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 .
Detailed Action
This application is a national stage application of PCT/US2022/021322, filed March 22, 2022, which claims benefit of provisional application 63/166567, filed March 26, 2021. Claims 1-33 are pending in this application and examined on the merits herein.
Claim Objections
Claim 4 is objected to because of the following informalities: the identification of the RNA virus as “SAR2-CoV-2.” This appears to be a typographical error, with the correct name being “SARS-CoV-2.” Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, 4-8, 10-11, 13, 16, 18, 19, 22, and 27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deans et al. (US pre-grant publication 2019/0209598, cited in PTO-1449)
Independent claim 1 is directed to a method of treating a subject infected with an RNA virus comprising administering to the subject a cytidine deaminase inhibitor. Dependent claims 2-3 further define the cytidine deaminase inhibitor as one of a number of tetrahydrouridine derivatives. Dependent claim 4 defines the RNA virus as a coronavirus. Dependent claims 5-7 specify that the subject is further administered a pyrimidine synthesis inhibitor.
Deans et al. discloses compositions and methods for treating viral infections by administering a dihydroorotate dehydrogenase (DHODH) inhibitor and a pyrimidine salvage inhibitor to a subject. (p. 1 paragraph 6) Note that since DHODH is involved in pyrimidine synthesis, DHODH inhibitors are pyrimidine synthesis inhibitors. Viruses treatable in this manner include RNA viruses, such as SARS, which is a coronavirus. (p. 1 paragraph 13, p. 5 paragraph 49) Specific pyrimidine salvage pathway inhibitors include cytidine deaminase inhibitors such as tetrahydrouridine. (p. 8 paragraph 73) Specific DHODH inhibitors include teriflunomide and leflunomide (p. 16 paragraph 165 – p. 17 paragraph 167) Regarding claims 8 and 16, additional active agents can be administered such as the polymerase inhibitors zidovudine and lamivudine. (p. 13 paragraph 135) Regarding claims 10-11, Deans et al. describes the subject as a human. (p. 13 paragraph 129) note that in the absence of further definition, “animal” is interpreted as including human subjects. While the last paragraph of p. 3 in the present specification describes an animal as “e.g. a dog, cat, horse, cow, pig, or other livestock,” this appears to be merely a listing of exemplary embodiments and not a limiting definition of “animal” as only these species or as excluding humans. Regarding claim 13, Deans et al. describes oral administration of the compound. (p. 12 paragraph 115) Regarding claim 18, the compositions can be provided including a buffering agent. (p. 13 paragraph 133)
Regarding claim 19, as discussed previously the pharmaceutical composition can be provided as an oral dosage form. Regarding claim 27, the term “in vitro composition” appears to merely describe an intended use and not to structurally limit the claims in a way that would exclude the therapeutic compositions described by Deans et al.
For these reasons Deans et al. anticipates the present claims.
Claims 24-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yusa et al. (Reference included with PTO-892)
Claim 24 claims a composition comprising a cytidine deaminase inhibitor and a RNA virus. Claim 25 further specifies that the RNA virus is selected from a number of specific compounds including tetrahydrouridine. Yusa et al. discloses a study of resistance of HIV-1 infected cells to ARA-C. (p. 16848 right column second paragraph) In one experiment HIV-1 infected cells were treated with THU to determine the effect on resistance to ARA-C. (p. 16850 left column last paragraph) This cell culture, containing HIV-infected cells, and THU, is a composition containing a cytidine deaminase inhibitor and a RNA virus according to claims 24 and 25, thereby anticipating the claimed invention.
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.
Claims 1, 2, 4-8, 10-13, 16, 18, 19, 22, and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. (US pre-grant publication 2019/0209598, cited in PTO-1449)
The disclosure of Deans et al. is discussed above. While as discussed previously, Deans et al. is seen to anticipate the present claims, even assuming for the sake of argument that Deans et al. is not specifically seen as disclosing the particular composition, methods, and pharmaceutical combinations described in the present claims. In particular, one of ordinary skill in the art would have seen the mentions of specific agents such as tetrahydrouridine, teriflunomide, and leflunomide as suggesting using these particular agents in combination therapies as described in the reference.
Regarding claim 12, the dosage of each active ingredient is listed as being selected from a number of different values ranging from 0.1 micrograms to 750 mg per day. (p. 14 paragraph 137) This would reasonably be considered to be an indication that the dosage of each of the different compounds is a result-effective variable. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to determine the appropriate dosage for these compounds.
Regarding claim 28, as discussed previously, Deans et al. describes the compositions as usable for treating a subject infected with an RNA virus. Therefore one of ordinary skill in the art would have seen this fact as motivation to include written instructions with the composition describing it as useful for such.
For these reasons the invention taken as a whole is prima facie obvious.
Claims 3 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. as applied to claims 1, 2, 4-8, 10-13, 16, 18, 19, 22, and 27-28 above, and further in view of Hamilton et al. (US pre-grant publication 2009/0137521, cited in PTO-1449)
The disclosure of Deans et al. is discussed above. Deans et al. does not specifically disclose an embodiment wherein the cytidine deaminase inhibitor has a structure falling within the scope of the structure recited in present claims 3 and 23, specifically wherein R1 and R2 are as defined so as to exclude tetrahydrouridine.
Hamilton et al. discloses compounds and compositions that inhibit CDA activity. (p. 2 paragraph 12) These compounds have a structure substantially overlapping with the structure recited in the present claims. (p. 2 paragraphs 13-18) Various specific structures of CDA inhibitors are disclose including ones falling within the scope of present claims 3 and 23. (pp. 3-6 paragraphs 23-24)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use any of the CDA inhibitors described by Hamilton et al. as the CDA inhibitor in place of tetrahydrouridine in the compositions and methods described by Deans et al. One of ordinary skill in the art would have regarded these two different CDA inhibitors as being equivalents usable for the same purpose.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Yusa et al. as applied to claims 24 and 25 above, and further in view of Hamilton et al. (US pre-grant publication 2009/0137521)
The disclosure of Yusa et al. are discussed above. Yusa et al. does not specifically disclose an embodiment wherein the cytidine deaminase inhibitor has a structure falling within the scope of the structure recited in present claim 26, specifically wherein R1 and R2 are as defined so as to exclude tetrahydrouridine.
Hamilton et al. discloses compounds and compositions that inhibit CDA activity. (p. 2 paragraph 12) These compounds have a structure substantially overlapping with the structure recited in the present claims. (p. 2 paragraphs 13-18) Various specific structures of CDA inhibitors are disclose including ones falling within the scope of present claims 3 and 23. (pp. 3-6 paragraphs 23-24)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use any of the CDA inhibitors described by Hamilton et al. as the CDA inhibitor in place of tetrahydrouridine in the method described by Yusa et al. One of ordinary skill in the art would have regarded these two different CDA inhibitors as being equivalents usable for the same purpose, in this case the study of drug resistance in HIV-infected cells.
For these reasons the invention taken as a whole is prima facie obvious.
Claims 14, 21, 29, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. as applied to claims 1, 2, 4-8, 10-13, 16, 18, 19, 22, and 27-28 above, and further in view of Ojewole et al. (Reference included with PTO-892)
The disclosure of Deans et al. is discussed above. Deans et al. does not specifically disclose an embodiment wherein the pharmaceutical composition is an orally ingestible pill or capsule. However, Deans et al. does disclose sustained release dosage forms. (p. 13 paragraph 134) Ojewole et al. discloses the use of sustained release enteric coating systems for delivering antiretroviral drugs. (pp. 698-699 section 3.1) Enteric coating was one sustained release technique used to improve the stability of a different nucleoside antiretroviral. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to provide the pharmaceutical compositions described by Deans et al. as enteric coated oral formulations such as pills. One of ordinary skill in the art would have understood that treatment of retroviral infection is an embodiment of the methods described by Deans, and would have seen enteric coating to prolong release and improve stability as predictable application of a known improvement to an existing prior art product.
For these reasons the invention taken as a whole is prima facie obvious.
Claims 30 and 31 are rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. in view of Ojewole et al. as applied to claims 14, 21, 29, and 32 above, and further in view of Pissinati et al. (Reference included with PTO-892)
The disclosures of Deans et al. and Ojewole et al. are discussed above. Deans et al. in view of Ojewole et al. does not specifically disclose an embodiment wherein the enteric coating is soft gelatin. However, Pissinati et al. describes soft gelatin coating as one form of enteric coating. Therefore it would have been obvious to one of ordinary skill in the art at the time of the invention to use soft gelatin as the enteric coating in the enteric coated compositions described by Ojewole et al. One of ordinary skill in the art would have seen Ojewole et al. as generally suggesting using any available enteric coating, and Pissinati et al. as indicating that soft gelatin was such a coating material.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. in view of Ojewole et al. as applied to claims 14, 21, 29, and 32 above, and further in view of Hamilton et al. (US pre-grant publication 2009/0137521)
The disclosures of Deans et al. and Ojewole et al. are discussed above. Deans et al. in view of Ojewole et al. does not specifically disclose an embodiment wherein the cytidine deaminase inhibitor has a structure falling within the scope of the structure recited in present claim 26, specifically wherein R1 and R2 are as defined so as to exclude tetrahydrouridine.
Hamilton et al. discloses compounds and compositions that inhibit CDA activity. (p. 2 paragraph 12) These compounds have a structure substantially overlapping with the structure recited in the present claims. (p. 2 paragraphs 13-18) Various specific structures of CDA inhibitors are disclose including ones falling within the scope of present claims 3 and 23. (pp. 3-6 paragraphs 23-24)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use any of the CDA inhibitors described by Hamilton et al. as the CDA inhibitor in place of tetrahydrouridine in the method described by Deans et al. One of ordinary skill in the art would have regarded these two different CDA inhibitors as being equivalents usable for the same purpose.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 26 is rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. in view of Ojewole et al. as applied to claims 14, 21, 29, and 32 above, and further in view of Hamilton et al. (US pre-grant publication 2009/0137521, cited in PTO-1449)
The disclosures of Deans et al. and Ojewole et al. are discussed above. Deans et al. in view of Ojewole et al. does not specifically disclose an embodiment wherein the cytidine deaminase inhibitor has a structure falling within the scope of the structure recited in present claims 3 and 23, specifically wherein R1 and R2 are as defined so as to exclude tetrahydrouridine.
Hamilton et al. discloses compounds and compositions that inhibit CDA activity. (p. 2 paragraph 12) These compounds have a structure substantially overlapping with the structure recited in the present claims. (p. 2 paragraphs 13-18) Various specific structures of CDA inhibitors are disclose including ones falling within the scope of present claims 3 and 23. (pp. 3-6 paragraphs 23-24)
It would have been obvious to one of ordinary skill in the art at the time of the invention to use any of the CDA inhibitors described by Hamilton et al. as the CDA inhibitor in place of tetrahydrouridine in the compositions and methods described by Deans et al. One of ordinary skill in the art would have regarded these two different CDA inhibitors as being equivalents usable for the same purpose.
For these reasons the invention taken as a whole is prima facie obvious.
Claims 9, 15, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. as applied to claims 1, 2, 4-8, 10-13, 16, 18, 19, 22, and 27-28 above, and further in view of Stasi et al. (Reference included with PTO-892)
The disclosure of Deans et al. is discussed above. Deans et al. does not disclose a method further comprising administering remdesivir and/or an anticoagulant, or one wherein the patient is on a ventilator. However, as discussed previously Deans et al. does generally describe treating RNA viruses including SARS.
Stasi et al. discloses a review of treatments for COVID-19, a condition caused by infection with the coronavirus (RNA virus) SARS-CoV2. (p. 1 left column, p. 2 left column second paragraph) Antiviral agents including remdesivir (p. 3 section 2.1.2) and anticoagulants (p. 7 section 2.3.5) are described as therapies used for this indication. In particular, patients are also described as requiring mechanical ventilation in some cases, particularly those being treated with remdesivir.
It would have been obvious to one of ordinary skill in the art at the time of the invention to administer the therapy described by Deans et al. in combination with remdesivir and/or an anticoagulant for the treatment of COVID-19. One of ordinary skill in the art would have recognized the disclosure of Deans et al. as being generally applicable for the treatment of RNA viruses including the closely related SARS coronavirus, and would therefore have expected it to be useful for treating COVID-19. As a result, combining this therapy with the other known agents would merely be a case of coadministering two different therapies known to be individually useful for the same purpose. Regarding the treatment of a patient on a ventilator, Satsi et al. indicates that a portion of patients suffering from severe COVID-19 require mechanical ventilation. Therefore this is a portion of patients whom it would be obvious to treat using available therapies for severe COVID-19.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Deans et al. as applied to claims 1, 2, 4-8, 10-13, 16, 18, 19, 22, and 27-28 above, and further in view of Parvathaneni et al. (Reference included with PTO-892)
The disclosure of Deans et al. is discussed above. Deans et al. does not disclose an article of manufacture comprising a nebulizer. However, Parvathaneni et al. discloses that there exists a need for inhalable antiviral therapies for COVID-19. (p. 106 second paragraph) Furthermore Parvathaneni et al. describes the use of nebulizers to deliver said inhaled therapy. (p. 107 first paragraph)
It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to administer the therapy described by Deans et al. using a nebulizer. One of ordinary skill in the art would have seen Parvathaneni et al. as providing a motivation to use nebulizers for inhaled delivery of antiviral agents.
For these reasons 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 19 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11376270. (Cited in PTO-892, herein referred to as ‘270) Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘270 claims an orally ingestible dosage form including the cytidine deaminase inhibitor tetrahydrouridine, thereby anticipating present claims 19 and 22.
Claims 19 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9265785. (Cited in PTO-892, herein referred to as ‘785) Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘785 claims an orally ingestible dosage form including the cytidine deaminase inhibitor tetrahydrouridine, thereby anticipating present claims 19 and 22.
Claims 19 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 9259469. (Cited in PTO-892, herein referred to as ‘469) Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘469 claims an orally ingestible dosage form including the cytidine deaminase inhibitor tetrahydrouridine, thereby anticipating present claims 19 and 22.
Claims 19 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 10517884. (Cited in PTO-892, herein referred to as ‘884) Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘884 claims an orally ingestible dosage form including the cytidine deaminase inhibitor tetrahydrouridine, thereby anticipating present claims 19 and 22.
Claims 19 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11096953. (Cited in PTO-892, herein referred to as ‘953) Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘953 claims an orally ingestible dosage form including the cytidine deaminase inhibitor tetrahydrouridine, thereby anticipating present claims 19 and 22.
Claims 19 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/239460 (reference application, pre-grant publication 2024/0058367, cited in PTO-892, herein referred to as ‘460). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of ‘460 claims an orally ingestible dosage form including the cytidine deaminase inhibitor tetrahydrouridine, thereby anticipating present claims 19 and 22.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed in this action.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 1/7/2026