modifications (e.g., altering nitro or oxo groups, acetylation, hydroxylation) is speculative and not accompanied by specific synthetic routes, predicted activity profiles, or guidance on which modifications are expected to work for which disorder.
The article “A New Anti-Depressive Strategy for the Elderly: Ablation of FKBP51/ FKBP5” describes the challenges of translating FKBP51 modulation into antidepressant strategies, highlighting the need for disease-specific pharmacodynamics, patient selection, and longitudinal assessment of HPA-axis function and cognitive outcomes (O'Leary, John C 3rd et al. “A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51.” PloS one vol. 6,9 (2011): e24840).
This reinforces that, without detailed therapeutic guidance or in vivo data, the present specification’s general suggestions are inadequate to enable the claimed broad treatment of depression and other neurological disorders (O'Leary, John C 3rd et al. “A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51.” PloS one vol. 6,9 (2011): e24840).
The Presence or Absence of Working Examples and Quantity of Experimentation:
The specification contains only three in vitro examples: modulation of FKBP51 protein levels in H$ and HT-22 neural cell lines and GRE-luciferase reporter activity in HeLa cells.
These examples show that the three fatty acids inhibit dexamethasone-induced FKBP51 expression and alter glucocorticoid receptor response in cell culture, but they do not demonstrate treatment or prevention of any neurological disorder in a subject, nor any behavioral or cognitive endpoints (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
With respect to depression in claim 5:
There is no animal depression models (e.g., forced swim test, tail suspension, chronic mild stress) using the claimed compounds, and no evidence that FKBP51 reduction by these compounds produces antidepressant-like behavioral effects (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
The specification does not show any change in DSM-5-consistent depressive symptom endpoints, despite discussing DSM-5 criteria in the description of “depression” (O'Leary, John C 3rd et al. “A new anti-depressive strategy for the elderly: ablation of FKBP5/FKBP51.” PloS one vol. 6,9 (2011): e24840.).
For PTSD, anxiety, and Alzheimer's disease, there are likewise no working in vivo examples in relevant models (e.g., fear conditioning paradigms, anxiety tests, transgenic APP/PS1 mice) (Jeanne et al. “The role of the FKBP51–Hsp90 complex in Alzheimer’s disease: An emerging new drug target” Cell Stress and Chaperones (2024) 29:792–804. (Year: 2024)).
The study “The Disease-Associated Chaperone FKBP51 Impairs Cognitive Function” shows that altering FKBP51 levels in vivo affects cognition and disease-related phenotypes, but emphasizes that these effects were established through rigorous animal behavioral and neuropathological analyses (Blair, Laura J et al. “The Disease-Associated Chaperone FKBP51 Impairs Cognitive Function by Accelerating AMPA Receptor Recycling.” eNeuro vol. 6,1 ENEURO.0242-18.2019. 1 Mar. 2019).
Furthermore, the specification contains only cell-based experiments demonstrating that the three identified fatty acids reduce FKBP51 levels and alter GRE-dependent reporter activity in cultured and non-neural cell lines under glucocorticoid stimulation.
A person of ordinary skill in the art would need to perform substantial, multistage experimentation to determine if and how modulation of FKBP51 by the claimed fatty acids translates into clinically effective treatment of each claimed neurological disorder, including:
Selection and validation of appropriate animal models for depression, PTSD, anxiety, and Alzheimer's disease (e.g., chronic stress paradigms, fear conditioning, transgenic AD mice), none of which are described or even referenced with protocol detail in the specification (Jeanne et al. “The role of the FKBP51–Hsp90 complex in Alzheimer’s disease: An emerging new drug target” Cell Stress and Chaperones (2024) 29:792–804.).
Systematic dose-finding studies to establish effective, non-toxic systemic doses, frequency, and routes of administration (oral, IV, intracranial) for each indication across species, with monitoring of pharmacokinetics, brain exposure, and long-term effects.
The review by Li et al., “FKBP51/ FKBP5-mediated signaling pathways in neuropsychiatric diseases” (Neurobiol. Stress, 2025) explains that FKBP51’s role in neuropsychiatric disease is multifactorial and that developing targeted therapies requires elaboration of disease-specific pathways, biomarkers, and treatment frameworks beyond simple modulation of FKBP51 expression (Liu, Yinglong et al. “FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies.” Neurobiology of stress vol. 39 100762. 18 Sep. 2025).
This underscores that the single-cell-line FKBP51 modulation data in the present application are far from sufficient to enable therapeutic treatment across the broad set of claimed disorders without significant, unpredictable experimentation.
Note that lack of a working example, is a critical factor to be considered, especially in a case involving an unpredictable and undeveloped art. See MPEP 2164. Genentech, Inc. v. Novo Nordisk, 108 F.3d at 1366, states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable". Therefore, in view of the Wands factors, e.g., the amount of direction or guidance provided, absence of working examples, and the predictability of the art discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation in order to practice invention based on the details provided and scope of invention defined in claims 1-10.
Consequently, claims 1-10 are rejected for lacking scope of enablement.
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.
Claims 1-10 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 claim 1, the phrase "effective amount" at line 2 renders the claim indefinite, because PHOSITA could not determine specific values for the amount based on the disclosure. See MPEP § 2173.05(c)(III). For example, see above enablement rejection regarding guidance provided and unpredictability in the art. With respect to independent claim 1, although this claim recites “a therapeutically effective amount,” and the specification paragraph [0062] recites a laundry list of dosages, there is no guidance in the specification as to which dose(s) would be appropriate for which neurological disorder. Consequently, what is an “effective amount” in the context of the claimed method is ambiguous and cannot be ascertained reasonably by PHOSITA.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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(a) are summarized as follows:
1. Applicant Claims
2. Determining the scope and contents of the prior art.
3. Ascertaining the differences between the prior art and the claims at issue, and resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5 and 7-10 are rejected under 35 U.S.C. 103(a) as being unpatentable over Wulfert et al. (“MODULATION OF PROSTAGLANDIN/CYCLOOXYGENASE METABOLIC PATHWAYS”, Pub. No.: US 2010/0137270 A1; Pub. Date: Jun 3, 2010) herein referred to as Wulfert in view of Lockwood et al. (“PREVENTION OF PRETERM BIRTH (PTB) BY INHIBITION OF FKBP51”, Pub. No.: US 2019/0388433 A1; Pub. Date: Dec. 26, 2019).
Regarding claims 1-5 and 7-10, Wulfert discloses a method of treating a neurological disorder in a subject (use of an agent which enhances the production of 15-deoxy-prostaglandin J2 for the manufacture of a medicament to promote neurite outgrowth or to treat peripheral neuropathy (para [0036]). Wulfert teaches the compounds of the present invention may be used in the treatment and prophylaxis of chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and peripheral neuropathies, comprising administering to the subject a therapeutically effective amount of an agent that enhance the level of 15-deoxy-delta 12,14- prostaglandin J2 (para [0029], 7-beta-OH-EPIA could have beneficial effects in the prevention and treatment of neurodegenerative conditions such as stroke, spinal cord injury, traumatic brain injury and AD, and in cardiovascular conditions such as myocardial infarction (MI) [0042]. Wulfert teaches that incubation of human monocytic blood cells (hMBC) with nanomolar concentrations of 7-beta- OH-EPIA causes an almost 10-fold increase in prostaglandin 15-deoxy-delta12,14-J2 (15d-PGJ2) production. This effect of the 7-hydroxysteroid appears to be specific for 15d-PGJ2, since the steroid did not significantly alter the production of prostaglandin E2 (PGE2) in these cells [0031]. Wulfert specifically teaches neurological disorder; Alzheimer's disease (claim 44, and [0042]). Wulfert teaches compounds which may be used in the present invention include those compounds of formula (1) [0058].
Wulfert does not specifically teach administering to the subject a therapeutically effective amount of a composition comprising 15-deoxy-delta 14-prostaglandin J2, 9-nitro-9E-octadecenoic acid, 10-nitro-9E-octadecenoic acid, a derivative thereof, or a combination thereof.
Lockwood teaches that 15-deoxy-delta 14-prostaglandin J2 can be administered as a therapeutic agent to a subject in need thereof. Lockwood teaches the methods involve decreasing FKBP51 expression in a mammal comprising administering a composition comprising 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) to a mammal in need thereof [0036]. Lockwood teaches as demonstrated herein, 15dPGJ2 may completely block glucocorticoid (e.g., dexamethasone (DEX)) induced FKBP51 expression). Lockwood also teaches obtaining a biological sample from the subject, blood sampling was performed [0053].
It would have been obvious to one of ordinary skill in the art to have administered 15-deoxy-delta12,14-prostaglandin J2 to treat the neurological disorder of Wulfert, given that administering 15-deoxy-delta12,14-prostaglandin J2 has been practiced by Lockwood. One skilled in the art would be motivated to do so, with a reasonable expectation of success, in order to evaluate safety outcomes as well as better understand the treatment and prophylaxis of pain associated with inflammation; chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple Sclerosis and peripheral neuropathies [0042] as taught by Wulfert.
Claim 6 is rejected under 35 U.S.C. 103(a) as being unpatentable over Wulfert et al. (“MODULATION OF PROSTAGLANDIN/CYCLOOXYGENASE METABOLIC PATHWAYS”, Pub. No.: US 2010/0137270 A1; Pub. Date: Jun 3, 2010) herein referred to as Wulfert in view of Lockwood et al. (“PREVENTION OF PRETERM BIRTH (PTB) BY INHIBITION OF FKBP51”, Pub. No.: US 2019/0388433 A1; Pub. Date: Dec. 26, 2019) and further in view of Sabbagh et al. (“INHIBITORS OF THE FKBP51 PROTEIN FROM A HIGH-THROUGHPUT DRUG SCREEN AND METHODS OF USE”, Pub. No.: US 2017/0000785 A1; Pub. Date: Jan. 05, 2017).
Regarding claims 6, Wulfert and Lockwood teach method of claim 1. However, Wulfert and Lockwood do not specifically teach wherein the subject has an increased level of FK506-binding protein (FKBP51) relative to a reference control and a measure of increased level of FKBP51 when compared to a control sample as recited in claim 6.
Sabbagh teaches methods for treating depression, stress disorders, such as PTSD, anxiety disorders, and/or a neurodegenerative disease or condition in a person or animal. Sabbagh teaches a person or animal in need of treatment is administered one or more compounds or drugs, or a composition comprising the one or more compounds or drugs, that inhibit FKBP51 activity or function (abstract). Sabbagh further teaches the person or animal exhibits elevated levels of FKBP51 relative to pre-established control levels or to levels of a healthy or normal person or animal, the person or animal has Alzheimer's disease or a disease similar to Alzheimer's disease [0005, claims 2 and 7]. Sabbagh teaches wherein the compound or drug is one that lessens or attenuates the suppressive effect of FKBP51 on glucocorticoid receptor (GR) activity (claim 3). Sabbagh teaches the subject compounds and drugs can be formulated in a physiologically or pharmaceutically-acceptable form and administered by any suitable route known in the art including, for example, oral, nasal, rectal, and parenteral routes of administration [0013]. Sabbagh teaches the cell is a human cell, the cell is a neural cell [0006].
It would have been obvious to one of ordinary skill in the art to have administered 15-deoxy-delta12,14-prostaglandin J2 to treat the neurological disorder of Wulfert and Lockwood, given that administering 15-deoxy-14-prostaglandin J2 has been used by Lockwood to reduce FKBP51 expression. One skilled in the art would be motivated to do so, with a reasonable expectation of success, in order to evaluate an increased level of FK506-binding protein (FKBP51) relative to a reference control as well as recognize an optimal method for reducing an increased level and inhibiting activity of the FKBP51 protein in a cell; wherein a cell exhibits an increased level of FKBP51 protein relative to a control cell and is contacted with an effective amount of a compound, or a composition comprising the compound or drug, that inhibits activity or function of a FKBP51 protein [0006] as taught by Sabbagh.
Conclusion
Claims 1-10 are rejected. No claims are allowed.
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/SAHAR INAM/
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/
Supervisory Patent Examiner, Art Unit 1622
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