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 .
Priority
The present application, filed September 19, 2022, is a national stage application of PCT/US2021/023180, filed March 19, 2021, and claims the benefit of U.S. provisional application 62/992577, filed March 20, 2020.
Status of the Application
Applicant’s communication, received November 6, 2025, wherein claims 1, 3-4, 7, 9-11, 15-16, 18-19 are amended, claims 2, 12, and 17 are canceled, and new claims 49-52 are added, is acknowledged.
Claims 1, 3-11, 13-16, 18-20, and 49-52 are pending and examined on the merits herein.
Withdrawn Objections
Applicant’s amendment, received November 6, 2025, with respect to the objection to claims 1, 3-4, 7, 9-12, 15, and 18-19 for reciting optional limitations has been fully considered and found to be persuasive to remove the rejection because the optional limitations in these claims are removed or no longer optional. Therefore the objection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the objection to claims 4, 12, and 19 for minor informalities has been fully considered and found to be persuasive to remove the rejection because claim 12 is canceled and claims 4 and 19 are amended to remove the informalities. Therefore the objection is withdrawn.
Withdrawn Rejections
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 1 and 3-9 under 35 U.S.C. § 112(a) as lacking enablement for treating any disease, condition, and/or disorder in a subject, has been fully considered and found to be persuasive to remove the rejection because independent claim 1 is amended to recite a method for treating and/or inhibiting progression of a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, which is enabled by the specification. Therefore the rejection is withdrawn.
Applicant’s amendment and arguments, received November 6, 2025, with respect to the rejection of claims 1-20 under 35 U.S.C. § 112(b) as indefinite regarding the meaning of the parenthetical remarks included in the claims, has been fully considered and found to be persuasive to remove the rejection in view of Applicant’s arguments that the parenthetical abbreviations are recognized in the art as abbreviations for these specific compounds. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 4, 12, and 19 under 35 U.S.C. § 112(b) as indefinite regarding the scope of compounds and derivatives thereof, has been fully considered and found to be persuasive to remove the rejection because claim 12 is canceled and claims 4 and 19 are amended to remove derivatives thereof and to include alkylated derivatives of the compounds recited in the claims, which is not indefinite. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 1-5 and 10-13 under 35 U.S.C. § 102 as anticipated by Ambati ‘327, has been fully considered and found to be persuasive to remove the rejection because independent claim 1 is amended to limit the diseases treated to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, which the embodiments of Ambati ‘327 cited in the previous rejection do not teach, because independent claim 10 is amended to limit the compounds used for treating macular degeneration to 3'-Azido-3'-deoxythymidine β-D-glucuronide (GAZT), 3'-Amino-3'-deoxythymidine (AMT), and Lamivudine (R)-sulfoxide (LSO), which the embodiments of Ambati ‘327 cited in the previous rejection do not teach, and because claims 2 and 12 are canceled. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 1-7 and 10-15 under 35 U.S.C. § 102 as anticipated by Dobmeyer, has been fully considered and found to be persuasive to remove the rejection because independent claim 1 is amended to limit the diseases treated to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, which the embodiments of Dobmeyer cited in the previous rejection do not teach, because independent claim 10 is amended to limit the compounds used for treating macular degeneration to 3'-Azido-3'-deoxythymidine β-D-glucuronide (GAZT), 3'-Amino-3'-deoxythymidine (AMT), and Lamivudine (R)-sulfoxide (LSO), which the embodiments of Dobmeyer cited in the previous rejection do not teach, and because claims 2 and 12 are canceled. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 1-2, 5, 8-9, and 18-20 under 35 U.S.C. § 102 as anticipated by Frieman, has been fully considered and found to be persuasive to remove the rejection of claims 2 and 19 because claim 2 is canceled and because claim 19 is amended to limit the compounds used for treating coronavirus infection. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 1-5, 8-9, and 18-20 under 35 U.S.C. § 102 as anticipated by Perry, has been fully considered and found to be persuasive to remove the rejection because independent claim 1 is amended to limit the diseases treated to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, which Perry does not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 6 and 14 under 35 U.S.C. § 103 as unpatentable over Ambati ‘327, has been fully considered and found to be persuasive to remove the rejection because independent claim 1 is amended to limit the diseases treated to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, which the embodiments of Ambati ‘327 cited in the previous rejection do not teach and because independent claim 10 is amended to limit the compounds used for treating macular degeneration to 3'-Azido-3'-deoxythymidine β-D-glucuronide (GAZT), 3'-Amino-3'-deoxythymidine (AMT), and Lamivudine (R)-sulfoxide (LSO), which the embodiments of Ambati ‘327 cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 6, 8-9, 14, and 16-17 under 35 U.S.C. § 103 as unpatentable over Dobmeyer, has been fully considered and found to be persuasive to remove the rejection because independent claim 1 is amended to limit the diseases treated to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, which the embodiments of Dobmeyer cited in the previous rejection do not teach, and because independent claim 10 is amended to limit the compounds used for treating macular degeneration to 3'-Azido-3'-deoxythymidine β-D-glucuronide (GAZT), 3'-Amino-3'-deoxythymidine (AMT), and Lamivudine (R)-sulfoxide (LSO), which the embodiments of Dobmeyer cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the rejection of claims 3-4 under 35 U.S.C. § 103 as unpatentable over Frieman, has been fully considered and found to be persuasive to remove the rejection as applied to claim 4, because claim 4 is amended to limit the scope of compounds encompassed the claim. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 1 and 3-4 over claims 1-3 of U.S. Patent 10,294,220 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘220 are directed to treating retinal degeneration with the compound 3-Et-AZT and the scope of independent claim 1 no longer includes retinal degeneration as a disease. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 2, 5-6 and 10-14 over claims 1-5 of U.S. Patent 10,294,220 in view of Ambati ‘327 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘220 are directed to treating retinal degeneration with the compound 3-Et-AZT, and independent claim 1 no longer recites macular degeneration as a disease. In addition, present claim 10, which is drawn to teaching macular degeneration, does not recite 3-Et-AZT as a potential therapeutic compound. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 1-2 and 10 over claims 8, 10, and 12 of U.S. Patent 11,717,520 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘520 are directed to treating macular degeneration with a derivative of lamivudine, and independent claim 1 no longer recites macular degeneration as a disease. In addition, claim 10, which is drawn to teaching macular degeneration, does not recite lamivudine as a potential therapeutic compound. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 3-6 and 11-14 over claims 8, 10, and 12 of U.S. Patent 11,717,520 in view of Ambati ‘327 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘520 are directed to treating macular degeneration with a derivative of lamivudine, and independent claim 1 no longer recites macular degeneration as a disease. In addition, claim 10, which is drawn to teaching macular degeneration, does not recite lamivudine as a potential therapeutic compound. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 1 and 3-4 over claims 1 and 9 of U.S. Patent 9,326,983 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘983 are directed to treating retinal degeneration with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 no longer encompasses retinal degeneration as a disease. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 2, 5-6, and 10-14 over claims 1, 2, and 9 of U.S. Patent 9,326,983 in view of Ambati ‘327 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘983 are directed to treating retinal degeneration with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 no longer encompasses retinal degeneration as a disease. In addition, independent claim 10, which is drawn to teaching macular degeneration, does not recite any of the reverse transcriptase inhibitors claimed by ‘983. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 1-2, 8-10, and 16-17 over claims 1, 11, and 16 of U.S. Patent 12,274,701 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘701 are directed to blocking inflammasome activation to treat macular degeneration with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 no longer recites macular degeneration as a disease. In addition, independent claim 10, which is drawn to treating macular degeneration, does not recite any of the reverse transcriptase inhibitors claimed by ‘701. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 3-6 and 11-14 over claims 1, 11, and 16 of U.S. Patent 12,274,701 in view of Ambati ‘327 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘701 are directed to blocking inflammasome activation to treat macular degeneration with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 no longer recites macular degeneration as a disease. In addition, independent claim 10, which is drawn to teaching macular degeneration, does not recite any of the reverse transcriptase inhibitors claimed by ‘701. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 1 and 3-4 over claim 1 of U.S. Patent 10,300,057 has been fully considered and found to be persuasive to remove the rejection because claim 1 of ‘057 is directed to treating rheumatoid arthritis with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 limits the diseases to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and fibrosis. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 1 and 3-4 over claims 1 and 10 of U.S. Patent 10,864,212 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘212 are directed to treating Parkinson's disease, Alzheimer's disease, and multiple sclerosis with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 limits the diseases to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and fibrosis. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the non-statutory double patenting rejection of claims 1 and 3-4 over claims 1 and 10 of U.S. Patent 11,602,535 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘535 are directed to treating a disease listed in the claim with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 limits the diseases to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and fibrosis, which were not addressed in the previous rejection. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the provisional non-statutory double patenting rejection of claims 1, 5-6, 10, and 13-14 over claims 1, 5, and 9 of copending U.S. patent application 17/283626 has been fully considered and found to be persuasive to remove the rejection because the previous rejection cited the claims of ‘626 as treating age-related macular degeneration with a reverse transcriptase inhibitor listed in the claim, and independent claim 1 limits the diseases to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and fibrosis. In addition, independent claim 10, which is drawn to teaching macular degeneration, requires a specific therapeutic compound listed in the claim that is not claimed by ‘626. Therefore the rejection is withdrawn.
Applicant’s amendment, received November 6, 2025, with respect to the provisional non-statutory double patenting rejection of claims 1, 8, 10, and 16 over claims 1-4 of copending U.S. patent application 17/637557 has been fully considered and found to be persuasive to remove the rejection because the claims of ‘557 are directed to treating a disease, disorder, or condition associated with an NLR family CARD domain containing 4 (NLRC4) inflammasome with a reverse transcriptase inhibitor, and independent claim 1 limits the diseases to a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and fibrosis. In addition, independent claim 10, which is drawn to teaching macular degeneration, requires a specific therapeutic compound listed in the claim that is not claimed by ‘557. Therefore the rejection is withdrawn.
The following are new and/or modified grounds of rejection, necessitated by Applicant’s amendments received November 6, 2025.
Claim Objections
Claims 9 and 50 are objected to because of the following informalities:
Claim 9 depends from claim 8 and requires the additional treatment is a treatment designed to treat or reduce the progression of the viral infection, the acute respiratory distress syndrome, the cytokine storm syndrome, or the fibrosis.
Because the scope of claim 1 has been narrowed to include treating a coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, please amend “viral infection” to recite “coronavirus infection” to remain consistent with claim 1. In addition, please amend “viral infection” to recite “coronavirus infection” in claim 50, to remain consistent with claim 9.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5, 8-9, 18, 20, 50, and 52 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Frieman (U.S. pre-grant publication no. US 20170027975 A1; cited in previous office action).
Frieman teaches and claims a method for treating a coronavirus infection in a subject, comprising the step of administering to said subject a therapeutically effective amount of a neurotransmitter inhibitor (p. 11, claim 1), and further claims the coronavirus is Middle East respiratory syndrome coronavirus or severe acute respiratory syndrome coronavirus (p. 11, claim 2). Severe acute respiratory syndrome coronavirus is interpreted as SARS-CoV as recited in claims 50 and 52.
Frieman additionally claims the method of claim 1, further comprising administering an antiviral drug, and claims the antiviral drug is selected from the group of interferon, ribavirin, adefovir, tenofovir, acyclovir, brivudin, cidofovir, fomivirsen, foscarnet, ganciclovir, penciclovir, amantadine, rimantadine and zanamivir (p. 11, claims 6 and 7). Adefovir is an NRTI, as evidenced by the present specification (p. 2, line 28).
Frieman teaches that the methods of their invention may be administered to either human or non-human subjects (p. 3, [0032]), and may be administered orally or intravenously (p. 3, [0033]).
Regarding the additional treatment recited in claims 8 and 9, the administration of a neurotransmitter inhibitor with adefovir is interpreted as satisfying the limitation of the additional treatment as required by claim 8. In addition, because Frieman teaches and claims administering the neurotransmitter inhibitor for treating a coronavirus infection, this treatment is reasonably considered a treatment to treat the coronavirus infection as recited in claim 9.
Thus Frieman anticipates claims 1, 5, 8-9, 18, 20, 50, and 52.
Response to Applicant’s amendments: With respect to the previous rejection of claims 1, 2, 5, 8, 9, and 18-20 under 35 U.S.C. §§ 102(a)(l) and 102(a)(2), Applicant argues that Frieman teaches treating coronavirus infection with a neurotransmitter inhibitor, a signaling kinase inhibitor, an estrogen receptor inhibitor, a DNA metabolism inhibitor or an anti-parasitic agent, and in some embodiments, the treatment can involve coadministration of an antiviral drug such as adefovir. However, applicant respectfully submits that there is no disclosure in Frieman whatsoever that would have led one of ordinary skill in the art to believe that any of the antiviral drugs recited in Frieman would themselves alone have any activity in treating any viral infection, particularly a coronavirus infection. Rather, the listed antivirals are only listed in a combination therapy along with, for example, a neurotransmitter inhibitor, a signaling kinase inhibitor, an
estrogen receptor inhibitor, a DNA metabolism inhibitor, or an anti-parasitic agent.
Applicant argues that when taken in the context of the instant application, in which the methods of claims 1 and 18 relate to treating a viral infection with a composition comprising a nucleoside reverse transcriptase inhibitor (NRTI) or other compounds listed in the claims as, in some embodiments, the sole therapeutically active agent, Frieman does not support a rejection of claims 1 and 18 under 35 U.S.C. §§ 102(a)(l) and 102(a)(2).
Applicant’s arguments have been fully considered but they are not found persuasive. Frieman claims a method of treating a coronavirus infection by administering a neurotransmitter with the NRTI adefovir. The present claims recite the transitional term “comprising”, which is inclusive and does not exclude additional, unrecited elements or method steps. See MPEP 2111.03. Accordingly, the method of treating a coronavirus disclosed by Frieman using a neurotransmitter and adefovir satisfies all limitations of claims 1, 5, 8-9, 18, 20, 50, and 52.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., that the present application includes, in some embodiments, treatment of a viral infection with an NRTI as the sole therapeutically active agent) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Therefore, for the reasons described above, the rejection of claims 1, 5, 8-9, 18, 20, 50, and 52 under 35 U.S.C. §§ 102(a)(l) and 102(a)(2) as anticipated by Frieman is maintained.
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.
Claims 1, 3, 5, 8-9, 18, 20, 50, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Frieman (U.S. pre-grant publication no. US 20170027975 A1; cited in previous office action).
As described in the above rejection under 35 U.S.C. 103, the examiner maintains that Frieman anticipates claims 1, 5, 8-9, 18, 20, 50, and 52. However, for the sake of argument, if the scope of compounds for treating the coronavirus infection disclosed by Frieman is sufficiently large such that Frieman does not anticipate claims 1, 5, 8-9, 18, 20, 50, and 52, then these claims would have been obvious over Frieman.
In addition, claim 3 would have been obvious over Frieman, as described below.
Claim 3 depends from claim 1 requires the composition further comprises a pharmaceutically acceptable carrier, diluent, or excipient.
Frieman teaches as described in the above rejection under 35 U.S.C. 102.
Frieman does not teach a specific embodiment wherein the composition administered as part of claim 1 further comprises a pharmaceutically acceptable carrier, diluent, or excipient, as required by claim 3.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to treat a coronavirus infection with the combination of neurotransmitter and adefovir. One of ordinary skill in the art to treat a coronavirus infection with the combination of neurotransmitter and adefovir because Frieman teaches a method of treating a coronavirus infection using neurotransmitter and an antiviral drug, and because Frieman further claims the antiviral drug is selected from a group that includes adefovir. Accordingly, one of ordinary skill in the art would have selected an antiviral from the group claimed by Frieman, such as adefovir, for the purposes of treating a coronavirus infection. Adefovir is an NRTI, as evidenced by the present specification (p. 2, line 28).
Regarding claim 3, it would have been prima facie obvious to one of ordinary skill in the art to formulate the treatment of Frieman comprising a neurotransmitter and adefovir with a pharmaceutically acceptable pharmaceutically acceptable carrier, diluent, or excipient. One of ordinary skill in the art would have been motivated to formulate the treatment of Frieman comprising a neurotransmitter and adefovir with a pharmaceutically acceptable pharmaceutically acceptable carrier, diluent, or excipient because Frieman teaches other formulations of compounds with carriers such as DMSO (for example, see Figure 12B), and further teaches that their composition may be administered orally or intravenously, the latter of which would require an excipient or carrier to prepare a formulation suitable for intravenous administration.
Therefore the invention taken as a whole is prima facie obvious.
Claims 4 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Frieman (U.S. pre-grant publication no. US 20170027975 A1; cited in previous office action) as applied to claims 1, 3, 5, 8-9, 18, 20, 50, and 52 above, and further in view of Watkins (Watkins, M. E.; et al. Journal of Pharmaceutical Sciences 2017, vol. 106, pp. 906-919; cited in PTO-892).
Claim 4 depends from claim 3 and requires an NRTI selected from those listed in the claim. Claim 19 depends from claim 18 and requires an NRTI selected from those listed in the claim.
Frieman teaches as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103. In addition, Frieman teaches the additional antiviral drug is selected from a group that includes tenofovir (p. 11, claim 7).
Frieman does not teach a method of administering specifically tenofovir disoproxil (TDF) or tenofovir alafenamide (GS-7340), as recited in claims 4 and 19.
Watkins teaches that tenofovir disoproxil fumarate (TDF) is a prodrug of tenofovir (TFV), a potent, well-tolerated nucleoside reverse-transcriptase inhibitor (NRTI) (p. 906, right column, second full paragraph, lines 1-2). Watkins teaches that TFV has very low intestinal permeability due to its highly charged phosphonate group, thereby eliminating its use as an orally administered drug. Watkins teaches TDF was designed to improve oral bioavailability, and oral administration of TDF was shown to increase bioavailability of TFV to 20% in mice, 30% in dogs, and slightly under 30% in humans (p. 907, left column, first paragraph, lines 1-6). Tenofovir disoproxil fumarate (TDF) taught by Watkins is interpreted as equivalent to tenofovir disoproxil (TDF) recited in claim 4.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to modify the method of Frieman and administer tenofovir disoproxil fumarate taught by Watkins in place of tenofovir. One of ordinary skill in the art would have been motivated to modify the method of Frieman and administer tenofovir disoproxil fumarate taught by Watkins in place of tenofovir because Frieman teaches a method of treating a coronavirus infection using neurotransmitter and an antiviral drug, and further claims the antiviral drug is selected from a group that includes tenofovir, and because Watkins teaches that tenofovir disoproxil fumarate has improved oral bioavailability compared with tenofovir. Accordingly, one of ordinary skill in the art would have contemplated substituting tenofovir disoproxil fumarate in place of tenofovir, because such a substitution may allow oral administration of the NRTI and because the method with tenofovir disoproxil fumarate may be a more effective therapy for treating coronavirus infection than the tenofovir taught by Frieman.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1, 3-9, 18-20, 50, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Rappuoli (U.S. pre-grant publication no. US 20060257852 A1; cited in PTO-892).
Rappuoli teaches and claims a method for treating a patient suffering from SARS,
comprising: administering to the patient a therapeutically effective dose of a compound selected from the group that includes zidovudine, didanosine and zalcitabine (p. 693, claim 81). These are NRTIs recited in claims 4 and 18.
Rappuoli teaches SARS is severe acute respiratory syndrome (p. 1, [0004], lines 102), and that isolates of the SARS virus appear to have homology with at least the RNA polymerase gene of several known coronaviruses (p. 1, [0004], lines 6-8). Accordingly, SARS is interpreted as a coronavirus infection as recited in claims 1 and 18 and equivalent to SARS-CoV as recited in claims 50 and 52.
Rappuoli teaches that small molecules for treating SARS may be administered orally or parenterally (p. 2, [0015], lines 7-9). Rappuoli teaches that their compositions may be administered to the subject as a pharmaceutical composition (p. 100, [1107], lines 1-3), and that pharmaceutical compositions may also include a pharmaceutically acceptable carrier (p. 100, [1107], lines 10-12).
Rappuoli teaches that injectable depot forms are made by forming microencapsule matrices of the drug in biodegradable polymers, and depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled (p. 101, [1112], lines 1-6). Rappuoli teaches that depot injectable formulations are prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues (p. 101, [1112], lines 7-10).
Finally, Rappuoli teaches and claims a method for treating a patient suffering from SARS, comprising: administering to the patient a steroidal anti-inflammatory drug in combination with at least one antiviral compound (p. 693, claim 80).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer to a patient a therapeutically effective dose zidovudine, didanosine, or zalcitabine for the purposes of treating a patient suffering from SARS. One of ordinary skill in the art would have been motivated to administer to a patient a therapeutically effective dose zidovudine, didanosine, or zalcitabine for the purposes of treating a patient suffering from SARS because Rappuoli teaches and claims a method for treating a patient suffering from SARS by administering a therapeutically effective amount of a compound recited in the claim, and specifically recites zidovudine, didanosine, and zalcitabine as exemplary compounds. Accordingly, one of ordinary skill in the art would have considered administering the full scope of compounds claimed by Rappuoli, including zidovudine, didanosine, and zalcitabine, for the purposes of treating a patient suffering from SARS.
Regarding the administration of an additional treatment as recited in claim 8 and wherein the additional treatment is a treatment designed to treat or reduce the progression of the viral infection as recited in claim 9, because Rappuoli claims a method of treating SARS by administering a therapeutically effective dose of zidovudine, didanosine, or zalcitabine, and because Rappuoli teaches a method of treating a patient suffering from SARS comprising administering to the patient a steroidal anti-inflammatory drug in combination with at least one antiviral compound, one of ordinary skill in the art would have considered a combination therapy comprising administering zidovudine, didanosine, or zalcitabine with a steroidal anti-inflammatory drug, because one of ordinary skill in the art would have recognized zidovudine, didanosine, or zalcitabine as antiviral drugs because they are claimed for treating a patient suffering from SARS. In addition, because the steroidal anti-inflammatory drug is claimed in a method for treating a patient suffering from SARS, it is reasonably considered as a treatment designed to treat or reduce progression of the coronavirus infection, as required by claim 9.
Regarding the compound as formulated for administration in a depot and/or for sustained release as recited in claim 6 and formulated in a drug delivery system as recited in claim 7, because Rappuoli teaches that depot injectable formulations may be prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues, one of ordinary skill in the art would have considered administering formulations in which the compounds above are formulated for administration in an injectable depot or liposome, because said formulation may permit one to control the rate of drug release. Such an injectable formulation would also satisfy the limitation of claim 5, wherein the composition is formulated for administration by injection.
Therefore the invention taken as a whole is prima facie obvious.
Claims 1 and 3-9 are rejected under 35 U.S.C. 103 as being unpatentable over Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022).
Ambati ‘327 teaches compounds, compositions, and methods for treating diseases associated with retinal damage and/or degradation (cover page, Abstract, lines 8-14).
Ambati ‘327 teaches that a composition of their invention comprise a nucleoside and/or a nucleoside reverse transcriptase inhibitor (NRTI) (p. 6, [0120], lines 1-3), and that exemplary compositions may comprise compounds such as stavudine (d4T), azidothymidine (AZT), and abacavir (ABC) (p. 6, [0121], lines 3-6). These compounds are recited in the present claim 4 as specific NRTI compounds.
Ambati ‘327 teaches an example in which the compounds ABC and AZT are used to reduce choroidal neovascularization in a model of wet AMD (p. 4, [0085]; Figure 79), as well as an example in which the alkylated derivatives OMe-d4T, O-Me-N-Et-d4T, 2Et-AZT or 3Et-3TC reduce choroidal neovascularization in a model of wet AMD (p. 4, [0086]; Figure 80). Ambati ‘327 further teaches that Alu RNA-induced RPE degeneration in a model of dry AMD is blocked by the alkylated NRTI derivative 3Me-3TC (p. 4, [0089]; Figure 83). In describing these examples, Ambati ‘327 teaches this reduction in choroidal neovascularization was compared to injection of DMSO as a vehicle control (p. 27, left column, lines 2-5). Because DMSO is described as a vehicle control, the examiner is interpreting the compositions comprising the NRTIs or NRTI alkylated derivatives as being administered in DMSO as a vehicle, which satisfies the limitations of claim 3.
Ambati ‘327 teaches that their invention includes pharmaceutical compositions comprising the compounds described herein together with a pharmaceutically acceptable carrier (p. 7, [0127], lines 1-4), as required by present claim 3. Ambati ‘327 further teaches suitable formulations of their invention include aqueous and nonaqueous sterile injection solutions (p. 7, [0129], lines 1-2), which would satisfy the requirements of present claim 5.
More generally, Ambati ‘327 teaches that NRTIs are mainstay therapeutics for HIV, and they block retrovirus replication. Ambati ‘327 teaches that Alu RNA, an endogenous retroelement that also requires reverse transcriptase (RT) for its life cycle, activates the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, which is the untreatable form of age-related macular degeneration that blinds millions of individuals, and that NRTIs, as a class, are novel inhibitors of the NLRP3 inflammasome (p. 19, [0172], lines 1-10).
Ambati ‘327 further teaches and claims a method of treating a condition selected from conditions associated with retinal damage and/or degradation, which includes renal fibrosis, pulmonary fibrosis, and cystic fibrosis (p. 38, claim 29, lines 10-11, 44) (emphasis added), by administering compounds of claim 1, examples of which are provided in claim 17 and several of which are alkylated derivates of NRTIs, such as 2-Me-AZT (p. 31, right column, bottom left structure), 2-Et-d4T (p. 32, left column, top right structure), and 3-Me-3TC (p. 34, left column, top right structure). These diseases are interpreted as exemplary types of fibrosis, and thus satisfy the disease requirement of claim 1.
Ambati ‘327 further teaches that their invention includes a method for treating conditions associated with retinal damage and/or degradation, which involve administering an effective amount of a compound or composition to a subject in need thereof, wherein the composition comprises a compound as disclosed herein or combinations thereof (p. 8, [0142], lines 1-7) (emphasis added).
Regarding formulations of their therapeutics, Ambati ‘327 teaches injectable depot forms may be made by forming microencapsule matrices of the drug in biodegradable polymers, and depending upon the ratio of drug to polymer and the nature of the particular polymer employed, the rate of drug release can be controlled. Ambati ‘327 further teaches that depot injectable formulations are prepared by entrapping the drug in liposomes or microemulsions which are compatible with body tissues (p. 7, right column, first paragraph, lines 11-18).
Ambati ‘327 does not expressly teach administering the NRTI compounds listed above, including stavudine (d4T), azidothymidine (AZT), and abacavir (ABC), for the purposes of treating coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, as required by claim 1.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer an NRTI taught by Ambati ‘327 for the purposes of treating fibrosis. One of ordinary skill in the art would have been to administer an NRTI for the purposes of treating fibrosis because Ambati ‘327 teaches methods of treating diseases associated with retinal damage or degradation by administering effective amounts of the NRTI recited therein, and further suggests that their methods may be applied for the purposes of treating renal fibrosis, pulmonary fibrosis, and cystic fibrosis (p. 18, [0169], lines 5-6 and 39). Accordingly, one of ordinary skill in the art would have considered the guidance from Ambati ‘327 regarding the effectiveness of their methods for treating additional diseases, and would have considered practicing these methods for the purposes of treating the additional diseases, including renal fibrosis, pulmonary fibrosis, and cystic fibrosis.
Regarding the selection of a specific NRTI for the purposes of treating fibrosis, because Ambati ‘327 suggests their method for the purposes of treating fibrosis, and because Ambati ‘327 includes in their suggested method NRTIs such as stavudine (d4T), azidothymidine (AZT), and abacavir (ABC), one of ordinary skill in the art would have considered these specific NRTIs when practicing the method of Ambati ‘327 for the purposes of treating fibrosis.
Regarding the formulations recited in claims 6 and 7, because Ambati ‘327 teaches formulations that include injectable depot forms and liposome formulations, one of ordinary skill in the art would have contemplated practicing the method of Ambati ‘327 using injectable depot forms and liposome formulations, because said formulations may enable control of the release rate of drug, as taught by Ambati ‘327.
Regarding the additional therapeutic agent recited in claim 8, because Ambati ‘327 teaches that combinations of compounds disclosed in their invention may be used in their methods, one of ordinary skill in the art would have considered administering combinations of compounds taught by Ambati ‘327 for the purposes of treating fibrosis. Moreover, because Ambati ‘327 teaches combinations of compounds may be used for treating the diseases encompassed by their invention, including fibrosis, the additional compound would reasonably be considered as a treatment designed to treat fibrosis, as required by claim 9.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: Regarding the previous rejection of claims 1-5 and 10-13 under 35 U.S.C. §102(a)(l) as anticipated by Ambati ‘327, Applicant argues that claim 1 does not relate to treating AMD, but rather relates to treating a viral infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis. Applicant respectfully submits that Ambati '327 does not disclose any of these conditions, and thus does not support a rejection of claim 1 under 35 U.S.C. §102(a)(l).
Applicant’s arguments have been fully considered but they are not found persuasive. As described in the above rejection, Ambati ‘327 teaches fibrosis as associated with retinal damage and/or degradation. Accordingly, one of ordinary skill in the art would have recognized the potential to practice the method of Ambati ‘327 for the purposes of treating diseases or conditions associated with retinal damage and/or degradation, including pulmonary fibrosis, renal fibrosis, or cystic fibrosis..
Therefore, for the reasons described above, the present rejection of claims 1 and 3-9 under 35 U.S.C. §103 as unpatentable over Ambati ‘327 is maintained.
Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022) as applied to claims 1 and 3-9 above, and further in view of Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
Ambati ‘327 teaches as described in the above rejection under 35 U.S.C. 103.
Ambati ‘327 does not teach the method of claim 7, wherein the nanoparticle, microparticle, or liposome comprises a targeting molecule, as recited in claim 49.
Togami teaches efficient delivery to human lung fibroblasts of liposomes modified with truncated basic fibroblast growth factor and comprising the therapeutic pirfenidone for inhibiting collagen synthesis in idiopathic pulmonary fibrosis (p. 270, Title). Togami teaches that aerosolized formulations using polyethylene glycol (PEG)ylated liposomes enabled sustained drug distribution in the lung by avoiding uptake by alveolar macrophages, but that fibroblasts showed poor intracellular accumulation compared with other cells such as macrophages and epithelial cells (p. 270, left column, second paragraph, lines 1-6). Togami teaches that liposomes modified with truncated basic fibroblast growth factor (tbFGF) peptide KRTGQYKLC have been shown to accumulate in cells by binding to the fibroblast growth factor receptors (FGFRs) on cell surface, and suggests that tbFGF-modified PEGylated liposomes (tbFGF-liposomes) may efficiently accumulate in lung fibroblasts and can be a viable drug delivery system for the treatment of idiopathic pulmonary fibrosis (p. 270, left column, second paragraph, lines 6-13).
Togami compares the accumulation of tbFGF-liposomes and non-modified liposomes in an in vitro model of lung fibroblasts, showing increased accumulation of liposomes modified with the tbFGF targeting peptide in WI-38 lung fibroblast cells compared with unmodified liposomes, and no increased accumulation of modified liposomes in HEK293 cells compared with unmodified liposomes (p. 272, Figure 2 and Figure 2 caption).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to modify the liposome formulations taught by Ambati ‘327 with a targeting molecule, such as a targeting peptide taught by Togami, to promote delivery to specific tissues, such as lung fibroblasts, for the purposes of treating pulmonary fibrosis. One of ordinary skill in the art would have been motivated to modify the liposome formulations taught by Ambati ‘327 with a targeting molecule, such as a targeting peptide taught by Togami, to promote delivery to specific tissues, such as lung fibroblasts, for the purposes of treating pulmonary fibrosis, because Ambati ‘327 renders obvious a method of treating pulmonary fibrosis using the NRTI compounds described above and formulations that include encapsulation of the drug in liposomes, and because Togami teaches liposomes modified with a truncated basic fibroblast growth factor peptide that enables improved drug delivery to lung fibroblasts for treating idiopathic pulmonary fibrosis. Accordingly, one of ordinary skill in the art would have contemplated modifying the liposome formulation taught by Ambati ‘327 with a targeting molecule, such as the targeting peptide taught by Togami, to improve drug delivery to lung fibroblasts when treating pulmonary fibrosis.
Therefore the invention taken as a whole is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-9, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent 10,294,220 B2 (reference patent, hereinafter ‘220) in view of Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022), Artlett (Artlett, C. M. The Open Rheumatology Journal 2012, vol. 6, supplement 1:M3, pp. 80-86; cited in PTO-892) and Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
The present application and ‘220 each include Jayakrishna Ambati and Kameshwari Ambati as inventors.
Claim 1 of ‘220 claims a compound with structure shown therein. Claim 2 claims a pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier. Claim 3 claims a method for treating retinal degeneration, comprising: administering an effective amount of a compound of the structure shown therein. Claim 4 claims a method for inhibiting inflammasome activation by Alu RNA associated with a cell, comprising: administering an inhibitory amount of the compound shown therein, and claim 5 requires the inflammasome is selected from an NLRP3 inflammasome, an IL-1 beta inflammasome, and a combination thereof.
As evidence, Ambati ‘327 teaches the compound claimed by ‘220 as 2ET-AZT and referred to therein as Kamuvudine 8 (p. 11, right column, structure XII). Because present claim 4 recites both alkylated derivatives of the NRTIs and Kamuvudines, the compound of claim 1 of ‘220 falls within the scope of compounds recited in present claim 4.
The claims of ‘220 do not claim treating fibrosis as recited in claim 1, the specific limitations regarding formulation and administration as recited in claims 5-7 and 49, or the additional therapeutic agent as required by claims 8-9.
Ambati ‘327 teaches as described in the above rejections under 35 U.S.C. 103. In addition, Ambati ‘327 teaches their methods may inhibit inflammasome activation by Alu RNA associated with a cell (cover page, Abstract, lines 1-4).
Artlett teaches that the inflammasome can directly control collagen synthesis, leading to the increased deposition of collagens in the tissues such as the lung, liver, heart, and skin, and that mice lacking the inflammasome adaptor protein, ASC, failed to become fibrotic when exposed to bleomycin. Artlett teaches that inhibition of caspase-1 activity in fibroblasts from patients with the fibrotic disease systemic sclerosis, decreased collagen synthesis and reduced α-smooth muscle actin expression in myofibroblasts. Artlett teaches that these observations suggest that the inflammasome can drive the fibrotic response (p. 80, Abstract, lines 8-13).
Togami teaches as described in the above rejections under 35 U.S.C. 103.
It would therefore have been prima facie obvious to administer the compound claimed by ‘220 for the purposes of treating fibrosis, because the claims of ‘220 acknowledge their compound as inhibiting inflammasome activation, Artlett teaches inflammasome activation contributes to the development of fibrosis, and Ambati ‘327 teaches compounds for inhibiting inflammasome activation and treating additional conditions, including pulmonary fibrosis. Accordingly, it would have been obvious to practice the method claimed by ‘220 of inhibiting inflammasome activation for the purposes of treating fibrosis, such as pulmonary fibrosis, because Artlett teaches that inhibition of the inflammasome can reduce symptoms of fibrosis and Ambati ‘327 teaches methods of inhibiting inflammasome activity and treating pulmonary fibrosis.
Regarding formulations and drug delivery systems of claims 6-7 and 49, because Ambati ‘327 acknowledges that drug depots and liposome formulations can control the drug release and Togami teaches targeted delivery of therapeutics to lung fibroblast cells using liposomes modified with truncated basic fibroblast growth factor for treating pulmonary fibrosis, one of ordinary skill in the art would have contemplated these formulations when practicing the method claimed by ‘220, because said formulations may enable more effective treatment of pulmonary fibrosis.
Regarding combinations of therapeutics, because Ambati ‘327 recites additional therapeutics for inhibiting the inflammasome, including the specific compounds recited in claim 17 of Ambati ‘327, it would have been obvious to administer the compound claimed by ‘220 with a compound recited by Ambati ‘327 for the purposes of treating pulmonary fibrosis, because the combination of said compounds may be more effective for inhibiting inflammasome activation than either compound administered alone.
Claims 1, 3-9, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent 11,717,520 B2 (reference patent, hereinafter ‘520) in view of Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022), Artlett (Artlett, C. M. The Open Rheumatology Journal 2012, vol. 6, supplement 1:M3, pp. 80-86; cited in PTO-892) and Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
The present application and ‘520 each include Jayakrishna Ambati and Kameshwari Ambati as inventors.
Claim 8 of ‘520 recites a method of treating a condition associated with inflammasome activation, wherein the condition is selected from dry AMD, wet AMD, Parkinson's disease, Alzheimer's disease, and multiple sclerosis, comprising administering to a subject having said condition an effective amount of a compound having a structure selected from the group consisting of the compounds shown therein.
Using Ambati ‘327 as an evidentiary reference, the compounds claimed by ‘520 are alkylated derivates of lamivudine (lamivudine (3TC) derivatives recited on pp. 15-18, [0167]), which is an NRTI. Because present claim 4 recites both alkylated derivatives of the NRTIs, the compounds claimed by ‘520 thus fall within the scope of compounds recited in present claim 4.
The claims of ‘220 do not claim treating fibrosis as recited in claim 1, the specific limitations regarding formulation and administration as recited in claims 5-7 and 49, or the additional therapeutic agent as required by claims 8-9.
Ambati ‘327 teaches as described in the above rejections under 35 U.S.C. 103.
Artlett teaches as described in the above non-statutory double patenting rejection.
Togami teaches as described in the above rejections under 35 U.S.C. 103.
It would therefore have been prima facie obvious to administer a compound claimed by ‘520 for the purposes of treating fibrosis, because the claims of ‘520 acknowledge their compounds as inhibiting inflammasome activation, Artlett teaches inflammasome activation contributes to the development of fibrosis, and Ambati ‘327 teaches compounds for inhibiting inflammasome activation and treating additional conditions, including pulmonary fibrosis. Accordingly, it would have been obvious to practice the method claimed by ‘520 of inhibiting inflammasome activation for the purposes of treating fibrosis, such as pulmonary fibrosis, because Artlett teaches that inhibition of the inflammasome can reduce symptoms of fibrosis and Ambati ‘327 teaches methods of inhibiting inflammasome activity and treating pulmonary fibrosis.
Regarding formulations and drug delivery systems of claims 6-7 and 49, because Ambati ‘327 acknowledges that drug depots can control the rate of drug release and Togami teaches targeted delivery of therapeutics to lung fibroblast cells using liposomes modified with truncated basic fibroblast growth factor for treating pulmonary fibrosis, one of ordinary skill in the art would have contemplated these formulations when practicing the method claimed by ‘520, because said formulations may enable more effective treatment of pulmonary fibrosis.
Regarding combinations of therapeutics, because Ambati ‘327 recites additional therapeutics for inhibiting the inflammasome, including the specific compounds recited in claim 17 of Ambati ‘327, it would have been obvious to administer a compound claimed by ‘520 in combination with a compound recited by Ambati ‘327 for the purposes of treating pulmonary fibrosis, because the combination of said compounds may be more effective for inhibiting inflammasome activation and thus treating pulmonary fibrosis than either compound administered alone.
Claims 1, 3-9, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 9, and 14-16 of U.S. Patent 9,326,983 B2 (reference patent, hereinafter ‘983) in view of Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022), Artlett (Artlett, C. M. The Open Rheumatology Journal 2012, vol. 6, supplement 1:M3, pp. 80-86; cited in PTO-892) and Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
The present application and ‘983 each include Jayakrishna Ambati as an inventor.
Claim 1 of ‘983 recites a method for treating retinal degeneration, comprising: administering an effective amount of a composition to a subject in need of treatment for retinal degeneration, wherein the composition comprises a reverse transcriptase inhibitor selected from those listed therein, which includes stavudine, lamivudine, cordycepin, azidothymidine, and abacavir. Claim 2 of ‘983 claims the method of claim 1, comprising inhibiting inflammasome activation by Alu RNA associated with a cell, and claim 9 requires the composition comprises a pharmaceutically acceptable carrier.
Claim 14 of ‘983 claims a method for treating retinal degeneration, comprising:
administering an effective amount of a composition to a subject in need of treatment for retinal degeneration, wherein the composition comprises a compound of structure (i) or (ii) as shown. Claim 15 requires the composition further comprises: stavudine (d4T), lamivudine (3TC), cordycepin, azidothymidine (AZT), abacavir (ABC), or a combination thereof, and claim 16 requires inhibiting inflammasome activation by Alu RNA associated with a cell.
The claims of ‘983 do not claim treating fibrosis as recited in claim 1 or the specific limitations regarding formulation and administration as recited in claims 5-7 and 49.
Ambati ‘327 teaches as described in the above rejections under 35 U.S.C. 103. In addition, Ambati ‘327 teaches their methods may inhibit inflammasome activation by Alu RNA associated with a cell (cover page, Abstract, lines 1-4).
Artlett teaches as described in the above non-statutory double patenting rejection.
Togami teaches as described in the above rejections under 35 U.S.C. 103.
It would therefore have been prima facie obvious to administer a compound claimed by ‘983 for the purposes of treating fibrosis, because the claims of ‘983 acknowledge their compounds as inhibiting inflammasome activation, Artlett teaches inflammasome activation contributes to the development of fibrosis, and Ambati ‘327 teaches compounds for inhibiting inflammasome activation and treating additional conditions, including pulmonary fibrosis. Accordingly, it would have been obvious to practice the method claimed by ‘983 of treating retinal degeneration and inhibiting inflammasome activation for the purposes of treating fibrosis, such as pulmonary fibrosis, because Artlett teaches that inhibition of the inflammasome can reduce symptoms of fibrosis and Ambati ‘327 teaches methods of inhibiting inflammasome activity and treating pulmonary fibrosis.
Regarding administration, formulations and drug delivery systems of claims 5-7 and 49, because Ambati ‘327 acknowledges that drug depots can control the rate of drug release and Togami teaches targeted delivery of therapeutics to lung fibroblast cells using liposomes modified with truncated basic fibroblast growth factor for treating pulmonary fibrosis, one of ordinary skill in the art would have contemplated these formulations when practicing the method claimed by ‘520, because said formulations may enable more effective treatment of pulmonary fibrosis. Moreover, because Ambati ‘327 acknowledges formulations for, for example, oral administration, one of ordinary skill in the art would have contemplated practicing the method claimed by ‘983 with their compounds formulated for oral administration.
Regarding the additional therapeutic agent of claims 8-9, because the claims of ‘983 claim combinations of said therapeutics, one of ordinary skill in the art would have contemplated administering a combination of therapeutics as recited in claim 1 of ‘983, because said combination may be more effective for inhibiting inflammasome activation and thus treating fibrosis than administration of one of the single compounds claimed by ‘983. In addition, because the additional compound is expected to inhibit inflammasome activation, one of ordinary skill in the art would have recognized said compound as a treatment to inhibit progression of fibrosis, which as taught by Artlett, is correlated with progression of fibrosis.
Claims 1, 3-9, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, and 16 of U.S. Patent 12,274,701 B2 (reference patent, hereinafter ‘701) in view of Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022), Artlett (Artlett, C. M. The Open Rheumatology Journal 2012, vol. 6, supplement 1:M3, pp. 80-86; cited in PTO-892) and Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
The present application and ‘701 each include Jayakrishna Ambati as an inventor.
Claim 1 of ‘701 claims a method of blocking inflammasome activation, the method comprising administering to a patient in need thereof a nucleoside reverse transcriptase inhibitor (NRTI), whereby the NRTI blocks inflammasome activation, wherein the NRTI is selected from stavudine, lamivudine, abacavir, 5′-methoxy-d4T, or combinations thereof. Claim 11 claims the method of claim 1, wherein blocking inflammasome activation treats dry age-related macular degeneration in a patient having dry age-related macular degeneration. Claim 16 claims the method of claim 1, wherein the NRTI is a combination of at least two NRTIs selected from stavudine, lamivudine, abacavir, and 5′-methoxy-d4T.
The claims of ‘701 do not claim treating fibrosis as recited in claim 1 or the specific limitations regarding composition, formulation, and administration as recited in claims 3, 5-7 and 49.
Ambati ‘327 teaches as described in the above rejections under 35 U.S.C. 103. In addition, Ambati ‘327 teaches their methods may inhibit inflammasome activation by Alu RNA associated with a cell (cover page, Abstract, lines 1-4).
Artlett teaches as described in the above non-statutory double patenting rejection.
Togami teaches as described in the above rejections under 35 U.S.C. 103.
It would therefore have been prima facie obvious to administer a compound claimed by ‘701 for the purposes of treating fibrosis, because ‘701 claims a method for blocking inflammasome activation, Artlett teaches inflammasome activation contributes to the development of fibrosis, and Ambati ‘327 teaches compounds for inhibiting inflammasome activation and treating additional conditions, including pulmonary fibrosis. Accordingly, it would have been obvious to practice the method claimed by ‘701 for treating retinal degeneration and inhibiting inflammasome activation for the purposes of treating fibrosis, such as pulmonary fibrosis, because Artlett teaches that inhibition of the inflammasome can reduce symptoms of fibrosis and Ambati ‘327 teaches methods of inhibiting inflammasome activity and treating pulmonary fibrosis.
Regarding compositions, administration formulations, and drug delivery systems of claims 3, 5-7, and 49, because Ambati ‘327 acknowledges that drug depots and liposomes can control the rate of drug release and Togami teaches targeted delivery of therapeutics to lung fibroblast cells using liposomes modified with truncated basic fibroblast growth factor for treating pulmonary fibrosis, one of ordinary skill in the art would have contemplated these formulations when practicing the method claimed by ‘701, because said formulations may enable more effective drug delivery and more effective treatment of pulmonary fibrosis. Moreover, because Ambati ‘327 acknowledges formulations for, for example, oral administration, and teaches pharmaceutical compositions comprising the NRTI and pharmaceutically acceptable carriers, one of ordinary skill in the art would have contemplated practicing the method claimed by ‘701 with said pharmaceutical compositions and with their compounds formulated for oral administration.
Regarding the additional therapeutic agent of claims 8-9, because the claims of ‘701 claim combinations of said therapeutics, one of ordinary skill in the art would have contemplated administering a combination of therapeutics as recited in claim 1 of ‘701, because said combination may be more effective for inhibiting inflammasome activation and thus treating fibrosis than administration of one of the single compounds claimed by ‘701. In addition, because the additional compound is expected to inhibit inflammasome activation, one of ordinary skill in the art would have recognized said compound as a treatment to inhibit progression of fibrosis, which as taught by Artlett, is correlated with progression of fibrosis.
Claims 1, 3-9, and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent 10,300,057 B2 (reference patent, hereinafter ‘057) in view of Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022), Artlett (Artlett, C. M. The Open Rheumatology Journal 2012, vol. 6, supplement 1:M3, pp. 80-86; cited in PTO-892) and Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
The present application and ‘057 each include Jayakrishna Ambati as an inventor.
Claim 1 of ‘057 claims a method for treating rheumatoid arthritis, comprising:
administering an effective amount of a composition to a subject in need thereof, wherein the composition comprises a pharmaceutically acceptable carrier and a compound selected from a group that includes (iii) stavudine (d4T); (iv) azidothymidine (AZT); (v) abacavir (ABC); and (vi) a combination thereof. Claim 2 depends from claim 1 and requires inhibiting inflammasome activation by Alu RNA associated with a cell.
The claims of ‘057 do not claim treating fibrosis as recited in claim 1. In addition, the claims of ‘057 do not claim the specific limitations regarding composition, formulation, and administration as recited in claims 3, 5-7, and 49.
Ambati ‘327 teaches as described in the above rejections under 35 U.S.C. 103. In addition, Ambati ‘327 teaches their methods may inhibit inflammasome activation by Alu RNA associated with a cell (cover page, Abstract, lines 1-4).
Artlett teaches as described in the above non-statutory double patenting rejection.
Togami teaches as described in the above rejections under 35 U.S.C. 103.
It would therefore have been prima facie obvious to administer a compound claimed by ‘057 for the purposes of treating fibrosis, because ‘057 claims a method for treating rheumatoid arthritis that requires inhibiting inflammasome activation, Artlett teaches inflammasome activation contributes to the development of fibrosis, and Ambati ‘327 teaches compounds for inhibiting inflammasome activation and treating additional conditions, including pulmonary fibrosis. Accordingly, it would have been obvious to practice the method claimed by ‘057 of treating rheumatoid arthritis and inhibiting inflammasome activation for the purposes of treating fibrosis, such as pulmonary fibrosis, because Artlett teaches that inhibition of the inflammasome can reduce symptoms of fibrosis and Ambati ‘327 teaches methods of inhibiting inflammasome activity and treating pulmonary fibrosis.
Regarding compositions, administration formulations, and drug delivery systems of claims 3, 5-7, and 49, because Ambati ‘327 acknowledges that drug depots can control the rate of drug release and Togami teaches targeted delivery of therapeutics to lung fibroblast cells using liposomes modified with truncated basic fibroblast growth factor for treating pulmonary fibrosis, one of ordinary skill in the art would have contemplated these formulations when practicing the method claimed by ‘057, because said formulations may enable more effective treatment of pulmonary fibrosis. Moreover, because Ambati ‘327 acknowledges formulations for, for example, oral administration, and teaches pharmaceutical compositions comprising the NRTI and pharmaceutically acceptable carriers, one of ordinary skill in the art would have contemplated practicing the method claimed by ‘057 with said pharmaceutical compositions and with their compounds formulated for oral administration.
Regarding the additional therapeutic agent of claims 8-9, because the claims of ‘057 claim combinations of said therapeutics, one of ordinary skill in the art would have contemplated administering a combination of therapeutics as recited in claim 1 of ‘057, because said combination may be more effective for inhibiting inflammasome activation and thus treating fibrosis than administration of one of the single compounds claimed by ‘057. In addition, because the additional compound is expected to inhibit inflammasome activation, one of ordinary skill in the art would have recognized said compound as a treatment to inhibit progression of fibrosis, which as taught by Artlett, is correlated with progression of fibrosis.
Claims 1, 3-4, and 8-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, and 10 of U.S. Patent 11,602,535 B2 (reference patent, hereinafter ‘535).
The present application and ‘535 each include Jayakrishna Ambati as an inventor.
Claim 1 of ‘535 claims a method of treating a condition selected from those listed therein, including renal fibrosis, pulmonary fibrosis, and cystic fibrosis, comprising administering to a subject in need thereof a compound selected from the group that includes stavudine, lamivudine, and abacavir. Claim 9 requires the compound is selected from (vi) stavudine (d4T); (vii) lamivudine (3TC); (viii) cordycepin; (x) abacavir (ABC); and (xi) a combination thereof. Claim 10 requires the method comprises administering a composition comprising the compound and a pharmaceutically acceptable carrier.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to administer a compound claimed by ‘535 for the purposes of treating renal fibrosis, pulmonary fibrosis, or cystic fibrosis, because these are diseases claimed by ‘535, and thus one of ordinary skill in the art would have recognized these diseases as effectively treated by administering a compound of claim 9 of ‘535. In addition, the combination of drugs recited in claim 9 of ‘535 would satisfy the requirements of claims 8 and 9, wherein the second drug is reasonably considered a therapeutic for treating fibrosis, because it is claimed by ‘535 for treating diseases that include fibrosis.
Claims 5-7 and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, and 10 of U.S. Patent 11,602,535 B2 (reference patent, hereinafter ‘535) as applied to claims 1, 3-4, and 8-9 above, and further in view of Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022) and Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
The present application and ‘535 each include Jayakrishna Ambati as an inventor.
The claims of ‘535 claim as described in the above non-statutory double patenting rejection.
The claims of ‘535 do not claim the formulations of present claims 5-7 or 49.
Ambati ‘327 and Togami teach as described in the above rejections under 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to practice the method of treating fibrosis claimed by ‘535 with compounds formulated for administration by injection, in a depot, or in a liposome, because Ambati ‘327 teaches formulations that may be used in their method of treating fibrosis, such as pulmonary fibrosis, and because Togami teaches liposome formulations with targeting peptides to improve delivery of therapeutics to lung fibroblasts. Accordingly, one of ordinary skill in the art would have considered formulating the compounds claimed by ‘535 as taught by Ambati ‘327 and Togami when practicing the method claimed by ‘535 for treating fibrosis.
Claims 1 and 8-9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 4 of copending U.S. patent application 17/637557 (reference application, hereinafter ‘557) in view of Biswas (Biswas, R.; et al. Pulmonary Medicine 2011, Article ID 10570; cited in PTO-892).
The present application and ‘557 each include Jayakrishna Ambati and Kameshwari Ambati as inventors and are assigned to the University of Virginia Patent Foundation.
The claims received August 1, 2022 are cited in this provisional non-statutory double patenting rejection.
Claim 1 of ‘557 claims a method for treating and/or preventing a disease, disorder, or condition associated with an NLR family CARD domain containing 4 (NLRC4) inflammasome biological activity, the method comprising administering to a subject in need thereof a composition comprising, consisting essentially of, or consisting of a nucleoside reverse transcriptase inhibitor (NRTI).
Claim 2 of ‘557 claims the NRTI is selected from the group consisting of abacavir (ABC), adefovir (bis-POM PMEA), amdoxovir, apricitabine (AVX754), censavudine, didanosine (DOI), elvucitabine, emtricitabine (FTC), entecavir (ETV), lamivudine (3TC), racivir, stampidine, stavudine (d4T), tenofovir disoproxil (TDF), tenofovir alafenamide (GS-7340), zalcitabine (ddC), zidovudine (ZDV)/azidothymidine (AZT), derivatives thereof, optionally alkylated derivatives thereof, further optionally tri-methoxy-3TC.
Claim 4 of ‘557 requires further comprising administering to the subject in need thereof at least one additional inhibitor of the NLRC4 inflammasome biological activity.
The claims of ‘557 do not claim a method for treating and/or inhibiting progression of fibrosis, as recited in present claim 1.
Biswas teaches the potential role of inflammasome-derived inflammatory cytokines in pulmonary fibrosis (p. 1, Title). Biswas teaches pulmonary fibrosis is a progressive, disabling disease with treatment options limited due to poor understanding of the molecular mechanisms of the disease progression. Biwas teaches recent progress in inflammasome research has greatly contributed to our understanding of its role in inflammation and fibrosis development (p. 1, Abstract, lines 1-5).
Biswas teaches that activation of proinflammatory cytokines following inflammasome assembly, such as IL-1β and IL-18, has been associated with development of pulmonary fibrosis, and that components of the inflammasome complex itself, such as the adaptor protein ASC, have been associated with pulmonary fibrosis development. Biwas teaches that recent evidence suggesting that the fibrotic process can be reversed via blockade of pathways associated with inflammasome activity may provide hope for future drug strategies (p. 1, Abstract, lines 6-9).
Biswas teaches that the NALP is a member of the NOD-like receptor (NLR) family, and other family members of NLR are NAIP and NLRC4 (p. 3, left column, Section 3, second paragraph, lines 1-4) (emphasis added). Biswas teaches it is thought that the main function of the NLR is the regulation of proinflammatory cytokines such as IL-1β and IL-18, and diverse molecular entities including bacteria, viruses, components of dying cells, immune activators, and crystalline or aggregated materials can activate NLR protein (p. 3, right column, first paragraph, lines 5-10).
It would therefore have been prima facie obvious to one of ordinary skill in the art to practice the method claimed by ‘557 for treating fibrosis. One of ordinary skill in the art would have been motivated to practice the method claimed by ‘557 for treating fibrosis because ‘557 claims a method for treating a condition associated with an NLR family CARD domain containing 4 (NLRC4) inflammasome biological activity, and because Biswas teaches the connection between fibrosis and inflammasome activity, specifically citing NLRC4 as one such NLR protein involved in inflammasome signaling via IL-1β and IL-18. Accordingly, one of ordinary skill in the art would have recognized fibrosis as one such disease associated with NLCR4 inflammasome activity, and thus would have considered practicing the method claimed by ‘557 for the purposes of treating fibrosis.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 3-7 and 49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 4 of copending U.S. patent application 17/637557 (reference application, hereinafter ‘557) in view of Biswas (Biswas, R.; et al. Pulmonary Medicine 2011, Article ID 10570; cited in PTO-892) as applied to claims 1 and 8-9 above, and further in view of Ambati ‘327 (U.S. pre-grant publication no. US 20180044327 A1; cited in IDS received September 19, 2022) and Togami (Togami, K.; et al. Biological and Pharmaceutical Bulletin 2015, vol. 38, pp. 270-276; cited in PTO-892).
The present application and ‘557 each include Jayakrishna Ambati and Kameshwari Ambati as inventors and are assigned to the University of Virginia Patent Foundation.
The claims of ‘557 claim as described in the above non-statutory double patenting rejection.
The claims of ‘557 do not claim the compositions or formulations of present claims 3-7 or 49.
Ambati ‘327 and Togami teach as described in the above rejections under 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to practice the method of treating pulmonary fibrosis obvious over the claims of ‘557 in view of Biswas with compounds formulated for administration by injection, in a depot, or in a liposome, because Ambati ‘327 teaches these formulations that may be used in their method of treating fibrosis, including pulmonary fibrosis, and because Togami teaches liposome formulations with targeting peptides to improve delivery of therapeutics to lung fibroblasts. Accordingly, one of ordinary skill in the art would have considered formulating the compounds claimed by ‘557 as taught by Ambati ‘327 and Togami when practicing the method of treating pulmonary fibrosis obvious over the claims of ‘557 in view of Biswas. Moreover, because Ambati ‘327 acknowledges formulations for, for example, oral administration, and teaches pharmaceutical compositions comprising an NRTI and pharmaceutically acceptable carriers, one of ordinary skill in the art would have contemplated practicing the method claimed by ‘557 with said pharmaceutical compositions and with their compounds formulated for oral administration.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not been patented.
Response to Applicant’s arguments: Regarding the previous nonstatutory double patenting rejections over the above U.S. patents and co-pending applications, Applicant argues that the present claim 1 is amended to relate to treating coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis, and none of ‘220, ‘520, ‘983, ‘701, ‘057, and ‘535 claim independent inventions not related to treating coronavirus infection, acute respiratory distress syndrome, cytokine storm syndrome, and/or fibrosis.
Applicant’s arguments have been fully considered, and insofar as these arguments apply to the above nonstatutory double patenting rejections, these arguments are not persuasive. As described, inflammasome activation is correlated with fibrosis, as taught by Artlett, and methods of inhibiting inflammasome activation may be reasonably practiced for the purposes of treating disease, including pulmonary fibrosis, renal fibrosis, and cystic fibrosis, as taught by Ambati ‘327. Accordingly, the claimed inventions described in the above U.S. patents and patent applications render obvious the treating of fibrosis by administration of the compounds recited in the present claims.
In addition, regarding Applicant’s arguments that the compound and composition claims in ‘220 are distinct inventions from the methods claimed in ‘220 and thus cannot support the obviousness of the present invention, the examiner maintains that a pharmaceutical composition comprising the compound of ‘220 for use in practicing the method of ‘220 would have been obvious in view of the claims of ‘220. However, even if the composition of ‘220 were not used to support an obviousness rejection, the composition required for practicing the method of the present claims would have been obvious over ‘220 in view of Ambati ‘327, because Ambati ‘327 renders obvious practicing the method of the present claims with a pharmaceutical composition.
Allowable Subject Matter
Claims 10, 11, 13, 14, 15, 16, and 51 are allowed.
Independent claim 10 claims a method for inhibiting development of macular degeneration in a subject at risk therefor, the method comprising administering to the subject a composition comprising, consisting essentially of, or consisting of 3'-Azido-3'-deoxythymidine β-D-glucuronide (GAZT), 3'-Amino-3'-deoxythymidine (AMT), lamivudine (R)-sulfoxide (LSO) in an amount and via a route effective for inhibiting development of macular degeneration in the subject. The prior art does not provide an expectation that administration of any of these compounds would be effective for inhibiting development of macular degeneration. Claims 11, 13-16, and 51 depend from claim 10 and further limit its subject matter.
The closest prior art to the method of claim 10 is considered Narendran (Narendran, S.; et al. Investigative Ophthalmology and Visual Science 2020, vol. 61, article 4; cited in PTO-892). Narendran teaches a study in which their aim was to evaluate the efficacy of 5’-glucuronyl
azidothymidine (GAZT), an antiretrovirally inert hepatic clinical metabolite of AZT, in
mouse models of retinal pigment epithelium (RPE) degeneration and choroidal neovascularization (CNV), which are hallmark features of dry and wet age-related macular degeneration (AMD) (p. 1, Abstract, Purpose section, lines 3-7). Narendran teaches that GAZT inhibited Alu RNA-induced RPE degeneration and laser-induced CNV, and reduced Alu RNA-induced caspase-1 activation and IL-1β release in bone marrow-derived macrophages (p. 1, Abstract, Results section, lines 1-2). Narendran concludes by stating that GAZT possesses dual anti-inflammatory and anti-angiogenic properties and could be a viable treatment option for both forms of AMD (p. 1, Abstract, Conclusions section, lines 1-2).
However, Narendran was published online on August 4, 2020, later than the effective filing date of the present application. Because the subject matter of claims 10, 11, 13, 14, 15, 16, and 51 is supported by U.S. provisional application 62/992577 (for example, see claims 10-11, 13-15, specification p. 46, lines 3-8 of 62/992577), Narendran is not eligible as prior art under 35 U.S.C. 102(a)(1) or 102(a)(2).
In addition, the examiner has not identified prior art that identifies a biological activity of lamivudine (R)-sulfoxide, much less an activity that would be useful for inhibiting development of macular degeneration. Johnson (Johnson, M. A.; et al. British Journal of Clinical Pharmacology 1998, vol. 46, pp. 21-27; cited in PTO-892) teaches the conversion of lamivudine to the lamivudine metabolite lamivudine sulfoxide (p. 21, Figure 1). Johnson teaches that the pharmacokinetics of the sulfoxide metabolite in subjects with renal dysfunction have not been established, but that significantly higher systemic exposure to lamivudine and therefore the metabolite in toxicological studies in rat and dog has yielded no effects of clinical concern, and the metabolite has been shown to be pharmacologically inactive in in-vitro antiviral screens (p. 26, left column, third full paragraph) (emphasis added). Therefore, because the prior art does not teach another biological activity for lamivudine (R)-sulfoxide, and because Johnson teaches it as pharmacologically inactive in antiviral screens, one of ordinary skill in the art would not have administered it to a subject with a reasonable expectation of inhibiting development of macular degeneration.
Although 3'-Amino-3'-deoxythymidine is recognized as having anti-cancer activity, the prior art does not teach it as effective for inhibiting development of macular degeneration. Lin (Lin, T.-S.; Prusoff, W. H. Journal of Medicinal Chemistry 1978, vol. 21, pp. 109-112; cited in PTO-892) teaches 3'-Amino-3'-deoxythymidine is a potent inhibitor of the replication of both murine sarcoma 180 cells (ED50 = 5 µM) and murine L1210 cells (ED50 = 1 µM) in vitro (p. 109, Abstract, lines 4-5). Therefore, one of ordinary skill in the art would recognize 3'-Amino-3'-deoxythymidine as a potential anti-cancer therapy. However, Lin does not teach or suggest these compounds as effective for treating macular degeneration, and thus one would not have administered it to a subject with a reasonable expectation of inhibiting development of macular degeneration.
Accordingly, one of ordinary skill in the art would not have been motivated to administer any of 3'-Azido-3'-deoxythymidine β-D-glucuronide (GAZT), 3'-Amino-3'-deoxythymidine (AMT), lamivudine (R)-sulfoxide (LSO) in an amount and via a route effective for treating and/or inhibiting development of macular degeneration to a subject for the purposes of inhibiting development of macular degeneration.
Conclusion
Claims 10-11, 13-16, and 51 are allowed.
Claims 1, 3-9, 18-20, 49-50, and 52 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN BRANDSEN whose telephone number is (703)756-4780. The examiner can normally be reached Monday - Friday from 9:00 am to 5:00 pm.
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.
/B.M.B./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693