DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ Amendments and Remarks, filed 23 February 2026, in the matter of Application N° 18/256,733. 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 8, 13, and 18-22 have been canceled. No claims have been added.
Claims 1 and 11 have been amended with the limitations of canceled claims 8 and 13. Claim 10 has been amended to remove permeation enhancer.
No new matter has been added.
Thus, claims 1, 3, 5, 7, 10-12, and 14-17 now represent all claims currently under consideration.
Information Disclosure Statement
No new Information Disclosure Statements (IDS) have been filed for consideration.
Maintained Rejections
The following rejections are maintained from the previous Office Correspondence dated 21 August 2025 since the art that was previously cited continues to read on the amended and previously recited limitations.
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 1, 3, 5, 7, 10-12, and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Gamache et al. (USPN 6,872,382 B1) in view of Sreedharala et al. (IN201941006472A; published 5 April 2019; original document attached and cited; Espacenet copy attached as evidence of publication date). [emphasis added to reflect canceled claims]
The instantly claimed invention is directed to a stable ophthalmic composition for topical administration comprising: 0.001-0.9% w/w apremilast, 0.2-10% w/w of a surfactant or solubilizer, and a buffering agent, wherein the pH of the composition ranges from 3.0-9.0. The composition is additionally recited as being effective for the treatment of inflammatory disorders of the ophthalmic system.
Claim 11 recites a method of treating symptoms of dry eye comprising administering a composition comprising: 0.001-0.9% w/w apremilast, and at least one surfactant or solubilizer in an amount ranging from 2-10% w/w, and a buffering agent, wherein the pH of the composition is 3.0-9.0.
Gamache discloses a method for the treatment of dry eye comprising administering to a mammal, a composition comprising a pharmaceutically acceptable carrier and a pharmaceutically effective amount of one or more selective PDE-IV (phosphodiesterase IV) inhibitors (claim 1).
Claim 2 discloses that the pharmaceutically effective amount of the one or more PDE-IV inhibitors is 0.001-1.0% (w/v).
The reference additionally discloses that the practiced compositions will contain other ingredients such as surfactants and buffers (see e.g., col. 4, lines 20-24).
The preferred pH range of the practiced compositions is disclosed as ranging from 6-7.5 (see e.g., col. 4, lines 40-42).
The practiced formulations are disclosed as being in the form of solutions and gels, all of which are disclosed as being topically applied (see e.g., col. 4, lines 9-19). Though not expressly disclosed as a form of composition, the Examiner submits that Gamache also teaches and suggests that the composition may be in the form of an emulsion, notably as surfactants (emulsifiers) are component that may be included.
Gamache is considered to teach the instantly claimed composition and method of treatment with the notable exception that it does not expressly disclose apremilast as the administered PDE-IV inhibitor.
Sreedharala discloses lipophilic topical composition comprising apremilast, whereby apremilast is present in an amount as low as 1% w/w (see e.g., claims 1 and 10). The practiced compositions are also noted as including both at least one emulsifier (surfactant) and a pH adjusting agent to maintain a pH in the suitable range for better stability of the formulation (see e.g., pg. 5, lines 1-3). Topical pharmaceutical compositions of the practiced invention are disclosed as having a pH in the physiological range between 3 to 8, or 4 to 7, or 4.5 to 6.5 (see e.g., pg. 7, lines 26-27).
Emulsifiers are taught as being present in amounts ranging from 2-30% and co-emulsifiers are also taught as being present in amounts ranging from 2-25% w/w (see e.g., pg. 8, lines 17-30).
The Examiner does acknowledge that the majority of the disclosure of Sreedharala is directed to topical compositions that are applied to the skin. However, MPEP §2123(I) states that “[a] reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments.” MPEP §2123(II) also states that “[d]isclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments.”
In the instant case, the Examiner notes that Sreedharala also discloses that the practiced composition may be provided in the form of an ophthalmic gel (see e.g., pg. 7, lines 1-2). The Examiner additionally notes that the reference defines “topical administration” as referring to delivery to the skin or mucosa, thus providing a local effect (see pg. 14, lines 6-7). [emphasis added]
The foregoing disclosures of Sreedharala are considered to convey to the ordinarily skilled artisan that a stable, ophthalmic composition is available for administration as a “topical” composition to the ocular surface of the requisite user.
Sreedharala does not disclose that the practiced ophthalmic gel is administered to treat the symptoms of dry eye as instantly claimed.
Despite their respective deficiencies, the Examiner submits that a person of ordinary skill in the art, in possession of the above combined teachings, would have had a reasonable expectation of success at producing the instantly claimed compositions and arriving at the recited method of treatment.
MPEP §2144.06(II) states that “[i]n order to rely on equivalence as a rationale supporting an obviousness rejection, the equivalency must be recognized in the prior art, and cannot be based on applicant’s disclosure or the mere fact that the components at issue are functional or mechanical equivalents.”
MPEP §2144.06(I) states that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.”
In the instant case, the Examiner has pointed out that both references disclose compositions (e.g., solutions, gels, emulsions) that comprise a phosphodiesterase-IV (PDE-IV) inhibitor as its active ingredient, additionally containing one or more surfactants, and one or more buffers. Where Gamache expressly discloses administering the composition for the purposes of treating a disorder of the eyes (i.e., dry eye), Sreedharala teaches and suggests topical, ophthalmic administration. Of note is that Sreedharala does not disclose treating ocular disorders, but does teach and suggest that symptoms alleviated by apremilast would be.
To this point, both references disclose the exact same mechanism by which PDE-IV active agents function.
Gamache discloses (see col. 2, lines 40-63):
Phosphodiesterase enzymes catalyze the degradation of cyclic nucleotides such as cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Both cAMP and cGMP have been shown to stimulate lacrimal gland secretion and increase tear volume (Gilbard J P, Rossi S R, Heyda K G, and Dartt D A. Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels. IOVS 31(7):1381-8, 1990). Therefore, nonspecific inhibitors of phosphodiesterases have, been proposed to be therapeutically useful in dry eye by stimulating tear production. However, phosphodiesterase enzymes which have the capacity to suppress inflammation may treat dry eye by virtue of an anti-inflammatory property. Phosphodiesterase type-IV (PDE-IV) is the predominant cyclic nucleotide hydrolyzing enzyme found in inflammatory leukocytes, such as mast cells, neutrophils, monocytes and T-lymphocytes. The substrate for PDE-IV is cAMP, a known anti-inflammatory second messenger. Elevated cAMP levels inhibit leukocyte function and suppress cytokine production in a variety of cells. PDE-IV hydrolyzes the anti-inflammatory nucleotide, cAMP, thereby reducing its intracellular level. PDE-IV inhibitors prevent the breakdown of cAMP and thereby exhibit antiinflammatory activity. Therefore, PDE-IV inhibitors would be useful therapeutic agents in reducing inflammatory processes contributing to the manifestations of dry eye. [emphases added]
Sreedharala also discloses (see pg. 2, lines 18-20):
Apremilast being a selective phosphodiesterase 4 (PDE4) inhibitor acts by increasing the intracellular cyclic adenosine monophosphate (cAMP) which decreases the expression of inflammatory cytokines such as tumour necrosis factor and interleukin-23 (IL-23).
Based on the common activity and function of PDE-IV inhibitors disclosed by the references, the Examiner advances that the ordinarily skilled artisan would have been motivated to modify the treatment method of Gamache to administer apremilast to topically treat the user’s eye for disorders such as dry eye.
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.
Response to Arguments
Applicants’ arguments with regard to the rejection of claims 1, 3, 5, 7, 10-12, and 14-17 under 35 USC 103(a) as being unpatentable over the combined teachings of Gamache et al. and Sreedharala et al. have been fully considered, but they are not persuasive.
Applicants initially traverse the rejection on the grounds that Gamache discloses a preference for compositions as aqueous solutions (e.g., eye drops), while also acknowledging that the reference teaches other forms such as suspensions, gels, etc. The Examiner also acknowledges that Gamache suggests that the suspension form may be preferred for selective PDE IV inhibitors which are sparingly soluble in water. However, to Applicants’ remark echoing the Examiner’s discussion, Gamache does not expressly list apremilast as one such inhibitor.
Regarding the overall teachings of Gamache, Applicants argue that the skilled artisan would not be guided to arrive at the claimed subject matter of the present invention since Gamache fails to disclose apremilast and surfactant/solubilizer with amounts.
Applicants next argue that Sreedharala fails to disclose the range of apremilast as instantly claimed.
Regarding the latter assertion, the Examiner respectfully disagrees and submits that Sreedharala discloses that practiced embodiments will contain apremilast in amounts ranging from about 1-8% by weight of the composition (see Sreedharala, pg. 7, first paragraph of machine translation).
This disclosure is considered to align with Gamache’s generic disclosure of PDE IV inhibitor amounts in the practiced compositions.
Thus, in direct opposition to Applicants’ remarks, the combined teachings of Gamache and Sreedharala teach and suggest the recited amount of apremilast in the recited composition.
Additionally, the Examiner acknowledges that Gamache teaches and suggests the use of surfactants, buffers, and solvents without providing specific amounts for them. However, the combined teachings of the references provide the skilled artisan with the requisite guidance for achieving the claimed composition. Sreedharala discloses formulations comprising the amounts of apremilast, surfactant, and buffering agents, all of which are formulated into a composition that is stable and non-irritating to the eye.
Applicants’ remark directed to Sreedharala’s observation that compositions of apremilast are unstable and precipitate on addition of water and that it is suggested to replace water with other suitable aqueous/non-aqueous solvents is acknowledged.
Applicants additionally state that the in the present application, water is an essential component in all compositions exemplified in the present specification.
However, in response to Applicants’ argument that the references fail to show certain features of the invention, it is noted that the feature upon which Applicants rely (i.e., water) is not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Furthermore, Applicants’ preceding remarks acknowledge that Sreedharala does in fact allow for the presence of water-based (i.e., aqueous) solvents to be used. Thus, there remains a reasonable expectation of success in achieving the instantly claimed invention since both Gamache and Sreedharala disclose the use of aqueous solvents. Thus, contrary to Applicants’ concluding remark directed at Sreedharala, the reference does not necessarily teach away from the use of water.
Applicants’ arguments, for the above reasons, are found unpersuasive. Said rejection is therefore maintained.
All claims under consideration remain rejected; no claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicants are 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.
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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