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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09 March 2026 has been entered.
Status
Applicant’s response dated 09 March 2026 to the previous Office action dated 10 September 2025 is acknowledged. Pursuant to amendments therein, claims 1, 5-9, 14-17, and 30 are pending in the application.
The rejection under 35 U.S.C. 103 made in the previous Office action is withdrawn in view of applicant’s claim amendments, but a new (modified) rejection under 35 U.S.C. 103 is made herein in view of applicant’s claim amendments.
Election/Restrictions
Claims 6-9 and 30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 18 April 2022. It is noted that claim 30 is incorrectly labeled as “Previously presented” but should be labeled as “Withdrawn” – Correction should be made in response hereto.
Claims 1, 5, and 14-17 are under current examination.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 5, and 14-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ciolkowski et al. (US 2009/0239836 A1; published 24 September 2009; of record) in view of Horn (US 2014/0378401 A1; published 25 December 2014; of record) and Matsumura et al. (US 2013/0102977 A1; published 25 April 2013; of record).
Ciolkowski et al. discloses an ophthalmic composition that includes a non-ionic oxygen-containing polymer and a surfactant and may include a drug (abstract) wherein a surfactant may be polysorbate 80 (paragraph [0043]) wherein a concentration of surfactant may be about 0.001-5 wt% (paragraph [0047]) wherein the nonionic oxygen-containing polymer may be poloxamer (paragraph [0040]) such as poloxamer 188 and poloxamer 407 (paragraph [0097]; Example 9) wherein the amount of a non-ionic oxygen-containing polymer therein may be about 0.1-25 wt% (paragraph [0041]); wherein the composition may include PEG-35 castor oil (i.e., polyoxyl 35 castor oil) (paragraphs [0099], [0102]; Examples 10, 12) wherein a solubility-enhancing agent therein may be beta-cyclodextrin (paragraphs [0063], [0065]) wherein a viscosity-adjusting agent therein may be hydroxypropylmethyl cellulose (paragraph [0062]) wherein the nonionic oxygen-containing polymer may be PEG-400 (paragraph [0038]) wherein a tonicity-adjusting agent therein may be sodium chloride, mannitol, or magnesium chloride in amounts of about 0.01-3 wt% to provide osmolality of about 200-400 milliosmoles (paragraph [0048]) wherein the composition can include preservative such as benzalkonium chloride in amounts of about 0.001-2 wt% (paragraphs [0063]-[0064]) wherein the composition can include buffer such as phosphate buffer (paragraphs [0063], [0066]) wherein the composition may have a pH of about 4-8 (paragraph [0068]) wherein permeation through the cornea is desirable for drug delivery (paragraph [0004]) wherein the composition may include 0.094-0.1 g in 1000 g (i.e., 0.0094-0.01% w/w) or preferably about 0.001-0.5% by weight EDTA (Table 2 Examples 1-4; paragraph [0064]).
Although Ciolkowski et al. does not disclose an exemplary formulation having all constituents and concentrations and pH as discussed above, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to follow the suggestions of Ciolkowski et al. as discussed above and to make the composition of Ciolkowski et al. having all constituents and concentrations and pH as discussed above, with a reasonable expectation of success.
Regarding the claimed poloxamer 407, poloxamer 188, and PEG-400, Ciolkowski et al. discloses all as nonionic oxygen-containing polymers (i.e., equivalents known for the same purpose), and it is prima facie obvious to combine equivalents known for the same purpose per MPEP 2144.06(I).
Regarding the claimed mannitol, magnesium chloride, and sodium chloride, Ciolkowski et al. discloses all as tonicity adjusting agents (i.e., equivalents known for the same purpose), and it is prima facie obvious to combine equivalents known for the same purpose per MPEP 2144.06(I).
Regarding the claimed amount of EDTA of about 0.05-0.12% w/w, the amount disclosed by Ciolkowski et al. of preferably about 0.001-0.5% by weight EDTA overlaps such claimed amount, and a prima facie case of obviousness exists where prior art and claimed ranges overlap per MPEP 2144.05(I).
Although Ciolkowski et al. discloses beta-cyclodextrin as a solubility enhancing agent, Ciolkowski et al. does not disclose hydroxypropyl gamma cyclodextrin as claimed, and although Ciolkowski et al. discloses phosphate buffer, Ciolkowski et al. does not disclose citrate buffer as claimed.
Horn discloses ophthalmic drug delivery formulations (title) wherein cyclodextrins enhance corneal permeation (paragraph [0250]) wherein cyclodextrins include hydroxypropyl-γ-cyclodextrin (paragraph [0102]) wherein polyoxyl 35 castor oil is a nonionic surfactant (paragraph [0033]) wherein buffer therein may be phosphate buffer or citrate buffer (paragraph [0035] at a concentration of 1-100 mM (paragraph [0036]).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ciolkowski et al. and Horn by adding hydroxypropyl-γ-cyclodextrin (i.e., hydroxypropyl gamma cyclodextrin) as suggested by Horn to the composition of Ciolkowski et al. as discussed above, with a reasonable expectation of success. A person of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so to enhance corneal permeability as suggested by Horn given that Ciolkowski et al. suggests the desirability of permeation through the cornea for drug delivery and given that Ciolkowski et al. teaches that a cyclodextrin is suitable for inclusion in the composition of Ciolkowski et al.
It also would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ciolkowski et al. and Horn by substituting 1-100 mM citrate buffer as in Horn for the phosphate buffer in the composition of Ciolkowski et al. as discussed above, with a reasonable expectation of success. A person of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because they are both buffers used in ophthalmic compositions and it is prima facie obvious to substitute such equivalents known for the same purpose per MPEP 2144.06(II). Such concentration of 1-100 mM overlaps the claimed range of about 2-5 mM, and a prima facie case of obviousness exists where prior art and claimed ranges overlap per MPEP 2144.05(I).
Ciolkowski et al. and Horn do not disclose potassium sorbate as claimed.
Matsumura et al. discloses an ophthalmic composition (title) that may contain a drug (paragraphs [0062]-[0071]) wherein suitable preservatives therein include benzalkonium chloride and potassium sorbate (paragraph [0078]).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Ciolkowski et al., Horn, and Matsumura et al. by substituting the potassium sorbate of Matsumura et al. for the benzalkonium chloride in the composition of Ciolkowski et al. in view of Horn as discussed above, with a reasonable expectation of success. A person of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do so because both benzalkonium chloride and potassium sorbate are known preservatives used in ophthalmic compositions (i.e., equivalents known for the same purpose) as disclosed by Matsumura et al., and it is prima facie obvious to substitute equivalents known for the same purpose per MPEP 2144.06(II).
The composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above results in a concentration of polysorbate 80 of about 0.001-5 wt%, which overlaps the claimed range of about 0.5-1 wt%; and a prima facie case of obviousness exists wherein prior art and claimed ranges overlap per MPEP 2144.05(I).
The composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above results in concentrations of poloxamer 407 and 188 and PEG 400 of about 0.1-25 wt%, which overlaps the claimed ranges of about 0.5-1 wt% for poloxamer 407; about 0.1-0.2 wt% for poloxamer 188; and about 0.2-1 wt% for PEG 400; and a prima facie case of obviousness exists wherein prior art and claimed ranges overlap per MPEP 2144.05(I).
The composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above results in concentrations of mannitol, magnesium chloride, and sodium chloride of about 0.01-3 wt%, which overlaps the claimed ranges of about 0.25-0.75 wt% for mannitol; about 0.01-0.1 wt% for magnesium chloride; and about 0.25-0.75 wt% for sodium chloride; and a prima facie case of obviousness exists wherein prior art and claimed ranges overlap per MPEP 2144.05(I).
The composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above results in a concentration of potassium sorbate of about 0.001-2 wt%, which overlaps the claimed range of about 0.1-0.15 wt%, and a prima facie case of obviousness exists wherein prior art and claimed ranges overlap per MPEP 2144.05(I).
The composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above results in a pH of about 4-8, which overlaps the claimed ranges of about 5-8 and about 6-7, and a prima facie case of obviousness exists wherein prior art and claimed ranges overlap per MPEP 2144.05(I).
The composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above results in an osmolality of about 200-400 milliosmoles, which overlaps the claimed ranges of osmolarity about 200-400 milliosmoles and about 250-350 milliosmoles (given that a basis of weight or volume is not claimed and thus osmolarity equals osmolality), and a prima facie case of obviousness exists wherein prior art and claimed ranges overlap per MPEP 2144.05(I).
Regarding the claimed concentration of polyoxyl 35 castor oil, since polyoxyl 35 castor oil is a surfactant as disclosed by Horn, and given that Ciolkowski et al. teaches use of a surfactant concentration of about 0.001-5 wt%, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to follow such suggestions of Ciolkowski et al. and Horn and to make the composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above with about 0.001-5 wt% polyoxyl 35 castor oil, with a reasonable expectation of success, which overlaps the claimed range of polyoxyl 35 castor oil of about 0.15-0.2 wt%, and a prima facie case of obviousness exists wherein prior art and claimed ranges overlap per MPEP 2144.05(I).
Regarding the claimed concentration of hydroxypropyl gamma cyclodextrin, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize corneal permeation of the composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above by varying the concentration of hydroxypropyl gamma cyclodextrin therein through routine experimentation per MPEP 2144.05(II), given that Horn teaches that hydroxypropyl gamma cyclodextrin enhances corneal permeation (i.e., is a known result-effective variable).
Regarding the claimed concentration of hydroxypropylmethylcellulose, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to optimize viscosity of the composition of Ciolkowski et al. in view of Horn and Matsumura et al. as discussed above by varying the concentration of hydroxypropylmethylcellulose therein through routine experimentation per MPEP 2144.05(II), given that Horn teaches that hydroxypropylmethylcellulose is a viscosity adjusting agent (i.e., is a known result-effective variable).
Response to Arguments
Applicant's arguments filed 09 March 2026 have been fully considered but they are not persuasive.
Applicant argues that the Horn declaration submitted 18 May 2023 and the Narendran declaration submitted 29 August 2024 demonstrate that a formulation containing the 13 claimed excipients at various concentrations are capable of both wetting the eye better than closely related formulations and also providing suppression of free DNA (remarks pages 4-5).
In response, although the Horn declaration has demonstrated unexpected results of superior wetting score of 2 for 25 minutes with respect to formulation 2-2, the claims are not tailored to formulation 2-2 in that the claimed composition does not recite all ingredients at the specific concentrations used in formulation 2-2, and thus the evidence of unexpected results is not commensurate in scope with the claims. Since only one tested formulation demonstrates unexpected results, there is no basis for extending the unexpected results to encompass any other ingredients or concentrations per MPEP 716.02(d).
The Narendran declaration is insufficient to overcome the obviousness rejection because: the reported test results merely show that the tested formulations of Composition A, Composition A with voriconazole, and Composition A with moxifloxacin are capable of binding and/or sequestering free DNA, but the results include no testing with a composition of the closest (or closer) prior art such that any unexpected results can be determined from a comparison between inventive and closest (or closer) prior art compositions with respect to binding and/or sequestering free DNA; and Composition A with or without voriconazole or moxifloxacin are not commensurate in scope with the claimed formulations with respect to constituents and concentrations thereof. Applicant is reminded that the burden is on applicant to establish that results are in fact unexpected and unobvious and of both statistical and practical significance, per MPEP 716.02(b). Such evidence of unexpected results must be commensurate in scope with the claimed invention per MPEP 716.02(d), and must compare the claimed subject matter with the closest prior art (or closer) per MPEP 716.02(e).
Applicant argues that claim 1 has been limited to particular concentration ranges commensurate in scope with the data (remarks page 5). In response, the claims have not been limited to formulation 2-2 or Composition A with or without voriconazole or moxifloxacin, in that the claimed composition does not recite all ingredients at the specific concentrations used in such formulations, and thus the evidence of unexpected results is not commensurate in scope with the claims. Moreover, the Narendran declaration does not appear to have comparative testing with respect to the closest prior art (or closer) such that unexpectedness of the Narendran data results cannot be determined, and thus Composition A with or without voriconazole or moxifloxacin has not been persuasively shown to exhibit unexpected results.
Applicant argues that Case 2 of Tibrewal 2013 shows that reduction of free DNA of 33% is sufficient to relieve dry eye symptoms (remarks page 5). In response, there does not appear to be comparative testing provided by the Narendran declaration with respect to the closest prior art (or closer) such that unexpectedness of the Narendran data results cannot be determined.
Conclusion
No claims are allowed.
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/MICHAEL B. PALLAY/Primary Examiner, Art Unit 1617