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 response filed 13 April 2026 has been received, entered and considered. The following information has been made of record in the instant response:
1. Claim 7 has been canceled.
2. New claims 22-27 have been added.
3. Claims 1-3, 9, 11, and 16 have been amended.
4. Remarks drawn to objections to specification and rejections under 35 USC 103.
The following has/have been overcome:
5. The objection to the disclosure for some formulas in the specification being fuzzy has been overcome by filing a substitute specification with clear formulae.
Claims 1-6 and 8-27 are pending in the case.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 27 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 27 depends from claim 26 which is drawn to AMD, whereas claim 27 recites glaucoma. Claim 27 should depend from claim 25.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 1-6 and 8-27 are rejected under 35 U.S.C. 103 as being unpatentable over Breunig et al (Sparking Change, May/June 2017, 43-45; cited in IDS filed 08/12/2022; of record) in view of Tuttle et al (The Journal of Biological Chemistry, 1984, 259(7), 4065-4069; cited in IDS filed 08/12/2022; of record).
Breunig et al teaches a regimen for treating glaucoma and inflammation which includes oral antivirals like acyclovir, valacyclovir and famciclovir. Oral agents are used for stromal or endothelial involvement or when there is concern about safety or toxicity from topical antivirals (method of treating age-related disease and reducing inflammation as in claims 1-2; limitation of claims 9, 22-oral administration; limitation of claims 13, 15 and new claim 27-glaucoma). Breunig teaches the case of a 70-year-old woman with glaucoma taking acyclovir after surgery (Abstract; limitation of claims 19-21). In view of this teaching one of ordinary skill in the art will select a subject having age-related retinal disease in the claimed method of treatment.
Breunig does not expressly teach that the acyclovir, valacyclovir and famciclovir are PNPase inhibitors and the specific PNPase inhibitors as in claims 1-3, and does not teach the limitations of claims 4-6, 8, 10-12, 14, 16-18, 23-24 and 26.
Tuttle teaches that acyclovir is an inhibitor of purine nucleoside phosphorylase (Abstract; page 4067, left col., sixth full para). In view of Tuttle, it would be obvious to one of ordinary skill in the art that a PNPase inhibitor and/or the PNPase purine nucleoside substrate can be administered to a subject for treating an age-related retinal disease or reducing inflammation in the retina as in claims 1-3. In view of Breunig and Tuttle it would be obvious to administer the PNPase inhibitor into the eye of the subject and also do repeat delivering as in claims 10-11, and also treat hypertensive retinopathy as in claim 13. Breuning teaches acyclovir which is guanine with a hydroxyethyl methoxy substitution at the 9-position. This is an analog of the compound of formula 1 at page 19 in the specification and PNPase inhibitors recited in amended claims 1-3. Acyclovir has alkoxy and hydroxyl substitutions at the 9-position (guanine as in claim 3 and alkoxy and hydroxyl groups as in claim 4). Valacyclovir is similar to acyclovir with an alkoxy, ester and amine functional groups (alkoxy, ester as in claim 4). In view of this one of ordinary skill in the art will have a reasonable expectation that a guanine substituted at the 8-position as in claims 3 and 4 with hydroxy, alkoxy, ester and the carbonate and their salts, which are close analogs will also function as PNPase inhibitors, and would therefore administer them in the methods of claims 1 and 2 (limitations of claims 3-4, and 8). A reasonable expectation also exists for using guanosine, hypoxanthine having a substituent at the 8-position as in claims 3 and 12.
Compounds which differ only in the placement of substituents in a ring system are not patentable absent unexpected results. In re Jones 162 F. 2d 638, 74, USPQ 152 (CCPA 1947).
The artisan would use the above active agents in a method of treating all the other age-related retinal diseases as in claims 13, 14, and 26 in view of Breunig and Tuttle. Since the active agent of Breunig teats inflammation there is a reasonable expectation of success that the administration of the PNPase inhibitors and the other inhibitors would produce a decrease in at least one inflammatory cytokine as in claims 16-17. The administration of the active agents to a human subject also renders the administration of the active agents of the instant claims to a veterinary subject as in claim 18. The artisan would also use the PNPase inhibitors having all of the other substitutions as in claims 4-6 in order to look for inhibitors that have enhanced effect in the claimed methods. Since Breunig teaches the use of IOP drops it would be obvious to the artisan to administer the PNPase inhibitor into the eye of the subject as in claim 23 and also delivering repeatedly to the eye of the subject as in claim 24 in order to maintain the disease/condition in a stable state.
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 under 35 U.S.C. 103 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."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, the active agents of Breunig are useful for treating glaucoma and inflammation of the retina, and according to Tuttle they are PNPase inhibitors. Thus, it is obvious to arrive at the claimed method.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. The artisan would be motivated to administer PNPase inhibitors as the active agents in the claimed methods since the administration would reduce risk of recurrence (Breunig: page 44, left col., first full para under sub-title).
Obviousness based on similarity of structure and function entails motivation to make the claimed compound in expectation that compounds similar in structure will have similar properties. Where prior art compound essentially brackets the claimed compounds and are well known PNPase agents, one of ordinary skill in the art would be motivated to make the claimed compounds in searching for new PNPase agents for use in the claimed methods. In re Payne, 606 F. 2d 303, 203, USPQ, 245, 254-55 (C.C.P.A. 1979).
Response to Applicant’s Remarks
Applicant has traversed the rejection of claims over Breunig in view of Tuttle arguing that the glaucoma in the patient was treated with a series of surgeries. For patients with herpetic eye disease and secondary glaucoma and OHT, suppressive antiviral and anti-inflammatory medications, along with topical IPO-lowering drops are successful in managing these patients. Breunig does not teach or suggest using acyclovir to treat glaucoma. Tuttle does not cure the deficiency of Breunig as it does not concern disease treatment at all.
Claim 1 has been amended to incorporate the feature from claim 3. The Office incorrectly assumes that Breunig teaches PNPase inhibitor as a class can be used in its method. It does not. Breunign teaches the use of a single compound, acyclovir, in its method, is used for its antiviral activity. Although acyclovir is disclosed in Tuttle as a relatively weak inhibitor of PNPase, Breunig did not use it for its PNPase inhibitor activity, thus providing no reasons for one of ordinary skill in the art to search for any other PNPase inhibitors for use in Breunig’s method, and Tuttle cannot cure this deficiency. Claim 3 is amended to incorporate the limitations of claim 7. Claims 4-6 and 8 depend from claim 3. Thus, the rejection is moot as applied to claims 3-6 and 8.
Inflammation in Breunig was treated by loteprednol etabonate. Absent any guidance in Breunig to use acyclovir to treat ocular inflammation, the artisan would have no motivation or reasonable expectation of success in applying acyclovir for such treatments. The Office only analyzes the ‘reducing inflammation’ element but fails to consider the improving or restoring vasculature element. The cited references do not disclose or suggest this feature of claim 2. Therefore, claim 2 and dependent claims 16-17 are not obvious over Breunig in view of Tuttle (Remarks-pages 9-11).
Applicant’s arguments have been considered but are not found to be persuasive.
Regarding glaucoma management Breunig teaches that in the setting herpetic eye disease depends on treating inflammation and treating the elevated IOP. The regimen includes oral acyclovir, valacyclovir or famciclovir (page 44, left col). The patient in Breunig is one as in the instant claims. Therefore, there is a suggestion in Breunig that even though the active agent is an antiviral it can also treat glaucoma and inflammation. According to Breunig surgery did not help.
Breunig need not use acyclovir for its PNPase inhibitor activity. Tuttle teaches that acyclovir is a PNPase inhibitor. Even though it is indicated as a weak inhibitor it can still inhibit PNPase. This suggests to one of ordinary skill in the art that a PNPase inhibitor and/or PNPase purine nucleoside substrate can be used to treat an age-related retinal disease or reducing inflammation. Tuttle need not necessarily teach treating any disease since Breunig suggests treating the claimed age-related retinal disease. Tuttle’s teaching is relevant regarding the function of acyclovir and further a suggestion to look at other structurally close PNPase inhibitors for use in the claimed method. Breunig teaches that loteprednol etabonate was used for rejection prophylaxis after trabeculectomy.
Claim 3 has been amended to incorporate the limitations of claim 7 regarding the use of specific transition state analogs. However, claim 3 is drawn to administering any one of PNPase inhibitor or PNPase purine nucleoside substrate or PNPase transition state analog. Since the combined teachings of Breunig and Tuttle suggest the use of a PNPase inhibitor, the rejection as applied to claims 3-6 and 8 is not moot. Treating inflammation and glaucoma is suggested using acyclovir. Such a treatment should also improve the vasculature in the retina of the subject as in claim 2.
The claims are rendered obvious by Breuning in view of Tuttle. The rejection is maintained.
Claim(s) 1-6 and 8-27 are rejected under 35 U.S.C. 103 as being unpatentable over Mahajan et al (Am. J. Ophthalmol, 2010, 150 (4), 511-518; cited in IDS filed 08/12/2022; document provided has pages numbers 1-13; of record) in view of Tuttle et al (The Journal of Biological Chemistry, 1984, 259(7), 4065-4069; cited in IDS filed 08/12/2022; of record).
Mahajan teaches administration of valacyclovir to three patients with bilateral acute zonal occult outer retinopathy, an inflammatory condition with progressive vision loss. Treatment with oral valacylovir reversed the vision loss. Visual acuity and visual field improved significantly and the patients remained stable without treatment for a follow-up period ranging from 1 to 3 years (page 512 results, Cases 1-3; method of treating age-related retinal disease and reducing inflammation as in claims 1-2; limitation of claims 9, 22-oral administration and limitation of claim 19-human subject).
Mahajan does not expressly teach that the acyclovir is PNPase inhibitor and the specific PNPase inhibitors as in claims 1-3, and does not teach the limitations of claims 3-6, 8, 10-18, 20-21, and 23-27.
Tuttle teaches that acyclovir is an inhibitor of purine nucleoside phosphorylase (Abstract; page 4067, left col., sixth full para). In view of Tuttle, it would be obvious to one of ordinary skill in the art that a PNPase inhibitor and/or the PNPase purine nucleoside substrate can be administered to a subject for treating an age-related retinal disease or reducing inflammation in the retina as in claims 1-3. In view of Mahajan and Tuttle it would be obvious to administer the PNPase inhibitor into the eye of the subject and also do repeat delivering as in claims 10-11, and also treat hypertensive retinopathy as in claim 13. Mahajan teaches valacyclovir which has an alkoxy, ester and amine functional groups (alkoxy, ester as in claim 4). It is also an analog of the compound of formula 1 at page 19 in the specification. In view of this one of ordinary skill in the art will have a reasonable expectation that a guanine substituted at the 8-position as in claims 3 and 4 with hydroxy, alkoxy, ester and the carbonate and their salts, which are close analogs, will also function as PNPase inhibitors, and would therefore administer them in the methods of claims 1-3 (limitations of claims 3-4, and 8). A reasonable expectation also exists for using guanosine, hypoxanthine having a substituent at the 8-position as in claims 3, and 12. The artisan would use the above active agents in a method of treating all the other age-related retinal diseases as in claims 13-15 and 25-27 in view of Mahajan and Tuttle. Since the active agent of Mahajan treats an inflammatory condition there is reasonable expectation of success that the administration of the PNPase inhibitors and the other inhibitors would produce a decrease in at least one inflammatory cytokine as in claims 16-17. The administration of the active agents to a human subject also renders obvious the administration of the active agents of the instant claims to a veterinary subject as in claim 18. The artisan would also use the PNPase inhibitors having all of the other substitutions as in claims 4-6 in order to look for inhibitors that have enhanced effect in the claimed methods. It would be obvious to the artisan to administer the instant active agents to the human subjects as in claims 20-21, administer the active agents as in claims 22-24 in view of the teachings of the prior art.
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 under 35 U.S.C. 103 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."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, the active agent of Mahajan is useful for treating an inflammatory condition of the retina, and according to Tuttle Mahajan’s active agent is a PNPase inhibitor. Thus, it is obvious to arrive at the claimed method.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. The artisan would be motivated to administer PNPase inhibitors as the active agents in the claimed methods since the administration prevents recurrence of the condition for a long time (Mahajan-see cases 1-3).
Obviousness based on similarity of structure and function entails motivation to make the claimed compound in expectation that compounds similar in structure will have similar properties. Where prior art compound essentially brackets the claimed compounds and are well known PNPase agents, one of ordinary skill in the art would be motivated to make the claimed compounds in searching for new PNPase agents for use in the claimed methods. In re Payne, 606 F. 2d 303, 203, USPQ, 245, 254-55 (C.C.P.A. 1979).
Response to Applicant’s Remarks
Applicant has traversed the rejection of claims over Mahajan in view of Tuttle arguing that the AZOOR described in Mahajan is not age related. AZOOR has a viral etiology, arising from herpetic viral infection, and hence valacyclovir was used for treatment. Age is not discussed as a factor in causing AZOOR in Mahajan. Tuttle does not cure the deficiency of Mahajan.
The Office incorrectly assumes that Mahajan teaches that PNPase inhibitors as a class can be used in its method, which it does not. Mahajan teaches the use of valacyclovir for its antiviral activity. Although valacyclovir is a prodrug of acyclovir, disclosed in Tuttle as a relatively weak inhibitor of PNPase, Mahajan did not use it for its PNPase activity. Therefore, there is no reason for the artisan to search for other PNPase inhibitors for use in Mahajan’s method. Claim 3 has been amended to incorporate the limitation of claim 7. Claims 4-6 and 8 depend from claim 3. Therefore, the rejection of claims 3-6 and 8 is rendered moot.
Mahajan does not disclose or suggest valacyclovir can reduce ocular inflammation. Tuttle does not cure this deficiency. Therefore, claim 2 and its dependents cannot be rendered obvious. Additionally, the Office fails to fully consider the limitation of reducing inflammation and improving or restoring vasculature in the retina as in claim 2. The Office does not consider the “improving or restoring vasculature” element as in claim 2. For the above reasons claim 2 and dependent claims are not obvious (Remarks-pages 11-14).
Applicant’s arguments have been considered but are not found to be persuasive. Mahajan teaches the use of valacyclovir for treating an inflammatory condition in a patient. Mahajan may not expressly discuss that age is a factor. However, cases 1-3 disclosed in Mahajan teaches patients of different ages, which means that it can happen at any age, and hence it is age related.
It has been acknowledged in the rejection that Mahajan does not teach that valacyclovir is a PNPase inhibitor. However, Tuttle teaches that acyclovir is a PNPase inhibitor. Applicant also acknowledges that valacyclovir is a prodrug of acyclovir. Therefore, Mahajan’s method administers a PNPase inhibitor. In view of this the artisan will search for other PNPase inhibitors for use in Mahajan’s method.
Claim 3 has been amended to incorporate the limitations of claim 7 regarding the use of specific transition state analogs. However, claim 3 is drawn to administering any one of PNPase inhibitor or PNPase purine nucleoside substrate or PNPase transition state analog. Since the combined teachings of Breunig and Tuttle suggest the use of a PNPase inhibitor, the rejection as applied to claims 3-6 and 8 is not moot.
Mahajan teaches administration of valacyclovir to three patients with bilateral acute zonal occult outer retinopathy, an inflammatory condition. Tuttle need not cure the deficiency of Mahajan because Mahajan teaches the method of reducing inflammation as in claim 2 via administration of a PNPase inhibitor as suggested by Tuttle. The treatment of an inflammatory condition as disclosed by Mahajan should also improve the vasculature in the retina of the subject as in claim 2.
The combined teachings of Mahajan and Tuttle do render the instant claims obvious. The rejection is maintained.
Conclusion
1. Pending claims 1-6 and 8-27 are rejected.
2. Claim 7 has been canceled.
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.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693
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