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 .
Effective Filing Date
The instant application was filed April 1, 2024. Accordingly, the claims are examined with an effective US filing date of April 1, 2024.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on April 1, 2024 was in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the IDS document was considered and a signed copy of the 1449 form is attached.
Election/Restrictions
Applicant’s election of the species of glutaric anhydride as the agent capable of disrupting corneal cell junctures in the reply filed on July 9, 2026 is acknowledged. Since Applicant’s reply did not present any specific traversal, the election is treated as an election without traverse. All of claims 1-20 read on the elected species.
In accordance with the MPEP, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended (see MPEP 803.02). If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. Id. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. Id. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final. Id.
As indicated above, the examiner searched the method based on the elected species above, wherein: prior art was discovered over the elected species of agent. Therefore, the scope of the search and consideration was not extended further beyond the scope of the elected species, although additional art discovered incidental to the search for the elected species is presented herein for the purpose of promoting compact prosecution.
Status of Claims
Currently, claims 1-20 are pending in the instant application. All of claims 1-20 read on the elected invention/species and are therefore under consideration herein.
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(a) 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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2009/120549 in view of CN 111011385.
The rejected claims are drawn to a method of treating an eye of a subject comprising administering the elected species of glutaric anhydride as an agent capable of disrupting corneal cell junctures with a therapeutically effective amount of riboflavin. The claim notes that the claimed administration results in the riboflavin diffusing through the eye to penetrate the stroma within 10 minutes after application, though it is noted that administering the same two agents via the same route would necessarily have the same result as claimed. Dependent claims require further limitations on the timing of the riboflavin administration, further administration of a buffer solution, and concentration/pH of the solution.
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
The ‘549 publication discloses a method of increasing the permeability of corneal epithelium to facilitate the diffusion of agents into the corneal stroma and temporarily destabilize the collagen fibrillar network of the stroma (see Abstract). The reference goes on to teach the use of this method for enhancing ocular drug delivery comprising administration to the cornea of the disrupting agent before application of the ocular drug (see prior art, claim 8). The prior art specifically names glutaric anhydride as the agent that disrupts the epithelium (prior art claim 10, paragraph [0029]). In addition to the elected species, the prior art also teaches that suitable agents for this purpose are also: anhydrides including maleic anhydride, succinic anhydride, glutaric anhydride, citractonic anhydride, methyl succinic anhydride, itaconic anhydride, methyl glutaric anhydride, dimethyl glutaric anhydride, phthalic anhydride, and many other such anhydrides. Acid chlorides include, but are not limited to, oxalyl chloride, malonyl chloride, and many others. Sulfonyl chlorides include, but are not limited to, chlorosulfonylacetyl chloride, chlorosulfonylbenzoic acid, 4-chloro-3-(chlorosulfonyl)-5-nitroebnzoic acid, 3-(chlorosulfonyl)-P-anisic acid, and others. Sulfonic acids include, but are not limited to, 3-suIfobenzoic acid and others (paragraph [0052]). With regard to instant claims 7-13, the prior art teaches “Usually, the agents are administered to the surface of the cornea after the cornea has been treated with a solution to deprotonate free amines on corneal proteins. The deprotonation solutions exhibit a pH range of from 7.5-10.0, often from 8.0-9.0, and usually from 8.3-8.7. They generally include buffer solutions and salt solutions exhibiting a pH in the desired range, such as buffers that are mixtures of dibasic sodium phosphate and monobasic sodium phosphate, or disodium phosphate alone. The concentration of the buffers and solutions ranges from 0.05-1.0M, is often between 0.1-0.7M, and is usually between 0.2 and 0.5M” (paragraph [0042]). The prior art finally notes that the method can be applied to enhance the delivery of “any ocular drug” (paragraph [0039]).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The difference between the ‘549 publication and the instant claims is that the primary reference does not teach the administration of riboflavin as the ocular drug to be administered to the stroma.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2141.02)
To this end, MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection for obviousness should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.’" KSR, 550 U.S. at ___, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention." Further, MPEP 2144.06 states that it is obvious to substitute art-recognized equivalents which are known for the same purpose.
Referring to rationale (D) above, it would have been prima facie obvious to apply the art-known technique of enhancing penetration of ocular drugs by first administering an agent to disrupt the corneal epithelium, such as glutaric anhydride. The ‘549 publication teaches the method is applicable for any corneal drug.
Wollensak et al. describes the effect of administration of riboflavin with UVA therapy to induce collagen crosslinking for the treatment of keratoconus (see title, Abstract). Regarding the concentration required by instant claim 13, the art teaches 1mg/mL of riboflavin in dextran-T-500. The combination of riboflavin with UVA administration (as in instant claim 20) was found to be useful for crosslinking collagen in the treatment of keratoconus (p. 626). Absent a showing of unexpected results, it would have been obvious for the skilled artisan to apply the teachings of the ‘549 publication with Wollensak et al. because both references relate to treating ocular conditions, where there would have been a reasonable expectation that the permeation enhancing method of the ‘549 publication would enhance the efficacy of the therapeutic method described in Wollensak.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alicia L. Otton whose telephone number is (571)270-7683. The examiner can normally be reached on Monday - Thursday, 8:00-6:00.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Mr. Fereydoun Sajjadi can be reached on 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALICIA L OTTON/Primary Examiner, Art Unit 1699
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