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
Status
Claims 1-4, 6-14, 16, and 18-29 are pending. Claims 12, 13 and 25-29 are withdrawn from further consideration, 37 CFR 1.142(b), as being drawn to a non-elected invention (Claims 27-29) and species (Claims 12, 13, 25 and 26). Therefore, Claims 1-4, 6-11, 14, 16, and 18-24 are under active examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/20/2026 has been entered.
Election/Restriction
During a telephone conversation with Judith Toffenetti on 2/8/2023 a provisional election was made without traverse to prosecute the invention of Group I (method of treating), presbyopia as the visual acuity, pilocarpine as the ophthalmic miotic agent and caffeine as the methylated xanthine.
Priority
This application’s claim to priority benefit to U.S. Provisional Appl. No. 63/077142, filed on September 11, 2020.
Information Disclosure Statement
The Information Disclosure Statement filed 2/20/2026 has been considered by the Examiner. The submission is in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
Claim Rejections - 35 USC § 103
Rejection maintain, slightly modified to address amendments
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.
Claims 1-4, 6-11, 14, 16, and 18-24 are rejected under 35 U.S.C. 103 as being unpatentable over Abad et al. (US 9,301,933 – cited previously 3/16/2023 PTO892) in view of Nanduri et al. (US PG-PUB 2015/0174211 A1 – cited previously 3/16/2023 PTO892).
Claimed invention
Claim 1 is drawn to a method of treating and improving impaired visual acuity (a genus that encompasses presbyopia) and maintaining the aperture of the pupil within the physiological pupillary size for at least 4 hours in a subject in need thereof without causing at least one of ciliary muscle spasms, myopia, miosis, and decreased contrast sensitivity, comprising topically applying a composition comprising:
about 0.05-10 wt.% of a methylated xanthine (e.g., caffeine) and
about 5-9 wt.% pilocarpine to the outer skin surface of at least one eyelid of the subject.
Independent Claim 14 is similar to Claim 1 but more specifically identifies the impaired visual acuities as being either presbyopia, hyperopia, astigmatism, decreased contrast sensitivity, or decreased stereopsis.
Prior art
Abad teaches the treatment of presbyopia using a composition containing pilocarpine, as a cholinergic agent, and an alpha agonist. The cholinergic agent is present at from about 0.01% to about 4%.
“It has been found that an alpha agonist having an imidazoline group or non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity in combination with a cholinergic agent, such as pilocarpine, act synergistically to improve the accommodative and focusing ability of the eye while minimizing the side effects from each compound.”
See Abad, abstract. Emphasis added. See also title.
“The compositions of the invention are suitable for ophthalmic use. The compositions generally include from about 0.01% to about 4% w/w cholinergic agent.”
See Abad, col. 6:37.
Abad teaches the treatment of the composition is effective for at least 6 hours.
“A method of treating an ocular condition in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising pilocarpine and oxymetazoline; wherein the ocular condition is selected from the group consisting of presbyopia, and wherein the composition is effective for at least six hours.”
See Abad, Claim 1. Emphasis added.
While Abad teaches treatment of presbyopia with a composition containing pilocarpine, Abad does not explicitly teach
about 0.05-10% of a methylated xanthine (such as caffeine),
the specific amount of about 5-9% pilocarpine, or
application to the outer skin if the eyelid.
Regarding 1) about 0.05-10% of a methylated xanthine (such as caffeine)
However, it was already known that pilocarpine can be combined with caffeine in topical ophthalmic compositions for application to the outer skin of eyelids for the treatment of other eye conditions. For example, Nanduri discloses methods and compositions for the topical sustained delivery of therapeutic agents wherein the agent is released slowly over an extended period of time (see 0043). See abstract. Topical application of compositions containing a muscle fasciculating agent (e.g., caffeine, theophylline, pentoxifyline or theobromide – see 0009) results in the sustained release of any therapeutic agent contained within the composition. More particularly, topical application of such compositions to the outer surface of the eyelid of a patient results in increased absorption and sustained release of the therapeutic agent. See abstract. The therapeutic agent may include pilocarpine, a cholinergic agent. See 0065-0067. Nanduri exemplifies topical application of a composition to the outer eyelid of subjects for the treatment of dry eye wherein the composition comprises pilocarpine and 0.16% caffeine:
“Two human patients with preexisting symptomatic severe dry eye were treated as follows. … Each subject received a single application of a lotion containing 1% of pilocarpine and 0.16% caffeine applied to the upper eyelid of the more severely affected eye by direct application of the lotion to the upper eyelid.”
See Nanduri, Example 1 at 0126. Emphasis added. See also Title; Abstract.
A person of ordinary skill in the art (POSA) would have found it obvious to incorporate caffeine in disclosed amounts into an ophthalmic topical composition with pilocarpine and applied to an eyelid for treatment of presbyopia because Abad teaches that presbyopia is treatable with a composition comprising pilocarpine and Nanduri provides a topical ophthalmic composition of pilocarpine (as the therapeutic agent) and 0.16% caffeine for application to the outer eyelid to provide increased absorption and sustained release of the therapeutic agent. The artisan would have reasonably sought to combine 0.16% caffeine with pilocarpine because 0.16% caffeine and pilocarpine can be suitably formulated together to provide increased absorption and sustained deliver of pilocarpine (Nanduri), the artisan would have had a reasonable expectation of success that the combination of pilocarpine and caffeine would be suitable for application to the outer eyelid for providing pilocarpine therapy to the eye.
Regarding 2) about 5-9% pilocarpine
Abad teaches a range of pilocarpine that overlaps the claimed range of pilocarpine. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. MPEP 2144.05 [R5]. Note, while the prior art does not disclose the exact claimed values, but does overlap, in such instances even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). In this case, Abad teaches pilocarpine at a concentration ranging from about 0.01 to about 4% as outlined above. The claimed range is prima facie obvious because the claimed range of from about 5-9% is sufficiently overlapped by Abad’s teaching of pilocarpine at a concentration ranging from about 0.01-4%.
To the extent this claimed range is not considered to overlap Abad’s about 0.01% to about 4%, it is nonetheless obvious as the routine optimization of the result-effective variable. Abad discloses that pilocarpine concentration is a result-effective variable by correlating concentration with efficacy and the degree of ocular effect. See Abad, paragraph bridging columns 4 and 5 – stating that concentrations below 0.5% produce minimal effect in the accommodation of the eye while concentrations of pilocarpine effective enough to improve the reading rendered the eye myopic. Where a parameter is recognized as a result-effective variable, its optimization through routine experimentation is prima facie obvious. See MPEP § 2144.05(II). Here, a POSA would have reasonably sought higher pilocarpine amounts when formulated for the slow-release route across the eyelid as it is the slow-release mechanism taught by Nanduri that allows for higher drug amounts. See Nanduri, abstract, 0043. Applicant’s specification confirms that formulating for the eyelid “rather than directly to the eyeball, the cholinergic agent or other miotic drug contained therein is slowly released into and across the eyelid and into the eye, enabling the use of higher dosages of active ingredient and hence, longer lasting beneficial effect on vision.” See specification, US 20220079922, 0062, 0067. The as-filed specification explains explicitly why more drug can be used; and it is by employing the eyelid application method already described by Nanduri:
In general, the compositions of the disclosure comprise one or more cholinergic or other miotic agents in therapeutically effective amounts of from about 0.1 to about 10 wt. % of the composition. Because the compositions described herein are applied to the eyelid, rather than directly to the eyeball as in the case of eyedrops, higher amounts of the active agent, e.g., a cholinergic agent can be included in the compositions, thereby improving the beneficial effects on vision observed with use of these agents, without the usual side effects seen with their direct use in the eye.” Specification, US 2022/0079922, 0067. Emphasis added.
Given that pilocarpine concentration is a result-effective variable, arriving at about 5-9 wt.% pilocarpine to achieve a therapeutic concentration transdermally across the eyelid barrier as described by Nanduri is therefore routine optimization with reasonable expectation of success.
Regarding the limitations wherein the method of treating the impaired acuity without causing ciliary muscle spasms, myopia, miosis and decreased contrast sensitivity, and maintaining the aperture of the pupil within the pupillary physiological size, because the prior art suggest the topical administration to the outer eyelid of a combination of pilocarpine and caffeine, the reduction of at least one side effect caused by direct ocular administration of pilocarpine (e.g., myopia, miosis, decreased contrast sensitivity, etc.) would intrinsically result from the indirect ocular administration of pilocarpine to the eyelid. This is evidenced by Applicant’s specification at page 8 which teaches the topical application of a composition of the disclosure comprising a combination of a methylated xanthine and a cholinergic agent or other miotic drug to the eyelid results in improved vision without occurrence of miosis or myopia (see instant specification, p. 8:24-28). Thus, the administration to the outer eyelid as suggested by the prior art (Nanduri, Example 1 at 0126) “results in lower incidence of at least one or more adverse events” as claimed as evidenced by the instant specification:
Application of the disclosed compositions to the eyelid of a subject in need of treatment results in a lower incidence of at least one or more adverse events such as ocular blurring, ocular discomfort, eye pain, brow ache, blurry vision, light sensitivity, night blindness, pinhole vision, loss of contrast sensitivity, myopia and decreased far vision, compared to administration of an eyedrop solution comprising, carbachol, physostigmine or other cholinergic agent.
See specification, 9. 10:24-29.
Furthermore, Nanduri teaches applying the therapeutics according to the invention avoids unwanted side effects. See 0058, 0067.
The specification further defines miosis as “excessive constriction of the pupil” and fixes the physiological range at approximately 2-8 mm with miotics applied directly to the eye causing constriction “below 2.5 mm”. Applicant’s own disclosure establishes that maintenance of the pupil size within the physiological range, and the avoidance of excessive (miotic) constriction, is the intrinsic consequence of the eyelid route relied upon in Nanduri, not a distinguishing feature of the claims. Thus, the absence of at least one of the side effects is a “natural result of the combination of elements explicitly disclosed by the prior art.” See MPEP § 2112 IV.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Claim 2 limits Claim 1, wherein the impaired visual acuity is selected from the group consisting of presbyopia, hyperopia, astigmatism, decreased contrast sensitivity, and decreased stereopsis. Presbyopia is taught by Abad as outlined above. This meets the limitation of Claim 6.
Claim 3 limits Claim 1, wherein the method treats and improves the impaired visual acuity for at least 12 hours. Claim 3 claims that the method has intended results that do not give further meaning and purpose to the manipulative steps of the claimed method. Therefore, the limitation is not given patentable weight because it simply express the intended result of the process steps positively recited. Accordingly, a reference need not expressly teach the intended outcomes to meet the claim limitations. Similar to Claim 3, Claim 16 is also drawn to intended results that do not give further meaning and purpose to the manipulative steps. Claim 19 has the same issue of being drawn to intended results.
Claim 4 limits Claim 1, wherein the methylated xanthine is selected from caffeine, theophylline, dyphylline, theobromine, aminophylline, and pentoxifylline and pharmaceutically acceptable salts thereof. Nanduri teaches caffeine as outlined above. Caffeine also meets the limitation of Claim 18.
Claim 7 limits Claim 1, wherein the composition comprises about 6 to 9 wt.% pilocarpine. Claim 8 limits Claim 7, wherein the composition comprises about 0.05 to 1 wt.% caffeine. Claim 11 limits Claim 1, wherein the composition comprises about 0.05 to 1 wt.% caffeine and about 3 to 8 wt.% pilocarpine. Abad teaches pilocarpine at a concentration ranging from about 0.01-4% as outlined above. See Abad, col. 6:37. Given that pilocarpine concentration is a result-effective variable, arriving at about 5-9 wt.% pilocarpine to achieve a therapeutic concentration transdermally across the eyelid barrier as described by Nanduri is therefore routine optimization with reasonable expectation of success. Nanduri teaches 0.16% caffeine in a composition which meets the claimed range of 0.05-1% as it falls inside of the range being claimed. These teachings also meet the limitations of Claim 20, Claim 21 and Claim 24.
Claim 9 limits Claim 1, wherein the composition is applied to at least one outer eyelid at least once daily. Claim 10 limits Claim 9, wherein the composition is applied to at least one outer skin of at least one eyelid of both eyes of the subject. Abad teaches that the composition can be applied to one or both eyes and Nanduri teaches that the composition can be applied to the eyelids. Thus, one of ordinary skill in the art would have found it obvious to treat the subject by administering the composition to both eyes’ eyelids. The artisan would have had a reasonable expectation of success that the administration to both eyes can be beneficial for treating presbyopia in each eye. These teachings meet the limitations of Claim 22 and Claim 23.
Response to arguments and 1.132 Declaration
Applicant's arguments and declaration support have been fully considered but have not been found to be persuasive.
Applicant alleges Abad teaches away from the claimed invention by relying on pilocarpine-induced miosis to improve near vision.
Applicant’s reliance on Abad’s disclosure of miosis as a side effect is misplaced. Abad explicitly teaches the use of pilocarpine for improving near vision associated with presbyopia, demonstrating its utility despite known side effects. A reference’s recognition of drawbacks of a disclosed feature does not constitute a “teaching away” as it still teaches that feature for beneficial utility. Regarding Applicant’s remarks that Abad does not teach improving visual acuity without causing ciliary muscle spasms, while Abad teaches the composition is added to the eye to improve the accommodation and focusing ability of the eye by “contracting the ciliary muscle and reducing pupillary diameter” (Abad at para. 0023), ciliary muscle contractions is not synonymous to ciliary muscle spasms. Thus, Abad does not teach that spasms are required for the invention to work. Regarding miosis, constriction of the pupil does not equate to miosis. Miosis involves excessive constriction of the pupil. It is noted that the instant specification defines miosis to mean “excessive constriction of the pupil”. (Specification, p. 7, line 10). Abad does not teach that the treatment for presbyopia is to cause miosis by excessive constriction of the pupil. Abad teaches the improvement of vision to treat presbyopia, not to make vision blurry or excessively constrict the pupil. Thus, while Abad discloses the constriction of the pupil, Abad does not require miosis (i.e., “excessive constriction of the pupil”) in the treatment of presbyopia as alleged by Applicant. Furthermore, as presented in the rejection outlined above, one of the main benefits of application of the therapeutic to the eyelid disclosed by Nanduri is to bypass side effects caused by the therapeutic. A POSA would have found the reduction of known side effects of a therapeutic to be obvious and not surprising when administered to the eyelid per the teachings of Nanduri. It is the route of administration to the eyelid instead of the directly to the eye surface that inhibits the side effects. This is evidenced by Applicant’s specification at pages 8 and 9. Therefore, from the teachings of the prior art, the POSA would have found it obvious to treat the condition without causing the unwanted effects claimed.
Nanduri fails to teach or suggest treatment of presbyopia and, indeed, discloses miosis when combining caffeine with a miotic agent.
Applicant pointed to one example in Nanduri with a single normal patient that responded to outer eyelid application of a composition containing caffeine and physostigmine with miosis in the treated eye and dilation in the other. However, the rejection is not based on physostigmine. Furthermore, another patient with myopia had a decrease in myopia when administered pilocarpine. (Abad col. 2: lines 26-28.) Thus, application of pilocarpine to the eye will not necessarily cause miosis as suggested by Applicant.
Applicant contends in the form of Declaration that the absence of miosis is not inherent and that achieving therapeutic near vision at about 5-9wt% pilocarpine without miosis is an unexpected result. that absence of miosis, myopia, and decreased contrast sensitivity in the present claims is not an inherent result of the prior art.
First, the Declaration does not support the claimed limitation. The claims recite a composition concentration (about 5-9 wt.% pilocarpine and about 0.05-10 wt.% caffeine). They recite no applied amount, delivered does, or dosing frequency. The Declaration’s asserted “surprise” is directed to the intraocular pilocarpine exposure achieved upon a particular eyelid administration (e.g., minipig iris/ciliary body level of 3841 nmol/L). Composition concentration and delivered ocular exposure are distinct variables. Evidence that a particular exposure did not produce miosis does not establish that the claimed concentration produces an unexpected result – particularly when the delivered-exposure response is an intrinsic property of the prior art eyelid route of administration (Nanduri).
Second, the value relied upon (Decl. ¶¶ 10, 19) is a total pilocarpine concentration in the dissected, homogenized tissue, which is not equivalent to the free drug available at the receptor.
Third, the assert unexpected result is a difference in degree, not kind. A difference in degree of a known dose response is not unexpected.
Applicant argues optimization requires recognition of a relevant parameter. However, here, Nanduri explicitly recognized that site of application affects pharmacokinetics and safety. The POSA would have recognized that route of any pilocarpine-based ocular indication, including presbyopia, with a reasonable expectation of improved tolerability. Adjusting known variables such as site of application and concentration falls within routine optimization of treatment.
Double Patenting
Rejection maintained
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-4, 6-11, 14, and 16-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, 12-25 of U.S. Patent No. 9,034,830 (“reference claims” or “reference” – cited previously 3/16/2023 PTO892) in view of Abad et al. (US 9,301,933– cited previously 3/16/2023 PTO892), Nanduri et al. (US 2015/0174211 A1– cited previously 3/16/2023 PTO892).
Claimed invention
Claim 1 is drawn to a method of treating and improving impaired visual acuity (a genus that encompasses presbyopia) and maintaining the aperture of the pupil within the physiological pupillary size for at least 4 hours in a subject in need thereof without causing at least one of ciliary muscle spasms, myopia, miosis, and decreased contrast sensitivity, comprising topically applying a composition comprising:
about 0.05-10 wt.% of a methylated xanthine (e.g., caffeine) and
about 5-9 wt.% pilocarpine to the outer skin surface of at least one eyelid of the subject.
Independent Claim 14 is similar to Claim 1 but more specifically identifies the impaired visual acuities as being either presbyopia, hyperopia, astigmatism, decreased contrast sensitivity, or decreased stereopsis.
Reference claims in view of prior art
The reference claims teach a method for treating an ophthalmic condition of the surface or interior of the eyeball or an ocular gland in a human patient in need thereof comprising topically administering a composition to the outer surface of at least one upper eyelid of the patient, said composition comprising:
a therapeutically effective amount of at least one therapeutic agent effective for treatment of the ophthalmic condition, particularly claiming pilocarpine as the therapeutic agent (see reference claim 10),
from 0.001% to 50 wt. % of a muscle fasciculating agent particularly claiming caffeine (see claim 10), wherein said administration results in delivery of the therapeutic agent across the eyelid and to target tissue of the eyeball or ocular gland.
However, the reference claims do not explicitly teach that the composition is used to treat presbyopia as the specific condition.
Abad teaches the treatment of presbyopia using a composition containing pilocarpine, as a cholinergic agent, and an alpha agonist. The cholinergic agent is present at from about 5-9 wt.%.
“It has been found that an alpha agonist having an imidazoline group or non-steroidal anti-inflammatory agent (NSAID) having COX-2 selectivity in combination with a cholinergic agent, such as pilocarpine, act synergistically to improve the accommodative and focusing ability of the eye while minimizing the side effects from each compound.”
See Abad, abstract. Emphasis added. See also title.
“The compositions of the invention are suitable for ophthalmic use. The compositions generally include from about 0.01% to about 4% w/w cholinergic agent.”
See Abad, col. 6:37.
Abad teaches the treatment of the composition is effective for at least 6 hours.
“A method of treating an ocular condition in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising pilocarpine and oxymetazoline; wherein the ocular condition is selected from the group consisting of presbyopia, and wherein the composition is effective for at least six hours.”
See Abad, Claim 1. Emphasis added.
It was already known that pilocarpine can be combined with caffeine in topical ophthalmic compositions for application to the outer skin of eyelids for the treatment of other eye conditions. For example, Nanduri discloses methods and compositions for the topical sustained delivery of therapeutic agents wherein the agent is released slowly over an extended period of time (see 0043). See abstract. Topical application of compositions containing a muscle fasciculating agent (e.g., caffeine, theophylline, pentoxifyline or theobromide – see 0009) results in the sustained release of any therapeutic agent contained within the composition. More particularly, topical application of such compositions to the outer surface of the eyelid of a patient results in increased absorption and sustained release of the therapeutic agent. See abstract. The therapeutic agent may include pilocarpine, a cholinergic agent. See 0065-0067. Nanduri exemplifies topical application of a composition to the outer eyelid of subjects for the treatment of dry eye wherein the composition comprises pilocarpine and 0.16% caffeine:
“Two human patients with preexisting symptomatic severe dry eye were treated as follows. … Each subject received a single application of a lotion containing 1% of pilocarpine and 0.16% caffeine applied to the upper eyelid of the more severely affected eye by direct application of the lotion to the upper eyelid.”
See Nanduri, Example 1 at 0126. Emphasis added. See also Title; Abstract.
One of ordinary skill in the art would have found it obvious to use the reference claims’ combination of caffeine and pilocarpine in disclosed amounts in an ophthalmic topical composition by applying it to an outer surface of an eyelid for treatment of presbyopia because the reference claims teach a composition containing pilocarpine and caffeine can be applied to the eyelids for treating an ophthalmic condition and Abad teaches that pilocarpine can be used for treating presbyopia and Nanduri provides that a topical ophthalmic composition of pilocarpine and 0.16% caffeine can be applied to the outer eyelid in order to provide a formulation with sustained release properties for pilocarpine. The artisan would have reasonably sought to use the combination composition because caffeine and pilocarpine can be suitably formulated together (reference claims; Nanduri), the artisan would have had a reasonable expectation of success that the combination of pilocarpine and caffeine would be suitable for application to the outer eyelid for providing known pilocarpine therapy (e.g., treating presbyopia) to the eye.
Abad teaches a range of pilocarpine that overlaps the claimed range of pilocarpine. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. MPEP 2144.05 [R5]. Note, while the prior art does not disclose the exact claimed values, but does overlap, in such instances even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003). In this case, Abad teaches pilocarpine at a concentration ranging from about 0.01-4% as outlined above. The claimed range is prima facie obvious because the claimed range of from about 1-10% is overlapped by Abad’s teaching of pilocarpine at a concentration ranging from about 0.01-4%.
Regarding the limitations wherein the method of treating the impaired acuity without causing ciliary muscle spasms, myopia, miosis and decreased contrast sensitivity comprising, because the prior art suggest the topical administration to the outer eyelid of a combination of pilocarpine and caffeine, the reduction of at least one side effect caused by direct ocular administration of pilocarpine (e.g., myopia, miosis, decreased contrast sensitivity, etc.) would intrinsically result from the indirect ocular administration of pilocarpine to the eyelid. This is evidenced by Applicant’s specification at page 8 which teaches the topical application of a composition of the disclosure comprising a combination of a methylated xanthine and a cholinergic agent or other miotic drug to the eyelid results in improved vision without occurrence of miosis or myopia (see instant specification, p. 8:24-28). Thus, the administration to the outer eyelid as suggested by the prior art (Nanduri, Example 1 at 0126) “results in lower incidence of at least one or more adverse events” as claimed as evidenced by the instant specification:
Application of the disclosed compositions to the eyelid of a subject in need of treatment results in a lower incidence of at least one or more adverse events such as ocular blurring, ocular discomfort, eye pain, brow ache, blurry vision, light sensitivity, night blindness, pinhole vision, loss of contrast sensitivity, myopia and decreased far vision, compared to administration of an eyedrop solution comprising, carbachol, physostigmine or other cholinergic agent.
See specification, 9. 10:24-29.
Furthermore, Nanduri teaches applying the therapeutics according to the invention avoids unwanted side effects. See 0058, 0067. Thus, the POSA would have found it obvious to treat the impaired acuity without causing ciliary muscle spasms, myopia, miosis and decreased contrast sensitivity. Additionally, because the prior art suggest the topical administration to the outer eyelid of a combination of pilocarpine and caffeine to treat presbyopia, the absence of at least one of the side effects is a “natural result of the combination of elements explicitly disclosed by the prior art.” See MPEP § 2112 IV.
Therefore, the claimed invention as a whole would have been prima facie obvious at the time the invention application was filed.
Claim 2 limits Claim 1, wherein the impaired visual acuity is selected from the group consisting of presbyopia, hyperopia, astigmatism, decreased contrast sensitivity, and decreased stereopsis. Presbyopia is taught by Abad as outlined above. This meets the limitation of Claim 6.
Claim 3 limits Claim 1, wherein the method treats and improves the impaired visual acuity for at least 12 hours. Claim 3 claims that the method has intended results that do not give further meaning and purpose to the manipulative steps of the claimed method. Therefore, the limitation is not given patentable weight because it simply express the intended result of the process steps positively recited. Accordingly, a reference need not expressly teach the intended outcomes to meet the claim limitations. Similar to Claim 3, Claim 16 is also drawn to intended results that do not give further meaning and purpose to the manipulative steps. Claim 19 has the same issue of being drawn to intended results.
Claim 4 limits Claim 1, wherein the methylated xanthine is selected from caffeine, theophylline, dyphylline, theobromine, aminophylline, and pentoxifylline and pharmaceutically acceptable salts thereof. Nanduri teaches caffeine as outlined above. Caffeine also meets the limitation of Claim 18.
Claim 7 limits Claim 1, wherein the composition comprises about 3 to 8 wt.% pilocarpine. Claim 8 limits Claim 7, wherein the composition comprises about 0.05 to 1 wt.% caffeine. Claim 11 limits Claim 1, wherein the composition comprises about 0.05 to 1 wt.% caffeine and about 3 to 8 wt.% pilocarpine. Abad teaches pilocarpine at a concentration ranging from about 0.01-4% as outlined above. See Abad, col. 6:37. The claimed range is prima facie obvious because the claimed range of from about 3-8% is overlapped by Abad’s teaching of pilocarpine at a concentration ranging from about 0.01-4%. Nanduri teaches 0.16% caffeine in a composition which meets the claimed range of 0.05-1% as it falls inside of the range being claimed. These teachings also meet the limitations of Claim 20, Claim 21 and Claim 24.
Claim 9 limits Claim 1, wherein the composition is applied to at least one outer eyelid at least once daily. Claim 10 limits Claim 9, wherein the composition is applied to at least one outer skin of at least one eyelid of both eyes of the subject. Abad teaches that the composition can be applied to one or both eyes and Nanduri teaches that the composition can be applied to the eyelids. Thus, one of ordinary skill in the art would have found it obvious to treat the subject by administering the composition to both eyes’ eyelids. The artisan would have had a reasonable expectation of success that the administration to both eyes can be beneficial for treating presbyopia in each eye. These teachings meet the limitations of Claim 22 and Claim 23.
Claim 17 limits Claim 14 wherein the ophthalmic miotic agent is pilocarpine, carbachol, cevimeline, or physostigmine or a pharmaceutically acceptable salt thereof. Abad and Nanduri teach pilocarpine as outlined above.
Response to arguments/Declaration
Applicant argues that the reference claims do not teach treating presbyopia or other decreased visual acuity. This is not persuasive because the reference claims are combined with Abad, which teaches that pilocarpine can be used for treating presbyopia.
Conclusion
No claims are allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) 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 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.
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/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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