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 .
DETAILED ACTION
This Office Action is in response to Applicant’s Arguments and Amendment filed, 02/05/2026, wherein the Amendment amended claims 1-2, 24, and 35-37, and cancelled claims 17-23.
Claims 1-3, 5-7, 9, 11, 13-16, 24, and 35-39 are pending.
Priority
This application claims the following priority:
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Election/Restriction
Applicant’s election without traverse of Group I, a method of treating retinal degeneration, and 3-(dibutylamino)-1-(1,3-dichloro-6-)trifluoromethyl)phenanthrene-9-yl)propan-1-ol hydrochloride as the compound, in the reply filed on 08/22/2025 is acknowledged.
In the course of the search, a method of treating retinal degeneration by administering 3-(dibutylamino)-1-(1,3-dichloro-6-)trifluoromethyl)phenanthrene-9-yl)propan-1-ol hydrochloride was found to be free of the prior art. In the previous Office Action of 11/05/2025, the examination of the Markush claim was extended to chloroquine,
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, a compound of instant Formula III.
The instant amendment of 02/05/2026, deleted compounds of Formula III. Per MPEP 803.02, the examination of the Markush claim has been extended. If a Markush grouping as set forth in a claim is proper and election of species has been required, the examiner must continue to search the species of the claim unless the claim has been found to be unpatentable over prior art. MPEP 803.02.
As detailed in the following prior art rejections, the generic claim encompassing the elected species was not found patentable. Therefore, the provisional election of species is given effect, the examination is restricted to the elected species only, and claims not reading on the elected species are held withdrawn. MPEP 803.02; Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (Bd. Pat. App. lnt. 1987).
Claim 24 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Claims 1-3, 5-7, 9, 11, 13-16, and 35-39 are examined on the merits herein.
REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
Claim Objections
Claim Objections
Applicant’s amendment to claim 2 is sufficient to overcome this objection.
35 U.S.C. § 112(a)-New Matter and 35 U.S.C. § 112(b)
Applicant’s amendment to claims 1 and 35-37 that deletes “or another form thereof,” is sufficient to overcome these rejections.
35 U.S.C. § 112(a)-Scope of Enablement
Applicant’s amendment to independent claims 1 and 35 that limits the compounds to those of Formula (I), 3-(dibutyl)-1-(1,3-dichloro-6-(trifluoromethyl)phenanthrene-90yl)propan-1-ol, or
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, and pharmaceutically acceptable salts, prodrugs, solvates, hydrates or tautomers thereof, and the Declaration filed 02/05/2026, is sufficient to overcome this rejection. As discussed on pgs. 14-15 of the previous Office Action, the instant specification provides examples showing compounds of formula (I), i.e., reserpine and rescimetol, as demonstrating higher immunostaining of markers for rod and/or cone photoreceptors in rd16 organoid cultures.
The Declaration under 37 CFR 1.132 filed 11/05/2025, is sufficient to overcome the rejection of claims 1-3, 5-7, 9, 11, 21-22, 24, and 35-39 based upon 35 U.S.C. § 112(a)-Scope of Enablement.
The Declaration provides data showing that halofantrine, which is 3-(dibutyl)-1-(1,3-dichloro-6-(trifluoromethyl)phenanthrene-90yl)propan-1-ol, and ROC-325, which is
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, increase rhodopsin expression in rd16 mouse retinal organoids, wherein rd16 mouse retinal organoids are lab-grown tissue models derived from mice with a mutation that causes LCA, a retinal degenerative disease:
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(pg. 3, Declaration), wherein A3 is halofantrine and F2 is ROC-325.
Moreover, as pointed out in paragraph 8, Declaration, instant Example 13 indicates that a positive effect on photoreceptors was observed for ROC-325, as shown by instant Figure 9B.
As such, the amendment to independent claims 1 and 35, in combination with the Declaration, is sufficient to overcome this rejection.
35 U.S.C. § 102 and 35 U.S.C. § 103
Applicant’s amendments to the claims that deletes compounds of formula (III) from the claims is sufficient to overcome these rejections, since the rejections were based on compounds of Formula (III).
REJECTIONS-MAINTAINED, MODIFIED, and NEW
The below prior art rejections are new and are necessitated by Applicant’s amendments to the claims.
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 following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
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.
(New) Claims 1-3, 5-7, 9, 13-16, 35 and 38-39 are rejected under 35 U.S.C. 103 as being unpatentable over WO 91/02527 to Sharpe (published 1991, PTO-892) in view of Egwuagu (Chronic Intraocular Inflammation and Development of Retinal Degenerative Disease, Adv Exp Med Biol, published 2014, PTO-892), Kauppinen (Inflammation and its role in age-related macular degeneration, Cell and Molec Life Sci, published 2016, PTO-892), and Whitcup (Inflammation in Retinal Disease, Int Jn of Inflamm, published 2013, PTO-892).
Sharpe teaches a method and composition for the topical treatment of cutaneous, mucosal or ocular hypersensitivity reactions, inflammation, or epithelial hyperproliferation states, applied directly to an affected area of the skin, eye, or mucosal membrane, consisting of a therapeutically effective amount of reserpine, spiperone, or other serotonin antagonists which have been incorporated into a vehicle suitable for topical administration (title, abstract).
Sharpe specifically teaches a method for the treatment of ocular inflammation or prevention/reduction of the formation of scar tissue in and around the eye comprising administering a therapeutically effective amount of a serotonin antagonist to an affected area of the eye (pg. 21, claims 3, 4), wherein the serotonin antagonist is reserpine (pg. 22, claims 5-6; title, abstract).
Reserpine is a compound of instant Formula (I),
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, when:
n is 1,
R1 is heteroaliphatic (-OCH3)
R2 is OR5, wherein R5 is aliphatic (CH3)
R3 is aliphatic (CH3)
R4 is acyl.
Regarding claims 1 and 35, while Sharpe teaches a method of treating ocular inflammation or scare tissue by administering a compound of instant formula (I), it differs from that of instant claims 1 and 35 in that it does not teach the method as treating retinal degeneration in a subject.
Egwuagu teaches that elevated levels of inflammatory cytokines in the vitreous of patients with chronic intraocular inflammation contribute to the pathogenesis of retinal degenerative diseases (abstract). Recent studies in mouse models of chronic uveitis reveal that prolonged inflammation causes retinal degeneration (pg. 2, 2nd full paragraph). Chronic intraocular inflammation induces retina degeneration, severe vision loss, and blindness (pg. 4, “Conclusions”).
Kauppinen teaches that chronic inflammation is involved in the pathogenesis of age- related macular degeneration, which results in degeneration of the retinal pigment epithelium (abstract).
Kauppinen teaches that macular degeneration is an ocular disease with inflammation strongly interwoven into its pathogenesis (pg. 1776, “Conclusion”).
Whitcup teaches inflammation as an underlying pathogenesis for a wide array of retinal diseases, including age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and retinitis pigmentosa, wherein anti-inflammatory therapies can alter the severity and course of these disorders (pg. 1, 1st paragraph).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select the methods of Sharpe to treat the inflammation of retinal degeneration, such as retinitis pigmentosa or age-related macular degeneration, to arrive at instant claims 1 and 35. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Sharpe teaches its methods as treating ocular inflammation,
-Egwuagu teaches that intraocular inflammation contributes to the pathogenesis of retinal degenerative diseases,
-Kauppinen teaches that chronic inflammation is involved in the pathogenesis of age- related macular degeneration, which results in degeneration of the retinal pigment epithelium, and
-Whitcup teaches inflammation as an underlying pathogenesis for a wide array of retinal diseases, including age-related macular degeneration, and retinitis pigmentosa, wherein anti-inflammatory therapies can alter the severity and course of these disorders.
As such, an ordinary skilled artisan would have been motivated to make such a selection, to predictably arrive at a method of treating the inflammation of retinal degeneration in diseases such as age-related macular degeneration and retinitis pigmentosa, to thereby treat retinal degeneration or slow its progression.
Regarding claim 2, the combination of Sharpe, Egwuagu, Kauppinen, and Whitcup teach age-related macular degeneration and retinitis pigmentosa.
Regarding claim 3, Sharpe teaches administration to the eye, i.e., local administration.
Regarding claim 5, Kauppinen teaches intravitreal administration for treatments for age-related macular degeneration (paragraph spanning pgs. 1766-1767). Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly filed application, to select intravitreal administration as the administration to the eye in the combined method of Sharpe, Egwuagu, Kauppinen, and Whitcup, to arrive at instant claim 5. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, since Sharpe teaches administration to the eye and Kauppinen teaches intravitreal administration as a type of administration to the eye. As such, an ordinary skilled artisan would have been motivated to make such a selection to predictably arrive at an effective mode of administration to administer the reserpine.
Regarding claim 6, Sharpe teaches its methods for use in humans (pg. 24, claim 11).
Regarding claims 7, 9, and (i)-(iii) of claim 35, the combination of Sharpe, Egwuagu, Kauppinen, and Whitcup, administers a compound of instant formula (I) in an amount effective to treat the inflammation of retinal degeneration.
While the combination of Sharpe, Egwuagu, Kauppinen, and Whitcup, does not explicitly teach the functional limitations of instant claims 7, 9, and 35, it is reasonable to assume that administering, to the eye, the reserpine of the combination of Sharpe, Egwuagu, Kauppinen, and Whitcup, would have the same properties since it is administered for the same purpose (treating retinal degeneration in patients with diseases, such as retinitis pigmentosa and age-related macular degeneration), in a therapeutically effective amount, to the same patient population (patients with retinal degeneration), as that taught by the instant specification and claims. Thus, while the prior art does not explicitly teach these properties, burden is on Applicant to show that the prior art does not have these properties.
Applicants are reminded that the office does not have the facilities and resources to provide the factual evidence needed in order to establish that the product of the prior art does not possess the same material, structural and functional characteristics of the claimed product. In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences. See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
See also MPEP 2112.02.
Regarding claims 13-16, reserpine is a compound of formula IC, wherein R4 is
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and R5 is Me, and reserpine is the second depicted compound in claim 16.
Further regarding claims 13-15, stereoisomers are generally of sufficiently
close structural similarity that there is a presumed expectation that such compounds possess
similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See MPEP
2144.09.
Regarding claims 38 and 39, Sharpe teaches its composition comprising reserpine and a suitable carrier (pg. 6, 1st full paragraph; pg. 12, line 24-pg. 13, line 26).
(New) Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over WO 91/02527 to Sharpe (published 1991, PTO-892) in view of Egwuagu (Chronic Intraocular Inflammation and Development of Retinal Degenerative Disease, Adv Exp Med Biol, published 2014, PTO-892), Kauppinen (Inflammation and its role in age-related macular degeneration, Cell and Molec Life Sci, published 2016, PTO-892), and Whitcup (Inflammation in Retinal Disease, Int Jn of Inflamm, published 2013, PTO-892), as applied to claims 1-3, 5-7, 9, 13-16, 35 and 38-39, above, and further in view of Wolpert (Electroretinography, Electroretinograms, published 2011, PTO-892 of 11/05/2025).
Sharpe, Egwuagu, Kauppinen, and Whitcup are applied as discussed above and incorporated herein.
While Sharpe, Egwuagu, Kauppinen, and Whitcup teaches a method of treating retinal degeneration, such as retinitis pigmentosa or age-related macular degeneration, by administering reserpine to the eye, it differs from that of instant claim 11 in that it does not teach performing electroretinography.
Wolpert teaches electroretinography as a mainstay of clinical ophthalmic diagnostic testing. The electroretinogram provides an objective, quantitative measure of retinal function and allows the clinician to monitor the function of rod cells, cone cells, and ganglion cells in each eye (pg. 3).
Wolpert teaches that there are several types of electroretinographic tests. Full-Field ERG is the most common form of electroretinographic testing and it provides an assessment of general retinal function and can distinguish between the various cell types, revealing the function of photoreceptors, bipolar cells, ganglion calls, and amacrine cells (pgs. 3-4; pg. 6, 4.1.1; pg. 7. 4.2.1; pg. 8, 4.3.1; pg. 10 EOG).
Wolpert teaches electroretinography as an important test with both diagnostic and prognostic application. It can help to diagnose a patient with various visual symptoms, and it can be of use when the symptoms seem incompatible. It can also help determine the significance of fundus abnormalities and provide an early diagnosis for patients with a family history of inherited retinal disease. ERG testing is especially significant because it provides an objective, quantifiable evaluation of visual function, unlike tests such as microperimetry that require reliable patient input (pg. 10, 6.)
Wolpert concludes by teaching that the quantitative results that ERG tests provide make them useful as tools for both prognosis and disease monitoring (pg. 19, Conclusion).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, at add performing electroretinography, to the combined method of Sharpe, Egwuagu, Kauppinen, and Whitcup, to arrive at claim 11. One of ordinary skill in the art would have been motivated to make such an addition, with a reasonable expectation of success, to predictably arrive at a method that monitors the effectiveness of the chloroquine treatment on the progression or regression of the retinitis pigmentosa or age-related macular degeneration.
Free of the prior art
Claims 36-37 are free of the prior art.
Claims 36-37 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Jim) Alstrum-Acevedo can be reached on 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAUREN WELLS/Examiner, Art Unit 1622