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 .
The amendments of 10/27/2025 have been entered in full. Claims 142-147 and 162-180 are pending.
All prior objection/rejections not specifically maintained in this Office action are hereby withdrawn in view of Applicants’ amendment and/or arguments filed 10/27/2025.
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 142-144, 162-171, and 174-177 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al., Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1389-1396 (Chen), .US 20190100555 (Huang; of record), US 20160058795 (Prockop), and US 20190046576 (Gangaraju; of record).
Claim 142 is drawn to an assay in which a composition comprising a mesenchymal stem cell (MSC) secretome and a tonicity modifying agent is tested in a transwell assay in which migration or proliferation of corneal epithelial cells is measured. The claim states that the result is indicative of the ability of the composition to induce migration and/or proliferation of the corneal cells, which in turn is taken to mean that the composition is able to induce ocular wound healing, as recited in the preamble of the claim.
Transwell assays that measure the migration and/or proliferation of corneal epithelial cells are known in vitro models of ocular wound healing. For example, Chen (whole document) teaches the use of transwell migration assays to study the influence of a substance previously used to prevent corneal scar formation, Mitomycin C, on stromal-epithelial communication. The premise of the approach is that fibroblasts secrete substances that induce epithelial cell migration. This is clearly analogous to the premise that mesenchymal stem cells may secrete substances that induce epithelial cell migration, which underlies the method of claim 142. In Chen, the assay was performed using culture dishes and 8-μm transwell culture inserts, the corneal epithelial cells were incubated in 0/1% growth supplement, and migration was detected by cell staining after 48 hours (Materials and Methods; Fig.4), as in pending claims 143, 144, and 167-171. Chen detected average numbers of migrating cells per field ranging from 36 to 456, which is inclusive of the values recited in claim 166 (Fig. 4B).
In another example, Huang demonstrated the ability a peptide to enhance the migration of corneal epithelial cells in transwell migration assays of 24-48 hours duration [0015-0016] [0043]. Huang interpreted the results as indicating that the peptide should be used to treat eye damage (claim 7). The pending claims likewise aim to indicate that a composition should be used to treat eye damage if it can induce migration of corneal epithelial cells in a transwell migration assay. Huang performed 24-hour and 48-hour assays, as in claims 143 and 144 (FIGs 1-4). In the assay, corneal epithelial cells were seeded into the upper chamber with an 8-μm pore size, as in pending claim 167 [0038].
The methods of Chen and Huang differ from the instant claims as they do not teach that the assays should be performed with a MSC secretome composition. It is, however, evident from Chen and Huang that transwell assays that measure the migration and/or proliferation of corneal epithelial cells are generally applicable to infer that a substance may be potentially useful to induce ocular wound healing and to study the mechanisms of wound healing activity. One of skill in the art prior to the filing of the instant application would be motivated to apply this method to MSC-conditioned media, as in claims 142-171 and 174, in view of Prockop and/or Gangaraju. Prockop discloses that MSC-conditioned media promote healing when applied to injured cornea (FIG. 4 [0015] [0049] [0190-0193]. Similar to the instant specification and claims, Gangaraju discloses a method of using mesenchymal stromal cell conditioned media for treating for eye diseases (whole document) including injury to the cornea [0048-0049]. Gangaraju discloses a concentrated, cell-free secretome of cultured adipose MSC cells [0013]. The disclosed method of producing the conditioned medium coincides with the methods recited in pending claims [0055]. The medium may be filtered, frozen, lyophilized, or buffer exchanged [0014] [0067-0069].
In summary, Chen, Huang, Prockop, and Gangaraju, taken together, provide ample and redundant teaching, suggestion, and motivation to perform the methods of the instant claims. The general conditions of the claimed methods are known from the cited references and any differences would be readily derived from routine optimization.
Conclusion
Claims 142-144, 162-171, and 174-177 are rejected.
Claims 172 and 173 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.
Claims 178-180 are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANIEL C GAMETT, Ph.D., whose telephone number is (571)272-1853. The examiner can normally be reached on M-W. Please note the examiner’s part-time schedule. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached on 5712722911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANIEL C GAMETT/Primary Examiner
Art Unit 1647