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 .
Claim Status
The claim set and Applicant’s remarks filed July 29, 2025 have been entered. Claims 1-27 are canceled. Thus, claims 28-49 as amended are examined on the merits herein.
Claim Interpretation
With respect to claim 28, lines 3-4, the claim recites an ophthalmic topical formulation comprising “xanthan gum” within said formulation for the treatment of an eye pathology having an inflammatory condition of the front segment of the eye in the presence of a bacterial infection as recited in claim 28, lines 1-2.
The Examiner respectfully notes “xanthan gum” is not explicitly defined within the specification. Therefore, the Examiner reasonably interprets the ophthalmic topical formulation recited in claim 28 may comprise any form of xanthan gum that is suitable for use in ophthalmic applications.
Moreover, the Examiner did not find anything within the specification that explicitly excluded any specific form of xanthan gum for inclusion within said ophthalmic topical formulation as described above, to the contrary, the Examiner respectfully notes the specification exemplifies the xanthan gum within the formulation according to the present invention may be of any xanthan gum commercially known and suitable for the use in ophthalmic applications (see pg. 4, lines 29-30).
Thus, the Examiner reasonably interprets the xanthan gum within said formulation as required in claim 28 may be in any form, for example in a deacylated form as discussed below, if the xanthan gum is suitable for use in ophthalmic applications as required in the treatment method of claim 28 as recited in lines 1-2.
Withdrawn Objections and Rejections
With respect to the objections and/or rejections mailed in the non-final office action on May 02, 2025:
(I) The objection of claims 29 and 41 are withdrawn in view of Applicants amendments to claims 29 and 41 respectively.
(II) The rejection of claims 48-49 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph are withdrawn in view of Applicants amendments to claims 48 and 49 respectively.
Response to Arguments
The rejection of claims 28-49 under 35 U.S.C. 103 are maintained.
Applicant argues:
(A) Kabra does not teach or suggest a composition with netilmicin or an ophthalmic composition with (not deacylated) xanthan gum, see Applicant’s remarks, pg. 7 of 10, fourth paragraph from the bottom of the page.
(B) The Examiner did not notice or acknowledge that Kabra requires the use of deacetylated xanthan gum and not xanthan gum which is not deacetylated, see Applicant’s remarks, pg. 7 of 10, third paragraph from the bottom of the page.
(C) Kabra’s deacetylated xanthan gum is a product different from xanthan gum that has not been deacetylated, where formulations with not deacetylated xanthan gum would be “unusable”; and wherein the conclusion of “unusability” of (not deacetylated) xanthan gum on pg. 12 of Kabra teaches away the skilled person from the composition according to amended claim 1, and this Kabra is not a promising starting point for assessing the inventiveness of claim 1, see Applicant’s remarks, pg. 7 of 10, second paragraph from the bottom of the page.
With respect to Applicants arguments (A)-(C), the Examiner respectfully disagrees with Applicants argument the xanthan gum recited in claim 28, line 4 is required to be not deacetylated xanthan gum in view of the Examiner’s interpretation of “xanthan gum” discussed in the Claim Interpretation section above. As the Examiner respectfully reminds Applicants the phrase “xanthan gum” is not explicitly defined in the specification. Therefore, the Examiner reasonably interpreted the ophthalmic topical formulation recited in claim 28 may comprise any form of xanthan gum that is suitable for use in ophthalmic applications.
Moreover, the Examiner did not find anything within the specification that explicitly excluded any specific form of xanthan gum for inclusion within said ophthalmic topical formulation as described above, to the contrary, the Examiner respectfully notes the specification exemplifies the xanthan gum within the formulation according to the present invention may be of any xanthan gum commercially known and suitable for the use in ophthalmic applications as discussed above.
Thus, the Examiner reasonably interprets the claims encompass any form of xanthan gum for use in ophthalmic applications, for example the deacetylated xanthan gum used in the ophthalmic compositions of Kabra for use in the treatment of ocular inflammatory conditions wherein an infection exists as taught by Kabra and discussed in the maintained 103 rejections below.
(D) Applicants observed and demonstrate that administration twice a day is equivalent in terms of efficacy for patient administration of four times a day, as demonstrated in Example 1, where the formulation of the present invention administered twice a day was found to be equivalent to the same formulation administered with a dosage regimen of four times a day. Thus, the formulations of the present invention reduce the number of administrations by half and maintain the level of efficacy of the formulation, thereby improving the compliance of the medical treatment of the patient, see Applicant’s remarks, pg. 8 of 10, paragraph 2.
(E) The experimental protocol described from page 12, last paragraph, to page 14 of the specification demonstrated the formulation in the form of a gel comprising netilmicin and xanthan gum showed an amplified antibiotic power and an increased QI value shows its increased activity against various bacterial strains associated with bacterial ocular infections, see Applicant’s arguments, pg. 8 of 10, paragraph 3.
With respect to Applicants arguments (D)-(E), the Examiner respectfully notes claim 28 does not require said ophthalmic topical formulation recited in line 4 be in the form of a gel.
The Examiner respectfully notes the combination of Kabra and Leonardi teach deacetylated xanthan gum and netilmicin in the treatment of ocular inflammatory conditions wherein an infection exists after LASIK surgery; as the composition of Kabra already contains the antibiotic tobramycin as discussed in the 103 rejections below.
The Examiner also notes Leonardi teaches a broad spectrum antibiotic is usually indicated after LASIK, see pg. 85, right column, paragraph 1. Leonardi also teaches aminoglycosides are broad spectrum antibiotics, see pg. 85, right column, paragraph 2.
Leonardi further teaches netilmicin is a third-generation aminoglycoside that has excellent in vitro and in vivo activity against the most common bacterial ocular pathogens.
Furthermore, Kabra teaches treatments can be performed by applying a small amount (e.g. one to two drops) of the composition to the affected eye or eyes of a patient two times per day.
(F) Kabra cannot be considered a good starting point because it does not describe netilmicin, and even if Leonardi is considered, Leonardi only teaches netilmicin is a known antibiotic that is safer than ofloxacin, see Applicant’s arguments, pg. 8 of 10, third paragraph from the bottom of the page.
(G) Leonardi teaches away from administering netilmicin in a topical formulation, since it does not easily penetrate by topical administration, see Applicant’s arguments, pg. 8 of 10, second paragraph from the bottom of the page.
(H) A person skilled in the art would not consider modifying Kabra with Leonardi to obtain the claimed topical formulation with a reasonable expectation of success since such a modification with netilmicin would not be expected to result in a topical formulation for treating an eye pathology having an inflammatory condition of the front segment of the sys in the presence of a bacterial infection, see Applicant’s arguments, pg. 9 of 10, paragraph 1.
With respect to Applicants arguments (F)-(H), the Examiner respectfully notes Kabra teaches the compositions comprise tobramycin, dexamethasone and deacetylated xanthan gum, wherein said composition provides a longer ocular retention for enhanced ocular bioavailability of tobramycin and dexamethasone, see Kabra, abstract.
Kabra further teaches upon application to the eye the viscosity of the compositions of the invention rise, thereby increasing the length of time during which the compositions are retained on the corneal surface and therefore enhance ocular bioavailability as demonstrated by Kabra wherein as a result of this enhanced ocular bioavailability it has been determined that a dexamethasone concentration of only 0.05 w/v% in the composition of the invention is bioequivalent to a dexamethasone concentration of 0.1 w/v% in TOBRADEX© Ophthalmic Suspension, see pg. 5, lines 4-10.
Moreover, Leonardi teaches tobramycin is an aminoglycoside antibiotic, see pg. 89, left column, paragraph 3.
Therefore, one of ordinary skill in the art would have been motivated to include netilmicin as a broad spectrum antibiotic into the composition of Kabra, as Kabra teaches the treatment of ocular inflammatory conditions wherein an infection exists after LASIK surgery as discussed above; Leonardi teaches a broad spectrum antibiotic is usually indicated after LASIK and aminoglycosides are broad spectrum antibiotics which include both netilmicin and tobramycin.
One of ordinary skill in the art would have had a reasonable expectation of success of including netilmicin into said compositions of Kabra above, as Kabra teaches said composition provides a longer ocular retention for enhanced ocular bioavailability of tobramycin as discussed above.
Thus, Applicants arguments have been fully considered but are not found persuasive.
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 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. Applicant is 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.
(I) Claims 28-47 remain rejected under 35 U.S.C. 103 as being unpatentable over Kabra (Published 29 December 2011, WO-2011162752-A1, IDS filed 12/02/2022) in view of Semoun et al. (Published January 2008, Cornea, Vol. 27, Number 1, pp. 114-116, PTO-892 mailed 05/02/2025) and Leonardi et al. (Published January 2006, Cornea, Vol. 25, Number 1, pp. 85-90, PTO-892, mailed 05/02/2025).
Regarding claim 28-47, Kabra teaches treatment of ocular inflammatory conditions wherein an infection exists, see pg. 10, lines 33-34. Kabra teaches treating ocular inflammation associated with ocular surgical procedures such as LASIK surgery (e.g. the front segment of the eye, required in claim 28, line 2) , see pg. 10, line 37 – pg. 11, line 2.
Kabra teaches treatments can be performed by applying a small amount (e.g. one to two drops) of a composition to the affected eye or eyes of a patient two times per day, however, the dosing frequency may be modified by clinicians, see pg. 11, lines 5-10.
Kabra teaches ophthalmic pharmaceutical compositions containing tobramycin, dexamethasone and deacetylated xanthan gum for topical application to the eye, see abstract. Kabra teaches the concentration of deacetylated xanthan gum at 0.9% (w/v), see pg. 6, lines 20-21. Kabra teaches the concentration of dexamethasone at 0.05% (w/v) and a range of 0.03 to 0.1% (w/v), see pg. 6, lines 19-20.
Although, Kabra does not teach (a) a bacterial infection, required in claim 28, line 2, claims 38-39 and 45-46; (b) netilmicin, required in claim 28, 32-33 and 41-43; and (c) the administration period, required in claim 40 and claim 47.
However, in the same field of endeavor of LASIK surgery, Semoun teaches early bacterial keratitis after presbyopic LASIK, see pg. 114, title; wherein the cause is a Propionibacterum acnes infection, see pg. 114, left column, abstract, conclusion. Semoun teaches Propionibacterum acnes is a Gram-positive bacteria, see ppg. 116, left column, paragraph 1.
Semoun teaches a 57-year-old woman underwent bilaterial LASIK, see pg. 114, left column, Case Report, paragraph 1. Semoun teaches the patient’s condition continued to deteriorate after surgery wherein after examination the right eye showed a corneal abscess with an overlying epithelial ulcer, see pg. 114, right column, last paragraph of the column.
Semoun teaches patients are treated with broad-spectrum antibiotics for a week after surgery (e.g. the duration administered, required in claim 40), see pg. 115, right column, Discussion, paragraph 1.
In addition, Leonardi teaches a broad spectrum antibiotic is usually indicated after LASIK, see pg. 85, right column, paragraph 1. Leonardi teaches aminoglycosides are broad spectrum antibiotics, see pg. 85, right column, paragraph 2.
Leonardi teaches netilmicin is a third-generation aminoglycoside that has excellent in vitro and in vivo activity against the most common bacterial ocular pathogens. Gram-positive organisms are those usually involved in post-refractive infectious keratitis and there susceptibility to netilmicin was 97%, see pg. 88, right column, Discussion, paragraph 2. Leonardi teaches netilmicin may be considered a good ‘‘surface’’ antibiotic for the treatment of external eye disease, see pg. 88, right column, Discussion, paragraph 5.
Leonardi teaches netilmicin is formulated as 0.3% (w/v) eye drops, see pg. 89, left column, paragraph 5. Leonardi teaches 3.0 mg/mL of netilmicin is normally used in the clinical setting, see pg. 89, left column, paragraph 3.
With respect to claim 32 and claim 42, given the teachings of Kabra that one drop can be administered twice a day as discussed above, and assuming a drop is 0.05 mL, the total volume of the two drops administered a day as taught by Kabra is 0.10 mL. In addition, using the concentration of 3.0 mg/mL of netilmicin as taught by Leonardi and multiplying it by the 0.10 mL volume that Kabra administers, the total mg/day of netilmicin administered as taught by Kabra and Leonardi is 0.3 mg/day and within the claimed mg/day range of netilmicin required in claim 32 and claim 42.
With respect to claim 36, Kabra teaches that one drop can be administered twice a day, and assuming a drop is 0.05 mL, the total volume of the two drops administered a day as taught by Kabra is 0.10 mL. In addition, using the concentration of 0.05% (w/v) of dexamethasone, which is 50 mg/100mL of dexamethasone as taught by Kabra and multiplying it by the 0.10 mL volume that Kabra administers, the total mg/day of dexamethasone administered as taught by Kabra is 0.05 mg/day and within the claimed mg/day range of dexamethasone required in claim 36.
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date to have incorporated limitations (a)-(c) into the treatment method of Kabra as discussed above, as Kabra teaches their compositions are effective at treating ocular inflammation conditions wherein an infection exists, and wherein the ocular inflammation is associated with ocular surgical procedures such as LASIK, as discussed above. In addition, Semoun teaches bacterial keratitis developed after presbyopic LASIK surgery caused by a P. acnes infection, wherein P. acnes is a Gram-positive bacteria as discussed above. Furthermore, Leonardi teaches netilmicin has excellent in vitro and in vivo activity against the most common bacterial ocular pathogens; where Gram-positive bacteria are those usually involved in post-refractive infectious keratitis, and wherein Gram-positive bacteria has a 97% susceptibility to netilimicin as discussed above.
Thus, one of ordinary skill in the art would have been motivated to incorporate the limitations (a)-(c) into the method of Kabra in order to treat the ocular inflammation associated with LASIK surgery where an infection exists as taught by Kabra, wherein the infection after LASIK is bacterial keratitis as taught by Semoun. One of ordinary skill in the art would have had a reasonable expectation of success to incorporate limitations (a)-(c) into the treatment method of Kabra, as Kabra, Semoun, and Leonardi are directed to the LASIK procedure where an infection exists, Semoun teaches the infection after the LASIK procedure is a Gram-positive bacterial infection; and Leonardi teaches Gram-positive bacteria had a 97% susceptibility to netilmicin and that netilmicin may be considered a good ‘‘surface’’ antibiotic for the treatment of external eye disease as discussed above.
With respect to the limitations, “xanthan gum acts as a mucomimetic substance”, required in claim 29; and “xanthan gum is an eye absorption promoter”, required in claim 30; the examiner is reasonably interpreting these limitations to be physical limitations of xanthan gum. In addition, since Kabra meets the structural limitations of xanthan gum for treatment of ocular inflammatory conditions wherein an infection exists as discussed above, the physical limitations of xanthan gum as discussed above will be met.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have added limitations (a)-(c) as discussed above into the treatment method of Kabra as taught above as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to treat ocular inflammatory conditions associated with LASIK wherein an infection exists as taught by Kabra, specifically bacterial keratitis as taught by Semoun, with netilmicin as taught by Leonardi. One of ordinary skill in the art would have had a reasonably expectation of success to incorporate limitations (a)-(c) into the treatment method of Kabra, as Semoun teaches a P. acnes (Gram-positive) bacterial infection resulting after a LASIK procedure; and wherein Leonardi teaches Gram-positive organisms usually involved in post-refractive infectious keratitis had a 97% susceptibility to netilmicin as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claims 48-49 remain rejected under 35 U.S.C. 103 as being unpatentable over Kabra (Published 29 December 2011, WO-2011162752-A1, IDS filed 12/02/2022), Semoun et al. (Published January 2008, Cornea, Vol. 27, Number 1, pp. 114-116, PTO-892 mailed 05/02/2025) and Leonardi et al. (Published January 2006, Cornea, Vol. 25, Number 1, pp. 85-90, PTO-892, mailed 05/02/2025) as applied to claims 28-47 above, and further in view of Mazzone et al. (Published 12 June 2008, US-20080139522-A1, PTO-892 mailed 05/02/2025).
Kabra, Semoun and Leonardi address claims 28-47 as written above. Kabra further teaches dexamethasone alcohol (required in claims 48-49), see pg. 3, lines 20-26.
Kabra further teaches inclusion of ionic species to control the ionic interaction between tobramycin and xanthan gum, so as to avoid formation of precipitates or clumps and maintain the viscosity of the tobramycin/dexamethasone suspensions or solutions within an acceptable range prior to application to the eye, see pg. 3, lines 28-32. Kabra further teaches the ionic species utilized for this purpose can be and are preferably inorganic electrolytes or organic buffering agents, see pg. 3, lines 34-37.
Although, Kabra, Semoun and Leonardi do not teach sodium hydrogen phosphate monohydrate, disodium phosphate dodecahydrate, sodium citrate and purified water at the percentage amounts required in claims 48-49.
However, in the same field of endeavor of corneal injury caused by surgical cuts and wounds, for example LASIK, and post-infective ulcers, Mazzone teaches epithelizing pharmaceutical compositions especially for ophthalmic use, see paragraph [0002]; for example corneal injury caused by a surgical wound, see paragraph [0003]; wherein the composition can accelerate re-epithelization, especially of the corneal tissue, see paragraph [0004]; where the goal is achieved by using xanthan gum for the preparation of a medication for the treatment of epithelial wounds, see paragraph [0005].
Mazzone teaches formulation 6, which comprises 0.1465 g sodium phosphate monobasic monohydrate (e.g. 0.1465% (w/v) sodium hydrogen phosphate monohydrate, required in claims 48-49); 0.5000 g sodium phosphate dibasic dodecahydrate (e.g. 0.5000% (w/v) disodium phosphate dodecahydrate, required in claims 48-49); 2.1000 g sodium citrate dihydrate (e.g. 2.1000% (w/v) sodium citrate, required in claims 48-49); and purified water q.s. to 100 mL, see pg. 3, left column, Formulation 6.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated sodium hydrogen phosphate monohydrate, disodium phosphate dodecahydrate, sodium citrate and purified water at the percentage amounts required in claims 48-49 as within the scope of the artisan as combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would have been motivated to add the teachings of Mazzone into the composition of Kabra as the specific ionic species to control the ionic interaction between tobramycin and xanthan gum so as to avoid formation of precipitates or clumps and to maintain the viscosity of the tobramycin/dexamethasone suspensions or solutions within an acceptable range prior to application to the eye as taught by Kabra above. One of ordinary skill in the art would have had a reasonable expectation of success to have incorporated these additions into the composition of Kabra, as Kabra teaches the ionic species utilized for this purpose can be and are preferably inorganic electrolytes or organic buffering agents.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
THIS ACTION IS MADE FINAL. 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 JARET J CREWS whose telephone number is (571)270-0962. The examiner can normally be reached Monday-Friday: 9:00am-5:30pm EST.
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/JARET J CREWS/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691