DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Preliminary Amendments and Remarks, filed 7 November 2024, in the matter of Application N° 18/784,569. Said documents have been entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-16 have been canceled. Claims 17-31 have been added and are supported by the originally-filed disclosure.
No new matter has been added.
Thus, claims 17-31 now represent all claims currently under consideration.
Information Disclosure Statement
Four Information Disclosure Statements (IDS) filed 7 November 2024, 19 September 2025, 13 November 2025, and 13 February 2026 are acknowledged and have been considered.
Claim Rejections - 35 USC §112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 17 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.
Regarding claim 17, the phrase “such treatment” renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP §2173.05(d).
More specifically, the claim recites a method that comprises measuring a subject’s baseline total corneal fluorescein staining (CFS) score, administering a nonspecific treatment that is effective to reduce ocular surface damage, and then remeasuring the subject to determine a new score following the administration of “such treatment”.
The recitation of “such treatment” renders the claim indefinite because a specific effect of reducing the total CFS score by three or more units is attached to the generically recited treatment composition. It is therefore unclear what composition Applicants are reciting that achieves the recited effect.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the Examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicants are 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 17-20 and 25-31 are rejected under 35 U.S.C. 103 as being unpatentable over Stonecipher et al. (Clinical Ophthalmology; 2016) in view of Alex et al. (Invest Ophthalmol Vis Sci.; 2013) and further evidenced by Chun et al. (Am J Ophthalmol.; 2014).
The instantly claimed invention is directed to a method for assessing improvement of visual function in a subject suffering from dry eye disease, wherein the method comprises:
measuring the subject’s baseline total corneal fluorescein staining (CFS) score;
administering a treatment which is effective to reduce ocular surface damage in the subject; and
measuring the subject’s total CFS following the treatment.
The afflicted patients to be treated are further recited as having a baseline total CFS score ranging from 10-15, and a successful treatment will see a decrease in total CFS score by three or more units as the indicator of improved visual function.
The Stonecipher publication reports out on the efficacy of cyclosporine ophthalmic treatment for improving visual performance in patients diagnosed with having dry eye (see e.g., Abstract). Baseline (day-0) readings were taken for dry eye patients and included fluorescein corneal staining which is defined in the article as evaluating the central, inferior, and superior regions and their total (see Methods, paragraph bridging pp. 888-889). Figures IA and IB also depict baseline and 6-month for the worse eye and fellow treated eye, respectively.
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Figure 1A above depicts the baseline measurement (left columns) followed by the 6-month follow-up readings (right columns). The article discloses treating the patients with a 0.05% (w/v) cyclosporine ophthalmic emulsion (Restasis®) (see e.g., Abstract; Methods).
What the above evaluation appears to omit from its study is the inclusion of the temporal and nasal corneal regions as part of its “total” corneal fluorescein staining scoring. Such is considered to represent the sole deficiency with the disclosure of the reference.
As defined by Applicants, the “total corneal fluorescein staining score” refers to a sum of scores from the inferior, superior, central, temporal, and nasal regions of the cornea (see Spe., pg. 59, lines 6-8).
The teachings of Alex and Chun are considered to bridge the gap in teaching provided by Stonecipher.
Chun provides state of the art discussion stating that “[t]he grading system recommended by the NEI Workshop on Clinical Trials in Dry Eyes divides the cornea into 5 zones: central, superior, temporal, nasal, and inferior. For each zone, the amount of corneal fluorescein staining is graded on a scale of 0 to 3: 0 = normal or negative slit-lamp findings; 1 = mild or superficial stippling; 2 = moderate or punctate staining, including superficial abrasion of the cornea; and 3 = severe abrasion or corneal erosion, deep corneal abrasion, or recur rent erosion. The maximum score is 15” (see pg. 1098, right col., second full paragraph).
What this defines is a recognized zonal set of criteria by which to evaluate the eye for dry eye using corneal fluorescein staining. The person of skill in the art evaluating an eye using this methodology and determining that each zone scores a “2”, for instance would understand that such an eye would be one that is within the scope of the instantly claimed method of assessment.
Chun provides the criteria with which to evaluate an eye afflicted with dry eye, but does not provide a zonal evaluation; only a four-eye comparison of different criteria in Figure 2 (pg. 1101).
The article published by Alex, however, does provide a baseline evaluation in a controlled experiment that served to reproduce stress placed on the eyes that represents the same damage incurred with dry eye. That is, ten of 25 total subjects represented “dry eye subjects” and wearing goggles, were exposed to a controlled, desiccating environment for 90 minutes, after which eye irritation symptoms such evaluations as corneal fluorescein staining. The results of the experiment showed that corneal staining significantly increased in all subjects following the 90-minute exposure to the desiccating environment, and that the magnitude of change was similar in normal and dry eye subjects, with the sole exception that the superior cornea staining was greater in dry eye. Table 2 discloses the mean results for all 25 subjects, and also both the 15 ‘normal’ subjects and 10 ‘dry eye’ subjects. Here, baseline values for all five zones and a total cornea staining are provided showing that the sum of all zones having a value of 13.70 ± 2.5 (or a range of 11.2-15.9).
The Examiner acknowledges that Stonecipher does not appear to measure or consider the temporal and nasal cornea zones in its efficacy evaluation of Restasis on dry eye. However, in view of the added disclosures of Chun and Alex, the Examiner submits that a person of ordinary skill in the art, before the effective filing date of the claimed invention, would have reasonably expected to be treating a patient having a total CFS score ranging from 11-15.
Owing to Alex’s disclosed baseline values for the superior, inferior, and central corneal staining values, the ordinarily skilled artisan obtaining the same measurements in the method of Stonecipher, would have reasonably expected similar values for the temporal and nasal zones, had they been measured.
Stated another way, given the values that are disclosed for the shared, measured zones in Stonecipher and Alex, the skilled artisan would have expected the unmeasured zones of Stonecipher to produce values that were similar to those provided by Alex’s baseline evaluation.
Thus, in treating the dry eye patients in the method of Stonecipher, the skilled artisan would have had a similar expectation of success in reducing the total corneal staining scores by three or more units as recited by instant claims 17 and 25.
Evidence supporting this position is taken from the above Figure 1A which shows reduced scoring values six months after treating with Restasis.
The limitations recited by instant claim 18 set forth that the treatment results in improvement in the number of words read per minute in an international reading speed texts (IReST). Claim 19 recites that the treatment results in improvement with regard to blurred vision, reading, driving at night, working with a computer, working at an ATM, reading at low contrast, or reading at low print size.
Stonecipher discloses that “[a]fter 6 months of treatment, patient responses on the OSDI showed a significant reduction in the frequency of blurred vision and significant improvement in visual functioning related to reading, night driving, computer or bank machine use, and watching television. Total corneal staining and staining in the central corneal region, which is known to be critical to visual function, had decreased significantly from baseline.”
The foregoing disclosure is considered to meet the recited limitations.
Stonecipher, as discussed above, is on record as conducting the study using Restasis® (0.05% w/v cyclosporine ophthalmic suspension), thereby meeting the limitations recited by instant claim 20.
Figure 1A above discloses a baseline central corneal fluorescein staining value of 2.31, thereby meeting the limitations of claim 26 (i.e., between 1 and 3), and claim 29 (i.e., about 3).
Figure 1A above also discloses a baseline conjunctiva (lissamine green conjunctival staining) of 4.21, thereby meeting the limitations recited by instant claim 27 (i.e., baseline score of 2 to 6), and instant claim 30 (i.e., baseline score of 3 to 5).
Figure 3A shows that the baseline value for the Schirmer test in the worse eye, on average, is 5.3 mm, thereby reading on the limitations recited by instant claim 28 (i.e., a range of about 4-6 mm) and 31 (i.e., about 5 mm).
Based on the combined teachings of the references, the Examiner submits that a person of ordinary skill in the art would have had a reasonable expectation of success in achieving the instantly claimed method of assessment and treatment.
As established by the disclosure of Stonecipher, each and every element of the claimed invention is disclosed, with the exception that the study does not appear to measure or evaluate the temporal or nasal corneal zones with respect to the total CFS score. The teachings of Chun are relied upon to demonstrate that consideration of the total CFS score is understood and established in the art as assessing all five zones, including the temporal and nasal zones. The teachings of Alex are further relied upon to demonstrate that baseline corneal fluorescein staining scores taken on eyes assessed as having dry eye will have an NEI scale score ranging from 11-15. Based on this assessment, the Examiner respectfully advances that patients presenting the baseline superior, central, and inferior CFS scores assessed in Stonecipher would also be expected to have measurable values for the temporal and nasal zones. Thus, while Stonecipher measures its dry eye patients with its interpretation of baseline total CFS (see e.g., Figure 1A), the ordinarily skilled artisan would have a reasonable expectation of that baseline being higher (e.g., 11-15), in view of the teachings presented by Chun and Alex.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Nonstatutory 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 17-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of Leo et al. (USPN 11,413,323 B2). Although the claims at issue are not identical, they are not patentably distinct from each other.
The limitations of instant claims 17-20 and 25-31 are discussed above.
The limitations recited by claims 21-23 are directed to Applicants’ inventive composition (CyclASol 0.1%) with the administered single drop volume of 8-12 µL and 10-12 µL. Claim 24 recites that the composition is administered twice per day.
Reference claim 1 discloses:
A method for improving symptoms of visual impairment or visual disturbance in a patient suffering from dry eye disease, wherein the patient is characterized by having at least one eye with a total ocular surface disease index score (OSDI) of equal or greater than 45 at baseline, wherein the method provides a reduction in the total corneal fluorescein staining score (NEI scale) by three or more units, and wherein the method comprises the step of administering to the eye of the patient a composition comprising 0.1% (w/v) cyclosporine dissolved in 1-(perfluorobutyl)-pentane and up to about 1% (w/w) ethanol; wherein said composition is administered twice per day per eye, at a dose of a single drop per eye of a volume of about 8 to 11 μL.
Reference claim 5 discloses:
The method of claim 1, wherein the patient has at least one eye with a total ocular surface disease index score (OSDI) of equal or greater than 55, and at least one eye with:
(i) a total corneal fluorescein staining score of 11 or higher (NEI scale); or
(ii) a central corneal fluorescein staining in the range of 1 to 3 (NEI scale); or
(iii) a total lissamine green conjunctival staining score in the range of 2 to 6; or
(iv) an unanesthetized Schirmer's test score in the range of 2 to 8 mm; or
(v) any combination of (i) to (iv); or
(vi) any combination of (i) to (iv), with the specified values in both eyes.
Reference claim 8 discloses:
The method according to claim 1, wherein method provides a reduction in the total corneal fluorescein staining score (NEI scale) of at least 3 units within a treatment period of at least 8 weeks.
Were the reference patent available as prior art, the Examiner respectfully advances that it would teach and suggest the instantly claimed method where it did not anticipate it.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, and absent a clear showing of evidence to the contrary.
Allowable Subject Matter
Claims 21, 22, and 24 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The combined limitations of the three foregoing claims are noted as presenting Applicants’ inventive composition (CyclASol 0.1%) and a dosing regimen that is commensurate in scope with the claimed method. Evidence supporting an amendment of these limitations into claim 17 is taken directly from originally-filed Figure 5.
All claims have been rejected; no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Jeffrey T. Palenik whose telephone number is (571) 270-1966. The Examiner can normally be reached on 9:30 am - 7:00 pm; M-F (EST).
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.
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/Jeffrey T. Palenik/
Primary Examiner, Art Unit 1615
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