DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 5, 2026, has been entered.
Response to Arguments
Applicant argues that the prior art teaches that limbal stem cell deficiency (LSCD) may occur in a patient concurrently. Applicant argues that the prior art does not teach treating LSCD. Applicant argues that the examiner is making an inherency argument that if it is present, it may be treated. Applicant then provides arguments as to what inherency means and how it is improper.
The examiner does not mention nor does he argue inherency. He is well aware that probabilities cannot be used to established inherency. He is arguing that the teachings of Applicant’s own prior art establish enough that the burden is shifted to Applicant to explain how teaching administration of the claimed agent to the claimed subject population at the same dosage through the same route of administration does not provide at least a reasonable and predictable expectation of success. Applicant does not provide a distinction in the form of a claim limitation in their open-ended claims that distinguishes over the prior art. The examiner expounds on his rationale below.
The prior art teaches administering an NK-1 antagonist, including Fosaprepitant, to treat and prevent corneal neovascularization (CNV). This is not LSCD. However, Applicant’s prior art teaches CNV is a sequela (i.e., a condition which is the consequence of) limbal stem cell deficiency. This is important because it is clear that the prior art is teaching treatment and prevention. Thus, if CNV is known to be caused by LSCD, CNV is a risk factor for LSCD.
Moreover, as evidenced by Lim et al., Limbal Stem Cell Deficiency and Corneal Neovascularization,” July 2, 2009, pp.139-148: “One key feature of limbal stem cell deficiency is corneal neovascularization.”
Further, preventing CNV is motivated in a subject that has LSCD because CNV is caused by and/or a sequela to LSCD. Even further, dosages of active NK-1 antagonists can be administered from 1 mg/ml to 10 mg/ml (i.e., 0.1 to 1%).
The examiner notes that Applicant has not indicated what specific limitation is not taught by the prior art. Applicant has merely argued that different active therapeutic agents do not have an effect on stem cells. The examiner notes that a problem with this argument is that bevacizumab is not the claimed agent and the claimed agent is taught by the prior art for administration to a treat and prevent a subject with CNV, including in subjects with LSCD. CNV is a key feature of LSCD. If nothing more, a POSA would treat a known feature of LSCD with the claimed agent.
Overall, when a subject with LSCD or LSCD and CNV is administered Fosaprepitant to treat and/or prevent CNV as explicitly taught by Applicant’s own cited prior art, and is administered at an identical dosage through a same topical route of administration, there is a reasonable expectation of success that treatment will result. A subject that has CNV resulting from, and a key feature of, LSCD is a subject with stem cell deficiency. Further, a subject with LSCD that is administered Fosaprepitant to prevent CNV is also a subject with LSCD.
Status of the Claims
Claims 1-9, 11-15, and 21-26 are pending and examined.
Claim Rejections - 35 USC § 112
Claim 4 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 4 recites the broad recitation at least 0.1 mg/ml, and the claim also recites at least 10 mg/ml, at least 20 mg/ml, at least 30 mg/ml, etc., which are additional narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 1-9, 11-15, and 17-26 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Ferrari (US2014/0128395).
Ferrari teaches an NK-1 antagonist for treating and preventing corneal neovascularization (CNV). See Abstract. CNV is a sequela of several inflammatory diseases including limbal stem cell deficiency, graft-versus-host disease, and anirdia. See par. 6. Fosaprepitant is taught for use and was applied topically to corneas in Figures 1-3. Any form of topical application including eye drops are acceptable. See par. 335. Dosages of active NK-1 antagonists can be administered from 1 mg/ml to 10 mg/ml. See par. 366. Combination therapy with an additional agent can be administered to include NSAIDs, analgesics, anti-inflammatory agents, and others. See par. 376. Compositions can be administered once or several times daily. See par. 369. Treatment of alkali burns corneal perforation was reduced and corneal transparency increase in eyes treated with NK-1 antagonists. See par. 426.
As such, claims 1-9, 11-15, and 17-26 are anticipated by the prior art.
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 1-9, 11-15, and 17-26 are rejected under 35 U.S.C. 103 as being unpatentable over Ferrari (US2014/0128395), as evidenced by Lim et al., Limbal Stem Cell Deficiency and Corneal Neovascularization,” July 2, 2009, pp.139-148, in view of Gonzalez et al., “Limbal Stem Cells: Identity, Development Origin and Therapeutic Potential,” Wiley Interdiscip Rev Dev Biol. 2018 March; 7(2), and in view of Rama et al., “Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration,” The New England Journal of Medicine, June 23, 2010 (cited in IDS).
Ferrari teaches an NK-1 antagonist for treating and preventing corneal neovascularization (CNV). See Abstract. CNV is a sequela of several inflammatory diseases including limbal stem cell deficiency, graft-versus-host disease, and anirdia. See par. 6. Fosaprepitant is taught for use and was applied topically to corneas in Figures 1-3. Any form of topical application including eye drops are acceptable. See par. 335. Dosages of active NK-1 antagonists can be administered from 1 mg/ml to 10 mg/ml. See par. 366. Combination therapy with an additional agent can be administered to include NSAIDs, analgesics, anti-inflammatory agents, and others. See par. 376. Compositions can be administered once or several times daily. See par. 369. Treatment of alkali burns corneal perforation was reduced and corneal transparency increase in eyes treated with NK-1 antagonists. See par. 426. As evidenced by Lim, “One key feature of limbal stem cell deficiency is corneal neovascularization.”
Gonzalez explains that limbal stem cells (LSC) enable efficient corneal regeneration and repair. See p2, last par. “It has been widely accepted that bona fide LSC are defined by their ability to establish and maintain long-term restoration of the corneal epithelium, i.e. properties that are only demonstrated by transplantation experiments (29).” See p3, 2nd par. LSC are essential for corneal homeostasis and normal wound healing. The critical role of LSC was shown in knockout mice with impaired wound healing. See p6, 2nd par. “Loss or deficiency of LSC causes destruction of corneal homeostasis and results in abnormal wound healing.” See p7, 2nd par.
Similarly, Rama teaches that during corneal repair, LSC multiply and migrate to regenerate corneal epithelium. See p148, 3rd full par.
Thus, when the claimed agents are administered to treat and prevent CNV in a subject that has LSCD or LSCD and CNV, this would appear to treat the symptoms of what limbal stem cell deficiency causes, including corneal stem cell deficiency wound healing and homeostasis of the cornea. There is no basis to think that the same agent at a same route of administration to a same subject population would not provide some level of treatment.
It would have been prima facie obvious prior to a person of ordinary skill in the art prior to the filing of the instant application to combine the teachings of Ferrari, Gonzalez, and Rama to arrive at the claimed methods. One would be motivated to do so because the claimed agent at the claimed dosage is taught to be administered to the eye of a subject with CNV, GVHD, anirdia, and limbal stem cell deficiency, as well many other inflammatory eye conditions. Further, the Gonzalez and Rama teaches that corneal repair and wound healing will be inhibited without limbal stem cells, which the claimed method can treat. As such, treating limbal stem cell deficiency will regenerate the corneal epithelium as LSC are stem cells that do so. Even further, the administration of the same agent to a subject with a same condition will have a similar and/or substantially similar effect absent evidence to the contrary. Thus, there is a reasonable and predictable expectation of success in treatment the claimed conditions in view of the cited prior art. The claims are examined based on the claimed agent and the subject population. Absent evidence to the contrary, when a same agent at a same dose is administered to a same subject, a similar result will ensure.
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 1-9, 11-15, and 17-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,782,397. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘397 patent teaches administration of an NK-1 antagonist to treat CNV caused by limbal stem cell deficiency, aniridia, and others by topical application to the eye. As explained in the publication of the same, this would have an impact on corneal epithelial wound healing and a dosage administered would fall within those claimed. Further, Fosaprepitant is listed in claim 21 for topical application to the cornea.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628