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 .
Claims 1-21 are pending in the application. Preliminary amendment filed 22 August 2022.
Priority
This application is a 371 of PCT/US2021/027991 filed 04/19/2021, which claims the benefit of 63012627 filed 04/20/2020. The parent application 63012627 to which priority is claimed is seen to provide adequate support under 35 U.S.C. 112 for claims 1-21 of this application.
Specification
The disclosure is objected to because of the following informalities: Formulas 3 and 4 at pages 21 and 22 are fuzzy. At page 23, in the last structural formula on the right in the table the -NH on the five membered ring is not clear. In the table at page 24, the first formula on the right needs to be replaced by a clear formula. At page 24, in the formula at the bottom of the page the substitution on the right between the two nitrogen atoms on the five membered ring is fuzzy. All the said formulas should be replaced by clear ones.
Appropriate correction is required.
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 8-21 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) in view of Tuttle et al (The Journal of Biological Chemistry, 1984, 259(7), 4065-4069; cited in IDS filed 08/12/2022).
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 claim 9-oral administration; limitation of claims 13 and 15-glaucoma). Breunig teaches the case of a 70-year-old woman with glaucoma taking acyclovir after surgery did not reduce the IOP (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 as in claims 1-2 and does not teach the limitations of claims 3-6, 8, 12, 14 and 16-18.
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 1-2. 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. 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. The artisan would use the above active agents in a method of treating all the other age-related retinal diseases as in claims 13 and 14 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.
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).
Claim(s) 1-6 and 8-21 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) in view of Tuttle et al (The Journal of Biological Chemistry, 1984, 259(7), 4065-4069; cited in IDS filed 08/12/2022.
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 claim 9-oral administration and limitation of claim 19-human subject).
Mahajan does not expressly teach that the acyclovir is PNPase inhibitor as in claims 1-2 and does not teach the limitations of claims 3-6, 8, 10-18 and 20-21.
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 1-2. 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 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. The artisan would use the above active agents in a method of treating all the other age-related retinal diseases as in claims 13 and 14 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.
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).
Conclusion
1. Pending claims 1-6 and 8-21 are rejected.
2. Claim 7 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHY KRISHNAN whose telephone number is (571)272-0654. The examiner can normally be reached M-F 8.30am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693