DETAILED ACTION
Status of Application
The response filed 07/23/2026 has been received, entered and carefully considered. The response affects the instant application accordingly:
Claims 1, 8-10, 13-14, 16 have been amended.
Claim 7 has been cancelled.
Applicant had previously elected the species for ocular graft-versus-host disease for the examination.
Upon review, the election of species is expanded to include dry eye and Sjogren’s.
Due to restriction, based on election of species, claim 4 is withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected species.
Claims 1-6, 8-16 are pending.
Claims 1-3, 5-6, 8-16 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
All grounds not addressed in the action are withdrawn or moot as a result of amendment.
New grounds of rejection are set forth in the current office action or moot as a result of amendment.
New Grounds of Rejection
Due to the amendment of the claims the new grounds of rejection are applied:
Claim Rejections - 35 USC § 103
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.
Claims 1-3, 5-6, 8-16 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (U.S. Pat. Pub. 2018/0064728) in view of Jain et al. (U.S. Pat. Pub. 2019/0000871) and Sabti et al. (Punctal occlusion is safe and efficient for the treatment of keratoconjunctivitis sicca in patients with ocular GvHD-abstract only) and www.picmonic.com (Eye Medication Administration – For Ophthalmic Ointment).
Rejection:
Chang et al. teaches treating a neurodegenerative condition like the exemplified ocular graft-versus-host disease with the topical administration of a composition containing progesterone (sex steroid) to the forehead, like the exemplified 1% progesterone gel that was 0.5-1mg per dose (abstract, Figure 2, Example 3-6, [100-116, 147]). The composition can be applied more than once per day [45] with the sex steroid i.e. progesterone, at a dose from 0.001-30mg/day [48]. Example 3 had topical application of 1% progesterone gel for ocular graft-versus-host disease twice a day (0.5-1mg per dose, twice a day=1mg-2mg day), Example 5 had topical application of 1% progesterone gel for ocular graft-versus-host disease once a day (0.5-1mg per dose once a day=0.5mg-1mg day, see full document specifically areas cited).
Chang et al. does not expressly teach the topical administration of a corticosteroid to the eye with punctal plugs, but does teach treating ocular graft-versus-host disease with progesterone and combination therapy.
Jain et al. teaches treating inflammatory ocular condition like ocular graft-versus-host disease (oGVHD) with the topical administration of heparin and optionally a second active like a steroid such as loteprednol etabonate from about 0.01-about 2%w/w and typically from about 0.05-about 1%w/w (abstract, claims 8-9,[15, 17, 19, 56, 58-59, 68], i.e. Example 15 and 27). The steroid can be given once a day [124] and the composition can be in the form of an ointment [11, 13] and the inclusion of substances capable of treating ocular surface disorders like punctal plugs [105].
Sabti et al. teaches that punctal plugs achieve significant improvement in symptoms in ocular GVHD.
www.picmonic.com teaches that an ophthalmic ointment is applied as a thin stream along the inner edge of the eyelid (eyelid margin) and then to close the eye (spreading the ointment along the eye/eyelid margin).
Wherein it would be obvious to one of ordinary skill in the art to topically administer corticosteroids to the eye with punctal plugs as suggested by Jain et al. and Sabti et al. and www.picmonic.com and produce the claimed invention; as it is prima facie obvious to incorporate known means for treating ocular graft-versus-host disease (oGVHD) and its dry eye symptoms - like corticosteroids (i.e. loteprednol etabonate and heparin in ointment to the eyelid margin with punctal plugs) for their additive effects with a reasonable expectation of success. While the prior art does not teach the exact claimed value for the steroid (i.e. 0.5% loteprednol etabonate) instantly claimed for claim 16, it is embraced by the prior art range (about 0.05-about 1%w/w) wherein it would be prima facie obvious to optimize within the taught range as a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed value.
Response to Arguments:
Applicant's arguments center on the assertion that the references do not teach application of the corticosteroid e.g. loteprednol etabonate to the eyelid margins as currently amended. This is fully considered but not persuasive as addressed by the rejection above which teaches the known conventional application of eye ointments to the eyelid margin. Applicant also asserts unexpected results pointing to the Examples of the specification. This is fully considered but not persuasive. Arguments without clear factual support are mere allegations and are not found persuasive. The Examples do not recite the concentration of loteprednol etabonate in the ointment used. The Examples also do not present a clear demonstration of objective testing/measurement of the effects of the unrecited amount of loteprednol etabonate with punctal plugs and the effects of the 1% progesterone topical gel to the forehead 2x/day separately, compared to the effects of the combination to ascertain that the resulting presentation is unexpected rather than additive. Arguments without clear factual support are mere allegations and are not found persuasive. The frequency of the loteprednol etabonate is also uncertain (some examples recite nightly, some are unclear). Example 3 is also unclear as there is a recitation of a crossover arm but the timeframe is unclear as the patient was in the placebo arm with a change in oral prednisone wherein the dates do not reflect the regimen used and effects presented. The examples also contain the inclusion of oral steroids and immunosuppressants and lubricant which would affect the outcome and are not recited in the claims wherein the showing is also not commensurate in scope with the claims.
Accordingly, the rejection stands.
Claims 1-3, 5-6, 8-16 are rejected under 35 U.S.C. 103 as being unpatentable over Chang et al. (U.S. Pat. Pub. 2015/0216877) in view of Jain et al. (U.S. Pat. Pub. 2019/0000871) and www.picmonic.com (Eye Medication Administration – For Ophthalmic Ointment).
Rejection:
Chang et al. teaches treating dry eye syndrome (aka keratoconjunctivitis sicca) with the topical administration of a composition containing progesterone to the forehead (claims 22-26, 28-30). The progesterone is from about 0.05-about 4%w/w progesterone like about 0.1-about 2.0%w/w progesterone and the exemplified 1% progesterone composition (claims 28-29 and Example 2), can be applied at least once a day or twice a day [30], and where the effective amount of progesterone is from about 0.05-5mg (claim 30) which can be per dose or application ([25], twice a day=0.10-10mg day). It can be in combination with one or more additional therapies including punctal plugs and steroids [27]. Example 3 exemplifies treating dry eye with 1% progesterone with punctal plugs ([46], see full document specifically areas cited).
Chang et al. does not expressly teach the topical administration of a corticosteroid to the eye, but does teach treating the dry eye in combination with one or more additional therapies like corticosteroids.
Jain et al. teaches treating inflammatory ocular conditions like dry eye including dry eye caused by ocular graft-versus-host disease (oGVHD), with the topical administration of heparin and optionally a second active like a steroid such as loteprednol etabonate from about 0.01-about 2%w/w and typically from about 0.05-about 1%w/w (abstract, claims 8-9, [15, 17, 19, 29, 56, 58-59, 68], Figure 2, i.e. Example 1, 11-12, 15,27). The steroid is exemplified to be in combination with the heparin (example 11) and it is known that steroid can be given once a day [124], and the composition can be in the form of an ointment [11, 13].
www.picmonic.com teaches that an ophthalmic ointment is applied as a thin stream along the inner edge of the eyelid (eyelid margin) and then to close the eye (spreading the ointment along the eye/eyelid margin).
Wherein it would be obvious to one of ordinary skill in the art to topically administer corticosteroids to the eye as suggested by Jain et al. and www.picmonic.com and produce the claimed invention; as Chang et al. teaches the inclusion of corticosteroids and it is prima facie obvious to incorporate the known topical means for applying corticosteroids for treating dry eye such as the dry eye from ocular graft-versus-host disease (oGVHD) with corticosteroids (i.e. loteprednol etabonate and heparin in ointment to eyelid margin) for their additive effects with a reasonable expectation of success. While the prior art does not teach the exact claimed value for the steroid (i.e. 0.5% loteprednol etabonate) instantly claimed for claim 16, it is embraced by the prior art range (about 0.05-about 1%w/w) wherein it would be prima facie obvious to optimize within the taught range as a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed value.
Response to Arguments:
Applicant's arguments center on the assertion that the references do not teach application of the corticosteroid e.g. loteprednol etabonate to the eyelid margins as currently amended. This is fully considered but not persuasive as addressed by the rejection above which teaches the known conventional application of eye ointments to the eyelid margin.
Accordingly, the rejection stands.
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.
Claims 1-3, 5-6, 8, 12, 14-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 8, 13-14 of U.S. Patent No. 10098895 in view of Jain et al. (U.S. Pat. Pub. 2019/0000871) and Sabti et al. (Punctal occlusion is safe and efficient for the treatment of keratoconjunctivitis sicca in patients with ocular GvHD-abstract only) and www.picmonic.com (Eye Medication Administration – For Ophthalmic Ointment).
The patented claims are directed to a method of treating ocular graft-versus-host disease with the topical administration of a sex steroid that is progesterone or testosterone, and/or a cannabinoid. The dependent patented claims are directed to the dose of the sex steroid like progesterone and the composition form.
The patented claims does not expressly teach the topical administration of a corticosteroid to the eye with punctal plugs, but does teach treating ocular graft-versus-host disease with progesterone and combination therapy.
Jain et al. teaches treating inflammatory ocular condition like ocular graft-versus-host disease (oGVHD) with the topical administration of heparin and optionally a second active like a steroid such as loteprednol etabonate from about 0.01-about 2%w/w and typically from about 0.05-about 1%w/w (abstract, claims 8-9,[15, 17, 19, 56, 58-59, 68], i.e. Example 15 and 27). The steroid can be given once a day [124] and the composition can be in the form of an ointment [11, 13] and the inclusion of substances capable of treating ocular surface disorders like punctal plugs [105].
Sabti et al. teaches that punctal plugs achieve significant improvement in symptoms in ocular GVHD.
www.picmonic.com teaches that an ophthalmic ointment is applied as a thin stream along the inner edge of the eyelid (eyelid margin) and then to close the eye (spreading the ointment along the eye/eyelid margin).
Wherein it would be obvious to one of ordinary skill in the art to topically administer corticosteroids to the eye with punctal plugs as suggested by Jain et al. and Sabti et al. and www.picmonic.com and produce the claimed invention; as it is prima facie obvious to incorporate known means for treating ocular graft-versus-host disease (oGVHD) and its dry eye symptoms - like corticosteroids (i.e. loteprednol etabonate and heparin in ointment to the eyelid margin with punctal plugs) for their additive effects with a reasonable expectation of success. While the prior art does not teach the exact claimed value for the steroid (i.e. 0.5% loteprednol etabonate) instantly claimed for claim 16, it is embraced by the prior art range (about 0.05-about 1%w/w) wherein it would be prima facie obvious to optimize within the taught range as a means of attaining the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed value.
Response to Arguments:
Applicant's arguments center on the assertion that the patented claims do not teach application of the corticosteroid to the eyelid margins as currently amended. This is fully considered but not persuasive as addressed by the rejection above which teaches the known conventional application of eye ointments to the eyelid margin.
Accordingly, the rejection stands.
Claims 9-11, 13, 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 8, 13-14 of U.S. Patent No. 10098895 in view of Jain et al. (U.S. Pat. Pub. 2019/0000871) and Sabti et al. (Punctal occlusion is safe and efficient for the treatment of keratoconjunctivitis sicca in patients with ocular GvHD-abstract only) and www.picmonic.com (Eye Medication Administration – For Ophthalmic Ointment) as applied to claims 1-3, 5-6, 8, 12, 14-15 above, further in view of Chang et al. (U.S. Pat. Pub. 2018/0064728).
The teachings of the patented claims in view of Jain et al. and Sabti et al. and www.picmonic.com are addressed above.
The patented claims in view of Jain et al. and Sabti et al. and www.picmonic.com does not expressly teach the concentration of the progesterone applied to the forehead.
Chang et al. teaches that topical administration of a composition containing progesterone (sex steroid) to the forehead, can be at 1% progesterone gel that was 0.5-1mg per dose (abstract, Figure 2, Example 3-6, [100-116, 147]). Example 3 had topical application of 1% progesterone gel for ocular graft-versus-host disease twice a day (0.5-1mg per dose, twice a day=1mg-2mg day), Example 5 had topical application of 1% progesterone gel for ocular graft-versus-host disease once a day (0.5-1mg per dose once a day=0.5mg-1mg day).
Wherein it would be obvious to one of ordinary skill in the art to topically administer the progesterone at 5% as suggested by Chang et al. and produce the claimed invention; as it is prima facie obvious to incorporate the progesterone at its known concentration with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments are those presented for the patented claims which are addressed above.
Accordingly, the rejection stands.
Claims 1-2, 5-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10251835 in view of Jain et al. (U.S. Pat. Pub. 2019/0000871) and Sakai (When Artificial Tears are not Enough) and www.picmonic.com (Eye Medication Administration – For Ophthalmic Ointment).
The patented claims are directed to a method of treating Sjogren’ syndrome (dry eye from Sjogren’s) with the topical administration of progesterone to the forehead. The dependent patented claims are directed to the dose of the progesterone.
The patented claims does not expressly teach the topical administration of a corticosteroid to the eye with punctal plugs, but does teach treating Sjogren’s syndrome with progesterone.
Jain et al. teaches treating inflammatory ocular condition like dry eye such as Sjogren’s syndrome with the topical administration of heparin and optionally a second active like a steroid such as loteprednol etabonate from about 0.01-about 2%w/w and typically from about 0.05-about 1%w/w (abstract, claims 8-9, [15, 17, 19, 58-59, 76], i.e. Example 22). The steroid can be given once a day [124] and the composition can be in the form of an ointment [11, 13] and the inclusion of substances capable of treating ocular surface disorders like punctal plugs [105].
Sakai teaches that punctal plugs are tiny devices inserted into the tear duct so the eyes retain more of their natural moisture and can be temporary or permanent. achieve significant improvement in symptoms in ocular GVHD.
www.picmonic.com teaches that an ophthalmic ointment is applied as a thin stream along the inner edge of the eyelid (eyelid margin) and then to close the eye (spreading the ointment alone the eye/eyelid margin).
Wherein it would be obvious to one of ordinary skill in the art to topically administer corticosteroids to the eye with punctal plugs as suggested by Jain et al. and Sakai and www.picmonic.com and produce the claimed invention; as it is prima facie obvious to incorporate known means for treating dry eye such as Sjogren’s - like corticosteroids (i.e. loteprednol etabonate and heparin in ointment with punctal plugs) for their additive effects with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments center on the assertion that the references do not teach application of the corticosteroid to the eyelid margins as currently amended. This is fully considered but not persuasive as addressed by the rejection above which teaches the known conventional application of eye ointments to the eyelid margin.
Accordingly, the rejection stands.
Claims 1-2, 5-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-12 of U.S. Patent No. 9925201 in view of Jain et al. (U.S. Pat. Pub. 2019/0000871) and Sakai (When Artificial Tears are not Enough) and www.picmonic.com (Eye Medication Administration – For Ophthalmic Ointment).
The patented claims are directed to a method of treating ocular surface conditions like Sjogren’ syndrome (dry eye from Sjogren’s) with the topical administration of progesterone to the forehead. The dependent patented claims are directed to the dose and concentration of the progesterone.
The patented claims does not expressly teach the topical administration of a corticosteroid to the eye with punctal plugs, but does teach treating Sjogren’s syndrome with progesterone.
Jain et al. teaches treating inflammatory ocular condition like dry eye such as Sjogren’s syndrome with the topical administration of heparin and optionally a second active like a steroid such as loteprednol etabonate from about 0.01-about 2%w/w and typically from about 0.05-about 1%w/w (abstract, claims 8-9, [15, 17, 19, 58-59, 76], i.e. Example 22). The steroid can be given once a day [124] and the composition can be in the form of an ointment [11, 13] and the inclusion of substances capable of treating ocular surface disorders like punctal plugs [105].
Sakai teaches that punctal plugs are tiny devices inserted into the tear duct so the eyes retain more of their natural moisture and can be temporary or permanent. achieve significant improvement in symptoms in ocular GVHD.
www.picmonic.com teaches that an ophthalmic ointment is applied as a thin stream along the inner edge of the eyelid (eyelid margin) and then to close the eye (spreading the ointment alone the eye/eyelid margin).
Wherein it would be obvious to one of ordinary skill in the art to topically administer corticosteroids to the eye with punctal plugs as suggested by Jain et al. and Sakai and www.picmonic.com and produce the claimed invention; as it is prima facie obvious to incorporate known means for treating dry eye such as Sjogren’s - like corticosteroids (i.e. loteprednol etabonate and heparin in ointment with punctal plugs) for their additive effects with a reasonable expectation of success.
Response to Arguments:
Applicant's arguments center on the assertion that the references do not teach application of the corticosteroid to the eyelid margins as currently amended. This is fully considered but not persuasive as addressed by the rejection above which teaches the known conventional application of eye ointments to the eyelid margin.
Accordingly, the rejection stands.
Conclusion
Claims 1-3, 5-6, 8-16 are rejected.
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 GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613
