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 .
Status of the Claims
Claims 1-4, 6-7, 11-12, 14-17, 21-23, and 25-32 are pending in this application. Claims 5, 8-10, 13, 18-20, 24, and 33 have been cancelled by applicant.
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 1-4, 7, 15-16, 21, 27, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold et al. (Org. Lett. 2002, 4, 1323-2325 – previously cited) (“Arnold”); in view of Arnold et al. (US 2005/0203069 A1 – From IDS – previously cited) (“US ‘069”).
Regarding claims 1-4, Arnold teaches the C-based diazenimdiolate compound 1 below as an NO-donor for use in biomedical research (abstract and col. 1, page 1323), reading on the instant compounds of Formula I-III when X is H and M is Na.
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Regarding claim 7, Arnold teaches their compound has a total releasable NO of 0.76 mol/mol of compound 1 (Table 1, page 1324, col. 2, end), with a half-life of 1.6 min (initial release) followed by a second reaction with a half-life of 51 min (page 1325, para. bridging col. 1-2).
Further regarding the instantly claimed ranges of 0.1-8.0 µmol/ g and a half-life of 0.1-24 h, etc. as recited in claim 7, Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
While Arnold doesn’t specifically teach: (i) treatment of cardiovascular disease (claim 15); (ii) metabolic syndrome (claim 16); (iii) platelet aggregation (claim 21); (iv) restenosis inhibition (claim 27); (v) gastrointestinal disorders (claim 29); or (vi) sexual dysfunction (claim 30); the teachings of US ‘069 are relied upon for these disclosures.
US ‘069 teaches their functionally equivalent, NO-releasing, C-based diazenimdiolate compounds having the formula below, wherein x can be 0, y can be 3, R-3 can be phenyl, and R2 can be a counterion (US ‘069 claims 1-2). US ‘069 discloses these compounds, like Arnold’s compounds, release NO under physiological conditions (US ‘069 claim 1) and thus discloses the applicability of the compounds as pharmaceutical agents for the treatment of conditions where administration of NO would be beneficial, specifically mentioning impotence (reading on sexual dysfunctions), irritable bowel syndrome (reading on gastrointestinal disorders), cancer, and microbial infections (reading on fever) [0045].
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Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to treat conditions wherein NO administration would be beneficial by administering Arnold’s compound 1 (instant compounds of Formula I-III). One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Arnold’s disclosure that their functionally equivalent NO donors are useful in biomedical research (column 1, page 1323); and US ‘069 discloses their functionally equivalent NO donors as beneficial for treating diseases, such as impotence (reading on sexual dysfunctions), irritable bowel syndrome (reading on gastrointestinal disorders), cancer, and microbial infections (reading on fever) [0045].
Regarding claim 15, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis and cardiovascular disorders [0006] and [0045]. US ‘069 specifically teaches treatment of pulmonary hypertension with their compounds [0066].
Regarding claim 16, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis [0006]. As mentioned in the claim interpretation of non-final action mailed 07/16/2025, metabolic syndrome increases the risk of coronary heart disease. Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Arnold’s NO-releasing compound to a subject suffering from metabolic syndrome. One of ordinary skill would have been motivated to do so to regulate cardiovascular homeostasis, as taught by US ‘069, which would be expected to be negatively impacted by the presence of metabolic syndrome. One of ordinary skill would have had a reasonable expectation of success in view of Arnold’s disclosure of their compound 1 as an NO-releasing agent for biomedical research; and US ‘069’s disclosure that their compounds release NO under physiological conditions and that NO can regulate cardiovascular homeostasis.
Regarding claim 21, US ‘069 discloses NO-releasing molecules as useful for inhibition of platelets, as NO is a known inhibitor of platelet aggregation [0058].
Regarding claim 27, US ‘069 discloses a vascular stent can be coated with their compounds to elute therapeutic amounts of NO, which would accelerate healing following stent deployment, specifically mentioning restenosis inhibition [0035] to [0037] and [0045].
Regarding claim 29, US ‘069 discloses the treatment of irritable bowel syndrome (reading on gastrointestinal disorders) with their NO releasing compounds [0045].
Regarding claim 30, US ‘069 discloses the treatment of impotence (reading on sexual dysfunctions) with their NO releasing compounds [0045] and further teaches oral and topical administration [0046].
Claims 1 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold et al. (Org. Lett. 2002, 4, 1323-2325 – previously cited) (“Arnold”); in view of Arnold et al. (US 2005/0203069 A1 – From IDS – previously cited) (“US ‘069”); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Shahinpoor et al. (US 2002/0182162 A1 – From IDS – previously cited) (“Shahinpoor”).
The teachings of Arnold in view of US ‘069 are disclosed in the 103 sections above and incorporated herein.
While Arnold in view of US ‘069 does not teach a method of treating baldness; the teachings of Shahinpoor are relied upon for these disclosures.
Shahinpoor teaches a method of enhancing hair growth or diminishing hair loss comprising administering topically a mixture of NO donors in a dermatologically acceptable solution mix (Shahinpoor claim 1).
Therefore, regarding claims 1 and 11, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Arnold’s compound 1 to treat baldness. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Arnold’s and US ‘069’s disclosure that the compound 1 is an NO-donor for biomedical research, further in view of Shahinpoor’s disclosure that NO donors are effective for enhancing hair growth or diminishing hair loss.
Claims 12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold et al. (Org. Lett. 2002, 4, 1323-2325 – previously cited) (“Arnold”); in view of Arnold et al. (US 2005/0203069 A1 – From IDS – previously cited) (“US ‘069”); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Huang et al. (J. Med. Chem., 2017, 60, 7617−7635 – previously cited).
The teachings of Arnold in view of US ‘069 are disclosed above and incorporated herein.
US ‘069 further teaches the applicability of their NO-donor compounds as pharmaceutical agents for the treatment of cancer [0045]. US ‘069 discloses their compounds may be administered with other agents [0051].
While Arnold in view of US ‘069 does not teach the specific cancers or specific anti-cancer agents to be co-administered with their NO-donors. The teachings of Huang et al. are relied upon for these disclosures.
Huang teaches different NO-donor compounds with applications in cancer therapy (page 7618, col. 2; and Figure 2, page 1719). Huang also teaches a number of cancer therapeutic agents that can be used in combination therapy with NO-donors (page 1720, Figure 4 and col. 1, section 2.2), including vinorelbine, cisplatin, 5-FU, and fludarabine, etc. Huang discloses the treatment of colon, prostate, and rectal cancers (page 1720, col. 2, para. 1) with their combination therapy.
Therefore, regarding the treatment of cancers by administering the instantly claimed NO-donors, as recited in claim 12, combined with a second anti-cancer agent, as recited in claim 14, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Arnold’s NO-donors compound 1 for the treatment of cancers, in view of US ‘069 and Huang. One of ordinary skill would have been motivated to do so in view of Arnold’s and US ‘069 disclosure that their compound 1 is an NO-donor for biomedical research; and Huang’s teachings that NO-donor compounds have applications in treating cancers, including colon, prostate, and rectal cancers. One of ordinary skill would have had a reasonable expectation of success in view of US ‘069’s disclosure that NO-donor compounds are applicable towards cancer treatment and may be administered with other agents, further in view of Huang’s disclosure of different cancers and anti-cancer agents that are effective for combination therapy.
Further regarding claim 14, Applicant is advised that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two agents.
Claims 6, 17, 23, 25-26 and 31-32 are rejected under 35 U.S.C. 103 as being unpatentable over Arnold et al. (Org. Lett. 2002, 4, 1323-2325 – previously cited) (“Arnold”); in view of Arnold et al. (US 2005/0203069 A1 – From IDS – previously cited) (“US ‘069”); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Haj-Yehia (US 2006/0247216 A1 – previously cited) (“Haj-Yehia”).
The teachings of Arnold in view of US ‘069 are disclosed in the 103 sections above and incorporated herein. As above.
While Arnold in view of US ‘069 does not teach: (i) administration as a nebulizable solution (claim 6); (ii) treatment of a central nervous system disorder (claim 17); (iii) treatment of diabetes, arthritis, or systemic lupus erythematosus (claim 23); (iv) chronic obstructive pulmonary disease (COPD), pneumonia, etc. (claim 25); (v) treatment of vascular disease (claim 26); (vi) ischemia-reperfusion tissue injury (claim 31); or (vii) coadministration with an anti-coagulant (claim 32); the teachings of Haj-Yehia are relied upon for these disclosures.
Regarding claim 6, Haj-Yehia teaches compositions with an NO-donor component for treating disorders associated with oxidative stress and free radical injury (abstract) and discloses their compounds may be administered as liquid nebulizers [0581] for treating Alzheimer’s and Parkinson’s diseases, as well as other conditions.
Regarding claim 17, Haj-Yehia teaches compositions with an NO-donor component for treating Alzheimer’s and Parkinson’s diseases (reading on central nervous system disorder) (Haj-Yehia claim 9).
Regarding claim 23, Haj-Yehia teaches compositions with an NO-donor component for treating diabetes, arthritis, or systemic lupus erythematosus (Haj-Yehia claim 9).
Regarding claim 25, Haj-Yehia teaches compositions with an NO-donor component for treating chronic obstructive pulmonary disease (COPD), pneumonia, etc. (Haj-Yehia claim 9).
Regarding claim 26, Haj-Yehia teaches compositions with an NO-donor component for treating vascular disease (Haj-Yehia claim 9).
Regarding claim 31, Haj-Yehia teaches compositions with an NO-donor component for treating ischemia-reperfusion tissue injury (Haj-Yehia claim 9).
Regarding administration of the NO-donor compounds as a nebulizable solution, as recited in claim 6, for the treatment of conditions such as those cited in claims 17, 23, 25-26 and 31, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Arnold’s NO-donor compound 1 as a nebulizable solution to treat these conditions in view of US ‘069 and Haj-Yehia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Arnold’s disclosure of their NO-donor compound for biomedical research; further in view of Haj-Yehia’s teachings that NO-donors may be administered as a liquid nebulizer to treat conditions like Alzheimer’s, arthritis, vascular disease, and ischemia etc, and that administration by inhalation is a practical, easy to use, and convenient form of administration [0583].
Regarding coadministration of the instantly claimed NO-donors with an anti-coagulant, as recited in claim 32, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer the instantly claimed NO-donor compounds along with an anti-coagulant agent. One of ordinary skill would have been motivated to do so in order to co-inhibit platelet aggregation and clot formation in order to restore blood flow to the ischemic individual. One of ordinary skill would have had a reasonable expectation of success in view of Arnold’s and US ‘069’s teachings that compound 1 is a platelet aggregation inhibitor (anti-coagulant); further in view of Haj-Yehia’s teachings that their NO-donors can treat ischemia/reperfusion injury.
Further regarding claim 32, Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two agents.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Arnold et al. (Org. Lett. 2002, 4, 1323-2325 – previously cited) (“Arnold”); in view of Arnold et al. (US 2005/0203069 A1 – From IDS – previously cited) (“US ‘069”); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Lee et al. (Electrolyte & Blood Pressure, 6:27-34, 2008 – previously cited) (“Lee”).
The teachings of Arnold in view of US ‘069 are disclosed in the 103 sections above and incorporated herein.
While Arnold in view of US ‘069 does not teach treatment of chronic kidney disease (claim 22); the teachings of Lee et al. are relied upon for these disclosures.
Lee teaches that pretreatment with nitric oxide donors may prevent ischemic acute renal injury. Lee also discloses chronic kidney disease is correlated with increased plasma level of asymmetric dimethylarginine, an inhibitor of NO synthase (abstract). Lee further teaches reduced NO production is associated with elevated arterial pressure (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Arnold’s and US ‘069’s NO-donor compound 1 to a subject suffering from chronic kidney disease (CKD). One of ordinary skill would have been motivated to do so in order to balance NO levels and prevent ischemic acute renal injury in a subject suffering from CKD, which is taught by Lee to result in reduced NO production. One of ordinary skill would have had a reasonable expectation of success in view of Arnold’s and US ‘069’s disclosure of NO-donor compound 1, for biomedical research.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Arnold et al. (Org. Lett. 2002, 4, 1323-2325 – previously cited) (“Arnold”); in view of Arnold et al. (US 2005/0203069 A1 – From IDS – previously cited) (“US ‘069”); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Gourine et al. (Gen. Pharmac. 26, 835-841, 1995 – previously cited) (“Gourine”).
The teachings of Arnold in view of US ‘069 are disclosed in the 103 sections above and incorporated herein.
While Arnold in view of US ‘069 does not specifically teach the treatment of fever; the teachings of Gourine et al. are relied upon for these disclosures.
Gourine teaches intravenous injections with nitric oxide-donors molsidomine and isosorbide reduced fever in rabbits (abstract; and page 837, col. 1; and Figure 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Arnold’s and US ‘069’s NO-donor compound 1 to a subject with fever. One of ordinary skill would have been motivated to do so in view of Gourine’s disclosure that NO-donors were successful in reducing fever. One of ordinary skill would have had a reasonable expectation of success in view of Arnold’s and US ‘069’s disclosure of the NO-donor compound 1 for biomedical research.
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 1-4, 7, 15-16, 21, 27, and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 7-8, and 12 of copending Application No. 17/797,899 (Copending ‘899); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS).
Regarding instant claims 1-4, Copending ‘899 speaks to formulations comprising the NO-donor compounds Formula II and III below:
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Regarding instant claim 7, Copending ‘899 speaks to the formulation comprising their NO-donor compounds of Formula I, with a total releasable NO storage range of 0.1-8.0 µmol of NO per mg of compound, etc.
Copending ‘899 does not teach: (i) the treatment of cardiovascular disease by administering the compounds of Formula II-III (instant claims 15-16); (ii) inhibition of platelet aggregation or inhibition of platelet adhesion (instant claim 21); (iii) the treatment of restenosis via a drug loaded stent (instant claim 27); (iv) treatment of gastrointestinal disorders (instant claim 29); or (v) the treatment of sexual dysfunction. The teachings of US ‘069 are relied upon for these disclosures.
Regarding claim 15, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis and cardiovascular disorders [0006] and [0045]. US ‘069 specifically teaches treatment of pulmonary hypertension with their compounds [0066].
Regarding claim 16, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis [0006]. As mentioned in the claim interpretation, metabolic syndrome increases the risk of coronary heart disease. Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s NO-releasing compounds to a subject suffering from metabolic syndrome. One of ordinary skill would have been motivated to do so to regulate cardiovascular homeostasis, which would be expected to be negatively impacted by the presence of metabolic syndrome. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘899’s NO-releasing compounds and US ‘069’s disclosure that NO can regulate cardiovascular homeostasis.
Regarding claim 21, US ‘069 discloses NO-releasing molecules as useful for inhibition of platelets, as NO is a known inhibitor of platelet aggregation [0058].
Regarding claim 27, US ‘069 discloses a vascular stent can be coated with their compounds to elute therapeutic amounts of NO, which would accelerate healing following stent deployment, specifically mentioning restenosis inhibition [0035] to [0037] and [0045].
Regarding claim 29, US ‘069 discloses the treatment of irritable bowel syndrome (reading on gastrointestinal disorders) with their NO releasing compounds [0045].
Regarding claim 30, US ‘069 discloses the treatment of impotence (reading on sexual dysfunctions) with their NO releasing compounds [0045] and further teaches oral and topical administration [0046].
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s compounds of Formula II-III for inhibition of platelet aggregation, restenosis, the treatment of irritable bowel syndrome, or impotence. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘899’s disclosure of NO-donor compounds and US ‘069’s disclosure that NO-releasing compounds are effective for treating these conditions.
This is a provisional nonstatutory double patenting rejection.
Claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 8, and 12 of copending Application No. 17/797,899 (Copending ‘899); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Shahinpoor et al. (US 2002/0182162 A1 – From IDS).
The teachings of Copending ‘899 and US ‘069 are disclosed above and incorporated herein.
Copending ‘899 in view of US ‘069 does not teach a method of treating baldness. The teachings of Shahinpoor are relied upon for these disclosures.
Shahinpoor teaches a method of enhancing hair growth or diminishing hair loss comprising administering topically a mixture of NO donors in a dermatologically acceptable solution mix (Shahinpoor claim 1).
Regarding claim 11, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s compounds of Formula II to treat baldness. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘899’s NO-donor compound formulations, further in view of Shahinpoor’s disclosure that NO donors are effective for enhancing hair growth or diminishing hair loss.
This is a provisional nonstatutory double patenting rejection.
Claims 12 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 8, and 12 of copending Application No. 17/797,899 (Copending ‘899); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS), as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Huang et al. (J. Med. Chem., 2017, 60, 7617−7635).
The teachings of Copending ‘899 and US ‘069 are disclosed above and incorporated herein.
US ‘069 further teaches the applicability of their NO-donor compounds as pharmaceutical agents for the treatment of cancer [0045]. US ‘069 discloses their compounds may be administered with other agents [0051].
While Copending ‘899 in view of US ‘069 does not teach the specific cancers or specific anti-cancer agents to be co-administered with their NO-donors. The teachings of Huang are relied upon for these disclosures.
Huang teaches different NO-donor compounds with applications in cancer therapy (page 7618, col. 2; and Figure 2, page 1719). Huang also teaches a number of cancer therapeutic agents that can be used in combination therapy with NO-donors (page 1720, Figure 4 and col. 1, section 2.2), including vinorelbine, cisplatin, 5-FU, and fludarabine, etc. Huang discloses the treatment of colon, prostate, and rectal cancers (page 1720, col. 2, para. 1) with their combination therapy.
Therefore, regarding the treatment of cancers by administering the instantly claimed NO-donors, as recited in claim 12, combined with a second anti-cancer agent, as recited in claim 14, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s NO-donors in view of US ‘069 and Huang. One of ordinary skill would have been motivated to do so in view of US ‘069’s disclosure that their compounds of Formula I are NO donors, further in view of Huang’s teachings that NO-donor compounds have applications in treating cancers, including colon, prostate, and rectal cancers. One of ordinary skill would have had a reasonable expectation of success in view of Copending 899’s disclosure of their NO-donor compounds, US ‘069’s teachings that their NO-donors are applicable towards cancer treatment and may be administered with other agents, and Huang’s teachings of different cancers and additional anti-cancer agents that are effective for combination treatment.
Further regarding claim 14, Applicant is advised that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claims 6, 17, 23, 25-26 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 8, and 12 of copending Application No. 17/797,899 (Copending ‘899); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Haj-Yehia (US 2006/0247216 A1).
The teachings of Copending ‘899 and US ‘069 are disclosed above and incorporated herein.
Copending ‘899 in view of US ‘069 does not teach: (i) administration as a nebulizable solution (claim 6); (ii) treatment of a central nervous system disorder (claim 17); (iii) treatment of diabetes, arthritis, or systemic lupus erythematosus (claim 23); (iv) chronic obstructive pulmonary disease (COPD), pneumonia, etc. (claim 25); (v) treatment of vascular disease (claim 26); (vi) ischemia-reperfusion tissue injury (claim 31); or (vii) coadministration with an anti-coagulant (claim 32). The teachings of Haj-Yehia et al. are relied upon for these disclosures.
Regarding claim 6, Haj-Yehia teaches compositions with an NO-donor component for treating disorders associated with oxidative stress and free radical injury (abstract) and discloses their compounds may be administered as liquid nebulizers [0581] and that administration by inhalation is a practical, easy to use, and convenient form of administration [0583].
Regarding claim 17, Haj-Yehia teaches compositions with an NO-donor component for treating Alzheimer’s and Parkinson’s diseases (reading on central nervous system disorder) (Haj-Yehia claim 9).
Regarding claim 23, Haj-Yehia teaches compositions with an NO-donor component for treating diabetes, arthritis, or systemic lupus erythematosus (Haj-Yehia claim 9).
Regarding claim 25, Haj-Yehia teaches compositions with an NO-donor component for treating chronic obstructive pulmonary disease (COPD), pneumonia, etc. (Haj-Yehia claim 9).
Regarding claim 26, Haj-Yehia teaches compositions with an NO-donor component for treating vascular disease (Haj-Yehia claim 9).
Regarding claim 31, Haj-Yehia teaches compositions with an NO-donor component for treating ischemia-reperfusion tissue injury (Haj-Yehia claim 9).
Regarding administration of the NO-donor compounds as a nebulizable solution, as recited in claim 6, for the treatment of conditions such as those cited in claims 17, 23, 25-26 and 31, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s NO-donor compounds of Formula II-III as a nebulizable solution to treat these conditions in view of Haj-Yehia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘899’s disclosure that the compounds of Formulas II-III serve as NO-donors, further in view of Haj-Yehia’s teachings that NO-donors may be administered as a liquid nebulizer to treat conditions like Alzheimer’s, arthritis, vascular disease, and ischemia etc.
Regarding instant claim 32, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s NO-donor compounds along with an anti-coagulant agent. One of ordinary skill would have been motivated to do so in order to co-inhibit platelet aggregation and clot formation in order to restore blood flow to the ischemic individual. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘899’s disclosure of the NO-releasing compounds of Formula II-III, US ‘069 teachings that NO-donor compounds serve as platelet aggregation inhibitors (anti-coagulant), further in view of Haj-Yehia’s teachings that their NO-donors can treat ischemia/reperfusion injury.
Further regarding claim 32, Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 8, and 12 of copending Application No. 17/797,899 (Copending ‘899), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Lee et al. (Electrolyte & Blood Pressure, 6:27-34, 2008).
The teachings of Copending ‘899 and US ‘069 are disclosed above and incorporated herein.
Copending ‘899 in view of US ‘069 does not teach treatment of chronic kidney disease (instant claim 22). The teachings of Lee et al. are relied upon for these disclosures.
Lee teaches that pretreatment with nitric oxide donors may prevent ischemic acute renal injury. Lee also discloses chronic kidney disease is correlated with increased plasma level of asymmetric dimethylarginine, an inhibitor of NO synthase (abstract). Lee further teaches reduced NO production is associated with elevated arterial pressure (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s NO-donor compounds to a subject suffering from chronic kidney disease (CKD). One of ordinary skill would have been motivated to do so in order to balance NO levels and prevent ischemic acute renal injury in a subject suffering from CKD, which is taught by Lee to result in reduced NO production. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘899’s disclosure of NO-donor compounds.
This is a provisional nonstatutory double patenting rejection.
Claim 28 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 8, and 12 of copending Application No. 17/797,899 (Copending ‘899), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Gourine et al. (Gen. Pharmac. 26, 835-841, 1995).
The teachings of Copending ‘899 and US ‘069 are disclosed above and incorporated herein.
Copending ‘899 in view of US ‘069 does not specifically teach the treatment of fever. The teachings of Gourine et al. are relied upon for these disclosures.
Gourine teaches intravenous injections with nitric oxide-donors molsidomine and isosorbide reduced fever in rabbits (abstract; and page 837, col. 1; and Figure 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘899’s NO-donor compounds to a subject with fever. One of ordinary skill would have been motivated to do so in view of Gourine’s disclosure that NO-donors were successful in reducing fever. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘899’s disclosure of NO-donor compound formulation.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 6-7, 15-16, 21, 27, and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-64 and 72 of copending Application No. 17/312,321 (Copending ‘321); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS).
Regarding instant claims 1-4, Copending ‘321 speaks to formulations comprising the NO-donor compound of Formula II below:
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Regarding instant claim 6, Copending ‘321 speaks to the formulation comprising Formula II for administration via nebulization (Copending ‘321 claim 56).
Regarding instant claim 7, Copending ‘321 speaks to the formulation comprising their NO-donor compounds of Formula I, with a total releasable NO storage range of 0.1-10.0 µmol of NO per mg of compound, etc. (Copending ‘321 claims 51-52).
Regarding instant claim 14, Copending ‘321 speaks to administration of additional active agents along with the NO-releasing compounds of Formula II.
Copending ‘321 does not teach: (i) the treatment of cardiovascular disease by administering the compounds of Formula II (instant claims 15-16); (ii) inhibition of platelet aggregation or inhibition of platelet adhesion (instant claim 21); (iii) the treatment of restenosis via a drug loaded stent (instant claim 27); (iv) treatment of gastrointestinal disorders (instant claim 29); or (v) the treatment of sexual dysfunction. The teachings of US ‘069 are relied upon for these disclosures.
Regarding claim 15, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis and cardiovascular disorders [0006] and [0045]. US ‘069 specifically teaches treatment of pulmonary hypertension with their compounds [0066].
Regarding claim 16, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis [0006]. As mentioned in the claim interpretation, metabolic syndrome increases the risk of coronary heart disease. Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s NO-releasing compounds to a subject suffering from metabolic syndrome. One of ordinary skill would have been motivated to do so to regulate cardiovascular homeostasis, which would be expected to be negatively impacted by the presence of metabolic syndrome. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘321’s NO-releasing compounds and US ‘069’s disclosure that NO can regulate cardiovascular homeostasis.
Regarding claim 21, US ‘069 discloses NO-releasing molecules as useful for inhibition of platelets, as NO is a known inhibitor of platelet aggregation [0058].
Regarding claim 27, US ‘069 discloses a vascular stent can be coated with their compounds to elute therapeutic amounts of NO, which would accelerate healing following stent deployment, specifically mentioning restenosis inhibition [0035] to [0037] and [0045].
Regarding claim 29, US ‘069 discloses the treatment of irritable bowel syndrome (reading on gastrointestinal disorders) with their NO releasing compounds [0045].
Regarding claim 30, US ‘069 discloses the treatment of impotence (reading on sexual dysfunctions) with their NO releasing compounds [0045] and further teaches oral and topical administration [0046].
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s compounds of Formula II for inhibition of platelet aggregation, restenosis, the treatment of irritable bowel syndrome, or impotence. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘321’s disclosure of NO-donor compounds and US ‘069’s disclosure that NO-releasing compounds are effective for treating these conditions.
This is a provisional nonstatutory double patenting rejection.
Claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-64 and 72 of copending Application No. 17/312,321 (Copending ‘321); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 6-7, 15-16, 21, 27, and 29-30; further in view of Shahinpoor et al. (US 2002/0182162 A1 – From IDS).
The teachings of Copending ‘321 and US ‘069 are disclosed above and incorporated herein.
Copending ‘321 in view of US ‘069 does not teach a method of treating baldness. The teachings of Shahinpoor et al. are relied upon for these disclosures.
Shahinpoor teaches a method of enhancing hair growth or diminishing hair loss comprising administering topically a mixture of NO donors in a dermatologically acceptable solution mix (Shahinpoor claim 1).
Regarding claim 11, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s compounds of Formula II to treat baldness. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘321’s NO-donor compound formulations, further in view of Shahinpoor’s disclosure that NO donors are effective for enhancing hair growth or diminishing hair loss.
This is a provisional nonstatutory double patenting rejection.
Claims 12 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-64 and 72 of copending Application No. 17/312,321 (Copending ‘321); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 6-7, 15-16, 21, 27, and 29-30; in view of Huang et al. (J. Med. Chem., 2017, 60, 7617−7635).
The teachings of Copending ‘321 and US ‘069 are disclosed above and incorporated herein.
US ‘069 further teaches the applicability of their NO-donor compounds as pharmaceutical agents for the treatment of cancer [0045]. US ‘069 discloses their compounds may be administered with other agents [0051].
While Copending ‘321 in view of US ‘069 does not teach the specific cancers or specific anti-cancer agents to be co-administered with their NO-donors. The teachings of Huang et al. are relied upon for these disclosures.
Huang teaches different NO-donor compounds with applications in cancer therapy (page 7618, col. 2; and Figure 2, page 1719). Huang also teaches a number of cancer therapeutic agents that can be used in combination therapy with NO-donors (page 1720, Figure 4 and col. 1, section 2.2), including vinorelbine, cisplatin, 5-FU, and fludarabine, etc. Huang discloses the treatment of colon, prostate, and rectal cancers (page 1720, col. 2, para. 1) with their combination therapy.
Therefore, regarding the treatment of cancers by administering the instantly claimed NO-donors, as recited in claim 12, combined with a second anti-cancer agent, as recited in claim 14, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s NO-donors in view of US ‘069 and Huang. One of ordinary skill would have been motivated to do so in view of US ‘069’s disclosure that their compounds of Formula I are NO donors, further in view of Huang’s teachings that NO-donor compounds have applications in treating cancers, including colon, prostate, and rectal cancers. One of ordinary skill would have had a reasonable expectation of success in view of Copending 321’s disclosure of their NO-donor compounds, US ‘069’s teachings that their NO-donors are applicable towards cancer treatment and may be administered with other agents, and Huang’s teachings of different cancers and additional anti-cancer agents that are effective for combination treatment.
Further regarding claim 14, Applicant is advised that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claims 17, 23, 25-26 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-64 and 72 of copending Application No. 17/312,321 (Copending ‘321); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 6-7, 15-16, 21, 27, and 29-30; further in view of Haj-Yehia (US 2006/0247216 A1).
The teachings of Copending ‘321 and US ‘069 are disclosed above and incorporated herein.
Copending ‘321 in view of US ‘069 does not teach: (i) treatment of a central nervous system disorder (claim 17); (ii) treatment of diabetes, arthritis, or systemic lupus erythematosus (claim 23); (iii) chronic obstructive pulmonary disease (COPD), pneumonia, etc. (claim 25); (iv) treatment of vascular disease (claim 26); (v) ischemia-reperfusion tissue injury (claim 31); or (vi) coadministration with an anti-coagulant (claim 32). The teachings of Haj-Yehia et al. are relied upon for these disclosures.
Regarding claim 17, Haj-Yehia teaches compositions with an NO-donor component for treating Alzheimer’s and Parkinson’s diseases (reading on central nervous system disorder) (Haj-Yehia claim 9).
Regarding claim 23, Haj-Yehia teaches compositions with an NO-donor component for treating diabetes, arthritis, or systemic lupus erythematosus (Haj-Yehia claim 9).
Regarding claim 25, Haj-Yehia teaches compositions with an NO-donor component for treating chronic obstructive pulmonary disease (COPD), pneumonia, etc. (Haj-Yehia claim 9).
Regarding claim 26, Haj-Yehia teaches compositions with an NO-donor component for treating vascular disease (Haj-Yehia claim 9).
Regarding claim 31, Haj-Yehia teaches compositions with an NO-donor component for treating ischemia-reperfusion tissue injury (Haj-Yehia claim 9).
Regarding administration of the NO-donor compounds for the treatment of conditions such as those cited in claims 17, 23, 25-26 and 31, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s NO-donor compounds of Formula II to treat these conditions in view of Haj-Yehia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘321’s disclosure that the compounds of Formulas II serve as NO-donors, further in view of Haj-Yehia’s teachings that NO-donors may be administered to treat conditions like Alzheimer’s, arthritis, vascular disease, and ischemia etc.
Regarding instant claim 32, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s NO-donor compounds along with an anti-coagulant agent. One of ordinary skill would have been motivated to do so in order to co-inhibit platelet aggregation and clot formation in order to restore blood flow to the ischemic individual. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘321’s disclosure of the NO-releasing compounds of Formula II, US ‘069 teachings that NO-donor compounds serve as platelet aggregation inhibitors (anti-coagulant), further in view of Haj-Yehia’s teachings that their NO-donors can treat ischemia/reperfusion injury.
Further regarding claim 32, Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-64 and 72 of copending Application No. 17/312,321 (Copending ‘321); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 6-7, 15-16, 21, 27, and 29-30; further in view of Lee et al. (Electrolyte & Blood Pressure, 6:27-34, 2008).
The teachings of Copending ‘321 and US ‘069 are disclosed above and incorporated herein.
Copending ‘321 in view of US ‘069 does not teach treatment of chronic kidney disease (instant claim 22). The teachings of Lee et al. are relied upon for these disclosures.
Lee teaches that pretreatment with nitric oxide donors may prevent ischemic acute renal injury. Lee also discloses chronic kidney disease is correlated with increased plasma level of asymmetric dimethylarginine, an inhibitor of NO synthase (abstract). Lee further teaches reduced NO production is associated with elevated arterial pressure (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s NO-donor compounds to a subject suffering from chronic kidney disease (CKD). One of ordinary skill would have been motivated to do so in order to balance NO levels and prevent ischemic acute renal injury in a subject suffering from CKD, which is taught by Lee to result in reduced NO production. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘321’s disclosure of NO-donor compounds.
This is a provisional nonstatutory double patenting rejection.
Claim 28 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47-64 and 72 of copending Application No. 17/312,321 (Copending ‘321); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 6-7, 15-16, 21, 27, and 29-30; further in view of Gourine et al. (Gen. Pharmac. 26, 835-841, 1995).
The teachings of Copending ‘321 and US ‘069 are disclosed above and incorporated herein.
Copending ‘321 in view of US ‘069 does not specifically teach the treatment of fever. The teachings of Gourine et al. are relied upon for these disclosures.
Gourine teaches intravenous injections with nitric oxide-donors molsidomine and isosorbide reduced fever in rabbits (abstract; and page 837, col. 1; and Figure 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘321’s NO-donor compounds to a subject with fever. One of ordinary skill would have been motivated to do so in view of Gourine’s disclosure that NO-donors were successful in reducing fever. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘321’s disclosure of NO-donor compound formulation.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 7, 15-16, 21, 27, and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-11 of copending Application No. 18/872,576 (Copending ‘576); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS).
Regarding instant claims 1-4, Copending ‘576 speaks to formulations comprising the NO-donor compound below:
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Copending ‘576 does not teach: (i) the treatment of cardiovascular disease by administering the compounds of Formula II-III (instant claims 15-16); (ii) inhibition of platelet aggregation or inhibition of platelet adhesion (instant claim 21); (iii) the treatment of restenosis via a drug loaded stent (instant claim 27); (iv) treatment of gastrointestinal disorders (instant claim 29); or (v) the treatment of sexual dysfunction. The teachings of US ‘069 are relied upon for these disclosures.
Regarding claim 15, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis and cardiovascular disorders [0006] and [0045]. US ‘069 specifically teaches treatment of pulmonary hypertension with their compounds [0066].
Regarding claim 16, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis [0006]. As mentioned in the claim interpretation, metabolic syndrome increases the risk of coronary heart disease. Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-releasing compounds to a subject suffering from metabolic syndrome. One of ordinary skill would have been motivated to do so to regulate cardiovascular homeostasis, which would be expected to be negatively impacted by the presence of metabolic syndrome. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘576’s NO-releasing compounds and US ‘069’s disclosure that NO can regulate cardiovascular homeostasis.
Regarding claim 21, US ‘069 discloses NO-releasing molecules as useful for inhibition of platelets, as NO is a known inhibitor of platelet aggregation [0058].
Regarding claim 27, US ‘069 discloses a vascular stent can be coated with their compounds to elute therapeutic amounts of NO, which would accelerate healing following stent deployment, specifically mentioning restenosis inhibition [0035] to [0037] and [0045].
Regarding claim 29, US ‘069 discloses the treatment of irritable bowel syndrome (reading on gastrointestinal disorders) with their NO releasing compounds [0045].
Regarding claim 30, US ‘069 discloses the treatment of impotence (reading on sexual dysfunctions) with their NO releasing compounds [0045] and further teaches oral and topical administration [0046].
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-releasing compounds for inhibition of platelet aggregation, restenosis, the treatment of irritable bowel syndrome, or impotence. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘576’s disclosure of NO-donor compounds and US ‘069’s disclosure that NO-releasing compounds are effective for treating these conditions.
This is a provisional nonstatutory double patenting rejection.
Claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-11 of copending Application No. 18/872,576 (Copending ‘576), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Shahinpoor et al. (US 2002/0182162 A1 – From IDS).
The teachings of Copending ‘576 and US ‘069 are disclosed above and incorporated herein.
Copending ‘576 in view of US ‘069 does not teach a method of treating baldness. The teachings of Shahinpoor et al. are relied upon for these disclosures.
Shahinpoor teaches a method of enhancing hair growth or diminishing hair loss comprising administering topically a mixture of NO donors in a dermatologically acceptable solution mix (Shahinpoor claim 1).
Regarding claim 11, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-releasing compounds to treat baldness. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘576’s NO-donor compound formulations, further in view of Shahinpoor’s disclosure that NO donors are effective for enhancing hair growth or diminishing hair loss.
This is a provisional nonstatutory double patenting rejection.
Claims 12 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-11 of copending Application No. 18/872,576 (Copending ‘576), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Huang et al. (J. Med. Chem., 2017, 60, 7617−7635).
The teachings of Copending ‘576 and US ‘069 are disclosed above and incorporated herein.
US ‘069 further teaches the applicability of their NO-donor compounds as pharmaceutical agents for the treatment of cancer [0045]. US ‘069 discloses their compounds may be administered with other agents [0051].
While Copending ‘576 in view of US ‘069 does not teach the specific cancers or specific anti-cancer agents to be co-administered with their NO-donors. The teachings of Huang et al. are relied upon for these disclosures.
Huang teaches different NO-donor compounds with applications in cancer therapy (page 7618, col. 2; and Figure 2, page 1719). Huang also teaches a number of cancer therapeutic agents that can be used in combination therapy with NO-donors (page 1720, Figure 4 and col. 1, section 2.2), including vinorelbine, cisplatin, 5-FU, and fludarabine, etc. Huang discloses the treatment of colon, prostate, and rectal cancers (page 1720, col. 2, para. 1) with their combination therapy.
Therefore, regarding the treatment of cancers by administering the instantly claimed NO-donors, as recited in claim 12, combined with a second anti-cancer agent, as recited in claim 14, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-donors in view of US ‘069 and Huang. One of ordinary skill would have been motivated to do so in view of US ‘069’s disclosure that their compounds of Formula I are NO donors, further in view of Huang’s teachings that NO-donor compounds have applications in treating cancers, including colon, prostate, and rectal cancers. One of ordinary skill would have had a reasonable expectation of success in view of Copending 576’s disclosure of their NO-donor compounds, US ‘069’s teachings that their NO-donors are applicable towards cancer treatment and may be administered with other agents, and Huang’s teachings of different cancers and additional anti-cancer agents that are effective for combination treatment.
Further regarding claim 14, Applicant is advised that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claims 6, 17, 23, 25-26 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-11 of copending Application No. 18/872,576 (Copending ‘576); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Haj-Yehia (US 2006/0247216 A1).
The teachings of Copending ‘576 and US ‘069 are disclosed above and incorporated herein.
Copending ‘576 in view of US ‘069 does not teach: (i) administration as a nebulizable solution (claim 6); (ii) treatment of a central nervous system disorder (claim 17); (iii) treatment of diabetes, arthritis, or systemic lupus erythematosus (claim 23); (iv) chronic obstructive pulmonary disease (COPD), pneumonia, etc. (claim 25); (v) treatment of vascular disease (claim 26); (vi) ischemia-reperfusion tissue injury (claim 31); or (vii) coadministration with an anti-coagulant (claim 32). The teachings of Haj-Yehia et al. are relied upon for these disclosures.
Regarding claim 6, Haj-Yehia teaches compositions with an NO-donor component for treating disorders associated with oxidative stress and free radical injury (abstract) and discloses their compounds may be administered as liquid nebulizers [0581] and that administration by inhalation is a practical, easy to use, and convenient form of administration [0583].
Regarding claim 17, Haj-Yehia teaches compositions with an NO-donor component for treating Alzheimer’s and Parkinson’s diseases (reading on central nervous system disorder) (Haj-Yehia claim 9).
Regarding claim 23, Haj-Yehia teaches compositions with an NO-donor component for treating diabetes, arthritis, or systemic lupus erythematosus (Haj-Yehia claim 9).
Regarding claim 25, Haj-Yehia teaches compositions with an NO-donor component for treating chronic obstructive pulmonary disease (COPD), pneumonia, etc. (Haj-Yehia claim 9).
Regarding claim 26, Haj-Yehia teaches compositions with an NO-donor component for treating vascular disease (Haj-Yehia claim 9).
Regarding claim 31, Haj-Yehia teaches compositions with an NO-donor component for treating ischemia-reperfusion tissue injury (Haj-Yehia claim 9).
Regarding administration of the NO-donor compounds as a nebulizable solution, as recited in claim 6, for the treatment of conditions such as those cited in claims 17, 23, 25-26 and 31, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-donor compounds as a nebulizable solution to treat these conditions in view of Haj-Yehia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘576’s disclosure that their compounds serve as NO-donors, further in view of Haj-Yehia’s teachings that NO-donors may be administered as a liquid nebulizer to treat conditions like Alzheimer’s, arthritis, vascular disease, and ischemia etc.
Regarding instant claim 32, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-donor compounds along with an anti-coagulant agent. One of ordinary skill would have been motivated to do so in order to co-inhibit platelet aggregation and clot formation in order to restore blood flow to the ischemic individual. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘576’s disclosure of the NO-releasing compounds, US ‘069 teachings that NO-donor compounds serve as platelet aggregation inhibitors (anti-coagulant), further in view of Haj-Yehia’s teachings that their NO-donors can treat ischemia/reperfusion injury.
Further regarding claim 32, Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-11 of copending Application No. 18/872,576 (Copending ‘576), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Lee et al. (Electrolyte & Blood Pressure, 6:27-34, 2008).
The teachings of Copending ‘576 and US ‘069 are disclosed above and incorporated herein.
Copending ‘576 in view of US ‘069 does not teach treatment of chronic kidney disease (instant claim 22). The teachings of Lee et al. are relied upon for these disclosures.
Lee teaches that pretreatment with nitric oxide donors may prevent ischemic acute renal injury. Lee also discloses chronic kidney disease is correlated with increased plasma level of asymmetric dimethylarginine, an inhibitor of NO synthase (abstract). Lee further teaches reduced NO production is associated with elevated arterial pressure (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-donor compounds to a subject suffering from chronic kidney disease (CKD). One of ordinary skill would have been motivated to do so in order to balance NO levels and prevent ischemic acute renal injury in a subject suffering from CKD, which is taught by Lee to result in reduced NO production. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘576’s disclosure of NO-donor compounds.
This is a provisional nonstatutory double patenting rejection.
Claim 28 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 7-11 of copending Application No. 18/872,576 (Copending ‘576), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Gourine et al. (Gen. Pharmac. 26, 835-841, 1995).
The teachings of Copending ‘576 and US ‘069 are disclosed above and incorporated herein.
Copending ‘576 in view of US ‘069 does not specifically teach the treatment of fever. The teachings of Gourine et al. are relied upon for these disclosures.
Gourine teaches intravenous injections with nitric oxide-donors molsidomine and isosorbide reduced fever in rabbits (abstract; and page 837, col. 1; and Figure 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘576’s NO-donor compounds to a subject with fever. One of ordinary skill would have been motivated to do so in view of Gourine’s disclosure that NO-donors were successful in reducing fever. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘576’s disclosure of NO-donor compound formulation.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4, 7, 15-16, 21, 27, and 29-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/197,332 (Copending ‘332), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS).
Regarding instant claims 1-4, Copending ‘322 speaks to formulations comprising the NO-donor compound below:
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Copending ‘322 does not teach: (i) the treatment of cardiovascular disease by administering the compounds of Formula II-III (instant claims 15-16); (ii) inhibition of platelet aggregation or inhibition of platelet adhesion (instant claim 21); (iii) the treatment of restenosis via a drug loaded stent (instant claim 27); (iv) treatment of gastrointestinal disorders (instant claim 29); or (v) the treatment of sexual dysfunction. The teachings of US ‘069 are relied upon for these disclosures.
Regarding instant claims 12 and 14, US ‘069 the applicability of the NO-donor compounds of Formula II-III as pharmaceutical agents for the treatment of cancer [0045].
Regarding claim 14, US ‘069 discloses the applicability of the compounds as pharmaceutical agents for the treatment of cancer [0045]. Regarding administration with a second anti-cancer agent, Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two agents.
Applicant is reminded, the arguments of counsel cannot take the place of evidence in the record.
Regarding claim 15, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis and cardiovascular disorders [0006] and [0045]. US ‘069 specifically teaches treatment of pulmonary hypertension with their compounds [0066].
Regarding claim 16, US ‘069 discloses NO as a bioregulatory molecule with diverse functional roles in cardiovascular homeostasis [0006]. As mentioned in the claim interpretation, metabolic syndrome increases the risk of coronary heart disease. Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘322’s NO-releasing compounds to a subject suffering from metabolic syndrome. One of ordinary skill would have been motivated to do so to regulate cardiovascular homeostasis, which would be expected to be negatively impacted by the presence of metabolic syndrome. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘322’s NO-releasing compounds and US ‘069’s disclosure that NO can regulate cardiovascular homeostasis.
Regarding claim 21, US ‘069 discloses NO-releasing molecules as useful for inhibition of platelets, as NO is a known inhibitor of platelet aggregation [0058].
Regarding claim 27, US ‘069 discloses a vascular stent can be coated with their compounds to elute therapeutic amounts of NO, which would accelerate healing following stent deployment, specifically mentioning restenosis inhibition [0035] to [0037] and [0045].
Regarding claim 29, US ‘069 discloses the treatment of irritable bowel syndrome (reading on gastrointestinal disorders) with their NO releasing compounds [0045].
Regarding claim 30, US ‘069 discloses the treatment of impotence (reading on sexual dysfunctions) with their NO releasing compounds [0045] and further teaches oral and topical administration [0046].
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘322’s NO-releasing compounds for inhibition of platelet aggregation, restenosis, the treatment of irritable bowel syndrome, or impotence. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘322’s disclosure of NO-donor compounds and US ‘069’s disclosure that NO-releasing compounds are effective for treating these conditions.
This is a provisional nonstatutory double patenting rejection.
Claim 11 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/197,332 (Copending ‘332); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Shahinpoor et al. (US 2002/0182162 A1 – From IDS).
The teachings of Copending ‘322 and US ‘069 are disclosed above and incorporated herein.
Copending ‘322 in view of US ‘069 does not teach a method of treating baldness. The teachings of Shahinpoor et al. are relied upon for these disclosures.
Shahinpoor teaches a method of enhancing hair growth or diminishing hair loss comprising administering topically a mixture of NO donors in a dermatologically acceptable solution mix (Shahinpoor claim 1).
Regarding claim 11, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘322’s NO-releasing compounds to treat baldness. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘322’s NO-donor compound formulations, further in view of Shahinpoor’s disclosure that NO donors are effective for enhancing hair growth or diminishing hair loss.
This is a provisional nonstatutory double patenting rejection.
Claims 12 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/197,332 (Copending ‘332), in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Huang et al. (J. Med. Chem., 2017, 60, 7617−7635).
The teachings of Copending ‘332 and US ‘069 are disclosed above and incorporated herein.
US ‘069 further teaches the applicability of their NO-donor compounds as pharmaceutical agents for the treatment of cancer [0045]. US ‘069 discloses their compounds may be administered with other agents [0051].
While Copending ‘332 in view of US ‘069 does not teach the specific cancers or specific anti-cancer agents to be co-administered with their NO-donors. The teachings of Huang et al. are relied upon for these disclosures.
Huang teaches different NO-donor compounds with applications in cancer therapy (page 7618, col. 2; and Figure 2, page 1719). Huang also teaches a number of cancer therapeutic agents that can be used in combination therapy with NO-donors (page 1720, Figure 4 and col. 1, section 2.2), including vinorelbine, cisplatin, 5-FU, and fludarabine, etc. Huang discloses the treatment of colon, prostate, and rectal cancers (page 1720, col. 2, para. 1) with their combination therapy.
Therefore, regarding the treatment of cancers by administering the instantly claimed NO-donors, as recited in claim 12, combined with a second anti-cancer agent, as recited in claim 14, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘332’s NO-donors in view of US ‘069 and Huang. One of ordinary skill would have been motivated to do so in view of US ‘069’s disclosure that their compounds of Formula I are NO donors, further in view of Huang’s teachings that NO-donor compounds have applications in treating cancers, including colon, prostate, and rectal cancers. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘332’s disclosure of their NO-donor compounds, US ‘069’s teachings that their NO-donors are applicable towards cancer treatment and may be administered with other agents, and Huang’s teachings of different cancers and additional anti-cancer agents that are effective for combination treatment.
Further regarding claim 14, Applicant is advised that the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claims 6, 17, 23, 25-26 and 31-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/197,332 (Copending ‘332); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Haj-Yehia (US 2006/0247216 A1).
The teachings of Copending ‘322 and US ‘069 are disclosed above and incorporated herein.
Copending ‘322 in view of US ‘069 does not teach: (i) administration as a nebulizable solution (claim 6); (ii) treatment of a central nervous system disorder (claim 17); (iii) treatment of diabetes, arthritis, or systemic lupus erythematosus (claim 23); (iv) chronic obstructive pulmonary disease (COPD), pneumonia, etc. (claim 25); (v) treatment of vascular disease (claim 26); (vi) ischemia-reperfusion tissue injury (claim 31); or (vii) coadministration with an anti-coagulant (claim 32). The teachings of Haj-Yehia et al. are relied upon for these disclosures.
Regarding claim 6, Haj-Yehia teaches compositions with an NO-donor component for treating disorders associated with oxidative stress and free radical injury (abstract) and discloses their compounds may be administered as liquid nebulizers [0581] and that administration by inhalation is a practical, easy to use, and convenient form of administration [0583].
Regarding claim 17, Haj-Yehia teaches compositions with an NO-donor component for treating Alzheimer’s and Parkinson’s diseases (reading on central nervous system disorder) (Haj-Yehia claim 9).
Regarding claim 23, Haj-Yehia teaches compositions with an NO-donor component for treating diabetes, arthritis, or systemic lupus erythematosus (Haj-Yehia claim 9).
Regarding claim 25, Haj-Yehia teaches compositions with an NO-donor component for treating chronic obstructive pulmonary disease (COPD), pneumonia, etc. (Haj-Yehia claim 9).
Regarding claim 26, Haj-Yehia teaches compositions with an NO-donor component for treating vascular disease (Haj-Yehia claim 9).
Regarding claim 31, Haj-Yehia teaches compositions with an NO-donor component for treating ischemia-reperfusion tissue injury (Haj-Yehia claim 9).
Regarding administration of the NO-donor compounds as a nebulizable solution, as recited in claim 6, for the treatment of conditions such as those cited in claims 17, 23, 25-26 and 31, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘322’s NO-donor compounds as a nebulizable solution to treat these conditions in view of Haj-Yehia. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of Copending ‘322’s disclosure that their compounds serve as NO-donors, further in view of Haj-Yehia’s teachings that NO-donors may be administered as a liquid nebulizer to treat conditions like Alzheimer’s, arthritis, vascular disease, and ischemia etc.
Regarding instant claim 32, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘322’s NO-donor compounds along with an anti-coagulant agent. One of ordinary skill would have been motivated to do so in order to co-inhibit platelet aggregation and clot formation in order to restore blood flow to the ischemic individual. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘322’s disclosure of the NO-releasing compounds, US ‘069 teachings that NO-donor compounds serve as platelet aggregation inhibitors (anti-coagulant), further in view of Haj-Yehia’s teachings that their NO-donors can treat ischemia/reperfusion injury.
Further regarding claim 32, Applicant is reminded the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art. It is therefore obvious to provide a mixture of the two agents.
This is a provisional nonstatutory double patenting rejection.
Claim 22 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/197,332 (Copending ‘332); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Lee et al. (Electrolyte & Blood Pressure, 6:27-34, 2008).
The teachings of Copending ‘322 and US ‘069 are disclosed above and incorporated herein.
Copending ‘322 in view of US ‘069 does not teach treatment of chronic kidney disease (instant claim 22). The teachings of Lee et al. are relied upon for these disclosures.
Lee teaches that pretreatment with nitric oxide donors may prevent ischemic acute renal injury. Lee also discloses chronic kidney disease is correlated with increased plasma level of asymmetric dimethylarginine, an inhibitor of NO synthase (abstract). Lee further teaches reduced NO production is associated with elevated arterial pressure (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘322’s NO-donor compounds to a subject suffering from chronic kidney disease (CKD). One of ordinary skill would have been motivated to do so in order to balance NO levels and prevent ischemic acute renal injury in a subject suffering from CKD, which is taught by Lee to result in reduced NO production. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘322’s disclosure of NO-donor compounds.
This is a provisional nonstatutory double patenting rejection.
Claim 28 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of copending Application No. 19/197,332 (Copending ‘332); in view of Arnold et al. (US ‘069) (US 2005/0203069 A1 – From IDS); as applied to claims 1-4, 7, 15-16, 21, 27, and 29-30; further in view of Gourine et al. (Gen. Pharmac. 26, 835-841, 1995).
The teachings of Copending ‘322 and US ‘069 are disclosed above and incorporated herein.
Copending ‘322 in view of US ‘069 does not specifically teach the treatment of fever. The teachings of Gourine et al. are relied upon for these disclosures.
Gourine teaches intravenous injections with nitric oxide-donors molsidomine and isosorbide reduced fever in rabbits (abstract; and page 837, col. 1; and Figure 1).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Copending ‘322’s NO-donor compounds to a subject with fever. One of ordinary skill would have been motivated to do so in view of Gourine’s disclosure that NO-donors were successful in reducing fever. One of ordinary skill would have had a reasonable expectation of success in view of Copending ‘322’s disclosure of NO-donor compound formulation.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Claims
Claim amendments are acknowledged. No new matter has been added.
Specification
Amendments to the specification are acknowledged and have been entered. No new matter has been added.
Claim Rejections - 35 USC § 112(b)
Applicant’s arguments, see page 8, filed 11/21/2025, with respect to 35 USC § 112(b) rejection of claims 1 and 11 have been fully considered and are persuasive. The 35 USC § 112(b) rejection of the claims has been withdrawn.
Claim Rejections - 35 USC § 103
Applicant's arguments filed 11/21/2025 have been fully considered but they are not persuasive.
Applicant cites para. [0014] and [0016] from US ‘069’s disclosure and emphasizes that the object of US ‘069 was to provide diazanimundiolate molecules that don’t decompose into nitrosamines or covalently bind proteins; or a composition that is covalently attached to phenyl. Applicant argues the compounds in US ‘069 (which Applicant refers to as Arnold) require phenyl at the position corresponding to X in instant Formula I so as to avoid nitrosamine formation, and that there is no motivation to substitute Ph for instantly claimed H or D. Applicant argues that US ‘069 teaches away from using anything other than phenyl. Applicant states this phenyl is needed to prevent formation of poisonous nitrosamines.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
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., NO-donors which do not decompose into nitrosamine) are not recited in the rejected claim(s). 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).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
In the present case, US ‘069 and Arnold disclose functionally equivalent NO-donor compounds, which read or anticipate the instant compounds; and US ‘069 teaches that NO-donor compounds can be used in the context of methods of treating conditions, which read on the instant claims.
Furthermore, regarding Applicant’s statement that US ‘069’s compounds require Ph in the position corresponding to instant X, Applicant is advised that this property in never disclosed in US ‘069.
US ‘069 discloses the mechanism through which N-diazanimundiolates may form nitrosamines (page 1, col. 2) – shown below – and states that C-based diazeniumdiolates are desirable because, in contrast to N-based diazeniumdiolates, they are structurally unable to form nitrosamines while maintaining their ability to spontaneously release NO under physiological conditions [0010]. Thus, the ability to form nitrosamines does not depend on the substituent corresponding to instant X being a Ph.
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Furthermore, Arnold – cited herein – discloses their C-based diazanimundiolate compound 1 (which anticipates the instant compounds) as an NO-donor for biomedical research.
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Double Patenting
Applicant's arguments filed 11/21/2025 have been fully considered but they are not persuasive.
Applicant states the numerous obviousness-type double patenting rejections all include a combination of Arnold (US ‘069 herein) and other references, and that US ‘069 provides no motivation to remove the phenyl at the X position; teaches away from replacing phenyl; and that no obviousness rejections based on Arnold can be sustained.
As stated above, in response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, as stated above, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art.
In the present case, US ‘069 and copending applications cited refer to functionally equivalent NO-donor compounds for the treatment of conditions, as outlined in the rejections above.
Furthermore, regarding Applicant’s statement that US ‘069’s compounds require Ph in the position corresponding to instant X, Applicant is reminded that this property in never disclosed in US ‘069.
US ‘069 discloses the mechanism through which diazanimundiolates may form nitrosamines (page 1, col. 2) – shown below – and states that C-based diazeniumdiolates are desirable because, in contrast to N-based diazeniumdiolates, they are structurally unable to form nitrosamines while maintaining their ability to spontaneously release NO under physiological conditions [0010]. Thus, the ability to form nitrosamines does not depend on the substituent corresponding to instant X being a Ph.
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Furthermore, Copending Applications 17/797,899; 17/312,321; 18/872,576; and 19/197,332; all disclose the C-based diazanimundiolate compound below (which anticipates the instant compounds) as NO-donors.
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, wherein M can be Na.
Thus, the instant claims stand rejected under provisional non-statutory double patenting over Copending Applications 17/797,899; 17/312,321; 18/872,576; and 19/197,332.
Conclusion
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 JACKSON J HERNANDEZ whose telephone number is (571)272-5382. The examiner can normally be reached Mon - Thurs 7:30 to 5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
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