DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/17/2025 has been entered.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/22/2025 has been considered by the examiner.
NPL which has been lined through has not been considered because a publication year has not been listed on the IDS.
Status of the Claims
The claims filed 11/17/2025 are under consideration.
Claims 1, 5-9, and 11-21 are pending.
Claims 1 and 9 are independent.
Claims 20 and 21 are new.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Amendment
The limitation of “without surgically removing the pterygium” has been deleted from claim 1.
Claim 10 was cancelled.
Formulation alternatives were deleted from claims 5 and 11.
Claims 20 and 21 were added.
Withdrawn
Rejections based on Ni under 35 U.S.C. 102(a)(1) have been withdrawn because of Applicant’s amendment. The claims as amended 11/17/2025 have a filing date of either 06/22/2015 or 05/27/2016. Claims 1, 6-9, 11-14, and 16-18 have a filing date of June 22, 2015 (06/22/2015). Claims 5, 15, 19, 20, and 21 have a filing date of May 27, 2016 (05/27/2016). See priority section below. Based on the current record, the Ni references qualify as prior art under 35 U.S.C. 102(a)(2) since they each enjoy the benefit of priority to June 6, 2015 corresponding to provisional application US 62172063.
The rejection of claims 1, 5-12, and 16 under 35 U.S.C. 103 as being unpatentable over Boral, US 20150166521 A1 also published as US 9266869 B2 in view of Huu, Journal of Controlled Release, 200, 2015 has been withdrawn. Boral does not directly link nintedanib to treating hyperemia or neovascularization in subjects suffering from pterygium. While Huu teaches administering nintedanib to subjects for treating neovascularization in the context of age-related macular degeneration, Huu does not expressly teach administering nintedanib topically to subjects having pterygium. Boral suggests molecules which inhibit VEGF and PDGF would be effective for treating subjects having vascular proliferative disorders (Boral, e.g., c3:5-13) including subjects having pterygia (Boral, e.g., c8:6-39). However, the present application presents evidence that nintedanib shows significant and unexpected results relative to the similar kinase inhibitor sorafenib. See Remarks, 11/17/2025, e.g., pp. 17/21-18/21 and table 8 reproduced from the published application at 0086. Further, in the ‘438 IPR, the PTAB found “comparative data of measuring the reduction in neovascularization in an established animal model … provides a sufficient nexus … to reducing hyperemia.” See ‘438 IPR, at p. 77, ¶ 1. On the balance, when all the evidence is considered, the unexpected results outweigh the prima facie case of obviousness based on the combined teachings of Boral and Huu. Therefore, the obviousness rejections based on the combined teachings of Boral and Huu have been withdrawn.
Rejections Addressing Applicant’s Amendment
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 112(a). The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 62183180, PCT/US2016/034822, US15/964235, and US17/750400 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The identified applications do not provide support for the following underlined claim limitations:
Claim 5 includes the limitations of cream, ointment, gel-forming liquid, and spray formulation. Prior filed Application No. 62183180 does not support these limitations. Therefore, claim 5 has a filing date of 27 May, 2016 corresponding to PCT/US2016/034822.
Claim 11 has a filing date of 06/22/2015 corresponding to provisional application No. 62183180 because the limitation of a solution or suspension is supported by the provisional application.
Claim 15 includes the limitation of “about 0.05% to 0.1% (w/v) of a surfactant.” Prior filed Application No. 62183180 does not support this limitation. Therefore, claim 15 has a filing date of 27 May, 2016 corresponding to PCT/US2016/034822.
Claim 19 includes the limitation of “about 0.05% to 0.1% (w/v) of the surfactant.” Prior filed Application No. 62183180 does not support this limitation. Therefore, claim 19 has a filing date of 27 May, 2016 corresponding to PCT/US2016/034822.
Claim 20 includes the limitation of “cream, ointment, gel-forming liquid, suspension containing liposomes or micelles or spray formulation.” Prior filed Application No. 62183180 does not support this limitation. Therefore, claim 20 has a filing date of 27 May, 2016 corresponding to PCT/US2016/034822.
Claim 21 includes the limitation of “wherein the suspension contains liposomes or micelles.” Prior filed Application No. 62183180 does not support this limitation. Therefore, claim 21 has a filing date of 27 May, 2016 corresponding to PCT/US2016/034822.
Claims 1, 6-9, 11-14, and 16-18 have a filing date of June 22, 2015 (06/22/2015).
Claims 5, 15, 19, 20, and 21 have a filing date of May 27, 2016 (05/27/2016).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5-9, 11-12, and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ni, US 20170172915 A1, also published as WO 2016200688 A1, and having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063.
Claims 1, 6-9, and 11-18, have a filing date of 06/22/2015.
Claims 5, 15, 19, 20, and 21 have a priority date of 05/27/2016.
Applicable to claim 1: Ni teaches a method for a pterygium in a subject, comprising administering to an affected eye of the subject a therapeutically effective amount of a multikinase inhibitor (Ni, e.g., claim 56 and provisional, pg. 7/10 and claim 1). Ni teaches treating patients having hyperemia (Ni, e.g., 0012, 0027 and provisional, claim 20). Ni teaches nintedanib (Ni, e.g., 0039-0042 and provisional claim 3) which inhibit kinases including VEGFR and PDGFR (Ni, e.g., 0042 and provisional claim 2). The disclosed methods reduce neovascularization and other symptoms in pterygium patients (Ni, e.g., 0004 and 0049-0050 and provisional, pg. 5/10 and 6/10). Ni teaches the composition is a topical ocular formulation, e.g., suspension, solution, gel, ointment, or emulsion (Ni, e.g., 0004 and claims 43-45 and 53-55 and 63-65 and provisional claims 7, 10, and 16), and wherein the topical composition comprises excipients (Ni, e.g., 0010, 0017, 0056, and provisional, pg. 8/10). Applicable to claim 7 and 16: Ni teaches treating primary pterygia which requires identifying a subject having pterygium (Ni, e.g., provisional, pg. 5/10).
Applicable to claims 1 and 9: The disclosed methods reduce hyperemia, abnormal neovascularization and other symptoms in pterygium patients (Ni, e.g., 0004 and 0049-0050 and provisional, pg. 5/10 and 6/10). Topical administration is taught (Ni, e.g., ‘063, e.g., claim 15), wherein the topical ocular formulation is administered topically to the affected eye (Ni, e.g., ‘063, e.g., claim 5). Ni teaches wherein the method is practiced prior to surgical removal of pterygium (Ni, e.g., Abstract, 0002, 0004, and 0017 and provisional pg. 7/10 and claim 23). Applicable to claim 11: Ni teaches a solution or suspension (Ni, e.g., ‘063, e.g., claims 7 and 10). Applicable to claim 12: compositions comprise an excipient. See, Ni, e.g., 0010, 0017, 0056, and provisional, pg. 8/10).
Ni anticipates the subject matter of instant claims 1, 5-9, 11-12, and 16.
Claims 1, 5-9, 11-12, and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ni, US 9987223 having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063.
Claims 1, 6-9, and 11-18, have a filing date of 06/22/2015.
Claims 5, 15, 19, 20, and 21 have a priority date of 05/27/2016.
Ni teaches and claims a method for inducing regression of a pterygium from the central cornea of an affected eye without surgically excising the pterygium, comprising administering to the affected eye of a subject in need of such treatment a therapeutically effective amount of a kinase inhibitor (Ni, e.g., claim 1). The kinase inhibitor is a tyrosine kinase inhibitor, e.g., VEGFR (Ni, e.g., claim 2). Inhibitors include nintedanib (Ni, e.g., claim 3). The composition is a topical ocular formulation which is administered topically to the affected eye (Ni, e.g., claim 6 and ‘063, claim 5 and claim 7). The method further comprises identifying a patient having pterygia (Ni, e.g., claims 8 and 16 and ‘063, claim 1 inducing regression pterygium regression from visual axis). The topical formulation may be a solution or suspension or emulsion (Ni, e.g., ¶ spanning c1-c2 and ‘063, e.g., claim 10). Formulations include carrier or excipients (Ni, e.g., c3:14-32 and ‘063, pg. 8, ¶ 3). Administering nintedanib as directed in Ni necessarily results in reducing hyperemia (Ni, ‘063 e.g., Abstract and claim 1), and inhibiting, reducing, or regressing neovascularization in an eye effected with pterygium (Ni, e.g., c5:¶ 1, c20:29-56, and ‘063, e.g., Fig. 2, fibrovascular growth).
Ni anticipates the subject matter of instant claims 1, 5-9, 11-12, and 16.
Claims 1, 5-9, 11-12, and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ni, US 10149820 (Ni ‘820) having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063.
Claims 1, 6-9, and 11-18, have a filing date of 06/22/2015.
Claims 5, 15, 19, 20, and 21 have a priority date of 05/27/2016.
Ni ‘820 teaches a method for reducing hyperemia or symptoms thereof in pterygium in an affected eye of a subject in need of such treatment, without surgically excising a pterygium, comprising administering to the affected eye of the subject a therapeutically effective amount of a multikinase inhibitor, wherein the multikinase inhibitor is nintedanib and the nintedanib is administered to the affected eye in the form of a topical ocular formulation and is administered topically to the affected eye (Ni ‘820, e.g., claim 4, ‘063 e.g., Abstract and claim 1), and inhibiting, reducing, or regressing neovascularization in an eye effected with pterygium (Ni ‘820, e.g., claim 11, and example 2, and ‘063, e.g., Fig. 2, fibrovascular growth). Ni ‘820 teaches a solution or suspension (Ni ‘820, e.g., claim 5 and ‘063, e.g., ‘063, e.g., claim 10). The method further comprises identifying a patient having pterygia (Ni ‘820, e.g., claim 9 and ‘063, claim 1 inducing regression pterygium regression from visual axis). Formulations include carrier or excipients (Ni ‘820, e.g., claim 6 and ‘063, pg. 8, ¶ 3).
Ni ‘820 anticipates the subject matter of instant claims 1, 5-9, 11-12, and 16.
Response to Arguments
Applicant's arguments filed 11/17/2025 have been fully considered but they are not persuasive.
With respect to the anticipation rejections based on Ni (US 2017/0172915) and Ni (US 9,987,223), and Ni (US 10149820), collectively referred to here as the Ni references:
Applicant has argued that to extent the rejections apply to the remaining claims as currently amended, Applicant respectfully traverses the rejections because the Ni references do not qualify as prior art with respect to the current claims.
Applicant and the declaration filed 08/13/2025 have previously argued that although references each claim the benefit of provisional application US 62/172,063 filed June 6, 2015, these cited references are not entitled to the effective filing date of the '063 provisional because the provisional lacks enablement and written description under 35 U.S.C. § 112 of the invention claimed by the cited Ni references. Applicant and the declaration argue the '063 provisional establishes that the inventors of the Ni references were not in possession of the invention as of its June 6, 2015 filing date. Applicant and the declaration argue the '063 provisional describes nothing more than a "treatment hypothesis" and recites only test results acknowledged by the provisional as being already published by others. See '063 Provisional, pp. 6-7.
Applicant and the declaration argue the examiner dismissed the above argument stating that the issue of written description and enablement regarding the '063 provisional with respect to administering nintedanib in an eye affected with pterygium in a subject in need of treatment was considered, and decided, by the PTAB in the decision entered Feb 15, 2022. Applicant argues the Board's decision was erroneous for the reasons Applicant briefed to the Federal Court in that appeal. Applicant's appeal briefing to the Federal Circuit and the Federal Circuit's decision were included as Appendix C and D, submitted to the USPTO on January 28, 2025 with the previous response. It is noted that the Federal Circuit dismissed Applicant's appeal based on procedural grounds and without reviewing the merits of the Board's decision in Allgenesis Biotherapeutics Inc. v. Cloudbreak Therapeutics, LLC, 85 F.4th 1377 (Fed. Cir. 2023). Applicant contends that that Board's decision is incorrect and the Ni' 915 and Ni '225 references are not entitled to a filing date of June 6, 2015, and do not qualify as prior art as further discussed below.
This argument is unpersuasive.
Applicant has previously argued before this examiner, the PTAB, and the Federal Circuit that the disclosure of the ‘063 provisional application does not entitle the family of applications including the US 20170172915 A1 application a priority date of June 6, 2015 because the ‘063 provisional application does not provide written description or enablement for the subject matter disclosed. In the IPR regarding US Pat 10149820 which issued from US 15991698, which is a continuation of 15375820 published as US 20170172915 A1, Applicant argued the ‘063 provisional application lacks the support required under 35 USC 112—neither written description nor enablement—to entitle the 06/06/2015 filing date. See IPR 2020-01438 which was filed on this record and referenced in the remarks dated 01/28/2025, e.g., pg. 9 of 16 (file pg. 5). See Other Reference-Patent/Application Search Documents filed 01/28/2025 labeled in the file as IPR 2020-01438. The issue of written description and enablement regarding the ‘063 provisional with respect to administering nintedanib in an eye affected with pterygium in a subject in need of treatment was considered, and decided, by the PTAB in the decision entered Feb 15, 2022 which challenged the patentability of the invention claimed by the 10149820 patent. On pg. 58 of the decision, the board determined that the ‘063 application provides sufficient written descriptive support and enablement for the treatment of hyperemia or symptoms thereof in a patient having pterygium using the multikinase inhibitor nintedanib. See Final Written Decision dated 15 Feb, 2022 at page 58:
PNG
media_image1.png
468
628
media_image1.png
Greyscale
The issue of Written description is addressed in detail at pp. 26-36 of the ‘438 IPR. The issue of Enablement is addressed in detail, including a full treatment of the relevant Wands factors, at pp. 36-52 of the ‘438 IPR. The rationale is reiterated here without reproduction.
The PTAB considered the “treatment hypothesis” argument at pg. 27. The PTAB considered the “many growth factors” argument, e.g., ‘438 IPR, pg. 29. The PTAB considered the “hypothesized several strategies” argument, e.g., ‘438 IPR, pg. 27. The PTAB considered the argument regarding nintedanib efficacy for treating pterygium at ‘438 IPR, pg. 28 and the predictability of efficacy for treating pterygium, e.g., ‘438 IPR, pg. 43. The PTAB considered the different structures, different targets, and different mechanisms of action argument (‘438 IPR, e.g., pg. 28). The PTAB considered the argument that treatment of pterygium cannot be predicted (‘438 IPR, e.g., pg. 43). The PTAB considered the ability to predict the efficacy of the compounds listed in the ‘063 application (‘438 IPR, e.g., pg. 50). The PTAB considered unexpected results in the context of enablement (‘438 IPR, e.g., pg. 37). The PTAB considered the issue of formulating nintedanib for topical application, including the pKa properties of nintedanib (‘438 IPR, e.g., pg. 48-52). See also ‘438 IPR, pp. 30-31 wherein it was found that sunitinib and nintedanib have similar LogP, cLogP, and pKa values.
The PTAB determined that claims 4-5 of the’820 patent are entitled to the filing date of June 6 2015 which is the filing date of the ‘063 provisional application. See IPR 2020-01438, e.g., pg. 59 section E. Claims 4-5 are directed to a method for reducing hyperemia or a symptom thereof in pterygium in an affected eye of a subject in need of such treatment, without surgically excising a pterygium, comprising administering to the affected eye of the subject a therapeutically effective amount of a multikinase inhibitor, wherein the multikinase inhibitor is administered in the form of a topical ocular formulation, e.g., a solution or suspension, and wherein the multikinase inhibitor is nintedanib. See claims 1-5 listed in IPR 2020-01438, e.g., pp. 3-4.
While Applicant alleges that Davis, Ni’ 915 and Ni ‘225 and Roskoski indicate nintedanib and sunitinib have several non-overlapping targets, it was found that there is still significant overlap between the kinase targets for sunitinib...and nintedanib (‘438 IPR, e.g., pg. 47) which led to the conclusion that nintedanib was expected to function similarly to sorafenib when topically applied as of the filing date of the ‘063 provisional application (‘438 IPR, e.g., pp. 47-48). Davis was considered at trial (‘438 IPR, e.g., pg. 23-24 and 50).
The declaration reiterates these arguments and has been given full consideration.
The predictability of the art for treating pterygium with kinase inhibitors was considered in the ‘438 IPR, e.g., pp. 43-44.
The physiochemical properties of multikinase inhibitors are addressed in the ‘438 IPR, e.g., pp. 30-34 and 46-49.
The “unexpected” statements are addressed in the ‘438 IPR, e.g., pg. 75.
Perez-Santonja et al. is discussed in the IPR wherein it is noted that Perez-Santonja also teaches multikinase inhibitors formulated as a topical composition for eyes to treat neovascularization (‘438 IPR, e.g., pp. 22-23 and 25). It was noted in the IPR decision that prior art on this record showed that monoclonal antibody multikinase inhibitor and small molecule multikinase inhibitors were each able to be formulated for topical administration to eyes to inhibit corneal neovascularization before the effective filing date of the ‘063 priority document (‘438 IPR, e.g., pg. 41 and 47). The prior art shows that topical formulation challenges had been surmounted for structurally diverse mulitkinase inhibitors including monoclonal antibodies which is a protein/peptide and small molecule drugs. Therefore, the skilled artisan was expected to be able to topically formulate other small molecule inhibitors like nintedanib to effectively treat corneal vascularization and therefore pterygium before the filing date of the of the ‘063 application.
The quantity of experimentation required to determine a formulation and effectiveness for the kinase inhibitors in the ‘063 provisional is addressed in the IPR, e.g., pp. 45-52
Accordingly, the Ni’ 915 and Ni ‘225 and Ni ‘820 references are supported by provisional application US 62172063, found to have a filing date of 06/06/2015, and therefore qualify as prior art under 35 U.S.C. 102(a)(2).
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 of this title, 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.
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, 5-9, and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ni, US 20170172915 A1, also published as WO 2016200688 A1, and having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063 in view of Bottger, US 20140235678.
The teachings of Ni ‘915 enumerated above apply here.
Ni (‘063) teaches the composition as a topical suspension (Ni, e.g., 0010; 063, claim 10 and 17).
Ni (‘063) teaches the composition including a pharmaceutically acceptable excipient (Ni, e.g., 0010; ‘063, pg. 5, ¶3).
Ni does not teach wherein the excipient comprises a surfactant or amounts claimed.
Bottger teaches topical ophthalmological pharmaceutical compositions containing sorafenib, and the preparation and use thereof (Bottger, e.g., Abstract, Example 3, claims 1-12). Bottger teaches the suspension including solid drug in the form of particulates having a mean size in the range of from 0.5 to 10 microns (Bottger, e.g., 0018). Bottger teaches aqueous suspensions comprising a kinase inhibitor similar to nintedanib, i.e., sorafenib wherein the suspension includes the drug in the form of particulates
Bottger teaches the aqueous suspension including additional excipients, e.g., hydroxypropylmethylcellulose (Bottger, e.g., Example 3), where the HMPC may be present in an amount ranging from 1-5 % by weight (Bottger, e.g., 0037).
Bottger teaches the composition comprising a surfactant, e.g., polysorbate 80 (i.e., polyoxyethylene sorbitan ester) in amounts ranging from 0.1 to 7% by weight (Bottger, e.g., 0038). Alternative surfactants include poloxamers or tyloxapol (Bottger, e.g., 0028).
Bottger teaches the composition having a pH ranging from 4-9 (Bottger, e.g., 0032).
Bottger suggests the compositions as effective for treating pterygium (Bottger, e.g., 0057, claim 10 and 12).
Bottger teaches the compositions surprising provides by topical administrations a sufficient amount of active agent into the eye which is effective for treating ophthalmological disorders in addition to sufficient stability without any meaningful degradation of the active agent (Bottger, e.g., 0008).
Based on the combined teachings of Ni and Bottger, the skilled artisan would have been motivated to formulate nintedanib in a topical ocular composition, e.g., an aqueous suspension which provides a sufficient amount of active agent into the eye for treatment of an eye affected with pterygium and which are sufficiently stable to minimize degradation of the active agent as suggested with respect to the similar tyrosine kinase inhibitor sorafenib for treating pterygium in Bottger. This may be viewed as applying a known technique, i.e., formulating a similar kinase inhibitor in an aqueous suspension comprising additional excipients, to improve a similar method as understood from Ni in the same way.
It would have been obvious before the effective filing date of the presently claimed invention to improve suspensions and methods understood from Ni according to the teachings of Bottger with a reasonable expectation of success. Both Ni and Bottger relate to compositions comprising kinase inhibitors and methods of use for treating the eye, and both references suggest compositions and methods for treating pterygium. Bottger provides a teaching which fills the gaps in the teachings of Ni with respect to formulating active agents for administration to the eye, e.g., where the active agent is formulated as an aqueous suspension which would have prompted one skilled in the art to make the modifications required to practice a method within the scope of the claimed invention. The skilled artisan would have been motivated to formulate a nintedanib suspension as employed in the method of Ni as an aqueous suspension comprising further excipients, e.g., surfactants and HPMC, based on the teaching in Bottger expressly suggesting this modification specifically for formulating similar kinase inhibitors to improve their stability and reduce the incidence of degradation in the same way in the context of treating pterygium. The skilled artisan, starting from Ni, would have been motivated to look to the teachings of the prior art like Bottger for guidance on how to formulate kinase inhibitors, e.g., nintedanib, in a topical aqueous suspension composition which provides a sufficient amount of active agent into the eye for treatment and which are sufficiently stable to minimize degradation of the active agent.
Because Ni teaches treating pterygium by administering a suspension formulation of nintedanib, and because Ni suggests nintedanib and sorafenib as equivalent active agents for treating pterygium, and because Bottger teaches formulating the equivalent kinase inhibitor sorafenib in an aqueous suspension with surfactants present in the topical ocular formulation in a range overlapping with the claimed range for treating pterygium to achieve a formulation effective for providing a sufficient amount of active agent into the eye for treatment and minimize degradation, the skilled artisan would have had a reasonable expectation of successfully practicing a method of treating pterygium by administering a composition comprising nintedanib in an aqueous suspension with a surfactant present in the composition in an amount ranging from, e.g., 0.1 to 7%.
Applicable to claim 20:
Ni (‘063) teaches the composition as a topical suspension (Ni, e.g., 0010; 063, claim 10 and 17).
Ni ‘915 teaches a gel or ointment (Ni ‘915, e.g., 0009 and claim 53). However, Ni ‘063 does not support a gel or ointment.
Nevertheless, before the effective filing date of the presently claimed invention, gels and ointments were known alternatives for solution or suspension topical formulations as evident from Bottger. Bottger teaches gels and ointments and drops as topical alternatives for suspensions (Bottger, e.g., 0023).
It would have been obvious before the effective filing date of the presently claimed invention to practice a method for treating pterygium by administering as understood from Ni by administering the topical formulation in the form of a gel or ointment or drop as suggested by Bottger with a reasonable expectation of success. The skilled artisan would have seen this modification as a substitution of one known topical formulation for another where each were known and suggested by the prior art as effective for topically administering kinase inhibitors to the eye. The skilled artisan would have had a reasonable expectation of success since the prior art of record suggests each of the known topical formulations were expected to be effective to deliver therapeutically effective amounts of the kinase inhibitors to the eye.
Accordingly, the subject matter of claims 1, 5-9, and 11-20 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11/17/2025 have been fully considered but they are not persuasive.
Applicant argues that Ni '915 is not entitled to the priority date of June 6, 2015, and is not prior art to the claimed invention. As such, the obviousness rejections based on Ni '915 and Bottger should be withdrawn.
This argument is unpersuasive because Applicant’s arguments that Ni '915 is not entitled to the priority date of June 6, 2015 are unpersuasive as discussed above under the 102 rejections.
Claims 1, 5-9, and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ni, US 9987223 having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063 in view of Bottger, US 20140235678.
The teachings of Ni ‘223 enumerated above apply here
Ni (‘063) teaches the composition as a topical suspension (Ni, e.g., 0010; 063, claim 10 and 17).
Ni (‘063) teaches the composition including a pharmaceutically acceptable excipient (Ni, e.g., 0010; ‘063, pg. 5, ¶3).
Ni does not teach the wherein the excipient comprises a surfactant or amounts claimed.
Bottger teaches topical ophthalmological pharmaceutical compositions containing sorafenib, and the preparation and use thereof (Bottger, e.g., Abstract, Example 3, claims 1-12). Bottger teaches the suspension including solid drug in the form of particulates having a mean size in the range of from 0.5 to 10 microns (Bottger, e.g., 0018). Bottger teaches aqueous suspensions comprising a kinase inhibitor similar to nintedanib, i.e., sorafenib wherein the suspension includes the drug in the form of particulates
Bottger teaches the aqueous suspension including additional excipients, e.g., hydroxypropylmethylcellulose (Bottger, e.g., Example 3), where the HMPC may be present in an amount ranging from 1-5 % by weight (Bottger, e.g., 0037).
Bottger teaches the composition comprising a surfactant, e.g., polysorbate 80 (i.e., polyoxyethylene sorbitan ester) in amounts ranging from 0.1 to 7% by weight (Bottger, e.g., 0038). Alternative surfactants include poloxamers or tyloxapol (Bottger, e.g., 0028).
Bottger teaches the composition having a pH ranging from 4-9 (Bottger, e.g., 0032).
Bottger suggests the compositions effective for treating pterygium (Bottger, e.g., 0057, claim 10 and 12).
Bottger teaches the compositions surprising provides by topical administrations a sufficient amount of active agent into the eye which is effective for treating ophthalmological disorders in addition to sufficient stability without any meaningful degradation of the active agent (Bottger, e.g., 0008).
Based on the combined teachings of Ni and Bottger, the skilled artisan would have been motivated to formulate nintedanib in a topical ocular composition, e.g., an aqueous suspension which provides a sufficient amount of active agent into the eye for treatment of an eye affected with pterygium and which are sufficiently stable to minimize degradation of the active agent as suggested with respect to the similar tyrosine kinase inhibitor sorafenib for treating pterygium in Bottger. This may be viewed as applying a known technique, i.e., formulating a similar kinase inhibitor in an aqueous suspension comprising additional excipients, to improve a similar method as understood from Ni in the same way.
It would have been obvious before the effective filing date of the presently claimed invention to improve suspensions and methods understood from Ni according to the teachings of Bottger with a reasonable expectation of success. Both Ni and Bottger relate to compositions comprising kinase inhibitors and methods of use for treating the eye, and both references suggest compositions and methods for treating pterygium. Bottger provides a teaching which fills the gaps in the teachings of Ni with respect to formulating active agents for administration to the eye, e.g., where the active agent is formulated as an aqueous suspension which would have prompted one skilled in the art to make the modifications required to practice a method within the scope of the claimed invention. The skilled artisan would have been motivated to formulate a nintedanib suspension as employed in the method of Ni as an aqueous suspension comprising further excipients, e.g., surfactants and HPMC, based on the teaching in Bottger expressly suggesting this modification specifically for formulating similar kinase inhibitors to improve their stability and reduce the incidence of degradation in the same way in the context of treating pterygium. The skilled artisan, starting from Ni, would have been motivated to look to the teachings of the prior art like Bottger for guidance on how to formulate kinase inhibitors, e.g., nintedanib, in a topical aqueous suspension composition which provides a sufficient amount of active agent into the eye for treatment and which are sufficiently stable to minimize degradation of the active agent.
Because Ni teaches treating pterygium by administering a suspension formulation of nintedanib, and because Ni suggests nintedanib and sorafenib as equivalent active agents for treating pterygium, and because Bottger teaches formulating the equivalent kinase inhibitor sorafenib in an aqueous suspension with surfactants present in the topical ocular formulation in a range overlapping with the claimed range for treating pterygium to achieve a formulation effective for providing a sufficient amount of active agent into the eye for treatment and minimize degradation, the skilled artisan would have had a reasonable expectation of successfully practicing a method of treating pterygium by administering a composition comprising nintedanib in an aqueous suspension with a surfactant present in the composition in an amount ranging from, e.g., 0.1 to 7%.
Applicable to claim 20:
Ni (‘063) teaches the composition as a topical suspension (Ni, e.g., 0010; 063, claim 10 and 17).
Ni ‘915 teaches a gel or ointment (Ni ‘915, e.g., 0009 and claim 53). However, Ni ‘063 does not support a gel or ointment.
Nevertheless, before the effective filing date of the presently claimed invention, gels and ointments were known alternatives for solution or suspension topical formulations as evident from Bottger. Bottger teaches gels and ointments and drops as topical alternatives for suspensions (Bottger, e.g., 0023).
It would have been obvious before the effective filing date of the presently claimed invention to practice a method for treating pterygium by administering as understood from Ni by administering the topical formulation in the form of a gel or ointment or drop as suggested by Bottger with a reasonable expectation of success. The skilled artisan would have seen this modification as a substitution of one known topical formulation for another where each were known and suggested by the prior art as effective for topically administering kinase inhibitors to the eye. The skilled artisan would have had a reasonable expectation of success since the prior art of record suggests each of the known topical formulations were expected to be effective to deliver therapeutically effective amounts of the kinase inhibitors to the eye.
Accordingly, the subject matter of claims 1, 5-9 and 11-20 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11/17/2025 have been fully considered but they are not persuasive.
Applicant and the declaration argue that Ni '223 is not entitled to the priority date of June 6, 2015, and is not prior art to the claimed invention. As such the obviousness rejections based on Ni '223 and Bottger should be withdrawn.
This argument is unpersuasive because Applicant’s arguments that Ni '223 is not entitled to the priority date of June 6, 2015 are unpersuasive as discussed above under the 102 rejections.
Claims 1, 5-9, and 11-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ni, US 10149820 (Ni ‘820) having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063 (Ni ‘820) in view of Bottger, US 20140235678.
The teachings of Ni ‘820 enumerated above apply here
Ni (‘063) teaches the composition as a topical suspension (Ni, e.g., 0010; 063, claim 10 and 17).
Ni (‘063) teaches the composition including a pharmaceutically acceptable excipient (Ni, e.g., 0010; ‘063, pg. 5, ¶3).
Ni does not teach wherein the excipient comprises a surfactant or amounts claimed.
Bottger teaches topical ophthalmological pharmaceutical compositions containing sorafenib, and the preparation and use thereof (Bottger, e.g., Abstract, Example 3, claims 1-12). Bottger teaches the suspension including solid drug in the form of particulates having a mean size in the range of from 0.5 to 10 microns (Bottger, e.g., 0018). Bottger teaches aqueous suspensions comprising a kinase inhibitor similar to nintedanib, i.e., sorafenib wherein the suspension includes the drug in the form of particulates
Bottger teaches the aqueous suspension including additional excipients, e.g., hydroxypropylmethylcellulose (Bottger, e.g., Example 3), where the HMPC may be present in an amount ranging from 1-5 % by weight (Bottger, e.g., 0037).
Bottger teaches the composition comprising a surfactant, e.g., polysorbate 80 (i.e., polyoxyethylene sorbitan ester) in amounts ranging from 0.1 to 7% by weight (Bottger, e.g., 0038). Alternative surfactants include poloxamers or tyloxapol (Bottger, e.g., 0028).
Bottger teaches the composition having a pH ranging from 4-9 (Bottger, e.g., 0032).
Bottger suggests the compositions effective for treating pterygium (Bottger, e.g., 0057, claim 10 and 12).
Bottger teaches the compositions surprising provides by topical administrations a sufficient amount of active agent into the eye which is effective for treating ophthalmological disorders in addition to sufficient stability without any meaningful degradation of the active agent (Bottger, e.g., 0008).
Based on the combined teachings of Ni and Bottger, the skilled artisan would have been motivated to formulate nintedanib in a topical ocular composition, e.g., an aqueous suspension which provides a sufficient amount of active agent into the eye for treatment of an eye affected with pterygium and which are sufficiently stable to minimize degradation of the active agent as suggested with respect to the similar tyrosine kinase inhibitor sorafenib for treating pterygium in Bottger. This may be viewed as applying a known technique, i.e., formulating a similar kinase inhibitor in an aqueous suspension comprising additional excipients, to improve a similar method as understood from Ni in the same way.
It would have been obvious before the effective filing date of the presently claimed invention to improve topical suspensions useful in methods of treating subjects having pterygia understood from Ni according to the teachings of Bottger with a reasonable expectation of success. Both Ni and Bottger relate to compositions comprising kinase inhibitors and methods of use for treating the eye, and both references suggest compositions and methods for treating pterygium. Bottger provides a teaching which fills the gaps in the teachings of Ni with respect to formulating active agents for topical administration to the eye, such as an aqueous suspension, which would have prompted one skilled in the art to make the modifications required to practice a method within the scope of the claimed invention. The skilled artisan would have been motivated to formulate a nintedanib suspension as employed in the method of Ni as an aqueous suspension comprising further excipients, e.g., surfactants and HPMC, based on the teaching in Bottger expressly suggesting this modification specifically for formulating similar kinase inhibitors to improve their stability and reduce the incidence of degradation in the same way in the context of treating pterygium. The skilled artisan, starting from Ni, would have been motivated to look to the teachings of the prior art like Bottger for guidance on how to formulate kinase inhibitors, e.g., nintedanib, in a topical aqueous suspension composition which provides a sufficient amount of active agent into the eye for treatment and which are sufficiently stable to minimize degradation of the active agent with a reasonable expectation of success.
Because Ni teaches treating pterygium by administering a suspension formulation of nintedanib, and because Ni suggests nintedanib and sorafenib as equivalent active agents for treating pterygium, and because Bottger teaches formulating the equivalent kinase inhibitor sorafenib in an aqueous suspension with surfactants present in the topical ocular formulation in a range overlapping with the claimed range for treating pterygium to achieve a formulation effective for providing a sufficient amount of active agent into the eye for treatment and minimize degradation, the skilled artisan would have had a reasonable expectation of successfully practicing a method of treating pterygium by administering a composition comprising nintedanib in an aqueous suspension with a surfactant present in the composition in an amount ranging from, e.g., 0.1 to 7%.
Applicable to claim 20:
Ni (‘063) teaches the composition as a topical suspension (Ni, e.g., 0010; 063, claim 10 and 17).
Ni ‘915 teaches a gel or ointment (Ni ‘915, e.g., 0009 and claim 53). However, Ni ‘063 does not support a gel or ointment.
Nevertheless, before the effective filing date of the presently claimed invention, gels and ointments were known alternatives for solution or suspension topical formulations as evident from Bottger. Bottger teaches gels and ointments and drops as topical alternatives for suspensions (Bottger, e.g., 0023).
It would have been obvious before the effective filing date of the presently claimed invention to practice a method for treating pterygium by administering as understood from Ni by administering the topical formulation in the form of a gel or ointment or drop as suggested by Bottger with a reasonable expectation of success. The skilled artisan would have seen this modification as a substitution of one known topical formulation for another where each were known and suggested by the prior art as effective for topically administering kinase inhibitors to the eye. The skilled artisan would have had a reasonable expectation of success since the prior art of record suggests each of the known topical formulations were expected to be effective to deliver therapeutically effective amounts of the kinase inhibitors to the eye.
Accordingly, the subject matter of claims 1, 5-9, and 11-20 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Ni, US 10149820 (Ni ‘820) having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063 (Ni ‘820) in view of Bottger, US 20140235678 as applied to claims 1 and 5-9, and 11-20 above and further in view of Sheardown, US 10611908 which has an effective filing date of Sep 1, 2015 as evidenced by provisional application US 62212784.
Claim 21 has an effective filing date of 05/27/2016 because claim 21 contains limitations which are not supported by the ‘180 provisional. See Priority section above.
Sheardown, having an effective filing date of 09/01/2015, qualifies as prior art under 102(a)(2) for claim 21.
The teachings of Ni and Bottger teach methods according to claims 1 and 9, wherein the formulation is topically administered as a suspension as enumerated above.
The combined teachings of Ni and Bottger do not expressly teach wherein the suspension contains liposomes or micelles.
However, topical formulations containing micelles were known formulations for administering drugs topically to the eye as evident from Sheardown, entire document, e.g., claims. Sheardown teaches micelles loaded with an ophthalmic drug (Sheardown, e.g., claim 14) for topical administration to the eye (Sheardown, e.g., claim 18 and 19-23). Sheardown teaches micelles formulated in suspensions for ophthalmic delivery (Sheardown, e.g., c12:15-42). Sheardown teaches micelles offer mucoadhesive delivery which may be effective to improve bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect (Sheardown, entire document, e.g., c1:50-64, c7:15-35, and c14:5-23).
It would have been obvious before the effective filing date of the presently claimed invention to modify topical formulations of nintedanib for use in methods of treating subjects having pterygium as set forth in the combined teachings of Ni and Bottger by including micellar nintedanib to improve delivery in the same way suggested by Sheardown with a reasonable expectation of success. The skilled artisan would have been motivated to formulate nintedanib in a micellar formulation for improved bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect in the same way suggested by Sheardown. The skilled artisan would have had a reasonable expectation of success since Sheardown teaches this technique for topically applied drugs such as ophthalmic drugs, including drugs which inhibit VEGF.
Accordingly, the subject matter of claim 21 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Ni, US 9987223 having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063 in view of Bottger, US 20140235678 as applied to claims 1, 5-9, and 11-20 above, and further in view of Sheardown, US 10611908 which has an effective filing date of Sep 1, 2015 as evidenced by provisional application US 62212784.
Claim 21 has an effective filing date of 05/27/2016 because claim 21 contains limitations which are not supported by the ‘180 provisional. See Priority section above.
Sheardown, having an effective filing date of 09/01/2015, qualifies as prior art under 102(a)(2) for claim 21.
The teachings of Ni and Bottger teach methods according to claims 1 and 9, wherein the formulation is topically administered as a suspension as enumerated above.
The combined teachings of Ni and Bottger do not expressly teach wherein the suspension contains liposomes or micelles.
However, topical formulations containing micelles were known formulations for administering drugs topically to the eye as evident from Sheardown, entire document, e.g., claims. Sheardown teaches micelles loaded with an ophthalmic drug (Sheardown, e.g., claim 14) for topical administration to the eye (Sheardown, e.g., claim 18 and 19-23). Sheardown teaches micelles formulated in suspensions for ophthalmic delivery (Sheardown, e.g., c12:15-42). Sheardown teaches micelles offer mucoadhesive delivery which may be effective to improve bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect (Sheardown, entire document, e.g., c1:50-64, c7:15-35, and c14:5-23).
It would have been obvious before the effective filing date of the presently claimed invention to modify topical formulations of nintedanib for use in methods of treating subjects having pterygium as set forth in the combined teachings of Ni and Bottger by including micellar nintedanib to improve delivery in the same way suggested by Sheardown with a reasonable expectation of success. The skilled artisan would have been motivated to formulate nintedanib in a micellar formulation for improved bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect in the same way suggested by Sheardown. The skilled artisan would have had a reasonable expectation of success since Sheardown teaches this technique for topically applied drugs such as ophthalmic drugs, including drugs which inhibit VEGF.
Accordingly, the subject matter of claim 21 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Ni, US 20170172915 A1, also published as WO 2016200688 A1, and having an effective filing date of June 6, 2015 corresponding to provisional application US 62172063 in view of Bottger, US 20140235678 as applied to claims 1, 5-9, and 11-20 above, and further in view of Sheardown, US 10611908 which has an effective filing date of Sep 1, 2015 as evidenced by provisional application US 62212784.
Claim 21 has an effective filing date of 05/27/2016 because claim 21 contains limitations which are not supported by the ‘180 provisional. See Priority section above.
Sheardown, having an effective filing date of 09/01/2015, qualifies as prior art under 102(a)(2) for claim 21.
The teachings of Ni and Bottger teach methods according to claims 1 and 9, wherein the formulation is topically administered as a suspension as enumerated above.
The combined teachings of Ni and Bottger do not expressly teach wherein the suspension contains liposomes or micelles.
However, topical formulations containing micelles were known formulations for administering drugs topically to the eye as evident from Sheardown, entire document, e.g., claims. Sheardown teaches micelles loaded with an ophthalmic drug (Sheardown, e.g., claim 14) for topical administration to the eye (Sheardown, e.g., claim 18 and 19-23). Sheardown teaches micelles formulated in suspensions for ophthalmic delivery (Sheardown, e.g., c12:15-42). Sheardown teaches micelles offer mucoadhesive delivery which may be effective to improve bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect (Sheardown, entire document, e.g., c1:50-64, c7:15-35, and c14:5-23).
It would have been obvious before the effective filing date of the presently claimed invention to modify topical formulations of nintedanib for use in methods of treating subjects having pterygium as set forth in the combined teachings of Ni and Bottger by including micellar nintedanib to improve delivery in the same way suggested by Sheardown with a reasonable expectation of success. The skilled artisan would have been motivated to formulate nintedanib in a micellar formulation for improved bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect in the same way suggested by Sheardown. The skilled artisan would have had a reasonable expectation of success since Sheardown teaches this technique for topically applied drugs such as ophthalmic drugs, including drugs which inhibit VEGF.
Accordingly, the subject matter of claim 21 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim(s) 1 and 5-9, and 11-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-15 of US 11369600 B2 in view of Boral, US 20150166521 A1 also published as US 9266869 B2 and Huu, Journal of Controlled Release, 200, 2015 and Sheardown, US 10611908 which has an effective filing date of Sep 1, 2015 as evidenced by provisional application US 62212784.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of the reference patent teach an aqueous suspension comprising a therapeutically effective amount of particles comprising nintedanib, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient comprising about 0.01% to 0.3% (w/v) of tyloxapol. The claims of the reference patent teach administering the composition to the eye of a subject. Tyloxapol is a surfactant. See specification, e.g., ¶ 0012.
The claims of the reference application teach administering the composition to a subject to treat a surface ocular disease (claims 9-15), but do not expressly teach the surface ocular disease is pterygium or hyperemia associated with pterygium or neovascularization in an eye affected with pterygium. However, the teachings of Boral and Huu enumerated above cure this defect.
Huu teaches nintedanib is effective to treat neovascularization when administered to the eye by inhibiting VEGF and PDGF.
Boral teaches inhibitors of VEGF and PDGF are effective to treat pterygium when topically administered to the eye. See Boral, e.g., c3:5-13 including subjects having pterygia (Boral, e.g., c8:6-39).
It would have been prima facie obvious before the effective filing date of the presently claimed invention to practice a method comprising administering the composition claimed by the reference patent to subjects having pterygium, including subjects suffering from hyperemia associated with pterygium and neovascularization in an eye affected with pterygium as identified in the combined teachings of Boral and Huu with a reasonable expectation of success. The skilled artisan would have been motivated to administer nintedanib compositions comprising nintedanib as claimed in the reference patent to subjects suffering a surface ocular disease such as pterygium identified in Boral because nintedanib was a known VEGFR and PDGF inhibitor as evident from Huu, and because Boral teaches VEGFR and PDGF inhibitor containing compositions could be administered topically to subjects having neovascularization related ocular diseases such as pterygium to inhibit the unregulated tyrosine kinase signal transduction contributing to the severity of the neovascularization related ocular disease with a reasonable expectation of success.
Applicable to claim 21:
The combined teachings of the reference claims, Boral, and Huu do not expressly teach a suspension comprising liposomes or micelles.
However, topical formulations containing micelles were known formulations for administering drugs topically to the eye as evident from Sheardown, entire document, e.g., claims. Sheardown teaches micelles loaded with an ophthalmic drug (Sheardown, e.g., claim 14) for topical administration to the eye (Sheardown, e.g., claim 18 and 19-23). Sheardown teaches micelles formulated in suspensions for ophthalmic delivery (Sheardown, e.g., c12:15-42). Sheardown teaches micelles offer mucoadhesive delivery which may be effective to improve bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect (Sheardown, entire document, e.g., c1:50-64, c7:15-35, and c14:5-23).
It would have been obvious before the effective filing date of the presently claimed invention to modify topical formulations of nintedanib for use in methods of treating subjects having pterygium by including micellar nintedanib to improve delivery in the same way suggested by Sheardown with a reasonable expectation of success. The skilled artisan would have been motivated to formulate nintedanib in a micellar formulation for improved bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect in the same way suggested by Sheardown. The skilled artisan would have had a reasonable expectation of success since Sheardown teaches this technique for topically applied drugs such as ophthalmic drugs, including drugs which inhibit VEGF.
Accordingly, the subject matter of instant claims 1 and 5-9, and 11-21 would have been obvious to one skilled in the art, absent evidence to the contrary.
Claim(s) 1 and 5-9, and 11-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-19 of US 10154994 B2 in view of Sheardown, US 10611908 which has an effective filing date of Sep 1, 2015 as evidenced by provisional application US 62212784.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of the reference patent teach a method of treating pterygium or a symptom thereof in a subject in need thereof, the method comprising administering to an eye of the subject (administered topically) an aqueous suspension (topical ocular formulation) comprising (i) about 0.01% to 1.0% (w/v) nintedanib particles or particles of a pharmaceutically acceptable salt thereof, (ii) about 0.01% to 0.3% (w/v) tyloxapol, and (iii) about 0.1% to 1.0% (w/v) of a viscosity regulator.
The claims of the reference patent teach wherein the treatment comprises at least one of inducing regression of pterygium lesions from the corneal region; preventing growth of recurrent pterygium lesions; reducing a recurrence rate of pterygium lesions; reducing hyperemia; and inhibiting or reducing lesion neovascularization in the anterior segment of the eye.
Applicable to claim 21:
The reference claims, do not expressly teach a suspension comprising liposomes or micelles.
However, topical formulations containing micelles were known formulations for administering drugs topically to the eye as evident from Sheardown, entire document, e.g., claims. Sheardown teaches micelles loaded with an ophthalmic drug (Sheardown, e.g., claim 14) for topical administration to the eye (Sheardown, e.g., claim 18 and 19-23). Sheardown teaches micelles formulated in suspensions for ophthalmic delivery (Sheardown, e.g., c12:15-42). Sheardown teaches micelles offer mucoadhesive delivery which may be effective to improve bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect (Sheardown, entire document, e.g., c1:50-64, c7:15-35, and c14:5-23).
It would have been obvious before the effective filing date of the presently claimed invention to modify topical formulations of nintedanib for use in methods of treating subjects having pterygium as set forth in the reference claims by including micellar nintedanib to improve delivery in the same way suggested by Sheardown with a reasonable expectation of success. The skilled artisan would have been motivated to formulate nintedanib in a micellar formulation for improved bioavailability, reduce dosing frequency, and reduce the total amount of drug required to be delivered to achieve therapeutic effect in the same way suggested by Sheardown. The skilled artisan would have had a reasonable expectation of success since Sheardown teaches this technique for topically applied drugs such as ophthalmic drugs, including drugs which inhibit VEGF.
Accordingly, the subject matter of instant claims 1 and 5-9, and 11-21 would have been obvious to one skilled in the art, absent evidence to the contrary.
Response to Arguments
Applicant's arguments filed 11/17/2025 have been fully considered but they are not persuasive.
Applicant has argued that because the current application is pending and the allowable claim scope has yet to be determined, Applicant respectfully requests that the double patenting rejections be held in abeyance until such time as the presence of otherwise-allowable subject matter is indicated.
The double patenting rejections are maintained at this time.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A WAX can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/WILLIAM CRAIGO/Examiner, Art Unit 1615