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 .
Response to Amendments
Applicant’s amendments to the claims of July 16, 2026, in response to the Office Action of March 17, 2026, are acknowledged.
Response to Arguments
The § 112 rejection is withdrawn in view of the amendments to claim 4.
Applicant argues that the claims are not anticipated, in part, because Ferrari “is solely concerned with treating angiogenesis models of CNV.”
The examiner notes that what Ferrari was concerned with does not comprise the breadth of his teachings. Ferarri teaches administration of fosaprepitant to treat and prevent corneal neovascularization including in subjects with LSCD and CNV. See prior art claim 5, e.g. Further, CNV is taught to be a consequence of limbal stem cell deficiency. Thus, LSCD is a known risk factor for CNV and the claimed agent is taught to be administered to a subject because it can treat and prevent CNV.
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.”
Applicant argues that Ferrari does not disclose treating LSCD. Ferrari “merely describes one antiangiogenic effect of NK1 antagonists.”
The examiner notes that the prior art teaches treating a subject with topical fosaprepitant at claimed dosages. Further, Ferrari teaches treating and preventing CNV, which is caused by inflammatory disease and conditions, including GVHD, limbal stem cell deficiency (including idiopathic, traumatic, aniridia, autoimmune polyendocrinopathy), and others. See par. 6. Thus, preventing CNV certainly entails treatment of those at risk of CNV. Those at risk of CNV are particularly defined to include limbal stem cell deficient subjects. This is the claimed subject population. A POSA would immediately envisage administering the claimed agent to the claimed subject at the dosage and route taught by the prior art.
The prior art does not need to explain each mechanism of action by which treatment occurs. Prior art is not even required to recognize how treatment occurs. Enablement of prior art does not require this. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
In this case, the examiner is determining if the prior art anticipates and/or motivates the administration of the claimed agent to the claimed subject population. Further, even if the mode of action of that agent is not recognized by the prior art, the examiner is determining if there was a reasonable expectation of success that it was occurring. The standard is not whether or not there was a reasonable expectation of success that the prior art recognizes the manner in which treatment was occurring at the time.
Here, Ferrari teaches treating and preventing CNV in a subject. Ferrari notes a main risk factor for CNV is LSCD and, 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.” Farrari did not happen to indicate that CNV is a common sequela of LSCD among other claimed conditions. Instant claim 6 includes many of those conditions described by Ferrari as a common sequela to CNV. The point was to teach administration to that subject. Otherwise, “prevention” would have been open to all subjects and not those at risk or higher risk of CNV. 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%).
Applicant argues that Ferrari does not teach treating LSCD.
The examiner notes that Ferrari teaches administering the same agent to a subject with LSCD at a same dosage through a same route of administration. If this active step is take to prevent CNV or to treat LSCD is immaterial if the subject population is the same. That subject I sone that has LSCD because they are at a high risk of CNV and Ferrari explicitly teaches prevention of CNV. A POSA would immediately envisage administration to a subject with LSCD.
The examiner notes that Applicant has not indicated what specific limitation of the active steps claimed 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.
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 the same result will occur. 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.
Applicant argues that LSCD is not necessarily present in CNV.
The examiner notes that this is acknowledged. However, if they do have LSCD, Ferrari is teaching administration of the claimed agent to prevent CNV. If the LSCD has developed into CNV, Ferrari teaches administration to treat that subject as well.
With regard to the Double Patenting Rejection over U.S. Patent No. 9,782,397, the examiner notes that claims 1 and 3 teaches administration to fosaprepitant to a subject with CNV “that is caused by…limbal stem cell deficiency…”. A subject that has CNV caused by LSCD is interpreted to have CNV and LSCD. Thus, the claims include administration of the claimed agent to a claimed subject. This rejection is maintained.
This DP basis further supports the 102 and 103 rejections based, in part, on Ferrari teaching administration to a subject that is inclusive of one having LSCD and CNV.
Status of the Claims
Claims 1-9, 11-15, 21, 22, and 24-26 are pending and examined.
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, 21, 22, and 24-26 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, 21, 22, and 24-26 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, 21, 22, and 24-26 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, 21, 22, and 24-26 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
THIS ACTION IS MADE FINAL. 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 extension fee 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 JARED D. BARSKY whose telephone number is (571)-272-2795. The examiner can normally be reached on Monday through Friday from 8:30 to 5:30. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Amy L. 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
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