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 1, which after amendment, consists of claims 1 and 5-7, in the reply filed on 13 February 2026 is acknowledged. Claims 8-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter.
With regard to the elected species, Applicant’s election without traverse of N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine is acknowledge.
The elected species has been examined, and no prior art was identified.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claim. Currently, the following elected claims are generic with respect to the elected species: claims 1, 6 and 7. However, no generic claim has been found allowable.
Because claim 5 encompasses both elected species and non-elected species, the full scopes of claim 5 has not been examined, and claim 5 has been withdrawn from consideration. Upon the allowance of a generic claim from which claim 5 depends or otherwise includes all the limitations of an allowed generic claim, claim 5 will be rejoined and additional non-elected species of claim 5 will be considered.
Status of Claims
Claims 1 and 5-9 are pending. Claims 5 is withdrawn as encompassing non-elected species. Claims 8 and 9 are withdrawn as being drawn to a non-elected invention(s). Claims 2-4 and 10-11 are canceled.
Priority
The instant application claims priority as follows:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1 March 2024 was in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The IDS was considered.
A signed copy of form 1449 is enclosed herewith.
Claim Interpretation
The preamble of claim 6 recites “[t]he method composition of claim 1” (emphasis added). And the preamble of claim 7 recites “[t]he method of composition of claim 1” (emphasis added). For the sake of expedient prosecution, and in view that Applicant elected Group I (drawn to methods), the examiner will interpret claims 6 and 7 as each being drawn to the method (not a composition) of claim 1. In the event that Applicant intended claim 6 to refer a “composition of claim 1” (rather than to a “method of claim 1”), the resulting claim would be withdrawn from consideration for falling outside of elected Group 1. Similarly, in the event that Applicant intended claim 7 to refer a “composition of claim 1” (rather than to a “method of claim 1”), the resulting claim would be withdrawn from consideration for falling outside of elected Group 1.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim 6 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. The preamble of the claim recites “[t]he method composition of claim 1” (emphasis added). “A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.” See MPEP at 2173.05(p)II. Correction or clarification is required.
Claim 7 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. The preamble of the claim recites “[t]he method of composition of claim 1” (emphasis added). “A single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.” See MPEP at 2173.05(p)II. Correction or clarification is required.
Claims 1 and 5 (along with claim 6 and 7 by way of dependency) 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. In the most recent amendments to the claims, applicant removed the structure corresponding to Chemical Formula 1 and replaced that structure with an unnamed generic formula (which unnamed generic formula was not found in the application as filed). However, despite removing Chemical Formula 1 and replacing it with an unnamed generic formula, claim 1 and claim 5 each continue to refer to Chemical Formula 1 elsewhere in the claims. For example, Chemical Formula 1 remains at line 3 of the claim 1 and at line 2 of claim 5. Under the circumstances, the claims could be construed to be referring the “Chemical Formula 1” found in the speciation, and not to the newly added unnamed generic formula. Appropriate correction is required.
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.
Claim 1 and 5-7 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 for treating a neurodegenerative disease, does not reasonably provide enablement for preventing a neurodegenerative disease, including Alzheimer's disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The ordinary meaning of the term “preventing” as used in claim 1 requires that no symptom of any neurodegenerative disease will ever occur in a subject in need thereof after treatment by the claimed method. Applying the broadest reasonable interpretation of the claims drawn to method for preventing a neurodegenerative disease, the “preventing” of said disease lacks enablement due to the undue amount of experimentation required by one of ordinary skill in the art to predictably practice the claimed method of preventing a neurodegenerative disease.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention encompasses a method of preventing a neurodegenerative diseases, including Alzheimer's disease, comprising administering a therapeutically effective amount of N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine to the subject in need thereof.
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain). As illustrative of the state of the art, the examiner cites Sabbagh et al (Neurobiology of Aging, 2013; 34:169–183) and Cummings et al (Alzheimer's Research & Therapy, (2016), 8(39), 1-12).
Sabbagh, cited for evidentiary purposes, teaches substantial resources and effort have been invested into the development of therapeutic agents for Alzheimer’s disease (AD) with mixed and limited success; research into the etiology of AD with animal models mimicking aspects of the disorder has substantially contributed to the advancement of potential therapies; although these models have shown utility in testing novel therapeutic candidates, large variability still exists in terms of methodology and how the models are utilized; no model has yet predicted a successful disease-modifying therapy for AD (abstract). Sabbagh teaches current pharmacological interventions for AD have symptomatic benefits but do not prevent or delay progressive neurodegeneration (page 169, left, 1st paragraph).
This article demonstrates that the art of developing and testing drugs for preventing Alzheimer’s disease, particularly for use in humans, is extremely unpredictable.
Cummings, cited for evidentiary purposes, discusses the recent shift in focus toward Disease Modifying Therapy (DMT) approaches in Alzheimer’s disease (AD), defined as therapies intended to affect the underlying disease process by targeting one or more of the numerous pathological changes characteristic of AD. Cummings reports that, despite extensive effort, numerous candidate agents have failed in clinical development, and that no DMTs have demonstrated a drug-placebo difference in Phase 3 studies or received marketing approval (page 2, left column, paragraph 3). Cummings further explains that these failures stem from an incomplete understanding of AD pathogenesis, the multifactorial etiology and complex pathophysiology of the disease, the slowly progressive nature of AD and the high level of comorbidity occurring in the elderly population (page 2, left column, fourth paragraph).
This reference demonstrates that therapeutic outcomes in Alzheimer’s disease are highly unpredictable, even when treatments are rationally designed to target disease mechanisms.
2. The breadth of the claims
Claims 1 and 5-7 broadly encompasses not only a method of treating a neurodegenerative diseases, but also a method of preventing a neurodegenerative diseases, including Alzheimer's disease, comprising administering a therapeutically effective amount of N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine to the subject in need thereof.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification at Example 7 (pages 38-41) provides data showing that N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine administered to 5xFAD mice in vivo improved cognitive function, reduced expression of cognitive dysfunction proteins, and increased expression of neuronal marker NeuN; but this limited in vivo data in 5xFAD mouse models is not sufficient to provide support for the full scope of preventing neurodegenerative diseases, including Alzheimer's disease, particularly in humans.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc) necessary to achieve treatment across the full scope of the claimed endpoints, noting that the specification provides no support for prevention of neurodegenerative diseases, including Alzheimer's disease, particularly in humans. At best, an "effective amount" is exemplified as a dosage sufficient to provide treatment for memory impairment in 5xFAD mouse models of Alzheimer’s disease.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed in supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any method of 1 and 5-7 could be predictably used as a preventative for neurodegenerative diseases, including Alzheimer's disease, particularly in humans.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent 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" (42 USPQ 2d 1001, Fed. Circuit 1997). Determining whether N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine and related compounds would prevent the aforementioned conditions or disorders would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra, in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of claims 1 and 5-7 do not comply with the scope of enablement requirement of 35 U.S.C 112(a), since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Copending Application No. 18/553,392
Claims 1 and 5-9 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claim 1-9 of copending Application No. 18/553,392 in view of Pathare et al. (Biomed Res J 2019;6:1-6.; Year: 2019) and Buchanan et al. (Kidney, Front. Endocrinol. 11:560.; Year: 2020).
At the time of filing the instant application, klothos was known to have a role in the onset of a variety of disease states, including neurodegenerative disease (see Pathare et al.) and kidney/renal disease (see Buchanan et al.). As evidenced by claim 7 of copending Application No. 18/553,392, administering the recited compounds increases the expression of the klotho gene. Similarly, as evidenced by claim 6 of the instant application, administering the recited compounds increases the expression of the klotho gene. That is, in both sets of claims, the recited compounds increase the expression of the klotho gene. Furthermore, in both sets of claims, compounds that increase the expression of the klotho gene include N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine as a species.
Here, while the claimed methods of the instant application and the claimed methods of copending Application No. 18/553,392 are drawn to differing disease states, the claimed methods rely on the same mechanism of action and at least one species of administered compound, namely N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine. Given the teaching of Pathare et al. (neurodegenerative disease) and Buchanan et al. (kidney/renal disease), one of ordinarily skill in the art would have recognized that the claimed methods of copending Application No. 18/553,392, which are drawn to treating kidney/renal disease, could be applied to treat neurodegenerative disease as claimed in the instant application. As such claims 1 and 5-9 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claim 1-9 of copending Application No. 18/553,392.
This is a provisional nonstatutory double patenting rejection.
Copending Application No. 17/766,174
Claim 1 and 5-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-13, 22 and 25 of copending Application No. 17/766,174 in view of Pathare et al. (Biomed Res J 2019;6:1-6.; Year: 2019), Yu et al., (Experimental and Therapeutic Medicine, 20: 124, 2020; Year: 2020) and Buchanan et al. (Kidney, Front. Endocrinol. 11:560.; Year: 2020).
At the time of filing the instant application, klothos was known to have a role in the onset of a variety of disease states, including neurodegenerative disease (see Pathare et al.), vascular disease (see Yu et al.) and kidney/renal disease (see Buchanan et al.). As evidenced by claim 7 of copending Application No. 18/553,392, administering the recited compounds increases the expression of the klotho gene. Similarly, as evidenced by claim 6 of the instant application, administering the recited compounds increases the expression of the klotho gene. That is, in both sets of claims, the recited compounds increase the expression of the klotho gene. Furthermore, in both sets of claims, compounds that increase the expression of the klotho gene include N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine as a species.
Here, while the claimed methods of the instant application and the claimed methods of copending Application No. 17/766,174 are drawn to differing disease states, the claimed methods rely on the same mechanism of action and at least one species of administered compound, namely N-(3,4-difluorophenyl)benzo[d]oxazol-2-amine. Given the teaching of Pathare et al. (neurodegenerative disease), Yu et al. (vascular disease) and Buchanan et al. (kidney/renal disease), one of ordinarily skill in the art would have recognized that the claimed methods of copending Application No. 17/766,174, which are drawn to treating vascular disease and kidney/renal disease, could be applied to treat neurodegenerative disease as claimed in the instant application.
As such claims 1 and 5-9 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claim 11-13, 22 and 25 of copending Application No. 17/766,174.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRADLEY S MAYHEW whose telephone number is
571-272-8428. The examiner can normally be reached Mon-Fri, 11:00 AM-7:00 PM.
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/BSM/ Examiner, Art Unit 1621
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