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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/04/2025 has been entered.
Status of Claims
Claims 1-14 are pending.
Information Disclosure Statement
No IDS has been filed.
Priority
Instant application 17/837,917, filed 06/10/2022, claims priority as follows:
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Response to Amendment/Arguments
The amendment filed 12/04/2025 has been entered. No claims have been amended. No claims have been cancelled. No new claims have been added.
With respect to the rejection of claims 1-14 under 35 U.S.C. § 112(a), Applicant asserts that the specification as submitted adequately describes all subject matter in the claims.
Applicant's arguments have been fully considered but they are not persuasive. As set forth in the rejection under 112(a) below, the genus of “an antioxidant carbazole moiety fused to a nicotine analog” is not fully structurally defined. Fig. 1 depicts the structure of carbazole. Fig. 2 depicts the structure of nicotine. Fig. 3 depicts the chemical structure of therapeutic agent 100 which comprises a carbazole moiety with a pyrrolidinyl substituent. Fig. 4 depicts tert-butyl hydroperoxide. It remains unclear what structures fall under the limitation of “a nicotine analog” or what is required of the nicotine analog for it to have the function of a “therapeutic agent” beyond the single embodiment disclosed in Fig. 3. A known correlation between the structure of the genus and function as a therapeutic agent has not been established or disclosed.
Additionally, applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the specification adequately describes all subject matter in the claims. Applicant’s remarks do not provide any specific reasons as to why either the findings of fact or the legal conclusion of a lack of written description is allegedly in error. However, Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. Therefore, the rejection under 35 U.S.C. § 112(a) is maintained.
With respect to the rejection of claims 1-14 under 35 U.S.C. § 103, applicant asserts that neither Rogers nor Joseph, alone or in combination with one another, disclose the invention as currently claimed.
Applicant's arguments have been fully considered but they are not persuasive. The requirements for a proper response to a rejection may be found in 37 CFR 1.111(b). Applicant’s remarks do not provide any specific reasons as to why either the findings of fact or the legal conclusion of obviousness is allegedly in error. Thus, the remarks in response to the obviousness rejection do not comply with 37 CFR 1.111(b). However, Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response. Therefore, the rejection under 35 U.S.C. § 103 is maintained.
Claim Rejections - 35 USC § 112(a) - Maintained
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 1-14 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, the claims are drawn to a method comprising administering a therapeutic agent comprising “an antioxidant carbazole moiety fused to a nicotine analog.”
The genus "an antioxidant carbazole moiety fused to a nicotine analog" is not fully structurally defined. Carbazole is a polycyclic aromatic hydrocarbon consisting of two six-membered benzene rings fused on either side of a five-membered nitrogen-containing ring and has the structure shown in Fig. 1 of the instant specification. A person of ordinary skill would readily recognize a “carbazole moiety” based on this definition, and thus some structural elements are present.
However, it is unclear what structures fall under the definition of “a nicotine analog” or what is required of the nicotine analog for it to have the function of a “therapeutic agent”. Nicotine is known in the art and its structure is provided in the specification in Fig. 2. No definition is provided for “a nicotine analog” in the specification. Notably, the sole embodiment of “an antioxidant carbazole moiety fused to a nicotine analog” disclosed in the specification (compound 100 below) does not include certain defining features of nicotine, such as the pyridine ring or N-methyl substituent on the pyrrolidine ring:
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A review of the prior art identifies nicotine analogs as compounds which have at least one of the features of nicotine that are missing in Applicant’s compound. For instance, Hukkanen et al (“Metabolism and Disposition Kinetics of Nicotine.” Pharmacological Reviews, vol. 57, no. 1, Mar. 2005, pp. 79–115) discloses nicotine analogs of potential therapeutic utility, and all of the compounds comprise an N-methyl pyrrolidine, pyridine ring, or a combination thereof (see pg. 106, Fig. 10):
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Similarly, Becerra et al (“Structural and Functional Computational Analysis of Nicotine Analogs as Potential Neuroprotective Compounds in Parkinson Disease.” Computational Biology and Chemistry, vol. 86, June 2020, p. 107266) discloses nicotine analogs as potential neuroprotective compounds, and all of the compounds comprise an N-methyl pyrrolidine, pyridine ring, or a combination thereof (see pg. 3, Fig. 1):
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Accordingly, Applicant’s structure having no pyridine ring and no N-methyl pyrrolidine, in use of the phrase “nicotine analog”, is antithetical to what is found in the prior art, and thus there is insufficient descriptive support for the genus of compounds claimed.
An alternative interpretation of the meaning of the phrase “nicotine analog” is compounds with comparable properties to nicotine. Stated differently, any compound which acts as a nicotinic agonist, i.e., a nicotinic acetylcholine receptor agonist, could be considered “a nicotine analog” in the broadest reasonable interpretation of the phrase.
Bodnar (“Discovery and Structure−Activity Relationship of Quinuclidine Benzamides as Agonists of Α7 Nicotinic Acetylcholine Receptors.” Journal of Medicinal Chemistry, vol. 48, no. 4, Feb. 2005, pp. 905–08) teaches quinuclidine benzamides as nicotinic agonists, and teaches the following compound which is substantially structurally distinct from nicotine (see abstract, Fig. 1):
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Rogers (US20050215584; published September 29, 2005) teaches methods of treating diseases (including age-related macular degeneration) in mammals comprising administering nicotinic acetylcholine receptor agonists, and teaches a variety of compounds, including quinuclidine benzamides fused to carbazole, as nicotinic acetylcholine receptor agonists (see paras. 0227-842, and claims 21, 33, and 59):
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These compounds disclosed by Rogers, being nicotinic agonists fused to carbazole, a known antioxidant, could reasonably be considered to fall under the genus of “an antioxidant carbazole moiety fused to a nicotine analog” with the function of a therapeutic agent. However, the specification fails to provide adequate written description to reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession such compounds, which are substantially different in structure from the single embodiment of compound 100.
Further to the points above, it is not clear how the two moieties (the carbazole and nicotine analog) should be fused to one another in order to achieve the function of a therapeutic agent, and no structure/function relationship is provided in the specification. The broadest reasonable interpretation of “an antioxidant carbazole moiety fused to a nicotine analog” encompasses a wide variety of fusions based on the above interpretation of “nicotine analog” and the limited disclosure provided in the specification. A few examples are contemplated below:
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A person of ordinary skill would not readily predict that each of these compounds, or any other compound in the broad universe of compounds encompassed by Applicant’s genus, would have the function of a therapeutic agent.
A review of the prior art does not provide the structure-function correlation which is absent from Applicant’s disclosure. For example, Pannala et al (“Synthesis, Molecular Docking, in Vitro Antiproliferative and Antioxidant Activity of Novel Pyrrolidinyl-Carbazole Derivatives.” Current Organic Synthesis, vol. 14, no. 8, pp. 1172–79) discloses novel pyrrolidinyl-carbazole derivatives having potential therapeutic activity (see pg. 1174, Table 2):
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The compounds disclosed in Pannala, which could be interpreted as falling under Applicant’s genus, have antiproliferative activity on both normal CHO cell line and breast and lung cancer cell lines (see pg. 1175, col. 1, para. 2). However, in these compounds, the pyrrolidine is attached at the carbazole 3-position as opposed to Applicant’s 4-substituted carbazole. Additionally, the compounds are proposed to act by a different mechanism of action (occupation of the colchicine binding site of tubulin) than Applicant’s compound, for treatment of a different disease (cancer). It is not clear if the difference in the position of substitution on carbazole is necessary for the antiproliferative activity of the compounds.
Methods of synthesizing compounds are, in general, known to the person of ordinary skill, however methods of making the myriad of compounds embraced by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as “a nicotine analog”, are merely described partially. As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what additional elements may be present in the therapeutic agent.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims 2-14 do not resolve these issues, since these claims do not further limit or provide further structure of the “antioxidant carbazole moiety fused to a nicotine analog”. Accordingly, these claims are also rejected.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-5 and 7-14 are rejected under 35 U.S.C. 103 as being unpatentable over Rogers (US20050215584; published September 29, 2005) in view of Joseph (Age-Related Macular Degeneration: Early Detection and Timely Treatment May Help Preserve Vision.” Harvard Health, 24 Nov. 2020, https://www.health.harvard.edu/blog/age-related-macular-degeneration-early-detection-and-timely-treatment-may-help-preserve-vision-2020112421362).
Rogers teaches methods of treating diseases in mammals comprising administering nicotinic acetylcholine receptor agonists, and teaches a variety of compounds comprising bicyclic-N-bridged-heteroaromatic carboxamides as nicotinic acetylcholine receptor agonists (see paras. 0227-842, and claims 21, 33, and 59):
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The broadest reasonable interpretation of “a nicotine analog” encompasses compounds which have comparable properties to nicotine. Stated differently, any compound which acts as a nicotinic agonist, i.e., a nicotinic acetylcholine receptor agonist, could be considered “a nicotine analog” in the broadest reasonable interpretation of the phrase. Therefore, the compounds disclosed by Rogers, being nicotinic agonists fused to carbazole, a known antioxidant, are considered to meet the limitation “a therapeutic agent comprising an antioxidant carbazole moiety fused to a nicotine analog” of claim 1.
Accordingly, with respect to claim 1, Rogers teaches a method of treating age-related macular degeneration in a mammal said method (see claim 73 and dependent claim 79, which recites age-related macular degeneration):
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comprising the steps of administering to said mammal a therapeutic agent comprising an antioxidant carbazole moiety fused to a nicotine analog (see compounds of paras. 0227-842, and claims 21, 33, and 59).
Rogers fails to teach monitoring said mammal to determine the state of said age-related macular degeneration.
However, monitoring of disease status is well-known in the treatment of age-related macular degeneration (AMD). Joseph teaches both home monitoring of vision with an Amsler grid (a grid of horizontal and vertical lines used to monitor the central visual field) and regular follow-up visits with an ophthalmologist (see pg. 5, para. 2-3).
Applying KSR prong (A), it would have been prima facie obvious to combine the elements taught by Rogers, i.e. a method of treating AMD comprising administering one of the carbazole compounds depicted above, with the monitoring element taught by Joseph. A person having ordinary skill in the art would have readily predicted that administering a compound of Rogers to a subject having AMD and monitoring said patient would effectively treat AMD in said patient.
With respect to claims 2-3, Rogers teaches wherein said age-related macular degeneration is wet disease age-related macular degeneration and wherein said age-related macular degeneration is dry disease age-related macular degeneration. Rogers teaches that AMD can take the form of either wet or dry AMD (see para. 1006):
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With respect to claims 4-5, Rogers teaches wherein said therapeutic agent is administered orally and wherein said therapeutic agent is administered by injection. Rogers teaches that the compounds can be administered orally (see para. 0973):
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and by injection (see para. 0959):
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With respect to claim 7, Rogers teaches wherein said mammal is a human. See para. 0947:
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Claims 8-14 recite limitations which are merely expressions of the intended result of a process step positively recited. As noted in MPEP 2111.04, “a ‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’” In the instant case, the results (preventing the progression to moderate dry-AMD, delaying the growth of, synergy with anti-VEGF, reducing burden of monthly injections, improving vascular status) are the intended result of the step of administering a therapeutic agent comprising an antioxidant carbazole moiety fused to a nicotine analog, and these claims do not recite any additional active steps in the method. Accordingly, claims 8-14 are obvious by virtue of their dependency from obvious claim 1.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Rogers in view of Joseph, and further in view of Yamada (US20220096410; published March 1, 2022).
The teachings of Rogers in view of Joseph are disclosed above and at least those teachings are incorporated reference herein. The combination of Rogers and Joseph teaches a method of treating age-related macular degeneration in a mammal of present claim 1.
With respect to claim 6, neither Rogers nor Joseph disclose wherein said therapeutic agent is administered via eye drops.
However, Yamada teaches pharmaceutical compositions for intraocular administration to treat age-related macular degeneration, and teaches that eye drops are a suitable formulation for intraocular administration:
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It would have been prima facie obvious to modify the method of treatment taught by the combination of Rogers and Joseph to incorporate the eye drop mode of administration taught by Yamada. A person having ordinary skill in the art would have been motivated to do so because eye drops are a convenient mode of administering a therapeutic agent to the eye, especially when compared with other modes of administration, such as injection to the eye. A skilled artisan would have reasonably expected that administering a compound of Rogers to a subject having AMD via eye drops and monitoring said patient would effectively treat AMD in said patient.
Additionally, applying KSR prong (B), it would have been prima facie obvious to substitute one known method of administration (the oral administration taught by para. 0973 of Rogers) for another (the eye drop administration taught by Yamada) in the method of treatment taught by the combination of Rogers and Joseph. A person having ordinary skill would have reasonably predicted that such a substitution would provide a result of treating AMD in a patient.
Conclusion
Claims 1-14 are rejected.
All claims are either identical to or patentably indistinct from claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 8:30 am - 5:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached on (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621